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

Recent Pat Anticancer Drug Discov. 2021;16(1):108-116. doi: 10.2174/1574892815666201127114224.

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.

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.

Keywords: Cerebral-spinal fluid; leptomeningeal metastases; next generation sequencing; non-small cell lung cancer; osimertinib; tumor heterogeneity..

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Anaplastic Lymphoma Kinase / genetics
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride / administration & dosage
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Indoles / administration & dosage
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Male
  • Meningeal Neoplasms / diagnosis*
  • Meningeal Neoplasms / genetics
  • Meningeal Neoplasms / secondary
  • Mutation
  • Patents as Topic
  • Progression-Free Survival
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Quinolines / administration & dosage

Substances

  • Indoles
  • Proto-Oncogene Proteins
  • Quinolines
  • anlotinib
  • Erlotinib Hydrochloride
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • ROS1 protein, human