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1.
J Pediatr Hematol Oncol ; 41(2): 105-111, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30570510

RESUMEN

This study evaluated the effect of an intensified pilot protocol, SCMCIE 94, on the outcome of Ewing sarcoma (EWS). The cohort included 121 patients with local or metastatic EWS treated at a tertiary pediatric medical center with the SCMCIE 94 (protocol 3, 1994 to 2011) or an earlier protocol (protocol 2, 1988 to 1994; protocol 1, 1985 to 1988). All protocols included 4 to 6 courses of chemotherapy, radiation, and surgery. Clinical data were collected retrospectively by chart review. Survival rates for protocol 3 were as follows: all patients-5-year event-free survival (EFS): 52.5%±5.6%, 10-year EFS: 49.3%±5.8%, 5-year overall survival (OS): 68.8%±5.3%, and 10-year OS: 51.1%±6.3%; patients with localized disease (any site)-5-year EFS: 63.5%±6.0% and 5-year OS: 77.2%±5.3%; patients with localized extremity disease-5-year EFS: 78.95%±8.3%, 10-year EFS: 68.6%±10.0%, 5-year OS: 90.7%±6.2%, and 10-year OS: 71.1%±11.2%. Protocol 3 was associated with an increase in 10-year EFS of 16% overall and 33% in patients with localized extremity disease compared with protocols 1+2, and a significant improvement in 5-year EFS and OS in patients with any localized disease (P=0.001). No survival benefit was found for metastatic disease. On multivariate analysis, protocol and metastatic disease were significantly independent prognostic factors. The intensified SCMCIE 94 protocol seems to increase survival in patients with localized but not metastatic EWS.


Asunto(s)
Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Sarcoma de Ewing/mortalidad , Sarcoma de Ewing/terapia , Adolescente , Adulto , Neoplasias Óseas/patología , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Masculino , Metástasis de la Neoplasia , Proyectos Piloto , Sarcoma de Ewing/patología , Tasa de Supervivencia
2.
Psychol Health Med ; 18(2): 135-44, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-22640693

RESUMEN

Four hundred and twenty-six participants volunteered to participate in this study. A total of 159 men and 281 women comprised the sample. The sample was composed of 99 cancer stricken patients, 97 caregivers, 124 participants from the general population, and 126 people who were related to them in a similar manner that caregivers were related to patients (i.e. spouse, intimate partner, child, family member, etc.). Utilizing the Loneliness Questionnaire, the Multidimensional Scale of Perceived Social Support (MPSS), and the Sense of Coherence (SOC) questionnaires, it was found that significant differences among the four groups were found on Reflection and Acceptance, Self-development and Understanding, Social Support Network, Distancing and Denial, and on the Increased Activity subscales. Significant differences were not found on the Religion and Faith subscale. The findings are interpreted in light of the analyses of the other two measures which address the social support that patients and caregivers received and their SOC.


Asunto(s)
Adaptación Psicológica , Cuidadores/psicología , Soledad/psicología , Neoplasias/enfermería , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Escolaridad , Salud de la Familia , Femenino , Humanos , Israel , Masculino , Estado Civil , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/psicología , Religión , Sentido de Coherencia , Apoyo Social , Encuestas y Cuestionarios , Adulto Joven
3.
Adv Radiat Oncol ; 7(6): 101007, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36420201

RESUMEN

Purpose: The main goal of treatment of soft-tissue sarcomas is achieving wide negative margins to improve local control and prevent recurrence. The role of radiation therapy (RT) is well established in sarcomas of the extremities; however, its role in unplanned surgery of soft-tissue sarcoma (when a mass presumed to be benign is resected and the pathology comes back as sarcoma, usually referred to as an "oops" operation) is inconclusive. This article reports on the effect of RT after an unplanned surgery before the reresection. Methods and Materials: A total of 65 patients who had undergone an unplanned resection of a postoperatively diagnosed soft-tissue sarcoma were treated with RT and/or surgery and retrospectively evaluated for disease progression. Treatment started with RT in 49 cases (75.4%), including 8 cases of no further surgery. A repeat wide resection was performed directly after the initial surgery in 16 patients, followed by RT in 15 of them. Results: The disease recurred in 7 out of 49 patients (14.3%) who received RT first and in 9 out of 16 (56.25%) who underwent reoperation before RT (P = .001). Disease-free progression was higher in cases of low-grade malignancy (P = .049). A clinical diagnosis of lipoma was associated with a better outcome than a diagnosis of nonlipoma (P = .034). The presence of residual tumor at reoperation did not affect disease control. Patient age, time between symptom onset and diagnosis, hospital level of initial diagnosis (tertiary versus nontertiary), anatomic site, tumor size, and margin status at the initial excisional biopsy were not significantly correlated with the outcome. Conclusion: Initiating treatment with RT followed by unplanned "oops" resection of soft-tissue sarcoma before the reresection improved disease-free survival as opposed to vice versa.

