Retinoblastoma in Ceara: An epidemiological study in a Brazilian pediatric oncology referral center.

PURPOSE: Although Brazil has a high prevalence of retinoblastoma, there is a lack of epidemiological data on the disease. Thus, in this study, we aimed to evaluate the epidemiological profile of patients diagnosed with retinoblastoma in the ophthalmology department of a pediatric tertiary referral hospital in Ceara, Brazil. METHODS: A descriptive and cross-sectional study was conducted by retrospectively analyzing the clinical and socioeconomic data from the medical records of pediatric patients followed-up at the hospital between 2007 and 2021. Retinoblastoma was diagnosed on the basis of a fundoscopic or histopathologic examination. RESULTS: The data of 105 patients were included in the study, and the mean patient age at the time of diagnosis was 1.7 years. Most of the patients were women (50.5%) and hailed from rural areas (57.4%), which was associated with a higher tumor stage. Of the 150 patients, 57.1% initially presented with leukocoria. Ocular hyperemia was associated with more advanced stages of retinoblastoma (p=0.004). Bilateral involvement was observed in 25.7% of the patients and at a significantly younger age (p=0.009). The presence of retinal detachment, vascularized lesions, and vitreous seeds significantly increased the likelihood of requiring enucleation. DISCUSSION: This study presents an epidemiological description of retinoblastoma in Brazil, which highlights the significance of early detection. Delayed diagnosis is associated with a poorer visual prognosis and higher mortality rate, particularly in patients with unilateral disease. Risk factors for a more severe disease were retinal detachment, vascularized lesions, and vitreous seeds. The correlation between histopathological features and clinical outcomes was limited. CONCLUSION: Further studies are required to assess the influence of ocular hyperemia, fundoscopic assessment, and histopathologic findings on the prognosis of retinoblastoma. Moreover, it is critical to devise interventions to reduce the time-to-diagnosis in rural areas.

Clinical, epidemiological, and care profile of hospitalized patients with retinoblastoma in Brazil.

PURPOSE: To describe the epidemiological and clinical profile of hospitalized patients with retinoblastoma in Brazil. METHODS: Using data from the Hospital Cancer Registry of the Instituto Nacional de Câncer, patients with the morphological codes of retinoblastoma who were diagnosed between 2000 to 2018, aged 0-19 years, and followed up in registered hospitals (analytical cases) were selected. The relative and absolute frequencies of demographic, clinical, diagnostic, therapeutic, and outcome variables were described. Hospital performance indicators were calculated and compared between hospitals qualified and not qualified to treat pediatric oncology cases and between hospitals with different case volumes (<20, 20-75, >75 cases). RESULTS: Of the 2,269 identified analytical cases from 86 institutions, 48% were from the Southeast, 54% were male, and 66% were aged <4 years. The proportion of missing data (NA) was too high for several variables. Approximately 84% of the patients were from the public health system, 40% had a positive family history, and 88% had unilateral involvement. The first treatment included surgery in 58.3% of the patients (NA=2), Approximately 36.6% of these patients achieved complete remission, 10.8% achieved partial remission, and 12.7% died (NA=59%). Hospital performance indicators were within the target in >90% of the patients. The median time between the first appointment and diagnosis (6 days, interquartile range [IQR] 1-14) was significantly lower and the median time to death was longer (343 days, IQR, 212-539) in high-volume hospitals (>75 cases) than in medium- and low-volume hospitals. CONCLUSIONS: Despite the high proportion of missing data, we found that the delay in diagnosis is due to prehospital factors. Additionally, there is a need for educational programs for healthcare professionals and families that emphasize early identification and referral to specialized centers. Future studies should focus on the impact of Hospital Cancer Registry data completeness on outcomes, causes of delay in diagnosis, regional inequalities, and barriers to accessing specialized services.

Retinoblastoma treatment in a Brazilian population. Presentation and long-term results.

