11. ASSOCIATION OF TUMOR EXPOSURE TO CEREBROSPINAL FLUID SPACES TO LEPTOMENINGEAL DISEASE IN PATIENTS WITH BRAIN METASTASES

BACKGROUND: Development of leptomeningeal disease in patients with brain metastases is associated with extremely poor survival. Identification of the underlying pathogenesis of leptomeningeal disease is unknown. METHODS: This retrospective case control study included consecutive adult patients with at least one cerebral metastasis from a known extracranial primary solid malignancy and at least 3 month follow up (n=366). Patients were treated with radiotherapy with or without surgical resection and primary outcome was development of leptomeningeal disease. RESULTS: The overall rate of leptomeningeal disease was 15.0%. Rates of development of leptomeningeal disease correlated with the presence of a dural based lesion (65.7% vs. 9.7%; P<0.0001), intraventricular lesion (29.4% vs. 14.3%; P=0.0897), and with dural based lesions with sulcal or cortical enhancement (100% vs. 12.9%; P<0.0001). Rates of developing leptomeningeal disease were not independently associated with surgical resection (17.2% vs. 14.2%; P=0.4859), however did occur significantly more often with piecemeal, as opposed to en bloc, resection (31.3% vs. 8.1%; P=0.0138) or when the ventricle was entered (61.5% vs. 18.9%; P<0.0001). CONCLUSIONS: Metastases that are in contact with cerebrospinal fluid spaces are associated with a higher rate of subsequent leptomeningeal disease, with or without surgical resection. Future studies should investigate the use of neoadjuvant radiation, whole brain radiation therapy or adherence to strict surgical technique in high risk brain metastasis patients to mitigate this probability.