4.
Sarcoma ; 2010: 927972, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20224682

RESUMEN

Radiotherapy (RT) is our preferred modality for local palliation of metastatic soft tissue sarcoma (STS). A short and intense course of RT is usually needed for rapid palliation and local control of metastatic disease. Seventeen patients at a median age of 61 had symptomatic metastatic sarcoma and required rapid palliation. The symptoms related to the metastases were either pain or discomfort. All patients were treated by a short and intensive course of administration: 39 Gy were given in 13 fractions of 3 Gy/day, 5 times a week. Median follow-up period was 25 weeks. The treatment was well tolerated. Acute side effects included grade one skin toxicity. No wound complications were noted among those undergoing surgery. Late side effects included skin pigmentation and induration of irradiated soft tissues. Durable pain control was achieved in 12 out 15 cases treated for gross metastases. Tumor progression was seen in the 3 other cases within a period of two to nine months. Among 5 lesions which were irradiated as an adjunctive treatment following resection, no local recurrence was observed. The results of this series, although limited in size, point to the safety and feasibility of hypofractionated RT for palliation of musculoskeletal metastases from sarcoma.

5.
Clin Biomech (Bristol, Avon) ; 80: 105155, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32916567

RESUMEN

BACKGROUND: Most benign active and latent lesions of proximal femur do not predispose a patient to a pathologic fracture. Nonetheless, there is a tendency to perform internal fixation due to the lack of accurate clinical tools that may reliably confirm low risk of pathologic fracture. As many as 30% of these surgeries may be unnecessary. A patient-specific CT-based finite element analysis may quantify bone strength and risk of fracture under normal weight-bearing conditions. METHODS: The clinical relevance of such finite element analysis was investigated in a retrospective study on a cohort of 17 patients. Finite element analysis results (high risk = indication for surgery, low or moderate risk = follow-up) were compared to actual clinical decisions (surgery vs follow-up). All patients predicted by the finite element analysis as high risk underwent internal fixation and had good outcomes (n = 6). FINDINGS: Four of the 11 low- and moderate-risk finite element analysis patients (36%) were operated immediately, and seven (64%) were either operated after a delay of at least 6 months or were never operated. None sustained a pathologic fracture. Patients who were predicted as low fracture risk by finite element analysis remained fracture-free for a minimal period of 6 months. Prediction of high risk of pathologic fracture by finite element analysis was in complete agreement with the conventional clinical evaluation. INTERPRETATION: We consider finite element analysis a promising decision support system for the management of patients with benign tumors of femur, and that it may reliably endorse the decision to withhold surgery for patients at low fracture-risk.


Asunto(s)
Fémur/diagnóstico por imagen , Fémur/lesiones , Análisis de Elementos Finitos , Fracturas Óseas/diagnóstico por imagen , Adulto , Anciano , Estudios de Cohortes , Femenino , Fémur/patología , Fémur/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Tomografía Computarizada por Rayos X/métodos , Soporte de Peso
6.
Pediatr Blood Cancer ; 53(6): 1023-8, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19637319

RESUMEN

BACKGROUND: Ewing sarcoma (ES) is the second most common solid bone and soft tissue malignancy in children and young adults with low cure rates indicating the need to identify further prognostic markers. The importance of methylation in the inactivation of key tumor suppressor genes including RASSF1A has begun to be appreciated in context of cancer development, prognosis and therapy. However there is lack of similar broad based studies in ES. The objective of this study was to analyze RASSF1A methylation and assess its clinical significance in ES. PROCEDURE: The methylation of RASSF1A was determined 31 ES tumor samples and 4 ES cell lines. ES cell lines were also treated with demethylating agent 5-aza-2'-deoxycytidine to ascertain its effect on methylation. RASSF1A expression was studied in 12 ES tumors. The association between RASSF1A methylation, clinical parameters and outcome was also analyzed. RESULTS: Methylation of RASSF1A was observed in 21/31 (68%) tumors and in 3/4 ES cell lines. A significant correlation of methylation to reduced expression of RASSF1A was observed in 12 ES tumors analyzed (P = 0.0013) and in all cell lines. ES patients with methylated RASSF1A had worse prognosis compared to the unmethylated group (P = 0.049). Treatment with 5-aza-2'-deoxycytidine resulted in the re-expression of the unmethylated form of RASSF1A in two ES cell lines. CONCLUSION: RASSF1A is frequently methylated in ES.


