Circulating tumor DNA (ctDNA) analysis predicts recurrence following surgery in patients with stage I-IIIA non-small-cell lung cancer (NSCLC): Results of GASTO1035 and GASTO1018.

Abstract

9023 Background: Circulating tumor DNA can be detected in the plasma and serum of patients with solid tumors and has emerged as a noninvasive biomarker for dynamically monitoring tumor. Postsurgical ctDNA analysis of early-stage NSCLC may identify patients at high risk of recurrence and facilitate early intervention and personalized cancer therapy. Methods: These studies recruited 123 patients with newly diagnosed resectable stage I-IIIA NSCLC. Preoperative and postoperative plasma and postoperative tissue samples were subjected to next-generation sequencing (Nanjing Shihe Jiyin Biotechnology Inc.) using a 425 cancer-related genes panel. Peripheral blood samples were collected before surgery, postoperatively within 1 month, and every 3-6 months for up to 3 years. Plasma samples with at least 1 variants detected in tissue samples were defined as ctDNA positive. Results: After 4 exclusions, 119 eligible patients were enrolled from June 2016 to February 2019. Presurgical ctDNA was detectable in 31 of 117 (26.5%) patients and was associated with inferior recurrence-free survival (HR, 3.90, 95% CI, 1.44-10.58, P = 0.004). Similarly, ctDNA was detected in 13 of 116 (11.2%) of the first postsurgical samples and was associated with shorter RFS (HR, 3.54, 95% CI, 1.22-10.23, P = 0.002). During surveillance after surgery, ctDNA-positive patients (38/119, 31.9%) were more than 9 times more likely to experience disease recurrence than ctDNA-negative patients (HR, 9.17, 95% CI, 2.60-32.42, P <0.001). Serial ctDNA detection preceded radiologic disease recurrence by a median lead time of 4.23 months (95% CI, 0.91-7.54 months). We also observed a positive correlation between the ctDNA detection rate and the disease stage. Conclusions: These results suggest that detection of ctDNA before and after surgery is associated with the identification of a high risk of disease recurrence of resectable NSCLC. Perioperative ctDNA analyses identify disease recurrence earlier than standard-of-care radiologic imaging, and thus could facilitate personalized cancer treatment at early time points. Clinical trial information: NCT03465241 and NCT03172156.