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Patients with gastrointestinal (GI) cancer frequently experience unplanned hospitalizations, but predictive tools to identify high-risk patients are lacking. We developed a machine learning model to identify high-risk patients.In the study, 1341 consecutive patients undergoing GI (abdominal or pelvic) radiation treatment (RT) from March 2016 to July 2018 (derivation) and July 2018 to January 2019 (validation) were assessed for unplanned hospitalizations within 30 days of finishing RT. In the derivation cohort of 663 abdominal and 427 pelvic RT patients, a machine learning approach derived random forest, gradient boosted decision tree, and logistic regression models to predict 30-day unplanned hospitalizations. Model performance was assessed using area under the receiver operating characteristic curve (AUC) and prospectively validated in 161 abdominal and 90 pelvic RT patients using Mann-Whitney rank-sum test. Highest quintile of risk for hospitalization was defined as "high-risk" and the remainder "low-risk." Hospitalizations for high- versus low-risk patients were compared using Pearson's χOverall, 13% and 11% of patients receiving abdominal and pelvic RT experienced 30-day unplanned hospitalization. In the derivation phase, gradient boosted decision tree cross-validation yielded AUC = 0.823 (abdominal patients) and random forest yielded AUC = 0.776 (pelvic patients). In the validation phase, these models yielded AUC = 0.749 and 0.764, respectively (P.001 and P = .002). Validation models discriminated high- versus low-risk patients: in abdominal RT patients, frequency of hospitalization was 39% versus 9% in high- versus low-risk groups (P.001) and 6-month survival was 67% versus 92% (P = .001). In pelvic RT patients, frequency of hospitalization was 33% versus 8% (P = .002) and survival was 86% versus 92% (P = .15) in high- versus low-risk patients.In patients with GI cancer undergoing RT as part of multimodality treatment, machine learning models for 30-day unplanned hospitalization discriminated high- versus low-risk patients. Future applications will test utility of models to prompt interventions to decrease hospitalizations and adverse outcomes.

BACKGROUND Sporadic optic pathway/hypothalamic gliomas represent a unique entity within pediatric low-grade glioma. Despite favorable survival, location makes treatment difficult and local progression debilitating. This study is a longitudinal assessment of visual acuity (VA) among children treated within the last 2 decades. METHODS Clinical characteristics were abstracted for patients treated from 2000 to 2018 at Texas Children's Cancer Center in Houston. Ophthalmologic data taken at 3- to 6-month intervals were examined with age-appropriate VA metrics converted to the LogMAR (logarithm of the minimum angle of resolution) scale. Kaplan-Meier blindness-free survival (BFS) curves, calculated as time-to-bilateral functional blindness (LogMAR ≥0.8 in both eyes), were calculated for patients receiving early radiation therapy (RT; upfront or as first-line salvage treatment) or chemotherapy (CT) and evaluated using the log-rank test. RESULTS Thirty-eight patients with a median follow-up of 8.5 years (range, 2-17 years) were identified. Median age at diagnosis was 3 years (interquartile range

Purpose Pediatric patients with rhabdomyosarcoma (RMS) are treated with multimodal therapy, often with radiation therapy (RT) as part of local therapy. We report on the efficacy and patterns of failure after proton beam therapy (PBT) for RMS. Methods and Materials Between January 2006 and February 2017, patients with RMS were enrolled in a prospective institutional review board–approved registry protocol for pediatric patients undergoing PBT. Demographics, clinical characteristics, and treatment related outcomes were reviewed. Results Ninety-four RMS patients were treated with a combination of chemotherapy (CT) and PBT. The majority of patients had head and neck (49%) and genitourinary (30%) primaries. Median tumor size was 4.1 cm (range, 1.0-16.5 cm); 33 patients (35%) had primary tumors >5 cm. Median cyclophosphamide equivalent dose was 14.4 g/m2 (range, 0-30.8 g/m2). Median time from CT initiation to RT initiation was 13 weeks (range, 1-58 weeks). With median follow-up of 4 years, 4-year overall survival (OS) was 71%, and 4-year progression-free survival (PFS) was 63%. Thirty patients (32%) experienced relapse (13% with local failure [LF]). Four-year local control (LC) was 85% overall; 4-year LC rates were 100% for low-risk, 85% for intermediate-risk, and 55% for high-risk patients (P = .02). Tumor size predicted LC (P = .007), with 7% versus 33% LF rate by tumor size (≤5 cm vs >5 cm). Delayed RT delivery (≥13 weeks from initiation of CT) predicted worse LC (P = .01). Increased tumor size predicted both inferior PFS (P = .02) and OS (P = .01). Delayed RT delivery predicted both inferior PFS (P = .04) and OS (P = .03). Conclusions PBT provides LC comparable to prior studies using photon RT. Inferior LC, PFS, and OS rates were observed for patients with larger tumors and those treated with delayed RT. This finding supports ongoing prospective efforts to dose-escalate treatment of tumors >5 cm; however, these data call into question the optimal timing of local therapy, particularly for patients treated with reduced-dose cyclophosphamide.

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (D...

Phase 3 clinical trials are widely recognized as the highest level of evidence to support a particular intervention/therapy in the medical literature. The ability to draw clinically meaningful conc...

Background Despite accounting for a minority of malignant pleural mesothelioma (MPM) diagnoses, females may experience differential survival relative to males. It is unclear if there are gender-based differences in receipt of treatment or disease-related outcomes for patients with MPM. We therefore utilized the National Cancer Database (NCDB) to assess patterns-of-care and overall survival (OS) among patients with MPM by gender. Materials and Methods Patients with histologically confirmed MPM treated from 2004 to 2013 were identified from the NCDB. The association between female gender and OS was assessed using multivariable Cox proportional hazards models with propensity score matching. Patterns-of-care were assessed using multivariable logistic regression. The overall treatment effect was tested in subsets of patients by treatment strategy, histology, and clinical stage. Results A total of 18,799 patients were identified, of whom 14,728 (78%) were male and 4071 (22%) were female. Females were statistically more likely to present at a younger age, with fewer comorbidities, and with epithelioid histology. Despite these favorable prognostic features, women were less likely to receive surgery (P ≤ .001) or chemotherapy (P ≤ .001) compared with males. On multivariable analysis, female gender was associated with improved OS (hazard ratio, 0.83; 95% confidence interval, 0.80-0.86; P ≤ .001). Gender-based survival differences were seen across all stages, but only among patients with epithelioid (P ≤ .001) and not biphasic (P = .17) or sarcomatoid (P = 1.00) histology. Conclusions Surgery and chemotherapy are disproportionately underutilized in female patients with MPM. Despite this concerning disparity, female gender is independently associated with improved survival relative to males. Further research to understand factors that lead to gender disparities in MPM is warranted.