INTRODUCTION: Retinoblastoma is a malignant tumor with a high cure potential when proper therapy is used. The purpose of this paper is to report the clinical features and outcomes of patients with retinoblastoma who were treated with a combination of local and systemic chemotherapy-based protocols. METHOD: We retrospectively studied patients treated with systemic chemotherapy plus local treatment between 2003 and 2015 with a follow-up ≥2 years. We correlated clinical and pathological characteristics with decimal visual acuity (VA) and death. RESULTS: Among 119 patients, 60% had unilateral disease (UNI), and 52% were male. The median presentation age was 19.5 months, 10% had a positive family history, and the most frequent sign was leukocoria (68.8%). Advanced disease was more frequent in eyes with UNI (98.4%) than in eyes with bilateral retinoblastoma (BIL: 55.3%). Enucleation was performed in 97% of UNI eyes and in 55.8% of BIL eyes. The overall globe salvage was 26.6%, 44.25% of BIL eyes. Bilateral enucleation was required in 5%. High-risk pathologic features occurred in 50% and 37% of eyes enucleated without and with neoadjuvant chemotherapy, respectively. High-risk features were related to the presence of goniosynechiae in the pathologic specimen and were more frequent in children younger than 10 months or older than 40 months. Extraocular disease was present in 5% of patients, and the death rate related to metastasis of the tumor was 8%. The final VA was ≥ 0.7 in 72.8% and ≥0.1 in 91% of BIL patients. CONCLUSIONS: Treatment of retinoblastoma with conservative systemic-based chemotherapy was associated with an excellent survival rate (92%). Albeit the low overall globe salvage rate, in BIL patients, approximately half the eyes were conserved, and a satisfactory functional visual result was achieved The evaluated protocol is an important treatment option, especially in developing countries.

Presence of cataract in patients treated for retinoblastoma at the national institute of pediatrics in Mexico (2011-2021).

PURPOSE: The goal of this study is to describe the presence of secondary cataract in patients with retinoblastoma treated at the National Institute of Pediatrics of Mexico (INP) over the past 10 years. METHODS: This was a single center observational, retrospective and descriptive study. We included all eyes diagnosed with retinoblastoma and cataract between June 2011 and June 2021. RESULTS: In total, 833 records of patients diagnosed with Retinoblastoma at the National Institute of Pediatrics during the period between June 2011 and June 2021 were reviewed. Out of all of them, only 14 developed cataract (1.6%). The median age at retinoblastoma diagnosis was 10.5 months (Rank: 6-13 months), and the median age at cataract diagnosis was 51.5 months (Rank: 25-73 months). The majority (13, 92.9%) of the patients had bilateral involvement. 42% of the eyes were Stage D according to the international classification of retinoblastoma. Cryotherapy was applied in 57.1%, intravitreal chemotherapy in 85.7%, radiation therapy in 42.6%, and only 7.1% of cases were treated with intra-arterial chemotherapy. CONCLUSIONS: The presence of cataract in patients with retinoblastoma is a rare but important entity impacting the development of vision in children and detection of intraocular tumors. These probably occur late as a result of the multiple treatments to which the children have been subjected, without being able to determine in this study which is the risk factor most associated with the development of this pathology.

Subsequent malignant neoplasms in the pediatric age in retinoblastoma survivors in Argentina.

BACKGROUND: Retinoblastoma survivors in low- and middle-income countries are exposed to high-intensity treatments that potentially place them at higher risk of early subsequent malignant neoplasms (SMNs). METHODS: We followed 714 (403 [56.4%] nonhereditary and 311 [43.5%] hereditary) retinoblastoma survivors diagnosed from August 1987 to December 2016, up to the age of 16 years. We quantified risk of SMNs with cumulative incidence (CI) and standardized incidence ratios (SIR) analysis. Multivariate regression Cox model was used to determine the association of treatments and risk of SMNs. RESULTS: Median follow-up was of 9 years (range: 0.18-16.9) and 24 survivors (3.36%) developed 25 SMNs (n = 22 hereditary, n = 2 nonhereditary). SMNs included sarcomas (osteosarcomas, Ewing sarcomas, rhabdomyosarcomas; n = 12), leukemias (n = 5), and central nervous system tumors (CNS; n = 3). All cases of acute myeloid leukemia (AML) and most of Ewing sarcomas occurred within 5 years of retinoblastoma diagnosis. The type of SMN was the main indicator of mortality (five of five patients with leukemias, six of 12 with sarcomas, and zero of three with CNS tumors died). Compared to the general population, radiation increased the risk of Ewing sarcoma in hereditary survivors by 700-fold (95% CI = 252-2422.6) and chemotherapy increased the risk of AML by 140-fold (95% CI = 45.3-436). The CI of SMNs for hereditary survivors was 13.7% (95% CI = 8.4-22.1) at 15 years. CONCLUSION: Retinoblastoma survivors from Argentina are at higher risk of developing SMNs early in life compared to the general Argentinean population, especially those treated with radiation plus chemotherapy. AML and Ewing sarcoma presented within 5 years of retinoblastoma diagnosis are associated with chemotherapy and radiation exposure.

