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Daniel Chang, MD

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Specialties

Radiation Oncology

Work and Education

Professional Education

Wayne State University, Detroit, MI, 2002

Internship

Oakwood Healthcare System, Dearborn, MI, 2003

Residency

University of Florida, Gainesville, FL, 2007

Board Certifications

Radiation Oncology, American Board of Radiology

All Publications

Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. Journal of clinical oncology Durkee, B. Y., Qian, Y., Pollom, E. L., King, M. T., Dudley, S. A., Shaffer, J. L., Chang, D. T., Gibbs, I. C., Goldhaber-Fiebert, J. D., Horst, K. C. 2016; 34 (9): 902-909

Abstract

The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab.We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions.Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.82 life-years gained, or 0.64 QALYs, at a cost of $713,219 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained.THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States.

View details for DOI 10.1200/JCO.2015.62.9105

View details for PubMedID 26351332

A Novel Biomarker Panel Examining Response to Gemcitabine with or without Erlotinib for Pancreatic Cancer Therapy in NCIC Clinical Trials Group PA.3 PLOS ONE Shultz, D. B., Pai, J., Chiu, W., Ng, K., Hellendag, M. G., Heestand, G., Chang, D. T., Tu, D., Moore, M. J., Parulekar, W. R., Koong, A. C. 2016; 11 (1)

Abstract

NCIC Clinical Trials Group PA.3 was a randomized control trial that demonstrated improved overall survival (OS) in patients receiving erlotinib in addition to gemcitabine for locally advanced or metastatic pancreatic cancer. Prior to therapy, patients had plasma samples drawn for future study. We sought to identify biomarkers within these samples.Using the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies for 35 key proteins selected from a global genetic analysis of pancreatic cancers, and used to quantify protein levels in 20 uL of patient plasma. To determine if any of these proteins levels independently associated with OS, univariate and mulitbaraible Cox models were used. In addition, we examined the associations between biomarker expression and disease stage at diagnosis using Fisher's exact test. The correlation between Erlotinib sensitivity and each biomarkers was assessed using a test of interaction between treatment and biomarker.Of the 569 eligible patients, 480 had samples available for study. Samples were randomly allocated into training (251) and validation sets (229). Among all patients, elevated levels of interleukin-8 (IL-8), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1-alpha (HIF-1 alpha), and interleukin-6 were independently associated with lower OS, while IL-8, CEA, platelet-derived growth factor receptor alpha and mucin-1 were associated with metastatic disease. Patients with elevated levels of receptor tyrosine-protein kinase erbB-2 (HER2) expression had improved OS when treated with erlotinib compared to placebo. In conclusion, PLA is a powerful tool for identifying biomarkers from archived, small volume serum samples. These data may be useful to stratify patient outcomes regardless of therapeutic intervention.ClinicalTrials.gov NCT00040183.

View details for DOI 10.1371/journal.pone.0147995

View details for Web of Science ID 000369527800261

View details for PubMedID 26808546

Statin and Metformin Use Prolongs Survival in Patients With Resectable Pancreatic Cancer. Pancreas Kozak, M. M., Anderson, E. M., von Eyben, R., Pai, J. S., Poultsides, G. A., Visser, B. C., Norton, J. A., Koong, A. C., Chang, D. T. 2016; 45 (1): 64-70

Abstract

The aim of this study was to investigate the impact of statin and metformin therapy on disease outcome for patients with pancreatic ductal adenocarcinoma (PDAC).This retrospective study included 171 PDAC patients who underwent surgical resection at the Stanford Cancer Institute between 1998 and 2013. No patients received neoadjuvant therapy. Statin and metformin use was defined as use during initial consult and continuing upon discharge from the hospital after surgery. Dose of each medication was recorded, as was the type of statin taken.The median follow-up for all patients was 11.23 months (range, 0.2-105.0 months). Among the 171 patients included in our analysis, 18 patients (10.5%) took metformin and 34 patients (19.9%) took statins. Statin use was associated with better overall survival (OS) in patients with PDAC (P = 0.011). Metformin use was also associated with better OS (P = 0.035). The use of statins remained significant on multivariate analysis for OS (P = 0.014; hazards ratio, 0.33; 95% confidence interval, 0.139-0.799), but metformin use did not (P = 0.33; hazards ratio 0.60, 95% confidence interval, 0.211-1.675).Statin and metformin use is associated with improved OS in patients with resectable PDAC. These medications should be further investigated for possible long-term use in the general population.

View details for DOI 10.1097/MPA.0000000000000470

View details for PubMedID 26474429

Serum Transforming Growth Factor-beta 1 Change After Neoadjuvant Chemoradiation Therapy Is Associated With Postoperative Pulmonary Complications in Esophageal Cancer Patients Undergoing Combined Modality Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lu, S., Hsu, F., Tsai, C., Wu, J., Lee, J., Huang, P., Hsu, C., Koong, A. C., Chang, D. T., Cheng, J. C. 2015; 93 (5): 1023-1031
Stereotactic body radiation therapy and central liver toxicity: A case report. Practical radiation oncology Shaffer, J. L., Osmundson, E. C., Visser, B. C., Longacre, T. A., Koong, A. C., Chang, D. T. 2015; 5 (5): 282-285

View details for DOI 10.1016/j.prro.2015.04.011

View details for PubMedID 26127008

Expert Consensus Contouring Guidelines for Intensity Modulated Radiation Therapy in Esophageal and Gastroesophageal Junction Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Wu, A. J., Bosch, W. R., Chang, D. T., Hong, T. S., Jabbour, S. K., Kleinberg, L. R., Mamon, H. J., Thomas, C. R., Goodman, K. A. 2015; 92 (4): 911-920

Abstract

Current guidelines for esophageal cancer contouring are derived from traditional 2-dimensional fields based on bony landmarks, and they do not provide sufficient anatomic detail to ensure consistent contouring for more conformal radiation therapy techniques such as intensity modulated radiation therapy (IMRT). Therefore, we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume (CTV) in esophageal or gastroesophageal junction (GEJ) cancer.Eight expert academically based gastrointestinal radiation oncologists participated. Three sample cases were chosen: a GEJ cancer, a distal esophageal cancer, and a mid-upper esophageal cancer. Uniform computed tomographic (CT) simulation datasets and accompanying diagnostic positron emission tomographic/CT images were distributed to each expert, and the expert was instructed to generate gross tumor volume (GTV) and CTV contours for each case. All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and to generate draft consensus contours. The panel then refined these contours to generate the contouring atlas.The statistics indicated substantial agreement between panelists for each of the 3 test cases. A consensus CTV atlas was generated for the 3 test cases, each representing common anatomic presentations of esophageal cancer. The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases.This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas. This atlas will serve as a reference for IMRT contours for clinical practice and prospective trial design. Subsequent patterns of failure analyses of clinical datasets using these guidelines may require modification in the future.

View details for DOI 10.1016/j.ijrobp.2015.03.030

View details for Web of Science ID 000356460300030

View details for PubMedID 26104943

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollom, E. L., Deng, L., Pai, R. K., Brown, J. M., Giaccia, A., Loo, B. W., Shultz, D. B., Quynh Thu Le, Q. T., Koong, A. C., Chang, D. T. 2015; 92 (3): 568-576
Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy. International journal of radiation oncology, biology, physics Pollom, E. L., Deng, L., Pai, R. K., Brown, J. M., Giaccia, A., Loo, B. W., Shultz, D. B., Le, Q. T., Koong, A. C., Chang, D. T. 2015; 92 (3): 568-576

Abstract

Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action of toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.

View details for DOI 10.1016/j.ijrobp.2015.02.016

View details for PubMedID 26068491

Survival benefit for adjuvant radiation therapy in minor salivary gland cancers ORAL ONCOLOGY Zeidan, Y. H., Pekelis, L., An, Y., Holsinger, F. C., Kong, C. S., Chang, D. T., Quynh-Thu Le, Q. T. 2015; 51 (5): 438-445

Abstract

The goal of the current study is to investigate the role of adjuvant radiation therapy (adjuvant RT) in minor salivary gland tumors (mSGT) using an established national database.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients treated with or without adjuvant RT for mSGT from 1988 to 2008. Regression analyses were performed to identify factors associated with improved overall survival (OS).Most tumors were located within the oral cavity (75%) followed by nasal cavity/paranasal sinuses (15%). Multivariate Cox analysis showed that adjuvant RT was associated with better OS compared to surgery alone. Using logistic regression analysis, we provide a novel web based tool for predicting survival impact of adjuvant RT in patients with mSGT.Adjuvant RT is associated with improved survival in patients with mSGT and adverse clinicopathologic factors such as advanced T/N category, adenoid cystic histology, high grade, and nasopharynx location.

View details for DOI 10.1016/j.oraloncology.2015.02.096

View details for Web of Science ID 000354027100095

View details for PubMedID 25771077

Smad4 inactivation predicts for worse prognosis and response to fluorouracil-based treatment in colorectal cancer JOURNAL OF CLINICAL PATHOLOGY Kozak, M. M., von Eyben, R., Pai, J., Vossler, S. R., Limaye, M., Jayachandran, P., Anderson, E. M., Shaffer, J. L., Longacre, T., Pai, R. K., Koong, A. C., Chang, D. T. 2015; 68 (5): 341-345

Abstract

To determine whether expression of Smad4, a tumour suppressor found to be absent in 10% of colorectal cancer (CRC), is associated with outcomes in patients with CRC.Tumour samples from 241 consecutive patients with CRC who underwent upfront colon resection between 2005 and 2009 were obtained. Triplicate tissue cores from resected primary colon tumours and matched normal controls were used to construct the tissue microarrays (TMAs). We examined the expression of Smad4 using immunohistochemistry. Clinicopathological records were obtained for all patients. TMAs were reviewed by two pathologists and scored as either 'positive' or 'negative' for nuclear staining. In total, 21 of 241 tumours (8.6%) were Smad4 negative.Loss of Smad4 expression correlated with significantly worse overall survival (OS) (p=0.011) and disease-free survival (DFS) (p=0.024). Patients with loss of Smad4 expression had a median OS of 31months compared with 89months positive Smad4 expression. Loss of Smad4 remained significant on multivariate analysis for OS (p=0.0097). In patients with node-positive disease, loss of Smad4 predicts for worse DFS (p=0.012). In patients with metastatic and recurrent disease, Smad4 loss predicts for worse OS (p=0.012). Of the patients that received capecitabine over the course of their treatment, those with Smad4 loss (n=13) had significantly worse DFS (p=0.003) and OS (p=0.0007).Loss of Smad4 expression is associated with worse DFS and OS in multiple subsets of patients with CRC. Further studies are required to validate our findings and ascertain the role of Smad4 status in the management of this disease.

View details for DOI 10.1136/jclinpath-2014-202660

View details for Web of Science ID 000353420500004

View details for PubMedID 25681512

Predictors of Toxicity Associated With Stereotactic Body Radiation Therapy to the Central Hepatobiliary Tract INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Osmundson, E. C., Wu, Y., Luxton, G., Bazan, J. G., Koong, A. C., Chang, D. T. 2015; 91 (5): 986-994

Abstract

To identify dosimetric predictors of hepatobiliary (HB) toxicity associated with stereotactic body radiation therapy (SBRT) for liver tumors.We retrospectively reviewed 96 patients treated with SBRT for primary (53%) or metastatic (47%) liver tumors between March 2006 and November 2013. The central HB tract (cHBT) was defined by a 15-mm expansion of the portal vein from the splenic confluence to the first bifurcation of left and right portal veins. Patients were censored for toxicity upon local progression or additional liver-directed therapy. HB toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. To compare different SBRT fractionations, doses were converted to biologically effective doses (BED) by using the standard linear quadratic model /=10 (BED10).Medianfollow-up was 12.7months after SBRT. Median BED10 was 85.5Gy (range: 37.5-151.2). The median number of fractions was 5 (range: 1-5), with 51 patients (53.1%) receiving 5 fractions and 29 patients (30.2%) receiving 3 fractions. In total, there were 23 (24.0%) grade 2+ and 18 (18.8%) grade 3+HB toxicities. Nondosimetric factors predictive of grade 3+HB toxicity included cholangiocarcinoma (CCA) histology (P<.0001), primary liver tumor (P=.0087), and biliary stent (P<.0001). Dosimetric parameters most predictive of grade 3+HB toxicity were volume receiving above BED10 of 72 Gy (VBED1072)21cm(3) (relative risk [RR]: 11.6, P<.0001), VBED106624cm(3) (RR: 10.5, P<.0001), and mean BED10 (DmeanBED10) cHBT 14Gy (RR: 9.2, P<.0001), with VBED1072 and VBED1066 corresponding to V40 and V37.7 for 5 fractions and V33.8 and V32.0 for 3 fractions, respectively. VBED107221cm(3), VBED106624cm(3), and DmeanBED10 cHBT 14Gy were consistently predictive of grade 3+toxicity on multivariate analysis.VBED1072, VBED1066, and DmeanBED10 to cHBT are associated with HB toxicity. We suggest VBED1072<21cm(3) (5-fraction: V40<21cm(3); 3-fraction: V33.8<21cm(3)), VBED1066<24cm(3) (5-fraction: V37.7<24cm(3); 3-fraction: V32<24cm(3)) as potential dose constraints for the cHBT when clinically indicated.

View details for DOI 10.1016/j.ijrobp.2014.11.028

View details for Web of Science ID 000351734000015

View details for PubMedID 25659885

Phase 2 Multi-institutional Trial Evaluating Gemcitabine and Stereotactic Body Radiotherapy for Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma CANCER Herman, J. M., Chang, D. T., Goodman, K. A., Dholakia, A. S., Raman, S. P., Hacker-Prietz, A., Iacobuzio-Donahue, C. A., Griffith, M. E., Pawlik, T. M., Pai, J. S., O'Reilly, E., Fisher, G. A., Wild, A. T., Rosati, L. M., Zheng, L., Wolfgang, C. L., Laheru, D. A., Columbo, L. A., Sugar, E. A., Koong, A. C. 2015; 121 (7): 1128-1137

Abstract

This phase 2 multi-institutional study was designed to determine whether gemcitabine (GEM) with fractionated stereotactic body radiotherapy (SBRT) results in acceptable late grade 2 to 4 gastrointestinal toxicity when compared with a prior trial of GEM with single-fraction SBRT in patients with locally advanced pancreatic cancer (LAPC).A total of 49 patients with LAPC received up to 3 doses of GEM (1000 mg/m(2) ) followed by a 1-week break and SBRT (33.0 gray [Gy] in 5 fractions). After SBRT, patients continued to receive GEM until disease progression or toxicity. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0] and the Radiation Therapy Oncology Group radiation morbidity scoring criteria. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and pancreatic cancer-specific QLQ-PAN26 module before SBRT and at 4 weeks and 4 months after SBRT.The median follow-up was 13.9 months (range, 3.9-45.2 months). The median age of the patients was 67 years and 84% had tumors of the pancreatic head. Rates of acute and late (primary endpoint) grade 2 gastritis, fistula, enteritis, or ulcer toxicities were 2% and 11%, respectively. QLQ-C30 global quality of life scores remained stable from baseline to after SBRT (67 at baseline, median change of 0 at both follow-ups; P>.05 for both). Patients reported a significant improvement in pancreatic pain (P=.001) 4 weeks after SBRT on the QLQ-PAN26 questionnaire. The median plasma carbohydrate antigen 19-9 (CA 19-9) level was reduced after SBRT (median time after SBRT, 4.2 weeks; 220 U/mL vs 62 U/mL [P<.001]). The median overall survival was 13.9 months (95% confidence interval, 10.2 months-16.7 months). Freedom from local disease progression at 1 year was 78%. Four patients (8%) underwent margin-negative and lymph node-negative surgical resections.Fractionated SBRT with GEM results in minimal acute and late gastrointestinal toxicity. Future studies should incorporate SBRT with more aggressive multiagent chemotherapy. Cancer 2015;121:1128-1137. 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

View details for DOI 10.1002/cncr.29161

View details for Web of Science ID 000351615800022

Stereotactic body radiation therapy in pancreatic cancer: the new frontier EXPERT REVIEW OF ANTICANCER THERAPY Moningi, S., Marciscano, A. E., Rosati, L. M., Ng, S. K., Forbang, R. T., Jackson, J., Chang, D. T., Koong, A. C., Herman, J. M. 2014; 14 (12): 1461-1475

Abstract

Pancreatic cancer (PCA) remains a disease with a poor prognosis. The majority of PCA patients are unable to undergo surgical resection, which is the only potentially curative option at this time. A combination of chemotherapy and chemoradiation (CRT) are standard options for patients with locally advanced, unresectable disease, however, local control and patient outcomes remains poor. Stereotactic body radiation therapy (SBRT) is an emerging treatment option for PCA. SBRT delivers potentially ablative doses to the pancreatic tumor plus a small margin over a short period of time. Early studies with single-fraction SBRT demonstrated excellent tumor control with high rates of toxicity. The implementation of SBRT (3-5 doses) has demonstrated promising outcomes with favorable tumor control and toxicity rates. Herein we discuss the evolving role of SBRT in PCA treatment.

View details for DOI 10.1586/14737140.2014.952286

View details for Web of Science ID 000346639100008

Single-versus Multifraction Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma: Outcomes and Toxicity INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollom, E. L., Alagappan, M., von Eyben, R., Kunz, P. L., Fisher, G. A., Ford, J. A., Poultsides, G. A., Visser, B. C., Norton, J. A., Kamaya, A., Cox, V. L., Columbo, L. A., Koong, A. C., Chang, D. T. 2014; 90 (4): 918-925
LEF-1 is Frequently Expressed in Colorectal Carcinoma and Not in Other Gastrointestinal Tract Adenocarcinomas: An Immunohistochemical Survey of 602 Gastrointestinal Tract Neoplasms APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Kermanshahi, T. R., Jayachandran, P., Chang, D. T., Pai, R. 2014; 22 (10): 728-734

Abstract

LEF-1 is a DNA-binding protein that interacts with -catenin and activates Wnt-responsive target genes. We analyzed the immunohistochemical expression of LEF-1 in 602 gastrointestinal and pancreatobiliary neoplasms in an attempt to (1) investigate the utility of LEF-1 immunohistochemistry as an ancillary marker in gastrointestinal/pancreatobiliary neoplasia, and (2) to perform a clinicopathologic and survival analysis of colorectal carcinoma stratified by LEF-1 expression. LEF-1 nuclear positivity was frequently identified in colorectal carcinoma (89/241, 37%) and only infrequently identified in other neoplasms: 11% esophagus/esophagogastric adenocarcinomas, 7% gastric adenocarcinomas, 1% pancreatic ductal adenocarcinomas, 4% pancreatic intraductal papillary mucinous neoplasms, and in no cases of appendiceal mucinous neoplasms or pancreatic mucinous cystic neoplasms. LEF-1 expression was identified in 35% of colorectal carcinomas that lacked CK20 and CDX2 expression. In colorectal carcinomas, LEF-1-positive tumors more frequently harbored KRAS mutations compared with LEF-1-negative tumors (39% vs. 16%, P=0.005). Patients with moderate/strong LEF-1-positive colorectal carcinoma had a trend of worse overall survival compared with patients with colorectal carcinomas with weak/negative LEF-1 expression (5 y overall survival, 31% vs. 47%, P=0.15). In conclusion, LEF-1 is most commonly expressed in colorectal carcinoma and infrequently observed in the upper gastrointestinal tract and pancreatic adenocarcinoma. LEF-1 Immunohistochemistry may be especially useful as an ancillary diagnostic marker in colorectal carcinomas, which lack the expression of both CK20 and CDX2. LEF-1 expression is associated with the presence of KRAS mutations and may have prognostic value as a trend of worse overall survival is seen in patients with LEF-1-positive colorectal carcinoma.

View details for DOI 10.1097/PAI.0000000000000109

View details for Web of Science ID 000345341500004

View details for PubMedID 25394300

Dosimetric Modeling of Central Liver Toxicity After SBRT to the Liver INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Osmundson, E., Wu, Y., Bazan, J. G., Koong, A. C., Chang, D. T. 2014; 90: S382-S382
Hepatobiliary Cancers, Version 2.2014 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Benson, A. B., D'Angelica, M. I., Abrams, T. A., Are, C., Bloomston, P. M., Chang, D. T., Clary, B. M., Covey, A. M., Ensminger, W. D., Iyer, R., Kelley, R. K., Linehan, D., Malafa, M. P., Meranze, S. G., Park, J. O., Pawlik, T., Posey, J. A., Scaife, C., Schefter, T., Sigurdson, E. R., Tian, G. G., Vauthey, J., Venook, A. P., Yen, Y., Zhu, A. X., Hoffmann, K. G., McMillian, N. R., Sundar, H. 2014; 12 (8): 1152-1182

Abstract

Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma), gall bladder, and bile ducts (cholangiocarcinomas). Gallbladder cancer and cholangiocarcinomas are collectively known as biliary tract cancers. Gallbladder cancer is the most common and aggressive type of all the biliary tract cancers. Cholangiocarcinomas are diagnosed throughout the biliary tree and are typically classified as either intrahepatic or extrahepatic cholangiocarcinoma. Extrahepatic cholangiocarcinomas are more common than intrahepatic cholangiocarcinomas. This manuscript focuses on the clinical management of patients with gallbladder cancer and cholangiocarcinomas (intrahepatic and extrahepatic).

View details for Web of Science ID 000340218200009

View details for PubMedID 25099447

Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Dholakia, A. S., Chaudhry, M., Leal, J. P., Chang, D. T., Raman, S. P., Hacker-Prietz, A., Su, Z., Pai, J., Oteiza, K. E., Griffith, M. E., Wahl, R. L., Tryggestad, E., Pawlik, T., Laheru, D. A., Wolfgang, C. L., Koong, A. C., Herman, J. M. 2014; 89 (3): 539-546
Postradiotherapy CA19-9 Kinetics Correlate With Outcomes in Patients With Pancreatic Adenocarcinoma PANCREAS Shultz, D. B., Chan, C., Shaffer, J. L., Kunz, P. L., Koong, A. C., Chang, D. T. 2014; 43 (5): 777-783

Abstract

We sought to determine if carbohydrate antigen 19-9 (CA19-9 ) nadir (nCA19-9), time to nadir (TTN), and doubling time (DT) after radiotherapy (RT) correlate with outcomes in pancreatic ductal adenocarcinoma.We examined the records of 102 patients treated with RT for primary, nonmetastatic pancreatic ductal adenocarcinoma between August 1998 and July 2011. Of these, 33 patients were treated with postoperative chemoradiotherapy (PORT) and 69 patients with definitive chemoradiotherapy (CRT).Among the patients treated with PORT, TTN and DT were associated with both overall survival (OS; P = <0.01 for both) and freedom from progression (FFP; P = <0.01 for both). In patients treated with CRT, nCA19-9 and TTN correlated with both OS (P = <0.01 and P = 0.02, respectively) and FFP (P = 0.01 and <0.01, respectively). On multivariable analysis, in patients treated with PORT, TTN remained independently correlated with OS and FFP (P = 0.01; hazard ratios [HR], 6.43 and P = 0.02; HR, 4.00, respectively), whereas DT remained independently correlated to FFP (P = 0.04; HR, 0.27). In patients treated with CRT, controlling for pretreatment CA19-9, nCA19-9 and TTN independently correlated with OS (P = <0.01; HR, 3.0 and P = 0.03; HR, 2.56, respectively) and FFP (P = 0.04; HR, 2.31 and P = <0.01; HR, 4.0, respectively).CA19-9 kinetics after RT correlate with disease progression and survival and could serve as a prognostic tool to guide treatment decisions.

View details for Web of Science ID 000338132700016

High Serum Levels of Vascular Endothelial Growth Factor-A and Transforming Growth Factor-beta 1 Before Neoadjuvant Chemoradiotherapy Predict Poor Outcomes in Patients with Esophageal Squamous Cell Carcinoma Receiving Combined Modality Therapy ANNALS OF SURGICAL ONCOLOGY Cheng, J. C., Graber, M. S., Hsu, F., Tsai, C., Castaneda, L., Lee, J., Chang, D. T., Koong, A. C. 2014; 21 (7): 2361-2368

Abstract

This study was aimed at using proximity ligation assay (PLA) followed by enzyme-linked immunosorbent assay (ELISA) to identify serum biomarkers that predict treatment response and survival for patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant concurrent chemoradiotherapy (CCRT) followed by esophagectomy.Seventy-nine patients with ESCC receiving CCRT of taxane-based/5-fluorouracil-based chemotherapy and 40 Gy followed by surgery were enrolled. Serum samples were collected before and <1 month after CCRT. Fifteen biomarkers were analyzed using PLA. Biomarkers significantly correlating with pathological response/survival were verified by ELISA. Associations of the serum level of biomarkers and clinical factors with pathological response, disease-free survival (DFS), and overall survival (OS) were evaluated by analysis of variance and log-rank tests.Thirty patients had complete response (38 %), 37 had microscopic residual disease (47 %), and 12 had macroscopic residual disease (15 %). With a median follow-up of 52.8 months, the median DFS was 43 months. Among the 15 biomarkers screened by PLA, vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)-1 were significantly associated with pathological response and/or DFS. These biomarkers were further analyzed by ELISA to confirm initial biomarker findings by PLA. After ELISA of these two markers, only VEGF-A levels were significantly correlated with pathological response. On multivariate analysis, patients with combined high pre-CCRT VEGF-A and TGF-1 levels (greater than or equal to the median), independent of pathological response, had significantly worse DFS (11 months vs. median not reached; p = 0.007) and OS (16 vs. 46 months; p = 0.07).Pre-CCRT serum VEGF-A and TGF-1 levels may be used to predict pathological response and survivals for ESCC patients receiving combined-modality therapy.

View details for DOI 10.1245/s10434-014-3611-z

View details for Web of Science ID 000337063400038

Combined-modality Therapy for Rectal Cancer Analysis of Potential Differences in Disease Presentation, Treatment Adherence, and Treatment Outcome According to Race AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Tonlaar, N., Song, S., Hong, J. C., Minsky, B. D., Chang, D. T., Polite, B. N., Liauw, S. L. 2014; 37 (2): 122-125
Stereotactic Body Radiotherapy in the Treatment of Pancreatic Cancer SEMINARS IN RADIATION ONCOLOGY Trakul, N., Koong, A. C., Chang, D. T. 2014; 24 (2): 140-147
Stereotactic body radiotherapy in the treatment of pancreatic cancer. Seminars in radiation oncology Trakul, N., Koong, A. C., Chang, D. T. 2014; 24 (2): 140-147

Abstract

Most patients diagnosed with pancreatic cancer are unable to have a curative surgical resection. Chemoradiation is a standard of care treatment for patients with locally advanced unresectable disease, but local failure rates are high with conventionally fractionated radiotherapy. However, stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy offers an alternative type of radiation therapy, which allows for the delivery of high-dose, conformal radiation. The high doses and shorter overall treatment time with SBRT may provide advantages in local control, disease outcomes, quality of life, and cost-effectiveness, and further investigation is currently underway. Here, we review the technology behind SBRT for pancreatic malignancy and its future direction in the overall management of pancreatic cancer.

View details for DOI 10.1016/j.semradonc.2013.11.008

View details for PubMedID 24635871

In reply to Leung. International journal of radiation oncology, biology, physics Chang, D. T., Haffty, B. G., Wilson, L. D. 2014; 88 (1): 241-242

View details for DOI 10.1016/j.ijrobp.2013.10.018

View details for PubMedID 24331676

False positive 18F-fluorodeoxyglucose positron emission tomography/computed tomography liver lesion mimicking metastasis in 2 patients with gastroesophageal cancer. Practical radiation oncology Paudel, N., Kunz, P. L., Poultsides, G. A., Koong, A. C., Chang, D. T. 2014; 4 (6): 368-371

View details for DOI 10.1016/j.prro.2013.11.005

View details for PubMedID 25407856

Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Bazan, J. G., Luxton, G., Kozak, M. M., Anderson, E. M., Hancock, S. L., Kapp, D. S., Kidd, E. A., Koong, A. C., Chang, D. T. 2013; 87 (5): 983-991

Abstract

To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy.We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade 3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters.Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0

View details for DOI 10.1016/j.ijrobp.2013.09.017

View details for Web of Science ID 000327496600029

Cone beam CT imaging with limited angle of projections and prior knowledge for volumetric verification of non-coplanar beam radiation therapy: a proof of concept study PHYSICS IN MEDICINE AND BIOLOGY Meng, B., Xing, L., Han, B., Koong, A., Chang, D., Cheng, J., Li, R. 2013; 58 (21): 7777-7789

Abstract

Non-coplanar beams are important for treatment of both cranial and noncranial tumors. Treatment verification of such beams with couch rotation/kicks, however, is challenging, particularly for the application of cone beam CT (CBCT). In this situation, only limited and unconventional imaging angles are feasible to avoid collision between the gantry, couch, patient, and on-board imaging system. The purpose of this work is to develop a CBCT verification strategy for patients undergoing non-coplanar radiation therapy. We propose an image reconstruction scheme that integrates a prior image constrained compressed sensing (PICCS) technique with image registration. Planning CT or CBCT acquired at the neutral position is rotated and translated according to the nominal couch rotation/translation to serve as the initial prior image. Here, the nominal couch movement is chosen to have a rotational error of 5 and translational error of 8mm from the ground truth in one or more axes or directions. The proposed reconstruction scheme alternates between two major steps. First, an image is reconstructed using the PICCS technique implemented with total-variation minimization and simultaneous algebraic reconstruction. Second, the rotational/translational setup errors are corrected and the prior image is updated by applying rigid image registration between the reconstructed image and the previous prior image. The PICCS algorithm and rigid image registration are alternated iteratively until the registration results fall below a predetermined threshold. The proposed reconstruction algorithm is evaluated with an anthropomorphic digital phantom and physical head phantom. The proposed algorithm provides useful volumetric images for patient setup using projections with an angular range as small as 60. It reduced the translational setup errors from 8mm to generally <1mm and the rotational setup errors from 5 to <1. Compared with the PICCS algorithm alone, the integration of rigid registration significantly improved the reconstructed image quality, with a reduction of mostly 2-3 folds (up to 100) in root mean square image error. The proposed algorithm provides a remedy for solving the problem of non-coplanar CBCT reconstruction from limited angle of projections by combining the PICCS technique and rigid image registration in an iterative framework. In this proof of concept study, non-coplanar beams with couch rotations of 45 can be effectively verified with the CBCT technique.

View details for DOI 10.1088/0031-9155/58/21/7777

View details for Web of Science ID 000326377100023

View details for PubMedID 24140954

Chemoradiotherapy Before and After Surgery for Locally Advanced Esophageal Cancer: A SEER-Medicare Analysis ANNALS OF SURGICAL ONCOLOGY Hong, J. C., Murphy, J. D., Wang, S. J., Koong, A. C., Chang, D. T. 2013; 20 (12): 3999-4007

Abstract

The optimal combination and timing of therapy for esophageal cancer remains controversial. The Surveillance, Epidemiology, and End Results (SEER)-Medicare registry was used to assess neoadjuvant and adjuvant therapy.Patients diagnosed with nonmetastatic T3+ or N1+ esophageal adenocarcinoma (ACA) or squamous cell carcinoma (SCC) from 1995 to 2002 who underwent surgical resection within 6months of diagnosis were studied. Medicare data defined preoperative chemoradiotherapy (preCRT), preoperative radiotherapy (preRT), postoperative CRT (postCRT), chemotherapy and surgery (CT+S), and surgery alone.Of 419 eligible patients, 126 received preCRT, 55 preRT, 40 postCRT, 29 CT+S, and 169 surgery alone. PreCRT yielded median overall survival (OS) of 37months, greater than surgery alone (17months, p=0.002) and postCRT (17months, p=0.06). PreRT (20months, p=0.20), postCRT (p=0.88), and CT+S (20months, p=0.42) were not associated with OS benefit versus surgery alone. For SCC, preCRT improved survival versus surgery alone (p=0.01), with a trend for ACA (p=0.07). ACA (22months) had greater OS than SCC (17months) (p=0.03). ACA, younger age, and married status were associated with increased OS. Adjusting for these, preCRT had longer OS versus surgery alone (p=0.02) and postCRT (p=0.03). Chemotherapy agents and surgical approach did not affect OS.In the SEER-Medicare cohort, preCRT significantly improved survival versus surgery alone and postCRT for locally advanced esophageal cancer, particularly for SCC. PreRT, postCRT, and CT+S were not associated with longer survival.

View details for DOI 10.1245/s10434-013-3072-9

View details for Web of Science ID 000325770600043

View details for PubMedID 23800897

Factors that Determine Academic Versus Private Practice Career Interest in Radiation Oncology Residents in the United States: Results of a Nationwide Survey INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chang, D. T., Shaffer, J. L., Haffty, B. G., Wilson, L. D. 2013; 87 (3): 464-470

Abstract

To determine what factors US radiation oncology residents consider when choosing academic or nonacademic careers.A 20-question online survey was developed and sent to all US radiation oncology residents to assess factors that influence their career interest. Residents were asked to rate their interest in academics (A) versus private practice (PP) on a 0 (strong interest in A) to 100 (strong interest in PP) scale. Responses were classified as A (0-30), undecided (40-60), and PP (70-100). Residents were also asked to rank 10 factors that most strongly influenced their career interest.Three hundred thirty-one responses were collected, of which 264 were complete and form the basis for this analysis. Factors that correlated with interest in A included having a PhD (P=.018), postgraduate year level (P=.0006), research elective time (P=.0003), obtaining grant funding during residency (P=.012), and number of publications before residency (P=.0001), but not number of abstracts accepted in the past year (P=.65) or publications during residency (P=.67). The 3 most influential factors for residents interested in A were: (1) baseline interest before residency; (2) academic role models; and (3) research opportunities during residency. The 3 most influential factors for residents interested in PP were: (1) baseline interest before residency; (2) academic role models; and (3) academic pressure and obligations.Interest in A correlated with postgraduate year level, degree, and research time during residency. Publications before but not during residency correlated with academic interest, and baseline interest was the most influential factor. These data can be used by residency program directors to better understand what influences residents' career interest.

View details for DOI 10.1016/j.ijrobp.2013.07.002

View details for Web of Science ID 000325165300014

View details for PubMedID 23972721

Long-Term Outcomes of Surgery Followed by Radiation Therapy for Minor Salivary Gland Carcinomas LARYNGOSCOPE Zeidan, Y. H., Shultz, D. B., Murphy, J. D., Chan, C., Kaplan, M. J., Colevas, A. D., Kong, C., Chang, D. T., Le, Q. 2013; 123 (11): 2675-2680

Abstract

OBJECTIVES/HYPOTHESIS: Postoperative radiation therapy is often used in patients with high-risk salivary gland carcinomas. In this study we evaluated the outcomes and prognostic factors in patients with minor salivary gland cancers treated with adjuvant radiation therapy. STUDY DESIGN: Retrospective cohort study. METHODS: We performed a retrospective analysis of 90 patients treated with curative intent. Median follow-up was 71 months. Fifty-eight patients (64%) had adenoid cystic carcinomas, 22 (24%) had adenocarcinomas, and 10 (11%) had mucoepidermoid cancers. Primary disease site included 39 (43%) sinonasal, 35 (39%) oral cavity, 10 (11%) oropharynx, and six (7%) others. Twenty-seven patients (30%) were treated with intensity-modulated radiation therapy. RESULTS: Eight local, four neck, and 24 distant relapses were detected. Local control rates at 5 and 10 years were 90% and 88%, respectively. Advanced T stage was associated with worse local control. Distant metastasis rates were 24% and 28% at 5 and 10 years, respectively. Tumor stage, histology, perineural invasion, and lymphovascular space invasion were significant predictors of distant metastasis on univariate analysis. However, on multivariate analysis only the American Joint Committee on Cancer stage was significant. Overall survival rates were 76% and 63% at 5 and 10 years, respectively. More advanced T stage and N stage correlated with worse overall survival. CONCLUSIONS: Tumor stage remains the best predictor for locoregional and distant disease control of minor salivary gland cancers. Postoperative radiation therapy for high-risk patients results in excellent long-term locoregional disease control. Further work is needed to improve systemic control. LEVEL OF EVIDENCE: 4. Laryngoscope, 2013.

View details for DOI 10.1002/lary.24081

View details for Web of Science ID 000326231200029

View details for PubMedID 23553253

Clinicopathologic Features of Synchronous Colorectal Carcinoma A Distinct Subset Arising From Multiple Sessile Serrated Adenomas and Associated With High Levels of Microsatellite Instability and Favorable Prognosis AMERICAN JOURNAL OF SURGICAL PATHOLOGY Hu, H., Chang, D. T., Nikiforova, M. N., Kuan, S., Pai, R. K. 2013; 37 (11): 1660-1670

Abstract

Analysis of synchronous colorectal carcinomas can provide a unique model to examine the underlying molecular alterations in colorectal carcinoma, as synchronous tumors arise in a background of common genetic and environmental factors. We analyzed the clinicopathologic and molecular features of synchronous colorectal carcinomas compared with solitary carcinomas to correlate the histologic findings with molecular alterations and to identify the prognostic significance, if any, of synchronous colorectal carcinoma. Of the 4760 primary colorectal carcinomas resected for the years 2002 to 2012 at our institution, 58 patients (1.2%) harbored 2 invasive primary adenocarcinomas and comprise the synchronous colorectal carcinoma study group. A control group of consecutively resected solitary colorectal carcinomas from 109 patients was also analyzed. Compared with solitary colorectal carcinomas, synchronous colorectal carcinomas more frequently were identified in older patients (median age 70 vs. 60 y; P=0.001), involved the right colon (42/58, 72% vs. 47/109, 43%; P=0.0003), were more often microsatellite instability-high (MSI-H) (21/58, 36% vs. 13/109, 12%; P=0.0005), and were more frequently associated with precursor sessile serrated adenomas (SSAs) (13/58, 22% vs. 2/109, 2%; P=0.0001). A statistically significant difference in overall survival was identified between patients with synchronous and solitary colorectal carcinomas (5 y overall survival 92% vs. 56%, P=0.02). A unique subgroup of 13 synchronous colorectal carcinomas demonstrated tumors arising from SSAs (SSA-associated). All SSA-associated synchronous colorectal carcinomas were seen in patients above 65 years of age, and 12/13 (92%) occurred in women. Most patients (12/13, 92%) with SSA-associated synchronous colorectal carcinomas demonstrated involvement of the right colon, and tumors were frequently stage I or II (9/13, 69%) and low grade (11/13, 85%). In 12/13 (92%) SSA-associated synchronous colorectal carcinomas, both tumors exhibited loss of MLH1 and PMS2 immunohistochemical expression with concurrent BRAF V600E mutation. Nine of 13 (69%) patients with SSA-associated colorectal carcinoma harbored additional SSAs. Three of 13 (15%) patients with SSA-associated synchronous colorectal carcinoma met the World Health Organization criteria for serrated polyposis. Notably, no patient with SSA-associated synchronous colorectal carcinoma developed disease recurrence or died of disease at last follow-up. In conclusion, synchronous colorectal carcinomas are enriched with MSI-H tumors, particularly those arising from SSAs, which contributes to the overall improved survival for patients with synchronous tumors compared with patients with solitary tumors. We demonstrate that SSA-associated synchronous colorectal carcinomas have a striking predilection for elderly women, are associated with a favorable prognosis, and are MSI-H and BRAF V600E positive.

View details for Web of Science ID 000330430900004

View details for PubMedID 23887157

Safety of Y-90 Radioembolization in Patients Who Have Undergone Previous External Beam Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lam, M. G., Abdelmaksoud, M. H., Chang, D. T., Eclov, N. C., Chung, M. P., Koong, A. C., Louie, J. D., Sze, D. Y. 2013; 87 (2): 323-329

Abstract

Previous external beam radiation therapy (EBRT) is theoretically contraindicated for yttrium-90 ((90)Y) radioembolization (RE) because the liver has a lifetime tolerance to radiation before becoming vulnerable to radiation-induced liver disease. We analyzed the safety of RE as salvage treatment in patients who had previously undergone EBRT.Between June 2004 and December 2010, a total of 31 patients who had previously undergone EBRT were treated with RE. Three-dimensional treatment planning with dose-volume histogram (DVH) analysis of the liver was used to calculate the EBRT liver dose. Liver-related toxicities including RE-induced liver disease (REILD) were reviewed and classified according to Common Terminology Criteria for Adverse Events version 4.02.The mean EBRT and RE liver doses were 4.40 Gy (range, 0-23.13 Gy) and 57.9 Gy (range, 27.0-125.9 Gy), respectively. Patients who experienced hepatotoxicity (grade2; n=12) had higher EBRT mean liver doses (7.96 8.55 Gy vs 1.62 3.39 Gy; P=.037), the only independent predictor in multivariate analysis. DVH analysis showed that the fraction of liver exposed to 30 Gy (V30) was the strongest predictor of hepatotoxicity (10.14% 12.75% vs 0.84% 3.24%; P=.006). All patients with V30 >13% experienced hepatotoxicity. Fatal REILD (n=2) occurred at the 2 highest EBRT mean liver doses (20.9 Gy and 23.1 Gy) but also at the highest cumulative liver doses (91.8 Gy and 149Gy).Prior exposure of the liver to EBRT may lead to increased liver toxicity after RE treatment, depending on fractional liver exposure and dose level. The V30 was the strongest predictor of toxicity. RE appears to be safe for the treatment of hepatic malignancies only in patients who have had limited hepatic exposure to prior EBRT.

View details for DOI 10.1016/j.ijrobp.2013.05.041

View details for Web of Science ID 000324310500019

Radiotherapy for nonadenoid cystic carcinomas of major salivary glands AMERICAN JOURNAL OF OTOLARYNGOLOGY Chung, M. P., Tang, C., Chan, C., Hara, W. Y., Loo, B. W., Kaplan, M. J., Fischbein, N., Le, Q., Chang, D. T. 2013; 34 (5): 425-430

Abstract

PURPOSE: To report outcomes in patients treated with postoperative radiotherapy for nonadenoid cystic carcinomas of the major salivary glands. MATERIALS AND METHODS: From 1998-2011, 37 patients with nonadenoid cystic carcinomas of the major salivary gland underwent postoperative radiotherapy. The median radiation dose was 60Gy (range, 45-70Gy). TNM distribution included T1-2 (n=16, 44%), T3-T4 (n=21, 56%), N0 (n=19, 51%), and N+ (n=18, 49%). Histologies included adenocarcinoma (n=13, 35%), squamous cell carcinoma (n=8, 22%), mucoepidermoid carcinoma (n=8, 22%), and other (n=8, 21%). Median follow-up was 4.7years for all patients (range, 0.3-14.1years) and 5.0years for living patients (range, 1.2-12.2years). RESULTS: Five-year local-regional control, overall survival (OS), and cancer-specific survival (CSS) were 97%, 76%, and 84%. On univariate analysis, OS was significantly worse for patients 65years old (p=0.04). CSS was significantly worse for positive perineural invasion (p=0.02), extraparenchymal extension (p=0.04), and in patients who received no chemotherapy (p=0.02). Doses >60Gy was significantly worse for OS (p=0.003) and CSS (p=0.003), although these patients had higher TNM (>T2, p=0.01) and trended towards a higher rate of extraparenchymal extension (p=0.08). Four patients (11%) developed grade 2 toxicities; 3 patients developed early toxicities and one patient developed late toxicities. CONCLUSIONS: Radiotherapy for salivary gland tumors provides excellent local-regional control when combined with surgery. Distant metastasis is the predominant pattern of failure, although chemotherapy seemed to improve cancer-specific survival.

View details for DOI 10.1016/j.amjoto.2013.03.007

View details for Web of Science ID 000324149400012

Signet Ring Cell Colorectal Carcinoma A Distinct Subset of Mucin-poor Microsatellite-stable Signet Ring Cell Carcinoma Associated With Dismal Prognosis AMERICAN JOURNAL OF SURGICAL PATHOLOGY Hartman, D. J., Nikiforova, M. N., Chang, D. T., Chu, E., Bahary, N., Brand, R. E., Zureikat, A. H., Zeh, H. J., Choudry, H., Pai, R. K. 2013; 37 (7): 969-977

Abstract

We evaluated a consecutive series of signet ring cell colorectal carcinomas in an attempt to correlate the histopathologic pattern of infiltration with molecular alterations and prognosis. Of the 4760 primary colorectal carcinomas surgically resected between the years 2002 and 2012, 53 (1%) were composed of >50% signet ring cells. Of the 53 signet ring cell carcinomas, 40 (75%) were composed of >50% extracellular mucin with signet ring cells floating within pools of mucin and were subclassified as mucin-rich signet ring cell carcinomas. Thirteen (25%) carcinomas were characterized by diffusely infiltrating carcinomas with minimal to no extracellular mucin and were subclassified as mucin-poor signet ring cell carcinomas. All 13 mucin-poor signet ring cell carcinomas were either stage III or IV, whereas many cases of mucin-rich signet ring cell carcinoma were stage I or II (17 cases) (P=0.005). Compared with mucin-rich tumors, mucin-poor signet ring cell carcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (13/13, 100% vs. 22/40, 55%; P=0.002), venous invasion (6/13, 46% vs. 3/40, 8%; P=0.004), and perineural invasion (11/13, 85% vs. 9/40, 23%; P=0.0001). Twenty-three of 53 (43%) signet ring cell carcinomas demonstrated high levels of microsatellite instability (MSI-H). Twenty-two of 23 (96%) MSI-H signet ring cell carcinomas were mucin rich; only 1 MSI-H signet ring carcinoma was mucin poor (P=0.0033). Mucin-poor signet ring cell carcinoma had significantly reduced overall and recurrence-free survival compared with mucin-rich signet ring cell carcinomas (P=0.0035 and 0.0001, respectively), even when adjusting for tumor stage. Mucin-poor signet ring cell carcinoma had a higher propensity for peritoneal dissemination (5/13, 38%) compared with mucin-rich signet ring cell carcinoma (5/40, 12.5%), although this was not statistically significant (P=0.052). Finally, MSI-H and microsatellite-stable signet ring cell carcinomas had similar overall and recurrence-free survival (P=0.2266 and 0.1055, respectively), even when adjusting for tumor stage. In conclusion, we identified a unique subset of signet ring cell colorectal carcinoma with diffuse infiltration and minimal to no extracellular mucin (mucin-poor signet ring cell carcinoma), which lacks MSI-H and has a dismal prognosis with an aggressive clinical course often with peritoneal dissemination. Further, our results confirm that MSI does not affect survival in colorectal signet ring cell carcinomas.

View details for Web of Science ID 000330377200004

View details for PubMedID 23681075

Seventh Edition (2010) of the AJCC/UICC Staging System for Gastric Adenocarcinoma: Is there Room for Improvement? ANNALS OF SURGICAL ONCOLOGY Patel, M. I., Rhoads, K. F., Ma, Y., Ford, J. M., Visser, B. C., Kunz, P. L., Fisher, G. A., Chang, D. T., Koong, A., Norton, J. A., Poultsides, G. A. 2013; 20 (5): 1631-1638

Abstract

The gastric cancer AJCC/UICC staging system recently underwent significant revisions, but studies on Asian patients have reported a lack of adequate discrimination between various consecutive stages. We sought to validate the new system on a U.S. population database.California Cancer Registry data linked to the Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (esophagogastric junction and gastric cardia tumors excluded) who underwent curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC stage was recalculated based on the latest seventh edition. Overall survival probabilities were calculated using the Kaplan-Meier method.Of 1905 patients analyzed, 54 % were males with a median age of 70 years. Median number of pathologically examined lymph nodes was 12 (range, 1-90); 40 % of patients received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The seventh edition AJCC/UICC system did not distinguish outcome adequately between stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system with improved discriminatory abilityIn this first study validating the new seventh edition AJCC/UICC staging system for gastric cancer on a U.S. population with a relatively limited number of lymph nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC/UICC staging system that better discriminates between outcomes.

View details for DOI 10.1245/s10434-012-2724-5

View details for Web of Science ID 000317308200032

View details for PubMedID 23149854

A Phase 2 Multi-institutional Study to Evaluate Gemcitabine and Fractionated Stereotactic Radiotherapy for Unresectable, Locally Advanced Pancreatic Adenocarcinoma. Practical radiation oncology Wild, A. T., Chang, D. T., Goodman, K. A., Laheru, D. A., Zheng, L., Raman, S. P., Columbo, L. A., Wolfgang, C. L., Koong, A. C., Herman, J. M. 2013; 3 (2): S4-5

View details for DOI 10.1016/j.prro.2013.01.016

View details for PubMedID 24674559

Dosimetric analysis of organs at risk during expiratory gating in stereotactic body radiation therapy for pancreatic cancer. International journal of radiation oncology, biology, physics Taniguchi, C. M., Murphy, J. D., Eclov, N., Atwood, T. F., Kielar, K. N., Christman-Skieller, C., Mok, E., Xing, L., Koong, A. C., Chang, D. T. 2013; 85 (4): 1090-1095

Abstract

To determine how the respiratory phase impacts dose to normal organs during stereotactic body radiation therapy (SBRT) for pancreatic cancer.Eighteen consecutive patients with locally advanced, unresectable pancreatic adenocarcinoma treated with SBRT were included in this study. On the treatment planning 4-dimensional computed tomography (CT) scan, the planning target volume (PTV), defined as the gross tumor volume plus 3-mm margin, the duodenum, and the stomach were contoured on the end-expiration (CTexp) and end-inspiration (CTinsp) phases for each patient. A separate treatment plan was constructed for both phases with the dose prescription of 33 Gy in 5 fractions with 95% coverage of the PTV by the 100% isodose line. The dose-volume histogram (DVH) endpoints, volume of duodenum that received 20 Gy (V20), V25, and V30 and maximum dose to 5 cc of contoured organ (D5cc), D1cc, and D0.1cc, were evaluated.Dosimetric parameters for the duodenum, including V25, V30, D1cc, and D0.1cc improved by planning on the CTexp compared to those on the CTinsp. There was a statistically significant overlap of the PTV with the duodenum but not the stomach during the CTinsp compared to the CTexp (0.38 0.17 cc vs 0.01 0.01 cc, P=.048). A larger expansion of the PTV, in accordance with a Danish phase 2 trial, showed even more overlapping volume of duodenum on the CTinsp compared to that on the CTexp (5.5 0.9 cc vs 3.0 0.8 cc, P=.0003) but no statistical difference for any stomach dosimetric DVH parameter.Dose to the duodenum was higher when treating on the inspiratory than on theexpiratory phase. These data suggest that expiratory gating may be preferable to inspiratory breath-hold and free breathing strategies for minimizing risk of toxicity.

