Abstract 5917: Patient-specific tumor-informed circulating tumor DNA (ctDNA) analysis for postoperative monitoring of patients with stages I-III colorectal cancer (CRC)
Authors: Zhou Jian , Yang Jian , Zhang Zixiang , Li Ye , Yi Bin , Tang Yuchen , Li Dechun , Li Xiaozhe , Peng Di , Li XI , Wang Yang , Li Haiyan , Li Bing , Wang Chenyang , Zhu Pengfei , Chen Longfei , Wu Shuailai , Fang Shuai , Li Chenxi , Qiu Fujun , Chuai Shannon , Zhang Zhihong 
Published: June 2022

Background: Identifying molecular residual disease (MRD) with tailored tumor-informed ctDNA based next-generation sequencing (NGS) assays after curative surgery could facilitate the individualized management of resected CRC patients. Here, we investigated the clinical utility of tumor-informed ctDNA mutation analysis using a novel Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (PROPHET) approach for accessing MRD in resected CRC patients. Using the same set of baseline and post-operative blood samples, we compared the performance of PROPHET assay with tumor-naïve fixed panel for detecting MRD and predicting recurrence in resected CRC patients.

Methods: The prospective study recruited 42 patients diagnosed with stage I-III CRC from May 2019 to Jun 2020 at the First Affiliated Hospital of Soochow University. Tumor tissue samples were collected at surgery. Blood samples collected before surgery (baseline), 8-day post-operative time point before any adjuvant therapy were analyzed. The detection and quantification of ctDNA for MRD assessment was investigated using PROPHET, a personalized, tumor-informed ctDNA assay designed to track up to 50 top-ranked patient-specific somatic variants based on whole-exome sequencing (WES) of the tumor tissue and matched white blood cells (WBCs). Tumor- naïve fixed assay was performed using targeted NGS panel, containing 41 gastrointestinal cancer-related genes.

Results: Baseline ctDNA status was detected in 95.23% (40/42) of the patients with PROPHET assay, and 69.05% (29/42) of the patients with fixed panel. Of 42 patients included in the analysis, 1, 25, and 16 patients had pathological stages I, II, and III CRC with baseline ctDNA detected in 100% (1/1), 92% (23/25), 100% (16/16) patients with PROPHET assay, and 100% (1/1), 64% (16/25), 75% (12/16) patients with fixed panel. Post-operative ctDNA-positive status with PROPHET assay was associated with 3-year DFS, compared with ctDNA-negative group (hazard ratio [HR], 16.57, 95% confidence interval [CI]:3.01-91.36, p=0.014). 15% (6/40) patients were identified to be MRD- positive and 83.33% (5/6) patients eventually relapsed at 3-years follow-up. Although fixed panel also showed high performance in predicting relapse HR, 4.48, 95% CI:1.9-10.9; p&lt; 0.001, 27.5% (11/40) patients were identified to be MRD-positive and only 45.45% (5/11) patients eventually relapsed. 3-year prognostication with PROPHET assay at 8-day post-operation yielded higher positive predictive value (83.33% vs 45.45%), negative predictive value (91.18% vs 89.66%), and specificity (96.88% vs 81.25%) as compared with tumor-naïve fixed panel.

Conclusion: Patient-specific PROPHET assay based on unique somatic mutation profiles detects patients with high-risk of recurrence, which achieved higher specificity than tumor-naïve fixed panel.

Citation Format: Jian Zhou, Jian Yang, Zixiang Zhang, Ye Li, Bin Yi, Yuchen Tang, Dechun Li, Xiaozhe Li, Di Peng, XI Li, Yang Wang, Haiyan Li, Bing Li, Chenyang Wang, Pengfei Zhu, Longfei Chen, Shuailai Wu, Shuai Fang, Chenxi Li, Fujun Qiu, Shannon Chuai, Zhihong Zhang. Patient-specific tumor-informed circulating tumor DNA (ctDNA) analysis for postoperative monitoring of patients with stages I-III colorectal cancer (CRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5917.