当前位置： SCI文献检索 > ANNALS OF INTERNAL MEDICINE期刊下所有文献 > 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.

Abstract：

BACKGROUND: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. OBJECTIVE: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. DESIGN:Markov model that incorporated risk for colorectal, endometrial, and ovarian cancers. DATA SOURCES:Published literature. TARGET POPULATION:All persons with newly diagnosed colorectal cancer and their relatives. TIME HORIZON:Lifetime. PERSPECTIVE:Third-party payer. INTERVENTION:Strategies based on clinical criteria, prediction algorithms, tumor testing, or up-front germline mutation testing, followed by tailored screening and risk-reducing surgery. OUTCOME MEASURES:Life-years, cancer cases and deaths, costs, and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: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. RESULTS OF SENSITIVITY ANALYSIS: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. LIMITATION:Other types of cancer, uncertain family pedigrees, and genetic variants of unknown significance were not considered. CONCLUSION: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. PRIMARY FUNDING SOURCE:National Institutes of Health.

journal_name

Ann Intern Med

journal_title

Annals of internal medicine

authors

Ladabaum U,Wang G,Terdiman J,Blanco A,Kuppermann M,Boland CR,Ford J,Elkin E,Phillips KA

doi

10.7326/0003-4819-155-2-201107190-00002

subject

Has Abstract

pub_date

2011-07-19 00:00:00

pages

69-79

issue

eissn

0003-4819

issn

1539-3704

pii

155/2/69

journal_volume

155

pub_type

杂志文章

在线工具

Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis.