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循环肿瘤DNA分析可检测II期结肠癌患者的微小残留病并预测复发。

Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.

作者信息

Tie Jeanne, Wang Yuxuan, Tomasetti Cristian, Li Lu, Springer Simeon, Kinde Isaac, Silliman Natalie, Tacey Mark, Wong Hui-Li, Christie Michael, Kosmider Suzanne, Skinner Iain, Wong Rachel, Steel Malcolm, Tran Ben, Desai Jayesh, Jones Ian, Haydon Andrew, Hayes Theresa, Price Tim J, Strausberg Robert L, Diaz Luis A, Papadopoulos Nickolas, Kinzler Kenneth W, Vogelstein Bert, Gibbs Peter

机构信息

Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia. Department of Medical Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.

Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.

出版信息

Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.

Abstract

Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

摘要

对II期结肠癌患者进行切除术后检测循环肿瘤DNA(ctDNA),可能会识别出复发风险最高的患者,并有助于辅助治疗决策。我们使用基于大规模平行测序的检测方法,评估ctDNA在230例接受手术切除的II期结肠癌患者前瞻性队列的1046份血浆样本中检测微小残留病灶的能力。在未接受辅助化疗的患者中,178例患者中有14例(7.9%)术后检测到ctDNA,其中11例(79%)在中位随访27个月时复发;ctDNA检测阴性的164例患者中只有16例(9.8%)复发[风险比(HR),18;95%置信区间(CI),7.9至40;P<0.001]。在接受化疗的患者中,化疗结束后ctDNA的存在也与无复发生存期较差相关(HR,11;95%CI,1.8至68;P=0.001)。II期结肠癌切除术后ctDNA检测为残留病灶提供了直接证据,并识别出复发风险非常高的患者。

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