How should childhood acute lymphoblastic leukemia relapses in low-income and middle-income countries be managed: The AHOPCA-ALL study group experience.

BACKGROUND: Children with relapsed acute lymphoblastic leukemia (ALL) in low-income and middle-income countries rarely survive. The Pediatric Hematology-Oncology Association of Central America (AHOPCA) developed the AHOPCA-ALL REC 2014 protocol to improve outcomes in resource-constrained settings without access to stem cell transplantation. METHODS: The AHOPCA-ALL REC 2014 protocol was based on a modified frontline induction phase 1A, a consolidation therapy with six modified R-blocks derived from the ALL-Berlin-Frankfurt-Munster REZ 2002 protocol and intermittent maintenance therapy. Children with B-lineage ALL were eligible after a late medullary relapse, an early or late combined relapse, or any extramedullary relapses. Those with T-lineage ALL were eligible after early and late extramedullary relapses, as were those with both B-lineage and T-lineage relapses occurring at least 3 months after therapy abandonment. RESULTS: The study population included 190 patients with T-lineage (n = 3) and B-lineage (n = 187) ALL. Of those with B-lineage ALL, 25 patients had a very early extramedullary relapse, 40 had an early relapse (32 extramedullary and 8 combined), and 125 had a late relapse (34 extramedullary, 19 combined, and 72 medullary). The main cause of treatment failure was second relapse (52.1%). The 3-year event-free survival rate (± standard error) was 25.9% ± 3.5%, and the 3-year overall survival rate was 36.7% ± 3.8%. The 3-year event-free survival rate was 47.2% ± 4.7% for late relapses. The most frequently reported toxicity was grade 3 or 4 infection. Mortality during treatment occurred in 17 patients (8.9%), in most cases because of infectious complications. CONCLUSIONS: Selected children with relapsed ALL in Central America can be cured with second-line regimens even without access to consolidation with stem cell transplantation. Children in low-income and middle-income countries who have lower risk relapses of ALL should be treated with curative intent.

Development of EPAT: An assessment tool for pediatric hematology/oncology training programs.

PURPOSE: In the absence of a standardized tool to assess the quality of pediatric hematology/oncology training programs, the Education Program Assessment Tool (EPAT) was conceptualized as a user-friendly and adaptable tool to evaluate and identify areas of opportunity, pinpoint needed modifications, and monitor progress for training programs around the world. METHODS: The development of EPAT consisted of three main phases: operationalization, consensus, and piloting. After each phase, the tool was iteratively modified based on feedback to improve its relevance, usability, and clarity. RESULTS: The operationalization process led to the development of 10 domains with associated assessment questions. The two-step consensus phase included an internal consensus phase to validate the domains and a subsequent external consensus phase to refine the domains and overall function of the tool. EPAT domains for programmatic evaluation are hospital infrastructure, patient care, education infrastructure, program basics, clinical exposure, theory, research, evaluation, educational culture, and graduate impact. EPAT was piloted in five training programs in five countries, representing diverse medical training and patient care contexts for proper validation of the tool. Face validity was confirmed by a correlation between the perceived and calculated scores for each domain (r = 0.78, p < .0001). CONCLUSIONS: EPAT was developed following a systematic approach, ultimately leading to a relevant tool to evaluate the different core elements of pediatric hematology/oncology training programs across the world. With EPAT, programs will have a tool to quantitatively evaluate their training, allowing for benchmarking with centers at the local, regional, and international level.

Implementation of a formalized evaluation and planning tool to improve pediatric oncology outcomes in Kenya.

BACKGROUND: Survival from pediatric cancers in low middle-income countries is often very low compared to that of high-income countries due to multifactorial etiologies, including late presentation, delayed diagnosis, difficulty with accessing healthcare, drug unavailability, and treatment abandonment. The St. Jude Pediatric Oncology Facility Integrated Local Evaluation Tool (PrOFILE) was developed to map and evaluate childhood cancer healthcare delivery in individual institutions and entire countries, identifying the strengths and weaknesses, as well as opportunities for advancement of care. PROCEDURE: Using the PrOFILE self-assessment tool, selected Kenyan pediatric oncology facilities entered data into 12 modules: national context, facility and local context, finances and resources, personnel, service capacity, service integration, diagnostics, chemotherapy, supportive care, surgery, radiation therapy, and patients and outcomes. These modules are grouped into five specific components, including Context, Workforce, Diagnostics, Therapy, and Patients and Outcomes. The St. Jude PrOFILE team analyzed the data and organized the first hybrid workshop, containing both in-person and virtual components. RESULTS: Multidisciplinary stakeholders prioritized recommendations for improving care and developed smart objectives to accomplish identified goals over the following 2 years. Strengths and weaknesses of conducting a hybrid global workshop were identified. CONCLUSIONS: We demonstrated successful use of the PrOFILE tool to conduct a hybrid workshop and identify strategies to improve pediatric oncology care in Kenya. The voluntarily structured work groups will methodically aim to achieve outcome-oriented goals moving forward.

