Efficacy and safety of whole brain low dose radiotherapy combined with immune checkpoint inhibitor and intrathecal chemotherapy for treatment of refractory meningeal metastasis of lung cancer.

e20060 Background: To explore the efficacy and safety of whole-brain low-dose radiotherapy combined with immune checkpoint inhibitor (ICI) and intrathecal pemetrexed (IP) for the treatment of refractory non-small cell lung cancer (NSCLC) with leptomeningeal metastases (LM). Methods: Retrospective analyses were performed on NSCLC 8 patients with LM at the West China Hospital of Sichuan University from December 1, 2022 to March 31, 2024. Among the 8 patients, there were 4 males and 4 females, with a median age of 49 years (ranging between 34 to 58 years). All patients were treated with whole-brain LDRT combined with ICI and intrathecal chemotherapy regimens, and therapeutic efficacy was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria and the Karnofsky Physical Status (KPS) score. Adverse reactions were assessed according to the Common Criteria for the Evaluation of Adverse Events (CTCAE version 5.0). Survival analysis was performed using the Kaplan-Meier method. The classification proportion of cerebrospinal fluid subsets before and after treatment was analyzed by single cell sequencing, and the differential analysis of gene expression in parallel cells were performed. Results: The best clinical treatment effects in 8 patients treated were evaluated by RANO criteria: 5 patients were evaluated as improved (62.5%) and 3 patients were evaluated as stable (37.5%). The median KPS score of 8 patients was 30 (20-50) before treatment, and it was significantly improved after treatment, which was 60 (40-90) ( P =0.0009). The remission rate of neurological symptoms was 100% (8/8) in 8 patients. The median neurological progression-free survival (NPFS) was 12 months. The results of single cell sequencing in CSF of patient (P1) showed that the proportion of T cells in samples of patient after whole brain LDRT treatment was significantly higher than that before treatment (6.08% VS 68.87%), and the proportion of tumor cell was largely lower (12.92% VS 0.6%). The differential analysis of gene expression showed that CCL5 and CXCL13 were significantly upregulated in T cells of CSF after WB-LDRT treatment. Conclusions: The combination of whole-brain LDRT with ICI and IP in the treatment of NSCLC with LM can significantly alleviate neurological symptoms, improve quality of life and prolong the NPFS of patients, which is a safe and effective treatment.