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.

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.

Fratura de órbita por queda de cavalo e correção de estrabismo / Orbit fracture by horse fall and strabismus correction

Descreve-se uma paciente com fratura orbitária grave causada por queda de cavalo. Relato do seu tratamento cirúrgico com correção do estrabismo e tentativa de correção da enoftamia.

Description of a patient with orbital fracture cause by a horse fall. Follow-up the surgical treatment of the strabismus and the enophtlamos.

Estudo comparativo entre o tonômetro de aplanação de Goldmann e o tonômetro de contorno dinâmico de Pascal no glaucoma primário de ângulo aberto e olhos normais / Dynamic contour tonometry (DCT) versus Goldmann applanation tonometry (GAT) in open-angle glaucoma and normal eyes: a comparative study

OBJETIVO: Comparar as medidas da pressão intra-ocular (PIO) obtidas com o tonômetro de aplanação de Goldmann (TAG) e o tonômetro de contorno dinâmico (TCD) e correlacioná-las com a espessura central da córnea (ECC). MÉTODOS: Estudo transversal, com os pacientes divididos em dois grupos: glaucoma primário de ângulo aberto (GPAA) e olhos normais (ON). As medidas da PIO foram obtidas em todos os pacientes com o TAG e o TCD. Um examinador realizou as tonometrias com o TAG e outro examinador com o TCD. A ECC foi obtida pelo paquímetro ultrassônico. Os resultados foram avaliados através do teste Z para amostras independentes, teste t de Student para amostras relacionadas, teste de correlação linear de Pearson e gráfico de Bland-Altman. RESULTADOS: Foram incluídos 134 olhos de 71 pacientes. O grupo GPAA foi constituído por 85 olhos de 45 pacientes e o grupo ON por 49 olhos de 26 indivíduos com olhos normais. Não houve diferença significativa da ECC entre os dois grupos em ambos os olhos (p= 0,54 OD; p= 0,71 OE). As tonometrias realizadas com o TCD foram maiores nos dois grupos (GPAA: p< 0,01; ON: p= 0,01). Houve correlação significativa entre as tonometrias do TAG e do TCD nos dois grupos separados ou em conjunto (p< 0,001). Não houve correlação significativa entre o TAG ou o TCD e a ECC, exceto no olho direito dos dois grupos em conjunto (p= 0,03; r² = 0,07). O gráfico de Bland-Altman mostrou pouca concordância entre os dois procedimentos. CONCLUSÃO: Nenhum dos métodos mostrou boa correlação com a ECC. Houve pouca concordância entre os dois métodos, sendo maiores, as tonometrias obtidas com o TCD. As medidas realizadas no TCD parecem ser menos influenciadas pelos valores da ECC do que as medidas realizadas no TAG.

PURPOSE: To compare intraocular pressure (IOP) readings of Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT), and to correlate central corneal thickness (CCT) with these readings. METHODS: This transversal study included patients in two groups: open-angle glaucoma (OAG) and normal eyes (NE). IOP measurements were obtained in all patients using GAT and DCT. The same examiner made all GAT measurements. Another examiner, who was masked to the GAT readings, made DCT measurements. CCT was determined by ultrasound pachimetry. RESULTS: The study included 134 eyes of 71 subjects. The groups were composed of 85 eyes from 45 patients with OAG and 49 eyes from 26 subjects with NE. There was no statically significant difference between CCT in the two groups (p = 0,54, right eye; p = 0,71, left eye). DCT readings consistently were higher than GAT measurements in the two groups (OAG: p < 0,001; NE: p = 0,01). There was good correlation between GAT and DCT in both groups (p < 0,001). Neither GAT nor DCT showed a significant correlation with CCT, except in the separate analysis of all right eyes (p = 0,03; r² = 0,07). Bland-Altman graphs showed disagreement between GAT and DCT. CONCLUSION: Measurements with both GAT and DCT were not correlated with CCT. The agreement between GAT and DCT were not good. The IOP measurements by GAT were lower when compared with DCT. DCT readings seem to be less dependent on CCT than TAG readings.