Reirradiation versus systemic therapy versus combination therapy for recurrent high-grade glioma: a systematic review and meta-analysis of survival and toxicity.

Purpose: This review compares reirradiation (reRT), systemic therapy and combination therapy (reRT & systemic therapy) with regards to overall survival (OS), progression-free survival (PFS), adverse effects (AEs) and quality of life (QoL) in patients with recurrent high-grade glioma (rHGG).

Methods: A search was performed on PubMed, Scopus, Embase and CENTRAL. Studies reporting OS, PFS, AEs and/or QoL and encompassing the following groups were included; reirradiation vs systemic therapy, combination therapy vs systemic therapy, combination therapy vs reRT, and bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy. Meta-analyses were performed utilising a random effects model. Certainty of evidence was assessed using GRADE.

Results: Thirty-one studies (three randomised, twenty-eight non-randomised) comprising 2084 participants were included. In the combination therapy vs systemic therapy group, combination therapy improved PFS (HR 0.57 (95% CI 0.41-0.79); low certainty) and OS (HR 0.73 (95% CI 0.56-0.95); low certainty) and there was no difference in grade 3 + AEs (RR 1.03 (95% CI 0.57-1.86); very low certainty). In the combination therapy vs reRT group, combination therapy improved PFS (HR 0.52 (95% CI 0.38-0.72); low certainty) and OS (HR 0.69 (95% CI 0.52-0.93); low certainty). In the bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy group, adding bevacizumab improved PFS (HR 0.46 (95% CI 0.27-0.77); low certainty) and OS (HR 0.42 (95% CI 0.24-0.72; low certainty) and reduced radionecrosis (RR 0.17 (95% CI 0.06-0.48); low certainty).

Conclusions: Combination therapy may improve OS and PFS with acceptable toxicities in patients with rHGG compared to reRT or systemic therapy alone. Particularly, combining bevacizumab with reRT prophylactically reduces radionecrosis.

Registration: CRD42022291741.