Retinoblastoma in children older than 5 years of age.

BACKGROUND: Retinoblastoma is a malignant tumor of the embryonic neural retina. About 80% of cases are diagnosed before age 4, with a median age at diagnosis of 2 years. OBJECTIVE: To determine characteristics and prognosis of retinoblastoma in children older than 5 years. PROCEDURES: From 1986 to 2002, medical records of 16 patients out of 453 cases referred to Hospital do Câncer AC Camargo, São Paulo, Brazil. RESULTS: Median age at diagnosis was 73.7 months (range 65-144) and there was an equal gender distribution. Fifteen patients presented with unilateral disease. The mean time between first symptoms and diagnosis was 9.6 months (range 0-48). Most cases were diagnosed in advanced stages and 15 eyes were enucleated. Eleven patients presented with intraocular tumor (1 Reese II and 10 Reese V) and five presented with extraocular disease (one CCG II and four CCG III). Twelve patients are still alive with a median follow-up of 92 months (range 65-199). CONCLUSIONS: Because of its low incidence at this age, diagnosis of retinoblastoma is usually delayed due to low level of suspicion. Therefore, it is important that physicians are aware of this disease in order to perform an earlier diagnosis, and decrease treatment-related morbidity.

Trilateral retinoblastoma.

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.

Treatment of retinoblastoma patients with chemoreduction plus local therapy: experience of the AC Camargo Hospital, Brazil.

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.

O papel do pediatra no diagnóstico precoce do retinoblastoma / The Pediatrician's ability to recognize the presenting signs and symptoms of retinoblastoma

OBJETIVO: O retinoblastoma é o tumor intra-ocular mais freqüente na infância. A forma de apresentação mais comum é leucocoria, seguida pelo estrabismo. Nos países em desenvolvimento, pela demora diagnóstica e maior tempo de encaminhamento, encontramos um grande número de pacientes portadores de tumores extra-oculares. MÉTODOS: Duzentos e trinta e nove pacientes com retinoblastoma admitidos nos departamentos de Pediatria e Oftalmologia do Hospital do Câncer AC Camargo, no período de 1986 a 1995, foram avaliados quanto ao tempo de encaminhamento e extensão do tumor. A análise estatística incluiu o cálculo de freqüências absolutas e relativas, bem como o teste exato de Fisher, para a verificação da associação entre variáveis categorias. RESULTADOS: Pacientes que foram encaminhados em um período menor que 6 meses apresentaram maior freqüência de doença intra-ocular quando comparados com pacientes com tempo de encaminhamento maior que seis meses (75 por cento vs. 25 por cento p<0,001). Não houve diferença estatisticamente significativa para tumores extra-oculares. CONCLUSÕES: O diagnóstico precoce é considerado o ponto mais importante no tratamento de pacientes com retinoblastoma. Os pediatras são capazes de detectar, em uma consulta simples de ambulatório, os sinais e sintomas desta doença e devem ter sempre em mente o diagnóstico de retinoblastoma, possibilitando o encaminhamento precoce a centros especializados.

[The Pediatrician's ability to recognize the presenting signs and symptoms of retinoblastoma]. / O papel do pediatra no diagnóstico precoce do retinoblastoma.

BACKGROUND: Retinoblastoma is the most frequent primary intraocular tumor in children. The most common presenting sign is leukocoria and the second one is strabism. In the developing countries extra ocular disease is seen more frequently because of delayed referral. METHODS: Two hundred and thirty-nine patients with retinoblastoma admitted at the Pediatrics and Ophthalmology Departments of the Hospital do Cancer AC Camargo from 1986 to 1995 were evaluated regarding lag-time and tumor extension. RESULTS: Patients referred within less than 6 months presented a higher rate of intraocular disease compared with patients having a lag-time greater than 6 months (75% vs. 25%, p<0.001). No statistically significant difference was noted for patients with extra-ocular tumors. CONCLUSION: Early diagnosis is the gold standard for patients with Retinoblastoma and the pediatrician's ability to recognize the presenting signs and symptoms can lead to early diagnosis and efficient treatment.

Extraocular retinoblastoma: a 13-year experience.

BACKGROUND: The current study was performed to evaluate two regimens of treatment and to describe clinical and epidemiologic characteristics in patients with extraocular retinoblastoma. METHODS: Eighty-three patients with extraocular retinoblastoma according to Childrens Cancer Group (CCG) classification were admitted to the Pediatric Department of the A. C. Camargo between 1987-2000. The age, gender, race, lag time, first clinical presentation, staging, laterality, and treatment regimen were analyzed. Treatment was comprised of cisplatin, teniposide, vincristine, doxorubicin, and cyclophosphamide during the first treatment period (1987-1991) or cisplatin and teniposide with alternating courses of ifosfamide and etoposide during the second treatment period (1992-2000). RESULTS: The mean age of the patients was 32.9 months (range, 2-145 months). The mean lag time was 10.5 months. Forty-three patients were treated in the first period and 40 patients were treated in the second period. Locally advanced tumors (Class I-III) were present in 83.1% of the patients. There was a positive correlation between lag time and age for unilateral tumors (correlation coefficient [r] = 0.35; P = 0.006), whereas the correlation was negative for bilateral tumors (r = -0.12; P = 0.63). The 5-year overall survival was 55.1% in the first treatment period and 59.4% in the second treatment period (P = 0.69). No significant differences with regard to survival rates were noted for unilateral tumors between the two treatment periods (44.6 noted for unilateral tumors vs. 59.1 noted for unilateral tumors). CONCLUSIONS: In the current study, the addition of ifosfamide and etoposide to a treatment regimen comprised of cisplatin, teniposide, vincristine, doxorubicin, and cyclophosphamide did not appear to improve the survival of patients with extraocular retinoblastoma. Patients with dissemination to the central nervous system or metastatic disease remain incurable and die of progressive disease, despite the aggressive treatment. A multicenter trial should be considered to evaluate the best strategy for these situations.

