Single cell RNA-sequencing of Ewing sarcoma tumors demonstrates transcriptional heterogeneity and clonal evolution.

Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients even prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. We also were able to identify the composition of the TME and molecularly dissect the transcriptional profile of circulating tumor cells in peripheral blood at the time of diagnosis.

Treatment of high-risk Hodgkin lymphoma with a modified Stanford V regimen in the AHOPCA: Substituting chemotherapy agents and hampered outcomes.

BACKGROUND/OBJECTIVES: High-risk Hodgkin lymphoma (HRHL) in children is curable with combined modality therapy. The Association of Pediatric Hematology-Oncology of Central America (AHOPCA) is a consortium of cancer centers from Central America. In 2004, AHOPCA implemented a guideline with a short course of chemotherapy (mStanfordV), strict diagnostics, and radiation guidelines, aimed at reducing abandonment and improving outcomes. METHODS: Newly diagnosed children less than 18 years of age with high-risk HL (Ann Arbor stages: IIB, IIIB, IV) from AHOPCA centers were staged with chest radiography and ultrasound or computed tomography. Therapy was a modified Stanford V (mStanfordV), substituting cyclophosphamide for mechlorethamine and involved field radiation. RESULTS: Of 219 patients with HRHL, 181 patients were eligible and evaluable; 146 (81%) were boys, 22% being less than 6 years; 43 were stage IIB, 84 IIIB, and 54 IV. Thirty-one (17%) abandoned therapy, 28 (15%) progressed, 30 (17%) relapsed, and eight (4%) died of toxicity. Radiation guidelines were not followed. Five-year abandonment-sensitive event-free survival and overall survival (AS-EFS, AS-OS ± SE) for the cohort were 46% ± 4% and 56% ± 4%; 5-year AS-OS for stages IIB, IIIB, and IV was 76% ± 7%, 59% ± 7%, and 35% ± 7% (p = .0006). CONCLUSION: Despite instituting a short treatment guideline, it did not improve the abandonment rate (17%) and did not achieve the reported outcomes of Stanford V. The cyclophosphamide dose used to replace merchlorethamine was inadequate. Despite strict guidelines, the radiation therapy application was inaccurate. Weekly chemotherapy may have adversely affected abandonment of therapy by increasing the burden of travel time. Based on these results, AHOPCA established a new abandonment strategy and a new guideline.

Global Initiative for Childhood Cancer: progress and challenges in Panama.

Despite being classified as a high-income country, Panama still faces challenges in providing care for children and adolescents with cancer. Annually, 170 new cases of childhood cancer are diagnosed in Panama, and the survival rate is around 60%. To improve this, the establishment of a Pediatric Cancer Commission comprised of healthcare professionals and nonprofit organizations has been a critical step toward the objectives outlined in the CureAll framework of the World Health Organization Global Initiative for Childhood Cancer (GICC). To improve childhood cancer care in Panama, a workshop for cancer in children and adolescents was conducted with the support of St. Jude Children's Research Hospital, Children's Hospital Colorado, the Ministry of Health of Panama, and the Pan American Health Organization. The commissions established were on: Nursing, Palliative Care, Psychosocial, Hospital Registry, Early Diagnosis, and Health Services. Each commission has a specific project to be implemented in the period 2021-2029 to continue the progress toward improving childhood cancer care. Since the start of implementation of the GICC in Panama, important achievements have included the launch in 2021 of the Guide for the Diagnosis of Cancer in Children and Adolescents, and training programs for primary care health personnel. Through these programs, more than 1 000 health professionals have been trained on diagnosis of cancer in childhood and adolescence. Challenges remain, such as access to quality care, and it is essential to continue efforts to improve childhood cancer care.

