Serial testing of tumor-derived DNA in cerebrospinal fluid to monitor leptomeningeal disease and assess therapeutic response in lung cancer metastasis to the central nervous system

Authors:

George Bobustuc, Alexandra Larson, Vindhya Udane, Kala F. Schilter, Qian Nie, Honey V. Reddi

Journal:

Annals of Clinical Case Reports. 2025.

Abstract:

Metastatic Leptomeningeal disease (LMD) most often seen in lung cancer, poses unique diagnostic and therapeutic challenges due to limited sensitivity of standard cerebrospinal fluid (CSF) workup and genetic divergence from the primary tumor associated with resistance to central nervous system (CNS) penetrating treatments. Among CNS complications, LMD is associated with poor outcomes and average survival following diagnosis is three to six months. Routine methods for diagnosing LMD currently fall short, making it difficult to investigate therapeutic options for this type of disease progression. Sequencing of tumor-derived DNA (tDNA) found in CSF is emerging as a useful clinical tool to inform diagnosis and monitoring of CNS malignancies with the potential to guide treatment. The present case of metastatic lung cancer illustrates the use of serial CSF tDNA analysis via Belay Summit™, a novel liquid biopsy assay, to interrogate LMD driver mutations and guide therapeutic decisions alongside tumor profiling.