Defining the role of intensity modulation in electron conformal therapy for the treatment of head and neck cancer.

Bolus electron conformal therapy (BECT) in the treatment of cancers of the head and neck is often limited by an inability to reduce dosimetric hot spots resulting from surface irregularity or tissue heterogeneity. We examined the potential benefits of using intensity modulation for electron therapy (IM-BECT) to reduce hotspots in patients undergoing electron beam therapy for superficial cancers of the head and neck (HN). Twenty patients with HN cancer previously treated with BECT were identified. Each case included the treatment targets and a primary organ at risk (OAR) that were defined by the radiation oncologist. A target +2 cm rind structure was created for analysis of the dose deposition in areas surrounding the target volume as a measure of conformality. Each patient plan was transferred into the novel IM-BECT planning software and each case was recomputed as per the original parameters. Next, each case was replanned with the inclusion of intensity modulation, as well as a new custom conformal bolus that was redesigned for optimized range compensation when paired with an intensity modulator. The plans were then normalized to prescription dose and compared for target coverage/dose and OAR dose. For patients who had a hotspot of 125% or greater, the hotspot was on average reduced by 13.1% with IM-BECT. For IM-BECT, the average primary OAR means dose and target+2cm rind mean dose increased slightly by 10.6% and 6.4%, respectively (primary OAR mean [p = 0.0001], and Target+2cm rind mean [p = 0.0001], paired t-test). IM-BECT is an effective method of reducing hotspots in patients with superficial HN cancer. Improvements came at the expense of slight increases in dose to the underlying tissues. This retrospective planning study represents the first example of IM-BECT to actual HN patient cases. Expanding the role of IM-BECT in other disease sites could potentially compared to conventional BECT.

Evaluating Carbon Footprint of Proton Therapy Based on Power Consumption and Possible Mitigation Strategies.

PURPOSE: There is increasing concern about rising carbon dioxide (CO2) emissions and their hazardous effect on human health. This study quantifies the energy utilization of proton therapy, assesses the corresponding carbon footprint, and discusses possible offsetting strategies toward carbon-neutral health care operations. METHODS AND MATERIALS: Patients treated between July 2020 and June 2021 using the Mevion proton system were evaluated. Current measurements were converted to kilowatts of power consumption. Patients were reviewed for disease, dose, number of fractions, and duration of beam. The Environmental Protection Agency calculator was used to convert power consumption to tons of CO2 equivalent (CO2e) for scope-based carbon footprint accounting. RESULTS: There were 185 patients treated and a total of 5176 fractions delivered (average, 28). Power consumption was 55.8 kW in standby/night mode and 64.4 kW during BeamOn, for an annual total of 490 MWh. BeamOn time was 149.6 hours, and BeamOn consumption accounted for 2% of the machine total. Power consumption was 52 kWh per patient (breast, highest at 140 kWh; prostate, lowest at 28 kWh). Annual power consumption of the administrative areas was approximately 96 MWh, for a program total of 586 MWh. The carbon footprint for BeamOn time was 4.17 metric tons of CO2e, or 23 kg per patient course (breast cancer, 60 kg; prostate, 12 kg). The annual carbon footprint for the machine was 212.2 tons CO2e, and for the proton program, 253.7 tons CO2e, with an attributed footprint of 1372 kg CO2e per patient. The corresponding CO2e offset for the program could be 4192 new trees planted and grown for 10 years (23 trees per patient). CONCLUSIONS: The carbon footprint varied by disease treated. On average, the carbon footprint was 23 kg of CO2e per patient and 253.7 tons of CO2e for the proton program. There are a number of reduction, mitigation, and offset strategies possible for radiation oncologists that should be explored, such as waste minimization, less treatment commuting, efficient energy use, and renewable electricity power use.

Patterns of utilization and clinical adoption of 0.35 Tesla MR-guided radiation therapy in the United States - Understanding the transition to adaptive, ultra-hypofractionated treatments.

Purpose/Objective: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology. Materials/Methods: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems. Results: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses. Conclusions: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35 T-MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy.

