Barzi Afsaneh, Sadeghi Sarmad, Kattan Michael W, Meropol Neal J
Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (AB, SS); Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH (MWK); Cleveland Clinic Lerner College of Medicine, Cleveland, OH (MWK); Department of Epidemiology and Biostatistics (MWK) and Department of Medicine (NJM), School of Medicine, and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH (NJM).
J Natl Cancer Inst. 2015 Mar 20;107(4). doi: 10.1093/jnci/djv005. Print 2015 Apr.
Colorectal cancer is the second leading cause of cancer death in the United States. Approximately 3% of colorectal cancers are associated with Lynch Syndrome. Controversy exists regarding the optimal screening strategy for Lynch Syndrome.
Using an individual level microsimulation of a population affected by Lynch syndrome over several years, effectiveness and cost-effectiveness of 21 screening strategies were compared. Modeling assumptions were based upon published literature, and sensitivity analyses were performed for key assumptions. In a two-step process, the number of Lynch syndrome diagnoses (Step 1) and life-years gained as a result of foreknowledge of Lynch syndrome in otherwise healthy carriers (Step 2) were measured.
The optimal strategy was sequential screening for probands starting with a predictive model, then immunohistochemistry for mismatch repair protein expression (IHC), followed by germline mutation testing (incremental cost-effectiveness ratio [ICER] of $35 143 per life-year gained). The strategies of IHC + BRAF, germline testing and universal germline testing of colon cancer probands had ICERs of $144 117 and $996 878, respectively.
This analysis suggests that the initial step in screening for Lynch Syndrome should be the use of predictive models in probands. Universal tumor testing and general population screening strategies are not cost-effective. When family history is unavailable, alternate strategies are appropriate. Documentation of family history and screening for Lynch Syndrome using a predictive model may be considered a quality-of-care measure for patients with colorectal cancer.
结直肠癌是美国癌症死亡的第二大主要原因。约3%的结直肠癌与林奇综合征相关。关于林奇综合征的最佳筛查策略存在争议。
通过对受林奇综合征影响的人群进行数年的个体水平微观模拟，比较了21种筛查策略的有效性和成本效益。建模假设基于已发表的文献，并对关键假设进行了敏感性分析。在一个两步过程中，测量了林奇综合征诊断的数量（第一步）以及在其他方面健康的携带者中因提前知晓林奇综合征而获得的生命年数（第二步）。
最佳策略是先对先证者进行序贯筛查，首先使用预测模型，然后进行错配修复蛋白表达的免疫组化（IHC），接着进行种系突变检测（每获得一个生命年的增量成本效益比[ICER]为35143美元）。IHC + BRAF、种系检测以及对结肠癌先证者进行普遍种系检测的策略，其ICER分别为144117美元和996878美元。
该分析表明，林奇综合征筛查的第一步应是在先证者中使用预测模型。普遍的肿瘤检测和一般人群筛查策略不具有成本效益。当家族史不可用时，其他策略是合适的。记录家族史并使用预测模型筛查林奇综合征可被视为结直肠癌患者的一项医疗质量指标。
