Abstract 1037: Circulating tumor DNA-based molecular residual disease predicts relapse in patients with resectable gastric cancer
Authors: Xue Pei , Shao Yanfei , Zhou Xueliang , Li Haiyan , Wang Yang , Wang Chenyang , Zhang Hao , Li Bing , Shi Shuo , Du Haiwei , Sun Jing 
Published: June 2023

Background: Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection has been shown to predict postoperative relapse in several cancers. Currently, fixed and personalized panel-based tumor-informed (TI) ctDNA testing strategies are available for MRD assessment. Here, we aim to evaluate the prognostic value of MRD in resectable gastric cancer (GC) and assess MRD with fixed and personalized panels for comparison.

Methods: We prospectively enrolled patients with stage I-III GC who underwent R0 resection at Ruijin Hospital. Blood samples were collected on the day of surgery preoperatively and during the second-fourth week postoperatively. Tissue samples were collected shortly thereafter at the time of curative-intent resection. Both the Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (brPROPHET, a personalized panel-based TI assay, Burning Rock Biotech) and a 168-gene panel-based TI assay (Burning Rock Biotech) were used to quantify ctDNA.

Results: A total of 55 patients (19 females and 36 males) with a median age of 65 years (range: 35-87) were enrolled. Precise 5 and 41 patients were treated with neoadjuvant therapy and adjuvant therapy, respectively. The median duration of follow-up was 784 days (range: 582-853). All patients underwent the fixed panel-based TI assay. Of which, 19 patients were collected with postoperative blood samples. The MRD status of postoperative blood by the fixed panel showed a significant association with recurrence-free survival (RFS, MRD-positive [MRD+] vs. MRD-negative [MRD-]: 484 days vs. not reached [NR], hazard ratio [HR] = 8.0, p = 0.02). Of the 55 enrolled patients, 19 patients underwent both personalized and fixed panel-based TI assays. For the personalized panel, preoperative ctDNA was detected in 94.7% (18/19) of the patients with 100% (4/4), 66.7% (2/3), and 91.7% (11/12) in stage I, II, and III, respectively. The numbers were 36.8% (7/19), 0% (0/4), 0% (0/3), and 58.3% (7/12) with the fixed panel, respectively. Among the 19 patients, three of the 13 patients who had postoperative blood samples developed tumor recurrence during the follow-up visit. The sensitivity of the personalized panel for predicting tumor recurrence achieved 100% (3/3) with 90% (9/10) specificity. The sensitivity of the fixed panel was 33.3% (1/3) with 100% (10/10) specificity. In addition, patients with MRD+ by the personalized panel had a significantly shorter RFS than those with MRD- (566 days vs. NR, HR &gt; 100, p = 0.003).

Conclusion: Our study indicates that MRD+ by either the personalized or fixed panel was associated with an unfavorable survival outcome. ctDNA-based MRD detection by the personalized panel-based TI assay might be a powerful prognostic biomarker to identify GC patients who underwent radical resection at a higher risk of relapse or with an unfavorable survival outcome.

Citation Format: Pei Xue, Yanfei Shao, Xueliang Zhou, Haiyan Li, Yang Wang, Chenyang Wang, Hao Zhang, Bing Li, Shuo Shi, Haiwei Du, Jing Sun. Circulating tumor DNA-based molecular residual disease predicts relapse in patients with resectable gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1037.