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Circulating epigenetic biomarkers for detection of recurrent colorectal cancer.
Cancer ( IF 6.2 ) Pub Date : 2020-01-07 , DOI: 10.1002/cncr.32695
Erin L Symonds 1, 2 , Susanne K Pedersen 3 , David Murray 3 , Susan E Byrne 1 , Amitesh Roy 1, 4 , Christos Karapetis 1, 4 , Paul Hollington 2 , Philippa Rabbitt 2 , Frederick S Jones 5 , Lawrence LaPointe 5 , Eva Segelov 6, 7 , Graeme P Young 1
Affiliation  

BACKGROUND The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence. METHODS Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched-chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc-finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold). RESULTS The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%-69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%-36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%-99.6%; CEA, 96.4%; 95% CI, 91.4%-99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9-1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3-20.6; P = .407). CONCLUSIONS The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.

中文翻译:

循环表观遗传标记物,用于检测复发性结直肠癌。

背景技术通过测量循环肿瘤DNA(ctDNA)敏感地检测复发性大肠癌(CRC)可能会增加治愈机会。这项研究将定量甲基化ctDNA测试与癌胚抗原(CEA)进行了复发监测。方法在监测期间或在确认复发后的12个月内收集的血样用于ctDNA(甲基化的支链氨基酸转氨酶1 [BCAT1] / Ikaros家族锌指1蛋白[IKZF1])和CEA的检测。最佳ctDNA阈值通过接受者操作特征分析确定,并将复发检测的测试性能与CEA(5 ng / mL阈值)进行比较。结果该研究队列包括144例合格患者,包括50例复发事件。甲基化ctDNA测试的复发敏感性为66.0%(95%置信区间[CI],57.1%-69.3%),显着高于CEA的敏感性(31.9%; 95%CI,22.8%-36.6% ; P <.001)。可切除复发的敏感性(n = 20)也更高(ctDNA,60.0%; CEA,20.0%; P = 0.01)。两次测试之间的特异性没有差异(ctDNA为97.9%; 95%CI为93.2%-99.6%; CEA为96.4%; 95%CI为91.4%-99.0%)。当对复发的其他​​预测因素进行调整时,ctDNA测试阳性是独立的预测因素(比值比为155.7; 95%CI为17.9-1360.6; P <0.001),而CEA则不是(比值比值为2.5) ; 95%CI,0.3-20.6; P = .407)。结论定量ctDNA测试显示出比CEA更高的灵敏度,并且在检测复发性CRC的特异性上没有差异。
更新日期:2020-01-07
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