Erqi Pollom, MD

Abstract

Purpose: We assessed the effectiveness of a virtual networking session tailored for third- and fourth-year medical students interested in radiation oncology, and report students' concerns about applying to radiation oncology during the pandemic.Methods and Materials: A multi-institutional networking session was hosted on Zoom and included medical students, faculty, and residents from across the country. The breakout room feature was used to divide participants into smaller groups. Participants were randomly shuffled into new groups every 10 to 15 minutes. Students completed pre- and post-session surveys.Results: Among the 134 students who registered, 69 students participated in the session, and 53 students completed a post-session survey. Most students reported the session was valuable or very valuable (79%), and it was easy or very easy to network through the virtual format (66%). After the session, 18 (33.9%) students reported their interest in radiation oncology increased, and 34 (64.2%) reported their interest remained the same. Most students believed COVID-19 (55%) and virtual interviews and platforms (55%) negatively or somewhat negatively affected their ability to select a residency program. Most students (62%) were concerned they will be inaccurately evaluated as an interviewee on a virtual platform. Although 30% agreed or strongly agreed the cost-savings and convenience of virtual interviews outweigh potential downsides, 66% of students were planning to visit cities of interest in person before rank list submission.Conclusions: Medical students reported significant concerns with their ability to be accurately evaluated and to choose among residency programs on a virtual platform. Students found the networking session to be a valuable resource for most students, and programs could continue similar efforts during the residency application cycle to better represent their program while maintaining certain financial and geographic advantages of a virtual environment.

View details for DOI 10.1016/j.adro.2021.100643

View details for PubMedID 33748546

View details for DOI 10.1016/j.ijrobp.2019.11.018

View details for PubMedID 33714521

Abstract

BACKGROUND: Elderly patients with gastrointestinal cancer and mental illness have significant comorbidities that can impact the quality of their care. We investigated the relationship between mental illness and frequent emergency department (ED) use in the last month of life, an indicator for poor end-of-life care quality, among elderly patients with gastrointestinal cancers.METHODS: We used SEER-Medicare data to identify decedents with gastrointestinal cancers who were diagnosed between 2004 and 2013 and were at least 66years old at time of diagnosis (median age: 80years, range: 66-117years). We evaluated the association between having a diagnosis of depression, bipolar disorders, psychotic disorders, anxiety, dementia, and/or substance use disorders and ED use in the last 30days of life using logistic regression models.RESULTS: Of 160,367 patients included, 54,661 (34.1%) had a mental illness diagnosis between one year prior to cancer diagnosis and death. Patients with mental illness were more likely to have>1 ED visit in the last 30days of life (15.6% vs. 13.3%, p<0.01). ED use was highest among patients with substance use (17.7%), bipolar (16.5%), and anxiety disorders (16.4%). Patients with mental illness who were male, younger, non-white, residing in lower income areas, and with higher comorbidity were more likely to have multiple end-of-life ED visits. Patients who received outpatient treatment from a mental health professional were less likely to have multiple end-of-life ED visits (adjusted odds ratio 0.82, 95% confidence interval 0.78-0.87).CONCLUSIONS: In elderly patients with gastrointestinal cancers, mental illness is associated with having multiple end-of-life ED visits. Increasing access to mental health services may improve quality of end-of-life care in this vulnerable population.

View details for DOI 10.1002/cam4.3792

View details for PubMedID 33621438

View details for DOI 10.1016/j.ijrobp.2020.08.067

View details for PubMedID 33422277

Abstract

BACKGROUND: Patients with cancer are at high risk for having mental disorders, resulting in widespread psychosocial screening efforts. However, there is a need for population-based and longitudinal studies of mental disorders among patients who have gastrointestinal cancer and particular among elderly patients.PATIENTS AND METHODS: We used the SEER-Medicare database to identify patients aged 65 years with colorectal, pancreatic, gastric, hepatic/biliary, esophageal, or anal cancer. Earlier (12 months before or up to 6 months after cancer diagnosis) and subsequent mental disorder diagnoses were identified.RESULTS: Of 112,283 patients, prevalence of an earlier mental disorder was 21%, 23%, 20%, 20%, 19%, and 26% for colorectal, pancreatic, gastric, hepatic/biliary, esophageal, and anal cancer, respectively. An increased odds of an earlier mental disorder was associated with pancreatic cancer (odds ratio [OR], 1.17; 95% CI, 1.11-1.23), esophageal cancer (OR, 1.10; 95% CI, 1.02-1.18), and anal cancer (OR, 1.17; 95% CI, 1.05-1.30) compared with colorectal cancer and with having regional versus local disease (OR, 1.09; 95% CI, 1.06-1.13). The cumulative incidence of a subsequent mental disorder at 5 years was 19%, 16%, 14%, 13%, 12%, and 10% for patients with anal, colorectal, esophageal, gastric, hepatic/biliary, and pancreatic cancer, respectively. There was an association with having regional disease (hazard ratio [HR], 1.08; 95% CI, 1.04-1.12) or distant disease (HR, 1.36; 95% CI, 1.28-1.45) compared with local disease and the development of a mental disorder. Although the development of a subsequent mental disorder was more common among patients with advanced cancers, there continued to be a significant number of patients with earlier-stage disease at risk.CONCLUSIONS: This study suggests a larger role for incorporating psychiatric symptom screening and management throughout oncologic care.

View details for DOI 10.6004/jnccn.2020.7620

View details for PubMedID 33401234

Abstract

Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described.We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed.A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10months, p=0.004), systemic TTF (15 vs. 4months, p<0.001) and intracranial TTF (14 vs. 5months, p=0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF.In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.

View details for DOI 10.1007/s11060-020-03686-3

View details for PubMedID 33415659

Abstract

To investigate the benefit of postoperative radiotherapy (PORT) for low-volume (pN1) nodal disease after resection of oral cavity squamous cell carcinoma.The National Cancer Database was queried for adults with nonmetastatic squamous cell carcinoma of the oral cavity treated by surgical resection with pathologic stage T1-2 N0-2 (American Joint Committee on Cancer 7th edition) and with the maximal exclusion of standard indications for PORT. Overall survival was compared within pN1 for observation versus PORT and then compared for pN1 versus pN0 and versus pN2 stratified by receipt of observation or PORT. Multivariable Cox regression was used to adjust for potential confounders between PORT and survival, including comorbidity and age.Overall 5017 pN0, 530 pN1, and 253 pN2 patients were identified, of whom 9%, 35%, and 64% received PORT, respectively. Within the pN1 cohort, PORT was associated with improved survival versus observation (adjusted hazard ratio, 0.66; 95% confidence interval, 0.46-0.97; P=0.03). Among observed patients, the prognosis of pN1 was equivalent to pN2 and inferior to pN0; in contrast, among patients treated with PORT, the prognosis of pN1 was equivalent to pN0 and superior to pN2. Without PORT, pN1 remained an adverse risk factor relative to pN0 regardless of the depth of invasion, lymph node size, lymph node location, and extent of lymph node dissection.PORT was associated with a survival benefit compared with observation. Notably, pN1 was an adverse risk factor relative to pN0 if, and only if, patients did not receive PORT, suggesting pN1 by itself may be an indication for PORT.

View details for DOI 10.1097/COC.0000000000000792

View details for PubMedID 33417322

View details for Web of Science ID 000582521502446

View details for Web of Science ID 000590061300769

View details for Web of Science ID 000582521502233

View details for Web of Science ID 000582521502092

View details for Web of Science ID 000582521501380

View details for Web of Science ID 000582521502101

View details for Web of Science ID 000582521503339

Abstract

The clinical and financial effects of mental disorders are largely unknown among gastrointestinal (GI) cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified patients whose first cancer was a primary colorectal, pancreatic, gastric, hepatic/biliary, esophageal, or anal cancer as well as those with coexisting depression, anxiety, psychotic, or bipolar disorder. Survival, chemotherapy use, total healthcare expenditures, and patient out-of-pocket expenditures were estimated and compared based on the presence of a mental disorder. We identified 112,283 patients, 23,726 (21%) of whom had a coexisting mental disorder. Median survival for patients without a mental disorder was 52months (95% CI 50-53months) and for patients with a mental disorder was 43months (95% CI 42-44months) (p<0.001). Subgroup analysis identified patients with colorectal, gastric, or anal cancer to have a significant association between survival and presence of a mental disorder. Chemotherapy use was lower among patients with a mental disorder within regional colorectal cancer (43% vs. 41%, p=0.01) or distant colorectal cancer subgroups (71% vs. 63%, p<0.0001). The mean total healthcare expenditures were higher for patients with a mental disorder in first year following the cancer diagnosis (increase of $16,823, 95% CI $15,777-$18,173), and mean patient out-of-pocket expenses were also higher (increase of $1,926, 95% CI $1753-$2091). There are a substantial number of GI cancer patients who have a coexisting mental disorder, which is associated with inferior survival, higher healthcare expenditures, and greater personal financial burden.

View details for DOI 10.1002/cam4.3509

View details for PubMedID 33022135

View details for Web of Science ID 000579885400086

View details for DOI 10.1016/j.annonc.2020.08.317

View details for Web of Science ID 000573469100195

Abstract

Locally recurrent pancreatic cancer after prior radiotherapy is a therapeutic challenge with limited treatment options. This study examines the safety and efficacy of stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma after prior conventional fractionation radiotherapy (CRT).Outcomes from all patients treated with SBRT for locally recurrent pancreatic adenocarcinoma after prior CRT at our institution were reviewed. A total of 23 patients were identified. Prior CRT median dose was 50.4 Gy (range, 30-60 Gy). Twelve patients (52%) had previously undergone surgery and received CRT as neo- or adjuvant treatment. Nine patients (39.1%) were reirradiated with SBRT with a dose of 25 Gy in a single fraction, and 14 patients (60.8%) received a 5-fraction SBRT schedule with a median dose of 25 Gy (range, 20-33 Gy) in 5fractions (1-5 fractions).Median follow-up time was 28 months (range, 9-77 months). The median planning target volume was 46 cm(3) (range, 14-89 cm(3)). Median overall survival from diagnosis and from reirradiation were 27.5 months (range, 10-77 months) and 8.5 months (range, 1 month to not reached) respectively. The cumulative incidence of local failures at the last follow-up was 19%. For the 4 patients who presented with local failure, one was treated with a single fraction of 25 Gy, and the other 3 were treated with 25 Gy in 5 fractions. Three patients presented regional failure, with a cumulative incidence of 14%, all with concurrent distant progression. The cumulative incidence of distant progression was 64% at last follow-up. After reirradiation, 6patients (26.1%) developed a grade 2 or 3 gastrointestinal toxicity, 4 of them occurring among patients treated with a single-fraction SBRT regimen.Our report shows that SBRT for reirradiation of locally recurrent pancreas adenocarcinoma is a feasible option with good local control and acceptable toxicity rates, especially with a multifraction schedule.

View details for PubMedID 28740913

Abstract

Purpose: Our institution cancelled all in-person clerkships owing to the coronavirus disease 2019 pandemic. In response, we designed a virtual radiation oncology medical student clerkship.Methods and Materials: We convened an advisory panel to design a virtual clerkship curriculum. We implemented clerkship activities using a cloud-based learning management system, video web conferencing systems, and a telemedicine portal. Students completed assessments pre- and postclerkship to provide data to improve future versions of the clerkship.Results: The virtual clerkship spans 2 weeks and is graded pass or fail. Students attend interactive didactic sessions during the first week and participate in virtual clinic and give talks to the department during the second week. Didactic sessions include lectures, case-based discussions, treatment planning seminars, and material adapted from the Radiation Oncology Education Collaborative Study Group curriculum. Students also attend virtual departmental quality assurance rounds, cancer center seminars, and multidisciplinary tumor boards. The enrollment cap was met during the first virtual clerkship period (April 27 through May 8, 2020), with a total of 12 students enrolling.Conclusions: Our virtual clerkship can increase student exposure and engagement in radiation oncology. Data on clerkship outcomes are forthcoming.

View details for DOI 10.1016/j.adro.2020.05.006

View details for PubMedID 32775783

Abstract

To quantitatively assess the probability of tumor resection based on measurements of tumor contact with the major peripancreatic vessels.This is a retrospective cohort study of pancreatic cancer patients treated between January 2001 and December 2015 in a single academic comprehensive cancer center. Radiographic measurements of the circumferential degree and length of solid tumor contact with major peripancreatic vessels were obtained from diagnostic pancreatic protocol computed tomography images and tested for correlation with tumor resection and margin status.Of 294 patients analyzed, 113 (38%) were resected, with 71 (63%) with negative margins. Based on the individual measurements of vascular involvement, a resectability scoring system (RSS) was created. The RSS correlated strongly with resection (P < 0.0001) and R0 resection (P < 0.0001) probabilities. Moreover, the RSS correlated with overall survival (P < 0.0001) and metastasis-free survival (P < 0.0001), being able to substratify resectable (P = 0.022) and unresectable patients (P = 0.014) into subgroups with different prognosis based on RSS scores.Based on a comprehensive and systematic quantitative approach, we developed a scoring system that demonstrated excellent accuracy to predict tumor resection, surgical margin status, and prognosis.

View details for PubMedID 31091207

View details for DOI 10.1016/j.ijrobp.2020.02.018

View details for PubMedID 32386736

Abstract

BACKGROUND: The comparative risks of a second cancer diagnosis are uncertain after primary cancer treatment with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam radiotherapy (PBRT).METHODS: Pediatric and adult patients with a first cancer diagnosis between 2004 and 2015 who received 3DCRT, IMRT, or PBRT were identified in the National Cancer Database from 9 tumor types: head and neck, gastrointestinal, gynecologic, lymphoma, lung, prostate, breast, bone/soft tissue, and brain/central nervous system. The diagnosis of second cancer was modeled using multivariable logistic regression adjusting for age, follow-up duration, radiotherapy (RT) dose, chemotherapy, sociodemographic variables, and other factors. Propensity score matching also was used to balance baseline characteristics.RESULTS: In total, 450,373 patients were identified (33.5% received 3DCRT, 65.2% received IMRT, and 1.3% received PBRT) with median follow-up of 5.1years after RT completion and a cumulative follow-up period of 2.54million person-years. Overall, the incidence of second cancer diagnosis was 1.55 per 100 patient-years. In a comparison between IMRT versus 3DCRT, there was no overall difference in the risk of second cancer (adjusted odds ratio [OR], 1.00; 95% CI, 0.97-1.02; P=.75). By comparison, PBRT had an overall lower risk of second cancer versus IMRT (adjusted OR, 0.31; 95% CI, 0.26-0.36; P<.0001). Results within each tumor type generally were consistent in the pooled analyses and also were maintained in propensity score-matched analyses.CONCLUSIONS: The risk of a second cancer diagnosis was similar after IMRT versus 3DCRT, whereas PBRT was associated with a lower risk of second cancer risk. Future work is warranted to determine the cost-effectiveness of PBRT and to identify the population best suited for this treatment.

View details for DOI 10.1002/cncr.32938

View details for PubMedID 32426866

Abstract

Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56years (44-69years). With a median clinical and radiological follow-up of 44months (9-161months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p=0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r=-0.4, p=0.001), right-sided tumor (r=-0.3, p=0.03), primary SRS (r=-0.5, p0.001), and initial clinical presentation of hearing loss (r=-0.4, p=0.001). To achieve a LC 90%, a median marginal dose (Gy) of 15 (range, 12-30Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.

View details for DOI 10.1007/s10143-020-01292-5

View details for PubMedID 32318920

Abstract

BACKGROUND: Signet ring cell carcinoma (SRCC) of the ampulla of Vater is poorly understood, with approximately 22 reported cases. Our study sought to create a comprehensive review of cases in the United States.METHODS: We used the Surveillance, Epidemiology, and End Results Program to collect all cases of ampullary adenocarcinoma diagnosed between 2010 and 2015.RESULTS: The age-adjusted incidence rate of SRCC of the ampulla of Vater was 1.2 cases per 10,000,000 persons per year, with 50% more cases in males than females. We identified 3448 cases of adenocarcinoma of the ampulla of Vater, 81 of which were SRCC (2.3%). SRCC tended to present a later stage than other ampullary cancers, with median survival times of 17 vs. 25 months, (p=0.07). Survival was significantly worse for SRCC when accounting for other clinical features (HR 1.46, p=0.01). Factors portending worse prognosis in SRCC of the ampulla of Vater were advanced age, late stage and lack of surgical intervention.CONCLUSION: Our study represents the largest study of SRCC of the ampulla of Vater to date. SRCC has a poorer prognosis compared with other ampullary cancers. Optimal treatment regimen is the most important future area of study.

