RESUMO
BACKGROUND: We investigated whether non-enhancement MRI features, including measurement of the heterogeneity of the tumor with MR T2 imaging by calculating coefficient of variation (CV) values, were associated with the prognosis of non-metastatic malignant peripheral nerve sheath tumors (MPNST). METHODS: This retrospective study included 42 patients with MPNST who had undergone surgical resection (mean age, 50 years ± 21; 20 male participants). Non-enhancement MR images were evaluated for signal intensity heterogeneity on T1- and T2-weighted imaging, tumor margin definition on T1- and T2-weighted imaging, peritumoral edema on T2-weight imaging, and CV. We measured the signal intensities of MR T2-weighted images and calculated the corresponding CV values. CV is defined as the ratio of the standard deviation to the mean. The associations between factors and overall survival (OS) were investigated via the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model. RESULTS: The mean CV value of MR T2 images was 0.2299 ± 0.1339 (standard deviation) (range, 0.0381-0.8053). Applying receiver operating characteristics analysis, the optimal cut-off level for CV value was 0.137. This cut-off CV value was used for its stratification into high and low CV values. At multivariate survival analysis, a high CV value (hazard ratio = 3.63; 95% confidence interval = 1.16-16.0; p = 0.047) was identified as an independent predictor of OS. CONCLUSION: The CV value of the signal intensity of heterogenous MPNSTs MR T2-weighted images is an independent predictor of patients' OS.
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Neoplasias de Bainha Neural , Neurofibrossarcoma , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Imageamento por Ressonância Magnética/métodos , Neoplasias de Bainha Neural/diagnóstico por imagem , Neoplasias de Bainha Neural/patologiaRESUMO
BACKGROUND: It is known that several complications are caused by local surgery after radiotherapy. Clinical reports that describe the postoperative complications associated with surgery after carbon ion radiotherapy are sparse. This study aimed to elucidate local surgery feasibility after carbon ion radiotherapy specifically for primary bone sarcomas. METHODS: The medical, surgical, and irradiation records of patients who had local surgery at the area irradiated with carbon ion beams between 2004 and 2018 were reviewed retrospectively to evaluate the feasibility and indication of local surgery after CIRT. RESULTS: There were eight patients who had 10 local surgeries at the irradiated sites among the 42 carbon ion radiotherapy patients. There were seven males and one female with a median age of 50 years (range 26-73 years). The reasons for surgery were three for skin toxicity and associated infection, five for bone collapse, and associated implant failure, and two for tumor regrowth. All surgical fields included the area of more than 60 Gy (RBE) irradiated dose. All three surgical cases caused by skin toxicity and associated infection had Grade I wound complication after surgery according to the Clavien-Dindo Classification. CONCLUSION: Local surgery after CIRT appeared feasible in selected patients with primary bone sarcoma, especially for the patients with bone collapse and associated implant failure. However, infection and prescribed irradiation dose at the incision site must be carefully evaluated.
RESUMO
Background osteosarcoma is a rare, primary malignant bone tumour with limited available treatments for advanced or recurrent disease, resulting in a poor prognosis for patients. TAS-115 is a novel tyrosine kinase inhibitor under investigation in a phase I study in patients with solid tumours. We report data of osteosarcoma patients in the expansion cohort of this ongoing study. Patients and methods an analysis of this multicentre, open-label study was performed 6 months after the final patient was enrolled, and included patients aged ≥15 years, with unresectable or recurrent osteosarcoma, and who had refractory to standard therapy or for whom no standard therapy was available. TAS-115 650 mg/day was orally administered in a 5 days on/2 days off schedule. Results a total of 20 patients with osteosarcoma were enrolled. The most common adverse drug reactions (ADRs) were neutrophil count decreased (75%), aspartate aminotransferase increased (50%), and platelet count decreased (50%); 85% of patients had grade ≥ 3 ADRs. Long-term disease control (>1 year) with TAS-115 was achieved in three patients. The best overall response was stable disease (50%); no patient achieved a complete or partial response. Median progression-free survival was 3 months; 4-month and 12-month progression-free rates were 42% and 31%, respectively. Conclusion the safety and tolerability of TAS-115 and long-term disease stability for patients with unresectable or recurrent osteosarcoma were confirmed in this study, suggesting that TAS-115 is a promising novel therapy for advanced osteosarcoma patients. Trial registration number: JapicCTI-132333 (registered on November 8, 2013).
