Stage (stratigraphy)

Profiling (computer programming)

Prenatal diagnosis

Clinical trial

Lung cancer

Liquid biopsy

Fetus

Disease

Bioinformatics

Biology

Operating system

Cancer

Computer science

DNA sequencing

Circulating tumor DNA

Computational biology

Internal medicine

Cell-free fetal DNA

Leukemia

Minimal residual disease

Oncology

Paleontology

Pregnancy

Genetics

Medicine

Nature Reviews Clinical Oncology

Circulating tumour DNA (ctDNA) refers to the fraction of cell-free DNA in a patient’s blood that originates from a tumour. Advances in DNA sequencing technologies and our understanding of the molecular biology of tumours have resulted in increased interest in exploiting ctDNA as a tool to facilitate earlier detection of cancer and thereby improve therapeutic outcomes by enabling early intervention. ctDNA analysis might also have utility in the adjuvant therapeutic setting by enabling the identification of patients at a high risk of disease recurrence on the basis of the detection of post-surgical minimal (or molecular) residual disease (MRD). This approach could provide the capability to adapt clinical trials in the adjuvant setting in order to optimize risk stratification, and we argue that this objective is achievable with current technologies. Herein, we evaluate contemporary next-generation sequencing (NGS) approaches to ctDNA detection with a focus on non-small-cell lung cancer. We explain the technical and analytical challenges to low-frequency mutation detection using NGS-based ctDNA profiling and evaluate the feasibility of ctDNA profiling in both screening and MRD assessment contexts. Liquid biopsy approaches hold great promise in early cancer diagnosis or minimal residual disease monitoring for cancer recurrence. Herein, the authors evaluate contemporary next-generation sequencing approaches to circulating tumour DNA detection in these contexts, with a focus on studies in patients with non-small-cell lung cancer. They discuss the feasibility of introducing these strategies into the clinic, highlighting the technical and analytical challenges, as well as possible solutions.

Early stage NSCLC — challenges to implementing ctDNA-based screening and MRD detection