Search

Background/aim: Prostate cancer can be treated with radical prostatectomy (RP), external-beam radiotherapy (EBRT), or brachytherapy (BT). These modalities have similar cancer-related outcomes. We used an innovative method to analyze the cost of such treatment., Materials and Methods: We queried our Institution's Insurance Division [University of Pittsburgh Medical Center (UPMC) Health Plan] beneficiaries from 2003-2008, who were diagnosed with prostate cancer and also queried the UPMC tumor registry for all patients with prostate cancer treated at our Institution. In a de-identified manner, data from the Health Plan and Tumor Registry were merged., Results: A total of 354 patients with non-metastatic disease with treatment initiated within 9 months of diagnosis were included (RP=236, EBRT=55, and BT=63). Radiotherapy-treated patients tended to be older, higher-risk, and have more comorbidities. Unadjusted median total health care expenditures during the first year after diagnosis were: RP: $16,743, EBRT: $47,256, and BT: $23,237 (p<0.0005). A propensity score-matched model comparing RP and EBRT demonstrated median total health care expenditures during year one: RP: $8,189, EBRT: $10,081; p=0.48. In a propensity-matched model comparing RP and BT, the median total health care expenditures during year one were: RP: $18,143, BT: $26,531; p=0.015 and per year during years 2 through 5 from diagnosis were: RP: $5,913, BT: $6,110; p=0.68., Conclusion: This pilot study demonstrates the feasibility of combining healthcare costs from the payer's perspective with clinical data from a Tumor Registry within an IDFS and represents a novel approach to investigating the economic impact of cancer treatment., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Radiation oncology has always been deeply rooted in modeling, from the early days of isoeffect curves to the contemporary Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) initiative. In recent years, medical modeling for both prognostic and therapeutic purposes has exploded thanks to increasing availability of electronic data and genomics. One promising direction that medical modeling is moving toward is adopting the same machine learning methods used by companies such as Google and Facebook to combat disease. Broadly defined, machine learning is a branch of computer science that deals with making predictions from complex data through statistical models. These methods serve to uncover patterns in data and are actively used in areas such as speech recognition, handwriting recognition, face recognition, "spam" filtering (junk email), and targeted advertising. Although multiple radiation oncology research groups have shown the value of applied machine learning (ML), clinical adoption has been slow due to the high barrier to understanding these complex models by clinicians. Here, we present a review of the use of ML to predict radiation therapy outcomes from the clinician's point of view with the hope that it lowers the "barrier to entry" for those without formal training in ML. We begin by describing 7 principles that one should consider when evaluating (or creating) an ML model in radiation oncology. We next introduce 3 popular ML methods--logistic regression (LR), support vector machine (SVM), and artificial neural network (ANN)--and critique 3 seminal papers in the context of these principles. Although current studies are in exploratory stages, the overall methodology has progressively matured, and the field is ready for larger-scale further investigation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Resistance training may offer several unique advantages within breast cancer (BC) survivorship care; however, safety concerns have limited the application of high‐intensity compound movements necessary to elicit optimal changes in body composition, strength, and quality of life in this population. The EXERT‐BC trial assesses the safety and feasibility of an evidence‐based, dose‐escalated resistance training regimen among BC survivors, with the goal of improving physical and metabolic function, mobility, muscle mass, and body composition. Methods: Participants included women with breast cancer underwent a 3‐month thrice weekly exercise regimen involving dose escalation of high‐intensity compound exercises. Coprimary outcomes included safety and adherence. Pre‐ and post‐regimen assessment included body composition testing, functional mobility and balance, total load (weight × repetitions × sets) across compound exercises, and patient reported quality of life. Pairwise comparison was performed via the paired t test. Results: Fourty participants completed a 3‐month exercise regimen, with a median age of 57 years (range, 27–74 years) and 73% having stage 0–2 BC. BC therapies concurrent with exercise included anti‐estrogen therapy (80%), radiotherapy (30%), and non‐hormonal systemic therapy (15%). No adverse events were observed aside from a single case of self‐limited knee pain. Session attendance exceeded a prespecified threshold of 75%, and 98% patients reported ongoing compliance to an exercise regimen following regimen completion. Significant reductions in percent body fat (p < 0.001) and increases in percent muscle mass (p = 0.011) were observed. Significant increases in resting metabolic rate (p = 0.023), bilateral grip strength (p < 0.001), functional movement screen (p < 0.001), bilateral Y‐Balance testing (p < 0.001), and Godin questionnaire scores (p < 0.001) were observed. Conclusion: A 3‐month dose‐escalated resistance training regimen comprising high‐intensity compound movements appears safe with a high degree of adherence among breast cancer survivors, resulting in demonstrable improvements in body composition, metabolic parameters, strength increases, and patient‐reported quality of life. [ABSTRACT FROM AUTHOR]

Adaptive radiotherapy (ART) was introduced in the late 1990s to improve the accuracy and efficiency of therapy and minimize radiation-induced toxicities. ART combines multiple tools for imaging, assessing the need for adaptation, treatment planning, quality assurance, and has been utilized to monitor inter- or intra-fraction anatomical variations of the target and organs-at-risk (OARs). Ethos™ (Varian Medical Systems, Palo Alto, CA), a cone beam computed tomography (CBCT) based radiotherapy treatment system that uses artificial intelligence (AI) and machine learning to perform ART, was introduced in 2020. Since then, numerous studies have been done to examine the potential benefits of Ethos™ CBCT-guided ART compared to non-adaptive radiotherapy. This review will explore the current trends of Ethos™, including improved CBCT image quality, a feasible clinical workflow, daily automated contouring and treatment planning, and motion management. Nevertheless, evidence of clinical improvements with the use of Ethos™ are limited and is currently under investigation via clinical trials. [ABSTRACT FROM AUTHOR]

A recent Twitter poll of over 150 radiation oncology participants acknowledged nearly 90% of participants had not done hand calculations in the previous year.[15] However, rote memorization and hand calculations represent a substantial portion of the resident physics course and board exam. Here we will arbitrarily define "basic fundamental physics" to include the explicit constituents of the "Basic Physics" section of the radiation oncology physics examination blueprint from the American Board of Radiology - "fundamental physics, atomic and nuclear structure, production of kV x-ray beams, production of MV x-ray beams, and radiation interactions". Keywords: radiation oncology resident physics education; resident education EN radiation oncology resident physics education resident education 1 6 6 09/06/23 20230901 NES 230901 THREE DISCIPLINE COLLABORATIVE RADIATION THERAPY (3DCRT) DEBATE SERIES Radiation Oncology is a highly multidisciplinary medical specialty, drawing significantly from three scientific disciplines - medicine, physics, and biology. [Extracted from the article]