Pese a estar clasificado como un país de ingresos altos, Panamá aún debe hacer frente a distintos desafíos relacionados con la atención a la población infantil y adolescente con cáncer. Cada año, en Panamá se diagnostican 170 casos nuevos de cáncer pediátrico, con una tasa de supervivencia en torno al 60%. Para mejorar esta situación, la creación de una Comisión de Cáncer Pediátrico, conformada por profesionales de la salud y organizaciones sin fines de lucro, constituye un paso fundamental para lograr los objetivos planteados en el marco CureAll de la Iniciativa Mundial contra el Cáncer Infantil (GICC, por su sigla en inglés) de la Organización Mundial de la Salud.A fin de mejorar la atención de los pacientes pediátricos con cáncer en Panamá, se realizó un taller sobre el cáncer en la población infantil y adolescente. El evento contó con el apoyo del St. Jude Children's Research Hospital, el Children's Hospital Colorado, el Ministerio de Salud de Panamá y la Organización Panamericana de la Salud. Se crearon comisiones sobre enfermería, cuidados paliativos, aspectos psicosociales, registros hospitalarios, diagnóstico temprano y servicios de salud. Cada comisión está a cargo de un proyecto específico, que deberá ponerse en práctica en el período 2021-2029 para proseguir con los avances encaminados a mejorar la atención oncológica pediátrica.Desde que se inició el proceso de aplicación de la Iniciativa Mundial contra el Cáncer Infantil en Panamá se han obtenido logros importantes, como la publicación de la Guía para la detección temprana y atención oportuna de la sospecha del cáncer en niños y adolescentes 2021 y los programas de capacitación para el personal de atención primaria de salud. Estos programas han permitido capacitar a más de 1 000 profesionales de la salud en materia de diagnóstico del cáncer en la niñez y la adolescencia. Subsisten algunos desafíos, como el acceso a una atención de calidad, y es crucial proseguir con las medidas tendientes a mejorar la atención oncológica de los pacientes pediátricos.

Apesar de ser classificado como um país de alta renda, o Panamá enfrenta desafios para oferecer atendimento a crianças e adolescentes com câncer. Anualmente, são diagnosticados 170 casos novos de câncer infantil no Panamá, e a taxa de sobrevida gira em torno de 60%. Para melhorar essa situação, a criação de uma Comissão de Câncer Pediátrico, composta por profissionais de saúde e organizações sem fins lucrativos, foi uma etapa fundamental para atingir os objetivos delineados na estratégia CureAll da Iniciativa Global para o Câncer Infantil (GICC) da Organização Mundial da Saúde.Para melhorar o atendimento aos pacientes com câncer infantil no Panamá, realizou-se uma oficina sobre câncer em crianças e adolescentes, com o apoio do St. Jude Children's Research Hospital, do Children's Hospital Colorado, do Ministério da Saúde do Panamá e da Organização Pan-Americana da Saúde. As comissões estabelecidas foram as seguintes: Enfermagem, Cuidados Paliativos, Aspectos Psicossociais, Registro Hospitalar, Diagnóstico Precoce e Serviços de Saúde. Cada comissão tem um projeto específico a ser implementado no período de 2021 a 2029 a fim de continuar avançando na melhoria do atendimento a pacientes com câncer infantil.As realizações mais importantes alcançadas desde o início da implementação da GICC no Panamá incluem o lançamento do Guia para o Diagnóstico de Câncer em Crianças e Adolescentes em 2021 e os programas de capacitação para profissionais de saúde da atenção primária. Por meio desses programas, mais de mil profissionais de saúde receberam capacitação no diagnóstico de câncer na infância e adolescência. Ainda existem desafios, como o acesso a atendimento de qualidade; portanto, é essencial continuar os esforços para melhorar o atendimento de pacientes com câncer infantil.

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.

Global Initiative for Childhood Cancer: progress and challenges in Panama / Iniciativa Mundial contra el Cáncer Infantil: avances y desafíos en Panamá / Iniciativa Global para o Câncer Infantil: avanços e desafios no Panamá

[ABSTRACT]. Despite being classified as a high-income country, Panama still faces challenges in providing care for children and adolescents with cancer. Annually, 170 new cases of childhood cancer are diagnosed in Panama, and the survival rate is around 60%. To improve this, the establishment of a Pediatric Cancer Commission comprised of healthcare professionals and nonprofit organizations has been a critical step toward the objectives outlined in the CureAll framework of the World Health Organization Global Initiative for Childhood Cancer (GICC). To improve childhood cancer care in Panama, a workshop for cancer in children and adolescents was conducted with the support of St. Jude Children’s Research Hospital, Children’s Hospital Colorado, the Ministry of Health of Panama, and the Pan American Health Organization. The commissions established were on: Nursing, Palliative Care, Psychosocial, Hospital Registry, Early Diagnosis, and Health Services. Each commission has a specific project to be implemented in the period 2021–2029 to continue the progress toward improving childhood cancer care. Since the start of implementation of the GICC in Panama, important achievements have included the launch in 2021 of the Guide for the Diagnosis of Cancer in Children and Adolescents, and training programs for primary care health personnel. Through these programs, more than 1 000 health professionals have been trained on diagnosis of cancer in childhood and adolescence. Challenges remain, such as access to quality care, and it is essential to continue efforts to improve childhood cancer care.