View details for DOI 10.1016/j.ijrobp.2012.07.2366

View details for PubMedID 23273994

Dosimetric Analysis of Organs at Risk During Expiratory Gating in Stereotactic Body Radiation Therapy for Pancreatic Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Taniguchi, C. M., Murphy, J. D., Eclov, N., Atwood, T. F., Phd, K. N., Christman-Skieller, C., Mok, E., Xing, L., Koong, A. C., Chang, D. T. 2013; 85 (4): 1090-1095
Future directions in combined modality therapy for rectal cancer: reevaluating the role of total mesorectal excision after chemoradiotherapy ONCOTARGETS AND THERAPY Solanki, A. A., Chang, D. T., Liauw, S. L. 2013; 6: 1097-1110

Abstract

Most patients who develop rectal cancer present with locoregionally advanced (T3 or node-positive) disease. The standard management of locoregionally advanced rectal cancer is neoadjuvant concurrent chemoradiotherapy (nCRT), followed by radical resection (low-anterior resection or abdominoperineal resection with total mesorectal excision). Approximately 15% of patients can have a pathologic complete response (pCR) at the time of surgery, indicating that some patients can have no detectable residual disease after nCRT. The actual benefit of surgery in this group of patients is unclear. It is possible that omission of surgery in these patients, termed selective nonoperative management, can limit the toxicities associated with standard, multimodal combined modality therapy without compromising disease control. In this review, we discuss the clinical experiences to date using selective nonoperative management and various attempts at escalation of nCRT to improve the number of patients who have a pCR. We also explore several clinical, laboratory, imaging, histopathologic, and genetic biomarkers that have been tested as tools to predict which patients are most likely to have a pCR after nCRT.

View details for DOI 10.2147/OTT.S34869

View details for Web of Science ID 000323029400001

View details for PubMedID 23983475

Metabolic Tumor Volume Predicts Disease Progression and Survival in Patients with Squamous Cell Carcinoma of the Anal Canal JOURNAL OF NUCLEAR MEDICINE Bazan, J. G., Koong, A. C., Kapp, D. S., Quon, A., Graves, E. E., Loo, B. W., Chang, D. T. 2013; 54 (1): 27-32

Abstract

PET imaging has become a useful diagnostic tool in patients with anal cancer. We evaluated the prognostic value of metabolic tumor volume (MTV) in patients with anal cancer treated with definitive chemoradiotherapy.Patients with anal cancer who underwent PET imaging for pretreatment staging or radiation therapy planning from 2003 to 2011 were included. PET parameters included MTV and maximum standardized uptake value (SUVmax). Total MTV (MTV-T) was defined as the sum of the volumes above a standardized uptake value 50% of the SUVmax within the primary tumor and involved nodes. Kaplan-Meier and Cox regression models were used to test for associations between metabolic or clinical endpoints and overall survival (OS), progression-free survival (PFS), and event-free survival (EFS). Results: Thirty-nine patients were included. Median follow-up for the cohort was 22 mo. Overall, 6 patients died and 9 patients had disease progression. The 2-y OS, PFS, and EFS for the entire cohort were 88%, 74%, and 69%, respectively. Higher MTV-T was associated with worse OS (P = 0.04), PFS (P = 0.004), and EFS (P = 0.002) on univariate analysis. Patients with an MTV greater than 26 cm(3) had worse PFS than did those with an MTV of 26 cm(3) or less (33% vs. 82%, P = 0.003). SUVmax was not prognostic for any outcome. Higher T classification (T3/T4 vs. T1/T2) was associated with worse PFS and EFS. When adjusting for T classification, MTV-T remained a significant predictor for PFS (P = 0.01) and EFS (P = 0.02).MTV-T yields prognostic information on PFS and EFS beyond that of established prognostic factors in patients with anal cancer.

View details for DOI 10.2967/jnumed.112.109470

View details for Web of Science ID 000313606800026

View details for PubMedID 23236018

Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Patients Treated With Intensity-Modulated Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal Bazan, J. G., Luxton, G., Mok, E. C., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2012: 700-706

Abstract

To identify dosimetric parameters that correlate with acute hematologic toxicity (HT) in patients with squamous cell carcinoma of the anal canal treated with definitive chemoradiotherapy (CRT).We analyzed 33 patients receiving CRT. Pelvic bone (PBM) was contoured for each patient and divided into subsites: ilium, lower pelvis (LP), and lumbosacral spine (LSS). The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. Endpoints included grade ?3 HT (HT3+) and hematologic event (HE), defined as any grade ?2 HT with a modification in chemotherapy dose. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT and dosimetric/clinical parameters.Nine patients experienced HT3+ and 15 patients experienced HE. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.175, n = 1, and TD(50) = 32 Gy. With this model, mean PBM doses of 25 Gy, 27.5 Gy, and 31 Gy result in a 10%, 20%, and 40% risk of HT3+, respectively. Compared with patients with mean PBM dose of <30 Gy, patients with mean PBM dose ?30 Gy had a 14-fold increase in the odds of developing HT3+ (p = 0.005). Several low-dose radiation parameters (i.e., PBM-V10) were associated with the development of HT3+ and HE. No association was found with the ilium, LP, or clinical factors.LKB modeling confirms the expectation that PBM acts like a parallel organ, implying that the mean dose to the organ is a useful predictor for toxicity. Low-dose radiation to the PBM was also associated with clinically significant HT. Keeping the mean PBM dose <22.5 Gy and <25 Gy is associated with a 5% and 10% risk of HT, respectively.

View details for DOI 10.1016/j.ijrobp.2011.12.072

View details for Web of Science ID 000309560600053

View details for PubMedID 22414279

Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Patients Receiving Pelvic IMRT and Concurrent Chemotherapy Bazan, J. G., Luxton, G., Kozak, M. M., Anderson, E. M., Hancock, S. L., Kapp, D. S., Kidd, E. A., Hara, W. Y., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2012: S350-S350
SBRT as a Novel Treatment Option for Locally Recurrent Pancreatic Cancer After Failure of Definitive Multimodality Therapy: A Multi-institutional Case Series Wild, A., Hiniker, S. M., LIMAYE, M. R., Chang, D. T., Laheru, D. A., Tran, P. T., Pawlik, T. M., Wolfgang, C. L., Koong, A. C., Herman, J. M. ELSEVIER SCIENCE INC. 2012: S323-S323
Postchemoradiotherapy Positron Emission Tomography Predicts Pathologic Response and Survival in Patients With Esophageal Cancer Jayachandran, P., Pai, R. K., Quon, A., Graves, E., Krakow, T. E., La, T., Loo, B. W., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2012: 471-477

Abstract

To correlate the prechemoradiotherapy (CRT) and post-CRT metabolic tumor volume (MTV) on positron emission tomography (PET) scanning with the pathologic response and survival in patients receiving preoperative CRT for esophageal cancer.The medical records of 37 patients with histologically confirmed Stage I-IVA esophageal cancer treated with CRT with or without surgical resection were reviewed. Of the 37 patients, 21 received preoperative CRT (57%) and 16 received definitive CRT (43%). All patients had a pre-CRT and 32 had a post-CRT PET scan. The MTV was measured on the pre-CRT PET and post-CRT PET scan, respectively, using a minimum standardized uptake value (SUV) threshold x, where x = 2, 2.5, 3, or the SUV maximum 50%. The total glycolytic activity (TGA(x)) was defined as the mean SUV MTV(x). The MTV ratio was defined as the pre-CRT PET MTV/post-CRT MTV. The SUV ratio was defined similarly. A single pathologist scored the pathologic response using a tumor regression grade (TRG) scale.The median follow-up was 1.5 years (range, 0.4-4.9). No significant correlation was found between any parameters on the pre-CRT PET scan and the TRG or overall survival (OS). Multiple post-CRT MTV values and post-TGA values correlated with the TRG and OS; however, the MTV(2.5(Post)) and TGA(2.5(Post)) had the greatest correlation. The MTV(2) ratio correlated with OS. The maximum SUV on either the pre-CRT and post-CRT PET scans or the maximum SUV ratio did not correlate with the TRG or OS. Patients treated preoperatively had survival similar compared with those treated definitively with a good PET response (p = 0.97) and significantly better than that of patients treated definitively with a poor PET response (p < 0.0001).The maximum SUV was not a predictive or prognostic parameter. The MTV(2.5) and TGA(2.5) were useful markers for predicting the response and survival on the post-CRT PET scan. The MTV(2) ratio also correlated with survival. Post-CRT PET can potentially guide therapy after CRT.

View details for DOI 10.1016/j.ijrobp.2011.12.029

View details for Web of Science ID 000308062700055

View details for PubMedID 22381904

Esophageal tolerance to high-dose stereotactic ablative radiotherapy DISEASES OF THE ESOPHAGUS Abelson, J. A., Murphy, J. D., Loo, B. W., Chang, D. T., Daly, M. E., Wiegner, E. A., Hancock, S., Chang, S. D., Le, Q., Soltys, S. G., Gibbs, I. C. 2012; 25 (7): 623-629

Abstract

Dose-volume parameters are needed to guide the safe administration of stereotactic ablative radiotherapy (SABR). We report on esophageal tolerance to high-dose hypofractionated radiation in patients treated with SABR. Thirty-one patients with spine or lung tumors received single- or multiple-fraction SABR to targets less than 1 cm from the esophagus. End points evaluated include D(5cc) (minimum dose in Gy to 5 cm(3) of the esophagus receiving the highest dose), D(2cc) , D(1cc) , and D(max) (maximum dose to 0.01 cm(3) ). Multiple-fraction treatments were correlated using the linear quadratic and linear quadratic-linear/universal survival models. Three esophageal toxicity events occurred, including esophagitis (grade 2), tracheoesophageal fistula (grade 4-5), and esophageal perforation (grade 4-5). Chemotherapy was a cofactor in the high-grade events. The median time to development of esophageal toxicity was 4.1 months (range 0.6-6.1 months). Two of the three events occurred below a published D(5cc) threshold, all three were below a D(2cc) threshold, and one was below a D(max) threshold. We report a dosimetric analysis of incidental dose to the esophagus from SABR. High-dose hypofractionated radiotherapy led to a number of high-grade esophageal adverse events, suggesting that conservative parameters to protect the esophagus are necessary when SABR is used, especially in the setting of chemotherapy or prior radiotherapy.

View details for DOI 10.1111/j.1442-2050.2011.01295.x

View details for Web of Science ID 000308712300008

View details for PubMedID 22168251

Positron Emission Tomography for Predicting Pathologic Response After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer Chennupati, S. K., Quon, A., Kamaya, A., Pai, R. K., La, T., Krakow, T. E., Graves, E., Koong, A. C., Chang, D. T. LIPPINCOTT WILLIAMS & WILKINS. 2012: 334-339

Abstract

To investigate whether before and after chemoradiotherapy (CRT) positron emission tomography (PET) predict for pathologic response after preoperative CRT in patients with locally advanced rectal adenocarcinoma.Thirty-five patients who underwent pre-CRT and post-CRT PET scans before surgery were included. All patients were staged with endoscopic ultrasound or high resolution CT. CRT was given with 50.4 Gy at 1.8 Gy per fraction and concurrent 5-fluorouracil-based chemotherapy. Surgery occurred at a median of 46 days (range, 27 to 112 d) after completing CRT. The maximum standardized uptake value (SUV(max)) and the metabolic tumor volume (MTV) using various minimum SUV thresholds (2, 2.5, 3) on the PET scans (MTV(2.0), MTV(2.5), MTV(3.0)) were determined. Post-CRT PET scans were done 3 to 5 weeks after completion of CRT. Pathologic response was assessed using the tumor regression grade (TRG) scale. Patients with complete or near-complete response (TRG=0 to 1) were considered pathologic responders. The pre-CRT and post-CRT PET scan SUV(max) and MTV values were correlated with TRG. The ?SUV(max) and ?MTV were correlated with TRG.No correlation was seen with SUV(max) (P=0.99), MTV(2.0) (P=0.73), MTV(2.5) (P=0.73), or MTV(3.0) (P=0.31) on the pre-CRT PET between pathologic responders versus nonresponders. No correlation was noted between SUV(max) (P=0.49), MTV(2.0) (P=0.73), MTV(2.5) (P=0.49), or MTV(3.0) (P=0.31) on the post-CRT PET scan and pathologic response. Finally, the ?SUV(max) (P=0.32), ?MTV(2.0) (P=0.99), ?MTV(2.5) (P=0.31), ?MTV(3.0) (P=0.31) did not correlate with pathologic response.Changes seen on PET have limited value in predicting for pathologic response of rectal cancer after preoperative neoadjuvant therapy.

View details for DOI 10.1097/COC.0b013e3182118d12

View details for Web of Science ID 000306599200006

View details for PubMedID 21422989

Intrafraction Verification of Gated RapidArc by Using Beam-Level Kilovoltage X-Ray Images INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Li, R., Mok, E., Chang, D. T., Daly, M., Loo, B. W., Diehn, M., Quynh-Thu Le, Q. T., Koong, A., Xing, L. 2012; 83 (5): E709-E715

Abstract

To verify the geometric accuracy of gated RapidArc treatment using kV images acquired during dose delivery.Twenty patients were treated using the gated RapidArc technique with a Varian TrueBeam STx linear accelerator. One to 7 metallic fiducial markers were implanted inside or near the tumor target before treatment simulation. For patient setup and treatment verification purposes, the internal target volume (ITV) was created, corresponding to each implanted marker. The gating signal was generated from the Real-time Position Management (RPM) system. At the beginning of each fraction, individualized respiratory gating amplitude thresholds were set based on fluoroscopic image guidance. During the treatment, we acquired kV images immediately before MV beam-on at every breathing cycle, using the on-board imaging system. After the treatment, all implanted markers were detected, and their 3-dimensional (3D) positions in the patient were estimated using software developed in-house. The distance from the marker to the corresponding ITV was calculated for each patient by averaging over all markers and all fractions.The average 3D distance between the markers and their ITVs was 0.8 0.5 mm (range, 0-1.7 mm) and was 2.1 1.2 mm at the 95th percentile (range, 0-3.8 mm). On average, a left-right margin of 0.6 mm, an anterior-posterior margin of 0.8 mm, and a superior-inferior margin of 1.5 mm is required to account for 95% of the intrafraction uncertainty in RPM-based RapidArc gating.To our knowledge, this is the first clinical report of intrafraction verification of respiration-gated RapidArc treatment in stereotactic ablative radiation therapy. For some patients, the markers deviated significantly from the ITV by more than 2 mm at the beginning of the MV beam-on. This emphasizes the need for gating techniques with beam-on/-off controlled directly by the actual position of the tumor target instead of external surrogates such as RPM.

View details for DOI 10.1016/j.ijrobp.2012.03.006

View details for Web of Science ID 000306128100022

View details for PubMedID 22554582

Prognostic Value of Metabolic Tumor Volume and Velocity in Predicting Head-and-Neck Cancer Outcomes INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chu, K. P., Murphy, J. D., La, T. H., Krakow, T. E., Iagaru, A., Graves, E. E., Hsu, A., Maxim, P. G., Loo, B., Chang, D. T., Quynh-Thu Le, Q. T. 2012; 83 (5): 1521-1527

Abstract

We previously showed that metabolic tumor volume (MTV) on positron emission tomography-computed tomography (PET-CT) predicts for disease recurrence and death in head-and-neck cancer (HNC). We hypothesized that increases in MTV over time would correlate with tumor growth and biology, and would predict outcome. We sought to examine tumor growth over time in serial pretreatment PET-CT scans.From 2006 to 2009, 51 patients had two PET-CT scans before receiving HNC treatment. MTV was defined as the tumor volume ? 50% of maximum SUV (SUV(max)). MTV was calculated for the primary tumor, nodal disease, and composite (primary tumor + nodes). MTV and SUV velocity were defined as the change in MTV or SUV(max) over time, respectively. Cox regression analyses were used to examine correlations between SUV, MTV velocity, and outcome (disease progression and overall survival).The median follow-up time was 17.5 months. The median time between PET-CT scans was 3 weeks. Unexpectedly, 51% of cases demonstrated a decrease in SUV(max) (average, -0.1 cc/week) and MTV (average, -0.3 cc/week) over time. Despite the variability in MTV, primary tumor MTV velocity predicted disease progression (hazard ratio 2.94; p = 0.01) and overall survival (hazard ratio 1.85; p = 0.03).Primary tumor MTV velocity appears to be a better prognostic indicator of disease progression and survival in comparison to nodal MTV velocity. However, substantial variability was found in PET-CT biomarkers between serial scans. Caution should be used when PET-CT biomarkers are integrated into clinical protocols for HNC.

View details for DOI 10.1016/j.ijrobp.2011.10.022

View details for Web of Science ID 000306128100047

View details for PubMedID 22270168

Combined Modality Therapy for Rectal Cancer: The Relative Value of Posttreatment Versus Pretreatment CEA as a Prognostic Marker for Disease Recurrence ANNALS OF SURGICAL ONCOLOGY Song, S., Hong, J. C., McDonnell, S. E., Koong, A. C., Minsky, B. D., Chang, D. T., Liauw, S. L. 2012; 19 (8): 2471-2476

Abstract

To evaluate the prognostic significance of the first postsurgery carcinoembryonic antigen (CEA) level in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation (nCRT) and total mesorectal excision.A total of 100 patients underwent nCRT and had baseline and posttreatment CEA levels recorded within 6 months of surgery. The median radiotherapy dose was 50.4 Gy. Eighty-six patients received adjuvant 5-fluorouracil-based chemotherapy. Prognostic factors were analyzed for possible associations with freedom from failure (FFF) by univariate and multivariate analyses. Median follow-up was 30 months.The median CEA (ng/ml) levels at baseline before nCRT, after nCRT, and after total mesorectal excision were 3.6, 1.7, and 1.3, respectively. Pathologic complete response was observed in 22%. FFF at 36 months was 78%. Local failure and distant failure occurred in 4 and 20% of the patients, respectively. On univariate analysis, pathologic complete response, margin status, and both pretreatment and postsurgery CEA levels were associated with recurrence (all P < 0.05). On multivariate analysis, pathologic complete response (P < 0.007), margin status (P < 0.001), and postsurgery CEA level (P = 0.003), but not baseline CEA level (P = 0.2), were found to be associated with recurrence.After nCRT for rectal cancer, postsurgery CEA level may have more prognostic value than pretreatment level. Patients with a postsurgery CEA level of >2.5 ng/ml have higher rates of recurrence and may warrant closer surveillance.

View details for DOI 10.1245/s10434-012-2266-x

View details for Web of Science ID 000306789000009

View details for PubMedID 22327251

Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features MODERN PATHOLOGY Chang, D. T., Pai, R. K., Rybicki, L. A., DiMaio, M. A., Limaye, M., Jayachandran, P., Koong, A. C., Kunz, P. A., Fisher, G. A., Ford, J. M., Welton, M., Shelton, A., Ma, L., Arber, D. A., Pai, R. K. 2012; 25 (8): 1128-1139

Abstract

Recent literature suggests an increasing incidence of colorectal carcinoma in young patients. We performed a histologic, molecular, and immunophenotypic analysis of patients with sporadic early-onset (?40 years of age) colorectal carcinoma seen at our institution from the years 2000-2010 and compared these tumors to a cohort of consecutively resected colorectal carcinomas seen in patients >40 years of age. A total of 1160 primary colorectal adenocarcinomas were surgically resected for the years 2000 through 2010. Of these, 75 (6%) were diagnoses in patients ?40 years of age of which 13 (17%) demonstrated abnormalities in DNA mismatch repair, 4 (5%) were in patients with known germline genetic disorders (two patients with familial adenomatous polyposis, one patient with juvenile polyposis, and one patient with Li-Fraumeni syndrome), and three patients (4%) had long-standing chronic inflammatory bowel disease. The sporadic early-onset colorectal carcinoma group comprised a total of 55 patients (55/1160, 5%) and were compared with a control group comprising 73 consecutively resected colorectal carcinomas with proficient DNA mismatch repair in patients >40 years of age. For the early-onset colorectal carcinoma group, most cases (33/55, 60%) were diagnosed between the age of 35 and 40 years of age. Compared with the control group, the early-onset colorectal carcinoma group was significantly different with respect to tumor location (P<0.007) with 80% (44/55 cases) identified in either the sigmoid colon (24/55, 44%) or rectum (20/55, 36%). Morphologically, early-onset colorectal carcinomas more frequently displayed adverse histologic features compared with the control colorectal carcinoma group such as signet ring cell differentiation (7/55, 13% vs 1/73, 1%, P=0.021), perineural invasion (16/55, 29% vs 8/73, 11%, P=0.009) and venous invasion (12/55, 22% vs 4/73, 6%, P=0.006). A precursor adenomatous lesion was less frequently identified in the early-onset colorectal carcinoma group compared with the control group (19/55, 35% vs 39/73, 53%, P=0.034). Of the early-onset colorectal carcinomas, only 2/45 cases (4%) demonstrated KRAS mutations compared with 11/73 (15%) of the control group colorectal adenocarcinomas harboring KRAS mutations, although this difference did not reach statistical significance (P=0.13). BRAF V600E mutations were not identified in the early-onset colorectal carcinoma group. No difference was identified between the two groups with regard to tumor stage, tumor size, number of lymph node metastases, lymphatic invasion, tumor budding, mucinous histology, or tumor-infiltrating lymphocytes. Both groups had similar recurrence-free (P=0.28) and overall survival (P=0.73). However, patients in the early-onset colorectal carcinoma group more frequently either presented with or developed metastatic disease during their disease course compared with the control colorectal carcinoma group (25/55, 45% vs 18/73, 25%, P=0.014). In addition, 8/55 patients (15%) in the early-onset colorectal carcinoma group developed local recurrence of their tumor while no patients in the control colorectal carcinoma group developed local recurrence (P<0.001), likely due to the increased incidence of rectal carcinoma in the patients with early-onset colorectal carcinoma. Our study demonstrates that colorectal carcinoma is not infrequently diagnosed in patients ?40 years of age and is not frequently the result of underlying Lynch syndrome or associated with other cancer-predisposing genetic conditions or chronic inflammatory conditions. These tumors have a striking predilection for the distal colon, particularly the sigmoid colon and rectum and are much more likely to demonstrate adverse histologic factors, including signet ring cell differentiation, venous invasion, and perineural invasion.

View details for DOI 10.1038/modpathol.2012.61

View details for Web of Science ID 000307222200008

View details for PubMedID 22481281

Orthovoltage Intraoperative Radiotherapy for Locally Advanced and Recurrent Colorectal Cancer DISEASES OF THE COLON & RECTUM Daly, M. E., Kapp, D. S., Maxim, P. G., Welton, M. L., Tran, P. T., Koong, A. C., Chang, D. T. 2012; 55 (6): 695-702

Abstract

Locally advanced and recurrent colorectal cancers pose a significant therapeutic challenge. Orthovoltage intraoperative radiotherapy provides one potential means of improving disease control at the time of surgery.This study sought to analyze outcomes and identify prognostic factors of patients treated with orthovoltage intraoperative radiotherapy for locally advanced or recurrent colorectal cancer.This study is a retrospective chart review conducted at a tertiary medical center.Between January 1990 and July 2009, 55 patients underwent intraoperative radiotherapy to a total of 61 sites for locally advanced (n = 14) or recurrent (n = 41) cancers of colon (n = 18) or rectum/rectosigmoid junction (n = 37).Median dose was 12 Gy (range, 7.5-20 Gy). Among locally advanced rectal/rectosigmoid cases, surgery included abdominoperineal resection (n = 3) or low anterior resection (n = 9). Seven treated sites had gross residual (R2) disease, 28 had pathologic or clinical microscopic residual disease (R1), and 15 were complete resections (R0). Treated sites included sacrum (n = 22), anterior pelvis/pelvic sidewall (19), sacrum and sidewall (n = 1), aortic bifurcation (n = 2), vaginal cuff (n = 2), psoas (n = 3), perivesicular region (n = 2), and other (n = 10).Outcomes measures included in-field local control, locoregional control, overall survival, and grade ?3 toxicity.At a median follow-up of 27 months (range, 4-237) among living patients, 2-year Kaplan-Meier estimates of in-field local control, locoregional control, and overall survival were 69%, 51%, and 59%. Margin status predicted for improved locoregional control (p = 0.01) and overall survival (p = 0.01). Seventeen patients (31%) developed a grade 3 to 5 toxicity following surgery with intraoperative radiotherapy.This study was limited by its retrospective nature and relatively small sample size.Local control with intraoperative radiotherapy for locally advanced and recurrent colorectal cancers is good despite the high risk of residual disease. Among carefully selected patients, multimodality regimens including intraoperative radiotherapy may permit long-term survival.

View details for DOI 10.1097/DCR.0b013e31824d464c

View details for Web of Science ID 000304368500011

View details for PubMedID 22595850

A phase II multi-institutional study to evaluate gemcitabine and fractionated stereotactic body radiotherapy for unresectable, locally advanced pancreatic adenocarcinoma Herman, J. M., Chang, D. T., Goodman, K. A., Wild, A. T., Laheru, D., Zheng, L., Diaz, L. A., Dung Thi Le, D. T., Raman, S. P., Leal, J. P., Chaudhry, M. A., Sugar, E., Columbo, L. A., Tom, A., Limaye, M. R., Edil, B. H., Oteiza, K., Hacker-Prietz, A., Wolfgang, C. L., Koong, A. AMER SOC CLINICAL ONCOLOGY. 2012
Intensity-Modulated Radiotherapy for Tumors of the Nasal Cavity and Paranasal Sinuses: Clinical Outcomes and Patterns of Failure Wiegner, E. A., Daly, M. E., Murphy, J. D., Abelson, J., Chapman, C. H., Chung, M., Yu, Y., Colevas, A. D., Kaplan, M. J., Fischbein, N., Quynh-Thu Le, Q. T., Chang, D. T. ELSEVIER SCIENCE INC. 2012: 243-251

Abstract

To report outcomes in patients treated with intensity-modulated radiotherapy (IMRT) for tumors of the paranasal sinuses and nasal cavity (PNS/NC).Between June 2000 and December 2009, 52 patients with tumors of the PNS/NC underwent postoperative or definitive radiation with IMRT. Twenty-eight (54%) patients had squamous cell carcinoma (SCC). Twenty-nine patients (56%) received chemotherapy. The median follow-up was 26.6 months (range, 2.9-118.4) for all patients and 30.9 months for living patients.Eighteen patients (35%) developed local-regional failure (LRF) at median time of 7.2 months. Thirteen local failures (25%) were observed, 12 in-field and 1 marginal. Six regional failures were observed, two in-field and four out-of-field. No patients treated with elective nodal radiation had nodal regional failure. Two-year local-regional control (LRC), in-field LRC, freedom from distant metastasis (FFDM), and overall survival (OS) were 64%, 74%, 71%, and 66% among all patients, respectively, and 43%, 61%, 61%, and 53% among patients with SCC, respectively. On multivariate analysis, SCC and >1 subsite involved had worse LRC (p = 0.0004 and p = 0.046, respectively) and OS (p = 0.003 and p = 0.046, respectively). Cribriform plate invasion (p = 0.005) and residual disease (p = 0.047) also had worse LRC. Acute toxicities included Grade ?3 mucositis in 19 patients (37%), and Grade 3 dermatitis in 8patients (15%). Six patients had Grade ?3 late toxicity including one optic toxicity.IMRT for patients with PNS/NC tumors has good outcomes compared with historical series and is well tolerated. Patients with SCC have worse LRC and OS. LRF is the predominant pattern of failure.

View details for DOI 10.1016/j.ijrobp.2011.05.044

View details for Web of Science ID 000302993900057

View details for PubMedID 22019239

BRAF-mutated, Microsatellite-stable Adenocarcinoma of the Proximal Colon: An Aggressive Adenocarcinoma With Poor Survival, Mucinous Differentiation, and Adverse Morphologic Features AMERICAN JOURNAL OF SURGICAL PATHOLOGY Pai, R. K., Jayachandran, P., Koong, A. C., Chang, D. T., Kwok, S., Ma, L., Arber, D. A., Balise, R. R., Tubbs, R. R., Shadrach, B., Pai, R. K. 2012; 36 (5): 744-752

Abstract

The association of BRAF V600E mutation and the presence of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) often confound analysis of BRAF mutation status and survival in colorectal carcinoma. We evaluated a consecutive series of proximal colonic adenocarcinomas for mismatch repair protein abnormalities/MSI, BRAF V600E mutation, and KRAS mutations in an attempt to determine the prognostic significance of these abnormalities and to correlate histopathologic features with molecular alterations. Of the 259 proximal colon adenocarcinomas analyzed for mismatch repair protein abnormalities and/or MSI, 181 proximal colonic adenocarcinomas demonstrated proficient DNA mismatch repair using either MSI PCR (n=78), mismatch repair protein immunohistochemistry (n=91), or both MSI PCR and mismatch repair immunohistochemistry (n=12); these were tested for the BRAF V600E mutation and KRAS mutations. Compared with BRAF wild-type adenocarcinomas, BRAF-mutated adenocarcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (16/20, 80% vs. 75/161, 47%; P=0.008), mean number of lymph node metastases (4.5 vs. 2.2; P=0.01), perineural invasion (8/20, 40% vs. 13/161, 8%; P=0.0004), and high tumor budding (16/20, 80% vs. 83/161, 52%; P=0.02). BRAF-mutated adenocarcinomas frequently contained areas with mucinous histology (P=0.0002) and signet ring histology (P=0.03), compared with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas. Clinical follow-up data were available for 173 proximal colonic adenocarcinomas with proficient DNA mismatch repair. Patients with BRAF-mutated adenocarcinomas had a median survival of 12.3 months with a 1-year probability of survival of 54% and a 1-year disease-free survival of 56%. Patients with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas had significantly improved overall survival (unadjusted log-rank P=0.03 and unadjusted log-rank P=0.0002, respectively) and disease-free survival (unadjusted log-rank P=0.02 and unadjusted log-rank P=0.02, respectively) compared with patients with BRAF-mutated adenocarcinomas. When adjusting for tumor stage, survival analysis demonstrated that patients with BRAF-mutated adenocarcinoma had a significantly poor overall survival and disease-free survival (hazard ratios 6.63, 95% CI, 2.60-16.94; and 6.08, 95% CI, 2.11-17.56, respectively) compared with patients with KRAS/BRAF wild-type adenocarcinomas. No significant difference in overall or disease-free survival was identified between patients with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas. Our results demonstrate that BRAF-mutated proximal colon adenocarcinomas with proficient DNA mismatch repair have a dismal prognosis with an aggressive clinical course and often display mucinous differentiation, focal signet ring histology, and other adverse histologic features such as lymphatic and perineural invasion and high tumor budding.

View details for DOI 10.1097/PAS.0b013e31824430d7

View details for Web of Science ID 000302814000013

View details for PubMedID 22314188

Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma Abelson, J. A., Murphy, J. D., Minn, A. Y., Chung, M., Fisher, G. A., Ford, J. M., Kunz, P., Norton, J. A., Visser, B. C., Poultsides, G. A., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2012: E595-E601

Abstract

To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma.Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively.The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%).Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

View details for DOI 10.1016/j.ijrobp.2011.09.035

View details for Web of Science ID 000300980300003

View details for PubMedID 22197234

Modern Radiation Therapy Techniques for Pancreatic Cancer GASTROENTEROLOGY CLINICS OF NORTH AMERICA Trakul, N., Koong, A. C., Maxim, P. G., Chang, D. T. 2012; 41 (1): 223-?

Abstract

Radiation therapy is a rapidly evolving field, and recent technical advances have spurred an increasing number of new treatments as well as marked improvements in previously existing treatments. Despite a growing body of published evidence demonstrating that radiotherapy for the treatment of pancreatic cancer is improving in efficacy and safety, the ultimate effect on patient outcomes remains to be seen. It is an unfortunate fact that the majority of pancreatic cancer patients will ultimately have metastases and succumb to distant disease. Thus, improvements in local tumor control engendered by these recent advances will have little impact on overall survival without the coincident development of better systemic treatment regimens.

View details for DOI 10.1016/j.gtc.2011.12.011

View details for Web of Science ID 000301989100016

View details for PubMedID 22341260

Cost-effectiveness of modern radiotherapy techniques in locally advanced pancreatic cancer CANCER Murphy, J. D., Chang, D. T., Abelson, J., Daly, M. E., Yeung, H. N., Nelson, L. M., Koong, A. C. 2012; 118 (4): 1119-1129

Abstract

Radiotherapy may improve the outcome of patients with pancreatic cancer but at an increased cost. In this study, the authors evaluated the cost-effectiveness of modern radiotherapy techniques in the treatment of locally advanced pancreatic cancer.A Markov decision-analytic model was constructed to compare the cost-effectiveness of 4 treatment regimens: gemcitabine alone, gemcitabine plus conventional radiotherapy, gemcitabine plus intensity-modulated radiotherapy (IMRT); and gemcitabine with stereotactic body radiotherapy (SBRT). Patients transitioned between the following 5 health states: stable disease, local progression, distant failure, local and distant failure, and death. Health utility tolls were assessed for radiotherapy and chemotherapy treatments and for radiation toxicity.SBRT increased life expectancy by 0.20 quality-adjusted life years (QALY) at an increased cost of $13,700 compared with gemcitabine alone (incremental cost-effectiveness ratio [ICER] = $69,500 per QALY). SBRT was more effective and less costly than conventional radiotherapy and IMRT. An analysis that excluded SBRT demonstrated that conventional radiotherapy had an ICER of $126,800 per QALY compared with gemcitabine alone, and IMRT had an ICER of $1,584,100 per QALY compared with conventional radiotherapy. A probabilistic sensitivity analysis demonstrated that the probability of cost-effectiveness at a willingness to pay of $50,000 per QALY was 78% for gemcitabine alone, 21% for SBRT, 1.4% for conventional radiotherapy, and 0.01% for IMRT. At a willingness to pay of $200,000 per QALY, the probability of cost-effectiveness was 73% for SBRT, 20% for conventional radiotherapy, 7% for gemcitabine alone, and 0.7% for IMRT.The current results indicated that IMRT in locally advanced pancreatic cancer exceeds what society considers cost-effective. In contrast, combining gemcitabine with SBRT increased clinical effectiveness beyond that of gemcitabine alone at a cost potentially acceptable by today's standards.

View details for DOI 10.1002/cncr.26365

View details for Web of Science ID 000299834300031

View details for PubMedID 21773972

Combined-modality Therapy for Rectal Cancer: Analysis of Potential Differences in Disease Presentation, Treatment Adherence, and Treatment Outcome According to Race. American journal of clinical oncology Tonlaar, N., Song, S., Hong, J. C., Minsky, B. D., Chang, D. T., Polite, B. N., Liauw, S. L. 2012

Abstract

OBJECTIVES:: Population-based studies suggest African Americans (AAs) with rectal cancer have a worse overall outcome compared with non-AAs. This relationship was explored in a cohort of rectal cancer patients treated with preoperative chemoradiation therapy (CRT) and surgery at 2 academic cancer centers. METHODS:: A total of 146 patients (26 AA, 120 non-AA) underwent treatment with curative intent. The median age was 57 years. Median dose was 50.4 Gy, given with 5-fluorouracil-based concurrent chemotherapy. Differences in disease presentation, adherence to recommended therapy, and treatment outcome (freedom from failure) by race were analyzed. Median follow-up was 34 months from completion of CRT. RESULTS:: AAs had longer time from diagnosis to start of therapy (median, 45 vs. 35 d; P<0.01) and from CRT completion to surgery (median, 42 vs. 46 d; P=0.03). AA patients presented with more favorable disease (20% stage I, 33% stage III) compared with non-AA patients (0% stage I, 48% stage III, P<0.01). AA patients were less likely to receive adjuvant chemotherapy (58% vs. 89%, P=0.01). Log-rank analysis showed AAs were not more likely to recur after therapy (freedom from failure at 3 y, 100% for AA patients vs. 81% for non-AA patients, P=0.09). The difference in time from preoperative therapy to surgery and a lower rate of adjuvant therapy in AA patients did not seem to result in inferior disease outcome for this cohort. CONCLUSIONS:: Further study is necessary to explore the reasons underlying the delays in therapy and lower rates of adjuvant chemotherapy for AA patients.

View details for PubMedID 23211225

HER2 Expression in Gastric and Gastroesophageal Junction Adenocarcinoma in a US Population: Clinicopathologic Analysis With Proposed Approach to HER2 Assessment APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Kunz, P. L., Mojtahed, A., Fisher, G. A., Ford, J. M., Chang, D. T., Balise, R. R., Bangs, C. D., Cherry, A. M., Pai, R. K. 2012; 20 (1): 13-24

Abstract

Recent evidence suggests that trastuzumab, a monoclonal antibody which targets HER2, in combination with chemotherapy is a therapeutic option in patients with HER2-positive gastric or gastroesophageal junction cancer. Widely accepted guidelines for HER2 testing in gastric and gastroesophageal junction cancer have not been established. The purpose of this study was to analyze the incidence and patterns of HER2 expression in gastric and gastroesophageal junction cancer using a tissue microarray approach, which closely simulates small biopsies routinely tested for HER2. One hundred sixty-nine patients, including 99 primary gastric adenocarcinomas and 70 primary gastroesophageal junction carcinomas were analyzed for HER2 overexpression by immunohistochemistry and HER2 gene amplification by fluorescence in situ hybridization using scoring schemes proposed by both American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) and the results of the recently published Trastuzumab for Gastric Cancer (ToGA) trial. In our analysis, 19 adenocarcinomas were HER2 positive, defined as either a HER2/CEP17 ratio >2.2 and/or a 3+ HER2 immunohistochemistry score with either the ASCO/CAP or ToGA scoring schemes. Of the 19 HER2-positive adenocarcinomas, 8 (42%) exhibited a characteristic strongly intense basolateral membranous staining pattern which would be interpreted as negative (1+) using the accepted ASCO/CAP scoring scheme for HER2 assessment in breast carcinoma, but were correctly labeled as 3+ positive using the proposed ToGA scoring scheme. Of the 19 HER2-positive adenocarcinomas, 8 (42%) demonstrated heterogeneous HER2 protein expression by immunohistochemistry. Twelve of 99 (12%) gastric carcinomas were positive for HER2. Of these, HER2 was more often identified in intestinal-type adenocarcinomas (10 of 52, 19%) compared with diffuse (2 of 34, 6%) adenocarcinoma. Seven of 70 (10%) gastroesophageal junction carcinomas were positive for HER2 of which all were intestinal type (7 of 58, 12%). HER2 status or primary tumor site did not correlate with patient survival. Gastric and gastroesophageal junction adenocarcinomas typically display a characteristic basolateral membranous pattern of HER2 expression which is often heterogeneous rendering routine evaluation of HER2 status on small tissue samples challenging.

View details for DOI 10.1097/PAI.0b013e31821c821c

View details for Web of Science ID 000298846500003

View details for PubMedID 21617522

A rare case of an aldosterone secreting metastatic adrenocortical carcinoma and papillary thyroid carcinoma in a 31-year-old male. Rare tumors Wanta, S. M., Basina, M., Chang, S. D., Chang, D. T., Ford, J. M., Greco, R., Kingham, K., Merritt, R. E., Kunz, P. L. 2011; 3 (4)

Abstract

We report a rare synchronous presentation of adrenocortical carcinoma (ACC) and papillary thyroid carcinoma (PTC). A 31-year-old male first presented with a large left adrenal mass that was identified during the workup for refractory hypertension due to hyperaldosteronism. The mass was removed surgically with pathology showing ACC. The patient was then treated with adjuvant radiation therapy and mitotane chemotherapy. Four months post ACC resection, metastatic ACC to the right upper lung and PTC in the left lobe of the thyroid were found in surveillance imaging. He subsequently developed pulmonary, contralateral adrenal and brain metastases from his ACC. Li Fraumeni syndrome and Multiple Endocrine Neoplasia Type I (MEN I) were considered, but testing of both P53 and menin genes showed no mutation. We also performed a review of the literature and found three similar cases, however gene mutation analysis was not performed..

View details for DOI 10.4081/rt.2011.e45

View details for PubMedID 22355500

SINGLE-FRACTION STEREOTACTIC BODY RADIATION THERAPY AND SEQUENTIAL GEMCITABINE FOR THE TREATMENT OF LOCALLY ADVANCED PANCREATIC CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Schellenberg, D., Kim, J., Ciristman-Skieller, C., Chun, C. L., Columbo, L. A., Ford, J. M., Fisher, G. A., Kunz, P. L., Van Dam, J., Quon, A., Desser, T. S., Norton, J., Hsu, A., Maxim, P. G., Xing, L., Goodman, K. A., Chang, D. T., Koong, A. C. 2011; 81 (1): 181-188

Abstract

This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT).Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT.All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year.Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.

View details for DOI 10.1016/j.ijrobp.2010.05.006

View details for Web of Science ID 000294093300025

View details for PubMedID 21549517

Stereotactic Body Radiotherapy for Colorectal Liver Metastases A Pooled Analysis CANCER Chang, D. T., Swaminath, A., Kozak, M., Weintraub, J., Koong, A. C., Kim, J., Dinniwell, R., Brierley, J., Kavanagh, B. D., Dawson, L. A., Schefter, T. E. 2011; 117 (17): 4060-4069

Abstract

This study was undertaken to determine outcomes of stereotactic body radiotherapy for colorectal liver metastases in a pooled patient cohort.Patients with colorectal liver metastases from 3 institutions were included if they had 1 to 4 lesions, received 1 to 6 fractions of stereotactic body radiotherapy, and had radiologic imaging ? 3 months post-treatment. Sixty-five patients with 102 lesions treated from August 2003 to May 2009 were retrospectively analyzed. A tumor control probability (TCP) model was used to estimate the 3-fraction dose required for > 90% local control after converting the schedule into biologically equivalent dose (BED), single-fraction equivalent dose, or linear quadratic model-based single-fraction dose.Forty-seven (72%) patients had ? 1 chemotherapy regimen before stereotactic body radiotherapy, and 27 (42%) patients had ? 2 regimens. The median follow-up was 1.2 years (range, 0.3-5.2 years). The median dose was 42 gray (Gy; range, 22-60 Gy). When evaluated separately by multivariate analysis, total dose (P = .0015), dose/fraction (P = .003), and BED (P = .004) all correlated with local control by lesion. On multivariate analysis, nonactive extrahepatic disease was associated with overall survival (OS; P = .046), and sustained local control was closely correlated (P = .06). By using single-fraction equivalent dose, BED, or linear quadratic model-based single-fraction dose in the TCP model, the estimated dose range needed for 1-year local control > 90% is 46 to 52 Gy in 3 fractions.Liver stereotactic body radiotherapy is well tolerated and effective for colorectal liver metastases. The strong correlation between local control and OS supports controlling hepatic disease even for heavily pretreated patients. For a 3-fraction regimen of stereotactic body radiotherapy, a prescription dose of ? 48 Gy should be considered, if normal tissue constraints allow.

View details for DOI 10.1002/cncr.25997

View details for Web of Science ID 000294924800030

View details for PubMedID 21432842

Intensity-Modulated Radiation Therapy Versus Conventional Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal CANCER Bazan, J. G., Hara, W., Hsu, A., Kunz, P. A., Ford, J., Fisher, G. A., Welton, M. L., Shelton, A., Kapp, D. S., Koong, A. C., Goodman, K. A., Chang, D. T. 2011; 117 (15): 3342-3351

Abstract

The purpose of this study was to compare outcomes in patients with anal canal squamous cell carcinoma (SCCA) who were treated with definitive chemoradiotherapy by either intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT).Forty-six patients who received definitive chemoradiotherapy from January 1993 to August 2009 were included. Forty-five patients received 5-fluorouracil with mitomycin C (n = 39) or cisplatin (n = 6). Seventeen (37%) were treated with CRT and 29 (63%) with IMRT. The median dose was 54 Gy in both groups. Median follow-up was 26 months (CRT) and 32 months (IMRT). T3-T4 stage (P = .18) and lymph node-positive disease (P = .6) were similar between groups.The CRT group required longer treatment duration (57 days vs 40 days, P < .0001), more treatment breaks (88% vs 34.5%, P = .001), and longer breaks (12 days vs 1.5 days, P < .0001) than patients treated with IMRT. Eleven (65%) patients in the CRT group experienced grade >2 nonhematologic toxicity compared with 6 (21%) patients in the IMRT group (P = .003). The 3-year overall survival (OS), locoregional control (LRC), and progression-free survival were 87.8%, 91.9%, and 84.2%, respectively, for the IMRT groups and 51.8%, 56.7%, and 56.7%, respectively, for the CRT group (all P < .01). On multivariate analysis, T stage, use of IMRT, and treatment duration were associated with OS, and T stage and use of IMRT were associated with LRC.The use of IMRT was associated with less toxicity, reduced need for treatment breaks, and excellent LRC and OS compared with CRT in patients with SCCA of the anal canal.

View details for DOI 10.1002/cncr.25901

View details for Web of Science ID 000293103800008

View details for PubMedID 21287530

INTENSITY-MODULATED RADIOTHERAPY FOR ORAL CAVITY SQUAMOUS CELL CARCINOMA: PATTERNS OF FAILURE AND PREDICTORS OF LOCAL CONTROL INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Quynh-Thu Le, Q. T., Kozak, M. M., Maxim, P. G., Murphy, J. D., Hsu, A., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Chang, D. T. 2011; 80 (5): 1412-1422

Abstract

Few studies have evaluated the use of intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma (SCC) of the oral cavity (OC). We report clinical outcomes and failure patterns for these patients.Between October 2002 and June 2009, 37 patients with newly diagnosed SCC of the OC underwent postoperative (30) or definitive (7) IMRT. Twenty-five patients (66%) received systemic therapy. The median follow-up was 38 months (range, 10-87 months). The median interval from surgery to RT was 5.9 weeks (range, 2.1-10.7 weeks).Thirteen patients experienced local-regional failure at a median of 8.1 months (range, 2.4-31.9 months), and 2 additional patients experienced local recurrence between surgery and RT. Seven local failures occurred in-field (one with simultaneous nodal and distant disease) and two at the margin. Four regional failures occurred, two in-field and two out-of-field, one with synchronous metastases. Six patients experienced distant failure. The 3-year actuarial estimates of local control, local-regional control, freedom from distant metastasis, and overall survival were 67%, 53%, 81%, and 60% among postoperative patients, respectively, and 60%, 60%, 71%, and 57% among definitive patients. Four patients developed Grade ? 2 chronic toxicity. Increased surgery to RT interval predicted for decreased LRC (p = 0.04).Local-regional control for SCC of the OC treated with IMRT with or without surgery remains unsatisfactory. Definitive and postoperative IMRT have favorable toxicity profiles. A surgery-to-RT interval of < 6 weeks improves local-regional control. The predominant failure pattern was local, suggesting that both improvements in target delineation and radiosensitization and/or dose escalation are needed.

View details for DOI 10.1016/j.ijrobp.2010.04.031

View details for Web of Science ID 000293207600020

View details for PubMedID 20675073

Rectal and bladder deformation and displacement during preoperative radiotherapy for rectal cancer: Are current margin guidelines adequate for conformal therapy? Practical radiation oncology Daly, M. E., Murphy, J. D., Mok, E., Christman-Skieller, C., Koong, A. C., Chang, D. T. 2011; 1 (2): 85-94

Abstract

To evaluate rectal motion and estimate an appropriate target volume for preoperative radiotherapy (RT) for rectal cancer.Between January 2006 and December 2009, 17 rectal cancer patients undergoing preoperative RT underwent 39 cone-beam computed tomographic scans (CBCTs). CBCTs were fused to treatment planning CT scans by bony anatomy. The rectum and bladder were contoured on each scan. Margins of 2, 5, 10, and 15 mm were added to the rectum, and the volume and percent rectum on CBCT outside each of these margins were determined. The clinical target volume (CTV) was examined to determine the necessary margin beyond the posterior bladder edge to ensure coverage of the mesorectum at all time points.Median percentage rectum on CBCT outside the planning rectum was 7.77% (range, 0.19%-42.91%). Two patients had 1 or more CBCT with 1% or greater rectum outside a 1.5 cm margin. Five patients had 1 or more CBCT with 1% or greater rectum outside a 1.0 cm margin. A CTV extending 1 cm into the posterior bladder edge (CTV1.0) was adequate at all time points for 79% of evaluable patients, and a CTV with a 1.5 cm anterior margin was adequate for 93% of patients. For 2 patients, the rectum extended outside the CTV1.0 on CBCT.With a limited number of CBCT scans, we found that the rectum tended to remain within 1.5 cm of the initial location on treatment planning CT. However, an anterior margin of 1.5 cm beyond the posterior bladder edge provides better coverage of the mesorectum than 1 cm for the initial CTV.

