Strategies to Identify the Lynch Syndrome Among Patients With Colorectal Cancer

open here please ►Strategies to Identify the Lynch Syndrome Among Patients With Colorectal Cancer: "* Original Research

Strategies to Identify the Lynch Syndrome Among Patients With Colorectal Cancer
A Cost-Effectiveness Analysis

1. Uri Ladabaum, MD, MS;
2. Grace Wang, PhD, MPH;
3. Jonathan Terdiman, MD;
4. Amie Blanco, MS;
5. Miriam Kuppermann, PhD, MPH;
6. C. Richard Boland, MD;
7. James Ford, MD;
8. Elena Elkin, PhD; and
9. Kathryn A. Phillips, PhD

+ Author Affiliations

1. From Stanford University School of Medicine, Stanford, California; University of California, San Francisco, San Francisco, California; Baylor University Medical Center, Dallas, Texas; and Memorial Sloan-Kettering Cancer Center, New York, New York.

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.

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