[RESUMEN]. Pese a estar clasificado como un país de ingresos altos, Panamá aún debe hacer frente a distintos desafíos relacionados con la atención a la población infantil y adolescente con cáncer. Cada año, en Panamá se diagnostican 170 casos nuevos de cáncer pediátrico, con una tasa de supervivencia en torno al 60%. Para mejorar esta situación, la creación de una Comisión de Cáncer Pediátrico, conformada por profesionales de la salud y organizaciones sin fines de lucro, constituye un paso fundamental para lograr los objetivos planteados en el marco CureAll de la Iniciativa Mundial contra el Cáncer Infantil (GICC, por su sigla en inglés) de la Organización Mundial de la Salud. A fin de mejorar la atención de los pacientes pediátricos con cáncer en Panamá, se realizó un taller sobre el cáncer en la población infantil y adolescente. El evento contó con el apoyo del St. Jude Children's Research Hospital, el Children's Hospital Colorado, el Ministerio de Salud de Panamá y la Organización Panamericana de la Salud. Se crearon comisiones sobre enfermería, cuidados paliativos, aspectos psicosociales, registros hospitalarios, diagnóstico temprano y servicios de salud. Cada comisión está a cargo de un proyecto específico, que deberá ponerse en práctica en el período 2021-2029 para proseguir con los avances encaminados a mejorar la atención oncológica pediátrica. Desde que se inició el proceso de aplicación de la Iniciativa Mundial contra el Cáncer Infantil en Panamá se han obtenido logros importantes, como la publicación de la Guía para la detección temprana y atención oportuna de la sospecha del cáncer en niños y adolescentes 2021 y los programas de capacitación para el personal de atención primaria de salud. Estos programas han permitido capacitar a más de 1 000 profesionales de la salud en materia de diagnóstico del cáncer en la niñez y la adolescencia. Subsisten algunos desafíos, como el acceso a una atención de calidad, y es crucial proseguir con las medidas tendientes a mejorar la atención oncológica de los pacientes pediátricos.

[RESUMO]. Apesar de ser classificado como um país de alta renda, o Panamá enfrenta desafios para oferecer atendi- mento a crianças e adolescentes com câncer. Anualmente, são diagnosticados 170 casos novos de câncer infantil no Panamá, e a taxa de sobrevida gira em torno de 60%. Para melhorar essa situação, a criação de uma Comissão de Câncer Pediátrico, composta por profissionais de saúde e organizações sem fins lucrativos, foi uma etapa fundamental para atingir os objetivos delineados na estratégia CureAll da Iniciativa Global para o Câncer Infantil (GICC) da Organização Mundial da Saúde. Para melhorar o atendimento aos pacientes com câncer infantil no Panamá, realizou-se uma oficina sobre câncer em crianças e adolescentes, com o apoio do St. Jude Children's Research Hospital, do Children's Hospital Colorado, do Ministério da Saúde do Panamá e da Organização Pan-Americana da Saúde. As comissões estabelecidas foram as seguintes: Enfermagem, Cuidados Paliativos, Aspectos Psicossociais, Registro Hospitalar, Diagnóstico Precoce e Serviços de Saúde. Cada comissão tem um projeto específico a ser implementado no período de 2021 a 2029 a fim de continuar avançando na melhoria do atendimento a pacientes com câncer infantil. As realizações mais importantes alcançadas desde o início da implementação da GICC no Panamá incluem o lançamento do Guia para o Diagnóstico de Câncer em Crianças e Adolescentes em 2021 e os programas de capacitação para profissionais de saúde da atenção primária. Por meio desses programas, mais de mil profissionais de saúde receberam capacitação no diagnóstico de câncer na infância e adolescência. Ainda existem desafios, como o acesso a atendimento de qualidade; portanto, é essencial continuar os esforços para melhorar o atendimento de pacientes com câncer infantil.

