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.
Choroid plexus metastasis of a renal cell carcinoma—A case report and review of the literature
Authors:
Michael Youssef, Alexandra Larson, Kala F Schilter, Qian Nie, Honey V Reddi
Journal:
Neuro-Oncology Advances, Volume 7, Issue 1, January-December 2025, vdaf146.
Abstract:
This study presents a rare case of active renal cell carcinoma (RCC) presenting with a new CNS lesion that was diagnosed as a likely choroid plexus carcinoma using genomic testing. While a diagnosis of choroid plexus tumors typically leans heavily on histopathology, a biopsy is not always an option for this centrally located brain tumor type. An 80-year-old femalewith a history of RCC was found to have a tumor involving the choroid plexus, that was further evaluated via the Belay Summit test,1a novel molecular profiling test performed on cerebrospinal fluid (CSF). Summit detected a mutation in TP53, a tumor suppressor that is frequently altered in choroid plexus carcinoma (CPC). The case demonstrates the use of a less invasive approach to diagnose an unusual type of brain metastases.
CPC is a rare, malignant epithelial neoplasm of the choroid plexus, the tissue that lines the ventricles of the brain. CPC is most often observed as a primary cancer of the central nervous system (CNS), though there are several reports of metastasis to the choroid plexus from other primary lesions including prostate, thyroid, with kidney being the most common.2 CPC is a fast-growing tumor (WHO grade III) and the median survival rate of choroid plexus metastasis (CPM) from RCC is 2.8 years based on case reports.3 Diagnosis of CPM can be challenging as imaging is non-defining and tumor location can be unamendable to biopsy. When biopsy is an option, histological analysis is the current gold standard for diagnosis of CPM.4
Genomic profiling of CSF DNA has recently gained traction as a clinical tool to inform diagnosis, prognosis, and therapeutic options for CNS tumors. The sensitivity of this type of molecular diagnostic can be limited due to tumor heterogeneity and low variant allele fractions (VAFs) within the CSF. Summit uses targeted next-generation sequencing (NGS) of the Watson and Crick strands separately to detect variants at low VAF.5 The present case illustrates the clinical utility of genomic profiling of CSF-derived DNA to inform the diagnosis and management of CPM and reviews the literature regarding CPM molecular characteristics and therapeutic options.
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.