Abstract

Abstract Leptomeningeal Carcinomatosis (LMC) is a rare complication of ovarian cancer and there is no established first-line therapy. Treatment of LMC in general can include intrathecal chemotherapy and radiation as well as relevant systemic therapies with CNS activity. We employed the commercially available Biocept CNSide™ assay to detect, quantify, and molecularly characterize tumor cells in the cerebrospinal fluid (CSF). We report a 66-year-old female who was initially diagnosed with stage 3C serous ovarian carcinoma who developed brain metastases one year later, managed with resection and stereotactic radiosurgery. Serum CA-125 continued to rise despite local therapy and subsequent MRI demonstrated leptomeningeal enhancement of bilateral internal auditory canals and the cauda equine concerning for LMC. Exam was notable for a left cranial nerve VII palsy and gait instability. Lumbar puncture with CNSide quantified a baseline tumor cell count and identified HER2 amplification on tumor cells. She began intrathecal methotrexate (IT MTX), followed by decline in both CSF tumor cell count and serum CA-125. She demonstrated clinical benefit with improved imbalance. Over time, she experienced nausea and vomiting with IT MTX and was switched to anti-HER2 therapy with off-label lapatinib and she enjoyed improved quality of life. Notably, tumor cells lost HER2 amplification, raising possibility of clone selection. She later experienced focal progression of LMC and before other therapy could be offered, she succumbed to illness approximately one year from the initial radiographic finding of leptomeningeal enhancement, exceeding the average survival for LMC.Here we demonstrate the activity of IT MTX in ovarian LMC as well as the utility of serial CSF tumor quantification for disease monitoring in conjunction with imaging and the physical exam. Further studies are warranted to evaluate LMC therapy in a prospective setting as well as the possibility of clone selection in the CNS with targeted therapy.

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