Regional collaboration for the development of national childhood cancer plans in Latin America and the Caribbean.

This article aims to describe the activities conducted by the National Childhood Cancer Plan Working Group to support the development of national childhood cancer plans in Latin America and the Caribbean in the period 2019-2022, and to present the stage of plan development. The Working Group activities were supported by the Pan American Health Organization and St. Jude Children's Research Hospital, which is the World Health Organization (WHO) Collaborating Centre for Childhood Cancer. Year after year, the workshops and activities developed with the Working Group mobilized key stakeholders: pediatric oncologists, representatives of the Ministry of Health, foundations supporting childhood cancer initiatives, and hospital administrators. As of February 2023, one regional framework is in place, approved by the Council of Ministries of Health of Central America and the Dominican Republic, nine countries are currently implementing national plans or laws that include childhood cancer, and ten countries are writing new plans. The WHO three-step framework helped to guide the Working Group activities. All plans were supported by a situational analysis, which highlighted the importance of having systematized data for evidence-based policies. To increase implementation success, an accompanying budget and timeline help to ensure the adequate implementation of the interventions. More than anything, committed stakeholders remain the most fundamental element to successfully write and approve a national childhood cancer plan. This is an opportunity to share these countries' experience so the strategy can be adapted to support other countries developing a childhood cancer plan and extended to other public health areas.

En este artículo se describen las actividades realizadas por el grupo de trabajo del plan nacional contra el cáncer infantil dirigidas a brindar apoyo para la formulación de planes nacionales contra el cáncer infantil en América Latina y el Caribe en el período 2019-2022, así como la presentación de la etapa de formulación de los planes. Las actividades del Grupo de Trabajo contaron con el apoyo de la Organización Panamericana de la Salud y el St. Jude Children's Research Hospital, que es el centro colaborador de la Organización Mundial de la Salud (OMS) contra el cáncer infantil. Año tras año, los talleres y actividades llevados a cabo con el grupo de trabajo han logrado convocar a las principales partes interesadas: especialistas en oncología pediátrica, representantes del Ministerio de Salud, fundaciones que apoyan iniciativas contra el cáncer infantil y gerentes de los hospitales. Desde febrero del 2023, existe un marco regional, aprobado por el Consejo de Ministerios de Salud de Centroamérica y República Dominicana; nueve países ya están aplicando planes o leyes nacionales en los que se incluye el cáncer infantil, y diez países están redactando nuevos planes. Para orientar las actividades del Grupo de Trabajo, se recurrió al marco en tres pasos de la OMS. Todos los planes se sustentaron en un análisis de situación lo que subraya la importancia de contar con datos sistematizados para que las políticas puedan estar basadas en evidencias. Asimismo, si se pretende aumentar el éxito de la aplicación, sería conveniente contar con un presupuesto y un cronograma que aseguren la aplicación adecuada de las intervenciones. Las partes interesadas implicadas siguen siendo, ante todo, el componente más trascendente en la redacción y aprobación exitosa de un plan nacional contra el cáncer infantil. Esta es una oportunidad para transmitir la experiencia de estos países, con el fin de que la estrategia pueda adaptarse para brindar apoyo a otros países que estén elaborando un plan contra el cáncer infantil y que puede hacerse extensiva a otros ámbitos de la salud pública.

Este artigo visa a descrever as atividades realizadas pelo Grupo de Trabalho para Planos Nacionais de Combate ao Câncer infantil a fim de prestar apoio ao desenvolvimento de planos nacionais de combate ao câncer infantil na América Latina e no Caribe no período de 2019 a 2022 e apresentar a atual fase de desenvolvimento dos planos. As atividades do Grupo de Trabalho receberam apoio da Organização Pan-Americana da Saúde e do St. Jude Children's Research Hospital, o Centro Colaborador em Câncer infantil da Organização Mundial da Saúde (OMS). Ano após ano, as oficinas e atividades desenvolvidas com o Grupo de Trabalho mobilizaram as principais partes interessadas: oncologistas pediátricos, representantes dos ministérios da saúde, fundações que apoiam iniciativas de combate ao câncer infantil e administradores de hospitais. Até fevereiro de 2023, havia uma estrutura regional em vigor aprovada pelo Conselho de Ministros da Saúde da América Central e da República Dominicana, nove países estavam implementando planos ou leis nacionais que incluíam o câncer infantil e dez países estavam elaborando novos planos. A estrutura de três etapas da OMS ajudou a orientar as atividades do Grupo de Trabalho. Todos os planos estavam embasados em uma análise situacional, o que destacou a importância de dispor de dados sistematizados para políticas baseadas em evidências. Para aumentar o sucesso da implementação, um orçamento e um cronograma correspondentes ajudam a garantir a implementação adequada das intervenções. Acima de tudo, o compromisso das partes interessadas continua sendo o elemento mais fundamental para elaborar e aprovar com sucesso um plano nacional de combate ao câncer infantil. Esta é uma oportunidade de compartilhar a experiência desses países para que a estratégia possa ser adaptada a fim de apoiar outros países na elaboração de um plano de combate ao câncer infantil e possa ser estendida a outras áreas de saúde pública.

