Citations

Abstract BACKGROUND The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown. OBJECTIVE To examine these uncertainties. METHODS NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan–Meier method. RESULTS A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings ( P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire ( P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test–Revised Delayed Recognition [ P = .048], Trail Making Test Part A [ P = .035], and Controlled Oral Word Association [ P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures. CONCLUSION STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.

3 Background: Previous reports suggested that AAT when combined with salvage RT following RP in patients may improve prostate cancer control outcomes. Methods: Post-RP patients with pT3pN0 or with pT2pN0 and positive margins who had or developed elevated PSA levels from 0.2 to 4.0 ng/ml were randomized on a phase III, double-blind, trial of RT + placebo (64.8 Gy in 36 fractions of 1.8 Gy) vs. RT + AAT (24 months bicalutamide, 150 mg daily) during and after RT. The primary end-point was overall survival. Trial design required 725 patients and provided 80% power to detect a reduction in death rate by at least 28.5% and a 1-sided significance level of 0.046. Results: From 3/98 to 3/03, 761 eligible patients (median age 65) were randomized to RT + AAT (384) or RT + placebo (377). 248 patients (33%) were pT2pN0 and 513 (67%) were pT3pN0. 671 (88%) had a PSA nadir after RP of < 0.5 ng/ml. 649 (85%) had an entry PSA value of <1.6, 112 patients (15%) had an entry PSA of 1.6-4. Median follow up was 12.6 years. Actuarial overall survival at 10 years was 82% for RT plus AAT and 78% for RT + placebo and a hazard ratio of 0.75 (95% CI: 0.58-0.98) with a 1-sided p value of 0.018 (2-sided p = 0.036). The 12-year incidence of PC central-reviewed deaths were 2.3% for RT + AAT and 7.5% for RT + placebo ( p< 0.001).The cumulative incidence of metastatic PC at 12 years was less in the RT + AAT arm, 14% (51 patients), vs. 23% (83 patients) in the RT + placebo arm (p < 0.001). Subgroup analyses of the relative benefits of the addition of AAT to RT are planned and will be presented. Late grade III and IV toxicity were similar in the AAT and placebo arms. The combined grade III and IV toxicities for RT + AAT and RT + placebo were: bladder 7.0% vs. 6.7%, bowel 2.7% vs. 1.6%. Gynecomastia differed significantly by treatment arm, 70% vs. 11%. Conclusions: 24 months of AAT using 150mg bicalutamide daily during and after salvage RT significantly improved long term overall survival and reduced the incidence of metastatic PC and PC death. Support: NCI grants U10CA21661, U10CA180868, U10CA180822, and U10CA37422 and AstraZeneca. Clinical trial information: NCT00002874.

Objectives: The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. Materials and Methods: Eligible patients included stage II-IIIB non–small cell lung cancer, stage I central non–small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. Results: Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients’ refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. Conclusions: Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.