Cells (Jul 2021)

Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic

  • Maria Gabriela O. Fernandes,
  • Catarina Sousa,
  • Joana Pereira Reis,
  • Natália Cruz-Martins,
  • Conceição Souto Moura,
  • Susana Guimarães,
  • Ana Justino,
  • Maria João Pina,
  • Adriana Magalhães,
  • Henrique Queiroga,
  • José Agostinho Marques,
  • José Carlos Machado,
  • José Luís Costa,
  • Venceslau Hespanhol

DOI
https://doi.org/10.3390/cells10081912
Journal volume & issue
Vol. 10, no. 8
p. 1912

Abstract

Read online

Introduction: Cell-free DNA (cfDNA) analysis offers a non-invasive method to identify sensitising and resistance mutations in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Next-generation sequencing (NGS) of circulating free DNA (cfDNA) is a valuable tool for mutations detection and disease′s clonal monitoring. Material and methods: An amplicon-based targeted gene NGS panel was used to analyse 101 plasma samples of advanced non-small cell lung cancer (NSCLC) patients with known oncogenic mutations, mostly EGFR mutations, serially collected at different clinically relevant time points of the disease. Results: The variant allelic frequency (VAF) monitoring in consecutive plasma samples demonstrated different molecular response and progression patterns. The decrease in or the clearance of the mutant alleles was associated with response and the increase in or the emergence of novel alterations with progression. At the best response, the median VAF was 0% (0.0% to 3.62%), lower than that at baseline, with a median of 0.53% (0.0% to 9.9%) (p = 0.004). At progression, the VAF was significantly higher (median 4.67; range: 0.0–36.9%) than that observed at the best response (p = 0.001) and baseline (p = 0.006). These variations anticipated radiographic changes in most cases, with a median time of 0.86 months. Overall, the VAF evolution of different oncogenic mutations predicts clinical outcomes. Conclusion: The targeted NGS of circulating tumour DNA (ctDNA) has clinical utility to monitor treatment response in patients with advanced lung adenocarcinoma.

Keywords