ABSTRACT
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.
ABSTRACT
Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of Arthrobacter luteus elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.
