BACKGROUND AND AIMS: The optimal algorithm to identify Lynch syndrome (LS) among patients with colorectal cancer (CRC) is unclear. The definitive test for LS, germline testing, is too expensive to be applied in all cases. Initial screening with the revised Bethesda Guidelines (RBG) cannot be applied in a considerable number of cases due to missing information. METHODS: We developed a model to evaluate the cost-effectiveness of 10 strategies for diagnosing LS. Three main issues are addressed: modeling estimates (20-40%) of RBG applicability; comparing sequential or parallel use of microsatellite instability (MSI) and immunohistochemistry (IHC); and a threshold analysis of the charge value below which universal germline testing becomes the most cost-effective strategy. RESULTS: LS detection rates in RBG-based strategies decreased to 64.1-70.6% with 20% inapplicable RBG. The strategy that uses MSI alone had lower yield, but also lower cost than strategies that use MSI sequentially or in parallel with IHC. The use of MSI and IHC in parallel was less affected by variations in the sensitivity and specificity of these tests. Universal germline testing had the highest yield and the highest cost of all strategies. The model estimated that if charges for germline testing drop to $633-1,518, universal testing of all newly diagnosed CRC cases becomes the most cost-effective strategy. CONCLUSIONS: The low applicability of RBG makes strategies employing initial laboratory-based testing more cost-effective. Of these strategies, parallel testing with MSI and IHC offers the most robust yield. With a considerable drop in cost, universal germline testing may become the most cost-effective strategy for the diagnosis of LS.
BACKGROUND AND AIMS: The optimal algorithm to identify Lynch syndrome (LS) among patients with colorectal cancer (CRC) is unclear. The definitive test for LS, germline testing, is too expensive to be applied in all cases. Initial screening with the revised Bethesda Guidelines (RBG) cannot be applied in a considerable number of cases due to missing information. METHODS: We developed a model to evaluate the cost-effectiveness of 10 strategies for diagnosing LS. Three main issues are addressed: modeling estimates (20-40%) of RBG applicability; comparing sequential or parallel use of microsatellite instability (MSI) and immunohistochemistry (IHC); and a threshold analysis of the charge value below which universal germline testing becomes the most cost-effective strategy. RESULTS: LS detection rates in RBG-based strategies decreased to 64.1-70.6% with 20% inapplicable RBG. The strategy that uses MSI alone had lower yield, but also lower cost than strategies that use MSI sequentially or in parallel with IHC. The use of MSI and IHC in parallel was less affected by variations in the sensitivity and specificity of these tests. Universal germline testing had the highest yield and the highest cost of all strategies. The model estimated that if charges for germline testing drop to $633-1,518, universal testing of all newly diagnosed CRC cases becomes the most cost-effective strategy. CONCLUSIONS: The low applicability of RBG makes strategies employing initial laboratory-based testing more cost-effective. Of these strategies, parallel testing with MSI and IHC offers the most robust yield. With a considerable drop in cost, universal germline testing may become the most cost-effective strategy for the diagnosis of LS.
Authors: Scott M Weissman; Randall Burt; James Church; Steve Erdman; Heather Hampel; Spring Holter; Kory Jasperson; Matt F Kalady; Joy Larsen Haidle; Henry T Lynch; Selvi Palaniappan; Paul E Wise; Leigha Senter Journal: J Genet Couns Date: 2011-12-14 Impact factor: 2.537
Authors: M Aarnio; R Sankila; E Pukkala; R Salovaara; L A Aaltonen; A de la Chapelle; P Peltomäki; J P Mecklin; H J Järvinen Journal: Int J Cancer Date: 1999-04-12 Impact factor: 7.396
Authors: Tuan A Dinh; Benjamin I Rosner; James C Atwood; C Richard Boland; Sapna Syngal; Hans F A Vasen; Stephen B Gruber; Randall W Burt Journal: Cancer Prev Res (Phila) Date: 2010-11-18
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Authors: Erin L Young; Bryony A Thompson; Deborah W Neklason; Matthew A Firpo; Theresa Werner; Russell Bell; Justin Berger; Alison Fraser; Amanda Gammon; Cathryn Koptiuch; Wendy K Kohlmann; Leigh Neumayer; David E Goldgar; Sean J Mulvihill; Lisa A Cannon-Albright; Sean V Tavtigian Journal: BMC Cancer Date: 2018-06-27 Impact factor: 4.430
Authors: Paul J Goodfellow; Caroline C Billingsley; Heather A Lankes; Shamshad Ali; David E Cohn; Russell J Broaddus; Nilsa Ramirez; Colin C Pritchard; Heather Hampel; Alexis S Chassen; Luke V Simmons; Amy P Schmidt; Feng Gao; Louise A Brinton; Floor Backes; Lisa M Landrum; Melissa A Geller; Paul A DiSilvestro; Michael L Pearl; Shashikant B Lele; Matthew A Powell; Richard J Zaino; David Mutch Journal: J Clin Oncol Date: 2015-11-09 Impact factor: 44.544