ABSTRACT
BACKGROUND: Inborn Errors of Immunity (IEI) comprise several genetic anomalies that affect different components of the innate and adaptive responses, predisposing to infectious diseases, autoimmunity and malignancy. Different studies, mostly in adults, have reported a higher prevalence of cancer in IEI patients. However, in part due to the rarity of most of these IEI subtypes (classified in ten categories by the Primary Immunodeficiency Committee of the International Union of Immunological Societies), it is difficult to assess the risk in a large number of patients, especially during childhood. OBJECTIVE: To document the cancer prevalence in a pediatric cohort from a single referral institution, assessing their risk, together with the type of neoplasia within each IEI subgroup. METHOD: An extensive review of clinical records from 1989 to 2022 of IEI patients who at some point developed cancer before the age of sixteen. RESULTS: Of a total of 1642 patients with IEI diagnosis, 34 developed cancer before 16 years of age, showing a prevalence (2.1%) significantly higher than that of the general age matched population (0.22). Hematologic neoplasms (mostly lymphomas) were the most frequent malignancies. CONCLUSION: This study represents one of the few reports focused exclusively in pediatric IEI cases, describing not only the increased risk of developing malignancy compared with the age matched general population (a fact that must be taken into account by immunologists during follow-up) but also the association of the different neoplasms with particular IEI subtypes, thus disclosing the possible mechanisms involved.
Subject(s)
Neoplasms , Humans , Child , Prevalence , Neoplasms/epidemiology , Neoplasms/immunology , Neoplasms/etiology , Male , Female , Child, Preschool , Adolescent , Infant , Immunologic Deficiency Syndromes/epidemiology , Immunologic Deficiency Syndromes/immunology , Infant, NewbornABSTRACT
Introducción. Los ensayos clínicos cooperativos han aumentado el conocimiento sobre los tumores pediátricos; sin embargo, no es el caso de los tumores raros (TR). Objetivo. Describir prevalencia, características clínicas y evolución de los TR en la edad pediátrica diagnosticados en el Hospital Garrahan. Material y métodos. Estudio descriptivo retrospectivo de pacientes entre 0 y 18 años con diagnóstico de TR ingresados entre enero de 2007 y diciembre de 2017.Resultados. De 1 657 pacientes con diagnóstico de tumores sólidos, 164 (9,9 %) correspondieron a TR, 71,95 % (118) eran menores de 14 años y 81,7 % (130) eran varones. En orden de frecuencia, los TR fueron: carcinoma de tiroides (60), carcinoma suprarrenal (14), tumores pulmonares (14), melanoma (13), carcinoma de glándulas salivales (11), tumores gastrointestinales (8), tumores gonadales no germinales (7), tumores pancreáticos (7), carcinomas renales (6), carcinomas nasofaríngeos (5), feocromocitoma y paraganglioma (5) y carcinoma de timo en 1 paciente. El tratamiento recibido dependió del tipo de tumor y del estadio. Con una mediana de seguimiento de 34,9 meses (rango: 1-128,5 meses), 133 pacientes (78,7 %) están vivos y solo 10 pacientes (6 %) se perdieron durante el seguimiento. Conclusión. La prevalencia de TR fue del 9,9 %. El 27 % se presentaron en adolescentes. Los tumores más frecuentemente diagnosticados fueron carcinoma de tiroides, carcinoma suprarrenal y melanoma. El tratamiento y la evolución varió según el tipo histológico. Se hallaron alteraciones moleculares predisponentes en el 5,3 % de los pacientes, el 3,5 % tenían antecedente de patología oncológica.
Introduction. Collaborative clinical trials have enlarged the knowledge base about pediatric tumors; however, this is not the case for rare tumors (RT). Objective. To describe the prevalence, clinical characteristics, and course of RT in pediatric patients diagnosed at Hospital Garrahan. Material and methods. Descriptive, retrospective study of patients aged 0-18 years diagnosed with a RT and admitted between January 2007 and December 2017. Results. Out of 1657 patients diagnosed with solid tumors, 164 (9.9 %) were RT; 71.95 % (118) of patients were younger than 14 years and 81.7 % (130) were males. In order of frequency, RT were thyroid carcinoma (60), adrenal carcinoma (14), lung tumors (14), melanoma (13), salivary gland cancer (11), gastrointestinal tumors (8), non-germ cell gonadal tumors (7), pancreatic tumors (7), renal carcinomas (6), nasopharyngeal carcinomas (5), pheochromocytoma and paraganglioma (5), and thymic carcinoma in 1 patient. Treatment depended on tumor type and stage. The median follow-up was 34.9 months (range: 1-128.5 months);133 patients (78.7 %) are alive and only 10 patients (6 %) were lost-to-follow-up. Conclusion. The prevalence of RT was 9.9 %. Twenty-seven percent occurred in adolescents. The most frequent tumors included thyroid carcinoma, adrenal carcinoma, and melanoma. Treatment and course varied based on tumor histology. Predisposing molecular alterations were found in 5.3 % of patients; 3.5 % had a history of cancer.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Pediatrics , Pheochromocytoma , Adrenal Gland Neoplasms , Argentina/epidemiology , Epidemiology, Descriptive , Prevalence , Retrospective StudiesABSTRACT
Introduction: Collaborative clinical trials have enlarged the knowledge base about pediatric tumors; however, this is not the case for rare tumors (RT). Objective: To describe the prevalence, clinical characteristics, and course of RT in pediatric patients diagnosed at Hospital Garrahan. Material and methods: Descriptive, retrospective study of patients aged 0-18 years diagnosed with a RT and admitted between January 2007 and December 2017. Results: Out of 1657 patients diagnosed with solid tumors, 164 (9.9 %) were RT; 71.95 % (118) of patients were younger than 14 years and 81.7 % (130) were males. In order of frequency, RT were thyroid carcinoma (60), adrenal carcinoma (14), lung tumors (14), melanoma (13), salivary gland cancer (11), gastrointestinal tumors (8), non-germ cell gonadal tumors (7), pancreatic tumors (7), renal carcinomas (6), nasopharyngeal carcinomas (5), pheochromocytoma and paraganglioma (5), and thymic carcinoma in 1 patient. Treatment depended on tumor type and stage. The median follow-up was 34.9 months (range: 1-128.5 months); 133 patients (78.7 %) are alive and only 10 patients (6 %) were lost-to-follow-up. Conclusion: The prevalence of RT was 9.9 %. Twenty-seven percent occurred in adolescents. The most frequent tumors included thyroid carcinoma, adrenal carcinoma, and melanoma. Treatment and course varied based on tumor histology. Predisposing molecular alterations were found in 5.3 % of patients; 3.5 % had a history of cancer.