We aimed to investigate whether implicit linguistic biases exist in letters of recommendation (LORs) for applicants to radiation oncology (RO) residency. LORs (n = 487) written for applicants (n = 125) invited to interview at a single RO residency program from the 2015 to 2019 application cycles were included for analysis. Linguistic Inquiry and Word Count (LIWC) software was used to evaluate LORs for length and a dictionary of predetermined themes. Language was evaluated for gender bias using a publicly available gender bias calculator. Non-parametric tests were used to compare linguistic domain scores. The median number of the LORs per applicant was 4 (range 3–5). No significant differences by applicant gender were detected in LIWC score domains or gender bias calculator (P > 0.05). However, LORs for applicants from racial/ethnic backgrounds underrepresented in medicine were less likely to include standout descriptors (P = 0.008). Male writers were less likely to describe applicant characteristics related to patient care (P < 0.0001) and agentic personality (P = 0.006). LORs written by RO were shorter (P < 0.0001) and included fewer standout descriptors (P = 0.014) but were also more likely to include statements regarding applicant desirability (P = 0.045) and research (P = 0.008). While language was globally male-biased, assistant professors were less likely than associate professors (P = 0.0064) and full professors (P = 0.023) to use male-biased language. Significant linguistic differences were observed in RO residency LORs, suggesting that implicit biases related to both applicants and letter writers may exist. Recognition, and ideally eradication, of such biases are crucial for fair and equitable evaluation of a diverse applicant pool of RO residency candidates. Electronic supplementary material The online version contains supplementary material available at 10.1007/s13187-020-01907-x.

Background The use of professional medical writers (PMWs) has been historically low, but contemporary data regarding PMW usage are scarce. In this study, we sought to quantify PMW use in oncologic phase III randomized controlled trials (RCTs). Methods We performed a database query through ClinicalTrials.gov to identify cancer‐specific phase III RCTs; we then identified whether a PMW was involved in writing the associated trial manuscript reporting primary endpoint results. Results Two‐hundred sixty trials of 600 (43.3%) used a PMW. Industry‐funded trials used PMWs more often than nonindustry trials (54.9% vs. 3.0%, p < .001). Increased PMW usage was further noted among trials meeting their primary endpoint (53.4% vs. 32.9%, p < .001) and trials that led to subsequent Food and Drug Administration approval (63.1% vs. 36.3%, p < .001). By treatment interventions, PMW use was highest among systemic therapy trials (50.2%). Lastly, the use of PMWs increased significantly over time (odds ratio: 1.11/year, p = .001). Conclusion PMW use rates are high among industry‐funded trials. We urge continued and increased transparency in reporting the funding and use of PMWs., Considering the increase in industry‐sponsored cancer clinical trials, the use of professional medical writers for publication of trial results has become an increasingly important topic. This brief communication reports the current rate of involvement of medical writers in publications of cancer clinical trials.

BackgroundPatients with gastrointestinal (GI) cancers experience a high symptom burden due to the effects of both cancer and treatment. As such, trials assessing symptom burden and supportive interventions are crucial. Here, we characterise the landscape of phase III GI cancer clinical trials and explore study outcomes centred on the patient’s quality of life (QoL).MethodsWe searched ClinicalTrials.gov for phase III randomised controlled trials (RCTs) registered between 2000 and 2017 that are assessing a therapeutic intervention in adult patients with cancer and grouped trials by GI disease sites.ResultsOverall, we identified 76 phase III trials specific to GI cancers that enrolled a total of 53 725 patients. When analysing the primary outcomes measured, the vast majority of studies (n=71, 86%) measured disease-related endpoints such as progression-free survival or overall survival. All trials had a secondary endpoint that measured adverse events, but only 30 trials (39%) included QoL measures as secondary endpoints. Of the 30 trials that included QoL secondary endpoints, only 16 (53%) reported these results. Only five trials (7%) assessed interventions aimed at supportive measures impacting disease-related or treatment-related toxicity. None of the supportive trials included QoL as a primary endpoint and only two of these trials (40%) included QoL as a secondary endpoint.ConclusionsMost GI cancer trials failed to incorporate patient-centred outcomes or QoL measures when studying new interventions. These findings call for greater integration of patient-reported metrics, which may lead to better care and outcomes for patients with GI malignancies.

Purpose To determine the clinical outcomes and toxicities of proton beam therapy (PBT) versus 3D-conformal photon radiation therapy (XRT) in patients with testicular seminoma. Materials and Methods This observational study evaluated consecutive patients with testicular seminoma who were treated with inguinal orchiectomy and radiation therapy at a single, tertiary, high-volume center in 2008-19. Acute toxicity was scored with the Common Terminology Criteria for Adverse Events V 4.0. Organs at risk were contoured retrospectively by 2 investigators. Recurrences and secondary malignancies were based on routine follow-up imaging, either computed tomography or magnetic resonance imaging. Results Fifty-five patients were treated with radiation therapy, 11 in the PBT-arm and 44 in the XRT-arm, with a median follow-up interval of 61 months (interquartile range [IQR]: 32-79 months). Acute treatment-related diarrhea, grade 1 to 2, was more common among XRT-treated patients (0% vs 29.5%, P = .039), and dermatitis, grade 1, was more likely among PBT-treated patients (27.3% vs 2.3%, P = .004). Dosimetrically, PBT-treated patients, relative to XRT-treated patients, had lower dose to organs at risk including the kidney, bladder, femoral head, spinal cord, bowel, pancreas, and stomach. The 5-year overall survival rate was 100% and disease-free survival rate was 96.4% for all patients. Two patients, all in the XRT-arm, had disease recurrence: 1 in the pelvis and 1 in the lung. Three patients, all in the XRT-arm, were diagnosed with a secondary malignancy: 1 in-field pancreaticoblastoma, 1 in-field colon adenocarcinoma, and a stage IV T-cell lymphoma. Conclusion Proton beam therapy for testicular seminoma resulted in excellent clinical outcomes and was associated with lower rates of acute diarrhea but higher rates of acute dermatitis. Proton beam therapy resulted in no in-field secondary malignancies and a more favorable dosimetric profile for organs at risk relative to XRT. Reduced dose to organs at risk, such as the kidneys, may result in long-term improvement in function.

Background and purpose To report physician-assessed toxicities (PATs) and patient-reported outcomes (PROs) in a prospective cohort of patients treated using proton beam therapy (PBT). Methods and materials From 2011 to 2019, PBT-treated patients with a sinonasal malignancy were enrolled with a primary endpoint of toxicity assessment. PATs and PROs were assessed at baseline, acute (during PBT), subacute (within 90 days after PBT), and chronic time points. PATs were graded with the Common Terminology Criteria for Adverse Events V4.0. PROs were assessed with the Xerostomia-Related Quality-of-Life Scale (XeQoLS), MD Anderson Dysphagia Inventory (MDADI), and Functional Assessment of Cancer Therapy (FACT). PRO changes from baseline to follow-up were defined as significantly different based on a paired t-test plus a minimal clinically important difference. Results Sixty-four patients had a median follow-up time of 33 months (interquartile range: 10–52 months). The most common histology was olfactory neuroblastoma (28%) and most patients had T4 disease (46%). One acute G3 neurologic PAT (blurred vision) resolved, and no late G3–4 neurologic PATs were observed. Feeding tube placement occurred in 6% of patients. No significant changes were noted in PROs from baseline to the chronic period. Significant worsening from baseline was noted in the XeQoLS acute-subacute physical functioning, pain, personal/psychological distress, and social function; acute-subacute MDADI physical function; and acute-subacute FACT head/neck subscale. The 3-year local control, disease-free survival, and overall survival rates were 88%, 76%, and 82%, respectively. Conclusions We demonstrate low grade ≥3 toxicity and encouraging disease outcomes with PBT. PROs suggest significant changes in the acute-subacute period but no chronic sequelae.

During the coronavirus disease 2019 pandemic, minimizing exposure risk for patients with cancer and health care personnel was of utmost importance. Here, we present steps taken to date to flatten the curve at the radiation oncology division of a tertiary cancer center with the goal of mitigating risk of exposure among patients and staff, and optimizing resource utilization. Response to the coronavirus disease 2019 pandemic in this large tertiary referral center included volume reduction, personal protective equipment recommendations, flexible clinic visit interaction types dictated by need and risk reduction, and numerous social distancing strategies. We hope these outlined considerations can assist the wider radiation oncology community as we collectively face this ongoing challenge.

