Risk factors for Type I leptomeningeal metastasis derived from non-small cell lung cancer and the impact of treatment for brain metastases on its development

Abstract Background Preventing Type I leptomeningeal metastasis (LM) is critical when treating brain metastases (BMs). The aim of this study was to extract risk factors for Type I LM and to clarify the optimal treatment for BMs from the perspective of Type I LM prevention. Methods The clinical course of consecutive cases of BMs derived from non-small cell lung cancer (NSCLC) treated at our hospital was retrospectively evaluated. The relationship between clinicopathological factors, including molecular background, and Type I LM development was verified. In addition, the difference in the time to Type I LM because of treatment for BMs was evaluated to clarify the effectiveness of each treatment in preventing Type I LM. Results Of 784 patients with BMs, 44 exhibited Type I LM at the onset of BMs. Poor performance status (P < .0001) and mutated epidermal growth factor receptor (EGFR) gene (P = .004) were significant risk factors for Type I LM. Among the 740 patients without LMC at diagnosis, 85 developed Type I LM. Younger age (P = .011) and mutated EGFR (P < .0001) were risk factors for developing LMC after BMs. Osimertinib reduced the incidence of Type I LM (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.24-0.97) in EGFR-mutated cases. Immune checkpoint inhibitors (ICIs) showed a tendency to prolong the time to Type I LM (HR: 0.15; 95% CI: 0.02-1.11) in EGFR-wild-type cases. Conclusions Patients with EGFR-mutated NSCLC are prone to developing Type I LM. Osimertinib for EGFR-mutated cases and ICIs are expected to prevent Type I LM after the diagnosis of BMs.