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Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment., Competing Interests: Disclosures Rohann J. M. Correa reports research funding from Droplet Biosciences. Alan Dal Pra reports research support from Veracyte. Tugce Kutuk reports a travel stipend from GammaTile. Simon S. Lo reports research support from Elekta AB and the Kuni Foundation, travel support from the Japanese Society for Radiation Oncology, and leadership roles as a member of the ICON Gamma Knife Expert Group, American College of Radiology, and the Radiosurgery Society. Alexander Louie reports honoraria from AstraZeneca and serves on an AstraZeneca advisory board. Sarah P. Psutka reports grants from the National Institutes on Aging, Bladder Cancer Advisory Network, and PRIME Education, as well as serving on advisory or data safety monitoring boards for Janssen, Merck, Immunity Bio, and CG Oncology, and leadership roles for European Urology journal, Bladder Cancer journal, and American Urological Association. Shankar Siva reports research funding from Merck-Sharp-Dohme, Bayer Pharmaceuticals, and Varian Medical Systems. Karin A. Skalina reports a leadership role with the Radiosurgical Society. Anand Swaminath reports honoraria from AstraZeneca and Bristol Myers Squibb, as well as serving on an AstraZeneca advisory board. Chad Tang reports consulting fees from Telix Pharmaceutical, as well as advisory board service for Siemens Healthineer, Lantheus Pharmaceutical, and Bayer, as well as clinical trial research support from Merck and Myriad. Rituraj Upadhyay reports payment or honoraria and travel support from Varian Medical Systems. Nicholas G. Zaorsky reports support from the American Cancer Society – Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG-20-013-01-CCE and the Department of Defense, as well as remuneration from the American College of Radiation Oncology for chart review and accreditation of radiation oncology facilities nationally and remuneration from Spring Nature for the textbook Absolute Clinical Radiation Oncology Review; he was supported by the National Institutes of Health Grant LRP 1 L30 CA231572-01. All other authors report no disclosures., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors have no conflicts of interest or disclosures.

What are the factors that physicians could consider in an academic radiation oncology practice job offer? In this minireview, we discuss how prospective academic faculty could evaluate the "big 3" domains: (1) the compensation, including the direct and indirect payments; (2) the daily job, including aspects of the clinic, research, and education; and (3) the location, including geography, atmosphere, environment, and culture. If a prospective academic radiation oncologist believes that the academic practice is "great" in at least 2 of the 3 and "good" in the remaining 1, then they should likely sign the contract., Competing Interests: Disclosures Nicholas G. Zaorsky is supported by the American Cancer Society – Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG-20-013-01-CCE (2020-) and the Department of Defense (2020 - ). Nicholas G. Zaorsky receives remuneration from the American College of Radiation Oncology for chart review and accreditation of radiation oncology facilities nationally (2020-). Nicholas G. Zaorsky was supported by the National Institutes of Health Grant LRP 1 L30 CA231572-01 (2018-2022). Nicholas G. Zaorsky and Daniel M Trifiletti received remuneration from Springer Nature for the textbook, Absolute Clinical Radiation Oncology Review (2019). Nicholas G. Zaorsky received payments from Weatherby Healthcare, unrelated to research (2018-2019)., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Recognizing sexual orientation and gender identity (SOGI) is paramount in the management of genitourinary cancers, as sexual and gender minority (SGM) individuals encounter unique healthcare challenges leading to disparities. SGM patients often confront systemic barriers, provider biases, and scarcity of tailored resources, resulting in diminished satisfaction and adverse health outcomes. The evaluation and treatment of genitourinary cancers in SGM patients demand a nuanced, multidisciplinary approach that focuses on the unique health determinants often overlooked by the healthcare system. This review highlights recommendations for the inclusivity of SGM patients within the clinic, from inclusive signage to gender inclusive language. For the evaluation and treatment of SGM patients with genitourinary cancers, it is recommended to employ organ-based language, to utilize validated questionnaires encompassing mental health, sexual