Evolução da terapêutica do retinoblastoma / Development in the treatment of retinoblastoma

OBJETIVO: Mostrar a evoluçäo do tratamento do retinoblastoma ao longo de uma década e suas implicaçöes na sobrevida global e na preservaçäo da visäo. MÉTODOS: Trezentos e dezenove pacientes foram avaliados no estudo. Analisamos 257 pacientes portadores de retinoblastoma admitidos no Hospital do Câncer, entre janeiro de 1986 a dezembro de 1996, divididos em dois grupos de acordo com tratamento a que foram submetidos (1986 a 1990 e 1991 a 1996). Analisamos ainda 62 pacientes portadores de retinoblastoma intra-ocular entre janeiro de 1996 e maio de 2000 que foram submetidos a quimiorreduçäo, aliada a medidas oftalmológicas, sem enucleaçäo ou radioterapia externa. RESULTADOS: Em pacientes com doença intra-ocular, nos dois períodos, näo houve significância estatística com relaçäo à sobrevida. Analisamos 59 pacientes com retinoblastoma extra-ocular, de acordo com a classificaçäo do CCG (Children´s Cancer Group), e a sobrevida global em 5 anos foi maior no 2º período, (63,7 por cento vs. 41 por cento; p= 0,059). Entre 1996 e 2000 analisamos 62 pacientes com retinoblastoma intra-ocular com visäo preservada, sendo 47 (75,8 por cento) com doença bilateral e 15 (24,2 por cento) com tumor unilateral. Os portadores de tumor bilateral tiveram uma taxa de preservaçäo de visäo de 49,8 por cento, versus 26,7 por cento para os pacientes com tumor unilateral. CONCLUSÖES: Tumores intra-oculares mantêm altas taxas de cura e preservaçäo da visäo. Novas combinaçöes de drogas poderäo melhorar a sobrevida dos extra-oculares. Quanto às perspectivas futuras, há pesquisas envolvendo terapia gênica/molecular e terapêutica anti-angiogênese. Apesar de toda a evoluçäo, o diagnóstico precoce é a arma mais poderosa, na cura dos portadores deste tumor

Results of high dose rate afterloading brachytherapy boost to conventional external beam radiation therapy for initial and locally advanced prostate cancer.

PURPOSE: To evaluate the impact on biochemical control (bNED), acute and late gastro-intestinal (GI) and urological (GU) morbidity of initial and locally advanced prostate cancer treated with fractionated transrectal ultrasound-guided (TRUS) high dose rate after loading brachytherapy (HDR-B) as a boost to conventional external beam radiation therapy (EBRT). PATIENTS AND METHODS: From March 1997 to February 2000 a total of 119 patients with any of the following characteristics were eligible for study entry: biopsy proven adenocarcinoma Gleason scored (GS), initial prostatic specific antigen (PSA) level dosage 1992 AJCC clinical stage T3a or less, and prostatic volume <60 cc. All patients had prior to HDR-B a course of EBRT 6 MV photons to a median dose of 45 Gy, in 1.8 Gy fractions, to the prostate and seminal vesicles only. HDR-B treatment planning and dosimetric calculations were generated with the Nucletron Planning System. Patients were grouped into two groups, according to their risk for biochemical failure: low-risk group without (LR) or with neoadjuvant total androgen deprivation (AD) prior to EBRT (LR+AD) and high-risk group without (HR) or with neoadjuvant AD (HR+AD), for bNED and dose-escalation protocol. LR encompassed patients who presented GS<6, T1 or T2a and or initial PSA<10 ng/ml, who were treated with 16 Gy (4 Gy fractions, b.i.d.) HDR-B. The remaining patients were grouped into HR or HR+AD and received 20 Gy (5 Gy fractions, b.i.d.) HDR-B. The planning was optimized using the standard geometric optimization. Biological effective doses (BED) for tumor control and late responding tissue were calculated using a alpha/beta ratio of 1.5 and 3 Gy, respectively. They were matched with bNED, acute and late gastrointestinal (GI) and urological (GU) morbidity, according to the RTOG/EORTC scoring criteria. RESULTS: Median age of patients was 68 years (range 47-83), with a median follow-up of 41 months (range 18-48). The crude and actuarial biochemical controls (bNED) in 48 months for all patients were 69.5 and 75.3%, respectively. When grouped into LR, LR+AD, HR and HR+AD the actuarial bNED were 78.2, 76, 76 and 72.3% (P=0.89), respectively. Acute GU and GI morbidity G1-2 were seen in 18.5% (20/108) and 10.2% (11/108) of patients with spontaneous regression. Late GI and GU morbidity G1-2 were seen in 12% (13/108) and 4.6 (5/108) of patients, with no need of intervention. No acute or late G3-4 GU or GI morbidity was seen. CONCLUSIONS: There are many advantages in HDR-B, but the most important ones are the capability of on-line dosimetry, quality control and the procedure being very conformal. There is a low incidence of GU and GI acute and late morbidity with acceptable bNED when treating initial and locally advanced prostate cancer with HDR-B as a boost to EBRT, but we still need to wait for results of phase III open trials that analyze HDR-B and conformal therapy.