Modern treatment of retinoblastoma: A 2020 review.

Retinoblastoma management remains complex, requiring individualized treatment based on International Classification of Retinoblastoma (ICRB) staging, germline mutation status, family psychosocial factors and cultural beliefs, and available institutional resources. For this 2020 retinoblastoma review, PubMed was searched for articles dated as early as 1931, with an emphasis on articles from 1990 to the present day, using keywords of retinoblastoma, chemotherapy, intravenous chemotherapy, chemoreduction, intra-arterial chemotherapy, ophthalmic artery chemosurgery, intravitreal chemotherapy, intracameral chemotherapy, cryotherapy, transpupillary thermotherapy, laser, radiation, external beam radiotherapy, plaque radiotherapy, brachytherapy, and enucleation. We discuss current treatment modalities as used in the year 2020, including intravenous chemotherapy (IVC), intra-arterial chemotherapy (IAC), intravitreal chemotherapy (IvitC), intracameral chemotherapy (IcamC), consolidation therapies (cryotherapy and transpupillary thermotherapy [TTT]), radiation-based therapies (external beam radiotherapy [EBRT] and plaque radiotherapy), and enucleation. Additionally, we present a consensus treatment algorithm based on the agreement of three North American retinoblastoma treatment centers, and encourage further collaboration amongst the world's most expert retinoblastoma treatment centers in order to develop consensus management plans and continue advancement in the identification and treatment of this childhood cancer.

Preventing treatment abandonment for children with solid tumors: A single-center experience in Brazil.

BACKGROUND: High rates of treatment abandonment have been considered one of the major limitations to achieving high cure rates of childhood cancer in developing countries. The aims of this study were to report the prevalence and factors associated with treatment abandonment for children diagnosed with solid tumors in one reference center in Brazil and to describe effective strategies to prevent it. PROCEDURES: A retrospective review was conducted using data from 1139 children (0-18 years) treated for solid tumors at the Brazilian National Cancer Institute, during the period between January 2012 and December 2017. Treatment abandonment was defined as recommended by the International Society of Pediatric Oncology. The impact of implementing a patient-tracking system was evaluated. Descriptive statistics were used to analyze patient characteristics. Chi-square test was used for statistical analysis, with the significance level <0.05. RESULTS: Of 1139 patients, 1.66% refused or abandoned treatment. Although from 2012 to 2013 there was an increase in the abandonment rate, it then decreased by 63.8% from 2013 to 2017 (2.5% to 0.9%). In the multivariate model, only retinoblastoma diagnosis was associated with abandonment (odds ratio = 5.0; 95% confidence interval, 1.2-20.4; P = 0.025). In our cohort, abandonment rates were not associated with increased death. CONCLUSION: Monitoring missed appointments, and early interventions to address issues associated with providing resources to help families during treatment were effective in achieving very low abandonment rates.

Systematic review of the current status of programs and general knowledge of diagnosis and management of retinoblastoma / Revisión sistemática del estado actual de los programas y conocimiento general de la diagnosis y manejo de retinoblastoma

Abstract: Background: This systematic review aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico. We analyzed clinical and demographic data of patients with Rb at select hospitals with Rb programs or that treat and refer patients with Rb, and identified the gaps in practice. We propose solutions to improve diagnosis, provide adequate treatment, and improve patient uptake. Methods: A general review was conducted on PubMed of peer-reviewed literature on Rb in Mexico. Ophthalmology Department Heads or Directors of Rb programs at seven hospitals in Mexico were contacted for data available on their patients with Rb. Results: Five hospitals provided clinical data on 777 patients with Rb in a period spanning 2000-2015. Of the 122 patients with treatment, 83.4% underwent enucleation. From 33 to 45.3% of Rb tumors in Mexico reach an advanced intraocular stage of development. Knowledge of the disease is limited, despite the fact that the Mexican Retinoblastoma Group has elaborated Rb treatment guidelines and is developing a national Rb registry. Especially in the Southern states, prevalence and outcomes are comparable to African and Asian countries, and only few patients are referred to national treatment centers. Only three institutions have comprehensive Rb programs. Conclusions: There is an immediate need in Mexico to expand primary care providers' knowledge of Rb and to expand and upgrade current Rb programs to meet the needs of the population adequately. Diagnosis and care of Rb patients in Mexico can also be improved by the establishment of a national Rb registry and a national early detection program, and by increased use of the national treatment protocol.