Assuntos
Antineoplásicos/uso terapêutico , Osteossarcoma/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Tioureia/análogos & derivados , Adolescente , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Análise de Sobrevida , Tioureia/administração & dosagem , Tioureia/efeitos adversos , Tioureia/uso terapêutico , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: The aim of this study is to assess the survival, function, radiographic appearance, and modes of failure of extracorporeal irradiated (ECI) autografts in a long-term setting. METHODS: We retrospectively reviewed 87 patients who were treated for bone and soft tissue tumors using ECI autografts between 1988 and 2009. RESULTS: The 56 patients had a minimum follow-up of 10 years, and the median follow-up period was 16.5 years. The reimplantation procedures included 24 osteoarticular grafts, 16 intercalary grafts, 10 autograft-prosthetic composite grafts, and 6 hemicortical grafts. The 15-year graft and event-free survival rates were 76.8% and 47.9%, respectively. Infection and structural failure were the most common reasons for additional surgery. The time for additional surgery was significantly longer in patients with composite grafts (P < .01). The median Musculoskeletal Tumor Society score and the International Society of Limb Salvage score were 80% and 84%, respectively. CONCLUSIONS: ECI autografts are a durable option for reconstruction after resection of musculoskeletal tumors and provide good function over more than 15 years. Most graft failures occurred within 5 years of the index surgery. However, composite grafts showed a tendency to fail more than 10 years after the surgery.
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Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Salvamento de Membro/métodos , Neoplasias de Tecidos Moles/cirurgia , Adulto , Autoenxertos , Neoplasias Ósseas/patologia , Extremidades/patologia , Extremidades/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Estudos Retrospectivos , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Chondroblastoma (CB) is a rare locally aggressive bone tumor that commonly occurs in the epiphysis or apophysis of long bones. Although surgical treatment of CB carries potential risk for physeal or articular cartilage damage, risk factors for joint degeneration have not been well described. In addition, we have mainly used synthetic bone substitute (SBS) to fill the bone defect after intralesional curettage as treatment for CB. This study thus aimed to evaluate the incidence of and risk factors for adjacent-joint radiographic degeneration after SBS treatment for CB. METHODS: We retrospectively reviewed 48 patients treated for CB at our institutions between 1996 and 2017. Clinical data, radiographic images, treatments, and local recurrence were analyzed. RESULTS: We identified 40 patients [29 males and 11 females with a mean age of 19 years (range, 8-35 years)] who received SBS to fill the defect after curettage with a minimum follow-up of 1 year. The mean follow-up period was 71 months (range, 13-239 months). A total of 8 patients (20%) developed local recurrence. Radiographic analysis showed that 5 patients (16.7%) developed radiographic joint degeneration. Joint degeneration was significantly associated with the affected joint (p = 0.004). CONCLUSIONS: Curettage and SBS filling had been found to be a reasonable treatment method for CB, which commonly occurs in the epiphysis or apophysis. Radiographic joint degeneration was not uncommon after CB treatment, especially in the talus and proximal humerus.