Introducción. Los ensayos clínicos cooperativos han aumentado el conocimiento sobre los tumores pediátricos; sin embargo, no es el caso de los tumores raros (TR). Objetivo. Describir prevalencia, características clínicas y evolución de los TR en la edad pediátrica diagnosticados en el Hospital Garrahan. Material y métodos. Estudio descriptivo retrospectivo de pacientes entre 0 y 18 años con diagnóstico de TR ingresados entre enero de 2007 y diciembre de 2017. Resultados. De 1 657 pacientes con diagnóstico de tumores sólidos, 164 (9,9 %) correspondieron a TR, 71,95 % (118) eran menores de 14 años y 81,7 % (130) eran varones. En orden de frecuencia, los TR fueron: carcinoma de tiroides (60), carcinoma suprarrenal (14), tumores pulmonares (14), melanoma (13), carcinoma de glándulas salivales (11), tumores gastrointestinales (8), tumores gonadales no germinales (7), tumores pancreáticos (7), carcinomas renales (6), carcinomas nasofaríngeos (5), feocromocitoma y paraganglioma (5) y carcinoma de timo en 1 paciente. El tratamiento recibido dependió del tipo de tumor y del estadio. Con una mediana de seguimiento de 34,9 meses (rango: 1-128,5 meses), 133 pacientes (78,7 %) están vivos y solo 10 pacientes (6 %) se perdieron durante el seguimiento. Conclusión. La prevalencia de TR fue del 9,9 %. El 27 % se presentaron en adolescentes. Los tumores más frecuentemente diagnosticados fueron carcinoma de tiroides, carcinoma suprarrenal y melanoma. El tratamiento y la evolución varió según el tipo histológico. Se hallaron alteraciones moleculares predisponentes en el 5,3 % de los pacientes, el 3,5 % tenían antecedente de patología oncológica.
Subject(s)
Adrenal Gland Neoplasms , Pediatrics , Pheochromocytoma , Adolescent , Argentina/epidemiology , Child , Humans , Male , Retrospective StudiesABSTRACT
El nefroma mesoblastico congénito es un tumor renal infrecuente, pero común en el periodo neonatal. De comportamiento benigno y pronóstico excelente en su variedad clásica pero en el subtipo celular puede presentar recurrencia local, invasión retroperitoneal y metástasis pulmonares y cerebrales. El tratamiento es la nefrectomía radical. Los factores pronósticos son la edad menor a tres meses y la resección quirúrgica completa. Paciente de 17 días nacida a las 35 semanas por polihidramnios, con diagnóstico prenatal de masa abdominal. Al examen físico masa en flanco derecho e hipertensión arterial (121/79 mm Hg, TAM 77mm Hg). Ecografía abdominal con riñón derecho aumentado de tamaño y voluminosa formación sólida, de 4,4 x 4,3 x 4,8 cm, heterogénea y vascularizada al Doppler en polo inferior. Tomografía de abdomen con formación nodular heterogénea de 5,0 x 4,1 x 5,1 cm en polo inferior del riñón derecho. Se realizó nefrectomía radical derecha sin complicaciones. Evolución en los últimos 20 meses satisfactoria y libre de enfermedad.
Congenital mesoblastic nephroma is an uncommon renal tumor, but frequent in neonates. Classical variety usually benign with excellent prognosis. Cellular cases may be recurrent with retroperitoneal invasion, brain and lung metastasis. Radical nephrectomy is the treatment of choice. Relevant prognostic factors are diagnosis before three months of age and complete resection. A 17 day old patient, borned at 35 weeks due to polyhydramnios, with prenatal diagnosis of abdominal mass. On examination, right flank abdominal mass and arterial hypertension (121/79 mm Hg, MAP 77 mm Hg). Abdominal ultrasound showed an enlarged right kidney with a voluminous solid heterogeneous mass, 4.4 x 4.3 x 4.8 cm in the lower pole, vascularized on Doppler scan. Computed tomography showed a big 5.0 x 4.1 x 5.1 cm, nodular, heterogeneous mass in the lower pole of the right kidney. Right radical nephrectomy was performed with an uneventful recovery. Follow up for the last 20 months satisfactory and free of disease.