behavior, and patient-reported outcomes, and to provide timely referrals to social work and onco-fertility when appropriate. Ultimately, approaching inclusivity through education targeted at both SGM patients and healthcare providers is pivotal for centering care around the patient, improving the quality of life and outcomes for SGM patients facing genitourinary cancers., Competing Interests: Declaration of competing interest There are no conflicts of interests or disclosures to report for all authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Castration-sensitive metastatic prostate cancer is heterogeneous. Our objective is to identify metastatic prostate cancer phenotypes and their prognostic impact on survival., Materials and Methods: The National Cancer Database was queried. The Surveillance, Epidemiology, and End Results database was used for validation. Patterns were split into: nonregional lymph node, bone only, and visceral (any brain/liver/lung). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for the univariate and multivariate Cox proportional hazards regression models, odds ratios were calculated, Kaplan-Meier curves were generated, and a nomogram of the multivariate regression model was created., Results: The training set included 13,818 men; bone only was most common (n = 11,632, 84.2%), then nonregional lymph node (n = 1388, 10.0%), and any visceral (brain/liver/lung; n = 798, 5.8%). Risk of death was increased by metastases to a visceral organ versus nonregional lymph node (HR = 2.26; 95% CI [2.00, 2.56]), bone only metastases versus nonregional lymph node (HR = 1.57; 95% CI [1.43, 1.72]), T-stage 4 versus 1 (HR = 1.27; 95% CI [1.17, 1.36]), Grade Group 5 versus 1 (HR = 1.93; 95% CI [1.61, 2.31]), PSA > 20 ng/mL versus < 10 ng/mL (HR = 1.32; 95% CI [1.23, 1.42]), and age ≥ 80 versus < 50 (HR = 1.96; 95% CI [1.69, 2.29]). On internal validation, the model had C-indices 20.5%, 22.7%, and 14.6% higher than the current staging system for overall survival, 1-year, and 5-year survival, respectively., Conclusion: We developed and validated prognostic metastatic prostate cancer phenotypes that can assist risk stratification to potentially personalize therapy. Our nomogram (https://tinyurl.com/prostate-met) may be used to predict survival., (Copyright © 2022. Published by Elsevier Inc.)

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that originate in endocrine tissues throughout the body. Though most are indolent, clinical outcomes vary greatly based on histologic differentiation and grade. Peptide receptor radionuclide therapy has emerged as a promising treatment for patients with locally advanced and/or metastatic disease refractory to standard of care treatment. The phase III NETTER-1 trial found that [ 177 Lu] Lu-DOTA-[Tyr 3 ]-octreotate improved disease-free survival versus octreotide alone for somatostatin receptor-positive gastroenteropancreatic NETs and had a favorable toxicity profile, leading to Food and Drug Administration approval. [ 177 Lu] Lu-DOTA-[Tyr 3 ]-octreotate is an important new treatment that expands the role of radiation in the treatment of NETs. Several important trials are ongoing to better elucidate the role of this treatment., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Prostate-specific membrane antigen is a transmembrane protein found predominately on prostate epithelium and is expressed at high levels in prostate cancer. In this review, we discuss the background, clinical data, patient selection, side effects, and necessary resources to deliver lutetium-177 prostate-specific membrane antigen in the research setting, or as standard of care if approved by the United States Food and Drug Administration. Targeted radionuclide therapeutics require understanding of fundamental principles of radiobiology and physics, and radiation oncologists and medical physicists are well-suited to play an integral role in their delivery and treatment response monitoring as key components of a multidisciplinary care team., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the impact of RTOG-9601 and GETUG-AFU-16 on the routine use of combination androgen deprivation therapy (ADT) with postoperative radiotherapy (PORT) for prostate cancer (CaP)., Material and Methods: Patients with localized CaP treated with radical prostatectomy (RP) and PORT with or without ADT at a comprehensive cancer center from January 2006 to June 2007 (Period 1 = P1), July 2011 to December 2012 (Period 2 = P2), and January 2017 to June 2018 (Period 3 = P3) were included. Clinicopathologic features and treatment characteristics were analyzed and compared. Multivariable logistic regression was used to