Adapting to the Adaptive Radiation Workflow: Incorporating Video Sign Out for Improved Safety and Efficiency as Part of Magnetic Resonance Image Guided Adaptive Radiation.

 : Magnetic resonance image guided adaptive radiation therapy (MRgART) represents a significant improvement in our ability to deliver therapeutic radiation. However, for the process of MRgART to be carried out safely and efficiently, the covering radiation oncologist must be aware of all aspects of a patient's case, because they will be required to recontour and replan the patient before each treatment. In this report, we will demonstrate our initial experience with a video sign-out process to convey the detailed level of information required for the covering physician to treat patients safely and effectively with MRgART. We then describe our optimized video sign-out process to allow for other centers to adopt a similar approach.

Proposal and Evaluation of a Physician-Free, Real-Time On-Table Adaptive Radiotherapy (PF-ROAR) Workflow for the MRIdian MR-Guided LINAC.

With the implementation of MR-LINACs, real-time adaptive radiotherapy has become a possibility within the clinic. However, the process of adapting a patient's plan is time consuming and often requires input from the entire clinical team, which translates to decreased throughput and limited patient access. In this study, the authors propose and simulate a workflow to address these inefficiencies in staffing and patient throughput. Two physicians, three radiation therapists (RTT), and a research fellow each adapted bladder and bowel contours for 20 fractions from 10 representative patient plans. Contouring ability was compared via calculation of a Dice Similarity Index (DSI). The DSI for bladder and bowel based on each potential physician-therapist pair, as well as an inter-physician comparison, exhibited good overlap amongst all comparisons (p = 0.868). Plan quality was compared through calculation of the conformity index (CI), as well as an evaluation of the plan's dose to a 'gold standard' set of structures. Overall, non-physician plans passed 91.2% of the time. Of the eight non-physician plans that failed their clinical evaluation, six also failed their evaluation against the 'gold standard'. Another two plans that passed their clinical evaluation subsequently failed in their evaluation against the 'gold standard'. Thus, the PF-ROAR process has a success rate of 97.5%, with 78/80 plans correctly adapted to the gold standard or halted at treatment. These findings suggest that a physician-free workflow can be well tolerated provided RTTs continue to develop knowledge of MR anatomy and careful attention is given to understanding the complexity of the plan prior to treatment.

Technical Report: Diagnostic Scan-Based Planning (DSBP), A Method to Improve the Speed and Safety of Radiation Therapy for the Treatment of Critically Ill Patients.

PURPOSE: Treating critically ill patients in radiation oncology departments poses multiple safety risks. This study describes a method to improve the speed of radiation treatment for patients in the intensive care unit by eliminating the need for computed tomography (CT) simulation or on-table treatment planning using patients' previously acquired diagnostic CT scans. METHODS AND MATERIALS: Initially, a retrospective planning study was performed to assess the applicability and safety of diagnostic scan-based planning (DSBP) for 3 typical indications for radiation therapy in patients in the intensive care unit: heterotopic ossification (10), spine metastases (cord compression; 10), and obstructive lung lesions (5). After identification of an appropriate diagnostic CT scan, treatment planning was performed using the diagnostic scan data set. These treatment plans were then transferred to the patients' simulation scans, and a dosimetric comparison was performed between the 2 sets of plans. Additionally, a time study of the first 10 patients treated with DSBP in our department was performed. RESULTS: The retrospective analysis demonstrated that DSBP resulted in treatment plans that, when transferred to the CT simulation data sets, provided excellent target coverage, a median D95% of 96% (range, 86%-100%) of the prescription dose with acceptable hot spots, and a median Dmax108% (range, 102%-113%). Subsequently, DSBP has been used for 10 critically ill patients. The patients were treated without CT simulation, and the median time between patient check-in to the department and completion of radiation therapy was 28 minutes (range, 18-47 minutes.) CONCLUSIONS: This study demonstrates that it is possible to safely use DSBP for the treatment of critically ill patients. This method has the potential to simplify the treatment process and improve the speed and safety of treatment.

