RESUMEN
Introducción: el Sarcoma de Ewing es una neoplasia maligna de origen mesenquimático. Al momento del diagnóstico el 75% se presentan en forma localizada. Objetivo: comunicar un caso que por su presentación multifocal, generó dificultades diagnósticas. Caso clínico: niña de 6 años. Consulta por traumatismo de mano derecha tras caída de su altura 24 horas previas, constatándose en mano y puño derecho edema, calor y eritema, movilidad conservada. No fiebre. Radiografía: aumento del diámetro del tercer metacarpiano, imagen esmerilada, no trazos de fracturas. Ingresa con planteo de celulitis. Anemia leve microcítica, hipocrómica. Proteína C reactiva 82 mg/l. Recibe clindamicina intravenosa 72 horas, completa 14 días vía oral. Persistencia de alteraciones en puño y mano derecha, agrega tumoración de raíz nasal con desviación del eje, indolora. Fosfatasa alcalina, lactato deshidrogenasa, fosfatemia, calcemia normales. Resonancia magnética: alteración morfoestructural de radio, olecranon y tercer metacarpiano, fractura de olecranon y radio, reacción perióstica. Pet-Scan: lesión extensa ósea en macizo facial, tibias, cúbitos, humero derecho y clavícula. Biopsia 3er metacarpiano: tumor de células pequeñas, redondas azules, CD99 y vimentina positivo. Comienza poliquimioterapia y radioterapia sin complicaciones. Conclusiones: es frecuente que las manifestaciones clínicas iniciales sean confundidas con entidades más frecuentes, como post-traumáticas y/o inflamatorias, tal como ocurrió en este caso. Posteriormente, la aparición de nuevas lesiones y compromiso del estado general orientó el abordaje diagnóstico de la patología tumoral. La confirmación exige el estudio anatomopatológico con estudio inmunohistoquímico. La presencia de metástasis óseas constituye un factor de mal pronóstico y dificulta el abordaje terapéutico.
Introduction: Ewing's sarcoma is a malignant neoplasm of mesenchymal origin. At the time of diagnosis 75% of the cases are localized. Objective: to report a case that, due to its multifocal presentation, generated diagnostic difficulties. Clinical case: 6-year-old girl. She consulted for right hand trauma after a fall from her height 24 hours earlier, with edema, warmth and erythema in the right hand and fist, with preserved mobility. No fever. X-ray: increase in the diameter of the 3rd metacarpal, frosted image, no traces of fractures. Admitted with cellulitis. Mild microcytic anemia, hypochromic. C-reactive protein 82mg/l. Receives intravenous clindamycin 72 hours, completes 14 days orally. Persistence of alterations in fist and right hand, adds tumor of nasal root with deviation of the axis, painless. Alkaline phosphatase, lactate dehydrogenase, phosphatemia, normal calcemia. MRI: morphostructural alteration of radius, olecranon and 3rd metacarpal, fracture of olecranon and radius, periosteal reaction. Pet-Scan: extensive bone lesion in facial mass, tibiae, ulnae, right humerus and clavicle. Biopsy 3rd metacarpal: small cell tumor, blue round, CD 99 and vimentin positive. Polychemotherapy and radiotherapy were started without complications. Conclusions: it is frequent that the initial clinical manifestations are confused with more frequent entities, such as post-traumatic and/or inflammatory, as occurred in this case. Subsequently, the appearance of new lesions and compromise of the general condition guided the diagnostic approach of the tumor pathology. Confirmation requires anatomopathological study with immunohistochemical study. The presence of bone metastases constitutes a poor prognostic factor and hinders the therapeutic approach.