Advances in the Global Initiative for Childhood Cancer: implementation in Latin America and the Caribbean.

This report describes the status of childhood cancer control initiatives in Latin America and the Caribbean (LAC). Progress between 2017 and 2023 is measured using the outcome indicators from the Pan American Health Organization (PAHO) childhood cancer logic model aligned with the World Health Organization Global Initiative for Childhood Cancer (GICC). This report also describes the advances, barriers, and facilitators for the implementation of the GICC at the Regional level. Methods used in this report encompassed a comprehensive approach, incorporating a literature review, interviews, surveys, and a Delphi study developed by the technical team of the PAHO Non-Communicable Diseases and Mental Health Department and by the GICC LAC working group. Since 2017, there has been a substantial increase in the number of countries that have included childhood cancer in their national regulations. Currently, 21 LAC countries are involved in the GICC implementation, activities, and dialogues. However, the objectives for 2030 will only be achieved if Member States overcome the barriers to accelerating the pace of initiative implementation. There is an urgent need to increase the efforts in childhood cancer control in LAC, especially regarding the prioritization of timely detection, essential diagnostics, access to cancer treatment, palliative care, and close follow-up of children and adolescents with cancer.

En este artículo se describe la situación de las iniciativas para el control del cáncer infantil en América Latina y el Caribe. Para medir los progresos entre el 2017 y el 2023, se utilizan los indicadores de resultados del modelo lógico del cáncer infantil de la Organización Panamericana de la Salud (OPS) que es coherente con la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud. También se describen los avances, los obstáculos y los elementos que han facilitado la aplicación de esa iniciativa en la Región Los métodos utilizados en este trabajo incluyeron un enfoque integral que incorporó una revisión bibliográfica, entrevistas, encuestas y un estudio de tipo Delfos llevado a cabo por el equipo técnico del Departamento de Enfermedades No Transmisibles y Salud Mental de la OPS y por el grupo de trabajo de América Latina y el Caribe de la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud.Desde el 2017 ha habido un incremento considerable en el número de países que incorporan el cáncer infantil en sus regulaciones nacionales. En la actualidad, 21 países de América Latina y el Caribe participan en la puesta en práctica, las actividades y las deliberaciones de la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud. No obstante, los objetivos para el 2030 solo podrán alcanzarse si los Estados Miembros son capaces de superar los obstáculos que dificultan la aceleración del ritmo de aplicación de esta iniciativa. Existe una necesidad urgente de aumentar las actividades dirigidas al control del cáncer infantil en América Latina y el Caribe, en especial en lo que respecta a priorizar la detección temprana, los medios de diagnóstico esenciales, el acceso a los tratamientos oncológicos, los cuidados paliativos y el seguimiento estricto de la población infantil y adolescente con cáncer.

Este relatório descreve a situação das iniciativas de controle do câncer infantil na Região da América Latina e do Caribe (ALC). O progresso alcançado entre 2017 e 2023 foi medido usando os indicadores de resultados intermediários do modelo lógico de câncer infantil da Organização Pan-Americana da Saúde (OPAS), em linha com a Iniciativa Global para o Câncer Infantil (GICC) da Organização Mundial da Saúde. O relatório também descreve os avanços, as barreiras e os facilitadores para a implementação da iniciativa em nível regional. Os métodos utilizados neste relatório aplicaram uma abordagem abrangente que incluiu revisão da literatura, entrevistas, levantamentos e um estudo Delphi desenvolvido pela equipe técnica do Departamento de Doenças Não Transmissíveis e Saúde Mental da OPAS e pelo grupo de trabalho da GICC para a ALC.Desde 2017, houve um aumento significativo no número de países que passaram a incluir o câncer infantil em regulamentações nacionais. Atualmente, 21 países da América Latina e do Caribe estão envolvidos na implementação da GICC, bem como em atividades e diálogos relacionados. No entanto, os objetivos para 2030 só serão alcançados se os Estados Membros superarem as barreiras ao aceleramento do ritmo de implementação da iniciativa. Existe uma necessidade urgente de intensificar os esforços de controle do câncer infantil na ALC, especialmente no tocante à priorização da detecção em tempo hábil, diagnósticos essenciais, acesso a tratamentos oncológicos, cuidados paliativos e acompanhamento cuidadoso de crianças e adolescentes com câncer.