Patterns of care and outcomes of adjuvant therapy for high-risk head and neck cancer after surgery.

BACKGROUND: Postoperative chemoradiotherapy (CRT) is considered standard of care in patients with locally advanced head and neck cancer with positive margins and/or extracapsular extension (ECE). METHODS: The National Cancer Data Base (NCDB) was queried to identify patients with squamous cell carcinoma of the head and neck with stages III to IVB disease or with positive margins and/or ECE diagnosed between 2004 and 2012 receiving postoperative radiotherapy (RT). Using univariable and multivariable logistic and Cox regression, we assessed for predictors of CRT use and covariables impacting overall survival (OS), including in a propensity-matched subset. RESULTS: Of 12 224 patients, 67.1% with positive margins and/or ECE received CRT as well as 54.0% without positive margins and/or ECE. The 5-year OS was 61.6% for RT alone versus 67.4% for CRT. In the propensity-matched cohort, OS benefit persisted with CRT, including in a subset with positive margins and/or ECE but not without. CONCLUSION: Postoperative CRT seems underutilized with positive margins and/or ECE and overutilized without positive margins and/or ECE. The CRT was associated with improved OS but the benefit persisted only in the subset with positive margins and/or ECE.

Patterns of Progression in Metastatic Estrogen Receptor Positive Breast Cancer: An Argument for Local Therapy.

PURPOSE: Despite advances in endocrine therapy (ET), metastatic estrogen receptor positive breast cancer (BrCA) remains incurable. Though the mechanisms of resistance to ET have been studied extensively, the anatomic pattern of disease progression remains poorly characterized. The purpose of this study was to characterize the pattern of progression for patients receiving ET for metastatic BrCA. METHODS: The records of 108 patients with metastatic BrCA who progressed on ET were reviewed. Progression was characterized as follows: diffuse progression, progression in greater than 3 sites; oligoprogression, progression in fewer than 3 sites with prior diffuse metastases; and oligometastatic disease with progression, progression in 3 or fewer sites with prior limited metastases. RESULTS: Seventy-four patients (69%) displayed only diffuse disease progression. Conversely, 23 patients (21%) displayed oligoprogression and 11 patients (10%) displayed oligometastases with progression at least once in their disease course. Further analysis of the patients with oligoprogression suggested that in 14 patients the sites of progression would have been amenable to local therapy. CONCLUSION: Oligoprogressive disease occurs in a significant subset of patients with metastatic BrCA treated with ET. These patients with oligoprogressive disease may be eligible for local therapy, potentially obviating the need to change of systemic therapy.

A Randomized Phase 2 Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy-Induced Esophagitis During the Treatment of Lung Cancer: Results of NRG Oncology RTOG 1012.

PURPOSE: Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. METHODS: The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy. The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and patient-reported adverse events, weight loss, dysphagia, nutritional status, and quality of life. RESULTS: 53 patients were randomized to supportive care, 54 were randomized to liquid honey, and 56 were randomized to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms, which was found to be significant (P=.03), with more patients on the supportive care arm taking opioids. CONCLUSION: Honey as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed.

Does the Presence of a Major Psychiatric Disorder Affect Tolerance and Outcomes in Men With Prostate Cancer Receiving Radiation Therapy?