PURPOSE Updates to consensus guidelines in October 2018 recommending moderately hypofractionated external beam radiotherapy (mHF-EBRT) in prostate cancer lagged several years after publication of evidence supporting its efficacy. In January 2018, we amended our prostate cancer clinical pathway (CP) to facilitate adoption of mHF-EBRT. Herein, we analyze patterns of care and changes in mHF-EBRT use after the CP modification. METHODS Our prostate CP was amended in January 2018 to make mHF-EBRT the recommended treatment for patients with low- and intermediate-risk prostate cancer pursuing curative EBRT monotherapy. Normal-tissue dose constraints accompanied the CP modification to guide planning. Use of mHF-EBRT from 2015 to 2017 was compared with use in 2018 after the CP modification, using the Cochran-Armitage test for trend. Predictors of mHF-EBRT use and adherence to dose constraints were analyzed with binary logistic regression. RESULTS In 560 patients treated with EBRT monotherapy, mHF-EBRT use increased from 3.7% in 2015- 2017 to 85.6% in 2018 (P, .001), whereas conventionally fractionated EBRT (CF-EBRT) use decreased from 96.3% to 14.4% (P, .001). Consultation year of 2018 (odds ratio [OR], 214.6; 95% CI, 94.5 to 484.6; P, .001), treatment at an academic facility (OR, 4.5; 95% CI, 1.8 to 11.3; P50.001), and having a smaller prostate (OR, 0.99; 95% CI, 0.97 to 1.00; P 5 .028) predicted for mHF-EBRT use. At least five of six recommended bladder and rectal dose constraints were met in 89.4% of patients. CONCLUSION Modification of our prostate cancer CP, in concert with institutional policies to monitor and audit CP compliance, facilitated rapid adoption of mHF-EBRT in our large, integrated cancer center with good adherence to dosimetric constraints. [ABSTRACT FROM AUTHOR]

The role of consolidative radiotherapy (RT) is less substantiated in uncommon peripheral T-cell lymphomas (PTCLs). Anaplastic lymphoma kinase (ALK) mutation sub-categorizes PTCLs, with ALK (+) having a distinctly favorable prognosis. We aimed to use the National Cancer Database to examine the potential role of RT in PTCLs and if ALK mutation can be used to predict the benefit of consolidative RT after multi-agent chemotherapy (combined modality therapy). We identified 3670 stage I–II PTCL patients treated with multi-agent chemotherapy alone or combined modality therapy (CMT) between 1998–2012. After adjusting for immortal-time and indication bias, CMT was associated with better OS than multi-agent chemotherapy alone for ALK (−) patients (HR 0.69, 95% CI 0.52–0.92, p =.01); no significant difference was noted for ALK (+) (HR 1.03, 95% CI 0.75–1.41, p =.85). CMT is associated with improved OS for ALK (−) PTCLs; while no such benefit was seen for the ALK (+) subgroup. [ABSTRACT FROM AUTHOR]

Background: The TEACHH and Chow models were developed to predict life expectancy (LE) in patients evaluated for palliative radiotherapy (PRT). We sought to validate the TEACHH and Chow models in patients who died within 90 days of PRT consultation. Methods: A retrospective review was conducted on patients evaluated for PRT from 2017 to 2019 who died within 90 days of consultation. Data were collected for the TEACHH and Chow models; one point was assigned for each adverse factor. TEACHH model included: primary site of disease, ECOG performance status, age, prior palliative chemotherapy courses, hospitalization within the last 3 months, and presence of hepatic metastases; patients with 0‐1, 2‐4, and 5‐6 adverse factors were categorized into groups (A, B, and C). The Chow model included non‐breast primary, site of metastases other than bone only, and KPS; patients with 0‐1, 2, or 3 adverse factors were categorized into groups (I, II, and III). Results: A total of 505 patients with a median overall survival of 2.1 months (IQR: 0.7‐2.6) were identified. Based on the TEACHH model, 10 (2.0%), 387 (76.6%), and 108 (21.4%) patients were predicted to live >1 year, >3 months to ≤1 year, and ≤3 months, respectively. Utilizing the Chow model, 108 (21.4%), 250 (49.5%), and 147 (29.1%) patients were expected to live 15.0, 6.5, and 2.3 months, respectively. Conclusion: Neither the TEACHH nor Chow model correctly predict prognosis in a patient population with a survival <3 months. A better predictive tool is required to identify patients with short LE. [ABSTRACT FROM AUTHOR]

To develop expert consensus recommendations regarding radiation therapy for gynecologic malignancies during the COVID-19 pandemic. An international committee of ten experts in gynecologic radiation oncology convened to provide consensus recommendations for patients with gynecologic malignancies referred for radiation therapy. Treatment priority groups were established. A review of the relevant literature was performed and different clinical scenarios were categorized into three priority groups. For each stage and clinical scenario in cervical, endometrial, vulvar, vaginal and ovarian cancer, specific recommendations regarding dose, technique, and timing were provided by the panel. Expert review and discussion generated consensus recommendations to guide radiation oncologists treating gynecologic malignancies during the COVID-19 pandemic. Priority scales for cervical, endometrial, vulvar, vaginal, and ovarian cancers are presented. Both radical and palliative treatments are discussed. Management of COVID-19 positive patients is considered. Hypofractionated radiation therapy should be used when feasible and recommendations regarding radiation dose, timing, and technique have been provided for external beam and brachytherapy treatments. Concurrent chemotherapy may be limited in some countries, and consideration of radiation alone is recommended. The expert consensus recommendations provide guidance for delivering radiation therapy during the COVID-19 pandemic. Specific recommendations have been provided for common clinical scenarios encountered in gynecologic radiation oncology with a focus on strategies to reduce patient and staff exposure to COVID-19. • An international panel of gynecologic radiation oncologists offer recommendations for RT during the COVID-19 pandemic. • Recommendations for cervical cancer, uterine cancer, vulvar cancer, vaginal cancer and ovarian cancer have been provided. • Recommendations for RT timing, fractionation, and dose have been provided for external beam radiation and brachytherapy. • The panel emphasizes strategies to reduce risk of transmission of the novel SARS-CoV-2 to patients and healthcare workers. • These recommendations may be used any time an event occurs which limits healthcare resources, including natural disasters. [ABSTRACT FROM AUTHOR]

Because of the critical role of brachytherapy in the management of a variety of cancers, it is important for institutions to consider offering brachytherapy if appropriate staff and personal protective equipment are available for the protection of patients and staff. Albuquerque, B.A. Hrycushko, M.M. Harkenrider, Compendium of fractionation choices for gynecologic HDR brachytherapy-an American brachytherapy society Task group report. 11, 2012, 68-75 25 A.S. Taggar, T. Phan, L. Traptow, Cervical cancer brachytherapy in Canada: A focus on interstitial brachytherapy utilization. 105, 2019, 1005-1011 69 E.C. Rijkmans, A. Cats, R.A. Nout, Endorectal brachytherapy boost after external beam radiation therapy in elderly or medically inoperable patients with rectal cancer: Primary outcomes of the phase 1 HERBERT study. [Extracted from the article]

Background: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival.Methods: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed.Results: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM.Conclusions: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes. [ABSTRACT FROM AUTHOR]