Asunto(s)
Metilación de ADN , Silenciador del Gen , Sarcoma de Ewing/genética , Proteínas Supresoras de Tumor/genética , Línea Celular Tumoral , Niño , Humanos , Proteínas Supresoras de Tumor/metabolismo
7.
Pediatr Hematol Oncol ; 26(6): 473-8, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19657999

RESUMEN

The authors describe a 6-year-old boy diagnosed with alveolar rhabdomyosarcoma located in the thigh, with distal metastases to lungs, bones, and bone marrow. A very good partial response to first-line chemotherapy was obtained, but the child developed fatal leptomeningeal dissemination immediately after complete resection of the primary tumor. This case demonstrates the rapidity with which leptomeningeal spread of extracranial metastatic alveolar rhabdomyosarcoma can occur and underscores the importance of diagnostic lumbar puncture and brain radiological investigations at diagnosis, even when the tumors are not in the parameningeal location.


Asunto(s)
Neoplasias de la Médula Ósea/secundario , Neoplasias Encefálicas/secundario , Neoplasias Pulmonares/secundario , Neoplasias Meníngeas/secundario , Rabdomiosarcoma Alveolar/secundario , Neoplasias de los Tejidos Blandos/patología , Neoplasias de la Médula Ósea/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Niño , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/tratamiento farmacológico , Muslo
8.
Cancer Chemother Pharmacol ; 83(5): 859-866, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30770960

RESUMEN

PURPOSE: We report the unexpected absence of early relapse (before 30 months) in 24 consecutive patients with isolated limb primary Ewing sarcoma treated with an intensified pilot protocol, SCMCIE94. METHODS: Clinical data for the study were collected retrospectively from the patient files. The protocol included 6 courses of chemotherapy, split radiation, and limb salvage surgery. This SCMCIE94 protocol had been used in almost all the patients described in an earlier report, in whom those with non-pelvic isolated tumors and low/absent CD56 expression in Ewing sarcoma tumor cells were all long-term survivors. RESULTS: The 5-year (10-year) event-free survival rate for the patients with isolated limb primary Ewing sarcoma was 78.95 ± 8.3% (68.6 ± 10.0%) and the overall survival rate was 90.7 ± 6.2% (71.1 ± 11.2%). There were no relapses before 30 months in any of these patients. CONCLUSION: The intensified SCMCIE94 pilot protocol has been shown previously to cure patients with localized CD56-negative non-pelvic Ewing sarcoma. The present study shows that among all patients with localized extremity disease who were treated with this protocol, there were no cases of early relapse. Although our cohort was small, the difference in results from studies using other protocols is so striking, that it would seem reasonable to assume it is attributable to the changes made in the protocol itself rather than risk factors. Late relapses of isolated limb CD56-positive Ewing sarcoma suggest minimal residual disease warranting additional therapeutic approaches such as autologous stem cell rescue after Busulfan Melfelan.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Óseas/terapia , Sarcoma de Ewing/terapia , Neoplasias Óseas/patología , Antígeno CD56/metabolismo , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Recuperación del Miembro/métodos , Recurrencia Local de Neoplasia , Proyectos Piloto , Estudios Retrospectivos , Sarcoma de Ewing/patología , Tasa de Supervivencia
9.
Eur J Cancer ; 44(7): 954-62, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18396035