Subject(s)
Nephroma, MesoblasticABSTRACT
Desmoid-type fibromatosis (DF) is a tumor with high local recurrence rate. Sixteen patients (18 desmoid tumors) were retrospectively evaluated. Initial surgery was performed in 13/18 tumors, with complete resection in 6 (one with free margin and five with microscopic residual disease); 10/13 had local relapse. Eleven patients with 13 tumors underwent treatment with methotrexate-vinblastine. The response rate to chemotherapy was 54%, and up to 81% if stable disease cases were included. The best response was partial remission. Only 2 had grade 4 toxicity. Twelve of 15 patients had sequelae. In 8 cases sequelae were directly related to the surgical intervention and 3 of them were severe. The 5-year progression-free survival and overall survival were 30% and 93.3%, respectively. DF has a high local relapse rate, regardless of surgical margin involvement. Low dose chemotherapy achieved stable disease and even remission of the lesions with low toxicity. The high rate of sequelae is probably related to the initial surgery performed in the majority of patients and may be avoided by the use of neoadjuvant low dose chemotherapy.
La fibromatosis tipo desmoide (FD) es un tumor con alta tasa de recurrencia local. Dieciséis pacientes (18 tumores desmoides) fueron evaluados retrospectivamente. La cirugía inicial se realizó en 13/18 tumores, con resección completa en 6 (uno con margen libr e y cinco con margen microscópicamente comprometido); 10/13 tuvieron recaída local. Once pacientes con 13 tumores recibieron tratamiento con metotrexato/ vinblastina. La tasa de respuesta a la quimioterapia fue del 54% y de hasta el 81% si se incluyen los casos que lograron enfermedad estable. La mejor respuesta fue remisión parcial. Solo 2 tuvieron toxicidad grado 4. Doce de 15 pacientes tuvieron secuelas. En 8 casos, las secuelas estuvieron directamente relacionadas con la intervención quirúrgica y 3 de ellas fueron graves. La sobrevida libre de progresión a 5 años y la supervivencia global fueron del 30% y del 93.3%, respectivamente. La FD tiene una alta tasa de recaída local, independientemente del margen quirúrgico. Dosis bajas de quimioterapia lograron una enfermedad estable e incluso la remisión de las lesiones, con baja toxicidad. La alta tasa de secuelas probablemente esté relacionada con la cirugía inicial realizada en la mayoría de los pacientes y podría evitarse mediante el uso de quimioterapia neoadyuvante en dosis bajas, como sugieren las estrategias actuales de tratamiento.
Subject(s)
Gaucher Disease/diagnosis , Child , Fibromatosis, Aggressive/drug therapy , Fibromatosis, Aggressive/surgery , Follow-Up Studies , Humans , Methotrexate , Neoplasm Recurrence, Local , Retrospective StudiesABSTRACT
Abstract Desmoid-type fibromatosis (DF) is a tumor with high local recurrence rate. Sixteen patients (18 desmoid tumors) were retrospectively evaluated. Initial surgery was performed in 13/18 tumors, with complete resection in 6 (one with free margin and five with microscopic residual disease); 10/13 had local relapse. Eleven patients with 13 tumors underwent treatment with methotrexate-vinblastine. The response rate to chemotherapy was 54%, and up to 81% if stable disease cases were included. The best response was partial remission. Only 2 had grade 4 toxicity. Twelve of 15 patients had sequelae. In 8 cases sequelae were directly related to the surgical intervention and 3 of them were severe. The 5-year progression-free survival and overall survival were 30% and 93.3%, respectively. DF has a high local relapse rate, regardless of surgical margin involvement. Low dose chemotherapy achieved stable disease and even remission of the lesions with low toxicity. The high rate of sequelae is probably related to the initial surgery performed in the majority of patients and may be avoided by the use of neoadjuvant low dose chemotherapy.
Resumen La fibromatosis tipo desmoide (FD) es un tumor con alta tasa de recurrencia local. Dieciséis pacientes (18 tumores desmoides) fueron evaluados retrospectivamente. La cirugía inicial se realizó en 13/18 tumores, con resección completa en 6 (uno con margen libre y cinco con margen microscópicamente comprometido); 10/13 tuvieron recaída local. Once pacientes con 13 tumores recibieron tratamiento con metotrexato/vinblastina. La tasa de respuesta a la quimioterapia fue del 54% y de hasta el 81% si se incluyen los casos que lograron enfermedad estable. La mejor respuesta fue remisión parcial. Solo 2 tuvieron toxicidad grado 4. Doce de 15 pacientes tuvieron secuelas. En 8 casos, las secuelas estuvieron directamente relacionadas con la intervención quirúrgica y 3 de ellas fueron graves. La sobrevida libre de progresión a 5 años y la supervivencia global fueron del 30% y del 93.3%, respectivamente. La FD tiene una alta tasa de recaída local, independientemente del margen quirúrgico. Dosis bajas de quimioterapia lograron una enfermedad estable e incluso la remisión de las lesiones, con baja toxicidad. La alta tasa de secuelas probablemente esté relacionada con la cirugía inicial realizada en la mayoría de los pacientes y podría evitarse mediante el uso de quimioterapia neoadyuvante en dosis bajas, como sugieren las estrategias actuales de tratamiento.