Collaboration for success: the Global Initiative for Childhood Cancer in Latin America.

The Global Initiative for Childhood Cancer (GICC) aims to increase the cure rate for children with cancer globally by improving healthcare access and quality. The Pan American Health Organization (PAHO), St. Jude Children's Research Hospital (St. Jude), and collaborators have joined efforts to improve outcomes of children with cancer in Latin America and the Caribbean (LAC) using the CureAll framework. In this article, we describe the process of developing regional resources aimed at accelerating the GICC implementation in LAC. In March 2021, PAHO formed regional working groups to develop core projects aligned with CureAll pillars and enablers. Seven working groups emerged from regional dialogues: early detection, nursing, psychosocial, nutrition, supportive care, treatment abandonment, and palliative care. PAHO arranged regular online meetings under the mentorship and support of St. Jude regional/transversal programs and international mentors. Between April and December 2021, 202 multidisciplinary experts attended 43 online meetings to promote the dialogue between stakeholders to improve childhood cancer outcomes. Fourteen technical outputs were produced: four regional snapshots, four technical documents, two virtual courses, one set of epidemiological country profiles, one educational content series for parents/caregivers, and two communication campaigns. The ongoing dialogue and commitment of PAHO, St. Jude, LAC working committees, and international collaborators are essential foundations to successfully accelerate GICC implementation. This is achievable through the development of materials of regional and global relevance. Further research and evaluation are needed to determine the impact of these strategies and resources on childhood cancer outcomes in LAC and other regions.

La Iniciativa Mundial contra el Cáncer Infantil tiene como objetivo aumentar a nivel mundial la tasa de curación del cáncer infantil mediante la mejora del acceso a la atención de salud y de su calidad. La Organización Panamericana de la Salud (OPS), el St. Jude Children's Research Hospital y los colaboradores han aunado esfuerzos para mejorar los resultados en la población infantil con cáncer en América Latina y el Caribe valiéndose del marco CureAll. En este artículo describimos el proceso de elaboración de recursos regionales destinados a acelerar la aplicación de la Iniciativa Mundial en América Latina y el Caribe.En marzo del 2021, la OPS formó grupos de trabajo regionales para elaborar proyectos básicos que estuvieran en consonancia con los pilares y los elementos facilitadores del CureAll. De los diálogos regionales surgieron siete grupos de trabajo: detección temprana, enfermería, aspectos psicosociales, nutrición, tratamientos de apoyo, abandono del tratamiento y cuidados paliativos. La OPS organizó con regularidad reuniones virtuales en las que se contó con la tutoría y el apoyo de programas regionales o transversales del St. Jude Children's Research Hospital y de mentores internacionales.Entre abril y diciembre del 2021 hubo 43 reuniones virtuales a las que asistieron 202 expertos multidisciplinarios, con el objetivo de promover el diálogo entre las partes interesadas para mejorar los resultados en materia de cáncer infantil. Se elaboraron catorce productos técnicos: cuatro panoramas regionales, cuatro documentos técnicos, dos cursos virtuales, un conjunto de perfiles epidemiológicos de países, una serie con contenidos educativos para padres y cuidadores y dos campañas de comunicación.El diálogo y el compromiso constantes de la OPS, el St. Jude Children's Research Hospital, los comités de trabajo de América Latina y el Caribe y los colaboradores internacionales son las bases fundamentales para conseguir que se acelere la aplicación de la Iniciativa Mundial. Esto se puede lograr mediante la elaboración de materiales que resulten pertinentes a nivel regional y mundial. Son necesarias más investigaciones y evaluaciones para determinar el impacto que tienen estas estrategias y recursos en los resultados que se obtienen en el cáncer infantil en América Latina y el Caribe y en otras subregiones.