assess prognostic factors and association with ADT use. Statistical tests were two-sided and a P value <0.05 was considered significant. To validate the findings, United States National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results (SEER) data were collected to assess rates of combined ADT and PORT from 2004 to 2015., Results: Five hundred and two patients were included: 152 (P1), 185 (P2), and 165 (P3). PORT was most commonly delivered as early SRT (delivered >1 year post-RP with undetectable PSA or PSA >0.05 and ≤0.5 ng/ml) in all periods. The use of combination PORT and ADT increased over time: 14.5% (P1), 32% (P2), and 41% (P3) (P < 0.001). The proportion of patients that met eligibility criteria for either GETUG-AFU-16 or RTOG-9601 decreased from 47% (P1) to 35% (P3) (P = 0.04). International Society of Urological Pathology grade ≥4 (P < 0.002) and pre-PORT PSA >0.5 ng/ml (P < 0.001) were associated with use of ADT. Positive surgical margin status had a negative association (RR 0.5, P < 0.002). The NCDB demonstrated similar trends for use of combined ADT with PORT, increasing from 37% to 49% from 2004 to 2015., Conclusion: The use of combined ADT with PORT increased over time. However, only a third of contemporary patients undergoing PORT are represented in the major trials supporting the evidence for combination treatment, highlighting the need to characterize the modern impact of this intensification strategy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: The objectives of this study were to (1) characterize the epidemiology of liver metastases at the time of primary cancer diagnosis (synchronous liver metastases), (2) characterize the incidence trends of synchronous liver metastases from 2010-2015 and (3) assess survival of patients with synchronous liver metastases., Methods: The Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 was queried to obtain cases of patients with liver metastases at the time of primary cancer diagnosis. The primary cancers with an incidence rate of liver metastasis >0.1 are presented in this analysis., Results: Among 2.4 million cancer patients, 5.14 % of cancer patients presented with synchronous liver metastases. The most common primary site was breast cancers for younger women (ages 20-50), and colorectal cancers for younger men. As patients get older, a more heterogenous population of the top cancers with liver metastases emerges including esophageal, stomach, small intestine, melanoma, and bladder cancer in addition to the large proportion of lung, pancreatic, and colorectal cancers. The 1-year survival of all patients with liver metastases was 15.1 %, compared to 24.0 % in those with non-hepatic metastases. Regression analysis showed that the presence of liver metastasis was associated with reduced survival, particularly in patients with cancers of the testis, prostate, breast, and anus, and in those with melanoma., Conclusions: The most common primary sites for patients with liver metastases varied based on age at diagnosis. Survival for patients with liver metastasis was significantly decreased as compared to patients without liver metastasis., Competing Interests: Declaration of Competing Interest No conflicts of interest to report for any of the authors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Numerous trials have been launched over the prior decade examining the safety and efficacy of therapy de-escalation in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC). Because no summative assessment of these prospective trials exists to date, we systematically reviewed the outcomes and toxicities associated with therapy de-intensification for this population. PRISMA-guided systematic PubMed searches (along with articles known to the authors and references thereof) were performed for prospective studies reporting clinical outcomes and/or toxicities of de-intensified RT and/or systemic therapy (with or without surgery), exclusively for HPV-associated OPC. Ten prospective studies were analyzed. Performing a meta-analysis was not entirely possible owing to the heterogeneity of treatment paradigms and the lack of >2 studies for most paradigms; however, because just one paradigm (induction chemotherapy followed by reduced-dose RT and/or systemic therapy) had 4 associated articles, an exploratory meta-analysis was conducted for that subset. Two trials of dose-reduced concurrent chemoradiotherapy (60 Gy/weekly cisplatin) demonstrated 3-year distant metastasis-free survival and overall survival (OS) ranging from 91 to 100% and 95%, respectively; acute grade 3+ mucositis and dysphagia occurred in 33-35% and 21-39%, respectively. In the four trials