Collaboration for success: the Global Initiative for Childhood Cancer in Latin America / Colaborar para tener éxito: la Iniciativa Mundial contra el Cáncer Infantil en América Latina / Colaboração para o sucesso: a Iniciativa Global para o Câncer Infantil na América Latina

[ABSTRACT]. 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 deter- mine the impact of these strategies and resources on childhood cancer outcomes in LAC and other regions.

[RESUMEN]. 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.

[RESUMO]. 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 alinha- dos 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 colabora- dores 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.

Toxicity and feasibility of vincristine, etoposide, and carboplatin alternating with vincristine, doxorubicin, and cyclophosphamide in children with advanced retinoblastoma in Guatemala.

Retinoblastoma is highly curable, with event-free survival (EFS) of greater than 95% in high-income countries. However, in lower middle-income countries, outcomes of EFS are 30%-60% due to delayed diagnosis and lack of resources resulting in extra-ocular disease. We report the toxicity profile and outcomes of intensified therapy for advanced retinoblastoma: vincristine, etoposide, carboplatin (VEC) alternating with vincristine, doxorubicin, and cyclophosphamide (VDoCx) in Guatemala. Compared to VEC alone, similar rates of neutropenia, anemia, and thrombocytopenia were seen, with no toxic deaths. Although survival was not a primary objective, a modest survival benefit supports further investigation of VEC+VDoCx for advanced retinoblastoma.

Global Initiative for Childhood Cancer: progress and challenges in Panama / Iniciativa Mundial contra el Cáncer Infantil: avances y desafíos en Panamá / Iniciativa Global para o Câncer Infantil: avanços e desafios no Panamá

ABSTRACT Despite being classified as a high-income country, Panama still faces challenges in providing care for children and adolescents with cancer. Annually, 170 new cases of childhood cancer are diagnosed in Panama, and the survival rate is around 60%. To improve this, the establishment of a Pediatric Cancer Commission comprised of healthcare professionals and nonprofit organizations has been a critical step toward the objectives outlined in the CureAll framework of the World Health Organization Global Initiative for Childhood Cancer (GICC). To improve childhood cancer care in Panama, a workshop for cancer in children and adolescents was conducted with the support of St. Jude Children's Research Hospital, Children's Hospital Colorado, the Ministry of Health of Panama, and the Pan American Health Organization. The commissions established were on: Nursing, Palliative Care, Psychosocial, Hospital Registry, Early Diagnosis, and Health Services. Each commission has a specific project to be implemented in the period 2021-2029 to continue the progress toward improving childhood cancer care. Since the start of implementation of the GICC in Panama, important achievements have included the launch in 2021 of the Guide for the Diagnosis of Cancer in Children and Adolescents, and training programs for primary care health personnel. Through these programs, more than 1 000 health professionals have been trained on diagnosis of cancer in childhood and adolescence. Challenges remain, such as access to quality care, and it is essential to continue efforts to improve childhood cancer care.

RESUMEN Pese a estar clasificado como un país de ingresos altos, Panamá aún debe hacer frente a distintos desafíos relacionados con la atención a la población infantil y adolescente con cáncer. Cada año, en Panamá se diagnostican 170 casos nuevos de cáncer pediátrico, con una tasa de supervivencia en torno al 60%. Para mejorar esta situación, la creación de una Comisión de Cáncer Pediátrico, conformada por profesionales de la salud y organizaciones sin fines de lucro, constituye un paso fundamental para lograr los objetivos planteados en el marco CureAll de la Iniciativa Mundial contra el Cáncer Infantil (GICC, por su sigla en inglés) de la Organización Mundial de la Salud. A fin de mejorar la atención de los pacientes pediátricos con cáncer en Panamá, se realizó un taller sobre el cáncer en la población infantil y adolescente. El evento contó con el apoyo del St. Jude Children's Research Hospital, el Children's Hospital Colorado, el Ministerio de Salud de Panamá y la Organización Panamericana de la Salud. Se crearon comisiones sobre enfermería, cuidados paliativos, aspectos psicosociales, registros hospitalarios, diagnóstico temprano y servicios de salud. Cada comisión está a cargo de un proyecto específico, que deberá ponerse en práctica en el período 2021-2029 para proseguir con los avances encaminados a mejorar la atención oncológica pediátrica. Desde que se inició el proceso de aplicación de la Iniciativa Mundial contra el Cáncer Infantil en Panamá se han obtenido logros importantes, como la publicación de la Guía para la detección temprana y atención oportuna de la sospecha del cáncer en niños y adolescentes 2021 y los programas de capacitación para el personal de atención primaria de salud. Estos programas han permitido capacitar a más de 1 000 profesionales de la salud en materia de diagnóstico del cáncer en la niñez y la adolescencia. Subsisten algunos desafíos, como el acceso a una atención de calidad, y es crucial proseguir con las medidas tendientes a mejorar la atención oncológica de los pacientes pediátricos.

