RESUMEN
Studies are lacking on long-term effects among retinoblastoma patients in low- and middle-income countries. Therefore, we examined cause-specific mortality in a retrospective cohort of retinoblastoma patients treated at Antonio Candido de Camargo Cancer Center (ACCCC), São Paulo, Brazil from 1986 to 2003 and followed up through December 31, 2018. Vital status and cause of death were ascertained from medical records and multiple national databases. We estimated overall and cause-specific survival using the Kaplan-Meier survival method, and estimated standardized mortality ratios (SMRs) and absolute excess risk (AER) of death. This cohort study included 465 retinoblastoma patients (42% hereditary, 58% nonhereditary), with most (77%) patients diagnosed at advanced stages (IV or V). Over an 11-year average follow-up, 80 deaths occurred: 70% due to retinoblastoma, 22% due to subsequent malignant neoplasms (SMNs) and 5% to non-cancer causes. The overall 5-year survival rate was 88% consistent across hereditary and nonhereditary patients (p = .67). Hereditary retinoblastoma patients faced an 86-fold higher risk of SMN-related death compared to the general population (N = 16, SMR = 86.1, 95% CI 52.7-140.5), corresponding to 42.4 excess deaths per 10,000 person-years. This risk remained consistent for those treated with radiotherapy and chemotherapy (N = 10, SMR = 90.3, 95% CI 48.6-167.8) and chemotherapy alone (N = 6, SMR = 80.0, 95% CI 35.9-177.9). Nonhereditary patients had only two SMN-related deaths (SMR = 7.2, 95% CI 1.8-28.7). There was no excess risk of non-cancer-related deaths in either retinoblastoma form. Findings from this cohort with a high proportion of advanced-stage patients and extensive chemotherapy use may help guide policy and healthcare planning, emphasizing the need to enhance early diagnosis and treatment access in less developed countries.
Asunto(s)
Retinoblastoma , Humanos , Retinoblastoma/mortalidad , Retinoblastoma/terapia , Brasil/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Lactante , Niño , Neoplasias de la Retina/mortalidad , Neoplasias de la Retina/terapia , Causas de Muerte , Tasa de Supervivencia , Adolescente , Adulto , Adulto Joven , Estimación de Kaplan-MeierRESUMEN
BACKGROUND: The objective of this study was to identify the ocurrence of hearing loss in children treated for retinoblastoma using a multidisciplinary approach. PATIENTS AND METHODS: Thirty-two children were evaluated pre- and post-treatment. Eleven children were treated exclusively with enucleation, fifteen with carboplatin and six with cisplatin. Otoacoustic emissions were performed with the ILO 88, before and after the treatment. RESULTS: In our study we found 5 children (24%) with hearing loss among the 21 evaluated. However in the group of children treated with carboplatin (N=15), 1 case (6.6%) presented hearing loss, while among those treated with cisplatin (N=6) we found 4 cases (66.6%) with hearing loss (p=0.0114). CONCLUSION: We concluded that patients who are treated with cisplatin are at risk for developing hearing loss.
Asunto(s)
Antineoplásicos/efectos adversos , Pérdida Auditiva/etiología , Retinoblastoma/complicaciones , Retinoblastoma/tratamiento farmacológico , Pruebas de Impedancia Acústica/métodos , Audiología/métodos , Audiometría/métodos , Niño , Cisplatino/efectos adversos , Enfermedades del Oído/etiología , Femenino , Humanos , Masculino , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , RiesgoRESUMEN
Retinoblastoma is the most frequent intra-ocular malignant tumor of the childhood, occurring in 1 of 18,000-30,000 live births. Little is known about the causes of sporadic retinoblastoma and only a few authors have investigated the etiologic role of human papillomavirus (HPV), with controversial results. Formalin-fixed, paraffin-embedded tissue blocks containing retinoblastoma were retrieved from the archives of the Department of Pathology at Hospital A C Camargo, São Paulo, Brazil. All patients were treated with enucleation (21 children had both eyes enucleated). Retinoblastoma and, when possible, normal retina of each specimen, were micro-dissected under direct light microscopic visualization by using a PixCell II Laser Capture Micro-dissection System. The DNA quality was evaluated by polymerase chain reaction (PCR) amplification of 110 base pairs fragment of the human ß-globin gene using primers PCO3+/PCO4+. All globin positive specimens were analyzed by PCR for the presence of HPV DNA using consensus primers GP5+/GP6+. A total of 154 specimens were evaluated. Forty-four patients also had normal retinal specimens available for analysis of DNA HPV. The DNA HPV prevalence among all tumor specimens was 4.6% (95% CI 2.0; 8.8) (7 positive specimens/153 adequate specimens). Among normal retinal specimens, the DNA HPV prevalence was 9.1% (95% CI 2.9; 20.5) (4 positive specimens/44 specimens). There was no statistically significant difference between these rates (P = 0.318). Excluding any experimental failure, our results indicate a low prevalence of HPV DNA in retinoblastomas. We were therefore unable to conclude about the association between these oncogenic viruses and this rare pediatric neoplasm.
