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Background: The relative benefits of radiotherapy (RT) dose escalation and the addition of short-term or long-term androgen deprivation therapy (STADT or LTADT) in the treatment of prostate cancer are unknown., Objective: To perform a network meta-analysis (NMA) of relevant randomized trials to compare the relative benefits of RT dose escalation ± STADT or LTADT., Design, Setting, and Participants: An NMA of individual patient data from 13 multicenter randomized trials was carried out for a total of 11862 patients. Patients received one of the six permutations of low-dose RT (64 to <74 Gy) ± STADT or LTADT, high-dose RT (≥74 Gy), or high-dose RT ± STADT or LTADT., Outcome Measurements and Statistical Analyses: Metastasis-free survival (MFS) was the primary endpoint. Frequentist and Bayesian NMAs were performed to rank the various treatment strategies by MFS and biochemical recurrence-free survival (BCRFS)., Results and Limitations: Median follow-up was 8.8 yr (interquartile range 5.7-11.5). The greatest relative improvement in outcomes was seen for addition of LTADT, irrespective of RT dose, followed by addition of STADT, irrespective of RT dose. RT dose escalation did not improve MFS either in the absence of ADT (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.80-1.18) or with STADT (HR 0.99, 95% CI 0.8-1.23) or LTADT (HR 0.94, 95% CI 0.65-1.37). According to P-score ranking and rankogram analysis, high-dose RT + LTADT was the optimal treatment strategy for both BCRFS and longer-term outcomes., Conclusions: Conventionally escalated RT up to 79.2 Gy, alone or in the presence of ADT, does not improve MFS, while addition of STADT or LTADT to RT alone, regardless of RT dose, consistently improves MFS. RT dose escalation does provide a high probability of improving BCRFS and, provided it can be delivered without compromising quality of life, may represent the optimal treatment strategy when used in conjunction with ADT., Patient Summary: Using a higher radiotherapy dose when treating prostate cancer does not reduce the chance of developing metastases or death, but it does reduce the chance of having a rise in prostate-specific antigen (PSA) signifying recurrence of cancer. Androgen deprivation therapy improves all outcomes. A safe increase in radiotherapy dose in conjunction with androgen deprivation therapy may be the optimal treatment., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

More than 40% of men with intermediate-risk or high-risk prostate cancer will experience a biochemical recurrence after radical prostatectomy. Clinical guidelines for the management of these patients largely focus on the use of salvage radiotherapy with or without systemic therapy. However, not all patients with biochemical recurrence will go on to develop metastases or die from their disease. The optimal pre-salvage therapy investigational workup for patients who experience biochemical recurrence should, therefore, include novel techniques such as PET imaging and genomic analysis of radical prostatectomy specimen tissue, as well as consideration of more traditional clinical variables such as PSA value, PSA kinetics, Gleason score and pathological stage of disease. In patients without metastatic disease, the only known curative intervention is salvage radiotherapy but, given the therapeutic burden of this treatment, importance must be placed on accurate timing of treatment, radiation dose, fractionation and field size. Systemic therapy also has a role in the salvage setting, both concurrently with radiotherapy and as salvage monotherapy., (© 2021. Springer Nature Limited.)

Background: To assess: (a) cancer treatment in prostate cancer survivors (PCS) by age at diagnosis (ADx) and prostate cancer (PC) aggressiveness; (b) potential impact on PC mortality; and (c) these results in the context of environmental/behavioral risk factors on PCS in Pennsylvania., Methods: Prostate cancer survivors ages ≥40 years were identified from the 2004-2014 Pennsylvania Cancer Registry (PCR). Demographic/clinical descriptors and PC treatment were extracted from PCR. Prostate cancer aggressiveness was defined by clinical/pathologic Gleason score and tumor stage. Logistic and Cox regression analyses tested associations between treatment received and PC-specific mortality. County-level data from the Pennsylvania BRFSS were used to estimate cancer-related behavioral risk factors (eg, smoking, physical inactivity, fruit/vegetable consumption [FV], alcohol use) and used as covariates., Results: There were 90 694 PCS ages 40-105 years (mean age = 66.19 years, SD = 9.25) included. Most were non-Hispanic white men (83%). Prostate cancer survivors ≥75 years were least likely to receive any treatment but men ages 65-74 were more likely to receive combined therapies (OR = 1.47; 95% CI 1.28, 1.69) vs PCS ages 40-54 years, controlling for covariates. Prostate cancer survivors 55-75+ with aggressive PC who received any treatment vs no definitive treatment had significantly reduced mortality. Men from counties with high obesity and smoking rates were significantly less likely to receive any treatment than men living in counties with lower rates of these risk factors. Prostate cancer survivors who lived in counties with high rates of physical inactivity and had high rates of sufficient FV consumption were slightly more likely to receive cancer treatment vs no definitive treatment compared to men who lived in counties with high rates of physical activity and lower FV consumption., Conclusions: We observed a general age-related decline in receipt of treatment. Prostate cancer survivors ages ≥75 years were significantly less likely to get any cancer treatment compared to younger PCS. However, most men with more aggressive disease who received any treatment had greatly reduced PC mortality, regardless of age. Considering environmental/behavioral risk factors may attenuate PC risk and inform treatment options., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The understanding of the relationship between genetic variation and an individual patient's response to radiation therapy (RT) has gained significant ground over the past several years. Genetic markers have been identified that could ultimately serve as the foundation for predictive models in clinical practice, and that hold the potential to revolutionize the delivery of precision medicine in oncology. Single nucleotide polymorphisms, single genes, and/or gene signatures could ultimately serve as the basis for patient stratification in prospective clinical trials. Currently, molecular markers relevant to breast, lung, and head and neck cancers have been integrated into clinical practice and serve as predictive tools to guide systemic therapy. In the future, the use of predictive models based on genomic determinants may become standard practice in radiation oncology, offering the potential to further personalize the delivery of RT and optimize the therapeutic ratio.

Aim: To analyze malpractice trials in radiation oncology and assess how ASTRO APEx ® and RO-ILS™ apply to such cases., Methods: The Westlaw database was reviewed using PICOS/PRISMA methods. Fisher's exact and Mann-Whitney U tests were used to find factors associated with outcomes., Results: Of 34 cases identified, external beam was used in 26 (77%). The most common factors behind malpractice were excessive toxicity (80%) and lack of informed consent (66%). ASTRO APEx pillars and ROI-LS had applicability to all but one case. Factors favoring the defendant included statute of limitations (odds ratio: 8.1; 95% CI: 1.3-50); those favoring the plaintiff included patient death (odds ratio: 0.7; 95% CI: 0.54-0.94)., Conclusion: APEx and RO-ILS are applicable to malpractice trials in radiation oncology.

