Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.733
Filtrar
1.
Med Oncol ; 37(2): 13, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31879796

RESUMO

Soft tissue myoepithelial carcinomas are a rare, malignant subgroup of myoepithelial tumours mostly arising in the extremities with equal predilection for women and men. The mainstay of management of localised disease is complete surgical resection. Despite optimal treatment, 40-45% of tumours recur. Data regarding the efficacy of systemic therapy for advanced and metastatic disease are lacking. The primary aim of this study was to evaluate the outcome of all patients with soft tissue myoepithelial carcinoma treated at a single referral centre. The secondary aim was to establish the efficacy of systemic therapies in patients with advanced disease. A retrospective review of the prospectively maintained Royal Marsden Sarcoma Unit database was performed to identify soft tissue myoepithelial carcinoma patients treated between 1996 and 2019. Patient baseline characteristics and treatment history were recorded. Response to systemic therapy was evaluated using RECIST 1.1. We identified 24 patients treated at our institution between 1996 and 2019,12 males and 12 females. Median age at presentation was 49.6 years [interquartile range (IQR) 40.5-63.3 years]. Twenty-two out of 24 patients (91.7%) underwent primary surgical resection. Nine patients (37.5%) received systemic treatment. A partial response was documented in one patient treated with doxorubicin. The median progression-free survival for first-line chemotherapy was 9.3 months. Myoepithelial carcinoma frequently recurs after complete surgical resection. Conventional chemotherapy demonstrated some activity in myoepithelial carcinoma, however, more effective systemic therapies are required and enrolment in clinical trial should be encouraged.


Assuntos
Doxorrubicina/uso terapêutico , Mioepitelioma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Inibidores da Topoisomerase II/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mioepitelioma/patologia , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida , Resultado do Tratamento
2.
Medicine (Baltimore) ; 98(45): e17872, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702654

RESUMO

RATIONALE: Ewing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) is a rare type of soft tissue sarcomas (STS), especially in infants, with poor prognosis. It is a so-called "small round cell" sarcoma, and has many features of Ewing sarcoma, but lacks rearrangements in EWSR1. The diagnosis and treatment of this kind of STS remains challenging. BCOR genetic abnormalities have been found in some Ewing-like sarcomas. PATIENT CONCERNS: This report presents an ELS case of a female infant, who was 2 months old when initially diagnosed, with the clinical stage of IIIA (G2T2N0M0). Histologic findings revealed an undifferentiated neoplasm composed of small round tumor cells with round, open chromatic nuclei, and scant cytoplasm in a sheet growth pattern. Fluorescence in situ hybridization (FISH) analysis showed absence of EWSR1 and ETV6 gene rearrangement. Molecular genetic testing found no established variants of clinical significance but variants of unknown significance in APC, KMT2D, and MSH6 were detected. Immunostaining revealed that the tumor cells were positive for TLE1 and BCOR, and negative for cytokeratin (AE1/AE3), Desmin, CD45, S100, CD31, HMB45, and SATB2. INI-1 was retained. DIAGNOSIS: Ewing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) INTERVENTIONS:: After initial diagnosis, the patient received 4 cycles of combination chemotherapy for 2 months. Radical amputation of left upper extremity was performed 3 months after diagnosis. Postoperative chemotherapy was continued for 6 cycles. OUTCOMES: The patient died of intracranial metastasis with hemorrhage in 13 months after initial diagnosis, 5 months after the last cycle of chemotherapy. LESSONS: ELS in infancy is extremely rare and has a poorer prognosis than Ewing sarcoma or infantile fibrosarcoma. APC and MSH6 variation might be related with the disease progression and predict a poorer prognosis. This rare case promotes better understanding of the disease and suggests a promising role for the combination chemotherapy regimen in treating infantile ELS. Importantly, it brings to light the possibility of intracranial metastasis, which requires proactive screening for timely detection.