of induction chemotherapy (platinum/taxane-based) followed by dose-reduced RT, 2-year progression-free and OS ranged from 80 to 95% and 83 to 98%, respectively; acute grade 3+ dysphagia, dermatitis, and mucositis ranged from 9 to 15%, 7 to 20%, and 9 to 30% (excluding one outlier), respectively. For these four trials, the exploratory meta-analysis showed a pooled 2-year PFS and OS of 89% (95% confidence interval, 80-96%) and 96% (92-99%). The pooled rates of grade ≥3 dysphagia, dermatitis, and mucositis were 13% (7-19%), 9% (5-14%), and 28% (9-53%). However, there was significant heterogeneity in the 2-year PFS (I 2  = 57%, p = 0.07) and grade ≥3 mucositis (I 2  90%, p < 0.01). Next, both randomized trials which replaced concurrent tri-weekly cisplatin with weekly cetuximab illustrated superior outcomes with the former. Lastly, two remaining trials (one using functional imaging to guide reduced-dose RT, and another examining reduced-dose postoperative RT) also showed satisfactory outcomes and toxicities. Taken together, dose-reduced chemoradiotherapy (with or without induction chemotherapy for patient/biology selection purposes) seems to be a promising de-escalation strategy for HPV-associated OPC, although replacement of concurrent cisplatin by cetuximab is not recommended. Long-term follow-up is required for firmer conclusions., Competing Interests: Declaration of Competing Interest There are no acknowledgements. There was no funding for this study. This study has not been presented or published in part or full form elsewhere. All authors declare no conflicts of interest. DMT reports clinical trial research support from Novocure and publishing fees from Springer Inc., outside of submitted work. NGZ has startup funding from Penn State Cancer Institute, and is supported by the National Institutes of Health LRP 1 L30 CA231572-01. NGZ received personal fees from Springer Nature, Inc and Weatherby Healthcare, unrelated to the submitted work. S.A. received grants from Accuray International, Sàrl, and Merck Serono GmbH outside the submitted work. All other authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Industry payments to physicians are financial conflicts of interest and may influence research findings and medical decisions. We aim to (1) characterize industry payments within radiation oncology; and (2) explore the potential correlation between receiving disclosed industry payments and academic productivity., Materials/methods: CMS database was used to extract 2015 industry payments. For academic radiation oncologists, research productivity was characterized by h- and m-indices, as well as receipt of National Institutes of Health (NIH) funding, which is not an industry payment. Logistic regression models were used to determine whether publication metrics (m-index, h-index) and other study characteristics such as gender, PhD status, NIH institution funding status, were associated with the endpoints, research and general payments. Associations between the amount of payments (if any) and publication metrics were further studied using linear regression models., Results: A total of 22,543 individual payments totaling $25,532,482 to 2,995 radiation oncologists were included. Among the 1,189 academic radiation oncologists, 75% received less than $167; on the other hand, 10 (<1%) individuals received $6,425,728 (51%) of payments. On multiple logistic regression, research payments were significantly associated with the m-index, odds ratio 2.86 (95% confidence interval, 1.84-4.45, p-value <0.0001); as well as with the h-index, odds ratio 1.03 (95% confidence interval, 1.01-1.05, p-value <0.0001). The linear regression model shows that both m-index and h-index were significantly positively associated with the amount of general payments (p-values <0.0001)., Conclusion: There is an association between disclosed payment from the industry and increased individual research productivity metrics. Further research to find the cause behind this association is warranted., (Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Introduction: Combined immune checkpoint blockade has led to rare autoimmune complications, such as fatal myocarditis. Recent approvals of several anti-programmed death 1 (anti-PD-1) drugs for lung cancer treatment prompted ongoing clinical trials that directly combine PD-1 inhibitors with thoracic radiotherapy for locally advanced lung cancer. Overlapping toxicities from either modality have the potential to increase the risk for radiation-induced cardiotoxicity (RICT), which is well documented among patients with Hodgkin's disease and breast cancer., Methods: To investigate cardiotoxicity without the compounding