View details for DOI 10.1016/j.prro.2010.11.006

View details for PubMedID 24673921

PROSPECTIVE RANDOMIZED DOUBLE-BLIND PILOT STUDY OF SITE-SPECIFIC CONSENSUS ATLAS IMPLEMENTATION FOR RECTAL CANCER TARGET VOLUME DELINEATION IN THE COOPERATIVE GROUP SETTING INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Fuller, C. D., Nijkamp, J., Duppen, J. C., Rasch, C. R., Thomas, C. R., Wang, S. J., Okunieff, P., Jones, W. E., Baseman, D., Patel, S., Demandante, C. G., Harris, A. M., Smith, B. D., Katz, A. W., McGann, C., Harper, J. L., Chang, D. T., Smalley, S., Marshall, D. T., Goodman, K. A., Papanikolaou, N., Kachnic, L. A. 2011; 79 (2): 481-489

Abstract

Variations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based visual atlas on contouring the target volumes.A representative case was contoured (Scan 1) by 14 physician observers and a reference expert with and without target volume delineation instructions derived from a proposed rectal cancer clinical trial involving conformal radiotherapy. The gross tumor volume (GTV), and two clinical target volumes (CTVA, including the internal iliac, presacral, and perirectal nodes, and CTVB, which included the external iliac nodes) were contoured. The observers were randomly assigned to receipt (Group A) or nonreceipt (Group B) of a consensus guideline and atlas for anorectal cancers and then instructed to recontour the same case/images (Scan 2). Observer variation was analyzed volumetrically using the conformation number (CN, where CN = 1 equals total agreement).Of 14 evaluable contour sets (1 expert and 7 Group A and 6 Group B observers), greater agreement was found for the GTV (mean CN, 0.75) than for the CTVs (mean CN, 0.46-0.65). Atlas exposure for Group A led to significantly increased interobserver agreement for CTVA (mean initial CN, 0.68, after atlas use, 0.76; p = .03) and increased agreement with the expert reference (initial mean CN, 0.58; after atlas use, 0.69; p = .02). For the GTV and CTVB, neither the interobserver nor the expert agreement was altered after atlas exposure.Consensus guideline atlas implementation resulted in a detectable difference in interobserver agreement and a greater approximation of expert volumes for the CTVA but not for the GTV or CTVB in the specified case. Visual atlas inclusion should be considered as a feature in future clinical trials incorporating conformal RT.

View details for DOI 10.1016/j.ijrobp.2009.11.012

View details for Web of Science ID 000286451000023

View details for PubMedID 20400244

Pattern of Lymph Node Involvement and Prognosis in Pancreatic Adenocarcinoma: Direct Lymph Node Invasion Has Similar Survival to Node-Negative Disease AMERICAN JOURNAL OF SURGICAL PATHOLOGY Pai, R. K., Beck, A. H., Mitchem, J., Linehan, D. C., Chang, D. T., Norton, J. A., Pai, R. K. 2011; 35 (2): 228-234

Abstract

Lymph node status is one of the most important predictors of survival in pancreatic ductal adenocarcinoma. Surgically resected pancreatic adenocarcinoma is often locally invasive and may invade directly into peripancreatic lymph nodes. The significance of direct invasion into lymph nodes in the absence of true lymphatic metastases is unclear. The purpose of this study was to retrospectively compare clinical outcome in patients with pancreatic ductal adenocarcinoma with direct invasion into peripancreatic lymph nodes with patients with node-negative adenocarcinomas and patients with true lymphatic lymph node metastasis. A total of 380 patients with invasive pancreatic ductal adenocarcinoma classified as pT3, were evaluated: ductal adenocarcinoma with true lymphatic metastasis to regional lymph nodes (248 cases), ductal adenocarcinoma without lymph node involvement (97 cases), and ductal adenocarcinoma with regional lymph nodes involved only by direct invasion from the main tumor mass (35 cases). Isolated lymph node involvement by direct invasion occurred in 35 of 380 (9%) patients. Overall survival for patients with direct invasion of lymph nodes (median survival, 21 mo; 5-year overall survival, 36%) was not statistically different from patients with node-negative adenocarcinomas (median survival, 30 mo; 5-year overall survival, 31%) (P=0.609). Patients with node-negative adenocarcinomas had an improved survival compared with patients with lymph node involvement by true lymphatic metastasis (median survival, 15 mo; 5-year overall survival, 8%) (P<0.001) regardless of the number of lymph nodes involved by adenocarcinoma. There was a trend toward decreased overall survival for patients with 1 or 2 lymph nodes involved by true lymphatic metastasis compared with patients with direct invasion of tumor into lymph nodes (P=0.056). However, this did not reach statistical significance. Our results indicate that patients with isolated direct lymph node invasion have a comparable overall survival with patients with node-negative adenocarcinomas as opposed to true lymphatic lymph node metastasis.

View details for DOI 10.1097/PAS.0b013e318206c37a

View details for Web of Science ID 000286581700007

View details for PubMedID 21263243

INTENSITY-MODULATED RADIOTHERAPY FOR LOCALLY ADVANCED CANCERS OF THE LARYNX AND HYPOPHARYNX HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Daly, M. E., Le, Q., Jain, A. K., Maxim, P. G., Hsu, A., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Colevas, A. D., Pinto, H., Chang, D. T. 2011; 33 (1): 103-111

Abstract

Limited data evaluate intensity-modulated radiotherapy (IMRT) for cancers of the hypopharynx and larynx. We report clinical outcomes and failure patterns for these patients.Between September 2001 and December 2007, 42 patients with squamous cell carcinoma (SCC) of the hypopharynx (n = 23) and larynx (n = 19) underwent IMRT, 11 postoperatively and 31 definitively. Thirty-six received systemic therapy. Median follow-up was 30 months among surviving patients.Three local failures occurred within the high-dose region and 3 occurred in regional nodes. Seven patients developed distant metastasis as the initial failure. Three-year actuarial estimates of locoregional control, freedom from distant metastasis, and overall survival rates were, respectively, 80%, 72%, and 46%.IMRT provides good locoregional control for SCC of the hypopharynx and larynx compared with historical controls. Locoregional relapses occurred in the high-dose volumes, suggesting adequate target volume delineation. Hypopharyngeal tumors, which fare worse than laryngeal tumors, warrant investigation of more aggressive treatment.

View details for DOI 10.1002/hed.21406

View details for Web of Science ID 000286290400017

View details for PubMedID 20848427

Gastrointestinal Normal Tissue Toxicity Prediction In Stereotactic Body Radiotherapy Murphy, J. D., Abelson, J., Chung, M. P., Chang, D. T., Koong, A. C. ELSEVIER SCIENCE INC. 2011: S378-S378
Multimodality Therapy for Esophageal Cancer: The Benefit of Chemoradiation Vossler, S. R., Bavan, B., Kunz, P., Ford, J. M., Fisher, G. A., Whyte, R., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2011: S309-S309
Radiotherapy For Adenoid Cystic Carcinomas Of The Head and Neck: Clinical Outcomes And Patterns Of Failure Shultz, D. B., Murphy, J. D., Daly, M. E., Hara, W., Le, Q. T., Chang, D. T. ELSEVIER SCIENCE INC. 2011: S528-S528
Dosimetric Comparison of RapidArc versus CyberKnife for Stereotactic Body Radiation Therapy for Pancreatic Cancer Atwood, T. F., Mok, E., Lo, A., Xing, L., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2011: S345-S346
Stereotactic Body Radiation Therapy for Gastrointestinal Malignancies IMRT IGRT SBRT- ADVANCES IN THE TREATMENT PLANNING AND DELIVERY OF RADIOTHERAPY Minn, A. Y., Koong, A. C., Chang, D. T. 2011; 43: 412-427

Abstract

Stereotactic body radiotherapy (SBRT) is an emerging treatment for pancreas cancer and liver tumors. Early data suggest excellent control rates for locally advanced pancreas cancer. However, due to the close proximity of the duodenum and stomach, steps to effectively minimize toxicities must be taken through image guidance of treatments. SBRT for liver tumors has also shown high rates of local control with low risks for hepatic toxicity. Careful selection of cases for SBRT is essential to achieve disease control and to minimize toxicity for patients. In treatment, attention must be paid to minimizing exposure of nearby normal tissues, including ribs, skin and bowel as well as the functioning organs surrounding the tumors. There is no accepted standard for the SBRT dose/fractionation schedule for these cases and the optimal strategy will likely depend on the size, number and location of lesions for each patient. However, the published data seem to suggest an overall dose-response effect. To realize the clinical potential of SBRT for these tumors, investigations are needed to determine optimum fractionation schedules and to integrate its use with systemic chemotherapy programs.

View details for Web of Science ID 000292117400021

View details for PubMedID 21625166

A DOSIMETRIC MODEL OF DUODENAL TOXICITY AFTER STEREOTACTIC BODY RADIOTHERAPY FOR PANCREATIC CANCER Murphy, J. D., Christman-Skieller, C., Kim, J., Dieterich, S., Chang, D. T., Koong, A. C. ELSEVIER SCIENCE INC. 2010: 1420-1426

Abstract

Dose escalation for pancreas cancer is limited by the tolerance of adjacent normal tissues, especially with stereotactic body radiotherapy (SBRT). The duodenum is generally considered to be the organ at greatest risk. This study reports on the dosimetric determinants of duodenal toxicity with single-fraction SBRT.Seventy-three patients with locally advanced unresectable pancreatic adenocarcinoma received 25 Gy in a single fraction. Dose-volume histogram (DVH) endpoints evaluated include V(5) (volume of duodenum that received 5 Gy), V(10), V(15), V(20), V(25), and D(max) (maximum dose to 1 cm(3)). Normal tissue complication probability (NTCP) was evaluated with a Lyman model. Univariate and multivariate analyses were conducted with Kaplan-Meier and Cox regression models.The median time to Grade 2-4 duodenal toxicity was 6.3 months (range, 1.6-11.8 months). The 6- and 12-month actuarial rates of toxicity were 11% and 29%, respectively. V(10)-V(25) and D(max) all correlated significantly with duodenal toxicity (p<0.05). In particular, V(15)?9.1 cm(3) and V(15)<9.1 cm(3) yielded duodenal toxicity rates of 52% and 11%, respectively (p=0.002); V(20)?3.3 cm(3) and V(20)<3.3 cm(3) gave toxicity rates of 52% and 11%, respectively (p=0.002); and D(max)?23 Gy and D(max)<23 Gy gave toxicity rates of 49% and 12%, respectively (p=0.004). Lyman NTCP model optimization generated the coefficients m=0.23, n=0.12, and TD(50)=24.6 Gy. Only the Lyman NTCP model remained significant in multivariate analysis (p=0.001).Multiple DVH endpoints and a Lyman NTCP model are strongly predictive of duodenal toxicity after SBRT for pancreatic cancer. These dose constraints will be valuable in future abdominal SBRT studies.

View details for DOI 10.1016/j.ijrobp.2009.09.075

View details for Web of Science ID 000284987800019

View details for PubMedID 20399033

Expression of p16(INK4A) But Not Hypoxia Markers or Poly Adenosine Diphosphate-Ribose Polymerase Is Associated With Improved Survival in Patients With Pancreatic Adenocarcinoma Chang, D. T., Chapman, C. H., Norton, J. A., Visser, B., Fisher, G. A., Kunz, P., Ford, J. M., Koong, A. C., Pai, R. K. WILEY-BLACKWELL. 2010: 5179-5187

Abstract

Pancreatic cancer is associated with mutations in the tumor suppressor gene cyclin-dependent kinase inhibitor 2A (p16(INK4A) ), a regulator of the cell cycle and apoptosis. This study investigates whether immunohistochemical expression of p16(INK4A) as well as hypoxia markers and poly adenosine diphosphate-ribose polymerase (PARP) correlates with survival in patients with resected pancreatic adenocarcinoma.Seventy-three patients with pancreatic adenocarcinoma who underwent curative resection at Stanford University were included. From the surgical specimens, a tissue microarray was constructed using triplicate tissue cores from the primary tumor and used for immunohistochemical staining for the following markers: carbonic anhydrase IX, dihydrofolate reductase, p16(INK4A) , and PARP1/2. Staining was scored as either positive or negative and percentage positive staining. Staining score was correlated with overall survival (OS) and progression-free survival (PFS).Of the markers tested, only immunohistochemical expression of p16(INK4A) correlated with clinical outcome. On univariate analysis, p16(INK4A) expression in the tumor was associated with improved OS (P = .038) but not PFS (P = .28). The median survival for patients with positive versus negative p16(INK4A) staining was 28.8 months versus 18 months. On multivariate analysis, p16(INK4A) expression was associated with improved OS (P = .026) but not PFS (P = .25). Age (P = .0019) and number of nodes involved (P = .025) were also significant for OS. Adjuvant chemotherapy and margin status did not correlate with OS or PFS.Expression of p16(INK4A) is associated with improved OS in patients with resected pancreatic adenocarcinoma. Further investigation is needed for validation, given conflicting data in the published literature. .

View details for DOI 10.1002/cncr.25481

View details for Web of Science ID 000284047400009

View details for PubMedID 20665497

Orthovoltage intraoperative radiation therapy for pancreatic adenocarcinoma RADIATION ONCOLOGY Bachireddy, P., Tseng, D., Horoschak, M., Chang, D. T., Koong, A. C., Kapp, D. S., Tran, P. T. 2010; 5

Abstract

To analyze the outcomes of patients from a single institution treated with surgery and orthovoltage intraoperative radiotherapy (IORT) for pancreatic adenocarcinoma.We retrospectively reviewed 23 consecutive patients from 1990-2001 treated with IORT to 23 discrete sites with median and mean follow up of 6.5 and 21 months, respectively. Most tumors were located in the head of the pancreas (83%) and sites irradiated included: tumor bed (57%), vessels (26%), both the tumor bed/vessels (13%) and other (4%). The majority of patients (83%) had IORT at the time of their definitive surgery. Three patients had preoperative chemoradiation (13%). Orthovoltage X-rays (200-250 kVp) were employed via individually sized and beveled cone applicators. Additional mean clinical characteristics include: age 64 (range 41-81); tumor size 4 cm (range 1.4-11); and IORT dose 1106 cGy (range 600-1500). Post-operative external beam radiation (EBRT) or chemotherapy was given to 65% and 76% of the assessable patients, respectively. Outcomes measured were infield control (IFC), loco-regional control (LRC), distant metastasis free survival (DMFS), overall survival (OS) and treatment-related complications.Kaplan-Meier (KM) 2-year IFC, LRC, DMFS and OS probabilities for the whole group were 83%, 61%, 26%, and 27%, respectively. Our cohort had three grade 3-5 complications associated with treatment (surgery and IORT).Orthovoltage IORT following tumor reductive surgery is reasonably well tolerated and seems to confer in-field control in carefully selected patients. However, distant metastases remain the major problem for patients with pancreatic adenocarcinoma.

View details for DOI 10.1186/1748-717X-5-105

View details for Web of Science ID 000284380900001

View details for PubMedID 21059255

Comparison of Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy as Adjuvant Therapy for Gastric Cancer Minn, A. Y., Hsu, A., La, T., Kunz, P., Fisher, G. A., Ford, J. M., Norton, J. A., Visser, B., Goodman, K. A., Koong, A. C., Chang, D. T. JOHN WILEY & SONS INC. 2010: 3943-3952

Abstract

The current study was performed to compare the clinical outcomes and toxicity in patients treated with postoperative chemoradiotherapy for gastric cancer using intensity-modulated radiotherapy (IMRT) versus 3-dimensional conformal radiotherapy (3D CRT).Fifty-seven patients with gastric or gastroesophageal junction cancer were treated postoperatively: 26 with 3D CRT and 31 with IMRT. Concurrent chemotherapy was capecitabine (n=31), 5-fluorouracil (5-FU) (n=25), or none (n=1). The median radiation dose was 45 Gy. Dose volume histogram parameters for kidney and liver were compared between treatment groups.The 2-year overall survival rates for 3D CRT versus IMRT were 51% and 65%, respectively (P=.5). Four locoregional failures occurred each in the 3D CRT (15%) and the IMRT (13%) patients. Grade>or=2 acute gastrointestinal toxicity was found to be similar between the 3D CRT and IMRT patients (61.5% vs 61.2%, respectively) but more treatment breaks were needed (3 vs 0, respectively). The median serum creatinine from before radiotherapy to most recent creatinine was unchanged in the IMRT group (0.80 mg/dL) but increased in the 3D CRT group from 0.80 mg/dL to 1.0 mg/dL (P=.02). The median kidney mean dose was higher in the IMRT versus the 3D CRT group (13.9 Gy vs 11.1 Gy; P=.05). The median kidney V20 was lower for the IMRT versus the 3D CRT group (17.5% vs 22%; P=.17). The median liver mean dose for IMRT and 3D CRT was 13.6 Gy and 18.6 Gy, respectively (P=.19). The median liver V30 was 16.1% and 28%, respectively (P<.001).Adjuvant chemoradiotherapy was well tolerated. IMRT was found to provide sparing to the liver and possibly renal function.

View details for DOI 10.1002/cncr.25246

View details for Web of Science ID 000280677100025

View details for PubMedID 20564136

(18)FLUORODEOXYGLUCOSE PET IS PROGNOSTIC OF PROGRESSION-FREE AND OVERALL SURVIVAL IN LOCALLY ADVANCED PANCREAS CANCER TREATED WITH STEREOTACTIC RADIOTHERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Schellenberg, D., Quon, A., Minn, A. Y., Graves, E. E., Kunz, P., Ford, J. M., Fisher, G. A., Goodman, K. A., Koong, A. C., Chang, D. T. 2010; 77 (5): 1420-1425

Abstract

This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT).Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed.For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03).PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients.

View details for DOI 10.1016/j.ijrobp.2009.06.049

View details for Web of Science ID 000280459700020

View details for PubMedID 20056345

Pathological response after chemoradiation for T3 rectal cancer. Colorectal disease Chennupati, S. K., Kamaya, A., Fisher, G. A., Ford, J. M., Kunz, P., Itakura, H., Welton, M. L., Shelton, A., Van Dam, J., Koong, A. C., Chang, D. T. 2010; 12 (7 Online): e24-30

Abstract

The aim of this study was to investigate the effect of preoperative chemoradiotherapy (CRT) on nodal disease in locally advanced rectal adenocarcinoma.Thirty-two patients staged uT3N0 and 27 patients staged uT3N1 rectal adenocarcinoma who underwent pre-CRT staging using endoscopic ultrasound or rectal protocol CT were included. The median radiation dose was 50.4 Gy (range: 45-50.4 Gy) at 1.8 Gy per fraction and all patients received concurrent 5-FU or capecitabine-based chemotherapy. Low anterior resection or abdomino-perineal resection occurred at a median of 46 days (range: 27-112 days) after CRT.Eleven of 32 uT3N0 patients (34.4%) and 13 of 26 uT3N1 patients (50.0%) had ypN+ (P = 0.29). For patients with uT3N0, 10 of 20 (50.0%) with ypT2-3 and 1 of 12 (8.3%) with ypT0-1 were ypN+ (P = 0.02). For patients with uT3N1, 12 of 20 (60.0%) with ypT2-3 and 1 of 6 (16.7%) with ypT0-1 were ypN+ (P = 0.16). Overall, the ypN+ rate was 11.1% in the ypT0-yT1 group compared with 55.0% in the ypT2-yT3 group (P = 003). Among patients with uT3N0 disease, the ypN+ rate in patients who had surgery > 46 days vs 46 days vs 46 days vs

View details for DOI 10.1111/j.1463-1318.2009.02013.x

View details for PubMedID 19614668

Pathological response after chemoradiation for T3 rectal cancer COLORECTAL DISEASE Chennupati, S. K., Kamaya, A., Fisher, G. A., Ford, J. M., Kunz, P., Itakura, H., Welton, M. L., Shelton, A., Van Dam, J., Koong, A. C., Chang, D. T. 2010; 12 (7): E24-E30
INTENSITY-MODULATED RADIOTHERAPY IN THE TREATMENT OF OROPHARYNGEAL CANCER: CLINICAL OUTCOMES AND PATTERNS OF FAILURE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Le, Q., Maxim, P. G., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Pinto, H., Chang, D. T. 2010; 76 (5): 1339-1346

Abstract

To report outcomes, failures, and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma of the oropharynx.Between Aug 2001 and Oct 2007, 107 patients were treated with IMRT with curative intent at Stanford University. Twenty-two patients were treated postoperatively, and 85 were treated definitively. Concurrent platinum-based chemotherapy was administered to 86 patients (80%) and cetuximab to 8 patients (7%). The prescribed dose was 66 Gy at 2.2 Gy/fraction for definitively treated cases and 60 Gy at 2 Gy/fraction for postoperative cases. Median follow-up was 29 months among surviving patients (range, 4-105 months).Eight patients had persistent disease or local-regional failure at a median of 6.5 months (range, 0-9.9 months). Six local failures occurred entirely within the high-risk clinical target volume (CTV) (one with simultaneous distant metastasis). One patient relapsed within the high- and intermediate-risk CTV. One patient had a recurrence at the junction between the IMRT and low-neck fields. Seven patients developed distant metastasis as the first site of failure. The 3-year local-regional control (LRC), freedom from distant metastasis, overall survival, and disease-free survival rates were 92%, 92%, 83%, and 81%, respectively. T stage (T4 vs. T1-T3) was predictive of poorer LRC (p = 0.001), overall survival (p = 0.001), and disease-free survival (p < 0.001) rates. Acute toxicity consisted of 58% grade 3 mucosal and 5% grade 3 skin reactions. Six patients (6%) developed grade >or=3 late complications.IMRT provides excellent LRC for oropharyngeal squamous cell carcinoma. Distant metastases are a major failure pattern. No marginal failures were observed.

View details for DOI 10.1016/j.ijrobp.2009.04.006

View details for Web of Science ID 000276675300012

View details for PubMedID 19540068

EUS-guided gold fiducial insertion for image-guided radiation therapy of pancreatic cancer: 50 successful cases without fluoroscopy GASTROINTESTINAL ENDOSCOPY Park, W. G., Yan, B. M., Schellenberg, D., Kim, J., Chang, D. T., Koong, A., Patalano, C., Van Dam, J. 2010; 71 (3): 513-518

Abstract

Image-guided radiation therapy (IGRT) accurately delivers a high dose of potentially tumoricidal radiation to its target while sparing adjacent healthy tissue. Application of IGRT to unresectable pancreatic cancer requires the use of fiducials to track the precise location of the tumor. Fiducial markers have been successfully placed endoscopically.To determine the feasibility of EUS-guided gold fiducial placement for IGRT.Prospective case series.Tertiary medical center.Consecutively referred patients with locally advanced unresectable pancreatic adenocarcinoma for EUS-guided insertion of gold fiducials from December 2006 to February 2009.Under only EUS guidance, fiducial markers were deployed into or near the tumor by using a 19-gauge needle. In most cases, a sterile water injection technique was used to insert the fiducials. Fluoroscopy was not used in any case.Successful placement of an adequate number of fiducials to proceed with IGRT as determined by CT.Fifty-seven consecutive patients were included. Fifty cases (88%) were successful. Of the cases in which fiducial placement was attempted and follow-up was adequate, 94% (50 of 53) of cases were successful.Single-center, nonrandomized study.EUS-guided fine-needle insertion was safe and effective in delivering gold fiducial markers for image-guided radiation therapy. Fluoroscopy was not required for successful fiducial placement.

View details for DOI 10.1016/j.gie.2009.10.030

View details for Web of Science ID 000275897900012

View details for PubMedID 20189509

INTERFRACTIONAL UNCERTAINTY IN THE TREATMENT OF PANCREATIC CANCER WITH RADIATION INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Jayachandran, P., Minn, A. Y., Van Dam, J., Norton, J. A., Koong, A. C., Chang, D. T. 2010; 76 (2): 603-607

Abstract

To compare the interfractional variation in pancreatic tumor position using bony anatomy and implanted fiducial markers.Five consecutively treated patients with pancreatic adenocarcinoma who received definitive intensity-modulated radiation therapy at Stanford University (Stanford, CA) underwent fiducial seed placement and treatment on the Varian Trilogy system (Varian, Palo Alto, CA) with respiratory gating. Daily orthogonal kilovoltage imaging was performed to verify patient positioning, and isocenter shifts were made initially to match bony anatomy. Next, a final shift to the fiducial seeds was made under fluoroscopic guidance to confirm the location of the pancreatic tumor during the respiratory gated phase. All shifts were measured along three axes, left (+)-right (-), anterior (-)-posterior (+), and superior (+)-inferior (-), and the overall interfractional tumor movement was calculated based on these values.A total of 140 fractions were analyzed. The mean absolute shift to fiducial markers after shifting to bony anatomy was 1.6 mm (95th percentile, 7 mm; range, 0-9 mm), 1.8 mm (95th percentile, 7 mm; range, 0-13 mm), and 4.1 mm (95th percentile, 12 mm; range, 0-19 mm) in the anterior-posterior, left-right, and superior-inferior directions, respectively. The mean interfractional vector shift distance was 5.5 mm (95th percentile, 14.5 mm; range, 0-19.3 mm). In 28 of 140 fractions (20%) no fiducial shift was required after alignment to bony anatomy.There is substantial residual uncertainty after alignment to bony anatomy when radiating pancreatic tumors using respiratory gating. Bony anatomy matched tumor position in only 20% of the radiation treatments. If bony alignment is used in conjunction with respiratory gating without implanted fiducials, treatment margins need to account for this uncertainty.

View details for DOI 10.1016/j.ijrobp.2009.06.029

View details for Web of Science ID 000274121500040

View details for PubMedID 19879062

Multimodality treatment with intensity modulated radiation therapy for esophageal cancer DISEASES OF THE ESOPHAGUS La, T. H., Minn, A. Y., Su, Z., Fisher, G. A., Ford, J. M., Kunz, P., Goodman, K. A., Koong, A. C., Chang, D. T. 2010; 23 (4): 300-308

Abstract

The objective of this study is to determine the feasibility and report the outcome of patients with locally advanced esophageal cancer treated with preoperative or definitive chemoradiotherapy (CRT) using intensity-modulated radiation therapy (IMRT). Between 2003 and 2007, 30 patients with non-cervical esophageal cancer received concurrent chemotherapy and IMRT at Stanford University. Eighteen patients were planned for definitive CRT and 12 were planned for preoperative CRT. All patients had computed tomography-based treatment planning and received IMRT. The median dose delivered was 50.4 Gy. Patients planned for preoperative CRT underwent surgery 4-13 weeks (median 8.3 weeks) following completion of CRT. Median follow-up of surviving patients from start of RT was 24.2 months (range 8.2-38.3 months). The majority of tumors were adenocarcinomas (67%) and poorly differentiated (57%). Tumor location was 7% upper, 20% mid, 47% lower, and 27% gastroesophageal junction. Actuarial 2-year local-regional control (LRC) was 64%. High tumor grade was an adverse prognostic factor for LRC and overall survival (OS) (P= 0.015 and 0.012, respectively). The 2-year LRC was 83% vs. 51% for patients treated preoperatively vs. definitively (P= 0.32). The 2-year disease-free and OS were 38% and 56%, respectively. Twelve patients (40%) required feeding tube placement, and the average weight loss from baseline was 4.8%. Twelve (40%) patients experienced grade 3+ acute complications and one patient died of complications following feeding tube placement. Three patients (10%) required a treatment break. Eight patients (27%) experienced grade 3 late complications. No grade 4 complications were seen. IMRT was effective and well tolerated. Disease recurrence remains a challenge and further investigation with dose escalation to improve LRC and OS is warranted.

View details for DOI 10.1111/j.1442-2050.2009.01004.x

View details for Web of Science ID 000278109300005

View details for PubMedID 19732129

Stereotactic Body Radiotherapy for Colorectal Liver Metastases: A Pooled Analysis Chang, D. T., Swaminath, A., Kozak, M., Weintraub, J., Koong, A. C., Kim, J., Dawson, L. A., Kavanagh, B. D., Schefter, T. E. ELSEVIER SCIENCE INC. 2010: S56-S57
Prognostic Value of Metabolic Tumor Volume and Velocity in Predicting Head and Neck Cancer Outcomes Chu, K. P., Murphy, J., La, T. H., Loo, B. W., Krakow, T. E., Hsu, A., Maxim, P. G., Graves, E., Chang, D., Le, Q. ELSEVIER SCIENCE INC. 2010: S460-S460
Combined Modality Therapy for Rectal Cancer: Analysis of Potential Differences in Disease Presentation, Treatment Adherence, and Treatment Outcome According to Race Liauw, S., Song, S., Tonlaar, N., Hong, J. C., Minsky, B. D., Chang, D. T., Polite, B. ELSEVIER SCIENCE INC. 2010: S198-S198
Significant Duodenal Dose Variation within the Respiratory Cycle during Stereotactic Body Radiotherapy for Pancreatic Cancer Taniguchi, C. M., Kielar, K. N., Murphy, J. D., Atwood, T. F., Christman-Skieller, C., Dieterich, S., Xing, L., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2010: S329-S329
Comparison of RapidArc vs. Conventional Intensity Modulated Radiation Therapy for Stereotactic Body Radiation Therapy for Pancreatic Cancer Kielar, K. N., Atwood, T. F., Taniguchi, C. M., Christman-Skieller, C., Xing, L., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2010: S785-S785
Intensity Modulated Radiation Therapy vs. Conventional Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal Bazan, J. G., Hara, W., Kunz, P., Fisher, G. A., Ford, J. M., Welton, M. L., Koong, A., Shelton, A., Goodman, K. A., Chang, D. T. ELSEVIER SCIENCE INC. 2010: S300-S301
Identification of a biomarker panel using a multiplex proximity ligation assay improves accuracy of pancreatic cancer diagnosis JOURNAL OF TRANSLATIONAL MEDICINE Chang, S. T., Zahn, J. M., Horecka, J., Kunz, P. L., Ford, J. M., Fisher, G. A., Le, Q. T., Chang, D. T., Ji, H., Koong, A. C. 2009; 7

Abstract

Pancreatic cancer continues to prove difficult to clinically diagnose. Multiple simultaneous measurements of plasma biomarkers can increase sensitivity and selectivity of diagnosis. Proximity ligation assay (PLA) is a highly sensitive technique for multiplex detection of biomarkers in plasma with little or no interfering background signal.We examined the plasma levels of 21 biomarkers in a clinically defined cohort of 52 locally advanced (Stage II/III) pancreatic ductal adenocarcinoma cases and 43 age-matched controls using a multiplex proximity ligation assay. The optimal biomarker panel for diagnosis was computed using a combination of the PAM algorithm and logistic regression modeling. Biomarkers that were significantly prognostic for survival in combination were determined using univariate and multivariate Cox survival models.Three markers, CA19-9, OPN and CHI3L1, measured in multiplex were found to have superior sensitivity for pancreatic cancer vs. CA19-9 alone (93% vs. 80%). In addition, we identified two markers, CEA and CA125, that when measured simultaneously have prognostic significance for survival for this clinical stage of pancreatic cancer (p < 0.003).A multiplex panel assaying CA19-9, OPN and CHI3L1 in plasma improves accuracy of pancreatic cancer diagnosis. A panel assaying CEA and CA125 in plasma can predict survival for this clinical cohort of pancreatic cancer patients.

View details for DOI 10.1186/1479-5876-7-105

View details for Web of Science ID 000272889900001

View details for PubMedID 20003342

Pharmacologically Increased Tumor Hypoxia Can Be Measured by F-18-Fluoroazomycin Arabinoside Positron Emission Tomography and Enhances Tumor Response to Hypoxic Cytotoxin PR-104 CLINICAL CANCER RESEARCH Cairns, R. A., Bennewith, K. L., Graves, E. E., Giaccia, A. J., Chang, D. T., Denko, N. C. 2009; 15 (23): 7170-7174

Abstract

Solid tumors contain microenvironmental regions of hypoxia that present a barrier to traditional radiotherapy and chemotherapy, and this work describes a novel approach to circumvent hypoxia. We propose to overcome hypoxia by augmenting the effectiveness of drugs that are designed to specifically kill hypoxic tumor cells.We have constructed RKO colorectal tumor cells that express a small RNA hairpin that specifically knocks down the hypoxia-inducible factor 1a (HIF1a) transcription factor. We have used these cells in vitro to determine the effect of HIF1 on cellular sensitivity to the hypoxic cytotoxin PR-104, and its role in cellular oxygen consumption in response to the pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA). We have further used these cells in vivo in xenografted tumors to determine the role of HIF1 in regulating tumor hypoxia in response to DCA using (18)F-fluoroazomycin arabinoside positron emission tomography, and its role in regulating tumor sensitivity to the combination of DCA and PR-104.HIF1 does not affect cellular sensitivity to PR-104 in vitro. DCA transiently increases cellular oxygen consumption in vitro and increases the extent of tumor hypoxia in vivo as measured with (18)F-fluoroazomycin arabinoside positron emission tomography. Furthermore, we show that DCA-dependent alterations in hypoxia increase the antitumor activity of the next-generation hypoxic cytotoxin PR-104.DCA interferes with the HIF-dependent "adaptive response," which limits mitochondrial oxygen consumption. This approach transiently increases tumor hypoxia and represents an important method to improve antitumor efficacy of hypoxia-targeted agents, without increasing toxicity to oxygenated normal tissue.

View details for DOI 10.1158/1078-0432.CCR-09-1676

View details for Web of Science ID 000272363700011

View details for PubMedID 19920111

Treatment of Esophageal Cancer Based on Histology A Surveillance Epidemiology and End Results Analysis AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Chang, D. T., Chapman, C., Shen, J., Su, Z., Koong, A. C. 2009; 32 (4): 405-410

Abstract

The majority of esophageal cancer is either adenocarcinoma (ACA) or squamous cell carcinoma (SCCA). Recent randomized trials suggest that definitive chemoradiotherapy may be equally effective as surgery. However, the responsiveness of ACA versus SCCA to radiotherapy (RT) has never been compared. This Surveillance Epidemiology and End Results registry analysis investigates whether survival differed between ACA and SCCA based on the treatment modality.Patients with T2-4N0 or N+ SCCA and ACA in the cervical or thoracic esophagus diagnosed from 1983 to 2004 were obtained from the Surveillance Epidemiology and End Results database. Patients with multiple primary cancers, underwent a surgical procedure other than partial or total esophagectomy, had metastatic or T1N0 disease, or received RT that did not include external beam radiation were excluded. Patients were grouped according to treatment received: RT alone, preoperative RT, any surgery (regardless of use of RT), and surgery alone.A total of 4752 patients were included, 2680 (56%) had ACA and 2072 (44%) had SCCA. After adjusting for age, marital status, cost of living, and race, the overall survival (OS) and cause-specific survival was similar for all treatment groups except the RT-alone group where OS and SCC were superior for ACA. However, no difference in 3- and 5-year OS and cause-specific survival rates for all groups.No difference in survival was seen between patients with ACA and SCCA across any of the major treatment modalities for esophageal cancer, suggesting that both histologies respond to treatment similarly.

View details for DOI 10.1097/COC.0b013e3181917158

View details for Web of Science ID 000268761600014

View details for PubMedID 19415029

Pancreatic Tumor Motion on a Single Planning 4D-CT Does Not Correlate With Intrafraction Tumor Motion During Treatment AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Minn, A. Y., Schellenberg, D., Maxim, P., Suh, Y., McKenna, S., Cox, B., Dieterich, S., Xing, L., Graves, E., Goodman, K. A., Chang, D., Koong, A. C. 2009; 32 (4): 364-368

Abstract

To quantify pancreas tumor motion on both a planning 4D-CT and during a single fraction treatment using the CyberKnife linear accelerator and Synchrony respiratory tracking software, and to investigate whether a single 4D-CT study is reliable for determining radiation treatment margins for patients with locally advanced pancreas cancer.Twenty patients underwent fiducial placement, biphasic pancreatic protocol CT scan and 4D-CT scan in the treatment position while free-breathing. Patients were then treated with a single 25 Gy fraction of stereotactic body radiotherapy. Predicted pancreas motion in the superior-inferior (SI), left-right (LR), and anterior-posterior (AP) directions was calculated from the maximum inspiration and maximum expiration 4D-CT scan. For CyberKnife treatments, mean respiratory cycle motion and maximum respiratory cycle motion was determined in the SI, LR, and AP directions.The range of centroid movement based on 4D-CT in the SI, LR, and AP directions were 0.9 to 28.8 mm, 0.1 to 13.7 mm, and 0.2 to 7.6 mm, respectively. During CyberKnife treatment, in the SI direction, the mean motion of the centroid ranged from 0.5 to 12.7 mm. In the LR direction, the mean motion range was 0.4 to 9.4 mm. In the AP direction, the mean motion range was 0.6 to 5.5 mm. The maximum range of movement (mean) during CyberKnife treatment in the SI, LR, and AP directions were 4.5 to 48.8 mm (mean 20.8 mm), 1.5 to 41.3 mm (mean 11.3 mm), and 1.6 to 68.1 mm (mean 13.4 mm), respectively. Neither the maximum or mean motion correlated with the 4D-CT movement.There is substantial respiratory associated motion of pancreatic tumors. The 4D-CT planning scans cannot accurately predict the movement of pancreatic tumors during actual treatment on CyberKnife.

View details for DOI 10.1097/COC.0b013e31818da9e0

View details for Web of Science ID 000268761600007

View details for PubMedID 19398901

Long-term Outcomes for Stage I-II Aggressive Non-Hodgkin Lymphoma of Waldeyer's Ring AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Chang, D. T., Mendenhall, N. P., Lynch, J. W., Morris, C. G., Olivier, K. R. 2009; 32 (3): 233-237

Abstract

To determine the long-term outcome of patients treated at the University of Florida for aggressive non-Hodgkin lymphoma (NHL) of Waldeyer's ring.Forty-six patients treated with radiotherapy (RT) at the University of Florida from 1964 to 2006 for biopsy-proven aggressive NHL of Waldeyer's ring were included in this study. Of this group, 20 patients were treated with RT alone and 26 with combined-modality therapy (CMT) with the addition of chemotherapy: 24 patients with induction and 2 with concurrent or adjuvant chemotherapy.The 5-year and 10-year in-field control rates were 95% and 85%, respectively, and the out-of-field control rates were 67% and 63%, respectively. The 10-year disease-free survival (DFS), cause-specific survival, and overall survival (OS) rates were 47%, 50%, and 37%, respectively. The CMT group had superior 10-year DFS compared with the RT-alone group (57% vs. 37%), but this difference was not statistically significant. No difference in 10-year OS was seen between the CMT group and the RT-alone group.Similar to other sites, out-of-field recurrences are the primary pattern of failure for NHL of Waldeyer's ring. DFS was superior with CMT compared with RT alone and remains the standard of care.

View details for DOI 10.1097/COC.0b013e318187ddbb

View details for Web of Science ID 000266733600002

View details for PubMedID 19433961

Percutaneous Implantation of Fiducial Markers for Imaging-Guided Radiation Therapy AMERICAN JOURNAL OF ROENTGENOLOGY Kothary, N., Dieterich, S., Louie, J. D., Chang, D. T., Hofmann, L. V., Sze, D. Y. 2009; 192 (4): 1090-1096

Abstract

The use of imaging-guided radiation therapy (IGRT) to treat thoracic and abdominal tumors is increasing. In this article, we review the process of IGRT and describe techniques to implant fiducial markers in the optimal geometry.Implantation of fiducial markers can be challenging. A better understanding of the physics of IGRT can help optimize fiducial marker placement for precise tumor targeting.

View details for DOI 10.2214/AJR.08.1399

View details for Web of Science ID 000264358900038

View details for PubMedID 19304719

Xerostomia in Long-term Survivors of Aggressive Non-Hodgkin's Lymphoma of Waldeyer's Ring A Potential Role for Parotid-Sparing Techniques? AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Chang, D. T., Amdur, R. J., Pacholke, H., Mendenhall, N. P., Morris, C. G., Byer, G. A., Olivier, K. R. 2009; 32 (2): 145-149

Abstract

The degree of xerostomia in patients treated for intermediate-and high-grade non-Hodgkin lymphoma (NHL) of Waldeyer's ring (WR) is unknown.Fifteen patients treated for stage I-IV NHL of WR with radiotherapy (RT) were administered a xerostomia questionnaire. Numerical responses (0 = no xerostomia; 100 = maximum xerostomia) were compared with responses from 5 sets of patients treated for head and neck squamous cell carcinoma who were grouped by amount of parotid in RT field: larynx-only, ipsilateral parotid, bilateral-partial parotid, bilateral-total parotid, parotid-sparing intensity-modulated radiotherapy.Waldeyer's patients' median xerostomia questionnaire score was 31, which was significantly different from the larynx-only group, bilateral-partial parotid group, and bilateral-total parotid group, but not significantly different from the ipsilateral parotid group or parotid-sparing intensity-modulated radiotherapy group.Xerostomia in survivors WR NHL is a detectable toxicity with severity like that in head and neck squamous cell carcinoma patients who receive ipsilateral parotid irradiation, and warrants parotid-sparing RT techniques.

View details for DOI 10.1097/COC.0b013e3181841f42

View details for Web of Science ID 000265056900007

View details for PubMedID 19307951

Safety and Efficacy of Percutaneous Fiducial Marker Implantation for Image-guided Radiation Therapy JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Kothary, N., Heit, J. J., Louie, J. D., Kuo, W. T., Loo, B. W., Koong, A., Chang, D. T., Hovsepian, D., Sze, D. Y., Hofmann, L. V. 2009; 20 (2): 235-239

Abstract

To evaluate the safety and technical success rate of percutaneous fiducial marker implantation in preparation for image-guided radiation therapy.From January 2003 to January 2008, we retrospectively reviewed 139 percutaneous fiducial marker implantations in 132 patients. Of the 139 implantations, 44 were in the lung, 61 were in the pancreas, and 34 were in the liver. Procedure-related major and minor complications were documented. Technical success was defined as implantation enabling adequate treatment planning and computed tomographic simulation.The major and minor complication rates were 5% and 17.3%, respectively. Pneumothorax after lung implantation was the most common complication. Pneumothoraces were seen in 20 of the 44 lung implantations (45%); a chest tube was required in only seven of the 44 lung transplantations (16%). Of the 139 implantations, 133 were successful; in six implantations (4.3%) the fiducial markers migrated and required additional procedures or alternate methods of implantation.Percutaneous implantation of fiducial marker is a safe and effective procedure with risks that are similar to those of conventional percutaneous organ biopsy.

View details for DOI 10.1016/j.jvir.2008.09.026

View details for Web of Science ID 000263075000012

View details for PubMedID 19019700

Stereotactic Radiotherapy for Unresectable Adenocarcinoma of the Pancreas CANCER Chang, D. T., Schellenberg, D., Shen, J., Kim, J., Goodman, K. A., Fisher, G. A., Ford, J. M., Desser, T., Quon, A., Koong, A. C. 2009; 115 (3): 665-672

Abstract

The authors report on the local control and toxicity of stereotactic body radiotherapy (SBRT) for patients with unresectable pancreatic adenocarcinoma.Seventy-seven patients with unresectable adenocarcinoma of the pancreas received 25 gray (Gy) in 1 fraction. Forty-five patients (58%) had locally advanced disease, 11 patients (14%) had medically inoperable disease, 15 patients (19%) had metastatic disease, and 6 patients (8%) had locally recurrent disease. Nine patients (12%) had received prior chemoradiotherapy. Sixteen patients (21%) received between 45 to 54 Gy of fractionated radiotherapy and SBRT. Various gemcitabine-based chemotherapy regimens were received by 74 patients (96%), but 3 patients (4%) did not receive chemotherapy until they had distant failure.The median follow-up was 6 months (range, 3-31 months) and, among surviving patients, it was 12 months (range, 3-31 months). The overall rates of freedom from local progression (FFLP) at 6 months and 12 months were 91% and 84%, respectively. The 6- and 12-month isolated local recurrence rates were 5% and 5%, respectively. There was no difference in the 12-month FFLP rate based on tumor location (head/uncinate, 91% vs body/tail, 86%; P = .52). The progression-free survival (PFS) rates at 6 months and 12 months were 26% and 9%, respectively. The PFS rate at 6 months was superior for patients who had nonmetastatic disease versus patients who had metastatic disease (28% vs 15%; P = .05). The overall survival (OS) rates at 6 months and 12 months from SBRT were 56% and 21%, respectively. Four patients (5%) experienced grade > or = 2 acute toxicity. Three patients (4%) experienced grade 2 late toxicity, and 7 patients (9%) experienced grade > or = 3 late toxicity. At 6 months and 12 months, the rates of grade > or = 2 late toxicity were 11% and 25%, respectively.SBRT for pancreatic adenocarcinoma was effective for local control with associated risk of toxicity and should be used with rigorous attention to quality assurance. Efforts to reduce complications are warranted. Distant metastases account for the vast majority of disease-related mortality.

View details for DOI 10.1002/cncr.24059

View details for Web of Science ID 000263003400025

View details for PubMedID 19117351

A Prospective Randomized Pilot Study of Site-specific Atlas Incorporation into Target Volume Delineation Instructions in the Cooperative Group Setting: Preliminary Results from a Southwest Oncology Group Pilot using Big Brother Fuller, C. D., Duppen, J., Rasch, C. R., Kachnic, L., Wang, S. J., Chang, D., Goodman, K. A., Katz, A. W., OKUNIEFF, P., Thomas, C. R. ELSEVIER SCIENCE INC. 2009: S136-S137
Stereotactic body radiotherapy for unresectable adenocarcinoma of the pancreas Chang, D. T., Schellenberg, D., Shen, J., Kim, J., Goodman, K., Fisher, G., Ford, J., Desser, T., Quon, A., Koong, A. ELSEVIER SCIENCE INC. 2008: S249-S249
Do pre-irradiation dental extractions reduce the risk of osteoradionecrosis of the mandible? HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Chang, D. T., Sandow, P. R., Morris, C. G., Hollander, R., Scarborough, L., Amdur, R. J., Mendenhall, W. M. 2007; 29 (6): 528-536

Abstract

This study was done to determine if pre-radiotherapy (pre-RT) dental extractions reduce the risk of osteoradionecrosis (ORN).Between 1987 and 2004, 413 patients with oropharyngeal carcinomas were treated with definitive RT at the University of Florida. Dentate patients underwent pretreatment dental evaluation. Teeth in the RT field were usually extracted if thought to have poor long-term prognosis from dental disease. The endpoint was > or = grade 2 ORN using a modified staging system. Patients were excluded for local recurrence, additional RT above the clavicles, or head and neck surgery besides neck dissection.ORN rates were as follows: edentulous, <1%; teeth in-field with pre-RT extractions, 15%; and teeth in-field without pre-RT extractions, 9%. Patients with poor in-field teeth and pre-RT extractions had a higher 5-year incidence of ORN than those who did not have pre-RT extractions (16% vs 6%, p = .48). Likewise, for those with in-field teeth in good condition and pre-RT extractions, the 5-year ORN incidence was higher than for those who did not undergo extractions (15% vs 2%, p = .42). Multivariate analysis revealed increased ORN risk with doses of >70 Gy, once-daily fractionation, or brachytherapy.Pre-RT extractions do not appear to reduce the risk of ORN.

View details for DOI 10.1002/hed.20538

View details for Web of Science ID 000246958600002

View details for PubMedID 17230555

Long-term outcomes in breast cancer patients with ten or more positive axillary nodes treated with combined-modality therapy: The importance of radiation field selection INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chang, D. T., Feigenberg, S. J., Indelicato, D. J., Morris, C. G., Lightsey, J., Grobmyer, S. R., Copeland, E. M., Mendenhall, N. P. 2007; 67 (4): 1043-1051

Abstract

To determine the long-term outcome of a consistent treatment approach with electron beam postmastectomy radiation therapy (PMRT) in breast cancer patients with > or =10 positive nodes treated with combined-modality therapy.TSixty-three breast cancer patients with > or =10 positive lymph nodes were treated with combined-modality therapy using an electron beam en face technique for PMRT at the University of Florida. Patterns of recurrence were studied for correlation with radiation fields. Potential clinical and treatment variables were tested for possible association with local-regional control (LRC), disease-free survival (DFS), and overall survival (OS).TAt 5, 10, and 15 years, OS rates were 57%, 36%, and 27%, respectively; DFS rates were 46%, 37%, and 34%; and LRC rates were 87%, 87%, and 87%. No clinical or treatment variables were associated with OS or DFS. The use of supplemental axillary radiation (SART) (p = 0.012) and pathologic N stage (p = 0.053) were associated with improved LRC. Patients who received SART had a higher rate of LRC than those who did not. Moderate to severe arm edema developed in 17% of patients receiving SART compared with 7% in patients not treated with SART (p = 0.28).TA substantial percentage of patients with > or =10 positive lymph nodes survive breast cancer. The 10-year overall survival in these patients was 36%. The addition of SART was associated with better LRC.