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Neoplasias Ósseas/cirurgia , Substitutos Ósseos/uso terapêutico , Condroblastoma/cirurgia , Articulações/patologia , Adolescente , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Criança , Condroblastoma/diagnóstico por imagem , Condroblastoma/patologia , Feminino , Humanos , Articulações/diagnóstico por imagem , Masculino , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Extraskeletal osteosarcoma (ESOS) is an extremely rare soft tissue sarcoma. Their prognosis remains poor. Our purposes were to identify the effective chemotherapeutic regimen for ESOS. METHODS: We retrospectively reviewed 16 patients with ESOS treated at the Osaka University Orthopaedic Oncology Group between 1992 and 2012. We extracted the clinical data on patients. Kaplan-Meier method and the log-rank test were used for survival analyses. RESULTS: Median age of the patients was 61.5 years (range 25-79 years). Wide local excision was performed for 11 patients and 9 patients were treated combined with chemotherapy. The 5-year disease-specific survival (DSS) rate was 53.9%. The 5-year DSS rates for patients treated with adjuvant/neoadjuvant chemotherapy or not were 66.7% or 25%, respectively (p = 0.0215). Furthermore, the 5-year DSS rates for patients treated with adjuvant/neoadjuvant chemotherapy consisting of doxorubicin and ifosfamide and those treated with other regimens were 100% or 40%, respectively (p = 0.0327). CONCLUSION: The present study demonstrated that adjuvant/neoadjuvant chemotherapy, especially consisting of doxorubicin and ifosfamide, was potentially efficacious for ESOS. Further prospective study using this multimodality treatment approach to patients with ESOS should be strongly warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/patologia , Terapia Neoadjuvante , Osteossarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Idoso , Neoplasias Ósseas/tratamento farmacológico , Quimioterapia Adjuvante , Doxorrubicina/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Osteossarcoma/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Neoplasias de Tecidos Moles/tratamento farmacológico , Taxa de SobrevidaRESUMO
BACKGROUND: The development of effective chemotherapy regimens and molecular targeting agents are improving the overall survival rates in patients with cancer. However, patients who are non-ambulatory due to metastatic epidural spinal cord compression (MESCC) may be assessed as unable to tolerate chemotherapy secondary to poor performance status. This means that the ambulatory status of patients with cancer might be significant for survival time. METHODS: We investigated the functional outcomes and factors influencing overall survival in 31 patients who were non-ambulatory due to MESCC and underwent decompression surgery. The functional outcome was determined by the Frankel grading system. RESULT: Twenty-one patients (68%) improved by at least 1 Frankel grade; 17 patients (55%) became ambulatory postoperatively. Most of postoperatively ambulatory patients could undergo postoperative chemotherapy (14/17, 82%). On the other hand, only a few postoperatively non-ambulatory patients could undergo postoperative chemotherapy (2/15, 13%). We observed a complication rate of 35.5% with specific complications including wound infection, pneumonia, and deep vein thrombosis/pulmonary embolus. The median survival duration was 7.0 months. Factors that significantly affected the overall survival in univariate analyses were revised Tokuhashi score (RTS) ≥ 4, postoperative chemotherapy, ambulatory status, and complications (RTS ≥ 4, P < 0.05; postoperative chemotherapy, P < 0.001; ambulatory status, P < 0.001; complications, P < 0.01). CONCLUSIONS: Decompression surgery for patients who are non-ambulatory due to MESCC directly contributes to functional outcomes and may indirectly contribute to overall survival. If non-ambulatory patients who are assessed as unable to tolerate chemotherapy due to poor performance status regain the ability to walk by decompression surgery, they will have a chance to receive postoperative chemotherapy, thereby increasing their chances of prolonging survival. However, postoperative complications may shorten their survival; therefore, we should carefully consider the surgical indications. RTS is useful for judging the surgical indication.
