Abstract
Liquid biopsy is a rapidly emerging tool of precision oncology enabling minimally invasive molecular diagnostics and longitudinal monitoring of treatment response. For the clinical management of advanced stage lung cancer patients, detection and quantification of circulating tumor DNA (ctDNA) is now widely adopted into clinical practice. Still, interpretation of results and validation of ctDNA-based treatment decisions remain challenging. We report here our experience implementing liquid biopsies into the clinical management of lung cancer. We discuss advantages and limitations of distinct ctDNA assay techniques and highlight our approach to the analysis of recurrent molecular alterations found in lung cancer. Moreover, we report three exemplary clinical cases illustrating the complexity of interpreting liquid biopsy results in clinical practice. These cases underscore the potential and current limitations of liquid biopsy, focusing on the difficulty of interpreting discordant findings. In our view, despite all current limitations, the analysis of ctDNA in lung cancer patients is an essential and highly versatile complementary diagnostic tool for the clinical management of lung cancer patients in the era of precision oncology.
Highlights
State of the Art and Uses of Liquid Biopsy in Lung CancerLiquid biopsy is an increasingly relevant diagnostic tool in the management of patients with lung cancer [1]
This method is based on detection of circulating cancer cell markers in liquid samples, predominantly plasma. Such markers include circulating free DNA, circulating tumor DNA, exosomes, circulating tumor cells (CTCs), microRNAs, as well as antigens and antibodies derived from cancer cells [2]
Liquid biopsy is mainly used in lung cancer for patients with metastatic disease in order to monitor response or to detect emerging resistance mechanisms, while further uses such as early tumor detection are still under investigation [3,4]
Summary
Liquid biopsy is an increasingly relevant diagnostic tool in the management of patients with lung cancer [1]. This method is based on detection of circulating cancer cell markers in liquid samples, predominantly plasma. An increasing number of clinical trials in lung cancer have incorporated the use of liquid biopsy, in addition to tissue genomic testing. For the most frequently targeted genes in lung cancer, such as EGFR, a high concordance rate of more than 90% has been shown between alterations detected in liquid biopsy and matched tissue samples [7,8]. The analytical sensitivity is variable, depending on the implemented assay [9]. Our work reports a series of controversial clinical cases and reviews related literature data
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