# Feasibility of a ctDNA multigenic panel for non‐small‐cell lung cancer early detection and disease surveillance

## TL;DR

This study shows that analyzing ctDNA with a multigene panel can detect lung cancer mutations, aiding early detection and treatment decisions.

## Contribution

The study demonstrates the feasibility of a commercial ctDNA multigene panel for actionable mutation detection in Brazilian NSCLC patients.

## Key findings

- TP53, KRAS, and EGFR were the most frequently mutated genes in NSCLC patients.
- EGFR p.T790M resistance mutations were detected in a previously treated patient.
- TP53 p.R248Q was identified in an asymptomatic patient before diagnosis.

## Abstract

The detection of actionable mutations in liquid biopsies is a crucial tool for precision oncology in patients with non‐small‐cell lung cancer (NSCLC). We evaluated actionable alterations using a multigene panel in circulating tumor DNA (ctDNA) from Brazilian NSCLC patients. We analyzed 32 samples from 30 patients with NSCLC, including four samples from a lung cancer screening program. ctDNA isolation and library preparation were performed using the Oncomine Lung cfDNA Assay, which covers 11 actionable genes, and sequenced on an Ion S5 Sequencer. The IonReporter 5.20 software was used for variant calling. Median read coverage reached 80 967, with a detection limit of 0.1%. TP53 (40.6%), KRAS (28.1%), and EGFR (12.5%) were the most frequently mutated genes, particularly in patients who had previously received treatment. BRAF, MAP2K1, PIK3CA, and ALK mutations were observed at lower frequencies (6.2%, 3.1%, 3.1%, and 3.1%, respectively). The EGFR p.T790M mutations related to resistance were identified in a patient who had been previously treated, and the TP53 p.R248Q mutation was discovered in an asymptomatic patient before diagnosis. No variants were observed in NRAS, ROS1, and MET genes. Our data showed that this commercial NGS panel could detect actionable mutations, enabling early detection, treatment monitoring, and disease surveillance.

Plasma‐based detection of actionable mutations is a promising approach in lung cancer management. Analysis of ctDNA with a multigene NGS panel identified TP53, KRAS, and EGFR as the most frequently altered, with TP53 and KRAS in treatment‐naïve patients and TP53 and EGFR in previously treated patients. These findings highlight liquid biopsy as a feasible strategy enabling faster clinical decision‐making.