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Descompressão Cirúrgica/métodos , Avaliação da Deficiência , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Estudos de Coortes , Descompressão Cirúrgica/mortalidade , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Compressão da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/mortalidade , Neoplasias da Medula Espinal/secundário , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , CaminhadaRESUMO
BACKGROUND: Few studies have described the characteristics and prognostic factors of elderly patients with osteosarcoma. We retrospectively investigated clinico-pathological features and prognostic factors in osteosarcoma patients > 40 years old. METHODS: Patients with high-grade osteosarcoma > 40 years old who were treated at our institutions from 2000 to 2016 were recruited for this study. Information on patient, tumour, and treatment-related factors was collected and statistically analyzed. The median follow-up was 26.5 months (range, 5-139 months) for all patients. RESULTS: Fifty patients (30 males and 20 females) were included. The median age at diagnosis was 59.5 years (range, 41-81 years). The primary lesions were found in the limbs in 32 patients, trunk in 12, and craniofacial bones in six. Primary and secondary osteosarcoma occurred in 41 and 9 patients, respectively. Eight patients exhibited initial distant metastasis. Definitive surgery and chemotherapy were performed in 39 patients each. The rate of good responders after neoadjuvant chemotherapy was 38%. The five year overall survival (OS) rates for all patients and those without distant metastasis at diagnosis were 44.5% and 51.1%, respectively. Multivariate analysis showed that definitive surgery was the only significant prognostic factor in non-metastatic patients. The five year OS and disease-free survival (DFS) rates for non-metastatic patients who received definitive surgery were 64.3% and 60%, respectively. Among these patients, neoadjuvant and/or adjuvant chemotherapy significantly improved both OS and DFS. CONCLUSIONS: Complete surgical resection and intensive chemotherapy should be performed for osteosarcoma patients > 40 years old despite distinct clinicopathological characteristics from those of younger patients.
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Neoplasias Ósseas/mortalidade , Osteossarcoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/terapia , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
PURPOSE: An epithelioid sarcoma is a rare histological subtype of a soft tissue sarcoma with a high local recurrence rate, which frequently shows lymph node metastasis. However, because of the rarity of this tumor, the impact of nodal metastasis and its appropriate management remain unclear. The present study investigated the clinical outcomes of patients with epithelioid sarcomas, with a focus on lymph node metastasis. METHODS: We retrospectively evaluated the clinical outcomes of 27 patients with epithelioid sarcomas treated between 1985 and 2015. The log-rank test was used to assess the prognostic variables. RESULTS: The overall local recurrence rate was 33%, and the estimated overall 5-year survival rate was 62%. Hand and foot locations were associated with favorable overall survival. During the follow-up period, new nodal metastasis was noted in 14 patients (52%). The incidence of local recurrence was higher in patients with new nodal metastasis than in patients who did not develop nodal metastasis. The development of new nodal metastasis had a tendency to worsen survival; however, this association was not statistically significant. Lymphadenectomy did not affect overall survival. CONCLUSIONS: Peripheral tumor location is associated with a better prognosis. The development of new nodal metastasis tends to be associated with poor prognosis; however, among patients with nodal metastasis, resection of the metastatic lesions has a low impact on survival.
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Metástase Linfática/patologia , Sarcoma/mortalidade , Sarcoma/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The prognosis of synovial sarcoma (SS), an aggressive soft tissue sarcoma, remains poor. We previously reported that c-MET or platelet-derived growth factor receptor α (PDGFRα) signalling pathway is related to SS progression based upon the findings of phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs. Here we aimed to investigate the therapeutic potential of TAS-115 against SS. METHODS: We first evaluated which signalling pathway was relevant to the viability of three human SS cell lines: Yamato-SS, SYO-1 and HS-SY-II. Next, we assessed the anticancer activity and mechanism of action of TAS-115 in these SS cell lines. Finally, we compared the ability of TAS-115 to inhibit c-MET and PDGFRα phosphorylation with that of pazopanib. RESULTS: We classified the SS cell lines as c-MET-dependent or PDGFRα-dependent based upon the differences in the signalling pathway relevant for growth and/or survival. We also found that c-MET and PDGFRα were the primary activators of both phosphatidylinositol 3-kinase/AKT and mitogen-activated protein kinase pathways in c-MET-dependent and PDGFRα-dependent SS cells, respectively. TAS-115 treatment blocked the phosphorylation of PDGFRα as well as that of c-MET and their downstream effectors, leading to marked growth inhibition in both types of SS cell lines in in vitro and in vivo studies. Furthermore, PDGFRα phosphorylation, on at least four representative autophosphorylation sites, was impeded by TAS-115 equivalently to pazopanib. CONCLUSIONS: These experimental results have demonstrated the significance of c-MET and PDGFRα signalling for growth and/or survival of SS tumours. TAS-115 monotherapy may benefit SS patients whose tumours are dependent upon either c-MET or PDGFRα signalling by functioning as a multiple tyrosine kinase inhibitor to suppress c-MET as well as PDGFRα pathways.
