Cerebrospinal fluid cell-free DNA as a liquid biopsy tool for detecting and monitoring genomic alterations in thalamic colorectal cancer metastases.

Background: Cerebrospinal fluid cell-free DNA (cfDNA) can detect and monitor leptomeningeal disease but has not been previously used to monitor parenchymal lesions. Methods: Herein, we report our initial experience with CSF cfDNA monitoring for 2 patients with colorectal cancer (CRC) metastases to the thalamus, causing obstructive hydrocephalus. Results: CSF samples were obtained during ventriculoperitoneal shunt placement, demonstrating high levels of cfDNA in both cases. Several genomic alterations detected in the cfDNA sequencing matched those in the tumor tissue biopsy. Follow-up CSF evaluations after subsequent therapy were used to help adjudicate pseudo-progression versus true progression. Conclusions: Neither patient developed leptomeningeal disease, demonstrating CSF's utility in evaluating solitary brain metastases in direct contact with a CSF compartment.