Purpose: Left-digit bias is a phenomenon in which the leftmost digit of a number disproportionately influences decision making. We measured the effect of left-digit age bias on treatment recommendations for localized prostate cancer. Materials and Methods: We included men with clinically localized prostate adenocarcinoma in Surveillance, Epidemiology, and End Results from 2004 to 2018 and the National Cancer Database from 2004 to 2016. Primary outcomes were recommendations for radiation therapy and radical prostatectomy. Regression discontinuity was used to assess whether age increase from 69 to 70 years was associated with disproportionate changes in treatment recommendations. Results: In Surveillance, Epidemiology, and End Results, discontinuities were found in the proportion of patients recommended for radiation among the entire cohort (effect size 2.2%, P < .01) and among patients with Gleason 6 (1.6%, P < .01), Gleason 7 (2.5%, P < .01), and Gleason ≥8 (2.1%, P < .01) cancer, while the proportion recommended for prostatectomy decreased in the entire cohort (−1.4%, P < .01) and in patients with Gleason 7 cancer (−2.4%, P < .01). In the National Cancer Database, discontinuity from age 69 to 70 was found in recommendations for radiation in the entire cohort (effect size: 3.1%, P < .01) and in patients with Gleason 6 (2.2%, P < .01), Gleason 7 (4.0%, P < .01), and Gleason ≥8 (2.3%, P < .02) cancer, while the proportion recommended for prostatectomy decreased at this cutoff in the entire cohort (effect size: −2.7%, P < .01) and patients with Gleason 6 (−2.2%, P < .01) and Gleason 7 (−3.7%, P < .01) cancer. Conclusions: In patients with localized prostate cancer, left-digit age change from 69 to 70 was associated with disproportionately increased recommendations for radiation and decreased recommendations for prostatectomy. [ABSTRACT FROM AUTHOR]

Background: This study examined whether radiation therapy facility volumes correlate with survival after curative intent treatment of solid tumors. Methods: The National Cancer Database was queried for patients with solid tumors treated with curative‐intent radiation therapy from 2004‐2013. Facilities were stratified into 4 volume categories: low, intermediate, high, and very high. Primary cancer sites were divided into neoadjuvant, adjuvant, or definitive radiation subgroups. Kaplan‐Meier curves of 5‐year postradiation survival probability, stratified by facility volume, were generated with log‐rank tests for group comparisons. Cox proportional hazard models were used to evaluate the effect of facility volume on survival, adjusted for multiple covariates. Results: There were 253,422 patients treated at 1289 facilities: 6231 received neoadjuvant radiation, 147,980 received adjuvant radiation, and 99,211 received definitive radiation without surgery. Among patients receiving neoadjuvant radiation, survival correlated with facility volume for patients with rectal cancer (hazard ratio [HR], 0.75; 95% CI, 0.6‐0.94; P =.01). For cancers of the breast and uterus, patients receiving adjuvant radiation at very high‐volume facilities (vs low volume) had improved survival (HR, 0.83; 95% CI, 0.77‐0.90; P <.001 and HR, 0.77, 95% CI, 0.62‐0.97; P =.03, respectively). For patients receiving definitive radiation for prostate, non–small cell lung, pancreas, and head and neck cancer, there was an improvement in survival for patients treated at very high‐volume centers (P <.05). Conclusions: For select cancer patients, treatment with curative radiation at higher volume facilities is associated with improved survival. In particular, patients receiving radiation therapy in the definitive setting without surgery may benefit most from treatment at high‐volume centers. For select cancer patients, treatment with curative radiation at higher volume facilities is associated with improved survival. Metrics to ensure radiation therapy quality, such as centralized quality‐assurance checks or the integration of small‐volume facilities into larger health networks with mandated peer review, may be considered. [ABSTRACT FROM AUTHOR]