View details for DOI 10.1016/j.hpb.2020.03.024

View details for PubMedID 32317226

View details for Web of Science ID 000580656800057

Abstract

With the recent CyberKnife treatment planning system (TPS) upgrade from Precision 1.0 to Precision 2.0, the new VOLO optimizer was released for plan optimization. The VOLO optimizer sought to overcome some of the limitations seen with the Sequential optimizer from previous TPS versions. The purpose of this study was to investigate the clinical impact of the VOLO optimizer on treatment plan quality and clinical treatment efficiency as compared to the Sequential optimizer. Treatment plan quality was evaluated in four categories of patients: Brain Simple (BS), Brain Complex (BC), Spine Complex (SC), and Prostate (PC). A total of 60 treatment plans were compared using both the Sequential and VOLO optimizers with Iris and MLC collimation with the same clinical constraints. Metrics evaluated included estimated treatment time, monitor units (MUs) delivered, conformity index (CI), and gradient index (GI). Furthermore, the clinical impact of the VOLO optimizer was evaluated through statistical analysis of the patient population treated during the 4months before (n=297) and 4months after (n=285) VOLO introduction. Significant MU and time reductions were observed for all four categories planned. MU reduction ranged from -14% (BS Iris) to -52% (BC MLC), and time reduction ranged from -11% (BS Iris) to -22% (BC MLC). The statistical analysis of patient population before and after VOLO introduction for patients using 6D Skull tracking with fixed cone, 6D Skull tracking with Iris, and Xsight Spine tracking with Iris were -4.6%, -22.2%, and -17.8% for treatment time reduction, -1.1%, -22.0%, and -28.4% for beam reduction and -3.2%, -21.8%, and -28.1% for MU reduction, respectively. The VOLO optimizer maintains or improves the plan quality while decreases the plan complexity and improves treatment efficiency. We anticipate an increase in patient throughput with the introduction of the VOLO optimizer.

View details for DOI 10.1002/acm2.12851

View details for PubMedID 32212374

Abstract

PURPOSE: To report the outcome of stereotactic ablative radiotherapy (SABR) to the primary tumor for patients with metastatic pancreatic cancer.MATERIALS AND METHODS: We examined the records of patients with metastatic pancreatic cancer treated with SABR to the primary tumor between 2002 and 2018. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Pain intensity pre- and post-SABR was scored according to the Stanford Pain Scale as reported by the patient. Time-to-events were calculated from the date of end of SABR delivery.RESULTS: In total, 27 patients were identified that met the inclusion criteria. Seventeen (63%) patients received single fraction SABR with a median dose of 25 Gy (range: 12.5-25), while 10 (37%) patients were treated in 5 fractions with a median dose of 33 Gy (range: 25-40). Prior to the start of SABR, 17 (63%) patients reported having abdominal pain, with a median intensity of 5 in the 0 to 10 pain scale (range: 1-9), 11 (41%) of them necessitating continuous opioid use. The median follow-up was of 6 months (range: 0-18). Median overall survival was of 7 months (95% CI, 3-10), with a cumulative incidence of local failures at 1 year of 25% (95% CI, 10-44). After SABR, there was a significant reduction in the mean intensity of pain (P = 0.01), and a 46% relative reduction in continuous opioid use. Only two patients (7%) presented a grade 3 toxicity that could be attributed to treatment.CONCLUSION: In this small series, SABR demonstrated to be a safe and effective option for the local palliation of metastatic pancreatic cancer, with measurable improvements in abdominal pain and opioid necessity.

View details for DOI 10.1016/j.prro.2020.02.010

View details for PubMedID 32119922

Abstract

BACKGROUND AND PURPOSE: The optimal neoadjuvant approach in patients with resectable pancreas cancer is unclear. We investigated outcomes after preoperative chemotherapy alone, chemotherapy with conventionally-fractionated radiation (CFRT), or chemotherapy with stereotactic body radiotherapy (SBRT).MATERIALS AND METHODS: The NCDB was queried for patients with resectable pancreatic adenocarcinoma (pretreatment stage T1-3, N0-1, M0) who received preoperative, multiagent chemotherapy and definitive surgery from 2010 to 2015. CFRT was 40-60Gy in 20-35 fractions. SBRT was 20-25Gy in 1 fraction or 30-50Gy using at least 5Gy per fraction. Multivariable regression and propensity score matching were used to adjust for potential confounders, including age, comorbidity score, and pretreatment extent of disease. The primary outcome was overall survival measured from surgery.RESULTS: In total, 1355 patients received preoperative chemotherapy alone, 552 patients received preoperative chemotherapy with CFRT, and 175 patients received preoperative chemotherapy with SBRT. Receipt of SBRT was associated with significantly improved overall survival compared to chemotherapy alone (median 30 vs 21months, p=0.02; adjusted hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.47-0.90, p=0.01). Similarly, SBRT was associated with significantly improved overall survival compared to CFRT (median 29 vs 16months, p=0.002; adjusted HR 0.53, 95% CI 0.37-0.76, p=0.001). Additionally, SBRT was associated with significantly increased rates of pathological complete response and margin-negative resection. Rates of postoperative readmissions and mortality were comparable.CONCLUSIONS: Neoadjuvant chemotherapy with SBRT is associated with favorable survival and pathological outcomes, warranting consideration for prospective validation.

View details for DOI 10.1016/j.radonc.2020.01.007

View details for PubMedID 32044168

View details for Web of Science ID 000530922700539

View details for Web of Science ID 000530922700781

Abstract

Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is the standard treatment for locally-advanced rectal cancer. There is interest in de-escalating local therapy after a clinical complete response (cCR) to CRT. We hypothesized that a watch-and-wait (WW) strategy offers comparable cancer-specific survival (CSS), superior quality-adjusted survival, and reduced cost compared to upfront TME.We developed a decision-analytic model to compare WW, low anterior resection (LAR), and abdominoperineal resection (APR) for patients achieving a cCR to CRT. Rates of local regrowth, pelvic recurrence, and distant metastasis were derived from series comparing WW to TME after pathologic complete response. Lifetime incremental costs and quality-adjusted life-years (QALYs) were calculated between strategies, and sensitivity analyses were performed to study model uncertainty.The base case 5-year CSS was 93.5% (95% confidence interval [CI] 91.5 to 94.9%) on a WW program, compared to 95.9% (95% CI 93.6 to 97.4%) after upfront TME. WW was dominant relative to LAR, with cost savings of $28,500 (95% CI $22,200 to $39,000) and incremental QALY of 0.527 (95% CI 0.138 to 1.125). WW was also dominant relative to APR, with cost savings of $32,100 (95% CI $21,800 to $49,200) and incremental QALY of 0.601 (95% CI 0.213 to 1.208). WW remained dominant in sensitivity analysis unless the rate of surgical salvage fell to 73.0%.Using current multi-institutional recurrence estimates, we observed comparable CSS, superior quality-adjusted survival, and decreased costs with WW compared to upfront TME. Upfront TME was preferred when surgical salvage rates were low.

View details for DOI 10.1093/jnci/djaa003

View details for PubMedID 31930400

Abstract

To quantify the survival impact of prolongation of definitive radiotherapy (RT) for head and neck cancer in a national, modern cohort, and to identify predictive factors for prolongation.The National Cancer Database was queried for adults with non-metastatic cancer of the nasopharynx, oropharynx, larynx, or hypopharynx diagnosed 2004-2015, treated with definitive RT to 66-70 Gy in 30-35 fractions at 2-2.2 Gy per fraction. Multivariable Cox regression and propensity score matching were used to model the survival impact of RT prolongation, adjusting for potential confounders such as age and comorbidity. Predictors of RT prolongation were identified using multivariable multinomial logistic regression.In total, 36,367 patients were identified. As a continuous variable, RT prolongation increased the relative hazard of death by 2% per day (P < .0001). In the matched cohorts, patients with short (4-8 days) or long prolongation (> 8 days) had lower absolute 4-year overall survival by 4% and 12% respectively (P < .0001), while prolongation of 1-3 days was not significantly adverse. Major predictors of increased risk of prolongation were administration of systemic therapy, baseline comorbidity, lack of private insurance, and tumor/nodal stage. Conversely, higher facility volume was significantly protective, with a 55% lower risk of long prolongation within the topmost quartile (> 11.5 patients/year).RT prolongation, especially > 8 days, is significantly deleterious. Systemic therapy and facility volume were major predictors. Early identification of patients at increased risk of treatment interruptions may facilitate implementation of preventive measures.

View details for DOI 10.1016/j.radonc.2020.12.025

View details for PubMedID 33383061

Abstract

Cerebellar glioblastoma (GB) is much rarer than its supratentorial counterpart, and potentially of different molecular origin. Prior database studies are of limited size and reported on patients who preceded the validation of temozolomide. Thus, we provide an updated population-based analysis of the treatment trends and outcomes since the standardization of GB adjuvant chemoradiation. Patients diagnosed with primary cerebellar and supratentorial GB were identified from the National Cancer Database spanning 2005-2015. Patients were characterized by demographics, extent of resection, and adjuvant chemotherapy or radiation status. Cohorts were primarily and secondarily assessed for overall survival by tumor site and treatment history, respectively. A total of 655 patients with cerebellar GB were identified (0.6%). Cerebellar GB patients, compared to supratentorial GB were more likely to undergo a biopsy or subtotal resection (13.4% vs 9.3% and 16.0% vs 13.4%, p-value<0.001), and less likely to pursue adjuvant therapy (48.4% vs 52.7%, p-value<0.001). Overall median survivals were 9.3 and 9.4months, respectively. On multivariable analysis, gross total resection, radiation, and chemotherapy were found to be predictors of improved overall survival (HR 0.77, p=0.038; HR 0.67, p<0.001; and HR=0.77, p=0.030, respectively). While many management principles are currently shared between cerebellar and supratentorial GB, aggressive regimens appear less frequently prescribed. Survival continues to match supratentorial outcomes and may benefit from future, systemic guidance by distinguishing molecular features.

View details for DOI 10.1016/j.jocn.2020.10.049

View details for PubMedID 33317719

Abstract

Despite putative benefits associated with proton radiotherapy in the setting of CNS tumors, numerous barriers limit treatment accessibility. Given these challenges, we explored the association of proton use with variations in treatment timing.Pediatric and adult patients with histologically confirmed CNS tumors were identified from the National Cancer Database (2004-2015). Univariable and multivariable regression models were constructed to assess factors impacting radiation timing. Multivariable Cox regression was used to evaluate the effect of treatment delay on survival.A total of 76 157 patients received photon or proton radiotherapy. Compared to photons, time to proton administration was longer in multiple pediatric (embryonal, ependymal, nonependymal glial, and other) and adult (ependymal, nonependymal glial, meningeal, other) tumor histologies. On adjusted analysis, proton radiotherapy was associated with longer delays in radiotherapy administration in pediatric embryonal tumors (+3.00 weeks, P = .024) and in all adult tumors (embryonal [+1.36 weeks, P = .018], ependymal [+3.15 weeks, P < .001], germ cell [+2.65 weeks, P = .024], glial [+2.15 weeks, P < .001], meningeal [+5.05 weeks, P < .001], and other [+3.06 weeks, P < .001]). In patients with high-risk tumors receiving protons, delays in adjuvant radiotherapy were independently associated with poorer survival (continuous [weeks], adjusted hazard ratio = 1.09, 95% CI = 1.02-1.16).Proton radiotherapy is associated with later radiation initiation in pediatric and adult patients with CNS tumors. In patients with high-risk CNS malignancies receiving protons, delayed adjuvant radiotherapy is associated with poorer survival. Further studies are needed to understand this discrepancy to maximize the potential of proton radiotherapy for CNS malignancies.

View details for DOI 10.1093/nop/npaa034

View details for PubMedID 33312677

View details for PubMedCentralID PMC7716142

Abstract

Being able to predict a patient's life expectancy can help doctors and patients prioritize treatments and supportive care. For predicting life expectancy, physicians have been shown to outperform traditional models that use only a few predictor variables. It is possible that a machine learning model that uses many predictor variables and diverse data sources from the electronic medical record can improve on physicians' performance. For patients with metastatic cancer, we compared accuracy of life expectancy predictions by the treating physician, a machine learning model, and a traditional model.A machine learning model was trained using 14600 metastatic cancer patients' data to predict each patient's distribution of survival time. Data sources included note text, laboratory values, and vital signs. From 2015-2016, 899 patients receiving radiotherapy for metastatic cancer were enrolled in a study in which their radiation oncologist estimated life expectancy. Survival predictions were also made by the machine learning model and a traditional model using only performance status. Performance was assessed with area under the curve for 1-year survival and calibration plots.The radiotherapy study included 1190 treatment courses in 899 patients. A total of 879 treatment courses in 685 patients were included in this analysis. Median overall survival was 11.7 months. Physicians, machine learning model, and traditional model had area under the curve for 1-year survival of 0.72 (95% CI 0.63-0.81), 0.77 (0.73-0.81), and 0.68 (0.65-0.71), respectively.The machine learning model's predictions were more accurate than those of the treating physician or a traditional model.

View details for DOI 10.1093/jamia/ocaa290

View details for PubMedID 33313792

Abstract

Our purpose was to report outcomes of elderly patients who underwent definitive treatment involving radiation therapy for esophageal cancer at our institution.We performed a retrospective review of patients aged 75 years with esophageal cancer treated with definitive radiation therapy (45 Gy) at our institution from 1997 to 2019. Acute and late Radiation Therapy Oncology Group grade 3+ toxicities were recorded. Survival was estimated using the Kaplan-Meier method.Of the 89 patients included, median age was 80 and 78% were male. Median adjusted Charlson Comorbidity Index and Karnofsky Performance Status were 5 (3-12) and 80 (50-100), respectively. The majority of cancers were adenocarcinoma (58%), distal (67%), and stage III (62%). Fifty-eight percent underwent definitive chemoradiotherapy, and one-third underwent preoperative intent chemoradiotherapy. Median prescribed dose was 50 Gy (45-66 Gy), and intensity modulated radiation therapy was used in 76%. Eighty-five percent completed the radiation therapy course. Among these, 20% had radiation therapy breaks. For those receiving concurrent chemotherapy, 37% had a dose reduction and 39.5% had a break/cycle reduction. Acute grade 3+ toxicity was 22%, with 2% grade 5 toxicity. Twenty-one of the 29 patients (72%) treated with preoperative intent underwent surgery. There were no deaths 90 days postoperatively. For patients who underwent surgery, 1- and 2-year overall survival were 95% and 84%. For those who did not undergo surgery, 1- and 2-year overall survival were 70% and 52%.There is a role for aggressive radiation therapy in well-selected elderly patients with esophageal cancer. However, optimization of supportive care, chemotherapy regimens, radiation therapy dose/fractionation, and surgical indications are needed to reduce toxicity.

View details for DOI 10.1016/j.adro.2020.05.001

View details for PubMedID 33305080

View details for PubMedCentralID PMC7718494

Abstract

Management of symptomatic brain metastases often includes surgical resection with postoperative radiotherapy. Postoperative whole brain radiotherapy (WBRT) improves intracranial control but detrimentally impacts quality of life and neurocognition. We sought to characterize the use in the United States of postoperative stereotactic radiosurgery (SRS), an evolving standard-of-care associated with reduced cognitive effects.With the MarketScan Commercial Claims and Encounters Database from 2007 to 2015, we identified patients aged 18-65 years treated with resection of a brain metastasis followed by SRS or WBRT within 60 days of surgery. Logistic regression estimated associations between co-variables (treatment year, age, sex, geographic region, place of service, insurance type, disease histology, comorbidity score, and median area household income and educational attainment) and SRS receipt.Of 4,007 patients included, 1,506 (37.6%) received SRS and 2,501 (62.4%) received WBRT. Postoperative SRS increased from 16.5% (2007-2008) to 56.8% (2014-2015). Patients residing in areas with a median household income or an educational attainment below 50th percentile were significantly less likely to receive SRS after controlling for treatment year and other demographic characteristics (p<0.01). Factors associated with higher odds of receiving SRS included younger age, female sex, melanoma histology, Western region location, hospital-based facility, and high-deductible health plan enrollment (p<0.05 for each).Postoperative SRS for brain metastases has increased from 2007 to 2015, with the majority of patients now receiving SRS over WBRT. Patients in areas of lower socioeconomic class were less likely to receive SRS, warranting further investigation of barriers to SRS adoption.

View details for DOI 10.1016/j.wneu.2020.09.085

View details for PubMedID 32971279

View details for DOI 10.1016/j.adro.2020.07.015

View details for PubMedID 32904388

View details for PubMedCentralID PMC7456273

Abstract

PURPOSE: We evaluated the impact of a virtual radiation oncology clerkship.METHODS AND MATERIALS: We developed a 2-week virtual radiation oncology clerkship that launched on April 27, 2020. Clerkship components included a virtual clinic with radiation oncology faculty and residents, didactic lectures, student talks, and supplemental sessions such as tumor boards and chart rounds. Medical students completed pre- and post-clerkship self-assessments. Faculty and resident participants also completed surveys on their experience with virtual lectures and clinics. Pre- and post-clerkship results were compared using a 2-sided paired t test. An analysis of variance model was used to analyze the clerkship components.RESULTS: Twenty-six medical students, including 4 visiting students, enrolled over 2 clerkship periods (4 weeks). All students completed the pre- and post-clerkship self-assessments and agreed that the clerkship improved their understanding of radiation oncology. Compared with 3 (11.5%) students who agreed that they understood the daily responsibilities of a radiation oncologist before the clerkship, 22 (84.6%) students agreed and 3 (11.5%) strongly agreed that they understood the daily responsibilities of a radiation oncologist after the clerkship (P < .0001). Although 15 students (57.7%) reported an increased interest in radiation oncology because of the clerkship, the mean level of interest in radiation oncology as a career remained the same, with pre- and post-clerkship scores of 3.0 (0.9) and 3.0 (1.1) on a 5-point scale, respectively (P = .7). Students found virtual clinic and didactic lectures to be the most valuable components of the clerkship. Most respondents agreed (30.8%) or strongly agreed (65.4%) to recommend the clerkship to their classmates.CONCLUSIONS: Our virtual clerkship was effective in increasing medical student interest in and knowledge about radiation oncology. These data will help optimize a new paradigm of virtual radiation oncology education for medical students during COVID-19 and beyond.

