Recommendations for a practical implementation of circulating tumor DNA mutation testing in metastatic non-small-cell lung cancer

New article in ESMO Open

From: E. Heitzer, D. van den Broek, M. G. Denis, P. Hofman, M. Hubank, F. Mouliere, L. Paz-Ares, E. Schuuring, H. Sültmann, G. Vainer, E. Verstraaten, L. de Visser & D. Cortinovis

2022 April


Background: Liquid biopsy (LB) is a rapidly evolving diagnostic tool for precision oncology that has recently found its
way into routine practice as an adjunct to tissue biopsy (TB). The concept of LB refers to any tumor-derived
material, such as circulating tumor DNA (ctDNA) or circulating tumor cells that are detectable in blood. An LB is not
limited to the blood and may include other fluids such as cerebrospinal fluid, pleural effusion, and urine, among others.

Patients and methods: The objective of this paper, devised by international experts from various disciplines, is to
review current challenges as well as state-of-the-art applications of ctDNA mutation testing in metastatic non-smallcell
lung cancer (NSCLC). We consider pragmatic scenarios for the use of ctDNA from blood plasma to identify
actionable targets for therapy selection in NSCLCs.

Results: Clinical scenarios where ctDNA mutation testing may be implemented in clinical practice include complementary
tissue and LB testing to provide the full picture of patients’ actual predictive profiles to identify resistance mechanism (i.e.
secondary mutations), and ctDNA mutation testing to assist when a patient has a discordant clinical history and is
suspected of showing intertumor or intratumor heterogeneity. ctDNA mutation testing may provide interesting
insights into possible targets that may have been missed on the TB. Complementary ctDNA LB testing also provides
an option if the tumor location is hard to biopsy or if an insufficient sample was taken. These clinical use cases
highlight practical scenarios where ctDNA LB may be considered as a complementary tool to TB analysis.

Conclusions: Proper implementation of ctDNA LB testing in routine clinical practice is envisioned in the near future. As
the clinical evidence of utility expands, the use of LB alongside tissue sample analysis may occur in the patient cases
detailed here.

Full article here