2564 - Application of Whole Brain Radiation Therapy in Leptomeningeal Metastatic NSCLC Patients in Target Therapy Age: A Retrospective Cohort Study on Dose-Fractionation Regimens and Prognostic Factors

Purpose/Objective(s): Leptomeningeal metastasis (LM) is a fatal complication of advanced non-small cell lung cancer (NSCLC) with no definitive treatment protocol. Whole brain radiation therapy (WBRT) is a key component of LM management, but its survival benefits and optimal dosing remain unclear. This retrospective cohort study aims to evaluate the survival impact of WBRT in NSCLC patients with LM and to identify the optimal dose-fractionation regimen, alongside assessing additional clinicodemographic variables for prognostic analysis.

Materials/Methods: A total of 105 patients with leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC) were included in the study, with clinicodemographic data obtained from the electronic medical records of Guangdong Sanjiu Brain Hospital for those who received treatment between September 2014 and April 2020. Two radiologists, both with extensive experience in brain tumors, were responsible for analyzing the imaging data. The median follow-up was 8.1 months (IQR, 4–16.7 months) following LM diagnosis. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognosticators.

Results: Among the 105 patients, 47 (44.8%) were male, and 58 (55.2%) were female, with a median age of 53 years (range 29–76 years). Notably, 83 patients (79%) had EGFR/ALK/ROS1 mutations, while 22 (21%) were wild-type. Univariate Cox regression analysis indicated that targeted therapy (HR 0.168, 95% CI 0.092 - 0.307, P<0.001), WBRT (HR 1.604, 95% CI 0.402 – 0.907, P=0.015), and the presence of mutations (HR 0.146, 95% CI 0.079 – 0.266, P<0.001) were associated with improved OS. In multivariate analysis, WBRT (HR 0.633, 95% CI 0.418 – 0.959, P=0.031) and mutations (HR 0.089, 95% CI 0.019 – 0.401, P=0.001) emerged as independent prognosticators. The median OS recorded was 252 days (8.4 months). Patients with mutations had a significantly better OS than wild-type patients (348 days vs. 114 days, P<0.001). WBRT recipients demonstrated improved OS compared to non-recipients (348 days vs. 133 days, P=0.014). However, no significant survival difference was observed between WBRT and non-WBRT in the mutant subgroup (385 days vs. 214 days, P=0.16), while wild-type patients showed a significant difference (128 days vs. 63 days, P=0.021). No considerable survival variance was noted among the 40Gy/20F, 36Gy/18F, and 30Gy/10F regimen subgroups.

Conclusion: WBRT provides clear survival benefits in NSCLC-LM patients, particularly in wild-type cases. This study recommends upfront WBRT for wild-type patients, while it can be deferred but not omitted in the mutant population. Based on safety, a regimen of 36Gy in 18 fractions over 5 days per week is recommended. These findings support the integration of WBRT into LM management protocols with tailored approaches based on genetic mutations. Further prospective research is warranted to validate these results and further elucidate the role of WBRT in the management of NSCLC patients with leptomeningeal metastasis.