Pediatric Acute Promyelocytic Leukemia: Epidemiology, Molecular Features, and Importance of GST-Theta 1 in Chemotherapy Response and Outcome.

Previous studies have suggested a variation in the incidence of acute promyelocytic leukemia (APL) among the geographic regions with relatively higher percentages in the Latin American population. We aimed to explore the population burden of pediatric APL, gathering information from the population-based cancer registry (PBCR) and the diagnosis of APL obtained through incident cases from a hospital-based cohort. The homozygous deletion in glutathione S-transferases (GSTs) leads to a loss of enzyme detoxification activity, possibly affecting the treatment response. Mutations in the RAS pathway genes are also considered to be a key component of the disease both in the pathogenesis and in the outcomes. We have assessed mutations in a RAS-MAP kinase pathway (FLT3, PTPN11, and K-/NRAS) and GST variant predisposition risk in the outcome. Out of the 805 children and adolescents with acute myeloid leukemia (AML) who are registered in the PBCR, 35 (4.3%) were APL cases. The age-adjusted incidence rate (AAIR) was 0.03 per 100,000 person-years. One-hundred and sixty-three patients with APL were studied out of 931 AML cases (17.5%) from a hospital-based cohort. Mutations in FLT3, KRAS, and NRAS accounted for 52.1% of the cases. Patients with APL presented a 5-year probability of the overall survival (OS) of 67.3 ± 5.8%. A GST-theta 1 (GSTT1) null genotype conferred adverse prognosis, with an estimated hazard ratio of 2.8, 95% confidence interval (CI) 1.2-6.9. We speculate that the GSTT1 polymorphism is associated with therapeutics and would allow better OS of patients with APL with a GSTT1 null genotype.

Delays in the health care system for children, adolescents, and young adults with bone tumors in Brazil / Atrasos no sistema de saúde para crianças, adolescentes e adultos jovens com tumores ósseos no Brasil

ABSTRACT Objective: To identify delays in the health care system experienced by children and adolescents and young adults (AYA; aged 0-29 years) with osteosarcoma and Ewing sarcoma using information from the Brazilian hospital-based cancer registries. Methods: Patient data were extracted from 161 Brazilian hospital-based cancer registries between 2007 and 2011. Hospital, diagnosis, and treatment delays were analyzed in patients without a previous histopathological diagnosis. Referral, hospital, and health care delays were calculated for patients with a previous histopathological diagnosis. The time interval was measured in days. Results: There was no difference between genders in overall delays. All delays increased at older ages. Patients without a previous histopathological diagnosis had the longest hospital delay when compared to patients with a previous histopathological diagnosis before first contact with the cancer center. Patients with Ewing sarcoma had longer referral and health care delays than those with osteosarcoma who had a previous histopathological diagnosis before first contact with the cancer center. The North and Northeast regions had the longest diagnosis delay, while the Northeast and Southeast regions had the longest treatment delay. Conclusion: Health care delay among patients with a previous diagnosis was longer, and was probably associated with the time taken for to referral to cancer centers. Patients without a previous histopathological diagnosis had longer hospital delays, which could be associated with possible difficulties regarding demand and high-cost procedures. Despite limitations, this study helps provide initial knowledge about the healthcare pathway delays for patients with bone cancer inside several Brazilian hospitals.

RESUMO Objetivo: Identificar atrasos no sistema de saúde em crianças e adolescentes e adultos jovens (AAJ; até 29 anos) com osteossarcoma e sarcoma de Ewing com informações dos registros de câncer de base hospitalar do Brasil. Métodos: Os dados dos pacientes foram extraídos de 161 registros de câncer de base hospitalar brasileiros entre 2007 e 2011. Os atrasos no hospital, no diagnóstico e no tratamento foram analisados em pacientes sem um diagnóstico histopatológico anterior. Os atrasos no encaminhamento, no hospital e no sistema de saúde foram calculados para pacientes com diagnóstico histopatológico anterior. O intervalo de tempo foi medido em dias. Resultados: Não houve diferença entre os sexos nos atrasos em geral. Todos os atrasos aumentaram na faixa etária mais velha. Os pacientes sem um diagnóstico histopatológico anterior apresentaram o atraso hospitalar mais longo em comparação com os pacientes com diagnóstico histopatológico anterior antes do primeiro contato com o centro de câncer. Os pacientes com sarcoma de Ewing apresentaram atrasos no encaminhamento e no sistema de saúde mais longos do que os com osteossarcoma, que apresentaram diagnóstico histopatológico anterior antes do primeiro contato com o centro oncológico. As regiões Norte e Nordeste apresentaram o atraso mais longo no diagnóstico, ao passo que as regiões Nordeste e Sul apresentaram o atraso mais longo no tratamento. Conclusão: O atraso no sistema de saúde entre os pacientes com diagnóstico anterior foi maior e provavelmente associado ao tempo de encaminhamento para os centros oncológicos. Os pacientes sem um diagnóstico histopatológico anterior apresentaram atrasos mais longos no hospital, o que pode ser associado a possíveis dificuldades com relação à demanda e aos procedimentos de alto custo. Apesar das limitações, nosso estudo ajuda a fornecer um conhecimento inicial sobre os atrasos no sistema de saúde para tratamento de pacientes com câncer em vários hospitais brasileiros.