Dose escalation via stereotactic radiation therapy techniques has been necessary for hepatobiliary malignancies in the primary and oligometastatic setting, but such dose escalation is challenging for spine metastases due to spinal cord proximity. Here, we investigate the role of spine stereotactic radiosurgery (SSRS) in the management of such metastases. We retrospectively reviewed patients treated with SSRS to spinal metastases from hepatobiliary malignancies between 2004 and 2017 at our Institution. We used the Kaplan–Meier method to calculate overall survival (OS) and local control (LC) and Cox regression analysis to identify factors associated with disease-related outcomes. We identified 28 patients treated to 43 spinal metastases with SSRS for either HCC or cholangiocarcinoma. The 1-year LC and OS were 85% and 23%, respectively. The median time to death was 6.2 months, while median time to local failure was not reached. Tumor volume > 60 cc (SHR 6.65, p = 0.03) and Bilsky ≥ 1c (SHR 4.73, p = 0.05) predicted for poorer LC, while BED10 > 81 Gy trended towards better local control (SHR 4.35, p = 0.08). Child–Pugh Class (HR 3.02, p = 0.003), higher PRISM Group (HR 3.49, p = 0.001), and systemic disease progression (HR 3.65, p = 0.001) were associated with worse mortality based on univariate modeling in patients treated with SSRS; on multivariate analysis, PRISM Group (HR 2.28, p = 0.03) and systemic disease progression (HR 2.67, p = 0.03) remained significant. Four patients (10%) developed compression deformity and one patient (2%) developed radiation neuritis. SSRS provides durable local control in patients with metastatic hepatobiliary malignancies, with higher BED necessary to ensure excellent LC. PRISM scoring is a promising prognostic tool to aid SSRS patient selection.

There is a large variability regarding the definition and choice of primary endpoints in phase 2 and phase 3 multimodal rectal cancer trials, resulting in inconsistency and difficulty of data interpretation. Also, surrogate properties of early and intermediate endpoints have not been systematically assessed. We provide a comprehensive review of clinical and surrogate endpoints used in trials for non-metastatic rectal cancer. The applicability, advantages, and disadvantages of these endpoints are summarised, with recommendations on clinical endpoints for the different phase trials, including limited surgery or non-operative management for organ preservation. We discuss how early and intermediate endpoints, including patient-reported outcomes and involvement of patients in decision making, can be used to guide trial design and facilitate consistency in reporting trial results in rectal cancer.

Male breast cancer treatment regimens are often extrapolated from female-based studies because of a paucity of literature analyzing male breast cancer. Using ClinicalTrials.gov, we analyzed breast cancer randomized clinical trials (RCTs) to determine which factors were associated with male-gender inclusion. Of 131 breast cancer RCTs identified, male patients represented 0.087% of the total study population, which is significantly less than the proportion of male patients with breast cancer in the U.S. (0.95%; p < .001). Twenty-seven trials included male patients (20.6%). Lower rates of male inclusion were seen in trials that randomized or mandated hormone therapy as part of the trial protocol compared with trials that did not randomize or mandate endocrine therapy (2.5% vs. 28.6% male inclusion; p < .001). It is imperative for breast cancer clinical trials to include men when allowable in order to improve generalizability and treatment decisions in male patients with breast cancer.

Background Metastatic head and neck cancers (HNCs) predominantly affect the lungs and have a two-year overall survival (OS) of 15% to 50%, if amenable for pulmonary metastasectomy. Methods Retrospective review of the two-year local control (LC), local-regional control (LRC) within the same lobe, OS, and toxicity rates in consecutive patients with metastatic pulmonary HNC who underwent stereotactic ablative radiotherapy (SABR) January 2007 to May 2018. Results Evaluated 82 patients with 107 lung lesions, most commonly squamous cell carcinoma (SCC; 64%). Median follow-up was 20 months (range: 9.0-97.6). Systemic therapy administered in 34%. LC, LRC, and OS rates were 94%, 90%, and 62%. Patients with oligometastatic disease had a higher OS than polymetastatic disease, 72% vs 44% (HR = 0.30, 95% CI: 0.14-0.64; P = .008). OS in oligometastatic non-SCC and SCC were 100% and 66% (P = .03). There were no grade ≥3 toxicities. Conclusions Metastatic pulmonary HNCs after SABR have a two-year OS rate comparable to pulmonary metastasectomy.

Highlights • Proton pelvic reirradiation results in lower bone marrow dose compared to photons. • Proton pelvic reirradiation of the pelvis is well tolerated with limited toxicities., Introduction Pelvic reirradiation (re-RT) presents challenges due to concerns for late toxicity to tissues-at-risk including pelvic bone marrow (PBM). We routinely utilize a hyperfractionated, accelerated re-RT for recurrent rectal or anal cancer in the setting of prior radiation. We hypothesized that proton beam radiation (PBR) is uniquely suited to limit doses to pelvic non-target tissues better than photon-based approaches. Materials and methods All patients who received hyperfractionated, accelerated PBR re-RT to the pelvis from 2007 to 2017 were identified. Re-RT was delivered twice daily with a 6 h minimum interfraction interval at 1.5 Gray Relative Biological Effectiveness (Gy(RBE)) per fraction to a total dose of 39–45 Gy(RBE). Concurrent chemotherapy was given to all patients. Comparison photon plans were generated for dosimetric analysis. Dosimetric parameters compared using a matched-pair analysis and the Wilcoxon signed-rank test. Survival analysis was performed Kaplan Meier curves. Results Fifteen patients were identified, with a median prior pelvic RT dose of 50.4 Gy (range 25–80 Gy). Median time between the initial RT and PBRT re-RT was 4.7 years (range 1.0–36.1 years). In comparison to corresponding photon re-RT plans, PBR re-RT plans had lower mean PBM dose, and lower volume of PBM getting 5 Gy, 10 Gy, 20 Gy, and 30 Gy (p

Purpose To characterize local relapse after surgical fixation and postoperative radiotherapy (RT) for multiple myeloma (MM) with cortical involvement of long bones. Patients and Methods We retrospectively identified patients with MM involving cortical long bones treated with surgical fixation followed by postoperative RT at our institution. Local failures, defined as radiographic recurrence along the surgical hardware, were documented, and potential associations of independent variables (RT dose, fractionation, and extent of hardware coverage) with local failure were assessed by univariate Cox regression. Results We identified 33 patients with 40 treated sites with a median follow-up of 25.7 months; 68% of treatments were for pathologic fracture, and 32% were for impending fracture. The most common dose and fractionation were 20 to 25 Gy in 8 to 12 fractions. On average, 76% of the surgical hardware was covered by the postoperative RT field (median, 80%; range, 28%-100%). Local failure was observed in 5 cases (12.5%), 2 within the RT field and 3 out of field. None of the relapses resulted in hardware failure, and 2 were retreated with RT. The extent of hardware coverage predicted disease relapse along the hardware (hazard ratio = 6.44; 95% confidence interval, 1.09-37.97; P = .04); however, total RT dose, biologically effective dose, and number of fractions did not. Conclusion After internal fixation of long bones with MM, full hardware coverage with the RT field could reduce the risk, though small, of disease developing in the future in the proximate hardware. Postoperative RT doses of 20 to 25 Gy in 8 to 10 fractions can achieve excellent local control.