Subject(s)
Humans , Child , Gaucher Disease/diagnosis , Methotrexate , Retrospective Studies , Follow-Up Studies , Fibromatosis, Aggressive/surgery , Fibromatosis, Aggressive/drug therapy , Neoplasm Recurrence, LocalABSTRACT
The purpose of the study was to evaluate the outcome of patients under 18 months diagnosed with neuroblastoma. Between April 2006 and December 2013, 45 consecutive patients followed in Hospital de Pediatría Garrahan, were retrospectively reviewed. With a median age of 9.3 months (1-18 months) N-myc amplification was detected in 5 out of 38 patients, 1p deletion (del1p) in 4 patients, and 11q aberration in one patient. With a median follow-up of 53 (range: 6-109 months), at 24 months the event free survival (EFS) of all patients was 83% (SE 6%) and overall survival (OS) of 88% (SE 5%). Significant difference was found in OS and EFS between patients with stages L1, L2 and Ms vs. stage M (p = 0.01 and p = 0.01 respectively). EFS for each stage: L1 85% (SE 7%), L2 100%, MS 100%, vs. M 55% (SE 16%). OS: L1 90% (SE 6%), L2 100%, MS 100%, vs. M 66% (SE 15%). OS and EFS results are similar to those reported in international studies. However, better identification of biological prognostic factors will warr ant accurate staging and consequently an appropriate treatment.
El objetivo del trabajo fue evaluar las características y evolución de pacientes menores de 18 meses de edad, con diagnóstico de neuroblastoma. Se realizó un análisis descriptivo, retrospectivo entre abril/2006 y diciembre/2013, de 45 pacientes diagnosticados en forma consecutiva. La edad media fue 9.3 meses (1-18 meses). La amplificación del gen N-myc fue detectada en 5 pacientes, deleción del cromosoma 1p (del1p) en 4, y aberración de 11q en uno. Con una media de seguimiento de 53 meses (6-109 meses), la supervivencia libre de eventos (SLE) de todos los pacientes, a 24 meses fue 83% (ES 6%) y la supervivencia global (SG) de 88% (ES 5%). Se encontró diferencia significativa en la SG y SLE entre los pacientes con estadios L1, L2 y Ms, y aquellos con estadio M (p = 0.01). La SLE para cada estadio fue: L1 85% (ES 7%), L2 100%, MS 100%, M 55% (ES 16%). SG para cada estadio: L1 90% (ES 6%), L2 100%, MS 100%, y M 66% (ES 15%). Aunque los resultados de SG y SLE son similares a los publicados en estudios internacionales, una mejor identificación de los factores pronósticos biológicos permitirá una estadificación precisa y, en consecuencia, un tratamiento adecuado.
Subject(s)
Antineoplastic Agents/administration & dosage , Neuroblastoma/diagnosis , Neuroblastoma/drug therapy , Antineoplastic Protocols , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Kaplan-Meier Estimate , Male , Neoplasm Staging , Neuroblastoma/mortality , Prognosis , Retrospective StudiesABSTRACT
The purpose of the study was to evaluate the outcome of patients under 18 months diagnosed with neuroblastoma. Between April 2006 and December 2013, 45 consecutive patients followed in Hospital de Pediatría Garrahan, were retrospectively reviewed. With a median age of 9.3 months (1-18 months) N-myc amplification was detected in 5 out of 38 patients, 1p deletion (del1p) in 4 patients, and 11q aberration in one patient. With a median follow-up of 53 (range: 6-109 months), at 24 months the event free survival (EFS) of all patients was 83% (SE 6%) and overall survival (OS) of 88% (SE 5%). Significant difference was found in OS and EFS between patients with stages L1, L2 and Ms vs. stage M (p = 0.01 and p = 0.01 respectively). EFS for each stage: L1 85% (SE 7%), L2 100%, MS 100%, vs. M 55% (SE 16%). OS: L1 90% (SE 6%), L2 100%, MS 100%, vs. M 66% (SE 15%). OS and EFS results are similar to those reported in international studies. However, better identification of biological prognostic factors will warr ant accurate staging and consequently an appropriate treatment.
El objetivo del trabajo fue evaluar las características y evolución de pacientes menores de 18 meses de edad, con diagnóstico de neuroblastoma. Se realizó un análisis descriptivo, retrospectivo entre abril/2006 y diciembre/2013, de 45 pacientes diagnosticados en forma consecutiva. La edad media fue 9.3 meses (1-18 meses). La amplificación del gen N-myc fue detectada en 5 pacientes, deleción del cromosoma 1p (del1p) en 4, y aberración de 11q en uno. Con una media de seguimiento de 53 meses (6-109 meses), la supervivencia libre de eventos (SLE) de todos los pacientes, a 24 meses fue 83% (ES 6%) y la supervivencia global (SG) de 88% (ES 5%). Se encontró diferencia significativa en la SG y SLE entre los pacientes con estadios L1, L2 y Ms, y aquellos con estadio M (p = 0.01). La SLE para cada estadio fue: L1 85% (ES 7%), L2 100%, MS 100%, M 55% (ES 16%). SG para cada estadio: L1 90% (ES 6%), L2 100%, MS 100%, y M 66% (ES 15%). Aunque los resultados de SG y SLE son similares a los publicados en estudios internacionales, una mejor identificación de los factores pronósticos biológicos permitirá una estadificación precisa y, en consecuencia, un tratamiento adecuado.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Neuroblastoma/diagnosis , Neuroblastoma/drug therapy , Antineoplastic Agents/administration & dosage , Prognosis , Retrospective Studies , Follow-Up Studies , Antineoplastic Protocols , Kaplan-Meier Estimate , Neoplasm Staging , Neuroblastoma/mortalityABSTRACT
Purpose The use of traditional complementary/alternative medicine (TCAM) among children with cancer has been well documented. South America has a rich history of traditional healers and medicinal resources; however, little is known about the use of TCAM among children with cancer. We sought to investigate patterns, beliefs, and determinants of TCAM use among South American children with cancer. Methods A cross-sectional survey was administered to 199 children treated for cancer at institutions located in Buenos Aires, Argentina, and Montevideo, Uruguay. Participants were queried about the type of TCAM and strength of beliefs associated with its use. Logistic regression analysis was used to estimate the odds ratios with 95% CIs. Results We found that the use of TCAM was common in both Argentina (47%) and Uruguay (76%). Variations in the forms of TCAM used were observed between the countries; however, both countries used TCAM primarily for supportive care. Mother's education, wealth index, and TCAM belief system were significant predictors of TCAM. Conclusion To our knowledge, this study is the first to report on the use of TCAM in pediatric oncology in South America. The study identifies several predictors of TCAM use, which may serve as target variables for educational and research initiatives. The finding that most families use TCAM for supportive care suggests that future efforts could evaluate the role of TCAM to enhance existing supportive care regimens, particularly in settings where access to conventional medications are limited.
