Serial Testing of Tumor-Derived DNA in Cerebrospinal Fluid (CSF) to Monitor Leptomeningeal Disease and Assess Therapeutic Response in Lung Cancer Metastasis to the Central Nervous System – A Case Report
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.
Cerebrospinal Fluid based liquid biopsy to inform diagnosis and management of Leptomeningeal Metastases in EGFR-Mutant Lung Cancer – A Case Report
Authors:
Michael Youssef, Vindhya Udhane, Alexandra Larson, Kala F Schilter, Qian Nie, Honey V Reddi
Journal:
European Society of Medicine, Vol 13 No 6 (2025): Vol.13, Issue 6, June 2025.
Abstract:
Leptomeningeal disease (LMD) in advanced non-small cell lung cancer (NSCLC) carries a poor prognosis and is challenging to diagnose without invasive biopsy. Traditional cerebrospinal fluid (CSF) cytology considered the gold standard in diagnosis is only 33% sensitive and often requires patients to undergo multiple lumbar punctures to receive an accurate diagnosis. Innovative technologies that utilize cerebrospinal fluid (CSF) based liquid biopsy have facilitated the detection of tumor derived DNA as a surrogate for cytology, at a much earlier time period than imaging would indicate a definitive diagnosis. This study presents a 47-year-old male diagnosed with non-small cell lung cancer who presented with an increase in intraocular pressure. Subsequent testing using the Belay Summit™ test revealed an EGFR T790M mutation in the CSF. Following the detection of this variant, the patient received treatment with osimertinib (Tagrisso®), which proved beneficial for his condition.