The median age at diagnosis for malignant pleural mesothelioma (MPM) is approximately 72 years. Elderly patients pose unique management challenges because of the increased risk of therapy-related toxicities and mortality. Because there are no high-volume retrospective studies, prospective trials, or dedicated treatment recommendations for this population, this investigation addresses a major knowledge gap by examining national practice patterns and postoperative/survival outcomes in elderly MPM patients. The National Cancer Database was queried for patients aged ≥ 80 years with newly diagnosed nonmetastatic MPM. Multivariable logistic regression ascertained factors associated with observation and surgery. Kaplan–Meier analysis assessed overall survival (OS), and multivariable Cox proportional hazards modeling examined factors associated with OS. Survival was also calculated following propensity matching. Additionally, postoperative outcomes were evaluated in surgical patients. Of 4526 patients, 2% received surgery and chemotherapy, 22% underwent chemotherapy alone, and 63% were observed. Respective median OS was 12.2, 9.5, and 4.1 months (p

BACKGROUND A better understanding of the impact of body-mass index (BMI) on the course of multimodal therapy and oncologic outcome in locally advanced rectal cancer could provide new insights for optimization of treatment and supportive strategies. PATIENTS AND METHODS Correlations of BMI with pretreatment clinical, surgical, and pathological characteristics, toxicity and treatment adherence using the Pearson's Chi-squared test or logistic regression were analyzed in the CAO/ARO/AIO-04 III trial cohort (n = 1236). One-way ANOVA or Welch test were used to analyze correlations of baseline blood-parameters and BMI. The prognostic role of BMI was examined with log-rank test and multivariate cox regression. RESULTS Obese had a better ECOG performance status (P = 0.027) but were less likely to undergo sphincter preserving surgery (P = 0.01). Post-surgical complications did not differ significantly between BMI classes, whereas underweight was associated with increased neutrophil (P = 0.025) and platelet counts (P

Background Venous thromboembolism (VTE) is a very common adverse event for astrocytoma patients, but validation of proposed risk biomarkers has been elusive. We examine whether the status of the isocitrate dehydrogenase (IDH) gene is a risk factor for the development of venous thromboembolism (VTE) in astrocytoma patients. Methods We conducted a retrospective chart review of 282 astrocytoma patients enrolled in the PROACTIVE (Prospective Assessment of Correlative Biomarker) study at MD Anderson Cancer Center (MDACC) from 9/1/2000 until 12/31/2013. Results We identified 282 astrocytoma patients consisting of 49 IDH mutant astrocytomas and 233 IDH wildtype astrocytomas. Glioblastoma was the initial histopathologic diagnosis in 30 (61.2%) of the IDH mutated astrocytomas compared to 227(97.4%) of the IDH wild type astrocytomas. VTE was identified in 52 (18.4%) of patients. VTE was diagnosed in 7 (14.3%) of the IDH mutated astrocytomas compared to 45(19.3%) of the IDH wild type astrocytoma s (p = 0.4094). Median time to VTE from diagnosis was 2.71 months. Median time to VTE from diagnosis was 2.6 months for IDH mutated astrocytomas compared to 3.06 months for the IDH wild type astrocytomas (p = 0.8663). Conclusions IDH gene status did not appear as a significant risk factor for the development of venous thromboembolism (VTE) in our cohort of astrocytoma patients. Further research into potential biomarkers for VTE may be warranted.

In the United States, the COVID-19 pandemic has caused profound changes in radiation oncology practices, including delays to treatment and reductions in patient volume, staff, and practice revenue....

BACKGROUND: For malignant pleural mesothelioma (MPM), the benefit of resection, as well as the optimal surgical technique, remain controversial. In efforts to better refine patient selection, this retrospective observational cohort study queried the National Cancer Database in an effort to quantify and evaluate predictors of 30- and 90-day mortality between extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D), as well as nonoperative management. METHODS: After applying selection criteria, cumulative incidences of mortality by treatment paradigm were graphed for the unadjusted and propensity-matched populations, as well as for six a priori age-based intervals (≤60, 61–65, 66–70, 71–75, 76–80, and ≥81 years). The interaction between age and hazard ratio (HR) for mortality between treatment paradigms was also graphed. Cox multivariable analysis ascertained factors independently associated with 30- and 90-day mortality. RESULTS: Of 10,723 patients, 2,125 (19.8%) received resection (n=438 EPP, n=1,687 P/D) and 8,598 (80.2%) underwent nonoperative management. The unadjusted 30/90-day mortality for EPP, P/D, and all operated cases was 3.0%/8.0%, 5.4%/14.1%, and 4.9%/12.8%, respectively. There were no short-term mortality differences between EPP and P/D following propensity-matching, within each age interval, or between age subgroups on interaction testing (P>0.05 for all). Nonoperative patients had a crude 30- and 90-day mortality of 9.9% and 24.6%, respectively. Several variables were identified as predictors of short-term mortality, notably patient age (HR 1.022, P

On May 1 and May 22, 2020, a pair of high-profile articles were fast-track reviewed and published by the New England Journal of Medicine (NEJM) and The Lancet, venues widely regarded as among the most prestigious of medical journals.1Mehra M.R. Desai S.S. Ruschitzka F. Patel A.N. Retracted: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis.Lancet. 2020; https://doi.org/10.1016/S0140-6736(20)31180-6Crossref Scopus (123) Google Scholar,2Mehra M.R. Desai S.S. Kuy S. Henry T.D. Patel A.N. Cardiovascular disease, drug therapy, and mortality in COVID-19.N Engl J Med. 2020; 102: 1-7Google Scholar The Lancet article reported a multinational registry analysis of chloroquine with or without macrolide antibiotics in patients who were infected with the novel severe acute respiratory syndrome corona virus-2 virus, and an NEJM manuscript from the same group investigated angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in patients who tested positive for coronavirus disease 2019 (COVID-19). These papers would have been a pinnacle achievement for the academic coauthors, in addition to the supporting company Surgisphere, who reportedly supplied the data. Led by the vascular surgeon Sapan Desai, this small company with “big data” aspirations redefined research priorities and patient study allocation with their remarkable results. Unfortunately, these august journals would soon be roiled by controversy when it became evident that the data may have been falsified for both papers.3Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Retraction: Cardiovascular disease, drug therapy, and mortality in COVID-19. N Engl J Med. https://doi.org/10.1056/nejmc2021225. Accessed June 27, 2020.Google Scholar The subsequent debacle serves as a cautionary tale of the systematic failure modes of traditional avenues of sharing and verifying clinical science, particularly when applied to fast-tracked research.