Purpose: Varian Halcyon linear accelerator version 2 (The Halcyon 2.0) was recently released with new upgraded features. The aim of this study was to report our clinical experience with Halcyon 2.0 for a dual‐isocenter intensity‐modulated radiation therapy (IMRT) planning and delivery for gynecological cancer patients and examine the feasibility of in vivo portal dosimetry. Methods: Twelve gynecological cancer patients were treated with extended‐field IMRT technique using two isocenters on Halcyon 2.0 to treat pelvis and pelvic/or para‐aortic nodes region. The prescription dose was 45 Gy in 25 fractions (fxs) with simultaneous integrated boost (SIB) dose of 55 or 57.5 Gy in 25 fxs to involved nodes. All treatment plans, pretreatment patient‐specific QA and treatment delivery records including daily in vivo portal dosimetry were retrospectively reviewed. For in vivo daily portal dosimetry analysis, each fraction was compared to the reference baseline (1st fraction) using gamma analysis criteria of 4 %/4 mm with 90% of total pixels in the portal image planar dose. Results: All 12 extended‐field IMRT plans met the planning criteria and delivered as planned (a total of 300 fractions). Conformity Index (CI) for the primary target was achieved with the range of 0.99–1.14. For organs at risks, most were well within the dose volume criteria. Treatment delivery time was from 5.0 to 6.5 min. Interfractional in vivo dose variation exceeded gamma analysis threshold for 8 fractions out of total 300 (2.7%). These eight fractions were found to have a relatively large difference in small bowel filling and SSD change at the isocenter compared to the baseline. Conclusion: Halcyon 2.0 is effective to create complex extended‐field IMRT plans using two isocenters with efficient delivery. Also Halcyon in vivo dosimetry is feasible for daily treatment monitoring for organ motion, internal or external anatomy, and body weight which could further lead to adaptive radiation therapy. [ABSTRACT FROM AUTHOR]

Background: Randomized trials describe differing sets of high–intermediate risk criteria. Objective: To use the National Cancer Database to compare the impact of radiation therapy in patients with stage I endometrial cancer meeting different criteria, and define a classification of "unfavorable risk." Methods: Patients with stage I endometrial cancer between January 2010 and December 2014 were identified in the National Cancer Database and stratified into two cohorts: (1) patients meeting Gynecologic Oncology Group (GOG)-99 criteria only for high–intermediate risk, but not Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 criteria and (2) those meeting PORTEC-1 criteria only. High-risk stage I patients with both FIGO stage IB (under FIGO 2009 staging) and grade 3 disease were excluded. In each cohort, propensity score-matched survival analyses were performed. Based on these analyses, we propose a new classification of unfavorable risk. We then analyzed the association of adjuvant radiation with survival, stratified by this classification. Results: We identified 117,272 patients with stage I endometrial cancer. Of these, 11,207 patients met GOG-99 criteria only and 5,920 patients met PORTEC-1 criteria only. After propensity score matching, adjuvant radiation therapy improved survival (HR=0.73; 95% CI 0.60 to 0.89; p=0.002) in the GOG-99 only cohort. However, there was no benefit of adjuvant radiation (HR=0.89; 95% CI 0.69 to 1.14; p=0.355) in the PORTEC-1 only cohort. We, therefore, defined unfavorable risk stage I endometrial cancer as two or more of the following risk factors: lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB. Adjuvant radiation improved survival in stage I patients with adverse risk factors (HR=0.74; 95% CI 0.68 to 0.80; p<0.001), but not in other stage I patients (HR=1.02; 95% CI 0.91 to 1.15; p=0.710; p interaction <0.001). Conclusion: Our study showed that adjuvant radiation was associated with an overall survival benefit in patients meeting GOG-99 criteria only; however, no survival benefit was seen in patients meeting PORTEC-1 criteria only. We propose a definition of unfavorable risk stage I endometrial cancer: ≥2 risk factors from among lymphovascular invasion, age ≥70, grade 2–3 disease, and FIGO stage IB disease. [ABSTRACT FROM AUTHOR]

Objectives: To determine the impact of histological grade on overall survival in patients with clinical stage I endometrioid endometrial adenocarcinoma when radiation therapy is used as primary definitive treatment. Methods: Patients with stage I endometrioid endometrial adenocarcinomas who underwent definitive radiation therapy with brachytherapy ± external beam radiation therapy were identified from the National Cancer Database. Overall survival was estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine factors affecting overall survival. Inverse probability of treatment weights were also used in multivariable analysis to estimate casual effects of external beam radiation therapy. Results: A total of 947 patients were identified. Median overall survival for grade 1, grade 2, and grade 3 tumors was 62 months (95% CI 53.8 to 70.2), 48.5 months (95% CI 38.2 to 58.8), and 33.5 months (95% CI: 23.1 to 43.8), respectively. Grade, age, and insurance status were associated with overall survival in univariate analysis with only grade and age remaining significant in multivariate analysis. Brachytherapy with external beam radiation therapy was not associated with survival in comparison with brachytherapy alone. Compared with grade 1 tumors, patients with grade 3 (HR 1.4, 95% CI 1.15 to 1.89), but not grade 2 (HR 1.0, 95% CI 0.82 to 1.26), had an increased risk of death, which persisted in an inverse probability of treatment weights-adjusted model (HR 1.56, 95% CI 1.21 to 1.93). Conclusions: Patients with grade 3 stage I endometrioid endometrial adenocarcinoma treated with primary definitive radiation therapy have worse survival than those with lower grade tumors. Addition of external beam radiation therapy to brachytherapy did not affect survival. [ABSTRACT FROM AUTHOR]

Background: Extranodal natural killer T-cell lymphoma, nasal-type (NKTCL), is a rare malignancy in Western populations and is thus challenging for standardization of care and a prospective study. This study was aimed at defining patterns of care for NKTCL in the context of radiotherapy (RT) use and dose selection in the United States.Methods: Six hundred forty-two stage I-II NKTCL patients from 1998 to 2012 were identified from the National Cancer Data Base. Binary logistic regression analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of the treatment selection and RT dose. Overall survival (OS) analyses were completed with the Kaplan-Meier and Cox multivariate methods, including a propensity score adjustment for a potential indication bias.Results: Of the 642 included NKTCL patients, 70% were at stage I, 79% were white, and 66% were ≤ 60 years old. Fifty-five percent received chemotherapy plus RT, 19% received RT alone, and 27% received chemotherapy alone. The median RT dose was 50 Gy (interquartile range, 43.2-54 Gy), 37% received < 45 Gy, and 43% received < 50 Gy. A multivariate survival analysis showed improved OS in comparison with chemotherapy alone for RT alone at ≥50 Gy (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23-0.70; P < .01), for chemotherapy plus RT at <50 Gy (HR, 0.55, 95% CI, 0.36-0.86; P < .01), and for chemotherapy plus RT at ≥50 Gy (HR, 0.41; 95% CI, 0.27-0.63; P < .01).Conclusions: Stage I-II NKTCL patients in the United States commonly receive chemotherapy alone or suboptimal-dose RT. The omission of RT or the use of suboptimal RT is negatively associated with OS. Efforts to continue improving evidenced-based management are warranted. Cancer 2017;123:3176-85. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: We determined factors associated with morbidity and outcomes of a series of non-small cell lung cancer (NSCLC) patients treated with dose-escalated chemoradiotherapy at the University of Pittsburgh Lung Cancer Program. Methods and materials: The records of 170 stage III NSCLC patients treated with definitive intent were retrospectively reviewed. All patients received four-dimensional CT simulation scan and had respiratory gating if tumor movement exceeded 5 mm. Overall survival (OS), locoregional control (LRC), and freedom from distant metastasis (FFDM) were calculated using log-rank and Cox regression analysis. results: For the present series of patients, median follow-up was 36.6 months, median survival 27.4 months, and the 2- and 4-year OS was 56.0 and 30.7%, respectively. The 4-year LRC and FFDM were 43.9 and 40.7%, respectively. No benefit was associated with irradiation doses above 66 Gy in OS (p = 0.586), LRC (p = 0.440), or FFDM (p = 0.230). On univariate analysis, variables associated with worse survival included: clinical stage IIIB (p = 0.037), planning target volume (PTV) over 450 cc (p < 0.001), heart V30 over 40% (p = -0.048), and esophageal mean dose over 20% (p = 0.024), V5 (p = -0.015), and V60 (p = -0.011). On multivariable analysis, PTV above 450 cc (52.2 vs. 25.3 months, p < 0.001) and esophageal V60 >20% (43.8 vs. 21.3 months, p = -0.01) were associated with lower survival. Grade 2 or higher acute lung toxicity and esophagitis were detected in 9.5 and 59.7%, respectively of patients. Grade 2 or higher acute lung toxicity was reduced if lung V5 was ≤65 (7.4 vs. 23.8%, p = 0.03). Grade 2 or higher acute esophagitis was reduced if V60 ≤ 20% (62 vs. 81.3%, p = 0.018). The use of intensity-modulated radiation therapy was more frequent in stage IIIB compared to stage IIIA patients (56.5 vs. 39.5%, p = 0.048) and was associated with a higher lung V5 and V10. conclusion: The outcomes of a program of dose-escalated chemoradiotherapy for unresectable stage IIIA and IIIB NSCLC patients were consistent with other studies and showed no benefit to radiation doses above 66 Gy. Furthermore, maintaining low esophageal V60 and lung V5 were associated with lower morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background Anaplastic thyroid cancer (ATC) represents a rare, aggressive malignancy. We analyzed factors predictive for overall survival (OS) and treatment modality utilization. Methods Using the National Cancer Data Base, we identified 3552 patients with ATC. Factors associated with surgery, high-dose radiotherapy (RT; ≥59.4 Gy), and chemotherapy utilization were evaluated using multivariable logistic regression. From this, an inverse probability-weighted propensity score was incorporated into multivariable Cox regression analyses for OS. Results Numerous factors predictive for high-dose RT, total thyroidectomy, and chemotherapy utilization are described. Factors associated with improved survival were absence of clinical or pathologic lymph node involvement, absence of metastasis, tumor size ≤6 cm, negative surgical margins, surgery, RT, and chemotherapy. On conditional landmark analysis, improved survival seen with chemotherapy and surgery other than total thyroidectomy was lost, but persisted for total thyroidectomy and high-dose RT. Conclusion Even after correction for selection and immortal time bias, high-dose RT resulted in improved survival. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2083-E2090, 2016 [ABSTRACT FROM AUTHOR]

