Implementing ctDNA Analysis in the Clinic: Challenges and Opportunities in Non-Small Cell Lung Cancer

Abstract

Tumor genomic profiling has a dramatic impact on the selection of targeted treatment and for the identification of resistance mechanisms at the time of progression. Solid tissue biopsies are sometimes challenging, and liquid biopsies are used as a non-invasive alternative when tissue is limiting. The clinical relevance of tumor genotyping through analysis of ctDNA is now widely recognized at all steps of the clinical evaluation process in metastatic non-small cell lung cancer (NSCLC) patients. ctDNA analysis through liquid biopsy has recently gained increasing attention as well in the management of early and locally advanced, not oncogene-addicted, NSCLC. Its potential applications in early disease detection and the response evaluation to radical treatments are promising. The aim of this review is to summarize the landscape of liquid biopsies in clinical practice and also to provide an overview of the potential perspectives of development focusing on early detection and screening, the assessment of minimal residual disease, and its potential role in predicting response to immunotherapy. In addition to available studies demonstrating the clinical relevance of liquid biopsies, there is a need for standardization and well-designed clinical trials to demonstrate its clinical utility.

Current status of ctDNA in precision oncology for hepatocellular carcinoma

“…Conventional approaches involve complicated sample preparation steps, including sample collection, matrix selection, conservation, thawing, sample processing, and ctDNA extraction. The interval between venipuncture and sample processing should be short, while a specialized blood collection tube containing a preservative, such as Streck (Streck, Omaha, NE) or PAXgene (PreAnalytiX GmbH, Hombrechtikon Switzerland) blood collection tubes, make samples stable [15][16][17]. Furthermore, a storage temperature up to − 80°C is required and < 3 freeze and thaw cycles are recommended [18].…”

The Practicality of the Use of Liquid Biopsy in Early Diagnosis and Treatment Monitoring of Oral Cancer in Resource-Limited Settings

“…Similar to the pre-analytical stage, sample processing is a consolidated effort of many laboratory aspects aiming to produce high-quality clinical data. Easily identifiable is a varying range of methodologies including reagents and applied technologies (including different instruments) used by separate laboratories to achieve the same goal of generating high-quality clinical data [ 74 ]. Different laboratories may use different ‘clinically validated’ consumables yet with differing clinical results, particularly when different commercial suppliers are used for supposedly similar clinical assessments [ 75 ].…”

Current Technologies for RNA-Directed Liquid Diagnostics

“…For instance, in 2017, the average cost for solid biopsy for lung cancer was $8869, while the total cost for a patient reached $37,745 because of 20% complications from needle biopsies [132,143]. Moreover, a transthoracic needle biopsy under computer tomography control may cost around $500, which is more than enough for a blood test as the current cost of single ct-DNA mutant detection with digital PCR is approximately $100 [99,133]. In addition, researchers from Johns Hopkins University have developed a multi-analysis blood assay that currently costs less than $500 [133,134].…”