Braquiterapia de alta taxa de dose associada a radioterapia externa no tratamento de angiossarcoma extenso do couro cabeludo: relato de caso / Combination of high-dose rate brachytherapy and external beam radiotherapy for the treatment of advanced scalp angiosarcoma: case report

Os autores apresentam um caso de extenso angiossarcoma do couro cabeludo submetido a radioterapia exclusiva, pela associação de roentgenterapia de ortovoltagem e braquiterapia de alta taxa de dose utilizando um molde. Descrevem os aspectos clínicos, técnicos e a evolução terapêutica. Destacam as particularidades e a utilidade da braquiterapia de alta taxa de dose, nesta situação em particular, e fazem uma análise comparativa das dificuldades e limitações caso a braquiterapia de baixa taxa de dose fosse empregada. Concluem ser a braquiterapia de alta taxa de dose uma opção útil, prática e segura para as lesões neoplásicas superficiais do escalpe, podendo ser considerada uma alternativa ao tratamento com elétrons.

Melanoma maligno: achados histopatológicos em olhos enucleados pós-braquiterpia com cobalto-90 / Malignant melanoma: histopathological findings in enucleated eyes after coblat-60 plaque therapy

Os autores avaliam os achados histopatológicos de 13 olhos com melanoma uveal submetidos à braquiterapia e posteriormente enucleados por insucesso com o tratamento ou por complicaçöes como hemorragia vítrea, descolamento total da retina e glaucoma neovascular. Os achados säo comparados com os de 13 olhos com emlanoma uveal, de dimensöes equivalentes, enucleados no mesmo período, sem qualquer tratamento prévio. Foram avaliados: o tipo histológico, pigmentaçäo, ruptura da membrana de Bruch, infiltraçäo linfocitária, fibrose, necrose, alteraçöes vasculares, infiltraçäo de esclera, assim como dos vasos episclerais e número de mitoses em 10 campos de aumento. Fibrose ocorreu somente no grupo irradiado. Houve predomínio da necrose difusa no grupo

Braquiterapia intraluminar de alta taxa de dose: uma nova perspectiva no tratamento do câncer do esôfago / Intraluminal high-dose-rate brachytherapy: a new perspective on treatment of esophageal cancer

Braquiterapia com microfonte radioativa operada por controle remoto comandado por computador trouxe nova perspectiva no tratamento intraluminar de vários tumores. Este relato apresenta a experiência preliminar do Serviço de Braquiterapia do Departamento de Radioterapia do Hospital A.C. Camargo no tratamento do carcinoma de esôfago com braquiterapia de alta taxa de dose. A técnica utiliza a inserção de um aplicador esofágico sob videoendoscopia após a radioterapia externa. Três inserções de 6 Gy, em intervalo de duas semanas, iniciando-se 15 dias após radioterapia externa com 54 Gy em 30 frações, são empregadas para os tratamentos curativos. Nos tratamentos paliativos, duas inserções de 7,5 Gy, com uma semana de intervalo, são utilizadas e a dose de radioterapia externa limita-se a 40 Gy em 20 frações. A extensão do esôfago a ser tratada é determinada pelo esofagograma e pela reação actínica residual após a radioterapia externa, detectável à endoscopia de controle, com margem de 2 cm. O cálculo da dose se faz a 10 mm do centro do cateter. De janeiro/93 a dezembro/94, 100 procedimentos foram realizados em 35 pacientes. Vinte e cinco foram tratados com intenção curativa e dez, com intenção paliativa. A idade variou dos 43 aos 82 anos (mediana de 64 anos), com predominância do sexo masculino (9:1). A braquiterapia foi bem tolerada e realizada em caráter ambulatorial. Reações agudas, representadas por esofagite transitória, ocorreram em todos os pacientes. Reações tardias, como fístulas e estenoses, foram observadas em 16 por cento e 40 por cento dos casos, respectivamente. A sobrevida média foi de oito meses para os tratamentos curativos e de quatro meses para os paliativos. Capacidade de alimentação por via oral se manteve em 85 por cento dos pacientes até o óbito. Os resultados preliminares concluem que o procedimento é seguro, prático e efetivo, e deve ser estimulado na abordagem terapêutica multidisciplinar do carcinoma do esôfago.