BACKGROUND: Pseudoprogression (PsP) is a recognized phenomenon after radiotherapy (RT) for high-grade glioma but is poorly characterized for low-grade glioma (LGG). We sought to characterize PsP for pediatric LGG patients treated with RT, with particular focus on the role of RT modality using photon-based intensity-modulated RT (IMRT) or proton beam therapy (PBT). METHODS: Serial MRI scans from 83 pediatric LGG patients managed at 2 institutions between 1998 and 2017 were evaluated. PsP was scored when a progressive lesion subsequently decreased or stabilized for at least a year without therapy. RESULTS: Thirty-two patients (39%) were treated with IMRT, and 51 (61%) were treated with PBT. Median RT dose for the cohort was 50.4 Gy(RBE) (range, 45-59.4 Gy[RBE]). PsP was identified in 31 patients (37%), including 8/32 IMRT patients (25%) and 23/51 PBT patients (45%). PBT patients were significantly more likely to have post-RT enlargement (hazard ratio [HR] 2.15, 95% CI: 1.06-4.38, P = 0.048). RT dose >50.4 Gy(RBE) similarly predicted higher rates of PsP (HR 2.61, 95% CI: 1.20-5.68, P = 0.016). Multivariable analysis confirmed the independent effects of RT modality (P = 0.03) and RT dose (P = 0.01) on PsP incidence. Local progression occurred in 10 patients: 7 IMRT patients (22%) and 3 PBT patients (6%), with a trend toward improved local control for PBT patients (HR 0.34, 95% CI: 0.10-1.18, P = 0.099). CONCLUSIONS: These data highlight substantial rates of PsP among pediatric LGG patients, particularly those treated with PBT. PsP should be considered when assessing response to RT in LGG patients within the first year after RT.

Aim: To explore management trends in preinvasive and cT1–T3 penile cancer. Materials & methods: The National Cancer Database was queried (2004–2013) for cT1–T3 M0 penile cancer with specified nonpalliative surgical techniques and histologies (n = 5,728). Results: Local excision (39%) and partial penectomy (38%) were most commonly utilized. Patients with cTis/Ta or cT1 disease more often received nonpenectomy approaches (p < 0.05); cT2–T3 cases more likely underwent penectomy (p < 0.001). No survival differences were observed between penectomy (49.3 months) and nonpenectomy approaches (50.3 months) in the overall cohort (p = 0.107) and when stratifying by T-stage (p > 0.20 for all). Conclusion: This study provides contemporary insight into the landscape for management of this rare disease and can serve as a benchmark for future evaluation of treatment trends.

We describe the institutional guidelines of a major tertiary cancer center with regard to using hypofractionated radiation regimens to treat glioblastoma as a measure to minimize exposure to coronavirus disease 2019 (COVID-19) while not sacrificing clinical outcomes. Our guidelines review level one evidence of various hypofractionated regimens, and recommend a multidisciplinary approach while balancing the risk of morbidity and mortality among individuals at high risk for severe illness from COVID-19 infection. We also briefly outline strategies our department is taking in mitigating risk among our cancer patients undergoing radiation.

BACKGROUND: The use of overall survival (OS) as the gold standard primary endpoint (PEP) in metastatic oncologic randomized controlled trials (RCTs) has declined in favor of progression-free survival (PFS) without a complete understanding of the degree to which PFS reliably predicts for OS. METHODS: Using ClinicalTrials.gov, we identified 1,239 phase 3 oncologic RCTs, 260 of which were metastatic solid tumor trials with a superiority-design investigating a therapeutic intervention using either a PFS or OS PEP. Each individual trial was reviewed to quantify RCT design factors and disease-related outcomes. RESULTS: A total of 172,133 patients were enrolled from 1999–2015 in RCTs that utilized PFS (56.2%, 146/260) or OS (43.8%, 114/260) as the PEP. PFS trials were more likely to restrict patient eligibility using molecular criteria (15.1% vs. 4.4%, p=0.005), utilize targeted therapy (80.1% vs. 67.5%, p=0.048), accrue fewer patients (median 495 vs. 619, p=0.03), and successfully meet the trial PEP (66.9% vs. 33.3%, p

Patient-reported outcome measures (PROMs) are increasingly incorporated as endpoints in oncology clinical trials but are often only validated in English. ClinicalTrials.gov was queried for cancer-specific randomized control trials (RCTs) addressing a therapeutic intervention and enrolling primarily in the USA. Peer-reviewed validation of Spanish and Chinese versions of each PROM was assessed. Of 103 eligible trials, a PROM was used as a primary endpoint in 25 RCTs (24.3%) and as a secondary endpoint in 78 RCTs (75.7%). A total of 61 of the 103 eligible trials (59.2%) and 17 of the 25 trials with a PROM primary endpoint (68.0%) used a PROM with either no Spanish or Chinese validation. The absence of validated PROM translations may diminish the voices of non-English language speaking trial participants. With an increasingly diverse US population, validation of non-English PROM translations may decrease disparities in trial participation and improve generalizability of study results.

Ethan B Ludmir,1,* Tyler Gutschenritter,1,* Chelsea C Pinnix,1 Jillian R Gunther,1 Loretta J Nastoupil,2 Joseph D Khoury,3 L Jeffrey Medeiros,3 Bouthaina S Dabaja,1 Sarah A Milgrom1 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA *These authors contributed equally to this work Abstract: Gastrointestinal stromal tumor (GIST) is an uncommon mesenchymal tumor, and has been shown to be associated with synchronous or metachronous second malignancies. Rare cases of coincident GIST and non-Hodgkin lymphomas (NHL) have been reported previously. Here, we report two cases of GIST and coincident primary breast lymphoma, an uncommon subtype of extranodal NHL. We propose that the exceedingly low likelihood of both these cancers occurring in these two patients by chance warrants examination for possible common oncogenic pathways in these lesions, possibly involving shared anti-apoptotic mechanisms. Further research is vital to elucidate common oncogenic pathways between such rare lesions. Keywords: diffuse large B-cell lymphoma, mucosa-associated lymphoid tissue lymphoma, anti-apoptosis, gastrointestinal stromal tumor, primary breast lymphoma

Treatment strategies and outcomes were assessed in 25 patients with primary breast diffuse large B-cell lymphoma (PB-DLBCL) treated between 1995 and 2016. We specifically investigated the timing of recurrence, and the roles of radiotherapy (RT) and central nervous system prophylaxis (CNS PPX). Fifty-two percent of patients received RT, and 28% received CNS PPX. Fourteen patients (56%) experienced recurrence, with 76% of relapses occurring ≥24 months after diagnosis, in contrast to reports supporting the use of 24-month event-free survival as a surrogate endpoint in the general DLBCL population. Use of RT was associated with a trend toward improved progression-free survival (PFS). Twenty percent of patients experienced CNS relapse, with no clear benefit to CNS PPX. These data emphasize the importance of long-term follow-up for PB-DLBCL patients, suggest a PFS benefit with the addition of RT, and highlight high rates of CNS relapse.

Cardiophrenic lymph nodes (CPLNs) are occasionally involved in Hodgkin lymphoma (HL). We characterized the incidence of CPLN involvement among 169 HL patients and evaluated outcomes after treatment with omission of the CPLN region from the involved-site radiation therapy (ISRT) field. Three types of RT fields were used: standard (S)-ISRT, reduced-dose (RD)-ISRT (lower dose to CPLNs, standard to other sites), or modified (M)-ISRT (omission of CPLNs). CPLNs were involved at diagnosis in 29 patients (17%). Of the 20 patients who received RT after complete response to chemotherapy, 4(20%) received S-ISRT, 8(40%) RD-ISRT, and 8(40%) M-ISRT. The four-year progression-free survival was 94.7%. One relapse occurred at a non-CPLN site after RD-ISRT. The mean heart dose and volume of the heart that received 25 Gy was higher for S-ISRT patients compared to M-ISRT (p = .043 and p = .025, respectively). Re-planning the M-ISRT cases as S-ISRT resulted in significant increase in cardiac doses.