BACKGROUND Despite international practice guidelines endorsing radiotherapy (RT) as the preferred initial therapy, treatment approaches vary for patients with early-stage follicular lymphoma. The authors engaged the National Cancer Data Base to analyze patterns of care and survival outcomes for patients with early-stage follicular lymphoma in the era of modern therapy. METHODS A National Cancer Data Base retrospective cohort study was conducted of 35,961 patients with lymph node and extranodal, American Joint Committee on Cancer stage I to II, WHO grade 1 to 2 follicular lymphoma who were diagnosed between 1998 and 2012. Univariate and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics that were predictive of overall survival (OS) and treatment use. Propensity score-adjusted Cox proportional hazards ratios for survival in patients treated for follicular lymphoma were used. RESULTS Of the 35,961 patients with follicular lymphoma included in the current study, 63% had stage I disease, 79% were without extranodal disease, and 61% were aged >60 years. RT use decreased from 37% in 1999 to 24% in 2012 ( P<.0001), with corresponding significant increases in observation and single-agent chemotherapy. Patients who received RT had 5-year and 10-year OS rates of 86% and 68%, respectively, compared with 74% and 54%, respectively, for those who did not receive RT ( P<.0001). On multivariable survival analysis, including a propensity score to account for potential uncaptured confounding variables due to a lack of randomization, upfront RT remained independently associated with improved OS (hazard ratio of death, 0.54; 95% confidence interval, 0.47-0.63 [ P<.0001]). CONCLUSIONS RT is an increasingly underused treatment approach in the era of modern therapy for patients with early-stage follicular lymphoma. The use of RT appears to improve OS and should remain standard practice as encouraged by clinical practice guidelines. Cancer 2015;121:3325-3334. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background This retrospective study aims to assess the usefulness of SUVmax from FDG-PET imaging as a prognosticator for primary biopsy-proven stage I NSCLC treated with SBRT. Methods This study includes 95 patients of median age 77 years, with primary, biopsy-confirmed peripheral stage IA/IB NSCLC. All patients were treated with 60Gy in 3 fractions with a median treatment time of six days. Local, regional, and distant failures were evaluated independently according to the terms of RTOG1021. Local, regional, and distant control, overall- and progression-free survival were estimated by the Kaplan-Meier method. Cox proportional hazards regression was performed to determine whether SUVmax, age, KPS, gender, tumor size/T stage, or smoking history influenced outcomes. SUVmax was evaluated as both a continuous and as a dichotomous variable using a cutoff of <5 and ≥5. Results Median follow-up for the cohort was 16 months. Median OS and PFS were 25.3 and 40.3 months, respectively. SUV with a cutoff value of 5 predicted for OS and PFS (p = .024 for each) but did not achieve significance for LC (p = .256). On Cox univariate regression analysis, SUV as a dichotomous variable predicted for both OS and PFS (p = .027 and p = .030, respectively). Defined as a continuous variable, SUVmax continued to predict for OS and PFS (p = .032 and p = .003), but also predicted LC (p = .045) and trended toward significance for DC (p = .059). SUVmax did not predict for OS as a dichotomous or continuous variable. It did, however, predict for PFS as a continuous variable (p = .008), neared significance for local control (p = .057) and trended towards, significance for distant control (p = .092). Conclusions SUVmax appears to be a statistically and clinically significant independent prognostic marker for progression-free survival in patients with stage I NSCLC treated with SBRT. Prospective studies to more accurately define the role of tumor FDG uptake in the prognosis of NSCLC are warranted. [ABSTRACT FROM AUTHOR]

Objective: To determine the dosimetric parameters predictive of acute gastrointestinal (GI) toxicity in anal cancer patients treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy. Methods: Fifty-eight anal cancer patients were treated with concurrent chemotherapy and IMRT. The bowel was delineated on the planning CT and included the intestinal cavity. Regression models with multiple independent predictors were used to test associations of clinical factors and dosimetric parameters with clinically significant GI toxicity (grade ≥3). Significant dosimetric factors were fitted to a normal tissue complication probability curve using a logit function and subsequently analyzed at multiple bowel volumes to determine the threshold for clinically significant GI toxicity. Results: Two patients (3.4%) experienced no acute GI toxicity, whereas 20 (34.5%) experienced grade 1 toxicity, 20 (34.5%) experienced grade 2, 16 (27.6%) experienced grade 3 and none experienced grade 4. Analysis showed that the volumes of bowel receiving 30 Gy (V30) and 40 Gy (V40) both correlated with clinically significant acute GI toxicity. In patients whose V30 was >310 cm3, the rate of clinically significant acute GI toxicity was 38.9%, compared to 9.1% if V30 was ≤310 cm3 (p = 0.016). If V40 was ≤70 cm3, the rate of acute grade ≥3 toxicity was 6.3%, versus 35.7% if V40 was >70 cm3 (p = 0.045). Conclusion: This analysis demonstrates that the bowel dosimetric parameters are associated with clinically significant acute GI toxicity when IMRT is used in the management of anal cancer patients. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To develop recommendations for the use of adjuvant vaginal cuff brachytherapy after hysterectomy and update previous American Brachytherapy Society (ABS) guidelines. Methods and Materials: A panel of members of the ABS performed a literature review, supplemented their clinical experience, and formulated recommendations for adjuvant vaginal cuff brachytherapy. Results: The ABS endorses the National Comprehensive Cancer Network guidelines for indications for radiation therapy for patients with endometrial cancer and cervical cancer and the guidelines on quality assurance of the American Association on Physicists in Medicine. The ABS made specific recommendations for applicator selection, insertion techniques, target volume definition, dose fractionation, and specifications for postoperative adjuvant vaginal cuff therapy. The ABS recommends that applicator selection should be based on patient anatomy, target volume geometry, and physician judgment. The dose prescription point should be clearly specified. Suggested doses were tabulated for treatment with brachytherapy alone, and in combination with external beam radiation therapy, when applicable. A properly fitted brachytherapy applicator should be selected that conforms to the vaginal apex and achieves mucosal contact with optimal tumor and normal tissue dosimetry. Dose prescription points may be individually selected but doses should be reported at the vaginal surface and at 0.5-cm depth. Conclusions: Recommendations are made for adjuvant vaginal cuff brachytherapy. Practitioners and cooperative groups are encouraged to use these recommendations to formulate their treatment and dose reporting policies. These recommendations will permit meaningful comparisons of reports from different institutions and lead to better and more appropriate use of vaginal brachytherapy. [Copyright &y& Elsevier]

