How we approach conservative treatment of retinoblastoma in South America in the era of local ocular treatments: A consensus of the Grupo America Latina de Oncologia Pediatrica (GALOP).

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6 months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.

Globe Salvage With Intra-Arterial Topotecan-Melphalan Chemotherapy in Children With a Single Eye.

INTRODUCTION: Intra-arterial chemotherapy is a novel therapeutic modality for retinoblastoma patients. Intra-arterial chemotherapy involves the administration of a super-selective drug through the ophthalmic artery, resulting in better ocular penetration and low systemic toxicity. OBJECTIVE: The aim of this report was to evaluate the feasibility of intra-arterial chemotherapy in a large referral center in Mexico City. METHODS: We included patients with bilateral retinoblastoma, one enucleation, and active disease in the other eye after at least two courses of systemic chemotherapy combined with topical treatments. All patients were treated with three courses of a combination of melphalan 4 mg and topotecan 1 mg. Patients were examined under general anesthesia three weeks after each chemotherapy cycle. RESULTS: From 14 eligible patients, three could not be treated due to inaccessibility of the ophthalmic artery. A complete response was observed in 5/11 patients, three in Stage C according to the International Classification for Intraocular Retinoblastoma, one in Stage D, and one in Stage B. The eyes of three patients were enucleated as a result of active/progressive disease, one in Stage B and two in Stage D. Eye preservation was 55% after a mean follow-up of 171 days (range 21-336). CONCLUSIONS: Super-selective intra-arterial chemotherapy is safe and effective for preventing the enucleation of 55% of affected eyes in this group of patients.

[Use of alternative and complementary medicine in pediatric cancer: investigation of 100 cases at a level III care institute]. / Uso de la medicina alternativa y complementaria (MAC) en cáncer infantil: encuesta de 100 casos en un instituto del tercer nivel de atención.

INTRODUCTION: Alternative medicine is well accepted and widely used in Mexico so we researched the frequency and reasons for the use of alternative or complementary treatment (ACT) in pediatric oncologic patients at the Instituto Nacional de Pediatría (INP). METHODS: One hundred questionnaires were applied to caregivers of children with cancer in a course of 100 hundred consecutive patients. RESULTS: Fifty-one percent of caregivers interviewed accepted the use of some kind of ACT; biological therapies were the most frequent treatments used, and 73% felt satisfied with the results. Caregivers told their physicians they were using ACT in 35% of the questionnaires analyzed, and only 2% of the physicians asked directly about its use. None of the caregivers substituted or stopped allopathic treatment. ANALYSIS: These questionnaires reveal that more than a half of the caregivers use ACT. We believe superstitious and cultural beliefs, as well as the desire of the caregivers to participate actively in their patient's treatment, are the main reasons for the use of ACT; nevertheless, some caregivers do not notify their physicians and this may affect chemotherapy treatment in ways not investigated yet. CONCLUSIONS: The wide use of ACT in Mexico obliges every physician to enquire into it intentionally. It is therefore necessary to establish a stratification risk according to the combination of ACT and allopathic treatment used.

[The use of alternative or complementary treatment in pediatric oncologic patients: Survey of 100 cases in a level III attention institute]. / Uso de la medicina alternativa y complementaria (MAC) en el cáncer infantil: encuesta de 100 casos en un instituto de tercer nivel de atención.

INTRODUCTION: Alternative medicine is well accepted and widely used in Mexico, so we researched the frequency and causes of the use of alternative or complementary treatment (ACT) in pediatric oncologic patients at the Instituto Nacional de Pediatría (INP). METHODS: One hundred questionnaires were applied to caregivers of children with cancer in a course of 100 hundred consecutive patients. RESULTS: Fifty-one percent of caregivers interviewed accepted the use of some kind of ACT; biologic therapies were the most frequent treatments used, and 73% felt satisfied with the results. Caregivers told their physicians they were using ACT in 35% of the questionnaires analyzed, and only 2% of the physicians asked directly about its use. None of the caregivers substituted or stopped allopathic treatment. ANALYSIS: These questionnaires reveal that more than a half of the caregivers use ACT. We believe superstitious and cultural beliefs, as well as the desire of the caregivers to participate actively in their patient's treatment, are the main causes of the use of ACT; nevertheless, some do not notify their physicians and this may affect chemotherapy treatment in ways not investigated yet. CONCLUSIONS: The wide use of ACT in Mexico obliges every physician to enquire into it intentionally; it is therefore necessary to establish a stratification risk according to the combination of ACT and allopathic treatment used.

