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PURPOSE To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities. METHODS NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression ≥ 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression. RESULTS From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; P = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; P = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, P = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM. CONCLUSION To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS.

To introduce an educational intervention-specifically, a specialized training course-and perform a formative evaluation of the effect of the intervention on novice reader interpretation of computed tomography (CT) colonographic data.The study was institutional review board approved. Ten normal and 50 abnormal cases, those of 60 patients with 93 polyps-61 polyps 6-9 mm in diameter and 32 polyps 10 mm or larger-were selected from a previously published trial. Seven novice readers underwent initial training that consisted of a 1-day course, reading assignments, a self-study computer module (with 61 limited data sets), observation of an expert interpreting three cases, and full interpretation of 10 cases with unblinding after each case. After training, the observers independently interpreted 60 cases by means of primary two-dimensional reading with unblinding after each case. For each case, the reading time and the location and maximal diameter of the polyp(s) were recorded. A t test was used to evaluate the observers' improvements, and empirical receiver operating characteristic (ROC) curves were constructed.By-patient sensitivities and specificities were determined for each observer. The lowest by-patient sensitivity at the 6 mm or larger polyp threshold was 86%, with 90% specificity. Four observers had 100% by-patient sensitivity at the 10 mm or larger polyp threshold, with 82%-97% specificity. For polyps 10 mm or larger, mean sensitivity and specificity were 98% and 92%, respectively. For the last 20 cases, the average interpretation time per case was 25 minutes. The range of areas under the ROC curve across observers was low: 0.86-0.95.In the described polyp-enriched cohort, novice CT colonographic data readers achieved high sensitivity and good specificity at formative evaluation of a comprehensive training program. Use of a similar comprehensive training method might reduce interreader variability in interpretation accuracy and be useful for reader certification.

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor and is approved for the treatment of patients with recurrent glioblastoma (GBM). Previous authors have reported differential response to bevacizumab on an individual basis. Bevacizumab-induced hypertension is a well-documented side effect, and some reports have suggested this occurrence to be related to treatment outcome in other cancers. In the current study, the authors analyzed patients with recurrent GBM who were treated with bevacizumab based on whether the patients developed drug-induced hypertension.All patients with GBM treated within the Emory Healthcare system from 2007 through 2012 were reviewed. A total of 82 patients were identified who received bevacizumab for the treatment of recurrent GBM and were included in the current study. Patients were classified as normotensive or hypertensive depending on whether hypertension developed that was attributable to therapy. Progression-free survival (PFS) and overall survival (OS) were graphed by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards method.The median follow-up was 19.7 months. Of the 82 patients with recurrent GBM who were treated with bevacizumab, 30 developed drug-induced hypertension. The median time to the development of hypertension was 21 days. The median PFS for the normotensive and hypertensive groups were 2.5 months (95% confidence interval [95% CI], 1.6-3.0 months) and 6.7 months (95% CI, 4.6-10.0 months), respectively (P.001). The median OS times for the normotensive and hypertensive groups were 4.9 months (95% CI, 4.4-6.8 months) and 11.7 months (95% CI, 9.0-20.5 months), respectively (P.001).Patients with recurrent GBM who developed bevacizumab-induced hypertension demonstrated significantly better PFS and OS compared with normotensive individuals. Bevacizumab-induced hypertension may be a physiologic marker of outcome in patients with recurrent GBM.

To compare the characteristics and outcome of adults and children diagnosed with Wilms' tumor.The Surveillance, Epidemiology and End Results (SEER) database was analyzed for patients diagnosed with Wilms' tumor between 1973 and 2007. Patients were stratified into pediatric (16 years) or adult (≥16 years) groups. Overall survival was the primary endpoint.A total of 2342 patients (2190 pediatric and 152 adult) with Wilms' tumor were identified. Adult patients were statistically more likely to be staged as localized than pediatric patients (62.5% vs 44.7%), to not receive any lymph node sampling (57.9% vs 16.2%), and to not receive any radiation treatment (74.3% vs 53.9%). Adults had a statistically worse overall survival (OS) than pediatric patients (5-year OS, 69% vs 88%, P.001) despite the earlier tumor stage. When stratified by treatment era, the OS of all patients treated after 1981 was statistically higher than those treated before (5-year OS, 75% vs 89%, P.001). Significant predictors of OS on univariate analysis for adults included treatment era, SEER stage, surgery, and radiation treatment. Significant predictors of OS on multivariate analysis of all patients included adult status (hazard ratio, 4.14; P.001), treatment era, SEER stage, and surgery.Adults in the SEER database had statistically worse OS than pediatric patients despite previous studies showing comparable outcome when treated on protocol. The worse outcome of SEER adults likely stems from incorrect diagnosis, inadequate staging and undertreatment. We recommend lymph node samplings for all adult Wilms' tumor patients and collaboration with pediatric oncologists.