nutch_noindex
CANCEL
COVID-2019 Alert

Information about the 2019 Novel Coronavirus. Read the latest >

Información sobre el coronavirus 2019 (COVID-19). Aprenda más >

/nutch_noindex

Steven Hancock, MD

  • No Image

Specialties

Radiation Oncology

Therapeutic Radiology

Work and Education

Professional Education

Stanford University School of Medicine, Palo Alto, CA, 06/30/1976

Internship

Stanford University School of Medicine, Stanford, CA, 06/30/1977

Residency

Stanford University Dept of Radiation Oncology, Stanford, CA, 06/30/1978

Stanford University Internal Medicine Residency, Stanford, CA, 06/30/1980

Stanford University Radiation Oncology Residency, Stanford, CA, 06/30/1981

Board Certifications

Internal Medicine, American Board of Internal Medicine

Therapeutic Radiology, American Board of Radiology

All Publications

A Phase I/II Trial of 5-Fraction Stereotactic Radiosurgery with 5-mm Margins with Concurrent Temozolomide in Newly Diagnosed Glioblastoma: Primary Outcomes. Neuro-oncology Azoulay, M., Chang, S. D., Gibbs, I. C., Hancock, S. L., Pollom, E. L., Harsh, G. R., Adler, J. R., Harrahar, C., Li, G., Hayden Gephart, M., Nagpal, S., Thomas, R. P., Recht, L. D., Jacobs, L. R., Modlin, L. A., Wynne, J., Seiger, K., Fujimoto, D., Usoz, M., von Eyben, R., Choi, C. Y., Soltys, S. G. 2020

Abstract

We sought to determine the maximum tolerated dose (MTD) of 5-fraction stereotactic radiosurgery (SRS) with 5-mm margins delivered with concurrent temozolomide in newly diagnosed glioblastoma.We enrolled adult patients with newly diagnosed glioblastoma to 5 days of SRS in a 3+3 design on 4 escalating dose levels: 25, 30, 35, and 40 Gy. Dose limiting toxicity (DLT) was defined as CTCAE Grade 3-5 acute or late CNS toxicity, including adverse radiation effect (ARE), the imaging correlate of radiation necrosis.From 2010 to 2015, 30 patients were enrolled. The median age was 66 years (range 51-86 years). The median target volume was 60 cm3 (range 14.7-137.3 cm3). DLT occurred in 2 patients: one for post-treatment cerebral edema and progressive disease at 3 weeks (Grade 4, Dose 40 Gy); another patient died 1.5 weeks following SRS from post-operative complications (Grade 5, Dose 40 Gy). Late grade 1-2 ARE occurred in 8 patients at a median of 7.6 months (range 3.2-12.6 months). No grade 3-5 ARE occurred. With a median follow-up of 13.8 months (range 1.7-64.4 months), the median survival times were: PFS 8.2 months (95%CI 4.6-10.5), OS 14.8 months (95%CI 10.9-19.9), MGMT hypermethylated 19.9 months (95%CI 10.5-33.5) vs. 11.3 months (95%CI 8.9-17.6) for no/unknown hypermethylation (p=0.03), and 27.2 months (95%CI 11.2-48.3) if late ARE occurred vs. 11.7 months (95%CI 8.9-17.6) for no ARE (p=0.08).The per-protocol MTD of 5-fraction SRS with 5-mm margins with concurrent temozolomide was 40 Gy in 5 fractions. ARE was limited to grade 1-2 and did not statistically impact survival.

View details for DOI 10.1093/neuonc/noaa019

View details for PubMedID 32002547

Intracranial Tumor Control Following Immune-Related Adverse Events and Discontinuation of Immunotherapy for Melanoma. World neurosurgery Zhang, M., Rodrigues, A. J., Bhambhvani, H. P., Fatemi, P., Pollom, E. L., Gibbs, I. C., Thomas, R. P., Soltys, S. G., Hancock, S. L., Chang, S. D., Reddy, S. A., Gephart, M. H., Li, G. 2020

Abstract

Immunotherapy for melanoma patients with brain metastasis has significantly improved outcomes; however, they have also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports suggest these reactions can precede improved treatment responses. We sought to identify if such association exists for intracranial disease control.We conducted a retrospective chart review of melanoma patients who underwent immunotherapy treatment following diagnosis of brain metastasis. The study cohort was then stratified into two groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analysis were used to evaluate survival and predictors of outcomes.Fifty-two patients met inclusion criteria, seventeen of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 vs 10.5 months (p = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival, mean (33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (p = 0.013, HR = 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (p = 0.015, HR = 10.73) CONCLUSION: Immune related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to demonstrate promising outcomes as a first-line agent for melanoma with brain metastasis.

View details for DOI 10.1016/j.wneu.2020.08.124

View details for PubMedID 32853767

NCCN Guidelines Insights: Kidney Cancer, Version 1.2021. Journal of the National Comprehensive Cancer Network : JNCCN Motzer, R. J., Jonasch, E., Boyle, S., Carlo, M. I., Manley, B., Agarwal, N., Alva, A., Beckermann, K., Choueiri, T. K., Costello, B. A., Derweesh, I. H., Desai, A., George, S., Gore, J. L., Haas, N., Hancock, S. L., Kyriakopoulos, C., Lam, E. T., Lau, C., Lewis, B., Madoff, D. C., McCreery, B., Michaelson, M. D., Mortazavi, A., Nandagopal, L., Pierorazio, P. M., Plimack, E. R., Ponsky, L., Ramalingam, S., Shuch, B., Smith, Z. L., Somer, B., Sosman, J., Dwyer, M. A., Motter, A. D. 2020; 18 (9): 116070

Abstract

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to certain systemic therapy recommendations for patients with relapsed or stage IV RCC. They also discuss the addition of a new section to the guidelines that identifies and describes the most common hereditary RCC syndromes and provides recommendations for genetic testing, surveillance, and/or treatment options for patients who are suspected or confirmed to have one of these syndromes.

View details for DOI 10.6004/jnccn.2020.0043

View details for PubMedID 32886895

Stereotactic Radiosurgery for Resected Brain Metastases - Does the Surgical Corridor Need to be Targeted? Practical radiation oncology Shi, S., Sandhu, N., Jin, M., Wang, E., Liu, E., Jaoude, J. A., Schofield, K., Zhang, C., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Gephart, M. H., Pollom, E. L., Soltys, S. G. 2020

Abstract

Although consensus guidelines for post-resection stereotactic radiosurgery (SRS) for brain metastases recommend the surgical corridor leading to the resection cavity be included in the SRS plan, no study has reported patterns of tumor recurrence based on inclusion or exclusion of the corridor as a target. We reviewed tumor control and toxicity outcomes of post-resection SRS for deep brain metastases based on whether or not the surgical corridor was targeted.We retrospectively reviewed patients who had resected brain metastases treated with SRS between 2007 and 2018 and included only 'deep' tumors (defined as located 1.0 cm from the pial surface prior to resection).In 66 deep brain metastases in 64 patients, the surgical corridor was targeted in 43 (65%). There were no statistical differences in the cumulative incidences of progression at 12-months for targeting vs. not targeting the corridor, respectively, for: overall local failure 2% (95% Confidence Interval [CI],0-11%) vs. 9% (95% CI,1-25%; p=0.25), corridor failure 0% (95% CI,0-0%) vs. 9% (95% CI,1-25%; p=0.06), cavity failure 2% (95% CI,0-11%) vs. 0% (95% CI,0-0%; p=0.91), adverse radiation effect 5% (95% CI,1-15%) vs. 13% (95% CI,3-30%; p=0.22). Leptomeningeal disease (7% (95% CI,2-18%) vs. 26% (95% CI,10-45%; p=0.03)) was higher in those without the corridor targeted.Omitting the surgical corridor in post-operative SRS for resected brain metastases was not associated with statistically significant differences in corridor or cavity recurrence or adverse radiation effect. As seen in recent prospective trials of post-resection SRS, the dominant pattern of progression is within the resection cavity; omission of the corridor would yield a smaller SRS volume that could allow for dose escalation to potentially improve local cavity control.

View details for DOI 10.1016/j.prro.2020.04.009

View details for PubMedID 32428766

Local control and toxicity outcomes of stereotactic radiosurgery for spinal metastases of gastrointestinal origin. Journal of neurosurgery. Spine Sandhu, N., Benson, K. R., Kumar, K. A., Eyben, R. V., Chang, D. T., Gibbs, I. C., Hancock, S. L., Meola, A., Chang, S. D., Li, G., Hayden-Gephart, M., Soltys, S. G., Pollom, E. L. 2020: 18

Abstract

Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers.A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray's test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method.A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53-70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%-33%) and 32% (95% CI 23%-42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; / = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24-6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%).Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED 20 Gy10 (biological equivalent dose 60 Gy10) is associated with superior local control.

View details for DOI 10.3171/2020.1.SPINE191260

View details for PubMedID 32114530

A Deep Learning Framework for Prostate Localization in Cone Beam CT Guided Radiotherapy. Medical physics Liang, X., Zhao, W., Hristov, D. H., Buyyounouski, M. K., Hancock, S. L., Bagshaw, H., Zhang, Q., Xie, Y., Xing, L. 2020

Abstract

To develop a deep learning-based model for prostate planning target volume (PTV) localization on cone-beam CT (CBCT) to improve the workflow of CBCT-guided patient setup.A two-step task-based residual network (T2 RN) is proposed to automatically identify inherent landmarks in prostate PTV. The input to the T2 RN is the pre-treatment CBCT images of the patient, and the output is the deep learning-identified landmarks in the PTV. To ensure robust PTV localization, the T2 RN model is trained by using over thousand sets of CT images with labeled landmarks, each of the CTs corresponds to a different scenario of patient position and/or anatomy distribution generated by synthetically changing the planning CT (pCT) image. The changes, including translation, rotation, and deformation, represent vast possible clinical situations of anatomy variations during a course of radiation therapy (RT). The trained patient-specific T2 RN model is tested by using 240 CBCTs from six patients. The testing CBCTs consists of 120 original CBCTs and 120 synthetic CBCTs. The synthetic CBCTs are generated by applying rotation/translation transformations to each of the original CBCT.The systematic/random setup errors between the model prediction and the reference are found to be less than 0.25/2.46 mm and 0.14/1.41 in translation and rotation dimensions, respectively. Pearson's correlation coefficient between model prediction and the reference is higher than 0.94 in translation and rotation dimensions. The Bland-Altman plots show good agreement between the two techniques.A novel T2 RN deep learning technique is established to localize the prostate PTV for RT patient setup. Our results show that highly accurate marker-less prostate setup is achievable by leveraging the state-of-the-art deep learning strategy.

View details for DOI 10.1002/mp.14355

View details for PubMedID 32583418

Testicular Cancer, Version 2.2020 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Gilligan, T., Lin, D. W., Aggarwal, R., Chism, D., Cost, N., Derweesh, I. H., Emamekhoo, H., Feldman, D. R., Geynisman, D. M., Hancock, S. L., LaGrange, C., Levine, E. G., Longo, T., Lowrance, W., McGregor, B., Monk, P., Picus, J., Pierorazio, P., Rais-Bahrami, S., Saylor, P., Sircar, K., Smith, D. C., Tzou, K., Vaena, D., Vaughn, D., Yamoah, K., Yamzon, J., Johnson-Chilla, A., Keller, J., Pluchino, L. A. 2019; 17 (12): 152954

Abstract

Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.

View details for DOI 10.6004/jnccn.2019.0058

View details for Web of Science ID 000500944300014

View details for PubMedID 31805523

Predicting Survival for Patients with Metastatic Disease. International journal of radiation oncology, biology, physics Benson, K. R., Aggarwal, S., Carter, J. N., von Eyben, R., Pradhan, P., Prionas, N. D., Bui, J. L., Soltys, S. G., Hancock, S., Gensheimer, M. F., Koong, A. C., Chang, D. T. 2019

Abstract

PURPOSE: This prospective study aimed to determine the accuracy of radiation oncologists in predicting the survival of patients with metastatic disease receiving radiotherapy and to understand factors associated with their accuracy.METHODS AND MATERIALS: This single-institution study surveyed 22 attending radiation oncologists to estimate patient survival. Survival predictions were defined as accurate if the observed survival (OS) was within the correct survival prediction category (0-6 months, >6-12 months, >12-24 months, and >24 months). The physicians made survival estimates for each course of radiation, yielding 877 analyzable predictions for 689 unique patients. Data analysis included Stuart's Tau C, logistic regression models, ordinal logistic regression models, and stepwise selection to examine variable interactions.RESULTS: Of the 877 radiation oncologists' predictions, 39.7% were accurate, 26.5% underestimations, and 33.9% overestimations. Stuart's Tau C showed low correlation between OS and survival estimates (0.3499), consistent with the inaccuracy reported in literature. However, results showed less systematic over-prediction than reported in the literature. Karnofsky performance status (KPS) was the most significant predictor of accuracy with greater accuracy for patients with shorter OS. Estimates were also more accurate for patients with lower KPS. Accuracy by patient age varied by primary site and race. Physician years of experience did not correlate with accuracy.CONCLUSIONS: The sampled radiation oncologists have relatively low accuracy in predicting patient survival. Future investigation should explore how survival estimates influence treatment decisions and how to improve survival prediction accuracy.

View details for DOI 10.1016/j.ijrobp.2019.10.032

View details for PubMedID 31682969

Kidney Cancer, Version 2.2020 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Jonasch, E., Michaelson, M., Nandagopal, L., Gore, J. L., George, S., Alva, A., Haas, N., Harrison, M. R., Plimack, E. R., Sosman, J., Agarwal, N., Bhayani, S., Choueiri, T. K., Costello, B. A., Derweesh, I. H., Gallagher, T. H., Hancock, S. L., Kyriakopoulos, C., LaGrange, C., Lam, E. T., Lau, C., Lewis, B., Manley, B., McCreery, B., McDonald, A., Mortazavi, A., Pierorazio, P. M., Ponsky, L., Redman, B. G., Somer, B., Wile, G., Dwyer, M. A., Hammond, L. J., Zuccarino-Catania, G. 2019; 17 (11): 127985

Abstract

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal cell carcinoma, and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize the NCCN Kidney Cancer Panel discussions for the 2020 update to the guidelines regarding initial management and first-line systemic therapy options for patients with advanced clear cell renal cell carcinoma.

View details for DOI 10.6004/jnccn.2019.0054

View details for Web of Science ID 000499645400003

View details for PubMedID 31693980

Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors NEUROSURGERY Chin, A. L., Fujimoto, D., Kumar, K. A., Tupper, L., Mansour, S., Chang, S. D., Adler, J. R., Gibbs, I. C., Hancock, S. L., Dodd, R., Li, G., Gephart, M., Ratliff, J. K., Tse, V., Usoz, M., Sachdev, S., Soltys, S. G. 2019; 85 (5): 70816
Stereotactic Radiosurgery for Resected Brain Metastases: Single-Institutional Experience of over 500 Cavities Shi, S., Sandhu, N., Wang, E. H., Liu, E., Jaoude, J., Jin, M., Schofield, K., Zhang, C., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden, M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E90
Vertebral Compression Fracture Rates after Stereotactic Radiosurgery for Spinal Metastases Usoz, M., Dhillon, J., Kumar, K. A., Von Eyben, R., White, E. C., Ho, C. K., Azoulay, M., Fujimoto, D. K., Gibbs, I. C., Chang, S. D., Hancock, S. L., Pollom, E., Soltys, S. G. ELSEVIER SCIENCE INC. 2019: E126E127
Factors Associated with Treatment Failure and Radiation Necrosis Following Cavity Radiosurgery for Resected Brain Metastases Wang, E. H., Shi, S., Sandhu, N., Liu, E., Jin, M., Schofield, K., Zhang, C., Jaoude, J., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden, M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E92
Stereotactic Radiosurgery for Small Cell Lung Cancer Brain Metastases Bagshaw, H. P., Taggarsi, R. S., Moding, E. J., Fawaz, Z. S., Von Eyben, R., Pollom, E., Chang, S. D., Gibbs, I. C., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2019: E70E71
Incorporating imaging information from deep neural network layers into image guided radiation therapy (IGRT). Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Zhao, W., Han, B., Yang, Y., Buyyounouski, M., Hancock, S. L., Bagshaw, H., Xing, L. 2019; 140: 16774

Abstract

BACKGROUND AND PURPOSE: To investigate a novel markerless prostate localization strategy using a pre-trained deep learning model to interpret routine projection kilovoltage (kV) X-ray images in image-guided radiation therapy (IGRT).MATERIALS AND METHODS: We developed a personalized region-based convolutional neural network to localize the prostate treatment target without implanted fiducials. To train the deep neural network (DNN), we used the patient's planning computed tomography (pCT) images with pre-delineated prostate target to generate a large amount of synthetic kV projection X-ray images in the geometry of onboard imager (OBI) system. The DNN model was evaluated by retrospectively studying 10 patients who underwent prostate IGRT. Three out of the ten patients who had implanted fiducials and the fiducials' positions in the OBI images acquired for treatment setup were examined to show the potential of the proposed method for prostate IGRT. Statistical analysis using Lin's concordance correlation coefficient was calculated to assess the results along with the difference between the digitally reconstructed radiographs (DRR) derived and DNN predicted locations of the prostate.RESULTS: Differences between the predicted target positions using DNN and their actual positions are (meanstandard deviation) 1.580.43mm, 1.640.43mm, and 1.670.36mm in anterior-posterior, lateral, and oblique directions, respectively. Prostate position identified on the OBI kV images is also found to be consistent with that derived from the implanted fiducials.CONCLUSIONS: Highly accurate, markerless prostate localization based on deep learning is achievable. The proposed method is useful for daily patient positioning and real-time target tracking during prostate radiotherapy.

View details for DOI 10.1016/j.radonc.2019.06.027

View details for PubMedID 31302347

Prostate cancer classification with multiparametric MRI transfer learning model MEDICAL PHYSICS Yuan, Y., Qin, W., Buyyounouski, M., Ibragimov, B., Hancock, S., Han, B., Xing, L. 2019; 46 (2): 75665

View details for DOI 10.1002/mp.13367

View details for Web of Science ID 000459616200032

Feasibility of Image Registration for Ultrasound-Guided Prostate Radiotherapy Based on Similarity Measurement by a Convolutional Neural Network TECHNOLOGY IN CANCER RESEARCH & TREATMENT Zhu, N., Najafi, M., Han, B., Hancock, S., Hristov, D. 2019; 18
Stereotactic radiosurgery for resected brain metastases: single-institutional experience of over 500 cavities. International journal of radiation oncology, biology, physics Shi, S., Sandhu, N., Jin, M. C., Wang, E., Jaoude, J. A., Schofield, K., Zhang, C., Liu, E., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden-Gephart, M., Adler, J. R., Soltys, S. G., Pollom, E. L. 2019

Abstract

Post-operative stereotactic radiosurgery (SRS) has less detrimental impact on cognition and quality of life compared to whole brain radiotherapy (WBRT) and is increasingly used for resected brain metastases (BMs). Post-operative SRS techniques are not standardized, and there is a concern for a different pattern of failure following post-operative SRS compared to WBRT. We aim to study the efficacy, toxicity, and failure pattern of post-operative SRS.We retrospectively reviewed outcomes of patients with resected BMs treated with post-operative SRS between 2007 and 2018. Overall survival (OS) and cumulative incidences of local failure (LF), overall distant intracranial failure [distant parenchymal failure (DPF), nodular leptomeningeal disease (nLMD), classical leptomeningeal disease (cLMD)], and adverse radiation effect (ARE) were reported. Neurological death was determined for patients with leptomeningeal disease (LMD).A total of 442 patients with 501 resected BMs were treated over 475 total SRS courses. Median clinical follow-up and OS after SRS were 10.1 months [interquartile range (IQR) 3.6-20.7 months] and 13.9 months [95% confidence interval (CI) 11.8-15.2 months], respectively. At 12 months, event rates were 7% (95% CI 5%-10%) for LF, 9% (95% CI 7%-12%) for ARE, 44% (95% CI 40%-49%) for overall distant intracranial failure, 37% (95% CI 33%-42%) for DPF and 13% (95% CI 10%-17%) for LMD. The overall incidence of LMD was 15.8% (53% cLMD, 46% nLMD). cLMD was associated with shorter survival than nLMD (2.0 versus 11.2 months, p<0.01) and a higher proportion of neurological death (67% versus 41%, p=0.02). A total of 15% of patients ultimately received WBRT.We report the largest clinical experience of post-operative SRS for resected BMs, showing excellent local control and low toxicity. Intracranial failure was predominantly distant, with a rising incidence of LMD.