Resumen: Introducción: Esta es una revisión sistemática de los conocimientos actuales del retinoblastoma (Rb) y sus implicaciones en los centros de referencia más importantes del país. Se presenta un análisis situacional de los programas de Rb en México, se identificaron las brechas en la práctica, y se proponen soluciones para mejorar el diagnóstico, tratamiento y referencia oportuna de pacientes. Métodos: Se realizó una revisión general de la literatura publicada sobre Rb en México a través de PubMed. Los datos sociodemográficos de pacientes con Rb fueron obtenidos a través de los directores de programas de retinoblastoma en siete hospitales. Resultados: Casi una tercera parte de los casos Rb se diagnostican en estadios avanzados. A pesar de la existencia del Grupo Mexicano de Retinoblastoma, el conocimiento de esta patología entre los médicos es limitado. Las diferencias en el tratamiento son notorias en el sur del país, donde la prevalencia y los resultados son comparables con África y Asia. Solamente tres instituciones a nivel nacional tienen un programa establecido de Rb. Conclusiones: Existe la necesidad inmediata de consolidar los programas de Rb para cubrir las necesidades reales de la población. Se requiere mejorar la educación del médico de primer contacto, establecer el registro nacional de casos y el programa de detección temprana, establecer los programas de salvamento ocular nacional, y reforzar las instituciones que brindan tratamiento.

Systematic review of the current status of programs and general knowledge of diagnosis and management of retinoblastoma.

BACKGROUND: This systematic review aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico. We analyzed clinical and demographic data of patients with Rb at select hospitals with Rb programs or that treat and refer patients with Rb, and identified the gaps in practice. We propose solutions to improve diagnosis, provide adequate treatment, and improve patient uptake. METHODS: A general review was conducted on PubMed of peer-reviewed literature on Rb in Mexico. Ophthalmology Department Heads or Directors of Rb programs at seven hospitals in Mexico were contacted for data available on their patients with Rb. RESULTS: Five hospitals provided clinical data on 777 patients with Rb in a period spanning 2000-2015. Of the 122 patients with treatment, 83.4% underwent enucleation. From 33 to 45.3% of Rb tumors in Mexico reach an advanced intraocular stage of development. Knowledge of the disease is limited, despite the fact that the Mexican Retinoblastoma Group has elaborated Rb treatment guidelines and is developing a national Rb registry. Especially in the Southern states, prevalence and outcomes are comparable to African and Asian countries, and only few patients are referred to national treatment centers. Only three institutions have comprehensive Rb programs. CONCLUSIONS: There is an immediate need in Mexico to expand primary care providers' knowledge of Rb and to expand and upgrade current Rb programs to meet the needs of the population adequately. Diagnosis and care of Rb patients in Mexico can also be improved by the establishment of a national Rb registry and a national early detection program, and by increased use of the national treatment protocol.

Association of Cone-Rod Homeobox Transcription Factor Messenger RNA With Pediatric Metastatic Retinoblastoma.