RESUMEN

BACKGROUND: Postoperative pain in patients with bone and soft tissue cancer is different from that of other surgical patients due to the severity of the pain generated during surgery and because many of them have already been in pain preoperatively. The search for optimal intravenous pharmacologic management for this population is an ongoing one. We conducted a 10-month prospective, randomised, double blind study to compare the effects of a standard morphine dose to a 35%-lower dose plus a subanaesthetic dose of ketamine for postoperative pain control in patients undergoing bone and soft tissue cancer surgery under standardised general anaesthesia. METHODS: After extubation, when objectively awake (>or=5/10 on a 0-10 visual analogue scale (VAS)) and complaining of pain (>or=5/10 VAS), patients were connected to an intravenous patient-controlled analgesia (IV-PCA) device that delivered 1.5 mg morphine/bolus (MO group) or 1 mg morphine+5mg ketamine/bolus (MK group), with a 7 min lockout time. Rescue intramuscular diclofenac 75 mg was available Q4/day. Follow-up lasted 96 h. RESULTS: Fifty-seven patients (24 males, aged 18-74 years) completed the study. Pain scores were lower in the MK group compared to the MO patients, although MO patients (n=29) used 32.9+/-24.9 mg/patient morphine during the first 24 postoperative h compared to 14.6+/-11.4 mg/patient (P<0.05) for the MK patients (n=28). At that time point, 11 MO versus 4 MK patients still required IV-PCA (P<0.05). Diclofenac was also used more in the MO group. All vital signs were similar between the groups. The physiotherapy score was 35% higher for the MK patients (P<0.05). No patient had hallucinations. Postoperative nausea and vomiting rates were higher in the MO group. CONCLUSIONS: The use of subanaesthetic ketamine plus 2/3 the standard dose of morphine following bone and tissue resections results in 1) lower and more stable pain score, 2) approximately 60% morphine sparing effect, 3) a shorter period of postoperative IV-PCA dependence. Such therapy is also associated with better early physical performance.


Asunto(s)
Analgésicos/administración & dosificación , Neoplasias Óseas/cirugía , Ketamina/administración & dosificación , Morfina/administración & dosificación , Dolor Postoperatorio/prevención & control , Neoplasias de los Tejidos Blandos/cirugía , Adolescente , Adulto , Anciano , Análisis de Varianza , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Infusiones Intravenosas , Ketamina/efectos adversos , Masculino , Persona de Mediana Edad , Morfina/efectos adversos , Dimensión del Dolor , Modalidades de Fisioterapia , Náusea y Vómito Posoperatorios/inducido químicamente , Estudios Prospectivos
10.
Clin Cancer Res ; 13(19): 5777-83, 2007 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-17908968

RESUMEN

PURPOSE: Despite advances in therapy, >50% of patients with Ewing sarcoma will relapse. The current prognostic factors are not optimal for risk prediction. Studies have shown that telomere length could predict outcome in different malignancies. Our aim was to evaluate whether telomere length could be a better prognostic factor in Ewing sarcoma and correlate the results with clinical variables, outcome, and chromosomal instability. EXPERIMENTAL DESIGN: Telomere length was determined in the primary tumor and peripheral blood of 32 patients with Ewing sarcoma. Chromosomal instability was evaluated by combining classical cytogenetics, comparative genomic hybridization and random aneuploidy. Telomere length was correlated to clinical variables, chromosomal instability, and outcome. RESULTS: In 75% of the tumors, changes in telomere length, when compared with the corresponding peripheral blood lymphocytes, were noted. The majority of changes consisted of a reduction in telomere length. Patients harboring shorter telomeres had a significantly adverse outcome (P = 0.015). Chromosomal instability was identified in 65% of tumors, significantly correlating with short telomeres (P = 0.0094). Using multivariate analysis, telomere length remained the only significant prognostic variable (P = 0.034). Patients with short telomeres had a 5.3-fold risk of relapse as compared to those with unchanged or longer telomeres. CONCLUSION: We have shown that tumors with telomere length reduction result in genomic instability. In addition, telomere length reduction was the only significant predictor of outcome. We suggest that reduction of telomere length in tumor cells at diagnosis could serve as a prognostic marker in Ewing sarcoma.


