Session Item

To compare the impact of reirradiation versus systemic therapy on overall survival (OS), progression free survival (PFS), adverse events (AEs) and quality of life (QoL) in patients with recurrent high-grade glioma (rHGG).

The systematic review was conducted in accordance with PRISMA guidelines. A search was performed on the PubMed, Scopus, Embase and CENTRAL databases on 18 March 2022. Studies published from 2010 comparing OS, PFS, AEs and/or QoL in patients with rHGG, and encompassing the following three groups were included; systemic therapy vs reirradiation, systemic therapy vs systemic therapy & reirradiation (combination therapy), reirradiation vs combination therapy. Data was extracted including information on study characteristics, participants, interventions, and relevant outcome measures. The logHR and SE(logHR) for OS and PFS, and logRR and SE(logRR) for AEs were extracted or estimated if not reported for each study. Data was pooled by each comparator group using the generic inverse variance method, and the DerSimionian and Laird random effects model was utilised. A subgroup analysis was performed on studies which accounted for confounders through methodology or multivariate analysis. Risk of bias (RoB) was assessed for randomised control trials (RCTs) using the Cochrane RoB 2 tool, while the ROBINS-I tool was used to assess RoB for non-randomised studies.

28 studies were included. In the systemic therapy vs reirradiation group; there was no difference in OS (3 studies, 237 participants; HR 0.83 (95%CI 0.51-1.35), p=0.45, I2=37%) and PFS (2 studies, 185 participants; HR 0.80 (95%CI 0.55-1.18), p=0.26, I2=0%). In the systemic therapy vs combination therapy group (Table 1); combination therapy improved OS (5 studies, 290 participants; HR 0.59 (95%CI 0.44-0.77), p=0.0002, I2=0%) and PFS (4 studies, 232 participants; HR= 0.53 (95%CI 0.36-0.77), p=0.001, I2=44%), and there was no difference in grade 3+ AEs (3 studies, 151 participants; RR 1.32 (95%CI 0.58-3.01), p=0.50, I2=0%). In the reirradiation vs combination therapy group (Table 2); combination therapy improved OS (14 studies, 805 participants; HR 0.60 (0.48-0.75), p<0.0001, I2=29%) and PFS (5 studies, 259 participants; HR 0.48 (95%CI 0.35-0.65), p<0.00001, I2=0%), and combining reirradiation with bevacizumab reduced radionecrosis (3 studies, 129 participants; RR 0.04 (95%CI 0.01-0.23, p=0.0002, I2=0%). Subgroup analysis of studies accounting for confounders through methodology or multivariate analysis reaffirmed these results. A meta-analysis could not be conducted on QoL outcomes due to insufficient reporting.

Combination therapy may improve OS and PFS with acceptable toxicity in select patients with rHGG. Limitations of current literature include the small number of studies, selection bias and confounders. RCTs accounting for these factors are required for further investigation. Additional studies comparing QoL outcomes are also required.