Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice

Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer

“…Selecting which techniques are most appropriate for clinical application in an individual practice setting should be the economic and technical resources available and local regulatory or reimbursement considerations, including the clinicopathological characteristics of the patient (e.g., morphological subtype, disease extent, treatments received, therapeutic options available). As the list of guideline-recommended genes to be tested in advanced NSCLC grows, 8,12,13 the use of broader NGS panels is destined to increase not only in tissue, where it is more cost effective than sequential single-gene testing, 32 but also in plasma.…”

“…Limitations of liquid biopsy include low ctDNA shedding tumors, notably in the presence of low total body tumor burden, low extrathoracic metastatic spread, or solitary involvement of sanctuary sites. 8,10 In addition, careful consideration should be given to nontumor mutations occurring through clonal hematopoiesis of indeterminate potential. As reported by Genovese et al, 44 such mutations were noted in ctDNA in 10% of individuals aged more than 65 years and in particular in TP53 and KRAS genes.…”

“…As previously described, although plasma cell-free DNA (cfDNA) refers to all circulating DNA and in its entirety is largely nonmalignant, even in patients with cancer, circulating tumor DNA (ctDNA) is that component of cell-free DNA which is tumor related. 8 From a clinical point of view, plasma ctDNA is the most extensively studied and widely adopted alternative to tissue tumor genotyping in solid tumors, including NSCLC, first entering clinical practice for detection of EGFR mutations in NSCLC. 9,10 Since the publication of the first IASLC liquid biopsy position paper 11 in 2018, several additional advances have been made in this field, leading to changes in the therapeutic decision-making algorithm for advanced NSCLC and prompting this 2021 update.…”

Detection of EGFR Mutations From Plasma of NSCLC Patients Using an Automatic Cartridge-Based PCR System

“…The introduction of liquid biopsies (LB) for the detection of Epidermal growth factor receptor (EGFR) mutations at diagnosis as well as at tumor progression during treatment to identify resistance to tyrosine kinase inhibitors (TKIs) treatment has revolutionized care of non-small-cell lung cancer (NSCLC) patients (Oellerich et al, 2019). Today, several assays using either qPCR (such as the Cobas or Therascreen assays) or Next Generation Sequencing (NGS) [such as the FoundationOne Liquid CDX (Foundation Medicine, Cambridge, United States) assay or the Guardant 360 assays (Guardant Health, Redwood City, United States)] are approved in the United States and many other countries for the detection of EGFR mutations and are used in routine clinical care (Aggarwal et al, 2021). However, while LB demonstrated an improved turn-around time (TAT) compared to tissue biopsy testing, the time needed to generate results in routine, notably when using NGS, still requires several days and is mainly limited by batching (the time until sufficient samples are gathered to start a batch of analysis).…”

Diagnostic and prognostic biomarkers in oligometastatic non-small cell lung cancer: a literature review

“…The main point is that the oligometastatic disease is currently described using clinical and morphological definitions rather than its biological features; data from prospective clinical trials in an early stage of disease, coupled with knowledge of genetic characteristic of lung tumors are warranted since they may further clarify diagnostic and prognostic features of this sub-group of disease (97). These efforts would lead to improving the possibility to eradicate the residual disease in these low burden tumoral settings, enhancing the definitive cure perspectives.…”