Appendix Table 1.
Assumptions regarding the participation of CRC Index cases and their FDRs in every step of the patient flow diagram, and the positivity rates of the genetic tests.
| Parameter | Value (Rangea) | Source |
|---|---|---|
| LS Testing of Index CRC Cases | ||
| Combined proportion of possible LS cases | 4.5% (2.25–6.75%) | Ontario Estimateb |
| Proportion of index CRC cases with an MLH1 deficiency, subsequently tested for BRAF V600E | 13.3% | |
| Proportion of MLH1 deficient BRAF wildtype tumors without MLH1 promoter hypermethylation | 64% | |
| Proportion of MLH1 deficient BRAF wildtype tumors without MLH1 promoter hypermethylation, referred to genetic counseling | 33% | |
| Proportion of index CRC cases with an MSH2/6 or PMS2 deficiency, subsequently referred to genetic counseling | 1.7% | |
| Index Case Genetic Pathway | ||
| Proportion of patients accepting genetic counseling | 84% (42-100%) | 2 |
| Proportion of patients that once seen by genetic counselor will undergo genetic testing | 80% (40-100%) | 3,4 |
| Proportion of patients undergoing genetic testing that are positive for LS | 67% (33-100%) | 5–8 |
| FDRs LS cases | ||
| Average number of FDRs of identified LS case | 5.96 (2.98-8.94) | 9 |
| Proportion of FDRs that accept genetic counseling | 52% (26-78%) | 10 |
| Proportion of FDRs that once seen by genetic counselor will undergo genetic testing | 95% (47.5-100%) | 10 |
| Proportion of FDRs testing positive on a germline test | 50% (25-75%) | 11 |
| Colonoscopy participation c | ||
| Colonoscopy screening participation not diagnosed with LS | 60% (40-80%)d | 12 |
| Colonoscopy surveillance participation diagnosed with LS | 80% (70-90%)d | 10,13–15 |
CRC=Colorectal cancer, FDR=first-degree relative, LS= Lynch Syndrome
a.
Alternative values evaluated in sensitivity analyses. Ranges evaluated were mean*0.5 –mean*1.5.
b.
Estimates were based on experience at the Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, Toronto, Ontario
c.
In the Probabilistic Sensitivity Analysis, the participation when not being diagnosed with LS was never lower than the participation when being diagnosed with LS, using preference ordering.16
d.
As we are more certain of these estimated, smaller ranges were evaluated.