View details for DOI 10.1016/j.ijrobp.2019.11.022

View details for PubMedID 31785338

PROSTATE SEGMENTATION WITH ENCODER -DECODER DENSELY CONNECT CONVOLUTIONAL NETWORK (ED-DENSENET) Yuan, Y., Qin, W., Guo, X., Buyyounouski, M., Hancock, S., Hai, B., Xing, L., IEEE IEEE. 2019: 43437
Milestones in stereotactic radiosurgery for the central nervous system. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Mitrasinovic, S., Zhang, M., Appelboom, G., Sussman, E., Moore, J. M., Hancock, S. L., Adler, J. R., Kondziolka, D., Steinberg, G. K., Chang, S. D. 2019; 59: 1219

Abstract

INTRODUCTION: Since Lars Leksell developed the first stereotactic radiosurgery (SRS) device in 1951, there has been growth in the technologies available and clinical indications for SRS. This expansion has been reflected in the medical literature, which is built upon key articles and institutions that have significantly impacted SRS applications. Our aim was to identify these prominent works and provide an educational tool for training and further inquiry.METHOD: A list of search phrases relating to central nervous system applications of stereotactic radiosurgery was compiled. A topic search was performed using PubMed and Scopus databases. The journal, year of publication, authors, treatment technology, clinical subject, study design and level of evidence for each article were documented. Influence was proposed by citation count and rate.RESULTS: Our search identified a total of 10,211 articles with the top 10 publications overall on the study of SRS spanning 443-1313 total citations. Four articles reported on randomized controlled trials, all of which evaluated intracranial metastases. The most prominent subtopics included SRS for arteriovenous malformation, glioblastoma, and acoustic neuroma. Greatest representation by treatment modality included Gamma Knife, LINAC, and TomoTherapy.CONCLUSIONS: This systematic reporting of the influential literature on SRS for intracranial and spinal pathologies underscores the technology's rapid and wide reaching clinical applications. Moreover the findings provide an academic guide to future health practitioners and engineers in their study of SRS for neurosurgery.

View details for PubMedID 30595165

Milestones in stereotactic radiosurgery for the central nervous system JOURNAL OF CLINICAL NEUROSCIENCE Mitrasinovic, S., Zhang, M., Appelboom, G., Sussman, E., Moore, J. M., Hancock, S. L., Adler, J. R., Kondziolka, D., Steinberg, G. K., Chang, S. D. 2019; 59: 1219
Feasibility of Image Registration for Ultrasound-Guided Prostate Radiotherapy Based on Similarity Measurement by a Convolutional Neural Network. Technology in cancer research & treatment Zhu, N., Najafi, M., Han, B., Hancock, S., Hristov, D. 2019; 18: 1533033818821964

Abstract

PURPOSE:: Registration of 3-dimensional ultrasound images poses a challenge for ultrasound-guided radiation therapy of the prostate since ultrasound image content changes significantly with anatomic motion and ultrasound probe position. The purpose of this work is to investigate the feasibility of using a pretrained deep convolutional neural network for similarity measurement in image registration of 3-dimensional transperineal ultrasound prostate images.METHODS:: We propose convolutional neural network-based registration that maximizes a similarity score between 2 identical in size 3-dimensional regions of interest: one encompassing the prostate within a simulation (reference) 3-dimensional ultrasound image and another that sweeps different spatial locations around the expected prostate position within a pretreatment 3-dimensional ultrasound image. The similarity score is calculated by (1) extracting pairs of corresponding 2-dimensional slices (patches) from the regions of interest, (2) providing these pairs as an input to a pretrained convolutional neural network which assigns a similarity score to each pair, and (3) calculating an overall similarity by summing all pairwise scores. The convolutional neural network method was evaluated against ground truth registrations determined by matching implanted fiducial markers visualized in a pretreatment orthogonal pair of x-ray images. The convolutional neural network method was further compared to manual registration and a standard commonly used intensity-based automatic registration approach based on advanced normalized correlation.RESULTS:: For 83 image pairs from 5 patients, convolutional neural network registration errors were smaller than 5 mm in 81% of the cases. In comparison, manual registration errors were smaller than 5 mm in 61% of the cases and advanced normalized correlation registration errors were smaller than 5 mm only in 25% of the cases.CONCLUSION:: Convolutional neural network evaluation against manual registration and an advanced normalized correlation -based registration demonstrated better accuracy and reliability of the convolutional neural network. This suggests that with training on a large data set of transperineal ultrasound prostate images, the convolutional neural network method has potential for robust ultrasound-to-ultrasound registration.

View details for PubMedID 30803364

Prostate Cancer Classification with Multi-parametric MRI Transfer Learning Model. Medical physics Yuan, Y., Qin, W., Buyyounouski, M., Ibragimov, B., Hancock, S., Han, B., Xing, L. 2018

Abstract

PURPOSE: Prostate cancer classification has significantly impact on the prognosis and treatment planning of patients. Currently, the classifying is based on the Gleason score analysis of biopsied tissues, which is neither accurate nor risk-free. This study aims to learn discriminative features for prostate images and assist physicians to classify prostate cancer automatically.METHODS: We develop a novel multi-parametric magnetic resonance transfer learning (MPTL) method to automatically stage prostate cancer. We first establish a deep convolutional neural network with three branch architectures, which transfer pre-trained model to compute features from multi-parametric MRI images (mp-MRI) : T2w transaxial, T2w sagittal and apparent diffusion coefficient (ADC). The learned features are concatenated to represent information of mp-MRI sequences. A new image similarity constraint is then proposed to enable the distribution of the features within the same category in a narrow angle region. With the joint constraints of softmax loss and image similarity loss in the fine-tuning process, the MPTL can provide descriptive features with intraclass compactness and interclass separability.RESULTS: Two cohorts: 132 cases from our institutional review board approved patient database and 112 cases from the PROSTATEx-2 Challenge are utilized to evaluate the robustness and effectiveness of the proposed MPTL model. Our model achieved high accuracy of prostate cancer classification (accuracy of 86.92%). Moreover, the comparison results demonstrate that our method outperforms both hand-crafted feature based methods and existing deep learning models in prostate cancer classification with higher accuracy.CONCLUSION: The experiment results showed that the proposed method can learn discriminative features for prostate images and classify the cancer accurately. Our MPTL model could be further applied in the clinical practice to provide valuable information for cancer treatment and precision medicine. This article is protected by copyright. All rights reserved.

View details for PubMedID 30597561

Prostate Cancer Staging and Radiation Treatment Planning Using Deep Learning on MRI Han, B., Yuan, Y., Hancock, S. L., Bagshaw, H. P., Buyyounouski, M. K., Xing, L. ELSEVIER SCIENCE INC. 2018: S102
Visualizing the Invisible in Prostate Radiation Therapy: Markerless Prostate Target Localization Via a Deep Learning Model and Monoscopic Kv Projection X-Ray Image Zhao, W., Han, B., Yang, Y., Buyyounouski, M. K., Hancock, S. L., Bagshaw, H. P., Xing, L. ELSEVIER SCIENCE INC. 2018: S128S129
Automatic Prostate Segmentation using Deep Learning and MR Images Yuan, Y., Qin, W., Buyyounouski, M. K., Hancock, S. L., Bagshaw, H. P., Han, B., Xing, L. ELSEVIER SCIENCE INC. 2018: E379
Evaluation of transperineal ultrasound imaging as a potential solution for target tracking during hypofractionated radiotherapy for prostate cancer. Radiation oncology (London, England) Han, B., Najafi, M., Cooper, D. T., Lachaine, M., von Eyben, R., Hancock, S., Hristov, D. 2018; 13 (1): 151

Abstract

BACKGROUND: Emerging hypofractionated prostate radiotherapy regimens require solutions for accurate target tracking during beam delivery. The goal of this study is to evaluate the performance of the Clarity ultrasound monitoring system for prostate motion tracking.METHODS: Five prostate patients underwent continuous perineum ultrasound imaging during their daily treatments. Initial absolute 3D positions of fiducials implanted in the prostate were estimated from the KV images. Fiducial positions in MV images acquired during beam delivery were compared with predicted positions based on Clarity 3D tracking. The uncertainty in the comparison results was evaluated in a phantom validation study.RESULTS: Continuous real-time ultrasound motion tracking was recorded in 5 patients and 167 fractions for overall of 39.7h. Phantom validation of the proposed procedure demonstrated that predicted and observed fiducial positions agree within 1.1mm. In patients agreement between predicted and actual fiducial positions varied between 1.3mm and 3.3mm. On average ultrasound tracking reduced the maximum localization error in patients by 20% on average. With the motion corrected, the duration prostate beyond 1mm from its initial treatment position can be reduced from 37 to 22% of the total treatment time.CONCLUSION: Real-time ultrasound tracking reduces uncertainty in prostate position due to intra-fractional motion.TRIAL REGISTRATION: IRB Protocol #27372 . Date of registration of trial: 12/17/2013.

View details for PubMedID 30126434

Evaluation of transperineal ultrasound imaging as a potential solution for target tracking during hypofractionated radiotherapy for prostate cancer RADIATION ONCOLOGY Han, B., Najafi, M., Cooper, D. T., Lachaine, M., von Eyben, R., Hancock, S., Hristov, D. 2018; 13
Incorporating Deep Layer Image Information Into Image Guided Radiation Therapy Zhao, W., Han, B., Yang, Y., Buyyounouski, M., Hancock, S., Bagshaw, H., Xing, L. WILEY. 2018: E686
Prospective Evaluation of Ga-68-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Findings on Conventional Imaging JOURNAL OF NUCLEAR MEDICINE Minamimoto, R., Sonni, I., Hancock, S., Vasanawala, S., Loening, A., Gambhir, S. S., Iagaru, A. 2018; 59 (5): 8038
Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery Chin, A. L., Fujimoto, D., Kumar, K. A., Tupper, L., Mansour, S., Chang, S. D., Adler, J. R., Gibbs, I. C., Hancock, S. L., Dodd, R., Li, G., Gephart, M. H., Ratliff, J. K., Tse, V., Usoz, M., Sachdev, S., Soltys, S. G. 2018

Abstract

Stereotactic radiosurgery (SRS) for benign intracranial tumors is an established standard of care. The widespread implementation of SRS for benign spinal tumors has been limited by lack of long-term data.To update our institutional experience of safety and efficacy outcomes after SRS for benign spinal tumors.We performed a retrospective cohort study of 120 patients with 149 benign spinal tumors (39 meningiomas, 26 neurofibromas, and 84 schwannomas) treated with SRS between 1999 and 2016, with follow-up magnetic resonance imaging available for review. The primary endpoint was the cumulative incidence of local failure (LF), with death as a competing risk. Secondary endpoints included tumor shrinkage, symptom response, toxicity, and secondary malignancy.Median follow-up was 49 mo (interquartile range: 25-103 mo, range: 3-216 mo), including 61 courses with>5 yr and 24 courses with>10 yr of follow-up. We observed 9 LF for a cumulative incidence of LF of 2%, 5%, and 12% at 3, 5, and 10 yr, respectively. Excluding 10 tumors that were previously irradiated or that arose within a previously irradiated field, the 3-, 5-, and 10-yr cumulative incidence rates of LF were 1%, 2%, and 8%, respectively. At last follow-up, 35% of all lesions had decreased in size. With a total of 776 patient-years of follow-up, no SRS-related secondary malignancies were observed.Comparable to SRS for benign intracranial tumors, SRS provides longer term local control of benign spinal tumors and is a standard-of-care alternative to surgical resection.

View details for PubMedID 30445557

A Phase 1/2 Trial of 5 Fraction Stereotactic Radiosurgery With 5 mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma Multiforme: Pattern of Recurrence Analysis Azoulay, M., Gibbs, I. C., Hancock, S. L., Ho, C. K., Fujimoto, D. K., Chang, S. D., Harsh, G., Nagpal, S., Thomas, R., Recht, L., Choi, C. H., Soltys, S. G. ELSEVIER SCIENCE INC. 2017: S102S103
Stereotactic Radiosurgery for Spinal Metastases from Melanoma, Sarcoma, Renal Cell Carcinoma, and Hepatocellular Carcinoma Fujimoto, D. K., Kumar, K. A., White, E. C., Ho, C. K., Azoulay, M., Aggarwal, S., Pradhan, P., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Choi, C. H., Soltys, S. G. ELSEVIER SCIENCE INC. 2017: E73
Spine Stereotactic Radiosurgery: Outcomes and Predictors of Local Recurrence Kumar, K. A., Fujimoto, D. K., White, E. C., Ho, C. K., Azoulay, M., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Desai, A., Ratliff, J., Soltys, S. G., Choi, C. H. ELSEVIER SCIENCE INC. 2017: E86
Kidney Cancer, Version 2.2017 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Jonasch, E., Agarwal, N., Bhayani, S., Bro, W. P., Chang, S. S., Choueiri, T. K., Costello, B. A., Derweesh, I. H., Fishman, M., Gallagher, T. H., Gore, J. L., Hancock, S. L., Harrison, M. R., Kim, W., Kyriakopoulos, C., LaGrange, C., Lam, E. T., Lau, C., Michaelson, M., Olencki, T., Pierorazio, P. M., Plimack, E. R., Redman, B. G., Shuch, B., Somer, B., Sonpavde, G., Sosman, J. 2017; 15 (6): 80434

Abstract

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.

View details for DOI 10.6004/jnccn.2017.0100

View details for Web of Science ID 000403152400009

View details for PubMedID 28596261

Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in NewlyDiagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results. International journal of radiation oncology, biology, physics Pollom, E. L., Fujimoto, D., Wynne, J., Seiger, K., Modlin, L. A., Jacobs, L. R., Azoulay, M., von Eyben, R., Tupper, L., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Harraher, C., Nagpal, S., Thomas, R. P., Recht, L. D., Choi, C. Y., Soltys, S. G. 2017; 98 (1): 123-130

Abstract

We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40Gy in 5 fractions) with concurrent and adjuvant temozolomide.HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (global quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point.With a median follow-up time of 10.4months (range, 0.4-52months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01).On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.

View details for DOI 10.1016/j.ijrobp.2017.01.242

View details for PubMedID 28586949

Consolidative Radiotherapy in Metastatic Urothelial Cancer. Clinical genitourinary cancer Shah, S., Zhang, C. A., Hancock, S., Fan, A., Skinner, E., Srinivas, S. 2017

Abstract

We report outcomes of a retrospective, single-institution experience with consolidative radiation after chemotherapy in metastatic urothelial cancer (MUC).From our single-institution database of 2597 patients with urothelial carcinoma treated since 1997, we identified 22 patients with MUC who underwent consolidative radiotherapy after a partial response to chemotherapy with the intent of rendering them disease-free. All patients had undergone primary surgical therapy with either cystectomy or nephroureterectomy. Progression-free survival (PFS) was defined as time from completion of radiation therapy to relapse or last follow-up. Overall survival (OS) was defined as time from start of chemotherapy to death or last follow-up.In the selected group of patients with MUC, the median age was 67 years; 59% had received previous cisplatin-based chemotherapy. The most common sites radiated were the regional lymph nodes (64%). Other radiated sites included the lung, adrenal glands, and omental metastases. Median survival from diagnosis to cystectomy was 48 months. Median PFS was 13 months and median OS was 29 months. Eight patients (36%) were alive and disease-free 6 years after radiation therapy. Patients who were rendered disease-free were those with nodal metastases and delivery of radiation to a single site of metastasis.In this highly selective cohort of patients with MUC treated with consolidative radiation after chemotherapy, 36% were rendered disease-free. This suggests that radiation is feasible and might contribute to long-term disease control. Further prospective studies are needed to better characterize the benefit of combined modality treatment.

View details for DOI 10.1016/j.clgc.2017.04.007

View details for PubMedID 28465049

Very high-energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS. Medical physics Schler, E., Eriksson, K., Hynning, E., Hancock, S. L., Hiniker, S. M., Bazalova-Carter, M., Wong, T., Le, Q., Loo, B. W., Maxim, P. G. 2017

Abstract

The aim of this study was to evaluate the performance of very high-energy electron beams (VHEE) in comparison to clinically derived treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PPBS) technology. We developed a custom optimization script that could be applied automatically across modalities to eliminate operator bias during IMRT optimization.Four clinical cases were selected (prostate cancer, lung cancer, pediatric brain tumor, and head and neck cancer (HNC)). The VHEE beams were calculated in the EGSnrc/DOSXYZnrc Monte Carlo code for 100 and 200MeV beams. Treatment plans with VHEE, VMAT, and PPBS were optimized in a research version of RayStation using an in-house developed script to minimize operator bias between the different techniques.The in-house developed script generated similar or superior plans to the clinically used plans. In the comparisons between the modalities, the integral dose was lowest for the PPBS-generated plans in all cases. For the prostate case, the 200MeV VHEE plan showed reduced integral dose and reduced organ at risk (OAR) dose compared to the VMAT plan. For all other cases, both the 100 and the 200MeV VHEE plans were superior to the VMAT plans, and the VHEE plans showed better conformity and lower spinal cord dose in the pediatric brain case and lower brain stem dose in the HNC case when compared to the PPBS plan.The automated optimization developed in this study generated similar or superior plans as compared to the clinically used plan and represents an unbiased approach to compare treatment plans generated for different modalities. In the present study, we also show that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases, and VHEE plans can even achieve reductions in OAR doses compared to PPBS plans for shallow targets. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses are achieved. On the whole, VHEE was intermediate between photon VMAT and PPBS for OAR sparing.

View details for DOI 10.1002/mp.12233

View details for PubMedID 28339108

Imaging changes over 18 months following stereotactic radiosurgery for brain metastases: both late radiation necrosis and tumor progression can occur. Journal of neuro-oncology Fujimoto, D., von Eyben, R., Gibbs, I. C., Chang, S. D., Li, G., Harsh, G. R., Hancock, S., Fischbein, N., Soltys, S. G. 2017

Abstract

Following stereotactic radiosurgery (SRS) for brain metastases, the median time range to develop adverse radiation effect (ARE) or radiation necrosis is 7-11months. Similarly, the risk of local tumor recurrence following SRS is <5% after 18months. With improvements in systemic therapy, patients are living longer and are at risk for both late (defined as >18months after SRS) tumor recurrence and late ARE, which have not previously been well described. An IRB-approved, retrospective review identified patients treated with SRS who developed new MRI contrast enhancement >18months following SRS. ARE was defined as stabilization/shrinkage of the lesion over time or pathologic confirmation of necrosis, without tumor. Local failure (LF) was defined as continued enlargement of the lesion over time or pathologic confirmation of tumor. We identified 16 patients, with a median follow-up of 48.2months and median overall survival of 73.0 months, who had 19 metastases with late imaging changes occurring a median of 32.9months (range 18.5-63.2months) after SRS. Following SRS, 12 lesions had late ARE at a median of 33.2months and 7 lesions had late LF occurring a median of 23.6months. As patients with cancer live longer and as SRS is increasingly utilized for treatment of brain metastases, the incidence of these previously rare imaging changes is likely to increase. Clinicians should be aware of these late events, with ARE occurring up to 5.3years and local failure up to 3.8years following SRS in our cohort.

View details for PubMedID 29098569

Prospective Evaluation of 68Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Conventional Imaging. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Minamimoto, R., Sonni, I., Hancock, S., Vasanawala, S., Loening, A., Gambhir, S. S., Iagaru, A. 2017

Abstract

Purpose:68Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (68Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors (GRPr). GRPr proteins are highly overexpressed in several human tumors, including prostate cancer. We present data from the use of 68Ga-RM2 in patients with biochemical recurrence (BCR) of prostate cancer (PC) and negative conventional imaging (CI). Methods: We enrolled 32 men with BCR PC, 59-83 year-old (meanstandard deviation (SD): 68.76.4). Imaging started at 40-69 minutes (meanSD: 50.56.8) after injection of 133.2-151.7 MBq (meanSD: 140.67.4) of 68Ga-RM2 using a time-of-flight (TOF)-enabled simultaneous positron emission tomography (PET) / magnetic resonance imaging (MRI) scanner. T1-weighted (T1w), T2-weighted (T2w) and diffusion-weighted images (DWI) were acquired. Results: All patients had rising prostate specific antigen (PSA) (range: 0.3-119.0 ng/mL; meanSD: 10.1 21.3) and negative CI (CT or MRI, and 99mTc MDP bone scan) prior to enrollment. The observed 68Ga-RM2 PET detection rate was 71.8%. 68Ga-RM2 PET identified recurrent prostate cancer in 23 of the 32 participants, while the simultaneous MRI scan identified findings compatible with recurrent prostate cancer in 11 of the 32 patients. PSA velocity (PSAv) values were 0.320.59 ng/ml/year (range: 0.04-1.9) in patients with negative PET scans and 2.512.16 ng/ml/year (range: 0.13-8.68) in patients with positive PET scans (P: 0.006). Conclusion:68Ga-RM2 PET can be used for assessment of GRPr expression in patients with BCR PC. High uptake in multiple areas compatible with cancer lesions suggests that 68Ga-RM2 is a promising PET radiopharmaceutical for localization of disease in participants with BCR PC and negative CI.

