Outcomes for patients managed by Redo Craniotomy or Bevacizumab for pseudo-progression or true progression occurring within six months of adjuvant RT for glioblastoma

Abstract

PURPOSE: Minimal evidence exists to support decision-making that occurs at the time of symptomatic steroid refractory pseudo-progression or true progression occurring within six months of IMRT for GBM. This study aimed to audit the survival outcome of patients with managed with either redo craniotomy (Re-doSx) or Bevacizumab (BEV).METHODS: Patients with GBM managed with IMRT and temozolomide between 2007 and 2017 as per the EORTC-NCIC (Stupp) Protocol were entered into a prospective ethics approved database. Eligible patients were those with GBM requiring either Re-doSx or BEV within 6 months of completion of IMRT because of symptomatic steroid refractory mass effect. For the primary endpoint of median overall survival (OS) data post intervention, outcome was analysed in regards to potential prognostic factors. RESULTS: 348 patients were managed with Stupp Protocol, and 59 required an intervention for true progression or pseudo-progression (38 with Re-doSx and 21 with BEV) within 6 months post-IMRT. Of 38 patients managed with Re-doSx, 14 were subsequently salvaged with BEV. Patients managed with Re-doSx or BEV had median OS of 6 months (95%CI:3.0-9.0) and 9 months (95%CI:7.6-10.4) respectively (p=0.19). Age (p=0.21), time from IMRT (p=0.37) and ECOG (p=0.31) also were not associated with survival. However for Re-doSx patients, subsequent BEV salvage was associated with improved survival (8 months vs 4 months, p=0.02).The histopathology of 38 patients at RedoSx was pure necrosis (7patients); residual glioma cells (18patients), and gross tumour (13patients). Presence of residual glioma cells did not correlate with survival. However immunohistochemical features were predictive of survival including Ki-67 level of <10% (p<0.01); >50% reduction in Ki-67 (p<0.01); and >80% tumour necrosis (p=0.01).CONCLUSION: At symptomatic steroid refractory true or pseudo-progression following IMRT for GBM, BEV was equivalent to Re-doSx in terms of overall survival. Additionally, in those undergoing Re-doSx, subsequent BEV was associated with improved survival.