Asunto(s)
Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Retinoblastoma/complicaciones , Retinoblastoma/virología , Brasil/epidemiología , Niño , Preescolar , Cartilla de ADN/genética , ADN Viral/genética , ADN Viral/aislamiento & purificación , Femenino , Humanos , Lactante , Masculino , Infecciones por Papillomavirus/virología , Patología Molecular/métodos , Reacción en Cadena de la Polimerasa/métodos , PrevalenciaRESUMEN
Retinoblastoma is the most frequent intra-ocular malignant tumor of the childhood, occurring in 1 of 18,00030,000 live births. Little is known about the causes of sporadic retinoblastoma and only a few authors have investigated the etiologic role of human papillomavirus (HPV), with controversial results. Formalin-fixed, paraffin-embedded tissue blocks containing retinoblastoma were retrieved from the archives of the Department of Pathology at Hospital A C Camargo, São Paulo, Brazil. All patients were treated with enucleation (21 children had both eyes enucleated). Retinoblastoma and, when possible, normal retina of each specimen, were micro-dissected under direct light microscopic visualization by using a PixCell II Laser Capture Micro-dissection System. The DNA quality was evaluated by polymerase chain reaction (PCR) amplification of 110 base pairs fragment of the human β-globin gene using primers PCO3 +/PCO4+. All globin positive specimens were analyzed by PCR for the presence of HPV DNA using consensus primers GP5+/GP6+. A total of 154 specimens were evaluated. Forty-four patients also had normal retinal specimens available for analysis of DNA HPV. The DNA HPV prevalence among all tumor specimens was 4.6% (95% CI 2.0; 8.8) (7 positive specimens/153 adequate specimens). Among normal retinal specimens, the DNA HPV prevalence was 9.1% (95% CI 2.9; 20.5) (4 positive specimens/44 specimens). There was no statistically significant difference between these rates (P = 0.318). Excluding any experimental failure, our results indicate a low prevalence of HPV DNA in retinoblastomas. We were therefore unable to conclude about the association between these oncogenic viruses and this rare pediatric neoplasm
Asunto(s)
Masculino , Femenino , Humanos , Lactante , Preescolar , Niño , Brasil/epidemiología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Patología Molecular/métodos , Retinoblastoma/complicaciones , Retinoblastoma/virología , Cartilla de ADN , Prevalencia , Reacción en Cadena de la Polimerasa/métodosRESUMEN
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.
Asunto(s)
Neoplasias de la Retina/epidemiología , Retinoblastoma/epidemiología , Preescolar , Estudios de Cohortes , Países en Desarrollo , Humanos , Lactante , Recién Nacido , Neoplasias de la Retina/mortalidad , Retinoblastoma/mortalidad , Estudios RetrospectivosRESUMEN
BACKGROUND: Trilateral retinoblastoma (TRB) is a syndrome consisting of unilateral or bilateral hereditary retinoblastoma (Rb) associated with an intracranial neuroblastic tumor. Although its incidence is low, the prognosis is very poor. This article reports four cases of TRB and discusses the role of neuroimaging screening for early detection. PROCEDURE: From January 1986 to December 2003, 470 children with Rb were admitted to the Pediatrics and Ophthalmology Departments, A C Camargo Hospital, São Paulo, Brazil. RESULTS: There were four patients with pineoblastoma, two of whom had a positive familial history. The age at diagnosis of Rb was 4, 6, 10, and 24 months while the age of diagnosis of TRB was 10, 25, 57, and 72 months. One patient presented TRB at initial diagnosis of Rb. Three patients had bilateral disease and all of them had one eye enucleated, followed by chemotherapy and/or external beam radiation therapy (EBRT). One child with unilateral disease was only submitted to enucleation. In spite of intensive treatment, all patients died with progressive disease within 7, 8, 12, and 12 months after diagnosis of TRB. CONCLUSIONS: Early diagnosis as well as new therapeutic approaches are needed to achieve better results.