Background: The purpose of this study was to compare the change in depth of target volume and dosimetric parameters between the supine and lateral decubitus positions for breast boost treatment with electron beam therapy. Methods: We analyzed 45 patients who were treated, between 2009-2010, with whole breast radiation (WBRT) followed by a tumor bed boost in the lateral decubitius position. Tumor bed volume, distance from skin to the maximal depth of the tumor bed, D90 (dose covering 90% of the tumor bed volume), maximal dose, electron energy and doses to heart and lungs were compared. Additional variables of body mass index (BMI) and tumor bed location were also analyzed to see if there was a benefit limited to any subgroup. Results: Median BMI for the 45 patients treated was 30.6 (20.6-42.4). When comparing the supine scan to the lateral decubitus scan, there was no significant difference in the tumor bed volume (p = 0.116). There was a significant difference between depth to the tumor bed in the supine scan and lateral decubitus scan (p < 0.001). The mean maximum doses and D90 between the two scans were 110.7 (100.0-133.0)% vs 106.1 (95.1-116.9)% (p < 0.05) and 93.9 (81.3-01.0-101.0)% vs. 98.2 (89.1-108.0)% (p = 0.004) respectively. There was no difference in dose delivered to the lungs or heart between the two scans (p = 0.848 and p = 0.992 respectively). On subset analysis, there was a difference in depth to tumor that was seen across all BMI classes, including normal (p ≤ 0.001, overweight (p ≤ 0.001) and obese (p ≤ 0.001). The majority of patients had a tumor in the upper outer quadrant (77.8%) and on subset analysis, there was a significant difference in tumor bed volume (p < 0.01), depth to tumor (p < 0.01), tumor bed coverage [D90] (p < 0.05), maximum dose (p < 0.05) and energy (p < 0.001) for this location. Conclusions: Delivering a tumor bed boost in the lateral decubitus position reduces the distance to the tumor bed allowing for a lower energy treatment to be used to treat breast cancer. It improves coverage and decreases maximal dose to the target volume, all of which would help reduce skin morbidities and should be considered for patients with upper outer quadrant disease, irrespective of BMI status. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: With the increasing elderly population, more women with newly diagnosed endometrial cancer may not be surgical candidates due to medical comorbidities. Definitive radiation therapy with external beam radiation (EBRT) and/or brachytherapy is a reasonable primary treatment for endometrial cancer in patients who cannot undergo surgery. Methods: A retrospective review identified 26 women 75 years and older with endometrial cancer who were not operative candidates due to comorbidities and received definitive radiation. Results: The median age of the treated patients was 83, all of whom had significant medical comorbidities precluding surgical treatment. Seventy-three percent of the patients had stage T1 disease, 19% were stage T2, and 8% were stage T3. Seventy-three percent of patients received EBRT before brachytherapy (median dose: 45 Gy). The median brachytherapy dose was 20 Gy in 5 fractions. The types of brachytherapy used were Rotte Y applicator (42%), tandem and cylinder (42%), and ring and tandem (16%). Median followup was 12 months (1–60 months). No treatment breaks were required for the entire group and only 2 patients (8%) developed late toxicity. The overall survival for all patients was 89% and 28% at 1 and 2 years, respectively. Disease-specific survival for all patients was 93% at 1 year and 73% at 3 years. Conclusions: The results in this study indicate that definitive radiation with EBRT and/or brachytherapy for endometrial cancer is feasible and well tolerated in an elderly population. [Copyright &y& Elsevier]

To analyze the initial clinical outcomes for breast cancer patients treated with intensity-modulated radiation therapy (IMRT) in a large integrated cancer center network. A total of 495 patients with breast cancer received IMRT following breast conserving surgery among nine cancer centers. Seven community cancer centers span a 100-mile radial distance from the two central academic sites. All nine cancer centers followed the same clinical pathway guidelines for the radiotherapeutic management of breast cancer. IMRT planning for all centers was performed at one central location, D3 Advanced Radiation Planning Service. The median IMRT prescription dose was 50 Gy followed by a boost with median dose of 10 Gy. The median breast volume was 918 cm3. The median Dose Homogeneity Index (DHI) was 93%. The median % of ipsilateral lung volume receiving >20 Gy was 4.6%. For left breast IMRT, the median % heart volume receiving more than 5% of prescription dose was 13.1. There was no statistical difference in the mean DHI, heart and lung dose between the academic and community sites. For all patients, NCI CTC Grades 0,1,2,3 for acute skin erythema was 16%, 55%, 28%, and 1%, respectively. The rates of Grade 0,1,2,3 acute skin desquamation were 75%, 20%, 4%, and 1%, respectively. There was no statistically significant difference in acute skin toxicities (>grade 2) among the academic and community cancer centers. With centralized processes, IMRT can be safely and effectively delivered in a large health system with an admixture of academic and community centers but long-term follow-up is necessary. [ABSTRACT FROM AUTHOR]

Objectives: To assess early clinical outcome of intensity-modulated radiation therapy (IMRT) in the treatment of vulvar cancer and compare dosimetric parameters with 3D conformal radiotherapy (3D CRT). Methods: Fifteen patients with vulvar cancer were treated with IMRT. Seven patients were treated with preoperative chemoradiation, and 8 patients were treated with adjuvant postoperative radiation therapy. Median dose was 46 Gy in the preoperative and 50.4 Gy in the postoperative group. Results: The mean volume of small bowel, rectum, and bladder that received doses in excess of 30 Gy with IMRT was reduced when compared with 3D CRT. Treatment was well tolerated, and only 1 patient had acute Grade 3 small-bowel toxicity. Median follow-up was 12 months. In the preoperative group, 5 patients (71%) had clinical complete response and 3 patients (42.8%) had pathologic complete response. In the adjuvant group, 2 patients had recurrences in the treatment field. No patients had late Grade 3 toxicity. The 2-year actuarial disease-specific survival was 100%. Conclusions: Intensity-modulated RT appears to offer advantages over 3D CRT treatment of vulvar cancer by elimination of dose modulation across overlapping regions and reduction of unnecessary dose to the bladder, rectum, and small bowel. Early results with a small number of patients show promising results, with a low incidence of severe toxicity. [Copyright &y& Elsevier]

