386P - Comparison between CSF circulating tumor DNA, cytology and imaging for diagnosis of leptomeningeal metastases in non-small cell lung cancer: A retrospective study

Background

Cerebrospinal fluid (CSF) cytology and MRI are commonly used for diagnosis of leptomeningeal metastasis (LM) but have limited sensitivity. The value of CSF circulating tumor DNA (ctDNA) in diagnosing LM remains underexplored. This study compared the detection rate of CSF cytology, CSF ctDNA and imaging in patients (pts) with NSCLC and symptoms suggestive of LM.

Methods

Pts with NSCLC who presented with LM symptoms, had CSF cytology and ctDNA analysis, and brain imaging (contrast CT/MRI) were retrospectively enrolled. Their demographics, radiological findings, CSF cytology and ctDNA, and treatment outcomes were collated. CtDNA was analyzed by droplet digital polymerase chain reaction (ddPCR) and regarded as positive if ≥ 2 copies of mutant DNA were present.

Results

A total of 38 pts were enrolled, of which 11 were excluded as a driver mutation was absent for ddPCR testing (median age 60, 19 female). Twenty five had EGFR mutations and 2 had KRAS mutations. Symptoms included confusion (52%), limb weakness (48%), headache (26%), vomiting (26%), cranial nerve palsy (22%), seizure (22%), unsteady gait (19%), dysphasia (11%) and neck pain (7%). All pts had elevated white cell and protein in CSF. Brain imaging, CSF cytology and ctDNA were positive in 13 (48%), 4 (15%), and 17 (63%) patients respectively. Seven pts (26%) with negative radiological and cytological findings had positive CSF ctDNA (Table), of which 4 had change in therapeutic decision based on ctDNA findings. CtDNA was negative in all 5 pts with confirmed alternative diagnoses (CNS infection, drug related confusion, cord compression, pituitary metastasis, paraneoplastic syndrome).

Number of subjects with cytology, imaging and cfDNA results

Conclusions

CtDNA was frequently detected in NSCLC pts with LM symptoms, including those with negative radiological and cytological findings. Further research should be done to study role of CSF ctDNA in diagnosis of LM.

Funding

Has not received any funding

Disclosure

All authors have declared no conflicts of interest.