ctDNA-based minimal residual disease detection in lung cancer patients treated with curative intended chemoradiotherapy using a clinically transferable approach.

ABSTRACT

BACKGROUND: Reliable biomarkers are needed to identify tumor recurrence of non-small cell lung cancer (NSCLC) patients after chemoradiotherapy (CRT) with curative intent. This could improve consolidation therapy of progressing patients. However, the approach of existing studies has limited transferability to the clinic. MATERIALS AND METHODS: A retrospective analysis of 135 plasma samples from 56 inoperable NSCLC patients who received CRT with curative intent was performed. Plasma samples collected at baseline, at the first check-up (average 1.6 months post-RT), and at the second check-up (average 4.5 months post-RT) were analyzed by deep sequencing with a commercially available cancer personalized profiling strategy (CAPP-Seq) using a tumor-agnostic approach. RESULTS: Detection of circulating tumor DNA (ctDNA) at 4.5 months after therapy was significantly associated with higher odds of tumor recurrence (OR 5.4 (CI 1.1-31), Fisher's exact test p-value = 0.022), and shorter recurrence-free survival (RFS) (HR 4.1 (CI 1.7-10); log-rank test p-value = 9e-04). In contrast, detection of ctDNA at 1.6 months after therapy was not associated with higher odds of tumor recurrence (OR 2.7 (CI 0.67-12), Fisher's exact test p-value = 0.13) or shorter RFS (HR 1.5 (CI 0.67-3.3); log-rank test p-value = 0.32). CONCLUSION: This study demonstrates that the detection of ctDNA can be used to identify minimal residual disease 4.5 months after CRT in NSCLC patients using a commercially available kit and a tumor-agnostic approach. Furthermore, the time point of collecting the plasma sample after CRT has decisive importance for the prognostic value of ctDNA. MICRO ABSTRACT This study analysed 135 plasma samples from 56 NSCLC patients treated with curative intent chemoradiotherapy using a tumor-agnostic approach. Detecting ctDNA at 4.5 months post-treatment was linked to higher recurrence odds, indicating ctDNA's potential as a biomarker for identifying residual disease after treatment with curative intent. Importantly, the study emphasizes the importance of timing for accurate ctDNA analysis results.