Background We hypothesized that the addition of receptor tyrosine kinase inhibitors (RTKis, e.g. lapatinib, erlotinib, cetuximab, bevacizumab, panitumumab) to radiotherapy-based treatment for solid tumors does not increase overall survival but may increase toxicity. Methods Population, Intervention, Control, Outcome, Study Design; Preferred Reporting Items for Systematic Reviews and Meta-Analyses; and Meta-analysis of Observational Studies in Epidemiology methods were used to identify prospective randomized studies including patients with solid tumor cancers treated with radiotherapy with or without RTKis. Extracted variables included use of radiotherapy vs chemoradiotherapy, RTKi type (antibody vs small molecule), outcomes, and toxicities. The primary endpoint was overall survival; the secondary endpoint was grade 3+ toxicity. Random-effects meta-analyses were performed for each outcome measure. All statistical tests were 2-sided. Results A total of 405 studies met the initial search criteria, of which 13 prospective randomized trials of radiotherapy with or without RTKi met the inclusion criteria, encompassing 5678 patients. The trials included cancers of the head and neck (6 trials, 3295 patients), esophagus (3 trials, 762 patients), lung (2 trials, 550 patients), and brain (2 trials, 1542 patients). Three studies evaluated a small molecule and radiotherapy in 949 patients, and 10 studies evaluated antibodies and radiotherapy in 4729 patients. The addition of RTKis to radiotherapy-based treatment did not improve overall survival (hazard ratio = 1.02, 95% confidence interval = 0.90 to 1.15, P  =  .76) but increased grade 3+ toxicity (relative risk = 1.18, 95% confidence interval = 1.06 to 1.33, P  =  .009). Conclusions The addition of RTKis to radiotherapy does not improve survival and worsens toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Exercise therapy (ET) is shown to improve toxicity and surrogates of survival for patients receiving chemotherapy. Current National Comprehensive Cancer Network (NCCN) guidelines lack recommendations for concurrent radiation therapy (RT) and ET. The main objective was to determine the impact of concurrent ET + RT with respect to (1) acceptability, feasibility, safety; and (2) to demonstrate how incorporating ET in cancer treatment can enhance patient-reported outcomes (PROs) and physical function-defined as strength or exercise capacity.Methods and Materials: A PICOS/PRISMA selection protocol was used to search PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Review for prospective randomized controlled trials evaluating concurrent ET + RT, including >10 patients and with 1 or more study arms. Acceptability, feasibility, and safety rates were calculated. PROs were assessed with study-specific metrics. Physical function was defined as improvements in strength or range of motion. Statistically significant improvement was defined by P <.05.Results: Twenty-six of 693 screened studies including 1563 patients (831 receiving exercise, 732 controls) with localized breast cancer (67.1% of patients), prostate cancer (27.4%), head and neck cancers (2.8%), and spinal metastases (2.8%) were assessed. Objective 1: Among 3385 patients approached for ET, 1864 (55.1%) accepted the treatment; of those, 1563 patients (83.9%) completed the trials. Objective 2: Statistical improvements were noted in these PROs: quality of life (14 of 15 studies), fatigue (12 of 16 studies), mood/depression (9 of 13), and anxiety (6 of 7). Physical function improved statically in 16 of 16 studies.Conclusions: Combination ET + RT is safe and well-tolerated with improvements in PROs and physical function. Additional studies are needed in patients with metastatic cancers to assess survival and to compare effectiveness of different exercise regimens. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to characterize the efficacy and safety of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy with concurrent chemotherapy (CFRT) for the definitive treatment of locally advanced pancreatic cancer. The primary outcome measure was efficacy, defined by 2-year overall survival (OS). Secondary outcomes were incidence of any grade 3/4 toxicity and 1-year OS.Methods: A PICOS/PRISMA/MOOSE selection protocol was used to identify eligible studies. Inclusion criteria were: 1) patients diagnosed with locally advanced N0-1 M0 pancreatic cancer; 2) CFRT 1.8 to 2.0 Gy/fraction with chemotherapy per protocol or SBRT ≥5 Gy/fraction in ≤5 fractions; 3) either no control group or another definitive chemotherapy or radiation therapy arm; 4) at least 1 of the outcome measures reported; and 5) single or multi-arm phase 2/3 prospective study for CFRT and/or phase 1/2 or retrospective study for SBRT. Neoadjuvant and/or adjuvant chemotherapy was prescribed per protocol specifications. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method to characterize summary effect sizes for each outcome.Results: A total of 470 studies were initially screened; of these, 9 studies assessed SBRT and 11 studies assessed CFRT. For SBRT, the median dose was 30 Gy, and the most common regimen was 30 Gy/5 fractions. For CFRT, doses ranged from 45 to 54 Gy in 1.8- to 2.0-Gy fractions, with the majority of studies delivering 50.4 Gy in 28 fractions with concurrent gemcitabine. The random effects estimate for 2-year OS was 26.9% (95% CI, 20.6%-33.6%) for SBRT versus 13.7% (95% CI, 8.9%-19.3%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for 1-year OS was 53.7% (95% CI, 39.3%-67.9%) for SBRT versus 49.3% (95% CI, 39.3%-59.4%) for CFRT, and was not statistically significant. The random effects estimate for acute grade 3/4 toxicity was 5.6% (95% CI, 0.0%-20.0%) for SBRT versus 37.7% (95% CI, 24.0%-52.5%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for late grade 3/4 toxicity was 9.0% for SBRT (95% CI, 3.3%-17.1%) versus 10.1% (95% CI, 1.8%-23.8%) for CFRT, which was not statistically significant.Conclusion: These results suggest that SBRT for LAPC may result in a modest improvement in 2-year OS with decreased rates of acute grade 3/4 toxicity and no change in 1-year-OS or late toxicity. Further study into the use of stereotactic body radiation therapy for these patients is needed. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly fatal malignancy for which surgery is currently considered to be the only curative treatment. However, less than a quarter of patients have disease amenable to definitive surgical resection. Local treatment with radiation therapy is a promising alternative to surgery for those patients with unresectable disease. However, conventional radiation techniques with computed tomography (CT)-guided therapy have yielded disappointing results due to the inability to deliver ablative doses of ionizing radiation, while sparing the radiosensitive adjacent organs at risk. Magnetic resonance-guided radiotherapy (MRgRT) has emerged as an alternative to CT-guided radiation treatment which allows for the delivery of higher doses of radiation with low toxicity to surrounding structures. Further study into the use of MRgRT and dose escalation for locally advanced unresectable pancreatic cancer is needed. [ABSTRACT FROM AUTHOR]

Background: The role of chemotherapy in extremity/trunk soft-tissue sarcoma (ET-STS) is controversial, even for patients at high risk for distant recurrence and death (those with high-grade tumors ≥5 cm in size). This study examines the impact of integrating chemotherapy with neoadjuvant radiotherapy (RT) on overall survival (OS) for patients with high-risk ET-STS.Methods: The National Cancer Data Base was queried for adult patients with high-risk ET-STS who received neoadjuvant RT and limb salvage surgery between 2006 and 2014. Patients were stratified into RT and chemoradiotherapy (CRT) cohorts. OS for the RT and CRT cohorts was analyzed with the Kaplan-Meier method, log-rank tests, and Cox proportional hazards models. Propensity score matching (PSM) analysis was used to account for a potential treatment selection bias between the cohorts.Results: A total of 884 patients were identified: 639 (72.3%) in the RT cohort and 245 (27.7%) in the CRT cohort. The unadjusted 5-year Kaplan-Meier OS rate was significantly higher in the CRT cohort: 72.0% versus 56.1% (P < .001). Neoadjuvant chemotherapy was associated with improved OS in univariate and multivariable analyses (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.41-0.78; P < .001). PSM identified 2 evenly matched cohorts of 212 patients each. The 5-year matched Kaplan-Meier OS rates were 69.8% and 55.4% for the CRT and RT cohorts, respectively (P = .002). The addition of neoadjuvant chemotherapy remained prognostic for OS on PSM (HR, 0.56; 95% CI, 0.39-0.83; P = .003).Conclusions: The addition of chemotherapy to neoadjuvant RT was associated with improved OS for patients with high-risk ET-STS. In the absence of randomized data evaluating CRT versus RT, these findings warrant further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Early‐stage nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is associated with a favorable prognosis. Our aim was to evaluate the patterns of care of radiotherapy utilization in this disease and to define the relationship between treatment modality and survival. The National Cancer Database was queried for patients with stages I‐II NLPHL diagnosed from 2004 to 2012. Patients were compared based on primary therapy into four categories: radiotherapy, chemotherapy, both, or neither. Covariate‐adjusted and propensity score‐weighted (PS) Cox proportional hazards models were used, adjusting for potential factors confounding survival. After exclusions, 1420 patients were evaluated, 571 (40%) received radiotherapy alone, 318 (22%) received chemotherapy alone, 351 (25%) received both, and 180 (13%) received neither. Younger patient age (P = 0.001), female gender (P = 0.019), and chemotherapy use (P < 0.001) were associated with decreased radiotherapy utilization. On PS, radiation alone (HR = 0.298, P < 0.001) and chemoradiotherapy (HR = 0.258, P < 0.001) were associated with improved survival compared to no upfront therapy, but the use of chemotherapy alone did not statistically differ compared to no initial therapy (HR = 0.784, P = 0.078). In this large database analysis, over one‐third of patients with early‐stage NLPHL did not receive radiotherapy as a component of initial therapy. The omission of upfront radiotherapy was associated with inferior survival. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate if interruptions of external beam radiation therapy impact outcomes in men with localized prostate cancer (PCa).Methods: We included men with localized PCa treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) of escalated dose (≥74 Gy in 1.8 or 2 Gy fractions) between 1992 and 2013 at an NCI-designated cancer centre. Men receiving androgen deprivation therapy were excluded. The non-treatment day ratio (NTDR) was defined as the number of non-treatment days divided by the total elapsed days of therapy. NTDR was analysed for each National Comprehensive Cancer Network (NCCN) risk group.Results: There were 1728 men included (839 low-risk, 776 intermediate-risk and 113 high-risk), with a median follow up of 53.5 months (range 12-185.8). The median NTDR was 31% (range 23-71%), translating to approximately 2 breaks (each break represents a missed treatment that will be made up) for 8 weeks of RT with 5 treatments per week. The 75 percentile of NTDR was 33%, translating to approximately 4 breaks, which was used as the cutoff for analysis. There were no significant differences in freedom from biochemical failure, freedom from distant metastasis, cancer specific survival, or overall survival for men with NTDR ≥33% compared to NTDR<33% for each risk group. Multivariable analyses including NTDR, age, race, Gleason score, T stage, and PSA were performed using the proportional hazards regression procedure. NTDR≥33% was not significantly associated with increased hazard ratio for outcomes in each risk group compared to NTDR<33%.Conclusion: Unintentional treatment breaks during dose escalated external beam radiation therapy for PCa did not cause a significant difference in outcomes, although duration of follow up limits the strength of this conclusion. [ABSTRACT FROM AUTHOR]