A Iniciativa Global para o Câncer Infantil tem como objetivo aumentar a taxa de cura de crianças com câncer no mundo todo, melhorando o acesso a cuidados e a qualidade da assistência médica. A Organização Pan-Americana da Saúde (OPAS), o St. Jude Children's Research Hospital (St. Jude) e colaboradores uniram esforços para melhorar o desfecho de crianças com câncer na América Latina e no Caribe (ALC) no âmbito do marco CureAll. Neste artigo, descrevemos o processo de desenvolvimento de recursos regionais com o objetivo de acelerar a implementação da Iniciativa na ALC.Em março de 2021, a OPAS formou grupos de trabalho regionais para desenvolver projetos centrais alinhados com os pilares e facilitadores do CureAll. A partir das reuniões de diálogo regionais, foram criados sete grupos de trabalho: detecção precoce, enfermagem, atenção psicossocial, nutrição, cuidados de suporte, abandono do tratamento e cuidados paliativos. A OPAS organizou reuniões virtuais regulares sob a orientação e o apoio dos programas regionais e transversais do St. Jude e de mentores internacionais.Entre abril e dezembro de 2021, 202 especialistas multidisciplinares participaram de 43 reuniões virtuais para promover o diálogo entre as partes interessadas a fim de melhorar os desfechos do câncer infantil. Foram produzidos 14 materiais técnicos: quatro panoramas regionais, quatro documentos técnicos, dois cursos virtuais, um conjunto de perfis epidemiológicos nacionais, uma série de conteúdo educacional para pais e cuidadores e duas campanhas de comunicação.O diálogo e o compromisso contínuos da OPAS, do St. Jude, dos comitês de trabalho da ALC e dos colaboradores internacionais são bases essenciais para acelerar com sucesso a implementação da Iniciativa Global para o Câncer Infantil. Isso é possível por meio do desenvolvimento de materiais de relevância regional e mundial. São necessárias mais pesquisas e avaliações para determinar o impacto dessas estratégias e recursos nos resultados do câncer infantil na ALC e em outras regiões.

Strengthening public health policies for childhood cancer: Peru's achievements through the WHO Global Initiative for Childhood Cancer.

Objective: To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the CureAll framework, which can be replicated in low- and middle-income countries. Methods: A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services. Results: Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology. Conclusions: The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study.

BACKGROUND: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. METHODS: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. FINDINGS: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8-8·8]; p<0·0001) and upper-middle-income (1·6 [1·2-2·2]; p=0·0024) country status; age 15-18 years (1·6 [1·1-2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8-3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3-2·4]; p=0·0001), and intensive treatment (1·8 [1·3-2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3-0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3-0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3-2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1-2·3]; p=0·020). INTERPRETATION: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. FUNDING: American Lebanese Syrian Associated Charities and the National Cancer Institute.

Sustainable care for children with cancer: a Lancet Oncology Commission.

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020-50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.

Young Female Donors Do Not Increase the Risk of Graft-versus-Host Disease or Impact Overall Outcomes in Pediatric HLA-Matched Sibling Hematopoietic Stem Cell Transplantation.

Optimal donor selection is critical in hematopoietic stem cell transplantation (HSCT). Donor-recipient sex mismatch, donor age, and female donor-donor parity are known to impact graft-versus-host disease (GVHD) and outcomes in adults. Minor histocompatibility antigens encoded by the human Y chromosome can result in specific antibody formation in some female donors, may increase in frequency with increasing donor age, and may be contributory to the increased incidence of GVHD. To better understand the role of donor age/sex and sex matching in HSCT outcomes, we conducted a retrospective study of pediatric patients receiving their first myeloablative sibling donor HSCT (n = 244) from 1998 to 2012. Observed rates of GVHD were low: 17% of patients surviving past engraftment (n = 243) developed grades II to IV acute GVHD (aGVHD) and 14% surviving ≥ 100 days (n = 229) developed chronic GVHD (cGVHD). On multivariate analysis the risk of aGVHD, cGVHD, and death increased with patient age as expected. Female donor sex and sex mismatch (female donor-male recipient) had no impact on the development of aGVHD. cGVHD was increased with female donors only if the donor was ≥12 years old. No cGVHD was observed among 109 patients aged < 10 years who received a 6/6 HLA-matched marrow HSCT, regardless of donor age or sex. Survival was mostly driven by diagnosis. Results suggest that in pediatric HSCT, young HLA-matched siblings are equivalently good donors regardless of sex or donor-recipient sex mismatch.

Delivery of radiation therapy in resource-limited settings: A pilot quality assessment study.

Progress has been made in resource-limited countries in treating acute lymphoblastic leukemia, but advances in solid malignancies have been slower. Multidisciplinary care coordination is challenging, assessing adherence to guidelines through quality improvement initiatives is essential. We characterized deviations from guidelines in the delivery of radiation in a middle-income country program as a pilot for evaluating adequacy of local control and as surrogate for integration of multidisciplinary care. One-third of patients for whom it was indicated did not receive radiation. Of the patients who received radiation, 95% had a deviation. This study underscores the importance of quality assessment in resource-limited settings.

Paediatric cancer stage in population-based cancer registries: the Toronto consensus principles and guidelines.

Population-based cancer registries generate estimates of incidence and survival that are essential for cancer surveillance, research, and control strategies. Although data on cancer stage allow meaningful assessments of changes in cancer incidence and outcomes, stage is not recorded by most population-based cancer registries. The main method of staging adult cancers is the TNM classification. The criteria for staging paediatric cancers, however, vary by diagnosis, have evolved over time, and sometimes vary by cooperative trial group. Consistency in the collection of staging data has therefore been challenging for population-based cancer registries. We assembled key experts and stakeholders (oncologists, cancer registrars, epidemiologists) and used a modified Delphi approach to establish principles for paediatric cancer stage collection. In this Review, we make recommendations on which staging systems should be adopted by population-based cancer registries for the major childhood cancers, including adaptations for low-income countries. Wide adoption of these guidelines in registries will ease international comparative incidence and outcome studies.

