Comprehensive mutation analysis in NRG Oncology/RTOG 9813: A phase III trial of RT + TMZ vs RT + nu for anaplastic astrocytoma and mixed anaplastic oligoastrocytoma (Astrocytoma Dominant).

2016Background: This study sought to examine the prognostic value of mutations within IDH1/2, ATRX, CIC, FUBP1, and the TERT promoter in a phase III study of grade III astrocytomas using multivariate analyses (MVAs). Methods: IDH mutations were determined by immunohistochemistry and/or next-generation sequencing. A custom Ion AmpliSeq DNA panel was used for mutation analysis; TERT promoter mutations were detected by Sanger sequencing. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated and tested using the Cox proportional hazard model and the log-rank test. MVAs were performed including age, treatment, surgery, and performance status as covariates. Results: Mutations within IDH1/2 were found in 55% (57/104), ATRX in 46% (28/61), the TERT promoter in 20% (11/55), CIC in 10% (6/61), and FUBP1 in 2% (1/61) of analyzed cases. In the univariate analyses on OS, IDH1/2 (HR=0.41; p<0.001) and ATRX mutations (HR=0.45; p=0.02) ...