Subject(s)
Complementary Therapies/methods , Neoplasms/therapy , Child , Cross-Sectional Studies , Humans , Male , South AmericaABSTRACT
INTRODUCTION: Childhood acute leukemias (AL) and lymphomas achieve good survival rates. However, second neoplasms (SN) are a devastating event. METHODS: From August 1987 to December 2016, 34 of 3321 (1%) patients with diagnosis of AL or lymphoma developed SN. SN were AL (n=16), CNS tumors (n=5), endocrinal tumors (n=3), lymphomas (n=2), schwannoma (n=2) assorted sarcomas (n=4), retinal melanoma (n=1), and Vanek tumor (n=1). Median latency was 51 (range, 10 to 110) months for hematological malignancies and 119 (range, 25 to 236) months for solid tumors (P=0.001). RESULTS: A total of 33 patients with SN were treated taking into account cumulative doses of anthracyclines and radiotherapy. Twenty-three (67.6%) patients achieved complete remission (CR), 5 died early during therapy and 5 were refractory or partial responders. Six patients presented relapses of the SN and 1 died in CR. Seventeen patients remain alive in CR, with a median follow-up of 110 (range, 4 to 276) months. CONCLUSIONS: (1) The latency period was significantly longer for patients developing solid tumors than for those developing AL. (2) AL was the most frequent SN. (3) Our results strongly encourage giving standard therapy to SN, considering cumulative doses of previous treatment, since similar probabilities of surviving as "de novo" counterparts can be achieved.
Subject(s)
Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Adolescent , Argentina/epidemiology , Child , Child, Preschool , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Databases, Factual , Female , Follow-Up Studies , Humans , Infant , Male , Neoplasms, Second Primary/diagnosis , Population Surveillance , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapyABSTRACT
BACKGROUND: The purpose of this study was to evaluate the feasibility and safety of ambulatory high-dose methotrexate (HDMTX) administration with oral hydration, alkalinization, and leucovorin rescue. HDMTX (12 g/m) was given intravenously over 4 hours after urine alkalinization. Families and patients were instructed to continue ambulatory oral hydration and alkalinization to monitor urine pH and to adjust bicarbonate according to our institution's treatment algorithm. Clinical status and MTX levels were controlled every 24 hours, and oral leucovorin dose was adjusted accordingly. RESULTS: From April 2007 to December 2010, 150 of 447 courses of HDMTX (31.4%) were given on an outpatient basis, and 91.2% were successfully completed. The main causes of failure were poor oral tolerance (n=6) and fever (n=4). Most patients (81%) had MTX levels of <10 µmol/L 24 hours post-HDMTX; only in 1 course the levels were >50 µmol/L (50.96 µmol/L). Neutropenia grade III/IV was observed in 18.3% of the courses, grade III/IV leukopenia in 2.7%, and grade III/IV thrombocytopenia and anemia in 4.7%. Around 39% were associated with grade III/IV hepatic toxicity (asymptomatic hypertransaminasemia), grade III-IV gastrointestinal toxicity (vomiting and diarrhea) (5%), grade III-IV mucositis (4%), and none of the patients developed renal toxicity. CONCLUSIONS: Ambulatory HDMTX administration is feasible and safe in a population with poor resources in a developing country.
Subject(s)
Methotrexate/administration & dosage , Osteosarcoma/drug therapy , Adolescent , Algorithms , Ambulatory Care , Anemia/chemically induced , Antacids/administration & dosage , Argentina , Chemical and Drug Induced Liver Injury , Child , Diarrhea/chemically induced , Female , Humans , Hydrogen-Ion Concentration , Leucovorin/administration & dosage , Leukopenia/chemically induced , Male , Methotrexate/adverse effects , Mucositis/chemically induced , Neutropenia/chemically induced , Osteosarcoma/complications , Retrospective Studies , Thrombocytopenia/chemically induced , Vomiting/chemically inducedABSTRACT
BACKGROUND: Metronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an antitumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high-grade operable osteosarcomas (OSTs) of the extremities was investigated. METHODS: Patients with high-grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP). After surgery, patients were randomized between 2 arms to complete 31 weeks of MAP or receive 73 weeks of MC after MAP. The primary endpoint was event-free survival (EFS) from randomization. RESULTS: There were 422 nonmetastatic patients registered (May 2006 to July 2013) from 27 sites in 3 countries (Brazil, Argentina and Uruguay), and 296 were randomized to MAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP-MC group and the MAP-alone group were 61% (standard error [SE], 0.5%) and 64% (SE, 0.5%), respectively, and they were not statistically different (Wilcoxon [Gehan] statistic = 0.724; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS. CONCLUSIONS: According to the current follow-up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high-grade, resectable OSTs of the extremities. Cancer 2017;123:1003-10. © 2016 American Cancer Society.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/diagnosis , Bone Neoplasms/drug therapy , Extremities/pathology , Osteosarcoma/diagnosis , Osteosarcoma/drug therapy , Administration, Metronomic , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Neoplasms/mortality , Child , Combined Modality Therapy , Disease Management , Female , Humans , Male , Neoplasm Grading , Neoplasm Staging , Osteosarcoma/mortality , Proportional Hazards Models , Treatment Outcome , Tumor BurdenABSTRACT