IMPORTANCE: Disseminated retinoblastoma is usually fatal. Identification of small amounts (minimal dissemination [MD]) of tumor cells in extraocular sites might be a tool for designing appropriate treatments. OBJECTIVE: To test cone-rod homeobox (CRX) transcription factor as a lineage-specific molecular marker for metastatic retinoblastoma and for evaluation of MD. DESIGN, SETTING, AND PARTICIPANTS: In a prospective cohort design study, we evaluated CRX messenger RNA (mRNA) by retrotranscription followed by real-time polymerase chain reaction as a diagnostic test in samples obtained from bone marrow, peripheral blood, and cerebrospinal fluid (CSF) at diagnosis, after induction chemotherapy, and during follow-up. The study was conducted from June 30, 2008, to June 30, 2014. Seventeen retinoblastoma primary tumors, 2 retinoblastoma cell lines, and 47 samples of bone marrow from other cancers (controls) were studied. Seventeen patients with metastatic retinoblastoma (9 at diagnosis, 8 at relapse; age range: 18-41 months) were included. MAIN OUTCOMES AND MEASURES: Detection of CRX mRNA as a marker for metastatic retinoblastoma and MD in bone marrow and CSF and its correlation with clinical findings. RESULTS: Cone-rod homeobox mRNA was expressed in all tumors (relative expression levels range, 8.1 × 10-5 to 5.6) and cell lines. In control samples, there was no amplification of CRX; only the housekeeping gene (GAPDH) demonstrated amplification. Bone marrow metastatic cells showed expression of CRX mRNA in all 9 children presenting with metastasis at the diagnosis (relative expression levels, 6.0 × 10-5 to 0.67). After induction chemotherapy, no evidence of MD of tumor cells was seen in any of the 8 responding children since only GAPDH showed amplification. In the CSF of children who had a metastatic relapse, CRX mRNA detection was positive in 2 patients in whom no conclusive results were reached by immunocytology for disialoganglioside GD2. Minimal dissemination in the CSF was associated with a clinical relapse in 2 cases. No concomitant MD was evident in the bone marrow in any case. CONCLUSIONS AND RELEVANCE: These data suggest that CRX mRNA is a novel marker for retinoblastoma at extraocular sites. In this study among patients with bone marrow metastasis, there was a quick, complete, and sustained molecular response after induction chemotherapy. In all patients with secondary metastasis, CSF relapse occurred independently from the bone marrow, suggesting a sanctuary site.

A population-based study of retinoblastoma incidence and survival in Argentine children.

BACKGROUND: An increased incidence of retinoblastoma in some developing countries has been reported but no conclusive data are available from population-based studies at national level. PURPOSE: To report the incidence and survival of retinoblastoma in Argentina from the National Pediatric Cancer Registry (ROHA) and the influence of socio-economical indicators on outcome. PROCEDURE: Cases reported to the ROHA (2000-2009) were analyzed. Incidence rates were calculated using National Vital Statistics and survival was estimated. The extended human development index (EHDI) was used as a socio-economical indicator. RESULTS: With 438 patients reported, an incidence of 5.0 cases per million children 0-14 years old (95% CI 3.5-6.4) was calculated. Median age at diagnosis was significantly higher for children from provinces with lower EHDI; (24 vs. 35 months for unilateral, (P = 0.003) and 9 versus 11.5 months for bilateral retinoblastoma (P = 0.027). The 3-year probability of survival was 0.87 and 0.94 for unilateral and bilateral retinoblastoma, respectively. Residents in provinces with higher EHDI had a better 3-year survival (0.93 vs. 0.77 for lower EHDI, P < 0.0001). Probability of survival was higher for patients treated at tertiary level institutions (P = 0.0015). The combination of low EHDI residence province with no treatment at a tertiary institution was associated with the worst survival outcome. For both, unilateral and bilateral disease, children who died were in average diagnosed at older age. CONCLUSIONS: The incidence of retinoblastoma in Argentina is comparable to that of developed countries. Retinoblastoma is diagnosed later and survival is lower in the less developed areas of the country.

Anterior segment invasion in retinoblastoma: is it a risk factor for extraocular relapse?

We report a retrospective review of patients with retinoblastoma and anterior segment invasion (ASI) as risk factors for extraocular relapse. Only those with ASI combined with postlaminar optic nerve invasion and/or scleral invasion received adjuvant chemotherapy and those with tumor at the resection margin received orbital radiotherapy. Those with only uveal invasion did not receive adjuvant therapy. Of 479 evaluable patients, 67 patients had pathologically confirmed ASI, including 52 with anterior chamber invasion and 47 with iris or ciliary body invasion. ASI occurred with other pathology risk factors (25 had concomitant posterior uveal invasion, 36 had postlaminar optic nerve invasion, 11 with cut-end invasion, and 25 with scleral invasion). The 5-year disease-free survival (pDFS) was 0.9 (95% CI, 0.8-0.95) for children with ASI with no significant differences among children with other pathology risk factors with and without ASI. ASI was not significantly associated with extraocular relapse in multivariate analysis. There were no significant differences in pDFS for patients with anterior chamber invasion and those with iris-ciliary body invasion (pDFS 0.89 [95% CI, 0.65-0.96] vs. 0.93 [95% CI, 0.61-0.98]). To conclude, ASI was seen with other pathology risk factors and it did not add a significant risk for extraocular relapse.