Asunto(s)
Sarcoma de Ewing/genética , Sarcoma de Ewing/patología , Telómero/ultraestructura , Adolescente , Adulto , Niño , Preescolar , Inestabilidad Cromosómica , Cromosomas/ultraestructura , Femenino , Humanos , Lactante , Masculino , Análisis Multivariante , Hibridación de Ácido Nucleico , Pronóstico , Recurrencia , Riesgo , Factores de Riesgo , Sarcoma de Ewing/diagnóstico , Resultado del Tratamiento
11.
Gynecol Obstet Invest ; 65(2): 89-95, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-17878735

RESUMEN

OBJECTIVE: The incidence of musculoskeletal tumors during pregnancy is very low. The aim of this study was to summarize our experience in treating a large cohort of pregnant patients diagnosed with these rare tumors. METHODS: Women diagnosed with musculoskeletal tumors during pregnancy or immediately after delivery were identified retrospectively in our database between 1996 and 2006. Relevant maternal and neonatal data were collected. RESULTS: Twenty patients, 8 with bone sarcomas (BS) and 12 with soft tissue sarcomas (STS) were identified. Two women were treated by wide excision of mass during pregnancy. In all other cases oncological treatment was delayed until delivery or termination of pregnancy. Vaginal delivery was possible in 9 patients, cesarean section was performed in 7, spontaneous abortion occurred in 1, and 3 underwent termination of pregnancy. Three newborns were premature, but normal growth and development were observed. Different techniques of fertility preservation were used in our patients. Five patients with BS and 5 patients with STS received preoperative chemotherapy, with different grades of toxicity. The degree of tumor necrosis tended to correlate with dose-intensity of chemotherapy. Seven patients with BS received adjuvant chemotherapy. Two patients with STS received adjuvant chemotherapy, two - radiotherapy, and four - both modalities. Median disease-free survival was 15.1 months, median overall survival - 25.4 months. CONCLUSIONS: Musculoskeletal tumors diagnosed during pregnancy, or after delivery, do not appear to have a significant impact on the prognosis. A multidisciplinary team should tailor the oncological approach individually.


Asunto(s)
Neoplasias Óseas/terapia , Parto Obstétrico , Complicaciones Neoplásicas del Embarazo/terapia , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/terapia , Aborto Inducido , Adulto , Neoplasias Óseas/complicaciones , Neoplasias Óseas/mortalidad , Estudios de Cohortes , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Embarazo , Complicaciones Neoplásicas del Embarazo/mortalidad , Resultado del Embarazo , Pronóstico , Estudios Retrospectivos , Sarcoma/complicaciones , Sarcoma/mortalidad , Neoplasias de los Tejidos Blandos/complicaciones , Neoplasias de los Tejidos Blandos/mortalidad , Sobrevida
12.
Eur J Cancer ; 43(14): 2060-5, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17720491

RESUMEN

BACKGROUND: Dedifferentiated chondrosarcoma has a very poor prognosis. Because of its rarity, there are few large studies of outcome which might identify potential prognostic factors. In particular there remains uncertainty about the value of chemotherapy for this condition. METHOD: A retrospective study was done using data supplied by members of the European Musculo Skeletal Oncology Society (EMSOS). We obtained data on 337 patients from nine European centres with this rare condition, with details on patients, treatment and outcome which were then analysed in an attempt to identify prognostic features. RESULTS: The median age was 59 years and there was a slight predominance of males (53%). The most common sites were the femur and pelvis. Twenty-nine percent of patients with a long bone tumour had a pathological fracture. 71 patients (21%) had metastases at the time of diagnosis and these patients had a median survival of 5 months with a 10% chance of survival at 2 years. For the 266 patients without metastases at diagnosis, 254 underwent surgery with 79% having limb salvage. Thirty-one percent of these 266 patients had chemotherapy with 47% of those under 60 receiving it. In this group of 266 patients, overall survival was 28% at 10 years and poor prognostic factors were the presence of a pathological fracture at diagnosis, a pelvic location and increasing age. Local recurrence and overall survival were related to inadequate margins of excision. We did not find that the histological subtype, size of the tumour or the use of chemotherapy significantly affected outcome. For all patients the overall survival was 24% at 5 years. CONCLUSIONS: The prognosis for patients with dedifferentiated chondrosarcoma remains dismal. Surgery with clear margins remains the principal treatment for this condition. Further use of chemotherapy should be within a trial or treatment protocol.