Asunto(s)
Neoplasias del Ojo/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Secundarias/patología , Pinealoma/patología , Retinoblastoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Preescolar , Cisplatino/administración & dosificación , Terapia Combinada , Irradiación Craneana , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Etopósido/administración & dosificación , Enucleación del Ojo , Neoplasias del Ojo/tratamiento farmacológico , Neoplasias del Ojo/genética , Neoplasias del Ojo/radioterapia , Neoplasias del Ojo/cirugía , Resultado Fatal , Femenino , Humanos , Idarrubicina/administración & dosificación , Ifosfamida/administración & dosificación , Masculino , Metotrexato/administración & dosificación , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/radioterapia , Neoplasias Primarias Múltiples/cirugía , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/radioterapia , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/patología , Pinealoma/tratamiento farmacológico , Pinealoma/genética , Pinealoma/radioterapia , Pinealoma/cirugía , Pronóstico , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/genética , Retinoblastoma/radioterapia , Retinoblastoma/cirugía , Vincristina/administración & dosificaciónRESUMEN
OBJECTIVE: To assess the outcome and determine risk factors for extraocular relapse in patients with retinoblastoma who had been enucleated after failure of chemoreduction. METHODS: Retrospective study (1995-2002) at three institutions. Pathological risk factors (PRF) were defined as invasion of the anterior segment, choroid, post-laminar optic nerve, subarachnoid space, or sclera according to the local pathology report. Extraocular relapse was defined as an event. RESULTS: One hundred twenty-two patients were included (17 had bilateral enucleation). Chemoreduction included vincristine, carboplatin, and etoposide (n=80, 65.6%), vincristine, and carboplatin (n=17, 13.9%), or carboplatin (n=25, 20.5%). Thirty-five also received external beam radiotherapy (28.7%). PRF included: 39 with choroidal involvement, 9 with anterior segment, 9 with scleral, and 2 with post-laminar optic nerve with subarachnoid invasion. Adjuvant chemotherapy was given to eight patients (6.5%) because of scleral invasion. Four patients had an extraocular relapse after enucleation, two of whom survive after intensive treatment including stem cell rescue. Five-year probability of event-free survival is 0.96. Only scleral invasion and bilateral enucleation were significantly associated with extraocular relapse. CONCLUSIONS: The risk of extraocular relapse is low after enucleation following failure of chemoreduction. Patients who underwent bilateral enucleation and those with scleral invasion are at higher risk of extraocular relapse.
Asunto(s)
Enucleación del Ojo , Neoplasias de la Retina/cirugía , Retinoblastoma/secundario , Retinoblastoma/cirugía , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Quimioterapia Adyuvante , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Invasividad Neoplásica , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/patología , Retinoblastoma/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
To evaluate the efficacy of conservative management of intraocular retinoblastoma with chemoreduction combined with local therapy with or without plaque radiation in the preservation of the eye, and avoidance of external beam radiation therapy (EBRT) (success rate). From 1995 to 2000, 84 newly diagnosed patients with intraocular retinoblastoma were admitted to the Pediatric Department of the Hospital do Cancer A.C. Camargo, São Paulo, Brazil. All children were treated with 2 to 6 cycles of chemotherapy (carboplatin, vincristine, and etoposide) plus local therapy (cryotherapy, laser photocoagulation, and thermotherapy), or plaque radiation therapy during and/or after the chemotherapy. The Mann-Whitney test was used to compare means of quantitative variables. The chi test or the Fisher exact test were employed to verify the association between the outcome and the independent variables. For all tests alpha=5% was adopted. Success rate was higher for patients with bilateral tumors (54%) than for children with unilateral tumors (19%) (P=0.003). For patients with Reese-Ellsworth stages I, II, and III, no statistically significant differences in the success rates were noted in the group of unilateral (50%) and bilateral tumors (79.1%) (P=0.179). Among children with Reese-Ellsworth stages IV and V, the success rate was significantly higher for patients with bilateral tumors (40.7%) than for those with unilateral (0%) (P=0.012). Chemoreduction combined with local therapy, with or without plaque radiotherapy, is efficacious in avoiding enucleation and the use of external beam radiation therapy for children with intraocular retinoblastoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Adolescente , Adulto , Antineoplásicos Fitogénicos/administración & dosificación , Brasil , Carboplatino/administración & dosificación , Niño , Preescolar , Terapia Combinada , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , Lactante , Masculino , Neoplasias de la Retina/mortalidad , Retinoblastoma/mortalidad , Estudios Retrospectivos , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Although intra-retinal tumor has long been staged presurgically according to the Reese-Ellsworth (R-E) system, retinoblastoma differs from other pediatric neoplasms in never having had a widely accepted classification system that encompasses the entire spectrum of the disease. Comparisons among studies that consider disease extension, risk factors for extra-ocular relapse, and response to therapy require a universally accepted staging system for extra-ocular disease. PROCEDURE: A committee of retinoblastoma experts from large centers worldwide has developed a consensus classification that can encompass all retinoblastoma cases and is presented herein. Patients are classified according to extent of disease and the presence of overt extra-ocular extension. In addition, a proposal for substaging considering histopathological features of enucleated specimens is presented to further discriminate between Stage I and II patients. RESULTS: The following is a summary of the classification system developed-Stage 0: Patients treated conservatively (subject to presurgical ophthalmologic classifications); Stage I: Eye enucleated, completely resected histologically; Stage II: Eye enucleated, microscopic residual tumor; Stage III: Regional extension [(a) overt orbital disease, (b) preauricular or cervical lymph node extension]; Stage IV: Metastatic disease [(a) hematogenous metastasis: (1) single lesion, (2) multiple lesions; (b) CNS extension: (1) prechiasmatic lesion, (2) CNS mass, (3) leptomeningeal disease]. A proposal is also presented for substaging of enucleated Stages I and II eyes. CONCLUSIONS: The proposed staging system is the product of an international effort to adopt a uniform staging system for patients with retinoblastoma to cover the whole spectrum of the disease.
Asunto(s)
Estadificación de Neoplasias/normas , Neoplasias de la Retina/clasificación , Neoplasias de la Retina/diagnóstico , Retinoblastoma/clasificación , Retinoblastoma/diagnóstico , Humanos , Neoplasias de la Retina/patología , Retinoblastoma/patologíaRESUMEN
Durante o período de janeiro de 1970 a dezembro de 1991, 30 lactentes portadores de sarcoma de partes moles primário do tronco e extremidades foram admitidos no Departamento de Pediatria do Hospital do Câncer. Treze neoplasias eram originárias da parede torácica e abdominal; 13, de membros inferiores; e quatro, de membros superiores. Dez pacientes apresentavam doença localizada e 20, doença avançada. Em relaçäo ao tipo histológico, 18 tumores foram classificados como sarcomas de partes moles näo rabdomiossarcoma. Quinze crianças estäo vivas sem evidência de doença; uma, viva com segundo tumor (LLA); três foram perdidos de seguimento e 11 foram a óbito (10 por progressäo de doença e um por toxicidade). A intervençäo cirúrgica, a quimioterapia e a radioterapia utilizadas isoladamente ou combinadas na dependência do tipo histológico e extensäo da doença nos pacientes portadores de sarcomas de partes moles foram responsáveis pelo aumento da taxa de cura nesses casos. As características intrínsecas do lactente fazem com que cada vez mais esses recursos terapêuticos venham a ser aprimorados a fim de que os efeitos colaterais decorrentes do tratamento sejam evitados ou minimizados. Ao analisarmos lactentes portadores de sarcomas de partes moles, pudemos avaliar os efeitos deletérios decorrentes da terapêutica preconizada nos anos 70 e 80, atentando para o fato de que cada vez mais, cura e qualidade de vida devem caminhar paralelamente. Os avanços em biologia molecular poderÝo, num futuro próximo, selecionar pacientes de maior ou menor risco, preconizando tratamentos mais e menos agressivos na dependência do prognóstico. O fator prognóstico mais importante foi a extensäo da doença ao diagnóstico.
Asunto(s)
Humanos , Lactante , Sarcoma/diagnóstico , Sarcoma/tratamiento farmacológico , Sarcoma/mortalidad , Sarcoma/radioterapia , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía , Estudios de Seguimiento , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
Retinoblastoma é o tumor intra-ocular mais comum na infância, representando 1 porcento de todos os tumores pediátricos. Em muitos casos a predisposiçÝo genética é observada. Anomalias congênitas têm sido descritas. Nós reportamos dois casos de retinoblastoma associado com estenose pulmonar. IdentificaçÝo precoce e tratamento deste defeito cardíaco associado a terapia efetiva para retinoblastoma têm resultado em longa sobrevida livre de doença para estes dois pacientes sem seqüela cardíaca. Uma avaliaçÝo de todos os pacientes com retinoblastoma é justificada para excluir outras anomalias que poderiam comprometer o excelente resultado destes pacientes.