Lynch Patrick M, Morris Jeffrey S, Wen Sijin, Advani Shailesh M, Ross William, Chang George J, Rodriguez-Bigas Miguel, Raju Gottumukkala S, Ricciardiello Luigi, Iwama Takeo, Rossi Benedito M, Pellise Maria, Stoffel Elena, Wise Paul E, Bertario Lucio, Saunders Brian, Burt Randall, Belluzzi Andrea, Ahnen Dennis, Matsubara Nagahide, Bülow Steffen, Jespersen Niels, Clark Susan K, Erdman Steven H, Markowitz Arnold J, Bernstein Inge, De Haas Niels, Syngal Sapna, Moeslein Gabriela
Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Gastrointest Endosc. 2016 Jul;84(1):115-125.e4. doi: 10.1016/j.gie.2015.12.029. Epub 2016 Jan 6.
It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis.
Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments.
The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode.
The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.
在许多家族性腺瘤性息肉病（FAP）患者中，准确计数腺瘤是不可能的。然而，息肉计数对于评估每位患者对干预措施的反应至关重要。然而，美国食品药品监督管理局不再将息肉负担的减轻视为化学预防试验治疗终点的充分依据，认为还需要衡量“临床获益”。为了制定未来由行业赞助的化学预防试验的终点，国际胃肠道遗传性肿瘤学会（InSIGHT）制定了下消化道息肉病的FAP分期和干预分类方案。
26位熟悉FAP诊断和治疗的临床医生对24份结肠镜检查或乙状结肠镜检查视频进行了评估。评估人员使用提议的系统独立为病例分配一个分期，并为每个病例选择特定分期的干预措施。我们的终点是评估人员在分期和干预评估方面的一致程度。
26位评估人员的分期和干预评级高度一致（ρ = 0.710；95%可信区间，0.651 - 0.759）。62%的评估人员对FAP分期达成一致，90%的评分在众数的±1个分期范围内。60%的评估人员对干预措施达成一致，86%的人选择了在众数的±1个等级范围内的干预措施。
提议的FAP结肠息肉病分期系统和特定分期的干预措施基于专家在审查单个息肉病病例时的高度一致性。因此，可以开发出可靠且与临床相关的衡量试验结果的方法。在分期分配上显示出广泛离散的异常病例需要个体化关注，因此可能不适合纳入此类临床试验。