View details for DOI 10.1016/j.ijrobp.2006.10.049

View details for Web of Science ID 000245021100012

View details for PubMedID 17336214

Predicting changes in dose distribution to tumor and normal tissue when correcting for heterogeneity in radiotherapy for lung cancer AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Chang, D., Liu, C., Dempsey, J. F., Palta, J. R., Kopea, J., Louis, D., Morris, C., Chopra, R., Olivier, K. R. 2007; 30 (1): 57-62

Abstract

The purposes of this study were to examine dose alterations to gross tumor volume (GTV) and lung using heterogeneity corrections and to predict the magnitude of these changes.Three separate conformal plans were generated for 37 patients with lung cancer: plan 1 corrected for heterogeneity, plan 2 did not correct for heterogeneity, and plan 3 used identical beams and monitor units from plan 2 but with heterogeneous calculations. Plans 1 and 2 were normalized to the 95% isodose line. Mean dose (MeanDGTV), maximum dose (MaxDGTV), and minimum dose (MinDGTV) to GTV and V20 were compared between plans 1 and 3. For each patient, the amount of lung in all beam paths of plan 3 was quantified by a density correction factor and correlated with the percent change.The median percent change in MeanDGTV, MaxDGTV, and MinDGTV between plan 3 and plan 1 was -4.7% (-0.1% to -19.1%, P < 0.0001), -5.59% (0.16% to -31.86%, P < 0.0001), and -4.88% (2.90% to -24.88%, P < 0.0001), respectively. The median V20 difference was -1% (1% to -8%). The density correction factor correlated with larger differences in MeanDGTV on univariate analysis.Heterogeneity correction lowers the dose to GTV by 5%. This difference can be correlated with the density correction factor.

View details for DOI 10.1097/01.coc.0000251222.36417.3b

View details for Web of Science ID 000244196300011

View details for PubMedID 17278896

Adjuvant radiotherapy for cutaneous melanoma: Comparing hypofractionation to conventional fractionation INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chang, D. T., Amdur, R. J., Morris, C. G., Mendenhall, W. M. 2006; 66 (4): 1051-1055

Abstract

To examine locoregional control after adjuvant radiotherapy (RT) for cutaneous melanoma and compare outcomes between conventional fractionation and hypofractionation.Between January 1980 and June 2004, 56 patients with high-risk disease were treated with adjuvant RT. Indications for RT included: recurrent disease, cervical lymph node involvement, lymph nodes >3 cm, more than three lymph nodes involved, extracapsular extension, gross residual disease, close or positive margins, or satellitosis. Hypofractionation was used in 41 patients (73%) and conventional fractionation was used in 15 patients (27%).The median age was 61 years (21->90). The median follow-up among living patients was 4.4 years (range, 0.6-14.4 years). The primary site was located in the head and neck in 49 patients (87%) and below the clavicles in 7 patients (13%). There were 7 in-field locoregional failures (12%), 3 out-of-field regional failures (5%), and 24 (43%) distant failures. The 5-year in-field locoregional control (ifLRC) and freedom from distant metastases (FFDM) rates were 87% and 43%, respectively. The 5-year cause-specific (CSS) and overall survival (OS) was 57% and 46%, respectively. The only factor associated with ifLRC was satellitosis (p = 0.0002). Nodal involvement was the only factor associated with FFDM (p = 0.0007), CSS (p = 0.0065), and OS (p = 0.016). Two patients (4%) who experienced severe late complications, osteoradionecrosis of the temporal bone and radiation plexopathy, and both received hypofractionation (5%).Although surgery and adjuvant RT provides excellent locoregional control, distant metastases remain the major cause of mortality. Hypofractionation and conventional fractionation are equally efficacious.

View details for DOI 10.1016/j.ijrobp.2006.05.056

View details for Web of Science ID 000241598600013

View details for PubMedID 16973303

The impact of heterogeneity correction on dosimetric parameters that predict for radiation pneumonitis INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chang, D. T., Olivier, K. R., Morris, C. G., Liu, C., Dempsey, J. F., Benda, R. K., Palta, J. R. 2006; 65 (1): 125-131

Abstract

To determine if heterogeneity correction significantly affects commonly measured dosimetric parameters predicting pulmonary toxicity in patients receiving radiation for lung cancer.Sixty-eight patients treated for lung cancer were evaluated. The conformal treatment technique mostly employed anteroposterior/posterior-anterior fields and off-cord obliques. The percent total lung volume receiving 20 Gy or higher (V20) and mean lung dose (MLD) were correlated with the incidence of radiation pneumonitis. Parameters from both heterogeneity-corrected and heterogeneity-uncorrected plans were used to assess this risk.Univariate analysis revealed a significant correlation between the development of radiation pneumonitis and both V20 and MLD. A best-fit line to a plot of V20 from the homogeneous plan against the corresponding V20 heterogeneous value produced a slope of 1.00 and zero offset, indicating no difference between the two parameters. For MLD, a similarly significant correlation is seen between the heterogeneous and homogeneous parameters, indicating a 4% difference when correcting for heterogeneity. A significant correlation was also observed between the MLD and V20 parameters (p < 0.0001).A high degree of correlation exists between heterogeneity-corrected and heterogeneity-uncorrected dosimetric parameters for lung and the risk of developing pneumonitis. Either V20 or MLD predicts the pneumonitis risk with similar effect.

View details for DOI 10.1016/j.ijrobp.2005.09.047

View details for Web of Science ID 000238162600018

View details for PubMedID 16427214

Re-examining the role of elective nodal irradiation - Finding ways to maximize the therapeutic ratio AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Chang, D. T., Zlotecki, R. A., Olivier, K. R. 2005; 28 (6): 597-602

Abstract

Elective nodal irradiation (ENI) of regional lymphatics has been a foundational paradigm for radiation oncologists in the treatment of nonsmall-cell lung cancer (NSCLC), but its utility has recently been called into question. This review summarizes the controversies surrounding ENI and reviews the therapeutic options available to treat regional lymphatics in NSCLC.Local failure after conventional radiotherapy (RT) occurs in 40% to 80% of patients fueling the investigation of more aggressive RT regimens. As the dose is increased and accelerated the volume of normal lung tissue treated becomes a limiting factor. Thus elimination of ENI followed by further dose escalation has become a commonly pursued solution. When ENI is excluded, treatment is restricted to clinically positive disease and negative lymph node stations are left untreated.Radiographic and surgical data suggest our ability to determine the true extent of disease is imperfect and therefore the elimination of ENI likely leaves microscopic NSCLC untreated.At our institution we have concluded that the prophylactic treatment of regional lymph nodes is best reserved for patients most likely to achieve local control and are designing treatment protocols including chemotherapy to take advantage of this improvement in local control.

View details for DOI 10.1097/01.coc.0000187927.06051.ec

View details for Web of Science ID 000233811900012

View details for PubMedID 16317271

Merkel cell carcinoma of the skin with leptomeningeal metastases AMERICAN JOURNAL OF OTOLARYNGOLOGY Chang, D. T., Mancuso, A. A., Riggs, C. E., Mendenhall, W. M. 2005; 26 (3): 210-213

Abstract

Merkel cell carcinoma is a rare skin tumor that is thought to arise from epithelial cells that have undergone neuroendocrine differentiation. It usually presents in older adults and has a slight male predominance. The most frequent site of occurrence is in the head and neck. It is an aggressive disease that has a high rate of local-regional and distant recurrence. Optimal treatment is controversial but generally consists of surgery and adjuvant radiotherapy. The role of chemotherapy is less defined. This report documents the first known case of Merkel cell carcinoma with perineural spread to the central nervous system with leptomeningeal dissemination. Whether this represents a more aggressive variant is unknown. Regardless, this pattern of spread is likely a rare event.

View details for DOI 10.1016/j.amjoto.2004.11.013

View details for Web of Science ID 000229206000013

View details for PubMedID 15858780

Role of p53 in cell cycle regulation and apoptosis following exposure to proteasome inhibitors CELL GROWTH & DIFFERENTIATION Chen, F., Chang, D., Goh, M., Klibanov, S. A., Ljungman, M. 2000; 11 (5): 239-246

Abstract

In this study, we explored what effect inhibitors of the 26S proteasome have on cell cycle distribution and induction of apoptosis in human skin fibroblasts and colon cancer cells differing in their p53 status. We found that proteasome inhibition resulted in nuclear accumulation of p53. This was surprising because it is thought that the degradation of p53 is mediated by cytoplasmic 26S proteasomes. Nuclear accumulation of p53 was accompanied by the induction of both p21WAF1 mRNA and protein as well as a decrease in cells entering S phase. Interestingly, cells with compromised p53 function showed a marked increase in the proportion of cells in the G2-M phase of the cell cycle and an attenuated induction of apoptosis after proteasome inhibition. Taken together, our results suggest that proteasome inhibition results in nuclear accumulation of p53 and a p53-stimulated induction of both G1 arrest and apoptosis.

View details for Web of Science ID 000087482700002

View details for PubMedID 10845424

Dose-dependent effects of DNA-damaging agents on p53-mediated cell cycle arrest CELL GROWTH & DIFFERENTIATION Chang, D., Chen, F., Zhang, F. F., McKay, B. C., Ljungman, M. 1999; 10 (3): 155-162

Abstract

We examined the dose-dependent effects of DNA-damaging agents on G1 arrest in isogenic human cell lines differing in their p53 status. As expected, 5 or 20 Gy of ionizing radiation induced a p53-dependent G1 arrest. In contrast, UV light or actinomycin D induced a modest G1 arrest that was p53-dependent only at lower doses. At higher doses, cells were arrested in G1 in a p53-independent manner coinciding with inhibition of RNA synthesis and abolished cyclin E expression. Interestingly, expression of cyclin E was enhanced after exposure to moderate doses of UV light and actinomycin D, and this enhancement was suppressed by wild-type p53. We propose that agents inducing transcription-blocking DNA lesions will at higher doses inhibit the progression of cells into S phase by a p53-independent mechanism involving the attenuation of E2F-mediated transcription of genes, such as cyclin E.

View details for Web of Science ID 000079180000003

View details for PubMedID 10099829

Stereotactic radiosurgery for intramedullary spinal arteriovenous malformations JOURNAL OF CLINICAL NEUROSCIENCE Kalani, M. A., Choudhri, O., Gibbs, I. C., Soltys, S. G., Adler, J. R., Thompson, P. A., Tayag, A. T., Samos, C. H., Chang, S. D. 2016; 29: 162-167

Abstract

Spinal cord arteriovenous malformations (AVM) are rare lesions associated with recurrent hemorrhage and progressive ischemia. Occasionally a favorable location, size or vascular anatomy may allow management with endovascular embolization and/or microsurgical resection. For most, however, there is no good treatment option. Between 1997 and 2014, we treated 37 patients (19 females, 18 males, median age 30years) at our institution diagnosed with intramedullary spinal cord AVM (19 cervical, 12 thoracic, and six conus medullaris) with CyberKnife (Accuray, Sunnyvale, CA, USA) stereotactic radiosurgery. A history of hemorrhage was present in 50% of patients. The mean AVM volume of 2.3cc was treated with a mean marginal dose of 20.5Gy in a median of two sessions. Clinical and MRI follow-up were carried out annually, and spinal angiography was repeated at 3years. We report an overall obliteration rate of 19% without any post-treatment hemorrhagic events. In those AVM that did not undergo obliteration, significant volume reduction was noted at 3years. Although the treatment paradigm for spinal cord AVM continues to evolve, radiosurgical treatment is capable of safely obliterating or significantly shrinking most intramedullary spinal cord AVM.

View details for DOI 10.1016/j.jocn.2015.12.005

View details for Web of Science ID 000378449800032

View details for PubMedID 26869363

Multiple Subsets of Brain Tumor Initiating Cells Coexist in Glioblastoma STEM CELLS Rennert, R. C., Achrol, A. S., Januszyk, M., Kahn, S. A., Liu, T. T., Liu, Y., Sahoo, D., Rodrigues, M., Maan, Z. N., Wong, V. W., Cheshier, S. H., Chang, S. D., Steinberg, G. K., Harsh, G. R., Gurtner, G. C. 2016; 34 (6): 1702-1707

Abstract

Brain tumor-initiating cells (BTICs) are self-renewing multipotent cells critical for tumor maintenance and growth. Using single-cell microfluidic profiling, we identified multiple subpopulations of BTICs co-existing in human glioblastoma, characterized by distinct surface marker expression and single-cell molecular profiles relating to distinct bulk tissue molecular subtypes. These data suggest BTIC subpopulation heterogeneity as an underlying source of intra-tumoral bulk tissue molecular heterogeneity, and will support future studies into BTIC subpopulation-specific therapies. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/stem.2359

View details for Web of Science ID 000378089500025

View details for PubMedID 26991945

Computational Identification of Tumor Anatomic Location Associated with Survival in 2 Large Cohorts of Human Primary Glioblastomas AMERICAN JOURNAL OF NEURORADIOLOGY Liu, T. T., Achrol, A. S., MITCHELL, L. A., Du, W. A., Loya, J. J., Rodriguez, S. A., Feroze, A., Westbroek, E. M., Yeom, K. W., Stuart, J. M., Chang, S. D., Harsh, G. R., Rubin, D. L. 2016; 37 (4): 621-628

Abstract

Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma. The purpose of this study was to characterize glioblastoma lesions by identifying MR imaging voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics, and clinical outcomes.Preoperative T1 anatomic MR images of 384 patients with glioblastomas were obtained from 2 independent cohorts (n = 253 from the Stanford University Medical Center for training and n = 131 from The Cancer Genome Atlas for validation). An automated computational image-analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival of >17 months) and poor (overall survival of <11 months) survival groups identified in the training cohort were used to classify patients in The Cancer Genome Atlas cohort into 2 brain-location groups, for which clinical features, messenger RNA expression, and copy number changes were compared to elucidate the biologic basis of tumors located in different brain regions.Tumors in the right occipitotemporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both, log-rank P < .05) and had larger tumor volume compared with tumors in other locations. Tumors in the right periatrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies.Voxel-based location in glioblastoma is associated with patient outcome and may have a potential role for guiding personalized treatment.

View details for DOI 10.3174/ajnr.A4631

View details for Web of Science ID 000373346900014

Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery SEMINARS IN RADIATION ONCOLOGY Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97-104

Abstract

Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using / = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

View details for DOI 10.1016/j.semradonc.2015.11.008

View details for Web of Science ID 000373242700003

View details for PubMedID 27000505

CyberKnife radiosurgery for brainstem metastases: Management and outcomes and a review of the literature JOURNAL OF CLINICAL NEUROSCIENCE Liu, S., Murovic, J., Wallach, J., Cui, G., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2016; 25: 105-110

Abstract

To our knowledge this paper is the first to use recursive partitioning analysis (RPA) for brainstem metastasis (BSM) patient outcomes, after CyberKnife radiosurgery (CKRS; Accuray, Sunnyvale, CA, USA); nine similar previous publications used mainly Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden). Retrospective chart reviews from 2006-2013 of 949 CKRS-treated brain metastasis patients showed 54BSM patients (5.7%): 35 RPA Class II (65%) and 19 Class III (35%). There were 30 women (56%) and 24 men (44%). The median age was 59years (range 36-80) and median follow-up was 5months (range 1-52). Twenty-three patients (43%) had lung carcinoma BSM and 12 (22%) had breast cancer BSM. Fifty-four RPA Class II and III BSM patients had a median overall survival (OS) of 5months, and for each Class 8 and 2months, respectively. Of 36 RPA Class II and III patients with available symptoms (n=31) and findings (n=33), improvement/stability occurred in the majority for symptoms (86%) and findings (92%). Of 35 cases, 28 (80%) achieved BSM local control (LC); 13/14 with breast histology (93%) and 10/13 with lung histology (77%). All six RPA Class II and III patients with controlled extracranial systemic disease (ESD) experienced LC. Median tumor volume was 0.14cm(3); of 34 RPA Class II and III cases, 26 LC patients had a 0,13cm(3) median tumor volume while it was 0.27cm(3) in the eight local failures. Of 35 cases, single session equivalent dosages less than the median (n=13), at the 17.9Gy median (n=5) and greater than the median (n=17) had BSM LC in 10 (77%), four (80%) and 14 cases (82%), respectively. Univariate analysis showed Karnofsky Performance Score, RPA Class and ESD-control predicted OS. CKRS is useful for RPA Class II and III BSM patients with effective clinical and local BSM control.

View details for DOI 10.1016/j.jocn.2015.10.013

View details for Web of Science ID 000370304500020

View details for PubMedID 26778047

Stereotactic radiosurgery for metastasis to the craniovertebral junction preserves spine stability and offers symptomatic relief JOURNAL OF NEUROSURGERY-SPINE Azad, T. D., Esparza, R., Chaudhary, N., Chang, S. D. 2016; 24 (2): 241-247
Supracerebellar infratentorial sitting craniotomy for a pinealoblastoma NEUROSURGICAL FOCUS Choudhri, O., Chang, S. D. 2016; 40
Subfrontal trans-lamina terminalis approach to a third ventricular craniopharyngioma NEUROSURGICAL FOCUS Choudhri, O., Chang, S. D. 2016; 40
Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities SCIENCE TRANSLATIONAL MEDICINE Itakura, H., Achrol, A. S., Mitchell, L. A., Loya, J. J., Liu, T., Westbroek, E. M., Feroze, A. H., Rodriguez, S., Echegaray, S., Azad, T. D., Yeom, K. W., Napel, S., Rubin, D. L., Chang, S. D., Harsh, G. R., Gevaert, O. 2015; 7 (303)
Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Shultz, D. B., Modlin, L. A., Jayachandran, P., von Eyben, R., Gibbs, I. C., Choi, C. Y., Chang, S. D., Harsh, G. R., Li, G., Adler, J. R., Hancock, S. L., Soltys, S. G. 2015; 92 (5): 993-999

Abstract

Toreport the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS).We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS.Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15months (range, 3-98months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites.Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

View details for DOI 10.1016/j.ijrobp.2015.04.036

View details for Web of Science ID 000357900600018

View details for PubMedID 26194677

Persistent trigeminal artery supply to an intrinsic trigeminal nerve arteriovenous malformation: A rare cause of trigeminal neuralgia JOURNAL OF CLINICAL NEUROSCIENCE Choudhri, O., Heit, J. J., Feroze, A. H., Chang, S. D., Dodd, R. L., Steinberg, G. K. 2015; 22 (2): 409-412

Abstract

Infratentorial arteriovenous malformations (AVM) associated with the trigeminal nerve root entry zone are a known cause of secondary trigeminal neuralgia (TN). The treatment of both TN and AVM can be challenging, especially if the AVM is embedded within the trigeminal nerve. A persistent trigeminal artery (PTA) can rarely supply these intrinsic trigeminal nerve AVM. We present a 64-year-old man with TN from a right trigeminal nerve AVM supplied by a PTA variant. The patient underwent microvascular decompression and a partial resection of the AVM with relief of facial pain symptoms. His residual AVM was subsequently treated with CyberKnife radiosurgery (Accuray, Sunnyvale, CA, USA). A multimodality approach may be required for the treatment of trigeminal nerve associated PTA AVM and important anatomic patterns need to be recognized before any treatment. Herein, we report to our knowledge the third documented patient with a posterior fossa AVM supplied by a PTA and the first PTA AVM presenting as facial pain.

View details for DOI 10.1016/j.jocn.2014.06.007

View details for Web of Science ID 000349580500036

View details for PubMedID 25070632

The pathophysiology of cerebral radiation necrosis and the role of laser interstitial thermal therapy. World neurosurgery Murovic, J. A., Chang, S. D. 2015; 83 (1): 23-26

View details for DOI 10.1016/j.wneu.2014.03.015

View details for PubMedID 24631912

Experience with intraoperative navigation and imaging during endoscopic transnasal spinal approaches to the foramen magnum and odontoid. Neurosurgical focus Choudhri, O., Mindea, S. A., Feroze, A., Soudry, E., Chang, S. D., Nayak, J. V. 2014; 36 (3): E4-?

Abstract

Object In this study the authors share their experience using intraoperative spinal navigation and imaging for endoscopic transnasal approaches to the odontoid in 5 patients undergoing C1-2 surgery for basilar invagination at Stanford Hospital and Clinics from 2010 to 2013. Methods Of these 5 patients undergoing C1-2 surgery for basilar invagination, 4 underwent a 2-tiered anterior C1-2 resection with posterior occipitocervical fusion during a first stage surgery, followed by endoscopic endonasal odontoidectomy in a separate setting. Intraoperative stereotactic navigation was performed using a surgical navigation system in all cases. Navigation accuracy, characterized as target registration error, ranged between 0.8 mm and 2 mm, with an average of 1.2 mm. Intraoperative imaging using a CT scanner was also performed in 2 patients. Results Endoscopic decompression of the brainstem was achieved in all patients, and no intraoperative complications were encountered. All patients were extubated within 24 hours after surgery and were able to swallow within 48 hours. After appropriate initial reconstruction of the defect at the craniocervical junction, no postoperative CSF leakage, arterial injury, or need for reoperation was encountered; 1 patient developed mild postoperative velopharyngeal insufficiency that resolved by the 6-month follow-up evaluation. There were no deaths and no patients required tracheostomy placement. The average inpatient stay after surgery varied between 72 and 96 hours, without extended intensive care unit stays for any patient. Conclusions Technologies such as intraoperative CT scanning and merged MRI/CT can provide the surgeon with detailed, virtual real-time information about the extent of complex endoscopic vertebral segment resection and brainstem decompression and lessens the prospect of revision or secondary procedures in this challenging surgical corridor. Moreover, patients experience limited morbidity and can tolerate early oral intake after transnasal endoscopic odontoidectomy. Essential to the successful undertaking of these endoscopic adventures is 1) an understanding of the endoscopic nasal, skull base, and neurovascular anatomy; 2) advanced and extended-length instrumentation including navigation; and 3) a team approach between experienced rhinologists and spine surgeons comfortable with endoscopic skull base techniques.

View details for DOI 10.3171/2014.1.FOCUS13533

View details for PubMedID 24580005

Experience with intraoperative navigation and imaging during endoscopic transnasal spinal approaches to the foramen magnum and odontoid NEUROSURGICAL FOCUS Choudhri, O., Mindea, S. A., Feroze, A., Soudry, E., Chang, S. D., Nayak, J. V. 2014; 36 (3)
Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Atalar, B., Modlin, L. A., Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Nagpal, S., Hanlon, A., Soltys, S. G. 2013; 87 (4): 713-718

Abstract

We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients.We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other).With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004).In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

View details for DOI 10.1016/j.ijrobp.2013.07.034

View details for Web of Science ID 000325763300022

Multi-Session Radiosurgery of Benign Intracranial Tumors NEUROSURGERY CLINICS OF NORTH AMERICA Yeung, J. T., Karim, S. A., Chang, S. D. 2013; 24 (4): 543-?

Abstract

Multi-session stereotactic radiosurgery (SRS) enables a high dose per fraction to be delivered to the tumor bed with rapid dose falloff that allows for sparing of critical structures, resulting in less radiation-associated toxicity. In this article, the authors review the basic concepts and techniques of multi-session SRS, indications for this technique, outcomes from single-session and multi-session SRS using 3 commonly treated benign intracranial tumors (meningiomas, vestibular schwannomas, pituitary adenomas), and discuss why multi-session SRS is an attractive approach for the treatment of these tumors.

View details for DOI 10.1016/j.nec.2013.06.003

View details for Web of Science ID 000326659600007

View details for PubMedID 24093572

Cochlea Radiation Dose Correlates with Hearing Loss After Stereotactic Radiosurgery of Vestibular Schwannoma WORLD NEUROSURGERY Gephart, M. G., Hansasuta, A., Balise, R. R., Choi, C., Sakamoto, G. T., Venteicher, A. S., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Adler, J. R., Chang, S. D. 2013; 80 (3-4): 359-363

Abstract

OBJECTIVE: For multisession radiosurgery, no published data relate the volume and dose of cochlear irradiation to quantified risk of hearing loss. We conducted a retrospective, dosimetric study to evaluate the relationship between hearing loss after stereotactic radiosurgery (SRS) and the dose-volume of irradiated cochlea. METHODS: Cochlear dose data were retrospectively collected on consecutive patients who underwent SRS (18 Gy in 3 sessions) for vestibular schwanoma between 1999 and 2005 at Stanford University Hospital. Inclusion criteria included Gardner-Robertson (GR) grade I or II hearing prior to radiosurgical treatment, complete audiograms, and magnetic resonance imaging (MRI) follow-up. A cochlea dose-volume histogram was generated for each of the 94 patients who qualified for this study. RESULTS: GR grade I-II hearing posttreatment was maintained in 74% of patients (70/94). Median time to last follow-up audiogram was 2.4 years (range 0.4-8.9) and to last MRI was 3.6 years (range 0.5-9.4). Each higher level of cochlear irradiation was associated with increased risk of hearing loss. Larger cochlear volume was associated with lower risk of hearing loss. Controlling for differences in cochlear volume among subjects, each additional mm(3) of cochlea receiving 10 to 16 Gy (single session equivalent doses of 6.6-10.1 Gy3) significantly increased the odds of hearing loss by approximately 5%. CONCLUSIONS: Larger cochlear volume is associated with lower risk of hearing loss following trisession SRS for vestibular schwannoma. Controlling for this phenomenon, higher radiation dose and larger irradiated cochlear volume are significantly associated with higher risk of hearing loss. This study confirms and quantifies the risk of hearing loss following trisession SRS for vestibular schwannoma.

View details for DOI 10.1016/j.wneu.2012.04.001

View details for Web of Science ID 000326653900061

A critical analysis of the literature review in "Stereotactic radiosurgery for trigeminal pain secondary to benign skull base tumors" by Tanaka et al. and presentation of an algorithm for management of these tumors. World neurosurgery Murovic, J. A., Chang, S. D. 2013; 80 (3-4): 287-289

View details for DOI 10.1016/j.wneu.2012.04.027

View details for PubMedID 22548891

CyberKnife radiosurgery for the management of skull base and spinal chondrosarcomas JOURNAL OF NEURO-ONCOLOGY Jiang, B., Veeravagu, A., Feroze, A. H., Lee, M., Harsh, G. R., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2013; 114 (2): 209-218

Abstract

The use of CyberKnife (CK) stereotactic radiosurgery (SRS) for the management of central nervous system chondrosarcomas has not been previously reported. To evaluate outcomes of primary, recurrent, and metastatic chondrosarcomas of the skull base and spine treated with CK SRS, a retrospective observational study of 16 patients treated between 1996 and 2011 with CK SRS was performed using an IRB-approved database at Stanford University Medical Center. Twenty lesions (12 cranial, 8 spinal) across six males and ten females were analyzed. The median age at SRS was 51years and median follow-up was 33months. Median tumor volume was 11.0cm(3) and median marginal dosages were 22, 24, 26, 27, and 30Gy for one to five fractionations, respectively. Overall Kaplan-Meier survival rates were 88, 88, 80, and 66% at 1, 3, 5, and 10years after initial presentation. Survival rates at 1, 3, and 5years after CK were 81, 67, and 55%, respectively. Actuarial tumor control was 4113% at 60months. At 36months follow-up, tumor control was 80% in primary lesions, 50% in recurrent lesions, and 0.0% in metastatic disease (p=0.07). Tumor control was 58% in cranial lesions and 38% in spinal lesions. Radiation injury was reported in one patient. CK SRS appears to be a safe adjuvant therapy and offers moderate control for primary cranial chondrosarcoma lesions. There appears to be a clinically, albeit not statistically, significant trend towards poorer outcomes in similarly treated metastatic, recurrent, and spinal chondrosarcomas (p=0.07). Lesions not candidates for single fraction SRS may be treated with hypofractionated SRS without increased risk for radiation necrosis.

View details for DOI 10.1007/s11060-013-1172-9

View details for Web of Science ID 000323107500007

Volumetric Analysis of Intracranial Arteriovenous Malformations Contoured for CyberKnife Radiosurgery With 3-Dimensional Rotational Angiography vs Computed Tomography/Magnetic Resonance Imaging. Neurosurgery Veeravagu, A., Hansasuta, A., Jiang, B., Karim, A. S., Gibbs, I. C., Chang, S. D. 2013; 73 (2): 262-270

Abstract

BACKGROUND:: Accurate target delineation has significant impact on brain arteriovenous malformations (AVMs) obliteration, treatment success, and potential complications of stereotactic radiosurgery. OBJECTIVE:: We compare the nidal contouring of AVMs using fused images of contrasted computerized tomography (CT) and magnetic resonance (MRI) with matched images of three-dimensional (3-D) cerebral angiography for Cyberknife radiosurgery (CKRS) treatment planning. METHODS:: Between May 2009 and April 2012, 3-D cerebral angiography was integrated into CKRS target planning for thirty consecutive patients. The AVM nidal target volumes were delineated using fused CT and MRI scans versus fused CT, MRI, and 3-D cerebral angiography for each patient. RESULTS:: The mean volume of the AVM nidus contoured with the addition of 3-D cerebral angiography to the CT/MRI fusion (9.09 cm, 95% CI 5.39-12.8 cm) was statistically smaller than the mean volume contoured with CT/ MRI fused scans alone (14.1 cm, 95% CI 9.16-19.1 cm), with a mean volume difference of =5.01 cm (p=0.001). Diffuse AVM nidus was associated with larger mean volume differences in comparison to a compact nidus (=6.51 vs. 2.11 cm, p=0.02). The mean volume difference was not statistically associated with the patient's gender (male =5.61, female =5.06, p=0.84), prior hemorrhage status (yes =5.69, no =5.23, p=0.86), or prior embolization status (yes =6.80, no =5.95, p=0.11). CONCLUSION:: For brain AVMs treated with CKRS, the addition of 3-D cerebral angiography to CT/MRI fusions for diagnostic accuracy results in a statistically significant reduction in contoured nidal volume as compared to standard CT/MRI fusion-based contouring.

View details for DOI 10.1227/01.neu.0000430285.00928.30

View details for PubMedID 23615081

Pituitary stalk Langerhans cell histiocytosis treated with CyberKnife radiosurgery CLINICAL NEUROLOGY AND NEUROSURGERY Hong, W., Murovic, J. A., Gibbs, I., Vogel, H., Chang, S. D. 2013; 115 (5): 573-577

Abstract

Langerhans cell histiocytosis (LCH) is a rare idiopathic disease that is characterized by clonal proliferation of Langerhans histiocytes in various parts of the body. These atypical cells have been found to infiltrate single or multiple organs, including bone, lungs, liver, spleen, lymph nodes, and skin. Central nervous system invasion in LCH patients has rarely been reported, especially in the adult population.We describe three histopathologically confirmed cases of adult LCH that involves both the pituitary stalk and hypothalamus, and report our limited experience of such cases in this location that has been treated with CyberKnife radio surgery.The treatment goal of controlling lesion growth is achieved by CyberKnife radiosurgery in this case series. All patients tolerated the treatment well without obvious complications.

View details for DOI 10.1016/j.clineuro.2012.07.004

View details for Web of Science ID 000318318100013

View details for PubMedID 22835714

Literature review of various treatment plans and outcomes for brain metastases from colorectal cancer. World neurosurgery Murovic, J. A., Chang, S. D. 2013; 79 (3-4): 435-436

View details for DOI 10.1016/j.wneu.2011.12.071

View details for PubMedID 22381286

Cavity Volume Dynamics After Resection of Brain Metastases and Timing of Postresection Cavity Stereotactic Radiosurgery NEUROSURGERY Atalar, B., Choi, C. Y., Harsh, G. R., Chang, S. D., Gibbs, I. C., Adler, J. R., Soltys, S. G. 2013; 72 (2): 180-185

Abstract

An alternative treatment option to whole-brain irradiation after surgical resection of brain metastases is resection cavity stereotactic radiosurgery (SRS).To review the dynamics of cavity volume change after surgical resection with the goal of determining the optimal timing for cavity SRS.Preresection tumor, postresection/pre-SRS cavity, and post-SRS cavity volumes were measured for 68 cavities in 63 patients treated with surgery and postresection cavity SRS. Percent differences between volumes were calculated and correlation analyses were performed to assess volume changes before and after SRS.For the majority of tumors, the postresection cavity volume was smaller than the preresection tumor volume by a median percent volume change of -29% (range, -82% to 1258%), with larger preresection tumors resulting in greater cavity shrinkage (P < .001). To determine the optimal timing for cavity SRS, we examined cavity volume dynamics by comparing the early postresection (postoperative days 0-3) and treatment planning magnetic resonance imaging scans (median time to magnetic resonance imaging, 20 days; range, 9-33 days) and found no association between the postresection day number and volume change (P = .75). The volume decrease resulting from tumor resection was offset by the addition of a 2-mm clinical target volume margin, which is our current technique.The greatest volume change occurs immediately after surgery (postoperative days 0-3) with no statistically significant volume change occurring up to 33 days after surgery for most patients. Therefore, there is no benefit of cavity shrinkage in waiting longer than the first 1 to 2 weeks to perform cavity SRS.

View details for DOI 10.1227/NEU.0b013e31827b99f3

View details for Web of Science ID 000313734400028

Robotic skull base surgery via supraorbital keyhole approach: a cadaveric study. Neurosurgery Hong, W., Tsai, J., Chang, S. D., Sorger, J. M. 2013; 72: 33-38

Abstract

The supraorbital keyhole approach has been used in anterior skull base tumor and aneurysm surgery. However, there are debates regarding the safety and limitations of this kind of approach.To determine the feasibility and potential benefits of surgical robotic technology in minimally invasive neurosurgery.Two fresh cadaver heads were studied with the da Vinci Surgical System with 0 and 30 stereoscopic endoscopes to visualize neuroanatomy. The ability of the system to suture and place clips under the keyhole approach was tested.The da Vinci Surgical System was used throughout the supraorbital transeyebrow keyhole approach. With the use of standard microdissection techniques, the optic nerve, optic chiasm, carotid artery, and third cranial nerve were visualized. The sylvian fissure was then exposed from the proximal sylvian membrane to the distal M1 segment. With the EndoWrist microforceps, suturing can be achieved smoothly to close a defect created on the M2 artery. Although the benefits in adjusting clips during aneurysm surgery could be provided by an articulating applier, a proper robotic applier is not currently available.The minimally invasive supraorbital keyhole surgery can be achieved with the da Vinci Surgical System in cadaver models. This system provides neurosurgeons with broader vision and articulable instruments, which standard microsurgical systems do not provide. Further studies are necessary to evaluate the safety and benefits of using the da Vinci Surgical System in minimally invasive neurosurgery.

View details for DOI 10.1227/NEU.0b013e318270d9de

View details for PubMedID 23254810

Robotic Skull Base Surgery via Supraorbital Keyhole Approach: A Cadaveric Study NEUROSURGERY Hong, W., Tsai, J., Chang, S. D., Sorger, J. M. 2013; 72: A33-A38
Aberrant expression of lymphatic-associated proteins in human brain arteriovenous malformations Shoemaker, L., Fuentes, L., Santiago, S., Steinberg, G., Chang, S. SPRINGER. 2013: 269-270
Spontaneous intracranial hypotension secondary to anterior thoracic osteophyte: Resolution after primary dural repair via posterior approach. International journal of surgery case reports Veeravagu, A., Gupta, G., Jiang, B., Berta, S. C., Mindea, S. A., Chang, S. D. 2013; 4 (1): 26-29

Abstract

Spontaneous intracranial hypotension (SIH) is an uncommon syndrome widely attributed to CSF hypovolemia, typically secondary to spontaneous CSF leak. Although commonly associated with postural headache and variable neurological symptoms, one of the most severe consequences of SIH is bilateral subdural hematomas with resultant neurological deterioration.We present the case of a patient diagnosed with SIH secondary to an anteriorly positioned thoracic osteophyte with resultant dural disruption, who after multiple attempts at nonsurgical management developed bilateral subdural hematomas necessitating emergent surgical intervention. The patient underwent a unilateral posterior repair of his osteophyte with successful anterior decompression. At 36months follow up, the patient reported completely resolved headaches with no focal neurological deficits.We outline our posterior approach to repair of the dural defect and review the management algorithm for the treatment of patients with SIH. We also examine the current hypotheses as to the origin, pathophysiology, diagnosis and treatment of this syndrome.A posterior approach was utilized to repair the dural defect caused by an anterior thoracic osteophyte in a patient with severe SIH complicated by bilateral subdural hematomas. This approach minimizes morbidity compared to an anterior approach and allowed for removal of the osteophyte and repair of the dural defect.

View details for DOI 10.1016/j.ijscr.2012.06.009

View details for PubMedID 23108168

Outcomes After Stereotactic Radiosurgery and Various Adjuvant Treatments for Recurrent Glioblastoma Multiforme: A Current Literature Review and Comparison of Multiple Factors that Impact Outcome WORLD NEUROSURGERY Murovic, J. A., Chang, S. D. 2012; 78 (6): 588-591

View details for DOI 10.1016/j.wneu.2012.06.005

View details for Web of Science ID 000312950100013

View details for PubMedID 22705758

What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Chang, S. D., Gibbs, I. C., Adler, J. R., Harsh, G. R., Atalar, B., Lieberson, R. E., Soltys, S. G. 2012; 84 (3): 688-693

Abstract

Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity.We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by the Kaplain-Meier product-limit method.The median imaging follow-up duration for all patients was 10 months (range, 1-80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%-16.1%), and the median time to LF was 6 months (range, 3-17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%-63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status (?80 vs. <80; hazard ratio 0.54; 95% CI 0.31-0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08-1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity.Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.

View details for DOI 10.1016/j.ijrobp.2012.01.028

View details for Web of Science ID 000309560600051

View details for PubMedID 22445007

Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases Modlin, L. A., Atalar, B., Choi, C. Y., Gibbs, I. C., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G. ELSEVIER SCIENCE INC. 2012: S116-S117
Stereotactic Radiosurgery for the Treatment of Spinal Metastases: Analysis of Tumor Control and Patterns of Failure Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D., Modlin, L. A., Choi, C. Y. ELSEVIER SCIENCE INC. 2012: S195-S195
Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Chang, S. D., Gibbs, I. C., Adler, J. R., Harsh, G. R., Lieberson, R. E., Soltys, S. G. 2012; 84 (2): 336-342

Abstract

Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity.We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests.The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients.Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

View details for DOI 10.1016/j.ijrobp.2011.12.009

View details for Web of Science ID 000308062700035

View details for PubMedID 22652105

Intracranial hypotension producing reversible coma: a systematic review, including three new cases A review JOURNAL OF NEUROSURGERY Loya, J. J., Mindea, S. A., Yu, H., Venkatasubramanian, C., Chang, S. D., Burns, T. C. 2012; 117 (3): 615-628

Abstract

Intracranial hypotension is a disorder of CSF hypovolemia due to iatrogenic or spontaneous spinal CSF leakage. Rarely, positional headaches may progress to coma, with frequent misdiagnosis. The authors review reported cases of verified intracranial hypotension-associated coma, including 3 previously unpublished cases, totaling 29. Most patients presented with headache prior to neurological deterioration, with positional symptoms elicited in almost half. Eight patients had recently undergone a spinal procedure such as lumbar drainage. Diagnostic workup almost always began with a head CT scan. Subdural collections were present in 86%; however, intracranial hypotension was frequently unrecognized as the underlying cause. Twelve patients underwent one or more procedures to evacuate the collections, sometimes with transiently improved mental status. However, no patient experienced lasting neurological improvement after subdural fluid evacuation alone, and some deteriorated further. Intracranial hypotension was diagnosed in most patients via MRI studies, which were often obtained due to failure to improve after subdural hematoma (SDH) evacuation. Once the diagnosis of intracranial hypotension was made, placement of epidural blood patches was curative in 85% of patients. Twenty-seven patients (93%) experienced favorable outcomes after diagnosis and treatment; 1 patient died, and 1 patient had a morbid outcome secondary to duret hemorrhages. The literature review revealed that numerous additional patients with clinical histories consistent with intracranial hypotension but no radiological confirmation developed SDH following a spinal procedure. Several such patients experienced poor outcomes, and there were multiple deaths. To facilitate recognition of this treatable but potentially life-threatening condition, the authors propose criteria that should prompt intracranial hypotension workup in the comatose patient and present a stepwise management algorithm to guide the appropriate diagnosis and treatment of these patients.

View details for DOI 10.3171/2012.4.JNS112030

View details for Web of Science ID 000307627100031

View details for PubMedID 22725982

Esophageal tolerance to high-dose stereotactic ablative radiotherapy DISEASES OF THE ESOPHAGUS Abelson, J. A., Murphy, J. D., Loo, B. W., Chang, D. T., Daly, M. E., Wiegner, E. A., Hancock, S., Chang, S. D., Le, Q., Soltys, S. G., Gibbs, I. C. 2012; 25 (7): 623-629

Abstract

Dose-volume parameters are needed to guide the safe administration of stereotactic ablative radiotherapy (SABR). We report on esophageal tolerance to high-dose hypofractionated radiation in patients treated with SABR. Thirty-one patients with spine or lung tumors received single- or multiple-fraction SABR to targets less than 1 cm from the esophagus. End points evaluated include D(5cc) (minimum dose in Gy to 5 cm(3) of the esophagus receiving the highest dose), D(2cc) , D(1cc) , and D(max) (maximum dose to 0.01 cm(3) ). Multiple-fraction treatments were correlated using the linear quadratic and linear quadratic-linear/universal survival models. Three esophageal toxicity events occurred, including esophagitis (grade 2), tracheoesophageal fistula (grade 4-5), and esophageal perforation (grade 4-5). Chemotherapy was a cofactor in the high-grade events. The median time to development of esophageal toxicity was 4.1 months (range 0.6-6.1 months). Two of the three events occurred below a published D(5cc) threshold, all three were below a D(2cc) threshold, and one was below a D(max) threshold. We report a dosimetric analysis of incidental dose to the esophagus from SABR. High-dose hypofractionated radiotherapy led to a number of high-grade esophageal adverse events, suggesting that conservative parameters to protect the esophagus are necessary when SABR is used, especially in the setting of chemotherapy or prior radiotherapy.

View details for DOI 10.1111/j.1442-2050.2011.01295.x

View details for Web of Science ID 000308712300008

View details for PubMedID 22168251

CyberKnife stereotactic radiosurgery for the treatment of intramedullary spinal cord metastases JOURNAL OF CLINICAL NEUROSCIENCE Veeravagu, A., Lieberson, R. E., Mener, A., Chen, Y., Soltys, S. G., Gibbs, I. C., Adler, J. R., Tian, A. G., Chang, S. D. 2012; 19 (9): 1273-1277

Abstract

Spinal cord intramedullary metastases are uncommon and treatment options are limited. We reviewed our experience treating these lesions with radiosurgery to assess safety and efficacy, and to define preliminary treatment recommendations. With Institutional Review Board approval, we identified nine patients with 11 metastases treated with radiosurgery at Stanford University Hospital, between 2000 and 2010. We also reviewed all available published series discussing the treatment of spinal cord metastases. Our patients ranged in age from 33 years to 77 years (median 63 years) and included seven women and two men. Tumors ranged in size from 0.12 cm(3) to 6.4 cm(3) (median 0.48 cm(3)). Five were from breast cancer, two were non-small cell lung cancers, one was a cystic adenocarcinoma, and one was from an epithelioid hemangioepithelioma. All patients had neurologic deficits and multiple other metastases. We delivered 14 Gy to 27 Gy (median 21 Gy) in one to five (median 3) fractions. Complete follow-up was available for all nine patients. One patient remains alive 14 months after therapy. Of the eight deceased patients, survival ranged from one month and two days to nine months and six days (median four months and four days). There were no local recurrences or worsened neurological deficits. To our knowledge this is the largest reported series of spinal cord intramedullary metastases treated with radiosurgery. Survival was poor due to systemic disease, but radiosurgery appears to be safe and prevented local recurrences. With fewer sessions than conventional radiation and less morbidity than surgery, we feel radiosurgery is appropriate for the palliative treatment of these lesions.

View details for DOI 10.1016/j.jocn.2012.02.002

View details for Web of Science ID 000308730900014

View details for PubMedID 22766103

Management of intracranial and extracranial chordomas with CyberKnife stereotactic radiosurgery JOURNAL OF CLINICAL NEUROSCIENCE Jiang, B., Veeravagu, A., Lee, M., Harsh, G. R., Lieberson, R. E., Bhatti, I., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2012; 19 (8): 1101-1106

Abstract

Chordomas are rare, malignant bone tumors of the axial skeleton, occurring particularly at the cranial base or in the sacro-coccygeal region. Although slow growing, chordomas are locally aggressive and challenging to treat. We evaluate the outcomes of skull base and spinal chordomas in 20 patients treated with CyberKnife (CK) stereotactic radiosurgery (SRS) (Accuray, Sunnyvale, CA, USA) between 1994 and 2010 at Stanford Hospital. There were 12 males and eight females (10-78 years; median age: 51.5 years). Eleven patients received CK as primary adjuvant therapy and nine patients received CK for multiple recurrences. The average tumor volume treated was 16.1cm(3) (2.4-45.9 cm(3)), with a mean marginal dose of 32.5 Gy (18-50 Gy). Median follow-up was 34 months (2-131 months). Overall, tumor control was achieved in 11 patients (55%), with eight patients showing tumor size reduction. However, nine patients showed progression and eventually succumbed to the disease (mean time from CK to death was 26.3 months). Of the patients treated with CK as the primary adjuvant therapy, 81.8% had stable or improved outcomes. Only 28.6% of those treated with CK for recurrences had stable or improved outcomes. The overall Kaplan-Meyer survival at five years from the first CK treatment was 52.5%. Moderate tumor control rates can be achieved with few complications with CK SRS. Poor control is associated with complex multiple surgical resections, long delay between initial resection and CK therapy, and recurrently aggressive disease uncontrolled by prior radiation.

View details for DOI 10.1016/j.jocn.2012.01.005

View details for Web of Science ID 000306500400009

View details for PubMedID 22727205

Neurocognitive Changes in Pituitary Adenoma Patients After Fractionated External Beam Radiotherapy versus Gamma Knife Radiosurgery WORLD NEUROSURGERY Murovic, J., Chang, S. 2012; 78 (1-2)

View details for DOI 10.1016/J.WNEU.2011.12.060

View details for Web of Science ID 000307933400016

View details for PubMedID 22381297

Multimodality management of Spetzler-Martin Grade III arteriovenous malformations JOURNAL OF NEUROSURGERY Pandey, P., Marks, M. P., Harraher, C. D., Westbroek, E. M., Chang, S. D., Do, H. M., Levy, R. P., Dodd, R. L., Steinberg, G. K. 2012; 116 (6): 1279-1288

Abstract

Grade III arteriovenous malformations (AVMs) are diverse because of their variations in size (S), location in eloquent cortex (E), and presence of central venous drainage (V). Because they may have implications for management and outcome, the authors evaluated these variations in the present study.Between 1984 and 2010, 100 patients with Grade III AVMs were treated. The AVMs were categorized by Spetzler-Martin characteristics as follows: Type 1 = S1E1V1, Type 2 = S2E1V0, Type 3 = S2E0V1, and Type 4 = S3E0V0. The occurrence of a new neurological deficit, functional status (based on modified Rankin Scale [mRS] score) at discharge and follow-up, and radiological obliteration were correlated with demographic and morphological characteristics.One hundred patients (49 female and 51 male; age range 5-68 years, mean 35.8 years) were evaluated. The size of AVMs was less than 3 cm in 28 patients, 3-6 cm in 71, and greater than 6 cm in 1; 86 AVMs were located in eloquent cortex and 38 had central drainage. The AVMs were Type 1 in 28 cases, Type 2 in 60, Type 3 in 11, and Type 4 in 1. The authors performed embolization in 77 patients (175 procedures), surgery in 64 patients (74 surgeries), and radiosurgery in 49 patients (44 primary and 5 postoperative). The mortality rate following the management of these AVMs was 1%. Fourteen patients (14%) had new neurological deficits, with 5 (5%) being disabling (mRS score > 2) and 9 (9%) being nondisabling (mRS score ? 2) events. Patients with Type 1 AVMs (small size) had the best outcome, with 1 (3.6%) in 28 having a new neurological deficit, compared with 72 patients with larger AVMs, of whom 13 (18.1%) had a new neurological deficit (p < 0.002). Older age (> 40 years), malformation size > 3 cm, and nonhemorrhagic presentation predicted the occurrence of new deficits (p < 0.002). Sex, eloquent cortex, and venous drainage did not confer any benefit. In 89 cases follow-up was adequate for data to be included in the obliteration analysis. The AVM was obliterated in 78 patients (87.6%), 69 of them (88.5%) demonstrated on angiography and 9 on MRI /MR angiography. There was no difference between obliteration rates between different types of AVMs, size, eloquence, and drainage. Age, sex, and clinical presentation also did not predict obliteration.Multimodality management of Grade III AVMs results in a high rate of obliteration, which was not influenced by size, venous drainage, or eloquent location. However, the development of new neurological deficits did correlate with size, whereas eloquence and venous drainage did not affect the neurological complication rate. The authors propose subclassifying the Grade III AVMs according to their size (< 3 and ? 3 cm) to account for treatment risk.