Retinoblastoma in Mexico: part I. A review of general knowledge of the disease, diagnosis, and management / Retinoblastoma en México: parte I. Revisión del conocimiento general de la enfermedad, diagnóstico y tratamiento

AbstractThis is the first of a two-part review that aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico (including the authors' experience at the leading Rb centers), identify the gaps in practice, and propose solutions to improve diagnosis, treatment, and patient uptake. In this first part, general knowledge of Rb diagnosis and management is summarized with a focus on the latest advances in chemotherapy. A general review of peer-reviewed literature of Rb was conducted on PubMed. Key findings were summarized.Provided there is early detection and referral of patients followed by appropriate conservative management, Rb is curable. In developed countries, the primary treatment outcome is ocular salvage with sight preservation. Advanced chemotherapeutic options such as intra-arterial and intravitreal chemotherapy can now save even the most advanced tumors.Advances in Rb therapy are generally limited to developed countries. The implications in Mexico, of the findings from this review will be discussed in Part 2, which will be a comprehensive situational analysis of the state of Rb programming in Mexico, including a review of current demographic data available from hospitals that have Rb programs or treat Rb.

ResumenEsta es la primera parte de un trabajo de revisión donde se reportan los conocimientos actuales del retinoblastoma (Rb) y sus implicaciones en México (incluyendo la experiencia de los autores en los principales centros de referencia), así como las brechas en la práctica y las posibles soluciones para mejorar el diagnóstico, tratamiento y referencia de pacientes. En esta parte se resumen los conocimientos generales del Rb, su diagnóstico y tratamiento. Se realizó una revisión de los avances más recientes en esta enfermedad publicados en PubMed y se resumieron los hallazgos más importantes.La sospecha oportuna y la referencia adecuada de pacientes permiten que el tratamiento conservador del Rb sea curativo. En países en vías de desarrollo, el tratamiento primario es el salvamento ocular y la preservación de la visión. Las opciones de quimioterapia intraarterial o intravítrea permiten ofrecer opciones terapéuticas en estos pacientes.Los avances en el tratamiento del Rb están generalmente limitados a países industrializados. Las implicaciones de los hallazgos de esta revisión serán discutidas en la segunda parte, la cual será un análisis de la situación de los programas hospitalarios del Rb en México, incluyendo la revisión de los datos demográficos disponibles de los centros de referencia más importantes.

Treating retinoblastoma in the first year of life in a national tertiary paediatric hospital in Mexico.

AIM: Retinoblastoma is the most common primary ocular malignancy in childhood, but little has been documented on the clinical and biological differences in children diagnosed before one year of age. We observed patients in this age group and followed them for up to 19 years. METHODS: This retrospective, descriptive, observational study reviewed the medical records of Mexican patients, who were diagnosed with retinoblastoma before one year of age at a national paediatric hospital from 1995 to 2014. The variables analysed were age at diagnosis, weight, presenting signs, the time from first symptoms to diagnosis, family history, laterality, ocular rescue and survival rate. RESULTS: The 108 patients had a mean age of 7.65 months and 15.7% had a family history of retinoblastoma. The majority (55.5%) had bilateral retinoblastoma, the most common presenting sign was leukocoria (86.1%), and the most common stage of diagnosis was Group V (84.1%). More than half were underweight for their age. The overall survival rate was 92% and the disease-free survival rate was 84%. CONCLUSION: Retinoblastoma is a malignancy that can be present at birth, especially if it is a bilateral hereditary form of the disease. Leukocoria was the main presenting sign. Early diagnosis dramatically improved the prognosis for ocular rescue.

Retinoblastoma in Mexico: part I. A review of general knowledge of the disease, diagnosis, and management.

This is the first of a two-part review that aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico (including the authors' experience at the leading Rb centers), identify the gaps in practice, and propose solutions to improve diagnosis, treatment, and patient uptake. In this first part, general knowledge of Rb diagnosis and management is summarized with a focus on the latest advances in chemotherapy. A general review of peer-reviewed literature of Rb was conducted on PubMed. Key findings were summarized. Provided there is early detection and referral of patients followed by appropriate conservative management, Rb is curable. In developed countries, the primary treatment outcome is ocular salvage with sight preservation. Advanced chemotherapeutic options such as intra-arterial and intravitreal chemotherapy can now save even the most advanced tumors. Advances in Rb therapy are generally limited to developed countries. The implications in Mexico, of the findings from this review will be discussed in Part 2, which will be a comprehensive situational analysis of the state of Rb programming in Mexico, including a review of current demographic data available from hospitals that have Rb programs or treat Rb.

SIOP-PODC recommendations for graduated-intensity treatment of retinoblastoma in developing countries.