The purpose of this study was to determine patterns of ipsilateral breast tumor recurrence (IBTR) and local-regional recurrence (LRR) after neoadjuvant chemotherapy and breast-conserving therapy (BCT). A total of 153 breast cancer patients were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy between 1980 and 2002. The clinical stage (American Joint Committee on Cancer [AJCC] 1997) at diagnosis was IIA in 22%, IIB in 28%, IIIA in 39%, and IIIB in 11%. The prechemotherapy T size distribution was less than 2 cm in 5 patients, 2.1–5 cm in 100 patients, and greater than 5.1 cm in 48 patients. Sixty-seven patients (44%) underwent cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based chemotherapy and 86 (56%) underwent Adriamycin-based chemotherapy. Thirty-seven patients (24%) had a complete pathologic response in the breast. All procedures were performed by a single surgeon (G.F.S.). The surgery was local excision alone in 19 patients, local excision and axillary lymph node dissection (ALND) in 130 patients, and ALND alone in 4 patients. Eleven patients had positive surgical margins. Rates of LRR-, IBTR-, and distant metastasis (DM)-free survival were calculated by the Kaplan–Meier method. Patient and pathologic variables were then analyzed in an attempt to identify predictors of clinical outcome. With a median follow-up period of 55 months (range 6–200 months), eight patients developed LRR, five of which were classified as IBTR. Five- and 10-year actuarial rates of LRR-free, IBTR-free, and DM-free survival were 93% and 88%, 96% and 91%, and 70% and 58%, respectively. Pretreatment and pathologic parameters that positively correlated with IBTR were advanced stage (p = 0.03) and margin positivity (p = 0.04). No other clinical factors were predictive of higher recurrence. BCT results in a low rate of IBTR and LRR in appropriately selected patients. Advanced stage at presentation is associated with increased risk of IBTR, although overall recurrence is low. In selected cases, BCT is safe and an effective alternative to mastectomy. [ABSTRACT FROM AUTHOR]

Brachytherapy is an essential technique to deliver radiation therapy and is involved in the treatment of multiple disease sites as monotherapy or as an adjunct to external beam radiation therapy. With a growing focus on the cost and value of cancer treatments as well as new payment models, it is essential that standardized quality measures and metrics exist to allow for straightforward assessment of brachytherapy quality and for the development of clinically significant and relevant clinical data elements. We present the American Brachytherapy Society consensus statement on quality measures and metrics for brachytherapy as well as suggested clinical data elements. Members of the American Brachytherapy Society with expertise in disease site specific brachytherapy created a consensus statement based on a literature review and clinical experience. Key quality measures (ex. workup, clinical indications), dosimetric metrics, and clinical data elements for brachytherapy were evaluated for each modality including breast cancer, cervical cancer, endometrial cancer, prostate cancer, keratinocyte carcinoma, soft tissue sarcoma, and uveal melanoma. This consensus statement provides standardized quality measures and dosimetric quality metrics as well as clinical data elements for each disease site to allow for standardized assessments of brachytherapy quality. Moving forward, a similar paradigm can be considered for external beam radiation therapy as well, providing comprehensive radiation therapy quality measures, metrics, and clinical data elements that can be incorporated into new payment models. [ABSTRACT FROM AUTHOR]

The article discusses the paper "Adjuvant radiation therapy and chemotherapy in Merkel cell carcinoma: Survival analyses of 6908 cases from the National Cancer Data Base," from S. Bhatia and colleagues. Topics discussed include the advantages of adjuvant radiotherapy in the treatment of patien with merkel cell carcinoma (MCC), the impact of surgical modality in adjuvant radiotherapy and overall survival, and the survival outcomes of patients with MCC.

Purpose Stereotactic body radiation therapy (SBRT) has been proposed for the palliation of painful vertebral bone metastases because higher radiation doses may result in superior and more durable pain control. A phase III clinical trial (Radiation Therapy Oncology Group 0631) comparing single fraction SBRT with single fraction external beam radiation therapy (EBRT) in palliative treatment of painful vertebral bone metastases is now ongoing. We performed a cost-effectiveness analysis to compare these strategies. Methods and Materials A Markov model, using a 1-month cycle over a lifetime horizon, was developed to compare the cost-effectiveness of SBRT (16 or 18 Gy in 1 fraction) with that of 8 Gy in 1 fraction of EBRT. Transition probabilities, quality of life utilities, and costs associated with SBRT and EBRT were captured in the model. Costs were based on Medicare reimbursement in 2014. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life years (QALYs). To account for uncertainty, 1-way, 2-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay (WTP) threshold of $100,000 per QALY gained. Results Base case pain relief after the treatment was assumed as 20% higher in SBRT. Base case treatment costs for SBRT and EBRT were $9000 and $1087, respectively. In the base case analysis, SBRT resulted in an ICER of $124,552 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of the utility of unrelieved pain; the utility of relieved pain after initial treatment and median survival were also sensitive to variation. If median survival is ≥11 months, SBRT cost <$100,000 per QALY gained. Conclusion SBRT for palliation of vertebral bone metastases is not cost-effective compared with EBRT at a $100,000 per QALY gained WTP threshold. However, if median survival is ≥11 months, SBRT costs ≤$100,000 per QALY gained, suggesting that selective SBRT use in patients with longer expected survival may be the most cost-effective approach. [ABSTRACT FROM AUTHOR]

Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram. Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The area under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram. Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801). Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients. [Copyright &y& Elsevier]

Purpose: Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes.Methods and Materials: In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method.Results: A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P < .05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P < .0001.Conclusions: The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens. [ABSTRACT FROM AUTHOR]

Globally, cervical cancer has the fourth highest cancer incidence and mortality in women. Cervical cancer is unique because it has effective prevention, screening, and treatment options. This review discusses the current cervical cancer advances with a focus on locally advanced cervical cancer. Topics discussed include diagnostic imaging principles, surgical management with adjuvant therapy and definitive concurrent chemoradiotherapy. Emphasis is given on current advances and future research directions in radiation therapy (RT) with an emphasis on three-dimensional brachytherapy, intensity-modulated RT, image-guided RT, proton RT and hyperthermia. [ABSTRACT FROM AUTHOR]

The optimal overall treatment time (OTT) from radical surgery to the end of adjuvant radiation therapy for some squamous cell carcinomas has been found to impact treatment outcomes. This study aims to identify the impact of OTT on overall survival (OS) for women with completely resected, node-positive squamous cell carcinomas of the vulva. The National Cancer Data Base was queried for women with surgically resected, node-positive vulvar squamous cell carcinomas between 2004 and 2016 who were treated with adjuvant radiation therapy. Kaplan-Meier analysis with log-rank test and Cox proportional hazards tests were utilized for OS calculations. A total of 1500 women met inclusion criteria. The median OTT was 104 days. Shorter OTT was associated with age, facility volume, private insurance, and duration of post-operative hospitalization. Median OS with OTT ≤ 104 days was 56.1 months vs 45.4 months if ≥105 days (p = 0.015). On multivariable Cox analysis, OTT was independently associated with an increased risk of death of 0.4% per additional day (95%CI 1.001–1.007, p = 0.003), as were age at diagnosis (HR 1.031 [95%CI 1.024–1.037], p < 0.001), number of nodes positive (HR 1.031 [95%CI 1.024–1.037], p = 0.006), the use of concurrent chemotherapy (HR 0.815 [95%CI 0.693–0.960], p = 0.014) and increasing pT/pN stage. After propensity adjustment for factors predicting a shorter OTT, OTT continued to be associated with an increased risk of death per additional day (HR 1.004 [95%CI 1.001–1.007], p = 0.007). Overall treatment time is an independent risk factor for death in women being treated with adjuvant radiation therapy following complete resection of node-positive squamous cell carcinoma of the vulva. • OTT of adjuvant radiation therapy is an independent risk factor for death in women with resected, node-positive vulvar cancer • Each additional day between surgery and completion of adjuvant radiation contributes to higher risk of death • This is the first study to evaluate the impact of OTT on overall survival in this population of patients [ABSTRACT FROM AUTHOR]