Introdução: O sarcoma de Ewing é um neoplasma maligno de origem mesenquimatosa. No momento do diagnóstico, 75% dos casos são localizados. Objetivo: Relatar um caso que, devido a sua apresentação multifocal, causou dificuldades diagnósticas. Caso clínico: Menina de 6 anos. Ela consultou por traumatismo à mão direita após cair de sua altura 24 horas antes, com edema, calor e eritema na mão direita e punho, com mobilidade preservada. Sem febre. Raio-X: aumento do diâmetro do 3º metacarpo, imagem fosca, sem vestígios de fraturas. Admitido com a sugestão de celulite. Anemia microcítica leve, hipocrómica. Proteína C reativa 82mg/l. Recebe clindamicina intravenosa por 72 horas, completa 14 dias por via oral. Persistência de alterações no punho e mão direita, tumor indolor da raiz nasal com desvio do eixo. Fosfatase alcalina, desidrogenase láctica, fosfataemia, calcemia normal. IRM: alteração morfo-estrutural do rádio, olecrânio e 3º metacarpo, fratura do olecrânio e do rádio, reação periosteal. Pet-Scan: extensa lesão óssea na massa facial, tíbia, ulnae, úmero direito e clavícula. Biópsia do 3º metacarpo: tumor de pequenas células, redondo azul, CD 99 e vimentina positiva. Ela iniciou a poli-quimioterapia e radioterapia sem complicações. Conclusões: É comum que as manifestações clínicas iniciais sejam confundidas com entidades mais freqüentes, tais como pós-traumáticas e/ou inflamatórias, como ocorreu neste caso. Posteriormente, o aparecimento de novas lesões e o envolvimento do quadro geral levaram a uma abordagem diagnóstica da patologia tumoral. A confirmação requer um estudo anatomopatológico com estudo imuno-histoquímico. A presença de metástases ósseas é um fator de mau prognóstico e dificulta a abordagem terapêutica.
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Humanos , Femenino , Niño , Sarcoma de Ewing/diagnóstico por imagen , Neoplasias Óseas/diagnóstico por imagen , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/radioterapia , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/radioterapiaRESUMEN
BACKGROUND: Ewing's sarcoma is the second most common bone and soft tissue malignancy in children and adolescents. Tumor necrosis factor-α-induced protein 8-like 1 (TIPE1) functions as a tumor suppressor in several cancers. Activation of Wnt/ß-catenin signaling in subpopulations of tumor cells contributes to phenotypic heterogeneity and disease progression in Ewing's sarcoma. The exact role of TIPE1 in Ewing's sarcoma remains to be elucidated. PURPOSE: This study aimed to assess the expression and function of TIPE1 in Ewing's sarcoma. METHODS: TIPE1 expression in Ewing's sarcoma cells was determined by qPCR and western blotting. Furthermore, the Ewing's sarcoma cell line RD-ES was transfected with a lentivirus-based TIPE1 expression system to upregulate the expression of TIPE1. The Cell Counting Kit 8 was used to assess the effect of TIPE1 on cell proliferation. The effects of TIPE1 on cell migration and invasion was detected by Transwell assay. Flow cytometry was performed to detect apoptosis. RESULTS: Our results suggested lower TIPE1 expression in Ewing's sarcoma cell lines compared with normal osseous cells. TIPE1 remarkably inhibited the growth and proliferation of Ewing's sarcoma cell; TIPE1 also induced apoptosis and inhibited invasion in vitro. TIPE1 inhibited Ewing's sarcoma growth, motility, and survival through regulation of Wnt/ß-catenin signaling. CONCLUSIONS: Our results demonstrated the anti-tumor function of TIPE1 in Ewing's sarcoma and reveal a novel therapeutic target.
Asunto(s)
Neoplasias Óseas , Sarcoma de Ewing , Adolescente , Niño , Humanos , Apoptosis , beta Catenina/genética , beta Catenina/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Proliferación Celular , Perfilación de la Expresión Génica , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/genética , Transducción de Señal , Proteínas Wnt/genética , Proteínas Wnt/metabolismoRESUMEN
Resistance to chemotherapy poses a major challenge for cancer treatment. Reactivating a stem cell program resembling that seen in embryonic development can lead cancer cells to acquire a stem-cell phenotype characterized by expression of stemness genes, pluripotency, high self-renewal ability, and tumor-initiating capability. These cancer stem cells (CSCs) are usually resistant to anticancer drugs and are likely involved in treatment failure in many cancer types. Ewing sarcoma (ES) is a pediatric cancer type typically resulting from a typical genetic alteration affecting bone or soft tissues. Despite advances in treatment, survival prognostic remains poor for patients with refractory or recurrent disease. Here, we review the increasing evidence indicating that ES tumors contain a CSC subpopulation expressing stem cell genes, including BM1, OCT3/4, NANOG, and SOX2, that plays a role in resistance to drug treatment, and current experimental strategies that successfully counteract chemoresistance mediated by CSCs in ES.
