医学
置信区间
内科学
肿瘤科
结直肠癌
微小残留病
多路复用
循环肿瘤DNA
胃肠病学
阶段(地层学)
癌症
佐剂
临床试验
化疗
辅助治疗
随机对照试验
作者
Tenna V Henriksen,Noelia Tarazona,Amanda Frydendahl,Thomas Reinert,F. Gimeno-Valiente,J.A. Carbonell-Asins,Shruti Sharma,Derrick Renner,Dina Hafez,Desamparados Roda,Marisol Huerta,Susana Roselló,Anders Husted Madsen,Uffe S. Løve,Per Vadgaard Andersen,Ole Thorlacius-Ussing,Lene Hjerrild Iversen,Kåre Andersson Gotschalck,Himanshu Sethi,Alexey Aleshin,Andrés Cervantes,Claus L. Andersen
标识
DOI:10.1158/1078-0432.ccr-21-2404
摘要
Sensitive methods for risk stratification, monitoring therapeutic efficacy, and early relapse detection may have a major impact on treatment decisions and patient management for stage III colorectal cancer patients. Beyond assessing the predictive power of postoperative ctDNA detection, we explored the added benefits of serial analysis: assessing adjuvant chemotherapy (ACT) efficacy, early relapse detection, and ctDNA growth rates.We recruited 168 patients with stage III colorectal cancer treated with curative intent at Danish and Spanish hospitals between 2014 and 2019. To quantify ctDNA in plasma samples (n = 1,204), 16 patient-specific somatic single-nucleotide variants were profiled using multiplex-PCR, next-generation sequencing.Detection of ctDNA was a strong recurrence predictor postoperatively [HR = 7.0; 95% confidence interval (CI), 3.7-13.5; P < 0.001] and directly after ACT (HR = 50.76; 95% CI, 15.4-167; P < 0.001). The recurrence rate of postoperative ctDNA-positive patients treated with ACT was 80% (16/20). Only patients who cleared ctDNA permanently during ACT did not relapse. Serial ctDNA assessment after the end of treatment was similarly predictive of recurrence (HR = 50.80; 95% CI, 14.9-172; P < 0.001), and revealed two distinct rates of exponential ctDNA growth, slow (25% ctDNA-increase/month) and fast (143% ctDNA-increase/month; P < 0.001). The ctDNA growth rate was prognostic of survival (HR = 2.7; 95% CI, 1.1-6.7; P = 0.039). Serial ctDNA analysis every 3 months detected recurrence with a median lead-time of 9.8 months compared with standard-of-care computed tomography.Serial postoperative ctDNA analysis has a strong prognostic value and enables tumor growth rate assessment. The novel combination of ctDNA detection and growth rate assessment provides unique opportunities for guiding decision-making.See related commentary by Morris and George, p. 438.
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