Background: Diagnosis of Leptomeningeal Metastases (LM) from Non-Small Cell
Lung Cancer (NSCLC) is usually based on clinical symptoms, Cerebral-Spinal Fluid (CSF) cytology,
and neuro-imaging. However, early diagnosis of LM in NSCLC is challenging due to the low
sensitivity of these approaches. The Next-Generation Sequencing (NGS) using CSF could help improve
the diagnosis of LM and guide its treatment options.
Case Presentation: We report a 39-year-old male NSCLC patient with negative molecular testing
results in the lung cancer tissue sample. The patient developed symptoms of LM with the negative
CSF cytology and MRI; however, the NGS analysis of CSF revealed an EGFR exon 19 del mutation.
The patient attained 6 months of Progression-Free Survival (PFS) by treating with erlotinib
and anlotinib before the neurological symptoms appeared again. EGFR Thr790Met was positive in
the CSF but negative in his plasma. The patient was then treated with osimertinib therapy and the
response was maintained for more than 1 year.
Results & Discussion: This case is the first study reporting the clinical benefit of using the combination
of erlotinib and anlotinib for the treatment of LM with the EGFR 19 del, osimertinib with
EGFR T790M mutation in CSF, but negative gene mutation in the blood or lung tumor biopsy specimens.
Our results support that genetic analysis should be performed with CSF samples in all cases
of suspected LM when the results of testing for EGFR/ALK/ROS1 mutation in blood samples or tumor
biopsy specimens are negative, as these patients could benefit from treatment of TKIs in a
poor prognostic setting.
Conclusion: In parallel to current patents, NGS could be applied as a novel strategy in the managing
of NSCLC patients with LM.