Next Generation Sequencing in the Management of Leptomeningeal Metastases of Non-Small Cell Lung Cancer: A Case Report and Literature Review

Abstract

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. Methods: We report a 39-year-old male NSCLC patient with negative molecular testing results in lung cancer tissue sample. The patient developed symptoms of LM with the negative CSF cytology and MRI, however the NGS analysis of CSF revealed a 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 on 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.

Clinicopathologic and genomic characterizations of brain metastases using a comprehensive genomic panel

“…Common potential therapeutic target genes such as BRCA1/2 , TP53 , and EGFRs were positive in our metastatic samples of breast cancer and renal cell tumors but not in primary tumors ( Figures 2A,C ). Novel mutations in these genes in brain metastatic tumors have been reported in previous studies, making the targeting of these genes a promising therapeutic approach to prevent or halt brain metastases in cancer patients ( 4 , 35 ).…”

“…In very few cases, these patients undergo an excisional biopsy (which can be curative of some signs and symptoms), or even CSF fluid aspiration ( 3 ). Such specimens allow the retrieval of the concentrated DNA of tumor cells via a cascade of steps needed for Next Generation Sequencing NGS and other helpful tumor analysis techniques ( 4 ).…”

A retrospective analysis of first-line PD-1 monoclonal antibodies treatment in patients with leptomeningeal metastasis from solid tumors

“…capecitabine, platinum, taxanes). Anti-angiogenesis drugs such as bevacizumab 23 and anlotinib 24 has been reported beneficial for patients with LM, and can be considered in combination with the PD-1 treatment. Several patients in our study showed sustained efficacy (> 3 months) after receiving both PD-1 mAb and anti-angiogenesis drugs; for example, patient no.…”