Prior studies have suggested that men with prostate cancer and psychiatric disorders (+Psy) have worse outcomes compared with those without (-Psy), particularly due to delayed diagnosis or reduced access to definitive treatment. In the current study, the toxicity and outcomes of men who were primarily diagnosed through prostate-specific antigen screening and who underwent definitive treatment with external beam radiation was investigated. The charts of 469 men diagnosed with prostate cancer from 2003 to 2010 were reviewed. The presence of +Psy was based on a Diagnostic and Statistical Manual of Mental Disorders-Fourth edition diagnosis of posttraumatic stress disorder, depression, schizophrenia, bipolar disorder, and/or generalized anxiety disorder. Kaplan-Meier analysis was used to analyze biochemical control, distant control, prostate cancer-specific survival, and overall survival. One hundred patients (21.3%) were identified as +Psy. At a median follow-up of 73 months, there were no differences regarding 6-year biochemical control (79.8% -Psy vs. 80.4% +Psy, p = .50) or 6-year distant metastatic-free survival (96.4% -Psy vs. 98.0% +Psy, p = .36). There were also no differences regarding the 6-year prostate cancer-specific survival (98.4% -Psy vs. 99.0% +Psy, p = .45) or 6-year overall survival (80.2% -Psy vs. 82.2% +Psy, p = .35). Short- and long-term genitourinary and gastrointestinal toxicities were similar between the groups. On multivariate analyses with propensity score adjustment, +Psy was not a significant predictor for toxicity, biochemical recurrence, or survival. The presence of +Psy was not associated with higher toxicity or worse clinical outcomes, suggesting that effective removal of screening and treatment barriers may reduce the survival disparities of these patients.

The Impact of Adjuvant Postoperative Radiation Therapy and Chemotherapy on Survival After Esophagectomy for Esophageal Carcinoma.

OBJECTIVE: The objective of this study was to analyze the impact on overall survival (OS) from the addition of postoperative radiation with or without chemotherapy after esophagectomy, using a large, hospital-based dataset. BACKGROUND: Previous retrospective studies have suggested an OS advantage for postoperative chemoradiation over surgery alone, although prospective data are lacking. METHODS: The National Cancer Data Base was queried to select patients diagnosed with stage pT3-4Nx-0M0 or pT1-4N1-3M0 esophageal carcinoma (squamous cell or adenocarcinoma) from 1998 to 2011 treated with definitive esophagectomy ± postoperative radiation and/or chemotherapy. OS was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with OS. RESULTS: There were 4893 patients selected, of whom 1153 (23.6%) received postoperative radiation. Most patients receiving radiation also received sequential/concomitant chemotherapy (89.9%). For the entire cohort, postoperative radiation was associated with a statistically significant but modest absolute improvement in survival (hazard ratio 0.77; 95% CI, 0.71-0.83; P < 0.001). On subgroup analysis, postoperative radiation was associated with improved OS for patients with node-positive disease (3-yr OS 34.3 % vs 27.8%, P < 0.001) or positive margins (3-yr OS 36.4% vs 18.0%, P < 0.001). When chemotherapy usage was incorporated, sequential chemotherapy was associated with the best survival (P < 0.001). Multivariate analysis revealed that the addition of chemotherapy to radiation therapy, whether sequentially or concurrently, was a strong prognostic factor for OS. CONCLUSIONS: In this hospital-based study, the addition of postoperative chemoradiation (either sequentially or concomitantly) after esophagectomy was associated with improved OS for patients with node-positive disease or positive margins.

Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in Nonmetastatic Small Cell Lung Carcinoma.

BACKGROUND: The optimal timing of thoracic radiation therapy (RT) in relation to chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on overall survival (OS) of RT timing with chemotherapy for patients with SCLC. MATERIALS AND METHODS: The NCDB was queried for patients diagnosed with nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation. The patients were stratified into quartiles according to the interval between the start of chemotherapy and the start of RT. The first and second quartiles (RT started 0-20 days after chemotherapy) were classified as "early" RT and the third and fourth quartiles (RT started 21-126 days after chemotherapy) as "late" RT. Patients were included if they had received hyperfractionated 45 Gy in 30 fractions or standard fractionation of ≥ 60 Gy in 1.8- to 2-Gy fractions. Kaplan-Meier analyses of OS were performed, and multivariable Cox regression analysis was conducted to assess the effect of the covariates on OS. RESULTS: A total of 8391 patients were included (50.5% had received early RT). Early RT was associated with significant improvement in survival (5-year OS, 21.9% vs. 19.1%; P = .01). On subgroup analysis, the survival advantage for early RT was significant for patients receiving hyperfractionated RT (5-year OS, 28.2% vs. 21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs. 18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.85-0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94-1.04; P = .53). CONCLUSION: These data support the early initiation of hyperfractionated thoracic RT for nonmetastatic SCLC.