Asunto(s)
Neoplasias Óseas/mortalidad , Condrosarcoma/mortalidad , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Condrosarcoma/tratamiento farmacológico , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia
13.
Oncogene ; 23(55): 8997-9006, 2004 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-15467746

RESUMEN

Ewing's sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Currently accepted clinical prognostic factors fail to classify ES patients' risk to relapse at diagnosis. We aimed to find a new strategy to distinguish between poor and good prognosis ES patients already at diagnosis. We analysed the gene expression profiles of 14 primary tumor specimens and six metastases from ES patients, using oligonucleotide microarray analysis. The over-expression of two genes was validated by quantitative PCR using the LightCycler system. We identified two distinct gene expression signatures distinguishing high-risk ES patients that are likely to progress from low-risk ES patients with a favorable prognosis of long-term progression-free survival. The microarray-based classification was superior to currently used prognostic parameters. Over-expressed genes in the poor prognosis patients included genes regulating the cell cycle and genes associated with invasion and metastasis, while among the downregulated genes were tumor suppressor genes and inducers of apoptosis. Our results indicate the existence of a specific gene expression signature of outcome in ES already at diagnosis, and provide a strategy to select patients who would benefit from risk-adapted improved therapy.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Sarcoma de Ewing/genética , Adolescente , Adulto , Ciclo Celular , Niño , Análisis por Conglomerados , Regulación hacia Abajo , Humanos , Modelos Genéticos , Familia de Multigenes , Invasividad Neoplásica , Metástasis de la Neoplasia , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Riesgo , Factores de Tiempo , Resultado del Tratamiento
14.
Eur J Cancer ; 41(18): 2806-11, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16290134

RESUMEN

Periosteal osteosarcoma is a rare primary malignant bone tumour. Treatment is by surgical excision, but controversy remains about the value of chemotherapy. The members of the European Musculo Skeletal Oncology Society (EMSOS) collaborated to produce a dataset of 119 patients. The predominant site for the tumour was the femur, followed by the tibia. All but 2 patients underwent surgery, with 9 requiring amputation and the others having limb salvage. A total of 81 patients had chemotherapy, of whom 50 had neoadjuvant chemotherapy. There was no standard chemotherapy regime, but all patients receiving chemotherapy were given doxorubicin combined with at least one other agent. The overall survival was 89% at 5 years and 83% at 10 years. Eight patients developed local recurrence, of whom 5 died. Survival was related to appearance of local recurrence (P < 0.0001) but no other single factor. The use of chemotherapy was not shown to be a prognostic factor, but was used in two-thirds of the patients in this study.


Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Adolescente , Adulto , Distribución por Edad , Anciano , Neoplasias Óseas/mortalidad , Niño , Europa (Continente)/epidemiología , Femenino , Peroné , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/mortalidad , Osteosarcoma/mortalidad , Análisis de Supervivencia , Tibia , Resultado del Tratamiento
15.
Radiother Oncol ; 77(3): 295-300, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16300847

RESUMEN

BACKGROUND: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). PATIENTS AND METHODS: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. RESULTS: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. CONCLUSIONS: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory.


Asunto(s)
Recuperación del Miembro , Sarcoma/radioterapia , Sarcoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Radioterapia Conformacional , Sarcoma/patología , Resultado del Tratamiento
16.
Oncol Rep ; 14(4): 1071-6, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16142374

RESUMEN

Malignant fibrous histiocytoma (MFH) is the most common subtype of soft-tissue sarcoma (STS). When located in a limb, MFH, is currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). During 8 years, 42 adult patients with high-grade limb MFH were approached by LSS and RT. Our results reflect a single-team experience and point to several important conclusions. High grade MFH, treated by conservative approach, lead to a 10-year relapse-free survival of 62% and a 10-year overall survival rate of 80%. Recurrences of MFH tend to occur during the first 2 years. Relapse-free survival was affected mainly by location in the lower limb vs. the upper limb, irrespective of the tumor size. Patients who had their diagnostic biopsies in another medical center had a greater tendency to local and systemic relapse. It seems that the most important clues for disease-free survival are the team experience and cooperation. All other factors are tumor-biology dependent, and thus far are beyond our control.


Asunto(s)
Extremidades/patología , Histiocitoma Fibroso Benigno/radioterapia , Histiocitoma Fibroso Benigno/cirugía , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Recurrencia , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
17.
Cancer Chemother Pharmacol ; 76(5): 909-16, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26365289

