Review articleLeptomeningeal failure in patients with breast cancer receiving stereotactic radiosurgery for brain metastases

•Breast cancer patients have higher incidence of leptomeningeal failure (LMF) compared to other cancers.•Breast cancer patients have longer survival after diagnosis of LMF compared with other cancers.•Hormone receptor status and Her2 status did not predict for LMF.•Prior craniotomy and prior whole brain radiation therapy did not predict for LMF.

PurposePrior studies suggest a high incidence of leptomeningeal failure (LMF) in breast cancer metastatic to brain. This study examines breast cancer-specific variables affecting development of LMF and survival after Gamma-Knife Radiosurgery (GKS).MethodsBetween 2000-2010, 149 (breast) and 658 other-histology patients were treated with GKS. Hormone/HER2, age, local/distant brain failure, prior craniotomy, and prior whole-brain radiotherapy (WBRT) were assessed. Median follow-up was 54 months (range, 0-106). Serial MRI determined local and distant-brain failure and LMF. Statistical analysis with categorical/continuous data comparisons were done with Fisher's-exact, Wilcoxon rank-sum, log-rank tests, and Cox-Proportional Hazard models.ResultsOf 149 patients, 21 (14%) developed LMF (median time of 11.9 months). None of the following predicted for LMF: Her2-status (HR = 0.49, p = 0.16), hormone-receptor status (HR = 1.15, p = 0.79), prior craniotomy (HR = 1.58, p = 0.42), prior WBRT (HR = 1.36, p = 0.55). Non-significant factors between patients that did (n = 21) and did not (n = 106) develop LMF included neurologic death (p = 0.34) and median survival (8.6 vs 14.2 months, respectively). Breast patients who had distant-failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2, p = 0.005); including 15/65 (23%) patients who had distant-failure and developed LMF. Median time-to-death for patients experiencing LMF was 6.1 months (IQR 3.4-7.8) from onset of LMF. Median survival from LMF to death was much longer in breast (6.1 months) than in other (1.7 months) histologiesConclusionBreast cancer patients had a longer survival after diagnosis of LMF versus other histologies. Neither ER/PR/HER2 status, nor prior surgery or prior WBRT predicted for development of LMF in breast patients.