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Antineoplásicos , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Células Madre Neoplásicas/metabolismoRESUMEN
BACKGROUND: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing sarcoma (ES), although studies are largely limited to paediatric populations. METHODS: We retrospectively reviewed paediatric (< 18 years) and adult patients (≥ 18 years) treated with salvage IT at two institutions. Haematologic toxicities were graded according to common terminology criteria of adverse events. Survival was estimated by the Kaplan-Meier method and compared by the Log Rank test. RESULTS: Fifty-three patients were treated with IT from Jan, 2010 to Dec, 2018 (n = 16 paediatric; n = 37 adult). IT was given as second-line (n = 34; 64%) or ≥ third-line (n = 19; 36%). There was no difference in ≥ grade 3/4 haematologic toxicity between paediatrics and adults (31% vs. 35% respectively; p = 0.76). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 12 (28%) stable disease and 19 (44%) disease progression. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.2 months, p = 0.039). CONCLUSION: Irinotecan and temozolomide (IT) chemotherapy has activity for relapsed ES, with favourable toxicity and equally observed objective responses in the paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in future studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Irinotecán/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Temozolomida/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/mortalidad , Niño , Diarrea/inducido químicamente , Progresión de la Enfermedad , Esquema de Medicación , Humanos , Irinotecán/efectos adversos , Estimación de Kaplan-Meier , Recurrencia Local de Neoplasia/mortalidad , Supervivencia sin Progresión , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , Terapia Recuperativa , Sarcoma de Ewing/mortalidad , Temozolomida/efectos adversosRESUMEN
PURPOSE: To compare the outcomes of extraskeletal and skeletal Ewing sarcomas treated with standard chemotherapy protocol. METHODS: We retrospectively collected data on primary localized skeletal and extraskeletal ES patients. Demographics and disease characteristics were compared between the two groups. The influence of presentation (skeletal vs. extraskeletal) on overall survival (OS) and local recurrence-free survival (LRFS) was assessed and compared by the log-rank test. RESULTS: A total of 120 patients were included; 29 (24%) had extraskeletal and 91 (76%) had skeletal ES. All patients received vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE) chemotherapy, with a plan for local control at week 12. At a median follow-up of 38 months, there was no difference in OS between skeletal and extraskeletal ES; 5-year OS 70% and 67% respectively, p = 0.96. Patients with extraskeletal ES had inferior 5-year LRFS compared to skeletal ES; 74% vs. 83%; p = 0.042. Local recurrence occurred at a higher frequency in the extraskeletal group; 28% vs. 11%, p = 0.034, although more extraskeletal patients received adjuvant radiotherapy; 73% vs. 36%, p = 0.01. Among patients who underwent surgery (n = 76), there was no difference in R0 resection rate (skeletal: 89%, extraskeletal: 86%, p = 0.52, or good ( ≥ 90%) tumor necrosis; skeletal: 54%, extraskeletal: 38%, p = 0.31. CONCLUSION: Patients with localized extraskeletal ES have comparable OS outcomes to patients with skeletal ES utilizing the standard VDC-IE chemotherapy. However, extraskeletal patients are at significantly higher risk for local recurrence.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Terapia Combinada , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Humanos , Ifosfamida/uso terapéutico , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Sarcoma de Ewing/mortalidad , Sarcoma de Ewing/patología , Sarcoma de Ewing/terapia , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapia , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/uso terapéuticoAsunto(s)
Neoplasias de Cabeza y Cuello/diagnóstico , Sarcoma de Ewing/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Biopsia con Aguja Fina , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética , Masculino , Sarcoma de Ewing/tratamiento farmacológicoAsunto(s)
Humanos , Masculino , Adulto , Sarcoma de Ewing/diagnóstico , Neoplasias de Cabeza y Cuello/diagnóstico , Sarcoma de Ewing/tratamiento farmacológico , Imagen por Resonancia Magnética , Protocolos de Quimioterapia Combinada Antineoplásica , Biopsia con Aguja Fina , Neoplasias de Cabeza y Cuello/tratamiento farmacológicoRESUMEN
PURPOSE: Survival in Ewing's sarcoma (ES) has increased with the use of chemotherapy. Surgical techniques such as limb salvage (LS) have been developed. Survival and adverse events have been widely studied in general series of ES, but there are few specific series of ES cases treated by LS, despite this being the most commonly used (surgical) approach. The aim of this study was to determine survival and prognostic factors in ES patients undergoing LS. PATIENTS AND METHODS: We analysed all ES patients treated between January 1984 and May 2008 and selected all those treated by systemic multimodal therapy and LS. We assessed the influence of patient characteristics, tumour parameters and therapeutic results in event-free survival (EFS). RESULTS: Ninety patients were included. Fifty of them were treated by systemic multimodal therapy and locally by LS. ean age was 20 years. Overall survival (OS) was 68.8% and EFS was 60.6% at years. In the univariate analysis, pelvic location, age and response to chemotherapy were associated with poor prognosis. After multivariate analysis, poor response to treatment, pelvis location and age between 12 and 17 years were found to be independent prognostic factors. Dissemination at diagnosis was not a prognostic factor. CONCLUSIONS: OS and EFS in ES treated by LS were similar to findings in previous ES studies. factors are no different, except for the presence of metastasis at diagnosis.
