Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC

Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase 2b, multicentre, single-arm, open-label study.

Introduction: Precision medicine is already a reality in oncology, since biomarker-driven therapies have clearly improved patient survival. Furthermore, a new, minimally invasive strategy termed 'liquid biopsy' (LB) has revolutionized the field by allowing comprehensive cancer genomic profiling through the analysis of circulating tumor DNA (ctDNA). However, its detection requires extremely sensitive and efficient technologies. A powerful molecular tool based on the principle of 'divide and conquer' has emerged to solve this problem. Thus, digital PCR (dPCR) allows absolute and accurate quantification of target molecules.Areas covered: In this review we will discuss the fundamentals of dPCR and the most common approaches used for partition of samples and quantification. The advantages and limitations of dPCR will be mentioned in the context of LB in oncology.Expert opinion: In our opinion, dPCR has proven to be one of the most sensitive methods available for LB analysis, albeit some aspects such as its capacity of multiplexing and protocol standardization still require further improvements. Furthermore, the increasing sensitivities and lower costs of next generation sequencing (NGS) methods position dPCR as a confirmatory and complementary technique for NGS results which will likely prove to be very useful for treatment monitoring and assessing minimal residual disease.

dPCR application in liquid biopsies: divide and conquer.

With advances in target therapy, molecular analysis of tumors is routinely required for treatment decisions in patients with advanced non-small cell lung cancer (NSCLC). Liquid biopsy refers to the sampling and analysis of circulating cell-free tumor DNA (ctDNA) in various body fluids, primarily blood. Because the technique is minimally invasive, liquid biopsies are the future in cancer management. Epidermal growth factor receptor (EGFR) ctDNA tests have been performed in routine clinical practice in advanced NSCLC patients to guide tyrosine kinase inhibitor treatment. In the near future, liquid biopsy will be a crucial prognostic, predictive, and diagnostic method in NSCLC. Here we present the current status and future perspectives of liquid biopsy in NSCLC.

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Current status and future perspectives of liquid biopsy in non-small cell lung cancer.

Isolation and analysis of circulating tumor DNA (ctDNA) have emerged as an effective and promising tool for genomic profiling in non-small cell lung cancer. Analysis of ctDNA can be particularly useful in situations where tissue biopsy is not safely obtainable due to poor physical condition or inaccessible tumor biopsy location. In addition to identifying oncogenic driver mutations which can be treated with targetable therapy in the treatment naive advanced non-small cell lung cancer (NSCLC) setting, ctDNA is being utilized in novel ways including monitoring during an advanced NSCLC patient’s treatment course (real-time monitoring), determining mechanisms of resistance and, lastly, as a tool to identify minimal residual disease in early-stage NSCLC. Recent research demonstrates that ctDNA testing can provide a useful adjunct to tissue genotyping in NSCLC. Utilization of ctDNA into routine clinical practice for NSCLC should be strongly considered.

The Role of Circulating Tumor DNA in Lung Cancer: Mutational Analysis, Diagnosis, and Surveillance Now and into the Future

1331PDetection of EGFR T790M in Asia-Pacific patients (pts) with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): Circulating tumour (ct) DNA analysis across 3 platforms

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1331PDetection of EGFR T790M in Asia-Pacific patients (pts) with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): Circulating tumour (ct) DNA analysis across 3 platforms