Clinical Significance of a Circulating Tumor Cell-Based Classifier in Stage IB Lung Adenocarcinoma: A Multicenter, Cohort Study.

Abstract

To investigate the effectiveness of a circulating tumor cell (CTC)-based classifier in stratifying stage IB lung adenocarcinoma (LUAD). Stage IB LUADs have an approximately 70% 5-year survival rate. The clinical application of adjuvant chemotherapy (ACT) is controversial due to inconsistent results in a series of trials and few useful guide biomarkers. Thus, there is a pressing need for robust biomarkers to stratify stage IB patients to define which group would most likely benefit from ACT. 212 stage IB LUAD patients were enrolled and were divided into three independent cohorts. The aptamer-modified NanoVelcro system was used to enrich the CTCs. A cutoff of < 4 or ≥ 4 CTCs as the optimal prognostic threshold for stage IB LUAD was generated to stratify the patients in a 70-patient cohort into low-risk and high-risk groups. Patients with ≥ 4 CTCs in the training cohort had shorter progression-free survival (PFS, P < 0.0001) and overall survival (OS, P < 0.0001) than patients with < 4 CTCs. CTC number remained the strongest predictor of PFS and OS even in a multivariate analysis including other clinicopathological parameters. Furthermore, a nomogram based on the CTC count was developed to predict the 3-year and 5-year survival in the training cohort and performed well in the other two validation cohorts (C-index: 0.862, 0.853 and 0.877). The presence of ≥ 4 CTCs can define a high-risk subgroup, providing a new strategy to make optimal clinical decisions for stage IB LUAD.