View details for DOI 10.1016/j.ijrobp.2020.06.050

View details for PubMedID 32890529

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

Abstract

We aimed to report the long-term impact of modern chemotherapy and SABR dose regimens on oncologic outcomes of unresectable pancreatic adenocarcinoma (PA).We reviewed the treatment characteristics and outcomes of all patients who received multi-fraction SABR for unresectable PA between February 2007 and August 2018 at our institution. Time-to-events were calculated from date of diagnosis treating death as a competing risk.A total of 149 patients were identified. Median follow-up was 15 months (range: 5-47). Median SABR dose was 33 Gy (range: 20-45) delivered in 5 fractions in 143 patients, and 3 or 6 fractions in 6 patients. 107 patients (72%) received gemcitabine-based chemotherapy while 31 (21%) received modified FOLFIRINOX (mFFX). Median OS was 16 months (95% CI, 14-17), with a 1-year cumulative incidence of LF of 14%. The combination of SABR doses 40 Gy and mFFX (n = 21) showed a superior PFS and OS to the use of GEM-based chemotherapy with <40 Gy SABR doses (median PFS: 14 vs. 10 months, HR: 0.46, 95% CI: 0.29-0.71, P = 0.003; median OS: 24 vs. 14 months, HR: 0.36, 95% CI: 0.22-0.59, P = 0.002), with 1-year PFS and OS of 67% and 90% compared to 35% and 59% for those who received GEM-based chemotherapy with <40 Gy SABR doses, respectively.The use of mFFX and a SABR dose 40 Gy in 5 fractions may be superior compared to regimens that utilize gemcitabine-based chemotherapy or SABR doses <40 Gy.

View details for DOI 10.1016/j.radonc.2020.07.053

View details for PubMedID 32763253

View details for DOI 10.1093/nop/npaa034

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

Abstract

Introduction: Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited. Methods: Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions. Results: Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], p = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001-0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02-0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001-0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1-79.6] months vs. 5.45 [1.8-26.3], p = 0.0092) and OS (median 56.73 months [7.8-104.5] vs. 14.83 [3.8 to 29.1], p = 0.0252). Conclusion: Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.

View details for DOI 10.3389/fonc.2020.00337

View details for PubMedID 32219069

View details for PubMedCentralID PMC7078164

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

Abstract

Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.Older patients (age4 yr) experienced improved overall survival compared to younger patients (age<4 yr) (hazard ratio [HR]=0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR=3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR=0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P=.041); extent of resection was not associated with survival in younger patients (P=.880).Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.

View details for DOI 10.1093/neuros/nyaa023

View details for PubMedID 32110805

Abstract

Purpose: To review our institutional experience of treating cholangiocarcinoma using stereotactic body radiation therapy (SBRT).Methods and Materials: A total of 40 patients with intrahepatic (n=25) or perihilar (n=15) cholangiocarcinoma treated with SBRT were retrospectively reviewed. SBRT was delivered in 1 to 5 fractions with median dose of 40Gy. Competing risk analysis was used to estimate cumulative incidence of local in-field, local out-of-field, regional, and distant failure. Kaplan-Meier and log-rank tests were used to calculate overall survival (OS). Toxicity was scored using Common Terminology Criteria for Adverse Events, version 4.0.Results: The median follow-up time was 18months. The 1-year incidence of local in-field, local out-of-field, regional, and distant failure was 8%, 23%, 13%, and 22%, respectively. Median OS was 23months and 1- and 2-year OS rates were 69% and 39%, respectively. Patients with perihilar tumors had a 1-year incidence of regional failure of 24% and worse OS (P=.013). Patients with regional failure were more likely to develop distant metastases, 32% versus 19% at 1year (P=.11). Acute grade 3+hepatobiliary toxicity developed in 15 patients (36%).Conclusions: In this series of cholangiocarcinoma patients treated with definitive SBRT, patterns of failure reveal that regional failures are not insignificant, particularly for perihilar tumors. Elective nodal irradiation of regional lymphatics should be considered when using SBRT. A prospective study of elective nodal irradiation in patients with perihilar tumors would further clarify whether this approach improves outcomes without increasing hepatobiliary toxicity.

View details for DOI 10.1016/j.adro.2019.08.003

View details for PubMedID 32051893

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

Abstract

OBJECTIVE: For patients with head and neck squamous cell carcinoma (HNSCC), delays in the initiation of radiotherapy (RT) have been closely associated with worse outcomes. We sought to investigate whether RT modality (proton vs. photon) is associated with differences in the time to initiation of RT.METHODS: The National Cancer Database was queried for patients diagnosed with nonmetastatic HNSCC between 2004 and 2015 who received either proton or photon RT as part of their initial treatment. Wilcoxon rank-sum and chi-square tests were used to compare continuous and categorical variables, respectively. Multivariable logistic regression was used to determine the association between use of proton RT and delayed RT initiation.RESULTS: A total of 175,088 patients with HNSCC receiving either photon or proton RT were identified. Patients receiving proton RT were more likely to be white, reside in higher income areas, and have private insurance. Proton RT was associated with delayed RT initiation compared to photon RT (median 59days vs. 45, P <0.001). Receipt of proton therapy was independently associated with RT initiation beyond 6weeks after diagnosis (adjusted OR [aOR, definitive RT] = 1.69; 95% confidence interval [CI] 1.26-2.30) or surgery (aOR [adjuvant RT] = 4.08; 95% CI 2.64-6.62). In the context of adjuvant proton RT, increases in treatment delay were associated with worse overall survival (weeks, adjusted hazard ratio =1.099, 95% CI 1.011-1.194).CONCLUSION: Use of proton therapy is associated with delayed RT in both the definitive and adjuvant settings for patients with HNSCC and could be associated with poorer outcomes.LEVEL OF EVIDENCE: 2b Laryngoscope, 122:0000-0000, 2019 Laryngoscope, 2019.

View details for DOI 10.1002/lary.28458

View details for PubMedID 31837165

View details for DOI 10.7759/cureus.5748

View details for Web of Science ID 000487712800013

View details for DOI 10.1016/j.ijrobp.2019.06.2266

View details for Web of Science ID 000485671500201

View details for DOI 10.1016/j.ijrobp.2019.06.1470

View details for Web of Science ID 000485671501289

View details for DOI 10.1016/j.ijrobp.2019.06.1227

View details for Web of Science ID 000485671501593

View details for DOI 10.1016/j.ijrobp.2019.06.444

View details for Web of Science ID 000485671502476

View details for DOI 10.1016/j.ijrobp.2019.06.2001

View details for Web of Science ID 000485671500531

View details for DOI 10.1016/j.ijrobp.2019.06.1979

View details for Web of Science ID 000485671500509

View details for DOI 10.1016/j.ijrobp.2019.06.1939

View details for Web of Science ID 000485671500568

View details for DOI 10.1016/j.ijrobp.2019.06.2111

View details for Web of Science ID 000485671500441

View details for DOI 10.1016/j.ijrobp.2019.06.1198

View details for Web of Science ID 000485671501662

View details for DOI 10.1016/j.ijrobp.2019.06.2016

View details for Web of Science ID 000485671500446

View details for DOI 10.1016/j.ijrobp.2019.06.2155

View details for Web of Science ID 000485671500386

View details for DOI 10.1016/j.ijrobp.2019.06.2292

View details for Web of Science ID 000485671500227

View details for DOI 10.1016/j.ijrobp.2019.06.142

View details for Web of Science ID 000485671502710

View details for DOI 10.1016/j.ijrobp.2019.06.1200

View details for Web of Science ID 000485671501664

View details for DOI 10.1016/j.ijrobp.2019.06.2248

View details for Web of Science ID 000485671500283

View details for DOI 10.1016/j.ijrobp.2019.06.2134

View details for Web of Science ID 000485671500365

View details for DOI 10.1016/j.ijrobp.2019.06.2250

View details for Web of Science ID 000485671500285

View details for DOI 10.1016/j.ijrobp.2019.06.2271

View details for Web of Science ID 000485671500206

View details for DOI 10.1016/j.ijrobp.2019.06.2323

View details for Web of Science ID 000485671500158

Abstract

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing. Disease stage and smoking history are often used in current clinical trials to select patients for de-intensification therapy, but these features lack sufficient accuracy for predicting disease relapse. Purpose: To develop an imaging signature to assess early response and predict outcomes of OPSCC. Methods: We retrospectively analyzed 162 OPSCC patients treated with concurrent chemoradiotherapy, equally divided into separate training and validation cohorts with similar clinical characteristics. A robust consensus clustering approach was used to spatially partition the primary tumor and involved lymph nodes into subregions (i.e., habitats) based on fluorine 18 (18F) fluorodeoxyglucose (FDG) PET and contrast CT imaging. We proposed quantitative image features to characterize the temporal volumetric change of the habitats and peritumor/nodal tissue between baseline and mid-treatment. The reproducibility of these features was evaluated. We developed an imaging signature to predict progression-free survival (PFS) by fitting an L1-regularized Cox regression model. Results: We identified three phenotypically distinct intratumoral habitats, which were (1) metabolically active and heterogeneous, (2) enhancing and heterogeneous, and (3) metabolically inactive and homogeneous. The final Cox model consisted of four habitat evolution-based features. In both cohorts, this imaging signature significantly outperformed traditional imaging metrics including mid-treatment metabolic tumor volume for predicting PFS, with C-index: 0.72 vs 0.67 (training) and 0.66 vs 0.56 (validation). The imaging signature stratified patients into high-risk vs low-risk groups with 2-year PFS rates: 59.1% vs 89.4% (HR=4.4, 95% CI: 1.4-13.4, training), and 61.4% vs 87.8% (HR=4.6, 95% CI: 1.7-12.1, validation). It remained an independent predictor of PFS in multivariable analysis adjusting for stage, human papillomavirus status, and smoking history. Conclusion: The proposed imaging signature allows more accurate prediction of disease progression and, if prospectively validated, may refine OPSCC patient selection for risk-adaptive therapy.

View details for DOI 10.2967/jnumed.119.230037

View details for PubMedID 31420498

Abstract

There are very few reported cases of stereotactic radiosurgery delivered in children under 3 years of age. We report an 18 month old boy with metastatic recurrence of undifferentiated round cell sarcoma to the brain which was treated with chemotherapy, resection, and robotic frameless stereotactic radiosurgery (SRS). Frameless SRS was delivered without technical difficulties, acute adverse events, or clinical sequelae 1.5 months post-radiation. Longer term follow-up will be needed to evaluate local tumor control and effects on neurocognitive development, endocrine function, and growth. This report adds to the literature of the few reported cases of successfully attempted SRS in very young children.

View details for DOI 10.1080/00207454.2019.1655015

View details for PubMedID 31401906

View details for DOI 10.1016/j.wneu.2019.04.103

View details for Web of Science ID 000475895100024

View details for DOI 10.1093/neuonc/noz126.301

View details for Web of Science ID 000493085900303

View details for DOI 10.1016/j.ijrobp.2019.03.036

View details for Web of Science ID 000471624800037

View details for DOI 10.1177/0194599819832593

View details for Web of Science ID 000473507100011

View details for DOI 10.1158/1538-7445.AM2019-LB-162

View details for Web of Science ID 000488129900353

View details for DOI 10.1158/1538-7445.AM2019-CT205

View details for Web of Science ID 000488129900182

Abstract

Gross total resection (GTR) of large intracranial meningiomas (LIMs) can be challenging and cause significant morbidity and mortality. The aim of this systematic review is to determine the clinical effectiveness and safety of Stereotactic Radiosurgery (SRS) either as primary or adjuvant therapy for LIMs, with tumor 2.5 cm in maximum dimension (tumor volume 8.1 cm3). A total of 452 tumors in 496 patients [350 females (69.3%) and 146 males (30.6%)] with median age 60 years (48 to 65 years) were included. The median tumor volume at the time of diagnosis was 16.7 cm3 (10 to 53.3cm3). The tumors were typically located in the skull-base (77.2%), while only 14.6% were in the supratentorial space. The median follow-up after SRS was 54 months (18-90 months). 87.8% of patients were treated with single session gamma knife radiosurgery (SS GKS), while the remaining 12.1% patients received non-single session (non-SS) GKS. Of 452 LIMs assessed for clinical response, 45.1% showed improvement, and 15.7% deteriorated after SRS. Radiographic tumor control at last follow-up (2-7.5 years) ranged from 84% to 100%. Overall, radiation-induced toxicity occurred in 23% of patients; with the most common adverse effect being cranial nerve neuropathy (5.5%) and peritumoral edema (PTE) (5.3%). Sub-group analysis revealed that there is 2-fold higher likelihood of improvement in clinical symptoms in patients with non-SS GKS than SS GKS [OR: 2.47; 95% (1.38-4.44); p=0.002].SRS is safe and effective in the treatment of LIMs as primary or adjuvant treatment. Further prospective studies are required to validate our results.

View details for DOI 10.1016/j.wneu.2019.06.064

View details for PubMedID 31226450

View details for DOI 10.1016/j.wneu.2019.03.110

View details for Web of Science ID 000469222400177

View details for DOI 10.1093/jnci/djy178

View details for Web of Science ID 000474267400007

View details for DOI 10.1200/JCO.2019.37.15_suppl.2068

View details for Web of Science ID 000487345804449

View details for DOI 10.1200/JCO.2019.37.15_suppl.1503

View details for Web of Science ID 000487345804299

View details for DOI 10.1200/JCO.2019.37.15_suppl.2055

View details for Web of Science ID 000487345804437

View details for DOI 10.1080/13696998.2019.1614933

View details for Web of Science ID 000469585600001

View details for DOI 10.1097/MPA.0000000000001314

View details for Web of Science ID 000480685300015

Abstract

BACKGROUND: There is a lack of literature guiding treatment of giant cell glioblastoma (gcGBM), a rare subtype of glioblastoma (GBM). We used a national hospital-based registry to explore treatment patterns and outcomes associated with gcGBM.METHODS: Adult patients (age 18+) diagnosed with gcGBM or GBM between 2004-2014 were identified from the National Cancer Database (NCDB). Chi-squared analysis and Wilcoxon rank sum testing were used to compare characteristics between the gcGBM and GBM cohorts. Kaplan-Meier statistics, univariable and multivariable Cox regression, and propensity score matching were used to evaluate association between patient, tumor and treatment factors and survival outcomes. Correlation analysis was used to evaluate historical trends in the treatment of gcGBM. Landmark analysis allowed for accounting of immortal time.RESULTS: In total, 683 patients with gcGBM were identified. Patients with gcGBM had improved survival compared to patients with GBM (15.5 months from landmark vs 11.7, p < 0.001). Increased age (p < 0.001) was associated with worse survival while being of female sex (p = 0.023) and having a median income of higher than $63,000 (p = 0.004) predisposed patients to improved outcomes. Patients receiving trimodal therapy (biopsy and/or surgery, radiotherapy, and chemotherapy) experienced better outcomes compared to those receiving either biopsy and/or surgery only or biopsy and/or surgery and radiotherapy without systemic therapy (median survival 17.55 months vs 6.68 months; p < 0.001).CONCLUSION: gcGBM has favorable prognosis compared with GBM and should be aggressively managed with trimodal therapy. Prospective studies on gcGBM are warranted to better characterize gcGBM treatment outcomes.

View details for PubMedID 31009783

View details for DOI 10.1016/S0360-3016(19)30470-5

View details for Web of Science ID 000463350600070

Abstract

PURPOSE: Prognostic biomarkers of disease relapse are needed for risk-adaptive therapy of oropharyngeal cancer (OPC). This work aims to identify an imaging signature to predict distant metastasis in OPC.MATERIALS/METHODS: This single-institution retrospective study included 140 patients treated with definitive concurrent chemoradiotherapy, for whom both pre and mid-treatment contrast-enhanced CT scans were available. Patients were divided into separate training and testing cohorts. Forty-five quantitative image features were extracted to characterize tumor and involved lymph nodes at both time points. By incorporating both imaging and clinicopathological features, a random survival forest (RSF) model was built to predict distant metastasis-free survival (DMFS). The model was optimized via repeated cross-validation in the training cohort, and then independently validated in the testing cohort.RESULTS: The most important features for predicting DMFS were the maximum distance among nodes, maximum distance between tumor and nodes at mid-treatment, and pre-treatment tumor sphericity. In the testing cohort, the RSF model achieved good discriminability for DMFS (C-index=0.73, P=0.008), and further divided patients into two risk groups with different 2-year DMFS rates: 96.7% vs. 67.6%. Similar trends were observed for patients with p16+ tumors and smoking 10 pack-years. The RSF model based on pre-treatment CT features alone achieved lower performance (C-index=0.68, P=0.03).CONCLUSION: Integrating tumor and nodal imaging characteristics at baseline and mid-treatment CT allows prediction of distant metastasis in OPC. The proposed imaging signature requires prospective validation, and if successful, may help identify high-risk HPV-positive patients who should not be considered for de-intensification therapy.

View details for PubMedID 30940529

Abstract

Patients with triple negative breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Competing risks analysis was used to assess the cumulative incidence of breast cancer-specific mortality (BCSM). Multivariable Fine-Gray regression was used to identify predictors of BCSM. Women age 70+ (n=4221) were less likely to receive chemotherapy and radiation treatment (P<0.0001) and had higher BCSM compared to younger women (P<0.0001). There were no differences in BCSM in patients who received adjuvant treatment (P=0.10). Stage II patients derived the greatest relative and absolute benefit from adjuvant treatment. Age was not a significant predictor of BCSM.