RESUMEN

PURPOSE: Aggressive chemotherapy protocols for non-metastatic limb osteosarcoma have improved histological response without affecting prognosis. This study evaluated the toxicity and outcome of a dose-intensive, high-dose 3- to 5-drug pilot protocol, SCOS 89. METHODS: The cohort included 26 patients (14 male; ages 6.5-22 years) with non-metastatic limb osteosarcoma treated at a tertiary pediatric medical center between 1989 and 2013. Preoperatively, patients received two courses of once-weekly pulses of high-dose methotrexate (12-30 g/m(2)) for 2 weeks; doxorubicin (90 mg/m(2)) with dexrazoxane, combined with cisplatin (200 mg/m(2)), was added in week 3. Following methotrexate, 760 mg/m(2) of folinic acid was administered. Postoperative chemotherapy was continued to a total of 14 courses of methotrexate, doxorubicin (up to a total dose of 360 mg/m(2)), and cisplatin (up to a total dose of 560 mg/m(2)). If toxicity occurred or <90 % tumor necrosis, ifosfamide (12 g/m(2)) plus etoposide (500 mg/m(2)) was substituted for doxorubicin, cisplatin, or methotrexate. Toxicity and death rates were calculated. RESULTS: All patients underwent definitive limb salvage surgery. Six patients died of infection, recurrent disease, or secondary malignancy. Median follow-up was 100 months (range 2-290). Event-free and overall survival rates, respectively, were 88 and 96 % at 2 years, 80 and 87.6 % at 5 years, 80 and 78 % at 10 years. Eleven patients required ifosfamide/etoposide substitution. One patient had a transient decreased left ventricular ejection fraction. Two patients developed acute nephrotoxicity during therapy, but no neurotoxicity. Seven patients had hearing impairment. CONCLUSIONS: The SCOS 89 yields a high event-free survival rate with reduced nephro-/neuro-/cardiotoxicity in patients with non-metastatic limb osteosarcoma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/cirugía , Niño , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Sustitución de Medicamentos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Estudios de Seguimiento , Pérdida Auditiva/inducido químicamente , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Enfermedades Renales/inducido químicamente , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Osteosarcoma/cirugía , Proyectos Piloto , Volumen Sistólico/efectos de los fármacos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
18.
Oncotarget ; 6(32): 33834-48, 2015 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-26393682

RESUMEN

Ewing Sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. microRNAs (miRNAs) are involved in cancer as tumor suppressors or oncogenes. We studied the involvement of miRNAs located on chromosomes 11q and 22q that participate in the most common translocation in ES. Of these, we focused on 3 that belong to the let-7 family.We studied the expression levels of let-7a, and let-7b and detected a significant correlation between low expression of let-7b and increased risk of relapse. let-7 is known to be a negative regulator of the RAS oncogene. Indeed, we detected an inverse association between the expression of let-7 and RAS protein levels and its downstream target p-ERK, following transfection of let-7 mimics and inhibitors. Furthermore, we identified let-7 as a negative regulator of HIF-1α and EWS-FLI-1. Moreover, we were able to show that HIF-1α directly binds to the EWS-FLI-1 promoter. Salirasib treatment in-vitro resulted in the reduction of cell viability, migration ability, and in the decrease of cells in S-phase. A significant reduction in tumor burden and in the expression levels of both HIF-1α and EWS-FLI-1 proteins were observed in mice after treatment.Our results support the hypothesis that let-7 is a tumor suppressor that negatively regulates RAS, also in ES, and that HIF-1α may contribute to the aggressive metastatic behavior of ES. Moreover, the reduction in the tumor burden in a mouse model of ES following Salirasib treatment, suggests therapeutic potential for this RAS inhibitor in ES.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , MicroARNs/metabolismo , Sarcoma de Ewing/metabolismo , Proteínas ras/metabolismo , Adolescente , Adulto , Animales , Antineoplásicos/uso terapéutico , Ciclo Celular , Movimiento Celular , Supervivencia Celular , Niño , Preescolar , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 22/genética , Supervivencia sin Enfermedad , Farnesol/análogos & derivados , Farnesol/uso terapéutico , Femenino , Silenciador del Gen , Genes Supresores de Tumor , Humanos , Lactante , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Trasplante de Neoplasias , Proteínas de Fusión Oncogénica/metabolismo , Proteína Proto-Oncogénica c-fli-1/metabolismo , Proteína EWS de Unión a ARN/metabolismo , Distribución Aleatoria , Salicilatos/uso terapéutico , Sarcoma de Ewing/patología , Transducción de Señal , Adulto Joven
19.
Int J Radiat Oncol Biol Phys ; 58(5): 1468-73, 2004 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-15050325