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Inibidores da Angiogênese/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Pirimidinas/uso terapêutico , Quinolinas/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Sarcoma Sinovial/tratamento farmacológico , Sulfonamidas/uso terapêutico , Tioureia/análogos & derivados , Animais , Linhagem Celular Tumoral , Humanos , Indazóis , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular/métodos , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Sarcoma Sinovial/patologia , Transdução de Sinais/efeitos dos fármacos , Tioureia/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with a poor prognosis and, thus, novel therapeutic strategies for SS are urgently required. In the present study, we investigated the functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS. Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells. c-MET-activated Yamato-SS cells showed higher anchorage-independent growth ability and less sensitivity to chemotherapeutic agents than did c-MET-inactivated SYO-1 or HS-SY-II cells. INC280, a selective c-MET inhibitor, inhibited growth of Yamato-SS cells both in vitro and in vivo but not that of SYO-1 or HS-SY-II cells. INC280 induced cell cycle arrest and apoptosis, and blocked phosphorylation of c-MET and its downstream effectors in Yamato-SS cells. Co-expression of HGF and c-MET in SS clinical samples correlated with a poor prognosis in patients with SS. Taken together, activation of HGF/c-MET signaling in an autocrine fashion leads to an aggressive phenotype in SS and targeting of this signaling exerts superior antitumor effects on c-MET-activated SS. HGF/c-MET expression status is a potential biomarker for identification of SS patients with a worse prognosis who can benefit from c-MET inhibitors.
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Fator de Crescimento de Hepatócito/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Sarcoma Sinovial/metabolismo , Transdução de Sinais , Animais , Antineoplásicos/farmacologia , Comunicação Autócrina , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Expressão Gênica , Inativação Gênica , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/farmacologia , Xenoenxertos , Humanos , Camundongos , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/genética , Sarcoma Sinovial/genética , Sarcoma Sinovial/mortalidade , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: The incidence of Ewing sarcoma is lower in non-Caucasian populations, compared with Caucasian populations, for unknown reasons. Most studies from western countries have reported improvement in outcomes following multi-agent chemotherapy, with no difference in outcome between skeletal and extraskeletal Ewing sarcoma. However, there are few studies of Ewing sarcoma in non-Caucasian populations, with especially few comparing outcomes between skeletal and extraskeletal Ewing sarcoma. Thus, the purpose of this study is to determine whether the outcomes and prognostic factors of Ewing sarcoma in the Japanese population are similar to those in Caucasian populations and to determine whether skeletal and extraskeletal Ewing sarcoma have similar outcomes in Japanese patients. METHODS: We retrospectively evaluated the outcomes of 74 Japanese patients with Ewing sarcoma treated between 1981 and 2011 from the Osaka University Orthopaedic Oncology Group. RESULTS: Extraskeletal Ewing sarcoma, tumors in the extremities, localized disease at presentation and diagnosis after 2000 were significantly associated with a favorable outcome. Among patients with localized disease at presentation, a significantly better outcome was observed for those with extraskeletal Ewing sarcoma, those who underwent a VDC/IE based or VAIA chemotherapy protocol, and those who were diagnosed after 2000. In the multivariable analyses, extraskeletal Ewing sarcoma was an independent predictor of increased overall survival among