Cost-effectiveness of the McGill interactive pediatric oncogenetic guidelines in identifying Li-Fraumeni syndrome in female patients with osteosarcoma.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a penetrant cancer predisposition syndrome (CPS) associated with the development of many tumor types in young people including osteosarcoma and breast cancer (BC). The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) decision-support tool provides a standardized approach to identify patients at risk of CPSs. METHODS: We conducted a cost-utility analysis, from the healthcare payer perspective, to compare MIPOGG-guided, physician-guided, and universal genetic testing strategies to detect LFS in female patients diagnosed at an age of less than 18 years with osteosarcoma. We developed a decision tree and discrete-event simulation model to simulate the clinical and cost outcomes of the three genetic referral strategies on a cohort of female children diagnosed with osteosarcoma, especially focused on BC as subsequent cancer. Outcomes included BC incidence, quality-adjusted life-years (QALYs), healthcare costs, and incremental cost-utility ratios (ICURs). We conducted probabilistic and scenario analyses to assess the uncertainty surrounding model parameters. RESULTS: Compared to the physician-guided testing, the MIPOGG-guided strategy was marginally more expensive by $105 (-$516; $743), but slightly more effective by 0.003 (-0.04; 0.045) QALYs. Compared to MIPOGG, the universal testing strategy was $1333 ($732; $1953) more costly and associated with 0.011 (-0.043; 0.064) additional QALYs. The ICUR for the MIPOGG strategy was $33,947/QALY when compared to the physician strategy; the ICUR for universal testing strategy was $118,631/QALY when compared to the MIPOGG strategy. DISCUSSION: This study provides evidence for clinical and policy decision-making on the cost-effectiveness of genetic referral strategies to identify LFS in the setting of osteosarcoma. MIPOGG-guided strategy was most likely to be cost-effective at a willingness-to-pay threshold value of $50,000/QALY.

Cost-effectiveness of early cancer surveillance for patients with Li-Fraumeni syndrome.

INTRODUCTION: Patients with germline TP53 pathogenic variants (Li-Fraumeni syndrome [LFS]) are at extremely high lifetime risk of developing cancer. Recent data suggest that tumor surveillance for patients with LFS may improve survival through early cancer detection. The objective of this study was to assess the cost-effectiveness of a cancer surveillance strategy for patients with LFS compared with those whose tumors present clinically. METHODS: A Markov decision analytic model was developed from a third-party payer perspective to estimate cost-effectiveness of routine cancer surveillance over a patient's lifetime. The model consisted of four possible health states: no cancer, cancer, post-cancer survivorship, and death. Model outcomes were costs (2015 United States Dollars [USD]), effectiveness (life years [LY] gained), and incremental cost-effectiveness ratio (ICER; change in cost/LY gained). One-way sensitivity analyses and probabilistic sensitivity analyses examined parameter uncertainty. RESULTS: The model showed a mean cost of $46 496 and $117 102 and yielded 23 and 27 LY for the nonsurveillance and surveillance strategies, respectively. The ICER for early cancer surveillance versus no surveillance was $17 125 per additional LY gained. At the commonly accepted willingness to pay threshold of $100 000/life-year gained, surveillance had a 98% probability of being the most cost-effective strategy for early cancer detection in this high-risk population. CONCLUSIONS: Presymptomatic cancer surveillance is cost-effective for patients with germline pathogenic variants in TP53. Lack of insurance coverage or reimbursement in this population may have significant consequences and leads to undetected cancers presenting in later stages of disease with worse clinical outcomes.