美国弗雷德·哈钦森癌症中心William M. Grady团队研究了无细胞DNA血液检测对结直肠癌筛查的准确性。相关论文于2024年3月13日发表在《新英格兰医学杂志》上。

结直肠癌是美国成年人中诊断出的第三大癌症。早期检测可以预防90%以上的结直肠癌相关死亡，尽管有多种可用的检测，但超过三分之一符合筛查条件的人群仍没有进行及时筛查。基于血液的检测有可能提高筛查的依从性，更早发现结直肠癌，并降低结直肠癌癌症相关死亡率。

研究组评估了无细胞DNA（cfDNA）血液检测在符合癌症筛查条件人群中的表现特征。与筛查结肠镜检查相比，共同主要结局是对结直肠癌的敏感性和对晚期肿瘤（癌症或晚期癌前病变）的特异性。次要结局是检测晚期癌前病变的敏感性。

临床验证队列包括10258人，其中7861人符合资格标准并可评估。通过结肠镜检查检测到的患有结直肠癌的参与者中，共有83.1%的cfDNA检测呈阳性，16.9%的cfDNA测试呈阴性，这表明cfDNA检测对结直肠癌的敏感性为83.1%（95%置信区间[CI]，72.2至90.3）。对癌症I、II或III期的敏感性为87.5%（95%置信区间，75.3至94.1），对晚期癌前病变的敏感性为13.2%（95%可信区间，11.3至15.3）。

在结肠镜检查中确定的没有任何晚期结直肠肿瘤（癌症或晚期癌前病变）的参与者中，共有89.6%的人cfDNA血液检测呈阴性，而10.4%的人cfDNA血液检测呈阳性，这表明该检测方法对任何晚期肿瘤的特异性为89.6%（95%CI，88.8至90.3）。阴性结肠镜检查（无癌症、晚期癌前病变或非晚期癌前病灶）的特异性为89.9%（95%CI，89.0至90.7）。

研究结果表明，在平均风险筛查人群中，这种cfDNA血液检测对结直肠癌的敏感性为83%，对晚期肿瘤的特异性为90%，对晚期癌前病变的敏感性为13%。

附：英文原文

Title: A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening

Author: Daniel C. Chung, Darrell M. Gray II, Harminder Singh, Rachel B. Issaka, Victoria M. Raymond, Craig Eagle, Sylvia Hu, Darya I. Chudova, AmirAli Talasaz, Joel K. Greenson, Frank A. Sinicrope, Samir Gupta, William M. Grady

Issue&Volume: 2024-03-13

Abstract:

Background

Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer–related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer–related mortality.

Methods

We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions.

Results

The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7).

Conclusions

In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions.

DOI: NJ202403143901107

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2304714