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Neoplasias Óseas/cirugía , Recuperación del Miembro , Sarcoma de Ewing/cirugía , Adolescente , Adulto , Análisis de Varianza , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Recuperación del Miembro/efectos adversos , Recuperación del Miembro/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) recovery have been shown to be associated with prognosis in several types of cancer in adults. However, evidence in pediatric cancer is scarce. The aim of our study was to evaluate whether pretreatment NLR and lymphocyte recovery are prognostic factors in pediatric sarcomas. MATERIALS AND METHODS: Study participants were identified from a retrospective cohort of 100 children with osteosarcoma (n=55), rhabdomyosarcoma (n=22), and Ewing sarcoma (n=23). Data for the hematological variables were obtained from medical records and analyzed with other known prognostic factors in univariate and multivariate analyses. RESULTS: In multivariate analysis, NLR>2 was an independent prognostic factor for OS in patients with osteosarcoma (hazard ratio [HR], 2.27, 95% confidence interval [CI], 1.07-5.30; P=0.046) along with metastatic disease and poor histologic response; as well as in patients with rhabdomyosarcoma (HR, 4.76, 95% CI, 1.01-22.24; P=0.0237) along with metastatic disease and risk group. ALC recovery correlated for inferior OS in osteosarcoma (HR, 3.34, 95% CI, 1.37-8.12; P=0.008) and rhabdomyosarcoma (HR, 3.89; 95% CI, 1.01-14.89; P=0.0338). CONCLUSIONS: Our study confirms that NLR and ALC recovery are independent prognostic factors for pediatric sarcomas, implying an important role of immune system in survival. Clinical utility of these prognostic biomarkers should be validated in larger pediatric studies.
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Linfocitos/patología , Neutrófilos/patología , Pronóstico , Sarcoma/diagnóstico , Biomarcadores , Niño , Estudios de Cohortes , Femenino , Humanos , Recuento de Leucocitos , Masculino , Metástasis de la Neoplasia , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/mortalidad , Estudios Retrospectivos , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/mortalidad , Sarcoma/sangre , Sarcoma/mortalidad , Sarcoma/patología , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/mortalidad , Tasa de SupervivenciaRESUMEN
Ewing sarcoma (ES) is a highly aggressive pediatric cancer that may arise from neuronal precursors. Neurotrophins stimulate neuronal devlopment and plasticity. Here, we found that neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as their receptors (TrkA and TrkB, respectively) are expressed in ES tumors. Treatment with TrkA (GW-441756) or TrkB (Ana-12) selective inhibitors decreased ES cell proliferation, and the effect was increased when the two inhibitors were combined. ES cells treated with a pan-Trk inhibitor, K252a, showed changes in morphology, reduced levels of ß-III tubulin, and decreased mRNA expression of NGF, BDNF, TrkA and TrkB. Furthermore, combining K252a with subeffective doses of cytotoxic chemotherapeutic drugs resulted in a decrease in ES cell proliferation and colony formation, even in chemoresistant cells. These results indicate that Trk inhibition may be an emerging approach for the treatment of ES.
