Abstract
Simple SummaryScreening for genomic alterations in treatment-naïve non-small cell lung carcinoma (NSCLC) is mainly done by tissue biopsy (TB), an invasive approach. However, it may not be possible to obtain a TB, the patient does not consent to it and/or the extracted nucleic acids are of poor quantity and/or quality for further genomic analyses, so a liquid biopsy (LB) is the only option to detect molecular target(s) for first-line treatment in these patients. However, a LB at diagnosis is still not often used in clinical centers since a TB is currently the gold standard approach for histological diagnosis, assessment of the PD-L1 status on tumor cells and evaluation of the molecular alterations. A number of different approaches are already available for the assessment of genetic abnormalities with LB, but next-generation sequencing (NGS) is the most promising. This review provides an overview of the main studies currently using LB NGS at diagnosis for NSCLC. We discuss its advantages and limitations in comparison with a TB and the perspectives for the future.Recently, the liquid biopsy (LB), a non-invasive and easy to repeat approach, has started to compete with the tissue biopsy (TB) for detection of targets for administration of therapeutic strategies for patients with advanced stages of lung cancer at tumor progression. A LB at diagnosis of late stage non-small cell lung carcinoma (NSCLC) is also being performed. It may be asked if a LB can be complementary (according to the clinical presentation or systematics) or even an alternative to a TB for treatment-naïve advanced NSCLC patients. Nucleic acid analysis with a TB by next-generation sequencing (NGS) is gradually replacing targeted sequencing methods for assessment of genomic alterations in lung cancer patients with tumor progression, but also at baseline. However, LB is still not often used in daily practice for NGS. This review addresses different aspects relating to the use of LB for NGS at diagnosis in advanced NSCLC, including its advantages and limitations.
Highlights
Evaluation of the tumor mutation burden (TMB) with blood has been done at diagnosis for non-small cell lung cancers (NSCLC) and used as a predictive biomarker of immunotherapy [52,75]
One of the major interests in using a liquid biopsy (LB) for a next-generation sequencing (NGS) approach at diagnosis is to increase the number of patients included into clinical trials, since this noninvasive approach can allow better and faster selection of patients who may benefit from newly developed therapeutic molecules [80,81,82]
The following question could be asked: are we able to increase the level of extraction of nucleic acids from plasma with new technologies and/or new improvements in the pre-analytical phases? This is of significant importance when using a LB for NGS at diagnosis since according to the tumor and/or to the different metastatic sites, the quantity of circulating free DNA (cf-DNA) at baseline may not be sufficient in quantity for robust analysis of the different genomic alterations [112]
Summary
Genomic studies on patients with lung cancer have led to the discovery of prognostic factors and predictive biomarkers of therapeutic agents targeting genetic alterations [1,2,3,4,5,6]. Current therapeutic strategy in naïve-treated late stage NSCLC is based first on the presence of a genomic alteration actionable by a targeted therapy allowing to a personalized treatment (Figure 1A). According to the algorithms defined by a clinical laboratory and/or by the care organization, approach at diagnosis in late stage and molecular pathology laboratory and/or the by the care organization, the NGS approach. One active driver genomic alteration is detected on one of theshould currently ommended genes (B),Ifno immunotherapy alone or in combination with chemotherapy be recommended genesthe (B),patient no immunotherapy alonewith or ina combination with (C). This review addresses the main published studies into the use of a LB for NGS at diagnosis of late stage NSCLC and deals with the advantages and limitations of this approach, notably for future development in a routine clinical practice
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