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 (r2 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most prevalent cancer diagnosed in men in the United States besides skin cancer. Stereotactic body radiation therapy (SBRT; 6–15 Gy per fraction, up to 45 minutes per fraction, delivered in five fractions or less, over the course of approximately 2 weeks) is emerging as a popular treatment option for prostate cancer. The American Society for Radiation Oncology now recognizes SBRT for select low- and intermediate-risk prostate cancer patients. SBRT grew from the notion that high doses of radiation typical of brachytherapy could be delivered noninvasively using modern external-beam radiation therapy planning and delivery methods. SBRT is most commonly delivered using either a traditional gantry-mounted linear accelerator or a robotic arm-mounted linear accelerator. In this systematic review article, we compare and contrast the current clinical evidence supporting a gantry vs robotic arm SBRT for prostate cancer. The data for SBRT show encouraging and comparable results in terms of freedom from biochemical failure (>90% for low and intermediate risk at 5–7 years) and acute and late toxicity (<6% grade 3–4 late toxicities). Other outcomes (eg, overall and cancer-specific mortality) cannot be compared, given the indolent course of low-risk prostate cancer. At this time, neither SBRT device is recommended over the other for all patients; however, gantry-based SBRT machines have the abilities of treating larger volumes with conventional fractionation, shorter treatment time per fraction (~15 minutes for gantry vs ~45 minutes for robotic arm), and the ability to achieve better plans among obese patients (since they are able to use energies >6 MV). Finally, SBRT (particularly on a gantry) may also be more cost-effective than conventionally fractionated external-beam radiation therapy. Randomized controlled trials of SBRT using both technologies are underway. [ABSTRACT FROM AUTHOR]

Purpose: The purposes of this study were to assess the exposure that medical students (MSs) have to radiation oncology (RO) during the course of their medical school career, as evidenced by 2 time points in current medical training (ie, first vs fourth year; MS1s and MS4s, respectively) and to assess the knowledge of MS1s, MS4s, and primary care physicians (PCPs) about the appropriateness of RT in cancer management in comparison with RO attendings.Methods: We developed and beta tested an electronic survey divided into 3 parts: RO job descriptions, appropriateness of RT, and toxicities of RT. The surveys were distributed to 7 medical schools in the United States. A concordance of >90% (either yes or no) among RO attendings in an answer was necessary to determine the correct answer and to compare with other subgroups using a χ(2) test (P<.05 was significant).Results: The overall response rate for ROs, MS1s, MS4s, and PCPs was 26%; n (22 + 315 + 404 + 43)/3004. RT misconceptions decreased with increasing level of training. More than 1 of 10 MSs did not believe that RT alone could cure cancer. Emergent oncologic conditions for RT (eg, spinal cord compression, superior vena cava syndrome) could not be identified by >1 of 5 respondents. Multiple nontoxicities of RT (eg, emitting low-level radiation from the treatment site) were incorrectly identified as toxicities by >1 of 5 respondents. MS4s/PCPs with an RO rotation in medical school had improved scores in all prompts.Conclusions: Although MS knowledge of general RT principles improves from the first to the fourth year, a large knowledge gap still exists between MSs, current PCPs, and ROs. Some basic misconceptions of RT persist among a minority of MSs and PCPs. We recommend implementing formal education in RO fundamentals during the core curriculum of medical school. [ABSTRACT FROM AUTHOR]

BACKGROUND Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose-escalated RT. METHODS The authors identified patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity-modulated RT and image-guided RT from 2001 through 2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI and the risk of biochemical failure (BF), distant metastases (DM), cause-specific mortality (CSM), and overall mortality. RESULTS Of the 1442 patients identified, approximately 20% had a BMI <25 kg/m2, 48% had a BMI of 25 to 29.9 kg/m2, 23% had a BMI of 30 to 34.9 kg/m2, 6% had a BMI of 35 to 39.9 kg/m2, and 4% had a BMI of ≥40 kg/m2. The median follow-up was 47.6 months (range, 1-145 months), with a median age of 68 years (range, 36-89 years). The median dose was 78 grays (range, 76-80 grays) and 30% of patients received androgen deprivation therapy. Increasing BMI was found to be inversely associated with age ( P<.001) and pretreatment prostate-specific antigen level ( P = .018). On multivariable analysis, increasing BMI was associated with an increased risk of BF (hazard ratio [HR], 1.03; 95% confidence interval [95% CI], 1.00-1.07 [ P = .042]), DM (HR, 1.07; 95% CI, 1.02-1.11 [ P = .004]), CSM (HR, 1.15; 95% CI, 1.07-1.23 [ P<.001]), and overall mortality (HR, 1.05; 95% CI, 1.02-1.08 [ P = .004]). CONCLUSIONS For patients with CaP receiving dose-escalated intensity-modulated RT with daily image-guidance, increasing BMI appears to be associated with an increased risk of BF, DM, CSM, and overall mortality. Cancer 2015;121:3010-3017. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose To determine if increasing the biologically equivalent dose (BED) via various radiation fractionation regimens is correlated with clinical outcomes or toxicities for prostate cancer. Methods and materials We performed a meta-analysis that included 12,756 prostate cancer patients from 55 studies published from 2003 to 2013 who were treated with non-dose-escalated conventionally fractionated external beam radiation therapy (non-DE-CFRT), DE-CFRT, hypofractionated RT, and high dose rate brachytherapy (HDR-BT; either mono or boost) with ⩾5-year actuarial follow-up. BEDs were calculated based on the following formula: ( nd [1 + d /( α / β )]), where n is the number of fractions, and d is dose per fraction; assuming an α / β of 1.5 for prostate cancer and 3.0 for late toxicities. Mixed effects meta-regression models were used to estimate weighted linear relationships between BED and the observed percentages of patients experiencing late toxicities or 5-year freedom from biochemical failure (FFBF). Results Increases in 10 Gy increments in BED (at α / β of 1.5) from 140 to 200 Gy were associated with 5-unit improvements in percent FFBF. Dose escalation of BED above 200 Gy was not correlated with FFBF. Increasing BED (at α / β of 3.0) from 98 to 133 Gy was associated with increased gastrointestinal toxicity. Dose escalation above 133 Gy was not correlated with toxicity. Conclusions An increase in the BED to 200 Gy (at α / β of 1.5) was associated with increased disease control. Doses above 200 Gy did not result in additional clinical benefit. [ABSTRACT FROM AUTHOR]

