Prognostic prediction of combined pre- and post-operative ctDNA detection in non-small cell lung cancer.

Abstract

e15050 Background: Circulating tumor DNA (ctDNA) serves as a valuable biomarker for monitoring relapse, with postoperative ctDNA shown to predict patient outcomes. However, the utility of preoperative ctDNA remains unclear, particularly concerning its combined predictive value before and after surgery. Methods: We analyzed 131 patients with stage I-III resected non-small cell lung cancer (NSCLC) in the POEM study (ChiCTR2100054987). Tumor samples were collected during surgery, and both preoperative and postoperative blood samples were analyzed using tumor-informed patient-specific panels called Hi-SECURE. These panels were performed by using ultra-deep (100,000x) next-generation sequencing with customized 40 single nucleotide variants. Results: The preoperative ctDNA detection rate was 48.1% (63/131). There was a significant difference in ctDNA detection rates between LUAD and non-LUAD patients (33.7% vs. 96.7%, P < 0.001). The positivity of ctDNA both before and after surgery was predictive of relapse in patients (before: HR 4.93, 95%CI 1.99-12.23; after: HR 6.26, 95%CI 1.78-21.99). Based on the ctDNA detection status from perioperative blood (PB), patients were classified into three groups: PB-III (post-ctDNA positive), PB-II (post-ctDNA negative/pre-ctDNA positive), and PB-I (post-ctDNA negative/pre-ctDNA negative). Notably, preoperative ctDNA status could effectively stratify postoperative ctDNA-negative patients (PB-I vs PB-II, P = 0.068; PB-II vs PB-III, P = 0.002; PB-I vs PB-III, P < 0.001). This distinction was even more significant among LUAD patients (PB-I vs PB-II, P = 0.023; PB-II vs PB-III, P = 0.03; PB-I vs PB-III, P < 0.001). Conclusions: Preoperative ctDNA status demonstrates a prognostic impact on patient outcomes, potentially aiding in the identification of individuals who may benefit from neoadjuvant therapy. The perioperative blood (PB) ctDNA status provides a more effective stratification of NSCLC patients, particularly those with LUAD, compared to relying solely on postoperative ctDNA status.