Repeat Next-Generation Sequencing (15-Gene Panel) in Unifocal, Synchronous, and Metachronous Non-Small-Cell Lung...

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Next-generation sequencing (NGS) is standard for identifying actionable genomic alterations (AGAs) in advanced non-squamous non-small-cell lung cancer (NSCLC).
• The clinical utility of repeated NGS testing on multiple synchronous or metachronous NSCLC tumors remains incompletely understood.

Purpose of the Study:

• To evaluate the therapeutic implications of repeated NGS testing on synchronous and metachronous NSCLC tumors.
• To assess the frequency and nature of genomic alterations in multiple NSCLC tumor samples from the same patient.

Main Methods:

• A retrospective analysis of NSCLC samples from 38 patients with multiple NGS results (82 samples total) tested between February 2017 and October 2020.
• Utilized a targeted 15-gene NGS panel (TruSight Tumor 15, Illumina) for reflex testing.
• Categorized samples into single unifocal, synchronous, and metachronous tumors.

Main Results:

• Genomic alterations in key genes (EGFR, KRAS, PI3KCA, TP53) varied in 58% of patients' samples.
• No changes were observed in single unifocal tumors, but alterations were detected in 60% of synchronous and 71% of metachronous tumors.
• Significant differences in overall survival were noted between synchronous separate primaries and metastases. 26% of patients showed AGA differences between samples.

Conclusions:

• Repeat NGS testing of synchronous and metachronous NSCLC tumors frequently identifies differing variants, potentially indicating separate primary tumors, metastasis heterogeneity, or clonal evolution.
• These findings suggest that comprehensive NGS profiling of multiple tumors can improve the identification of therapeutic targets.
• NGS testing of multiple tumors may enhance treatment decisions for NSCLC patients.