Background: Li-Fraumeni Syndrome (LFS) is an autosomal dominant condition that predisposes to a wide range of pediatric and early-onset adult cancers. Its underlying cause is a germline pathogenic variant in the main tumor suppressor gene, TP53. In Brazil, there is a higher prevalence of LFS due to the founder mutation in the TP53 gene p.R337H, however, a large portion of the population, that depends on National Health Care System, does not have access to effective screening through the Toronto Protocol guidelines that enables early diagnosis and improves overall survival. The main strategy in LFS screening is an annual Rapid Whole-body MRI at diagnosis, preferably starting in childhood from birth. Population strategies for early cancer detection recommended in Brazil are limited and additional screening is not offered to patients at a high risk, leading to late diagnoses and higher cancer mortality. This study aims to assess the cost-effectiveness of introducing annual screening that follows the Toronto Protocol for patients diagnosed with LFS in Brazil.Methods: A Markov decision analytic model was developed to estimate cost-effectiveness of 1,000 LFS carriers under surveillance and non-surveillance strategies over a patient's lifetime. The main outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost per additional life year gained compared surveillance and non-surveillance strategies in p.R337H TP53 carriers. Findings: For females, the model showed a mean cost of $2,222 and $14,640 and yielded 22 and 26·2 life years for non-surveillance and surveillance strategies, respectively. The ICER for early cancer surveillance versus no surveillance was $2,982 per additional life year gained. For males, the model predicts mean lifetime costs of $1,165 and $12,883 and average life years of 23·5 and 26·3 for non-surveillance and surveillance strategies, respectively. This amounts to an ICER of $ 4,185 per additional life year. Surveillance had 64% and 45% probabilities of being the most cost-effective strategy for early cancer detection in female and male carriers, respectively. Interpretation: The adoption of surveillance for LFS patients by the Brazilian National Health Care System is cost-beneficial for both males and females.

Acknowledgements

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References

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