Background and aim: Limited-stage combined small cell esophageal carcinoma (LS-CSCEC) is a rare, poorly understood, underdiagnosed disease, with components of both small cell esophageal cancer and non–small cell esophageal cancer. We investigated the optimal treatment strategy and prognostic factors in patients with LS-C-SCEC. Patients and methods: LS-C-SCEC patients included in the analysis (from our hospital and the literature) were treated between January 1966 and December 2013. Patient treatment strategies included surgery (S), chemotherapy (CT), and radiation therapy (RT). The primary end point was overall survival (OS); the secondary end points included tumor complete response rates, patterns of failure, and toxicity. Kaplan–Meier curves were compared with the log-rank test. Univariate and multivariate analyses were used to determine prognosticators for OS. Results: A total of 72 patients were included in the analysis: 24 (33%) from our hospital and 48 (67%) from the literature. The median OS of all patients was 15.0 months. Patients who received CT had a significantly longer median OS than did those who did not (OS 22.8 months vs 10.0 months) (P=0.03). Patients treated with multimodality therapy (including RT+CT [18%], S+CT [40%], or S+RT+CT [17%]) vs monotherapy (typically, S [18%]) had significantly improved OS (15.5 months vs 9.3 months) (P=0.02) and complete response rates. On multivariate analysis, tumor location (upper third of the esophagus) and type of treatment (monotherapy) were the only factors predictive of poor OS. Conclusion: Multimodality therapy (including RT+CT, S+CT, or S+RT+CT) improves OS for patients with LS-C-SCEC compared with monotherapy (typically, S). Additional studies are necessary to personalize multimodal treatment approaches to individual patients. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

Abstract: 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 (1.8–2.0Gy/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 1.5Gy, which has prompted investigators around the world to explore moderately hypofractionated radiation therapy (2.1–3.5Gy/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 3.5Gy and greater) are alternative approaches to hypofractionation, but are beyond the scope of this report. [Copyright &y& Elsevier]

External beam radiation therapy (EBRT) combined with brachytherapy (BT) is an attractive treatment option for select patients with clinically localized prostate cancer. Either low- or high-dose rate BT may be combined with EBRT ('LDR-BT boost,' 'HDR-BT boost,' respectively). HDR-BT boost has potential theoretical benefits over LDR-BT boost or external beam radiation therapy monotherapy in terms of radiobiology, radiophysics and patient convenience. Based on prospective studies in this review, freedom from biochemical failure (FFBF) rates at 5 years for low-, intermediate- and high-risk patients have generally been 85-100%, 68-97%, 63-85%, respectively; late Radiotherapy and Oncology Group Grades 3 and 4 genitourinary and gastrointestinal toxicities are seen in <8% of patients. HDR-BT boost is now a relatively well-established treatment modality for certain intermediate-risk and high-risk prostate cancer patients, though limitations exist in drawing conclusions from the currently published studies. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

Abstract: Background: This retrospective study evaluates the efficacy and safety of surgery and chemotherapy (S +CT) vs. radiotherapy and CT (RT+CT) in patients with limited stage small cell esophageal cancer (LS-SCEC). Patients and methods: Patients included in analysis (from our hospital and the literature) were treated with S+CT or RT+CT between 1989 and 2012. The primary end point was overall survival (OS); secondary end points included tumor response and toxicity. Kaplan–Meier OS curves were compared with the log-rank test. Cox regression analysis was used to determine prognosticators for OS. Results: A total of 127 patients were included: 14 from our hospital and 113 from the literature. Fifty-four (43%) and 73 (57%) patients received S+CT or RT+CT, respectively. The median OS of all patients was 21.0months. OS was longer for those who received RT+CT rather than S+CT (33.0 vs. 17.5months, p =0.02), especially those with N1 disease. Uni- and multi-variate analyses showed tumor location (upper 1/3rd of esophagus) and type of treatment (S+CT) were poor prognostic factors of OS. Conclusion: LS-SCEC patients treated with RT+CT had an improved OS compared to those treated with S+RT. Thus, RT+CT should be considered as a primary approach for these patients. [Copyright &y& Elsevier]

BACKGROUND: The objective of this study was to compare the prognostic value of the sixth and seventh editions of the American Joint Cancer Committee (AJCC) Cancer Staging Manual and the risk-stratification model of the National Comprehensive Cancer Network (NCCN). METHODS: Two-thousand four hundred twenty-nine men who received definitive radiotherapy with or without androgen-deprivation therapy (median follow-up, 74 months) were analyzed. RESULTS: There was a migration of stage II patients to stage I with AJCC seventh edition (stage I increased from 1% to 38%, and stage II decreased from 91% to 55%). One pair-wise comparison (4%) of Kaplan-Meier estimates of biochemical failure, distant metastasis, prostate cancer-specific survival, and overall survival between stages was statistically significant for the AJCC sixth edition. Conversely, 16 of 24 comparisons (67%) were significant for the AJCC seventh edition. With the NCCN risk-stratification model, 9 of 12 comparisons (75%) were significant. Concordance probability estimate (CPE) and standard error (SE) analysis indicated uniform and significant improvement in the predictive power of the AJCC seventh edition versus the sixth edition for all outcomes. CPE ± SE values for the AJCC seventh edition versus the sixth edition were 0.51 ± 0.009 versus 0.59 ± 0.02, respectively, for biochemical failure; 0.54 ± 0.02 versus 0.70 ± 0.05, respectively, for distant metastasis; 0.57 ± 0.009 versus 0.76 ± 0.007, respectively, for prostate cancer-specific survival; and 0.52 ± 0.006 versus 0.57 ± 0.01, respectively, for overall survival. CPE ± SE values for the NCCN model were 0.59 ± 0.02 for biochemical failure, 0.72 ± 0.05 for distant metastasis, 0.80 ± 0.01 for prostate cancer-specific survival, and 0.57 ± 0.01 for overall survival. CONCLUSIONS: The current results indicated that the seventh edition of the AJCC Cancer Staging Manual is a major improvement over the sixth edition, because it distributes patients better among the stages and is more prognostic. However, the NCCN model was superior to the AJCC seventh edition and remains the preferred method for risk-based clinical management of prostate cancer with radiotherapy. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Salivary gland dysfunction is a common side effect of cancer treatments. Salivary function plays key roles in critical daily activities. Consequently, changes in salivary function can profoundly impair quality of life for cancer patients. We discuss salivary gland anatomy and physiology to understand how anticancer therapies such as chemotherapy, bone marrow transplantation, immunotherapy, and radiation therapy impair salivary function. We discuss approaches to quantify xerostomia in the clinic, including the advantages and limitations of validated quality-of-life instruments and approaches to directly measuring salivary function. Current and emerging approaches to treat cancer therapy-induced dry mouth are presented using radiation-induced salivary dysfunction as a model. Limitations of current sialagogues and salivary analogues are presented. Emerging approaches, including cellular and gene therapy and novel pharmacologic approaches, are described. [ABSTRACT FROM AUTHOR]

