[Hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost for multiple brain metastases...

Objective: To explore the safety and feasibility of hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost (HA-WBRT+SIB) in the treatment of multiple brain metastases ( ≥4 lesions) in non-small cell lung cancer (NSCLC). Methods: In this prospective, single-arm phase Ⅱ clinical study, twenty-three patients with multiple brain metastases of NSCLC were enrolled in the Affiliated Cancer Hospital of Nanjing Medical University from January 2021 to June 2023. All patients received HA-WBRT (30 Gy/12 fractions, with the maximum dose to the hippocampus ≤ 17 Gy and the average dose ≤ 12 Gy) + SIB (48 Gy/12 fractions). Patients were assessed for the therapeutic effect by the response evaluation criteria for brain metastases of the International Society for Neuro-Oncology, adverse reactions by Common Terminology Criteria for Adverse Events 5.0 (CTCAE5.0), cognitive function by the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) 2 and 4 months after radiotherapy, as well as before radiotherapy. The patients' intracranial local progression-free survival (iLPFS), intracranial progression-free survival (iPFS), and intracranial tumor control were followed up. Results: One month after radiotherapy, among the 172 local tumor brain metastases of the 23 patients, 13 lesions were lost to follow-up. The remaining 159 lesions showed the following outcomes: 106 lesions (66.7%) achieved complete remission, 37 lesions (23.3%) achieved partial remission, 12 lesions (7.5%) showed stable disease, and 4 lesions (2.5%) had disease progression. Three patients had intraregional progression in the brain metastases and three patients had extraregional progression (one patient of the three patients developed two new metastases within the hippocampal avoidance area). The incidence of treatment-related adverse reactions was 26.1% (6/23), among which only one patient experienced grade 4 memory impairment. The HVLT-R DR scores before and 2 and 4 months after radiotherapy were 14.9 (13.3, 15.1) points, 14.1 (12.9, 14.6) points, and 13.7 (13.1, 13.8) points respectively, and the difference was statistically significant (P＜0.001). The median follow-up period was 11.1 months. The median iLPFS was 16.4 months and the median iPFS was 11.1 months. The cumulative incidence of local failure in the brain region over one year was 9.6%. Conclusion: For patients with multiple brain metastases of NSCLC, HA-WBRT+SIB emerges as a promising and safe therapeutic alternative, protecting cognitive function and demonstrating improved intracranial tumor control.