Barriers to effective treatment of pediatric solid tumors in middle-income countries: can we make sense of the spectrum of nonbiologic factors that influence outcomes?

BACKGROUND: The delivery of effective treatment for pediatric solid tumors poses a particular challenge to centers in middle-income countries (MICs) that already are vigorously addressing pediatric cancer. The objective of this study was to improve the current understanding of barriers to effective treatment of pediatric solid tumors in MICs. METHODS: An ecologic model centered on pediatric sarcoma and expanded to country as the environment was used as a benchmark for studying the delivery of solid tumor care in MICs. Data on resources were gathered from 7 centers that were members of the Central American Association of Pediatric Hematologists and Oncologists (AHOPCA) using an infrastructure assessment tool. Pediatric sarcoma outcomes data were available, were retrieved from hospital-based cancer registries for 6 of the 7 centers, and were analyzed by country. Patients who were diagnosed from January 1, 2000 to December 31, 2009 with osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and other soft tissue sarcomas were included in the analysis. To explore correlations between resources and outcomes, a pilot performance index was created. RESULTS: The analyses identified specific deficits in human resources, communication, quality, and infrastructure. The treatment abandonment rate, the proportion of metastatic disease at diagnosis, the relapse rate, and the 4-year abandonment-sensitive overall survival (AOS) rate varied considerably by country, ranging from 1% to 38%, from 15% to 54%, from 24% to 52%, and from 21% to 51%, respectively. The treatment abandonment rate correlated inversely with health economic expenditure per capita (r = -0.86; P = .03) and life expectancy at birth (r = -0.93; P = .007). The 4-year AOS rate correlated inversely with the mortality rate among children aged <5 years (r = -0.80; P = 0.05) and correlated directly with the pilot performance index (r = 0.98; P = 0.005). CONCLUSIONS: Initiatives to improve the effectiveness of treatment for pediatric solid tumors in MICs are warranted, particularly for pediatric sarcomas. Building capacity and infrastructure, improving supportive care and communication, and fostering comprehensive, multidisciplinary teams are identified as keystones in Central America. A measure that meaningfully describes performance in delivering pediatric cancer care is feasible and needed to advance comparative, prospective analysis of pediatric cancer care and to define resource clusters internationally.

Determining the cost and cost-effectiveness of childhood cancer treatment in Haiti.

Haiti is a low-income country with one of the lowest human development index rankings in the world. Its childhood cancer services are provided by a single hospital with the only dedicated paediatric oncology department in the country. Our objective was to assess the cost and cost-effectiveness of all types of childhood cancer in Haiti to help prioritise investments and to support national cancer control planning. All costing data were collected from the year 2017 or 2018 hospital records. Costs were classified into 11 cost categories, and the proportion of the overall budget represented by each was calculated and converted from Haitian Gourde to United States dollars. The 5-year survival rate was retrieved from hospital records and used to calculate the cost-effectiveness of disability-adjusted life year (DALY) averted, using a healthcare costing perspective. Additional sensitivity analyses were conducted accounting for late-effect morbidity and early mortality and discounting rates of 0%, 3% and 6%. The annual cost of operating a paediatric oncology unit in Haiti treating 74 patients with newly diagnosed cancer was $803,184 overall or $10,854 per patient. The largest cost category was pharmacy, constituting 25% of the overall budget, followed by medical personnel (20%) and administration (12%). The cost per DALY averted in the base-case scenario was $1,128, which is 76% of the gross domestic product per capita, demonstrating that treating children with cancer in Haiti is very cost-effective according to the World Health Organisation Choosing Interventions that are Cost-Effective (WHO-CHOICE) threshold. In the most conservative scenario, the cost per DALY averted was cost-effective by WHO-CHOICE criteria. Our data will add to the growing body of literature illustrating a positive return on investment associated with diagnosing and treating children with cancer in even the most resource-limited environments. We anticipate that these data will aid local stakeholders and policymakers when identifying cancer control priorities and making budgetary decisions.

Preventing and Treating Pain and Anxiety during Needle-Based Procedures in Children with Cancer in Low- and Middle-Income Countries.

