[Prognostic and survival factors among pediatric patients with ependymomas]. / Factores pronósticos y sobrevida de pacientes pediátricos con ependimomas.

BACKGROUND: Ependymomas constitute the third most common intracranial tumors in children. Risk factors include age, location, extent of surgical excision, and radiation therapy. Recently, chromosomal imbalances have been described. OBJECTIVE: Determine global survival of patients with ependymomas according to different prognostic factors. METHODS: We reviewed the medical charts of every pediatric patient with ependymoma from 1996 to 2005. Genomic imbalances were determined using comparative genomic hybridization (CGH). Survival was calculated using the Kaplan and Meier method. We used the Log Rank test for each risk factor. Death risk was calculated by odds ratio (OR). RESULTS: We included 24 patients. Global survival was 58.04%. The presence of chromosomal imbalances, particularly in chromosome 21, significantly affected survival Being under 5 years of age, anaplastic histology, chemotherapy other than ICE (ifosfamida-carboplatin-etoposide) and partial resection increased the risk of death. CONCLUSIONS: Known risk factors were confirmed in our study, including chromosomal imbalances. We describe a new chromosomal imbalance in chromosome 21 among 30% of study participants.

Factores pronósticos y sobrevida de pacientes pediátricos con ependimomas / Prognostic and survival factors among pediatric patients with ependymomas

Antecedentes: El ependimoma es el tercer tumor intracraneano más frecuente en pediatría. Los factores que influyen en el pronóstico son la localización, la edad del paciente, la resección quirúrgica y el tratamiento con radioterapia. Recientemente se ha descrito la presencia de alteraciones cromosómicas en el tumor como factor de mal pronóstico. El objetivo de esta investigación fue determinar la sobrevida de pacientes pediátricos con ependimoma de acuerdo con los diferentes factores pronósticos. Métodos: Se revisaron los expedientes de pacientes pediátricos con ependimoma de 1996 a 2005. Se determinaron las alteraciones cromosómicas mediante hibridación genómica comparativa. Se calculó la sobrevida de acuerdo con el método Kaplan-Meier y prueba de log rank de acuerdo a cada factor pronóstico. Se calculó el riesgo de morir para cada factor de acuerdo con la razón de momios. Resultados: Se incluyeron 24 pacientes. La sobrevida global fue de 58.04%. La presencia de alteraciones cromosómicas, particularmente en el cromosoma 21, afectó significativamente la sobrevida. La edad menor a cinco años, la histología anaplásica, la quimioterapia diferente a ifosfamida-carboplatino-etopósido y la resección parcial aumentaron el riesgo de morir. Conclusiones: Se confirman los factores descritos anteriormente en la literatura, incluyendo alteraciones cromosómicas. Se describe un nuevo desbalance en el cromosoma 21 en 30% de los pacientes.

BACKGROUND: Ependymomas constitute the third most common intracranial tumors in children. Risk factors include age, location, extent of surgical excision, and radiation therapy. Recently, chromosomal imbalances have been described. OBJECTIVE: Determine global survival of patients with ependymomas according to different prognostic factors. METHODS: We reviewed the medical charts of every pediatric patient with ependymoma from 1996 to 2005. Genomic imbalances were determined using comparative genomic hybridization (CGH). Survival was calculated using the Kaplan and Meier method. We used the Log Rank test for each risk factor. Death risk was calculated by odds ratio (OR). RESULTS: We included 24 patients. Global survival was 58.04%. The presence of chromosomal imbalances, particularly in chromosome 21, significantly affected survival Being under 5 years of age, anaplastic histology, chemotherapy other than ICE (ifosfamida-carboplatin-etoposide) and partial resection increased the risk of death. CONCLUSIONS: Known risk factors were confirmed in our study, including chromosomal imbalances. We describe a new chromosomal imbalance in chromosome 21 among 30% of study participants.

Rare tumor of the tongue in a child: alveolar soft part sarcoma.

