Propensity score-matched analysis comparing Hippocampus-Avoidance Whole-Brain Radiotherapy plus Simultaneous Integrated Boost with Hippocampus-Avoidance Whole-Brain Radiotherapy alone for multiple brain metastases-a retrospective study in multiple institutions

Abstract Background: The optimal treatment for multiple brain metastases has been recently controversially discussed.This study was aimed to explore the feasibility of Hippocampus-Avoidance Whole-Brain Radiotherapy plus a simultaneous integrated boost(HA-WBRT+SIB) in the treatment of multiple brain metastases and assess tumor control in compared with Hippocampus-Avoidance Whole-Brain Radiotherapy(HA-WBRT) alone for brain metastases. Methods: In this study, 63 patients with multiple brain metastases(≥4 metastases) had undergone HA-WBRT+SIB between January 2016 and December 2020 in the observation group：HA-WBRT (30Gy in 12 fractions, the maximum dose of the hippocampus≤14Gy) plus a simultaneous integrated boost(48Gy in 12 fractions) for brain metastases.Overall Survival (OS),Median survival,intracranial control (IC=control within the entire brain), intracranial progression-free survival(iPFS) and adverse events were compared with the control group(a HA-WBRT retrospective cohort) by propensity score matching analysis. Results: After 1:1 propensity score matching,there were 56 patients in each group(the observation group,the control group). OS, media survival and iPFS were significantly longer in the observation group(18.4 vs 10.9 months,P＜0.001),(13.0 vs 8.0 months,P＜0.001),(13.9vs7.8 months,P＜0.001). In comparison of 1-year-IC rates, the observation group also demonstrated higher than the control group (51.8% vs 21.4%,P=0.002), respectively. Seven hippocampal metastases were found in the control group (4/56,7.1%) and observation group(3/56,5.4%) after HA-WBRT. The death rate of intracranial progression were 23.2% in the observation group and 37.5% in the control group.All adverse events were not significant difference between the two groups(P＞0.05). Conclusions: HA-WBRT+SIB resulted in better OS,media survival,IC,iPFS, an acceptable risk of radiation response,and a potential way of declining neurocognitive adverse events,which may be a better treatment for patients with multiple brain metastases.