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BACKGROUND: Re-irradiation has recently garnered interest as a treatment option for recurrent high grade glioma. Evidence supporting benefits in this population is evolving, but little is known about impact on quality of life (QOL). QOL patient reports were collected in a phase II hypofractionated re-irradiation study. METHODS: Patients with recurrent anaplastic glioma or glioblastoma were stratified into four groups based on histology and prior bevacizumab exposure. Treatment consisted of 45 Gy radiation delivered in 25 fractions with daily temozolomide 75 mg/m2 and bevacizumab 10 mg/kg every 2 weeks. This was followed by adjuvant daily temozolomide 50 mg/m2 for 6 weeks and bevacizumab 10 mg/kg every 2 weeks in an 8 week cycle for up to 6 cycles, or until progression or intolerance. FACT-Brain and FACIT-Fatigue were collected as secondary end-point data prior to treatment start, at end of the concurrent phase, and after each cycle. RESULTS: Of 54 patients treated, 42 (78%) had evaluable QOL data. Mean baseline FACT-Br and FACIT-Fatigue scores were within expected ranges for persons with brain tumors. Significant declines were noted in FACT-Br Total (p=0.4), FACT-Br TOI (p=.05) and FACIT-Fatigue (p

PURPOSE: NRG CC001, a phase III trial of WBRT plus memantine with or without hippocampal avoidance, sought to evaluate the neuro-protective effects of avoiding the hippocampus using intensity-modulated radiotherapy. METHODS: Adult patients with brain metastases were stratified by RPA class and receipt of prior radiosurgery/surgery and randomized to WBRT+memantine (WBRT+M) versus hippocampal-avoidant WBRT+memantine (HA-WBRT+M) (30Gy in 10 fractions). Standardized NCF tests were performed at baseline, 2, 4, 6, and 12 months. The primary endpoint was time to NCF failure, defined as decline on at least one of the following tests using the reliable change index: Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence was used to estimate time to NCF failure (death without NCF failure was treated as competing risk) with between-arms differences tested using Grays test. To detect an 11% absolute reduction in 6-month NCF failure, 382 analyzable patients were required for 90% power with two-sided =0.05. Due to possible non-compliance, the sample size was increased by 25% (510 patients). RESULTS: From July 2016 to March 2018, 518 patients were randomized. Median age was 61.5 years. Median follow-up for alive patients was 6.1 months. Treatment arms did not differ in grade3 toxicity, overall survival, intracranial progression, or baseline NCF. Time to NCF failure was significantly longer in favor of HA-WBRT+M (p=0.012). The 6-month NCF failure rates were 69.1% (95% CI:61.8–75.3%) vs. 58.0% (95% CI:50.2–64.9%) for WBRT+M vs. HA-WBRT+M, respectively. After adjusting for stratification factors, HA-WBRT+M (hazard ratio (HR)=0.73, 95%CI:0.56–0.94, p=0.016) and age 61 years (HR=0.61, 95%CI:0.46–0.81, p=0.0006) remained significant. CONCLUSION: Preliminary analysis confirms that conformal avoidance of the neuro-regenerative hippocampal stem cell compartment during WBRT preserves neurocognitive function while achieving similar intracranial control and survival. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute.

INTRODUCTION: This study tested the hypothesis that ABT-888 (veliparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, can modulate temozolomide (TMZ) resistance in recurrent, TMZ-refractory glioblastoma (GBM) patients. METHODS: The combination regimen (TMZ/ABT-888) was tested using 2 randomized schedules (5 or 21 days of a 28 day cycle). Two cohorts were studied: bevacizumab naive (BEV-N), and BEV refractory (BEV-R). Six-month progression free survival (PFS6) was the primary endpoint, with hypothesized rates of 30% for BEV-N and 15% for BEV-R; using one-sample binomial tests; alpha = 0.10 and 90% power. Arm 1 combined 40 mg BID ABT-888 with TMZ using the 21/ 28 day schedule at 75 mg/m2. Arm 2 combined ABT-888 (40 mg BID) with TMZ using the 5/ 28 day TMZ at 150-200 mg/m2. RESULTS: Of 151 BEV-N and 74 BEV-R patients, 10 were ineligible. The incidence rate of grade 3/4 myelosuppression was 20.0%. For both arms, PFS6 for BEV-N was 17.0%; 4.4% for BEV-R. Median overall survival (OS) was 10.3 months (95% CI, 8.4-12.0) for BEV-N and 4.7months (95%CI, 3.5-5.6) for BEV-R. The median PFS was essentially the same for both arms and both cohorts at ∼2.0M (95% CI, 1.9-2.1). CONCLUSIONS: The combination of TMZ and ABT-888 did not significantly improve PFS6 for either BEV-N or BEV-R patients with recurrent GBM who had been previously treated with TMZ. For both groups of patients, the objective response rate was low, and did not differ by treatment arm, and the OS and PFS were similar for both treatment arms. Although MGMT status was not included for eligibility and therefore not analyzed, the low response rates, low PFS and low OS suggest that the likelihood of a clinically meaningful benefit for an MGMT-defined subset is remote. Support: Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, and UG1CA189867 from the National Cancer Institute (NCI) and AbbVie.