BSLD-09 Cerebral Spinal Fluid (CSF) Predictors of Developing Disseminated Necrotizing Leukoencephalopathy in Leptomeningeal Carcinomatosis (LMC): A Single Institutional Review

Abstract

BACKGROUND: LMC is a rapidly fatal rare complication of systemic cancer with metastasis to the leptomeninges. Despite improved diagnostic capabilities, treatment options remain few and most clinical trials exclude LMC patient participation. Whole brain radiation therapy (WBRT) and intrathecal (IT) chemotherapy are commonly employed and there is growing evidence for systemic therapies that cross the blood brain barrier. However, complications related to treatment can confound response assessment, leading to early discontinuation of effective therapies. One such poorly understood complication is the development of disseminated necrotizing leukoencephalopathy (DNL). DNL is a, typically self-limited, rare treatment-related radiographic finding variably associated with clinical decline and often misdiagnosed as progression or infection. DNL has been reported in patients exposed to IT chemotherapy and CNS irradiation. Our lab published improved LMC control with extended survival after standardization of Ommaya clinic IT treatment regimens, although with increased incidence of DNL. METHODS: We retrospectively analyzed patients with LMC treated with IT chemotherapy after WBRT between 2017 – 2020. We reviewed sequential brain imaging over the treatment course to determine if there were predictive CSF markers associated with the development of DNL. RESULTS: Of 41 patients evaluated, 24% (n=10) developed DNL at a median 24-weeks after start of IT chemotherapy and WBRT. Of the patients with radiographically assessed DNL, 80% (n=8) experienced elevated CSF protein and 40% (n=4) had elevated white blood cells within 8-weeks prior to radiographic determination of DNL. Cytology remained benign and glucose was not significantly changed prior to DNL development. CONCLUSION: Given the poor outcome of LMC, there is a need for treatment standardization and better understanding of treatment-associated radiographic changes. Evaluation of CSF markers to predict impending development of DNL in this treatment population might limit radiographic misdiagnoses and patient clinical decline as well as offer a potential window of opportunity for treatment de-escalation.