View details for DOI 10.1111/tbj.13251

View details for PubMedID 30925635

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are increasingly used together to manage brain metastases (BMs). We assessed adverse radiation effect, disease control, and overall survival in patients with BMs who received SRS with anti-CTLA-4 and/or anti-PD-1/PD-L1 therapies.METHODS: We retrospectively reviewed the records of patients with intact or resected BMs treated with SRS and ICIs within 5 months of SRS between 2010 and 2018. Patients were defined as receiving 'concurrent' SRS and ICI if a dose of ICI was given within 4 weeks of SRS. Local failure (LF), distant intracranial failure (DIF), extracranial failure (EF), and adverse radiation effect (ARE) were assessed using cumulative incidence rates and competing risk regressions with death as a competing risk. Overall survival was assessed using the Kaplan-Meier method and Cox proportional hazards models.RESULTS: A total of 97 patients with 580 BMs were included in our analysis. Competing risk analyses demonstrated that concurrent SRS-ICI therapy is associated with higher rates of ARE (6.4% vs 2.0% at 1 year; multivariable HR 4.47; 95% CI, 1.57-12.73; p=0.005), lower rates of EF (69.7% vs 80.8% at 1 year; multivariable HR 0.60; 95% CI, 0.42-0.87; p=0.007), and better overall survival (48.6% vs 25.4% at 1 year; multivariable HR 0.57; 95% CI, 0.33-0.99; p=0.044) as compared to non-concurrent therapy. SRS-ICI timing was not associated with LF or DIF.CONCLUSIONS: Concurrent SRS-ICI therapy has a tolerable adverse event profile and may improve extracranial disease control and overall survival, supporting concurrent use in the management of BMs.

View details for PubMedID 30902777

Abstract

OBJECTIVE: Most patients with nasopharyngeal carcinoma (NPC) in the United States are diagnosed with stage III-IV disease. Screening for NPC in endemic areas results in earlier detection and improved outcomes. We examined the cost-effectiveness of screening for NPC with plasma Epstein-Barr virus DNA among Asian American men in the United States.STUDY DESIGN: We used a Markov cohort model to estimate discounted life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios for screening as compared with usual care without screening.SETTING: The base case analysis considered onetime screening for 50-year-old Asian American men.SUBJECTS AND METHODS: Confirmatory testing was magnetic resonance imaging and nasopharyngoscopy. Cancer-specific outcomes, health utility values, and costs were determined from cancer registries and the published literature.RESULTS: For Asian American men, usual care without screening resulted in the detection of NPC at stages I, II, III-IVB, and IVC among 6%, 29%, 54%, and 11% of those with cancer, respectively, whereas screening resulted in earlier detection with a stage distribution of 43%, 24%, 32%, and 1%. This corresponded to an additional 0.00055 QALYs gained at a cost of $63 per person: an incremental cost of $113,341 per QALY gained. In probabilistic sensitivity analysis, screening Asian American men was cost-effective at $100,000 per QALY gained in 35% of samples.CONCLUSION: Although screening for NPC with plasma Epstein-Barr virus DNA for 50-year-old Asian American men may result in earlier detection, in this study it was unlikely to be cost-effective. Screening may be reasonable for certain subpopulations at higher risk for NPC, but clinical studies are necessary before implementation.

View details for PubMedID 30832545

View details for DOI 10.1002/cncr.31910

View details for Web of Science ID 000456686000010

View details for DOI 10.1200/JCO.2019.37.4_suppl.92

View details for Web of Science ID 000489107600139

View details for DOI 10.7759/cureus.3918

View details for Web of Science ID 000461367200006

Abstract

PURPOSE:: For patients treated with palliative radiation, we examined the association between life expectancy predictions by radiation oncologists and aggressive end-of-life care.MATERIALS AND METHODS:: We included decedents from a study that assessed the ability of oncologists to predict survival of patients with metastatic cancer who received radiation. We identified patients who died within 12 months of study enrollment to assess accuracy of predictions. Aggressive end-of-life care was defined by the National Quality Forum, ASCO Quality Oncology Practice Initiative metrics, and advanced radiation modalities in the last month of life. Survival predictions were categorized as follows: correct (< 12 months), 12 to 18 months, 18 to 24 months, and more than 24 months. We assessed association between prediction and aggressive end-of-life care using a generalized estimation equation.RESULTS:: Of 489 decedents, we identified 467 encounters with survival estimates. Overall, 156 decedents (32%) met at least one metric of aggressive end-of-life care. Factors associated with aggressive end-of-life care included younger age, female sex, primary cancer diagnosis, no brain metastases, and private insurance. In each encounter when an oncologist predicted survival, 363 predictions (78%) were correct (< 12 months), 54 (11%) incorrectly predicted 12 to 18 months, 27 (6%) predicted 18 to 24 months, and 23 (5%) predicted more than 24 months. Compared with patients who had encounters that had correct survival predictions, patients predicted to live more than 24 months were more likely to meet at least one metric of aggressive end-of-life care (odds ratio, 2.55; 95% CI, 1.09 to 5.99; P = .03).CONCLUSION:: Inaccurate survival predictions by oncologists are associated with more aggressive end-of-life care for patients with advanced cancer.

View details for DOI 10.1200/JOP.18.00516

View details for PubMedID 30620629

Abstract

Avoidance of radiation-induced optic neuropathy (RION) from stereotactic radiosurgery (SRS) requires precise anatomical localization; however, no prior studies have characterized the physiologic motion of the optic chiasm. We measured the extent of chiasm motion and its impact on SRS dose.In this cross-sectional study, serial magnetic resonance imaging was performed in multiple planes in 11 human subjects without optic pathway abnormalities to determine chiasm motion across time. Subsequently, the measured displacement was applied to the hypothetical chiasm dose received in 11 patients treated with SRS to a perichiasmatic lesion.On sagittal images, the average anteroposterior chiasm displacement was 0.51mm (95 % confidence interval [CI] 0.27 - 0.75mm), and the average superior-inferior displacement was 0.48mm (95%CI 0.22 - 0.74mm). On coronal images, the average superior-inferior displacement was 0.42mm (95%CI 0.13 - 0.71mm), and the average lateral displacement was 0.75mm (95%CI 0.42 - 1.08mm). In 11 patients who underwent SRS to a perichiasmatic lesion, the average displacements increased the maximum chiasm dose (Dmax) by a mean of 14 % (range 6 - 23 %; p < 0.001).Average motion of the optic chiasm was approximately 0.50 - 0.75mm, which increased chiasm Dmax by a mean of 14 %. In the occasional patient with higher-than-average chiasm motion in a region of steep dose gradient, the increase in chiasm Dmax and risk of RION could be even larger. Similarly, previously reported chiasm dose constraints may underestimate the true dose received during radiosurgery.To limit the risk of RION, clinicians may consider adding a 0.50 - 0.75mm expansion to the chiasm avoidance structure.

View details for PubMedID 31067077

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

Abstract

Purpose There is growing interest in delivering radiation preoperatively (preopRT) rather than postoperatively (postopRT) for breast cancer. Using the National Cancer Database, we evaluated the use and outcomes of preopRT in breast cancer. Methods We identified adult females diagnosed with non-metastatic breast cancer treated with definitive surgery and radiation between 2004 and 2014. Logistic regression models evaluated factors associated with use of preopRT in early-stage (clinical T1-3/N0-1) and locally advanced (clinical T4/N2-3) disease. Rates of breast-conserving surgery, breast reconstruction, positive surgical margins, and 30-day surgical readmissions were compared between patients receiving preopRT and postopRT. Results Of 373,595 patients who met our inclusion criteria, 1,245 (0.3%) patients received preopRT. Patients receiving preopRT were more likely to be of lower socioeconomic status and have tumors with higher T stage. Younger age and N1 (vs N0) disease predicted for use of preopRT in early-stage disease, while older age and N0 disease predicted for use of preopRT in the locally advanced setting. PreopRT patients were less likely to undergo breast-conserving surgery and more likely to have positive surgical margins. Rates of unplanned readmissions within 30 days of surgery were similar among patients treated with preopRT and postopRT. Conclusions PreopRT is a new treatment strategy for patients with breast cancer with different clinical and sociodemographic drivers of its use in the early-stage and locally advanced settings. We await the results of clinical trials studying the efficacy of this approach.

View details for DOI 10.7759/cureus.5748

View details for PubMedID 31723509

View details for PubMedCentralID PMC6825433

Abstract

Historically, it is stated that large intracranial tumors, herein defined as a maximum dimension of > 3cm or tumor volume >14.2 cm3, are not candidates for Stereotactic Radiosurgery (SRS). We report outcomes of patients with large benign intracranial tumors treated with SRS.With IRB approval, we retrospectively identified 74 patients with large benign intracranial tumors (59 meningiomas, 9 vestibular schwannomas, and 6 glomus jugulare tumors) treated with robotic SRS (2007-2018). Patients received definitive SRS in 47.3% of the cases, adjuvant to surgical resection in 44.6%, and salvage following past radiation treatment in 8.1%. A median tumor volume of 16.0 cm3 (10.1-65.5 cm3) received a median dose of 24.0 Gy (14.0-30.0 Gy) in a median of 3 fractions (1-5), for a median single fraction equivalent dose (SFED) (with alpha/beta of 3) of 14.8 Gy (11.3-18.0 Gy). The Kaplan-Meier estimate of tumor local control (LC) was calculated from date of SRS.With a median clinical follow-up of 32.8 months (0.6-125.9 months) and median radiological follow-up of 28.5 months (0.6-121.4 months), LC was 96.5% (95%CI:92.4-100%) at 3-years and 91.7% (95%CI:87.6-95.7%) at 5-years. Adverse radiation effect (ARE) was seen in 10 patients (13.5%) at a median of 13.5 months (7.8-34.5 months). ARE occurred in 9% of those with prior treatment compared to 5% radiation-nave (p=0.23). With 236.4 person-years of follow-up, no secondary malignancies were seen.Despite the historical adage, we find that SRS provides high rates of LC for these large tumors, with rates of ARE similar to historical reports of SRS for smaller benign tumors.

View details for DOI 10.1016/j.wneu.2019.10.005

View details for PubMedID 31605862

Abstract

For brain metastases, surgical resection with postoperative stereotactic radiosurgery (SRS) is an emerging standard of care. Postoperative cavity SRS is associated with a specific, under-recognized pattern of intracranial recurrence, herein termed nodular leptomeningeal disease (nLMD), which is distinct from classical leptomeningeal disease (cLMD). We hypothesized that there is poor consensus regarding the definition of LMD, and that a formal, self-guided training module will improve inter-rater reliability (IRR) and validity in diagnosing LMD.Twenty-two physicians at 16 institutions, including 15 physicians with central nervous system (CNS) expertise, completed a two-phase survey that included MRI imaging and treatment information for 30 patients. In the "pre-training" phase, physicians labeled cases using 3 patterns of recurrence commonly reported in prospective studies: local recurrence (LR), distant parenchymal recurrence (DR), and LMD. After a self-directed training module, participating physicians completed the "post-training" phase and relabeled the 30 cases using the 4 following labels: LR, DR, cLMD, nLMD.Inter-rater reliability (IRR) increased 34% after training (Fleiss' Kappa K=0.41 to K=0.55, p<0.001). IRR increased most among non-CNS specialists (+58%, p<0.001). Prior to training, IRR was lowest for LMD (K=0.33). After training, IRR increased across all recurrence subgroups and increased most for LMD (+67%). After training, 27% of cases initially labeled LR or DR were later recognized as nLMD.This study highlights the large degree of inconsistency among clinicians in recognizing nLMD. Our findings demonstrate that a brief self-guided training module distinguishing nLMD can significantly improve IRR across all patterns of recurrence, and particularly in nLMD. To optimize outcomes reporting, prospective trials in brain metastases should incorporate central imaging review and investigator training.

View details for DOI 10.1016/j.ijrobp.2019.10.002

View details for PubMedID 31605786

Abstract

We report efficacy and toxicity outcomes with stereotactic radiosurgery (SRS) for intracranial and spinal ependymoma.We analyzed adult and pediatric patients with newly diagnosed or recurrent intracranial or spinal ependymoma lesions treated with SRS at our institution. Following SRS, local failure (LF) was defined as failure within or adjacent to the SRS target volume, while distant failure (DF) was defined as failure outside of the SRS target volume. Time to LF and DF was analyzed using competing risk analysis with death as a competing risk.Overall survival (OS) was calculated from the date of first SRS to the date of death or censored at the date of last follow-up using the Kaplan-Meier method.Twenty-one patients underwent SRS to 40 intracranial (n = 30) or spinal (n = 10) ependymoma lesions between 2007 and 2018, most commonly with 18 or 20 Gy in 1 fraction. Median follow-up for all patients after first SRS treatment was 54 months (range 2-157). The 1-year, 2-year, and 5-year rates of survival among patients with initial intracranial ependymoma were 86, 74, and 52%, respectively. The 2-year cumulative incidences of LF and DF after SRS among intracranial ependymoma patients were 25% (95% CI 11-43) and 42% (95% CI 22-60), respectively. No spinal ependymoma patient experienced LF, DF, or death within 2 years of SRS. Three patients had adverse radiation effects.SRS is a viable treatment option for intracranial and spinal ependymoma with excellent local control and acceptable toxicity.

View details for DOI 10.1159/000502653

View details for PubMedID 31590165

View details for DOI 10.1259/bjr.20190170

View details for Web of Science ID 000472476700013

Abstract

Gastroesophageal junction (GEJ) cancers can be treated with equipoise using neoadjuvant chemoradiation (NACRT) or chemotherapy alone (NAC), but the comparative outcomes are unclear.Patients with non-metastatic T2-4 or N1-3 GEJ adenocarcinoma who underwent definitive surgery and NAC or NACRT were selected from the National Cancer Database. The primary outcome was overall survival (OS). Multivariable regression and propensity score analysis were used to adjust for age, comorbidity, and other characteristics.We identified 2435 patients treated with NACRT and 648 patients treated with NAC. OS was not significantly different between NACRT and NAC (51% versus 54% at 3years, respectively, P=0.11). Extent of pathological downstaging (complete, partial/mixed, none) after NACRT or NAC was highly prognostic of survival. Patients with no response did equally poorly after either preoperative regimen, and NAC was significantly less likely than NACRT to produce any response (adjusted odds ratio 0.62, P<0.0001). Rate of adjuvant chemotherapy usage was significantly lower after NACRT than after NAC (12% versus 34%, P<0.0001). In patients with residual tumor and nodal disease, adjuvant chemotherapy was associated with higher OS after NACRT (adjusted hazard ratio 0.81, P=0.05), but not after NAC. These results were further validated by propensity score analysis.NACRT had similar survival to NAC despite superior pathological downstaging. Adjuvant chemotherapy is relatively underused after NACRT and warrants further study as a risk-adapted means to improve survival, especially in patients with larger burden of residual disease.

View details for DOI 10.1007/s10120-019-00980-6

View details for PubMedID 31230228

Abstract

Randomized control trials and population-based studies do not demonstrate a definitive benefit for adjuvant chemotherapy (ACT) in stage II colon cancer (CC). Tumor sidedness and microsatellite instability (MSI) status may predict response to ACT, but previous studies have limited microsatellite data. We assessed the efficacy of ACT and possible interaction with MSI status and tumor sidedness in patients with resected stage II CC diagnosed between 2010 and 2013 using the National Cancer Database.Overall survival was evaluated with the Kaplan-Meier method and multivariate and propensity score matched Cox proportional hazards models. The interaction between receipt of ACT, MSI status, and tumor sidedness was evaluated. The efficacy of ACT was assessed in patient subgroups by MSI status and tumor sidedness.Among 6964 stage II CC patients with known MSI status, 1497 (21.5%) received ACT, 843 had MSI tumors, and 6121 had microsatellite stable (MSS) tumors. In multivariate and propensity score matched analyses, ACT was associated with improved survival after adjusting for factors including high-risk features, MSI status, and tumor sidedness (multivariate hazard ratio, 0.52; P<0.001). There was no interaction between receipt of ACT and MSI status (P=0.25). Patients with MSS tumors benefitted from ACT (multivariate hazard ratio, 0.47; P<0.001), even without other high-risk features. Patients with MSI tumors did not (P=0.671). ACT was associated with improved survival regardless of tumor sidedness.MSS alone may warrant ACT in stage II CC while patients with MSI tumors may not derive significant benefit from ACT.

