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.

[Survival and clinical features of retinoblastoma]. / Supervivencia y aspectos clínicos del retinoblastoma.

INTRODUCTION: Retinoblastoma (RB) is the most frequent intraocular tumor in the pediatric age group, representing 3 % of all childhood neoplasms. In Mexico, the annual incidence varies according to the geographical area studied, ranging from 4-24 cases/million in patients younger than 15 years. Ninety-five percent of cases occur in infants and pre-school children. PATIENTS AND METHOD: An observational, retrospective, descriptive, cross-sectional study of all children with RB admitted to the Oncology Department of the Pediatric Hospital of the National Medical Center in a 10-year period was performed. RESULTS: Fifty-six patients were included. The median age was 24 months. Forty-two children presented unilateral RB. Symptoms at diagnosis were leukokoria, strabismus and reduced visual sharpness. Distribution according to Prats' classification was the following: stage I, 5 patients; stage II, 32; stage III, 14; stage IV, 5. Histological analysis revealed 24 patients with poorly differentiated RB, 16 with well-differentiated RB, 13 with moderately differentiated RB and 7 with undifferentiated RB. In eight patients histological type was not identified. In 12 of the 56 patients cytogenetic and molecular studies were performed. All patients underwent surgery. Patients in the early stages were treated with chemotherapy. A total of 26.7 % of the group presented relapse. The disease-free survival at 10 years was 87.5 %. CONCLUSIONS: As with other childhood neoplasms, early diagnosis and multidisciplinary management of RB has improved prognosis and survival. The symptoms, treatment and survival reported in this pediatric cohort are similar to those of other published series.

Supervivencia y aspectos clínicos del retinoblastoma / Survival and clinical features of retinoblastoma

Introducción El retinoblastoma es el tumor intraocular maligno más frecuente en pediatría. Representa el 3 per cent de las neoplasias de la infancia. En México, la incidencia anual varía de acuerdo con la zona geográfica estudiada en un rango de 4 a 24 casos por millón en menores de 15 años y el 95 per cent de los casos se presenta en la etapa de lactante y preescolar. Pacientes y método Estudio observacional, retrospectivo, descriptivo y transversal. Se incluyeron todos los niños con retinoblastoma atendidos en 10 años en el Servicio de Oncología del Hospital de Pediatría del Centro Médico Nacional IMSS. Resultados Se incluyeron 56 pacientes. La mediana de edad fue de 24 meses. Presentaron retinoblastoma unilateral 42 casos. Los síntomas presentes al diagnóstico fueron: leucocoria, estrabismo y disminución de la agudeza visual. La distribución de acuerdo con la clasificación de Pratt fue: etapa I, 5; etapa II, 32; etapa III, 14; etapa IV, 5. Por histología: 24 pacientes con retinoblastoma pobremente diferenciado, 16 bien diferenciados y 13 moderadamente diferenciados, 7 casos no diferenciados y en 8 casos la variedad histológica no se identificó. En el grupo de pacientes estudiados 12 de los 56 se incluyeron en un protocolo de estudio citogenético y molecular. Todos los pacientes se sometieron a cirugía. La quimioterapia se indicó en los estadios tempranos. El 26,7 per cent presentaron recidivas. La supervivencia libre de enfermedad fue del 87,5 per cent a 10 años. Conclusiones El retinoblastoma al igual que en otras neoplasias en pediatría, el diagnóstico oportuno y el manejo multidisciplinario ha mejorado el pronóstico y la supervivencia. Los síntomas, el tratamiento y la supervivencia de la presente cohorte son similares a lo comunicado en la literatura (AU)

Preirradiation ifosfamide, carboplatin, and etoposide for the treatment of anaplastic astrocytomas and glioblastoma multiforme: a phase II study.

BACKGROUND: Central nervous system (CNS) tumors are the second most common pediatric tumors. Astrocytomas represent 35% of all CNS tumors in children. Traditional treatment of anaplastic astrocytoma (AA) and glioblastoma multiforme (GM) consisting of surgery-radiotherapy-chemotherapy with nitrosoureas has resulted in a survival rate of 26% at 1 year. Neoadjuvant chemotherapy has proven good results in the treatment of other solid tumors. Chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) permits synergism among the different drugs and sensitizes the tumor to radiotherapy. Our objective was to evaluate the efficacy, security, and survival rate of postoperative chemotherapy with ICE in pediatric patients with AA or GM. METHODS: Phase II study. We evaluated 11 children with AA or GM who had received no prior treatment. A magnetic resonance image (MRI) study of the tumor was made after surgery to evaluate residual tumor and routine laboratory analysis. Chemotherapy with carboplatin, ifosfamide and etoposide was given every 3 weeks for four courses. MRI studies were repeated after the second and last courses and laboratory analyses were carried out before each course to evaluate toxicity. Each patient then received hyperfractionated radiotherapy and a final MRI was done at the end of the treatment. RESULTS: Sixty percent of the patients had partial response, 30% complete response after two courses, and 60% of CR after four courses. Supratentorial and infratentorial tumors had a good response to chemotherapy. Brainstem tumors had an initial response after two courses and then increased in size. AA was the tumor with the greatest reduction of residual tumor after treatment. Overall and free survival at 53 months was 70%. To date, three patients have died secondary to tumoral progression. There have been no relapses in the seven patients with a CR. CONCLUSIONS: Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity. Brainstem responded poorly to treatment.

Security and maximal tolerated doses of fluvastatin in pediatric cancer patients.