OBJECTIVE: Wilms tumor (WT) is a disease with a good prognosis. The aim of this study was to evaluate the outcome of patients with WT, treated according to the SIOP-2001 strategy. METHODS: A retrospective analysis of 141 consecutive patients with WT diagnosed at our institution between December 2001 and 2013 was performed. RESULTS: A total of 114 patients, median age 38.8 months (3 to 155 mo), were assessable for analysis. Fine-needle aspiration was initially performed in 88 patients (84.6%). Stage distribution was: I: 33%, II: 9.6%, III: 28%, IV: 14%, V: 14.9%. Six patients were stage III because of tumor spillage. The remaining patients received preoperative chemotherapy. Adjuvant chemotherapy was given without randomization, using vincristine-actinomycin for stage II and vincristine-doxorubicin-actinomycin plus radiotherapy for stage III. After a median follow-up of 52 months, 5-year overall survival and event-free survival were 91% and 85%, respectively. Overall survival according to stage was: I: 96%, II: 99%, III: 88%, IV: 78%, V: 90% (P=0.16). There was no significant difference in event-free survival (P=0.7). Seventy-eight (85.7%) were intermediate-risk and 11 (12%) were high-risk patients. Seventeen patients (14.9%) relapsed within 2 to 99 months (median 29.9 mo). Eight patients (7%) died of progressive disease. There were no treatment-related deaths. CONCLUSIONS: The SIOP-01 protocol proposes a treatment strategy that is feasible in our institution, achieving good results.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Kidney Neoplasms/drug therapy , Wilms Tumor/drug therapy , Abnormalities, Multiple/epidemiology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Argentina , Chemotherapy, Adjuvant , Child, Preschool , Combined Modality Therapy , Comorbidity , Dactinomycin/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Infant , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/surgery , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Male , Neoadjuvant Therapy , Neoplasms, Multiple Primary/drug therapy , Neoplasms, Multiple Primary/surgery , Nephrectomy , Retrospective Studies , Treatment Outcome , Vincristine/administration & dosage , Wilms Tumor/mortality , Wilms Tumor/secondary , Wilms Tumor/surgeryABSTRACT
Between September 1995 and December 2010, 99 new consecutive assessable patients with extra-cranial MGCT were treated according to SFOP/SFCE TGM95 Protocol. A "watch and wait" strategy for completely resected stage I-II was observed in cases with preoperative high tumor markers levels. Metastatic disease or alpha fetoprotein levels > 15 000 ng/ml cases were treated by VIP chemotherapy (etoposide, ifosfamide and CDDP) 4-6-courses. All other cases were treated by VBP (vinblastine, bleomycin, and CDDP) 3-5 courses. Median age for the whole group was 11.1 (r: 0-17) years. Males: 49, females: 50. Stage I: 19 patients, stage II: 16, stage III: 31 and stage IV: 3. Gonadal disease occurred in 77 cases. Of 21 completely resected stage I-II patients with MGCT who did not receive chemotherapy after surgery, 6 presented disease progression and were successfully treated by chemotherapy and remained disease-free. There were no significant differences in outcome according to age, gender, initial site, staging, and histological variant or high levels of alpha-fetoprotein. Initial non-responsiveness to VIP chemotherapy was the only significant unfavorable prognostic feature. With a median follow-up of 64 (r: 5-204) months, at 10 years EFS and OS estimates for the whole group were 0.82 (SE = 0.05) and 0.90 (SE = 0.03) respectively. Therapy results of MGCT treated with the SFOP/SFCE 95 strategy were excellent. Initial non-response to front line chemotherapy was the only significant adverse prognostic feature. The "watch and wait" strategy for completely resected disease with initial positive markers proved to be safe with optimal outcome.
Subject(s)
Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Practice Guidelines as Topic , Adolescent , Age Distribution , Child , Child, Preschool , Female , Humans , Infant , Male , Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Gonadal Tissue/mortality , Neoplasms, Gonadal Tissue/pathology , Neoplasms, Gonadal Tissue/therapy , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Prognosis , Prospective Studies , Reproducibility of Results , Risk Assessment , Risk Factors , Sacrococcygeal Region , Sex Distribution , Testicular Neoplasms/mortality , Testicular Neoplasms/pathology , Testicular Neoplasms/therapy , Time Factors , Watchful Waiting/methodsABSTRACT
Between September 1995 and December 2010, 99 new consecutive assessable patients with extra-cranial MGCT were treated according to SFOP/SFCE TGM95 Protocol. A "watch and wait" strategy for completely resected stage I-II was observed in cases with preoperative high tumor markers levels. Metastatic disease or alpha fetoprotein levels > 15 000 ng/ml cases were treated by VIP chemotherapy (etoposide, ifosfamide and CDDP) 4-6-courses. All other cases were treated by VBP (vinblastine, bleomycin, and CDDP) 3-5 courses. Median age for the whole group was 11.1 (r: 0-17) years. Males: 49, females: 50. Stage I: 19 patients, stage II: 16, stage III: 31 and stage IV: 3. Gonadal disease occurred in 77 cases. Of 21 completely resected stage I-II patients with MGCT who did not receive chemotherapy after surgery, 6 presented disease progression and were successfully treated by chemotherapy and remained disease-free. There were no significant differences in outcome according to age, gender, initial site, staging, and histological variant or high levels of alpha-fetoprotein. Initial non-responsiveness to VIP chemotherapy was the only significant unfavorable prognostic feature. With a median follow-up of 64 (r: 5-204) months, at 10 years EFS and OS estimates for the whole group were 0.82 (SE = 0.05) and 0.90 (SE = 0.03) respectively. Therapy results of MGCT treated with the SFOP/SFCE 95 strategy were excellent. Initial non-response to front line chemotherapy was the only significant adverse prognostic feature. The "watch and wait" strategy for completely resected disease with initial positive markers proved to be safe with optimal outcome.