pulmonary toxicity from thoracic radiotherapy, we developed a technique to deliver cardiac irradiation (CIR) in a mouse model concurrently with PD-1 blockade to determine the presence of cardiac toxicity by using physiological testing and mortality as end points along with histological analysis., Results: We observed an acute mortality of 30% within 2 weeks after CIR plus anti-PD-1 antibody compared with 0% from CIR plus immunoglobulin G (p = 0.023). Physiological testing demonstrated a reduced left ventricular ejection fraction (p < 0.01) by echocardiogram. Tissue analyses revealed increased immune cell infiltrates within cardiac tissue. Depletion of CD8-positive lymphocytes with anti-CD8 antibody reversed the acute mortality, suggesting that the toxicity is CD8-positive cell-mediated. To validate these findings using a clinically relevant fractionated radiotherapy regimen, we repeated the study by delivering five daily fractions of 6 Gy. Similar mortality, cardiac dysfunction, and histological changes were observed in mice receiving fractionated radiotherapy with concurrent anti-PD-1 therapy., Conclusions: This study provides strong preclinical evidence that radiation-induced cardiotoxicity is modulated by the PD-1 axis and that PD-1 blockade should be administered with careful radiotherapy planning with an effort of reducing cardiac dose., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of the study was to determine the effect of type 2 diabetes mellitus (T2DM) on outcomes and toxicities among men with localized prostate cancer receiving definitive radiation therapy., Patients and Methods: We performed a retrospective review of 3217 patients, from 1998 to 2013, subdivided into 5 subgroups: (I) no T2DM; (II) T2DM receiving oral antihyperglycemic agent that contains metformin, no insulin; (III) T2DM receiving nonmetformin oral agent alone, no insulin; (IV) T2DM receiving any insulin; and (V) T2DM not receiving medication. Outcome measures were overall survival, freedom from biochemical failure (BF), freedom from distant metastasis, cancer-specific survival, and toxicities. Kaplan-Meier analysis, log rank tests, Fine and Gray competing risk regression (to adjust for patient and lifestyle factors), Cox models, and subdistribution hazard ratios (sHRs) were used., Results: Of the 3217 patients, 1295 (40%) were low-risk, 1192 (37%) were intermediate-risk, and 652 (20%) were high risk. The group I to V distribution was 81%, 8%, 5%, 3%, and 4%. The median dose was 78 Gy, and the median follow-up time was 50 (range, 1-190) months. Group V had increased mortality (sHR, 2.1; 95% confidence interval [CI], 0.66-1.54), BF (sHR, 2.14; 0.88-1.83), and cause-specific mortality (sHR, 3.87; 95% CI, 1.31-11). Acute toxicities were higher in group IV versus group I (genitourinary: 38% vs. 26%; P = .01; gastrointestinal: 21% vs. 5%; P = 001). Late toxicities were higher in groups IV and V versus group I (12%-14% vs. 2%-6%; P < .01)., Conclusion: Men with T2DM not receiving medication and men with T2DM receiving insulin had worse outcomes and toxicities compared to other patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016. The most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders; the most common regimen was 10Gy in 1Gy fractions over two weeks, and 27% of patients received retreatment. A partial or complete response (for symptoms, lab abnormalities) was obtained in 85-90% of treated patients, and 30% were retreated within 6-12months. There was no correlation between biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement (r 2 all <0.4); therefore, lower doses (e.g. 5Gy in 5 fractions) may be as effective as higher doses. Grade 3-4 toxicity (typically leukopenia, infection) was noted in 22% of courses, with grade 5 toxicity in 0.7% of courses. All grade 5 toxicities were due to either thrombocytopenia with hemorrhage or leukopenia with sepsis (or a combination of both); they were sequelae of cancer and not directly caused by SI. In summary, SI is generally a safe and efficacious method for treating patients with symptomatic splenomegaly., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Approximately 50% of newly diagnosed cancer patients start taking dietary supplements. Men's health supplements (MHSs), which we define as supplements that are specifically marketed with the terms men's health and prostate health (or similar permutations), are often mislabeled as having potential anticancer benefits., Objective: We evaluated the effects of MHSs on patient outcomes and toxicities in patients who were undergoing definitive intensity-modulated radiation therapy (IMRT) for localized prostate cancer., Design: This retrospective analysis included patients who were being treated at a National Cancer Institute-designated comprehensive cancer center and consented to have information stored in a prospective database. MHSs were queried online. Outcome measures were freedom from biochemical failure (FFBF) (biochemical failure was defined with the use of the prostate-specific antigen nadir + 2-ng/mL definition), freedom from distant metastasis (FFDM), cancer-specific survival (CSS), and overall survival (OS) as well as toxicities. Kaplan-Meier analysis, log-rank tests, Fine and Gray competing-risk regression (to adjust for patient and lifestyle factors), and Cox models were used., Results: From 2001 to 2012, 2207 patients were treated with IMRT with a median dose of 78 Gy, and a median follow-up of 46 mo. Of these patients, 43% were low risk, 37% were intermediate risk, and 20% were high risk; 10% used MHSs. MHSs contained a median of 3 identifiable ingredients (range: 0-78 ingredients). Patients who were taking an MHS compared with those who were not had improved 5-y OS (97% compared with 92%, respectively; P = 0.01), but there were no differences in the FFBF (94% compared with 89%, respectively; P = 0.12), FFDM (96% compared with 97%, respectively; P = 0.32), or CSS (100% compared with 99%, respectively; P = 0.22). The unadjusted association between MHS use and improved OS was attenuated after adjustment for patient lifestyle factors and comorbidities. There was no difference in toxicities between the 2 groups (late-grade 3-4 genitourinary <3%; gastrointestinal <4%)., Conclusion: The use of MHSs is not associated with outcomes or toxicities., (© 2016 American Society for Nutrition.)

Background: The purpose of the study was to identify the effect of final surgical margin (SM) status and re-excision on outcomes in patients with ductal carcinoma in situ (DCIS) who underwent breast conservation therapy (BCT)., Patients and Methods: The study population consisted of women diagnosed with DCIS who underwent BCT between 1989 and 2014. All women received adjuvant whole breast radiation and a boost. The primary end point was local control (LC). Final SMs were defined according to margin width: negative SM was defined as > 2 mm, close SM was defined as > 0 to ≤ 2 mm, and a positive SM was defined as tumor on ink. The Cox proportional hazards model was used to determine predictors of outcomes on multivariable analysis. Actuarial incidence of LC was estimated using the Kaplan-Meier method., Results: A total of 498 patients were included; 400 patients had a final negative SM, 87 had a close SM, and 11 had a positive SM. A total of 172 patients received adjuvant hormonal therapy, 265 patients required ≥ 1 re-excision. Patients with positive or close SMs were more likely to receive a radiation dose > 60 Gy (P < .001) and undergo re-excision (P < .01). The 10-year LC rates were not significantly different between patients with a negative (93.5%), close (91.8%), or positive (100%) SM (P = .57). There was no difference in LC in patients who underwent re-excision for initial close or positive SMs (P = .55)., Conclusion: This single-institution experience showed that risks of local recurrence remain poorly characterized. Re-excision and whole breast radiation with boost resulted in excellent LC for women with DCIS. Trials aimed at personalized deintensified local therapy are warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to assess the trends in use of clinical diagnosis and its impact on treatment outcomes in patients receiving radiation therapy for early-stage lung cancer., Methods: The Surveillance, Epidemiology, and End Results registry was queried from 2004 to 2012 for patients at least 18 years old in whom stage I (clinical stage T1a-T2a) lung cancer had been diagnosed and who underwent radiation therapy alone. Trends in diagnostic confirmation patterns were characterized. A Cox proportional hazards model was used to assess overall survival, and competing risk regression analysis was used to assess cancer-specific survival (CSS)., Results: A total of 7050 patients were included; the disease of 6399 of them (90.8%) was pathologically diagnosed and that of 651 (9.2%) was clinically diagnosed. There was no significant change in the utilization of clinical versus pathologic diagnosis (p = 0.172) over time. Patients with T1 disease (p < 0.001), tumors 0 to 1.9 cm in size (p < 0.001), and upper lobe tumors (p = 0.004) were more likely to have been clinically diagnosed. On multivariable analysis, clinical diagnosis was associated with an improved CSS (hazard ratio [HR] = 0.82, 95% confidence interval [CI]: 0.71-0.96) but was not associated with an improved overall survival (HR = 1.01, 95% CI: 0.90-1.13). When stratified by T stage, patients whose disease had been clinically diagnosed as stage T1a had an improved CSS (HR = 0.75, 95% CI: 0.58-0.96, p = 0.022). There was a trend toward improved CSS in patients with clinical stage T1b tumors (HR = 0.74, 95% CI: 0.55-1.00, p = 0.052)., Conclusions: The improved CSS in patients with a clinical diagnosis suggests treatment of benign disease, particularly in smaller tumors. Prudent patient selection is needed to reduce the potential for overtreatment., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

