Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer

Journal of Hematology & Oncology

Da Wang¹  Qian Xiao¹  Ke-Feng Ding²  Sanjun Cai³  Yaqi Li³  Junjie Peng³  Peirong Ding⁴  Gong Chen⁴  Xiaojun Wu⁴  Zhizhong Pan⁴  Fulong Wang⁴  Liren Li⁴  Qi Zhao⁵  Hao-Xiang Wu⁶  Rui-Hua Xu⁶  Feng Wang⁶  Hua Bao⁷  Yang Shao⁸ 

[1] Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China;Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China;Cancer Center Zhejiang University, 310009, Hangzhou, China;Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China;Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China;Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, China;Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, 510060, Guangzhou, China;Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, China;Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, 510060, Guangzhou, China;Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, 510060, Guangzhou, China;Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, 510060, Guangzhou, China;Nanjing Geneseeq Technology Inc., 210032, Nanjing, China;Nanjing Geneseeq Technology Inc., 210032, Nanjing, China;School of Public Health, Nanjing Medical University, 210029, Nanjing, China;

关键词: Stage II/III colorectal cancer;    Minimal residual disease;    Circulating tumor DNA;    Recurrence risk;    Adjuvant chemotherapy;   

DOI  :  10.1186/s13045-021-01089-z

来源: Springer

【 摘 要 】

BackgroundPrecise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk.MethodsFrom September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care.ResultsPreoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3–7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio [HR], 10.98; 95%CI, 5.31–22.72; P < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39–30.19; P < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79–95.08; P < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months.ConclusionsPostoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.

【 授权许可】

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