How we approach conservative treatment of retinoblastoma in South America in the era of local ocular treatments: A consensus of the Grupo America Latina de Oncologia Pediatrica (GALOP).

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6 months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.

Diverse mutational spectrum in the 13q14 chromosomal region in a Brazilian cohort of retinoblastoma.

Retinoblastoma is a rare childhood tumor caused by the inactivation of both copies of the RB1 gene. Early diagnosis and identification of heritable RB1 mutation carriers can improve the disease outcome and management via genetic counseling. We used the Multiplex Ligation-dependent Probe Amplification (MLPA) method to analyze the RB1 gene and flanking regions in blood samples from 159 retinoblastoma patients previously negative for RB1 point mutations via Sanger sequencing. We detected a wide spectrum of germline chromosomal alterations, ranging from partial loss or duplication of RB1 to large deletions spanning RB1 and adjacent genes. Mutations were validated via karyotyping, fluorescent in situ hybridization (FISH), SNP-arrays (Single Nucleotide Polymorphism-arrays) and/or quantitative relative real-time PCR. Patients with leukocoria as a presenting symptom showed reduced death rate (p = 0.013) and this sign occurred more frequently among carriers of two breakpoints within RB1 (p = 0.05). All unilateral cases presented both breakpoints outside of RB1 (p = 0.0075). Patients with one breakpoint within RB1 were diagnosed at earlier ages (p = 0.017). Our findings characterize the mutational spectrum of a Brazilian cohort of retinoblastoma patients and point to a possible relationship between the mutation breakpoint location and tumor outcome, contributing to a better prospect of the genotype/phenotype correlation and adding to the wide diversity of germline mutations involving RB1 and adjacent regions in retinoblastoma.

Dinâmica da Implantação de Humanização no Serviço de Radioterapia Pediátrica do Instituto Nacional de Câncer José Alencar Gomes da Silva, Brasil / Dynamics of Implementation of Humanization in the Pediatric Radiotherapy Service of the National Cancer Institute José Alencar Gomes da Silva, Brazil / Dinámica de la Implementación de la Humanización en el Servicio de Salud Radioterapia Pediátrica del Instituto Nacional de Cáncer José Alencar Gomes da Silva, Brasil

Introdução: O tratamento do câncer infantil é multidisciplinar, e a radioterapia faz parte dessa abordagem, sendo, em geral, um procedimento crítico em crianças. A necessidade de permanecerem sem acompanhante e imóveis no aparelho de tratamento, aliada ao receio da natureza dessa terapia, faz com que o uso de anestesia seja comum. Para que a criança pudesse se sentir mais confortável e confiante com esse tratamento, foram introduzidas medidas de humanização na rotina da radioterapia. Objetivo: Descrever a dinâmica do processo de humanização utilizado. Método: Estudo descritivo sobre a implantação de medidas de humanização, entre maio/2016 e dezembro/2017, no Serviço de Radioterapia do Instituto Nacional de Câncer José Alencar Gomes da Silva, RJ, Brasil. Resultado: A customização das máscaras de tratamento, a utilização de fantasias correspondentes, o certificado de coragem, as comemorações de datas festivas e as melhorias no ambiente foram as principais intervenções de humanização realizadas. Houve uma transformação no enfrentamento das adversidades inerentes ao tratamento, com evidente benefício para o ambiente e bem-estar da criança. Uma relação de confiança foi estabelecida entre a criança, sua família e a equipe profissional. Maior adesão, redução do absenteísmo e aparente redução de anestesia para o tratamento foram os resultados constatados. Conclusão: As ações implementadas trouxeram inequívoco ganho para o bem-estar geral dos envolvidos no processo de humanização. Aponta-se a necessidade de estudo quantitativo sobre a melhoria no fluxo de atendimento nesse Serviço, seja por meio da redução do uso de anestesia para o tratamento ou no tempo diário no aparelho de radioterapia