We review radiation therapy (RT) options available for prostate cancer, including external beam (EBRT; with conventional fractionation, hypofractionation, stereotactic body RT [SBRT]) and brachytherapy (BT), with an emphasis on the outcomes, toxicities, and contraindications for therapies. PICOS/PRISMA methods were used to identify published English-language comparative studies on PubMed (from 1980 to 2015) that included men treated on prospective studies with a primary endpoint of patient outcomes, with ⩾70 patients, and ⩾5year median follow up. Twenty-six studies met inclusion criteria; of these, 16 used EBRT, and 10 used BT. Long-term freedom from biochemical failure (FFBF) rates were roughly equivalent between conventional and hypofractionated RT with intensity modulation (evidence level 1B), with 10-year FFBF rates of 45-90%, 40-60%, and 20-50% (for low-, intermediate-, and high-risk groups, respectively). SBRT had promising rates of BF, with shorter follow-up (5-year FFBF of >90% for low-risk patients). Similarly, BT (5-year FFBF for low-, intermediate-, and high-risk patients have generally been >85%, 69-97%, 63-80%, respectively) and BT+EBRT were appropriate in select patients (evidence level 1B). Differences in overall survival, distant metastasis, and cancer specific mortality (5-year rates: 82-97%, 1-14%, 0-8%, respectively) have not been detected in randomized trials of dose escalation or in studies comparing RT modalities. Studies did not use patient-reported outcomes, through Grade 3-4 toxicities were rare (<5%) among all modalities. There was limited evidence available to compare proton therapy to other modalities. The treatment decision for a man is usually based on his risk group, ability to tolerate the procedure, convenience for the patient, and the anticipated impact on quality of life. To further personalize therapy, future trials should report (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education status; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Sparing the hippocampus during whole brain radiation therapy (WBRT) offers potential neurocognitive benefits. However, previously reported intensity modulated radiation therapy (IMRT) plans use multiple noncoplanar beams for treatment delivery. An optimized coplanar IMRT template for hippocampal-sparing WBRT would assist in clinical workflow and minimize resource utilization. In this study, we sought to determine the optimal patient position to facilitate coplanar treatment planning and delivery of hippocampal-sparing WBRT using IMRT., Methods and Materials: A variable angle, inclined board was utilized for patient positioning. An anthropomorphic phantom underwent computed tomography simulation at various head angles. The IMRT goals were designed to achieve target coverage of the brain while maintaining hippocampal dose-volume constraints designed to conform to the Radiation Therapy Oncology Group 0933 protocol. Optimal head angle was then verified using data from 8 patients comparing coplanar and noncoplanar WBRT IMRT plans., Results: Hippocampal, hippocampal avoidance region, and whole brain mean volumes were 1.1 cm(3), 12.5 cm(3), and 1185.1 cm(3), respectively. The hippocampal avoidance region occupied 1.1% of the whole brain planning volume. For the 30-degree head angle, a 7-field coplanar IMRT plan was generated, sparing the hippocampus to a maximum dose of 14.7 Gy; D100% of the hippocampus was 7.4 Gy and mean hippocampal dose was 9.3 Gy. In comparison, for flat head positioning the hippocampal Dmax was 22.9 Gy with a D100% of 9.2 Gy and mean dose of 11.7 Gy. Target coverage and dose homogeneity was comparable with previously published noncoplanar IMRT plans., Conclusions: Compared with conventional supine positioning, an inclined head board at 30 degrees optimizes coplanar whole brain IMRT treatment planning. Clinically acceptable hippocampal-sparing WBRT dosimetry can be obtained using a simplified coplanar plan at a 30-degree head angle, thus obviating the need for complex and time consuming noncoplanar IMRT plans.