Purpose: Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions.Methods and Materials: An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement between observers.Results: Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus.Conclusions: Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes. [ABSTRACT FROM AUTHOR]

GOG 205 safely increased clinical (cCR) and pathologic complete response (pCR) in locally-advanced vulvar cancer through dose escalation using three-dimensional radiotherapy (RT). The aim of this study is to assess the response of dose-escalated intensity modulated radiotherapy (IMRT) in locally-advanced vulvar cancer. A retrospective review of patients treated with dose-escalated (≥ 55Gy) IMRT from 2012 to 2018 for locally-advanced vulvar cancer was performed. Patients treated with preoperative or definitive intent were included. Rates of cCR and pCR were assessed, and predictors of disease-free survival (DFS) were analyzed using the Kaplan Meier method with log rank test between groups and a parsimonious multivariate Cox model. Median dose to the vulva was 66.0 Gy (Interquartile Range [IQR]: 66.0–68.0) for definitive and 59.4 Gy (IQR: 58.0–59.4) for preoperative IMRT. The overall rates of cCR and pCR were 76% and 70%, respectively. DFS at two years was 65% (95% Confidence Interval [CI] 50–80%) for all patients, 81% (95% CI 63% - 98%) for definitive IMRT, and 55% (95% CI 35% - 76%) for preoperative IMRT. On multivariate analysis, cCR predicted for disease-free survival (HR 0.21; 95% CI 0.06–0.76; p = 0.02), and pCR predicted for OS (HR 0.12; 95% CI 0.02–0.60; p = 0.01). Grade 3 acute and late RT toxicity was seen in 14 (29%) and 3 (6%) of patients, respectively. Dose-escalated IMRT for locally-advanced vulvar cancer is well tolerated, with rates of cCR and pCR that compare favorably with published data. • Median dose to the vulva was 66.0 Gy for definitive and 59.4 Gy for preoperative IMRT. • The rates of cCR and pCR were 48% and 31% in GOG 101, 64% and 50% in GOG 205, and 76% and 70% in the present study. • Patients node negative on imaging received 45–50 Gy to the groin without biopsy. • No isolated inguinal failures were observed in patients that were node negative on imaging. • On multivariate analysis, cCR predicted for disease-free survival and pCR predicted for OS. [ABSTRACT FROM AUTHOR]

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies. [ABSTRACT FROM AUTHOR]

Studies examining temporal trends in cervical brachytherapy use are conflicting and examined different health insurance populations. This study examined brachytherapy utilization over time by health insurance type and whether reported declines in brachytherapy have reversed. The National Cancer Database (NCDB) was queried for patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy between 2004 and 2014, identifying 17,442 patients. Brachytherapy utilization over time and by insurance type and other sociodemographic factors were compared using binary logistic regression. A sensitivity analysis was done in a sub-cohort of patients using the boost modality variable in the NCDB. Brachytherapy utilization declined during 2008–10 (52.6%) compared to 2004–2007 (54.4%; odds ratio [OR] 0.93, 95% confidence interval [CI] 0.86–1.01) and declines were disproportionately larger for patients with government insurance (49.4% vs 52.3%, respectively) than privately-insured patients (57.6% vs 58.9%, respectively). However, rates of brachytherapy use subsequently recovered during 2011–14 in all insurance groups (58.0%, OR 1.24, 95% CI 1.16–1.34) and was especially improved for Medicaid (OR 1.44, 95% CI 1.26–1.65) and uninsured patients (OR 1.28, 95% CI 1.03–1.57). Sensitivity analysis using the boost modality variable confirmed these trends. In patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy from 2004 to 2014, brachytherapy utilization declined during the late 2000s and disproportionately affected patients with government insurance, but subsequently recovered in the early 2010s. Since government insurance covers vulnerable patient populations at-risk for future declines in brachytherapy use, proposed alternative payment models should incentivize cervical brachytherapy to solidify gains in brachytherapy utilization. • Use of cervical brachytherapy (BT) declined in the late 2000s and disproportionately affected government-insured patients. • However, trends reversed in the early 2010s such that patients of all insurance types had increased BT use. • Awareness of declining BT use raised by researchers and the Affordable Care Act may have facilitated this improvement. • Proposed alternative payment models should incentivize cervical BT to encourage and solidify these gains. [ABSTRACT FROM AUTHOR]

Purpose: We sought to characterize temporal trends of radiation oncology resident-reported external beam radiation therapy (EBRT) case experience with respect to various disease sites, including trends in stereotactic radiosurgery and stereotactic body radiation therapy cases.Methods and Materials: Summarized, deidentified case logs for graduating radiation oncology residents between 2007 and 2018 were obtained from the Accreditation Council for Graduate Medical Education national summary data report. Mean number of cumulative cases and standard deviations per graduating resident by year were evaluated. Cases were subdivided into 12 disease-site categories using the Accreditation Council for Graduate Medical Education classification. Analysis of variance was used to determine significant differences, and strength of association was evaluated using Pearson correlation.Results: The number of graduating residents per year increased by 66% from 114 in 2007 to 189 in 2018 (P < .001, r = 0.88). The overall mean number of EBRT cases per graduating resident decreased by 13.2% from 521.9 in 2007 to 478.5 in 2018, with a decrease in the ratio of nonmetastatic to metastatic cases per graduating resident. There was significant variation among the disease categories analyzed; however, the largest proportionate decreases were seen in hematologic, lung, and genitourinary malignancies. Stereotactic radiosurgery volume per graduating resident increased from an average of 27.9 cases in 2007 to 50.3 in 2018 (P < .001, r = 0.96). Stereotactic body radiation therapy volume per graduating resident increased as well, from a mean of 6 cases in 2007 to 55.6 cases in 2018 (P < .001, r = 0.99).Conclusions: We report a longitudinal summary of resident-reported experience in EBRT cases. These findings have implications for future efforts to optimize residency training programs and requirements. [ABSTRACT FROM AUTHOR]