View details for PubMedID 29084827

Spinal Stereotactic Radiosurgery: Comparison of Targeting the Gross Tumor Volume Alone Versus With the Adjacent Vertebral Segment Kumar, K. A., White, E. C., Ho, C. K., Azoulay, M., Fujimoto, D. K., Aggarwal, S., Gibbs, I. C., Adler, J. R., Hancock, S. L., Choi, C. H., Soltys, S. G. ELSEVIER SCIENCE INC. 2016: S175
The Role of Stereotactic Radiosurgery in the Reirradiation of Metastatic Spinal Tumors. International journal of radiation oncology, biology, physics Ho, C. K., Kumar, K. A., White, E. C., Azoulay, M., Fujimoto, D. K., Aggarwal, S., Gensheimer, M. F., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Choi, C. Y., Soltys, S. G. 2016; 96 (2S): E131-?

View details for DOI 10.1016/j.ijrobp.2016.06.920

View details for PubMedID 27673858

A Phase I/II Trial of 5 Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma Multiforme. International journal of radiation oncology, biology, physics Azoulay, M., Ho, C. K., Fujimoto, D. K., Modlin, L. A., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Nagpal, S., Thomas, R., Recht, L., Choi, C. Y., Soltys, S. G. 2016; 96 (2S): E131-E132

View details for DOI 10.1016/j.ijrobp.2016.06.921

View details for PubMedID 27673859

Accuracy of Predicting Survival Outcomes in Palliative Radiation Therapy Patients Aggarwal, S., Prionas, N. D., Carter, J. N., Pradhan, P., Bui, J. L., von Eyben, R., Ho, C. K., Hancock, S. L., Soltys, S. G., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2016: S148S149
New Enhancement Over 18 Months Following Stereotactic Radiosurgery for Brain Metastases: Both Radiation Necrosis and Tumor Failure Can Occur Fujimoto, D. K., von Eyben, R., Li, G., Chang, S. D., Fischbein, N., Harsh, G. R., Hancock, S. L., Gibbs, I. C., Soltys, S. G. ELSEVIER SCIENCE INC. 2016: E129
The Outcome of Hypofractionated Stereotactic Radiosurgery for Large Vestibular Schwannomas. World neurosurgery Teo, M., Zhang, M., Li, A., Thompson, P. A., Tayag, A. T., Wallach, J., Gibbs, I. C., Soltys, S. G., Hancock, S. L., Chang, S. D. 2016; 93: 398-409

Abstract

Stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS) remains controversial. We studied the tumor local control and toxicity rates after hypofractionated SRS for VS > 3 cm.A total of 587 patients with VS treated with SRS between 1998 and 2014 were reviewed retrospectively, and 30 Koos grade IV VSs were identified. There were 6 patients with neurofibromatosis 2 (NF2), 8 with cystic tumors, 22 with solid tumors, 19 who underwent primary CyberKnife (CK), and 11 with >3 cm after previous resection. Patients were treated by a median of 3 fractions at 18 Gy.After a median 97 months, the 3- and 10-year Kaplan-Meier estimates of local control were 85% and 80%, respectively, with 20% requiring salvage treatment. For patients who had previous tumor resection rather than primary CK, the estimates were 46% and 5%, respectively, with progression, and 3-year control rates of 71% and 94% (P= 0.008). Tumor control was also lower among NF2 versus non-NF2 patients (40% vs. 95%; P= 0.0014). Among patients with good clinical baselines before CK, 88% were functionally independent (modified Rankin Scale score, 0-2), 88% had good facial function (House-Brackmann grade I-II), and 38% had serviceable hearing (Gardner-Robertson grade I-II) at last follow-up. Hearing worsening was more likely among patients treated with primary CK (33% vs. 90%; P= 0.04).Overall, 80% of large VSs were adequately controlled by CK with 97 months of median follow-up. Patients with previous surgery and NF2 also appeared to have higher rates of tumor progression, and less favorable functional outcomes.

View details for DOI 10.1016/j.wneu.2016.06.080

View details for PubMedID 27368508

Evaluation of Transperineal Ultrasound Imaging as a Potential Solution for Target Tracking During Ablative Body Radiotherapy for Prostate Cancer Najafi, M., Han, B., Cooper, D., Hancock, S., Hristov, D. WILEY. 2016: 3649

View details for DOI 10.1118/1.4956984

View details for Web of Science ID 000402122400060

Deep Convolutional Neural Network Image Matching for Ultrasound Guidance in Radiotherapy Zhu, N., Najafi, M., Hancock, S., Hristov, D. WILEY. 2016: 3331

View details for DOI 10.1118/1.4955603

View details for Web of Science ID 000401930600040

Breast Imaging in Women Previously Irradiated for Hodgkin Lymphoma. American journal of clinical oncology Horst, K. C., Fero, K. E., Hancock, S. L., Advani, R. H., Ikeda, D. M., Daniel, B., Rosenberg, S. A., Donaldson, S. S., Hoppe, R. T. 2016; 39 (2): 114-119

Abstract

Women treated with mantle irradiation for Hodgkin lymphoma (HL) are at an increased risk of developing breast cancer (BC). Current guidelines recommend screening breast magnetic resonance imaging (MRI) as an adjunct to mammography (M) in these patients. There are limited data, however, as to the impact of breast MRI on cancer detection rates. The aim of the current study is to evaluate the use of breast MRI in survivors of HL treated and followed at a single institution.We retrospectively reviewed 980 female patients treated with mantle irradiation for HL between 1961 and 2008. Records were reviewed to determine age at radiotherapy treatment, radiotherapy dose, breast imaging (including M and breast MRI), biopsy results if applicable, and incidence of BC.A total of 118 patients had breast imaging performed at our institution. Median age at HL diagnosis was 28 years (range, 10 to 69 y). Median radiotherapy dose was 36 Gy (range, 20 to 45 Gy). Seventy-nine patients (67%) underwent M screening only, 1 (1%) breast MRI only, and 38 (32%) both M and breast MRI. Of these 38, 19 (50%) underwent 54 screening MRI studies (range per patient=1 to 8), 13 (34%) underwent preoperative MRI for workup of BC, and 6 (16%) initiated screening MRI of the contralateral breast only after diagnosed with BC. Fifty-nine biopsies were performed: 47 were prompted by suspicious M findings only, 10 by palpable findings on physical examination (PE), and 2 by suspicious breast MRI findings. Of the 47 biopsies prompted by M, 24 revealed malignant disease, whereas 23 proved to be benign. All 10 biopsies performed by palpation were malignant. Both biopsies prompted by MRI findings were benign. With M, there were 34 true-positive findings in 32 patients, 23 false-positive findings, and 1 false-negative finding. With screening MRI, there were 2 false-positive findings, 1 false-negative finding, and no true-positive findings.The role of screening breast MRI in women previously irradiated for HL is evolving. Further education of patients and physicians is important to increase awareness of more sensitive BC screening modalities in this high-risk population. Future studies are necessary to determine the appropriate integration of screening breast MRI into the ongoing follow-up of these women.

View details for DOI 10.1097/COC.0000000000000025

View details for PubMedID 24390271

Pilot Comparison of Ga-68-RM2 PET and Ga-68-PSMA-11 PET in Patients with Biochemically Recurrent Prostate Cancer JOURNAL OF NUCLEAR MEDICINE Minamimoto, R., Hancock, S., Schneider, B., Chin, F. T., Jamali, M., Loening, A., Vasanawala, S., Gambhir, S. S., Iagaru, A. 2016; 57 (4): 557-562

Abstract

Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) is a PET tracer that can detect prostate cancer relapses and metastases by binding to the extracellular domain of PSMA.(68)Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 ((68)Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors. We present pilot data on the biodistribution of these PET tracers in a small cohort of patients with biochemically recurrent prostate cancer.Seven men (mean age SD, 74.3 5.9 y) with biochemically recurrent prostate cancer underwent both(68)Ga-PSMA-11 PET/CT and(68)Ga-RM2 PET/MRI scans. SUVmaxand SUVmeanwere recorded for normal tissues and areas of uptake outside the expected physiologic biodistribution.All patients had a rising level of prostate-specific antigen (mean SD, 13.5 11.5) and noncontributory results on conventional imaging.(68)Ga-PSMA-11 had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, whereas(68)Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake outside the expected physiologic biodistribution did not significantly differ between(68)Ga-PSMA-11 and(68)Ga-RM2; however,(68)Ga-PSMA-11 localized in a lymph node and seminal vesicle in a patient with no abnormal(68)Ga-RM2 uptake. Abdominal periaortic lymph nodes were more easily visualized by(68)Ga-RM2 in two patients because of lack of interference by radioactivity in the small intestine.(68)Ga-PSMA-11 and(68)Ga-RM2 had distinct biodistributions in this small cohort of patients with biochemically recurrent prostate cancer. Additional work is needed to understand the expression of PSMA and gastrin-releasing peptide receptors in different types of prostate cancer.

View details for DOI 10.2967/jnumed.115.168393

View details for PubMedID 26659347

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

Consolidative radiotherapy in metastatic urothelial cancer (MUC) Srinivas, S., Narayanan, S., Fan, A. C., Hancock, S., Skinner, E. C. AMER SOC CLINICAL ONCOLOGY. 2016
Ga-68-DOTA-Bombesin (Ga-68-RM2 or Ga-68-Bombesin) PET versus Ga-68-PSMA PET: A pilot prospective evaluation in patients with biochemical recurrence of prostate cancer. Iagaru, A., Minamimoto, R., Hancock, S., Mittra, E., Loening, A., Vasanawala, S. AMER SOC CLINICAL ONCOLOGY. 2016
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): 97104

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 PubMedID 27000505

Analysis of Tolerance of the Visual Pathway to Single Fraction and Hypofractionated Stereotactic Radiosurgery Hiniker, S. M., Modlin, L. A., Binkley, M. S., Harris, J. P., Seiger, K., Adler, J. R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2015: E116E117
A Phase I/II Dose-Escalation Trial of 3-Fraction Stereotactic Radiosurgery (SRS) for Large Resection Cavities of Brain Metastases Soltys, S. G., Seiger, K., Modlin, L. A., Gibbs, I. C., Hara, W., Kidd, E. A., Hancock, S. L., Diehn, M., Chang, S. D., Adler, J. R., Harsh, G. R., Li, G., Choi, C. H. ELSEVIER SCIENCE INC. 2015: S38
Spinal Stereotactic Radiosurgery: Dosimetric Correlates of Tumor Control Kumar, K. A., Choi, C. H., White, E. C., Qian, Y., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2015: E118
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

Testicular Cancer, Version 2.2015 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Jonasch, E., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Chang, S. S., Choueiri, T. K., Costello, B. A., Derweesh, I. H., Gupta, S., Hancock, S. L., Kim, J. J., Kuzel, T. M., Lam, E. T., Lau, C., Levine, E. G., Lin, D. W., Michaelson, M. D., Olencki, T., Pili, R., Plimack, E. R., Rampersaud, E. N., Redman, B. G., Ryan, C. J., Sheinfeld, J., Shuch, B., Sircar, K., Somer, B., Wilder, R. B., Dwyer, M., Kumar, R. 2015; 13 (6): 772-798

Abstract

Germ cell tumors (GCTs) account for 95% of testicular cancers. Testicular GCTs constitute the most common solid tumor in men between the ages of 20 and 34 years, and the incidence of testicular GCTs has been increasing in the past 2 decades. Testicular GCTs are classified into 2 broad groups-pure seminoma and nonseminoma-which are treated differently. Pure seminomas, unlike nonseminomas, are more likely to be localized to the testis at presentation. Nonseminoma is the more clinically aggressive tumor associated with elevated serum concentrations of alphafetoprotein (AFP). The diagnosis of a seminoma is restricted to pure seminoma histology and a normal serum concentration of AFP. When both seminoma and elements of a nonseminoma are present, management follows that for a nonseminoma. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Testicular Cancer outline the diagnosis, workup, risk assessment, treatment, and follow-up schedules for patients with both pure seminoma and nonseminoma.

View details for Web of Science ID 000356843400010

View details for PubMedID 26085393

Kidney cancer, version 3.2015. Journal of the National Comprehensive Cancer Network Motzer, R. J., Jonasch, E., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Chang, S. S., Choueiri, T. K., Costello, B. A., Derweesh, I. H., Gupta, S., Hancock, S. L., Kim, J. J., Kuzel, T. M., Lam, E. T., Lau, C., Levine, E. G., Lin, D. W., Michaelson, M. D., Olencki, T., Pili, R., Plimack, E. R., Rampersaud, E. N., Redman, B. G., Ryan, C. J., Sheinfeld, J., Shuch, B., Sircar, K., Somer, B., Wilder, R. B., Dwyer, M., Kumar, R. 2015; 13 (2): 151-159

Abstract

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These NCCN Guidelines Insights highlight the recent updates/changes in these guidelines, and updates include axitinib as first-line treatment option for patients with clear cell renal carcinoma, new data to support pazopanib as subsequent therapy for patients with clear cell carcinoma after first-line treatment with another tyrosine kinase inhibitor, and guidelines for follow-up of patients with renal cell carcinoma.

View details for PubMedID 25691606

Repeat Stereotactic Radiosurgery (SRS) for Brain Metastases Locally Recurrent Following Initial SRS Jayachandran, P., Shultz, D., Modlin, L., Von Eyben, R., Gibbs, I. C., Chang, S., Harsh, G., Li, G., Adler, J., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2014: S320
Quick Radiation Treatment Prostate Planning Using Matched-Plans: Improved Quality and Workflow Holcombe, C., King, M., Carpenter, C., Davidi, R., Mourlas, N., Lei, X., Kapp, D., Buyyounouski, M., Hancock, S., Bush, K., Atwood, T. ELSEVIER SCIENCE INC. 2014: S191S192
Repeat Stereotactic Radiosurgery (SRS) for New Brain Metastases Following Initial SRS: Accumulated Tumor Volume and Graded Prognostic Assessment (GPA) Score Calculated at Each Course Correlate With Overall Survival Shultz, D. B., Modlin, L. A., Jayachandran, P., Von Eiben, R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Adler, J. R., Adler, J. R., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2014: S311S312
Repeat Resection Cavity Stereotactic Radiosurgery (SRS) for Brain Metastases Locally Recurrent Following Initial Resection Cavity Boost Modlin, L. A., Shultz, D. B., Jayachandran, P., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Adler, J. R., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2014: S327
Patient-specific Dose Escalation Using Patient-Matching Machine Learning Bush, K., Holcombe, C., Kapp, D., Buyyounouski, M., Hancock, S., Xing, L., Atwood, T., King, M. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2014: 22

View details for DOI 10.1118/1.4894936

View details for Web of Science ID 000341068100155

Identification and Improvement of Patients Eligible for Dose Escalation with Matched Plans Bush, K., Holcombe, C., Kapp, D., Buyyounouski, M., Hancock, S., Xing, L., Atwood, T., King, M. WILEY. 2014: 371
Combined NaF/FDG PET/CT evaluation of prostate cancer patients Iagaru, A., Mosci, C., Keu, K., Mittra, E., Hancock, S., Pachynski, R., Srinivas, S., Gambhir, S. SOC NUCLEAR MEDICINE INC. 2014
Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma. Annals of oncology Horst, K. C., Hancock, S. L., OGNIBENE, G., Chen, C., Advani, R. H., Rosenberg, S. A., Donaldson, S. S., Hoppe, R. T. 2014; 25 (4): 848-851

Abstract

The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC.We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs.One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003).BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.

View details for DOI 10.1093/annonc/mdu017

View details for PubMedID 24608191

Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma. Annals of oncology : official journal of the European Society for Medical Oncology Horst, K. C., Hancock, S. L., Ognibene, G., Chen, C., Advani, R. H., Rosenberg, S. A., Donaldson, S. S., Hoppe, R. T. 2014; 25 (4): 84851

Abstract

BACKGROUND: The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC.MATERIALS AND METHODS: We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs.RESULTS: One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003).CONCLUSION(S): BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.

View details for DOI 10.1093/annonc/mdu017

View details for PubMedID 32018915

Kidney Cancer, Version 2.2014 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Jonasch, E., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Chang, S. S., Choueiri, T. K., Derweesh, I. H., Gupta, S., Hancock, S. L., Kim, J. J., Kuzel, T. M., Lam, E. T., Lau, C., Levine, E. G., Lin, D. W., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Plimack, E. R., Rampersaud, E. N., Redman, B. G., Ryan, C. J., Sheinfeld, J., Sircar, K., Somer, B., Wang, J., Wilder, R. B., Dwyer, M. A., Kumar, R. 2014; 12 (2): 175-182

Abstract

These NCCN Guidelines Insights highlight treatment recommendations and updates specific to the management of patients with advanced non-clear cell carcinoma included in the 2014 version of the NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer.

View details for Web of Science ID 000332213600004

Kidney cancer, version 2.2014. Journal of the National Comprehensive Cancer Network Motzer, R. J., Jonasch, E., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Chang, S. S., Choueiri, T. K., Derweesh, I. H., Gupta, S., Hancock, S. L., Kim, J. J., Kuzel, T. M., Lam, E. T., Lau, C., Levine, E. G., Lin, D. W., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Plimack, E. R., Rampersaud, E. N., Redman, B. G., Ryan, C. J., Sheinfeld, J., Sircar, K., Somer, B., Wang, J., Wilder, R. B., Dwyer, M. A., Kumar, R. 2014; 12 (2): 175-182

Abstract

These NCCN Guidelines Insights highlight treatment recommendations and updates specific to the management of patients with advanced non-clear cell carcinoma included in the 2014 version of the NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer.

View details for PubMedID 24586079

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 PubMedID 24161422

Automatic prostate tracking and motion assessment in volumetric modulated arc therapy with an electronic portal imaging device. International journal of radiation oncology, biology, physics Azcona, J. D., Li, R., Mok, E., Hancock, S., Xing, L. 2013; 86 (4): 762-768

Abstract

PURPOSE: To assess the prostate intrafraction motion in volumetric modulated arc therapy treatments using cine megavoltage (MV) images acquired with an electronic portal imaging device (EPID). METHODS AND MATERIALS: Ten prostate cancer patients were treated with volumetric modulated arc therapy using a Varian TrueBeam linear accelerator equipped with an EPID for acquiring cine MV images during treatment. Cine MV images acquisition was scheduled for single or multiple treatment fractions (between 1 and 8). A novel automatic fiducial detection algorithm that can handle irregular multileaf collimator apertures, field edges, fast leaf and gantry movement, and MV image noise and artifacts in patient anatomy was used. All sets of images (approximately 25,000 images in total) were analyzed to measure the positioning accuracy of implanted fiducial markers and assess the prostate movement. RESULTS: Prostate motion can vary greatly in magnitude among different patients. Different motion patterns were identified, showing its unpredictability. The mean displacement and standard deviation of the intrafraction motion was generally less than 2.0 2.0 mm in each of the spatial directions. In certain patients, however, the percentage of the treatment time in which the prostate is displaced more than 5 mm from its planned position in at least 1 spatial direction was 10% or more. The maximum prostate displacement observed was 13.3 mm. CONCLUSION: Prostate tracking and motion assessment was performed with MV imaging and an EPID. The amount of prostate motion observed suggests that patients will benefit from its real-time monitoring. Megavoltage imaging can provide the basis for real-time prostate tracking using conventional linear accelerators.

View details for DOI 10.1016/j.ijrobp.2013.03.007

View details for PubMedID 23608236

Development and clinical evaluation of automatic fiducial detection for tumor tracking in cine megavoltage images during volumetric modulated arc therapy MEDICAL PHYSICS Azcona, J. D., Li, R., Mok, E., Hancock, S., Xing, L. 2013; 40 (3)

Abstract

Real-time tracking of implanted fiducials in cine megavoltage (MV) imaging during volumetric modulated arc therapy (VMAT) delivery is complicated due to the inherent low contrast of MV images and potential blockage of dynamic leaves configurations. The purpose of this work is to develop a clinically practical autodetection algorithm for motion management during VMAT.The expected field-specific segments and the planned fiducial position from the Eclipse (Varian Medical Systems, Palo Alto, CA) treatment planning system were projected onto the MV images. The fiducials were enhanced by applying a Laplacian of Gaussian filter in the spatial domain for each image, with a blob-shaped object as the impulse response. The search of implanted fiducials was then performed on a region of interest centered on the projection of the fiducial when it was within an open field including the case when it was close to the field edge or partially occluded by the leaves. A universal template formula was proposed for template matching and normalized cross correlation was employed for its simplicity and computational efficiency. The search region for every image was adaptively updated through a prediction model that employed the 3D position of the fiducial estimated from the localized positions in previous images. This prediction model allowed the actual fiducial position to be tracked dynamically and was used to initialize the search region. The artifacts caused by electronic interference during the acquisition were effectively removed. A score map was computed by combining both morphological information and image intensity. The pixel location with the highest score was selected as the detected fiducial position. The sets of cine MV images taken during treatment were analyzed with in-house developed software written in MATLAB (The Mathworks, Inc., Natick, MA). Five prostate patients were analyzed to assess the algorithm performance by measuring their positioning accuracy during treatment.The algorithm was able to accurately localize the fiducial position on MV images with success rates of more than 90% per case. The percentage of images in which each fiducial was localized in the studied cases varied between 23% and 65%, with at least one fiducial having been localized between 40% and 95% of the images. This depended mainly on the modulation of the plan and fiducial blockage. The prostate movement in the presented cases varied between 0.8 and 3.5 mm (mean values). The maximum displacement detected among all patients was of 5.7 mm.An algorithm for automatic detection of fiducial markers in cine MV images has been developed and tested with five clinical cases. Despite the challenges posed by complex beam aperture shapes, fiducial localization close to the field edge, partial occlusion of fiducials, fast leaf and gantry movement, and inherently low MV image quality, good localization results were achieved in patient images. This work provides a technique for enabling real-time accurate fiducial detection and tumor tracking during VMAT treatments without the use of extra imaging dose.

