Cancer surveillance for patients with Li-Fraumeni Syndrome in Brazil: A cost-effectiveness analysis.

Background: In Brazil, there is a higher prevalence of Li-Fraumeni Syndrome (LFS) compared to worldwide, 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. 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, comparing 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 patients diagnosed with LFS by the Brazilian National Health Care System is cost-beneficial for both males and females. Funding: This research received no specific grant from any funding agency.

Introdução: No Brasil, há uma maior prevalência da Síndrome de Li-Fraumeni (LFS) em comparação ao mundo, devido à mutação fundadora no gene TP53 p.R337H. No entanto, uma grande parte da população brasileira, que depende do Sistema Único de Saúde (SUS), não tem acesso a um rastreamento eficaz através das diretrizes do Protocolo de Toronto, que possibilitam o diagnóstico precoce e ganho em sobrevida dos portadores da síndrome. As estratégias populacionais para detecção precoce do câncer recomendadas no Brasil são limitadas e o rastreamento adicional não é oferecido a pacientes de alto risco, levando a diagnósticos tardios e maior mortalidade por câncer. Este estudo tem como objetivo avaliar a relação custo-efetividade do rastreamento anual, conforme o Protocolo de Toronto, para pacientes diagnosticados com LFS no Brasil. Métodos: Foi desenvolvido o modelo analítico de decisão Markov para estimar a relação de custo-efetividade de 1.000 portadores da LFS sob estratégias de vigilância e de não-vigilância durante a vida útil do portador. O principal desfecho é a razão de custo-efetividade incremental (ICER), que expressa qual o custo adicional por ano de vida ganho, comparando as estratégias de vigilância e não-vigilância em portadores da mutação p.R337H TP53. Resultados: Para as mulheres, o modelo demonstrou o custo médio de $2.222 e $14.640 e resultou em 22 e 26·2 anos de vida útil para as estratégias de vigilância e não-vigilância, respectivamente. O ICER para rastreamento precoce do câncer versus nenhum rastreamento foi de $2.982 por ano de vida adicional ganho. Para os homens, o modelo prevê custos médios de vida de US$ 1.165 e US$ 12.883 e anos de vida médios de 23·5 e 26·3 anos para estratégias de vigilância e não-vigilância, respectivamente. Isto equivale a um ICER de US$ 4.185 por ano de vida adicional ganho. A realização do rastreamento conforme o Protocolo de Toronto tem probabilidades de 64% e 45% de ser a estratégia mais custo-efetiva para a detecção precoce do câncer em portadores do sexo feminino e masculino, respectivamente. Interpretação: A adoção do rastreamento para pacientes diagnosticados com LFS pelo Sistema Único de Saúde Brasileiro é custo-efetiva tanto para portadores do sexo masculino quanto feminino. Financiamento: Esta pesquisa não recebeu nenhum subsídio específico de nenhuma agência de financiamento.

Li-Fraumeni Exploration Consortium Data Coordinating Center: Building an Interactive Web-Based Resource for Collaborative International Cancer Epidemiology Research for a Rare Condition.

BACKGROUND: The success of multisite collaborative research relies on effective data collection, harmonization, and aggregation strategies. Data Coordination Centers (DCC) serve to facilitate the implementation of these strategies. The utility of a DCC can be particularly relevant for research on rare diseases where collaboration from multiple sites to amass large aggregate datasets is essential. However, approaches to building a DCC have been scarcely documented. METHODS: The Li-Fraumeni Exploration (LiFE) Consortium's DCC was created using multiple open source packages, including LAM/G Application (Linux, Apache, MySQL, Grails), Extraction-Transformation-Loading (ETL) Pentaho Data Integration Tool, and the Saiku-Mondrian client. This document serves as a resource for building a rare disease DCC for multi-institutional collaborative research. RESULTS: The primary scientific and technological objective to create an online central repository into which data from all participating sites could be deposited, harmonized, aggregated, disseminated, and analyzed was completed. The cohort now include 2,193 participants from six contributing sites, including 1,354 individuals from families with a pathogenic or likely variant in TP53. Data on cancer diagnoses are also available. Challenges and lessons learned are summarized. CONCLUSIONS: The methods leveraged mitigate challenges associated with successfully developing a DCC's technical infrastructure, data harmonization efforts, communications, and software development and applications. IMPACT: These methods can serve as a framework in establishing other collaborative research efforts. Data from the consortium will serve as a great resource for collaborative research to improve knowledge on, and the ability to care for, individuals and families with Li-Fraumeni syndrome.

Brazilian health-care policy for targeted oncology therapies and companion diagnostic testing.

A growing understanding of the molecular pathology of tumours combined with a surge of new drugs and associated diagnostic technologies (ie, precision medicine) has translated into substantial improvements in survival for patients with cancer. However, to achieve the promise that precision medicine has to offer will require overcoming hurdles within a national health-care system in which it is to be implemented. Brazil is one such nation, an emerging middle-income country with a very complex health-care system. To address the challenges associated with implementing precision medicine into a country such as Brazil, a group of experts convened (Nov 16-18, 2015, Miami) to discuss challenges related to precision medicine within an oncology setting. Complex regulatory hurdles, a shortage of human and technical resources, and the complexities of a two-tiered health-care delivery system were all identified as the main shortcomings to effectively implementing this new field of medicine. A path forward was proposed that relies on active collaboration between clinicians, private organisations, and government. It seems entirely possible that, despite many intrinsic economic and political problems, Brazil can readily emerge as a model for other countries in Latin America for the potential benefits of precision medicine and companion diagnostics.