Differentiation in retinoblastoma and histopathological risk factors in Mexico.

PURPOSE: To describe the relationship between retinoblastoma differentiation, histopathological risk factors, age at enucleation, laterality, and genetic type (hereditary or sporadic) in a series of enucleated eyes in a referral hospital. The criteria used in other studies to classify retinoblastoma differentiation are discussed. METHODS: The authors retrospectively studied histopathological preparations of eyes with retinoblastoma treated with primary enucleation. Tumors were classified as well differentiated, undifferentiated, and moderately differentiated. Patient age at enucleation, laterality of disease, genetic form (hereditary or sporadic), and presence of histopathological risk factors (massive choroidal infiltration, postlaminar optic nerve invasion, tumor in optic nerve cut, scleral invasion, and involvement of orbital soft tissues) were analyzed. The chi-square test was used for categorical variables and analysis of variance for test mean differences. RESULTS: Histopathological risk factors were present in 23 (36%) of 63 eyes. Moderately differentiated tumors occurred at advanced ages and were more frequently associated with histopathological risk factors. CONCLUSIONS: A consensus is needed to establish the histopathological criteria of retinoblastoma differentiation. The value of rosettes as a marker of cell differentiation should be reviewed.[J Pediatr Ophthalmol Strabismus 2013;50(3):174-177.].

Spectrum of RB1 mutations in argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma.

BACKGROUND: Retinoblastoma is a hereditary cancer of childhood caused by mutations in the RB1 tumor suppressor gene. An early diagnosis is critical for survival and eye preservation, thus identification of RB1 mutations is important for unequivocal diagnosis of hereditary retinoblastoma and risk assessment in relatives. METHODS: We studied 144 families for 20 years, performing methodological changes to improve detection of mutation. Segregation analysis of polymorphisms, MLPA, FISH and cytogenetic assays were used for detection of "at risk haplotypes" and large deletions. Small mutations were identified by heteroduplex/DNA sequencing. RESULTS: At risk haplotypes were identified in 11 familial and 26 sporadic cases, being useful for detection of asymptomatic carriers, risk exclusion from relatives and uncovering RB1 recombinations. Ten large deletions (eight whole gene deletions) were identified in six bilateral/familial and four unilateral retinoblastoma cases. Small mutations were identified in 29 cases (four unilateral retinoblastoma patients), being the majority nonsense/frameshift mutations. Genotype-phenotype correlations confirm that the retinoblastoma presentation is related to the type of mutation, but some exceptions may occur and it is crucial to be considered for genetic counseling. Three families included second cousins with retinoblastoma carrying different haplotypes, which suggest independent mutation events. CONCLUSION: This study enabled us to obtain information about molecular and genetic features of patients with retinoblastoma in Argentina and correlate them to their phenotype.

Clinical pathologic study of a cohort of patients with retinoblastoma from a developing country.

PURPOSE: To describe the histopathologic characteristics of all retinoblastoma biopsy specimens received at one institution. METHODS: All retinoblastoma biopsy specimens received between January 2000 and December 2005 were evaluated and a total of 109 eyes from 101 patients were studied. RESULTS: There were 9 (8.3%) well differentiated, 25 (23.0%) moderately differentiated, and 66 (60.5%) poorly differentiated retinoblastomas. The most common growth pattern was mixed, comprising 81 (74.4%) cases. Vitreous seeding, invasion of the anterior chamber, and invasion of the optic nerve beyond the lamina cribrosa, was present in 79 (72.5%), 24 (22.0%), and 44 (40.4%) eyes, respectively. The tumor was confined to the retina in only 26 (23.9%) cases, whereas 16 (14.8%) had minimal choroidal invasion, 45 (41.3%) had massive choroidal involvement, 10 (9.2%) had scleral invasion, and 11 (10.1%) had extraocular extension. CONCLUSION: In this study, the percentage of patients with choroidal and optic nerve invasion, reflecting a poor prognosis, was much higher than in previously reported North American series. However, similar findings have been described in other developing countries, where late diagnosis is common. This study emphasized the need for early diagnosis and treatment.