View details for DOI 10.1118/1.4791646

View details for Web of Science ID 000316369400011

View details for PubMedID 23464303

View details for PubMedCentralID PMC3592890

Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Patients Receiving Pelvic IMRT and Concurrent Chemotherapy 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) 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: S350S350
Assessment of the Prostate Motion During Volumetric Modulated Treatments Azcona, J., Li, R., Mok, E., Hancock, S., Xing, L. ELSEVIER SCIENCE INC. 2012: S739S740
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 PubMedID 22168251

Testicular Cancer Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Buyyounouski, M. K., Carducci, M. A., Chang, S. S., Choueiri, T. K., Gupta, S., Hancock, S. L., Hudes, G. R., Jonasch, E., Kuzel, T. M., Lau, C., Levine, E. G., Lin, D. W., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Ratliff, T. W., Redman, B. G., Robertson, C. N., Ryan, C. J., Sheinfeld, J., Wang, J., Wilder, R. B. 2012; 10 (4): 502-535

View details for Web of Science ID 000302445400009

View details for PubMedID 22491049

Kidney cancer. Journal of the National Comprehensive Cancer Network Motzer, R. J., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Carducci, M. A., Chang, S. S., Choueiri, T. K., Hancock, S. L., Hudes, G. R., Jonasch, E., Josephson, D., Kuzel, T. M., Levine, E. G., Lin, D. W., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Ratliff, T. W., Redman, B. G., Robertson, C. N., Ryan, C. J., Sheinfeld, J., Spiess, P. E., Wang, J., Wilder, R. B. 2011; 9 (9): 960-977

View details for PubMedID 21917622

NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Carducci, M. A., Chang, S. S., Choueiri, T. K., Hancock, S. L., Hudes, G. R., Jonasch, E., Josephson, D., Kuzel, T. M., Levine, E. G., Lin, D. W., Margolin, K. A., Michaelson, M. D., Olencki, T., Pill, R., Ratliff, T. W., Redman, B. G., Robertson, C. N., Ryan, C. J., Sheinfeld, J., Spiess, P. E., Wang, J., Wilder, R. B. 2011; 9 (9): 960-977
Clinical development of a failure detection-based online repositioning strategy for prostate IMRT-Experiments, simulation, and dosimetry study MEDICAL PHYSICS Liu, W., Qian, J., Hancock, S. L., Xing, L., Luxton, G. 2010; 37 (10): 5287-5297

Abstract

To implement and evaluate clinic-ready adaptive imaging protocols for online patient repositioning (motion tracking) during prostate IMRT using treatment beam imaging supplemented by minimal, as-needed use of on-board kV.The authors examine the two-step decision-making strategy: (1) Use cine-MV imaging and online-updated characterization of prostate motion to detect target motion that is potentially beyond a predefined threshold and (2) use paired MV-kV 3D localization to determine overthreshold displacement and, if needed, reposition the patient. Two levels of clinical implementation were evaluated: (1) Field-by-field based motion correction for present-day linacs and (2) instantaneous repositioning for new-generation linacs with capabilities of simultaneous MV-kV imaging and remote automatic couch control during treatment delivery. Experiments were performed on a Varian Trilogy linac in clinical mode using a 4D motion phantom programed with prostate motion trajectories taken from patient data. Dosimetric impact was examined using a 2D ion chamber array. Simulations were done for 536 trajectories from 17 patients.Despite the loss of marker detection efficiency caused by the MLC leaves sometimes obscuring the field at the marker's projected position on the MV imager, the field-by-field correction halved (from 23% to 10%) the mean percentage of time that target displacement exceeded a 3 mm threshold, as compared to no intervention. This was achieved at minimal cost in additional imaging (average of one MV-kV pair per two to three treatment fractions) and with a very small number of repositionings (once every four to five fractions). Also with low kV usage (approximation 2/fraction), the instantaneous repositioning approach reduced overthreshold time by more than 75% (23% to 5%) even with severe MLC blockage as often encountered in current IMRT and could reduce the overthreshold time tenfold (to < 2%) if the MLC blockage problem were relieved. The information acquired for repositioning using combined MV-kV images was found to have submillimeter accuracy.This work demonstrated with a current clinical setup that substantial reduction of adverse targeting effects of intrafraction prostate motion can be realized. The proposed adaptive imaging strategy incurs minimal imaging dose to the patient as compared to other stereoscopic imaging techniques.

View details for DOI 10.1118/1.3488887

View details for Web of Science ID 000283483700016

View details for PubMedID 21089763

View details for PubMedCentralID PMC2951998

A Real-time Low-dose Imaging Strategy for Online Patient Repositioning or Respiratory Gating during IMRT or VMAT 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Liu, W., Luxton, G., Mastoridis, T., Hancock, S. L., Xing, L. ELSEVIER SCIENCE INC. 2010: S724S725
Analysis of Breast Cancer Subtypes in Women who Develop Breast Cancer following Mantle Irradiation for Hodgkin's Disease Horst, K. C., Hancock, S., Advani, R., Horning, S., Rosenberg, S., Hoppe, R. T. ELSEVIER SCIENCE INC. 2010: S206S207
NCCN clinical practice guidelines in oncology: testicular cancer. Journal of the National Comprehensive Cancer Network Motzer, R. J., Agarwal, N., Beard, C., Bolger, G. B., Boston, B., Carducci, M. A., Choueiri, T. K., Figlin, R. A., Fishman, M., Hancock, S. L., Hudes, G. R., Jonasch, E., Kessinger, A., Kuzel, T. M., Lange, P. H., Levine, E. G., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Redman, B. G., Robertson, C. N., Schwartz, L. H., Sheinfeld, J., Wang, J. 2009; 7 (6): 672-693

View details for PubMedID 19555582

Testicular Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Agarwal, N., Beard, C., Bolger, G. B., Boston, B., Carducci, M. A., Choueiri, T. K., Figlin, R. A., Fishman, M., Hancock, S. L., Hudes, G. R., Jonasch, E., Kessinger, A., Kuzel, T. M., Lange, P. H., Levine, E. G., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Redman, B. G., Robertson, C. N., Schwartz, L. H., Sheinfeld, J., Wang, J. 2009; 7 (6): 672-693
Kidney Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Agarwal, N., Beard, C., Bolger, G. B., Boston, B., Carducci, M. A., Choueiri, T. K., Figlin, R. A., Fishman, M., Hancock, S. L., Hudes, G. R., Jonasch, E., Kessinger, A., Kuzel, T. M., Lange, P. H., Levine, E. G., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Redman, B. G., Robertson, C. N., Schwartz, L. H., Sheinfeld, J., Wang, J. 2009; 7 (6): 618-630
NCCN clinical practice guidelines in oncology: kidney cancer. Journal of the National Comprehensive Cancer Network Motzer, R. J., Agarwal, N., Beard, C., Bolger, G. B., Boston, B., Carducci, M. A., Choueiri, T. K., Figlin, R. A., Fishman, M., Hancock, S. L., Hudes, G. R., Jonasch, E., Kessinger, A., Kuzel, T. M., Lange, P. H., Levine, E. G., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Redman, B. G., Robertson, C. N., Schwartz, L. H., Sheinfeld, J., Wang, J. 2009; 7 (6): 618-630

View details for PubMedID 19555584

Mammographic screening in women at increased risk of breast cancer after treatment of Hodgkin's disease American-Society-of-Breast-Disease Symposium Kwong, A., Hancock, S. L., Bloom, J. R., Pal, S., Birdwell, R. L., Mariscal, C., Ikeda, D. M. BLACKWELL PUBLISHING. 2008: 3948

Abstract

Treatment regimens for Hodgkin's disease (HD) that have included radiation to lymph node regions in the thorax have contributed to high rates of long-term disease-free survival. However, incidental radiation exposure of breast tissue in young women has significantly increased the risk of breast cancer compared to expected rates in the general population. After informing patients about risks associated with previous treatment of HD, we studied screening mammograms and call-back rates in women at increased risk for developing breast cancer at a younger age. We contacted by mail a cohort of 291 women between 25 and 55 years of age who had received thoracic irradiation before 35 years of age for HD with or without chemotherapy. Subjects were offered information about risks identified after HD therapy with questionnaires to assess response to this information. Ten patients refused participation, 93 did not respond, and 21 were excluded after they reported a prior diagnosis of invasive (1) or in situ (2) breast cancer. One hundred and sixty seven women received information about secondary breast cancer risk and were advised to initiate or maintain mammographic screening. Available mammograms were reviewed by two radiologists and classified according to the ACR BI-RADS Mammography Lexicon. Abnormal findings were correlated to pathology results from biopsies. One hundred and fifteen subjects reported that they obtained new mammograms during the period of the study. Ninety-nine were available for secondary review. Patients were studied an average of 16.9 years after HD treatment (Range: 4.5-32.5 years) at an average of 41 years of age (range 25-55 years). High density breast tissue was identified in 60% (60/99). Seventeen of the women (17.2%) were recalled for further imaging. This was more common in women with heterogeneously dense breast tissue. Seven of those recalled (41%) were advised to undergo biopsies that identified ductal carcinoma in situ (DCIS) in one and benign findings in the others. Among 16 women whose mammograms were unavailable for review, three were diagnosed with DCIS; two of these had microscopic evidence of invasive breast cancer. The four in situ or microinvasive cancers were diagnosed in the study participants at 25-40 years of age and from 5 to 23 years after HD therapy. Biopsies were performed because mammograms detected microcalcifications without palpable abnormality in three of these cases. Women who have had thoracic nodal irradiation for Hodgkin's disease have an increased risk of developing secondary breast cancer at an unusually young age. As expected in younger women, high density breast tissue was common on mammography, and the recall and biopsy rates were unusually high. However, early mammographic screening facilitated diagnosis of in situ and early invasive cancer in 3.5% of our subjects.

View details for Web of Science ID 000252124800006

View details for PubMedID 18186864

A prospective trial of involved field radiation (IFRT) plus chemotherapy vs extended field (EFRT) radiation for favorable Hodgkin's disease (HD): Long-term follow-up and implications for current combined modality therapy 7th International Symposium on Hodgkins Lymphoma Horning, S. J., Hoppe, R. T., Advani, R. H., Breslin, S., McCormick, E., Allen, J., Hancock, S. L., Rosenberg, S. A. FERRATA STORTI FOUNDATION. 2007: 5353
Radiotherapy after prostatectomy: Improved biochemical relapse-free survival with whole pelvic compared with prostate bed only for high-risk patients INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Spiotto, M. T., Hancock, S. L., King, C. R. 2007; 69 (1): 54-61

Abstract

To compare the biochemical relapse-free survival (bRFS) among patients receiving whole pelvic radiotherapy (WPRT) vs. prostate bed RT (PBRT) after radical prostatectomy.Between 1985 and 2005, 160 patients underwent adjuvant or salvage RT after radical prostatectomy. A short course of total androgen suppression was also given concurrently to 87 patients. Of the 160 patients, 114 were considered at high risk of lymph node involvement because they had a pathologic Gleason score of >/=8, a preoperative prostate-specific antigen level >20 ng/mL, seminal vesicle or prostate capsule involvement, or pathologic lymph node involvement. Of this group, 72 underwent WPRT and 42 underwent PBRT. The median follow-up was >5 years for all patient subsets. Kaplan-Meier and Cox proportional hazards multivariate analyses were performed for all clinical, pathologic, and treatment factors predicting for bRFS.Whole pelvic RT resulted in superior bRFS compared with PBRT (p = 0.03). The advantage of WPRT was limited to high-risk patients, with a 5-year bRFS rate of 47% (95% confidence interval, 35-59%) after WPRT vs. 21% (95% confidence interval, 8-35%) after PBRT (p = 0.008). For low-risk patients, no difference (p = 0.9) was found. On multivariate analysis, only WPRT (p = 0.02) and a preoperative prostate-specific antigen level <1.0 ng/mL (p = 0.002) were significantly associated with bRFS. The benefit from total androgen suppression with postoperative RT was only observed when given concurrently with WPRT (p = 0.04) and not with PBRT (p = 0.4).The results of our study have indicated that WPRT confers superior bRFS compared with PBRT for high-risk patients receiving adjuvant or salvage RT after radical prostatectomy. This advantage was observed only with concurrent TAS. These results are analogous to the benefit from WPRT seen in the Radiation Therapy Oncology Group 94-13 study.

View details for DOI 10.1016/j.ijrobp.2007.02.035

View details for Web of Science ID 000248978300009

View details for PubMedID 17459606

A prospective trial of involved field radiation (IFRT) plus chemotherapy compared to extended field (EFRT) radiation for favorable Hodgkin disease: Survival differences and implications of mature follow-up for current combined modality therapy Horning, S. J., Hoppe, R. T., Advani, R. H., Breslin, S., Allen, J., Hancock, S. L., Rosenberg, S. A. AMER SOC CLINICAL ONCOLOGY. 2007
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

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
Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Heidenreich, P. A., Schnittger, I., Strauss, H. W., Vagelos, R. H., Lee, B. K., Mariscal, C. S., Tate, D. J., Horning, S. J., Hoppe, R. T., Hancock, S. L. 2007; 25 (1): 43-49

Abstract

Incidental cardiac irradiation during treatment of thoracic neoplasms has increased risks for subsequent acute myocardial infarction or sudden cardiac death. Identifying patients who have a high risk for a coronary event may decrease morbidity and mortality. The objective of this study was to evaluate whether stress imaging can identify severe, unsuspected coronary stenoses in patients who had prior mediastinal irradiation for Hodgkin's disease.We enrolled 294 outpatients observed at a tertiary care cancer treatment center after mediastinal irradiation doses 35 Gy for Hodgkin's disease who had no known ischemic cardiac disease. Patients underwent stress echocardiography and radionuclide perfusion imaging at one stress session. Coronary angiography was performed at the discretion of the physician.Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest, suggesting prior myocardial injury. During stress testing, 42 patients (14%) developed perfusion defects (n = 26), impaired wall motion (n = 8), or both abnormalities (n = 8). Coronary angiography showed stenosis 50% in 22 patients (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three patients developed coronary events during a median of 6.5 years of follow-up, with 10 acute myocardial infarctions (two fatal).Stress-induced signs of ischemia and significant coronary artery disease are highly prevalent after mediastinal irradiation in young patients. Stress testing identifies asymptomatic individuals at high risk for acute myocardial infarction or sudden cardiac death.

View details for DOI 10.1200/JCO.2006.07.0805

View details for Web of Science ID 000243725900009

View details for PubMedID 17194904

Improved biochemical relapse-free survival with whole pelvic compared to prostate bed only radiotherapy for high-risk patients after prostatectomy Spiono, M. T., Hancock, S., King, C. R. ELSEVIER SCIENCE INC. 2007: S173S174
Testicular cancer. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Motzer, R. J., Bolger, G. B., Boston, B., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Jonasch, E., Kantoff, P., Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Margolin, K. A., Pohar, K. S., Redman, B. G., Robertson, C. N., Samlowski, W. E., Sheinfeld, J. 2006; 4 (10): 1038-1058

View details for PubMedID 17112452

Kidney cancer. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Motzer, R. J., Bolger, G. B., Boston, B., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Jonasch, E., Kantoff, P., Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Margolin, K. A., Pohar, K., Redman, B. G., Robertson, C. N., Samlowski, W. E., Sheinfeld, J. 2006; 4 (10): 1072-1081

View details for PubMedID 17112454

Breast cancer screening in women surviving Hodgkin disease AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Bloom, J. R., Stewart, S. L., Hancock, S. L. 2006; 29 (3): 258-266

Abstract

To inform female Hodgkin disease (HD) survivors, younger than 35 at diagnosis, of their increased risk for breast cancer and encourage them to seek breast cancer screening.An evidence-based intervention, telephone counseling, was used in a pre-post test design, randomized trial with the control group being offered the intervention following the post-test. Women treated at Stanford University who received thoracic irradiation before age 35, alive and HD-free at last contact, were referred to the project (n = 471). Of 261 eligible women who could be located, 157 completed the pretest and were randomized (60% response rate) and 133 completed the post-test (85% retention rate).There was a positive intervention effect on mammography maintenance: the odds of being in maintenance at post-test compared with pretest were greater in the intervention group than in the control group [odds ratio (OR) = 3.6]. Women were more likely to be in mammography maintenance at pre- or post-test if at pretest they were married (OR = 5.7), employed (OR = 2.3), more worried about breast cancer (OR = 1.4 per unit of scale), or received an annual physical examination (OR = 2.2). Women under age 40 were much less likely to be in maintenance than were those age 45 and over (age 35-39, OR = 0.2; under age 35, OR = 0.07).The findings indicate that providing risk information encourages cancer survivors to take health preventive actions. Telephone counseling is a method that can provide risk information and is easily transferable to settings where people seek health information, such as telephone information lines.

View details for DOI 10.1097/01.coc.0000209447.63640.5a

View details for Web of Science ID 000238158800008

View details for PubMedID 16755179

Impact on nodal dose distribution from daily fiducial tracking for IMRT prostate and pelvic node treatments 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine Hsu, A., Pawlicki, T., King, C., Hancock, S., Luxton, G. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2006: 221616
Clinical manifestations of noncoronary atherosclerotic vascular disease after moderate dose irradiation CANCER Patel, D. A., Kochanski, J., Suen, A. W., Fajardo, L. F., Hancock, S. L., Knox, S. J. 2006; 106 (3): 718-725

Abstract

Accelerated atherosclerosis and carotid stenosis are well-established risks occurring after high radiation doses that are used to treat cancers of the head and neck. Noncoronary vascular disease has been observed and may relate to more moderate dose irradiation.A search of patients treated for Hodgkin disease, non-Hodgkin lymphoma, or seminoma was performed to identify cases with noncoronary vascular complications after irradiation. These three groups were chosen because of the use of intermediate dose radiation and prevalence of long-term survivors. Individual patient records were reviewed to document the type and presentation of the stenosis and the clinical factors that may have contributed to this risk.Twenty-one patients were identified who developed disease in noncoronary arteries after treatment. The median time from irradiation to diagnosis of vascular stenosis was 15 years. Antecedent risk factors for vascular disease were prevalent. Five patients had disease identified by auscultation of bruits before an adverse clinical event occurred. Five patients died from complications related to their vascular disease, which included three deaths after stroke and two after small bowel infarction.Twelve cases arose at an atypically young age for atherosclerotic vascular disease and featured unusual clinical presentations. Nine cases identified occurred at an advanced aged and at a shorter median interval, making a causal relation to irradiation uncertain. Incorporating careful auscultation for bruits in followup evaluation of irradiated patients may identify individuals who are at risk for adverse vascular events. The potential for early vasculopathy in individuals exposed to intermediate dose irradiation suggests a need to manage dyslipidemia and reduce vascular risk factors throughout the posttreatment period.

View details for DOI 10.1002/cncr.21636

View details for Web of Science ID 000234822700028

View details for PubMedID 16353211

On-board volumetric CT-based adaptive IMRT for improved prostate cancer treatment 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Xing, L., de la Zerd, A., Cao, M., Li, T., Armbrush, B., Yang, Y., Lee, P., Pawlicki, T., Hancock, S., King, C. ELSEVIER SCIENCE INC. 2006: S624S625
Diastolic dysfunction after mediastinal irradiation AMERICAN HEART JOURNAL Heidenreich, P. A., Hancock, S. L., Vagelos, R. H., Lee, B. K., Schnittger, I. 2005; 150 (5): 977-982

Abstract

Mediastinal irradiation is known to cause cardiac disease, but its effect on left ventricular diastolic function is unknown. The purpose of this study was to determine the prevalence of diastolic dysfunction and its association with prognosis in asymptomatic patients after mediastinal irradiation.We recruited 294 patients who had received at least 35 Gy to the mediastinum for treatment of Hodgkin disease. Each patient underwent resting echocardiography, stress echocardiography, and nuclear scintigraphy. Survival free from cardiac events was determined during 3.2 years of follow-up.The mean age of the included patients was 42 years, and 49% were male. Adequate measurements of diastolic function were obtained in 282 (97%) patients. Diastolic dysfunction was considered mild in 26 (9%) and moderate in 14 (5%). Exercise-induced ischemia was more common in patients with diastolic dysfunction (23%) than those with normal diastolic function (11%, P = .008). After adjustment for patient demographics, clinical characteristics, and radiation history, patients with diastolic dysfunction had worse event-free survival than patients with normal function (hazard ratio 1.66, 95% CI 1.06-2.4).There is a high prevalence of diastolic dysfunction in asymptomatic patients after mediastinal irradiation, and the presence of diastolic dysfunction is associated with stress-induced ischemia and a worse prognosis. Screening with Doppler echocardiography may be helpful in identifying patients at risk for subsequent cardiac events.