Patterns of adjuvant radiation usage and survival outcomes for stage I endometrial carcinoma in a large hospital-based cohort.

OBJECTIVE: Two randomized trials have demonstrated a local control advantage in the absence of a survival advantage for the addition of adjuvant radiation therapy (RT) to surgery in patients with stage I endometrial adenocarcinoma (EC). This study analyzed the National Cancer Data Base (NCDB) to evaluate the impact of adjuvant RT on overall survival (OS) for patients with stage I EC. METHODS: Patients with EC who underwent total hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011 were queried. Only those with AJCC stage pT1N0M0 were included. Patients surviving <4months excluded. Adjuvant RT included external beam RT (EBRT), brachytherapy, or external RT+brachytherapy. OS was analyzed using the Kaplan-Meier method. Multivariate Cox regression analysis and propensity matched analysis were performed to assess the impact of covariates on OS. RESULTS: There were 61,697 patients included. Most women (83.9%) did not receive adjuvant RT. Adjuvant RT usage increased with increasing stage/grade. Usage of brachytherapy alone decreased with increasing stage/grade (78.2% for IA/G1 to 36.1% for IB/G3) corresponding to an increase in the use of EBRT (21.8% for IA/G1 to 53.9% for IB/G3). On multivariable analysis, adjuvant EBRT (HR 0.83, 95%CI 0.74-0.93, p=0.002) and brachytherapy (HR 0.82, 95%CI 0.74-0.93, p=0.002) were each associated with improved survival for women with stage IB. In the propensity matched cohort, RT was associated with improved survival (0.85, 95% CI 0.78-0.92, p<0.001). CONCLUSION: The use of adjuvant RT for women with stage I EC is highly dependent on stage/grade and is associated with improved survival for stage IB.

Treatment and survival outcomes of small cell carcinoma of the esophagus: an analysis of the National Cancer Data Base.

Given the paucity of esophageal small cell carcinoma (SCC) cases, there are few large studies evaluating this disease. In this study, the National Cancer Data Base (NCDB) was utilized to analyze the clinical features, treatment, and survival of patients with esophageal SCC in a large, population-based dataset. We selected patients diagnosed with esophageal SCC from 1998 to 2011. Patients were identified as having no treatment, chemotherapy alone, radiation ± sequential chemotherapy, concurrent chemoradiation, and esophagectomy ± chemotherapy and/or radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was conducted to identify factors associated with OS. A total of 583 patients were identified. Most patients had stage IV disease (41.7%). Regarding treatment selection, chemoradiation was the most commonly utilized for patients with nonmetasatic disease, whereas chemotherapy alone was most common for metastatic patients. Esophagectomy (median survival 44.9 months with 3 year OS 50.5%) was associated with the best OS for patients with localized (node-negative) disease compared with chemotherapy alone (p < 0.001) or chemoradiation (p = 0.01). For locoregional (node-positive) disease, treatment with chemoradiation resulted in a median survival of 17.8 months and a 3 year OS 31.6%. On multivariate analysis, treatment with chemotherapy alone (p = 0.003) was associated with worse OS while esophagectomy (p = 0.04) was associated with improved OS compared to chemoradiation. Esophageal SCC is an aggressive malignancy with most patients presenting with metastatic disease. Either esophagectomy or chemoradiation as part of multimodality treatment appear to improve OS for selected patients with nonmetastatic disease.

Utilization of adjuvant therapies and their impact on survival for women with stage IIIC endometrial adenocarcinoma.