Adding high-dose-rate brachytherapy (BT) boost to external beam radiation therapy (EBRT) improves biochemical control but may affect patient-reported quality of life (QOL). We sought to determine long-term QOL outcomes for EBRT+BT versus EBRT alone. This was a post hoc analysis of the Trans-Tasman Radiation Oncology Group 03.04 Randomized Androgen Deprivation and Radiotherapy (TROG 03.04 RADAR) trial. Only patients who received 74 Gy conventionally fractionated EBRT (n = 260) or 46 Gy conventionally fractionated EBRT plus 19.5 Gy in 3 fractions high-dose-rate BT boost (n = 237) were included in this analysis. The primary endpoint was patient-reported QOL measured using the European Organisation for Research and Treatment of Cancer QOL (EORTC QLQ-C30) and prostate-specific QOL module (EORTC QLQ-PR25) questionnaires. We evaluated temporal changes in QOL scores, rates of symptom resolution, and the proportion of men who had decrements from baseline of >2 × the threshold for minimal clinically important change (2 × MCIC) for each domain. At 5, 17, and 29 months after radiation therapy, the EBRT+BT group had 2.5 times (95% confidence interval [CI], 1.4-4.2; P <.001), 2.9 times (95% CI, 1.7-4.9; P <.001), and 2.6 times (95% CI, 1.4-4.6; P =.002) greater odds of reporting 2 × MCIC in urinary QOL score compared with EBRT. There were no differences beyond 29 months. EBRT+BT led to a slower rate of urinary QOL symptom score resolution up to 17 months after radiation therapy compared with EBRT (P <.001) but not at later intervals. In contrast, at the end of the radiation therapy period and at 53 months after radiation therapy, the EBRT+BT group had 0.65 times (95% CI, 0.44-0.96; P =.03) and 0.51 times (95% CI, 0.32-0.79; P =.003) the odds of reporting 2 × MCIC in bowel QOL symptom scores compared with EBRT. There were no significant differences in the rate of bowel QOL score resolution. There were no significant differences in global health status or sexual activity scores between the 2 groups. There were no persistent differences in patient-reported QOL measures between EBRT alone and EBRT+BT. BT boost does not appear to negatively affect long-term, patient-reported QOL. [ABSTRACT FROM AUTHOR]

Pelvic radiation therapy may lead to decreased bone mineral density (BMD) and increased risk of fracture that could be of particular concern in patients with prostate cancer who also receive androgen deprivation therapy (ADT). We performed an exploratory analysis of a randomized, double-masked, placebo-controlled trial to determine whether exposure to prior pelvic external beam radiation therapy (XRT) affects BMD and risk of fracture in patients with prostate cancer treated with ADT. Patients with nonmetastatic prostate cancer aged ≥70 years or <70 years with low BMD (T-score < –1) or osteoporotic fracture who had been receiving ADT for ≥12 months were randomly assigned to receive densoumab or placebo every 6 months for 3 years. BMD was measured at baseline and at months 1, 3, 6, 12, 24, and 36. We applied multivariable linear mixed-effects models with an interaction term between the treatment arm and exposure to prior pelvic XRT to evaluate differential XRT effect on percent BMD change between the 2 treatment arms. Among 1407 eligible patients, 31% (n = 447) received prior pelvic XRT. There was no significant difference in any clinical fractures among patients with (5.8%, 26 of 447) or without (5.2%, 50 of 960) prior pelvic XRT (P =.42). Prior pelvic XRT was associated with a significant (0.54%) improvement in BMD (95% CI, 0.05-1.02) in the placebo group and a nonsignificant (0.04%) decline in BMD (95% CI, –0.47 to –0.35) in the denosumab group (interaction P =.007). There was no significant difference in pelvic XRT effect on percent BMD change in the lumbar spine (P =.65) or total hip (P =.39) between the 2 treatment groups. We did not find sufficient evidence to suggest any detrimental effect of pelvic XRT on the treatment effect from denosumab on percent BMD change, with only an approximately 5% incidence of clinical fractures. [ABSTRACT FROM AUTHOR]

The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Local treatment of the primary tumor for patients with metastases is controversial, and prospective data across many disease sites have conflicting conclusions regarding benefits.Methods and Materials: A comprehensive search was conducted in PubMed/MEDLINE including randomized controlled trials (RCTs) published in the past 50 years. Inclusion criteria were multi-institutional RCTs of patients with metastatic disease receiving systemic therapy randomized to addition of local treatment to the primary tumor. Two primary outcome measures, overall survival (OS) and progression-free survival (PFS), were quantitatively assessed using random effects, and meta-analyses were conducted using the inverse variance method for pooling. Secondary endpoints were qualitatively assessed and included toxicity and patient-reported quality of life. Exploratory analyses were performed by treatment type and volume of disease.Results: Eleven studies comprising 4952 patients were included (1558 patients received radiation therapy and 913 patients received surgery as primary tumor treatment). OS and PFS were not significantly improved from treatment of the primary (OS: hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.80-1.05; PFS: HR, 0.88; 95% CI, 0.72-1.07). Assessment of primary local treatment modality demonstrated a significant difference in summary effect size on PFS between trials using surgery (HR, 1.15; 95% CI, 0.99-1.33) compared with radiation therapy (HR, 0.73; 95% CI, 0.56-0.96) as the local treatment modality (P = .005). In low metastatic burden patients, radiation therapy was associated with significantly improved OS (HR, 0.67; 95% CI, 0.52-0.85), but surgery was not associated with improved OS compared with no local treatment (HR, 1.12; 95% CI, 0.94-1.34).Conclusions: In RCTs conducted to date enrolling a variety of cancer types with variable metastatic burden, there is no consistent improvement in PFS or OS from the addition of local therapy to the primary tumor in unselected patients with metastatic disease. Carefully selected patients may derive oncologic benefit and should be discussed in tumor boards. Future prospective studies should aim to further optimize patient selection and the optimal systemic and local therapy treatment types. [ABSTRACT FROM AUTHOR]