View details for DOI 10.1016/j.ahj.2004.12.026

View details for Web of Science ID 000233478800024

View details for PubMedID 16290974

Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy 6th International Symposium on Hodgkins Disease Mauch, P., Ng, A., Aleman, B., Carde, P., Constine, L., Diehl, V., Dinshaw, K., Gospodarowicz, M., Hancock, S., Hodgson, D., Hoppe, R., Liang, R., Loeffler, M., Specht, L., Travis, L. B., Wirth, A., Yahalom, J. WILEY-BLACKWELL. 2005: 6876

Abstract

A workshop, sponsored by the Rockefellar Foundation, was held between 9 to 16 July, 2003 to devise strategies to reduce mortality and improve quality of life of long-term survivors of Hodgkin's disease. Participants were selected for their clinical and research background on late effects after Hodgkin's disease therapy. Experts from both developed and developing nations were represented in the workshop, and efforts were made to ensure that the proposed strategies would be globally applicable whenever possible. The types of late complications, magnitude of the problem, contributing risk factors, methodology to assess the risk, and challenges faced by developing countries were presented. The main areas of late effects of Hodgkin's disease discussed were as follows: second malignancy, cardiac disease, infection, pulmonary dysfunction, endocrine abnormalities, and quality of life. This report summarizes the findings of the workshop, recommendations, and proposed research priorities in each of the above areas.

View details for Web of Science ID 000229591400012

View details for PubMedID 16007872

Metabolism of the 16-androstene steroids in primary cultured porcine hepatocytes JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY Sinclair, P. A., Hancock, S., Gilmore, W. J., Squires, E. J. 2005; 96 (1): 79-87

Abstract

The hepatic metabolism of the 16-androstene steroids was investigated using isolated porcine hepatocytes. This study demonstrated that the liver is capable of producing both phase I and phase II steroid metabolites from 16-androstene steroid precursors. 16-Androstene metabolites were recovered by solid-phase extraction and identified by gas chromatography-mass spectrometry (GC-MS). When 5alpha-androstenone was provided as a substrate, both 3beta- and 3alpha-androstenol were produced as well as a metabolite that showed evidence of hydroxylation. Incubations with the various 16-androstene steroids produced metabolic profiles which suggested that the major role of the liver is phase II conjugation. Sulfoconjugated 16-androstene steroids included androstadienol, 5alpha-androstenone, 3beta-, 3alpha-androstenol, and possibly the hydroxylated metabolite of 5alpha-androstenone. It was determined that hydroxysteroid sulfotransferase (HST) is the likely candidate for the sulfoconjugation of the 16-androstene steroids within the liver. Despite the capacity of the hepatocytes to sulfoconjugate the 16-androstene steroids, the principle metabolites produced from incubations with 5alpha-androstenone, 3beta-, and 3alpha-androstenol were glucuronide conjugates, accounting for approximately 68% of all phase II metabolism. These findings underline the importance of steroid conjugation and suggest that hepatic metabolism of the 16-androstene steroids may influence the levels of 5alpha-androstenone present in the circulation, and thus, capable of accumulating in fat.

View details for DOI 10.1016/j.jsbmb.2005.01.030

View details for Web of Science ID 000231480800009

View details for PubMedID 15896952

Testicular cancer. Clinical practice guidelines. Journal of the National Comprehensive Cancer Network Motzer, R. J., Bahnson, R. R., Boston, B., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Kantoff, P., Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Margolin, K. A., Redman, B. G., Richey, S., Robertson, C. N., Samlowski, W. E., Sheinfeld, J., Urban, D. A. 2005; 3 (1): 52-76

View details for PubMedID 19813323

Kidney cancer. Clinical practice guidelines. Journal of the National Comprehensive Cancer Network Motzer, R. J., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Kantoff, P., Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Margolin, K. A., Pili, R., Pohar, K. S., Redman, B. G., Richey, S., Robertson, C. N., Samlowski, W. E., Sheinfeld, J., Urban, D. A. 2005; 3 (1): 84-93

View details for PubMedID 19813325

A systolic murmur is a common presentation of aortic regurgitation detected by echocardiography CLINICAL CARDIOLOGY Heidenreich, P. A., Schnittger, I., Hancock, S. L., Atwood, J. E. 2004; 27 (9): 502-506

Abstract

The finding of aortic regurgitation at a classical examination is a diastolic murmur.Aortic regurgitation is more likely to be associated with a systolic than with a diastolic murmur during routine screening by a noncardiologist physician.In all, 243 asymptomatic patients (mean age 42 +/- 10 years) with no known cardiac disease but at risk for aortic valve disease due to prior mediastinal irradiation (> or = 35 Gy) underwent auscultation by a noncardiologist followed by echocardiography. A systolic murmur was considered benign if it was grade < or = II/VI, not holosystolic, was not heard at the apex, did not radiate to the carotids, and was not associated with a diastolic murmur.Of the patients included, 122 (49%) were male, and 86 (35%) had aortic regurgitation, which was trace in 20 (8%), mild in 52 (21%), and moderate in 14 (6%). A systolic murmur was common in patients with aortic regurgitation, occurring in 12 (86%) with moderate, 26 (50%) with mild, 6 (30%) with trace, and 27 (17%) with no aortic regurgitation (p < 0.0001). The systolic murmurs were classified as benign in 21 (78%) patients with mild and 8 (67%) with moderate aortic regurgitation. Diastolic murmurs were rare, occurring in two (14%) with moderate, two (4%) with mild, and three (2%) with no aortic regurgitation (p=0.15).An isolated systolic murmur is a common auscultatory finding by a noncardiologist in patients with moderate or milder aortic regurgitation. A systolic murmur in patients at risk for aortic valve disease should prompt a more thorough physical examination for aortic regurgitation.

View details for Web of Science ID 000223604300004

View details for PubMedID 15471160

Radiotherapy after radical prostatectomy: Does transient androgen suppression improve outcomes? 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology King, C. R., Presti, J. C., Gill, H., Brooks, J., Hancock, S. L. ELSEVIER SCIENCE INC. 2004: 34147

Abstract

The long-term biochemical relapse-free survival and overall survival were compared for patients receiving either radiotherapy (RT) alone or radiotherapy combined with a short-course of total androgen suppression for failure after radical prostatectomy.Between 1985 and 2001, a total of 122 patients received RT after radical prostatectomy at our institution. Fifty-three of these patients received a short-course of total androgen suppression (TAS) 2 months before and 2 months concurrent with RT with a nonsteroidal antiandrogen and an luteinizing hormone-releasing hormone (LHRH) agonist (combined therapy group); the remaining 69 patients received RT alone. Treatment failure was defined after postoperative RT as a detectable PSA >0.05 ng/mL. Clinical and treatment variables examined included: presurgical PSA, clinical T stage, pathologic Gleason sum (pGS), seminal vesicle (SV) involvement, lymph node involvement, surgical margins, pre-RT PSA, prostate dose, pelvic irradiation, indication for postoperative RT (salvage or adjuvant), and time interval between surgery and RT. Minimum follow-up after postoperative RT was 1 year and median follow-up was 5.9 years (maximum, 14 years) for patients receiving RT alone, and 3.9 years (maximum, 11 years) for patients receiving RT with TAS (combined therapy group). Kaplan-Meier analysis was performed for PSA failure-free survival (bNED) and for overall survival (OS). Cox proportional hazards multivariable analysis examined the influence all clinical and treatment variables predicting for bNED and OS.The median time to PSA failure after postoperative RT was 1.34 years for the combined therapy group and 0.97 years for the RT alone group (p = 0.19), with no failures beyond 5 years. At 5 years, the actuarial bNED rates were 57% for the combined therapy group compared with 31% for the RT alone group (p = 0.0012). Overall survival rates at 5 years were 100% for the combined therapy group compared with 87% for the RT alone group (p = 0.0008). For pGS or=8 the 5-year bNED rates were 65% for combined therapy and 17% for RT alone (p = 0.075). The 5-year OS rates for pGS or=8 was 100% for combined therapy and 54% for RT alone (p = 0.04). On multivariable analysis, only SV involvement (p = 0.0145) and the addition of short-course TAS to postoperative RT (p = 0.0019) were significant covariates predicting for bNED and, similarly, approached significance for overall survival (p = 0.0594 and p = 0.0856, respectively).Radiotherapy combined with a short-course TAS after radical prostatectomy appears to confer a PSA relapse-free survival advantage and possibly an overall survival advantage when compared with RT alone. The hypothesis that a transient course of androgen suppression with salvage or adjuvant RT after prostatectomy improves outcomes will need to be tested in a randomized trial.

View details for DOI 10.1016/j.ijribp.2003.10.015

View details for Web of Science ID 000221440800002

View details for PubMedID 15145146

IMRT versus conformal 3-D planning for prostate cancer: Comparison of biological model calculations of NTCP and TCP Luxton, G., Hancock, S. L., Boyer, A. L. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2004: 1894
Comparison of a computerized radiography system with an amorphous silicon electronic portal Imaging device Lo, A., Hai, J., Koumrian, T., Luxton, G., King, C., Hancock, S., Boyer, A. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2004: 1871
Dosimetry and radiobiologic model comparison of IMRT and 3D conformal radiotherapy in treatment of carcinoma of the prostate INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Luxton, G., Hancock, S. L., Boyer, A. L. 2004; 59 (1): 267-284

Abstract

Intensity-modulated radiotherapy (IMRT) has introduced novel dosimetry that often features increased dose heterogeneity to target and normal structures. This raises questions of the biologic effects of IMRT compared to conventional treatment. We compared dosimetry and radiobiologic model predictions of tumor control probability (TCP) and normal tissue complication probability (NTCP) for prostate cancer patients planned for IMRT as opposed to standardized three-dimensional conformal radiotherapy (3DCRT).Segmented multileaf collimator IMRT treatment plans for 32 prostate cancer patients were compared to 3DCRT plans for the same patients. Twenty-two received local-field irradiation (LFI), and 10 received extended-field irradiation (EFI) that included pelvic lymph nodes. For LFI, IMRT was planned for delivery of 2 Gy minimum dose to the prostate (> or =99% volume coverage) for 35 fractions. The 3DCRT plans, characterized by more homogenous dose to the target, were designed according to a different protocol to deliver 2 Gy to the center of the prostate for 37 fractions. Mean total dose from 35 fractions of IMRT was equal to mean total dose from 37 fractions of 3DCRT. For EFI, both IMRT and 3DCRT were planned for 2 Gy per fraction to a total dose of 50 Gy to prostate and pelvic lymph nodes, followed by 2 Gy per fraction to 20 Gy to the prostate alone. Treatment dose for EFI-IMRT was defined as minimum dose to the target, whereas for EFI-3DCRT, it was defined as dose to the center of the prostate. TCP was calculated for the prostate in the linear-quadratic model for two choices of alpha/beta. NTCP was calculated with the Lyman model for organs at risk, using Kutcher-Burman dose-volume histogram reduction with Emami parameters.Dose to the prostate, expressed as mean +/- standard deviation, was 74.7 +/- 1.1 Gy for IMRT vs. 74.6 +/- 0.3 Gy for 3D for the LFI plans, and 74.8 +/- 0.6 Gy for IMRT vs. 71.5 +/- 0.6 Gy for 3D for the EFI plans. For the studied protocols, TCP was greater for IMRT than for 3D across the full range of target sensitivity, for both localized- and extended-field irradiation. For LFI, this was due to the smaller number of fractions (35 vs. 37) used for IMRT, and for EFI, this was due to the greater mean dose for IMRT, compared to 3D. For all organs, mean NTCP tended to be lower for IMRT than for 3D, although NTCP values were very small for both 3D and IMRT. Differences were statistically significant for rectum (LFI and EFI), bladder (EFI), and bowel (EFI). For both LFI and EFI, the calculated NTCPs qualitatively agreed with early published clinical data comparing genitourinary and gastrointestinal complications of IMRT and 3D. Present calculations support the hypothesis that accurately delivered IMRT for prostate cancer can limit dose to normal tissue by reducing treatment margins relative to conventional 3D planning, to allow a reduction in complication rate spanning several sensitive structures while maintaining or increasing tumor control probability.

View details for DOI 10.1016/j.ijrobp.2004.01.024

View details for Web of Science ID 000221047500034

View details for PubMedID 15093924

Using finite-element method to register endorectal coil-based MRI/MRSI with treatment planning CT images 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Schreibmann, E., Kim, D., Hancock, S. L., Boyer, A., Spielman, D., Daniel, B., Xing, L. ELSEVIER SCIENCE INC. 2004: S592S593
Asymptomatic cardiac disease following mediastinal irradiation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Heidenreich, P. A., Hancock, S. L., Lee, B. K., Mariscal, C. S., Schnittger, I. 2003; 42 (4): 743-749

Abstract

This study was designed to evaluate the potential benefit of screening previously irradiated patients with echocardiography.Mediastinal irradiation is known to cause cardiac disease. However, the prevalence of asymptomatic cardiac disease and the potential for intervention before symptom development are unknown.We recruited 294 asymptomatic patients (mean age 42 +/- 9 years, 49% men, mean mantle irradiation dose 43 +/- 0.3 Gy) treated with at least 35 Gy to the mediastinum for Hodgkin's disease. After providing written consent, each patient underwent electrocardiography and transthoracic echocardiography. Valvular disease was common and increased with time following irradiation. Patients who had received irradiation more than 20 years before evaluation had significantly more mild or greater aortic regurgitation (60% vs. 4%, p < 0.0001), moderate or greater tricuspid regurgitation (4% vs. 0%, p = 0.06), and aortic stenosis (16% vs. 0%, p = 0.0008) than those who had received irradiation within 10 years. The number needed to screen to detect one candidate for endocarditis prophylaxis was 13 (95% confidence interval [CI] 7 to 44) for patients treated within 10 years and 1.6 (95% CI 1.3 to 1.9) for those treated at least 20 years ago. Compared with the Framingham Heart Study population, mildly reduced left ventricular fractional shortening (<30%) was more common (36% vs. 3%), and age- and gender-adjusted left ventricular mass was lower (90 +/- 27 g/m vs. 117 g/m) in irradiated patients.There is a high prevalence of asymptomatic heart disease in general, and aortic valvular disease in particular, following mediastinal irradiation. Screening echocardiography should be considered for patients with a history of mediastinal irradiation.

View details for DOI 10.1016/S0735-1097(03)00759-9

View details for Web of Science ID 000184780600027

View details for PubMedID 12932613

Post-irradiation polyradiculopathy mimics leptomeningeal tumor on MRI NEUROLOGY Hsia, A. W., Katz, J. S., Hancock, S. L., Peterson, K. 2003; 60 (10): 1694-1696

Abstract

Three patients with a remote history of Hodgkin's disease treated with total or subtotal lymphoid radiation 17 to 24 years earlier developed lumbosacral polyradiculopathy associated with nodular meningeal enhancement of the conus medullaris and cauda equina on MRI. None had evidence of recurrent Hodgkin's disease or second malignancy, and the MRI findings may be sequelae of radiation therapy.

View details for Web of Science ID 000183092400033

View details for PubMedID 12771271

Role of beam orientation optimization in intensity-modulated radiation therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pugachev, A., Li, J. G., Boyer, A. L., Hancock, S. L., Le, Q. T., Donaldson, S. S., Xing, L. 2001; 50 (2): 551-560

Abstract

To investigate the role of beam orientation optimization in intensity-modulated radiation therapy (IMRT) and to examine the potential benefits of noncoplanar intensity-modulated beams.A beam orientation optimization algorithm was implemented. For this purpose, system variables were divided into two groups: beam position (gantry and table angles) and beam profile (beamlet weights). Simulated annealing was used for beam orientation optimization and the simultaneous iterative inverse treatment planning algorithm (SIITP) for beam intensity profile optimization. Three clinical cases were studied: a localized prostate cancer, a nasopharyngeal cancer, and a paraspinal tumor. Nine fields were used for all treatments. For each case, 3 types of treatment plan optimization were performed: (1) beam intensity profiles were optimized for 9 equiangular spaced coplanar beams; (2) orientations and intensity profiles were optimized for 9 coplanar beams; (3) orientations and intensity profiles were optimized for 9 noncoplanar beams.For the localized prostate case, all 3 types of optimization described above resulted in dose distributions of a similar quality. For the nasopharynx case, optimized noncoplanar beams provided a significant gain in the gross tumor volume coverage. For the paraspinal case, orientation optimization using noncoplanar beams resulted in better kidney sparing and improved gross tumor volume coverage.The sensitivity of an IMRT treatment plan with respect to the selection of beam orientations varies from site to site. For some cases, the choice of beam orientations is important even when the number of beams is as large as 9. Noncoplanar beams provide an additional degree of freedom for IMRT treatment optimization and may allow for notable improvement in the quality of some complicated plans.

View details for Web of Science ID 000168781000033

View details for PubMedID 11380245

Management of breast cancer after Hodgkin's disease 39th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Wolden, S. L., Hancock, S. L., Carlson, R. W., Goffinet, D. R., Jeffrey, S. S., Hoppe, R. T. AMER SOC CLINICAL ONCOLOGY. 2000: 76572

Abstract

To evaluate the incidence, detection, pathology, management, and prognosis of breast cancer occurring after Hodgkin's disease.Seventy-one cases of breast cancer in 65 survivors of Hodgkin's disease were analyzed.The median age at diagnosis was 24.6 years for Hodgkin's disease and 42.6 years for breast cancer. The relative risk for invasive breast cancer after Hodgkin's disease was 4.7 (95% confidence interval, 3.4 to 6. 0) compared with an age-matched cohort. Cancers were detected by self-examination (63%), mammography (30%), and physician exam (7%). The histologic distribution paralleled that reported in the general population (85% ductal histology) as did other features (27% positive axillary lymph nodes, 63% positive estrogen receptors, and 25% family history). Although 87% of tumors were less than 4 cm, 95% were managed with mastectomy because of prior radiation. Two women underwent lumpectomy with breast irradiation. One of these patients developed tissue necrosis in the region of overlap with the prior mantle field. The incidence of bilateral breast cancer was 10%. Adjuvant systemic therapy was well tolerated; doxorubicin was used infrequently. Ten-year disease-specific survival was as follows: in-situ disease, 100%; stage I, 88%; stage II, 55%; stage III, 60%; and stage IV, zero.The risk of breast cancer is increased after Hodgkin's disease. Screening has been successful in detecting early-stage cancers. Pathologic features and prognosis are similar to that reported in the general population. Repeat irradiation of the breast can lead to tissue necrosis, and thus, mastectomy remains the standard of care in most cases.

View details for Web of Science ID 000085401800008

View details for PubMedID 10673517

Hodgkin's Lymphoma: Choice of Therapy and Late Complications. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program Linch, D. C., Gosden, R. G., Tulandi, T., Tan, S. L., Hancock, S. L. 2000: 20521

Abstract

This review focuses on the different treatment options available for the treatment of Hodgkin's disease, with an emphasis on the importance of the long-term sequelae of these therapies. In Section I, Dr. Linch reviews the current status of Hodgkin's disease treatment. Survival rates have improved over the last three decades due both to better initial therapies and associated supportive care and to the success of salvage therapy. Unlike most other malignancies, a similar survival endpoint can be achieved by different means, e.g., intensive initial therapy resulting in a low relapse rate or less intensive initial therapy and more reliance on salvage therapy. Overall survival has thus become a difficult end-point for clinical trials of primary therapy, and the value of disease-free survival as an end-point can also be questioned. Quality-of-life issues are to the fore of clinical decision and include the psychological trauma of relapse and fertility status. Patient choice is increasingly important. The high level of success in treating Hodgkin's disease also means that attention must be focused on the very long term results and in this context the occurrence of second malignancies is a major issue. In Section II, Dr. Gosden with Dr. Tulandi and Dr. Tan review the risks of infertility following radio-therapy and chemotherapy and address the actions that can be taken to overcome this problem, particularly for females and prepubertal boys and girls. Particular attention is paid to the recent developments in ovarian cryopreservation and harvesting immature germ cells. In Section III, Dr. Hancock gives a comprehensive update of the incidence of secondary acute leukemia, non-Hodgkin's lymphoma and solid tumors in a large population of patients treated for Hodgkin's disease. The roles of radiotherapy, chemotherapy and combined modality treatment as risk factors contributing to the development of these secondary malignancies are reviewed. The importance of efforts to prevent late-occurring solid tumors such as lung cancer through smoking cessation programs and early detection by screening for cancers of the breast, thyroid and skin are emphasized.