all patients and the subset of patients with localized disease. CONCLUSIONS: The outcome of patients with Ewing sarcoma in Japan has improved in the last decade. The outcomes and prognostic factors are similar for Japanese and Caucasian patients, though in this series of Japanese patients, a better prognosis was observed for patients with extraskeletal rather than skeletal Ewing sarcoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Sarcoma de Ewing/tratamento farmacológico , Adolescente , Adulto , Povo Asiático , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Dactinomicina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Ifosfamida/uso terapêutico , Lactente , Japão , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/patologia , Taxa de Sobrevida , Resultado do Tratamento , Extremidade Superior/patologia , Vincristina/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: As there are no reports of studies in patients with pelvic chondrosarcoma treated with carbon ion radiotherapy (CIRT), the aim of this study was to evaluate the applicability of CIRT for patients with chondrosarcoma of the pelvis. METHODS: The medical records of 31 patients with chondrosarcoma of the pelvis treated either by surgical resection or by CIRT between 1983 and 2014 were reviewed. There were 22 males and 9 females with a median age of 43 years (range 16-77 years). The median duration of follow-up was 66 months (range 5-289 months). Twenty-four patients underwent surgery, and 7 patients received CIRT (70.4 GyE in 16 fractions over 4 weeks). RESULTS: The overall local recurrence rate was 32 %, and the estimated overall 5- and 10-year survival rates were 72 and 57 %, respectively. The mean Musculoskeletal Tumor Society functional score was 59 %. The treatment procedures (surgery or CIRT) did not affect overall survival (P = 0.347). However, the patients who underwent surgery had impaired function compared with those who received CIRT (P = 0.03). CONCLUSION: Although more patients need to be monitored to assess the clinical and functional outcomes of CIRT for patients with chondrosarcoma of the pelvis, this treatment might offer an acceptable alternative.
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Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Condrossarcoma/radioterapia , Condrossarcoma/cirurgia , Radioterapia com Íons Pesados , Recidiva Local de Neoplasia , Ossos Pélvicos , Adolescente , Adulto , Idoso , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: This study aimed to report the clinical outcomes for patients with osteoid osteoma (OO) treated by radiofrequency ablation (RFA) using a three-dimensional (3D) navigation system. METHODS: We performed RFA using a 3D navigation system on 32 patients with clinically and radiologically diagnosed OO. This study included 25 males and 7 females with a median age of 20 years (range, 10-39 years). The median duration of follow-up was 18 months (range, 1-65 months). We investigated technical specifications, tumor localization, technical success, clinical success, biopsy success, complications, incomplete treatment, and recurrences. RESULTS: Eighteen tumors were located in the femur, seven in the tibia, two in the humerus, and one each in the fibula, scapula, patella, lumbar vertebra, and acetabula. All procedures were technically successful, and pain relief was achieved in all patients. However, local recurrence developed in one patient, needing additional RFA. The clinical success rate was 96.8%. Biopsy showed OO in 12 patients (37%). Complications occurred in three patients (9%), two cases of fractures and one of osteomyelitis. CONCLUSIONS: A 3D navigation provides real-time imaging and enables us to set the RFA needle in the correct position, particularly in case of OO-aroused complex anatomical structures. Our initial results indicated that radiofrequency ablation using a 3D navigation system is feasible and safe for patients with OO.