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Antineoplásicos/farmacología , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Glicoproteínas de Membrana/antagonistas & inhibidores , Factor de Crecimiento Nervioso/biosíntesis , Receptor trkA/antagonistas & inhibidores , Receptor trkB/antagonistas & inhibidores , Sarcoma de Ewing/tratamiento farmacológico , Azepinas/farmacología , Benzamidas/farmacología , Factor Neurotrófico Derivado del Encéfalo/genética , Carbazoles/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Doxorrubicina/farmacología , Inhibidores Enzimáticos/farmacología , Etopósido/farmacología , Humanos , Alcaloides Indólicos/farmacología , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Factor de Crecimiento Nervioso/genética , ARN Mensajero/biosíntesis , Receptor trkA/biosíntesis , Receptor trkA/genética , Receptor trkB/biosíntesis , Receptor trkB/genética , Sarcoma de Ewing/patología , Tubulina (Proteína)/metabolismo , Vincristina/farmacologíaRESUMEN
BACKGROUND: Response to chemotherapy is a prognostic factor in patients with Ewing sarcoma (ES); the role of FDG PET to predict response in these patients has not been thoroughly investigated. We evaluated the diagnostic accuracy and the potential of FDG PET to predict response to chemotherapy (CHT). MATERIALS AND METHODS: We analyzed data of 50 patients with ES (median age 12.6 years). All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had (18)F-FDG PET/CT at diagnosis and after induction CHT, prior to local control. We compared response assessed by histopathology with FDG PET using standard uptake values (SUVs). RESULTS: Median SUV at diagnosis (SUV I) was 5 (range 1.2-17), and median SUV after neoadjuvant chemotherapy (SUV II) was 1.8 (range 0-8.4). Median SUV II/I ratio was 0.3 (range 0-1). SUV at diagnosis was significantly lower in patients with good histological response than in patients with poor histological response (median 3.8 vs. 7.2, p 0.02). We found a significant correlation between SUV II and outcome; the positive predictive value of an SUV II ≤ 2.5 for favorable response was 84.21 %, and the median SUV II was significantly higher in patients with disease progression (2.3 vs. 1.6, p = 0.04). In multivariate analysis, necrosis and SUV II were significant predictors of outcome. CONCLUSIONS: (18)F-FDG PET demonstrates high diagnostic accuracy for response to initial chemotherapy in patients with ES and it correlates with outcome. The role of FDG PET in predicting response and outcome should be further investigated.
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Neoplasias Óseas/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Sarcoma de Ewing/diagnóstico por imagen , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Fluorodesoxiglucosa F18 , Humanos , Estimación de Kaplan-Meier , Masculino , Imagen Multimodal , Pronóstico , Modelos de Riesgos Proporcionales , Radiofármacos , Estudios Retrospectivos , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/patología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
Vocal cord paralysis after administration of the chemotherapeutic agent vincristine is a rare occurrence. Most occurrences are bilateral. Of the 24 cases referenced in this article, 19 are children. In all the reported cases, symptoms have occurred after multiple doses of vincristine have been administered. The authors report a case of a 39-year-old woman with unilateral vocal cord motion impairment occurring 3 days after the administration of the first dose of vincristine. This is the first case of vocal cord motion impairment reported after the administration of only 1 dose of this drug.
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Antineoplásicos Fitogénicos/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Vincristina/efectos adversos , Parálisis de los Pliegues Vocales/inducido químicamente , Adulto , Femenino , HumanosRESUMEN
BACKGROUND: Large cooperative group studies have shown the efficacy of risk-adapted treatment for Ewing sarcoma. However, validation and local adaptation by National cooperative groups is needed. A multicenter protocol to determine the efficacy and safety of a risk-adapted intensive regimen was developed by the Brazilian cooperative group. PROCEDURE: Patients <30 years old with Ewing sarcoma were eligible. Induction chemotherapy consisted of two cycles of ICE (ifosfamide, carboplatin, and etoposide) followed by two cycles of VDC (vincristine, doxorubicin, and cyclophosphamide), followed by local control. Patients with low risk (LR) disease (localized resectable with normal LDH) received 10 additional alternating courses of IE with VDC. For patients with high-risk (HR) disease (unresectable, pelvic, metastatic, or high LDH), two additional cycles of ICE were given. RESULTS: One-hundred seventy five patients (39% metastatic) were enrolled. Fifty-two patients (29.7%) were LR and 123 (70.3%) were HR. Overall response rate at end of induction was 27.4%. Five-year event-free survival (EFS) and overall survival (OS) estimates were 51.4% and 54.4%, respectively. Patients with localized disease had better outcomes than patients with metastases (5-year EFS 67.9% vs. 25.5%, and 5-year OS 70.3% vs. 29.1%, respectively). On multivariate analysis, the presence of metastatic disease was the only prognostic factor (P < 0.01). CONCLUSION: The VDC/ICE protocol was feasible, and considering the high tumor burden in our population, resulted in comparable results to those reported by cooperative groups in high-income countries. Further adaptation to maximize efficacy and minimize toxicity will be required.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Carboplatino/administración & dosificación , Sarcoma de Ewing/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Adolescente , Neoplasias Óseas/mortalidad , Brasil , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido , Femenino , Humanos , Ifosfamida/administración & dosificación , Quimioterapia de Inducción/métodos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Sarcoma de Ewing/mortalidad , Neoplasias de los Tejidos Blandos/mortalidad , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