PURPOSE/OBJECTIVES: Adjuvant treatment options following surgical staging for women with stage IIIC endometrial carcinoma include chemotherapy (CT) with or without radiation therapy (RT). We utilized the National Cancer Database (NCDB) to investigate utilization of adjuvant CT and RT for this group of patients and assess their impact on overall survival (OS). MATERIALS/METHODS: The NCDB was queried for patients diagnosed with non-metastatic surgically staged uterine adenocarcinoma between 2004 and 2011 with at least one pathologically positive lymph node. Overall survival (OS) was analyzed using the Kaplan-Meier method. Comparison was made between patients receiving no additional therapy, RT alone, CT alone, or a combination of CT and RT (CMT). Multivariable cox regression analysis (MVA) was performed to evaluate the effect of covariates on OS. RESULTS: A total of 6720 patients were included in this study. Of whom, 1409 received no adjuvant treatment, 1533 received CT only, 1265 received RT only, and 2522 received CMT. The 5-year OS for patients receiving no adjuvant therapy, RT alone, CT alone, and CMT were 54.9%, 63.9%, 64.4%, and 72.6%, respectively. On pairwise analysis, CMT was associated with improved survival compared to all other subgroups (p<0.001). On MVA, CMT (HR 0.58, 95% CI 0.52-0.66, p<0.001) was the strongest predictor for improved OS compared to RT alone (HR 0.79, 95% CI 0.69-0.89, p<0.001) or CT alone (HR 0.75, 95% CI 0.66-0.85, p<0.001). CONCLUSIONS: Both adjuvant CT and adjuvant RT were associated with improved OS for women with stage IIIC endometrial adenocarcinoma, but CMT was associated with the largest improvement in OS.

Assessing the Impact of Postoperative Radiation Therapy for Completely Resected Limited-Stage Small Cell Lung Cancer Using the National Cancer Database.

INTRODUCTION: Surgical resection is being increasingly used for early-stage small cell lung cancer (SCLC). However, there are sparse data regarding the role of adjuvant therapies, particularly postoperative radiation therapy (PORT). We investigated the impact of PORT on survival after complete surgical resection for SCLC using the National Cancer Database. METHODS: There were 3017 patients diagnosed with nonmetastatic SCLC between 1998 and 2011 who underwent R0 sublobar resection, lobectomy, or pneumonectomy. Patients were stratified by the use of PORT, and only those who received a minimum dose of 45 Gy were included. The overall survival (OS) of patients based on PORT use were analyzed by Kaplan-Meier analysis and compared using the log-rank test. Multivariate Cox regression analysis was used to identify factors associated with survival. RESULTS: For the entire study population, the 5-year OS was significantly poorer with the addition of PORT (33.9% versus 40.6%; p = 0.005). When analyzed by subgroup, patients with pN0 stage had significantly decreased OS with PORT (39.3% versus 46.3%; p = 0.07) and patients with pN2 stage had significantly improved OS with PORT (29.0% versus 18.6%; p < 0.001). No differences in OS were observed in patients with pN1 stage. On multivariate analysis, the hazard ratio for PORT in pN0 disease was 1.36 (95% confidence interval, 1.09-1.70; p < 0.001) and the hazard ratio for PORT in pN2 disease was 0.60 (95% confidence interval, 0.45-0.80; p < 0.001). CONCLUSION: The use of PORT was associated with a deleterious effect on OS in patients with pN0 disease but significantly improved OS in patients with pN2 disease.

Utilization of Hyperfractionated Radiation in Small-Cell Lung Cancer and Its Impact on Survival.

INTRODUCTION: Twice-daily radiation with concurrent chemotherapy is recognized as the standard of care for the treatment of limited stage small-cell lung carcinoma (SCLC), but its utilization in this setting is unclear. The objective of this study was to analyze modern patterns of treatment for limited stage SCLC and the impact on survival utilizing the National Cancer Database. METHODS: Between 1999 and 2012, there were 25,045 patients diagnosed with nonmetastatic SCLC who met the selection criteria, of whom 22,626 had survival data. Those receiving 45 Gy in 1.5 Gy fractions twice-daily (BID) were compared with those receiving 45 to 72 Gy in 1.8 or 2.0 Gy fractions. Overall survival was analyzed via Kaplan-Meier analysis and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with survival. RESULTS: The utilization of BID radiation overall was 11.3%. Treatment at an academic center was associated with a higher likelihood of receiving BID treatment (odds ratio: 2.29, 95% confidence interval [CI]: 1.95-2.69; p < 0.001). Median survival was 22.1, 17.2, 18.3, 19.2, and 19.5 months for patients receiving 45 Gy BID, 45 Gy once-daily, 46 to 59.4 Gy once-daily, 60 to 61.2 Gy once-daily, and 62 to 72 Gy once-daily, respectively (p < 0.001 for all pairwise comparisons to BID). On multivariate analysis, treatment at an academic center (hazard ratio: 0.88, 95% CI: 0.83-0.93; p < 0.001) and receipt of BID radiation (hazard ratio: 0.92, 95% CI: 0.86-0.98; p = 0.008) were associated with improved survival. CONCLUSIONS: The adoption of BID radiation remains very limited, but is more commonly utilized in the academic setting. In this hospital-based study, BID fractionation was associated with improved survival over once-daily fractionation, even at doses ≥60 Gy.