BACKGROUND: The role of cholesterol in neoplasic cell growth and its inhibition by drugs has recently been studied. Cholesterol biosynthesis inhibitors have been used as adjuvants in the treatment of cancer and possibly as prophylactic in carcinogenesis. OBJECTIVE: The objective of the study was to determine the maximal tolerated doses (MTD) and toxic effects of fluvastatin in pediatric cancer patients. METHODS: This study was carried out in a third level Social Security Hospital in Mexico City. We included pediatric patients from April 1996 to May 1997. All were terminal cancer patients who did not respond to conventional therapies. Fluvastatin was given p.o. at doses of 2 mg/kg/day for 14 days every 4 weeks in three patients. Subsequent cohorts of three patients each had increments of 2 mg/kg/day of the drug until maximal tolerated doses were found. Toxic effects of the drug were evaluated by physical exploration, laboratory assays and a questionnaire given to each patient. RESULTS: Twelve patients were included. Diagnoses included two osteosarcomas, eight central nervous system tumors, one lung tumor, and one Ewing's sarcoma. Ten patients died within 1 to 18 months. Two are alive 22 months after inclusion into the study, both with anaplasic astrocytoma. A total of 27 courses were administered. The MTD was 8 mg/kg/day. Toxic effects were insomnia, nausea, vomiting, abdominal distention and myalgias. Toxicity was dose-dependent. Laboratory assays demonstrated no significant changes during treatment. CONCLUSIONS: Fluvastatin can be safely used at doses of 8 mg/kg/day in pediatric patients with cancer. This dose should be used in additional trials.

Survival of patients with medulloblastoma treated with carboplatin and etoposide before and after radiotherapy.

BACKGROUND: Medulloblastoma represents 20% of all tumors of the central nervous system. Patients with partial resection of the tumor and those with extension into the neuraxis at diagnosis have been identified as high-risk patients. The objective of our study was to determine tumor response, survival rates and toxicity with a new scheme of treatment with carboplatin, etoposide and radiotherapy. METHODS: All patients received chemotherapy with carboplatin and etoposide every 4 weeks for four courses, hyperfractionated radiotherapy, and another four courses of the above chemotherapy scheme. Tumor response was classified, and global and disease-free survival rates were calculated according to the actuarial survival method. RESULTS: A total of 26 patients were included, with a median age of 6.9 years. Nineteen achieved complete response after the first four courses of chemotherapy, and two more had a complete response after radiotherapy. A total of seven children have died, three of whom did not respond to initial treatment. Global and disease-free survival rates were 69% and 64%, respectively, at 60 months of follow-up. There was no renal or auditory toxicity. Hematological toxicity was transitory and reversible. CONCLUSIONS: This scheme of treatment is effective and can be safely used for pediatric patients with high-risk medulloblastomas. Toxicity was not significant, and survival is similar to other reports.

[Astrocytomas in pediatrics. The prognostic factors and survival]. / Astrocitomas en pediatría. Factores pronósticos y sobrevida.

Tumors of the central nervous system are the second most frequent malignancy in children under the age of 15 the majority of which are astrocytomas. The purpose of this paper is to analyze the effect of some factors on the survival of patients with astrocytomas. We reviewed the clinical charts of patients with a diagnosis of astrocytoma from 1984 to 1995 and we analyzed the age, sex, location, malignant grade and survival according to the actuarial method and log rank tests. A total of 39 patients were detected, 43% were supratentorial, 13% cerebellar and 43% from the brain stem. There was a better prognosis for those located supratentorial or cerebellar with respect to those in the brain stem, with statistical significance. The treatment consisted in surgical resection in 26 patients, 17 of which were found to have a high grade of malignancy and 9 with low grade, with statistically better prognosis for low grade tumors. There were 17 deaths during the period, with 8 of these patients having a high grade tumor a 10, with brain stem tumors. Forty-one percent of the patients that died did so in the first year and 94% during the first two years after diagnosis. Patients with cerebellar astrocytoma and patients with low-grade astrocytomas had the best prognosis.

[Lactic dehydrogenase as a prognostic factor in the development of pulmonary metastatic disease in patients with osteosarcoma]. / La deshidrogenasa láctica como factor pronóstico del desarrollo de enfermedad metastásica pulmonar en pacientes con osteosarcoma.

Remarkable progress has been made in the treatment of osteosarcoma in the past two decades as a result of the development of effective adjuvant chemotherapy. However, the prognosis is poor in patients with early lung metastases. We review the lactate dehydrogenase release prognostic factor in the development of early lung metastases. This is a retrospective study. Eighteen patients with osteosarcoma were divided in two groups: Group A, patients with normal lactate dehydrogenase and Group B, patients with elevated lactate dehydrogenase. A univaried analysis was established. Ten patients (55%) had elevated levels of lactate dehydrogenase at diagnosis; nine of these patients developed lung metastases in the first twelve months. The difference in patients with normal levels of lactate dehydrogenase was significant (p: 0.02). The value of lactate dehydrogenase as an isolated single factor is limited. It is necessary to consider the tumoral volume, the patient's age and the histologic subtype in the prognosis of these patients, to predict the early development of pulmonary metastatic disease.

[Hodgkin's disease with the nephrotic syndrome. A case report]. / Enfermedad de Hodgkin con síndrome nefrótico. Informe de un caso.

It is presented a child with Hodgkin's disease which at diagnosis present associated at nephrotic syndrome. Male of nine years old which present a ganglionic growing of left jugular chain of one year evolution without systemic symptoms and anasarca. Were underwent a ganglionic biopsy with histopathology report of Hodgkin's disease mixed cellular variety and renal biopsy with histopathology report of minimal change disease. The patient present remission of nephrotic syndrome in simultaneous form at the control of the disease. In the reported cases of nephrotic syndrome associated with Hodgkin's disease it not clear the physiopathology. In this patient were realized immunologic studies of renal tissues to treat to find a possible mechanism of action of the neoplastic cells on the basal glomerular membrane but we can not found.