View details for DOI 10.1097/COC.0000000000000554

View details for PubMedID 31166206

Abstract

OBJECTIVEStereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have been used as a primary treatment or adjuvant to resection in the management of intracranial meningiomas (ICMs). The aim of this analysis is to compare the safety and long-term efficacy of SRS and SRT in patients with primary or recurrent ICMs.METHODSA systematic review of the literature comparing SRT and SRS in the same study was conducted using PubMed, the Cochrane Library, Google Scholar, and EMBASE from January 1980 to December 2018. Randomized controlled trials, case-control studies, and cohort studies (prospective and retrospective) analyzing SRS versus SRT for the treatment of ICMs in adult patients (age > 16 years) were included. Pooled and subgroup analyses were based on the fixed-effect model.RESULTSA total of 1736 patients from 12 retrospective studies were included. The treatment modality used was: 1) SRS (n = 306), including Gamma Knife surgery (n = 36), linear accelerator (n = 261), and CyberKnife (n = 9); or 2) SRT (n = 1430), including hypofractionated SRT (hFSRT, n = 268) and full-fractionated SRT (FSRT, n = 1162). The median age of patients at the time of treatment was 59 years. The median follow-up duration after treatment was 35.5 months. The median tumor volumes at the time of treatment with SRS, hFSRT, and FSRT were 2.84 cm3, 5.45 cm3, and 12.75 cm3, respectively. The radiographic tumor control at last follow-up was significantly worse in patients who underwent SRS than SRT (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.82, p = 0.007) with 7% less volume of tumor shrinkage (OR 0.93, 95% CI 0.61-1.40, p = 0.72). Compared to SRS, the radiographic tumor control was better achieved by FSRT (OR 0.46, 95% CI 0.26-0.80, p = 0.006) than by hFSRT (OR 0.81, 95% CI 0.21-3.17, p = 0.76). Moreover, SRS leads to a significantly higher risk of clinical neurological worsening during follow-up (OR 2.07, 95% CI 1.06-4.06, p = 0.03) and of immediate symptomatic edema (OR 4.58, 95% CI 1.67-12.56, p = 0.003) with respect to SRT. SRT could produce a better progression-free survival at 4-10 years compared to SRS, but this was not statistically significant (p = 0.29).CONCLUSIONSSRS and SRT are both safe options in the management of ICMs. However, SRT carries a better radiographic tumor control rate and a lower incidence of posttreatment symptomatic worsening and symptomatic edema, with respect to SRS. However, further prospective studies are still needed to validate these results.

View details for DOI 10.3171/2019.3.FOCUS1970

View details for PubMedID 31153149

Abstract

The EF-14 trial demonstrated that adding tumor treating fields (TTFields) to maintenance temozolomide (TMZ) significantly extends progression-free survival (PFS) and overall survival (OS) for newly diagnosed glioblastoma (GBM) patients. We assessed the cost-effectiveness of TTFields and TMZ for newly diagnosed GBM from the U.S. healthcare system perspective.Outcomes for newly diagnosed GBM patients were estimated over a lifetime horizon using an area under the curve model with three states: stable disease, progressive disease, or death. The survival model integrated the 5-year EF-14 trial results with long-term GBM epidemiology data and U.S. background mortality rates. Adverse event rates were derived from the EF-14 trial data. Utility values to determine quality-adjusted life-years, adverse event costs and supportive care costs were obtained from published literature. We applied a 3% discount rate to future costs and outcomes. One-way and probabilistic sensitivity analyses were performed to assess result uncertainty due to parameter variability.Treatment with TTFields and TMZ was estimated to result in a mean increase in survival of 1.25 life years (95% credible range [CR]: 0.89 to 1.67) and 0.96 quality-adjusted life years (QALYs) (95% CR: 0.67 to 1.30) compared to treatment with TMZ alone. The incremental total cost was $188,637 (95% CR: $145,324 to $225,330). The incremental cost-effectiveness ratio (ICER) was $150,452 per life year gained and $197,336 per QALY gained. The model was most sensitive to changes in the cost of TTFields treatment.Adding TTFields to maintenance TMZ resulted in a substantial increase in the estimated mean lifetime survival and quality-adjusted survival for newly diagnosed GBM patients. Treatment with TTFields can be considered cost-effective within the reported range of willingness-to-pay thresholds in the United States.

View details for PubMedID 31050315

Abstract

Background There is increasing concern among healthcare communities about the misinformation online about using cannabis to cure cancer. We have characterized this online interest in using cannabis as a cancer treatment and the propagation of this information on social media. Materials & methods We compared search activity over time for cannabis and cancer versus standard cancer therapies using Google Trends' relative search volume (RSV) tool and determined the impact of cannabis legalization. We classified news on social media about cannabis use in cancer as false, accurate, or irrelevant. We evaluated the cannabis-related social media activities of cancer organizations. Results The online search volume for cannabis and cancer increased at 10 times the rate of standard therapies (RSV 0.10/month versus 0.01/month, p<0.001), more so in states where medical or recreational cannabis is legal. The use of cannabis as a cancer cure represented the largest category (23.5%) of social media content on alternative cancer treatments. The top false news story claiming cannabis as a cancer cure generated 4.26 million engagements on social media, while the top accurate news story debunking this false news generated 0.036 million engagements. Cancer organizations infrequently addressed cannabis (average 0.7 Tweets; 0.4 Facebook posts), with low influence compared to false news (average 5.6 versus 527 Twitter retweets; 98 versus 452,050 Facebook engagements, p<0.001). Conclusions These findings reveal agrowing interest in cannabis use as acancer cure, and a crucial opportunity for physicians and medical organizations to communicate accurate information about the role of cannabis in cancer to patients, caregivers,and the general public.

View details for PubMedID 30931189

View details for PubMedCentralID PMC6426557

Abstract

BACKGROUND: Adherence to endocrine therapy for breast cancer is often inadequate, in part because of out-of-pocket costs for medication. Numerous states have enacted parity laws to limit patient cost-sharing for oral anticancer drugs. The objective of this study was to estimate the impact of these laws on patient copayments for and adherence to oral endocrine therapy for breast cancer.METHODS: Administrative health insurance claims data from 2007 to 2014 derived from a US health care database were used to identify female patients aged 18 to 64 years with invasive cancer or ductal carcinoma in situ of the breast who initiated endocrine therapy and were enrolled in fully insured health plans in states that either enacted parity legislation between 2008 and 2013 or had not yet enacted such legislation by 2015. Differences-in-differences analysis was used to compare copayments for and adherence to endocrine therapy during the 1-year period before and after each year of legislation enactment.RESULTS: In total, 6900 individuals who received 7778 unique drug therapy courses were identified. Parity legislation was associated with significant decreases in the 25th percentile of copayments for anastrozole of $4.39 (95% confidence interval [CI], -$4.52 to -$4.26; P < .001) and for exemestane of $3.08 (95% CI, -$4.80 to -$1.35; P < .001). The median copayment for exemestane decreased by $10.25 (95% CI, -$12.61 to -$7.89; P < .001). A higher median monthly copayment was significantly associated with a greater risk of medication nonadherence (adjusted risk ratio, 1.006 per dollar increase; P < .001).CONCLUSIONS: Parity laws had a modest effect on lowering the cost of anastrozole and exemestane, but more focused efforts to limit out-of-pocket costs for endocrine therapy may have a greater impact on medication adherence.

View details for PubMedID 30566762

View details for DOI 10.1002/ijc.31747

View details for Web of Science ID 000451115900020

View details for DOI 10.1016/j.jpainsymman.2018.08.021

View details for Web of Science ID 000451633700003

View details for DOI 10.1016/j.ijrobp.2018.03.045

View details for Web of Science ID 000447789700063

View details for DOI 10.1016/j.ijrobp.2018.07.425

View details for Web of Science ID 000447811600176

View details for Web of Science ID 000460646300488

View details for Web of Science ID 000460646300486

View details for DOI 10.1016/j.ijrobp.2018.07.815

View details for Web of Science ID 000447811600561

View details for DOI 10.1016/j.ijrobp.2018.07.942

View details for Web of Science ID 000447811600686

View details for DOI 10.1016/j.ijrobp.2018.07.1235

View details for Web of Science ID 000447811601257

View details for DOI 10.1016/j.ijrobp.2018.07.031

View details for Web of Science ID 000447811602596

View details for DOI 10.1016/j.ijrobp.2018.07.1091

View details for Web of Science ID 000447811601118

View details for DOI 10.1016/j.ijrobp.2018.07.888

View details for Web of Science ID 000447811600633

View details for DOI 10.1016/j.ijrobp.2018.06.287

View details for Web of Science ID 000447811602483

View details for DOI 10.1016/j.ijrobp.2018.07.1184

View details for Web of Science ID 000447811601207

View details for DOI 10.1016/j.ijrobp.2018.07.1621

View details for Web of Science ID 000447811601635

Abstract

Background: Oncologists use patients' life expectancy to guide decisions and may benefit from a tool that accurately predicts prognosis. Existing prognostic models generally use only a few predictor variables. We used an electronic medical record dataset to train a prognostic model for patients with metastatic cancer.Methods: The model was trained and tested using 12588 patients treated for metastatic cancer in the Stanford Health Care system from 2008 to 2017. Data sources included provider note text, labs, vital signs, procedures, medication orders, and diagnosis codes. Patients were divided randomly into a training set used to fit the model coefficients and a test set used to evaluate model performance (80%/20% split). A regularized Cox model with 4126 predictor variables was used. A landmarking approach was used due to the multiple observations per patient, with t0 set to the time of metastatic cancer diagnosis. Performance was also evaluated using 399 palliative radiation courses in test set patients.Results: The C-index for overall survival was 0.786 in the test set (averaged across landmark times). For palliative radiation courses, the C-index was 0.745 (95% confidence interval [CI] = 0.715 to 0.775) compared with 0.635 (95% CI = 0.601 to 0.669) for a published model using performance status, primary tumor site, and treated site (two-sided P<.001). Our model's predictions were well-calibrated.Conclusions: The model showed high predictive performance, which will need to be validated using external data. Because it is fully automated, the model can be used to examine providers' practice patterns and could be deployed in a decision support tool to help improve quality of care.

View details for PubMedID 30346554

Abstract

INTRODUCTION: Invasive nodal evaluation (INE) is used to improve staging for early stage non-small cell lung cancer (NSCLC), including when stereotactic ablative radiation (SABR) is used. Consensus guidelines from the NCCN recommend performing INE for patients with T2N0 tumors and considering INE for those with T1N0 tumors. We reasoned that if INE results in significant stage migration in the form of substantially fewer patients with occult nodal involvement, then patients treated with SABR who do not undergo INE should have worse overall survival (OS).METHODS: Patients diagnosed 2004-2014 with stage T1-2N0M0 NSCLC and treated with SABR were identified from the National Cancer Database. Factors associated with INE were determined using mixed effects logistic regression. We tested for an association between INE and OS for patients diagnosed 2004-2013 using mixed effects proportional hazards regression methods.RESULTS: 24,603 SABR patients were identified. 6% of the 19,322 patients with T1 tumors and 9% of the 5281 patients with T2 tumors had INE. Median OS was 2.8 years for the no-INE group and 2.7 years for the INE group (log-rank P=0.69). No significant association was observed between the use of INE and OS in the univariate analysis (HR 1.02, 95% CI 0.94-1.11) or the multivariate analysis (HR 0.94, 95% CI 0.86-1.02). These findings were confirmed using propensity score matched and instrumental variable analysis. On subgroup analysis, INE was associated with a non-significant trend for improved OS in patients with T2 tumors (HR 0.87, 95% CI 0.76-1.00) but not T1 tumors (HR 0.98, 95% CI 0.88-1.09).CONCLUSIONS: Despite current NCCN recommendations, the rate of INE was low for patients with stage T1 or T2 tumors. While omitting INE represents a compromise in the completeness of nodal evaluation, we found that it was not associated with a detriment in overall survival.

View details for PubMedID 30268484

View details for DOI 10.1093/annonc/mdy295.001

View details for PubMedID 32137428

View details for DOI 10.1016/j.clbc.2018.04.020

View details for Web of Science ID 000445702400046

View details for DOI 10.1158/1078-0432.CCR-18-0825

View details for Web of Science ID 000446207700015

View details for DOI 10.1016/j.lungcan.2018.07.033

View details for Web of Science ID 000448100600012

View details for Web of Science ID 000459277303282

View details for PubMedID 30201484

View details for Web of Science ID 000460645600146

View details for DOI 10.1093/neuonc/noy001

View details for Web of Science ID 000438338000014

View details for PubMedID 29893271

View details for DOI 10.1158/1538-7445.AM2018-LB-257

View details for Web of Science ID 000468818900403

Abstract

Purpose: We sought to evaluate whether pathologic nodal response was predictive of outcomes in women aged 40 years with breast cancer treated with neoadjuvant chemotherapy (NAC). Methods: A total of 220 patients treated with NAC between 1991 and 2015 were retrospectively reviewed. Pathologic complete response (pCR) was defined as no evidence of residual invasive tumor in the breast and lymph nodes (LNs) (ypT0/Tis ypN0); partial response if there was no tumor in the LNs but residual tumor in the breast (ypT+ ypN0) or residual tumor in the LNs (ypT0/Tis ypN+); and limited response if there was residual tumor in both the breast and the LNs (ypT+ ypN+). Kaplan-Meier and Cox proportional hazards analyses were performed to identify factors predictive for overall survival (OS). Results: A total of 155 patients were included. Following NAC, 39 patients (25.2%) achieved pCR, 57 (36.8%) achieved a partial response (either ypT+ ypN0 or ypT0/Tis ypN+), and 59 (38.1%) had a limited response. A total of 22 patients (14.2%) experienced local failure, 20 (12.9%) experienced regional failure, and 59 (38.1%) experienced distant failure. Median OS for patients who achieved pCR was not reached, and was significantly worse for patients who had residual disease in the breast and/or LNs (P<.001). No difference in OS was seen among patients who had residual disease in the breast alone versus those who remained LN-positive (97 vs 83 months, respectively; P=.25). Subset analysis did not reveal differences in OS based on year of treatment or cN1 disease at the time of initial diagnosis. Conclusions: Women aged 40 years who achieved pCR had excellent outcomes; however, those who achieved a pathologic response in the LNs but had residual disease in the breast continued to have outcomes similar to those who remained LN-positive.

View details for DOI 10.6004/jnccn.2018.7022

View details for PubMedID 30006427

View details for DOI 10.1200/JCO.2018.78.0403

View details for PubMedID 29945518

Abstract

PURPOSE: Breast cancer is a heterogeneous disease and not all patients respond equally to adjuvant radiotherapy. Predictive biomarkers are needed to select patients who will benefit from the treatment and spare others the toxicity and burden of radiation.EXPERIMENTAL DESIGN: We first trained and tested an intrinsic radiosensitivity gene signature to predict local recurrence after radiotherapy in three cohorts of 948 patients. Next, we developed an antigen processing and presentation-based immune signature by maximizing the treatment interaction effect in 129 patients. To test their predictive value, we matched patients treated with or without radiotherapy in an independent validation cohort for clinicopathologic factors including age, ER status, HER2 status, stage, hormone-therapy, chemotherapy, and surgery. Disease specific survival (DSS) was the primary endpoint.RESULTS: Our validation cohort consisted of 1,439 patients. After matching and stratification by the radiosensitivity signature, patients who received radiotherapy had better DSS than patients who did not in the radiation-sensitive group (hazard ratio [HR]=0.68, P=0.059, n=322), while a reverse trend was observed in the radiation-resistant group (HR=1.53, P=0.059, n=202). Similarly, patients treated with radiotherapy had significantly better DSS in the immuneeffective group (HR=0.46, P=0.0076, n=180), with no difference in DSS in the immunedefective group (HR=1.27, P=0.16, n=348). Both signatures were predictive of radiotherapy benefit (Pinteraction=0.007 and 0.005). Integration of radiosensitivity and immune signatures further stratified patients into three groups with differential outcomes for those treated with or without radiotherapy (Pinteraction=0.003).CONCLUSIONS: The proposed signatures have the potential to select patients who are most likely to benefit from radiotherapy.

View details for PubMedID 29921729

View details for Web of Science ID 000432447200062

View details for Web of Science ID 000432447200042

View details for Web of Science ID 000425489402128

View details for DOI 10.1200/JCO.2018.36.4_suppl.767

View details for Web of Science ID 000436174100741

Abstract

Radiation therapy (RT) remains a critical component of multimodality treatment for medulloblastoma. Traditionally, clinicians strive to start RT within 4-5 weeks of surgery, but the optimal timing after surgery remains unclear.Using the National Cancer Database, we identified pediatric and adolescent patients with medulloblastoma treated with curative-intent surgery, RT, and chemotherapy. Factors associated with early or delayed RT were identified using Pearson chi-squared tests. Overall survival (OS) differences based on RT timing were compared using the Kaplan-Meier estimator with log-rank tests. Patient, tumor, and treatment characteristics associated with OS were analyzed with univariate and multivariate Cox proportional hazard models.Among the 1338 patients analyzed, early RT (defined as initiation 3 weeks after surgery) was associated with younger age, M1-3 disease, and subtotal resection. Patients who initiated RT early had decreased five-year OS compared with patients who initiated RT 3.1-4, 4.1-5, or >5 weeks after surgery (72.5%, 80.5%, 79.4%, and 77.8%, respectively; p=0.019), but there was no significant difference in OS among the latter three groups (p=0.788). On multivariate analysis, early RT versus the 3.1-4-week interval was significantly associated with poorer OS (adjusted HR 1.72; 95% CI 1.19-2.48; p=0.004), while time to RT of >5 weeks but within 90 days of surgery did not adversely impact OS (p=0.563).In this large national database analysis, delaying RT within 90 days of surgery was not associated with inferior outcomes. Although clinical judgment remains paramount, postoperative RT timing should allow for healing and the development of an optimal treatment plan.