Alveolar soft part sarcoma (ASPS) is a rare, malignant tumor of uncertain histogenesis that has no benign counterpart. In some cases, a structural rearrangement of chromosome 17 involving band q25 has been reported. The neoplasm occurs most frequently in female adolescents and young adults, where it arises predominantly in the extremities. In contrast, the most common sites of occurrence in infants and children are the orbit (41%) and the tongue (25%). The primary therapeutic option is a complete surgical excision. Because of the indolent growth and lack of pain associated with the mass, 20% of patients have metastases at the time of initial diagnosis. Median survival time reported for all sites of the body is 79 months. When ASPS presents in the tongue region, however, the patients involved are usually children and have a better prognosis than patients affected in the extremities. The utility of adjuvant chemotherapy or radiation therapy in children is open to question. Because metastases may occur after several decades, children with ASPS should be followed throughout adolescence and well into adulthood. Only 10 cases of ASPS occurring in the tongues of children younger than 5 years of age were indexed by MEDLINE between 1952 and 2006. Here, we describe the 1st case consistent with typical ASPS of the tongue in 15 years at our hospital. The patient is a 2-year-old girl who has been disease-free for 32 months.

Phase II study of metronomic chemotherapy with thalidomide, carboplatin-vincristine-fluvastatin in the treatment of brain stem tumors in children.

BACKGROUND: Brain stem tumors (BST) constitute 20% of all intracranial tumors. Survival for these patients has been very poor worldwide. Four different treatment schemes have been evaluated at our institution, with only a discrete increment in survival when treated with carboplatin-vincristine and fluvastatin (CVF). Low-dose, continuous antiangiogenic treatment has been recently introduced in the treatment of cancer. Our objective was to determine tumor response to metronomic chemotherapy combined with an antiangiogenic drug and fluvastatin and to calculate the survival of pediatric patients with brain stem tumors. METHODS: This was a phase II study. A magnetic resonance (MRI) study was made at inclusion and after the fourth course. Routine laboratory analyses were performed prior to each treatment scheme. Patients received four courses of chemotherapy every 28 days consisting of thalidomide alternating with fluvastatin every 14 days and combined with carboplatin and vincristine every 14 days followed by radiotherapy (56 cGy) and four more courses of the same chemotherapy. Toxicity was evaluated according to Miller criteria. RESULTS: Nine recently diagnosed BST patients were included. Five patients had low-grade astrocytomas, three patients had glioblastoma multiforme, and one patient presented high-grade astrocytoma. There was a significant reduction in tumor volume and a significant increase in survival at 24 months. Two patients died. Toxicity included carboplatin allergy in one patient, grades 1 and 3 neutropenia in two patients, and grade 4 thrombocytopenia in two patients. CONCLUSIONS: Metronomic treatment with carboplatin and vincristine associated with fluvastatin and thalidomide significantly increased survival of pediatric brain stem tumor patients. Tumor volume showed a significant reduction. Quality of life was also increased. Sample size must be increased in order to make final conclusions.

Clinical and molecular parameters for risk stratification in Mexican children with medulloblastoma.

BACKGROUND: Clinical, histological, and more recently, molecular factors have been described as important in survival of the patient with medulloblastoma. Best survival results include aggressive chemotherapeutic protocols. More exact risk analysis may differentiate patients who require aggressive treatments from those with low risk who may respond adequately to less aggressive protocols. METHODS: Twenty six patients were included over a 10-year period and were followed for at least 5 years. Personal variables were obtained from their clinical records. Immunochemistry studies were performed on their formalin-fixed paraffin-embedded tissues. Statistical analysis included chi(2) test, odds risk, linear regression models, and Kaplan-Meier survival analysis. RESULTS: Metastatic disease and chemotherapy with VP16-carboplatin reduce the patient's probability of survival, whereas anaplastic histology increases the probability of death. Global survival and disease-free survival were 66.6 and 45.02%, respectively. Only two patients overexpressed the ERBB2 protein, and no significant difference was found in survival in terms of ERBB2 overexpression. CONCLUSIONS: Risk stratification has become very important in medulloblastoma. We found an increased hazard of death when metastatic disease was present. Gene expression in Mexican children requires a larger sample in order to be analyzed.