Assuntos
Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Dactinomicina/uso terapêutico , Evolução Fatal , Feminino , Antebraço/diagnóstico por imagem , Humanos , Lactente , Sarcoma/diagnóstico por imagem , Sarcoma/tratamento farmacológico , Sarcoma/genética , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/genética , Ultrassonografia Doppler em Cores , Vincristina/uso terapêutico
4.
Br J Radiol ; 92(1103): 20190158, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31509443

RESUMO

OBJECTIVE: To analyze patterns of response in soft tissue sarcomas exposed to pazopanib using CT-morphologic and textural features and their suitability for evaluating therapeutic response. METHODS: Retrospective evaluation of CT response and texture patterns in 33 patients (23 female; mean age: 61.2 years, range, 30-85 years) with soft tissue sarcomas treated with pazopanib from October 2008 to July 2017. Response evaluation was based on modified (m)CHOI-criteria and RECISTv.1.1 and classified as partial response (PR), stable disease (SD), progressive disease (PD). The following CT-texture (CTTA)-parameters were calculated: mean, entropy and uniformity of intensity/average/skewness/entropy of co-occurrence matrix and contrast of neighboring-gray-level-dependence-matrix. RESULTS: Following mCHOI-criteria, 12 patients achieved PR, 7 SD and 14 PD. As per RECISTv.1.1 9 patients obtained PR, 9 SD and 15 PD. Frequent patterns of response were tumor liquefaction and necrosis (n=4/33, 12.1% each). Further patterns included shrinkage and cavitation (n=2/33, 6.1% each). In responders, differences in mean heterogeneity (p=0.01), intensity (p=0.03), average (p=0.03) and entropy of skewness (p=0.01) were found at follow-up whereas in non-responders, CTTA-parameters did not change significantly. Baseline-CTTA-features differed between responders and non-responders in terms of uniformity of skewness (p=0.045). Baseline-CTTA-parameters did not correlate with any morphologic response pattern. CONCLUSION: Most frequent patterns of response to pazopanib were tumor liquefaction and necrosis. Single CT-textural features show strong association with the response to pazopanib-although limited in relation to specific response patterns. ADVANCES IN KNOWLEDGE: Tumor liquefication and necrosis are important patterns of response to pazopanib. CT-texture analysis has limited associations with specific response patterns.


Assuntos
Antineoplásicos/uso terapêutico , Pirimidinas/uso terapêutico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
5.
Medicine (Baltimore) ; 98(37): e16986, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517817

RESUMO

RATIONALE: Cavernous hemangiomas referred to as venous malformations (VMs), are not true vascular tumors. The treatment of cavernous hemangiomas is controversial. PATIENT CONCERNS: A five-year-old girl with a cavernous hemangioma on her right buttock had undergone surgery but recurred 1 month after the operation. DIAGNOSES: Cavernous hemangioma was diagnosed on the basis of physical examination, magnetic resonance imaging (MRI) and postoperative pathologic examination. INTERVENTIONS: We treated her with intralesional injection of triamcinolone acetonide (TCA) for 8 times. OUTCOMES: She was cured and had no recurrence during the 3-month follow-up. LESSONS: This prompts that TCA may provide a more effective and safer choice for the treatment of cavernous hemangiomas.


Assuntos
Antineoplásicos/administração & dosagem , Hemangioma Cavernoso/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Nádegas , Pré-Escolar , Feminino , Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/patologia , Hemangioma Cavernoso/cirurgia , Humanos , Injeções Intralesionais , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia
6.
BMC Cancer ; 19(1): 890, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492159

RESUMO

BACKGROUND: Soft-tissue sarcomas (STS) are rare malignant tumors those are resistant to chemotherapy. We have previously reported the 3-year follow-up result on the efficacy of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-risk STS of the extremities (JCOG0304). In the present study, we analyzed the 10-year follow-up results of JCOG0304. METHODS: Patients with operable, high-risk STS (T2bN0M0, AJCC 6th edition) of the extremities were treated with 3 courses of preoperative and 2 courses of postoperative chemotherapy, which consisted of 60 mg/m2 of DXR plus 10 g/m2 of IFM over a 3-week interval. The primary study endpoint was progression-free survival (PFS) estimated by Kaplan-Meier methods. Prognostic factors were evaluated by univariable and multivariable Cox proportional hazards model. RESULTS: A total of 72 patients were enrolled between March 2004 and September 2008, with 70 of these patients being eligible. The median follow-up period was 10.0 years for all eligible patients. Local recurrence and distant metastasis were observed in 5 and 19 patients, respectively. The 10-year PFS was 65.7% (95% CI: 53.4-75.5%) with no PFS events being detected during the last 5 years of follow-up. The 10-year overall survival was 78.1% (95% CI: 66.3-86.2%). Secondary malignancy was detected in 6 patients. The subgroup analysis demonstrated that there was significant difference in survival with regard to primary tumor size. CONCLUSIONS: Only a few long-term results of clinical trials for perioperative chemotherapy treatment of STS have been reported. Our results demonstrate that the 10-year outcome of JCOG0304 for patients with operable, high-risk STS of the extremities was stable and remained favorable during the last 5 years of follow-up. TRIAL REGISTRATION: This trial was registered at the UMIN Clinical Trials Registry as C000000096 on August 30, 2005.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Extremidades/patologia , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Esquema de Medicação , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/uso terapêutico , Japão , Masculino , Razão de Chances , Período Perioperatório , Sarcoma/mortalidade , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
7.
Pathol Res Pract ; 215(10): 152613, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471105