Introduction: The treatment of childhood cancer is multidisciplinary and radiotherapy is part of this approach, being, in general, a critical procedure in children. The need to remain unaccompanied and motionless in the treatment apparatus, together with the fear of the nature of this therapy, makes the use of anesthesia common. Humanization measures were introduced in the radiotherapy routine to help children to feel more comfortable and confident with this treatment. Objective: To describe the dynamics of the humanization process. Method: A descriptive study addressing the implementation of humanization measures was developed, between May 2016 and December 2017, in the Radiotherapy Service of the National Cancer Institute José Alencar Gomes da Silva, RJ, Brazil. Result: The customization of the treatment masks, the use of matching costumes, the certificate of courage, the celebrations of festive dates and the improvements in the environment were the main humanization interventions carried out. There was a transformation in coping with the adversities inherent to the treatment, with clear benefits for the environment and the child's well-being. A trusting relationship was established between the child, his family and the professional team. Greater adherence, reduced absenteeism and an apparent reduction in the use of anesthesia for treatment were found. Conclusion: The actions implemented brought an unambiguous gain in the general well-being of those involved in the humanization process. The necessity of quantitative study on improving the flow of care in the Radiotherapy Service, either by reducing the use of anesthesia for treatment or the daily time spent in the radiotherapy device is highlighted

Introducción: El tratamiento del cáncer infantil es multidisciplinario y la radioterapia forma parte de este abordaje, siendo, en general, un procedimiento crítico en los niños. La necesidad de permanecer sin compañía e inmóvil en el aparato de tratamiento, combinada con el miedo a la naturaleza de esta terapia, hace que el uso de anestesia sea común. Para que el niño se sintiera más cómodo y seguro con este tratamiento, se introdujeron medidas de humanización en la rutina de radioterapia. Objetivo: Describir la dinámica del proceso de humanización utilizado. Método: Estudio descriptivo sobre la implementación de medidas de humanización, entre mayo/2016 y diciembre/2017, en el Servicio de Radioterapia del Instituto Nacional del Cáncer José Alencar Gomes da Silva, RJ, Brasil. Resultado: La personalización de las máscaras de tratamiento, el uso de los trajes correspondientes, el certificado de valentía, las celebraciones de fechas festivas y las mejoras en el entorno fueron las principales intervenciones de humanización realizadas. Se produjo una transformación en el afrontamiento de las adversidades inherentes al tratamiento, con evidentes beneficios para el medio ambiente y el bienestar del niño. Se estableció una relación de confianza entre el niño, su familia y el equipo profesional. Se encontrón mayor adherencia, menor absentismo y una aparente reducción en el uso de anestesia para el tratamiento. Conclusión: Las acciones implementadas aportaron una ganancia inequívoca en el bienestar general de los involucrados en el proceso de humanización. Es necesario un estudio cuantitativo sobre la mejora del flujo de atención en esto Servicio, ya sea reduciendo el uso de anestesia para el tratamiento o el tiempo diario en el dispositivo de radioterapia

Socioeconomic status and retinoblastoma survival: Experience of a tertiary cancer center in Brazil.

BACKGROUND: Little is known about socioeconomic status (SES) and its effects in childhood cancer survival. This study aims to discuss the association between SES and survival of patients with retinoblastoma (RB) from a tertiary treatment center. PROCEDURE: A retrospective cohort study was conducted, including all patients with RB referred to the Brazilian National Institute of Cancer in Rio de Janeiro (January 2000-December 2016). RESULTS: Data from 160 patients were analyzed with mean age at diagnosis of 22.85 months (SD ± 14.29). Eighty-three patients (51.9%) had an interval to diagnosis equal to or longer than six months, and 13 children (8.1%) abandoned treatment. Five-year overall survival rate for all patients was 78.8% (95% CI, 72.4%-85.9%). In a multivariate model, patients whose fathers had more than nine years of study had a lower death risk. Patients from families having more than one child under five years had a 213% higher risk of death compared with those living with no other small child. Treatment abandonment also had a profound effect on death risk. CONCLUSION: Childhood cancer is notably important considering the potential years of life lost. RB has even more important elements, as the possibility of vision loss in cases with delayed diagnosis. Family characteristics seem to be highly related to RB survival, especially in low- and middle-income countries, where inequalities are still a public health issue. Strategies to improve survival should focus not only on large-scale settings such as improving national healthcare systems but also on more personalized actions that might help to mitigate disparities.

Time to diagnosis of retinoblastoma in Latin America: A systematic review.