Entre septiembre de 1995 y diciembre 2010 se registraron 99 nuevos pacientes evaluables consecutivos con tumores germinales malignos (TGM) extra-cerebrales. Los pacientes fueron tratados prospectivamente según los lineamientos del Protocolo SFOP/SFCE TGM95. Se siguió una estrategia de watch and wait para la enfermedad estadio I-II completamente resecada. La enfermedad con metástasis y los casos con niveles de alfa fetoproteína > 15 000 ng/ml fueron tratados con etopósido, ifosfamida y CDDP, 4-6 cursos. El resto fue tratado con vinblastina, bleomicina y CDDP, 3-5 ciclos. La mediana de edad fue de 11.1 (r: 0-17) años. Varones: 49, niñas: 50. Estadio I: 19 casos; II: 16; III: 31y IV: 33. De 21 enfermos con estadios tumorales I y II con resección completa inicial que no tuvieron tratamiento adyuvante, seis progresaron, todos fueron exitosamente tratados con quimioterapia y permanecieron libres de enfermedad. No hubo diferencias significativas en los resultados de supervivencia según edad, género, sitio inicial, estadificación, variante histológica o niveles elevados de alfa-fetoproteína. La resistencia primaria a la quimioterapia VIP fue el único factor pronóstico desfavorable significativo. Con una mediana de seguimiento de 64 (r: 5-204) meses, a 10 años las probabilidades de supervivencia libre de eventos y supervivencia global para todo el grupo fueron respectivamente de 0.82 (EE = 0.05) y 0.90 (EE = 0.03). Los resultados con la estrategia SFOP/SFCE 95 fueron excelentes. La ausencia de respuesta a la quimioterapia de primera línea fue el único factor pronóstico adverso significativo. La estrategia de watch and wait probó ser segura y eficaz.
Subject(s)
Humans , Female , Infant , Child, Preschool , Child , Adolescent , Practice Guidelines as Topic , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Ovarian Neoplasms/mortality , Prognosis , Sacrococcygeal Region , Testicular Neoplasms/mortality , Time Factors , Prospective Studies , Reproducibility of Results , Sex Distribution , Neoplasms, Gonadal Tissue/mortality , Neoplasms, Gonadal Tissue/pathology , Age Distribution , Neoplasms, Germ Cell and Embryonal/mortality , Risk Assessment , Watchful Waiting/methodsABSTRACT
BACKGROUND: There are reports indicating a low incidence of neuroblastoma (NB) in some developing countries but no conclusive data are available from population-based studies at a national level. PURPOSE: To describe the incidence and survival of 971 patients with NB in Argentina with data from the National Pediatric Cancer Registry (ROHA), and the impact of age, gender, stage, regional, and socioeconomic indicators on outcome. METHODS: All cases of NB reported to ROHA (2000-2012) were the subject of the analysis. Annual-standardized incidence rate (ASR) was calculated using the National Vital Statistics and survival was estimated. The extended human development index (EHDI) was used as the socioeconomic indicator. RESULTS: ASR was 8.3/1,000,000 children (0-14 years) and remained stable along this period. Regional variation in ASR ranged from 3.4 in the Northwest to 9.8 in the Central region, being most marked in the first year of life. Five-year survival rate (SR) was 47%, with no sex difference. For patients older than 18 months, it was 36%, for stage IV 23%, for those born in the Northeast region 38%, and for those with an amplified MYCN 15%. Residents in provinces with a higher EHDI had a better 5-year survival (57% vs. 41% for lower EHDI) and higher ASR (12.3 vs. 5.6 for lower EHDI). Stage and MYCN status showed an independent inferior prognosis. CONCLUSIONS: ASR of NB in Argentina is lower than in developed countries, with considerable regional variation. SRs are also lower than in developed countries.
Subject(s)
Neuroblastoma/epidemiology , Neuroblastoma/mortality , Adolescent , Argentina/epidemiology , Child , Child, Preschool , Female , Geography , Humans , Infant , Male , Prognosis , Registries , Survival RateABSTRACT
Neuroblastoma is the most frequent extracranial solid tumor in childhood, representing 5.6% according to the "Registro Oncopediatrico Hospitalario Argentino". For its diagnosis, several complementary methods (radiological, biological and biochemical) are required, and Multi-parametric Flow Cytometry (MFC) arises as a potential diagnostic method, despite not having been so far extensively explored. MFC is a method that allows to obtain several information about size, internal complexity and antigenic expression by the use of a laser and fluorescent monoclonal antibodies. There are an increasing number of reports in the literature, which reveal the importance of using MFC for diagnosis and monitoring of solid tumors. The aim in this presentation is to highlight the fundamental role that MFC had in the case of a patient affected by neuroblastoma, in which an early diagnosis using this methodology allowed prompt administration of adequate treatment.
