PP-11 Hippocampal avoidance in whole-brain radiotherapy: a systematic review and meta-analysis of neurocognitive and quality-of-life outcomes

Background and Aim Whole-brain radiotherapy (WBRT) remains a standard treatment for patients with multiple brain metastases but is associated with substantial cognitive decline, particularly affecting memory and executive functions. Hippocampal avoidance WBRT (HA-WBRT) has emerged as a promising approach to mitigate radiation-induced neurotoxicity while maintaining oncologic efficacy. This systematic review and meta-analysis aimed to evaluate the cognitive, quality-of-life, and survival outcomes associated with HA-WBRT compared to conventional WBRT. Methods A comprehensive search of PubMed, Embase, Scopus, Web of Science, and the Cochrane Library was performed from inception to September 16, 2025. Randomized, prospective, and observational studies assessing neurocognitive and quality-of-life outcomes in patients receiving HA-WBRT were included. Data were extracted on memory function, executive performance, quality of life (QoL), survival, and toxicity. Pooled estimates were calculated using random-effects models in R, with heterogeneity assessed via I2 and χ2 statistics. Results Fifteen studies (7 randomized controlled trials, 6 prospective phase II, and 2 cohorts) encompassing 1,300 patients were included. HA-WBRT significantly preserved memory (mean difference +20.6%, P < 0.001) and reduced the risk of cognitive failure (HR 0.74, 95% CI 0.58–0.95). Pooled analysis demonstrated improved QoL stability at 6 months (78% vs 49%; RR 1.52, 95% CI 1.24–1.85). Executive function deterioration was reduced (23.3% vs 40.4%; P = 0.01). There were no significant differences in overall survival (8.6 vs 8.0 months) or intracranial progression-free survival. Hippocampal metastasis rates remained low (4.2%), and grade ≥3 toxicity was rare (