Retinoblastoma (RB) is the most common intraocular tumor of childhood. In low income countries, Time to diagnosis (TTD: interval between first symptom and diagnosis) has been associated with extraocular disease, metastasis and mortality. However, the relationship between TTD and prognosis is complex and not simply a linear correlation, particularly if TTD is <6 months. This systematic review aims to identify studies reporting TTD of retinoblastoma in Latin America, highlighting factors affecting TTD, alongside proposals and initiatives to obtain shorter intervals. The review also aims to discuss the methodology linked to cancer pathways studies. The study respected PRISMA recommendations, was registered on Prospero, an international database for systematic review registries under number CRD42017076777. MEDLINE/PUBMED, LILACS and SCIELO databases were searched. Studies from Latin America and the Caribbean, published between 1997 and 2017, reporting TTD and age at diagnosis of patients with retinoblastoma were selected. Nine studies were selected, concerning 1560 patients from Argentina, Brazil, Chile, Honduras, Mexico and Peru. The median TTD ranged from 3 to 5 months and the median age at diagnosis ranged from 16.5 to 22.2 months. A prolonged TTD was observed and was associated to damaging results on retinoblastoma outcomes, particularly increasing extraocular disease, and mortality rates. Methodological heterogeneity was observed and reiterates the importance of standardization of TTD studies, allowing more reliable comparisons and greater knowledge about retinoblastoma pathways before diagnosis. Reports on successful initiatives against delayed diagnosis were scarce, emphasizing a need for further studies.

Prediagnostic Intervals in Retinoblastoma: Experience at an Oncology Center in Brazil.

PURPOSE: Retinoblastoma is the most common intraocular malignancy of childhood. In most cases, parents are the first to notice leukocoria and other symptoms before undergoing a prolonged period of stress before diagnosis. The purpose of this study was to determine prediagnostic intervals of patients with retinoblastoma at an oncology tertiary center (Instituto Nacional de Cancer) in Rio de Janeiro, Brazil, and relate them to stage at diagnosis, eye salvage, and survival. METHODS: Parents or caregivers of children with retinoblastoma registered between January 2006 and September 2013 were interviewed using a semistructured individually applied questionnaire, concerning their trajectory before registration. RESULTS: Out of 76 patients, 39 (51%) were girls, 52 (68%) had unilateral retinoblastoma, and 24 (32%) had bilateral retinoblastoma, totaling 100 affected eyes. The most common stage of diagnosis was the intraocular group, with 63 (83%) patients; nine (12%) were extraocular, and four (5%) had metastatic disease. During the follow-up time of 37 ± 24.5 months, 10 (13%) patients died and 70 (70%) eyes were enucleated. Mean family interval was 1.6 ± 2.6 months, mean medical interval was 5.0 ± 6.2 months, mean referral interval was 0.2 ± 1.4 months, and mean overall interval was 7.1 ± 6.9 months. In univariate analysis, age at diagnosis, maternal education, medical interval, and overall interval were significantly related to advanced stage at diagnosis and survival. In multivariate analysis, maternal education and medical interval were significantly related to advanced stage at diagnosis and survival. No variables affected eye salvage. CONCLUSION: Medical interval was responsible for 70% of the overall interval; therefore, programs or campaigns targeting retinoblastoma early diagnosis should focus emphasize in medical awareness.

Use of intra-arterial chemotherapy for retinoblastoma: results of a survey.

AIM: To obtain baseline knowledge about the current use of intra-arterial chemotherapy (SSOAIC) in centers worldwide. METHODS: A survey including questions about the use of SSOAIC was emailed to retinoblastoma experts. RESULTS: Seventy-nine (response rate 69.9%) doctors from 63 centers in 35 countries responded. Thirty-one centers from 19 countries use SSOAIC. Twelve performed more than 50 procedures. Melphalan is the most commonly used drug but 15 centers use more than one drug. First line therapy for advanced unilateral disease is the most common use of SSOAIC (74.2%). Centers with larger experience (>50 applications) were less likely using melphalan alone (P=0.06) and significantly more likely using SSOAIC in more situations such as second line in preference to radiotherapy P=0.05. Nineteen (61.2%) stated that SSOAIC improved their results and 21 (77.8%) reported less toxicity compared to other treatments. Three centers reported that SSOAIC did not improve their results. There were regional variations in the use of SSOAIC which is used more frequently as secondary treatment in Europe compared to the USA and Japan. Ten centers identified cost is the major limiting factor for SSOAIC. CONCLUSION: SSOAIC is used in an increasing number of centers worldwide with regional variations. Centers with more experience in SSOAIC use it in more situations including other drugs than melphalan. The majority of the centers using this technique reported improved results and few complications.