Who cares for adolescents and young adults with cancer in Brazil? / Onde são tratados os adolescentes e jovens adultos com câncer no Brasil?

Abstract Objective: Approximately 6% of all cancers arise in adolescents and young adults. Currently, the ward type best placed to treat this patient group remains controversial. The aim of this study was to evaluate exactly where adolescents and young adults with cancer are treated in Brazil. Methods: Data were extracted from 271 Brazilian hospital-based cancer registries (2007-2011), including all five national regions (North, Northeast, Midwest, South, and Southeast). Variables included gender, age, ethnicity, National Code of Health Establishment, hospital unit state, and region. Tumors were classified according to the World Health Organization classification for adolescents and young adults with cancer. Odds ratios with 95% confidence intervals were computed by unconditional logistic regression. Results: Most patients were managed on medical oncology wards, followed by pediatric oncology and then by non-specialist wards. Of patients aged 15-19 years, 49% were managed on pediatric wards; most of the older patients (96%; aged 20-24) were managed on adult wards. Patients were more likely to be seen in medical oncology wards as their age increased (OR = 2.03 [1.98-2.09]), or if they were based in the South (OR = 1.50 [1.29-1.73]). Conversely, bone tumors were less likely to be treated (decreased OR) on medical oncology wards, regardless of age, gender, and region. Conclusion: An elevated risk of treatment on medical oncology wards was observed for older patients and those treated in the South. Bone tumors were generally treated in pediatric oncology wards, while skin cancers were treated in medical oncology wards, regardless of age, gender, and region.

Resumo Objetivo: Aproximadamente 6% de todos os cânceres surgem em adolescentes e adultos jovens. Atualmente, o melhor tipo de enfermaria para tratar esse grupo de pacientes continua sendo controverso. O objetivo deste estudo foi avaliar exatamente onde os adolescentes e adultos jovens com câncer são tratados no Brasil. Métodos: Foram coletados dados de 271 registros de câncer de base hospitalar (2007-2011), inclusive de todas as cinco regiões nacionais (Norte, Nordeste, Centro-Oeste, Sul e Sudeste). As variáveis incluíram sexo, idade, etnia, o Código Nacional de Estabelecimento de Saúde e o estado e a região da unidade hospitalar. Os tumores foram classificados de acordo com a classificação da Organização Mundial de Saúde para adolescentes e adultos jovens com câncer. As razões de chance com intervalos de confiança de 95% foram calculadas por regressão logística incondicional. Resultados: A maioria dos pacientes foi tratada em enfermaria de oncologia médica, seguido da enfermaria de oncologia pediátrica e, então, a enfermaria sem especialidade. 49% dos pacientes entre 15-19 anos foram tratados em enfermarias pediátricas; os pacientes mais velhos (96%, entre 20-24) foram tratados em enfermarias de adultos. Os pacientes apresentaram maior propensão a serem vistos em enfermarias de oncologia conforme mais velhos (RC = 2,03 [1,98-2,09]) ou caso morassem na região Sul (RC = 1,50 [1,29-1,73]). Por outro lado, os tumores ósseos mostraram menor propensão a tratamento (redução da RC) em enfermarias de oncologia, independentemente da idade, sexo e região. Conclusão: Foi visto um risco elevado de tratamento, em enfermarias de oncologia, de pacientes mais velhos e os tratados na Região Sul. Os tumores ósseos foram, em geral, tratados em enfermarias de oncologia pediátrica, ao passo que os cânceres de pele foram tratados em enfermarias de oncologia médica, independentemente de idade, sexo e região.

Who cares for adolescents and young adults with cancer in Brazil?

OBJECTIVE: Approximately 6% of all cancers arise in adolescents and young adults. Currently, the ward type best placed to treat this patient group remains controversial. The aim of this study was to evaluate exactly where adolescents and young adults with cancer are treated in Brazil. METHODS: Data were extracted from 271 Brazilian hospital-based cancer registries (2007-2011), including all five national regions (North, Northeast, Midwest, South, and Southeast). Variables included gender, age, ethnicity, National Code of Health Establishment, hospital unit state, and region. Tumors were classified according to the World Health Organization classification for adolescents and young adults with cancer. Odds ratios with 95% confidence intervals were computed by unconditional logistic regression. RESULTS: Most patients were managed on medical oncology wards, followed by pediatric oncology and then by non-specialist wards. Of patients aged 15-19 years, 49% were managed on pediatric wards; most of the older patients (96%; aged 20-24) were managed on adult wards. Patients were more likely to be seen in medical oncology wards as their age increased (OR=2.03 [1.98-2.09]), or if they were based in the South (OR=1.50 [1.29-1.73]). Conversely, bone tumors were less likely to be treated (decreased OR) on medical oncology wards, regardless of age, gender, and region. CONCLUSION: An elevated risk of treatment on medical oncology wards was observed for older patients and those treated in the South. Bone tumors were generally treated in pediatric oncology wards, while skin cancers were treated in medical oncology wards, regardless of age, gender, and region.