Introduction: Children with cancer experience significant pain and anxiety during needle-based procedures. Undertreated pain in children has long-lasting consequences and reduces the efficacy of subsequent analgesic efforts. A validated quality improvement (QI) intervention, known as the "Children's Comfort Promise", includes (1) topical anesthetics, (2) sucrose or breastfeeding for infants, (3) comfort positioning, and (4) distraction techniques, and has been shown to be highly effective in decreasing procedural pain and anxiety in children. However, there is limited data about the adoption, adaptation, and implementation of these interventions in low- and middle-income countries (LMICs). Methods: A QI pilot project utilizing the Model for Improvement of the "Global Comfort Promise" was implemented in four global pediatric cancer hospitals (Lima, Peru; Barretos, Brazil; Pietermaritzburg, South Africa; and Manila, Philippines). Between August 2021 and January 2023, the pilot sites identified a specific aim, co-designed the measurement strategy with St. Jude Children's Research Hospital, and adopted, adapted, and implemented the project at their individual sites. Results: A total of 2,185 different procedures were recorded in the first year of implementation. Most patients were less than 10 years old (60.5%) and solid tumors (37.9%) were the most common diagnosis. Overall, healthcare professionals (98.3%) were satisfied with the procedures. Parents and patients reported that only 33.7% of patients experienced pain during the procedure. All (100%) parents and patients felt the healthcare teams adequately addressed their child's pain. Median self-reported adherence to ≥2 interventions was 98.0%. Challenges to the implementation of the QI initiative included lack of training, turnover of the medical staff, maintaining staff enthusiasm, and access to topical anesthetics. Each site had unique change ideas to implement the initiative. Conclusions: This multi-site, multi-country QI initiative was feasible and was successfully adopted, adapted, and implemented in the LMIC context to improve procedural pain in children (Global Comfort Promise). Additionally, this intervention resulted in high satisfaction of both healthcare professionals and patients/families. Further work is needed to overcome the challenges of topical anesthetic access and education of the workforce. Additional plans include modifying the Global Comfort Promise to include high-quality communication and expanding to additional sites with further refinement of the implementation strategy.

The Effect of COVID-19 on Oncology Care for Adolescents and Young Adults in Latin America.

Children with cancer in low- and middle-income countries were disproportionately impacted by the COVID-19 pandemic, but little is known about how adolescents and young adults (AYAs) with cancer were affected. Sixty-seven physicians and nonphysician providers were interviewed about their experiences caring for AYAs with cancer in Latin America. Quotes related to the COVID-19 pandemic were identified and grouped into themes. Barriers from the COVID-19 pandemic included limited space, restrictions on travel, reduced funding, limited staff, limited services, and changes to treatment. However, improvements to care that arose from the COVID-19 pandemic included better access to distance learning and telemedicine.

Impact of a Regional Pediatric Hematology/Oncology Fellowship Program in Guatemala.

PURPOSE: This study aimed to describe and assess the regional experience of a pediatric hematology/oncology fellowship program based in Guatemala. METHODS: The Unidad Nacional de Oncología Pediátrica (UNOP) in Guatemala City, Guatemala, is the only hospital in Central America dedicated exclusively to childhood and adolescent cancer. To address the regional need for specialists, a fellowship program in pediatric hematology/oncology was launched in 2003. The UNOP fellowship program comprises 3 years of training. Although the program is based at UNOP, it also includes rotations locally and internationally to enhance clinical exposure. The curriculum is based on international standards to cover clinical expertise, research, professionalism, communication, and health advocacy. Trainees are selected according to country or facility-level need for pediatric hematologists/oncologists, with a plan for them to be hired immediately after completing their training. RESULTS: Forty physicians from 10 countries in Latin America have completed training. In addition, there are currently 13 fellows from five countries in training. Of the graduates, 39 (98%) are now practicing in pediatric hematology/oncology in Latin America. Moreover, many of them have leadership positions within their institutions and participate in research, advocacy, and policy making. Graduates from the UNOP program contribute to institutions by providing care for an increasing number of patients with pediatric cancer. The UNOP program is the first pediatric hematology/oncology fellowship program in the world to be accredited by Accreditation Council for Graduate Medical Education-International, an international body accrediting clinical training programs. CONCLUSION: The UNOP program has trained specialists to increase the available care for children with cancer in Latin America. This regional approach to specialist training can maximize resources and serve as a model for other programs and regions.

Pediatric sarcoma in Central America: outcomes, challenges, and plans for improvement.