Many patients with endometrial cancer cannot undergo surgery and instead receive definitive radiation therapy (RT). We investigate the correlation between MRI response to RT and clinical outcomes. Women with inoperable, clinical Stage I endometrial cancer were treated with definitive brachytherapy (BT) with/without pelvic RT (PRT). Patients underwent MRI with functional diffusion-weighted imaging before and after RT. A radiologist retrospectively classified cases as complete, partial, or indeterminate response (CR, PR, or IR, respectively) vs. disease progression. Local control was clinicopathologically defined. From 2007 to 2017, 50 women underwent definitive RT. Thirty-five (70%) received BT alone (median dose 37.5 Gy). For combined therapy, the median PRT and BT doses were 45 and 25 Gy, respectively. Median gross tumor volume and high-risk clinical target volume were 7.1 cc and 90.0 cc, respectively. Median followup among living patients was 20 months. All patients underwent post-RT MRI with T1/T2 sequencing at a median of 3.2 months after RT; 40 patients (80%) underwent functional diffusion-weighted imaging sequences. On initial post-RT MRI, CR was documented in 42 patients (84%), IR in 1 patient (2%), and PR in seven patients (14%). At median followup of 16.3 months, no CR patients had uterine failure. Among eight patients with initial PR/IR, all were found to be clinicopathologically no evidence of disease at the uterus on further evaluation. Definitive RT with BT or BT + PRT is associated with high response rates on MRI. Overall, initial CR predicted for excellent outcome with no infield failure. [ABSTRACT FROM AUTHOR]

Purpose: There is limited long-term data on outcome and side effects of Cs-131 prostate brachytherapy and minimal patient-reported data on rectal bleeding with any isotope. We aimed to describe the incidence, prevalence, and predictors of late patient-reported rectal bleeding after Cs-131 brachytherapy.Methods and Materials: We reviewed a prospectively collected database of 620 men treated with Cs-131 prostate brachytherapy. Of 620 patients, 390 (62.9%) received brachytherapy as monotherapy; the remainder received combination therapy with external beam radiation therapy (EBRT). Patients were administered Expanded Prostate Cancer Index Composite questionnaires preoperatively and postoperatively at each follow-up visit. The primary outcome was late rectal bleeding, defined as rectal bleeding reported at the 6-month follow-up or later. Clinically significant rectal bleeding was defined as occurring more than "rarely," and clinically significant bother from rectal bleeding was defined as considering bleeding more than a "very small problem." Univariate and multivariate Cox regression were performed to identify factors predictive for rectal bleeding.Results: With a median follow-up time of 48 months, the cumulative incidence of clinically significant late rectal bleeding was 12.4%, with 15.2% reporting clinically significant bother from bleeding. At the time of last follow-up, the prevalence of clinically significant rectal bleeding and bother were 4.0% and 4.7%, respectively. On univariate analysis, acute clinically significant rectal bleeding, defined as occurring within the first 6 months (P = .001) and combination therapy with EBRT (P = .001) predicted for clinically significant late rectal bleeding. On multivariate analysis, both EBRT (P = .001; hazard ratio, 2.50; 95% confidence interval, 1.58-3.94) and acute rectal bleeding (P < .001; hazard ratio, 3.11; 95% confidence interval, 1.75-5.53) remained significant predictors for late rectal bleeding.Conclusions: Prostate brachytherapy with Cs-131 is well tolerated in the long term. Although the incidence of clinically significant patient-reported late rectal bleeding was 12.4%, the prevalence at last follow-up was only 4.0%, suggesting that this problem tends to resolve. [ABSTRACT FROM AUTHOR]

• Pathological downstaging after neoadjuvant chemotherapy affects survival in NSCLC. • Adjuvant therapy does not benefit patients with ypN0-1 or lymph node ratio < 15%. • Adjuvant chemotherapy and radiation benefit ypN2 and lymph node ratio > 15%. • The results may provide guidance in the absence of randomized trials. Optimal adjuvant therapy in patients with clinically N2 (cN2) non-small cell lung cancer (NSCLC) who undergo neoadjuvant chemotherapy followed by surgery is controversial. We evaluated the impact of adjuvant chemotherapy (CT) and/or radiation (RT) in this patient population. Patients with non-metastatic, cN2 NSCLC diagnosed from 2004 to 2015 were identified from the National Cancer Database, which captures 70% of cancer cases diagnosed in the United States. Patients underwent neoadjuvant CT and surgical resection. Patients couldn't receive RT before surgery. Survival was compared using log-rank and Cox proportional hazards modeling. Subset analyses were performed based on post-chemotherapy surgical nodal staging (ypN0-2) and lymph node ratio (LNR), including 0%, 1–15%, or >15% involvement. LNR was defined as number of nodes involved by tumor divided by number of nodes examined. We identified 1541 patients. The percentage of patients who received adjuvant CT and RT was 18.9% and 35.7% respectively. ypN status and LNR were predictive of survival on univariate analysis, but only LNR maintained significance on multivariate analysis. There was no benefit observed for adjuvant CT or RT in the entire cohort. On subset analyses, a survival benefit was observed in ypN2 patients with receipt of CT or RT (HRs 0.77 and 0.81, respectively, p < 0.05). In patients with LNR > 15%, there was a significant benefit of RT (HR 0.76, p = 0.007) and borderline benefit of CT (HR 0.78, p = 0.058). Patients with cN2 disease with subsequent ypN0-1 and/or LNR < 15% following induction chemotherapy do not benefit from adjuvant therapy. Patients with persistent N2 disease and LNR > 15% who receive adjuvant CT and RT have improved survival. Aggressive consolidative therapy appears to improve survival in patients with persistent or high nodal burden disease. [ABSTRACT FROM AUTHOR]

The purpose of this study was to study the correlation between intraoperative and postimplant dosimetry. We investigated the correlation between prostate (V 150) and urethra (D 30 , D 5) dose limits, and whether it is possible to increase prostate D 90 and V 100 in intraoperative planning without violating postimplant urethra and rectum dose limits. Seventy-nine patients who underwent real-time ultrasound-guided prostate implants using intraoperative planning from 2013 to 2017 were analyzed. Forty-one of the 79 implants were 125I as monotherapy and the remainder was 103Pd as boost to external beam radiation therapy or external beam radiation therapy plus androgen deprivation therapy. Prescriptions followed the guidelines of AAPM TG-137. The urethra was catheterized during intraoperative implantation and postimplant imaging to facilitate the urethra identification. T2-cubed MRI and CT were acquired on the same day and about 1 month after the low-dose-rate procedure, and MRI was later fused with the CT scan for accurate delineation of the prostate and postimplant dosimetry evaluation. An institutionally based peer-review process and document procedure were established based on national recommendations. Correlation of dose parameters: D 90 , V 150 , V 100 of prostate, D 30 , D 5 of urethra, and V 100 of rectum between intraoperative and postimplant plans were evaluated. D 90 and V 100 declined for all implants between intraoperative and postimplant dosimetry. On average, D 90 declined by 17.5% and 21.7% for 125I and 103Pb implants, respectively. V 100 declined for all implants between intraoperative and postimplant dosimetry but less pronounced. Prostate V 150 and urethra D 30 and D 5 also showed different tendency of decline. Of the 79 implants, 60 did not meet the postimplant dosimetry target for prostate (V 150 ≤ 50%), and 46 of the 60 implants met the optimal dosimetry targets for both D 30 (<125%) and D 5 (<150%), and the other 14 of the 60 implants failed to meet either the D 30 or the D 5 limits. All the implants met the postimplant target dose for rectum: V 100 ≤ 1.3 cc. Intraoperative implant dosimetry could not accurately predict postimplant dosimetry; however, to avoid underdosage of prostate, intraoperative D 90 should be close to 120% of prescribed dose and V 100 needs to be close to 100% of prescribed dose. Prostate V 150 > 50% does not necessarily indicate the violation of urethra D 30 and D 5 dose limits. For most of the implants, target intraoperative D 90 and V 100 could be raised without violating urethra D 30 and D 5 limits recommended by American Brachytherapy Society in postimplant evaluation. [ABSTRACT FROM AUTHOR]