View details for PubMedID 29309676

Abstract

Neoadjuvant chemotherapy is used to allow more limited breast surgery without compromising local control. We sought to evaluate nationwide surgical trends in patients with operable breast cancer treated with neoadjuvant chemotherapy and factors associated with surgical type. We used the National Cancer Database to identify 235,339 women with unilateral T1-3N0-3M0 breast cancer diagnosed between 2010 and 2014, and treated with surgery and chemotherapy. Of these, 59,568 patients (25.3%) were treated with neoadjuvant chemotherapy. Rates of pathologic complete response to neoadjuvant chemotherapy increased from 33.3% at the start of the study period in 2010 to 46.3% at the end of the period in 2014 (p=0.02). Rates of breast-conserving surgery changed little, from 37.0% to 40.8% (p=0.22). While rates of unilateral mastectomy decreased from 43.3% to 34.7% (p=0.02) and rates of bilateral mastectomy without immediate reconstruction remained similar (11.7% to 11.5%, p=0.82), rates of bilateral mastectomy with immediate reconstruction rose from 8.0% to 13.1% (p=0.02). Patients who were younger, with private/managed care insurance, and diagnosed in more recent years were more likely to achieve pathologic complete response; however, these same characteristics were associated with receipt of bilateral mastectomy (versus breast-conserving surgery). Additionally, non-Hispanic white race and higher area education attainment were both associated with bilateral mastectomy. These findings did not differ by age or molecular subtype. Further study of non-clinical factors that influence selection of more extensive surgery despite excellent response to neoadjuvant chemotherapy is warranted. This article is protected by copyright. All rights reserved.

View details for PubMedID 29992582

Abstract

To identify patterns of distant failure (DF) in premenopausal women receiving neoadjuvant chemotherapy (NAC) for breast cancer.Premenopausal patients treated with NAC between 2005 and 2015 at a single institution were retrospectively reviewed. Timing and location of local, regional, and distant metastases were described. Predictors for DF and overall survival (OS) were analyzed.Of 225 patients, there were 24 (10.7%) local, 30 (13.3%) regional, and 63 (28.0%) distant recurrences. Cumulative incidence of DF was higher in patients younger than age 40 (P= .01), in those with residual tumor size > 2 cm (P< .0001), in those with positive lymph nodes after NAC (P= .0003), and in those without pathologic complete response (P< .0001). Cumulative incidence of brain metastases was most common in patients with human epidermal growth factor receptor 2 (HER2)-positive disease (P= .05). Time from development of metastatic disease to death varied by breast cancer subtype (P= .019), as did 5-year OS (P= .024). Women with HER2-positive and triple-negative disease had the highest incidence of brain metastases and the shortest time from development of metastases to death. On multivariable analysis, luminal B subtype (P= .025), pathologic complete response (P= .0014), young age (P= .0008), lack of hormone therapy (P<.0001), lymphovascular space involvement (P< .0001), and pathologic size of the primary tumor (P< .0001) were all significant predictors for DF.Patterns of DF after NAC in premenopausal women vary by breast cancer subtype, with DF more common than locoregional failure. Young age remains an independent poor prognostic factor, and OS differs by breast cancer subtype.

View details for PubMedID 29843987

Abstract

Private insurance is associated with better outcomes in multiple common cancers. We hypothesized that insurance status would significantly impact outcomes in primary breast sarcoma (PBS) due to the additional challenges of diagnosing and coordinating specialized care for a rare cancer. Using the National Cancer Database, we identified adult females diagnosed with PBS between 2004 and 2013. The influence of insurance status on overall survival (OS) was evaluated using the Kaplan-Meier estimator with log-rank tests and Cox proportional hazard models. Among a cohort of 607 patients, 67 (11.0%) had Medicaid, 217 (35.7%) had Medicare, and 323 (53.2%) had private insurance. Compared to privately insured patients, Medicaid patients were more likely to present with larger tumors and have their first surgical procedure further after diagnosis. Treatment was similar between patients with comparable disease stage. In multivariate analysis, Medicaid (hazard ratio (HR), 2.47; 95% confidence interval (CI), 1.62-3.77; p < 0.001) and Medicare (HR, 1.68; 95% CI, 1.10-2.57; p=0.017) were independently associated with worse OS. Medicaid insurance coverage negatively impacted survival compared to private insurance more in breast sarcoma than in breast carcinoma (interaction p < 0.001). In conclusion, patients with Medicaid insurance present with later stage disease and have worse overall survival than privately insured patients with PBS. Worse outcomes for Medicaid patients are exacerbated in this rare cancer.

View details for PubMedID 29736143

View details for PubMedCentralID PMC5875066

Abstract

Atypical and malignant meningiomas are far less common than benign meningiomas. As aggressive lesions, they are prone to local recurrence and may lead to decreased survival. Although malignant meningiomas typically are treated with maximal surgical resection and adjuvant radiotherapy (RT), to the authors' knowledge the optimal treatment for atypical lesions remains to be defined. There are limited prospective data in this setting.The National Cancer Data Base was queried to investigate cases of histologically confirmed meningiomas diagnosed from 2004 to 2014. This included 7811 patients with atypical meningiomas (World Health Organization grade 2) and 1936 patients with malignant meningiomas (World Health Organization grade 3); during the same period, a total of 60,345 patients were diagnosed with benign meningiomas (World Health Organization grade 1). Data collected included patient and tumor characteristics, extent of surgical resection, and use of RT. Survival analysis was performed using Kaplan-Meier estimates with the log-rank test of significance and Cox univariate and multivariate regression. Logistic regression was used to determine factors associated with use of RT.The 5-year overall survival rate was 85.5% in patients with benign meningiomas, 75.9% in patients with atypical meningiomas, and 55.4% in patients with malignant meningiomas (P<.0001). In patients with atypical meningiomas, gross (macroscopic) total resection (GTR) and adjuvant RT were found to be associated with significantly improved survival, independently and especially in unison (GTR plus RT: hazard ratio, 0.47; P=.002). On multivariate analysis, the combination of GTR plus RT was found to be the most important factor for improved survival. However, GTR was associated with significantly lower rates of RT use.GTR and adjuvant RT appear to be highly associated with improved survival, independent of other factors, in patients with atypical meningiomas. Cancer 2018;124:734-42. 2017 American Cancer Society.

View details for PubMedID 29131312

Abstract

The optimal time for starting radiation in patients with glioblastoma (GBM) is controversial. We aimed to evaluate postoperative radiotherapy treatment patterns and the impact of timing of radiotherapy on survival outcomes in patients with GBM using a large, national hospital-based registry in the era of Stupp chemoradiation. We performed a retrospective cohort study using the National Cancer Data Base and identified adults with GBM diagnosed between 2010 and 2013 and treated with chemoradiation. We classified time from surgery/biopsy to radiation start into the following categories: <15 days, 15-21 days, 22-28 days, 29-35 days, 36-42 days and >42 days. We assessed the relation between time to radiation start and survival using Cox proportional hazards modeling adjusting for clinically relevant variables that were selected a priori. We used multivariate logistic modeling to determine factors independently associated with receipt of delayed radiation treatment. A total of 12 738 patients met our inclusion criteria after our cohort selection process. The majority of patients underwent either gross total (n = 5270, 41%) or subtotal (n = 4700, 37%) resection, while 2768 patients (22%) underwent biopsy only. Median time from definitive surgery or biopsy to initiation of radiation was 29 days (interquartile range 24-36 days). For patients who had biopsy or subtotal resection, earlier initiation of radiation did not appear to be associated with improved survival. However, among patients who underwent gross total resection, there appeared to be improved survival with early initiation of radiation. Patients who initiated radiation within 15-21 days of gross total resection had improved survival (hazard ratio 0.82, 95% confidence interval 0.69-0.98, P = 0.03) compared with patients who had delayed (>42 days after surgery) radiation. There was also a trend (P = 0.07 to 0.12) for improved survival for patients who initiated radiation within 22-35 days of gross total resection compared with patients who had delayed radiation. Patients who were black, had Medicaid or other government insurance or were not insured, and who lived in metropolitan areas or further away from the treating facility had higher odds of receiving radiation >35 days after gross total resection. Patients who lived in higher income areas had higher odds of receiving radiation within 35 days of a gross total resection. In a large cohort of patients with GBM treated with chemoradiation, our data suggest a survival benefit in initiating radiotherapy within 35 days after gross total resection. Further research is warranted to understand barriers to timely access to optimal therapy.

View details for PubMedID 29432548

View details for DOI 10.1016/j.ijrobp.2017.06.098

View details for Web of Science ID 000411559106163

Abstract

Emerging evidence suggests that extent of lymphovascular space invasion (LVSI) predicts for risk of lymph node metastasis in endometrioid uterine cancers. However, this correlation remains unknown in the setting of uterine serous carcinoma (USC). We sought to examine the association between extent of LVSI and other histopathologic characteristics with risk of nodal metastasis for women with USC.Pathological data from all cases of uterine serous carcinoma between July 1998 to July 2015 at our institution were reviewed. Descriptive, univariate, and multivariate logistic regression analysis of selected pathologic features were performed.88 patients with USC underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy. Surgical staging revealed the following FIGO stage distributions: I (41%), II (8%), III (32%), IV (19%). LVSI was present in 44 (50%) patients. 36 patients (41%) had LN metastases with median number of total nodes removed of 17 (range, 1-49). On univariate analysis, depth of myometrial invasion, LVSI, tumor size, and cervical stromal involvement were significantly associated with nodal involvement. In a multivariate model, LVSI (OR 6.25, 95% CI 2.2-18.0, p<0.01) and cervical stromal involvement (OR 3.33, 95% CI 1.10-10.0, p=0.03) were the only factors that remained significant. Among patients with LVSI-positive disease, extensive LVSI was associated with increased risk of nodal involvement compared to focal LVSI (90% vs 29%, p=0.04).Presence and extent of LVSI, and cervical stromal invasion are important predictors for lymph node metastasis in uterine serous carcinoma.

View details for PubMedID 28709703

View details for PubMedCentralID PMC5605436

View details for DOI 10.1016/j.ijrobp.2017.06.101

View details for Web of Science ID 000411559106166

View details for DOI 10.1016/j.ijrobp.2017.06.830

View details for Web of Science ID 000411559100235

Abstract

Although stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy has become an established standard of care for the treatment of a variety of malignancies, our understanding of normal tissue dose tolerance with extreme hypofractionation remains immature. Since Timmerman initially proposed normal tissue dose constraints for SBRT in the 2008 issue of Seminars of Radiation Oncology, experience with SBRT has grown, and more long-term clinical outcome data have been reported. This article reviews the modern toxicity literature and provides updated clinically practical and useful recommendations of SBRT dose constraints for extracranial sites. We focus on the major organs of the thoracic and upper abdomen, specifically the liver and the lung.

View details for DOI 10.1016/j.semradonc.2017.02.001

View details for PubMedID 28577827

View details for DOI 10.1016/j.ijrobp.2017.02.160

View details for Web of Science ID 000403079100103

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

Abstract

Evaluation of local tumor progression (LP) has typically been defined by contrast-enhanced computed tomography (CT) imaging after stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (PDAC). The purpose of this study is to determine the benefit of adding 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging to CT for LP assessment of PDAC after SBRT.We retrospectively reviewed pretreatment, follow-up images, and outcomes of all patients treated with definitive SBRT for unresectable PDAC between December 2002 and December 2015 at our institution. For each patient, we independently analyzed LP both by CT and by FDG-PET criteria, using the Response Evaluation Criteria In Solid Tumors version 1.1 and the FDG-PET Response Evaluation Criteria In Solid Tumors version 1.0, respectively.Among 206 patients treated with definitive SBRT for unresectable PDAC, we identified 30 with LP on follow-up. Four did not undergo follow-up FDG-PET. Median time to LP after SBRT was 7.5 months (range, 2-25 months). Of the 26 patients with LP who had follow-up FDG-PET, 21 were diagnosed by FDG-PET (80.7%), 14 by CT (53.8%), and 9 by both FDG-PET and CT (34.6%). Use of CT alone revealed only 53.8% of cases of LP detected when FDG-PET and CT were combined. The cumulative incidence of LP, based on competing risk of death, at 1 and 2 years after SBRT was 9.6% and 16.7% by CT and 11% and 29.1% by FDG-PET, respectively.FDG-PET increases the chance of detecting LP of unresectable PDAC after SBRT and can have an important impact on reported outcomes. We recommend obtaining FDG-PET to assess treatment response when evaluating efficacy of SBRT and taking its use into account when comparing clinical data.

View details for DOI 10.1016/j.prro.2016.09.002

View details for PubMedID 28274396

View details for Web of Science ID 000443300500123

Abstract

To characterize the patterns of care and potential barriers to access to care for elderly patients with oral cavity cancer in the adjuvant setting.We performed a retrospective cohort study using the National Cancer Data Base and identified patients with resected oral cavity squamous cell carcinoma diagnosed between 2004 and 2012, who survived for 3months after surgery. We used logistic regression models to assess the association between age (<70, 70-79, and 80years) and the receipt of adjuvant therapy within 3months of surgery. We additionally assessed the association between patient and tumor characteristics and the receipt of adjuvant therapy among those aged 70years.A total of 25,829 patients were included in the study. Compared with those aged <70years, older patients were more likely to have no neck dissection or have fewer lymph nodes dissected and were less likely to receive adjuvant therapy than younger patients. Among our cohort, 11,361 patients (44%) had pathologic T3-T4 disease or N2-N3 disease, and 4185 patients (16%) had extracapsular nodal extension or positive surgical margins. In multivariate analyses controlling for comorbidity and demographic characteristics, older age was independently associated with lower odds of receiving adjuvant radiation therapy in the subgroup with T3 or T4 disease or N2 or N3 disease and adjuvant chemoradiation therapy in the positive extracapsular nodal extension or positive surgical margin subgroup. Among elderly patients, both greater patient distance from reporting facility and older age were associated with lower odds of receiving both adjuvant radiation therapy (odds ratio 0.66; 95% confidence interval, 0.55-0.81) and chemoradiation therapy (odds ratio 0.56; 95% confidence interval, 0.40-0.79).In a national hospital-based cohort of patients with oral cavity cancer, elderly patients were less likely to receive adjuvant radiation or chemoradiation therapy. Greater patient distance from reporting facility, in addition to older age, was associated with lower odds of receiving both adjuvant radiation therapy and adjuvant chemoradiation therapy.

View details for DOI 10.1016/j.ijrobp.2017.01.224

View details for PubMedID 28366574

Abstract

We examined the impact of intensity modulated radiation therapy (IMRT) on hospitalization rates in the Surveillance, Epidemiology, and End Results (SEER)-Medicare population with anal squamous cell carcinoma (SCC).We performed a retrospective cohort study using the SEER-Medicare database. We identified patients with nonmetastatic anal SCC diagnosed between 2001 and 2011 and treated with chemoradiation therapy. We assessed the relation between IMRT and first hospitalization by use of a multivariate competing-risk model, as well as instrumental variable analysis, using provider IMRT affinity as our instrument.Of the 1165 patients included in our study, 458 (39%) received IMRT. IMRT use increased over time and was associated more with regional and provider characteristics than with patient characteristics. The 3- and 6-month cumulative incidences of first hospitalization were 41.9% (95% confidence interval [CI], 37.3%-46.4%) and 47.6% (95% CI, 43.0%-52.2%), respectively, for the IMRT cohort and 46.7% (95% CI, 43.0%-50.4%) and 52.1% (95% CI, 48.4%-55.7%), respectively, for the non-IMRT cohort.IMRT was associated with a decreased hazard of first hospitalization compared with 3-dimensional radiation techniques (hazard ratio, 0.70; 95% CI, 0.58-0.84; P=.0002).Instrumental variable analysis suggested an even greater reduction in hospitalizations with IMRT after controlling for unmeasured confounders. There was a trend toward improved overall survival with IMRT, with an adjusted hazard ratio of 0.77 (95% CI, 0.59-1.00; P=.05).The use of IMRT is associated with reduced hospitalizations in elderly patients with anal SCC. Further work is warranted to understand the long-term health and cost impact of IMRT, particularly for patient subgroups most at risk of toxicity and hospitalization.

View details for DOI 10.1016/j.ijrobp.2017.01.006

View details for PubMedID 28258896

Abstract

Purpose To assess the cost-effectiveness of stereotactic body radiation therapy (SBRT) versus radiofrequency ablation (RFA) for patients with inoperable localized hepatocellular carcinoma (HCC) who are eligible for both SBRT and RFA. Materials and Methods A decision-analytic Markov model was developed for patients with inoperable, localized HCC who were eligible for both RFA and SBRT to evaluate the cost-effectiveness of the following treatment strategies: (a) SBRT as initial treatment followed by SBRT for local progression (SBRT-SBRT), (b) RFA followed by RFA for local progression (RFA-RFA), (c) SBRT followed by RFA for local progression (SBRT-RFA), and (d) RFA followed by SBRT for local progression (RFA-SBRT). Probabilities of disease progression, treatment characteristics, and mortality were derived from published studies. Outcomes included health benefits expressed as discounted quality-adjusted life years (QALYs), costs in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analysis was performed to assess the robustness of the findings. Results In the base case, SBRT-SBRT yielded the most QALYs (1.565) and cost $197 557. RFA-SBRT yielded 1.558 QALYs and cost $193 288. SBRT-SBRT was not cost-effective, at $558 679 per QALY gained relative to RFA-SBRT. RFA-SBRT was the preferred strategy, because RFA-RFA and SBRT-RFA were less effective and more costly. In all evaluated scenarios, SBRT was preferred as salvage therapy for local progression after RFA. Probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100 000 per QALY gained, RFA-SBRT was preferred in 65.8% of simulations. Conclusion SBRT for initial treatment of localized, inoperable HCC is not cost-effective. However, SBRT is the preferred salvage therapy for local progression after RFA. () RSNA, 2017 Online supplemental material is available for this article.