Familial retinoblastoma in developing countries.

BACKGROUND: Although screening for familial retinoblastoma has been shown to be beneficial we suspected that such screening programs may be less than optimal in developing countries (DC). METHODS: Retrospective cohort study comparing patients with familial retinoblastoma from five centers in DC (Argentina, Brazil, Turkey, Jordan, and Venezuela) versus a reference center in the USA. RESULTS: Ninety-two (32 from the USA and 60 from DC) patients were included. Forty-one (44.6%) patients avoided enucleation, 42 (45.7%) had 1 eye removed, and 9 (9.8%) underwent bilateral enucleation. Eleven (11.9%) had major pathology risk factors at enucleation. There were no cases of metastatic disease at diagnosis. Detection via screening was significantly less common in DC than in the USA (23.3% vs. 71.8%, P < 0.0001). Patients in DC were diagnosed at a significantly later age and with more advanced intraocular disease that led to increased risk of bilateral enucleation. Patients detected by screening in DC were significantly younger at diagnosis, had less advanced intraocular disease, better ocular preservation rates and survival results than those whose retinoblastoma was not detected via early screening. Five-year pEFS was 0.92 for the patients treated in the USA and 0.81 for the patients in DC (P = 0.42). Seven events occurred (extraocular relapse four in patients from DC and second malignancies in three). CONCLUSIONS: Patients with familial retinoblastoma are less likely to be diagnosed by screening in DC and had higher morbidity and mortality caused by recurrent extraocular retinoblastoma.

Some clinical findings at presentation can predict high-risk pathology features in unilateral retinoblastoma.

AIMS: To identify clinical features at presentation to help in detecting patients with retinoblastoma and pathology risk factors (PRFs) preoperatively, and therefore selecting a high-risk population that could benefit from preoperative treatment. METHODS: A retrospective analysis of a prospectively filled form of 182 consecutive patients with unilateral retinoblastoma treated with initial enucleation from 1988 to 2006. Univariate and multivariate analyses were carried out. Major choroidal invasion and postlaminar optic nerve and scleral extension were considered PRFs. Within this subgroup, a higher-risk cohort (microscopical residual disease caused by trans-scleral invasion or invasion to the resection margin of the optic nerve) was analyzed separately. RESULTS: One hundred sixty-four patients had completely resected and 18 had microscopical residual disease. Seventy three had at least 1 PRF (massive invasion to the choroid in 25, to the postlaminar optic nerve in 41, intrascleral in 10, to the resection margin of the optic nerve in 12, and trans-scleral in 6). Seventy-one patients had glaucoma and 19 had buphthalmia. Intraocular pressure, glaucoma, and buphthalmia correlated significantly with the occurrence of both PRF and microscopical residual disease in multivariate analysis. Buphthalmia was the most specific factor but the sensitivity was lower. Glaucoma and buphthalmia had a high negative predictive value. CONCLUSIONS: Patients presenting with glaucoma and/or buphthalmia have a significantly higher risk for the occurrence of PRF, including those resulting in microscopically residual disease.

Retinoblastoma en pediatría, experiencia en un hospital pediátrico / Retinoblastoma in children, experience at a pediatric hospital

Methods: Retrospective analysis of clinical charts of 41 children (59 eyes) diagnosed with retinoblastoma and treated by a multidisciplinary team at Hospital Luis Calvo Mackenna in Santiago-Chile, between 1999 and 2007. The information included gender, laterality, diagnosis age, presenting signs, tumor spread, treatment modality and survival rate. Results: A total of 23 cases (56 percent) were unilateral and 18 cases (44 percent) were bilateral. The mean age at diagnosis was 21.6 months (range 2 - 84) and 27 children (65.9 percent) were male. The most common presenting signs were leucokoria (51.2 percent), strabismus (24.4 percent) and proptosis (4.9 percent). Enucleation was performed in 48 eyes (81.3 percent), being the only required treatment in 17 children (41.5 percent). The remaining 24 patients received systemic and/or local therapy with chemotherapy, focal therapy and external beam radiation. 5 children died during the follow - up study period, due to extraocular extension to the orbit, central nervous system and bone marrow. Conclusion: In spite of high enucleation rate as initial therapy for retinoblastoma, the survival rate with this current treatment protocol is similar to those from developed countries.