RESUMEN

PURPOSE: Spinal metastases of soft-tissue sarcoma (STS) occur rarely and pose a therapeutic problem. Although wide resection is warranted for best local control, it is rarely feasible. A radiotherapy (RT) dose of 70 Gy is usually needed to treat limb STS, but only 45 Gy can be given to the spine. In the present series, we report our experience using RT to treat spinal cord compression (SpCC) associated with STS. METHODS AND MATERIALS: The medical files of 19 adult patients with STS and SpCC were reviewed. RT was considered in all the cases, together with steroids and analgesics. The prescribed dose was 30 Gy in 10 fractions within 12 days. The effect of treatment was evaluated on a clinical basis. RESULTS: Twenty-three events of SpCC were found. The prevailing symptom was pain. The Karnofsky performance status was 40-70% at presentation. RT was given in all but 1 patient and surgical decompression in 3. Small, but important, improvements in signs and Karnofsky performance status were noted in 14 of 23 cases of SpCC, expressed mainly by pain alleviation and restoration of independence. The median survival after the diagnosis of SpCC was 5 months. CONCLUSION: Radiotherapy is an important tool in palliating SpCC in patients with STS.


Asunto(s)
Sarcoma/radioterapia , Compresión de la Médula Espinal/radioterapia , Neoplasias de la Columna Vertebral/radioterapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Dosificación Radioterapéutica , Sarcoma/clasificación , Sarcoma/secundario , Compresión de la Médula Espinal/etiología , Neoplasias de la Columna Vertebral/secundario
20.
J Nucl Med ; 45(2): 272-8, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14960647

RESUMEN

UNLABELLED: 18F-fluoride PET/CT was performed on 44 oncologic patients to evaluate its diagnostic accuracy in assessing malignant osseous involvement and in differentiating malignant from benign bone lesions. METHODS: (18)F-fluoride PET and (18)F-fluoride PET/CT were interpreted separately. Lesions showing increased (18)F-fluoride uptake were categorized as malignant, benign, or inconclusive. The final diagnosis of lesions was based on histopathology, correlation with contemporaneous diagnostic CT or MRI, or clinical follow-up of at least 6 mo (mean, 10 +/- 3 mo). RESULTS: Increased (18)F-fluoride uptake was detected at 212 sites, including 111 malignant lesions, 89 benign lesions, and 12 lesions for which the final diagnosis could not be determined. In a lesion-based analysis, the sensitivity of PET alone in differentiating benign from malignant bone lesions was 72% when inconclusive lesions were considered false negative and 90% when inconclusive lesions were considered true positive. On PET/CT, 94 of 111 (85%) metastases presented as sites of increased uptake with corresponding lytic or sclerotic changes, and 16 of the 17 remaining metastases showed normal-appearing bone on CT, for an overall sensitivity of 99% for tumor detection. For only 1 metastasis was PET/CT misleading, suggesting the false diagnosis of a benign lesion. The specificity of PET/CT was significantly higher than that of PET alone (97% vs. 72%, P < 0.001). PET/CT identified benign abnormalities at the location exactly corresponding to the scintigraphic increased uptake for 85 of 89 (96%) benign lesions. In a patient-based analysis, the sensitivity of PET and PET/CT was 88% and 100%, respectively (P < 0.05) and the specificity was 56% and 88%, respectively (not statistically significant). Among the 12 patients referred for (18)F-fluoride assessment because of bone pain despite negative findings on (99m)Tc-methylene diphosphonate bone scintigraphy, (18)F-fluoride PET/CT suggested malignant bone involvement in all 4 patients with proven skeletal metastases, a potential benign cause in 4 of 7 patients who had no evidence of metastatic disease, and a soft-tissue tumor mass invading a sacral foramen in 1 patient. CONCLUSION: The results indicate that (18)F-fluoride PET/CT is both sensitive and specific for the detection of lytic and sclerotic malignant lesions. It accurately differentiated malignant from benign bone lesions and possibly assisted in identifying a potential cause for bone pain in oncologic patients. For most lesions, the anatomic data provided by the low-dose CT of the PET/CT study obviates the performance of full-dose diagnostic CT for correlation purposes.


Asunto(s)
Neoplasias Óseas/diagnóstico , Fluoruros , Radioisótopos de Flúor , Tomografía Computarizada de Emisión , Tomografía Computarizada por Rayos X , Neoplasias Óseas/secundario , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Radiofármacos , Sensibilidad y Especificidad , Tomografía Computarizada de Emisión/métodos
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