Prognostic Utility of Targeted Circulating Cell-Free DNA versus Formalin-Fixed Paraffin-Embedded DNA Mutation Analysis for Advanced Lung Cancer

Tamm Madli,Kivistik Paula Ann,Jaal Jana,Annilo Tarmo,Nurm Miriam,Oselin Kersti,Keerma Katrin,Kals Mart,Saare Margot,Tõnisson Neeme

doi:10.23937/2643-4563/1710033

Abstract

Cancer burden is a globally growing problem. Early diagnosis and targeted treatment decrease patients' death rate, pain, and treatment expenses. Liquid biopsy can be used for early cancer detection, treatment selection, and progression and treatment response monitoring. We evaluated the performance of circulating cell-free DNA (cfDNA) and formalin-fixed paraffin-embedded (FFPE) tissue DNA analyses using a commonly employed targeted therapeutic pathway in predicting the outcomes of patients with lung cancer, a common cancer with a generally poor prognosis.

Highlights

The usefulness of the analysis of circulating cell-free Formalin-Fixed Paraffin-Embedded tissue DNA (DNA) from blood (“liquid biopsy”) for cancer diagnosis, monitoring, and treatment selection has been firmly established [1,2,3,4]
Our key finding was that cell-free DNA (cfDNA) analysis performs better than formalin-fixed paraffin-embedded (FFPE) tissue analysis in the prediction of patients’ overall survival (OS) and disease progression
AIH: Amplicon Indel Hunter; cfDNA T1: cell-free DNA collected at enrollment; cfDNA T2: cell-free DNA collected after cancer progression; CI: Confidence Interval; FFPE DNA: Formalin-Fixed Paraffin-Embedded tissue DNA; HR: Hazard Ratio; Indel: Insertion and Deletion; next-generation sequencing (NGS): NextGeneration Sequencing; non-small cell lung cancer (NSCLC): Non-Small Cell Lung Cancer; OS: Overall Survival; OS2: Overall Survival after cancer progression; tyrosine kinase inhibitor (TKI): Tyrosine Kinase Inhibitor; VAF: Variant Allele Frequency, a fraction of cfDNA that harbors a specific alteration

Summary

Introduction

The usefulness of the analysis of circulating cell-free DNA (cfDNA) from blood (“liquid biopsy”) for cancer diagnosis, monitoring, and treatment selection has been firmly established [1,2,3,4]. CfDNA analysis has been used successfully to identify actionable mutations in the epidermal growth factor receptor (EGFR) gene and other genes for the targeted treatment of non-small cell lung cancer (NSCLC) [1315]. Despite these potential advantages, the analysis of DNA from formalin-fixed paraffin-embedded solid-tumor tissue samples (FFPE DNA) remains much more common in the clinical setting. We evaluated the performance of circulating cell-free DNA (cfDNA) and formalin-fixed paraffin-embedded (FFPE) tissue DNA analyses using a commonly employed targeted therapeutic pathway in predicting the outcomes of patients with lung cancer, a common cancer with a generally poor prognosis

Methods

Results

Discussion

Conclusion