View details for PubMedID 11701543

Image-guided robotic radiosurgery: Clinical and radiographic results with the CyberKnife 4th International-Stereotactic-Radiosurgery-Society Congress Chang, S. D., MURPHY, M. J., Martin, D. P., Hancock, S. L., Doty, J. R., Adler, J. R. KARGER. 2000: 2333
Fractionated stereotactic radiosurgery and preservation of hearing in patients with vestibular schwannoma: A preliminary report NEUROSURGERY Poen, J. C., Golby, A. J., Forster, K. M., Martin, D. P., Chinn, D. M., Hancock, S. L., Adler, J. R. 1999; 45 (6): 1299-1305

Abstract

Microsurgery and stereotactic radiosurgery (SRS) for vestibular schwannomas are associated with a relatively high incidence of sensorineural hearing loss. A prospective trial of fractionated SRS was undertaken in an attempt to preserve hearing and minimize incidental cranial nerve injury.Thirty-three patients with vestibular schwannomas were treated with 2100 cGy in three fractions during a 24-hour period using conventional frame-based linear accelerator radiosurgery. The median tumor diameter was 20 mm (range, 7-42 mm). Baseline and follow-up evaluations included audiometry and contrast-enhanced magnetic resonance imaging. End points were tumor progression, preservation of serviceable hearing, and treatment-related complications.Thirty-one patients (32 tumors) were assessable for tumor progression and treatment-related complications and 21 patients for preservation of serviceable hearing, with a median follow-up interval of 2 years (range, 0.5-4.0 yr). Tumor regression or stabilization was documented in 30 patients (97%) and tumor progression in 1 (3%). The patient with tumor progression remains asymptomatic and has not required surgical intervention. Five patients (16%) developed trigeminal nerve injury at a median of 6 months (range, 4-12 mo) after SRS; two of these patients had preexisting trigeminal neuropathy. One patient (3%) developed facial nerve injury (House-Brackmann Class 3) 7 months after SRS. Preservation of useful hearing (Gardner-Robertson Class 1-2) was 77% at 2 years. All patients with pretreatment Gardner-Robertson Class 1 to 2 hearing maintained serviceable (Class 1-3) hearing as of their last follow-up examination.Three-fraction SRS with a conventional stereotactic frame is feasible and well tolerated in the treatment of acoustic neuroma. This study demonstrates a high rate of hearing preservation and few treatment-related complications among a relatively high-risk patient cohort (tumors >15 mm or neurofibromatosis Type 2). Longer follow-up will be required to assess the durability of tumor control.

View details for Web of Science ID 000084092000010

View details for PubMedID 10598696

The Janeway lecture. Hodgkin's disease--finding the balance between cure and late effects. cancer journal from Scientific American Donaldson, S. S., Hancock, S. L., Hoppe, R. T. 1999; 5 (6): 325-333

Abstract

The purpose of this review is to summarize the Stanford experience in Hodgkin's disease, the late effects of treatment, and strategies to improve management to maximize cure and decrease late effects in these patients.Between 1960 and 1999, 2617 consecutive patients with Hodgkin's disease have been seen, treated, and rigorously followed at Stanford. This population includes patients of all ages and stages of disease. The database summarizing this experience serves as the source of survival and mortality data over 4 decades. Two thousand two hundred thirty-two of the population comprise the group evaluated for secondary cardiac disease. Two thousand one hundred sixty-two patients have been evaluated for risk of secondary leukemia, non-Hodgkin's lymphoma, and solid tumors. Eight hundred eighty-five women were evaluated for secondary breast cancer, prompting a subsequent analysis of risk of secondary cancer among 694 pediatric patients.The probability of cure of Hodgkin's disease has dramatically improved over the past 40 years. Today, 94% of patients are expected to survive. Among those who do not survive, approximately half die of Hodgkin's disease, 20% of new cancers, and 14% of cardiovascular complications. Modifications in patient management and treatment have greatly reduced the serious late effects observed from prior therapy. With current combined-modality therapy using moderate doses of involved field of radiation and limited cycles of multiagent, risk adapted chemotherapy, serious cardiac complications and development of secondary cancers are expected to be greatly reduced. The Stanford 25-year pediatric Hodgkin's disease experience reveals that survival in favorable early-stage disease exceeds 95%. Newer protocols for children with advanced-stage disease continue to show these excellent survival rates and promise less late morbidity. Adult protocols using the risk-adapted Stanford V combined-modality program now parallel the pediatric experience, with greater than 90% survival in these patients.Thus today the likelihood of cure of Hodgkin's disease greatly exceeds the risk of late effects, a goal both Dr. Henry Janeway and Madame Marie Curie emphasized and taught from first-hand experience.

View details for PubMedID 10606471

Hodgkin's disease - Finding the balance between cure and late effects 81st Annual Meeting of the American-Radium-Society Donaldson, S. S., Hancock, S. L., Hoppe, R. T. LIPPINCOTT WILLIAMS & WILKINS. 1999: 32533

Abstract

The purpose of this review is to summarize the Stanford experience in Hodgkin's disease, the late effects of treatment, and strategies to improve management to maximize cure and decrease late effects in these patients.Between 1960 and 1999, 2617 consecutive patients with Hodgkin's disease have been seen, treated, and rigorously followed at Stanford. This population includes patients of all ages and stages of disease. The database summarizing this experience serves as the source of survival and mortality data over 4 decades. Two thousand two hundred thirty-two of the population comprise the group evaluated for secondary cardiac disease. Two thousand one hundred sixty-two patients have been evaluated for risk of secondary leukemia, non-Hodgkin's lymphoma, and solid tumors. Eight hundred eighty-five women were evaluated for secondary breast cancer, prompting a subsequent analysis of risk of secondary cancer among 694 pediatric patients.The probability of cure of Hodgkin's disease has dramatically improved over the past 40 years. Today, 94% of patients are expected to survive. Among those who do not survive, approximately half die of Hodgkin's disease, 20% of new cancers, and 14% of cardiovascular complications. Modifications in patient management and treatment have greatly reduced the serious late effects observed from prior therapy. With current combined-modality therapy using moderate doses of involved field of radiation and limited cycles of multiagent, risk adapted chemotherapy, serious cardiac complications and development of secondary cancers are expected to be greatly reduced. The Stanford 25-year pediatric Hodgkin's disease experience reveals that survival in favorable early-stage disease exceeds 95%. Newer protocols for children with advanced-stage disease continue to show these excellent survival rates and promise less late morbidity. Adult protocols using the risk-adapted Stanford V combined-modality program now parallel the pediatric experience, with greater than 90% survival in these patients.Thus today the likelihood of cure of Hodgkin's disease greatly exceeds the risk of late effects, a goal both Dr. Henry Janeway and Madame Marie Curie emphasized and taught from first-hand experience.

View details for Web of Science ID 000084144300003

Image-guided robotic radiosurgery NEUROSURGERY Adler, J. R., MURPHY, M. J., Chang, S. D., Hancock, S. L. 1999; 44 (6): 1299-1306
Radiation therapy for clinically localized prostate cancer - A multi-institutional pooled analysis JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Shipley, W. U., Thames, H. D., Sandler, H. M., Hanks, G. E., Zietman, A. L., Perez, C. A., Kuban, D. A., Hancock, S. L., Smith, C. D. 1999; 281 (17): 1598-1604

Abstract

Prostate-specific antigen (PSA) evaluation leads to the early detection of both prostate cancer and recurrences following primary treatment. Prostate-specific antigen outcome information on patients 5 or more years following treatment is limited and available mainly as single-institution reports.To assess the likelihood and durability of tumor control using PSA evaluation 5 or more years after radical external beam radiation therapy and to identify pretreatment prognostic factors in men with early prostate cancer treated since 1988, the PSA era.Retrospective, nonrandomized, multi-institutional pooled analysis of patients treated with external beam radiation therapy alone between 1988 and 1995 at 6 US medical centers. Follow-up lasted up to a maximum of 9 years. Outcome data were analyzed using Cox regression and recursive partitioning techniques.A total of 1765 men with stage T1b, T1c, and T2 tumors treated between 1988 and 1995 with external beam radiation. The majority (58%) of patients were older than 70 years and 24.2% had initial PSA values of 20 ng/mL or higher. A minimum of 2 years of subsequent follow-up was required for participation.Actuarial estimates of freedom from biochemical failure.The 5-year estimates of overall survival, disease-specific survival, and the freedom from biochemical failure are 85.0% (95% confidence interval [CI], 82.5%-87.6%), 95.1% (95% CI, 94.0%-96.2%), and 65.8% (95% CI, 62.8%-68.0%), respectively. The PSA failure-free rates 5 and 7 years after treatment for patients presenting with a PSA of less than 10 ng/mL were 77.8% (95% CI, 74.5%-81.3%), and 72.9% (95% CI, 67.9%-78.2%). Recursive partitioning analysis of initial PSA level, palpation stage, and the Gleason score groupings yielded 4 separate prognostic groups: group 1, included patients with a PSA level of less than 9.2 ng/mL; group 2, PSA level of at least 9.2 but less than 19.7 ng/mL; group 3, PSA level at least 19.7 ng/mL and a Gleason score of 2 to 6; and group 4, PSA level of at least 19.7 ng/mL and a Gleason score of 7 to 10. The estimated rates of survival free of biochemical failure at 5 years are 81 % for group 1, 69% for group 2, 47% for group 3, and 29% for group 4. Of the 302 patients followed up beyond 5 years who were free of biochemical disease, 5.0% relapsed from the fifth to the eighth year.Estimated PSA control rates in this pooled analysis are similar to those of single institutions. These rates indicate the probability of success for subsets of patients with tumors of several prognostic category groupings. These results represent a multi-institutional benchmark for evidence-based counseling of prostate cancer patients about radiation treatment.

View details for Web of Science ID 000080025900023

View details for PubMedID 10235152

Image-guided robotic radiosurgery Neurosurgery Adler, J. R., Murphy, M. J., Chang, S. D., Hancock, S. L. 1999; 44 (6): 12991306; discussion 13061307

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

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

View details for PubMedCentralID PMC1656740

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

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

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

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

Effect of combined transient androgen deprivation and irradiation following radical prostatectomy for prostatic cancer 38th ASTRO Annual Meeting Eulau, S. M., Tate, D. J., Stamey, T. A., Bagshaw, M. A., Hancock, S. L. ELSEVIER SCIENCE INC. 1998: 73540

Abstract

To evaluate whether transient androgen deprivation improves outcome in patients irradiated after radical prostatectomy for locally advanced disease, persistent or rising postoperative prostate specific antigen (PSA), or local recurrence.Records of 105 consecutive patients who were treated with pelvic irradiation after radical retropubic prostatectomy between August 1985 and December 1995 were reviewed. Seventy-four patients received radiation alone (mean follow up: 4.6 years), and 31 received transient androgen blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up 3.0 years) for a mean duration of 6 months. Two of these patients were excluded from further analysis because they received hormonal therapy for more than 1 year. Patients received a prostatic fossa dose of 60-70 Gy at 2 Gy per fraction; 48 patients also received pelvic nodal irradiation to a median dose of 50 Gy. Survival, freedom from clinical relapse (FFCR), and freedom from biochemical relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was defined as two consecutive PSA measurements exceeding 0.07 ng/ml.At 5 years after irradiation, actuarial survival for all patients was 92%, FFCR was 77%, and FFBR was 34%. FFBR was significantly better among patients who received transient androgen blockade before and during radiotherapy than among those treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014). Potential clinical prognostic factors before irradiation did not differ significantly between treatment groups, including tumor stage, summed Gleason histologic score, lymph node status, indication for treatment, and PSA levels before surgery or subsequent treatment. Multivariate analysis revealed that transient androgen deprivation was the only significant predictor for biochemical failure.This retrospective study of irradiation after radical prostatectomy suggests that transient androgen blockade and irradiation may improve freedom from early biochemical and clinically evident relapse compared to radiotherapy alone, although more prolonged follow-up will be needed to assess durability of impact upon clinical recurrence and survival rates.

View details for Web of Science ID 000074327100001

View details for PubMedID 9652832

Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol) JOURNAL OF UROLOGY Gross, C., Stamey, T., Hancock, S., Feldman, D. 1998; 159 (6): 2035-2039

Abstract

Substantial experimental and epidemiological data indicate that 1,25-dihydroxyvitamin D3 (calcitriol) has potent antiproliferative effects on human prostate cancer cells. We performed an open label, nonrandomized pilot trial to determine whether calcitriol therapy is safe and efficacious for early recurrent prostate cancer. Our hypothesis was that calcitriol therapy slows the rate of rise of prostate specific antigen (PSA) compared with the pretreatment rate.After primary treatment with radiation or surgery recurrence was indicated by rising serum PSA levels documented on at least 3 occasions. Seven subjects completed 6 to 15 months of calcitriol therapy, starting with 0.5 microg. calcitriol daily and slowly increasing to a maximum dose of 2.5 microg. daily depending on individual calciuric and calcemic responses. Each subject served as his own control, comparing the rate of PSA rise before and after calcitriol treatment.As determined by multiple regression analysis, the rate of PSA rise during versus before calcitriol therapy significantly decreased in 6 of 7 patients, while in the remaining man a deceleration in the rate of PSA rise did not reach statistical significance. Overall the decreased rate of PSA rise was statistically significant (p = 0.02 Wilcoxon signed rank test). Dose dependent hypercalciuria limited the maximal calcitriol therapy given (range 1.5 to 2.5 microg. daily).This pilot study provides preliminary evidence that calcitriol effectively slows the rate of PSA rise in select cases, although dose dependent calciuric side effects limit its clinical usefulness. The development of calcitriol analogues with decreased calcemic side effects is promising, since such analogues may be even more effective for treating prostate cancer.

View details for Web of Science ID 000073584400078

View details for PubMedID 9598513

Node-positive prostatic cancer: Taps or a call to arms? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hancock, S. L. 1998; 40 (4): 757-759

View details for Web of Science ID 000072639900001

View details for PubMedID 9531357

Mediastinal irradiation accelerates age-related diastolic dysfunction Heidenreich, P. A., Lee, B., Mariscol, C. S., Tate, D. J., Puryear, J. V., Hancock, S. L., Schnittger, I. ELSEVIER SCIENCE INC. 1998: 243A243A
Silent ischemia following mediastinal irradiation. Heidenreich, P. A., Lee, B., Mariscol, C. S., Tate, D. J., Strauss, W. H., Schnittger, I., Hancock, S. L. LIPPINCOTT WILLIAMS & WILKINS. 1997: 52727
Lung cancer after therapy of Hodgkin disease: Influence of treatment and smoking Tate, D., Wolden, S., Hancock, S. PERGAMON-ELSEVIER SCIENCE LTD. 1997: 58
Stanford-Kaiser permanente G1 study for clinical stage I to IIA Hodgkin's disease: Subtotal lymphoid irradiation versus vinblastine, methotrexate, and bleomycin chemotherapy and regional irradiation JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Hoppe, R. T., Mason, J., Brown, B. W., Hancock, S. L., Baer, D., Rosenberg, S. A. 1997; 15 (5): 1736-1744

Abstract

We have demonstrated that a relatively mild chemotherapy regimen, vinblastine, methotrexate, and bleomycin (VBM), and involved-field radiotherapy (IFRT) could substitute for extended-field radiotherapy in patients with favorable Hodgkin's disease (HD) who have been laparotomy-staged. The purpose of this study is to determine if VBM and regional radiotherapy can substitute for extended-field radiotherapy in favorable clinical stage (CS) I and II HD.Seventy-eight patients with favorable CS I to II HD were randomly assigned to subtotal lymphoid irradiation (STLI) or VBM chemotherapy and regional radiotherapy. Randomization was stratified on the basis of age, sex, number of Ann Arbor sites, histology, and institution. Patients were evaluated for freedom from progressive HD, survival, and toxicity. Results were compared with the predecessor trial in pathologically staged patients.With a median follow-up period of 4 years, the rate of freedom from progressive HD was 92% (95% confidence interval [CI], 88% to 96%) for patients treated with STLI and 87% (95% CI, 81% to 93%) for patients treated with VBM and regional radiotherapy. Six of seven patients who relapsed are alive and in remission following successful second-line therapy.Given the caveat of a small number of patients, the results of extended-field radiotherapy and VBM and regional radiotherapy are comparable with a median follow-up period of 4 years. VBM serves as a paradigm to reduce late effects in favorable early-stage HD. We do not advocate its routine use in clinical practice, but instead encourage participation in clinical trials with the objective of maintaining efficacy while reducing toxicity in CS I and II HD.

View details for Web of Science ID A1997WZ56400006

View details for PubMedID 9164180

Gastrointestinal cancer after treatment of Hodgkin's disease 37th Annual Scientific Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Birdwell, S. H., Hancock, S. L., Varghese, A., Cox, R. S., Hoppe, R. T. ELSEVIER SCIENCE INC. 1997: 6773

Abstract

This study aimed to quantify the risk of gastrointestinal cancer following Hodgkin's disease treatment according to age at treatment, type of treatment, and anatomic sites.Cases were identified from the records of 2,441 patients treated for Hodgkin's disease between 1961 and 1994. Follow-up averaged 10.9 years, representing 26,590 person-years of observation. Relative risks (RR) for gastrointestinal cancer incidence and mortality were computed by comparison with expected annualized rates for a general population matched for age, sex, and race.Gastrointestinal cancers developed in 25 patients. The incidence RR was 2.5 [95% confidence interval (CI), 1.5-3.5] and mortality RR was 3.8 (CI, 2.4-4.7). Sites associated with significantly increased risks included the stomach [RR 7.3 (CI, 3.4-13.8)], small intestine [RR 11.6 (CI, 1.9-38.3)], and pancreas [RR 3.5 (CI, 1.1-8.5)]. Risk was significantly elevated after combined modality therapy, RR 3.9 (CI, 2.2-5.6). The risk after radiotherapy alone was 2.0 (CI, 1.0-3.4), not a statistically significant elevation. The RR for gastrointestinal cancer was greatest after treatment at young age and decreased with advancing age. It was significantly elevated within 10 years after treatment [RR 2.0 (CI, 1.1-3.5)] and increased further after 20 years [RR 6.1 (CI, 2.5-12.7)]. Risk assessed by attained age paralleled risk according to age at treatment. Fifteen cases of gastrointestinal cancers arose within the irradiation fields.Patients treated for Hodgkin's disease are at modestly increased risk for secondary gastrointestinal cancer, especially after combined modality therapy and treatment at a young age. Risk was highest more than 20 years after treatment, but was significantly elevated within 10 years. Gastrointestinal sites with increased risk included the stomach, pancreas, and small intestine.

View details for Web of Science ID A1997WJ64600009

View details for PubMedID 9054878

Stereotaxic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: Impact on local control Tate, D. J., Eulau, S., Hancock, S., Poen, J., Chang, S., Adler, J., Goffinet, D. R. PERGAMON-ELSEVIER SCIENCE LTD. 1997: 304
Management of breast cancer following Hodgkin's disease Wolden, S. L., Carlson, R. W., Jeffrey, S. S., Hancock, S. L. PERGAMON-ELSEVIER SCIENCE LTD. 1997: 258
The cyberknife: A frameless robotic system for radiosurgery XIIth Meeting of the World Society for Stereotactic and Functional Neurosurgery Adler, J. R., Chang, S. D., MURPHY, M. J., Doty, J., Geis, P., Hancock, S. L. KARGER. 1997: 12428

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

Late effects of treatment for childhood Hodgkin's disease NEW ENGLAND JOURNAL OF MEDICINE Donaldson, S. S., Hancock, S. L. 1996; 335 (5): 35455
Long-Term Complications of Treatment and Causes of Mortality After Hodgkin's Disease. Seminars in radiation oncology Hancock, HOPPE 1996; 6 (3): 225-242

Abstract

The majority of newly diagnosed patients are expected to survive Hodgkin's disease because of effective therapies established during past 30 years. Long-term observations from large populations of treated patients have disclosed a variety of late effects of the disease and its therapy have contributed morbidity and excess mortality to Hodgkin's disease survivors. Secondary cancers have continued to accrue, and the risk relative to the general population has increased to 6.4 (95% confidence intervals: 5.5 to 7.3) in updated experience at Stanford University. Risks are significantly elevated for leukemia (primarily after chemotherapy regimens containing alkylating agents); non-Hodgkin's lymphoma; and tumors of the lung, breast, soft tissues, bone, stomach, pancreas, salivary gland, thyroid, and cutaneous melanoma. Early cardiovascular disease has also been observed and numerically exceeds second cancers as a cause of death in patients with early stage Hodgkin's disease (49 v 47 cases). Pulmonary dysfunction, thyroid dysfunction, infertility, psychosocial changes, gastrointestinal problems, soft-tissue changes, alterations in immunity, and risks for infection have also affected some treated patients. As these problems have been recognized, treatment approaches have been modified over the last 10 to 15 years, and early data suggest a decrease in some treatment sequellae.