RESUMO Apesar de ser classificado como um país de alta renda, o Panamá enfrenta desafios para oferecer atendimento a crianças e adolescentes com câncer. Anualmente, são diagnosticados 170 casos novos de câncer infantil no Panamá, e a taxa de sobrevida gira em torno de 60%. Para melhorar essa situação, a criação de uma Comissão de Câncer Pediátrico, composta por profissionais de saúde e organizações sem fins lucrativos, foi uma etapa fundamental para atingir os objetivos delineados na estratégia CureAll da Iniciativa Global para o Câncer Infantil (GICC) da Organização Mundial da Saúde. Para melhorar o atendimento aos pacientes com câncer infantil no Panamá, realizou-se uma oficina sobre câncer em crianças e adolescentes, com o apoio do St. Jude Children's Research Hospital, do Children's Hospital Colorado, do Ministério da Saúde do Panamá e da Organização Pan-Americana da Saúde. As comissões estabelecidas foram as seguintes: Enfermagem, Cuidados Paliativos, Aspectos Psicossociais, Registro Hospitalar, Diagnóstico Precoce e Serviços de Saúde. Cada comissão tem um projeto específico a ser implementado no período de 2021 a 2029 a fim de continuar avançando na melhoria do atendimento a pacientes com câncer infantil. As realizações mais importantes alcançadas desde o início da implementação da GICC no Panamá incluem o lançamento do Guia para o Diagnóstico de Câncer em Crianças e Adolescentes em 2021 e os programas de capacitação para profissionais de saúde da atenção primária. Por meio desses programas, mais de mil profissionais de saúde receberam capacitação no diagnóstico de câncer na infância e adolescência. Ainda existem desafios, como o acesso a atendimento de qualidade; portanto, é essencial continuar os esforços para melhorar o atendimento de pacientes com câncer infantil.

Collaboration for success: the Global Initiative for Childhood Cancer in Latin America / Colaborar para tener éxito: la Iniciativa Mundial contra el Cáncer Infantil en América Latina / Colaboração para o sucesso: a Iniciativa Global para o Câncer Infantil na América Latina

ABSTRACT 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.

RESUMEN 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.

RESUMO 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.

Impact of COVID-19 in pediatric oncology care in Latin America during the first year of the pandemic.

BACKGROUND: The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year. METHOD: Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners. RESULTS: Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability. CONCLUSION: Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.

Sex, gender, and retinoblastoma: analysis of 4351 patients from 153 countries.

OBJECTIVE: To investigate in a large global sample of patients with retinoblastoma whether sex predilection exists for this childhood eye cancer. METHODS: A cross-sectional analysis including 4351 treatment-naive retinoblastoma patients from 153 countries who presented to 278 treatment centers across the world in 2017. The sex ratio (male/female) in the sample was compared to the sex ratio at birth by means of a two-sided proportions test at global level, country economic grouping, continent, and for selected countries. RESULTS: For the entire sample, the mean retinoblastoma sex ratio, 1.20, was higher than the weighted global sex ratio at birth, 1.07 (p < 0.001). Analysis at economic grouping, continent, and country-level demonstrated differences in the sex ratio in the sample compared to the ratio at birth in lower-middle-income countries (n = 1940), 1.23 vs. 1.07 (p = 0.019); Asia (n = 2276), 1.28 vs. 1.06 (p < 0.001); and India (n = 558), 1.52 vs. 1.11 (p = 0.008). Sensitivity analysis, excluding data from India, showed that differences remained significant for the remaining sample (χ2 = 6.925, corrected p = 0.025) and for Asia (χ2 = 5.084, corrected p = 0.036). Excluding data from Asia, differences for the remaining sample were nonsignificant (χ2 = 2.205, p = 0.14). CONCLUSIONS: No proof of sex predilection in retinoblastoma was found in the present study, which is estimated to include over half of new retinoblastoma patients worldwide in 2017. A high male to female ratio in Asian countries, India in specific, which may have had an impact on global-level analysis, is likely due to gender discrimination in access to care in these countries, rather than a biological difference between sexes.

