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

Theresa A Cook; Dasantha T Jayamanne; Helen R Wheeler; Matthew H F Wong; Jonathon F Parkinson; Raymond J Cook; Marina A Kastelan; Nicola J Cove; Christopher Brown; Michael F Back

doi:10.1093/nop/npab034

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

Neurooncol Pract. 2021 Jun 9;8(5):601-608. doi: 10.1093/nop/npab034. eCollection 2021 Oct.

Authors

Theresa A Cook¹, Dasantha T Jayamanne², Helen R Wheeler^{2

3}, Matthew H F Wong¹, Jonathon F Parkinson^{3

4

5}, Raymond J Cook⁵, Marina A Kastelan^{2

4}, Nicola J Cove¹, Christopher Brown², Michael F Back^{1

2

6

3

4}

Affiliations

¹ Central Coast Cancer Centre, Gosford Hospital, Gosford, New South Wales, Australia.
² Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales, Australia.
³ Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
⁴ The Brain Cancer Group, Sydney, New South Wales, Australia.
⁵ Department of Neurosurgery, Royal North Shore Hospital, Sydney, New South Wales, Australia.
⁶ Genesis Cancer Care, Sydney, New South Wales, Australia.

Abstract

Background: There is minimal evidence to support decision making for symptomatic steroid-refractory pseudoprogression or true progression occurring after intensity-modulated radiation therapy (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) postintervention, outcome was analyzed in regards to potential prognostic factors, and differences between groups were assessed by log-rank analyses.

Results: Of the 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 postintervention 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 = .38). Subsequent use of BEV in RedoSx patients was not associated with improved survival compared with RedoSx alone (P = .10). Age, time from IMRT, and ECOG performance status were not associated with OS. In the RedoSx patients, immunohistochemical features such as Ki-67% reduction correlated with survival. The presence of pure necrosis and residual tumor cells only had improved survival compared with the presence of gross tumor (P < .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.

Keywords: bevacizumab; glioblastoma; pseudoprogression; redo craniotomy.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.