A population-based analysis of contemporary patterns of care in younger men (<60 years old) with localized prostate cancer.

PURPOSE: To analyze patterns of care in younger patients (<60 years old) with localized prostate cancer and to identify factors associated with selection of therapy using a large, population-based database. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify men <60 years old diagnosed with localized prostate cancer between 2010 and 2011. Patients were determined to have undergone no active treatment, local therapy, radiation therapy (RT), or radical prostatectomy (RP). Univariate and multivariate logistic regression analyses were performed to identify factors associated with the use of definitive therapy. RESULTS: A total of 12,732 men were included in this analysis. For the entire cohort, 12.5 % received no definitive treatment, 61.6 % RP, 22.0 % RT, and 3.3 % RP with adjuvant RT. Among men with low-, intermediate-, and high-risk prostate cancer, 17.2, 7.1, and 15.9 %, respectively, received no definitive therapy. RP was the most common choice of definitive therapy, utilized in 74.6 % of patients. Adjuvant RT after RP was utilized in 16.2 % of cases with positive margin and/or pT3/pT4 disease. African-American race, single marital status, and Medicaid/no insurance were associated with a decreased likelihood of receiving definitive treatment. CONCLUSIONS: A significant proportion of younger men diagnosed with localized prostate cancer, particularly with low- or high-risk disease, are not receiving definitive therapy. African-American men, uninsured men, and patients with Medicaid or no medical insurance are less likely to receive definitive treatment.

Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer.

PURPOSE: We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation. MATERIALS AND METHODS: From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (≥7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. RESULTS: The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. CONCLUSION: Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

Prostate biopsy concordance in a large population-based sample: a Surveillance, Epidemiology and End Results study.

AIMS: To use the Surveillance, Epidemiology and End Results database in order to evaluate prostate biopsy concordance in a large population-based sample. METHODS: We identified 34 195 men who were diagnosed with prostate cancer and underwent a radical prostatectomy from 2010 to 2011. All patients also had to have both clinical and pathological Gleason scores available for analysis. The concordance of the biopsy Gleason score to the pathological Gleason score was analysed using the coefficient of agreement (κ). Univariate and multivariate logistic regression analyses were performed to determine potential factors that may impact concordance of Gleason score. RESULTS: Overall, the clinical and pathological Gleason scores matched in 55.4% of patients. The concordance rates were 55.3% for Gleason 6, 66.9% for Gleason 3+4, 42.9% for Gleason 4+3 and 24.8% for Gleason 8, with frequent downgrading to Gleason 7. The κ for Gleason score concordance was 0.36 (95% CI 0.35 to 0.37), indicating fair agreement. The weighted κ for Gleason score concordance was 0.51 (95% CI 0.50 to 0.52), indicating moderate agreement. Additionally, the Bowker tests of symmetry were highly significant (p<0.001), indicating that when discordant findings were present, pathological upgrading was more common than downgrading. CONCLUSIONS: This study is, to our knowledge, the largest contemporary study of prostate biopsy concordance. We found that there continues to be significant Gleason migration both upward from biopsy Gleason 6 or 3+4 and downgrading from biopsy Gleason ≥8. Further studies are needed to better determine other potential genomic or biologic factors that may help increase the biopsy Gleason concordance.