title: Comparative effectiveness of screening strategies for Lynch syndrome.
abstract: BACKGROUND
  Colorectal cancer is the second leading cause of cancer death in the United States. Approximately 3% of colorectal cancers are associated with Lynch Syndrome. Controversy exists regarding the optimal screening strategy for Lynch Syndrome.
  
  
  METHODS
  Using an individual level microsimulation of a population affected by Lynch syndrome over several years, effectiveness and cost-effectiveness of 21 screening strategies were compared. Modeling assumptions were based upon published literature, and sensitivity analyses were performed for key assumptions. In a two-step process, the number of Lynch syndrome diagnoses (Step 1) and life-years gained as a result of foreknowledge of Lynch syndrome in otherwise healthy carriers (Step 2) were measured.
  
  
  RESULTS
  The optimal strategy was sequential screening for probands starting with a predictive model, then immunohistochemistry for mismatch repair protein expression (IHC), followed by germline mutation testing (incremental cost-effectiveness ratio [ICER] of $35 143 per life-year gained). The strategies of IHC + BRAF, germline testing and universal germline testing of colon cancer probands had ICERs of $144 117 and $996 878, respectively.
  
  
  CONCLUSIONS
  This analysis suggests that the initial step in screening for Lynch Syndrome should be the use of predictive models in probands. Universal tumor testing and general population screening strategies are not cost-effective. When family history is unavailable, alternate strategies are appropriate. Documentation of family history and screening for Lynch Syndrome using a predictive model may be considered a quality-of-care measure for patients with colorectal cancer.
authors: Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (AB, SS); Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH (MWK); Cleveland Clinic Lerner College of Medicine, Cleveland, OH (MWK); Department of Epidemiology and Biostatistics (MWK) and Department of Medicine (NJM), School of Medicine, and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH (NJM).
authors: Afsaneh
authors: A
authors: Barzi
authors: Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (AB, SS); Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH (MWK); Cleveland Clinic Lerner College of Medicine, Cleveland, OH (MWK); Department of Epidemiology and Biostatistics (MWK) and Department of Medicine (NJM), School of Medicine, and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH (NJM).
authors: Sarmad
authors: S
authors: Sadeghi
authors: Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (AB, SS); Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH (MWK); Cleveland Clinic Lerner College of Medicine, Cleveland, OH (MWK); Department of Epidemiology and Biostatistics (MWK) and Department of Medicine (NJM), School of Medicine, and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH (NJM).
authors: Michael W
authors: MW
authors: Kattan
authors: Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (AB, SS); Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH (MWK); Cleveland Clinic Lerner College of Medicine, Cleveland, OH (MWK); Department of Epidemiology and Biostatistics (MWK) and Department of Medicine (NJM), School of Medicine, and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH (NJM).
authors: Neal J
authors: NJ
authors: Meropol
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000191:economics*; D057186:Comparative Effectiveness Research; D003362:Cost-Benefit Analysis; D053843:DNA Mismatch Repair / Q000235:genetics; D055088:Early Detection of Cancer / Q000191:economics* / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing / Q000191:economics / Q000379:methods; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics; D008297:Male; D008403:Mass Screening / Q000191:economics* / Q000379:methods*; D008875:Middle Aged; D057285:Precision Medicine; D011237:Predictive Value of Tests; D019057:Quality-Adjusted Life Years; D012680:Sensitivity and Specificity