Characterization of Focal Leptomeningeal Extension in Patients with Brain Metastases: A Novel Entity

Abstract Background Classical leptomeningeal disease (cLMD) impacts the entire craniospinal axis, but isolated parenchymal metastases sometimes display focal leptomeningeal extension (fLME) without diffuse LMD elsewhere. We assessed whether patients with fLME can be managed with stereotactic radiation (SRS/SRT) as opposed to whole brain / craniospinal radiation without excess development of marginal recurrences or subsequent cLMD. Methods We identified 796 patients with 2,354 newly-diagnosed brain metastases (BrM) without cLMD at diagnosis managed at a tertiary center between 2007-2022. Each metastasis was assessed for fLME, defined as isolated leptomeningeal extension of an intact BrM without cytologic or radiographic evidence of cLMD. Multivariable Fine and Gray’s models were constructed for the primary outcomes of local recurrence and cLMD development. Results Among 796 patients, 138 (17.3%) displayed evidence of fLME, corresponding to 185 of 2,354 (7.9%) BrM. Patients with versus without fLME did not display excess local recurrences (1-year rate: 4.5% vs. 8.2%, respectively, p = 0.14; multivariable HR 0.56 [95% CI 0.30-1.07], p = 0.08), including in lesions managed with SRS/SRT (1-year rate: 4.4% vs. 4.9%, respectively; p = 0.63; multivariable HR 1.21 [95% CI 0.58-2.50], p = 0.61). The presence of fLME was not a significant predictor of subsequent cLMD (1-year rate: 5.2% vs 5.2%, p = 0.99; multivariable HR 0.87 [95% CI 0.44-1.71], p = 0.68), including following treatment with SRS/SRT (1-year rate: 6.2% vs. 4.1%, p = 0.83; multivariable HR 0.92 [95% CI 0.36-2.39], p = 0.87). Conclusions We describe a novel entity, fLME, which displays patterns of intracranial failure similar to parenchymal BrM. Stereotactic approaches may be viable in this population.