View details for DOI 10.3171/2012.3.JNS111575

View details for Web of Science ID 000304294000022

View details for PubMedID 22482792

Stereotactic Radiosurgery as the Primary Treatment for New and Recurrent Paragangliomas: Is Open Surgical Resection Still the Treatment of Choice? WORLD NEUROSURGERY Lieberson, R. E., Adler, J. R., Soltys, S. G., Choi, C., Gibbs, I. C., Chang, S. D. 2012; 77 (5-6): 745-761

Abstract

Paragangliomas (PGs) or glomus tumors are rare, and publications comparing treatment alternatives are few. We sought to analyze our experience with stereotactic radiosurgery (SRS), review the literature, and develop treatment guidelines.We retrospectively examined the outcomes of 41 PGs in 36 patients treated with SRS at Stanford. Our data from medical records, telephone interviews, and imaging studies were combined with previously reported SRS data and compared to results following other treatments.With a median clinical follow-up of 4.8 years (3.9 years radiographic), local control was 100%. Complications included increase in preexistent vertigo in one patient and transient cranial neuropathies in two patients. Published surgical series describe a lower local control rate as well as more frequent and severe complications. Published radiation therapy (RT) series document a slightly lower local control rate than SRS, but SRS can be delivered more quickly and conveniently. Open surgery and other combinations of treatments appear to be required for several subpopulations of PG patients.We feel that SRS should be the primary treatment for most new and recurrent PGs. Even some very large PGs are appropriate for SRS. RT remains an appropriate option in some centers, especially those where SRS is not available. PGs occurring in the youngest patients, catecholamine secreting PGs, and PGs causing rapidly progressing neurologic deficits may be more appropriate for open resection. Metastatic PGs may benefit from combinations of chemotherapy and SRS or RT. Treatment guidelines are proposed.

View details for DOI 10.1016/j.wneu.2011.03.026

View details for Web of Science ID 000307523800038

View details for PubMedID 22818172

Stereotactic radiosurgery for central neurocytoma: a quantitative systematic review JOURNAL OF NEURO-ONCOLOGY Park, H., Chang, S. D. 2012; 108 (1): 115-121

Abstract

Central neurocytoma was originally described as a rare benign neuronal tumor. However, progression and local recurrences after surgery are well recognized. Stereotactic radiosurgery is another option for treatment of CN. In order to evaluate the efficacy of SRS, we performed a quantitative systematic review of the available data on SRS for CN. To identify eligible studies, systematic searches for all CNs treated with SRS were conducted in major scientific publication databases. English studies published prior to May 2011 were reviewed and summarized with reference to the inclusion and exclusion criteria. Tumor local control was analyzed. Heterogeneity and publication bias were assessed, and the summary control rate and 95%confidence interval (CI) were calculated from the raw data.Of 35 eligible studies, five with a total of 64 CNs were included in this quantitative analysis. Four studies reported a mean or median follow-up time of[60 months. The test of heterogeneity was non-significant among the included studies. Publication bias was observed as indicated by an asymmetric funnel plot. There was non-significance in Beggs test and Eggers test. The estimated cumulative rate of neuro-imaging tumor control was 91.1% (95%CI = 80.296.3%) at a mean follow-up of 59.3 months(range 6140 months). The P-value was\0.0001 under a random-effect model. Sensitivity analysis showed a similar summary control rates (89.593.7%). Based on the summary local control rate of SRS for CN found in this quantitative analysis, we suggest that single session SRS is an effective and safe alternative therapy for recurrent or residual CN. However, the results of our analysis are limited by the predominance of case series studies due to scarcity of published research. Further randomized trials of CN patients via multicenter consortia should be considered for supplementing the weak points in our quantitative analysis.

View details for DOI 10.1007/s11060-012-0803-x

View details for Web of Science ID 000303469600013

View details for PubMedID 22442020

NORMAL TISSUE COMPLICATION PROBABILITY ESTIMATION BY THE LYMAN-KUTCHER-BURMAN METHOD DOES NOT ACCURATELY PREDICT SPINAL CORD TOLERANCE TO STEREOTACTIC RADIOSURGERY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Luxton, G., Choi, C. Y., Gibbs, I. C., Chang, S. D., Adler, J. R., Soltys, S. G. 2012; 82 (5): 2025-2032

Abstract

To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the Lyman-Kutcher-Burman (LKB) model, supplemented by linear-quadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS).From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 18-30 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.8-30.9 Gy) and 22.0 Gy (range, 20.2-26.6 Gy), respectively. By use of conventional values for ?/?, volume parameter n, 50% complication probability dose TD(50), and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of ?/? and n.In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximum-likelihood LKB fitting of ?/? and n yielded better predictions (0.7 complications), with n= 0.023 and ?/?= 17.8 Gy.The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high ?/? value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP may not apply to the dosimetry of SRS. Further research with additional NTCP models is needed.

View details for DOI 10.1016/j.ijrobp.2011.03.004

View details for Web of Science ID 000301891300082

View details for PubMedID 21531516

Trigeminal neuralgia treatment dosimetry of the Cyberknife MEDICAL DOSIMETRY Ho, A., Lo, A. T., Dieterich, S., Soltys, S. G., Gibbs, I. C., Chang, S. G., Adler, J. R. 2012; 37 (1): 42-46

Abstract

There are 2 Cyberknife units at Stanford University. The robot of 1 Cyberknife is positioned on the patient's right, whereas the second is on the patient's left. The present study examines whether there is any difference in dosimetry when we are treating patients with trigeminal neuralgia when the target is on the right side or the left side of the patient. In addition, we also study whether Monte Carlo dose calculation has any effect on the dosimetry. We concluded that the clinical and dosimetric outcomes of CyberKnife treatment for trigeminal neuralgia are independent of the robot position. Monte Carlo calculation algorithm may be useful in deriving the dose necessary for trigeminal neuralgia treatments.

View details for DOI 10.1016/j.meddos.2010.12.012

View details for Web of Science ID 000301035000009

View details for PubMedID 21723113

Junctional Visual Field Loss in a Case of Wyburn-Mason Syndrome JOURNAL OF NEURO-OPHTHALMOLOGY Liu, A., Chen, Y., Chang, S., Liao, Y. J. 2012; 32 (1): 42-44

Abstract

A previously healthy girl failed a routine eye screening at the age of 6 years. Her visual fields showed generalized depression in the right eye and a superotemporal defect in the left eye, consistent with a junctional scotoma. Funduscopic examination and fluorescein angiography revealed markedly dilated tortuous vascular loops with arteriovenous communications consistent with retinal arteriovenous malformations (AVMs). MRI of the brain and cerebral angiography demonstrated right ophthalmic and right thalamic AVMs, with compression and atrophy of the right optic chiasm. This represents a case of Wyburn-Mason syndrome with a junctional scotoma.

View details for DOI 10.1097/WNO.0b013e31821aeefb

View details for Web of Science ID 000300607000009

View details for PubMedID 21613961

Clinical Neuroproteomics and Biomarkers: From Basic Research to Clinical Decision Making NEUROSURGERY Shoemaker, L. D., Achrol, A. S., Sethu, P., Steinberg, G. K., Chang, S. D. 2012; 70 (3): 518-525

Abstract

Clinical neuroproteomics aims to advance our understanding of disease and injury affecting the central and peripheral nervous systems through the study of protein expression and the discovery of protein biomarkers to facilitate diagnosis and treatment. The general premise of the biomarker field is that in vivo factors present in either tissue or circulating biofluids, reflect pathological changes, and can be identified and analyzed. This approach offers an opportunity to illuminate changes occurring at both the population and patient levels toward the realization of personalized medicine. This review is intended to provide research-driven clinicians with an overview of protein biomarkers of disease and injury for clinical use and to highlight methodology and potential pitfalls. We examine the neuroproteomic biomarker field and discuss the hallmarks and the challenges of clinically relevant biomarker discovery relating to central nervous system pathology. We discuss the issues in the maturation of potential biomarkers from discovery to Food and Drug Administration approval and review several platforms for protein biomarker discovery, including protein microarray and mass spectrometry-based proteomics. We describe the application of microfluidic technologies to the evolution of a robust clinical test. Finally, we highlight several biomarkers currently in use for cancer, ischemia, and injury in the central nervous system. Future efforts using these technologies will result in the maturation of existing and the identification of de novo biomarkers that could guide clinical decision making and advance diagnostic and therapeutic options for the treatment of neurological disease and injury.

View details for DOI 10.1227/NEU.0b013e3182333a26

View details for Web of Science ID 000300781700008

View details for PubMedID 21866062

Intramedullary spinal cord metastasis from prostate carcinoma: a case report. Journal of medical case reports Lieberson, R. E., Veeravagu, A., Eckermann, J. M., Doty, J. R., Jiang, B., Andrews, R., Chang, S. D. 2012; 6 (1): 139-?

Abstract

Although vertebral and epidural metastases are common, intradural metastases and intramedullary spinal cord metastases are rare. The indications for the treatment of intramedullary spinal cord metastases remain controversial. We present the first biopsy-proven case of an intramedullary spinal cord metastasis from adenocarcinoma of the prostate.Our patient was a 68-year-old right-handed Caucasian man with a Gleason grade 4?+?3 prostate adenocarcinoma who had previously undergone a prostatectomy, androgen blockade and transurethral debulking. He presented with new-onset saddle anesthesia and fecal incontinence. Magnetic resonance imaging demonstrated a spindle-shaped intramedullary lesion of the conus medullaris. Our patient underwent decompression and an excisional biopsy; the lesion's pathology was consistent with metastatic adenocarcinoma of the prostate. Postoperatively, our patient received CyberKnife radiosurgery to the resection cavity at a marginal dose of 27Gy to the 85% isodose line. At three months follow-up, our patient remains neurologically stable with no new deficits or lesions.We review the literature and discuss the indications for surgery and radiosurgery for intramedullary spinal cord metastases. We also report the novel use of stereotactic radiosurgery to sterilize the resection cavity following an excisional biopsy of the metastasis.

View details for DOI 10.1186/1752-1947-6-139

View details for PubMedID 22657386

Potential application of hydrogen in traumatic and surgical brain injury, stroke and neonatal hypoxia-ischemia. Medical gas research Eckermann, J. M., Krafft, P. R., Shoemaker, L., Lieberson, R. E., Chang, S. D., Colohan, A. 2012; 2 (1): 11-?

Abstract

This article summarized findings of current preclinical studies that implemented hydrogen administration, either in the gas or liquid form, as treatment application for neurological disorders including traumatic brain injury (TBI), surgically induced brain injury (SBI), stroke, and neonatal hypoxic-ischemic brain insult (HI). Most reviewed studies demonstrated neuroprotective effects of hydrogen administration. Even though anti-oxidative potentials have been reported in several studies, further neuroprotective mechanisms of hydrogen therapy remain to be elucidated. Hydrogen may serve as an adjunct treatment for neurological disorders.

View details for DOI 10.1186/2045-9912-2-11

View details for PubMedID 22515516

Stereotactic radiosurgery for central neurocytoma: a quantitative systematic review. Journal of neuro-oncology Park, H. K., Chang, S. D. 2012

Abstract

Central neurocytoma was originally described as a rare benign neuronal tumor. However, progression and local recurrences after surgery are well recognized. Stereotactic radiosurgery is another option for treatment of CN. In order to evaluate the efficacy of SRS, we performed a quantitative systematic review of the available data on SRS for CN. To identify eligible studies, systematic searches for all CNs treated with SRS were conducted in major scientific publication databases. English studies published prior to May 2011 were reviewed and summarized with reference to the inclusion and exclusion criteria. Tumor local control was analyzed. Heterogeneity and publication bias were assessed, and the summary control rate and 95% confidence interval (CI) were calculated from the raw data. Of 35 eligible studies, five with a total of 64 CNs were included in this quantitative analysis. Four studies reported a mean or median follow-up time of >60months. The test of heterogeneity was non-significant among the included studies. Publication bias was observed as indicated by an asymmetric funnel plot. There was non-significance in Begg's test and Egger's test. The estimated cumulative rate of neuro-imaging tumor control was 91.1% (95% CI=80.2-96.3%) at a mean follow-up of 59.3months (range 6-140months). The P-value was <0.0001 under a random-effect model. Sensitivity analysis showed a similar summary control rates (89.5-93.7%). Based on the summary local control rate of SRS for CN found in this quantitative analysis, we suggest that single session SRS is an effective and safe alternative therapy for recurrent or residual CN. However, the results of our analysis are limited by the predominance of case series studies due to scarcity of published research. Further randomized trials of CN patients via multicenter consortia should be considered for supplementing the weak points in our quantitative analysis.

View details for PubMedID 22302467

A giant cell tumor of the cranial base treated by stereotactic radiosurgery Journal of Radiosurgery and SBRT Kim EY, Murovic JA, Gibbs IC, Shuer LM, Chang SD 2012; 1: 333-337
Multisession Stereotactic Radiosurgery for Vestibular Schwannomas: Single-Institution Experience With 383 Cases NEUROSURGERY Hansasuta, A., Choi, C. Y., Gibbs, I. C., Soltys, S. G., Tse, V. C., Lieberson, R. E., Hayden, M. G., Sakamoto, G. T., Harsh, G. R., Adler, J. R., Chang, S. D. 2011; 69 (6): 1200-1209

Abstract

Single-session stereotactic radiosurgery (SRS) treatment of vestibular schwannomas results in excellent tumor control. It is not known whether functional outcomes can be improved by fractionating the treatment over multiple sessions.To examine tumor control and complication rates after multisession SRS.Three hundred eighty-three patients treated with SRS from 1999 to 2007 at Stanford University Medical Center were retrospectively reviewed. Ninety percent were treated with 18 Gy in 3 sessions, targeting a median tumor volume of 1.1 cm3 (range, 0.02-19.8 cm3).During a median follow-up duration of 3.6 years (range, 1-10 years), 10 tumors required additional treatment, resulting in 3- and 5-year Kaplan-Meier tumor control rates of 99% and 96%, respectively. Five-year tumor control rate was 98% for tumors < 3.4 cm3. Neurofibromatosis type 2-associated tumors were associated with worse tumor control (P = .02). Of the 200 evaluable patients with pre-SRS serviceable hearing (Gardner-Robertson grade 1 and 2), the crude rate of serviceable hearing preservation was 76%. Smaller tumor volume was associated with hearing preservation (P = .001). There was no case of post-SRS facial weakness. Eight patients (2%) developed trigeminal dysfunction, half of which was transient.Multisession SRS treatment of vestibular schwannomas results in an excellent rate of tumor control. The hearing, trigeminal nerve, and facial nerve function preservation rates reported here are promising.

View details for DOI 10.1227/NEU.0b013e318222e451

View details for Web of Science ID 000296794500024

View details for PubMedID 21558974

RADIOSURGERY OF GLOMUS JUGULARE TUMORS: A META-ANALYSIS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Guss, Z. D., Batra, S., Limb, C. J., Li, G., Sughrue, M. E., Redmond, K., Rigamonti, D., Parsa, A. T., Chang, S., Kleinberg, L., Lim, M. 2011; 81 (4): E497-E502

Abstract

During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors.To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data when Cochrane's statistic was statistically insignificant and the inconsistency among studies was <25%. Bias was assessed using the Egger funnel plot test.Across all studies, 97% of patients achieved tumor control, and 95% of patients achieved clinical control. Eight studies reported a mean or median follow-up time of >36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control.The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.

View details for DOI 10.1016/j.ijrobp.2011.05.006

View details for Web of Science ID 000309412300039

View details for PubMedID 21703782

CyberKnife stereotactic radiosurgical rhizotomy for refractory trigeminal neuralgia JOURNAL OF CLINICAL NEUROSCIENCE Tang, C., Chang, S. D., Tseng, K., Liu, M., Ju, D. 2011; 18 (11): 1449-1453

Abstract

Stereotactic radiosurgery (SRS) has been established as an option for the treatment of trigeminal neuralgia (TN). Here, we report our experience of CyberKnife-based (Accuray, Sunnyvale, CA, USA) stereotactic rhizotomy on medically refractory patients to determine its clinical effectiveness. Between January 2007 and December 2009, 14 selected patients underwent SRS for TN at our CyberKnife Center. Patients were evaluated for pain relief using a visual analog scale (VAS) score, time to reach pain relief (latency), duration of pain control, decrease of pain medication, occurrence of new dysesthesia, and side effects at the 3-month, 6-month, 1-year and 2-year follow-up. A literature analysis revealed that compared with other SRS systems, which can provide a high rate of pain control, CyberKnife stereotactic rhizotomy yielded an earlier onset of pain relief in our cohort.

View details for DOI 10.1016/j.jocn.2011.03.012

View details for Web of Science ID 000296402800005

View details for PubMedID 21924911

A rare case of an aldosterone secreting metastatic adrenocortical carcinoma and papillary thyroid carcinoma in a 31-year-old male. Rare tumors Wanta, S. M., Basina, M., Chang, S. D., Chang, D. T., Ford, J. M., Greco, R., Kingham, K., Merritt, R. E., Kunz, P. L. 2011; 3 (4)

Abstract

We report a rare synchronous presentation of adrenocortical carcinoma (ACC) and papillary thyroid carcinoma (PTC). A 31-year-old male first presented with a large left adrenal mass that was identified during the workup for refractory hypertension due to hyperaldosteronism. The mass was removed surgically with pathology showing ACC. The patient was then treated with adjuvant radiation therapy and mitotane chemotherapy. Four months post ACC resection, metastatic ACC to the right upper lung and PTC in the left lobe of the thyroid were found in surveillance imaging. He subsequently developed pulmonary, contralateral adrenal and brain metastases from his ACC. Li Fraumeni syndrome and Multiple Endocrine Neoplasia Type I (MEN I) were considered, but testing of both P53 and menin genes showed no mutation. We also performed a review of the literature and found three similar cases, however gene mutation analysis was not performed..

View details for DOI 10.4081/rt.2011.e45

View details for PubMedID 22355500

Images in clinical medicine. Orbital and cerebral arteriovenous malformations. New England journal of medicine Choudhri, O., Chang, S. D. 2011; 365 (13)

View details for DOI 10.1056/NEJMicm1010443

View details for PubMedID 21991915

Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spinal Tumors NEUROSURGERY Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L., Gibbs, I. C. 2011; 69 (3): 533-539

Abstract

The role of stereotactic radiosurgery in the treatment of benign intracranial lesions is well established. Although a growing body of evidence supports its role in the treatment of malignant spinal lesions, a much less extensive dataset exists for treatment of benign spinal tumors.To examine the safety and efficacy of stereotactic radiosurgery for treatment of benign, intradural extramedullary spinal tumors.From 1999 to 2008, 87 patients with 103 benign intradural extramedullary spinal tumors (32 meningiomas, 24 neurofibromas, and 47 schwannomas) were treated with stereotactic radiosurgery at Stanford University Medical Center. Forty-three males and 44 females had a median age of 53 years (range, 12-86). Twenty-five patients had neurofibromatosis. Treatment was delivered in 1 to 5 sessions (median, 2) with a mean prescription dose of 19.4 Gy (range, 14-30 Gy) to an average tumor volume of 5.24 cm (range, 0.049-54.52 cm).After a mean radiographic follow-up period of 33 months (range, 6-87), including 21 lesions followed for ? 48 months, 59% were stable, 40% decreased in size, and a single tumor (1%) increased in size. Clinically, 91%, 67%, and 86% of meningiomas, neurofibromas, and schwannomas, respectively, were symptomatically stable to improved at last follow-up. One patient with a meningioma developed a new, transient myelopathy at 9 months, although the tumor was smaller at last follow-up.As a viable alternative to microsurgical resection, stereotactic radiosurgery provides safe and efficacious long-term control of benign intradural, extramedullary spinal tumors with a low rate of complication.

View details for DOI 10.1227/NEU.0b013e318218db23

View details for Web of Science ID 000293586200003

View details for PubMedID 21832967

Successful Repair of a Gunshot Wound to the Head with Retained Bullet in the Torcular Herophili WORLD NEUROSURGERY Pricola, K. L., Zou, H., Chang, S. D. 2011; 76 (3-4)

Abstract

Nonlethal missile injuries to the dural venous sinus system are rare. To date successful repair of isolated penetrating injury to the torcular herophili has not been reported without significant associated morbidity. We report the case of a gunshot wound injury to the occipital region with retained bullet fragment in the confluence of the sinuses causing traumatic sinus venous thrombosis.Occipital and suboccipital craniotomy for removal of bullet in the torcula, repair of sinus defect, and repair of depressed skull bone fragments was performed.The procedure resulted in restoration of proximal and distal flow across the dural sinus system and preservation of torcular sinus patency with excellent neurological outcome. Technical considerations in the repair of penetrating torcular injuries are discussed.Gunshot wounds with retained bullet fragments in the torcula can be successfully repaired with preservation of neurological function after retrieval of metallic foreign body and restoration of venous sinus patency.

View details for DOI 10.1016/j.wneu.2010.03.021

View details for Web of Science ID 000296145700036

View details for PubMedID 21986442

Management of Pediatric Intracranial Arteriovenous Malformations: Experience With Multimodality Therapy NEUROSURGERY Darsaut, T. E., Guzman, R., Marcellus, M. L., Edwards, M. S., Tian, L., Do, H. M., Chang, S. D., Levy, R. P., Adler, J. R., Marks, M. P., Steinberg, G. K. 2011; 69 (3): 540-556

Abstract

Successful management of pediatric arteriovenous malformations (AVMs) often requires a balanced application of embolization, surgery, and radiosurgery.To describe our experience treating pediatric AVMs.We analyzed 120 pediatric patients (< 18 years of age) with AVMs treated with various combinations of radiosurgery, surgery, and endovascular techniques.Between 1985 and 2009, 76 children with low Spetzler-Martin grade (1-3) and 44 with high-grade (4-5) AVMs were treated. Annual risk of hemorrhage from presentation to initial treatment was 4.0%, decreasing to 3.2% after treatment initiation until confirmed obliteration. Results for AVM obliteration were available in 101 patients. Initial single-modality therapy led to AVM obliteration in 51 of 67 low-grade (76%) and 3 of 34 high-grade (9%) AVMs, improving to 58 of 67 (87%) and 9 of 34 (26%), respectively, with further treatment. Mean time to obliteration was 1.8 years for low-grade and 6.4 years for high-grade AVMs. Disabling neurological complications occurred in 4 of 77 low-grade (5%) and 12 of 43 high-grade (28%) AVMs. At the final clinical follow-up (mean, 9.2 years), 48 of 67 patients (72%) with low-grade lesions had a modified Rankin Scale score (mRS) of 0 to 1 compared with 12 of 34 patients (35%) with high-grade AVMs. On multivariate analysis, significant risk factors for poor final clinical outcome (mRS ? 2) included baseline mRS ? 2 (odds ratio, 9.51; 95% confidence interval, 3.31-27.37; P < .01), left-sided location (odds ratio, 3.03; 95% confidence interval, 1.11-8.33; P = .03), and high AVM grade (odds ratio, 4.35; 95% confidence interval, 1.28-14.28; P = .02).Treatment of pediatric AVMs with multimodality therapy can substantially improve obliteration rates and may decrease AVM hemorrhage rates. The poor natural history and risks of intervention must be carefully considered when deciding to treat high-grade pediatric AVMs.

View details for DOI 10.1227/NEU.0b013e3182181c00

View details for Web of Science ID 000293586200005

View details for PubMedID 21430584

CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas JOURNAL OF HEMATOLOGY & ONCOLOGY Veeravagu, A., Jiang, B., Patil, C. G., Lee, M., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2011; 4

Abstract

Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas.In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively.Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%.CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.

View details for DOI 10.1186/1756-8722-4-26

View details for Web of Science ID 000291817100001

View details for PubMedID 21645367

Stereotactic Radiosurgery of Cranial Nonvestibular Schwannomas: Results of Single- and Multisession Radiosurgery NEUROSURGERY Choi, C. Y., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Sakamoto, G. T., Patel, D. A., Lieberson, R. E., Chang, S. D., Adler, J. R. 2011; 68 (5): 1200-1208

Abstract

Surgical resection of nonvestibular cranial schwannomas carries a considerable risk of postoperative complications. Stereotactic radiosurgery (SRS) offers a non-invasive treatment alternative. The efficacy and safety of multi-session SRS of nonvestibular cranial schwannomas has not been well studied.To analyze the results of single- and multi-session SRS of nonvestibular cranial schwannomas.From 2001 to 2007, 42 lesions in 40 patients were treated with SRS at Stanford University Medical Center, targeting schwannomas of cranial nerves IV (n = 1), V (n = 18), VII (n = 6), X (n = 5), XII (n = 2), jugular foramen (n = 8), and cavernous sinus (n = 2). SRS was delivered to a median marginal dose of 18 Gy (range, 15-33 Gy) in 1 to 3 sessions, targeting a median tumor volume of 3.2 cm (range, 0.1-23.7 cm). The median doses for treatments in 1 (n = 18), 2 (n = 9), and 3 (n = 15) sessions were 17.5, 20, and 18 Gy, respectively.With a median follow-up of 29 months (range, 6-84 months), tumor control was achieved in 41 of the 42 lesions. Eighteen of 42 lesions (43%) decreased in size; 23 tumors (55%) remained stable. There were 2 cases of new or worsening cranial nerve deficits in patients treated in single session; no patient treated with multi-session SRS experienced any cranial nerve toxicity (P = 0.18).SRS of nonvestibular cranial schwannomas provides excellent tumor control with minimal risk of complications. There was a trend towards decreased complications with multi-session SRS.

View details for DOI 10.1227/NEU.0b013e31820c0474

View details for Web of Science ID 000289230300033

View details for PubMedID 21273918

TOLERANCE OF THE SPINAL CORD TO STEREOTACTIC RADIOSURGERY: INSIGHTS FROM HEMANGIOBLASTOMAS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Choi, C. Y., Gibbs, I. C., Adler, J. R., Chang, S. D., Lieberson, R. E., Soltys, S. G. 2011; 80 (1): 213-220

Abstract

To evaluate spinal cord dose-volume effects, we present a retrospective review of stereotactic radiosurgery (SRS) treatments for spinal cord hemangioblastomas.From November 2001 to July 2008, 27 spinal hemangioblastomas were treated in 19 patients with SRS. Seventeen tumors received a single fraction with a median dose of 20 Gy (range, 18-30 Gy). Ten lesions were treated using 18-25 Gy in two to three sessions. Cord volumes receiving 8, 10, 12, 14, 16, 18, 20, 22, and 24 Gy and dose to 10, 100, 250, 500, 1000, and 2000 mm(3) of cord were determined. Multisession treatments were converted to single-fraction biologically effective dose (SFBED).Single-fraction median cord D(max) was 22.7 Gy (range, 17.8-30.9 Gy). Median V10 was 454 mm(3) (range, 226-3543 mm(3)). Median dose to 500 mm(3) cord was 9.5 Gy (range, 5.3-22.5 Gy). Fractionated median SFBED(3) cord D(max) was 14.1 Gy(3) (range, 12.3-19.4 Gy(3)). Potential toxicities included a Grade 2 unilateral foot drop 5 months after SRS and 2 cases of Grade 1 sensory deficits. The actuarial 3-year local tumor control estimate was 86%.Despite exceeding commonly cited spinal cord dose constraints, SRS for spinal hemangioblastomas is safe and effective. Consistent with animal experiments, these data support a partial-volume tolerance model for the human spinal cord. Because irradiated cord volumes were generally small, application of these data to other clinical scenarios should be made cautiously. Further prospective studies of spinal radiosurgery are needed.

View details for DOI 10.1016/j.ijrobp.2010.01.040

View details for Web of Science ID 000290006300031

View details for PubMedID 21481724

Predictors of Clinical and Angiographic Outcome After Surgical or Endovascular Therapy of Very Large and Giant Intracranial Aneurysms NEUROSURGERY Darsaut, T. E., Darsaut, N. M., Chang, S. D., Silverberg, G. D., Shuer, L. M., Tian, L., Dodd, R. L., Do, H. M., Marks, M. P., Steinberg, G. K. 2011; 68 (4): 903-915

Abstract

Risk factors for poor outcome in the treatment of very large (?20-24 mm) and giant (?25 mm) intracranial aneurysms remain incompletely defined.To present an aggregate clinical series detailing a 24-year experience with very large and giant aneurysms to identify and assess the relative importance of various patient, aneurysm, and treatment-specific characteristics associated with clinical and angiographic outcomes.The authors retrospectively identified 184 aneurysms measuring 20 mm or larger (85 very large, 99 giant) treated at Stanford University Medical Center between 1984 and 2008. Clinical data including age, presentation, and modified Rankin Scale (mRS) score were recorded, along with aneurysm size, location, and morphology. Type of treatment was noted and clinical outcome measured using the mRS score at final follow-up. Angiographic outcomes were completely occluded, occluded with residual neck, partly obliterated, or patent with modified flow.After multivariate analysis, risk factors for poor clinical outcome included a baseline mRS score of 2 or higher (odds ratio [OR], 0.23; 95% confidence interval [CI]: 0.08-0.66; P = .01), aneurysm size of 25 mm or larger (OR, 3.32; 95% CI: 1.51-7.28; P < .01), and posterior circulation location (OR, 0.18; 95% CI: 0.07-0.43; P < .01). Risk factors for incomplete angiographic obliteration included fusiform morphology (OR, 0.25; 95% CI: 0.10-0.66; P < .01), posterior circulation location (OR, 0.33; 95% CI: 0.13-0.83; P = .02), and endovascular treatment (OR, 0.14; 95% CI: 0.06-0.32; P < .01). Patients with incompletely occluded aneurysms experienced higher rates of posttreatment subarachnoid hemorrhage and had increased mortality compared with those with completely obliterated aneurysms.Our results suggest that patients with poor baseline functional status, giant aneurysms, and aneurysms in the posterior circulation had a significantly higher proportion of poor outcomes at final follow-up. Fusiform morphology, posterior circulation location, and endovascular treatment were risk factors for incompletely obliterated aneurysms.

View details for DOI 10.1227/NEU.0b013e3182098ad0

View details for Web of Science ID 000288123100038

View details for PubMedID 21221025

TECHNIQUE FOR TARGETING ARTERIOVENOUS MALFORMATIONS USING FRAMELESS IMAGE-GUIDED ROBOTIC RADIOSURGERY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hristov, D., Liu, L., Adler, J. R., Gibbs, I. C., Moore, T., Sarmiento, M., Chang, S. D., Dodd, R., Marks, M., Do, H. M. 2011; 79 (4): 1232-1240

Abstract

To integrate three-dimensional (3D) digital rotation angiography (DRA) and two-dimensional (2D) digital subtraction angiography (DSA) imaging into a targeting methodology enabling comprehensive image-guided robotic radiosurgery of arteriovenous malformations (AVMs).DRA geometric integrity was evaluated by imaging a phantom with embedded markers. Dedicated DSA acquisition modes with preset C-arm positions were configured. The geometric reproducibility of the presets was determined, and its impact on localization accuracy was evaluated. An imaging protocol composed of anterior-posterior and lateral DSA series in combination with a DRA run without couch displacement between acquisitions was introduced. Software was developed for registration of DSA and DRA (2D-3D) images to correct for: (a) small misalignments of the C-arm with respect to the estimated geometry of the set positions and (b) potential patient motion between image series. Within the software, correlated navigation of registered DRA and DSA images was incorporated to localize AVMs within a 3D image coordinate space. Subsequent treatment planning and delivery followed a standard image-guided robotic radiosurgery process.DRA spatial distortions were typically smaller than 0.3 mm throughout a 145-mm 145-mm 145-mm volume. With 2D-3D image registration, localization uncertainties resulting from the achievable reproducibility of the C-arm set positions could be reduced to about 0.2 mm. Overall system-related localization uncertainty within the DRA coordinate space was 0.4 mm. Image-guided frameless robotic radiosurgical treatments with this technique were initiated.The integration of DRA and DSA into the process of nidus localization increases the confidence with which radiosurgical ablation of AVMs can be performed when using only an image-guided technique. Such an approach can increase patient comfort, decrease time pressure on clinical and technical staff, and possibly reduce the number of cerebral angiograms needed for a particular patient.

View details for DOI 10.1016/j.ijrobp.2010.05.015

View details for Web of Science ID 000288471500036

View details for PubMedID 20801584

ECTOPIC ACROMEGALY DUE TO A PANCREATIC NEUROENDOCRINE TUMOR PRODUCING GROWTH HORMONE-RELEASING HORMONE ENDOCRINE PRACTICE Weiss, D. E., Vogel, H., Lopes, M. B., Chang, S. D., Katznelson, L. 2011; 17 (1): 79-84

Abstract

To present a case of acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion from a pancreatic neuroendocrine tumor in the context of multiple endocrine neoplasia type 1 (MEN 1).We describe the clinical, imaging, and pathologic findings of the study patient.A 46-year-old woman presented with clinical and biochemical findings diagnostic of acromegaly. Magnetic resonance imaging showed a 1.2-cm sellar mass. Following resection of the macroadenoma, serum insulin-like growth factor 1 (IGF-1) and growth hormone (GH) levels remained unchanged. Pathologic examination revealed adenomatous changes, including a nonsecretory focus and a prolactin immunopositive area (GH stain negative in both). Octreotide long-acting release was ineffective. Search for an ectopic tumor included normal octreoscan and abdominal computed tomography. GHRH was greater than 1000 pg/mL. Repeated abdominal computed tomography documented a 6.2-cm mass in the tail and body of the pancreas. Distal pancreatectomy revealed a pancreatic neuroendocrine tumor that stained positive for GHRH. Postoperatively, serum GHRH and IGF-1 normalized. Re-evaluation of the initial pituitary pathologic specimen revealed additional somatotroph hyperplasia of the adjacent, normal pituitary gland. Primary hyperparathyroidism was diagnosed, and multigland parathyroid hyperplasia was noted at surgery. Genetic testing was positive for a mutation in the MEN1 gene.This patient's acromegaly was resistant to somatostatin analogue therapy, reflecting the negative octreoscan imaging. In addition, this case is novel because the patient presented with pituitary adenomatous changes, which were presumably associated with MEN 1 and/or possibly the elevated GHRH levels.

View details for DOI 10.4158/EP10165.CR

View details for Web of Science ID 000289272700011

View details for PubMedID 20713338

Cyberknife Stereotactic Radiosurgery for Treatment of Atypical (Who Grade II) Cranial Meningiomas NEUROSURGERY Choi, C. Y., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Jackson, P. S., Lieberson, R. E., Chang, S. D., Adler, J. R. 2010; 67 (5): 1180-1188

Abstract

The optimal management of subtotally resected atypical meningiomas is unknown.To perform a retrospective review of patients with residual or recurrent atypical meningiomas treated with stereotactic radiosurgery (SRS).Twenty-five patients were treated, either immediately after surgery (n = 15) or at the time of radiographic progression or treatment failure (n = 10). SRS was delivered to with a median marginal dose of 22 Gy (range, 16-30) in 1 to 4 fractions (median, 1), targeting a median tumor volume of 5.3 cm (range, 0.3-26.0).With a median follow-up time of 28 months (range, 3-67), the 12-, 24-, and 36-month actuarial local and regional control rates for all patients were 94%, 94%, 74%, and 90%, 90%, 62%, respectively. There were 2 cases of radiation toxicity. On univariate analysis, the number of recurrences before SRS (P = .046), late SRS (ie, waiting until tumor progression to initiate treatment) (P = .03), and age at treatment ? 60 years (P = .01) were significant predictors of recurrence. Of the 20 radiation-nave patients, 2 patients failed with the targeted lesion and 3 elsewhere in the resection bed, resulting in 12-, 24- and 36-month actuarial local and regional control rates of 100%, 100%, 73% and 93%, 93%, 75%, respectively. The overall locoregional control rates at 12, 24, and 36 months were 93%, 93%, and 54%, respectively.Irradiation of the entire postoperative tumor bed may not be necessary for the majority of patients with subtotally resected atypical meningiomas. Patients in this series achieved outcomes comparable to that of historical control rates for larger volume, conventionally fractionated radiotherapy.

View details for DOI 10.1227/NEU.0b013e3181f2f427

View details for Web of Science ID 000283479500003

View details for PubMedID 20871435

STEREOTACTIC RADIOSURGERY FOR TREATMENT OF SPINAL METASTASES RECURRING IN CLOSE PROXIMITY TO PREVIOUSLY IRRADIATED SPINAL CORD INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Jackson, P. S., Minn, A. Y., Lieberson, R. E., Soltys, S. G. 2010; 78 (2): 499-506

Abstract

As the spinal cord tolerance often precludes reirradiation with conventional techniques, local recurrence within a previously irradiated field presents a treatment challenge.We retrospectively reviewed 51 lesions in 42 patients treated from 2002 to 2008 whose spinal metastases recurred in a previous radiation field (median previous spinal cord dose of 40 Gy) and were subsequently treated with stereotactic radiosurgery (SRS).SRS was delivered to a median marginal dose of 20 Gy (range, 10-30 Gy) in 1-5 fractions (median, 2), targeting a median tumor volume of 10.3 cm(3) (range, 0.2-128.6 cm(3)). Converting the SRS regimens with the linear quadratic model (?/? = 3), the median spinal cord maximum single-session equivalent dose (SSED) was 12.1 Gy(3) (range, 4.7-19.3 Gy(3)). With a median follow-up of 7 months (range, 2-47 months), the Kaplan-Meier local control and overall survival rates at 6/12 months were 87%/73% and 81%/68%, respectively. A time to retreatment of ?12 months and the combination of time to retreatment of ?12 months with an SSED of <15 Gy(10) were significant predictors of local failure on univariate and multivariate analyses. In patients with a retreatment interval of <12 months, 6/12 month local control rates were 88%/58%, with a SSED of >15 Gy(10), compared to 45%/0% with <15 Gy(10), respectively. One patient (2%) experienced Grade 4 neurotoxicity.SRS is safe and effective in the treatment of spinal metastases recurring in previously irradiated fields. Tumor recurrence within 12 months may correlate with biologic aggressiveness and require higher SRS doses (SSED >15 Gy(10)). Further research is needed to define the partial volume retreatment tolerance of the spinal cord and the optimal target dose.

View details for DOI 10.1016/j.ijrobp.2009.07.1727

View details for Web of Science ID 000282147000028

View details for PubMedID 20133079

Frameless image guided robotic radiosurgery of arteriovenous malformation localized on spatially correlated digital subtraction and C-arm CT angiography images JOURNAL OF NEUROINTERVENTIONAL SURGERY Hristov, D., Adler, J. R., Gibbs, I. C., Dodd, R., Marks, M., Chang, S. D., Do, H. M. 2010; 2 (3): 252-254

Abstract

A case is reported of frameless image guided robotic radiosurgery for an arteriovenous malformation (AVM). C-arm CT (CACT) and concurrent digital subtraction angiography images were used for AVM localization within the CACT volume. Treatment planning was performed on CT images registered with the CACT dataset. During delivery, a robotic linear accelerator tracked the target based on localization with frequent stereoscopic x-ray imaging. This case demonstrates that a frameless approach to AVM radiosurgery is possible.

View details for DOI 10.1136/jnis.2009.001941

View details for Web of Science ID 000281357900019

View details for PubMedID 21990637

The role of radiosurgery in the treatment of craniopharyngiomas NEUROSURGICAL FOCUS Veeravagu, A., Lee, M., Jiang, B., Chang, S. D. 2010; 28 (4)

Abstract

The treatment of craniopharyngiomas is composed of an intricate balance of multiple modalities. Resection and radiotherapy have been combined to synergistically control tumor growth while preventing undue harm to crucial neurovascular structures. Although a craniopharyngioma is a benign lesion pathologically, it may induce severe neurological injury due to its location and rate of growth. More recently, the advent of targeted, fractionated radiotherapy has allowed for more aggressive tumor control while reducing the necessity for large resections. Initial studies have demonstrated significant tumor control in patients who are treated with resection combined with radiation therapy, versus surgery alone, with a lower rate of treatment-associated neurological deficits. In this review, a detailed account of the current studies evaluating the role of stereotactic radiosurgery in the management of craniopharyngiomas is presented. The authors also provide a short account of their experience to aid in defining the role of CyberKnife radiosurgery.

View details for DOI 10.3171/2010.2.FOCUS09311

View details for Web of Science ID 000276212900014

View details for PubMedID 20367355

Peritumoral edema after stereotactic radiosurgery for meningioma JOURNAL OF CLINICAL NEUROSCIENCE Hsieh, C., Tsai, J., Chang, L., Lin, J., Chang, S. D., Ju, D. 2010; 17 (4): 529-531

Abstract

Peritumoral edema induced by radiosurgery after the treatment of intracranial meningioma has been reported and its mechanism remains unclear. A 65-year-old woman presented with a history of intermittent dizziness. A CT scan and MRI of the brain revealed an extra-axial space-occupying lesion in the left frontal region. She was treated by stereotactic radiosurgery (SRS). Seven months later, the patient began experiencing general weakness and drowsiness. She developed peritumoral edema around the left frontal tumor. Similarly, a 55-year-old woman complained of unstable gait and dizziness 1 month prior to admission. A CT scan and MRI of the brain revealed an extra-axial space-occupying lesion in the right posterior temporal region. Six months after SRS, this patient experienced deteriorated consciousness and general weakness. Peritumoral edema in the right temporal region was noted. We report these two patients, discuss possible causes and review the relevant literature.

View details for DOI 10.1016/j.jocn.2009.06.035

View details for Web of Science ID 000276014600030

View details for PubMedID 20116255

SUCCESSFUL TREATMENT OF METASTATIC BRAIN TUMOR BY CYBERKNIFE: A CASE REPORT KAOHSIUNG JOURNAL OF MEDICAL SCIENCES Hsieh, C., Chang, C., Liu, M., Chang, L., Hueng, D., Chang, S. D., Ju, D. 2010; 26 (3): 144-149

Abstract

Stereotactic radiosurgery plays an important role in management of metastatic brain tumors, especially when the tumor has recurred after treatment with previous whole brain radiotherapy. Most metastatic brain tumors less than 1 cm(3) show a complete response after stereotactic radio-surgery. However, there are few reports of a dramatic change in the complete response of large metastatic brain tumors. Here, we report a case of adenocarcinoma of lung that had metastasized to the brain. Because the recurrence of the metastatic brain tumor measured approximately 3 cm in diameter, the tumor was previously treated with two prior craniotomies followed by whole brain radiation to the resection cavity. The tumor subsequently recurred and was treated with stereotactic radiosurgery (CyberKnife). A dramatic response was noted 3 months after radiosurgery with complete disappearance of the recurrent tumor.

View details for Web of Science ID 000276378800005

View details for PubMedID 20227654

Clinical Management of Patients with Temporal Lobe Necrosis Krakow, T. E., Hara, W., Yun, S., Soltys, S., Chang, S., Fischbein, N., Loo, B., Le, Q. ELSEVIER SCIENCE INC. 2010: S455-S455
Survival following Stereotactic Radiosurgery for Newly Diagnosed and Recurrent Glioblastoma Multiforme: A Multicenter Experience RADIOSURGERY, VOL 7 Villavicencio, A. T., Burneikiene, S., Romanelli, P., McNeely, L., Lipani, J. D., Fariselli, L., McIntyre, M., Chang, S. D., Nelson, E. L., Broggi, G., Adler, J. R., Thramann, J. J. 2010; 7: 288-299
Stereotactic Radiosurgery of the Post-operative Resection Cavity for Brain Metastases: Optimization of the Treatment Technique Soltys, S. G., Gibbs, I. C., Chang, S. D., Adler, J. R., Harsh, G. R., LIEBERSON, R. E., Choi, C. Y. ELSEVIER SCIENCE INC. 2010: S7-S7
Radiosurgery of Glomus Jugulare Tumors: A Meta-analysis Guss, Z. D., Batra, S., Li, G., Chang, S. D., Parsa, A. T., Rigamonti, D., Kleinberg, L., Lim, M. ELSEVIER SCIENCE INC. 2010: S288-S289
Radiosurgery for glomus jugulare: history and recent progress NEUROSURGICAL FOCUS Guss, Z. D., Batra, S., Li, G., Chang, S. D., Parsa, A. T., Rigamont, D., Kleinberg, L., Lim, M. 2009; 27 (6)

Abstract

In this article the authors review the literature for recent studies of radiosurgical treatment for glomus jugulare. These studies demonstrate that radiosurgery results in similar glomus jugulare tumor control and a superior morbidity profile compared with surgical treatment. In addition, patients treated with radiosurgery usually remain stable clinically or improve. Given the indolent nature of these tumors, however, more follow-up is required to ensure that the immediate benefits are lasting. These preliminary reports demonstrate that the use of radiosurgery as a primary treatment for glomus jugulare should be extended to encompass more of the patients who are currently assigned to microsurgical treatment.

View details for DOI 10.3171/2009.9.FOCUS09195

View details for Web of Science ID 000272301500007

View details for PubMedID 19951058

MULTISESSION CYBERKNIFE STEREOTACTIC RADIOSURGERY OF LARGE, BENIGN CRANIAL BASE TUMORS: PRELIMINARY STUDY NEUROSURGERY Tuniz, F., Soltys, S. G., Choi, C. Y., Chang, S. D., Gibbs, I. C., Fischbein, N. J., Adler, J. R. 2009; 65 (5): 898-907

Abstract

Although radiosurgery plays an important role in managing benign cranial base lesions, the potential for increased toxicity with single-session treatment of large tumors is a concern. In this retrospective study, we report the intermediate-term rate of local control, morbidity, and clinical outcomes of patients with large cranial base tumors treated with multisession stereotactic radiosurgery with the CyberKnife (Accuray, Inc., Sunnyvale, CA).Between 1999 and 2008, 34 consecutive patients with large (>15 cm), benign cranial base tumors (21 meningiomas, 9 schwannomas, 4 glomus jugulare tumors) underwent primary or postoperative radiosurgical treatment using a multisession approach at Stanford University and were considered in this retrospective study. Forty-four percent of these patients had undergone previous subtotal surgical resection or radiotherapy. CyberKnife radiosurgery was delivered in 2 to 5 sessions (median, 3 sessions) to a median tumor volume of 19.3 cm (range, 15.8-69.3 cm). The median marginal dose was 24 Gy (range, 18-25 Gy) prescribed to a median 78% isodose line.After a median clinical follow-up of 31 months (range, 12-77 months), 21% of patients experienced clinical improvement of neurological symptoms, whereas neurological status remained unchanged among the rest. Four patients experienced prolonged use of glucocorticoids owing to transient neurological worsening and radiographic signs of radiation injury. No permanent neurotoxicity was seen. To date, all tumors remain locally controlled.Over our modest length of follow-up, multisession radiosurgery appears to be a safe and effective option for selected large, benign brain and cranial base lesions.

View details for DOI 10.1227/01.NEU.0000359316.34041.A8

View details for Web of Science ID 000270876100013

View details for PubMedID 19834402

Survival following stereotactic radiosurgery for newly diagnosed and recurrent glioblastoma multiforme: a multicenter experience NEUROSURGICAL REVIEW Villavicencio, A. T., Burneikiene, S., Romanelli, P., Fariselli, L., McNeely, L., Lipani, J. D., Chang, S. D., Nelson, E. L., McIntyre, M., Broggi, G., Adler, J. R. 2009; 32 (4): 417-424

Abstract

Despite decades of clinical trials investigating new treatment modalities for glioblastoma multiforme (GBM), there have been no significant treatment advances since the 1980s. Reported median survival times for patients with GBM treated with current modalities generally range from 9 to 19 months. The purpose of the current study is to retrospectively review the ability of CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA) radiosurgery to provide local tumor control of newly diagnosed or recurrent GBM. Twenty patients (43.5%) underwent CyberKnife treatment at the time of the initial diagnosis and/or during the first 3 months of their initial clinical management. Twenty-six patients (56.5%) were treated at the time of tumor recurrence or progression. CyberKnife was performed in addition to the traditional therapy. The median survival from diagnosis for the patients treated with CyberKnife as an initial clinical therapy was 11.5 months (range, 2-33) compared to 21 months (range, 8-96) for the patients treated at the time of tumor recurrence/progression. This difference was statistically significant (Kaplan-Meier analysis, P = 0.0004). The median survival from the CyberKnife treatment was 9.5 months (range, 0.25-31 months) and 7 months (range, 1-34 months) for patients in the newly diagnosed and recurrent GBM groups (Kaplan-Meier analysis, P = 0.79), respectively. Cox proportional hazards survival regression analysis demonstrated that survival time did not correlate significantly with treatment parameters (Dmax, Dmin, number of fractions) or target volume. Survival time and recursive partitioning analysis class were not correlated (P = 0.07). Patients with more extensive surgical interventions survived longer (P = 0.008), especially those who underwent total tumor resection vs. biopsy (P = 0.004). There is no apparent survival advantage in using CyberKnife in initial management of glioblastoma patients, and it should be reserved for patients whose tumors recur or progress after conventional therapy.

View details for DOI 10.1007/s10143-009-0212-6

View details for Web of Science ID 000269860300009

View details for PubMedID 19633875

Non-surgical management of hormone-secreting pituitary tumors JOURNAL OF CLINICAL NEUROSCIENCE Patil, C. G., Hayden, M., Katznelson, L., Chang, S. D. 2009; 16 (8): 985-993

Abstract

Hormone-secreting pituitary tumors account for about 30% of all pituitary tumors. Successful long-term management of patients with these tumors frequently requires a multimodality team approach. Given that the role and efficacy of neurosurgical resection of hormone-secreting pituitary tumors is well described, we focus this review on the other important treatment modalities that are becoming increasingly crucial in the management of acromegaly, Cushing's disease and prolactinomas. Medical management with standard and novel drugs as well as the role and effectiveness of radiation therapy and radiosurgery are discussed in detail.