View details for DOI 10.1148/radiol.2016161509

View details for PubMedID 28045603

Abstract

The benefits of radiotherapy for inoperable biliary tract cancer remain unclear due to the lack of randomized data. We evaluated the impact of radiotherapy on survival in elderly patients using the SEER-Medicare database. Patients in the SEER-Medicare database with inoperable biliary tract tumors diagnosed between 1998 and 2011 were included. We used multivariate logistic regression to evaluate factors associated with treatment selection, and multivariate Cox regression and propensity score matching to evaluate treatment selection in relation to subsequent survival. Of the 2343 patients included, 451 (19%) received radiotherapy within 4months of diagnosis. The use of radiotherapy declined over time, and was influenced by receipt of chemotherapy and patient age, race, marital status, poverty status, and tumor stage and type. Median survival was 9.3 (95% CI 8.7-9.7) months among patients who did not receive radiation and 10.0 (95% CI 9.1-11.3) months among those who received radiation, conditional on having survived 4months. In patients who received chemotherapy (n=1053), receipt of radiation was associated with improved survival, with an adjusted hazard ratio of 0.82 (95% 0.70-0.97, P=0.02). In patients who did not receive chemotherapy (n=1290), receipt of radiation was not associated with improved survival, with an adjusted hazard ratio of 1.09 (95% 0.91-1.30, P=0.34). Propensity-scored matched analyses showed similar results. Despite the survival benefit associated with the addition of radiotherapy to chemotherapy, the use of radiation for unresectable biliary tract cancers has declined over time.

View details for DOI 10.1002/cam4.975

View details for PubMedID 27891822

View details for DOI 10.1016/j.ijrobp.2017.06.1063

Abstract

Drivers of variation in the cost of care after chemoradiotherapy for the management of anal squamous cell carcinoma (SCC) have not been fully elucidated. We sought to characterize the direct and indirect impact of radiotherapy modality on health care costs among patients with anal SCC.A retrospective cohort study was performed using the 2014 linkage of the SEER-Medicare database. We identified 1,025 patients with anal SCC diagnosed between 2001 and 2011 and treated with chemoradiotherapy. Propensity score matching was used to balance baseline differences between patients treated with intensity-modulated radiotherapy (IMRT) and those treated with three-dimensional conformal radiotherapy (3D-CRT). Differences in total, cancer-attributable, and procedure-specific costs between groups were measured.Radiation-related, patient out-of-pocket, and total costs in the 1-year period after radiotherapy start were all higher for the IMRT group than the 3D-CRT group (median total cost, $35,890 v $27,262, respectively; P < .001). Patients who received IMRT had lower cumulative costs associated with urgent hospitalizations and emergency department visits at both 9 months and 1 year after treatment start compared with a matched cohort of patients who received 3D-CRT (median, $711 v $4,957 at 1 year, respectively; P = .021).Although total costs of care were higher for IMRT compared with 3D-CRT, primarily as a result of higher radiotherapy-specific costs, IMRT was associated with decreased unplanned health care utilization costs starting at 9 months after treatment start. Radiotherapy-centered episodes of care may need to encompass a longer time horizon to capture the full cost savings associated with more advanced radiation modalities.

View details for DOI 10.1200/JOP.2017.024810

View details for PubMedID 29035618

Abstract

Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with a median survival of less than 2years despite the standard of care treatment of 6weeks of chemoradiotherapy. We review the data investigating hypofractionated radiotherapy (HFRT) in the treatment of newly diagnosed GBM.Investigators have explored alternative radiotherapy strategies that shorten treatment duration with the goal of similar or improved survival while minimizing toxicity. HFRT over 1-3weeks is already a standard of care for patients with advanced age or poor performance status. For young patients with good performance status, HFRT holds the promise of radiobiologically escalating the dose and potentially improving local control while maintaining quality of life. Through the use of shorter radiotherapy fractionation regimens coupled with novel systemic agents, improved outcomes for patients with GBM may be achieved.

View details for PubMedID 28735440

Abstract

The addition of PCV (procarbazine, lomustine, vincristine) chemotherapy to radiotherapy (RT) for patients with high-risk ( 40 years old or sub-totally resected) low-grade glioma (LGG) results in an absolute median survival benefit of over 5 years. We evaluated the cost-effectiveness of this treatment strategy.A decision tree with an integrated three-state Markov model was created to follow patients with high risk LGG after surgery treated with RT vs. RT+PCV. Patients existed in one of 3 health states: stable, progressive, and dead. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Analysis was conducted from the healthcare perspective. Deterministic and probabilistic sensitivity analysis explored uncertainty in model parameters.Modeled outcomes demonstrated agreement with clinical data in expected benefit of addition of PCV to RT. The addition of PCV to RT yielded an incremental benefit of 4.77 quality-adjusted life-years (QALYs) (9.94 for RT+PCV vs. 5.17 for RT alone) at an incremental cost of $48,635 ($188,234 for RT+PCV vs. $139,598 for RT alone), resulting in an incremental cost-effectiveness ratio of $10,186 per QALY gained. Probabilistic sensitivity analysis demonstrates that within modeled distributions of parameters, RT+PCV has 99.96% probability of being cost-effectiveness at a willingness-to-pay threshold of $100,000 per QALY.The addition of PCV to RT is a cost-effective treatment strategy for patients with high-risk LGG.

View details for PubMedID 28666368

Abstract

Stereotactic ablative radiation therapy (SABR) is an established treatment for selected lung tumors. Sinoatrial node (SAN) toxicity after thoracic SABR has not been reported in the literature. We sought to understand the risk of SAN toxicity owing to incidental dose to the SAN from SABR.We conducted a retrospective review of patients with early-stage lung cancer or limited pulmonary metastases who underwent thoracic SABR to a right-sided central lung tumor (within 2 cm of the mainstem bronchus or other mediastinal structures) between January 2008 and December 2014, analyzed a subset whose treatment imparted dose to the SAN exceeding 10% of the prescription dose, and examined patient and treatment dosimetric characteristics. Mean follow-up interval was 28 months. Time to toxicity was defined from start of SABR.Of 47 patients with central tumors in the right lung treated with SABR reviewed, 13 met our study criteria. A contouring atlas of regional cardiac anatomy was created. One patient treated with SABR for non-small cell lung cancer at the right hilum developed symptomatic sick sinus syndrome, requiring pacemaker placement 6 months after treatment. Her acute presentation and short interval between SABR and onset of symptoms suggest that SAN toxicity was likely due to radiation-induced injury. Both her age and mean dose to her SAN were the third highest in our cohort. She remained free from cancer progression at 24 months' follow-up. Twelve additional patients who received significant dose to the SAN from SABR did not develop toxicity.While uncommon, SAN toxicity from SABR to right-sided central thoracic tumors should be recognized and followed in future studies.

View details for PubMedID 28669706

Abstract

Alternative treatment regimens are needed for patients with non-small cell lung cancer (NSCLC) who cannot receive definitive treatment with concurrent chemoradiotherapy, surgery, or stereotactic ablative radiotherapy (SABR).We report survival, patterns of failure and toxicity outcomes for patients with NSCLC who were not eligible for surgical resection, concurrent chemoradiotherapy, or SABR and underwent hypofractionated intensity-modulated radiotherapy (IMRT). Kaplan-Meier survival analysis was used to evaluate the progression-free and overall survival. Competing risk analysis was used to evaluate in-field, locoregional, and distant failure.A total of 42 patients treated to 52.5 to 60 Gy in 15 fractions were included. Most of the patients had metastatic or recurrent disease (64%) and a relatively large, centrally located tumor burden (74%). The median follow-up period was 13 months (interquartile range, 6-18 months). All patients received the total prescribed dose. The median survival was 15.1 months. The overall and progression-free survival rates at 1 year were 63% and 22.5%, respectively. The pattern of failure was predominantly distant, with only 2% of patients experiencing isolated in-field recurrence. The cumulative incidence of in-field failure at 6 and 12 months was 2.5% (95% confidence interval, 0.4%-15.6%) and 16.1% (95% confidence interval, 7.5%-34.7%), respectively. The risk of esophageal toxicity was associated with the esophageal mean dose, maximal point dose, and dose to the 5 cm(3) volume. The risk of pneumonitis was associated with the lung mean dose and volume receiving 18 Gy.Hypofractionated IMRT without concurrent chemotherapy provides favorable rates of local control and survival for well-selected patients with NSCLC who cannot tolerate standard definitive therapy.

View details for DOI 10.1016/j.cllc.2016.05.024

View details for PubMedID 27378172

Abstract

Prognostic metabolic imaging indices are needed for risk stratification for patients with locally advanced oropharyngeal cancer.We retrospectively examined pretreatment and midtreatment fluorodeoxyglucose-positron emission tomography (FDG-PET) parameters in patients with locally advanced oropharyngeal cancer who were treated with definitive chemoradiation.A total of 74 patients were evaluated. Pretreatment metabolic tumor volume (MTV) using threshold of 50% standardized uptake value (SUV) maximum (MTV50% ) was associated with progression-free survival (PFS; p = .003; hazard ratio [HR] = 1.57 per 10 cc; 95% confidence interval [CI] = 1.17-2.11) and overall survival (OS; p = .01; HR = 1.36 per 10 cc; 95% CI = 1.07-1.74). Midtreatment MTV using a threshold of SUV 2.0 (MTV2.0 ) was associated with PFS (p < .001; HR = 1.24 per 10 cc; 95% CI = 1.10-1.39) and OS (p = .009; HR = 1.21 per 10 cc; 95% CI = 1.05-1.39). Nodal total lesion glycolysis (TLG) velocity >5% decrease/week was associated with improved PFS (p = .04; HR = 0.37; 95% CI = 0.15-0.95).Metabolic response during chemoradiation is associated with survival in locally advanced oropharyngeal cancer and may aid with risk-adapting treatment. 2016 Wiley Periodicals, Inc. Head Neck, 2016.

View details for DOI 10.1002/hed.24454

View details for PubMedID 27043927

View details for DOI 10.1016/j.ijrobp.2016.06.1692

View details for Web of Science ID 000387655803354

View details for DOI 10.1016/j.ijrobp.2016.06.1915

View details for Web of Science ID 000387655803571

View details for DOI 10.1016/j.ijrobp.2016.06.938

View details for Web of Science ID 000387655802337

View details for Web of Science ID 000387655802500

View details for Web of Science ID 000387655802386

View details for Web of Science ID 000387655802501

Abstract

Pelvic lymphadenectomy in early-stage endometrial cancer is controversial, but the findings influence prognosis and treatment decisions. Noninvasive tools to identify women at high risk of lymph node metastasis can assist in determining the need for lymph node dissection and adjuvant treatment for patients who do not have a lymph node dissection performed initially. A retrospective review of surgical pathology was conducted for endometrioid endometrial adenocarcinoma at our institution. Univariate and multivariate logistic regression analysis of selected pathologic features were performed. A nomogram to predict for lymph node metastasis was constructed. From August 1996 to October 2013, 296 patients underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy for endometrioid endometrial adenocarcinoma. Median age at surgery was 62.7 yr (range, 24.9-93.6 yr). Median number of lymph nodes removed was 13 (range, 1-72). Of all patients, 38 (12.8%) had lymph node metastases. On univariate analysis, tumor size 4 cm, grade, lymphovascular space involvement, cervical stromal involvement, adnexal or serosal or parametrial involvement, positive pelvic washings, and deep (more than one half) myometrial invasion were all significantly associated with lymph node involvement. In a multivariate model, lymphovascular space involvement, deep myometrial invasion, and cervical stromal involvement remained significant predictors of nodal involvement, whereas tumor size of 4 cm was borderline significant. A lymph node predictive nomogram was constructed using these factors. Our nomogram can help estimate risk of nodal disease and aid in directing the need for additional surgery or adjuvant therapy in patients without lymph node surgery. Lymphovascular space involvement is the most important predictor for lymph node metastases, regardless of grade, and should be consistently assessed.

View details for DOI 10.1097/PGP.0000000000000246

View details for PubMedID 26598977

Abstract

To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis.In this institutional review board-approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT (18)F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162 robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy.The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6).Quantitative analysis identified novel (18)F-fluorodeoxyglucose positron emission tomography image features that showed improved prognostic value over conventional imaging metrics. If validated in large, prospective cohorts, the new prognostic signature might be used to identify patients for individualized risk-adaptive therapy.

View details for DOI 10.1016/j.ijrobp.2016.04.034

View details for PubMedID 27511850

View details for DOI 10.1200/JCO.2016.34.15_suppl.e18082

View details for Web of Science ID 000404711503222

Abstract

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

View details for DOI 10.1200/JCO.2015.62.9105

View details for PubMedID 26351332

View details for DOI 10.1016/j.ijrobp.2015.12.343

View details for Web of Science ID 000371581900289

View details for DOI 10.1158/1538-7445.SABCS15-P6-11-01

View details for Web of Science ID 000375622403068

Abstract

To determine if pretreatment nutritional status and inflammatory markers correlate with survival in patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiotherapy (SBRT).We retrospectively reviewed 208 patients with newly diagnosed, locally advanced pancreatic adenocarcinoma treated with SBRT at our institution from 2002 to 2014. Laboratory values were collected before SBRT, including hemoglobin, platelets, albumin, red blood cell, white blood cell, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and tumor markers CA 19-9 and CEA. Patients were followed every 3 months with computed tomography (CT) and/or positron emission tomography-CT imaging to monitor for local recurrence and overall survival (OS).Median follow-up after SBRT was 7.5 months (interquartile range, 4.6 to 12.0 mo) for all patients. Median OS for patients with NLR>5 compared with NLR5 was 6.9 and 8.5 months, respectively (P=0.0057). On univariate analysis, receipt of chemotherapy (P=0.05, hazard ratio [HR]=0.69), increased albumin (P=0.002, HR=0.64), increased red blood cell (P=0.05, HR=0.75), increased lymphocyte count (P=0.002, HR=0.66), decreased CEA (P=0.01, HR=0.96), and NLR5 (P=0.01, HR=0.65) correlated with improved OS. On multivariate analysis, higher albumin (P=0.03, HR=0.70), receipt of chemotherapy (P=0.007, HR=0.56), and NLR5 (P=0.02, HR=0.66) correlated with better survival.Preradiotherapy low albumin levels and NLR>5 correlate with decreased survival in patients with locally advanced pancreatic adenocarcinoma treated with SBRT, indicating the prognostic value of systemic inflammatory markers (such as NLR) and a role of nutritional supplementation to improve outcomes in these patients. Further investigation is warranted.

View details for PubMedID 26757436

Abstract

Electronic data collection is increasingly used for quality of life (QOL) assessments in the field of oncology. It is important to assess the feasibility of these new data capture technologies.Patients at our institution who were 18years or older with a pathological diagnosis of head and neck cancer were prospectively enrolled. Each patient completed two questionnaires [EORTC-QLQ-C30 and EORTC-QLQ-H&N35] administered on a touch-screen tablet device (iPad) at initial consult, during treatment, at the completion of treatment and at each subsequent follow up visit for one year after treatment.A total of 50 patients were included in this study. Although all patients completed the surveys at the initial consult, 86% of initially enrolled patients completed surveys at the end of radiation treatment, and 48% of initially enrolled patients completed surveys by the fourth follow-up visit. Average time to complete the survey for all patients over all time points was 9.8min (standard deviation 6.1). Age as a continuous variable was significantly associated with time for survey completion (p<0.001), with older age associated with longer survey completion times.QOL assessment using tablet devices in head and neck cancer patients is feasible, but may be more challenging in elderly patients. Patients 70years old may benefit from more assistance with electronic forms and should be allotted more time for completing tablet-based QOL surveys.

View details for DOI 10.1016/j.oraloncology.2015.10.003

View details for PubMedID 26475062

View details for DOI 10.1016/j.ijrobp.2015.07.219

View details for Web of Science ID 000373215301878

View details for DOI 10.1016/j.ijrobp.2015.07.1228

View details for Web of Science ID 000373215300670

View details for DOI 10.1016/j.ijrobp.2015.07.017

View details for Web of Science ID 000373215301679

View details for DOI 10.1200/jco.2015.33.29_suppl.201

View details for Web of Science ID 000378107000196

Abstract

Vismodegib is a targeted agent recently approved for treating patients who develop recurrent or locally advanced basal cell carcinoma (BCC), and will inevitably be integrated into existing therapy for advanced BCC as it becomes increasingly used. Improved understanding of how vismodegib interacts with other treatment modalities, including radiotherapy, would help optimize multidisciplinary therapy and clinical outcomes.We report 2 cases of recurrent, advanced BCC treated from April 1, 2012, through October 31, 2014, with concurrent radiotherapy and vismodegib. Concurrent treatment appeared to be well tolerated and efficacious, with both patients having no evidence of progressive disease at last follow-up.We found that the combination of vismodegib and radiotherapy is feasible for patients with recurrent or locally advanced BCC and that combined use of currently available therapies for advanced BCC warrants further prospective study.

View details for DOI 10.1001/jamadermatol.2015.0326

View details for PubMedID 25874733

Abstract

This article focuses on the management of locally advanced pancreatic cancer, which should be treated as a distinct entity separate from metastatic disease and borderline resectable disease. Although the role, timing, and sequencing of radiation relative to systemic therapy in this disease are controversial, an emerging treatment paradigm involves induction chemotherapy, followed by consolidative chemoradiation in patients who do not progress. In addition, new chemotherapy regimens as well as novel radiosensitizers have shown promise and need to be tested further in the locally advanced setting. Advances in radiotherapy have enabled stereotactic body radiotherapy and should continue to be prospectively evaluated.

