Characterization of Focal Leptomeningeal Disease among Patients with Brain Metastases: A Novel Entity.

Classical leptomeningeal disease (cLMD) has historically been considered a global phenomenon impacting the entire craniospinal axis, but isolated parenchymal metastases sometimes display focal leptomeningeal extension into the surrounding leptomeninges without diffuse LMD elsewhere. Descriptions of this phenomenon are lacking, and the optimal management of such patients remains unclear. We hypothesized that, in order to spare such patients the deleterious outcomes of whole brain radiation (WBRT), patients with focal LMD (fLMD) could be successfully managed with stereotactic radiation (SRS/SRT) without excess development of adverse sequelae such marginal recurrences or subsequent cLMD. We identified 796 patients with 2,354 newly-diagnosed brain metastases (BrM) secondary to a solid tumor primary without cLMD at diagnosis managed at a tertiary cancer center between 2007-2022. Each metastasis was assessed for fLMD, which was defined as isolated focal leptomeningeal extension of an intact brain metastasis or single, isolated focal leptomeningeal enhancement without cytologic or radiographic evidence of cLMD (enhancement of cranial nerves or multifocal involvement of subarachnoid spaces including the cerebellar folia and supratentorial sulci). Multivariable Fine and Gray's models were constructed for the primary outcomes of local recurrence and development of cLMD. Among 796 patients, 138 (17.3%) displayed evidence of fLMD, corresponding to 185 of 2,354 (7.9%) BrM. Patients with versus without fLMD were not more likely to display distant intracranial failures post-initial treatment (56.8% vs. 58.3% at 1 year, respectively, p=0.78) or local recurrence (4.4% vs. 8.2% at 1 year, respectively, p=0.14), including in lesions managed with SRS/SRT (1-year local recurrence: 4.4% vs. 4.9%, respectively; p=0.63). On a per-patient level, the presence of fLMD was not a significant predictor of development of cLMD (1-year rate: 5.2% vs 5.2%, HR: 0.99 [0.52-1.89], p=0.97). We describe a novel pattern of LMD that has not been well-characterized in prior literature; fLMD appears to be a distinct oncologic entity whose pattern of intracranial failure resembles that of parenchymal BrM. Nationally, it may be that patients with fLMD are managed as having cLMD with routine use of WBRT. Our study suggests that despite the presence of enhancing disease in the leptomeningeal space, stereotactic approaches may be viable in this population given the lack of detectable excess risk of local recurrence or development of cLMD. [ABSTRACT FROM AUTHOR]