View details for DOI 10.1016/j.jocn.2008.11.001

View details for Web of Science ID 000268608000001

View details for PubMedID 19443220

STEREOTACTIC RADIOSURGICAL TREATMENT OF CRANIAL AND SPINAL HEMANGIOBLASTOMAS NEUROSURGERY Moss, J. M., Choi, C. Y., Adler, J. R., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2009; 65 (1): 79-85

Abstract

Stereotactic radiosurgery has been used for nearly 2 decades to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. There is a paucity of long-term published radiosurgical treatment outcomes, particularly for spinal lesions, in a large patient population. The purpose of this study was to provide a long-term retrospective evaluation of radiosurgical hemangioblastoma treatment effectiveness, with a special emphasis on the relatively recent use of frameless, image-guided radiosurgery in the treatment of spinal lesions.From 1991 to 2007, 92 hemangioblastomas in 31 patients, 26 with von Hippel-Lindau disease, were treated with radiosurgery (27 tumors treated with frame-based linear accelerator radiosurgery, and 67 tumors were treated with CyberKnife radiosurgery). The mean patient age was 41 years (range, 18-81 years). The radiation dose to the tumor periphery averaged 23.4 Gy (range, 12-40 Gy). The mean tumor volume was 1.8 cm (range, 0.058-65.4 cm). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic, and magnetic resonance imaging scans.Clinical and radiographic follow-up data were available for 82 hemangioblastoma tumors. Only 13 (16%) of the treated hemangioblastomas progressed, whereas 18 tumors (22%) showed radiographic regression, and 51 tumors (62%) remained unchanged in size. With median follow-up of 69 months (range, 5-164 months), the actuarial local control rates at 36 and 60 months were 85% and 82%, respectively. Radiosurgery improved lesion-associated symptoms in 36 of 41 tumors. During the follow-up period, 9 patients died of causes unrelated to the progression of their treated hemangioblastomas, and 5 patients developed radiation necrosis.Stereotactic radiosurgery is safe and effective in the treatment of hemangioblastomas and is an attractive alternative to surgery for patients, including those with von Hippel-Lindau disease.

View details for DOI 10.1227/01.NEU.0000348015.51685.D2

View details for Web of Science ID 000268265600010

View details for PubMedID 19574828

Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course NEUROSURGICAL FOCUS Achrol, A. S., Guzman, R., Varga, M., Adler, J. R., Steinberg, G. K., Chang, S. D. 2009; 26 (5)

Abstract

Brain arteriovenous malformations (BAVMs) are an important cause of intracerebral hemorrhage (ICH) in young adults. Biological predictors of future ICH risk are lacking, and controversy exists over previous studies of natural history risk among predominantly ruptured BAVM cohorts. Recent studies have suggested that the majority of BAVMs are now diagnosed as unruptured lesions, and that the risk according to natural history among these lesions may be less than previously assumed. In the first part of this review, the authors discuss available data on the natural history of BAVMs and highlight the need for future studies that aim to develop surrogate biomarkers of disease progression that accurately predict future risk of ICH in BAVMs. The etiology of BAVM remains unknown. Recent studies have suggested a role for genetic factors in the pathogenesis of sporadic BAVM, which is further supported by reports of familial occurrence of BAVM and association with known systemic genetic disorders (such as Osler-Weber-Rendu disease, Sturge-Weber disease, and Wyburn-Mason syndrome). Molecular characterization of BAVM tissue demonstrates a highly angiogenic milieu with evidence of increased endothelial cell turnover. Taken together with a number of reports of de novo BAVM formation, radiographic growth after initial BAVM diagnosis, and regrowth after successful treatment of BAVM, these findings challenge the long-held assumption that BAVMs are static lesions of congenital origin. In the second part of this review, the authors discuss available data on the origins of BAVM and offer insights into future investigations into genetics and endothelial progenitor cell involvement in the pathogenesis of BAVM. Current treatment options for BAVM focus on removal or obliteration of the lesion in an attempt to protect against future ICH risk, including microsurgical resection, endovascular embolization, and stereotactic radiosurgery (SRS). In the third part of this review, the authors discuss available data on SRS in BAVMs and highlight the need for future studies on the radiobiology of BAVMs, especially in regard to biomarker detection for tracking SRS response during the latency period. Insights from future investigations in BAVM may not only prove important for the development of novel therapies and relevant biomarkers for BAVM, but could also potentially benefit a variety of other disorders involving new vessel formation in the CNS, including stroke, tumors, moyamoya disease, and other cerebrovascular malformations.

View details for DOI 10.3171/2009.2.FOCUS0926

View details for Web of Science ID 000265656800009

View details for PubMedID 19409010

CYBERKNIFE FOR BRAIN METASTASES OF MALIGNANT MELANOMA AND RENAL CELL CARCINOMA NEUROSURGERY Hara, W., Tran, P., Li, G., Su, Z., Puataweepong, P., Adler, J. R., Soltys, S. G., Chang, S. D., Gibbs, I. C. 2009; 64 (2): A26-A32

Abstract

To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with brain metastases of malignant melanoma and renal cell carcinoma.We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between March 1999 and December 2005. Sixty-two patients with 145 brain metastases of renal cell carcinoma or melanoma were identified.The median follow-up period was 10.5 months. Forty-four patients had malignant melanoma, and 18 patients had renal cell carcinoma. The median age was 57 years, and patients were classified as recursive partitioning analysis Class 1 (6 patients), 2 (52 patients) or 3 (4 patients). Thirty-three patients had been treated systemically with either chemotherapy or immunotherapy, and 33 patients were taking corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL (range, 0.02-35.7 mL), and the mean prescribed dose was 20 Gy (range, 14-24 Gy). The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12 months was 57 and 37%, respectively. On multivariate analysis, Karnofsky Performance Scale score (P < 0.01) and previous immunotherapy/clinical trial (P = 0.01) significantly affected overall survival. One-year intracranial progression-free survival was 38%, and local control was 87%. Intracranial control was impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P = 0.01), and control of the primary at the time of SRS (P = 0.02). Surgical resection had no effect on intracranial or local control. Radiographic evidence of radiation necrosis developed in 4 patients (6%).CyberKnife radiosurgery provided excellent local control with acceptable toxicity in patients with melanoma or renal cell brain metastases. Initial SRS alone appeared to be a reasonable option, as survival was dictated by systemic disease.

View details for DOI 10.1227/01.NEU.0000339118.55334.EA

View details for Web of Science ID 000262797700009

View details for PubMedID 19165071

CYBERKNIFE IMAGE-GUIDED RADIOSURGERY FOREWORD NEUROSURGERY Adler, J. R., Chang, S. D. 2009; 64 (2): A1-A1
COST-UTILITY ANALYSIS OF THE CYBERKNIFE SYSTEM FOR METASTATIC SPINAL TUMORS NEUROSURGERY Papatheofanis, F. J., Williams, E., Chang, S. D. 2009; 64 (2): A73-A83

Abstract

Using decision analysis, a cost-utility study evaluated the cost-effectiveness of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) in comparison to external beam radiation therapy in the treatment of metastatic spinal malignancies.The published literature provided evidence on the effectiveness of the comparator interventions in the absence of primary outcomes data. Costs of care were derived from Centers for Medicare and Medicaid Services fee schedules. A Markov model was constructed from the payer perspective to simulate the outcomes of patients undergoing nonchemotherapeutic interventions for metastatic spinal tumors. Because cancer therapies bear significant health and economic consequences, the impact of treatment-related toxicities was integrated into the model. Given the terminal nature of these conditions and the limited life expectancy of the patient population, the time horizon for the analysis was limited to 12 months.Patients treated with CyberKnife SRS gained an additional net health benefit of 0.08 quality-adjusted life year; the calculated cost of CyberKnife SRS was $1933 less than external beam radiation therapy for comparable effectiveness. The incremental cost per benefit for this strategy ($41 500 per quality-adjusted life year) met payers' willingness-to-pay criteria.Cost-utility analysis demonstrated that CyberKnife SRS was a superior, cost-effective primary intervention for patients with metastatic spinal tumors compared with conventional external beam radiation therapy.

View details for DOI 10.1227/01.NEU.0000341205.37067.DE

View details for Web of Science ID 000262797700015

View details for PubMedID 19165078

CYBERKNIFE STEREOTACTIC RADIOSURGICAL RHIZOTOMY FOR TRIGEMINAL NEURALGIA: ANATOMIC AND MORPHOLOGICAL CONSIDERATIONS NEUROSURGERY Borchers, J. D., Yang, H., Sakamoto, G. T., Howes, G. A., Gupta, G., Chang, S. D., Adler, J. R. 2009; 64 (2): A91-A95

Abstract

To search for correlations between specific anatomic, geometric, and morphological properties of the trigeminal nerve and the success of radiosurgical treatment and elimination of facial hypesthesia as a complication.Forty-six patients with at least 6 months of follow-up after CyberKnife (Accuray, Inc., Sunnyvale, CA) rhizotomy were retrospectively reviewed. Patients treated after 2004 were entered into the study after congruity in treatment parameters was established. Anatomic variations regarding the length of each nerve segment and angle of trigeminal nerve takeoff from brainstem to Meckel's cave in the axial and sagittal planes were studied. Dose distribution to surrounding critical structures (brainstem and trigeminal ganglion) was measured. After spatial relationships of involved structures and dose distributions were recorded, their relationship to treatment success, failure, or complication (primarily facial numbness) was tabulated.Forty-five patients (97.2%) experienced pain relief immediately or within weeks. Thirty-four patients maintained excellent outcome. Some degree of facial numbness developed in 18 patients (39.1%) and was mild in 11 of them (Grade II on the Barrow Neurological Institute scale). Patients with a sagittal-angle trigeminal nerve takeoff from the brainstem in the range of 150 to 170 degrees measured from the horizontal plane had a more favorable outcome (P = 0.03) than patients with less obtuse relationships to the proximal nerve origin. Patients who received higher doses of radiation to the brainstem/dorsal root entry zone of the trigeminal nerve experienced a higher rate of posttreatment facial anesthesia.There may be important anatomic and geometric relationships between the treated trigeminal nerve and surrounding critical structures that warrant pretreatment target volume placement and dose distribution considerations.

View details for DOI 10.1227/01.NEU.0000340795.87734.70

View details for Web of Science ID 000262797700017

View details for PubMedID 19165080

FORAMINAL NERVE SHEATH TUMORS: INTERMEDIATE FOLLOW-UP AFTER CYBERKNIFE RADIOSURGERY NEUROSURGERY Murovic, J. A., Gibbs, I. C., Chang, S. D., Mobley, B. C., Park, J., Adler, J. R. 2009; 64 (2): A33-A43

Abstract

To conduct a retrospective review of outcomes in 15 patients with 18 foraminal tumors, including 17 benign peripheral nerve sheath tumors and 1 malignant peripheral nerve sheath tumor, who underwent CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery at Stanford University Medical Center from 1999 to 2006.Symptoms and findings, neurofibromatosis (NF) association, previous radiation, imaging, dosimetry, tumor volume, central necrosis, and the relation of these factors to outcomes were evaluated.Before treatment, 1 asymptomatic patient had radiculopathic findings, 3 patients experienced local pain with intact neurological examinations, and 7 patients had radiculopathic complaints with intact (1 patient), radiculopathic (4 patients), or radiculomyelopathic examinations (2 patients). Five patients had myelopathic complaints and findings. Three patients had NF1-associated neurofibromas, 1 patient with NF2 had a schwannoma, and 1 patient had a schwannomatosis-related lesion. Two likely radiation-induced lesions, a neurofibroma and a malignant peripheral nerve sheath tumor, were observed. Prescribed doses ranging from 16 to 24 Gy, delivered in 1 to 3 fractions of 6 to 20 Gy, resulted in maximum tumor doses ranging from 20.9 to 30 Gy. Target volumes ranged from 1.36 to 16.9 mL. After radiosurgery, the asymptomatic case remained asymptomatic, and neurological findings improved. Thirteen of 15 symptomatic patients with (12 patients) or without (3 patients) neurological findings improved (3 cases after resection) or remained stable, and 2 patients worsened. Symptoms and examinations remained stable or improved in 8 (80%) of 10 patients with schwannomas and 3 (60%) of 5 patients with neurofibromas. Tumor volumes decreased in 12 (67%) of 18 tumors and increased in 3 tumors. Tumor volumes decreased in 8 of 10 schwannomas and 3 of 7 neurofibromas. Central necrosis developed in 8 (44%) of 18 tumors.CyberKnife radiosurgery resulted in pain relief and functional preservation in selected foraminal peripheral nerve sheath tumors and a malignant peripheral nerve sheath tumor. Symptomatic and neurological improvements were more noticeable with schwannomas. Myelopathic symptoms may necessitate surgical debulking before radiosurgery.

View details for DOI 10.1227/01.NEU.0000341632.39692.9E

View details for Web of Science ID 000262797700010

View details for PubMedID 19165072

NONISOCENTRIC RADIOSURGICAL RHIZOTOMY FOR TRIGEMINAL NEURALGIA NEUROSURGERY Adler, J. R., Bower, R., Gupta, G., Lim, M., Efron, A., Gibbs, I. C., Chang, S. D., Soltys, S. G. 2009; 64 (2): A84-A90

Abstract

Although stereotactic radiosurgery is an established procedure for treating trigeminal neuralgia (TN), the likelihood of a prompt and durable complete response is not assured. Moreover, the incidence of facial numbness remains a challenge. To address these limitations, a new, more anatomic radiosurgical procedure was developed that uses the CyberKnife (Accuray, Inc., Sunnyvale, CA) to lesion an elongated segment of the retrogasserian cisternal portion of the trigeminal sensory root. Because the initial experience with this approach resulted in an unacceptably high incidence of facial numbness, a gradual dose and volume de-escalation was performed over several years. In this single-institution prospective study, we evaluated clinical outcomes in a group of TN patients who underwent lesioning with seemingly optimized nonisocentric radiosurgical parameters.Forty-six patients with intractable idiopathic TN were treated between January 2005 and June 2007. Eligible patients were either poor surgical candidates or had failed previous microvascular decompression or destructive procedures. During a single radiosurgical session, a 6-mm segment of the affected nerve was treated with a mean marginal prescription dose of 58.3 Gy and a mean maximal dose of 73.5 Gy. Monthly neurosurgical follow-up was performed until the patient became pain-free. Longer-term follow-up was performed both in the clinic and over the telephone. Outcomes were graded as excellent (pain-free and off medication), good (>90% improvement while still on medication), fair (50-90% improvement), or poor (no change or worse). Facial numbness was assessed using the Barrow Neurological Institute Facial Numbness Scale score.Symptoms disappeared completely in 39 patients (85%) after a mean latency of 5.2 weeks. In most of these patients, pain relief began within the first week. TN recurred in a single patient after a pain-free interval of 7 months; all symptoms abated after a second radiosurgical procedure. Four additional patients underwent a repeat rhizotomy after failing to respond adequately to the first operation. After a mean follow-up period of 14.7 months, patient-reported outcomes were excellent in 33 patients (72%), good in 11 patients (24%), and poor/no improvement in 2 patients (4%). Significant ipsilateral facial numbness (Grade III on the Barrow Neurological Institute Scale) was reported in 7 patients (15%).Optimized nonisocentric CyberKnife parameters for TN treatment resulted in high rates of pain relief and a more acceptable incidence of facial numbness than reported previously. Longer follow-up periods will be required to establish whether or not the durability of symptom relief after lesioning an elongated segment of the trigeminal root is superior to isocentric radiosurgical rhizotomy.

View details for DOI 10.1227/01.NEU.0000341631.49154.62

View details for Web of Science ID 000262797700016

View details for PubMedID 19165079

CYBERKNIFE RADIOSURGERY FOR TRIGEMINAL SCHWANNOMAS NEUROSURGERY Sakarnoto, G. T., Borchers, D. J., Xiao, F., Yang, H., Chang, S. D., Adler, J. R. 2009; 64 (2): A14-A18

Abstract

Trigeminal schwannomas (TS) are benign tumors that are managed by surgical resection and/or stereotactic radiosurgery. Most radiosurgical series report results using the gamma knife. The CyberKnife (Accuray, Inc., Sunnyvale, CA) is a frameless, robotic stereotactic radiosurgical system. In this series, we report our experience using the CyberKnife in the treatment of TS.We retrospectively reviewed the medical records and diagnostic imaging in 13 consecutive patients with TS who were treated with the CyberKnife from 2003 to 2007. Seven patients had a previous surgical resection. The mean tumor volume was 6.3 mL (range, 0.39-19.98 mL), and the mean marginal dose was 18.5 Gy. Six of the tumors were treated in a single session. The mean clinical follow-up period was 21.8 months (range, 7-53 months).In this series, the tumor control rate was 100%. The average reduction in tumor volume was 45% (range, 14-98%). A modest improvement in facial pain was noted in 4 of the 6 patients who presented with this symptom. One patient had improvement in facial numbness, and another had improvement in pretreatment headaches. One patient developed jaw weakness and facial dysesthesia, and another patient developed asymptomatic radiation necrosis.Although the length of follow-up is limited, we report our initial experience with CyberKnife treatment of TS. Our results demonstrate tumor control rates and clinical outcomes that parallel those of previous reports using gamma knife radiosurgery; however, long-term follow-up studies are needed.

View details for DOI 10.1227/01.NEU.0000341629.57676.DB

View details for Web of Science ID 000262797700007

View details for PubMedID 19165068

Spinal Stereotactic Radiosurgery for Metastatic Tumor Recurrence within a Prior External Beam Irradiation Field Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D., Jackson, P. S., LIEBERSON, R. E., Choi, C. Y. ELSEVIER SCIENCE INC. 2009: S126-S126
Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spine Tumors Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L. A., Gibbs, I. C. ELSEVIER SCIENCE INC. 2009: S101-S101
Stereotactic radiosurgery for a cardiac sarcoma: A case report TECHNOLOGY IN CANCER RESEARCH & TREATMENT Soltys, S. G., Kalani, M. Y., Cheshier, S. H., Szabo, K. A., Lo, A., Chang, S. D. 2008; 7 (5): 363-367

Abstract

Pulmonary artery intimal sarcoma is an uncommon tumor with a poor prognosis. We report a case of a 75-year-old man with a pulmonary artery sarcoma, recurrent following surgical resection. To palliate symptoms of this recurrence, he underwent CyberKnife stereotactic radiosurgery with a clinical and radiographic response of his treated disease. No acute or sub-acute toxicity was seen until the patient's death due to metastatic disease 10 weeks following treatment. The feasibility and short-term safety of this technique are reviewed, with emphasis on the stereotactic planning considerations, such as mediastinal organ movement and radiation tolerance.

View details for Web of Science ID 000259799000003

View details for PubMedID 18783285

Predictors of peritumoral edema after stereotactic radiosurgery of supratentorial meningiomas NEUROSURGERY Patil, C. G., Hoang, S., Borchers, D. J., Sakamoto, G., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Chang, S. D., Adler, J. R. 2008; 63 (3): 435-440

Abstract

Anecdotal evidence suggests that radiosurgical ablation of parasagittal meningiomas may be associated with increased risk of subsequent edema. Potential predictors of postradiosurgical peritumoral edema, including parasagittal tumor location, tumor size, and treatment dose, were evaluated.We retrospectively reviewed records of 102 patients with 111 supratentorial meningiomas treated with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS). A median marginal dose of 18.0 Gy (range, 11.3-25.0 Gy) was delivered in 1 to 5 sessions (fractions). Potential predictors of posttreatment symptomatic edema were evaluated using Fisher's exact test.Of the 102 patients followed for a mean of 20.9 months (range, 6-77 mo), 15 (14.7%) developed symptomatic edema after SRS. Nine of 31 with parasagittal meningiomas (29.0%) and 6 of 80 with nonparasagittal supratentorial meningiomas (7.5%) developed symptomatic edema (P = 0.0053). Compared with patients with meningiomas in nonmidline supratentorial locations, patients with parasagittal meningiomas were more than 4 times as likely to develop symptomatic edema after SRS (odds ratio, 4.1; 95% confidence interval, 1.5-11.5). The 6-, 12-, and 18-month actuarial rates of symptomatic edema development were significantly greater for patients with parasagittal meningiomas than for patients with nonparasagittal meningiomas (17.8 versus 1.3%, 25.4 versus 5.8%, and 35.2 versus 7.8%, respectively).Patients with parasagittal meningiomas are at greater risk of developing peritumoral symptomatic edema after SRS. Close follow-up after SRS may be particularly important in such patients. These results highlight the need to pursue strategies that could decrease the incidence of postradiosurgical edema in patients with parasagittal meningioma.

View details for Web of Science ID 000259625600010

View details for PubMedID 18812954

Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hara, W., Loo, B. W., Goffinet, D. R., Chang, S. D., Adler, J. R., Pinto, H. A., Fee, W. E., Kaplan, M. J., Fischbein, N. J., Le, Q. 2008; 71 (2): 393-400

Abstract

To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

View details for DOI 10.1016/j.ijrobp.2007.10.027

View details for Web of Science ID 000255971100013

View details for PubMedID 18164839

Multimodality treatment of posterior fossa arteriovenous malformations JOURNAL OF NEUROSURGERY Kelly, M. E., Guzman, R., Sinclair, J., Bell-Stephens, T. E., Bower, R., Hamilton, S., Marks, M. P., Do, H. M., Chang, S. D., Adler, J. R., Levy, R. P., Steinberg, G. K. 2008; 108 (6): 1152-1161

Abstract

Posterior fossa arteriovenous malformations (AVMs) are relatively uncommon and often difficult to treat. The authors present their experience with multimodality treatment of 76 posterior fossa AVMs, with an emphasis on Spetzler-Martin Grades III-V AVMs.Seventy-six patients with posterior fossa AVMs treated with radiosurgery, surgery, and endovascular techniques were analyzed.Between 1982 and 2006, 36 patients with cerebellar AVMs, 33 with brainstem AVMs, and 7 with combined cerebellar-brainstem AVMs were treated. Natural history data were calculated for all 76 patients. The risk of hemorrhage from presentation until initial treatment was 8.4% per year, and it was 9.6% per year after treatment and before obliteration. Forty-eight patients had Grades III-V AVMs with a mean follow-up of 4.8 years (range 0.1-18.4 years, median 3.1 years). Fifty-two percent of patients with Grades III-V AVMs had complete obliteration at the last follow-up visit. Three (21.4%) of 14 patients were cured with a single radiosurgery treatment, and 4 (28.6%) of 14 with 1 or 2 radiosurgery treatments. Twenty-one (61.8%) of 34 patients were cured with multimodality treatment. The mean Glasgow Outcome Scale (GOS) score after treatment was 3.8. Multivariate analysis performed in the 48 patients with Grades III-V AVMs showed radiosurgery alone to be a negative predictor of cure (p = 0.0047). Radiosurgery treatment alone was not a positive predictor of excellent clinical outcome (GOS Score 5; p > 0.05). Nine (18.8%) of 48 patients had major neurological complications related to treatment.Single-treatment radiosurgery has a low cure rate for posterior fossa Spetzler-Martin Grades III-V AVMs. Multimodality therapy nearly tripled this cure rate, with an acceptable risk of complications and excellent or good clinical outcomes in 81% of patients. Radiosurgery alone should be used for intrinsic brainstem AVMs, and multimodality treatment should be considered for all other posterior fossa AVMs.

View details for DOI 10.3171/JNS/2008/108/6/1152

View details for Web of Science ID 000256245300024

View details for PubMedID 18518720

Radiation therapy and CyberKnife radiosurgery in the management of craniopharyngiomas NEUROSURGICAL FOCUS Lee, M., Kalani, M. Y., Cheshier, S., Gibbs, I. C., Adler, J. R., Chang, S. D. 2008; 24 (5)

Abstract

Many benign intracranial tumors are amenable to radiotherapy treatment including meningiomas, schwannomas, pituitary tumors, and craniopharyngiomas. The authors present their experience in the treatment of craniopharyngiomas in 16 patients using frameless CyberKnife stereotactic radiosurgery (SRS). The authors discuss the role of radiation therapy in the management of these tumors, and more specifically, the role of CyberKnife SRS.Sixteen patients were treated for residual or recurrent craniopharyngioma between 2000 and 2007 with CyberKnife SRS at Stanford University Medical Center. All patients underwent magnetic resonance imaging and visual and neuroendocrine evaluations before and at regular intervals after SRS. A multisession treatment regimen and a nonisocentric treatment plan for each patient were used with a mean marginal dose of 21.6 Gy and a mean maximal dose of 29.9 Gy.There were adequate clinical data to assess outcomes in 11 of 16 patients. Evaluation of patients between 13 and 71 years of age (mean 34.5 years) with a mean follow-up period of 15.4 months revealed no deterioration in visual or neuroendocrine function. Tumor shrinkage was achieved in 7 of these 11 patients, and tumor control in another 3. One patient had cystic enlargement of the residual tumor.The authors' early experience with the application of CyberKnife SRS to residual or recurrent craniopharyngiomas has been positive; control or shrinkage of the tumor was achieved in 91% of patients, with no visual or neuroendocrine complications. Longer-term follow-up with a larger group of patients is required to fully evaluate the safety and effectiveness of this treatment modality.

View details for DOI 10.3171/FOC/2008/24/5/E4

View details for Web of Science ID 000256374300004

View details for PubMedID 18447743

The use of TLD and Gafchromic film to assure submillimeter accuracy for image-guided radiosurgery MEDICAL DOSIMETRY Ho, A. K., Gibbs, I. C., Chang, S. D., Main, B., Adler, J. R. 2008; 33 (1): 36-41

Abstract

The Cyberknife is an image-guided radiosurgical system. It uses a compact X-band 6-MV linear accelerator mounted on a robotic arm to deliver radiosurgical doses. While routine quality assurance (QA) is essential for any radiosurgery system, QA plays an even more vital role for the Cyberknife system, due to the complexity of the system and the wide range of applications. This paper presents a technique for performing quality assurance using thermoluminescence detectors (TLDs) and Gafchromic films that is intended to be specific for the Cyberknife. However, with minor modification, the proposed method can also be used for QA of other radiosurgery systems. Our initial QA procedure for the CyberKnife utilized a 30 x 30 x 11-cm solid water phantom containing a planar array of slots for 1x 1 x 1-mm TLDs on a 2-mm grid. With the objective of significantly simplifying CyberKnife QA, a new procedure for verification was developed, which uses much fewer TLDs than the prior solid water phantom technique. This new method requires only that the system target dose to the center of a cluster of 7 TLDs. In a prior study with Gafchromic films, conducted at 3 different Cyberknife facilities, the mean clinically relevant error was demonstrated to be 0.7 mm. A similar Gafchromic film analysis replicated these error measurements as part of the present investigation. It cannot be emphasized enough the importance of implementing routine QA to verify the accuracy of any radiosurgery system. Our quality assurance procedure tests the treatment planning system, as well as the entire treatment delivery including the image targeting system and the robot system. Either TLDs or Gafchromic films may be used for QA test of a radiosurgery system. Using both methods for measurement has the advantage independently verifying the accuracy of the system. This approach, which is routinely in used at our institution, has repeatedly confirmed the submillimeter targeting accuracy of our Cyberknife.

View details for DOI 10.1016/j.meddos.2007.04.009

View details for Web of Science ID 000253610200006

View details for PubMedID 18262121

Cyberknife radiosurgery for trigeminal neuralgia treatment: A preliminary multicenter experience NEUROSURGERY Villavicencio, A. T., Lim, M., Burneikiene, S., Romanelli, P., Adler, J. R., McNeely, L., Chang, S. D., Fariselli, L., McIntyre, M., Bower, R., Broggi, G., Thramann, J. J. 2008; 62 (3): 647-654

Abstract

Radiosurgery has gained acceptance as a treatment option for trigeminal neuralgia. We report our preliminary multicenter experience treating trigeminal neuralgia with the CyberKnife (Accuray, Inc., Sunnyvale, CA).A total of 95 patients were treated for idiopathic trigeminal neuralgia between May 2002 and October 2005. Radiosurgical dose and volume parameters were retrospectively analyzed in relation to pain response, complications, and recurrence of symptoms. Optimal treatment parameters were identified for patients who had excellent and sustained pain relief with no complications, including severe or moderate hypesthesia.Excellent pain relief was initially experienced by 64 out of 95 patients (67%). The median time to pain relief was 14 days (range, 0.3-180 d). Posttreatment numbness occurred in 45 (47%) of the patients treated. Using higher radiation doses and treating longer segments of the nerve led to both better pain relief and a higher incidence of hypesthesia. The presence of posttreatment numbness was predictive of better pain relief. The overall rate of complications was 18%. At the mean follow-up time of 2 years, 47 of the 95 patients (50%) had sustained pain relief, all of whom were completely off pain medications.The results of this study suggest the following optimal radiosurgical treatment parameters for treatment of idiopathic trigeminal neuralgia: a median maximal dose of 78 Gy (range, 70-85.4 Gy) and a median length of the nerve treated of 6 mm (range, 5-12 mm).

View details for DOI 10.1227/01.NEU.0000297129.08066.137

View details for Web of Science ID 000255268500023

View details for PubMedID 18425011

Visual field preservation after multisession cyberknife radiosurgery for perioptic lesions. Neurosurgery Adler, J. R., Gibbs, I. C., Puataweepong, P., Chang, S. D. 2008; 62: 733-743

Abstract

The restricted radiation tolerance of the anterior visual pathways represents a unique challenge for ablating adjacent lesions with single-session radiosurgery. Although preliminary studies have recently demonstrated that multisession radiosurgery for selected perioptic tumors is both safe and effective, the number of patients in these clinical series was modest and the length of follow-up limited. The current retrospective study is intended to help address these shortcomings.Forty-nine consecutive patients with meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the optic apparatus underwent multisession image-guided radiosurgery at Stanford University Medical Center. Thirty-nine of these patients had previous subtotal surgical resection, and six had previously been treated with conventional fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to five sessions to an average tumor volume of 7.7 cm3 and a cumulative average marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months.After a mean visual field follow-up of 49 months (range, 6-96 mo), vision was unchanged postradiosurgery in 38 patients, improved in eight (16%), and worse in three (6%). In each instance, visual deterioration was accompanied by tumor progression that ultimately resulted in patient death. However, one of these patients, who had a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, initially experienced early visual loss without significant tumor progression after both a previous course of radiotherapy and three separate sessions of radiosurgery. After a mean magnetic resonance imaging follow-up period of 46 months, tumor volume was stable or smaller in all other cases. Two patients died of unrelated nonbrain causes.Multisession radiosurgery resulted in high rates of tumor control and preservation of visual function in this group of perioptic tumors. Ninety-four percent of patients retained or improved preradiosurgical vision. This intermediate-term experience reinforces the findings from earlier studies that suggested that multisession radiosurgery can be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions immediately adjacent to short segments of the optic apparatus.

View details for DOI 10.1227/01.neu.0000316277.14748.63

View details for PubMedID 18596432

Neurologic complications of arteriovenous malformation embolization using liquid embolic agents AMERICAN JOURNAL OF NEURORADIOLOGY Jayaraman, M. V., Marcellus, M. L., Hamilton, S., Do, H. M., Campbell, D., Chang, S. D., Steinberg, G. K., Marks, M. P. 2008; 29 (2): 242-246

Abstract

Embolization of arteriovenous malformations (AVMs) is commonly used to achieve nidal volume reduction before microsurgical resection or stereotactic radiosurgery. The purpose of this study was to examine the overall neurologic complication rate in patients undergoing AVM embolization and analyze the factors that may determine increased risk.We performed a retrospective review of all patients with brain AVMs embolized at 1 center from 1995 through 2005. Demographics, including age, sex, presenting symptoms, and clinical condition, were recorded. Angiographic factors including maximal nidal size, presence of deep venous drainage, and involvement of eloquent cortex were also recorded. For each embolization session, the agent used, number of pedicles embolized, the percentage of nidal obliteration, and any complications were recorded. Complications were classified as the following: none, non-neurologic (mild), transient neurologic deficit, and permanent nondisabling and permanent disabling deficits. The permanent complications were also classified as ischemic or hemorrhagic. Modified Rankin Scale (mRS) scores were collected pre- and postembolization on all patients. Univariate regression analysis of factors associated with the development of any neurologic complication was performed.Four hundred eighty-nine embolization procedures were performed in 192 patients. There were 6 Spetzler-Martin grade I (3.1%), 26 grade II (13.5%), 71 grade III (37.0%), 57 grade IV (29.7%), and 32 grade V (16.7%) AVMs. Permanent nondisabling complications occurred in 5 patients (2.6%) and permanent disabling complications or deaths occurred in 3 (1.6%). In addition, there were non-neurologic complications in 4 patients (2.1%) and transient neurologic deficits in 22 (11.5%). Five of the 8 permanent complications (2.6% overall) were ischemic, and 3 of 8 (1.6% overall) were hemorrhagic. Of the 178 patients who were mRS 0-2 pre-embolization, 4 (2.3%) were dependent or dead (mRS >2) at follow-up. Univariate analysis of risk factors for permanent neurologic deficits following embolization showed that basal ganglia location was weakly associated with a new postembolization neurologic deficit.Embolization of brain AVMs can be performed with a high degree of technical success and a low rate of permanent neurologic complications.

View details for DOI 10.3174/ajnr.A0793

View details for Web of Science ID 000253345200013

View details for PubMedID 17974613

Treatment of intraorbital lesions using the Accuray CyberKnife system. Orbit (Amsterdam, Netherlands) Hirschbein, M. J., Collins, S., Jean, W. C., Chang, S. D., Adler, J. R. 2008; 27 (2): 97-105

Abstract

The goal of this study was to better understand the safety and efficacy of CyberKnife image-guided radiosurgery for lesions immediately adjacent to the optic nerves.This retrospective, non-comparative, interventional case series included 16 patients (6 women and 10 men) with lesions located wholly within the orbit. Thirteen cases involved tumors (31% benign and 69% malignant), two cases presented with chronic orbital inflammation and one patient had intraorbital tissue growth secondary to Graves disease. Staged radiosurgical ablation was performed using CyberKnife image-guided technology. The main outcome measures analyzed were change in tumor/neoplasm size, pain, visual field preservation and visual acuity, which were followed for up to 15 months.Twelve patients had a postoperative MRI, which revealed either a decrease or stabilization of tumor size. In the five lymphoma cases there was complete disappearance of the tumor. Pretreatment pain resolved in all 10 patients who reported it before the procedure; improvement in pain typically occurred within 1-2 weeks of radiosurgery. All 16 patients had a visual evaluation performed after the procedure: of these, 15 had no change in their visual field and one reported improvement. Visual acuity was preserved in 13 patients and improved in two, while one patient developed diplopia.Staged CyberKnife radiosurgery is an effective option for the treatment of intraorbital lesions that controls tumor size, relieves pain, and preserves vision. The long-term safety of this treatment remains to be confirmed.

View details for DOI 10.1080/01676830601177471

View details for PubMedID 18415869

Stereotactic radiosurgery of the postoperative resection cavity for brain metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Soltys, S. G., Adler, J. R., Lipani, J. D., Jackson, P. S., Choi, C. Y., Puataweepong, P., White, S., Gibbs, I. C., Chang, S. D. 2008; 70 (1): 187-193

Abstract

The purpose of this study was to analyze results of adjuvant stereotactic radiosurgery (SRS) targeted at resection cavities of brain metastases without whole-brain irradiation (WBI).Patients who underwent SRS to the tumor bed, deferring WBI after resection of a brain metastasis, were retrospectively identified.Seventy-two patients with 76 cavities treated from 1998 to 2006 met inclusion criteria. The SRS was delivered to a median marginal dose of 18.6 Gy (range, 15-30 Gy) targeting an average tumor volume of 9.8 cm(3) (range, 0.1-66.8 cm(3)). With a median follow-up of 8.1 months (range, 0.1-80.5 months), 65 patients had follow-up imaging assessable for control analyses. Actuarial local control rates at 6 and 12 months were 88% and 79%, respectively. On univariate analysis, increasing values of conformality indices were the only treatment variables that correlated significantly with improved local control; local control was 100% for the least conformal quartile compared with 63% for the remaining quartiles. Target volume, dose, and number of sessions were not statistically significant.In this retrospective series, SRS administered to the resection cavity of brain metastases resulted in a 79% local control rate at 12 months. This value compares favorably with historic results with observation alone (54%) and postoperative WBI (80-90%). Given the improved local control seen with less conformal plans, we recommend inclusion of a 2-mm margin around the resection cavity when using this technique.

View details for DOI 10.1016/j.ijrobp.2007.06.068

View details for Web of Science ID 000251867700026

View details for PubMedID 17881139

Radiosurgery for glomus Jugulare tumors TECHNOLOGY IN CANCER RESEARCH & TREATMENT Lim, M., Bower, R., Nangiana, J. S., Adler, J. R., Chang, S. D. 2007; 6 (5): 419-423

Abstract

Results for treating glomus jugulare tumors with radiosurgery have been limited by short follow-up and small number of patients. We report our experience using LINAC or CyberKnife in 21 tumors with a median follow-up of 66 months (Mean follow-up of 60 months). In addition, we have a subset of eight patients that were followed out for more than 10 years. Patients were treated with doses ranging from 1400 cGy to 2700 cGy. We retrospectively assessed patients for efficacy and post treatment side effects. All patients had stable neurological symptoms, and two patients experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. One patient experienced transient ipsilateral vocal cord paresis; however, this patient received previous external beam radiotherapy. All tumors remained stable or decreased in size by MRI exam. Our results support radiosurgery as an effective and safe method of treatment for glomus jugulare tumors with low morbidity as evidenced by a larger number of patients and long term follow-up.

View details for Web of Science ID 000250211600007

View details for PubMedID 17877430

Cyberknife radiosurgery for lesions of the foramen magnum TECHNOLOGY IN CANCER RESEARCH & TREATMENT Cheshier, S. H., Hanft, S. J., Adler, J. R., Chang, S. D. 2007; 6 (4): 329-335

Abstract

The region of the foramen magnum (FM) presents an especially difficult area for therapeutic intervention. Indeed, this location is challenging to access surgically, particularly in the case of intramedullary and anterior lesions. Therefore, the potential for morbidity associated with therapy to the foramen magnum, most frequently in the form of lower cranial nerve deficits, has encouraged the search for methods that can effectively treat lesions of this region while sparing the important neighboring structures. We report our experience in the use of Cyberknife radiosurgery as a treatment option for these lesions. Thirty-five patients (17 men, 18 women; mean age, 51 yr; range, 18-83) with 35 lesions either spanning or approximating the foramen magnum were treated with the CyberKnife radiosurgical system. Histologies were determined either by prior surgery or radiographic criteria and included 25 benign tumors (nine meningiomas, five schwannomas, four neurofibromas, three hemangioblastomas, two ependymomas, one chordomas, and one pilocytic astrocytoma) along with 10 malignant growths (nine metastases and one chondrosarcoma). Twenty-seven (77%) patients presented with at least one sign and/or symptom, while eight (23%) patients were completely asymptomatic. The most common symptoms were headache, limb numbness, and limb/truncal ataxia, all of which were reported by ten (29%) patients. Among cranial neuropathies, CN XII dysfunction was evident in four (11%) patients. The specific fractionation schedule (mean of 1.8 sessions; range, 1-5) was based on the size of the treated lesion. The mean dose utilized was 19 Gy. Radiographic follow-up was obtained for twenty-three (66%) patients. Nine of the twenty-three (39%) were stable in size, ten lesions decreased in size (43%), and four lesions increased in size (17%). In terms of symptom relief, follow-up was collected for twenty-four (69%) patients. Eleven (46%) of these patients experienced no change in their signs or symptoms, while seven (29%) patients experienced improvement. Six (25%) patients witnessed deterioration in their signs and symptoms. Overall, eighteen (75%) patients had their signs and symptoms either stabilize or improve. There were eleven (31%) deaths in our series, eight of which were related to the disease (though not directly related to CyberKnife treatment) and three of which were from unrelated causes. Complications directly related to CyberKnife radiosurgery were noted in four (11%) of the thirty-five patients. These included one case of temporary emesis immediately following treatment, one case of cystic enlargement two months out, and two cases of radiation necrosis (occurring 1.5 yrs and 2.5 yrs out from treatment). Cyberknife radiosurgery can be an effective treatment for many foramen magnum lesions.

View details for Web of Science ID 000249073000010

View details for PubMedID 17668941

A 35-year-old woman with a dural-based mass. Brain pathology Haddix, T., Chang, S., Vogel, H. 2007; 17 (3): 331-332

View details for PubMedID 17598829

Surgical and endovascular management of symptomatic posterior circulation fusiform aneurysms JOURNAL OF NEUROSURGERY Coert, B. A., Chang, S. D., Do, H. M., Marks, M. P., Steinberg, G. K. 2007; 106 (5): 855-865

Abstract

Patients with fusiform aneurysms can present with subarachnoid hemorrhage (SAH), mass effect, ischemia, or unrelated symptoms. The absence of an aneurysm neck impedes the direct application of a clip and endovascular coil deployment. To evaluate the effects of their treatments, the authors retrospectively analyzed a consecutive series of patients with posterior circulation fusiform aneurysms treated at Stanford University Medical Center between 1991 and 2005.Forty-nine patients (mean age 53 years, male/female ratio 1.2:1) treated at the authors' medical center form the basis of the analysis. Twenty-nine patients presented with an SAH. The patients presenting without SAH had cranial nerve dysfunction (five patients), symptoms of mass effect (eight patients), ischemia (six patients), or unrelated symptoms (one patient). The aneurysms were located on the vertebral artery (VA) or posterior inferior cerebellar artery (PICA) (21 patients); vertebrobasilar junction (VBJ) or basilar artery (BA) (18 patients); and posterior cerebral artery (PCA) (10 patients). Pretreatment clinical grades were determined using the Hunt and Hess scale; for patients with unruptured aneurysms (Hunt and Hess Grade 0) functional subgrades were added. Outcome was evaluated using the Glasgow Outcome Scale (GOS) score during a mean follow-up period of 33 months. Overall long-term outcome was good (GOS Score 4 or 5) in 59%, poor (GOS Score 2 or 3) in 16%, and fatal (GOS Score 1) in 24% of the patients. In a univariate analysis, poor outcome was predicted by age greater than 55 years, VBJ location, pretreatment Hunt and Hess grade in patients presenting with SAH, and incomplete aneurysm thrombosis after endovascular treatment. In a multivariate analysis, age greater than 55 years was the confounding factor predicting poor outcome. Stratification by aneurysm location removed the effect of age. Of 13 patients with residual aneurysm after treatment, five (38%) subsequently died of SAH (three patients) or progressive mass effect/brainstem ischemia (two patients).Certain posterior circulation aneurysm locations (PCA, VA-PICA, and BA-VBJ) represent separate disease entities affecting patients at different ages with distinct patterns of presentation, treatment options, and outcomes. Favorable overall long-term outcome can be achieved in 90% of patients with PCA aneurysms, in 60% of those with VA-PICA aneurysms, and in 39% of those with BA-VBJ aneurysms when using endovascular and surgical techniques. The natural history of the disease was poor in patients with incomplete aneurysm thrombosis after treatment.

View details for Web of Science ID 000246047800008

View details for PubMedID 17542530

Cyberknife targeting the pterygopalatine ganglion for the treatment of chronic cluster headaches. Neurosurgery Lad, S. P., Lipani, J. D., Gibbs, I. C., Chang, S. D., Adler, J. R., Henderson, J. M. 2007; 60 (3): E580-?

Abstract

Cluster headache (CH) is a severe unilateral and periorbital facial pain syndrome that is often associated with autonomic symptoms, including ipsilateral lacrimation, nasal congestion, conjunctival injection, miosis, ptosis, and eyelid edema. We evaluated the treatment of medically refractory CH with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery targeting the pterygopalatine ganglion.A 56-year-old man presented with a 20-year history of medically refractory CH. His symptoms were described as left-sided, severe, stabbing, burning, and often being associated with tearing and rhinorrhea. These headaches occurred virtually every morning and interfered with sleep, lifestyle, and work performance.The patient underwent two pterygopalatine nerve block trials, both of which resulted in the complete relief of headaches for a 24-hour period. Contrast-enhanced computed axial tomography and magnetic resonance imaging scans were fused for target identification and treatment planning. The target volume measured 0.296 cm3 and a single fraction of 45.50 Gy was delivered to the 78% isodose line with a maximum dose of 65 Gy. The patient kept a detailed diary of his headaches and was followed for 12 months after treatment.Results of CyberKnife targeting of the pterygopalatine ganglion in a patient with medically intractable CHs have revealed a significant decrease in the severity and frequency of headaches after a 12-month follow-up period. In addition, the patient has been able to reduce his medication intake, allowing for a significant decrease in medication-related side effects. Longer follow-up periods and additional studies are required to determine the long-term efficacy and late side effects of this treatment strategy.

View details for PubMedID 17327771

CyberKnife targeting the pterygopalatine ganglion for the treatment of chronic cluster headaches NEUROSURGERY Lad, S. P., Lipani, J. D., Gibbs, I. C., Chang, S. D., Adler, J. R., Henderson, J. M. 2007; 60 (3): 580-581
A study of the accuracy of cyberknife spinal radiosurgery using skeletal structure tracking. Neurosurgery Ho, A. K., Fu, D., Cotrutz, C., Hancock, S. L., Chang, S. D., Gibbs, I. C., Maurer, C. R., Adler, J. R. 2007; 60 (2): ONS147-56

Abstract

New technology has enabled the increasing use of radiosurgery to ablate spinal lesions. The first generation of the CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery system required implanted radiopaque markers (fiducials) to localize spinal targets. A recently developed and now commercially available spine tracking technology called Xsight (Accuray, Inc.) tracks skeletal structures and eliminates the need for implanted fiducials. The Xsight system localizes spinal targets by direct reference to the adjacent vertebral elements. This study sought to measure the accuracy of Xsight spine tracking and provide a qualitative assessment of overall system performance.Total system error, which is defined as the distance between the centroids of the planned and delivered dose distributions and represents all possible treatment planning and delivery errors, was measured using a realistic, anthropomorphic head-and-neck phantom. The Xsight tracking system error component of total system error was also computed by retrospectively analyzing image data obtained from eleven patients with a total of 44 implanted fiducials who underwent CyberKnife spinal radiosurgery.The total system error of the Xsight targeting technology was measured to be 0.61 mm. The tracking system error component was found to be 0.49 mm.The Xsight spine tracking system is practically important because it is accurate and eliminates the use of implanted fiducials. Experience has shown this technology to be robust under a wide range of clinical circumstances.

View details for PubMedID 17297377

Hemorrhage rate in patients with Spetzler-Martin grades IV and V arteriovenous malformations - Is treatment justified? STROKE Jayaraman, M. V., Marcellus, M. L., Do, H. M., Chang, S. D., Rosenberg, J. K., Steinberg, G. K., Marks, M. P. 2007; 38 (2): 325-329

Abstract

We sought to examine the prospective annual risk of hemorrhage in patients harboring Spetzler-Martin grades IV and V arteriovenous malformations (AVMs) before and after initiation of treatment.Medical records of 61 consecutive patients presenting with Spetzler-Martin grades IV and V AVMs were retrospectively reviewed for demographics, angiographic features, presenting symptom(s), and time of all hemorrhage events, before or after treatment initiation. Pretreatment hemorrhage rates (excluding hemorrhages at presentation) and posttreatment rates were subsequently calculated. Modified Rankin Scale (mRS) scores before and after treatment were recorded.The annual pretreatment hemorrhage rate for all patients was 10.4% per year (95% CI, 2.2 to 15.4%), 13.9% (95% CI, 3.5 to 22.1%) in patients with hemorrhagic presentation and 7.3% (2.6 to 14.3%) in patients with nonhemorrhagic presentation. Posttreatment hemorrhage rates were 6.1% per year (95% CI, 2.5 to 13.2%) for all patients, 5.6% (95% CI, 2.1 to 11.8%) for patients presenting with hemorrhage and 6.4% (95% CI, 1.6 to 10.1%) in patients with nonhemorrhagic presentation. A noninferiority test showed that the posttreatment hemorrhage rate was less than or equal to the pretreatment hemorrhage rate (P<0.0001), with some indication that the reduction was greatest in patients with hemorrhagic presentation. Of the 62 patients, 51 (82%) had an mRS score of 0 to 2 before treatment, and 47 (76%) had an mRS score of 0 to 2 at the last follow-up after treatment.The annual rate of hemorrhage in grades IV and V AVMs is higher in this series than reported for all AVMs, which may reflect some referral bias in this single-center study. Nevertheless, initiation of treatment does not appear to increase the rate of subsequent hemorrhage. Treatment for these lesions may be warranted, given their poor natural history.