El neuroblastoma es el tumor sólido pediátrico extracraneal más frecuente, que representa un 5,6% según el Registro On-copediátrico Hospitalario Argentino. Se requieren, para su diagnóstico, varios métodos complementarios (radiológicos, biológicos y bioquímicos), entre los que la citometría de flujo multiparamétrica (CFM) surge con un potencial rol, aún no explorado. La CFM es una metodología que permite obtener información sobre el tamano, la complejidad y la expresión antigénica de la célula mediante el uso de un láser y anticuerpos monoclonales fluorescentes. Existe un creciente número de trabajos en la literatura que dan cuenta de la relevancia de la aplicación de la CFM en el diagnóstico y seguimiento de tumores sólidos. El objetivo de esta presentación es destacar el rol fundamental que tuvo la CFM en el caso de una paciente con neuroblastoma, en la cual un diagnóstico precoz permitió administrar rápidamente un adecuado tratamiento inicial.
Subject(s)
Flow Cytometry , Neuroblastoma/diagnosis , Humans , InfantABSTRACT
El neuroblastoma es el tumor sólido pediátrico extracraneal más frecuente, que representa un 5,6% según el Registro On-copediátrico Hospitalario Argentino. Se requieren, para su diagnóstico, varios métodos complementarios (radiológicos, biológicos y bioquímicos), entre los que la citometría de flujo multiparamétrica (CFM) surge con un potencial rol, aún no explorado. La CFM es una metodología que permite obtener información sobre el tamano, la complejidad y la expresión antigénica de la célula mediante el uso de un láser y anticuerpos monoclonales fluorescentes. Existe un creciente número de trabajos en la literatura que dan cuenta de la relevancia de la aplicación de la CFM en el diagnóstico y seguimiento de tumores sólidos. El objetivo de esta presentación es destacar el rol fundamental que tuvo la CFM en el caso de una paciente con neuroblastoma, en la cual un diagnóstico precoz permitió administrar rápidamente un adecuado tratamiento inicial.
Neuroblastoma is the most frequent extracranial solid tumor in childhood, representing 5.6% according to the "Registro Oncopediátrico Hospitalario Argentino". For its diagnosis, several complementary methods (radiological, biological and biochemical) are required, and Multi-parametric Flow Cytometry (MFC) arises as a potential diagnostic method, despite not having been so far extensively explored. MFC is a method that allows to obtain several information about size, internal complexity and antigenic expression by the use of a laser and fluorescent monoclonal antibodies. There is an increasing number of reports in the literature which reveal the importance of using MFC for diagnosis and monitoring of solid tumors. The aim in this presentation is to highlight the fundamental role that MFC had in the case of a patient affected by neuroblastoma, in whom an early diagnosis using this methodology allowed prompt administration of adequate treatment.
Subject(s)
Humans , Female , Infant , Flow Cytometry , Neuroblastoma/diagnosisABSTRACT
INTRODUCTION: Racotumomab (originally known as 1E10 mAb) is an anti-idiotype murine IgG1 directed to membrane glycoconjugates expressed in aggressive solid tumors. It was developed as a mirror image of the idiotype of another antibody against N-glycolyl-containing molecules, such as the NeuGcGM3 ganglioside. After a successful phase II/III study, racotumomab formulated in alum was conditionally approved in Latin American countries as maintenance therapy for advanced non-small cell lung cancer. AREAS COVERED: This review analyzes the biology of the target antigen, summarizes preclinical studies and discusses clinical trials in adults and the pediatric experience with racotumomab. EXPERT OPINION: Proper patient selection and combination with chemotherapy, radiotherapy or checkpoint inhibitors appear to be critical issues to maximize the effects of racotumomab vaccination in lung cancer. In a recent phase I clinical trial in children with relapsed or resistant neuroectodermal malignancies, racotumomab was well tolerated and immunogenic, and its evaluation as immunotherapy for high-risk neuroblastoma is warranted.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Cancer Vaccines/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Animals , Antibodies, Anti-Idiotypic/therapeutic use , Antibodies, Monoclonal, Murine-Derived , Child , G(M3) Ganglioside/analogs & derivatives , G(M3) Ganglioside/immunology , HumansABSTRACT
BACKGROUND: Pediatric neuroectodermal malignancies express N-glycolylated gangliosides including N-glycolyl GM3 (NeuGcGM3) as targets for immunotherapy. PROCEDURE: We evaluated the toxicity and maximum tolerated dose and immunological response of racotumomab, an anti-idiotype vaccine targeting NeuGcGM3 through a Phase I study enrolling children with relapsed or resistant tumors expressing NeuGcGM3. MATERIALS AND METHODS: Drug dose was escalated to three levels (0.15-0.25-0.4 mg) of racotumomab administered intradermally. Each drug level included three patients receiving a total of three doses, every 14 days. A confirmation cohort was added to the highest dose level. Antibody response was assessed upon study entry and at 4-week intervals for at least three immunological determinations for each patient. RESULTS: Fourteen patients were enrolled (10 with neuroblastoma, one with retinoblastoma, one with Wilms' tumor, and two with brainstem glioma). Three patients completed the three drug levels and three were enrolled in the confirmation cohort. One patient died of tumor progression before completing the three applications. Racotumomab was well tolerated. The only side effect observed was grade 1-2 toxicity at the injection site. Racotumomab elicited an IgM and/or IgG antibody response directed against NGcGM3 in nine patients and IgM against racotumomab in 11 of 13 evaluable patients. The maximum tolerated dose was not reached and no dose-limiting toxicity was seen. CONCLUSIONS: Racotumomab vaccination has a favorable toxicity profile up to a dose of 0.4 mg, and most patients elicited an immune response. Its activity as immunotherapy for neuroectodermal malignancies will be tested in further clinical trials.