View details for PubMedID 10717180

Linear accelerator-based stereotaxic radiosurgery for brain metastases: The influence of number of lesions on survival JOURNAL OF CLINICAL ONCOLOGY Joseph, J., Adler, J. R., Cox, R. S., Hancock, S. L. 1996; 14 (4): 1085-1092

Abstract

To evaluate the influence of the number of brain metastases on survival after stereotaxic radiosurgery and factors that affect the risk of delayed radiation necrosis after treatment.Between March 1989 and December 1993, 120 consecutive patients underwent linear accelerator-based stereotaxic radiosurgery for brain metastases identified by computed tomography (CT) or magnetic resonance imaging (MRI) scans. The influence of various clinical factors on outcome was assessed using Kaplan-Meier plots of survival from the date of radiosurgery, and univariate and multivariate analyses.The median survival time was 32 weeks. Progressive brain metastases, both local and regional, caused 25 of 104 deaths. Patients with two metastases (n = 30) or a solitary metastasis (n = 70) had equivalent actuarial survival times (P = .07; median, 37 weeks; maximum, 211+ weeks). Patients treated to three or more metastases (n = 20) had significantly shorter survival times (P < .002; median, 14 weeks; maximum, 63 weeks). Prognostic factors associated with prolonged survival included a pretreatment Karnofsky performance status > or = 70% and fewer than three metastases. Delayed radiation necrosis at the treated site developed in 20 patients and correlated with prior or concurrent delivery of whole-brain irradiation and the logarithm of the tumor volume.Survival duration is equivalent for patients with one or two brain metastases and is similar to that reported for patients with a solitary metastasis managed by surgical resection and whole-brain irradiation. Survival after radiosurgery for three or more metastases was similar to that reported for whole-brain irradiation.

View details for PubMedID 8648361

Second cancers after Hodgkin's disease in childhood NEW ENGLAND JOURNAL OF MEDICINE Donaldson, S. S., Hancock, S. L. 1996; 334 (12): 792-794

View details for Web of Science ID A1996TZ97900010

View details for PubMedID 8592556

CONSEQUENCES OF THERAPEUTIC MEDIASTINAL IRRADIATION ON THE HEART - AN ECHOCARDIOGRAPHIC STUDY LAU, Y. S., PURYEAR, J. V., MARISCAL, C. S., HANCOCK, S. L., SCHNITTGER AMER HEART ASSOC. 1995: 2854
PROSTATE-SPECIFIC ANTIGEN AFTER RADIOTHERAPY FOR PROSTATE-CANCER - A REEVALUATION OF LONG-TERM BIOCHEMICAL CONTROL AND THE KINETICS OF RECURRENCE IN PATIENTS TREATED AT STANFORD-UNIVERSITY JOURNAL OF UROLOGY Hancock, S. L., Cox, R. S., Bagshaw, M. A. 1995; 154 (4): 1412-1417

Abstract

We evaluated prostate specific antigen (PSA) evidence for control of prostatic cancer after irradiation.We studied 110 patients for whom more than 2 PSA measurements were obtained to establish trends and the initial measurement was done between April 1985 and January 1988.A total of 42 patients (38%) had stable, normal PSA levels with followup averaging 12.4 years (range 4.4 to 24.8). Increasing clinical stage or Gleason score correlated significantly with risk for PSA relapse, as did pretreatment PSA level. Short PSA doubling times were associated with distant metastasis rather than with local recurrence.We found that irradiation durably controlled 38% of prostatic cancers of various stages and grades and is unlikely to accelerate tumor growth.

View details for Web of Science ID A1995RU47200042

View details for PubMedID 7544843

BRIEF CHEMOTHERAPY, STANFORD-V, AND ADJUVANT RADIOTHERAPY FOR BULKY OR ADVANCED-STAGE HODGKINS-DISEASE - A PRELIMINARY-REPORT JOURNAL OF CLINICAL ONCOLOGY Bartlett, N. L., Rosenberg, S. A., Hoppe, R. T., Hancock, S. L., Horning, S. J. 1995; 13 (5): 1080-1088

Abstract

Although survival rates have improved for patients with bulky and advanced-stage Hodgkin's disease (HD), current treatments entail substantial acute morbidity and risks for late effects such as infertility, second malignancies, and cardiopulmonary toxicities. A novel, brief chemotherapy regimen (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone [Stanford V]) was designed to shorten the duration of treatment, significantly reduce cumulative doses of alkylating agents, doxorubicin, and bleomycin, and maintain dose-intensity (DI). This brief chemotherapy was combined with radiation therapy (RT) to bulky disease sites.Since May 1989, 65 previously untreated patients were treated for stage II HD with bulky mediastinal involvement (n = 21) or for stage III or IV HD (n = 44). Patients received weekly chemotherapy for 12 weeks. Consolidative RT was given to the first 25 patients to sites of initial bulky disease or radiographic abnormalities that persisted after chemotherapy; in the remaining 40 patients, RT was limited to bulky disease (adenopathy > or = 5 cm and/or macroscopic splenic nodules defined by computed tomography [CT]).With a median follow-up period of 2 years, actuarial 3-year survival rate is 96% and failure-free survival (FFS) rate is 87%. The 3-year FFS rate is 100% for stage II patients with bulky mediastinal disease and 82% for patients with stage III to IV disease. There were no treatment-related deaths. In a preliminary analysis on a subset of patients, female and male fertility appears to be preserved.These preliminary results indicate that the Stanford V chemotherapy regimen with or without RT is well-tolerated and effective therapy for bulky, limited-stage, and advanced-stage HD. Less cumulative exposure to alkylating agents, doxorubicin, and bleomycin and limited use of radiation is expected to decrease risks for second neoplasms and late cardiopulmonary toxicity. Based on these results, the Stanford V chemotherapy with or without RT regimen deserves further study in the context of a randomized clinical trial.

View details for Web of Science ID A1995QV95100006

View details for PubMedID 7537796

STEM-CELL FACTOR ENHANCES THE SURVIVAL OF MURINE INTESTINAL STEM-CELLS AFTER PHOTON IRRADIATION RADIATION RESEARCH Leigh, B. R., Khan, W., Hancock, S. L., Knox, S. J. 1995; 142 (1): 12-15

Abstract

Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic stem cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 micrograms/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 +/- 0.7 per duodenal cross section for controls to 30.0 +/- 1.7 after treatment with SCF (P = 0.03). The TBI dose producing 50% mortality at 6 days (LD50/6) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine.

View details for Web of Science ID A1995QP25100002

View details for PubMedID 7534934

THYROID ABNORMALITIES AFTER THERAPEUTIC EXTERNAL RADIATION Late Effects of Normal Tissues Consensus Conference Hancock, S. L., McDougall, I. R., Constine, L. S. ELSEVIER SCIENCE INC. 1995: 116570

Abstract

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves' disease or euthyroid Graves' ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity.

View details for Web of Science ID A1995QU29500009

View details for PubMedID 7713780

CONTROL OF PROSTATE-CANCER WITH RADIOTHERAPY - LONG-TERM RESULTS Conference on Detection and Treatment of Early Stage Prostate Cancer Bagshaw, M. A., Cox, R. S., Hancock, S. L. ELSEVIER SCIENCE INC. 1994: 178185

Abstract

The long-term outcome for 1,245 patients with carcinoma of the prostate treated with external beam radiation therapy is presented. The median survival for all patients without evidence of distant metastases but irrespective of T stage of the primary tumor, histopathological grade or lymph node status was 10 years compared to 15 years for an age-matched cohort of California men. The cause specific survival at 15 years was 52%. The data base is subdivided into a series of subsets that demonstrate the impact of T stage, Gleason pattern score and lymph node involvement on long-term outcome. The best results were shown in stages T1 and T2a cases with histopathologically proved negative lymph nodes. Survival at 15 years was 53%, which was essentially identical to the 55% survival rate of an age-matched cohort. The actuarial survival at 15 years for all stages T1 and T2N0M0 cancer patients was 45% compared to 56% for an age-matched cohort.

View details for Web of Science ID A1994PL68600029

View details for PubMedID 7933237

STEM-CELL FACTOR ENHANCES THE SURVIVAL OF IRRADIATED HUMAN BONE-MARROW MAINTAINED IN SCID MICE STEM CELLS Leigh, B. R., Webb, S., Hancock, S. L., Knox, S. J. 1994; 12 (4): 430-435

Abstract

The effect of recombinant human stem cell factor (SCF) on the response of human fetal bone marrow progenitor cells to irradiation was studied using immunodeficient mice with human fetal bone grafts (SCID/Hu mice). SCID/Hu mice were treated with three intraperitoneal injections of 500 micrograms/kg SCF at 20 h before, two h before, and four h after 100 cGy total body irradiation. Fourteen days following irradiation, the fetal bone grafts were harvested and studied. Most of the isolated bone marrow cells were human, as determined by flow cytometry. Colony forming assays were performed on the bone marrow to determine the survival of erythroid (BFU-E) and myeloid (CFU-GM) precursor cells. A statistically significant increase in BFU-E and CFU-GM survival after irradiation was observed for bone marrow maintained in the SCF treated mice when compared to bone marrow from mice not treated with SCF. The enhancement in colony forming unit survival after irradiation ranged from 4.3-fold for BFU-E (p = 0.05) to 13.1-fold for CFU-GM (p = 0.002). These findings suggest that SCF may be of potential clinical value for the prevention of radiation-induced myelosuppression.

View details for Web of Science ID A1994NY15600010

View details for PubMedID 7524895

MUSCLE CRAMPING IN PHASE-I CLINICAL-TRIALS OF TIRAPAZAMINE (SR-4233) WITH AND WITHOUT RADIATION 8th International Conference on Chemical Modifiers of Cancer Treatment Doherty, N., Hancock, S. L., Kaye, S., Coleman, C. N., Shulman, L., Marquez, C., Mariscal, C., Rampling, R., Senan, S., ROEMELING, R. V. PERGAMON-ELSEVIER SCIENCE LTD. 1994: 37982

Abstract

Tirapazamine (SR 4233) is a benzotriazine di-N-oxide which acts as a hypoxic cytotoxic agent and as a radiation enhancer when given shortly before or after radiation. Three Phase I clinical trials were designed to determine the maximum tolerated dose, toxicities, pharmacokinetics, and effects on irradiated tumors and normal tissues.Tirapazamine 9 mg/m2 to 21 mg/m2 was given i.v. 1/2 to 1 h prior to irradiation on a multiple dose schedule of 10 consecutive doses. This was later revised to a three times-per-week schedule for 12 doses. In a second clinical trial, tirapazamine was given in a single dose of 18 mg/m2 to 293 mg/m2 i.v. after irradiation. In a third trial, tirapazamine was administered without irradiation in single doses of 36 mg/m2 to 250 mg/m2, with an option for retreatment.Subjects reported muscle cramping of varying degrees of severity on all three dose schedules. One patient experienced Grade 3 cramping and treatment was discontinued. The most frequent site of cramping were the lower extremities. Creatine phosphokinase (CPK) values were elevated in three patients with associated muscle soreness in one patient. MB (cardiac) isoenzymes were elevated in one patient with no evidence of cardiac muscle damage, and returned to baseline at drug completion. No consistent abnormalities in clinical laboratory values were found. Stretching of the muscle was most effective in relieving the cramping.Muscle cramping has been the most frequently reported toxicity in Phase I studies of tirapazamine, though it does not appear to be dose limiting. Dose escalation on the three clinical trials continues. In vitro studies to investigate the cramping are ongoing.

View details for Web of Science ID A1994NN51200028

View details for PubMedID 8195037

COMPUTED-TOMOGRAPHY ASSESSMENT OF SPLENIC SIZE AS A PREDICTOR OF SPLENIC WEIGHT AND DISEASE INVOLVEMENT IN LAPAROTOMY STAGED HODGKINS-DISEASE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hancock, S. L., SCIDMORE, N. S., Hopkins, K. L., Cox, R. S., Bergin, C. J. 1994; 28 (1): 93-99

Abstract

To evaluate how well splenic size predicts the risk of splenic Hodgkin's disease and to assess how accurately splenic dimensions on computerized tomographic scans predict spleen size and involvement by Hodgkin's disease.Splenic weights were obtained from laparotomies performed on 897 patients who presented with Hodgkin's disease and were compared with histologic involvement using logistic regression. Splenic dimensions were measured from preoperative computerized tomographic scans in 94 of these patients, and unidimensional splenic measurements [length (L), width (W), thickness (T)] and their products were compared with splenic weight at laparotomy using linear regression.Hodgkin's disease involved 42% of the spleens at laparotomy and 31% of those assessed by computerized tomography. Splenic weight averaged 198 +/- 5 g (range 40-2000 g). Weight and involvement were greater with "unfavorable" histologies (mixed cellularity, lymphocyte depletion, and unclassified Hodgkin's disease: 229 +/- 12 g; 62.7% involved) than with "favorable" histologies (nodular sclerosing, lymphocyte predominant, and interfollicular Hodgkin's disease: 191 +/- 5 g; 37.8% involved). Splenic weight was the strongest independent risk factor correlated with Hodgkin's disease in univariate and multivariate analyses in all patients and the only identifiable univariate risk factor among those with computerized tomographic scans. For most patients, however, splenic weight poorly predicted involvement: The probability of involvement never fell below 20% and exceeded 80% when splenic weight exceeded 270 g with unfavorable histologies or 685 g in favorable histologies. Spleens of average weight had a probability of involvement of 36% with favorable histologies, 70% with unfavorable histologies. Unidimensional measurements of the spleen on computed tomography correlated poorly with splenic weight, but their product correlated well (Correlation coefficients: L: 0.73; W: 0.65; T: 0.78; [0.344485 x L x W x T]: 0.94).Splenic weight is the strongest factor correlating with the risk of splenic involvement by Hodgkin's disease and can be accurately estimated from three-dimensional measurements on computed tomographic scans, but not from unidimensional measurements. However, splenic weight is not a sensitive predictor of involvement of the spleen by Hodgkin's disease. Therefore, treatment approaches to Hodgkin's disease must be based upon intermediate risks of splenic involvement for most clinically staged patients.

View details for Web of Science ID A1994MP35300012

View details for PubMedID 8270463

FACTORS AFFECTING LATE MORTALITY FROM HEART-DISEASE AFTER TREATMENT OF HODGKINS-DISEASE JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Hancock, S. L., TUCKER, M. A., Hoppe, R. T. 1993; 270 (16): 1949-1955

Abstract

To assess the risk of death from heart disease after Hodgkin's disease therapy.Retrospective study comparing treated patients with a matched general population.Referral center.A total of 2232 consecutive Hodgkin's disease patients treated from 1960 through 1991. Follow-up averaged 9.5 years.Relative risks (RRs), the ratio of the observed to the expected cases with 95% confidence intervals (CIs), chi tests for trends, and Kaplan-Meier actuarial risks.Of the 2232 patients, 88 (3.9%) died of heart disease, 55 from acute myocardial infarction and 33 from other cardiac diseases, including congestive heart failure, radiation pericarditis or pancarditis, cardiomyopathy, or valvular heart disease. The RR for cardiac death was 3.1 (CI, 2.4 to 3.7). Mediastinal radiation of 30 Gy or less (n = 385 patients) did not increase risk; above 30 Gy (n = 1830), RR was 3.5 (CI, 2.7 to 4.3). Blocking to limit cardiac exposure reduced the RR for other cardiac diseases from 5.3 (CI, 3.1 to 7.5) to 1.4 (CI, 0.6 to 2.9), but not acute myocardial infarction (RR, 3.7 vs 3.4). The RRs increased with duration after treatment (trend in acute myocardial infarction, P = .02; in other cardiac diseases, P = .004). The RR for acute myocardial infarction was highest after irradiation before 20 years of age and decreased with increasing age at treatment (P < .0001 for trend).Mediastinal irradiation for Hodgkin's disease increases the risk of subsequent death from heart disease. Risk increased with high mediastinal doses, minimal protective cardiac blocking, young age at irradiation, and increasing duration of follow-up.

View details for Web of Science ID A1993MC51300026

View details for PubMedID 8411552

THE EFFECT OF STEM-CELL FACTOR ON IRRADIATED HUMAN BONE-MARROW CANCER RESEARCH Leigh, B. R., Hancock, S. L., Knox, S. J. 1993; 53 (17): 3857-3859

Abstract

This study evaluates the effect of recombinant human stem cell factor (SCF) on the in vitro response of human bone marrow progenitor cells to irradiation. Light density nonadherent mononuclear cells were isolated from human bone marrow and resuspended in either semisolid culture or liquid culture with or without 100 ng/ml SCF. After 24 h in culture, cells were irradiated and assessed for survival of erythroid burst-forming unit, granulocyte colony-forming unit(s), or granulocyte-macrophage colony-forming unit precursors in the presence of erythropoietin, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor, respectively. Incubation with SCF prior to irradiation (0-300 cGy) resulted in an increase in both absolute colony number and surviving fraction for erythroid burst-forming units, granulocyte colony-forming units, and granulocyte-macrophage colony-forming units as compared to cultures that did not contain SCF. The mean surviving fraction enhancement ratio after 100 cGy ranged from 1.2 to 3.7. An increased fraction of CD34+ progenitors in S-phase after exposure to SCF may explain in part the apparent radioprotective effect of SCF on human bone marrow progenitor cells.

View details for Web of Science ID A1993LU57900003

View details for PubMedID 7689418

CARDIAC DISEASE FOLLOWING TREATMENT OF HODGKINS-DISEASE IN CHILDREN AND ADOLESCENTS JOURNAL OF CLINICAL ONCOLOGY Hancock, S. L., Donaldson, S. S., Hoppe, R. T. 1993; 11 (7): 1208-1215

Abstract

Cardiac disease is second only to neoplastic disease as a cause of death after treatment for Hodgkin's disease. This study evaluates the risks of cardiac disease following treatment of Hodgkin's disease during childhood and adolescence.We reviewed records of 635 patients treated for Hodgkin's disease before 21 years of age at Stanford University between 1961 and 1991. Mean age was 15.4 years; mean follow-up duration was 10.3 years, representing 6,564 person-years of observation. Relative risks (RRs) of death from cardiac diseases were calculated by comparison with age-, sex-, and race-matched general population rates from United States decennial life-tables.Twelve patients have died of cardiac disease (RR, 29.6; 95% confidence interval [CI], 16.0 to 49.3), including seven deaths from acute myocardial infarction ([AMI] RR, 41.5; 95% CI, 18.1 to 82.1), three from valvular heart disease, and two from radiation pericarditis/pancarditis. Thus far, the risk of AMI death was comparable after radiation alone (RO) or after chemotherapy and radiation (CM) (RO-AMI RR, 52.2; 95% CI, 21.1 to 108.7; CM-AMI RR, 21.1; 95% CI, 0.0 to 104.4; P = .6). The risk for other cardiac death (CD) tended to be higher after combined treatment (RO-non-AMI RR, 7.4; 95% CI, 0.0 to 36.5; CM-non-AMI RR, 45.8; 95% CI, 14.4 to 110.6; P = .1). Deaths occurred 3 to 22 years after patients received 42 to 45 Gy to the mediastinum between 9 and 20 years of age. There have been no deaths among patients treated to lower mediastinal radiation doses or without mediastinal radiation. There are no clear trends in the latency of risk. One hundred six nonfatal abnormalities have also been diagnosed.Mediastinal radiation of 40 to 45 Gy increases the risk of death from coronary artery and other cardiac diseases. The risk increases within 5 years of irradiation. These observations support combined-modality, low-dose irradiation regimens in children and adolescents and suggest the need for careful cardiac screening of treated patients.

View details for Web of Science ID A1993LL23300003

View details for PubMedID 8315419

BREAST-CANCER AFTER TREATMENT OF HODGKINS-DISEASE JOURNAL OF THE NATIONAL CANCER INSTITUTE Hancock, S. L., TUCKER, M. A., Hoppe, R. T. 1993; 85 (1): 25-31

Abstract

Most studies of survivors of Hodgkin's disease have shown a low risk for subsequent breast cancer, even though much lower doses of radiation than those used for Hodgkin's disease have been shown to induce breast cancer in other settings.This study quantifies the risk of breast cancer following Hodgkin's disease treatment according to age at treatment and type of treatment.To evaluate the risk of breast cancer from irradiation, we reviewed records of 885 women treated for Hodgkin's disease between 1961 and 1990 (mean follow-up, 10 years). Risks for breast cancer incidence and mortality were calculated by comparison with expected rates for a general female population matched by age and race.Twenty-five patients have developed invasive breast cancer, yielding a relative risk (RR) of 4.1 (95% confidence interval [CI] = 2.5-5.7). An additional patient developed multifocal carcinoma in situ. Age at irradiation strongly influenced risk: RR was 136 for women treated before 15 years of age (95% CI = 34-371). RR declined with age at irradiation (P for trend < .0001), but the elevation remained statistically significant for subjects less than 30 years old at the time of irradiation (for those 15-24, RR = 19 [95% CI = 10.3-32]; for those 24-29, RR = 7 [95% CI = 3.2-14.4]). In women above 30 years of age, the risk was not elevated (RR = 0.7; 95% CI = 0.2-1.8). Risk of breast cancer increased significantly with time since treatment (P for trend < .0001). The RR was 2.0 (95% CI = 1.0-3.5) with follow-up under 15 years and 13.6 (95% CI = 7.9-18.2) with follow-up equal to or exceeding 15 years. The addition of mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy to irradiation increased the risk within the first 15 years. Most breast cancers (22 of 26) arose within or at the margin of the radiation field and were infiltrating ductal carcinomas. Stage distribution and outcome suggest that the increased incidence was not solely attributable to vigilant screening. RR of death from breast cancer was 5.1 (95% CI = 2.2-10.0).Women treated for Hodgkin's disease with radiation before 30 years of age are at markedly increased risk for breast cancer, with risk increasing dramatically more than 15 years after therapy.The high RR for development of breast cancer in women exposed to therapeutic radiation under 30 years of age raises important issues about optimal treatment strategies for patients with Hodgkin's disease, breast cancer, and other cancers.