Preirradiation ifosfamide, carboplatin and etoposide (ICE) for the treatment of high-grade astrocytomas in children.

BACKGROUND: Astrocytomas are the most common form of primary intracranial tumor; however, survival of patients with high-grade tumors has not changed much compared with that reported in the early 1970s. OBJECTIVE. Our objective was to assess the efficacy, security, and survival rate of postoperative chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) in pediatric patients with anaplastic astrocytomas (AA) and glioblastoma multiforme (GM). METHODS: In a phase II study, we evaluated 25 children with AA or GM. The proposed treatment was four courses of chemotherapy with ICE followed by hyperfractionated radiotherapy, and then four more courses of ICE. Patients were evaluated using MRI after surgery, after the second course of chemotherapy, and again after the last. Toxicity was determined before each course. RESULTS: The overall and disease-free survival at 60 months was 67% and 56% respectively. For supratentorial localization it was 92% at 60 months and 20% at 18 months for brain stem tumors. Fourteen patients had a complete response and 9 died as a result of tumor progression. CONCLUSIONS: Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity.

[Neuroblastoma: prognostic factors and survival. Experience in Hospital de Pediatria del Centro Medico Nacional del Siglo XXI and review of the literature]. / Neuroblastoma: factores pronósticos y sobrevida. Experiencia en el Hospital de Pediatría del Centro Médico Nacional Siglo XXI y revisión de la literatura.

Neuroblastoma (NB) is the most frequent extracranial solid tumor in children according to the literature. In Mexico it is less frequent, fallen to 8th place. Our objective was to analyze our experience and compare it with the one reported in other countries. We included all patients admitted to our hospital during the previous five years and who had not received any treatment. Patients with stages I, II, and IV received cyclophosphamide and epirrubicin. Patients with stages were III and IV received the same chemotherapy alternating with cisplatinum., ifosfamide and etoposide during 12 months as well as massive doses of 131-MIBG and surgical ablation of the remaining tumor when possible. We included 30 patients, 25 with initial presentation in the abdomen. Five were in early stages and 20 (70%) were advanced with an overall survival of 100% and 27% at 5 years respectively. When analyzed by age, 40% were 12 months of age and 60% older, with survival of 100% and 27% in the same period, respectively. According to histology there was 91% survival for differentiated and 23% for undifferentiated tumors. The chemotherapeutic regimen reported is effective but not better than that reported by other authors, in which some benefits are seen with use of transplant and immunotherapy. The most important prognostic factors are still considered to be age, stage and histology.

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. objetive. The objetive 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 thirid 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 give p.o. at doses of 2 mg/kg/day dor 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 aolive 22 months after inclusion into the study, both with anaplasic astrocytoma. A total of 27 courses wer administered. The MTD was 8 mg/kg/day. Toxic effects were insomnia, nausea, vomiting, abdominal distention and myalgias. Txocicity 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 percent 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 anew scheme of treatment with carboplatin, and 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 percent and 64 percent, 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 hig-risk medulloblastomas. Toxicity was not significants, and survival is similar to other reports

Astrocitomas en pediatría. Factores pronósticos y sobrevida / Pronostic factors and survival in pediatrics astrocytomas