Studies of dose-escalated external beam radiation therapy (EBRT) and low dose rate brachytherapy (LDR-BT) have shown excellent rates of tumor control and cancer specific survival. Moreover, LDR-BT combined with EBRT (i.e. "LDR-BT boost") is hypothesized to improve local control. While phase II trials with LDR-BT boost have produced mature data of outcomes and toxicities, high dose rate (HDR)-BT has been growing in popularity as an alternative boost therapy. Boost from HDR-BT has theoretical advantages over LDR-BT, including improved cancer cell death and better dose distribution from customization of catheter dwell times, locations, and inverse dose optimization. Freedom from biochemical failure rates at five years for low-, intermediate-, high-risk, and locally advanced patients have generally been 85-100%, 80-98%, 59-96%, and 34-85%, respectively. Late Radiation Therapy Oncology Group grade 3-4 toxicities have also been encouraging with <6% of patients experiencing any toxicity. Limitations of current HDR-BT boost studies include reports of only single-institution experiences, and unrefined reports of toxicity or patient quality of life. Comparative effectiveness research will help guide clinicians in selecting the most appropriate treatment option for individual patients based on risk-stratification, expected outcomes, toxicities, quality of life, and cost., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Prostate cancer is the second most prevalent solid tumor diagnosed in men in the United States and Western Europe. Conventionally fractionated external beam radiation therapy (1.8-2.0 Gy/fraction) is an established treatment modality for men in all disease risk groups. Emerging evidence from experimental and clinical studies suggests that the α/β ratio for prostate cancer may be as low as 1.5 Gy, which has prompted investigators around the world to explore moderately hypofractionated radiation therapy (2.1-3.5 Gy/fraction). We review the impetus behind moderate hypofractionation and the current clinical evidence supporting moderate hypofractionated radiation therapy for prostate cancer. Although hypofractionated radiation therapy has many theoretical advantages, there is no clear evidence from prospective, randomized, controlled trials showing that hypofractionated schedules have improved outcomes or lower toxicity than conventionally fractionated regimens. Currently, hypofractionated schedules should only be used in the context of clinical trials. High dose rate brachytherapy and stereotactic body radiation therapy (fraction size 3.5 Gy and greater) are alternative approaches to hypofractionation, but are beyond the scope of this report., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Prostate cancer is the second most prevalent solid tumor diagnosed in men in the United States and Western Europe. Stereotactic body radiation therapy (SBRT) is touted as a superior type of external beam radiation therapy (EBRT) for the treatment of various tumors. SBRT developed from the theory that high doses of radiation from brachytherapy implant seeds could be recapitulated from advanced technology of radiation treatment planning and delivery. Moreover, SBRT has been theorized to be advantageous compared to other RT techniques because it has a treatment course shorter than that of conventionally fractionated EBRT (a single session, five days per week, for about two weeks vs. eight weeks), is non-invasive, is more effective at killing tumor cells, and is less likely to cause damage to normal tissue. In areas of the US and Europe where there is limited access to RT centers, SBRT is frequently being used to treat prostate cancer, even though long-term data about its efficacy and safety are not well established. We review the impetus behind SBRT and the current clinical evidence supporting its use for prostate cancer, thus providing oncologists and primary care physicians with an understanding of the continually evolving field of prostate radiation therapy. Studies of SBRT provide encouraging results of biochemical control and late toxicity. However, they are limited by a number of factors, including short follow-up, exclusion of intermediate- and high-risk patients, and relatively small number of patients treated. Currently, SBRT regimens should only be used in the context of clinical trials., (Copyright © 2012 Elsevier Ltd. All rights reserved.)