Retinoblastoma remains incurable in many regions of the world. The major obstacles to cure are delayed diagnosis, poor treatment compliance, and lack of evidence-based recommendations for clinical management. Although enucleation is curative for intraocular disease, in developing countries retinoblastoma is often diagnosed after the disease has disseminated beyond the eye. A SIOP-PODC committee generated guidelines for the clinical management of retinoblastoma in developing countries and developed a classification system based on the resources available in those settings. Recommendations are provided for staging and treatment of unilateral and bilateral retinoblastoma and counseling of families for whom compliance is an issue.

First contact physicians and retinoblastoma in Mexico.

BACKGROUND: Early detection and timely referral are keys to improve survival in patients with retinoblastoma (Rb). In México, one of the main obstacles for an early diagnosis is the lack of knowledge of the disease. The objective of this study was to evaluate Rb comprehension in students in their last year of medical school. PROCEDURE: A questionnaire was completed by 791 students from 12 universities. Descriptive statistics from the population were obtained and every answer to each question was analyzed. RESULTS: Only 3.3% of the students got a proficiency grade. Less than 50% diagnosed Rb when an image was shown. CONCLUSIONS: The students evaluated do not have the knowledge to detect the disease. It is necessary to develop continuous educational programs for first contact physicians.

Hepatoblastoma. Clinical experience at a single institution using the Siopel staging system.

BACKGROUND: Staging in Hepatoblastoma has recently become controversial. In developing countries diagnosis occurs mostly in advanced stages under these circumstances, we propose another option that can be considered of prognostic value. METHOD: A retrospective analysis of cases diagnosed with Hepatoblastoma (HB), treated in a single Institution, in nine years was conducted. Chemotherapeutic regimens were analyzed, as well as the number of courses administered and response to treatment. RESULTS: Thirty-two patients were studied. Patients had symptoms from 1 to 25 weeks before diagnosis. SIOP stratification was used, finding 12 cases in PRETEXT II, 6 cases in PRETEXT III, and 14 cases in PRETEXT IV. No single case was identified in PRETEXT I. CONCLUSIONS: When comparing survival using the PRETEXT system, SIOP and our study showed marked differences. These results may not be comparable due to differences in tumor volume among the same PRETEXT stratification. We believe that tumor volume is related to prognosis.

Early death in children with acute lymphoblastic leukemia: does malnutrition play a role?

The study aim was to correlate malnutrition and early death in children with acute lymphoblastic leukemia (ALL). A study was conducted in 100 consecutive children with ALL. An analysis included clinical and laboratory parameters as well as co-morbidity factors. Forty patients were standard risk and 60 high risk. Multivariate analysis showed variables of statistical importance, including female gender (p 010), ALL high-risk (p 04), and infection (p 036). Malnutrition (p 1.0) and poverty (p 0.5) did not influence. Early mortality was documented in 15/100 (15%) patients. The study shows that high-risk ALL and infection represent the leading causes of early mortality.

[Evaluation of cisplatin ototoxicity by the audiometric curve in retinoblastoma]. / Evaluación de la ototoxicidad del cisplatino por el área bajo la curva audiométrica en retinoblastoma.

BACKGROUND: To evaluate hearing loss severity according to Brock's gradient and to compare it with the audiometric curve during cisplatin treatment in children with retinoblastoma. METHODS: This was an observational retrospective and retrolective study. Twenty children with the diagnosis of retinoblastoma under cisplatin treatment were included. Audiometric testing was performed before treatment, after the second and fourth doses, and after the final dose. RESULTS: Decreased audition was observed in 100% of the cases. Ototoxicity can be observed with cumulative doses of 240 mg/m(2) and higher. No improvement in audition was observed and the audition loss progressed from high to medium frequencies; 15% of the patients showed a grade II loss of high frequencies at the end of the second dose. This level was observed in 95% of the cases at the end of treatment. Two years after completion of therapy, no patient showed auditory recovery. Area below the curve showed higher sensitivity to identify initial auditory loss. CONCLUSIONS: Evaluation of audition with Brock's gradient can be performed. The area under the curve is a useful method to identify minor changes in serial conventional audiometry.

Survival in extra-orbital metastatic retinoblastoma:treatment results.