Landmark investigation two decades ago demonstrated sex-based disparities among participants in cancer cooperative group trials. Although federal efforts have aimed to improve representation of female patients in government-sponsored research, less is known about sex disparities in the broader landscape of modern oncologic randomized controlled trials. Using ClinicalTrials.gov, we identified randomized controlled trials related to colorectal or lung cancer (the two most common non-sex-specific disease sites). Among the 147 included trials, the proportion of female patients enrolled on trial was on average 6.8% (95% confidence interval = −8.8% to –4.9%) less than the proportion of female patients in the population by disease site (P

Two decades following the creation of the Office of Cancer Complementary and Alternative Medicine at the National Cancer Institute, the status of complementary and alternative medicine (CAM) research within oncology remains opaque. To better understand the landscape of CAM studies in oncology, we identified CAM-related phase III randomized controlled trials (RCTs) through ClinicalTrials.gov and compared these CAM trials to all non-CAM oncologic RCTs. Pearson χ2 testing was used to compare proportions across groups; all tests were two-sided. Comparing the 25 identified CAM RCTs with 739 non-CAM RCTs, CAM studies were more likely to be sponsored by a cooperative group (64.0% vs 28.6%, P

Historically, academic medical centers conducted oncologic clinical research trials, which limited trial access for the majority of cancer patients, who are treated at community centers. Over the l...

Despite ongoing efforts, patients with locally advanced pancreatic cancer (LAPC) continue to have a dismal prognosis. Such tumors are unresectable, and optimal treatment with chemotherapy and/or radiation therapy is still not established. While chemotherapy is conventionally aimed at preventing metastatic spread of disease, radiation therapy acts locally, improving local control which can potentially improve overall survival and most importantly quality of life. Here, we aim to review the primary literature assessing the role of diverse radiation therapy strategies for patients with LAPC. Many radiation regimens can be considered, and no standard treatment has demonstrated a clear improvement in clinical outcomes. We advise that the modality of choice be dependent on the availability of equipment, the dose and fractionation of treatment, as well as the dose received by normal tissue. Moreover, a candid discussion with the patient concerning treatment goals is equally as essential. Three notable strategies for LAPC are intensity-modulated radiation therapy, volumetric modulated arc therapy, and proton. These radiation modalities tend to have improved dose distribution to the target volumes, while minimizing the radiation dose to surrounding normal tissues. Stereotactic body radiation therapy can also be considered in LAPC patients in cases where the tumor does not invade the duodenum or other neighboring structures. Because of the high doses delivered by stereotactic body radiation therapy, proper respiratory and tumor motion management should be implemented to reduce collateral radiation dosing. Despite improved clinical outcomes with modern radiation modalities, evolving techniques, and more accurate planning, future studies remain essential to elucidate the optimal role for radiation therapy among patients with LAPC.

Background: Patients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We aimed to characterize trial-related factors associated with the use of PS eligibility criteria and analyze patient accrual breakdown by PS. Methods: Adult, therapeutic, multiarm phase III cancer-specific RCTs were identified through ClinicalTrials.gov. PS data were extracted from articles. Trials with a PS restriction ECOG score ≤1 were identified. Factors associated with PS restriction were determined, and the use of PS restrictions was analyzed over time. Results: In total, 600 trials were included and 238,213 patients had PS data. Of those trials, 527 studies (87.8%) specified a PS restriction cutoff, with 237 (39.5%) having a strict inclusion criterion (ECOG PS ≤1). Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (PPConclusions: Use of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring to ensure the generalizability of results while maintaining patient safety.

Stereotactic radiation therapy (RT) involves the delivery of high dose-per-fraction treatments to small intracranial (stereotactic radiosurgery [SRS]) and extracranial (stereotactic body radiotherapy [SBRT]) sites. SRS and SBRT share several overarching principles that differentiate stereotactic RT from conventionally fractionated radiation techniques. This review describes historical aspects of SRS/SBRT and definitions thereof, and a comparison with more modern semantics. Key principles of the stereotactic radiotherapeutic modalities are discussed, followed by an overview of the technical considerations involved. Lastly, the accepted appropriate clinical indications for stereotactic RT are outlined, and the potential role of stereotactic treatment in future oncologic management are also discussed.

Purpose This review explores the use of intensity modulated radiation therapy (IMRT) after lung-sparing surgery in malignant pleural mesothelioma (MPM). Because severe toxicities have been documented after radiation therapy for MPM, its use remains controversial, especially as modern surgical management has shifted toward lung-sparing pleurectomy/decortication. IMRT is an advanced technique that may allow for safer radiation therapy delivery, but there remains limited data (including no summative data) to support this notion. Methods and Materials We performed a systematic review evaluating the safety and efficacy of post-pleurectomy IMRT (P-IMRT). A systematic review of PubMed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted for publications of all dates that specifically reported clinical outcomes and/or toxicities of P-IMRT in patients with MPM. Ten original studies were included in this review. Results The incidence of grade 3 pneumonitis ranged from 0% to 16%, with all but 2 studies reporting rates below 9%. Grade 4 and 5 pneumonitis were observed in less than 1.5% of cases, except in one publication that used hypofractionated radiation therapy to doses >60 Gy. Crude local failure rates ranged from 19% to 60%, median progression free survival ranged from 12 to 16 months, and median overall survival ranged from 19 to 28 months. Conclusions P-IMRT produces relatively few higher-grade toxicities and has reasonable disease-related outcomes, especially when delivered using conventionally fractionated regimens to doses of 45 to 54 Gy and exercising careful attention to dose constraints during treatment planning. IMRT can thus be considered in well-selected patients in whom adequate survival after pleurectomy is expected. These data also support the initiation of the phase III NRG-LU006 trial of extended pleurectomy/decortication and chemotherapy with or without IMRT.

Background: Response of pancreatic adenocarcinoma to neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) may be associated with prognosis, but long-term outcomes based on response to neoadjuvant therapy have not been well evaluated to date. Methods: The National Cancer Database was queried for patients with pancreatic adenocarcinoma receiving nCT/nCRT. To evaluate response to nCT/nCRT, comparisons were made from cT and cN stage to the respective post-neoadjuvant therapy ypT and ypN stages. Based on these comparisons, patients were classified as responders, progressors, or non-responders. Statistical analyses included estimation of survival using Kaplan-Meier analysis, as well as multivariable Cox proportional hazards modeling. Results: Of 2,028 patients, 30% had a response, 32% progressed, and 38% had no response; 1% of patients experienced pathologic complete response (pCR). Responders were more likely to have received multi-agent chemotherapy (P=0.0001) as well as radiotherapy (RT) (P=0.02) in the neoadjuvant setting. Response to nCT/nCRT was also associated with a higher R0 resection rate (P=0.02). At a median follow-up of 49 months, median overall survival (OS) was higher in responders than non-responders or progressors (29.9 vs . 24.3 vs . 22.2 months, P

Objectives Comprehensive local consolidative therapy led to improved overall survival in oligometastatic non–small cell lung cancer in a recent phase II trial, yet the role of pulmonary resection in ongoing oligometastatic trials is a matter of controversy. We sought to examine outcomes after pulmonary resection with radiotherapy used as a benchmark comparator. Methods Patients treated at a single institution (2000-2017) with cT1-3N0-2M1 non–small cell lung cancer, 3 or less synchronous metastases, and performance status 0 to 1, and who received comprehensive local consolidative therapy were analyzed according to local consolidative therapy modality for the primary lesion. Progression was analyzed with death as a competing risk. Results Of 88 patients meeting inclusion criteria, 63 (71.6%) received radiotherapy for local consolidative therapy modality for the primary lesion and 25 (28.4%) underwent surgery (lobectomy 20/25 [80.0%], pneumonectomy 3/25 [12.0%], sublobar 2/25 [8.0%]). Time from diagnosis to local consolidative therapy modality for the primary lesion was similar. Surgical patients were younger and had lower intrathoracic disease burden. Ninety-day post-treatment mortality was low (surgery 0/25 [0.0%], radiotherapy 1/63 [1.6%]). Median postoperative survival time was 55.2 months (95% confidence interval, 20.1 to not reached), with 1- and 5-year overall survivals of 95.7% and 48.0%, respectively. After radiotherapy, median postoperative survival time was 23.4 months (confidence interval, 17.2-35.9); 1- and 5-year overall survivals were 74.3% and 24.2%, respectively. No differences were observed between modalities in site of first failure, cumulative incidence of locoregional failure (P = .635), or systemic progression (P = .747). Conclusions Pulmonary resection is feasible and associated with long-term survival in selected patients with synchronous oligometastatic non–small cell lung cancer. Surgery should remain a local consolidative therapeutic option for patients with operable oligometastatic non–small cell lung cancer enrolled in ongoing and future randomized clinical trials.