Introducción: Los sarcomas de Ewing extraesqueléticos son raros y representan menos del dos por ciento de los cánceres del adulto. Se caracterizan por su agresividad, alta incidencia de recurrencia local y metástasis. La afectación del sistema nervioso central es muy infrecuente.Casos clínicos: Se presentan dos enfermos de 21 y 27 años atendidos por el servicio de Neurocirugía del HospitalUniversitario Manuel Ascunce Domenech de Camagüey en los años 2012 y 2013. Ambos debutaron con dorsalgia seguida de un síndrome de compresión medular dorsal incompleto. La resonancia magnética demostró la presencia de un tumor intrarraquídeo por lo que se decidió el tratamiento quirúrgico para exéresis y descompresión de las estructuras nerviosas. El diagnóstico anatomapatológico sugirió un sarcoma de Ewing extraesquelético y se requirió de la confirmación por técnicas de inmunohistoquímica. En los dos primeros meses después de la cirugía, se constató la recurrencia de las lesiones conevolución clínica desfavorable. La quimioterapia multidrogas no logró el control local de la enfermedad.Conclusiones: La alta malignidad de este tipo de neoplasias requiere de una exéresis amplia, guiada por la histopatología transoperatoria para garantizar la efectividad de la cirugía, seguida de la quimioterapia multidrogas para favorecer el control sistémico y prevenir las recurrencias. Las claves para los mejores resultados son el diagnóstico precoz antes de la apariciónde las metástasis y el tratamiento multidisciplinario multimodal(AU)
Introduction: Extraskeletal Ewing sarcomas are a rare type of soft tissue tumors and represent the two percent of neoplasm in adults. It is characterized by the aggressiveness, high incidence of local recurrence and metastases. Central nervous system affection is uncommon.Clinical cases: Two patients of 21 and 27 years old each are presented treated by the Neurosurgery service of theUniversity Hospital Manuel Ascunce Domenech of Camagüey in 2012 and 2013. They complaint dorsal pain followed by a dorsal incomplete medullar compression syndrome. The Magnetic Resonance Imaging showed the presence of intraspine tumors, that´s why surgical treatment was mandatory for decompression of neurologic structures and tumor removal. The anatomopathologic diagnosis suggests an extra skeletal Ewing sarcoma and inmunohistochemistry techniques confirmation were required. Two month after surgery, recurrence appeared with unfavorable clinic evolution. Multidrug chemotherapy did not control local reappearance of the disease.Conclusions: the highly malignance of this kind of tumor required wide removal, supported by transoperatory histopathology to guarantee surgery effectiveness, followed by multidrug chemotherapy to help systemic control and prevent recurrence.The key for better results are a precocious diagnosis before metastases appearance and a multidisciplinary multimodal treatment(AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Sarcoma de Ewing/complicaciones , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/cirugía , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Ifosfamida/administración & dosificación , Ifosfamida/uso terapéutico , Mesna/administración & dosificación , Mesna/uso terapéutico , Laminectomía/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
Histone deacetylase inhibitors and bisphosphonates have a promising future in the treatment of cancer as targeted anticancer drugs, particularly when used together or in combination with other cytotoxic agents. However, the effects of these combined treatments have not yet been systematically evaluated in Ewing sarcoma. The in vitro effects on cellular proliferation, viability and survival were investigated in two Ewing sarcoma cell lines, SK-ES-1 and RD-ES. The cell lines were treated with sodium butyrate, a histone deacetylase inhibitor and zoledronic acid, a bisphosphonate, alone, together or in combination with chemotherapeutic drugs recommended for clinical treatment of Ewing sarcoma. The data demonstrated that the combination of sodium butyrate and zoledronic acid had a synergistic cytotoxic effect at 72 h following treatment, persisting for 10-14 days post-treatment, in both cell lines tested. All combinations between sodium butyrate or zoledronic acid and the traditional antineoplastic drugs (doxorubicin, etoposide and vincristine) demonstrated a synergistic cytotoxic effect at 72 h in SK-ES-1 and RD-ES cells, except for the combinations of sodium butyrate with vincristine and of zoledronic acid with doxorubicin, which showed only an additive effect in RD-ES cell lines as compared to each agent alone. These acute effects observed in both Ewing sarcoma cell lines were confirmed by the clonogenic assay. The present data suggest that combining histone deacetylase inhibitors and bisphosphonates with traditional chemotherapeutic drugs is a promising therapeutic strategy for the treatment of Ewing sarcoma, and provides a basis for further studies in this field.
