Screening for the Lynch Syndrome
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Hampel and colleagues (May 5 issue)1 suggest that a universal screening program for the detection of microsatellite instability in patients with colorectal cancer is feasible and probably desirable. However, it will not be inexpensive. We have estimated that such a screening program would cost in excess of $57,000 per germ-line–mutation carrier detected.2 Furthermore, the benefits to the proband are modest, since neither treatment nor outcome is likely to change on the basis of test results. The cost-effectiveness of such a program thus depends heavily on the ability to locate and test relatives, since they have the most to gain from early initiation of colorectal-cancer screening. Hampel and colleagues do not report the total number of living relatives of the 23 probands with a deleterious mutation; they report only the number who received counseling and testing. Finally, screening strategies that start with evaluation of probands' family history, such as the Bethesda guidelines,3 appear to be much more cost-effective than universal screening for microsatellite instability.2
Scott D. Ramsey, M.D., Ph.D.
Fred Hutchinson Cancer Research Center
Seattle, WA 98109
sramsey@fhcrc.org
References
Hampel H, Frankel WL, Martin E, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 2005;352:1851-1860.
Ramsey SD, Burke W, Clarke L. An economic viewpoint on alternative strategies for identifying persons with hereditary nonpolyposis colorectal cancer. Genet Med 2003;5:353-363.
Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004;96:261-268.
The authors and a colleague reply: Dr. Ramsey questions the validity of our strategy of universal screening mainly because of the perceived high cost relative to the benefit. The claim that benefits to the proband are modest is incorrect: the identification of mutation-positive Lynch syndrome dramatically alters management and outcome.1 We agree that the number of relatives tested influences the cost-effectiveness of screening. Our 23 probands had 148 first- and second-degree relatives over the age of 18 years who were at high risk. Of 117 relatives tested, 52 were mutation-positive and 65 were mutation-negative. Intensified clinical surveillance of mutation-positive persons significantly reduces cancer-related morbidity and mortality.2 Relaxation of clinical surveillance in those who are a priori at high risk and yet are found to be mutation-negative is highly beneficial. Unfortunately, too many carriers of the Lynch syndrome mutation are missed even by good evaluation of the family history, and those with strong family histories are often not referred for genetic evaluation.3 We calculate that our simplified method of immunohistochemical analysis as the first screen will reduce costs in terms of life-years saved. Finally, Dr. Ramsey's methodology (decision analysis and simulation), which resulted in his estimate of $57,000 per germ-line mutation detected, is not validated and is too unstable to predict economic outcomes. In his article, Dr. Ramsey acknowledges the instability of the research approach and execution.4
Heather Hampel, M.S.
Albert de la Chapelle, M.D., Ph.D.
W.C. Benton, M.B.A., Ph.D.
Ohio State University
Columbus, OH 43210
delachapelle-1@medctr.osu.edu
References
Lanspa SJ, Jenkins JX, Cavalieri RJ, et al. Surveillance in Lynch syndrome: how aggressive? Am J Gastroenterol 1994;89:1978-1980.
J?rvinen HJ, Aarnio M, Mustonen H, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000;118:829-834.
Sweet KM, Bradley TL, Westman JA. Identification and referral of families at high risk for cancer susceptibility. J Clin Oncol 2002;20:528-537.
Ramsey SD, Burke W, Clarke L. An economic viewpoint on alternative strategies for identifying persons with hereditary nonpolyposis colorectal cancer. Genet Med 2003;5:353-363.
Scott D. Ramsey, M.D., Ph.D.
Fred Hutchinson Cancer Research Center
Seattle, WA 98109
sramsey@fhcrc.org
References
Hampel H, Frankel WL, Martin E, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 2005;352:1851-1860.
Ramsey SD, Burke W, Clarke L. An economic viewpoint on alternative strategies for identifying persons with hereditary nonpolyposis colorectal cancer. Genet Med 2003;5:353-363.
Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004;96:261-268.
The authors and a colleague reply: Dr. Ramsey questions the validity of our strategy of universal screening mainly because of the perceived high cost relative to the benefit. The claim that benefits to the proband are modest is incorrect: the identification of mutation-positive Lynch syndrome dramatically alters management and outcome.1 We agree that the number of relatives tested influences the cost-effectiveness of screening. Our 23 probands had 148 first- and second-degree relatives over the age of 18 years who were at high risk. Of 117 relatives tested, 52 were mutation-positive and 65 were mutation-negative. Intensified clinical surveillance of mutation-positive persons significantly reduces cancer-related morbidity and mortality.2 Relaxation of clinical surveillance in those who are a priori at high risk and yet are found to be mutation-negative is highly beneficial. Unfortunately, too many carriers of the Lynch syndrome mutation are missed even by good evaluation of the family history, and those with strong family histories are often not referred for genetic evaluation.3 We calculate that our simplified method of immunohistochemical analysis as the first screen will reduce costs in terms of life-years saved. Finally, Dr. Ramsey's methodology (decision analysis and simulation), which resulted in his estimate of $57,000 per germ-line mutation detected, is not validated and is too unstable to predict economic outcomes. In his article, Dr. Ramsey acknowledges the instability of the research approach and execution.4
Heather Hampel, M.S.
Albert de la Chapelle, M.D., Ph.D.
W.C. Benton, M.B.A., Ph.D.
Ohio State University
Columbus, OH 43210
delachapelle-1@medctr.osu.edu
References
Lanspa SJ, Jenkins JX, Cavalieri RJ, et al. Surveillance in Lynch syndrome: how aggressive? Am J Gastroenterol 1994;89:1978-1980.
J?rvinen HJ, Aarnio M, Mustonen H, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000;118:829-834.
Sweet KM, Bradley TL, Westman JA. Identification and referral of families at high risk for cancer susceptibility. J Clin Oncol 2002;20:528-537.
Ramsey SD, Burke W, Clarke L. An economic viewpoint on alternative strategies for identifying persons with hereditary nonpolyposis colorectal cancer. Genet Med 2003;5:353-363.