Los tumores cerebrales corresponden a la segunda neoplasia más frecuente en pediatría, siendo los más frecuentes los de origen glial, con ligero predominio del sexo masculino y máxima incidencia a los ocho años de la vida. El presente estudio tiene como objetivo determinar cuáles son los factores que influyen en la sobrevida de estos pacientes. Se analizaron los expedientes clínicos de todos los pacientes con diagnóstico de astrocitoma realizado y manejado en el Hospital de Pediatría del CMN, SXXI, IMSS durante el período comprendido entre el 1 de junio de 1989 y el 1 de junio de 1995, registrando la edad, el sexo, el sitio de la tumoración, el grado de malignidad y la fecha de recaída o defunción. Se calcularon curvas de sobrevida global y libre de enfermedad con prueba de log rank para determinar diferencias. Del total de 39 pacientes se encontraron 43 por ciento supratentoriales, 13 por ciento infratentoriales y 43 por ciento de tallo cerebral, con diferencias significativas en la sobrevida al comparar los dos primeros en conjunto contra el último. Se realizó cirugía y estudio histopatológico en 26 de ellos, encontrando 17 pacientes con alto grado de malignidad y nueve de bajo grado, con mejor sobrevida para estos últimos en forma significativa. De las 17 defunciones, ocho pacientes tuvieron tumor de alto grado de malignidad y nueve de bajo grado, con mejor sobrevida para estos últimos en forma significativa. De las 17 defunciones, ocho pacientes tuvieron tumor de alto grado y de tallo cerebral 10. El 41 por ciento de las defunciones ocurrieron en el primer año y 94 por ciento en los primeros 24 meses. Los pacientes con astrocitoma en cerebelo y aquéllos con bajo grado de malignidad, tiene los mejores pronósticos, mientras que los pacientes con tumoración de tallo cerebral y/o de alto grado de malignidad tiene sobrevidas muy bajas

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

La sobrevida de los pacientes con osteosarcoma ha mejorado con el empleo de la quimioterapia; sin embargo, el pronóstico es malo en aquéllos que desarrollan metástasis en los primeros 12 meses. Se revisa el rol de la hidrogenasa láctica como indicador. Se estudiaron en forma retrospectiva a 18 pacientes con osteosarcoma en dos grupos: grupo A con niveles normales de deshidrogenasa láctica y grupo B con niveles elevados. Se realizó un análisis univariado de porcentajes para establecer la frecuencia de elevación de la enzima y el desarrollo de metástasis. De los 18 pacientes estudiados 10 (99 por ciento) presentaban niveles elevados al diagnóstico, de los cuales 9 (90 por ciento) desarrollan metástasis en los primeros 12 meses. La diferencia fue significativa con un intervalo de confianza del 95 por ciento y una razón de momios de 15 cuando existió deshidrogenasa elevada. El valor de la deshidrogenasa láctica como pronóstico de sobrevida está limitado si se pretende considerar como un dato de valor único aislado. El volumen tumoral, la variedad histológica y la edad del paciente influyen, pero es de utilidad para predecir enfermedad metastásica pulmonar temprana.

Quimioterapia postoperatoria con carboplatino y etopósido en niños con meduloblastoma de alto riesgo / Postoperative chemotherapy with carboplatin and etoposide in children with high-risk medulloblastoma

Introducción. Se estudiaron prospectivamente diez pacientes con meduloblastoma de alto riesgo que recibrieron quimioterapia postoperatoria con carboplatino y etopósido previo a radioterapia. Material y métodos. Se realizaron a cada uno de los pacientes estudios de resonancia magnética de cráneo y neuroeje antes de iniciado el tratamiento y al concluir, con el fin de valorar la respuesta tumoral obtenida. Se deretminó el grado de toxicidad hematológica secundaria al tratamiento y se calculó la sobrevida actuarial obtenida. Resultados. Ocho pacientes presentaron una respuesta superior al 50 por ciento; la toxicidad hematológica se presentó en el 34.2 por ciento de los cursos administrados. La sobrevida actuarial obtenida a 18 meses fue del 57 por ciento en el mismo periodo. Conclusiones. La asociación de carboplatino y etopósido empleados en conjunto tienen un buen efecto antitumoral en este tipo de neoplasias con mínimos efectos colaterales y con la posibilidad de mejorar la sobrevida de los pacientes con meduloblastoma de alto riesgo