Circulating tumor DNA (ctDNA)-based minimal residual disease in non-small cell lung cancer

Abstract

Lung cancer is the second most common cancer worldwide and the leading cause of cancer-related fatalities, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancers. Over the past forty years, patients with NSCLC have had a 5-year survival rate of only 16%, despite improvements in chemotherapy, targeted therapy, and immunotherapy. Circulating tumor DNA (ctDNA) in blood can be used to identify minimal residual disease (MRD), and ctDNA-based MRD has been shown to be of significance in prognostic assessment, recurrence monitoring, risk of recurrence assessment, efficacy monitoring, and therapeutic intervention decisions in NSCLC. The level of MRD can be obtained by monitoring ctDNA to provide guidance for more precise and personalized treatment, the scientific feasibility of which could dramatically modify lung cancer treatment paradigm. In this review, we present a comprehensive review of MRD studies in NSCLC and focus on the application of ctDNA-based MRD in different stages of NSCLC in current clinical practice.

Keywords: Circulating tumor DNA (ctDNA); Minimal residual disease (MRD); Non-small cell lung cancer (NSCLC); Prognostic assessment; Recurrence monitoring.

Fig. 1

Two strategic systems based on ctDNA-MRD detection. ctDNA: Circulating tumor DNA; MRD: Minimal residual disease.

Fig. 2

Process of drug holiday study based on ctDNA-MRD status in patients with advanced NSCLC. Advanced NSCLC patients must have genetic testing, and those with EGFR or ALK mutations will receive TKI treatment or combination LCT. Patients will receive ctDNA-based MRD detection after reaching CR as determined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, and the next route will be as follows: (1) If the MRD detection is positive, continue TKI therapy; (2) If the MRD detection is negative, take a drug holiday. During the drug holiday period, the ctDNA-based MRD detection is conducted every three months, and if the detection result is positive once again, TKI therapy is repeated; importantly, if the MRD is negative after retreatment, the patient can re-enter the drug holiday.