# The Impact on the Therapeutic Decision of Massive Gene Sequencing (NGS) in Plasma from Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)

## TL;DR

This study shows that analyzing DNA in the blood of advanced lung cancer patients can help guide treatment choices and may improve outcomes.

## Contribution

The study demonstrates the clinical utility of plasma-based NGS in identifying actionable mutations for targeted therapy in advanced NSCLC patients.

## Key findings

- Plasma NGS identified actionable genomic alterations in 10.25% of patients, enabling targeted therapy initiation.
- The concordance rate between tissue and plasma NGS for EGFR alterations was 57.02%.
- Patients receiving NGS-informed therapy showed numerically improved overall survival, though not statistically significant.

## Abstract

Lung cancer is one of the most frequent and lethal malignancies worldwide, with most cases diagnosed at an advanced stage. Identifying specific genetic alterations is crucial to guide targeted therapies, but obtaining tissue samples is often challenging in routine practice. Liquid biopsy using next-generation sequencing (NGS) enables the detection of tumor-derived DNA circulating in the blood, allowing a non-invasive and comprehensive genomic characterization. In this real-world study, we analyzed plasma samples from patients with advanced non-small cell lung cancer to evaluate the clinical utility of plasma-based NGS for therapeutic decision-making. Our findings show that ctDNA profiling can identify patients eligible for targeted therapies and provides complementary information to tissue analysis. This approach supports the integration of liquid biopsy into routine clinical management of lung cancer, with the potential to improve access to personalized treatment and patient outcomes.

Background: The use of next-generation sequencing (NGS) in liquid biopsy allows for a comprehensive molecular assessment of circulating tumor DNA (ctDNA) in patients with advanced malignancies. This approach facilitates the detection of clinically relevant mutations linked to prognosis and enables a personalized therapeutic strategy. The objective of this study was to assess the mutational landscape of ctDNA using NGS in patients with advanced non-small cell lung cancer (NSCLC), examine its relationship with clinical and molecular variables, and explore its association with overall survival (OS). Methods: We performed a retrospective observational study including 78 individuals with metastatic NSCLC treated at Arnau de Vilanova Hospital between 2019 and 2021. Plasma samples were analyzed using the AVENIO NGS platform, which targets the exons of 77 genes. Statistical analyses were conducted using SPSS version 25, applying a 95% confidence level. Results: A total of 143 genomic alterations were identified in the study population. NGS-directed therapies were initiated in eight patients (10.25%), including EGFR (n = 5), KRAS (n = 2), and BRCA1 (n = 1). The concordance rate between tissue and plasma NGS for EGFR alterations was 57.02%, with mutation frequencies of 11.4% in tissue and 6.5% in plasma. No BRAF mutations were detected by plasma analysis, despite being present in 4.3% of tissue samples. Patients receiving NGS-informed targeted therapy showed a numerically improved OS compared to those who did not, although this difference did not reach statistical significance (p = 0.34). Conclusions: Liquid biopsy based on NGS represents a reliable and minimally invasive approach for the genomic characterization of advanced NSCLC. In this real-world cohort, ctDNA profiling enabled the identification of actionable alterations in a relevant proportion of patients, supporting its integration into routine clinical practice for therapeutic decision-making.