View details for DOI 10.1016/j.hoc.2015.04.005

View details for PubMedID 26226908

Abstract

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

View details for DOI 10.1016/j.ijrobp.2015.02.016

View details for Web of Science ID 000355636800018

Abstract

This study aims to identify novel prognostic imaging biomarkers in locally advanced pancreatic cancer (LAPC) using quantitative, high-throughput image analysis.86 patients with LAPC receiving chemotherapy followed by SBRT were retrospectively studied. All patients had a baseline FDG-PET scan prior to SBRT. For each patient, we extracted 435 PET imaging features of five types: statistical, morphological, textural, histogram, and wavelet. These features went through redundancy checks, robustness analysis, as well as a prescreening process based on their concordance indices with respect to the relevant outcomes. We then performed principle component analysis on the remaining features (number ranged from 10 to 16), and fitted a Cox proportional hazard regression model using the first 3 principle components. Kaplan-Meier analysis was used to assess the ability to distinguish high versus low-risk patients separated by median predicted survival. To avoid overfitting, all evaluations were based on leave-one-out cross validation (LOOCV), in which each holdout patient was assigned to a risk group according to the model obtained from a separate training set.For predicting overall survival (OS), the most dominant imaging features were wavelet coefficients. There was a statistically significant difference in OS between patients with predicted high and low-risk based on LOOCV (hazard ratio: 2.26, p<0.001). Similar imaging features were also strongly associated with local progression-free survival (LPFS) (hazard ratio: 1.53, p=0.026) on LOOCV. In comparison, neither SUVmax nor TLG was associated with LPFS (p=0.103, p=0.433) (Table 1). Results for progression-free survival and distant progression-free survival showed similar trends.Radiomic analysis identified novel imaging features that showed improved prognostic value over conventional methods. These features characterize the degree of intra-tumor heterogeneity reflected on FDG-PET images, and their biological underpinnings warrant further investigation. If validated in large, prospective cohorts, this method could be used to stratify patients based on individualized risk.

View details for DOI 10.1118/1.4925593

View details for PubMedID 26128895

Abstract

To predict response to radiation treatment using computational FDG-PET and CT images in locally advanced head and neck cancer (HNC).68 patients with State III-IVB HNC treated with chemoradiation were included in this retrospective study. For each patient, we analyzed primary tumor and lymph nodes on PET and CT scans acquired both prior to and during radiation treatment, which led to 8 combinations of image datasets. From each image set, we extracted high-throughput, radiomic features of the following types: statistical, morphological, textural, histogram, and wavelet, resulting in a total of 437 features. We then performed unsupervised redundancy removal and stability test on these features. To avoid over-fitting, we trained a logistic regression model with simultaneous feature selection based on least absolute shrinkage and selection operator (LASSO). To objectively evaluate the prediction ability, we performed 5-fold cross validation (CV) with 50 random repeats of stratified bootstrapping. Feature selection and model training was solely conducted on the training set and independently validated on the holdout test set. Receiver operating characteristic (ROC) curve of the pooled Result and the area under the ROC curve (AUC) was calculated as figure of merit.For predicting local-regional recurrence, our model built on pre-treatment PET of lymph nodes achieved the best performance (AUC=0.762) on 5-fold CV, which compared favorably with node volume and SUVmax (AUC=0.704 and 0.449, p<0.001). Wavelet coefficients turned out to be the most predictive features. Prediction of distant recurrence showed a similar trend, in which pre-treatment PET features of lymph nodes had the highest AUC of 0.705.The radiomics approach identified novel imaging features that are predictive to radiation treatment response. If prospectively validated in larger cohorts, they could aid in risk-adaptive treatment of HNC.

View details for DOI 10.1118/1.4925515

View details for PubMedID 26128812

View details for Web of Science ID 000358036901362

Abstract

The role of surveillance studies in limited-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been well defined. We sought to evaluate the use of imaging (computed tomography [CT] and positron emission tomography [PET]-CT) scans and lactate dehydrogenase (LDH) in surveillance of patients with stage I to II DLBCL.A retrospective analysis was performed of patients who received definitive treatment between 2000 and2013.One hundred sixty-two consecutive patients with stage I to II DLBCL were treated with chemotherapy +/- rituximab, radiation, or combined modality therapy. The 5-year rates of overall survival (OS) and freedom from progression (FFP) were 81.2% and 80.8%, respectively. Of the 162 patients, 124 (77%) were followed up with at least 1 surveillance PET scan beyond end-of-treatment scans; of those, 94 of 124 (76%) achieved a complete metabolic response on PET scan after completion of chemotherapy, and this was associated with superior FFP (P=.01, HR=0.3) and OS (P=.01, HR 0.3). Eighteen patients experienced relapse after initial response to therapy. Nine relapses were initially suspected by surveillance imaging studies (8PET, 1 CT), and 9 were suspected clinically (5 by patient-reported symptoms and 4 by symptoms and physical examination). No relapses were detected by surveillance LDH. The median duration from initiation of treatment to relapse was 14.3months among patients with relapses suspected by imaging, and 59.8months among patients with relapses suspected clinically (P=.077). There was no significant difference in OS from date of first therapy or OS after relapse between patients whose relapse was suspected by imaging versus clinically. Thirteen of 18 patients underwent successful salvage therapy after relapse.A complete response on PET scan immediately after initial chemotherapy is associated with superior FFP and OS in stage I to II DLBCL. The use of PET scans as posttreatment surveillance is not associated with a survival advantage. LDH is not a sensitive marker for relapse. Our results argue for limiting the use of posttreatment surveillance in patients with limited-stage DLBCL.

View details for DOI 10.1016/j.ijrobp.2015.01.039

View details for PubMedID 25863757

View details for DOI 10.1200/jco.2015.33.3_suppl.433

View details for Web of Science ID 000356883800431

Abstract

Data guiding selection of nonsurgical treatment of hepatocellular carcinoma (HCC) are lacking. We therefore compared outcomes between stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) for HCC.From 2004 to 2012, 224 patients with inoperable, nonmetastatic HCC underwent RFA (n = 161) to 249 tumors or image-guided SBRT (n = 63) to 83 tumors. We applied inverse probability of treatment weighting to adjust for imbalances in treatment assignment. Freedom from local progression (FFLP) and toxicity were retrospectively analyzed.RFA and SBRT groups were similar with respect to number of lesions treated per patient, type of underlying liver disease, and tumor size (median, 1.8 v 2.2 cm in maximum diameter; P = .14). However, the SBRT group had lower pretreatment Child-Pugh scores (P = .003), higher pretreatment alpha-fetoprotein levels (P = .04), and a greater number of prior liver-directed treatments (P < .001). One- and 2-year FFLP for tumors treated with RFA were 83.6% and 80.2% v 97.4% and 83.8% for SBRT. Increasing tumor size predicted for FFLP in patients treated with RFA (hazard ratio [HR], 1.54 per cm; P = .006), but not with SBRT (HR, 1.21 per cm; P = .617). For tumors 2 cm, there was decreased FFLP for RFA compared with SBRT (HR, 3.35; P = .025). Acute grade 3+ complications occurred after 11% and 5% of RFA and SBRT treatments, respectively (P = .31). Overall survival 1 and 2 years after treatment was 70% and 53% after RFA and 74% and 46% after SBRT.Both RFA and SBRT are effective local treatment options for inoperable HCC. Although these data are retrospective, SBRT appears to be a reasonable first-line treatment of inoperable, larger HCC.

View details for DOI 10.1200/JCO.2015.61.4925

View details for PubMedID 26628466

Abstract

We report updated outcomes of single- versus multifraction stereotactic body radiation therapy (SBRT) for unresectable pancreatic adenocarcinoma.We included 167 patients with unresectable pancreatic adenocarcinoma treated at our institution from 2002 to 2013, with 1-fraction (45.5% of patient) or 5-fraction (54.5% of patients) SBRT. The majority of patients (87.5%) received chemotherapy.Median follow-up was 7.9months (range: 0.1-63.6). The 6- and 12-month cumulative incidence rates (CIR) of local recurrence for patients treated with single-fraction SBRT were 5.3% (95% confidence interval [CI], 0.2%-10.4%) and 9.5% (95% CI, 2.7%-16.2%), respectively. The 6- and 12-month CIR with multifraction SBRT were 3.4% (95% CI, 0.0-7.2%) and 11.7% (95% CI, 4.8%-18.6%), respectively. Median survival from diagnosis for all patients was 13.6months (95% CI, 12.2-15.0months). The 6- and 12- month survival rates from SBRT for the single-fraction group were 67.0% (95% CI, 57.2%-78.5%) and 30.8% (95% CI, 21.9%-43.6%), respectively. The 6-and 12- month survival rates for the multifraction group were 75.7% (95% CI, 67.2%-85.3%) and 34.9% (95% CI, 26.1%-46.8%), respectively. There were no differences in CIR or survival rates between the single- and multifraction groups. The 6- and 12-month cumulative incidence rates of gastrointestinal toxicity grade 3 were 8.1%(95% CI, 1.8%-14.4%) and 12.3% (95% CI, 4.7%-20.0%), respectively, in the single-fraction group, and both were 5.6% (95% CI, 0.8%-10.5%) in the multifraction group. There were significantly fewer instances of toxicity grade 2 with multifraction SBRT (P=.005). Local recurrence and toxicity grade 2 were independent predictors of worse survival.Multifraction SBRT for pancreatic cancer significantly reduces gastrointestinal toxicity without compromising local control.

View details for DOI 10.1016/j.ijrobp.2014.06.066

View details for Web of Science ID 000344734300029

Abstract

We report updated outcomes of single- versus multifraction stereotactic body radiation therapy (SBRT) for unresectable pancreatic adenocarcinoma.We included 167 patients with unresectable pancreatic adenocarcinoma treated at our institution from 2002 to 2013, with 1-fraction (45.5% of patient) or 5-fraction (54.5% of patients) SBRT. The majority of patients (87.5%) received chemotherapy.Median follow-up was 7.9months (range: 0.1-63.6). The 6- and 12-month cumulative incidence rates (CIR) of local recurrence for patients treated with single-fraction SBRT were 5.3% (95% confidence interval [CI], 0.2%-10.4%) and 9.5% (95% CI, 2.7%-16.2%), respectively. The 6- and 12-month CIR with multifraction SBRT were 3.4% (95% CI, 0.0-7.2%) and 11.7% (95% CI, 4.8%-18.6%), respectively. Median survival from diagnosis for all patients was 13.6months (95% CI, 12.2-15.0months). The 6- and 12- month survival rates from SBRT for the single-fraction group were 67.0% (95% CI, 57.2%-78.5%) and 30.8% (95% CI, 21.9%-43.6%), respectively. The 6-and 12- month survival rates for the multifraction group were 75.7% (95% CI, 67.2%-85.3%) and 34.9% (95% CI, 26.1%-46.8%), respectively. There were no differences in CIR or survival rates between the single- and multifraction groups. The 6- and 12-month cumulative incidence rates of gastrointestinal toxicity grade 3 were 8.1%(95% CI, 1.8%-14.4%) and 12.3% (95% CI, 4.7%-20.0%), respectively, in the single-fraction group, and both were 5.6% (95% CI, 0.8%-10.5%) in the multifraction group. There were significantly fewer instances of toxicity grade 2 with multifraction SBRT (P=.005). Local recurrence and toxicity grade 2 were independent predictors of worse survival.Multifraction SBRT for pancreatic cancer significantly reduces gastrointestinal toxicity without compromising local control.

View details for DOI 10.1016/j.ijrobp.2014.06.066

View details for PubMedID 25585785

View details for DOI 10.1016/j.ijrobp.2014.05.1993

View details for Web of Science ID 000342331402400

View details for DOI 10.1016/j.ijrobp.2014.05.1223

View details for Web of Science ID 000342331401321

View details for DOI 10.1016/j.ijrobp.2014.05.715

View details for Web of Science ID 000342331400430

View details for DOI 10.1016/j.ijrobp.2014.05.1218

View details for Web of Science ID 000342331401316

View details for DOI 10.1016/j.ijrobp.2014.05.1186

View details for Web of Science ID 000342331401284

View details for DOI 10.1016/j.ijrobp.2014.05.1211

View details for Web of Science ID 000342331401309

View details for DOI 10.1016/j.ijrobp.2014.05.1210

View details for Web of Science ID 000342331401308

View details for DOI 10.1016/j.ijrobp.2014.05.184

View details for Web of Science ID 000342331400113

View details for Web of Science ID 000358613204223

View details for DOI 10.1200/jco.2014.32.3_suppl.317

View details for Web of Science ID 000333682100318

Abstract

The full potential of stereotactic body radiation therapy (SBRT), in the treatment of unresectable intrahepatic malignancies, has yet to be realized as our experience is still limited. Thus, we evaluated SBRT outcomes for primary and metastatic liver tumors, with the goal of identifying factors that may aid in optimization of therapy.From 2005 to 2010, 62 patients with 106 primary and metastatic liver tumors were treated with SBRT to a median biologic effective dose (BED) of 100 Gy (42.6-180). The majority of patients received either three (47%) or five fractions (48%). Median gross tumor volume (GTV) was 8.8 cm(3) (0.2-222.4).With a median follow-up of 18 months (0.46-46.8), freedom from local progression (FFLP) was observed in 97 of 106 treated tumors, with 1- and 2-year FFLP rates of 93% and 82%. Median overall survival (OS) for all patients was 25.2 months, with 1- and 2-year OS of 81% and 52%. Neither BED nor GTV significantly predicted for FFLP. Local failure was associated with a higher risk of death [hazard ratio (HR) = 5.1, P = .0007]. One Child-Pugh Class B patient developed radiation-induced liver disease. There were no other significant toxicities.SBRT provides excellent local control for both primary and metastatic liver lesions with minimal toxicity. Future studies should focus on appropriate selection of patients and on careful assessment of liver function to maximize both the safety and efficacy of treatment.

View details for DOI 10.1593/tlo.12448

View details for Web of Science ID 000328361500007

View details for PubMedID 23908687

Abstract

We have recently shown that inhibition of HRR (homologous recombination repair) by Chk1 (checkpoint kinase 1) inhibition radiosensitizes pancreatic cancer cells and others have demonstrated that Chk1 inhibition selectively sensitizes p53 mutant tumor cells. Furthermore, PARP1 [poly (ADP-ribose) polymerase-1] inhibitors dramatically radiosensitize cells with DNA double strand break repair defects. Thus, we hypothesized that inhibition of HRR (mediated by Chk1 via AZD7762) and PARP1 [via olaparib (AZD2281)] would selectively sensitize p53 mutant pancreatic cancer cells to radiation. We also used 2 isogenic p53 cell models to assess the role of p53 status in cancer cells and intestinal epithelial cells to assess overall cancer specificity. DNA damage response and repair were assessed by flow cytometry, H2AX, and an HRR reporter assay. We found that the combination of AZD7762 and olaparib produced significant radiosensitization in p53 mutant pancreatic cancer cells and in all of the isogenic cancer cell lines. The magnitude of radiosensitization by AZD7762 and olaparib was greater in p53 mutant cells compared with p53 wild type cells. Importantly, normal intestinal epithelial cells were not radiosensitized. The combination of AZD7762 and olaparib caused G 2 checkpoint abrogation, inhibition of HRR, and persistent DNA damage responses. These findings demonstrate that the combination of Chk1 and PARP1 inhibition selectively radiosensitizes p53 mutant pancreatic cancer cells. Furthermore, these studies suggest that inhibition of HRR by Chk1 inhibitors may be a useful strategy for selectively inducing a BRCA1/2 'deficient-like' phenotype in p53 mutant tumor cells, while sparing normal tissue.

View details for DOI 10.4161/cc.10.24.18661

View details for Web of Science ID 000298407200033

View details for PubMedID 22134241

Abstract

With the recent regulations limiting resident work hours, it has become more important to understand how residents spend their time. The volume and content of the pages they receive provide a valuable source of information that give insight into their workload and help identify inefficiencies in hospital communication. We hypothesized that above a certain workload threshold, paging data would suggest breakdowns in communication and implications for quality of care. All pages sent to six general surgery interns at the University of Michigan over the course of one academic year (7/1/2008-6/30/2009) were retrospectively categorized by sender type, message type, message modifier, and message quality. Census, discharge, and admission information for each intern service were also collected, and intern duties were further analyzed with respect to schedule. "On-call" days were defined as days on which the intern bore responsibility for care of all admitted floor patients. The interns received a total of 9,843 pages during the study period. During on-call shifts, each intern was paged an average of 573 times, and those on non-call shifts received an average of 123 pages. Floor/intensive care unit (ICU) nurses represented 32% of the page volume received by interns. Interestingly, as patient volume increased, there was a decrease in the number of pages received per patient. By contrast, at higher patient volumes, there was a trend toward an increasing percentage of urgent pages per patient. At high intern workloads, our data suggest no major communication breakdowns but reveal the potential for inferior quality of care.

View details for DOI 10.1007/s00268-010-0740-9

View details for Web of Science ID 000282506500004

View details for PubMedID 20703470

View details for DOI 10.1097/ACM.0b013e3181dbe54b

View details for Web of Science ID 000279377300004

View details for PubMedID 20505384