Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis.
Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis.
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DOI：
10.7326/0003-4819-155-2-201107190-00002
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发表时间：
2011-07-19
影响因子：
39.2
通讯作者：
Phillips KA
中科院分区：
文献类型：
--
作者：
Ladabaum U;Wang G;Terdiman J;Blanco A;Kuppermann M;Boland CR;Ford J;Elkin E;Phillips KA
已经提倡对所有新诊断的结直肠癌患者进行检测，以确定患有Lynch综合征的家庭，Lynch综合征是一种常染色体显性癌症易感综合征，是个性化医学的典范。评估确定林奇综合征的策略的有效性和成本效益，并注意性别、筛查时的年龄以及对先证者和亲属的不同影响。马尔科夫模型包含了结直肠癌、子宫内膜癌和卵巢癌的风险。出版的文学作品。所有新诊断的结直肠癌患者及其亲属。终身监禁。第三方付款人。基于临床标准、预测算法、肿瘤检测或预先胚系突变检测的策略，然后进行量身定制的筛查和降低风险的手术。寿命年、癌症病例和死亡人数、成本和增量成本效益比。所有策略的益处主要受益于与林奇综合征相关的突变的亲属，特别是妇女，通过子宫切除和输卵管卵巢切除术以及遵守结直肠癌筛查建议，她们的预期寿命可能增加约4年。在目前的生殖系测试、筛查和预防性手术的比率下，这些策略将结直肠癌的死亡率降低了7%至42%，将子宫内膜癌和卵巢癌的死亡率降低了1%至6%。在肿瘤检测策略中，免疫组织化学和BRAF突变检测是首选，每获得一个生命年，成本-效果比增加36200美元。每名先证者接受检查的亲属数量是有效性和成本效益的关键决定因素，大多数战略需要测试3至4名亲属，以达到每获得的生命年50,000美元的门槛。在概率敏感性分析中，免疫组织化学和BRAF突变检测在59%的迭代中是首选的，阈值为每生命年10万美元。通过免疫组织化学筛查Lynch综合征，然后进行BRAF突变检测，与仅筛查60岁相比，每增加一个寿命年的成本为44000美元，与仅筛查70岁的生命年相比，没有年龄上限的筛查每增加一个生命年的成本为88700美元。其他类型的癌症、不确定的家系和未知意义的遗传变异没有被考虑在内。广泛开展结直肠肿瘤检测，以确定患有林奇综合征的家庭，可能会以可接受的成本产生可观的好处，特别是对于携带与林奇综合征相关的突变的女性，她们开始定期筛查，并接受降低风险的手术。这种检测的成本效益取决于有林奇综合症风险的亲属的参与率。美国国立卫生研究院。
Testing has been advocated for all persons with newly diagnosed colorectal cancer to identify families with the Lynch syndrome, an autosomal dominant cancer-predisposition syndrome that is a paradigm for personalized medicine. To estimate the effectiveness and cost-effectiveness of strategies to identify the Lynch syndrome, with attention to sex, age at screening, and differential effects for probands and relatives. Markov model that incorporated risk for colorectal, endometrial, and ovarian cancers. Published literature. All persons with newly diagnosed colorectal cancer and their relatives. Lifetime. Third-party payer. Strategies based on clinical criteria, prediction algorithms, tumor testing, or up-front germline mutation testing, followed by tailored screening and risk-reducing surgery. Life-years, cancer cases and deaths, costs, and incremental cost-effectiveness ratios. The benefit of all strategies accrued primarily to relatives with a mutation associated with the Lynch syndrome, particularly women, whose life expectancy could increase by approximately 4 years with hysterectomy and salpingo-oophorectomy and adherence to colorectal cancer screening recommendations. At current rates of germline testing, screening, and prophylactic surgery, the strategies reduced deaths from colorectal cancer by 7% to 42% and deaths from endometrial and ovarian cancer by 1% to 6%. Among tumor-testing strategies, immunohistochemistry followed by BRAF mutation testing was preferred, with an incremental cost-effectiveness ratio of $36 200 per life-year gained. The number of relatives tested per proband was a critical determinant of both effectiveness and cost-effectiveness, with testing of 3 to 4 relatives required for most strategies to meet a threshold of $50 000 per life-year gained. Immunohistochemistry followed by BRAF mutation testing was preferred in 59% of iterations in probabilistic sensitivity analysis at a threshold of $100 000 per life-year gained. Screening for the Lynch syndrome with immunohistochemistry followed by BRAF mutation testing only up to age 70 years cost $44 000 per incremental life-year gained compared with screening only up to age 60 years, and screening without an upper age limit cost $88 700 per incremental life-year gained compared with screening only up to age 70 years. Other types of cancer, uncertain family pedigrees, and genetic variants of unknown significance were not considered. Widespread colorectal tumor testing to identify families with the Lynch syndrome could yield substantial benefits at acceptable costs, particularly for women with a mutation associated with the Lynch syndrome who begin regular screening and have risk-reducing surgery. The cost-effectiveness of such testing depends on the participation rate among relatives at risk for the Lynch syndrome. National Institutes of Health.