Abstract 620: Monitoring leptomeningeal metastasis treatment response using tumor cell free DNA from cerebral spinal fluid

Abstract Background: Cerebral Spinal Fluid (CSF) from brain tumor patients contains tumor cell free DNA (cfDNA), which may provide a non-invasive and routinely accessible method to obtain tumor genomic information. This “liquid biopsy” method would prove considerably less morbid compared to an open removal of tumor tissue from the brain. The opportunities of cfDNA in CSF have not been systematically studied in CSF, particularly in relation to how metastatic brain tumor cfDNA may respond to intrathecal therapy. Methods: A patient who presented with elevated intracranial pressure from metastatic melanoma to the leptomeninges underwent serial therapuetic lumbar punctures, approximately every two weeks over a period of three months. CSF was obtained through an informed consent, IRB approved protocol. The primary melanoma tumor was known to have a BRAF mutation 1799T>A (V600E). cfDNA was isolated from the CSF, and sequenced to confirm the presence of this same tumor-specific BRAF mutation. Droplet Digital PCR (ddPCR) quantified the mutant DNA amount and fraction in CSF. These results were compared to the clinical cytology results from the same sample. Results: Six time points were collected in 61 days. Tumor cfDNA was detectable in the first five time points. Mutant DNA fraction decreased from 53% to almost zero. The total amount of mutant DNA decreased from 220 copies per ml of CSF to 4 copies per ml of CSF. This result was concordant with the patient's clinical response to therapy. Conclusion: Tumor cfDNA was found in CSF from a cancer patient with leptomeningeal metastases. Both the mutant fraction and total copies of mutant DNA corresponded with the patient's response to systemic therapy. This non-invasive method may provide a powerful tool for identifying and monitoring the genetic fingerprint of brain metastases. Citation Format: Melanie Hayden Gephart. Monitoring leptomeningeal metastasis treatment response using tumor cell free DNA from cerebral spinal fluid. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 620. doi:10.1158/1538-7445.AM2015-620