View details for Web of Science ID A1993KF02900011

View details for PubMedID 8416252

RADIATION OR SURGERY FOR CARCINOMA OF THE ESOPHAGUS - THE ROLE OF ORGAN-CONSERVING THERAPY 27TH ANNUAL SAN FRANCISCO CANCER SYMP Hancock, S. L. KARGER. 1993: 103117

View details for Web of Science ID A1993BY26H00008

View details for PubMedID 8504939

THE EFFECT OF STEM-CELL FACTOR ON IRRADIATED HUMAN BONE-MARROW (ASTRO RESEARCH FELLOWSHIP) LEIGH, B. R., HANCOCK, S. L., KNOX, S. J. PERGAMON-ELSEVIER SCIENCE LTD. 1993: 183
STEREOTAXIC RADIOSURGERY OF BRAIN METASTASES - THE INFLUENCE OF NUMBER OF LESIONS ON SURVIVAL JOSEPH, J., ADLER, COX, R. S., HANCOCK, S. L. PERGAMON-ELSEVIER SCIENCE LTD. 1993: 25758
THYROID-DISEASES AFTER TREATMENT OF HODGKINS-DISEASE NEW ENGLAND JOURNAL OF MEDICINE Hancock, S. L., Cox, R. S., McDougall, I. R. 1991; 325 (9): 599-605

Abstract

Thyroid disease, especially hypothyroidism, is common in patients with Hodgkin's disease who have been treated with irradiation. We reviewed the records of 1787 patients (740 women and 1047 men) with Hodgkin's disease who were treated with radiation therapy alone (810 patients), radiation and chemotherapy (920 patients), or chemotherapy alone (57 patients) at Stanford University between 1961 and 1989. Among these patients, 1533 were alive at the last follow-up, and 254 had died of causes other than Hodgkin's disease. (Four other patients were excluded from the analysis because they had undergone thyroidectomy before treatment for Hodgkin's disease. The thyroid was irradiated in 1677 patients. Follow-up averaged 9.9 years.A total of 573 patients had clinical or biochemical evidence of thyroid disease. Among the 1677 patients whose thyroid was irradiated, the actuarial risk of thyroid disease 20 years after treatment was 52 percent, and it was 67 percent at 26 years. Hypothyroidism was found in 513 patients. A total of 486 patients received thyroxine therapy for elevated serum thyrotropin concentrations and either low free thyroxine (208 patients) or normal free thyroxine values (278 patients); 27 had transient elevations of the serum thyrotropin level that were not treated. Graves' hyperthyroidism developed in 30 patients (2 of whom had not undergone thyroid irradiation), and ophthalmopathy developed in 17 of these patients. Ophthalmopathy developed in four other patients with Graves' disease during a period of hypothyroidism (n = 3) or euthyroidism (n = 1). The risk of Graves' disease was 7.2 to 20.4 times that for normal subjects. Silent thyroiditis with thyrotoxicosis developed in six patients. Forty-four patients were found to have single or multiple thyroid nodules, 26 of whom underwent thyroidectomy. Six of the 44 had papillary or follicular cancers. Among the patients who did not undergo operation, 12 had small functioning nodules, 4 had cysts, and 2 had multinodular goiters. The actuarial risk of thyroid cancer was 1.7 percent. The risk of thyroid cancer was 15.6 times the expected risk.High risks of thyroid disease persist more than 25 years after patients have received radiation therapy for Hodgkin's disease, reinforcing the need for continued clinical and biochemical evaluation. Prolonged follow-up confirms an elevated risk of thyroid cancer and Graves' disease as well as hypothyroidism in these patients.

View details for Web of Science ID A1991GC32800002

View details for PubMedID 1861693

INTERLEUKIN-1-BETA INITIALLY SENSITIZES AND SUBSEQUENTLY PROTECTS MURINE INTESTINAL STEM-CELLS EXPOSED TO PHOTON RADIATION CANCER RESEARCH Hancock, S. L., Chung, R. T., Cox, R. S., KALLMAN, R. F. 1991; 51 (9): 2280-2285

Abstract

Interleukin 1 (IL-1) has been shown to prevent early bone marrow-related death following total-body irradiation, by protecting hematopoietic stem cells and speeding marrow repopulation. This study assesses the effect of IL-1 on the radiation response of the intestinal mucosal stem cell, a nonhematopoietic normal cell relevant to clinical radiation therapy. As observed with bone marrow, administration of human recombinant IL-1 beta (4 micrograms/kg) to C3H/Km mice 20 h prior to total-body irradiation modestly protected duodenal crypt cells. In contrast to bone marrow, IL-1 given 4 or 8 h before radiation sensitized intestinal crypt cells. IL-1 exposure did not substantially alter the slope of the crypt cell survival curve but did affect the shoulder: the X-ray survival curve was offset to the right by 1.01 +/- 0.06 Gy when IL-1 was given 20 h earlier and by 1.28 +/- 0.08 Gy to the left at the 4-h interval. Protection was greatest when IL-1 was administered 20 h before irradiation, but minimal effects persisted as long as 7 days after a single injection. The magnitude of radioprotection at 20 h or of radiosensitization at 4 h increased rapidly as IL-1 dose increased from 0 to 4 micrograms/kg. However, doses ranging from 10 to 100 micrograms/kg produced no further difference in radiation response. Animals treated with saline or IL-1 had similar core temperatures from 4 to 24 h after administration, suggesting that thermal changes were not responsible for either sensitization or protection. Mice irradiated 20 h after IL-1 had significantly greater crypt cell survival than saline-treated irradiated controls at all assay times, which ranged from 54 to 126 h following irradiation. The intervals to maximum crypt depopulation and initiation of repopulation were identical in both saline- and IL-1-treated groups, suggesting that IL-1 altered absolute stem cell survival but not the kinetics of repopulation.

View details for Web of Science ID A1991FJ82100006

View details for PubMedID 2015592

DEATHS AFTER TREATMENT OF HODGKIN DISEASE - CORRECTION ANNALS OF INTERNAL MEDICINE Hancock, S. L., Cox, R. S., Rosenberg, S. A. 1991; 114 (9): 810-810
FINAL REPORT OF THE PHASE-I TRIAL OF THE HYPOXIC CELL RADIOSENSITIZER SR-2508 (ETANIDAZOLE) RADIATION-THERAPY ONCOLOGY GROUP-83-03 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Coleman, C. N., Wasserman, T. H., Urtasun, R. C., Halsey, J., Noll, L., Hancock, S., Phillips, T. L. 1990; 18 (2): 389-393

Abstract

In a Phase I trial SR 2508 was administered by rapid intravenous infusion to 102 patients receiving radiation therapy. The dose-limiting toxicity was peripheral sensory neuropathy (PN) which was related to the cumulative dose administered. The highest single daily dose, 3.7 g/m2, was tolerated without toxicity. The lowest cumulative toxic dose was 21.6 g/m2, and the highest non-toxic dose was 40.8 g/m2. Grade 1 neuropathies were mild and self-limited; grade 2 neuropathies were long-lasting and debilitating. In a retrospective analysis, the risk of developing neurotoxicity was related to the cumulative drug exposure calculated by the area-under-the-curve (AUC) of plasma concentration versus time. There was an increased incidence of neuropathy in patients with a cumulative AUC of greater than or equal to 36 mM-hr. At a total dose of 34 g/m2 over 6 weeks, the incidence of Grade 1 neuropathy was approximately 30%; no grade 2 neuropathy occurred at this dose and schedule. Additional toxicities observed included nausea and vomiting (6%), skin rash (4%), and transient arthralgias (3%). One patient had transient abnormalities in liver function tests of unknown etiology. (In a more recent Phase II trial neutropenia has been observed which may be related to SR2508). Approximately three times more SR 2508 is tolerable compared to misonidazole, and it appears that severe neuropathy can be avoided by monitoring individual patient pharmacokinetic parameters. Evaluation of the efficacy of this hypoxic cell sensitizer is in progress.

View details for Web of Science ID A1990CR71000017

View details for PubMedID 2154420

Current Stanford clinical trials for Hodgkin's disease. Recent results in cancer research. Fortschritte der Krebsforschung. Progrs dans les recherches sur le cancer Hoppe, R. T., Horning, S. J., Hancock, S. L., Rosenberg, S. A. 1989; 117: 182-190

View details for PubMedID 2690227

VINBLASTINE, BLEOMYCIN, AND METHOTREXATE - AN EFFECTIVE ADJUVANT IN FAVORABLE HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Hoppe, R. T., Hancock, S. L., Rosenberg, S. A. 1988; 6 (12): 1822-1831

Abstract

Sixty-seven patients with favorable pathologic stage (PS) I and IIA or B or IIIA Hodgkin's disease were randomized to receive subtotal or total lymphoid irradiation (STLI/TLI) alone or involved field irradiation (IF) plus six cycles of a novel adjuvant chemotherapy containing vinblastine, bleomycin, and methotrexate (VBM). With a follow-up from 6 to 72 months (median, 37 months), the actuarial freedom-from-progressive disease (FFP) at 5 years is 70% after STLI/TLI and 95% after IF plus VBM. One death has occurred in the irradiation-only treatment group. The data for IF plus VBM are significantly superior to previous actuarial results at 5 years using IF alone (FFP = 35%, P less than .00001) and compare favorably with prior results with IF plus nitrogen mustard, vincristine, procarbazine, +/- prednisone (MOP[P]) chemotherapy (FFP = 80% at 5 years, P = .10). VBM is well tolerated with greater than 90% of calculated doses delivered. As anticipated, VBM has had relatively little adverse effect on male or female fertility. Selected pulmonary functions are reduced early after IF plus VBM to a greater degree than with irradiation of the mediastinum alone, but the differences are modest. Based upon our current numbers and follow-up, we can be 90% confident that VBM as an adjuvant to irradiation in favorable Hodgkin's disease is as effective, or even superior, to MOP(P) chemotherapy. Because of its lesser toxicity, adjuvant VBM may have a broader role in the management of Hodgkin's disease.

View details for Web of Science ID A1988R308000006

View details for PubMedID 2462025

INTERCURRENT DEATH AFTER HODGKIN DISEASE THERAPY IN RADIOTHERAPY AND ADJUVANT MOPP TRIALS ANNALS OF INTERNAL MEDICINE Hancock, S. L., Hoppe, R. T., Horning, S. J., Rosenberg, S. A. 1988; 109 (3): 183-189

Abstract

To assess long-term differences in mortality associated with initial Hodgkin disease therapy.Retrospective review of patients treated in prospectively randomized clinical trials.Three hundred twenty-six patients with pathologic stage I, II, or III, A or B Hodgkin disease treated between 1967 and 1980 with median follow-up exceeding 14 years.Patients at the same stage of disease were randomized to receive radiation alone (167 patients) or radiation followed by 6 cycles of mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone (MOPP) chemotherapy (159 patients) with additional therapy for progression or recurrence.No significant differences between treatment regimens for actuarial survival, intercurrent disease, or Hodgkin disease mortality were seen. Thirty-three patients who received radiation alone and 30 patients who received adjuvant chemotherapy died without evident Hodgkin disease. Death was caused by second neoplasms in 28 patients (relative risk, 2.35; 95% CI, 1.46 to 3.24). Six patients developed acute myelogenous leukemia or a myeloproliferative disorder after treatment including MOPP. Chemotherapy exposure varied among the 8 patients with lung cancers, 6 with gastrointestinal and 3 with other adenocarcinomas, 3 with sarcomas, 1 with diffuse large cell lymphoma, and 1 with melanoma. Acute myocardial infarction caused 9 of 17 cardiovascular disease deaths with 5 occurring in patients between the ages of 33 and 43. Nonetheless, the risk for acute myocardial infarction was not clearly increased (relative risk, 0.86; 95% CI, 0.42 to 1.57). Fifteen patients died from infection: 5, opportunistic; 5, asplenic sepsis; and 5, other pneumonias. Two patients died in accidents, and 1 died from radiation pneumonitis.Adjuvant MOPP chemotherapy improved freedom from relapse without significant survival benefit or impairment. Leukemogenesis was the only lethal complication associated with MOPP. Survivors of Hodgkin disease had an increased risk for death from a second neoplasm, but no apparent increased risk for death from acute myocardial infarction.

View details for Web of Science ID A1988P606500005

View details for PubMedID 3291657

ESOPHAGEAL-CARCINOMA - MODEST BENEFITS FROM COMBINED MODALITY THERAPY RADIOLOGY Hancock, S. L., Goffinet, D. R., Carlson, R. W., Mark, J. B. 1987; 164 (3): 603-606

Abstract

Between 1969 and 1986, 109 consecutive patients with esophageal carcinoma were studied. Of the 77 patients who had squamous cell carcinoma, 62 received definitive treatment for disease confined to the esophagus and regional nodes. Survival was equivalent whether they were treated with radiation alone (n = 18), preoperative radiation and esophagectomy (n = 19), postoperative radiation (n = 5), or a combination of chemotherapy and radiation with or without esophagectomy (n = 20). Fifteen patients had significantly poorer survival after palliative irradiation for overt metastatic disease or severe debility. The pathologic specimens from four of the nine patients who underwent resection showed no histologic evidence of residual tumor; however, tumor recurred in three in the mediastinum, and only one remains alive and free of disease. Four of the 11 patients who received chemotherapy and radiation therapy without resection remain alive and free of disease after further mediastinal irradiation, suggesting a benefit from additional regional therapy. Chemotherapy improved median survival duration and complete response rate but did not produce a significant improvement in survival, as reported in other recent series.

View details for Web of Science ID A1987J665300003

View details for PubMedID 3112863

RELATIONSHIP BETWEEN THE NEUROTOXICITY OF THE HYPOXIC CELL RADIOSENSITIZER SR 2508 AND THE PHARMACOKINETIC PROFILE CANCER RESEARCH Coleman, C. N., Halsey, J., Cox, R. S., HIRST, V. K., Blaschke, T., HOWES, A. E., Wasserman, T. H., Urtasun, R. C., Pajak, T., Hancock, S., Phillips, T. L., Noll, L. 1987; 47 (1): 319-322

Abstract

Complete pharmacological data from 71 patients treated on the phase I trial of SR 2508 were analyzed to see if the dose-limiting toxicity of peripheral neuropathy is related to the individual patient's pharmacokinetic profile. In a retrospective analysis, the risk of toxicity was best predicted by using the bivariate model of total drug exposure and the time over which the treatment course was given. Drug exposure [area under the curve (AUC)] for a single treatment was calculated by the integral over time of the serum concentration of SR 2508. Since the AUC was constant during the course of a patient's treatment, the total drug exposure (total-AUC) was estimated by the product of the AUC times the number of drug administrations. While the clinical efficacy of hypoxic cell sensitizers remains to be proven, SR 2508 is better tolerated than its predecessors, misonidazole and desmethylmisonidazole, as three times the amount of SR 2508 can be given. If this model is confirmed in the current phase II and III trials, the probability of developing neuropathy would be predictable for an individual patient from measurements made at the time of the first drug dose, allowing for the adjustment of drug schedule to avoid all but minor toxicity.

View details for Web of Science ID A1987F447700056

View details for PubMedID 3024818

PHASE-I TRIAL OF THE HYPOXIC CELL RADIOSENSITIZER SR-2508 - THE RESULTS OF THE 5 TO 6 WEEK DRUG SCHEDULE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Coleman, C. N., Wasserman, T. H., Urtasun, R. C., Halsey, J., HIRST, V. K., Hancock, S., Phillips, T. L. 1986; 12 (7): 1105-1108

Abstract

Sixty-five patients were entered on the long schedule of the Phase I trial of SR-2508. The planned total doses ranged from 30 to 40.8 g/m2 using various treatment schema including daily, split course, and every-other-day schedules. The individual dose size was 2 g/m2 for 56 patients and 1.7 g/m2 for nine. In contrast to misonidazole and desmethylmisonidazole, more SR-2508 can be administered as the duration of therapy is lengthened. All six patients on the 30 g/m2 step tolerated the drug without toxicity. This total dose was not achievable in the three week schedule. Additionally, a number of patients did not develop neuropathy at a cumulative dose of 40.8 g/m2. Although the analysis is not yet complete, a given patient's drug exposure as measured by their total AUC (mMxhr), defined as the area-under-the-curve of serum concentration of SR-2508 vs. time for a single dose times the number of doses given, is useful in predicting toxicity for that patient. The recommended starting schedule for the Phase II and III trials is 34 g/m2 over a 6 week period (2 g/m2 every other day). A total AUC of approximately 39 mMxhr should be tolerable. The drug regimen must be altered for patients who have a high AUC. Therefore, it is mandatory to have an accurate and rapid pharmacokinetic analysis for each patient. The clinical efficacy of the hypoxic cell sensitizers remains to be proven. However, using the guidelines derived from the Phase I trial, SR-2508 should be a relatively safe drug, producing minor or no toxicity.

View details for Web of Science ID A1986D911200020

View details for PubMedID 3017904

ANTERIOR EYE PROTECTION WITH ORBITAL NEOPLASIA INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS HANCOCK, S. L. 1986; 12 (1): 12330

Abstract

The administration of adequate doses of radiation to tumors involving the orbit and surrounding facial structures and sinuses is often complicated by the need to protect the sensitive ocular components, the lens and cornea. A technique has been devised that uses four photon beam fields and an optional electron field to treat the contents of both orbits and adjacent sinuses with effective, reproducible protection of cornea and lens. Essential features include: alignment of the corneal surfaces with the central plane of rotation of the treatment machine, use of a narrow eye block across the entire beam to shield a strip equal to the width of the cornea, positioned symmetrically across the central plane of rotation, fine alignment of the eye block with both corneal surfaces by altering pedestal angle, treatment with paired, wedged, anterior oblique fields to encompass desired orbital and sinus volumes with additional blocking placed as needed, and complementary, lateral strip fields using collimators set to eye block thickness to equalize dose in the posterior orbit shielded by the strip eye block. A similar anterior electron beam strip field may be added to boost the medial orbit and ethmoid regions covered by the eye block. Bite block head immobilization and easy, direct daily visualization of block position assures eye protection for each treatment and provides substantial reduction in dose to the cornea, lens and iris. Additional blocking may be incorporated to provide partial lacrimal and parotid sparing.

View details for DOI 10.1016/0360-3016(86)90426-8

View details for Web of Science ID A1986AYV1700020

View details for PubMedID 3943984

INITIAL REPORT OF THE PHASE-I TRIAL OF THE HYPOXIC CELL RADIOSENSITIZER SR-2508 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Coleman, C. N., Urtasun, R. C., Wasserman, T. H., Hancock, S., Harris, J. W., Halsey, J., HIRST, V. K. 1984; 10 (9): 1749-1753

Abstract

From March 15, through August 31, 1983, 37 patients have been entered on the RTOG Phase I trial of SR-2508. The drug was given intravenously three times weekly for three weeks. The starting total dose was 11.7 g/m2 and the highest total dose given was 32 g/m2. The lower lipophilicity of SR-2508 has produced the expected decrease in terminal half-life (5.4 hrs) of drug excretion and increase in total drug excreted unchanged in the urine (71%) compared to misonidazole or desmethylmisonidazole. The maximum single dose (3.7 g/m2) administered was well tolerated. With multiple doses peripheral neuropathy is the dose-limiting toxicity. The lowest cumulative dose producing toxicity was 21.6 g/m2, the highest non-toxic dose was 29.7 g/m2. The use of an individual patient's drug exposure as measured by the area under the curve of drug concentration vs time may be an excellent predictor of toxicity. This may eventually permit individualization of dose and prevention of serious toxicity. A single dose of 2 g/m2 will produce a tumor concentration of drug (approx. 100 micrograms/ml) that will yield a sensitizer enhancement ratio of 1.5 to 1.7. Using a starting dose of 2 g/m2 three times weekly, patients are now being studied on a five week drug schedule to further evaluate predictability of drug toxicity in preparation for clinical trials of drug efficacy.

View details for Web of Science ID A1984TN36200054

View details for PubMedID 6237086

THERAPY OF NON-SEMINOMATOUS CARCINOMA OF TESTIS HANCOCK, S. L., PISTENMA, D. A., BAGSHAW, M. A. PERGAMON-ELSEVIER SCIENCE LTD. 1977: 58