Background Age disparities among cancer clinical trial participants are pervasive and worsening over time. Identification of factors associated with age disparities is critical to improve enrollment of older patients on trials. The incidence and impact of trial eligibility criteria that exclude patients on the basis of age remains opaque. Methods ClinicalTrials.gov was queried for completed oncologic randomized controlled trials (RCTs). Phase 3 RCTs assessing a therapeutic intervention among adult cancer patients were included. Trial eligibility criteria were assessed using the ClinicalTrials.gov website as well as trial publications and protocol documentation. Results Seven hundred and forty-two trials met inclusion criteria, with a total combined enrollment of 449,720 patients. Upper age restriction enrollment criteria were identified for 10.1% of RCTs; the median age cutoff for restricted trials was 72 years (interquartile range 70–80 years). Linear regression modeling revealed decreasing incidence of age restriction criteria over time, at a rate of −1.1% annually (p = .03); trials initiating enrollment in 2002–2005, for example, had a 16.1% rate of age-restrictive eligibility criteria, compared with 7.6% for trials initiating enrollment in 2010–2014. Conclusion Use of eligibility criteria that explicitly exclude patients on the basis of age appears to be decreasing with time. Future efforts should aim to better characterize the relationship between eligibility criteria (such as those that exclude patients on the basis of specific organ function) and their association with age disparities among enrolled patients.

Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival. A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63–0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11–0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67–4.12) were independently associated with improved OS. Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.

Purpose/objective(s) Bladder and prostate are unfavorable sites for rhabdomyosarcoma (B/P-RMS), and represent a challenging location for radiotherapy. Materials/methods Nineteen patients with B/P-RMS were enrolled on a prospective registry protocol (2008-2017) and treated with chemotherapy, proton beam therapy (PBT), and surgical resection (n = 8; 42%). Emphasis was given to treatment technique, disease-related outcomes, and toxicity associated with PBT. Results The majority of patients had bladder RMS (74%) of embryonal histology (95%), Group III (68%), and intermediate-risk disease by Children's Oncology Group (COG) risk stratification (89%). Seven patients (37%) had primary tumors >5 cm in size. All patients were treated according to COG protocols. With a median follow-up of 66.2 months, 5-year overall survival (OS) and progression-free survival (PFS) were 76%. Four patients (21%) experienced disease relapse, all presenting with local failure. The 5-year local control (LC) rate was 76%. Tumor size predicted LC, with 5-year LC for patients with >5 cm tumors being 43% versus 100% for those with ≤5 cm tumors (P = .006). Univariate analysis demonstrated an effect of tumor size on OS (tumor >5 cm, hazard ratio [HR] 17.7, P = .049) and PFS (HR 17.7, P = .049). Acute grade 2 toxicity was observed in two patients (11%, transient proctitis). Late grade 2+ toxicity was observed in three patients (16%; n = 1 grade 2 skeletal deformity; n = 3 transient grade 2 urinary incontinence; one patient experienced both). Conclusions PBT for B/P-RMS affords promising disease-related outcomes with an acceptable toxicity profile. Higher local failure rates were observed for larger tumors, supporting dose-escalation components of ongoing RMS clinical trials.

Background Local consolidative therapy (LCT) to optimize disease control is an evolving management paradigm in non–small-cell lung cancer (NSCLC) patients who present with a limited metastatic disease burden. We hypothesized that LCT to all sites of disease would be associated with improved overall survival (OS) among patients with synchronous oligometastatic NSCLC. Patients and Methods Patients presenting to a single institution (2000-2017) with stage IV NSCLC and ≤ 3 synchronous metastases were identified. Intrathoracic nodal disease was counted as one site. Landmark and propensity-adjusted Cox regression analyses were performed to identify factors associated with OS. Results Of 194 patients, 143 (74%) had 2 or 3 sites of metastasis. LCT was delivered to all sites of disease in 121 patients (62%), to some but not all sites in 52 (27%), and were not used in 21 (11%). Comprehensive LCT was independently associated with improved OS (hazard ratio [HR] = 0.67; 95% confidence interval [CI], 0.46-0.97; P = .034), with the greatest therapeutic effect among patients without thoracic nodal disease, bone metastases, or > 1 metastatic site. Among patients who underwent comprehensive LCT, tumor histology (squamous: HR = 2.32; 95% CI, 1.28-4.22; P = .006), intrathoracic disease burden (T3-4: HR = 1.67; 95% CI, 0.97-2.86; P = .065; N3: HR = 1.90; 95% CI, 0.90-4.03; P = .093), and bone metastases (HR = 1.74; 95% CI, 1.02-3.00; P = .044) were associated with poor OS. Conclusion Comprehensive LCT was associated with improved OS in this large cohort of patients with synchronous oligometastatic NSCLC. These results support ongoing prospective efforts to characterize the therapeutic benefits associated with this management strategy.

The treatment of locally advanced rectal cancer (LARC) has benefited from improved surgical techniques and from the implementation of neoadjuvant chemoradiotherapy (CRT), which have markedly decreased the rates of local recurrence. However, distant metastatic disease remains the most significant cause of death for these patients. Although adjuvant chemotherapy (ChT) after neoadjuvant CRT and definitive surgery is commonly recommended, the value of adjuvant systemic therapy remains less clear. Trials evaluating adjuvant ChT for rectal cancer have been handicapped by poor compliance rates and inconsistent survival results. Shifting systemic therapy delivery to the neoadjuvant setting has the promise to improve compliance rates, reduce toxicity, and decrease distant relapse rates. Recently, multiple prospective trials have reported on the use of total neoadjuvant therapy (TNT) for patients with LARC, incorporating both ChT and CRT in the neoadjuvant setting. Here, the authors review the promising results from those trials. Because the studies have largely focused on pathologic outcomes (primarily pathologic complete response rates), ongoing phase 2 and 3 trials are now underway assessing the long-term disease-related outcomes with TNT. In addition to improving survival, TNT has the potential to increase the pool of patients with LARC who are eligible for organ preservation, which is also being evaluated. Cancer 2017;123:1497-1506. © 2017 American Cancer Society.