Se presenta un estudio retrospectivo de las fichas clínicas de 41 niños (59 ojos) con diagnóstico de retinoblastoma tratados por un equipo multidisciplinario en el Hospital Luis Calvo Mackenna, Santiago, Chile, entre los a±os 1999-2007. Se recolectó información respecto al género, edad al diagnóstico, signos de presentación, lateralidad, diseminación del tumor, tipos de tratamiento y sobrevida. Veintitrés casos (56 por ciento) fueron unilaterales y 18 (44 por ciento) bilaterales. La edad promedio al momento del diagnóstico fue de 21,6 meses (rango 2-84) y 27 niños (65,9 por ciento) fueron hombres. Los signos de presentación más frecuentes fueron leucocoria (51,2 por ciento), estrabismo (24,4 por ciento) y proptosis (4,9 por ciento). Se realizó enucleación en 48 ojos afectados (81,3 por ciento), siendo el único tratamiento necesario en 17 niños (41,5 por ciento). Los 24 pacientes restantes recibieron tratamientos complementarios locales y/o sistémicos en la modalidad de quimioterapia, terapia focal y radioterapia externa. Durante el período de seguimiento del estudio fallecieron 5 niños, todos ellos con extensión extraocular de la enfermedad hacia la órbita, sistema nervioso central o médula ósea. Conclusiones: No obstante el alto porcentaje de pacientes con retinoblastoma que requieren enucleación como terapia inicial, la tasa de sobrevida con el protocolo actual de tratamiento es comparable a la de países desarrollados.

A multicentre report from the Mexican Retinoblastoma Group.

BACKGROUND: Retinoblastoma (RB) is a relatively uncommon tumour in childhood. The incidence of retinoblastoma in Mexico is probably higher than the incidence reported worldwide, however there is not enough information about the characteristics of this illness in Mexico. This report aims to present the results of a multicentre clinical survey of RB in Mexico. METHODS: A retrospective study was carried out on all RB cases treated in 16 institutions during the last six years. The variables analysed were age at diagnosis, sex, affected eyes, treatment modalities, and pathological staging. Overall survival was obtained. RESULTS: The authors analysed 500 cases; age range was 0-182 months. There were 364 unilateral cases (72.8%). Enucleation was performed in 84.9% of the patients. The St Jude's staging was: 7.4% stage I, 52.8% stage II, 18.0% stage III, 11.4% stage IV, 7.2% not evaluated, and 3.2% missing data. Chemotherapy was used in 74.4% of the patients. Disease free survival was 89% at 73 months follow up. CONCLUSIONS: The paper presents a great number of cases and pioneers multicentre studies in paediatric ophthalmology and oncology in this country. Given the great number of patients in advanced stages and the variability on treatment schemes, it is evident that it is mandatory to work in a cooperative group and develop a national early detection programme as well as a treatment protocol which include all specialists involved in the care of patients with RB.

Epidemiological characteristics of retinoblastoma in children attending the Mexican Social Security Institute in Mexico City, 1990-94.

The object of this study is to present descriptive epidemiological characteristics of retinoblastoma (Rb) in children aged 0-14 years, seen at the Mexican Social Security Institute hospitals in Mexico City (MC) from 1990 to 1994. This is a retrospective, observational hospital survey. Clinical records of 52 Rb cases were reviewed; 39 were patients who did not reside in MC (non-residents), and 13 were MC residents. The study period was 1990-94. The male/female ratio (M/F) was 1.6. Average annual incidence (AAI) was estimated by age and sex (rates per 1000000). Annual average percentage change (AAPC) in incidence rates was estimated in children from 0 to 14 years. The AAI for MC residents was 3.2; the highest rate being for those <1 year olds (rate of 20.8); AAPC was 6.9% [95% CI -27.5, 57.4]; the highest incidence was for the south-eastern region of MC residents (rate of 5.9); 13 cases (25%) were diagnosed at stage III or IV, and 11 cases (21.2%) were bilateral. Incidence of Rb is similar to that in developed countries and shows no increasing trend. Patients from communities outside MC are more frequently diagnosed at stages III and IV.