View details for DOI 10.1161/01.STR.0000254497.24545.de

View details for Web of Science ID 000244122600036

View details for PubMedID 17194881

Image-guided robotic radiosurgery for spinal metastases RADIOTHERAPY AND ONCOLOGY Gibbs, I. C., Kamnerdsupaphon, P., Ryu, M., Dodd, R., Kiernan, M., Change, S. D., Adler, J. R. 2007; 82 (2): 185-190

Abstract

To determine the effectiveness and safety of image-guided robotic radiosurgery for spinal metastases.From 1996 to 2005, 74 patients with 102 spinal metastases were treated using the CyberKnife at Stanford University. Sixty-two (84%) patients were symptomatic. Seventy-four percent (50/68) of previously treated patients had prior radiation. Using the CyberKnife, 16-25 Gy in 1-5 fractions was delivered. Patients were followed clinically and radiographically for at least 3 months or until death.With mean follow-up of 9 months (range 0-33 months), 36 patients were alive and 38 were dead at last follow-up. No death was treatment related. Eighty-four (84%) percent of symptomatic patients experienced improvement or resolution of symptoms after treatment. Three patients developed treatment-related spinal injury. Analysis of dose-volume parameters and clinical parameters failed to identify predictors of spinal cord injury.Robotic radiosurgery is effective and generally safe for spinal metastases even in previously irradiated patients.

View details for DOI 10.1016/j.radonc.2006.11.023

View details for Web of Science ID 000245151400011

View details for PubMedID 17257702

A study of the accuracy of CyberKnife spinal radiosurgery using skeletal structure tracking NEUROSURGERY Ho, A. K., Fu, D., Cotrutz, C., Hancock, S. L., Chang, S. D., Gibbs, I. C., Maurer, C. R., Adler, J. R. 2007; 60 (2): 147-156
CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve pain. Neurosurgical focus Patil, C. G., Veeravagu, A., Bower, R. S., Li, G., Chang, S. D., Lim, M., Adler, J. R. 2007; 23 (6): E9-?

Abstract

Patients with atypical trigeminal neuralgia (TN) have unilateral pain in the trigeminal distribution that is dull, aching, or burning in nature and is constant or nearly constant. Studies of most radiosurgical and surgical series have shown lower response rates in patients with atypical TN. This study represents the first report of the treatment of atypical TN with frameless CyberKnife stereotactic radiosurgery (SRS).Between 2002 and 2007, 7 patients that satisfied the criteria for atypical TN and underwent SRS were included in our study. A 6-8-mm segment of the trigeminal nerve was targeted, excluding the proximal 3 mm at the brainstem. All patients were treated in a single session with a median maximum dose of 78 Gy and a median marginal dose of 64 Gy.Outcomes in 7 patients with a mean age of 61.6 years and a median follow-up of 20 months are reported. Following SRS, 4 patients had complete pain relief, 2 had minimal pain relief with some decrease in the intensity of their pain, and 1 patient experienced no pain relief. Pain relief was reported within 1 week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up of 28 months, pain did not recur in any of the 4 patients who had reported complete pain relief. Complications after SRS included bothersome numbness in 3 patients and significant dysesthesias in 1 patient.The authors have previously reported a 90% rate of excellent pain relief in patients with classic TN treated with CyberKnife SRS. Compared with patients with classic TN, patients with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60% rate of success after SRS achieved in this study is still comparable to or better than results achieved with any other treatment modality for atypical TN.

View details for PubMedID 18081486

Trigeminal Neuralgia: Treatment with the Cyberknife Revista Medica Lim M, Bower R, Adler JR, Chang SD 2007; 13 (1): 195-200
Cyberknife radiosurgery for arteriovenous malformations Rivista Medica Chang SD, Adler JR 2007; 13 (1): 71-77
Efficacy and safety of CyberKnife radiosurgery for acromegaly. Pituitary Roberts, B. K., Ouyang, D. L., Lad, S. P., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G., Gibbs, I. C., Remedios, L., Katznelson, L. 2007; 10 (1): 19-25

Abstract

Acromegaly is a disease characterized by GH hypersecretion, and is typically caused by a pituitary somatotroph adenoma. The primary mode of therapy is surgery, and radiotherapy is utilized as an adjuvant strategy to treat persistent disease. The aim of this study was to determine the efficacy and tolerability of CyberKnife stereotactic radiosurgery in acromegaly.A retrospective review of biochemical and imaging data for subjects with acromegaly treated with CyberKnife stereotactic radiosurgery between 1998 and 2005 at Stanford University Hospital.Nine patients with active acromegaly were treated with radiosurgery using the CyberKnife (CK).Biochemical response based on serum insulin-like growth factor-1 (IGF-1), anterior pituitary hormone function, and tumor size with MRI scans were analyzed.After a mean follow up of 25.4 months (range, 6-53 months), CK radiosurgery resulted in complete biochemical remission in 4 (44.4%) subjects, and in biochemical control with the concomitant use of a somatostatin analog in an additional subject. Smaller tumor size was predictive of treatment success: baseline tumor volume was 1.28 cc (+/- 0.81, SD) vs. 3.93 cc (+/- 1.54) in subjects with a normal IGF-1 vs. those with persistent, active disease, respectively (P = 0.02). The mean biologically effective dose (BED) was higher in subjects who achieved a normal IGF-1 vs. those with persistent, active disease, 172 Gy(3) (+/-28) vs. 94 Gy(3) (+/-17), respectively (P < 0.01). At least one new anterior pituitary hormone deficiency was observed after CK in 3 (33%) patients: two developed hypogonadism, and one developed panhypopituitarism.CK radiosurgery may be a valuable adjuvant therapy for the management of acromegaly.

View details for PubMedID 17273921

Irradiation of glomus jugulare tumors: a historical perspective. Neurosurgical focus Li, G., Chang, S., Adler, J. R., Lim, M. 2007; 23 (6): E13-?

Abstract

Glomus jugulare tumors are rare, slow-growing vascular lesions that arise from the chief cells of the paraganglia within the jugular bulb. They can be associated with the tympanic branch of the glossopharyngeal nerve (Jacobsen nerve) or the auricular branch of the vagus nerve (Arnold nerve) and are also referred to as chemodectomas or nonchromaffin paragangliomas. Optimal treatment of these histologically benign tumors remains controversial. Surgery remains the treatment of choice, but can carry high morbidity rates. External-beam radiation was originally used for subtotal resections and in patients who were poor surgical candidates; however, radiosurgery has recently been introduced as an effective and safe treatment option for patients with these tumors. In this article the authors discuss the history of radiation therapy for glomus jugulare tumors, focusing on recent radiosurgical results.

View details for PubMedID 18081478

Robotic radiosurgery for the treatment of radioresistant brain metastases Hara, W., Li, G., Puataweepong, P., Adler, J., Chang, S., Gibbs, I. C. OXFORD UNIV PRESS INC. 2006: 486-486
Visual field preservation after multisession CyberKnife radiosurgery for perioptic lesions NEUROSURGERY Adler, J. R., Gibbs, I. C., Puataweepong, P., Chang, S. D. 2006; 59 (2): 244-253

Abstract

The restricted radiation tolerance of the anterior visual pathways represents a unique challenge for ablating adjacent lesions with single-session radiosurgery. Although preliminary studies have recently demonstrated that multisession radiosurgery for selected perioptic tumors is both safe and effective, the number of patients in these clinical series was modest and the length of follow-up limited. The current retrospective study is intended to help address these shortcomings.Forty-nine consecutive patients with meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the optic apparatus underwent multisession image-guided radiosurgery at Stanford University Medical Center. Thirty-nine of these patients had previous subtotal surgical resection, and six had previously been treated with conventional fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to five sessions to an average tumor volume of 7.7 cm3 and a cumulative average marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months.After a mean visual field follow-up of 49 months (range, 6-96 mo), vision was unchanged postradiosurgery in 38 patients, improved in eight (16%), and worse in three (6%). In each instance, visual deterioration was accompanied by tumor progression that ultimately resulted in patient death. However, one of these patients, who had a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, initially experienced early visual loss without significant tumor progression after both a previous course of radiotherapy and three separate sessions of radiosurgery. After a mean magnetic resonance imaging follow-up period of 46 months, tumor volume was stable or smaller in all other cases. Two patients died of unrelated nonbrain causes.Multisession radiosurgery resulted in high rates of tumor control and preservation of visual function in this group of perioptic tumors. Ninety-four percent of patients retained or improved preradiosurgical vision. This intermediate-term experience reinforces the findings from earlier studies that suggested that multisession radiosurgery can be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions immediately adjacent to short segments of the optic apparatus.

View details for DOI 10.1227/01.NEU.0000223512.09115.3E

View details for Web of Science ID 000239763800017

View details for PubMedID 16883165

Multisession cyberknife radiosurgery for intramedullary spinal cord arteriovenous malformations NEUROSURGERY Sinclair, J., Chang, S. D., Gibbs, I. C., Adler, J. R. 2006; 58 (6): 1081-1088

Abstract

Intramedullary spinal cord arteriovenous malformations (AVMs) have an unfavorable natural history that characteristically involves myelopathy secondary to progressive ischemia and/or recurrent hemorrhage. Although some lesions can be managed successfully with embolization and surgery, AVM size, location, and angioarchitecture precludes treatment in many circumstances. Given the poor outlook for such patients, and building on the successful experience with radiosurgical ablation of cerebral AVMs, our group at Stanford University has used CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) to treat selected spinal cord AVMs since 1997. In this article, we retrospectively analyze our preliminary experience with this technique.Fifteen patients with intramedullary spinal cord AVMs (nine cervical, three thoracic, and three conus medullaris) were treated by image-guided SRS between 1997 and 2005. SRS was delivered in two to five sessions with an average marginal dose of 20.5 Gy. The biologically effective dose used in individual patients was escalated gradually over the course of this study. Clinical and magnetic resonance imaging follow-up were carried out annually, and spinal angiography was repeated at 3 years.After a mean follow-up period of 27.9 months (range, 3-59 mo), six of the seven patients who were more than 3 years from SRS had significant reductions in AVM volumes on interim magnetic resonance imaging examinations. In four of the five patients who underwent postoperative spinal angiography, persistent AVM was confirmed, albeit reduced in size. One patient demonstrated complete angiographic obliteration of a conus medullaris AVM 26 months after radiosurgery. There was no evidence of further hemorrhage after CyberKnife treatment or neurological deterioration attributable to SRS.This description of CyberKnife radiosurgical ablation demonstrates its feasibility and apparent safety for selected intramedullary spinal cord AVMs. Additional experience is necessary to ascertain the optimal radiosurgical dose and ultimate efficacy of this technique.

View details for DOI 10.1227/01.NEU.0000215891.25153.BA

View details for Web of Science ID 000237785900023

View details for PubMedID 16723887

Cyberknife radiosurgery for benign intradural extramedullary spinal tumors NEUROSURGERY Dodd, R. L., Ryu, M. R., Kamnerdsupaphon, P., Gibbs, I. C., Chang, S. D., Adler, J. R. 2006; 58 (4): 674-684

Abstract

Microsurgical resection of benign intradural extramedullary spinal tumors is generally safe and successful, but patients with neurofibromatosis, recurrent tumors, multiple lesions, or medical problems that place them at higher surgical risk may benefit from alternatives to surgery. In this prospective study, we analyzed our preliminary experience with image-guided radiosurgical ablation of selected benign spinal neoplasms.Since 1999, CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery was used to manage 51 patients (median age, 46 yr; range, 12-86 yr) with 55 benign spinal tumors (30 schwannomas, nine neurofibromas, 16 meningiomas) at Stanford University Medical Center. Total treatment doses ranged from 1600 to 3000 cGy delivered in consecutive daily sessions (1-5) to tumor volumes that varied from 0.136 to 24.6 cm.Less than 1 year postradiosurgery, three of the 51 patients in this series (one meningioma, one schwannoma, and one neurofibroma) required surgical resection of their tumor because of persistent or worsening symptoms; only one of these lesions was larger radiographically. However, 28 of the 51 patients now have greater than 24 months clinical and radiographic follow-up. After a mean follow-up of 36 months, all of these later lesions were either stable (61%) or smaller (39%). Two patients died from unrelated causes. Radiation-induced myelopathy appeared 8 months postradiosurgery in one patient.Although more patients studied over an even longer follow-up period are needed to determine the long-term efficacy of spinal radiosurgery for benign extra-axial neoplasms, short-term clinical benefits were observed in this prospective analysis. The present study demonstrates that CyberKnife radiosurgical ablation of such tumors is technically feasible and associated with low morbidity.

View details for DOI 10.1227/01.NEU.0000204128.84742.8F

View details for Web of Science ID 000237047200026

View details for PubMedID 16575331

Stereotactic radiosurgery using CT cisternography and non-isocentric planning for the treatment of trigeminal neuralgia. Computer aided surgery Lim, M., Cotrutz, C., Romanelli, P., Schaal, D., Gibbs, I., Chang, S. D., Adler, J. R. 2006; 11 (1): 11-20

Abstract

Frame-based radiosurgical rhizotomy has been shown in clinical studies to be effective for managing trigeminal neuralgia (TN). To date, however, only a small pilot study has been published for the frameless, image-guided CyberKnife system. We present our preliminary experience with 29 trigeminal neuralgia patients treated with the frameless CyberKnife using X-ray image-guided targeting, a novel CT method for target definition, and non-isocentric planning.All 29 patients failed previous medical therapy and 14 had undergone prior surgical procedures. CT iohexal cisternography was used to identify the 6- to 8-mm segment of nerve to be lesioned. The marginal dose ranged from 60 to 70 Gy (median 66.4 Gy) as defined at an average 79th percentile. The corresponding Dmax varied from 71.4 to 86.4 Gy (median 77.91 Gy).After a median 10-month follow-up, 26 of 29 (90%) patients rated their pain control as excellent and 3 (10%) reported no improvement. Median time to improvement was 6 days. No or only minor progression in numbness was reported by 22 of 29 (76%) patients, 4 of 29 (14%) patients reported worsening, and 3 of 29 (10%) reported the onset of severe ipsilateral facial numbness. Two patients whose target volume inadvertently included the semi-lunar ganglion developed painful dysethesias in the distribution of their numbness.Although the optimal dose and length of nerve to be lesioned are still being refined, this preliminary experience suggests that image-guided robotic radiosurgery can effectively lesion the trigeminal nerve. Further follow-up is needed to determine whether our method has advantages over the more commonly used procedure for radiosurgical trigeminal rhizotomy.

View details for PubMedID 16531338

Visual field preservation after curative multi-modality treatment of occipital lobe artemovenous malformations NEUROSURGERY Sinclair, J., Marks, M. P., Levy, R. P., Adler, J. R., Chang, S. D., Lopez, J. R., Do, H. M., Bell-Stephens, T. E., Lim, M., Steinberg, G. K. 2005; 57 (4): 655-666

Abstract

Occipital lobe arteriovenous malformations (AVMs) provide challenging management decisions because of their proximity to the visual cortex and optic radiations. Preservation of visual function throughout treatment is the mainstay of therapeutic planning. We reviewed visual field (VF) outcomes of all patients who received curative treatment for occipital AVMs at Stanford University to evaluate the efficacy of different treatment strategies.We conducted a retrospective review of 55 patients with occipital AVMs treated at Stanford University between 1984 and 2003. Clinical presentation, AVM morphology, and treatment modality were correlated with VF function before and after therapeutic intervention.Of 55 patients, 48 (87.3%) underwent multimodality AVM treatment (7 patients < 3 yr from radiosurgery were excluded from final analysis). One patient died from intracerebral hemorrhage 11 months post-radiosurgery, and five patients deferred further treatment. Forty-two patients (87.5%) were cured, with no residual AVM on final angiography. Curative therapeutic modalities used included embolization alone (2 patients), microsurgery alone (6 patients), microsurgery with radiosurgery (1 patient), microsurgery with embolization (23 patients), radiosurgery with embolization (4 patients), and embolization with radiosurgery and microsurgery (6 patients). Mean follow-up was 5.8 years including treatment. VF follow-up was available in all 42 patients. Twenty-eight (66.7%) patients experienced no change in VFs, six (14.3%) patients with previously abnormal VFs improved, and eight (19.0%) patients showed worsening of VFs (although none developed a new homonymous VF deficit). Duration of treatment was related to VF outcome in patients who presented without a history of AVM-related hemorrhage.Occipital AVMs can be safely cured using multimodality strategies with minimal risk to visual function despite the proximity of these lesions to the visual cortex and associated pathways.

View details for DOI 10.1227/01.NEU.0000175547.05291.85

View details for Web of Science ID 000236681500018

View details for PubMedID 16239877

Staged stereotactic irradiation for acoustic neuroma NEUROSURGERY Chang, S. D., Gibbs, I. C., Sakamoto, G. T., Lee, E., Oyelese, A., Adler, J. R. 2005; 56 (6): 1254-1261

Abstract

Stereotactic radiosurgery has proven effective in the treatment of acoustic neuromas. Prior reports using single-stage radiosurgery consistently have shown excellent tumor control, but only up to a 50 to 73% likelihood of maintaining hearing at pretreatment levels. Staged, frame-based radiosurgery using 12-hour interfraction intervals previously has been shown by our group to achieve excellent tumor control while increasing the rate of hearing preservation at 2 years to 77%. The arrival of CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery now makes it more practical to treat acoustic neuroma with a staged approach. We hypothesize that such factors may further minimize injury of adjacent cranial nerves. In this retrospective study, we report our experience with staged radiosurgery for managing acoustic neuromas.Since 1999, the CyberKnife has been used to treat more than 270 patients with acoustic neuroma at Stanford University. Sixty-one of these patients have now been followed up for a minimum of 36 months and form the basis for the present clinical investigation. Among the treated patients, the mean transverse tumor diameter was 18.5 mm, whereas the total marginal dose was either 18 or 21 Gy using three 6- or 7-Gy fractions. Audiograms and magnetic resonance imaging were obtained at 6-months intervals after treatment for the first 2 years and then annually thereafter.Of the 61 patients with a minimum of 36 months of follow-up (mean, 48 mo), 74% of patients with serviceable hearing (Gardner-Robinson Class 1-2) maintained serviceable hearing at the last follow-up, and no patient with at least some hearing before treatment lost all hearing on the treated side. Only one treated tumor (2%) progressed after radiosurgery; 29 (48%) of 61 decreased in size and 31 (50%) of the 61 tumors were stable. In no patients did new trigeminal dysfunction develop, nor did any patient experience permanent injury to their facial nerve; two patients experienced transient facial twitching that resolved in 3 to 5 months.Although still preliminary, these results indicate that improved tumor dose homogeneity and a staged treatment regimen may improve hearing preservation in acoustic neuroma patients undergoing stereotactic radiosurgery.

View details for DOI 10.1227/01.NEU.0000159650.79833.2B

View details for Web of Science ID 000229690300018

View details for PubMedID 15918941

Revascularization of the posterior circulation SKULL BASE-AN INTERDISCIPLINARY APPROACH Coert, B. A., Chang, S. D., Marks, M. P., Steinberg, G. K. 2005; 15 (1): 43-62

Abstract

The primary objective of revascularization procedures in the posterior circulation is the prevention of vertebrobasilar ischemic stroke. Specific anatomical and neurophysiologic characteristics such as posterior communicating artery size affect the susceptibility to ischemia. Current indications for revascularization include symptomatic vertebrobasilar ischemia refractory to medical therapy and ischemia caused by parent vessel occlusion as treatment for complex aneurysms. Treatment options include endovascular angioplasty and stenting, surgical endarterectomy, arterial reimplantation, extracranial-to-intracranial anastomosis, and indirect bypasses. Pretreatment studies including cerebral blood flow measurements with assessment of hemodynamic reserve can affect treatment decisions. Careful blood pressure regulation, neurophysiologic monitoring, and neuroprotective measures such as mild brain hypothermia can help minimize the risks of intervention. Microscope, microinstruments and intraoperative Doppler are routinely used. The superficial temporal artery, occipital artery, and external carotid artery can be used to augment blood flow to the superior cerebellar artery, posterior cerebral artery, posterior inferior cerebellar artery, or anterior inferior cerebellar artery. Interposition venous or arterial grafts can be used to increase length. Several published series report improvement or relief of symptoms in 60 to 100% of patients with a reduction of risk of future stroke and low complication rates.

View details for Web of Science ID 000227387600005

View details for PubMedID 16148983

The Cyberknife: Potential in patients with central nervous system tumors American Journal of Cancer Chang SD 2005; 4 (6): 383-393
Stereotactic radiosurgery using CT cisternography and non-isocentric planning for the treatment of trigeminal neuralgia PROCEEDINGS OF THE 14TH MEETING OF THE WORLD SOCIETY OF STEREOTACTIC AND FUNCTIONAL NEUROSURGERY WSSFN Romanelli, P., Lim, M., Isidori, A., Chang, S. D., Adler, J. R. 2005: 219-223
CyberKnife radiosurgery for idiopathic trigeminal neuralgia. Neurosurgical focus Lim, M., Villavicencio, A. T., Burneikiene, S., Chang, S. D., Romanelli, P., McNeely, L., McIntyre, M., Thramann, J. J., Adler, J. R. 2005; 18 (5): E9-?

Abstract

Gamma knife surgery is an accepted treatment option for trigeminal neuralgia (TN). The safety and efficacy of CyberKnife radiosurgery as a treatment option for TN, however, has not been established.Forty-one patients were treated between May 2002 and September 2004 for idiopathic TN at Stanford University and the Rocky Mountain CyberKnife Center. Patients with atypical pain, multiple sclerosis, or previous radiosurgical treatment or a follow-up duration of less than 6 months were excluded. Patients were evaluated for the level of pain control, response rate, time to pain relief, occurrence of hypesthesia, and time to pain recurrence with respect to the length of the nerve treated and the maximum and the minimum dose to the nerve margin. Thirty-eight patients (92.7%) experienced initial pain relief at a median of 7 days after treatment (range, 24 hours-4 months). Pain control was ranked as excellent in 36 patients (87.8%), moderate in two (4.9%), and three (7.3%) reported no change. Six (15.8%) of the 38 patients with initial relief experienced a recurrence of pain at a median of 6 months (range 2-8 months). Long-term response after a mean follow-up time of 11 months was found in 32 (78%) of 41. Twenty-one patients (51.2%) experienced numbness after treatment.CyberKnife radiosurgery for TN has high rates of initial pain control and short latency to pain relief compared with those reported for other radiosurgery systems. The doses used for treatment were safe and effective. Higher prescribed doses were not associated with improvement in pain relief or recurrence rate. The hypesthesia rate was related to the length of the trigeminal nerve treated.

View details for PubMedID 15913285

Efficacy and safety of stereotactic radiosurgery for glomus jugulare tumors. Neurosurgical focus Lim, M., Gibbs, I. C., Adler, J. R., Chang, S. D. 2004; 17 (2): E11-?

Abstract

Since the mid-1990s the use of radiosurgery for glomus jugulare tumors has grown in popularity. Despite its increased use, follow-up periods for radiosurgery are short and the numbers of patients reported are small. To add to the available information, the authors report their experience with the application of linear accelerator (LINAC) or CyberKnife modalities in 13 patients with 16 tumors.All patients were treated with frame-based LINAC or CyberKnife radiosurgery, with doses ranging from 1400 to 2700 cGy. Patients were retrospectively assessed for posttreatment side effects, which included hearing loss, tongue weakness, and vocal hoarseness. The patients' most recent magnetic resonance (MR) images were also assessed for changes in tumor size. The median follow-up duration was 41 months and the mean follow-up period was 60 months. All tumors remained stable or decreased in size on follow-up MR images. All patients had stable neurological symptoms, and one experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. One patient experienced transient ipsilateral vocal cord paresis; however, this individual had received previous external-beam radiation therapy.The authors' findings continue to support radiosurgery as an effective and safe method of treatment for glomus jugulare tumors that results in low rates of morbidity.

View details for PubMedID 15329026

Preliminary visual field preservation after staged CyberKnife radiosurgery for perioptic lesions NEUROSURGERY Pham, C. J., Chang, S. D., Gibbs, I. C., Jones, P., Heilbrun, M. P., Adler, J. R. 2004; 54 (4): 799-810

Abstract

The limited radiation tolerance of the optic nerves and the optic chiasm makes it a challenge to treat immediately adjacent lesions with radiosurgery. Staged or hypofractionated radiosurgery has the virtue of combining the accuracy and conformality of radiosurgery with the normal tissue-sparing benefits of fractionation. We describe a consecutive series of patients with meningiomas and pituitary adenomas abutting the anterior visual pathways who were treated with staged, image-guided radiosurgery.Thirty-four patients with either meningiomas (20 patients) or pituitary adenomas (14 patients) within 2 mm of the optic apparatus were treated. Several patients had previously been treated with conventional fractionated radiotherapy (5 patients) or subtotal surgical resection (23 patients). Radiosurgery was delivered in two to five stages to a cumulative average marginal dose of 20.0 Gy. Visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months after treatment.The mean follow-up period was 29 months (range, 15-62 mo). Pre- and posttreatment vision was unchanged in 20 patients, improved in 10, and worse in 3. One patient died during follow-up as a result of an unrelated cardiac event. Visual loss was accompanied by tumor progression in two cases. In a third patient with a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, injury to one optic nerve occurred after both a prior course of radiotherapy and three separate sessions of radiosurgery.Staged radiosurgery resulted in high rates of tumor control and preservation of visual function. Ninety-one percent of patients retained their presurgical vision. Staged radiosurgery may be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions adjacent to the optic apparatus.

View details for DOI 10.1227/01.NEU.0000114261.18723.6A

View details for Web of Science ID 000220769100004

View details for PubMedID 15046645

Radiation tolerance of the spinal cord to staged radiosurgery RADIOSURGERY Gibbs, I. C., Chang, S. D., Pham, C., Adler, J. R. 2004; 5: 22-28
Temporal pattern of pain relief using Cyberknife radiosurgery for trigeminal neuralgia: A preliminary report Radiosurgery Romanelli P, Chang SD, Gibbs IC, Heit G, Adler JR 2004; 5: 181-189
Basic quality assurance of the Cyberknife system Radiosurgery Ho AK, Cotrutz C, Chang SD, Adler JR, Gibbs IC 2004; 5: 255-259
Radiation tolerance of the spinal cord to staged radiosurgery Radiosurgery Gibbs IC, Chang SD, Pham C, Adler JR 2004; 5: 22-28
Temporal pattern of pain relief using cyberknife radiosurgery for trigeminal neuralgia: A preliminary report RADIOSURGERY Romanelli, P., Chang, S., Gibbs, I. C., Heit, G., Adler, J. R. 2004; 5: 181-189
Quality assurance of the cyberknife fiducial and skull tracking systems RADIOSURGERY Ho, A., Cotrutz, C., Chang, S. D., Adler, J. R., Gibbs, I. C. 2004; 5: 255-259
Stereotactic radiosurgery for hemangiomas and ependymomas of the spinal cord. Neurosurgical focus Ryu, S. I., Kim, D. H., Chang, S. D. 2003; 15 (5): E10-?

Abstract

The optimal treatment for intramedullary spinal tumors is controversial, because both resection and conventional radiation therapy are associated with potential morbidity. Stereotactic radiosurgery can theoretically deliver highly conformal, high-dose radiation to surgically untreatable lesions while simultaneously mitigating radiation exposure to large portions of the spinal cord. The purpose of this study was to evaluate the authors' initial experience with frameless stereotactic radiosurgery for intramedullary spinal tumors.Between 1998 and 2003, 10 intramedullary spinal tumors were treated with stereotactic radiosurgery at the authors' institution. Seven hemangioblastomas and three ependymomas were treated in four men and three women. These patients either had recurrent tumors, had undergone several previous surgeries, had medical contraindications to surgery, or had declined open resection. Conformal treatment planning delivered a prescribed dose of 1800 to 2500 cGy (mean 2100 cGy) to the lesions in one to three stages. No significant treatment-related complications have been recorded. The mean radiographic and clinical follow-up duration was 12 months (range 1-24 months). One ependymoma and two hemangioblastomas were smaller on follow-up neuroimaging. The remaining tumors were stable at the time of follow-up imaging.Stereotactic radiosurgery for intramedullary spinal tumors is feasible and safe in selected cases and may prove to be another therapeutic option for these challenging lesions.

View details for PubMedID 15323467

Radiosurgery and radiotherapy for sacral tumors. Neurosurgical focus Gibbs, I. C., Chang, S. D. 2003; 15 (2): E8-?

Abstract

Sacral tumors represent a small subset of spinal lesions and typically include chordomas, metastases, other primary bone tumors, and benign schwannomas. Resection is the standard treatment for many sacral tumors, but many types of sacral lesions have the potential for recurrence after excision. In these cases, adjuvant radiotherapy is often beneficial. Although conventional radiotherapy plays an important role in the management of spinal lesions, the radiation doses required for adequate local control of many sacral lesions generally exceed the tolerance doses of normal tissues, thus limiting its definitive role in the management of sacral tumors. Recent advances in the field of stereotactic radiosurgery have allowed precise targeting of the sacrum. In this report the authors review the use of these two forms of radiation treatment and their role in managing sacral tumors.

View details for PubMedID 15350039

Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Le, Q. T., Tate, D., Koong, A., Gibbs, I. C., Chang, S. D., Adler, J. R., Pinto, H. A., Terris, D. J., Fee, W. E., Goffinet, D. R. 2003; 56 (4): 1046-1054

Abstract

Treatment of nasopharyngeal carcinoma using conventional external beam radiotherapy (EBRT) alone is associated with a significant risk of local recurrence. Stereotactic radiosurgery (STR) was used to boost the tumor site after EBRT to improve local control.Forty-five nasopharyngeal carcinoma patients received a STR boost after EBRT at Stanford University. Seven had T1, 16 had T2, 4 had T3, and 18 had T4 tumors (1997 American Joint Commission on Cancer staging). Ten had Stage II, 8 had Stage III, and 27 had Stage IV neoplasms. Most patients received 66 Gy of EBRT delivered at 2 Gy/fraction. Thirty-six received concurrent cisplatin-based chemotherapy. STR was delivered to the primary site 4-6 weeks after EBRT in one fraction of 7-15 Gy.At a medium follow-up of 31 months, no local failures had occurred. The 3-year local control rate was 100%, the freedom from distant metastasis rate was 69%, the progression-free survival rate was 71%, and the overall survival rate was 75%. Univariate and multivariate analyses revealed N stage (favoring N0-N1, p = 0.02, hazard ratio HR 4.2) and World Health Organization histologic type (favoring type III, p = 0.002, HR 13) as significant factors for freedom from distant metastasis. World Health Organization histologic type (p = 0.004, HR 10.5) and age (p = 0.01, HR 1.07/y) were significant factors for survival. Late toxicity included transient cranial nerve weakness in 4, radiation-related retinopathy in 1, and asymptomatic temporal lobe necrosis in 3 patients who originally had intracranial tumor extension.STR boost after EBRT provided excellent local control in nasopharyngeal carcinoma patients. The incidence of late toxicity was acceptable. More effective systemic treatment is needed to achieve improved survival.

View details for DOI 10.1016/S0360-3016(03)00117-2

View details for Web of Science ID 000183937500018

View details for PubMedID 12829140

Multimodality treatment of giant intracranial arteriovenous malformations NEUROSURGERY Chang, S. D., Marcellus, M. L., Marks, M. P., Levy, R. P., Do, H. M., Steinberg, G. K. 2003; 53 (1): 1-11

Abstract

Giant arteriovenous malformations (AVMs) (i.e., those greater than 6 cm at maximum diameter) are difficult to treat and often carry higher treatment morbidity and mortality rates than do smaller AVMs. In this study, we reviewed the treatment, angiographic results, and clinical outcomes in 53 patients with giant AVMs who were treated at Stanford between 1987 and 2001.The patients selected included 20 males (38%) and 33 females (62%). Their presenting symptoms were hemorrhage (n = 20; 38%), seizures (n = 18; 34%), headaches (n = 8; 15%), and progressive neurological deficits (n = 7; 13%). One patient was in Spetzler-Martin Grade III, 9 were in Spetzler-Martin Grade IV, and 43 were in Spetzler-Martin Grade V. The mean AVM size was 6.8 cm (range, 6-15 cm). AVM venous drainage was superficial (n = 7), deep (n = 20), or both (n = 26). At presentation, 31 patients (58%) were graded in excellent neurological condition, 17 were graded good (32%), and 5 were graded poor (9%).The patients were treated with surgery (n = 27; 51%), embolization (n = 52; 98%), and/or radiosurgery (n = 47; 89%). Most patients received multimodality treatment with embolization followed by surgery (n = 5), embolization followed by radiosurgery (n = 23), or embolization, radiosurgery, and surgery (n = 23). Nineteen patients (36%) were completely cured of their giant AVMs, 90% obliteration was achieved in 4 patients (8%), less than 90% obliteration was achieved in 29 patients (55%) who had residual AVMs even after multimodality therapy, and 1 patient was lost to follow-up. Of the 33 patients who either completed treatment or were alive more than 3 years after undergoing their most recent radiosurgery, 19 patients (58%) were cured of their AVMs. The long-term treatment-related morbidity rate was 15%. The clinical results after mean follow-up of 37 months were 27 excellent (51%), 15 good (28%), 3 poor (6%), and 8 dead (15%).The results in this series of patients with giant AVMs, which represents the largest series reported to date, suggest that selected symptomatic patients with giant AVMs can be treated successfully with good outcomes and acceptable risk. Multimodality treatment is usually necessary to achieve AVM obliteration.

View details for Web of Science ID 000183988600001

View details for PubMedID 12823868

The efficacy of linear accelerator stereotactic radiosurgery in treating glomus jugulare tumors TECHNOLOGY IN CANCER RESEARCH & TREATMENT Lim, M., Gibbs, I. C., Adler, J. R., Martin, D. P., Chang, S. D. 2003; 2 (3): 261-265

Abstract

Treatment of glomus jugulare tumors with radiosurgery has grown in acceptance since the first reported treatment in 1995, but only a few centers have reported their experiences with limited follow up time. We report our experience with stereotactic radiosurgery in nine patients with ten glomus tumors. All patients were treated either with frame based LINAC or Cyberknife with doses ranging from 1600 cGy to 2500 cGy. Three patients received no previous therapy and one patient received additional external beam radiation for concomitant treatment of carotid body tumors. Patients were then followed for post treatment side effects in addition to change in tumor size by MRI evaluation. The median clinical follow-up time was 26 months (mean 54 months), median radiographic follow-up was 21.5 months (mean 46 months), with a range from 3 to 126 months. The results from our center demonstrated nine of ten tumors to be stable in size by MRI exam, and one tumor which regressed in size. Nine patients had stable neurological symptoms, and one patient experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. Our results continue to support radiosurgery as a suitable form of treatment for glomus jugulare tumors as evidenced by results from this four and a half year follow-up.

View details for Web of Science ID 000183918300008

View details for PubMedID 12779355

The role of radiosurgery for hemangiopericytomas. Neurosurgical focus Chang, S. D., Sakamoto, G. T. 2003; 14 (5)

Abstract

Hemangiopericytomas represent a small subset of meningeal tumors. Despite their relatively uncommon nature, they are aggressive tumors known for recurrence. Resection is the standard treatment in most, although regrowth and metastases are common even after resection. The authors evaluate the role of stereotactic radiosurgery in the treatment of recurrent hemangiopericytomas.In a review of the Stanford radiosurgery patient database between 1989 and 2002, the authors found eight patients with recurrent hemangiopericytoma who underwent stereotactic radiosurgery. The mean age of this population was 45.1 years (range 24-67 years). All patients had been previously treated with resection, and five patients (63%) had undergone conventional radiotherapy. The mean radiosurgery dose to the tumor margin was 20.5 Gy (range 16-24 Gy). The mean clinical and radiographic follow-up period was 44 months (range 8-77 months). Of the eight tumors treated with radiosurgery, six decreased in size and two ultimately progressed. There were no radiosurgery-related complications.Stereotactic radiosurgery of hemangiopericytomas can result in increased tumor control and should be considered as a treatment option for patients in whom the diagnosis has been established and in whom residual tumor is demonstrated postoperatively. Close clinical and radiographic follow-up evaluation is necessary in this patient population because of the high rate of local recurrence and distant metastases.

View details for PubMedID 15669810

Parent vessel occlusion for vertebrobasilar fusiform and dissecting aneurysms AMERICAN JOURNAL OF NEURORADIOLOGY Leibowitz, R., Do, H. M., Marcellus, M. L., Chang, S. D., Steinberg, G. K., Marks, M. P. 2003; 24 (5): 902-907

Abstract

Previous reports of outcome with permanent vessel occlusion (PVO) for large, giant, or fusiform aneurysms in the posterior circulation have been limited. We undertook this study to evaluate the perioperative (within 30 days) and follow-up outcomes for patients treated with permanent occlusion of the vertebral artery for vertebrobasilar fusiform and dissecting aneurysms.Thirteen consecutive patients were studied. Two groups were defined for the study. Group I patients underwent PVO to achieve complete thrombosis of the aneurysm. Group II patients underwent PVO to reduce flow to the aneurysm where complete thrombosis was not desirable. Modified Rankin scores were obtained at presentation and at follow-up (follow-up range, 1-76 months; mean, 22.0 months).All group I aneurysms were shown to be thrombosed on the angiograms obtained at the immediate follow-up examinations. Improvement in outcome scores was achieved by all group I patients. Improvement in Rankin scores after endovascular treatment was statistically significant (P =.026). All group II patients had complete occlusion of the vertebral artery; however, continued filling of the fusiform aneurysm was still observed. Four patients in group II died during the follow-up period. Two of these deaths were attributable to the aneurysms. Of the remaining three patients, two experienced clinical worsening and one remained stable.In this series, PVO for chronic fusiform and acute dissecting aneurysms of the vertebrobasilar system proved to be a useful therapeutic endovascular technique. Long-term outcomes suggest that patients with aneurysms involving only one vertebral artery, where complete thrombosis can be achieved, have better clinical outcomes than those who have aneurysms involving the basilar artery or both vertebral arteries, where complete thrombosis cannot achieved by using PVO.

View details for Web of Science ID 000183021100024

View details for PubMedID 12748092

Patterns of patient movement during frameless image-guided radiosurgery INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Murphy, M. J., Chang, S. D., Gibbs, I. C., Le, Q. T., Hai, J., Kim, D., Martin, D. P., Adler, J. R. 2003; 55 (5): 1400-1408

Abstract

Image-guided radiosurgery aligns the treatment beam to the target site by using a radiographic imaging system to locate anatomic landmarks associated with the treatment target. Because the procedure is performed without a rigid frame, the precision of dose alignment can be affected by patient movement. Movement is limited by noninvasive restraints and compensated by remeasuring the target position at short intervals throughout treatment and then realigning the beam. Frameless image-guided radiosurgery has been used at our institution to treat 250 cranial, 23 spinal, 9 lung, and 3 pancreas cases involving malignant and benign tumors as well as vascular malformations. We have analyzed the target position records for all of these cases to assess the frequency, magnitude, and case-by-case patterns of patient movement.The position of the treatment site during image-guided radiosurgery was measured at approximately 1-2-min intervals, on average, using orthogonal amorphous silicon X-ray cameras and an image registration process that determined all six degrees of freedom in the target's position. The change in position from one measurement to the next was indicative of patient movement.The treatment site position along each axis of translation was observed to vary by an average of 0.45 mm for the cranium, 0.53 mm for the cervical spine, 0.53 mm for the lumbar and thoracic spine, 1.06 mm for the lung, and 1.50 mm for the pancreas. Half of all cranial cases showed systematic drifting of the target away from the initial setup position.Using noninvasive restraints and supports, short-term movement of the head and spine during image-guided radiosurgery was limited to a radius of 0.8 mm, which satisfies the prevailing standard for radiosurgical dose alignment precision, but maintaining this margin of error throughout a treatment fraction requires regular monitoring of the target site's position.

View details for DOI 10.1016/S0360-3016(02)04597-2

View details for Web of Science ID 000181803500035

View details for PubMedID 12654453

Extracranial radiosurgery using the CyberKnife TECHNIQUES IN NEUROSURGERY Romanelli, P., Chang, S. D., Koong, A., Adler, J. R. 2003; 9 (3): 226-231
Cyberknife radiosurgery for trigeminal neuralgia STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Romanelli, P., Heit, G., Chang, S. D., Martin, D., Pham, C., Adler, J. 2003; 81 (1-4): 105-109

Abstract

We present preliminary results using Cyberknife radiosurgery as a noninvasive treatment for trigeminal neuralgia (TN).Ten patients with medically refractory TN who were deemed unsuitable for conventional surgery underwent Cyberknife radiosurgery using CT cisternography for localization.Pain relief was achieved in 7 patients, in 5 of them within 24-72 h after irradiation.Cyberknife radiosurgery can achieve early-onset pain relief in a subset of TN patients. Improvements using this technique include the absence of a stereotactic ring, potentially improved targeting accuracy produced by CT cisternography and improved dose homogeneity.

View details for DOI 10.1159/000075112

View details for Web of Science ID 000188386000016

View details for PubMedID 14742972

Image-guided spinal stereotactic radiosurgery TECHNIQUES IN NEUROSURGERY Ryu, S. I., Kim, D. H., Martin, D. P., Chang, S. D., Adler, J. R. 2003; 8 (1): 56-64
An analysis of the accuracy of the Cyberknife: A robotic nameless stereotactic radiosurgical system NEUROSURGERY Chang, S. D., Main, W., Martin, D. P., Gibbs, I. C., Heilbrun, M. P. 2003; 52 (1): 140-146

Abstract

The use of stereotactic radiosurgical systems to treat intracranial and extracranial tumors and other lesions requires a high degree of accuracy in target identification and localization. The purpose of this study was to evaluate the total system accuracy of the CyberKnife (Accuray, Inc., Sunnyvale, CA), a frameless, image-guided, stereotactic radiosurgery system.Clinically relevant accuracy or application accuracy of the CyberKnife radiosurgery system is based on 1) the beam delivery accuracy, which combines the robot and the camera image tracking system, and 2) target localization accuracy, which combines computed tomographic (CT) imaging and treatment planning. Clinically relevant accuracy can be measured by delivering a radiation dose to phantoms, in which the target is defined on a set of CT images using all components of the CyberKnife system, including the treatment planning software, the robot, the camera tracking system, and the linear accelerator. Clinically relevant accuracy was measured in head phantoms loaded with packs of radiochromic film. The accuracy measured is the displacement of the dose contours from the treatment plan to that measured in the radiosurgically exposed phantom.Measurements of mean errors of the second-generation CyberKnife system at Stanford University Medical Center, installed in 2001, ranged from 0.7 mm for a CT slice thickness of 0.625 mm to 1.97 mm for a CT slice thickness of 3.75 mm.The frameless, image-guided, second-generation CyberKnife radiosurgery system has a clinically relevant accuracy of 1.1 +/- 0.3 mm when CT slice thicknesses of 1.25 mm are used. CyberKnife precision is comparable to published localization errors in current frame-based radiosurgical systems.

View details for DOI 10.1227/01.NEU.0000039162.72141.18

View details for Web of Science ID 000180195800031

View details for PubMedID 12493111

Downregulation of cerebrospinal fluid production in patients with chronic hydrocephalus JOURNAL OF NEUROSURGERY Silverberg, G. D., Huhn, S., Jaffe, R. A., Chang, S. D., Saul, T., Heit, G., Von Essen, A., Rubenstein, E. 2002; 97 (6): 1271-1275

Abstract

The goal of this study was to determine the effect of hydrocephalus on cerebrospinal fluid (CSF) production rates in patients with acute and chronic hydrocephalus.The authors studied CSF production both in patients presenting with acute and chronic hydrocephalus, and patients with Parkinson disease (PD) of a similar mean age, whose CSF production was known to be normal. A modification of the Masserman method was used to measure CSF production through a ventricular catheter. The CSF production rates (means +/- standard deviations) in the three groups were then compared. The patients with PD had a mean CSF production rate of 0.42 +/- 0.13 ml/minute; this value lies within the normal range measured using this technique. Patients with acute hydrocephalus had a similar CSF production rate of 0.4 +/- 0.13 ml/minute, whereas patients with chronic hydrocephalus had a significantly decreased mean CSF production rate of 0.25 +/- 0.08 ml/minute.The authors postulate that chronic increased intracranial pressure causes downregulation of CSF production.

View details for Web of Science ID 000179901000004

View details for PubMedID 12507122

Assessment of low-flow CSF drainage as a treatment for AD - Results of a randomized pilot study NEUROLOGY Silverberg, G. D., Levinthal, E., SULLIVAN, E. V., Bloch, D. A., Chang, S. D., Leverenz, J., Flitman, S., Winn, R., Marciano, F., Saul, T., Huhn, S., Mayo, M., McGuire, D. 2002; 59 (8): 1139-1145

Abstract

This prospective, randomized, controlled study was designed to investigate the safety, feasibility, and preliminary efficacy of long-term CSF drainage via a low-flow ventriculoperitoneal shunt in subjects suffering from AD.Twenty-nine subjects selected for probable AD (National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Dementias Association criteria) were screened to exclude normal pressure hydrocephalus or other etiologies of dementia and randomized to treatment (shunt) or no treatment groups. The study endpoint was the comparison of group performance on psychometric testing at quarterly intervals for 1 year. Shunted subjects had CSF withdrawn for MAP-tau and Abeta((1-42)) assays at the same time intervals.There was no mortality from the surgical procedure, and no patient sustained a subdural hematoma. Five notable postoperative adverse events, which resolved without permanent neurologic deficit, were reported in the shunt group. Group mean Mattis Dementia Rating Scale total scores showed little change over the year in the shunt-treatment group, in contrast to a decline in the control group (p = 0.06). Mini-Mental State Examination mean scores supported a trend in favor of shunt treatment (p = 0.1). There was a concomitant decrease in ventricular CSF concentrations of AD biomarkers MAP-tau and Abeta((1-42)).The surgical procedure and the device are reasonably safe. Adverse events were consistent with shunt procedures for hydrocephalus in this older population. The endpoint data show a trend in favor of the treated group. A larger, randomized, double-blinded, controlled, clinical trial is underway.

View details for Web of Science ID 000178726700007

View details for PubMedID 12391340

Image guided stereotactic radiosurgery for lesions in proximity to the anterior visual pathways: a preliminary report. Technology in cancer research & treatment Mehta, V. K., Lee, Q., Chang, S. D., Cherney, S., Adler, J. R. 2002; 1 (3): 173-180

Abstract

The incidence of optic neuropathy after stereotactic radiosurgery (SRS) is related to the total dose, fraction size, and treatment volume. Theoretically, fractionated SRS can decrease this risk. In this paper, we report our technique for fractionated SRS and assess its potential role in the management of tumors located adjacent to the anterior visual pathways. Since 1997, thirteen patients (median age: 50, range 21-76) with lesions in close proximity to the anterior visual pathways were treated on the CyberKnife image guided SRS system (Accuray, Inc., Sunnyvale, CA). The CyberKnife is a 6MV linear accelerator mounted on a robotic arm which can monitor and adjust to changes in the target position in real time thus eliminating skeletal frame immobilization and allowing for convenient multi-fraction SRS treatments. Magnetic Resonance Imaging (MRI) and computerized tomography (CT) imaging for treatment planning were obtained with the patients head immobilized in an aquaplast mask. After image fusion, the target and critical structures were delineated. Two to five fractions were prescribed with approximately a 24-hour interfraction interval. The patients received 25 Gy in 5 fractions (n=5), 21 Gy in 3 fractions (n=5), or 20 Gy in 2 fractions (n=3) to the 75-95% isodose line. Ten of the thirteen patients had good pretreatment vision. In nearly all instances, the volume of the optic nerve that received 80% of the prescribed dose was < 0.05 cm3. In all instances, the volume of the optic nerve that received 50% of the prescribed dose was 0.03 cm3 of optic nerve. With median follow up of 18 months (range 12 to 54), four patients have had improvement in their vision. No visual deterioration has been observed in any of the other patients. In addition, there has been no tumor progression within the treated field. Fractionated SRS using the CyberKnife is technically feasible and may decrease the risk of optic neuropathy. Greater patient accrual and longer follow up will be necessary to further determine the clinical benefit of this approach.

View details for PubMedID 12622510

The role of radiosurgery in the treatment of giant arteriovenous malformations RADIOSURGERY, VOL 4 Chang, S. D., Levy, R. P., Marks, M. P., Marcellus, M., Steinberg, G. K. 2002; 4: 42-53
Image-guided radiosurgery in the treatment of spinal metastases. Neurosurgical focus MURPHY, M. J., Chang, S., Gibbs, I., Le, Q. T., Martin, D., Kim, D. 2001; 11 (6)

Abstract

The authors describe a new method for treating metastatic spinal tumors in which noninvasive, image-guided, frameless stereotactic radiosurgery is performed. Stereotactic radiosurgery delivers a high dose of radiation in a single or limited number of fractions to a lesion while maintaining delivery of a low dose to adjacent normal structures.Image-guided radiosurgery was developed by coupling an orthogonal pair of real-time x-ray cameras to a dynamically manipulated robot-mounted linear accelerator that guides the radiation beam to treatment sites associated with radiographic landmarks. This procedure can be conducted in an outpatient setting without the use of framebased skeletal fixation. The system relies on skeletal landmarks or implanted fiducial markers to locate treatment targets. Four patients with spinal metastases underwent radiosurgery with total prescription doses of 1000 to 1600 cGy in one or two fractions. Alignment of the treatment dose with the target volume was accurate to within 1.5 mm. During the course of each treatment fraction, patient movement was less than 0.5 mm on average. Dosimetry was highly conformal, with a demonstrated ability to deliver 1600 cGy to the perimeter of an irregular target volume while keeping exposure to the cord itself below 800 cGy.These experiences indicate that frameless radiosurgery is a viable therapeutic option for metastatic spine disease.

