Liquid Biopsy for Biomarker Testing in Non-Small Cell Lung Cancer: A European Perspective

Abstract

The development of targeted therapies has improved survival rates for patients with advanced non-small cell lung cancer (NSCLC). However, tissue biopsy is unfeasible or inadequate in many patients, limiting biomarker testing and access to targeted therapies. The increasing numbers of established and emerging biomarkers with available targeted treatments highlights the challenges associated with sequential single-gene testing and limited tissue availability. Multiplex next-generation sequencing (NGS) offers an attractive alternative and represents a logical next step, and in cases where the tumour is inaccessible, tissue biopsy yields insufficient tumour content, or when the patient’s performance status does not allow a tissue biopsy, liquid biopsy can provide valuable material for molecular diagnosis. Here, we explore the role of liquid biopsy (i.e., circulating cell-free DNA analysis) in Europe. Liquid biopsies could be used as a complementary approach to increase rates of molecular diagnosis, with the ultimate aim of improving patient access to appropriate targeted therapies. Expert opinion is also provided on potential future applications of liquid biopsy in NSCLC, including for cancer prevention, detection of early stage and minimum residual disease, monitoring of response to therapy, selection of patients for immunotherapy, and monitoring of tumour evolution to enable optimal adaptation/combination of drug therapies.

Expert opinion on NSCLC small specimen biomarker testing — Part 2: Analysis, reporting, and quality assessment

“…Sequencing of plasma-circulating cell-free DNA (cfDNA) via liquid biopsy is a complementary approach to tissue-based biomarker testing, particularly when tissue samples are insufficient or unsuitable/inadequate for biomarker testing, or if re-biopsy cannot be performed safely [ 29 ]. In the authors’ experience, cfDNA sequencing analysis can be conducted using as little as 6 mL of peripheral whole blood stored at room temperature in ethylenediaminetetraacetic acid (EDTA) tubes.…”

Daily Practice Assessment of KRAS Status in NSCLC Patients: A New Challenge for the Thoracic Pathologist Is Right around the Corner

“…NGS approaches can routinely use a LB and thus provide access to the KRAS status and associated genomic alterations [ 15 , 190 , 214 , 215 , 216 , 217 ]. However, NGS with a LB is currently not often available in most laboratories, in Europe at least, and is set up for routine testing in only a few comprehensive cancer centers [ 191 , 215 , 218 ]. Therefore, many laboratories use targeted sequencing methods, such as RT-PCR or ddPCR [ 219 , 220 , 221 ].…”

“…However, there are still some gaps to fill in this setting in order to better use LBs in daily practice, but this method is certainly also pivotal to look for resistance mechanisms occurring under treatment, in particular with KRAS G12C inhibitors. In this setting, LBs definitively allows an easy monitoring of the disease [ 218 ].…”

Molecular Testing and Treatment Strategies in RET-Rearranged NSCLC Patients: Stay on Target to Look Forward

“…If a tissue sample is not available or exhausted, liquid biopsy may be considered [35][36][37][38]. Perhaps even more impactful is the ability for liquid biopsy to detect acquired RET rearrangements and/or mutations as resistance mechanisms alterations to targeted therapies in oncogene-addicted NSCLC [39,40].…”