Abstract
Background Patient-reported outcomes (PROs) are increasingly recognized as essential endpoints in neuro-oncology, yet their prognostic value for survival across brain tumor trials remains incompletely defined. We conducted a systematic review and meta-analysis to quantify the association between key PRO domains and overall survival (OS) and progression-free survival (PFS)in patients with glioma. Methods Following PRISMA 2020 guidelines, we included randomized controlled trials that reported baseline PROs using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 or European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Brain Neoplasm-20 questionnaires, with corresponding survival outcomes. Hazard ratios (HRs) per 10-point increase in each PRO domain were extracted. Random-effects models generated pooled HRs. Heterogeneity, risk of bias (ROB 2), and certainty of evidence (GRADE) were assessed. Results Eight trials comprising 6,846 patients were included. Higher baseline cognitive functioning was significantly associated with improved OS (HR = 0.94, 95% CI [0.91-0.97]), as was physical functioning (HR = 0.97, 95% CI [0.94-1.00]). Pooled functional domains showed a protective association (HR = 0.96, 95% CI [0.93-1.00]), while BN-20 domains showed no association with overall survival. Pooled analysis of studies reporting EORTC QLQ-C30 scales was associated with improved PFS (HR = 0.99, 95% CI [0.99-0.99]). Subgroup analysis of physical functioning showed an association with improved PFS (HR = 0.99, 95% CI [0.97-1.0]), and the pooled analysis of all functional scales showed the same direction (HR = 0.99, 95% CI [0.99-0.99]). Conclusions Functional and cognitive PRO domains appear to have potential to be robust prognostic markers of survival in glioma trials, and these findings support the complementary role of PROs alongside clinical, radiographic, and molecular measures. Our findings support integrating PROs into response assessment selection in future neuro-oncology trials.