View details for PubMedID 16463998

The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer's type NEUROLOGY Silverberg, G. D., Heit, G., Huhn, S., Jaffe, R. A., Chang, S. D., Bronte-Stewart, H., Rubenstein, E., Possin, K., Saul, T. A. 2001; 57 (10): 1763-1766

Abstract

To evaluate the production rate of CSF in patients with differing disease states.The authors measured the production rate of CSF in three groups of patients: five patients with PD below age 60 (aged 51 +/- 4 years, mean +/- SD), nine with PD over age 60 (aged 69 +/- 6 years, mean +/- SD), and seven with dementia of the Alzheimer's type (AD) (aged 72 +/- 9 years, mean +/- SD). This method, based on the Masserman technique, employs ventricular rather than a lumbar access to the CSF space. Furthermore, the volume of CSF removed during the procedure is only 3 mL rather than 10 mL.These measurements indicate that the mean rate of CSF production in patients with PD under age 60 was 0.47 +/- 0.13 mL/minute, in patients with PD aged 60 or older the mean rate was 0.40 +/- 0.12 mL/minute, and in patients with AD the mean rate was 0.20 +/- 0.06 mL/minute.These results indicate that the rate of CSF production in patients with PD is normal, and that the rate of CSF production in patients with AD is markedly reduced.

View details for Web of Science ID 000172334700006

View details for PubMedID 11723260

Image-guided hypo-fractionated stereotactic radiosurgery to spinal lesions NEUROSURGERY Ryu, S. I., Chang, S. D., Kim, D. H., MURPHY, M. J., Le, Q. T., Martin, D. P., Adler, J. R. 2001; 49 (4): 838-846

Abstract

This article demonstrates the technical feasibility of noninvasive treatment of unresectable spinal vascular malformations and primary and metastatic spinal tumors by use of image-guided frameless stereotactic radiosurgery.Stereotactic radiosurgery delivers a high dose of radiation to a tumor volume or vascular malformation in a limited number of fractions and minimizes the dose to adjacent normal structures. Frameless image-guided radiosurgery was developed by coupling an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator that guides the therapy beam to treatment sites within the spine or spinal cord, in an outpatient setting, and without the use of frame-based fixation. The system relies on skeletal landmarks or implanted fiducial markers to locate treatment targets. Sixteen patients with spinal lesions (hemangioblastomas, vascular malformations, metastatic carcinomas, schwannomas, a meningioma, and a chordoma) were treated with total treatment doses of 1100 to 2500 cGy in one to five fractions by use of image-guided frameless radiosurgery with the CyberKnife system (Accuray, Inc., Sunnyvale, CA). Thirteen radiosurgery plans were analyzed for compliance with conventional radiation therapy.Tests demonstrated alignment of the treatment dose with the target volume within +/-1 mm by use of spine fiducials and the CyberKnife treatment planning system. Tumor patients with at least 6 months of follow-up have demonstrated no progression of disease. Radiographic follow-up is pending for the remaining patients. To date, no patients have experienced complications as a result of the procedure.This experience demonstrates the feasibility of image-guided robotic radiosurgery for previously untreatable spinal lesions.

View details for Web of Science ID 000171279600017

View details for PubMedID 11564244

Posterior cerebral circulation revascularization NEUROSURGERY CLINICS OF NORTH AMERICA Chang, S. D., Ryu, S. I., Steinberg, G. K. 2001; 12 (3): 519-?

Abstract

Posterior circulation revascularization has evolved as a method to treat selected patients with vertebrobasilar ischemia who have inaccessible atherosclerotic occlusive disease and who have failed maximal medical therapy. In addition, complex unclippable aneurysms of the posterior circulation are another indication for revascularization of the vertebrobasilar territory. Careful preoperative evaluation and meticulous attention to detail intraoperatively yield good patient outcomes with minimal morbidity and mortality. This article reviews the vascular anatomy of the posterior circulation and the indications, preoperative evaluation, operative techniques, clinical outcomes, and alternative treatments for patients requiring posterior circulation revascularization procedures.

View details for Web of Science ID 000169857500006

View details for PubMedID 11390312

Current status and optimal use of radiosurgery ONCOLOGY-NEW YORK Chang, S. D., Adler, J. R. 2001; 15 (2): 209-216

Abstract

The field of stereotactic radiosurgery is rapidly advancing as a result of both improvements in radiosurgical equipment and better physician understanding of the clinical applications of stereotactic radiosurgery. This article will review recent developments in the field of radiosurgery, including advances in our understanding of the treatment of brain metastases and arteriovenous malformations, as well as the use of stereotactic radiosurgery as a boost following conventional radiation for nasopharyngeal carcinoma to minimize the rate of local recurrence. In addition, improved understanding of the radiobiology of normal neurologic structures adjacent to tumors undergoing radiosurgery has led to the use of fractionated stereotactic radiosurgery for the treatment of acoustic neuromas and tumors bordering the anterior visual pathways. Finally, a breakthrough in radiosurgery involving the development and use of frameless, image-guided stereotactic radiosurgery has allowed for both dose homogeneity and treatment of intracranial lesions based on nonisocentric treatment algorithms that result in improved target conformality. This same frameless radiosurgical system has also expanded the scope of radiosurgery to include the treatment of extracranial lesions throughout the body.

View details for Web of Science ID 000167070000017

View details for PubMedID 11252934

Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for residual or recurrent cranial base and cervical chordomas. Neurosurgical focus Chang, S. D., Martin, D. P., Lee, E., Adler, J. R. 2001; 10 (3): E5-?

Abstract

In patients with chordomas the lesions often recur. Furthermore, the location of some chordomas within the base of the skull and the cervical spine can prevent complete resection from being achieved. Previous series have shown that stereotactic radiosurgery can be used as a treatment for residual chordomas with good overall results. The authors review their experience in using linear accelerator (LINAC) stereotactic radiosurgery to treat patients with recurrent and/or residual cranial base and cervical chordomas.Ten patients with chordomas (eight with cranial base and two with cervical lesions [below C-2]) underwent LINAC stereotactic radiosurgery. The mean patient age was 49 years (range 30-73 years). There were seven men and three women. Three patients had undergone one prior surgery, five had undergone two previous surgeries, and two had undergone three prior operations. The mean radiation dose was 19.4 Gy (range 18-24 Gy), and the maximum intratumoral dose averaged 27 Gy (range 24.1-33.1 Gy). The mean secondary collimator size was 14.4 mm (range 7.5-20 mm). The volume of the tumor treated ranged from 1.1 to 21.5 ml. In five patients a standard frame-based LINAC radiosurgery system was used, whereas in the other five the CyberKnife, a frameless image-guided LINAC radiosurgical system, was used. All patients were available for follow-up review, which averaged 4 years (range 1-9 years). Over the course of follow up, one chordoma (10%) was smaller in size, seven were stable, and two chordomas progressed (one in a patient who underwent reoperation and a second course of stereotactic radiosurgery, and the second in a patient who underwent reoperation alone). There were no new neurological deficits noted following radiosurgery in the eight of 10 patients in whom there was no tumor progression, and no patient developed radiation-induced necrosis.Stereotactic radiosurgery can be used to treat patients with recurrent or residual chordomas with excellent tumor control rates. Longer follow-up review in larger series is warranted to confirm these findings.

View details for PubMedID 16734408

Robotics and radiosurgery - The cyberknife STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Chang, S. D., Adler, J. R. 2001; 76 (3-4): 204-208

Abstract

The Cyberknife is a dedicated image-guided robotic radiosurgical device. While clinical results with intracranial lesions are comparable to frame-based radiosurgical techniques, recent experience demonstrates the potential to broadly expand the scope of radiosurgery to many extracranial sites.

View details for Web of Science ID 000178706800015

View details for PubMedID 12378098

Image-guided extracranial radiosurgery PROGRESS IN RADIO-ONCOLOGY VII, PROCEEDINGS Sattah, M., Guerrero, T., Chang, S., Martin, D., Le, Q. T., Gibbs, I., Adler, J. 2001: 153-162
Acquired cerebral arteriovenous malformation induced by an anaplastic astrocytoma: An interesting case NEUROLOGICAL RESEARCH Harris, O. A., Chang, S. D., Harris, B. T., Adler, J. R. 2000; 22 (5): 473-477

Abstract

High grade gliomas foster an environment rich in angiogenic factors that promote neovascularity. We report a case of a cerebral arteriovenous malformation, which developed in the setting of a high grade astrocytoma. The patient presented with complaints of confusion and left hemiparesis. An initial cerebral angiogram was normal. Repeat angiography six weeks later demonstrated an extremely vascular lesion with arteriovenous shunting involving the right thalamus and occipital lobe. Histopathologic evaluation of open biopsy and autopsy specimens demonstrated a high grade astrocytoma in association with an arteriovenous malformation. Immunohistochemical staining with VEGF was diffusely positive. A possible role for the hyperangiogenic environment of a high grade astrocytoma resulting in the development of an arteriovenous malformation is discussed.

View details for Web of Science ID 000088406000007

View details for PubMedID 10935219

Microsurgical resection of brainstem, thalamic, and basal ganglia angiographically occult vascular malformations NEUROSURGERY Steinberg, G. K., Chang, S. D., Gewirtz, R. J., Lopez, J. R. 2000; 46 (2): 260-270

Abstract

To evaluate the clinical results for patients who underwent resection of angiographically occult vascular malformations (AOVMs) of the brainstem, thalamus, or basal ganglia, successfully resected after it exhibited rebleeding and presented to a pial surface.Between January 1990 and May 1998, 56 patients with 57 deep AOVMs underwent 63 operations, at Stanford University Medical Center, to treat AOVMs of the brainstem (42 AOVMs), thalamus (5 AOVMs), or basal ganglia (10 AOVMs). The surgical approach was suboccipital midline (27 operations), far lateral suboccipital (10 operations), transsylvian (9 operations), interhemispheric transcallosal or infracallosal (8 operations), infratentorial supracerebellar (6 operations), or subtemporal (3 operations). Four patients experienced recurrent bleeding from the same lesion after surgical resection, requiring a second operation. One patient required a planned second operation, using a different approach, to completely resect the lesion, and one patient underwent two surgical procedures to resect two separate brainstem AOVMs. One patient initially underwent exploration but not resection of her AOVM, because it did not present to a pial or ependymal surface. The AOVM was successfully resected after it exhibited rebleeding and presented to a pial surface.The immediate outcomes after surgery were unchanged for 31 patients (55%), worsened for 16 (29%), and improved for 9 (16%). The long-term outcomes were unchanged for 24 patients (43%), compared with their presenting grade, worse for 3 (5%), and improved for 29 (52%). Patients who had undergone previous radiotherapy or radiosurgery to treat these lesions experienced more difficult postoperative courses, and radiation necrosis was observed for two patients.AOVMs of the brainstem, thalamus, and basal ganglia can be safely removed, with a long-term neurological morbidity rate of only 5% and a complete lesion resection rate of 93% after the initial planned resection. The use of cranial base surgical approaches and intraoperative electrophysiological monitoring contributes to successful clinical outcomes.

View details for Web of Science ID 000085191800002

View details for PubMedID 10690715

Stereotactic radiosurgery in patients with multiple brain metastases. Neurosurgical focus Chang, S. D., Lee, E., Sakamoto, G. T., Brown, N. P., Adler, J. R. 2000; 9 (2)

Abstract

Patients with multiple brain metastases are often treated primarily with fractionated whole-brain radiation therapy (WBRT). In previous reports the authors have shown that patients with four or fewer brain metastases can benefit from stereotactic radiosurgery in addition to fractionated WBRT. In this paper the authors review their experience using linear accelerator stereotactic radiosurgery to treat patients with multiple brain metastases.Fifty-three patients with 149 brain metastases underwent stereotactic radiosurgery. The mean age of patients was 53.1 years (range 20-78 years). There were 23 men and 30 women. The primary tumor location was lung (27 patients), melanoma (10), breast (six), ovary (six), and other (four). All patients harbored at least two metastatic tumors treated with radiosurgery; 27 patients (51%) harbored two lesions, 17 (32%) three lesions, eight (15%) four lesions, and one patient (2%) harbored five lesions. The mean radiation dose administered was 19.6 Gy (range 14-30 Gy), and the mean secondary collimator size was 15.7 mm (range 7.5-40 mm). One hundred thirty-two (89%) of the 149 treated tumors were available for review on magnetic resonance (MR) imaging at 3 months posttreatment. Fifty-two percent were smaller in size, 31% were stable, 9% had increased in size, and 8% had disappeared. New metastatic tumors appeared in 12 (23%) of the 53 patients on MR imaging within 6 months posttreatment. Radiation-induced necrosis occurred at the site of eight (5.4%) of the 149 tumors at 6 months. Seven tumors (4.7%) subsequently required surgical resection for either tumor progression (four cases) or worsening edema from radiation-induced necrosis (three cases). Median actuarial survival was 9.6 months.Stereotactic radiosurgery can be used to treat patients with up to four brain metastases with a 91% rate of either decrease or stabilization in tumor size and a low rate of radiation-induced necrosis. In the authors' study only a small number of patients subsequently required surgical resection of a treated lesion.

View details for PubMedID 16836289

The treatment of giant intracranial arteriovenous malformations using multimodality therapy Chang, S. D., Lopez, J. R., Levy, R. P., Marks, M. P., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2000: 324-324
Image-guided robotic radiosurgery: Clinical and radiographic results with the CyberKnife Chang, S. D., MURPHY, M. J., Martin, D. P., Hancock, S. L., Doty, J. R., Adler, J. R. KARGER. 2000: 23-33
Current treatment of patients with multiple brain metastases. Neurosurgical focus Chang, S. D., Adler, J. R. 2000; 9 (2)

Abstract

The management of patients with multiple brain metastases remains a difficult challenge for neurosurgeons. This patient population has a poor prognosis when compared with those harboring a solitary brain metastasis, and historically treatment has generally consisted of administering whole-brain radiotherapy once the diagnosis of multiple brain metastases is made. Resection can be useful in a subset of patients with multiple metastases in whom one or two of the lesions are symptomatic, as this may provide rapid reduction of mass effect and edema. Furthermore, the authors of recent studies have shown that stereotactic radiosurgery can be used in certain patients with multiple brain metastases as part of the treatment regimen. In this review the authors outline the treatment options and indications as well as a management strategy for the treatment of patients with multiple brain metastases.

View details for PubMedID 16836291

Reply Muscle & nerve Chang, S. D., Lopez, J. R., Steinberg, G. K. 2000; 23 (9): 1446

View details for PubMedID 10951453

AAEM news and comments Muscle & nerve Chang, S. D., Lopez, J. R., Steinberg, G. K. 2000; 23 (9): 1450-1

View details for PubMedID 10951454

Treatment of intracranial arteriovenous malformations in the elderly population Chang, S. D., Lopez, J. R., Marks, M. P., Levy, R. P., Adler, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2000: 325-325
Intraoperative electrical stimulation for identification of cranial nerve nuclei Chang, S. D., Lopez, J. R., Steinberg, G. K. JOHN WILEY & SONS INC. 1999: 1538-1543

Abstract

The purpose of this study was to evaluate the feasibility and usefulness of cranial nerve nuclei monitoring during resection of brainstem cavernous malformations. Eleven patients with brainstem cavernous malformations underwent resection of their malformations utilizing cranial nerve nuclei monitoring. Cranial nerves V and VII were monitored by placing electrodes in muscle groups innervated by these nerves and recording manipulation-induced neurotonic discharges and triggered electromyographic (EMG) activity, after electrical stimulation of the corresponding brainstem nuclei. Seven of 11 procedures (64%) with cranial nerve nuclei monitoring were noted to have cranial nerve nuclei activity corresponding to manipulation of the nuclei. The cavernous malformation was completely resected in 5 of 7 cases with cranial nerve nuclei activity and in all 4 cases without activity. In the remaining 2 cases, the cavernous malformation was not resected due to the proximity of the monitored cranial nerve nuclei to the cavernous malformation and to increasing neurotonic activity as the cavernous malformation was approached. None of the 11 patients had new permanent postoperative deficits corresponding to the cranial nerve nuclei monitored; 1 patient had a transient partial facial palsy lasting 2 days. Preliminary results indicate that cranial nerve nuclei monitoring proves useful in preserving neurologic function and reducing surgical morbidity during resection of brainstem cavernous malformations, particularly indicating when lesion resection places these nuclei at risk.

View details for Web of Science ID 000083306000008

View details for PubMedID 10514231

The usefulness of electrophysiological monitoring during resection of central nervous system vascular malformations. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Chang, S. D., Lopez, J. R., Steinberg, G. K. 1999; 8 (6): 412-422

Abstract

Goal: The purpose of this study was to evaluate the usefulness of electrophysiological monitoring during the resection of vascular malformations. Methods: Between September 1994 and April 1996, we surgically resected vascular malformations (31 arteriovenous malformations, 22 angiographically occult vascular malformations) from 53 patients (56 procedures) and used intraoperative evoked potential monitoring. Somatosensory evoked potentials (SSEPs) were monitored in 54 procedures (96%), and brain stem auditory evoked potentials (BAEPs) in 17 (30%). The neurological status of the patients was evaluated before and after surgery. Findings: Five of the 54 patients (9%) monitored with SSEPs had SSEP changes (4 transient, 1 persistent) coinciding with new clinical neurological deficits in 4 patients (all transient). In all 4 patients who had transient SSEP changes, the changes resolved with adjustment or removal of clips on feeding vessels (2 patients) or with elevating mean arterial pressure (MAP) (2 patients). Forty-seven patients (91%) had neither SSEP or neurological examination alterations. One of 17 patients (6%) monitored with BAEPs had neurological and persistent BAEP changes, 15 (88%) had neither BAEP or neurological changes, and 1 (6%) had a neurological change despite no change in BAEP (false negative). The sensitivity of SSEP and BAEP for predicting a new postoperative deficit (transient or prolonged) in this series was 86% (6/7); specificity was 98% (55/56). Clinical outcome was excellent in 41 patients, good in 11 and poor in 1 (no patients died) and was largely related to pretreatment grade. Conclusion: SSEPs and BAEPs predict the likelihood of clinical neurological injury during resection of vascular malformations with high sensitivity and specificity and may prove a useful adjunct in treating these lesions.

View details for PubMedID 17895195

Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: Impact on local control Tate, D. J., Adler, J. R., Chang, S. D., Marquez, S., Eulau, S. M., Fee, W. E., PINTO, H., Goffinet, D. R. ELSEVIER SCIENCE INC. 1999: 915-921

Abstract

Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma.Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy).All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases.Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.

View details for Web of Science ID 000083624000013

View details for PubMedID 10571198

Intracranial nasal dermoid sinus cyst associated with colloid cyst of the third ventricle - Case report and new concepts PEDIATRIC NEUROSURGERY Cheng, M. L., Chang, S. D., Pang, D. L., Adler, J. R. 1999; 31 (4): 201-206

Abstract

A case of a 16-year-old male with both a nasal dermoid sinus cyst (NDSC) and a third ventricle colloid cyst is presented. The NDSC was excised via a single-stage combined intracranial-extracranial approach and the third ventricle colloid cyst was resected endoscopically. The pathogenetic theories of NDSC and third ventricle colloid cyst are discussed, and an embryological explanation for the simultaneous development of the two lesions in this patient is explored. This case is best classified among congenital developmental malformations in a category we propose to call 'anterior neuropore corridor defects.'

View details for Web of Science ID 000085112900007

View details for PubMedID 10705930

Correlation of magnetic resonance characteristics and histopathological type of angiographically occult vascular malformations NEUROSURGERY Vanefsky, M. A., Cheng, M. L., Chang, S. D., Norbash, A., Snipe, J., Marks, M. P., Steinberg, G. K. 1999; 44 (6): 1174-1180
Symptomatic vasospasm after resection of a suprasellar pilocytic astrocytoma: Case report and possible pathogenesis SURGICAL NEUROLOGY Chang, S. D., Yap, O. W., Adler, J. R. 1999; 51 (5): 521-526

Abstract

Cerebral vasospasm from pathology other than subarachnoid hemorrhage is uncommon. A case of severe vasospasm after resection of a suprasellar pilocytic astrocytoma is reported.A 45-year-old male presented with headache, left facial numbness, bilateral visual loss, and ataxia. Evaluation revealed a large suprasellar tumor, which was resected. Pathologic examination showed pilocytic astrocytoma. The patient developed hemiparesis and aphasia on the fifth postoperative day. Vascular spasm was documented on angiography and by transcranial Doppler.Intraarterial papaverine resulted in moderate angiographic improvement. Attempts to open middle cerebral artery branches with angioplasty were unsuccessful. The patient subsequently developed a left middle cerebral artery infarct.To our knowledge, this is the first description of vasospasm after resection of an astrocytoma. Possible mechanisms contributing to this unusual complication after resection of tumors are discussed.

View details for Web of Science ID 000080147200021

View details for PubMedID 10321883

Recanalization and rupture of a giant vertebral artery aneurysm after Hunterian ligation: Case report NEUROSURGERY Chang, S. D., Marks, M. P., Steinberg, G. K. 1999; 44 (5): 1117-1120

Abstract

Recanalization and subsequent rupture of giant aneurysms of the posterior circulation after Hunterian ligation is an extremely rare event that has been noted to occur with basilar apex, basilar trunk, and vertebrobasilar junction aneurysms. We report the case of a giant, previously unruptured right vertebral artery aneurysm, which recanalized from the contralateral vertebral artery and subsequently ruptured after previously performed angiography showed complete thrombosis of the aneurysm.A 72-year-old woman presented with headaches, ataxia, and lower extremity weakness. A giant 3-cm right vertebral artery aneurysm was found during the patient evaluation.Because of the size of the aneurysm and the absence of a discrete neck, Hunterian ligation was performed. After treatment, angiograms showed no filling of the aneurysm from either the right or left vertebral artery. Nine days later, after the patient developed lethargy and nausea, repeat angiography showed that a small portion of the aneurysmal base had recanalized. The next day, the patient had a massive subarachnoid hemorrhage and subsequently died.We think that this is a previously undescribed complication associated with direct arterial ligation of giant vertebral artery aneurysms. Patients with aneurysms treated using Hunterian ligation need to be followed up closely. Even aneurysms that have minimal recanalization are at risk for subarachnoid hemorrhage.

View details for Web of Science ID 000079903800096

View details for PubMedID 10232546

The use of electrophysiological monitoring in the intraoperative management of intracranial aneurysms JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Lopez, J. R., Chang, S. D., Steinberg, G. K. 1999; 66 (2): 189-196

Abstract

Somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs) have been increasingly utilised during surgery for intracranial aneurysms to identify cerebral ischaemia. Between July 1994 and April 1996, we surgically treated 70 aneurysms in 49 consecutive patients (58 operations) with the aid of intraoperative evoked potential monitoring. This study sought to evaluate the usefulness of SSEP and BAEP monitoring during intracranial aneurysm surgery.Mean patient age was 51.9 (range 18-79) years. The sizes of the aneurysms were 3-4 mm (15), 5-9 mm (26), 10-14 mm (11), 15-19 mm (seven), 20-24 mm (six), and >25 mm (five). SSEPs were monitored in 58 procedures (100%) and BAEPs in 15 (26%). The neurological status of the patients was evaluated before and after surgery.Thirteen of the 58 procedures (22%) monitored with SSEPs had SSEP changes (12 transient, one persistent); 45 (78%) had no SSEP changes. Three of 15 patients (20%) monitored with BAEPs had changes (two transient, one persistent); 12 (80%) had no BAEP changes. Of the 14 patients with transient SSEP or BAEP changes, these changes resolved with adjustment or removal of aneurysm clips (nine), elevating MAP (four), or retractor adjustment (one). Mean time from precipitating event to electrophysiological change was 8.9 minutes (range 3-32), and the mean time for recovery of potentials in patients with transient changes was 20.2 minutes (range 3-60). Clinical outcome was excellent in 39 patients, good in five, and poor in three (two patients died), and was largely related to pretreatment grade.SSEPs and BAEPs are useful in preventing clinical neurological injury during surgery for intracranial aneurysms and in predicting which patients will have unfavourable outcomes.

View details for Web of Science ID 000078450800011

View details for PubMedID 10071098

Image-guided robotic radiosurgery Neurosurgery Adler, J. R., Murphy, M. J., Chang, S. D., Hancock, S. L. 1999; 44 (6): 1299-306; discussion 1306-7

Abstract

PURPOSE: To describe the design and performance of a novel frameless system for radiosurgery. This technology, called image-guided radiosurgery (IGR), eliminates the need for stereotactic frame fixation by relating the identified lesion to radiographic landmarks. CONCEPT: IGR uses a lightweight x-band linear accelerator, computer-controlled robotic arm (Fanuc manipulator [Fanuc Robotics North America, Inc., Rochester Hills, MI]), paired orthogonal x-ray imagers, and a computer workstation that performs rapid image-to-image registration. During radiosurgery, the x-ray imaging system determines the location of the lesion and communicates these coordinates to the robot, which adjusts the pointing of the linear accelerator beam to maintain alignment with the target. RATIONALE: Existing stereotactic techniques require rigid cranial fixation to establish and maintain a system of reference for targeting. Such frames cause pain for the patient, limit the use of fractionation, and necessitate a prolonged period of general anesthesia if children are to be treated. Furthermore, skeletal or any other type of rigid fixation is difficult to achieve beyond the cranium. IGR was designed to overcome these limitations, which are inherent to nearly all current radiosurgical methods. DISCUSSION: Preliminary testing and early clinical experience have demonstrated the practicality and potential of the IGR concept and have identified the most important directions for improvement. For example, an IGR prototype accurately tracked target displacements in three dimensions but showed reduced accuracy when confronted by rotational movements. This observation led to development of a new generation of tracking algorithm that promises to improve tracking in all six dimensions. Further experience indicated that improvements in the quality of the x-ray images were needed to allow the system to locate and treat target sites outside the cranium. Consequently, a new x-ray imaging technology with superior resolution and increased sensitivity has been added to the system. These improvements should make it possible to apply IGR techniques to a variety of targets located throughout the body. This article describes and critiques the components of the IGR and summarizes our preliminary clinical experience.

View details for PubMedID 10371630

Management of the radiosurgery patient: Causes and treatment of adverse sequelae RADIATION INJURY Chang, S. D., Adler, J. R. 1999; 32: 155-165
Treatment of cavernous sinus tumors with linear accelerator radiosurgery SKULL BASE SURGERY Chang, S. D., Doty, J. R., Martin, D. P., Hancock, S. L., Adler, J. R. 1999; 9 (3): 195-199

Abstract

Since 1989, 79 patients with benign or malignant cavernous sinus tumors, have been treated at Stanford University with linear accelerator (linac) radiosurgery. Radiosurgery has been used as (1) a planned second-stage procedure for residual tumor following surgery, (2) primary treatment for patients whose medical conditions preclude surgery, (3) palliation of malignant lesions, and (4) definitive treatment for small, well-localized, poorly accessible tumors. Mean patient age was 52 years (range, 18 to 88); there were 28 males and 51 females. Sixty-one patients had benign tumors; 18 had malignant tumors. Mean tumor volume was 6.8 cm(3) (range 0.5 to 22.5 cm(3)) covered with an average of 2.3 isocenter (range, 1 to 5). Radiation dose averaged 17.1 Gy. Mean follow-up was 46 months. Tumor control or shrinkage, or both, varied with pathology. Radiographic tumor improvement was most pronounced in malignant lesions, with greater than 85% showing reduction in tumor size; benign tumors (meningiomas and schwannomas) had a 63% control rate and 37% shrinkage rate, with none enlarging. We concluded that stereotactic radiosurgery is a valuable tool in managing cavernous sinus tumors. There was excellent control and stabilization of benign tumors and palliation of malignant lesions.

View details for Web of Science ID 000083016700004

View details for PubMedID 17171089

Correlation of magnetic resonance characteristics and histopathological type of angiographically occult vascular malformations Neurosurgery Vanefsky, M. A., Cheng, M. L., Chang, S. D., Norbash, A., Snipe, J., Marks, M. P., Steinberg, G. K. 1999; 44 (6): 1174-80; discussion 1180-1

Abstract

OBJECTIVE: Histological and radiological classification of vascular malformations has previously been attempted in an effort to understand their nature and predict their biological behavior. There exists a subgroup of vascular malformations that are angiographically occult and share a common magnetic resonance imaging (MRI) appearance but may differ in their behavior. We sought to determine any correlation between MRI features and final histopathological diagnosis. METHODS: We reviewed our series of 72 patients with angiographically occult vascular malformations operated on at Stanford University Medical Center between 1988 and 1993. Radiographic magnetic resonance images and histopathological specimens were retrospectively evaluated for various diagnostic features. RESULTS: Our data indicate that lesions exhibiting a ring of hemosiderin are associated with the presence of a cavernous malformation (CM) component (86% of CMs versus 33% of non-CM lesions). A lesion associated with edema, mass effect, or a single prominent blood product on MRI correlates with the presence of an arteriovenous malformation (AVM) component. Sixty-three percent of AVMs and 80% of lesions with partial AVM components showed edema, compared with 8% of CMs and 0% of venous malformations. Sixty percent of AVMs and 63% of lesions with partial AVM components showed a single prominent blood product, compared with 8% of CMs and 0% of venous malformations. Finally, 60% of AVMs exhibited mass effect, compared with 20% of CMs. Additionally, an expansile hemorrhage is suggestive of an AVM. CONCLUSION: This study is the first to demonstrate that a particular MRI appearance of an angiographically occult vascular malformation is suggestive of an AVM component. This may have important implications with regard to the behavior of the lesion and planning of future treatment.

View details for PubMedID 10371616

Treatment of nasopharyngeal carcinoma: Stereotactic radiosurgical boost following fractionated radiotherapy Chang, S. D., Tate, D. J., Goffinet, D. R., Martin, D. P., Adler, J. R. KARGER. 1999: 64-67

Abstract

Treatment of patients with nasopharyngeal carcinoma (NPC) using external beam radiation therapy (XRT) alone results in significant local recurrence. To improve local control, stereotactic radiosurgery (SRS) was used to boost radiation to the primary tumor site following XRT in 23 patients with NPC. SRS was delivered utilizing a frame-based linear accelerator as a boost (range 7-15 Gy, median 12 Gy) following XRT (range 64.8- 70 Gy, median 66 Gy). In all 23 patients (100%) receiving SRS following XRT local control was achieved at a mean follow-up of 21 months (range 2-64 months). There have been no complications of treatment caused by SRS. However, 8 patients (35%) have subsequently developed regional or distant metastases. SRS boost following XRT provides excellent local control in NPC and should be considered for patients with skull base involvement.

View details for Web of Science ID 000087727900012

View details for PubMedID 10853100

The use of electrophysiologic monitoring during intracranial cerebrovascular surgery: A cost-benefit analysis Chang, S. D., Lopez, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 1999: 257-257
Clinical experience with image-guided robotic radiosurgery (the Cyberknife) in the treatment of brain and spinal cord tumors NEUROLOGIA MEDICO-CHIRURGICA Chang, S. D., Murphy, M., Geis, P., Martin, D. P., Hancock, S. L., Doty, J. R., Adler, J. R. 1998; 38 (11): 780-783

Abstract

The Cyberknife is an image-guided "frameless" dedicated radiosurgical device. This instrument has several distinct advantages over frame-based systems, including improved patient comfort, increased treatment degrees of freedom, and the potential to target extracranial lesions. Clinical results thus far with respect to the treatment of malignant intracranial tumors has been promising. Additionally, the Cyberknife will likely revolutionize the application of radiosurgery to extracranial sites. A description of the components, treatment planning, and clinical results of the Cyberknife will be reviewed.

View details for Web of Science ID 000077103400031

View details for PubMedID 9919913

Microsurgical resection of incompletely obliterated intracranial arteriovenous malformations following stereotactic radiosurgery NEUROLOGIA MEDICO-CHIRURGICA Chang, S. D., Steinberg, G. K., Levy, R. P., Marks, M. P., Frankel, K. A., Shuster, D. L., Marcellus, M. L. 1998; 38: 200-207

Abstract

Radiosurgery is effective in obliterating small arteriovenous malformations (AVMs), but less successful in thrombosing larger AVMs. This study reviewed patients who underwent surgical resection of their large AVMs following failed radiosurgical obliteration. AVMs from 36 patients (aged 7 to 64 years, mean 29.9) were surgically resected 1 to 11 years after radiosurgery. Initial AVM volumes were 0.7 to 117 cm3 (mean 21.6 cm3), and radiosurgical doses ranged from 4.6 to 45 Gray equivalent (GyE) (mean 21.1 GyE). Thirty AVMs (83%) were located in eloquent tissue. Venous drainage was deep (14), superficial (13), or both (9). Spetzler grades were II (2), III (12), IV (18), and V (4). Nine patients suffered rehemorrhage after radiosurgery but prior to surgery, while three patients developed radiation necrosis. Twenty-seven patients underwent endovascular embolization prior to surgery. During microsurgical resection, the AVMs were found to be significantly less vascular and more easily resected, compared to AVMs in patients who had not received radiosurgery. Histology showed endothelial proliferation with hyaline and mineralization in vessel walls. Partial or complete thrombosis of some AVM vessels, and evidence of vessel and brain necrosis were noted in many cases. Clinical outcome was excellent or good in 34 cases, with two patients dying of rebleeding from residual AVM. Five patients were neurologically worse following microsurgical resection. Final outcome was largely related to the pretreatment grade. Radiosurgery several years prior to surgical resection appears useful in treating unusually large and complex AVMs.

View details for Web of Science ID 000078035900037

View details for PubMedID 10235006

Bilateral cavernous malformations resulting from cranial irradiation of a choroid plexus papilloma NEUROLOGICAL RESEARCH Chang, S. D., Vanefsky, M. A., Havton, L. A., Silverberg, G. D. 1998; 20 (6): 529-532

Abstract

We report a case of multiple parietal cavernous malformations in a thirteen year old female who received cranial irradiation following incomplete resection of a choroid plexus papilloma. The cavernous malformations, which developed within the prior parietal radiation ports, were diagnosed nine years after the patients' radiation treatment when the patient presented with increasing frequency of seizures. Family history was negative for familial cavernous malformations. Due to the worsening frequency of seizures, the patient underwent resection of these two cavernous malformations with diagnosis confirmed by pathology. Post-operative, there was a significant reduction in seizure frequency. The origin and pathophysiology of cavernous malformations remains controversial. Cranial radiation treatment for tumors, particularly in children, may possibly lead to the development of these lesions, as occurred in this case. This is, to our knowledge, the first case of multiple cavernous malformations occurring within a previous radiation field following radiotherapy for a neoplasm.

View details for Web of Science ID 000075190700009

View details for PubMedID 9713844

Clinical uses of radiosurgery ONCOLOGY-NEW YORK Chang, S. D., Adler, J. R., Hancock, S. L. 1998; 12 (8): 1181-?

Abstract

Radiosurgery uses stereotactic targeting methods to precisely deliver highly focused, large doses of radiation to small intracranial tumors and arteriovenous malformations (AVMs). This article reviews the most common clinical applications of radiosurgery and the clinical results reported from a number of series using either a cobalt-60 gamma knife or linear accelerator as radiation sources. Radiosurgery is used to treat malignant tumors, such as selected cases of brain metastases and malignant gliomas (for which stereotactic radiosurgical boosts are utilized in conjunction with fractionated radiation therapy), as well as benign tumors, such as meningiomas, acoustic neuromas, and pituitary adenomas. Treatment of small AVMs is also highly effective. Although radiosurgery has the potential to produce complications, the majority of patients experience clinical improvement with less morbidity than occurs with surgical resection.

View details for Web of Science ID 000075449300014

View details for PubMedID 11236310

Acute hearing loss following fractionated stereotactic radiosurgery for acoustic neuroma - Report of two cases JOURNAL OF NEUROSURGERY Chang, S. D., Poen, J., Hancock, S. L., Martin, D. P., Adler, J. R. 1998; 89 (2): 321-325

Abstract

Two cases of acute hearing loss are reported following fractionated stereotactic radiosurgery for acoustic neuroma. Both patients had neurofibromatosis type 2 and were treated with a peripheral tumor dose of 21 Gy delivered in three fractions (7 Gy each) with a minimum interfraction interval of 10 hours. One patient who had previously undergone surgical resection of the treated tumor presented with only rudimentary hearing in the treated ear secondary to an abrupt decrease in hearing prior to treatment. That patient reported total loss of hearing before complete delivery of the third fraction. The second patient had moderately impaired hearing prior to treatment; however, within 10 hours after delivery of the final fraction, he lost all hearing. Both patients showed no improvement in response to glucocorticoid therapy. Possible explanations for this phenomenon are presented.

View details for Web of Science ID 000074994900022

View details for PubMedID 9688131

Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience NEUROSURGERY Chang, S. D., Levy, R. P., Adler, J. R., Martin, D. P., Krakovitz, P. R., Steinberg, G. K. 1998; 43 (2): 213-220

Abstract

Radiosurgery is generally effective in obliterating true arteriovenous malformations, but less is known about its effects on angiographically occult vascular malformations (AOVMs). Since July 1983, 57 patients with surgically inaccessible AOVMs of the brain were treated using helium ion (47 patients) or linear accelerator (10 patients) radiosurgery. This study retrospectively evaluates the response of these AOVMs to treatment.All patients presented with previous hemorrhage. The mean patient age was 35.6 years (range, 13-71 yr). The mean AOVM volume was 2.25 cm3 (range, 0.080-15.2 cm3), treated with a mean of 18.0 Gy equivalent (physical dose x relative biological effectiveness, which is 1.3 for helium ion Bragg peak) (range, 7.0-40 Gy equivalent). The Drake scale scores before treatment were as follows: excellent (25 patients), good (26 patients), and poor (6 patients). The mean follow-up period was 7.5 years (range, 9 mo-13.8 yr).Eighteen patients (32%) bled symptomatically (20 hemorrhages) after radiosurgery. Sixteen hemorrhages occurred within 36 months after radiosurgery (9.4% annual bleed rate; 16 hemorrhages/171 patient yr); 4 hemorrhages occurred more than 36 months after treatment (1.6% annual bleed rate; 4 hemorrhages/257 patient yr) (P < 0.001). Complications included symptomatic radiation edema (four patients, 7%), necrosis (one patient, 2%), and increased seizure frequency (one patient, 2%). Eight patients underwent surgical resection of their AOVMs 8 to 59 months after radiosurgery because of subsequent hemorrhage. The Drake scale scores after treatment were as follows: excellent (25 patients), good (24 patients), poor (3 patients), and dead (5 patients, 3 of whom died as a result of causes unrelated to the AOVMs or radiosurgery).Radiosurgery may be useful for AOVMs located in surgically inaccessible regions of the brain. A significant decrease in bleed rate exists more than 3 years after treatment compared with the bleed rate within 3 years of treatment. Because current neuroradiological techniques are not able to image obliterative response in these slow-flow vascular lesions, longer term clinical follow-up is required.

View details for Web of Science ID 000074979500010

View details for PubMedID 9696072

Arteriovenous malformations after radiosurgery JOURNAL OF NEUROSURGERY Chang, S. D., Steinberg, G. K. 1998; 89 (1): 170-170

View details for Web of Science ID 000074325600035

View details for PubMedID 9647195

Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery NEUROSURGERY Chang, S. D., Meisel, J. A., Hancock, S. L., Martin, D. P., McManus, M., Adler, J. R. 1998; 43 (1): 28-34

Abstract

Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas.From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo).Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic.Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.

View details for Web of Science ID 000074274500016

View details for PubMedID 9657185

LINAC radiosurgery for cavernous sinus meningiomas STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Chang, S. D., Adler, J. R., Martin, D. P. 1998; 71 (1): 43-50

Abstract

Radiosurgery is increasingly used to treat unresectable cavernous sinus tumors. Since 1989, 24 patients with cavernous sinus meningiomas have been treated at Stanford University Medical Center with linear accelerator (LINAC) radiosurgery. The mean age of the patients was 47.8 years (range 28-78). The mean volume treated was 6. 83 cm3 (range 0.45-22.45 cm3), covered with an average of 2.3 isocenters (range 1-5). Radiation dose averaged 17.7 Gy (range 14-20 Gy). This group of patients was retrospectively studied by sending clinical questionnaires to both the patient/family and referring physicians, and reviewing clinic charts. In addition, follow-up imaging studies were obtained to measure residual tumor volume. Follow-up averaged 45.6 months (range 19-80). Tumor control (stabilization) following radiosurgery was noted in 15 (63%) and tumor shrinkage in 9 (37%). Seven meningiomas (29%) showed evidence of central tumor necrosis on MRI imaging 1-3 years after radiosurgery. Neurologic status was improved in 10 patients (42%) and unchanged in 12 patients (50%). There was 1 case of symptomatic brain necrosis and 1 case of radiation edema (asymptomatic). All other complications were transient, including 4 cases of trigeminal hypesthesia and 1 case of worsening diplopia. The 2-year actuarial tumor control rate was 100%. Although follow-up is still short, this experience corroborates prior reports that radiosurgery can be used to treat selected small cavernous sinus meningiomas with good to excellent clinical results and minimal morbidity.

View details for Web of Science ID 000079497300005

View details for PubMedID 10072673

Cranial nerve nuclei monitoring during resection of brainstem cavernous malformations: Preliminary results Chang, S. D., Lopez, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 1998: 276-276
Management of intracranial aneurysms. Vascular medicine Chang, S. D., Steinberg, G. K. 1998; 3 (4): 315-326

Abstract

Intracranial aneurysms are lesions commonly encountered by neurosurgeons, usually as a result of subarachnoid hemorrhage. The preferred treatment of these aneurysms is either surgical clipping or endovascular coiling, both of which eliminate the aneurysm from the normal circulation to prevent aneurysmal enlargement or additional hemorrhage. Despite advances over the last several decades in the understanding of intracranial aneurysms, morbidity from treatment of these lesions remains significant. This review will discuss the epidemiology, anatomy and pathophysiology, clinical and radiographic diagnosis, various treatment options, and potential complications from aneurysm treatment.

View details for PubMedID 10102672

Treatment of cranial base meningiomas with linear accelerator radiosurgery NEUROSURGERY Chang, S. D., Adler, J. R. 1997; 41 (5): 1019-1025

Abstract

Radiosurgery is increasingly being used to treat cranial base tumors. Since 1989, 55 patients with cranial base meningiomas were treated at Stanford University Medical Center with linear accelerator radiosurgery. An analysis of the clinical and radiographic results of this patient population was the focus of this study.The mean patient age was 55.1 years (range, 28-82 yr). The mean tumor volume was 7.33 cm3 (range, 0.45-27.65 cm3). The radiation dose averaged 18.3 Gy (range, 12-25 Gy), delivered with an average of 2.2 isocenters (range, 1-5). Patients were evaluated retrospectively through clinic notes from follow-up examinations, and residual tumor volume was measured during follow-up imaging studies. The length of follow-up averaged 48.4 months (range, 17-81 mo).Tumor stabilization after radiosurgery was noted in 38 patients (69%), shrinkage in 16 patients (29%), and enlargement in only 1 patient (2%). The results of follow-up magnetic resonance imaging demonstrated decreased central contrast uptake in 11 meningiomas (20%), possibly indicating evidence of central tumor necrosis or tumor vessel obliteration. Neurological status was improved in 15 patients in the series (27%) and unchanged in 34 patients (62%). Three patients (5%) died during the follow-up period, all as a result of causes other than tumor progression. Three patients (5%) developed new permanent symptoms (one patient with seizures, one patient with mild right hemiparesis, and one patient with both vagal and hypoglossal nerve palsy). All other complications were transient, including partial trigeminal nerve palsy in seven patients and diplopia in three patients. The 2-year actuarial tumor control rate was 98%.Although our follow-up period is short, this experience corroborates previous reports that radiosurgery can be used to ablate selected small cranial base meningiomas, with good clinical results and modest morbidity.

View details for Web of Science ID A1997YE15600007

View details for PubMedID 9361055

Mixed arteriovenous malformation and capillary telangiectasia: A rare subset of mixed vascular malformations - Case report JOURNAL OF NEUROSURGERY Chang, S. D., Steinberg, G. K., Rosario, M., Crowley, R. S., Hevner, R. F. 1997; 86 (4): 699-703

Abstract

In this report, the authors discuss the case of a patient with a mixed cerebrovascular malformation in which an arteriovenous malformation (AVM) was associated with a capillary telangiectasia. Recent reports have contained reviews of various subsets of mixed malformations. To the authors' knowledge, however, this is the first report of a mixed vascular malformation with both arterial and capillary components. The patient underwent complete resection of the AVM after presenting with a clinical hemorrhage. She required a second operation to resect the capillary telangiectasia after new symptoms developed several months following the first procedure. The authors conclude that a mixed AVM-capillary telangiectasia is a rare but distinct entity.

View details for Web of Science ID A1997WP02000017

View details for PubMedID 9120635

Stereotactic radiosurgery of arteriovenous malformations: Pathologic changes in resected tissue CLINICAL NEUROPATHOLOGY Chang, S. D., Shuster, D. L., Steinberg, G. K., Levy, R. P., Frankel, K. 1997; 16 (2): 111-116

Abstract

Both stereotactic radiosurgery and microsurgery are treatment modalities for arteriovenous malformations (AVM), and more recently, multimodality treatment using these approaches has been utilized. We surgically resected AVMs from 33 patients (ages 7-64 years old, mean age 30.4) 1-11 years after radiosurgery. AVM volumes were 0.8-117 cm3 (mean 21.6 cm3), and doses ranged from 4.6-45 GyE (mean 21.2 GyE). AVMs resected were submitted for pathologic review. Each AVM was evaluated for the following radiation changes, and the number of AVMs demonstrating these changes were noted: endothelial proliferation (27), hyaline (18) and calcium (10) in AVM vessel walls, partial (9) or complete (24) thrombosis of some AVM vessels, and necrosis of vessels (15) and adjacent brain tissue (11). A semiquantitative scale (mild, moderate, severe) incorporating the aforementioned changes present in each case classified the extent of radiation-induced change. There was a significant correlation (r = 0.624, p < 0.01) between extent of radiation change and dose of radiation received. There was no absolute radiation dose threshold below which radiation-induced changes were absent. However, all but one patient receiving greater than 20 GyE developed moderate to severe radiation vascular changes and the 3 patients treated with greater than 30 GyE all had severe radiation-induced changes. Radiation changes in AVMs following stereotactic radiosurgery appear to be dose-related. The correlation of dose to extent of radiation change may allow the determination of the optimal dose of radiation to treat AVMs.

View details for Web of Science ID A1997WR10700012

View details for PubMedID 9101115

The use of electrophysiologic monitoring during resection of arteriovenous malformations and angiographically occult vascular malformations Chang, S. D., Lopez, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 1997: 172-172
The cyberknife: A frameless robotic system for radiosurgery STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Adler, J. R., Chang, S. D., MURPHY, M. J., Doty, J., Geis, P., Hancock, S. L. 1997; 69 (1-4): 124-128

Abstract

The Cyberknife is a unique instrument for performing frameless stereotactic radiosurgery. Rather than using rigid immobilization, the Cyberknife relies on an image-to-image correlation algorithm for target localization. Furthermore, the system utilizes a novel, light-weight, high-energy radiation source. The authors describe the technical specifications of the Cyberknife and summarize the initial clinical experience.

View details for Web of Science ID 000074800300019

View details for PubMedID 9711744

Surgical resection of large incompletely treated intracranial arteriovenous malformations following stereotactic radiosurgery JOURNAL OF NEUROSURGERY Steinberg, G. K., Chang, S. D., Levy, R. P., Marks, M. P., Frankel, K., Marcellus, M. 1996; 84 (6): 920-928

Abstract

Although radiosurgery is effective in obliterating small arteriovenous malformations (AVMs), it has a lower success rate for thrombosing larger AVMs. The authors surgically resected AVMs from 33 patients ranging in age from 7 to 64 years (mean 30.4 years) 1 to 11 years after radiosurgery. Initial AVM volumes were 0.8 to 117 cm3 (mean 21.6 cm3), and doses ranged from 4.6 to 45 GyE (mean 21.2 GyE). Of 27 AVMs in eloquent or critical areas, 10 were located in language, motor, sensory, or visual cortex, 11 in the basal ganglia/thalamus, one each in the brainstem, hypothalamus, and cerebellum, and three in the corpus callosum. Venous drainage was deep in 13, superficial in 12, or both in eight lesions. Spetzler-Martin grades were II in one, III in 12, IV in 16, and V in four patients. Eight patients experienced rebleeding after radiosurgery but prior to surgery. Three patients developed radiation necrosis and 25 underwent endovascular embolization prior to surgery. At surgery the AVMs were found to be markedly less vascular, partially thrombosed, and more easily resected, compared to those seen in patients who had not undergone radiosurgery. Pathological investigation showed endothelial proliferation with hyaline and calcium in vessel walls. There was partial or complete thrombosis of some AVM vessels and evidence of vessel and brain necrosis in many cases. Complete resection was achieved in 28 patients and partial resection in five. Clinical outcome was excellent or good in 31 cases, and two patients died of rebleeding from residual AVM. Four patients' conditions worsened following microsurgical resection. Final clinical outcome was largely related to the pretreatment grade. Radiosurgery several years prior to open microsurgery may prove to be a useful adjunct in treating unusually large and complex AVMs.

View details for Web of Science ID A1996UM58700003

View details for PubMedID 8847585