INTRODUCTION: Retinoblastoma (RB) is the most frequent malignant eye tumor in childhood. In developing countries advanced stages are common. The purpose of this paper is to present our 21-year clinical experience with metastatic extra ocular RB patients treated with 5 different chemotherapy schemas at a single Mexican Pediatric referral center. MATERIALS AND METHODS: A retrospective analysis was carried out reviewing the clinical characteristics of patients with metastatic RB. The information analyzed included the delay in diagnosis after first symptoms, age, sex, ocular staging, and anatomic site of metastases, treatment scheme, initial response and status at the last contact or date of death. RESULTS: Eighty-one patients were included; age range was from 3 to 80 months. The most common site of metastasis was central nervous system (83.9%). From those patients treated with chemotherapy (n = 74), 89.2% presented a complete initial response (n = 66). Early mortality occurred in 7 cases before any treatment. Fifty-six received treatment and died with progressive disease. All patients without radiotherapy died with tumor activity (n = 15). The use of cisplatin was related with longer disease free intervals; no other variable was related with survival. Four patients were alive and disease free at 33 to 144.3 months of follow up from diagnosis. The prevalent cause of death was tumor progression. CONCLUSIONS: In our experience, metastatic RB has a very high mortality rate in spite of the use of different chemotherapy regimens.

A proposal for an international retinoblastoma staging system.

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.

Brain tumors in children under 1 year of age: emphasis on the relationship of prognostic factors.

OBJECTS: Primary brain tumors in infants under 12 months of age have a different prognosis from older children. MATERIAL: A retrospective analysis was done in all patients less than 12 months old with primary brain tumors. RESULTS: Out of 1682 children with primary brain tumors, 61 (3.6%) were infants under 12 months old. The mean age at diagnosis was 181.6 days (SD 128) with a range of 1 to 364 days. There were 37 males (60.6%). The most common tumor was astrocytoma ( n=22) (36%). Supratentorial tumors were present in 63.9% but this was not related to survival ( p=0.1095). Complete surgical resection ( n=14) was favorable for survival ( p=0.039). Intracranial hypertension at diagnosis did not influence survival ( p=0.89). The overall survival rate was 32%, mean 42.08 (SD 7.38). A total of 24 patients are alive and without evidence of disease. CONCLUSION: Complete surgical resection was necessary for a favorable prognosis, and the long-term effects are a valid problem.

Sarcomas de partes blandas en la infancia / Chilhood soft tissue sarcomas

Se revisaron los expedientes de 72 pacientes con diagnóstico de sarcoma de partes blandas, registrados entre 1980 y 1994 en el Instituto Nacional de Pediatría de México. La edad promedio entre los casos con rabdomiosarcoma fue de 5.9 años y de 10.3 años en los que tenían no-rabdomiosarcomas. El 86 por ciento de los casos correspondieron a rabdomiosarcomas y el 14 por ciento restante no-rabdomiosarcomas. El tipo histológico más común en los rabdomiosarcoma fue el embrionario, seguido por la variedad alveolar. El 95 por ciento de los rabdiomiosarcomas se diagnosticaron en estadio III y IV. Se revisaron dos grupos de tratamiento: un grupo de enfermos tratados entre 1980 y 1990 con el esquema VC (vincristina, actinomicina D y ciclofosfamida) y otro de pacientes tratados entre 1990 y 1994 con VACP (esquema VAC más cisplatino); no hubo diferencia entre uno y otro grupos en cuanto a la supervivencia (p = 0.11). Se detectaron 10 casos de sarcomas no-rabdomiosarcomas; el más frecuente (50 por ciento de los casos) fue el Schwanoma maligno; todos los pacientes acudieron en etapas avanzadas; de éstos, sólo cuatro se encuentran con vida

B-Lineage acute lymphoblastic leukemia of childhood. An institutional experience

A total of 119 children (1990-95) with acute lymphoblastic leukemia (ALL) B-lineage either CD10+or CD10- were registered into a single non-randomized chemotherapy protoco. Only untreated patients with standard risk were included in the study. Their ages ranges from 1.8-10 years with a mean of 5.1 years. There were 82 (68 percent) children with early pre B-All, 35 (29 percent) with pre B-All and 2 (1.6 percent) with transititional pre B-All (p<0.00001). The patients were divided according to CD10 reactivity, either + (94 children) or -(25 patients). The event-free survival (EFS) at 60 months for the CD10+children was of 78 percent (alive 73/94), while for the CD10- was 71 percent (alive 18/25) (p=0.6) and 74 percent for both groups. The factors that influenced favorably the survival in the CD10+group were the age between 3 to 5.99 years (p<0.00001), sex (either male or female), leukocyte count between 10.24.9 x 10-9/l (p<0.00001), LDH under 300 U/I (p<0.00001) and L1 bone marrow cytomorphology (p<0.00001). In the CD10- patients, the EFS was favorably influenced by the female sex (p=0.04), leukocyte count under 10 x 10-9/l (p=0.05) and LDH < 300 U/l (p=0.02). CNS infiltration was documented in 4.2 percent (5/119). Mortality secondary to chemotherapy was seen in 7 percent. In conclusion, this is the first large series in Mexican children with B-lineage ALL published. Because of the relatively small number of patients in each group (pre B and transitional pre B), all the patients in the current serieswere treated alike. When the 119 patients were divided only on the basis of CD10 reactivity, the EFS for both groups (CD10+ and') was similar; therefore, the reactivity to CD10 has no prognostic value in this type of ALL

