The infratentorial localization of brain metastases in non-small cell lung cancer indicates poorer prognosis and a distinct selection of radiotherapy.

Infratentorial brain metastases (BMs) are life-threatening because of the unique anatomical features and physiological functions of the posterior cranial fossa. However, the comparative prognosis of infratentorial BM and supratentorial BM remains poorly understood. We conducted a matching comparison of the prognosis between non-small cell lung cancer (NSCLC) patients with and without infratentorial BM and analyzed prognostic factors, including the radiotherapy (RT) method. 392 NSCLC patients who underwent brain RT from July 2010 until June 2023 were analyzed. After 1:1 propensity matching, we compared 115 patients with only supratentorial BMs (supraT-alone group) and 115 patients with infratentorial ± supratentorial BMs (infraT ± supraT group). We assessed intracranial control and overall survival (OS) using Kaplan-Meier and Cox regression. There was no statistical difference for extracranial progression-free survival (PFS), intracranial local PFS, or distant PFS. The supraT-alone group had significantly better OS (median: 35.3 vs. 24.2 months, p=0.021). The supraT-alone group in the multivariate analysis had BM resection (p=0.031), targeted therapy (p<0.001), and immune therapy (p=0.006) associated with improved OS. The infraT ± supraT group had RT method (p=0.002), ≤60 years of age (p=0.002), targeted therapy (p=0.017), and number of extracranial metastases (p<0.001) when reporting OS. We confirmed that WBRT+boost and SRT improved OS compared to WBRT alone. There was no statistical difference in OS for WBRT+boost and SRT. The overall grade 3-4 acute toxicities were similar for both groups. Our study suggests that infratentorial BMs in NSCLC lead to worse OS. However, local high-dose RT strategies (SRT or WBRT+boost) may confer survival benefits to patients who present with infratentorial involvement.