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Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Ablação por Cateter/métodos , Osteoma Osteoide/diagnóstico por imagem , Osteoma Osteoide/cirurgia , Radiografia Intervencionista/métodos , Adolescente , Adulto , Biópsia por Agulha , Criança , Estudos de Coortes , Feminino , Fluoroscopia/métodos , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Medição de Risco , Cirurgia Assistida por Computador/métodos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Epithelioid sarcoma (EpS) is a high-grade malignant soft-tissue sarcoma characterized by local recurrences and distant metastases. Effective treatments for EpS have not been established and thus novel therapeutic approaches against EpS are urgently required. mTOR inhibitors exert antitumor effects on several malignancies but AKT reactivation by mTOR inhibition attenuates the antitumor effects of mTOR inhibitors. This reactivation is receptor tyrosine kinase (RTK)-dependent due to a release of negative feedback inhibition. We found that c-MET was the most highly activated RTK in two human EpS cell lines, Asra-EPS and VAESBJ. Here we investigated the functional and therapeutic relevance of mTOR and/or c-MET signaling pathways in EpS both in vitro and in vivo. METHODS: We first examined the effects of an mTOR inhibitor, RAD001 (everolimus), on cell proliferation, cell cycle, AKT/mTOR signaling, and xenograft tumor growth in EpS cell lines. Next, we determined whether RAD001-induced AKT reactivation was blocked by silencing of c-MET or treatment with a selective c-MET inhibitor, INC280. Finally, we evaluated the antitumor effects of RAD001 combined with INC280 on EpS cell lines compared with either single agent or control in vitro and in vivo. RESULTS: Constitutive AKT phosphorylation was observed in Asra-EPS and VAESBJ cells. RAD001 suppressed EpS cell growth by inducing cell cycle arrest but enhanced AKT phosphorylation, which resulted in intrinsic resistance to mTOR inhibitors. In both EpS cell lines, RAD001-induced AKT phosphorylation was dependent on c-MET signaling. INC280 inhibited phosphorylation of c-MET and its downstream molecules, and decreased RAD001-induced phosphorylation of both AKT and ERK in EpS. Compared with a single agent or control, the combination of RAD001 and INC280 exerted superior antitumor effects on the growth of EpS cell lines in vitro and in vivo. CONCLUSIONS: Targeting of mTOR and c-MET signaling pathways significantly abrogates the growth of EpS in preclinical models and may be a promising therapeutic approach for patients with EpS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Idoso , Animais , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Comunicação Autócrina/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Everolimo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Sarcoma/enzimologia , Transdução de Sinais/efeitos dos fármacos , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Clear cell sarcoma (CCS) is a therapeutically unresolved, aggressive, soft tissue sarcoma (STS) that predominantly affects young adults. This sarcoma is defined by t(12;22)(q13;q12) translocation, which leads to the fusion of Ewing sarcoma gene (EWS) to activating transcription factor 1 (ATF1) gene, producing a chimeric EWS-ATF1 fusion gene. We established a novel CCS cell line called Hewga-CCS and developed an orthotopic tumor xenograft model to enable comprehensive bench-side investigation for intensive basic and preclinical research in CCS with a paucity of experimental cell lines. METHODS: Hewga-CCS was derived from skin metastatic lesions of a CCS developed in a 34-year-old female. The karyotype and chimeric transcript were analyzed. Xenografts were established and characterized by morphology and immunohistochemical reactivity. Subsequently, the antitumor effects of pazopanib, a recently approved, novel, multitargeted, tyrosine kinase inhibitor (TKI) used for the treatment of advanced soft tissue sarcoma, on Hewga-CCS were assessed in vitro and in vivo. RESULTS: Hewga-CCS harbored the type 2 EWS-ATF1 transcript. Xenografts morphologically mimicked the primary tumor and expressed S-100 protein and antigens associated with melanin synthesis (Melan-A, HMB45). Pazopanib suppressed the growth of Hewga-CCS both in vivo and in vitro. A phospho-receptor tyrosine kinase array revealed phosphorylation of c-MET, but not of VEGFR, in Hewga-CCS. Subsequent experiments showed that pazopanib exerted antitumor effects through the inhibition of HGF/c-MET signaling. CONCLUSIONS: CCS is a rare, devastating disease, and our established CCS cell line and xenograft model may be a useful tool for further in-depth investigation and understanding of the drug-sensitivity mechanism.
Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Pirimidinas/farmacologia , Sarcoma de Células Claras/genética , Neoplasias de Tecidos Moles/genética , Sulfonamidas/farmacologia , Adulto , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Pontos de Quebra do Cromossomo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Humanos , Indazóis , Camundongos , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Sarcoma de Células Claras/tratamento farmacológico , Sarcoma de Células Claras/patologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/patologia , Fatores de Transcrição/genética , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Periosteal chondromas are rare benign cartilaginous tumors that arise adjacent to the cortex beneath the periosteum. These lesions are usually slow-growing and rarely exceed 3 cm in the greatest dimension. Here, we describe a 17-year-old boy who had a giant periosteal chondroma of the right distal femur, which was treated with intralesional resection and intensive curettage. In addition, we report a novel application of a bioresorbable plate in the management of the large bone defect after resection of a benign bone tumor.
Assuntos
Neoplasias Ósseas/cirurgia , Transplante Ósseo , Condroma/cirurgia , Fêmur/cirurgia , Periósteo/cirurgia , Procedimentos de Cirurgia Plástica , Adolescente , Neoplasias Ósseas/patologia , Condroma/patologia , Fêmur/patologia , Humanos , Masculino , Periósteo/patologia , Prognóstico , Próteses e ImplantesRESUMO
BACKGROUND: Sarculator is a validated nomogram designed to predict overall survival (OS) in extremity soft tissue sarcoma (STS). Inflammation plays a critical role in cancer development and progression. There were no reports which investigated the relationship between Sarculator and inflammation. METHODS: A total of 217 patients with extremity STS were included. The Sarculator-predicted 10-year probability of OS (pr-OS) was stratified into two subgroups: lower risk (10-year pr-OS ≥ 60%) and higher risk (10-year pr-OS < 60%). The modified Glasgow prognostic score (mGPS) varied from 0 to 2. RESULTS: Out of the 217 patients, 67 were classified as higher risk, while 150 were lower risk. A total of 181 patients had an mGPS of 0, and 36 had a score of 1 or 2. The 5-year OS was 83.3%. When patients were divided into two groups according to the 10-year pr-OS, those with a higher risk had poorer OS than those with a lower risk. Among the patients with a higher risk, those with an mGPS of 1 or 2 had poorer OS compared to those with a score of 0. CONCLUSIONS: The mGPS could potentially play an important role in identifying patients who are at high risk of death and metastasis in the higher-risk group on the Sarculator.
RESUMO
Synovial sarcoma (SS), a rare subtype of soft-tissue sarcoma distinguished by expression of the fusion gene SS18-SSX, predominantly affects the extremities of young patients. Existing anticancer drugs have limited efficacy against this malignancy, necessitating the development of innovative therapeutic approaches. Given the established role of SS18-SSX in epigenetic regulation, we focused on bromodomain and extra-terminal domain protein (BET) inhibitors and epigenetic agents. Our investigation of the BET inhibitor ABBV-075 revealed its pronounced antitumor effects, inducing G1-phase cell-cycle arrest and apoptosis, in four SS cell lines. Notably, BET inhibitors exhibited regulatory control over crucial cell-cycle regulators, such as MYC, p21, CDK4, and CDK6. Additionally, RNA sequencing findings across the four cell lines revealed the significance of fluctuating BCL2 family protein expression during apoptotic induction. Notably, variations in the expression ratio of the anti-apoptotic factor BCLxL and the pro-apoptotic factor BIM may underlie susceptibility to ABBV-075. Additionally, knockdown of SS18-SSX, which upregulates BCL2, reduced the sensitivity to ABBV-075. These findings suggest the potential utility of BET inhibitors targeting the SS18-SSX-regulated intrinsic apoptotic pathway as a promising therapeutic strategy for SS.