Purpose: Limited evidence is available on the utility of dose-escalated radiation therapy (DE-RT) with or without temozolomide (TMZ) versus standard-of-care radiation therapy (SoC-RT) for patients with newly diagnosed glioblastoma multiforme. We performed a systematic review/meta-analysis to compare overall survival (OS) and progression-free survival (PFS) between DE-RT and SoC-RT.Methods and Materials: We used a Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses/Meta-analysis of Observational Studies in Epidemiology selection criterion to identify studies. The primary and secondary outcomes were 1-year OS and 1-year PFS, respectively. Outcomes and comparisons were subdivided based on receipt of TMZ and MGMT status. DE-RT was defined based on equivalent dose calculations. Random effects meta-analyses using the Knapp-Hartung correction, arcsine transformation, and restricted maximum likelihood method were conducted. Meta-regression was used to compare therapeutic (eg, DE-RT or TMZ) and pathologic characteristics (eg, MGMT methylation status) using the Wald-type test.Results: Across 22 published studies, 2198 patients with glioblastoma multiforme were included; 507 received DE-RT. One-year OS after DE-RT alone was higher than SoC-RT alone (46.3% vs 23.4%; P = .02) as was 1-year PFS (17.9% vs 5.3%; P = .02). No significant difference in 1-year OS (73.2% vs 64.4%; P = .23) or 1-year PFS (44.5% vs 44.3%; P = .33) between DE-RT + TMZ and SoC-RT + TMZ was noted. No difference in 1-year OS was noted between DE-RT + TMZ and SoC-RT + TMZ in either MGMT methylated (83.2% vs 73.2%; P = .23) or MGMT unmethylated (72.6% vs 50.6%; P = .16) patients.Conclusions: DE-RT alone resulted in superior PFS and OS versus SoC-RT alone. DE-RT + TMZ did not lead to improved outcomes versus SoC-RT + TMZ. No differential benefit based on MGMT status was found. Future studies are warranted to define which subgroups benefit most from DE-RT. [ABSTRACT FROM AUTHOR]

Purpose: Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT.Methods and Materials: We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework.Results: A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent.Conclusions: There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice. [ABSTRACT FROM AUTHOR]

• This is a systematic review of radiomics based prognostic models in lung cancer. • It includes 40 studies of 55 datasets and 6223 patients. • There was heterogeneity in methodology and features included in prognostic models. • Meta-analysis found a C-index random effects estimate of 0.57 (95%CI 0.53 – 0.62). • Standard features and robust selection techniques should be used in future studies. Radiomics allows extraction of quantifiable features from imaging. This study performs a systematic review and meta-analysis of the performance of radiomics based prognostic models in non-small cell lung cancer (NSCLC). A literature review was performed following PRISMA guidelines. Medline, EMBASE and Cochrane databases were searched for articles investigating radiomics features predictive of overall survival (OS) in NSCLC treated with curative intent radiotherapy. A random-effects meta-analysis of Harrell's Concordance Index (C-index) was performed on the performance of radiomics models. Of the 2746 articles retrieved, 40 studies of 55 datasets and 6223 patients were eligible for inclusion in the systematic review. There was significant heterogeneity in the methodology for feature selection and model development. Twelve datasets reported the C-index of radiomics based models in predicting OS and were included in the meta-analysis. The C-index random effects estimate was 0.57 (95% CI 0.53–0.62). There was significant heterogeneity (I 2 = 70.3%). Based on this review, radiomics based models for lung cancer have to date demonstrated modest prognostic capabilities. Future research should consider using standardised radiomics features, robust feature selection and model development, and deep learning techniques, absolving the need for pre-defined features, to improve imaging-based models. [ABSTRACT FROM AUTHOR]

• Few studies characterize combined immunotherapy and radiation. • Toxicities similar after adding radiation to immunotherapy. • Anti-CTLA-4 associated with more toxicity than anti-PD-1/PD-L1. • No significant difference based on timing of immunotherapy and radiation. Immune checkpoint inhibitor with radiation therapy (ICI + RT) is under investigation for improved patient outcome, so we performed a systematic review/meta-analysis of toxicities for ICI + RT compared to immune checkpoint inhibitor (ICI) therapy alone. A PRISMA-compliant systematic review of studies in MEDLINE (PubMed) and in the National Comprehensive Cancer Network guidelines was conducted, with primary outcome grade 3 + toxicity. Criteria for ICI alone were: phase III/IV trials that compared immunotherapy to placebo, chemotherapy, or alternative immunotherapy; and for ICI + RT: prospective/retrospective studies with an arm treated with ICI + RT. Meta-analysis was performed by random effects models using the DerSimonian and Laird method. The I 2 statistic and Cochran's Q test were used to assess heterogeneity, while funnel plots and Egger's test assessed publication bias. This meta-analysis included 51 studies (n = 15,398), with 35 ICI alone (n = 13,956) and 16 ICI + RT studies (n = 1,442). Our models showed comparable grade 3–4 toxicities in ICI + RT (16.3%; 95% CI, 11.1–22.3%) and ICI alone (22.3%; 95% CI, 18.1–26.9%). Stratification by timing of radiation and irradiated site showed no significant differences, but anti-CTLA-4 therapy and melanoma showed increased toxicity. The grade 5 toxicities were 1.1% and 1.9% for ICI alone and ICI + RT respectively. There was significant heterogeneity, but not publication bias. The random effects model showed comparable grade 3–4 toxicity in using ICI + RT compared to ICI alone in CNS melanoma metastases, NSCLC, and prostate cancer. ICI + RT is safe for future clinical trials in these cancers. [ABSTRACT FROM AUTHOR]

• UHRT is becoming a widely adopted treatment in localized prostate cancer. • UHRT offers similar rates of disease-free survival to CFRT and HFRT at 85%. • Grade 2+ late GI toxicity is approximately 12% across all modalities. • Grade 2+ late GU toxicity is approximately 20% across all modalities. To characterize the efficacy (5-year disease-free survival [DFS]) and safety (incidence of grade 2+ late gastrointestinal or genitourinary toxicity) of ultrahypofractionated radiation therapy (UHRT) versus hypofractionated radiation therapy (HFRT) and conventionally fractionated radiation therapy (CFRT) by comparing patients treated on phase III protocols. A PICOS/PRISMA/MOOSE protocol was used to identify eligible studies. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method. Wald-type tests were used to compare treatment modalities for each outcome, where the null hypothesis was rejected for p < 0.05. Seven studies were included that consisted of 6795 patients (2849 CFRT, 3357 HFRT, and 589 UHRT). Median age was 68 years. Summary effect sizes for 5-year DFS were 85.1% (95% CI: 82.1%–87.8%) for CFRT, 86% (95% CI: 83%–88.7%) for HFRT, and 85% (95% CI: 80%–87%) for UHRT (p = 0.66 and p = 0.8 for CFRT vs. HFRT and CFRT versus UHRT, respectively). Summary effect sizes for late grade 2+ gastrointestinal toxicity were 12.1% (95% CI: 9.2%–15.4%) for CFRT, 14.6% (95% CI: 9.9%–20%) for HFRT, and 10% (95% CI: 7%–13%) for UHRT (p = 0.41 and p = 0.09 for CFRT versus HFRT and CFRT versusus UHRT, respectively). Summary effect sizes for late grade 2+ genitourinary toxicity were 19.4% (95% CI: 10.7–29.9%) for CFRT, 20.4% (95% CI: 10.2%–32.9%) for HFRT, and 18% (95% CI: 15%–22%) for UHRT (p = 0.89 and p = 0.92 for CFRT versus HFRT and CFRT versus UHRT, respectively). Ultrahypofrationated regimens appear to offer similar levels of safety and efficacy to CFRT and HFRT. These findings are hypothesis-generating and require further validation by ongoing prospective trials. [ABSTRACT FROM AUTHOR]

