Next-Generation Sequencing with Liquid Biopsies from Treatment-Naïve Non-Small Cell Lung Carcinoma Patients

Abstract

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.

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

“…In this regard, many targeted sequencing methods, allowing for results in a short amount of time from cytological or blood specimens, have been used in many hospitals [64][65][66]. More recently, NGS methods have developed from these specimens, notably for EGFR status evaluation at baseline [67]. NGS approaches are of strong interest in order to detect different genomic alterations associated in genes other than EGFR, which may explain, at least partially, some primary resistance of TKIs targeting EGFR mutations [68].…”

“…Moreover, it is crucial to detect an ALK fusion if a patient needs to be treated via immunotherapy due to an association of nonefficacy and of treatment toxicity of the immune checkpoint inhibitors (ICIs) in cases of ALK-positive tumors [73]. ALK status at baseline can be assessed not only in tissue biopsy but also in cytological specimens and in blood samples, notably on circulating free nucleic acids [47,67,74]. However, different studies demonstrated that the evaluation of ALK status can be made in circulating tumor cells at baseline.…”

“…ALK status can be assessed in cytological samples using ALK immunocytochemistry and ALK fluorescence in situ hybridization (FISH), which can be used at the same time for ROS1 status evaluation [75][76][77][78][79]. At diagnosis, the detection of ALK fusion in plasma is be possible, but the sensitivity of this detection in comparison with matched tissue samples is variable according to the different studies [46,67,74]. RNA NGS can be used from cytological samples for ALK status assessment and identification of the different partners of ALK fusion [75,80].…”

“…BRAFV600 mutations can be detectable in tissue biopsy and in cytological samples using RT-PCR and V600E IHC/ICC approaches or via NGS [88,89]. In plasma samples, BRAFV600 mutations can be detectable via RT-PCR or NGS [67,90].…”

“…Aside from the use of cytological materials, liquid biopsies can detect a molecular target when a tissue biopsy or a cytological sample cannot be obtained from an inaccessible tumor or in the case of an insufficient number of carcinoma cells [328][329][330]. However, liquid biopsies at baseline have their limits, in particular in the case of a low amount of circulating DNA from small-sized tumors or in the case of certain metastatic sites (like the brain) that release very little DNA material into the blood [67,331]. Thus, the sensitivity of the different tests for detection of genomic alterations, in particular fusions and amplifications, is globally lower than tests performed with tissue or cells [155].…”