Redo craniotomy or bevacizumab for symptomatic steroid-refractory true or pseudoprogression following IMRT for glioblastoma

Abstract

Objective There is minimal evidence to support decision-making for symptomatic steroid-refractory pseudoprogression or true progression occurring after IMRT for glioblastoma (GBM). This study audited the survival outcome of patients managed with redo craniotomy (RedoSx) or Bevacizumab (BEV) for steroid-refractory mass effect after IMRT for GBM. Methods Patients with GBM managed between 2008 and 2019 with the EORTC-NCIC Protocol were entered into a prospective database. Patients with symptomatic steroid-refractory mass effect within 6 months of IMRT managed with either RedoSx or BEV were identified for analysis. For the primary endpoint of median overall survival (OS) post intervention, outcome was analysed in regards to potential prognostic factors, and differences between groups assessed by log-rank analyses. Results Of 399 patients managed with the EORTC-NCIC Protocol, 78 required an intervention within 6 months of IMRT completion for either true or pseudoprogression (49 with RedoSx and 29 with BEV). Subsequently 20 of the 43 patients managed with RedoSx when BEV was clinically available, required salvage with BEV within 6 months after RedoSx. Median OS post intervention was 8.7 months (95%CI: 7.84-11.61) for the total group; and 8.7 months (95%CI: 6.8-13.1) for RedoSx and 9.4 months (95%CI: 7.8-13.6) for BEV (p=0.38). Subsequent use of BEV in RedoSx patients was not associated with improved survival compared with RedoSx alone (p=0.10).Age, time from IMRT, and ECOG performance status were not associated with OS. In the RedoSx patients, immunohistochemical features such as Ki67% reduction correlated with survival. Presence of pure necrosis and residual tumour cells only had improved survival compared with presence of gross tumour (p<0.001). Conclusions At time of symptomatic steroid-refractory true or pseudoprogression following IMRT for GBM, BEV was equivalent to RedoSx in terms of OS. Pseudoprogression with residual cells at RedoSx was not associated with worse outcome compared to pure necrosis.

DEGRO practical guideline for central nervous system radiation necrosis part 2: treatment

“…Surgery can potentially reduce the CNS tumor burden if RN is combined with residual tumor cells. Yet, at least for GBM, no difference was shown in overall survival for surgery or bevacizumab if RN consisted of necrosis only vs. residual tumor cells [ 32 ]. Thus, there seems to be no advantage of cytoreduction or RN resection in terms of survival.…”