AI Article Synopsis

  • Transformation to small cell lung cancer (SCLC) is a resistance mechanism seen in lung adenocarcinoma (LUAD) patients treated with tyrosine kinase inhibitors, particularly in those with leptomeningeal metastases (LM).
  • In a study of 237 non-small cell lung cancer (NSCLC) patients who had lumbar punctures, SCLC cells were identified in the cerebrospinal fluid (CSF) of 8 patients, all of whom showed resistance to targeted therapies.
  • The results suggest that SCLC transformation in CSF can be detected using cytological evaluation and ctDNA analysis, providing valuable insights into treatment resistance mechanisms, with this transformation correlating with reduced survival rates.

Article Abstract

Introduction: Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in -mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce.

Methods: We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing.

Results: Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the mutation, including four patients with and three patients with mutation. Another patient harbored insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that and mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0-17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2-29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0-5.9 mo).

Conclusions: SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399576PMC
http://dx.doi.org/10.1016/j.jtocrr.2024.100704DOI Listing

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