BACKGROUND: Children with cancer in middle-income countries have inferior outcomes compared with similar children in high-income countries. The magnitude and drivers of this survival gap are not well understood. In the current report, the authors sought to describe patterns of clinical presentation, magnitude of treatment abandonment, and survival in children with sarcoma in Central America. METHODS: A retrospective review was conducted of hospital-based registries from national pediatric oncology referral centers. Patients with newly diagnosed osteosarcoma, Ewing sarcoma, rhabdomyosarcoma (RMS), and soft tissue sarcoma (STS) between January 1, 2000 and December 31, 2009 were included. Survival analyses were performed first using standard definitions of overall survival (OS) and event-free survival (EFS) and then with abandonment included as an event (abandonment-sensitive OS and abandonment-sensitive EFS). RESULTS: In total, 785 new cases of pediatric sarcoma were reported (264 diagnoses of osteosarcoma, 175 diagnoses of Ewing sarcoma, 240 diagnoses of RMS, and 106 diagnoses of STS). The rate of metastatic disease at presentation was high (osteosarcoma, 38%; Ewing sarcoma, 39%; RMS, 29%; and STS, 21%). The treatment abandonment rate also was high, particularly among patients with extremity bone sarcomas (osteosarcoma, 30%; Ewing sarcoma, 15%; RMS, 25%; and STS, 15%). Of 559 patients who experienced a first event, 59% had either recurrent or progressive disease. The 4-year OS rate (±standard error) was 40% ± 3%, and the EFS rate was 30% ± 2%; however, these rates decreased further to 31% ± 2% and 24% ± 2%, respectively, when abandonment was taken into account. CONCLUSIONS: The current results indicated that high rates of metastases and treatment abandonment and difficulty with upfront treatment effectiveness are important contributors to the poor survival of children with pediatric sarcomas in Central America. Initiatives for early diagnosis, psychosocial support, quality improvement, and multidisciplinary care are warranted to improve outcomes.

Global challenges in pediatric oncology.

PURPOSE OF REVIEW: Reduction of child mortality is one of the Millennium Development Goals; as low-income and middle-income countries (LMICs) advance toward the achievement of this goal, initiatives aimed at reducing the burden of noncommunicable diseases, including childhood cancer, need to be developed. RECENT FINDINGS: Approximately 200 000 children and adolescents are diagnosed with cancer every year worldwide; of those, 80% live in LMICs, which account for 90% of the deaths. Lack of quality population-based cancer registries in LMICs limits our knowledge of the epidemiology of pediatric cancer; however, available information showing variations in incidence may indicate unique interactions between environmental and genetic factors that could provide clues to cause. Outcome of children with cancer in LMICs is dictated by late presentation and underdiagnosis, high abandonment rates, high prevalence of malnutrition and other comorbidities, suboptimal supportive and palliative care, and limited access to curative therapies. Initiatives integrating program building with education of healthcare providers and research have proven to be successful in the development of regional capacity. Intensity-graduated treatments adjusted to the local capacity have been developed. SUMMARY: Childhood cancer burden is shifted toward LMICs; global initiatives directed at pediatric cancer care and control are urgently needed. International partnerships facilitating stepwise processes that build capacity while incorporating epidemiology and health services research and implementing intensity-graduated treatments have been shown to be effective.

Ideal vs Actual Timing of Palliative Care Integration for Children With Cancer in Latin America.

Importance: Early integration of pediatric palliative care (PPC) for children with cancer is critical for the quality of life of both patient and family. To improve access to PPC in resource-limited settings, barriers to early integration must be understood. Objectives: To evaluate the ideal vs actual timing of PPC integration for children with cancer and to uncover barriers to early integration identified by physicians in Latin America. Design, Setting, and Participants: The Assessing Doctors' Attitudes on Palliative Treatment (ADAPT) survey was distributed electronically from August 1, 2020, to January 31, 2021, to physicians who treat children with cancer in 17 countries in Latin America. Main Outcomes and Measures: The ADAPT survey queried for understanding of ideal vs actual timing of PPC for children with cancer and for identification of barriers to PPC integration. Descriptive statistics were used to summarize the data. For secondary analyses, a comparison of the associations of previous palliative care training with physician specialty was performed using the Pearson χ2 test or the Fisher exact test. The McNemar test was used to assess responses regarding the actual vs ideal timing of PPC consultation. Analysis of variance was used to compare mean values for perceived barriers by country income level. Answers to open-ended questions were analyzed qualitatively. Results: A total of 831 physicians (578 women [69.6%]; 275 physicians [33.1%] aged <35 years and 556 physicians [66.9%] aged ≥35 years) from 17 countries participated, with an overall response rate of 37.9% (831 of 2193) and a median country response rate of 51.4% (range, 22.2%-88.9%). Most respondents (572 [68.8%]) said that PPC should be involved from diagnosis, but only 117 (14.1%) stated that this occurred at their institution (P < .001). The most significantly ranked barriers to PPC were lack of home-based services (713 [85.8%]), personnel (654 [78.7%]), and knowledge about PPC (693 [83.4%]), along with physician (676 [81.3%]) and family (603 [72.6%]) discomfort about PPC involvement. In addition, these barriers were rated as more important in lower-middle income countries compared with upper-middle income countries and high-income countries. Conclusions and Relevance: This study highlights the discrepancy between ideal and actual timing of PPC for children with cancer and barriers to early PPC integration in Latin America. Interventions addressing access to PPC resources, didactic training, and clinical education (with a particular focus on equitable access to basic resources and support) are critical to improve the timing and quality of PPC in the region.