455P - Phase II trial of hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost for multiple brain metastases in non-small cell lung cancer

Background

Conventional whole-brain radiation therapy (WBRT) exhibits poor local tumor control and decreased neurocognitive function (NCF). Herein, we investigated the safety and efficacy of a novel approach–hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost (HA-WBRT+SIB)– in patients of non-small cell lung cancer (NSCLC) with multiple brain metastases.

Methods

We conducted a prospective, single-arm phase II trial administering HA-WBRT (30 Gy in 12 fractions, Dmax of the hippocampal volume ≤ 17 Gy, Dmean of the hippocampal volume ≤12 Gy) +SIB (48 Gy in 12 fractions) for multiple brain metastases (≥4) of NSCLC. Survival and intracranial tumor control were compared with patients who underwent conventional WBRT (a retrospective cohort) by propensity score matching analysis (PSM). Cognitive performance in the HA-WBRT+SIB cohort was assessed by the Hopkins Verbal LearningTest–Revised delayed Recall (HVLT-R DR).

Results

Between January 2021 and July 2023, 23 patients were enrolled in the HA-WBRT+SIB cohort. After 1:2 PSM (HA-WBRT+SIB versus WBRT= 23:46), intracranial local progression-free survival (iLPFS) (16.43 versus 5.9 months; P = 0.004) and intracranial progression-free survival (iPFS) (11.1 versus 5.7 months; P = 0.014) were significantly improved following HA-WBRT+SIB. The cumulative incidence of intracranial local failure (9.6% versus 34.2% at 1 year; P= 0.027) was improved in the HA-WBRT+SIB cohort. One patients (4.3%) developed hippocampal metastases after hippocampus avoidance. There was an average decline of 7.08% ± 5.23% in the HVLT-R DR at 4 months post-HA-WBRT+SIB (95%CI: 10.0% to 6.5%).

Conclusions

For patients with multiple brain metastases of NSCLC, HA-WBRT+SIB emerges as a promising and safe therapeutic alternative, demonstrating improved intracranial tumor control and protecting cognitive function.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Yatian Liu.

Funding

This study was supported by the Nanjing Medical University of Collaborative Innovation Center for Cancer Personalized Medicine (JZ23349020200108) and Jiangsu Cancer Hospital level projects (ZM202021).

Disclosure

All authors have declared no conflicts of interest.