Asunto(s)
Ácido Butírico/farmacología , Difosfonatos/farmacología , Antagonistas de los Receptores Histamínicos/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Imidazoles/farmacología , Sarcoma de Ewing/tratamiento farmacológico , Antibióticos Antineoplásicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Conservadores de la Densidad Ósea/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacología , Sinergismo Farmacológico , Etopósido/farmacología , Humanos , Terapia Molecular Dirigida , Ensayo de Tumor de Célula Madre , Vincristina/farmacología , Ácido ZoledrónicoRESUMEN
Desmoplastic small round cell tumor is a very rare neoplasm, that usually appears in children and young adolescents. There is no standard therapy, and responses to chemotherapy are infrequent. Surgery is still the main treatment for this disease. We report the case of a 39 year-old man and briefly summarize the evidence about this tumor.
Asunto(s)
Sarcoma de Ewing/diagnóstico , Sarcoma de Células Pequeñas/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Progresión de la Enfermedad , Resultado Fatal , Humanos , Ganglios Linfáticos/patología , Masculino , Metástasis de la Neoplasia , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/patología , Peritoneo , Pronóstico , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/patología , Sarcoma de Células Pequeñas/tratamiento farmacológico , Sarcoma de Células Pequeñas/patología , Resultado del TratamientoRESUMEN
Los tumores óseos primitivos son neoplasias que se originan en el hueso, siendo los mas comunes en la infancia el osteosarcoma y el sarcoma de Ewing (aproximadamente 5% del total), aparecen en la segunda década de la vida son excepcionales antes de los 5 años de edad y es mas frecuente en el sexo masculino. Se presenta el caso de un escolar masculino de 6 años que inició enfermedad actual de 25 días de evolución caracterizada por dolor de fuerte intensidad a nivel de miembro inferior izquierdo que no mejora con la administración de analgésicos, posteriormente presenta aumento de volumen, e imposibilidad para la marcha. Asimetria de miembros inferiores dada por aumento de volumen de pierna izquierda con respecto a la derecha con 3 cm. de diferencia, dolorosa a la movilización. Rx de miembro inferior izquierdo: Levantamiento del periostio en tercio medio de peroné izquierdo. RMN de miembro inferior izquierdo se evidencia LOE en diáfisis de peroné izquierdo con infiltración de masa muscular. Se realizó exéresis del TU y tejidos adyacentes. La biopsia confirma el diagnóstico de sarcoma de Ewing con compromiso de partes blandas adyacentes y bordes libres de resección ósea libres de neoplasia. Recibió quimioterapia adyuvante. Finalizó tratamiento en Octubre del 2007. Actualmente Vivo sin enfermedad con excelente evolución pos-tratamiento y en seguimiento. El Sarcoma de Ewing es poco frecuente en menores de 10 años de edad, el pronóstico depende del tamaño, localización, metástasis al diagnóstico, niveles de LDH y respuesta a la quimioterapia inicial, debe individualizarse el tratamiento con el fin de lograr control local y erradicación de la enfermedad residual.
Asunto(s)
Humanos , Masculino , Niño , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma , Peroné/anatomía & histología , Peroné/lesiones , Biopsia/métodos , Sarcoma de Ewing/cirugía , Sarcoma de Ewing/patología , Sarcoma de Ewing/tratamiento farmacológico , Traumatismos de la Pierna/etiologíaRESUMEN
First described by James Ewing in 1921, Ewing's sarcoma (ES) or Ewing's tumor is one of the most aggressive bone tumors known. ES is an uncommon intra-osseous malignant tumor of questionable pathogenesis that occurs in children and young adults. Reports indicate that only 2 to 7% of cases involve the maxillofacial region, usually the mandible ramus, and few reported cases have involved the maxilla. In the present report of a case of ES of the mandible, we describe the results of imaging and evaluation after therapeutic treatment. This report provides a rare opportunity to observe radiologic features of ES in the mandible.