Wilms tumour.

Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as active in WT development. Decades of clinical and basic research have helped to gradually optimize clinical care. Curative therapy is achievable in 90% of affected children, even those with disseminated disease, yet survival disparities within and between countries exist and deserve commitment to change. Updated epidemiological studies have also provided novel insights into global incidence variations. Introduction of biology-driven approaches to risk stratification and new drug development has been slower in WT than in other childhood tumours. Current prognostic classification for children with WT is grounded in clinical and pathological findings and in dedicated protocols on molecular alterations. Treatment includes conventional cytotoxic chemotherapy and surgery, and radiation therapy in some cases. Advanced imaging to capture tumour composition, optimizing irradiation techniques to reduce target volumes, and evaluation of newer surgical procedures are key areas for future research.

Excellent Outcome for Pediatric Patients With High-Risk Hodgkin Lymphoma Treated With Brentuximab Vedotin and Risk-Adapted Residual Node Radiation.

PURPOSE: Brentuximab vedotin, an effective anti-CD30 antibody-drug conjugate approved for use in adults with classical Hodgkin lymphoma (HL), was introduced in this frontline trial to reduce prescribed radiation in children and adolescents with classical HL. METHODS: Open-label, single-arm, multicenter trial for patients (age ≤ 18 years) with stage IIB, IIIB, or IV classical HL was conducted. Brentuximab vedotin replaced each vincristine in the OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) regimen according to GPOH-HD2002 treatment group 3 (TG3); two cycles of AEPA and four cycles of CAPDac. Residual node radiotherapy (25.5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after two cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free (EFS) and overall survival (OS). The trials are registered at ClinicalTrials.gov (identifier: NCT01920932). RESULTS: Of the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3.4 years, the 3-year EFS was 97.4% (SE 2.3%) and the OS was 98.7% (SE 1.6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% of patients experienced grade 3 neuropathy. CONCLUSION: The integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated significant reduction in radiation exposure, and yielded excellent outcomes.

Circulating Plasma Tumor DNA Is Superior to Plasma Tumor RNA Detection in Ewing Sarcoma Patients: ptDNA and ptRNA in Ewing Sarcoma.

The detection of tumor-specific nucleic acids from blood increasingly is being used as a method of liquid biopsy and minimal residual disease detection. However, achieving high sensitivity and high specificity remains a challenge. Here, we perform a direct comparison of two droplet digital PCR (ddPCR)-based detection methods, circulating plasma tumor RNA and circulating plasma tumor DNA (ptDNA), in blood samples from newly diagnosed Ewing sarcoma patients. First, we developed three specific ddPCR-based assays to detect EWS-FLI1 or EWS-ERG fusion transcripts, which naturally showed superior sensitivity to DNA detection on in vitro control samples. Next, we identified the patient-specific EWS-FLI1 or EWS-ERG breakpoint from five patient tumor samples and designed ddPCR-based, patient-specific ptDNA assays for each patient. These patient-specific assays show that although plasma tumor RNA can be detected in select newly diagnosed patients, positive results are low and statistically unreliable compared with ptDNA assays, which reproducibly detect robust positive results across most patients. Furthermore, the unique disease biology of Ewing sarcoma enabled us to show that most cell-free RNA is not tumor-derived, although cell-free-DNA burden is affected strongly by tumor-derived DNA burden. Here, we conclude that, even with optimized highly sensitive and specific assays, tumor DNA detection is superior to RNA detection in Ewing sarcoma patients.

The threat of the COVID-19 pandemic on reversing global life-saving gains in the survival of childhood cancer: a call for collaborative action from SIOP, IPSO, PROS, WCC, CCI, St Jude Global, UICC and WHPCA.