To evaluate the risk of BlCa developing after radiation for PCa, stratified by ethnicity and follow-up duration. The 1973–2011 surveillance, epidemiology and end results database was used to determine the observed and expected number of BlCa after PCa radiation. The adjusted relative risks (RRs) of developing BlCa were calculated for the various radiation modalities relative to no radiation, stratified by ethnicity and follow-up duration. BlCa characteristics were compared between patients with a history of prostate radiation and those without PCa. PCa was radiated in 346,429 men, 6401 of whom developed BlCa versus 2464 expected cases [SIR (95 % CI) of 2.60 (2.53–2.66)]. All radiation modalities were found to have an increased RR of developing BlCa after 10 years, with brachytherapy having a significantly higher RR than external beam radiation (EBRT) or combined EBRT and brachytherapy in Caucasian men and a significantly higher RR than EBRT in men of other/unknown ethnicity. Post-radiation BlCa, in particular that after brachytherapy, had higher grade (P = 0.0001) and lower stage (P = 0.0001) versus the general population. The increased risk of BlCa after prostate radiation occurs predominantly after 10 years, regardless of ethnicity. The RR of developing BlCa after 10 years is significantly higher following brachytherapy than after EBRT or EBRT and brachytherapy. Bladder cancers after prostate radiation, especially after brachytherapy, are generally lower stage but higher grade than those in patients without PCa.

Simple Summary Cancer therapies should improve patient survival or at least improve the quality of their life as they receive treatment for their disease. This is particularly important in pancreatic cancer, where current treatments often have to balance between limiting tumor growth and minimizing patient toxicity. There has been an increasing appreciation among physicians to capture the patient’s voice using tools called patient-reported outcome measures (PROM). In this article, we describe the available PROMs and their relative strengths and weaknesses to help oncologists make sense of this rapidly growing field. Finally, we present a decision-making tool that can help researchers and clinicians select the ideal PROM that fits their needs. Abstract Pancreatic cancer and its treatment often dramatically impact patients’ quality of life (QoL). Given this, as well as increased focus on QoL measures in clinical oncology, there has been a rise in the number of instruments that measure patient-reported outcomes (PROs). In this review, we describe the landscape of different PRO instruments pertaining to pancreatic cancer, with specific emphasis on PRO findings related to pancreatic cancer patients receiving radiotherapy (RT). Twenty-five of the most commonly utilized PROs are compared in detail. Notably, most of the PRO tools discussed are not specific to pancreatic cancer but are generic and have been used in various malignancies. Published findings concerning PROs in pancreatic cancer involving RT are also extracted and summarized. Among the measures used, the European Organization for Research and Treatment Cancer QLQ-C30 was the most commonly utilized. We recommend a careful selection of PRO measures in clinical pancreatic cancer research and care and encourage the use of a combination of symptom-specific and global QoL tools to more fully capture patients’ perspectives.

Importance Despite numerous published phase 3 trials, the association of treatment adherence with outcomes for patients with rectal cancer remains largely unexplored. Objective To analyze the association of treatment adherence with disease-free survival (DFS) among patients with rectal cancer in the CAO/ARO/AIO-04 trial. Design, Setting, and Participants This post hoc analysis of a phase 3 randomized clinical trial was conducted from July 25, 2006, to February 26, 2010, among 1232 patients from 80 centers with T3 to T4 or node-positive rectal adenocarcinoma. Statistical analysis was performed from May 5, 2019, to February 2, 2020. Interventions A total of 625 patients received neoadjuvant fluorouracil-based chemoradiotherapy (nCRT), and a total of 607 patients received fluorouracil-based nCRT with addition of oxaliplatin. Of the 1126 patients who underwent curative surgery, 439 started fluorouracil-based adjuvant chemotherapy and 419 started fluorouracil-based adjuvant chemotherapy with oxaliplatin. Main Outcomes and Measures The association of adherence with nCRT and adjuvant chemotherapy with DFS was assessed in both groups in the as-treated population. Results Among the 625 patients (442 men; mean age, 63.0 years) who received fluorouracil nCRT and the 607 patients (430 men; mean age, 63.0 years) who received fluorouracil-based nCRT with addition of oxaliplatin, after a median follow-up of 50 months (interquartile range, 38-61 months), 3-year DFS in the as-treated population was 71.1% in the fluorouracil group and 75.8% in the fluorouracil-oxaliplatin group (hazard ratio [HR], 0.803; 95% CI, 0.651-0.990;P = .04). Overall, 419 patients in the fluorouracil nCRT group (67.0%) and 434 patients in the fluorouracil-oxaliplatin nCRT group (71.5%) received full doses of preoperative nCRT. Likewise, 253 of 439 patients in the fluorouracil group (57.6%) and 134 of 419 patients in the fluorouracil-oxaliplatin group (32.0%) received full doses of adjuvant chemotherapy. Adherence to nCRT was associated with 3-year DFS in both the fluorouracil group (complete vs near complete: HR, 1.325; 95% CI, 0.959-1.832;P = .09; complete vs reduced: HR, 1.877; 95% CI, 1.147-3.072;P = .01) and the fluorouracil-oxaliplatin group (complete vs near complete: HR, 1.501; 95% CI, 0.980-2.299;P = .06; complete vs reduced: HR, 1.724; 95% CI, 1.144-2.596;P = .009) in multivariable analyses. In contrast, adjuvant chemotherapy was not associated with DFS in both the fluorouracil group (complete vs near complete: HR, 0.900; 95% CI, 0.559-1.448;P = .66; complete vs incomplete: HR, 1.057; 95% CI, 0.807-1.386;P = .69) and the fluorouracil-oxaliplatin group (complete vs near complete: HR, 1.155; 95% CI, 0.716-1.866;P = .56; complete vs incomplete: HR, 1.073; 95% CI, 0.790-1,457;P = .65). Conclusions and Relevance To our knowledge, this is the first analysis of a phase 3 trial to assess the association of treatment adherence with some clinical outcomes for patients with rectal cancer. The findings emphasize the need for appropriate trial design with optimized nCRT dose and schedule and supportive strategies to facilitate good adherence and precision delivery, especially for intensified nCRT. Trial Registration ClinicalTrials.gov Identifier:NCT00349076

2059 Background: Patients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We sought to characterize trial-related factors associated with the use of eligibility criteria that restrict patients by PS, and analyze patient accrual breakdown by PS. Methods: We searched ClinicalTrials.gov for phase III RCTs between 2003-2018. Randomized multi-arm trials assessing a therapeutic intervention in cancer patients were included. PS data were extracted from corresponding manuscripts. Trials with PS restriction Eastern Cooperative Oncology Group (ECOG) ≤1 were identified. Factors associated with PS restriction were determined, and trial patient accrual was analyzed. Results: Six-hundred trials were included with PS data for 238,213 patients. In total, 527 studies (87.8%) specified an upper PS restriction cutoff as part of their exclusion criteria, and 237 studies (39.5%) had a strict inclusion criterion of patients with ECOG PS ≤1. Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (P< 0.001) and lung cancer trials (P < 0.001). Nearly half of trials that led to subsequent FDA approval included strict PS restrictions. Binary logistic regression revealed stable use of restrictive PS eligibility criteria between 2007-2018 (P= 0.789). The vast majority of patients enrolled across all trials had an ECOG PS of 0 to 1 (96.3%). Even among trials that allowed patients with ECOG PS ≥2, only 8.1% of enrolled patients had a poor PS (ECOG 2 or higher).Trials of hematologic cancers had the largest proportion of patients with ECOG PS ≥2 (8.7%), while lung, breast, gastrointestinal and genitourinary trials all included less than 5% of patients with poor PS (P< 0.001). Only 4.8% of patients enrolled in trials that led to subsequent FDA approval had a poor PS. Conclusions: The use of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring, to ensure generalizability of results, while maintaining patient safety.