Hepatoblastoma: experiencia en el tratamiento de 20 niños / Hepatoblastoma: experience in the treatment of 20 children

Introducción: el hepatoblastoma es el principal tumor maligno primario del hígado en niños. El objetivo del presente trabajo es analizar el perfil clínico, tipo de cirugía, complicaciones postoperatorias y sobrevida libre de enfermedad de acuerdo a la modalidad quirúrgica empleada, en niños con hepatoblastoma. Material y métodos: se revisaron los expedientes de pacientes con hepatoblastoma atendidos entre enero de 1985 y diciembre de 1995. Se registraron edad, sexo, manifestaciones clínicas, exámenes de laboratorio, alfa-feto proteína pre y postoperatoria, estudios de gabinete, tipo de procedimiento quirúrgico, complicaciones trans y postoperatorias variedad histológica, estudio, tipo de quimioterapia y sobrevida libre de enfermedad. Resultados: se analizaron 20 pacientes de cuatro meses a 13 años de edad. La principal e invariable manifestación clínica fue una masa abdominal. En once pacientes se encontraron niveles de alfa-feto proteína entre 100-10,000 ng/mL. En 12 pacientes se practicó hemihepatectomía; en cuatro, trisegmentectomía y en el resto, biopsia incisional diagnóstica. Hubo sangrado masivo en cuatro pacientes durante el transoperatorio; ninguno falleció. Todos los pacientes en estadio IV fallecieron. El tipo de resección, completa o incompleta, no fue estadísticamente significativo (p=0.49) para la sobrevida; ésta fue 7/20 con un seguimiento de cuatro a 104 meses. Conclusiones: 1. los niveles de alfa-feto proteína son útiles para la viginalcia y el diagnóstico de pacientes con hepatoblastoma. 2. La mayor sobrevida ocurre en pacientes operados y que recibieron quimioterapia. 3. Un segundo abordaje quirúrgico es preferible después de la citorreducción con quimioterapia en pacientes con tumores muy voluminosos o multicéntricos. 4. La conducta actual para el tratamiento del hepatoblastoma debe ser cirugía más quimioterapia independientemente del estadio

Frecuencia de neoplasias malignas en pacientes del Instituto Nacional de Pediatría provenientes de la Ciudad de México y área metropolitana / Frequency of malignant neoplasms in patients from Nacional Institute of Pediatry from Mexico City and metropolitan area

Se efectuó una revisión retrospectiva del periodo 1980 a 1992 en pacientes con diagnóstico histopatológico de cáncer registrados en el Instituto Nacional de Pediatría provenientes del distrito Federal y área metropolitana. Se observó un incremento de casos mayores al 100 por ciento duarante este periodo. El total fue de 2,385 pacientes. La edad fluctuó desde recién nacidos hasta los 18 años de edad, la media fue de 4.9 años. Sin embargo, al dividirse por grupos de edad, el que predominó fue el de uno a cuatro años (p 0.01). El sexo masculino estuvo representado por 1,360 pacientes y el femenino por 1,025 (p 0.00001); la mayor prevalencia de casos masculinos sobre los femeninos de detectó en el grupo de entre uno a cuatro años de edad (p 0.00002). Entre los antecedentes familiares más importantes destacó que cerca del 50 por ciento de los padres tuvieron una edad comprendida entre los 20 a 29 años (p 0.00001). El nivel educativo de los padres fue escolaridad primaria en el 44 por ciento. Las leucemias agudas representaron el 35 por ciento de todas las neoplasias malignas, mientras que el retinoblastoma constituyó el 12 por ciento y fue el tumor sólido más frecuente en esta serie. La tendencia de casos nuevos por año fue más ostensible para retinoblastoma que para el resto de las neoplasias. Con base en los resultados obtenidos se conluye que es necesario la creación de un nuevo registro nacional de tumores que permita definir las características epidemiológicas del cáncer infantil a nivel nacional y diseñar las estrategias del Sector Salud para la mejor atención del niño con neoplasias malignas en el Distrito Federal y la República Mexicana