Circulating tumour DNA analysis for early detection of lung cancer: a systematic review

Background: Circulating tumor DNA (ctDNA) analysis has been applied in cancer diagnostics including lung cancer. Specifically for the early detection purpose, various modalities of ctDNA analysis have demonstrated their potentials. Such analyses have showed diverse performance across different studies.

Methods: We performed a systematic review of original studies published before 1 January 2023. Studies that evaluated ctDNA alone and in combination with other biomarkers for early detection of lung cancer were included.

Results: The systematic review analysis included 56 original studies that were aimed for early detection of lung cancer. There were 39 studies for lung cancer only and 17 for pan-cancer early detection. Cancer and control cases included were heterogenous across studies. Different molecular features of ctDNA have been evaluated, including 7 studies on cell-free DNA concentration, 17 on mutation, 29 on methylation, 5 on hydroxymethylation and 8 on fragmentation patterns. Among these 56 studies, 17 have utilised different combinations of the above-mentioned ctDNA features and/or circulation protein markers. For all the modalities, lower sensitivities were reported for the detection of early-stage cancer.

Conclusions: The systematic review suggested the clinical utility of ctDNA analysis for early detection of lung cancer, alone or in combination with other biomarkers. Future validation with standardised testing protocols would help integration into clinical care.