1270P - Personalized tumor-informed circulating tumor DNA (ctDNA) analysis for molecular residual disease (MRD) detection in resected non-small cell lung cancer (NSCLC) with common driver genes

Background

This study aims to evaluate the feasibility of utilizing digital droplet polymerase chain reaction (ddPCR) for the detection of specific driver gene mutations (EGFR L858R/19del or KRAS G12C/D) in ctDNA for MRD monitoring in resected NSCLC patients with the mentioned mutations.

Methods

Plasma samples were collected every 3 or 6 months to detect EGFR L858R/19del or KRAS G12 C/D mutations from patients with resected NSCLC, using a single point assay. A binary logistic analysis was performed to assess the impact of these factors on MRD outcomes.

Results

Our study included 300 patients with resected NSCLC, with a median age of 62 years. Among them, 54% of patients had the EGFR L858R mutation, 34% had EGFR 19del, 10% had KRAS mutation, and the remaining 2% exhibited multiple mutations. The majority of participants were diagnosed with Stage IA NSCLC (71%), followed by 14% with Stage IB, 7% with Stage II, and 7% with Stage III. In terms of histological subtype, invasive adenocarcinoma accounted for 85% of cases, while 10% had Adenocarcinoma In Situ/Minimally Invasive Adenocarcinoma (AIS/MIA). The longest follow-up period was 39 months, with a median follow-up time of 33 months. A total of 607 blood samples were collected, with 10% of samples from AIS/MIA and 17% of samples from invasive adenocarcinoma showing MRD positivity. Among different gene mutations, the positive rates for MRD were 15% for EGFR L858R, 19% for EGFR 19del, and 18% for KRAS. In our binary logistic analysis, patients who received adjuvant therapy had a higher likelihood of MRD negativity (odds ratio: 0.50 [95% CI: 0.27, 0.95], p < 0.05). A higher TNM stage was associated with a higher likelihood of MRD positivity (OR: 2.13 [95% CI: 1.51, 2.99], p < 0.001).

Conclusions

Our findings indicate that ddPCR is a feasible option for detecting MRD in resected NSCLC with common driver genes, its accuracy was supported by the results of relevant subgroup analysis. Considering the elevated prevalence of EGFR mutations in the Asian population, our personalized tumor-informed approach targeting EGFR may offer a cost-effective solution. Nevertheless, additional data are necessary to substantiate its efficacy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Center for Respiratory Medicine; The First Affiliated Hospital of Guangzhou Medical University.

Disclosure

All authors have declared no conflicts of interest.