The COVID-19 pandemic poses an unprecedented health crisis in all socio-economic regions across the globe. While the pandemic has had a profound impact on access to and delivery of health care by all services, it has been particularly disruptive for the care of patients with life-threatening noncommunicable diseases (NCDs) such as the treatment of children and young people with cancer. The reduction in child mortality from preventable causes over the last 50 years has seen childhood cancer emerge as a major unmet health care need. Whilst survival rates of 85% have been achieved in high income countries, this has not yet been translated into similar outcomes for children with cancer in resource-limited settings where survival averages 30%. Launched in 2018, by the World Health Organization (WHO), the Global Initiative for Childhood Cancer (GICC) is a pivotal effort by the international community to achieve at least 60% survival for children with cancer by 2030. The WHO GICC is already making an impact in many countries but the disruption of cancer care during the COVID-19 pandemic threatens to set back this global effort to improve the outcome for children with cancer, wherever they may live. As representatives of the global community committed to fostering the goals of the GICC, we applaud the WHO response to the COVID-19 pandemic, in particular we support the WHO's call to ensure the needs of patients with life threatening NCDs including cancer are not compromised during the pandemic. Here, as collaborative partners in the GICC, we highlight specific areas of focus that need to be addressed to ensure the immediate care of children and adolescents with cancer is not disrupted during the pandemic; and measures to sustain the development of cancer care so the long-term goals of the GICC are not lost during this global health crisis.

The Global COVID-19 Observatory and Resource Center for Childhood Cancer: A response for the pediatric oncology community by SIOP and St. Jude Global.

The COVID-19 pandemic quickly led to an abundance of publications and recommendations, despite a paucity of information on how COVID-19 affects children with cancer. This created a dire need for a trusted resource with curated information and a space for the pediatric oncology community to share experiences. The Global COVID-19 Observatory and Resource Center for Childhood Cancer was developed, launched, and maintained by the International Society of Pediatric Oncology and St. Jude Children's Research Hospital. The three components (Resource Library, Global Registry, and Collaboration Space) complement each other, establishing a mechanism to generate and transfer knowledge rapidly throughout the community.

Classic Hodgkin lymphoma in Guatemalan children of age less than six years: analysis of immune regulatory pathways and the tumor microenvironment.

Classic Hodgkin lymphoma (cHL) in young children (ages 0-6) is rare in high income countries (HICs) but is more prevalent in low- and middle-income countries (LMICs) like Guatemala. Given that the majority of cHL studies have evaluated adolescent/adults, and the immune system changes with age, we sought to characterize Epstein-Barr virus (EBV) expression, immune regulatory pathway markers and the tumor microenvironment in 42 children ages 0-6 with cHL from Guatemala. We found a very high frequency of EBV expression (97.5%). Hodgkin cells showed increased expression of PD1 ligands and CD137, indicative of shared immune regulatory mechanisms with adult cHL. Pediatric cHL also showed an increase in CD8+ tumor infiltrating lymphocytes and tumor associated macrophages within the tumor microenvironment. Despite 25 having high risk disease, only 4 patients died from progressive disease, relapse or infection.

The COVID-19 pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP-E, SIOP-PODC, IPSO, PROS, CCI, and St Jude Global.

The COVID-19 pandemic is one of the most serious global challenges to delivering affordable and equitable treatment to children with cancer we have witnessed in the last few decades. This Special Report aims to summarize general principles for continuing multidisciplinary care during the SARS-CoV-2 (COVID-19) pandemic. With contributions from the leadership of the International Society for Pediatric Oncology (SIOP), Children's Oncology Group (COG), St Jude Global program, and Childhood Cancer International, we have sought to provide a framework for healthcare teams caring for children with cancer during the pandemic. We anticipate the burden will fall particularly heavily on children, their families, and cancer services in low- and middle-income countries. Therefore, we have brought together the relevant clinical leads from SIOP Europe, COG, and SIOP-PODC (Pediatric Oncology in Developing Countries) to focus on the six most curable cancers that are part of the WHO Global Initiative in Childhood Cancer. We provide some practical advice for adapting diagnostic and treatment protocols for children with cancer during the pandemic, the measures taken to contain it (e.g., extreme social distancing), and how to prepare for the anticipated recovery period.