• First meta-analysis comparing conventional RT to SRS for spinal metastases. • Single-fraction SRS resulted in improved LC compared to conventional RT. • BED 10 escalation of 10 Gy 10 via SRS resulted in roughly 5% LC benefit. • SRS was well-tolerated with <1% incidence of Grade 3–5 toxicities. • Single-fraction SRS with higher vertebral compression fracture rates than multiple-fraction SRS. To perform a systematic review/meta-analysis of outcomes for patients with spinal metastases treated with stereotactic radiosurgery (SRS) (either single-fraction (SF-SRS) or multiple-fraction (MF-SRS)) or conventional radiotherapy (RT). Thirty-seven studies were identified. Primary outcomes were 1-year local control (LC) and acute/late grade 3–5 toxicities (including vertebral compression fractures (VCF)). Weighted random effects meta-analyses using the DerSimonian and Laird methods and meta-regressions were conducted to characterize and compare effect sizes. Mixed effects regression models were used in dose analyses. A total of 3237 patients with 4911 lesions were included; 43.8%, 19.7%, and 36.5% of lesions received SF-SRS, MF-SRS, or RT, respectively. SF-SRS resulted in improved 1-year LC (92.9% (95% CI: 86.4–97.4%); p = 0.007) compared to RT (81.0% (95% CI: 69.2–90.5%)) with no difference between MF-SRS (82.1%; p = 0.86) and RT. On subgroup analysis of de novo metastases, superior 1-year LC following SF-SRS (95.5% (95% CI: 87.4–99.6%)) was maintained compared to RT (83.6% (95% CI: 70.4–93.5%); p = 0.007). A 4.7% increase in LC was noted for each 10 Gy 10 increase in biologically effective dose (BED 10 , assuming an alpha/beta = 10) with SRS (p < 0.001). No difference in toxicities were found between SF-SRS (0.4%), MF-SRS (0.2%), or RT (0%). Higher VCF rates were noted following SF-SRS (19.5%) vs. MF-SRS (9.6%; p = 0.039)) with no correlation between dose and VCF rates. SF-SRS resulted in superior LC with a roughly 5% LC benefit for every 10 Gy 10 increase in BED 10 with higher VCF rates compared to MF-SRS. If LC is the goal of treatment, then SRS may be a preferred treatment modality. However, these results are hypothesis-generating, and prospective randomized clinical trials are indicated to definitively address the question of whether SRS results in improved LC compared to RT. [ABSTRACT FROM AUTHOR]

Purpose: To investigate how necroptosis (ie, programmed necrosis) is involved in killing of non-small cell lung cancer (NSCLC) after ablative hypofractionated radiation therapy (HFRT).Methods and Materials: Deoxyribonucleic acid damage, DNA repair, and the death form of NSCLC cells were assessed after radiation therapy. The overexpression and silencing of receptor-interacting protein kinases 3 (RIP3, a key protein involved activation of necroptosis)-stable NSCLC cell lines were successfully constructed. The form of cell death, the number and area of colonies, and the regulatory proteins of necroptosis were characterized after radiation therapy in vitro. Finally, NSCLC xenografts and patient specimens were used to examine involvement of necroptosis after ablative HFRT in vivo.Results: Radiation therapy induced expected DNA damage and repair of NSCLC cell lines, but ablative HFRT at ≥10 Gy per fraction preferentially stimulated necroptosis in NSCLC cells and xenografts with high RIP3 expression, as characterized by induction and activation of RIP3 and mixed-lineage kinase domain-like protein and release of immune-activating chemokine high-mobility group box 1. In contrast, RNA interference of RIP3 attenuated ablative HFRT-induced necroptosis and activation of its regulatory proteins. Among central early-stage NSCLC patients receiving stereotactic body radiation therapy, high expression of RIP3 was associated with improved local control and progression-free survival (all P < .05).Conclusions: Ablative HFRT at ≥10 Gy per fraction enhances killing of NSCLC with high RIP3 expression via preferential stimulation of necroptosis. RIP3 may serve as a useful biomarker to predict favorable response to stereotactic body radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: To quantify and determine the relationship between oncology departmental/division heads and private industry vis-à-vis potential financial conflict of interests (FCOIs) as publicly reported by the Centers for Medicare and Medicaid Services Open Payments database.Methods and Materials: We extracted the names of the chairs/chiefs in medical oncology (MO) and chairs of radiation oncology (RO) for 81 different institutions with both RO and MO training programs as reported by the Association of American Medical Colleges. For each leader, the amount of consulting fees and research payments received in 2015 was determined. Logistic modeling was used to assess associations between the 2 endpoints of receiving a consulting fee and receiving a research payment with various institution-specific and practitioner-specific variables included as covariates: specialty, sex, National Cancer Institute designation, PhD status, and geographic region.Results: The majority of leaders in MO were reported to have received consulting fees or research payments (69.5%) compared with a minority of RO chairs (27.2%). Among those receiving payments, the average (range) consulting fee was $13,413 ($200-$70,423) for MO leaders and $6463 ($837-$16,205) for RO chairs; the average research payment for MO leaders receiving payments was $240,446 ($156-$1,234,762) and $295,089 ($160-$1,219,564) for RO chairs. On multivariable regression when the endpoint was receipt of a research payment, those receiving a consulting fee (odds ratio [OR]: 5.34; 95% confidence interval [CI]: 2.22-13.65) and MO leaders (OR: 5.54; 95% CI: 2.62-12.18) were more likely to receive research payments. Examination of the receipt of consulting fees as the endpoint showed that those receiving a research payment (OR: 5.41; 95% CI: 2.23-13.99) and MO leaders (OR: 3.06; 95% CI: 1.21-8.13) were more likely to receive a consulting fee.Conclusion: Leaders in academic oncology receive consulting or research payments from industry. Relationships between oncology leaders and industry can be beneficial, but guidance is needed to develop consistent institutional policies to manage FCOIs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (I2 = 57%, p = 0.07) and grade ≥3 mucositis (I2 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. [ABSTRACT FROM AUTHOR]