RESUMO

BACKGROUND: In Ewing sarcomas (ES), histological response to polychemotherapy is the main prognostic factor. We aimed at evaluating the histological response separately for the extraosseous and intraosseous tumor compartment as well as its prognostic influence. METHODS: Thirty-one patients with ES and marked soft tissue expansion, treated at our department between January 2006 and December 2015, were retrospectively included. Data was taken from medical records. Original histologic specimens of the resected tumors were re-evaluated separately for intra- and extraosseous tumor regression according to Salzer-Kuntschik regression grading. Multivariate survival analysis with stepwise backward variable selection was calculated to determine the impact of extraosseous and intraosseous regression on prognosis. RESULTS: All patients had received chemotherapy, 15 (48.4%) had been administered preoperative radiotherapy. Extraosseous tumor regression was significantly worse than intraosseous regression (Wilcoxon signed-rank test, p = 0.018). While neither intraosseous nor extraosseous tumor regression had an impact on overall survival, extraosseous complete remission had a beneficial impact on event-free-survival in the multivariate analysis (Cox-regression; hazard ratio: 0.148, 95% confidence interval 0.031-0.707, p = 0.017). CONCLUSIONS: On average, regression of ES seems to be worse in the extraosseous tumor compartment following preoperative chemotherapy. Moreover, extraosseous tumor regression may have a stronger prognostic influence on event-free survival than intraosseous regression.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Sarcoma de Ewing/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma de Ewing/patologia , Neoplasias de Tecidos Moles/patologia , Resultado do Tratamento , Adulto Jovem
8.
Indian J Cancer ; 56(3): 207-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389382

RESUMO

PURPOSE: There is no study till date determining the spectrum of adverse events of pazopanib in Indian patients with advanced sarcoma. MATERIALS AND METHODS: We conducted a retrospective study by analyzing the case records of metastatic sarcoma patients treated with pazopanib from January 2016 to July 2017 in sarcoma medical oncology clinic. Toxicity was assessed according to CTCAE v.4.03 criteria. SPSS version 23 was used for statistical evaluation. RESULTS: A total of 33 patients received pazopanib. The median age was 41 years (range, 19-75 years), with a male predominance (54.5%). Twenty-six patients (78.8%) had ECOG performance status 1 at the time of pazopanib initiation. The most common type of sarcoma was synovial sarcoma, and the mean duration of pazopanib intake in patients was 4.12 months. The median follow-up was 13 months. Median progression-free survival was 5 months, and median overall survival was 18 months. Overall response rate was 6.0%. Out of the 33 patients, 42.4% (n = 14) received it after first line of therapy. Six patients (18.2%) required dose reductions due to toxicity. Thirteen (39.4%) patients experienced CTCAE grade 3 or 4 toxicities. Most common grade 3 and 4 toxicities experienced among patients were hand-foot skin reaction (18.2%) and proteinuria (9.1%). No significant difference was seen when analyzed for variables such as age, sex, ECOG performance status, comorbidities, and number of previous lines received in patients experiencing grade 3 and 4 toxicities. CONCLUSIONS: The spectrum of adverse events in Indian patients at doses lower than the recommended dose is distinctly different from the western population. However, this unique toxicity profile needs to be validated in prospective studies.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Pirimidinas/efeitos adversos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Sulfonamidas/efeitos adversos , Adulto , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma/secundário , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida , Adulto Jovem
9.
Jpn J Clin Oncol ; 49(10): 938-946, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31365116

RESUMO

BACKGROUND: Although eribulin is used to treat soft tissue sarcomas (STSs), treatment data for rare subtypes are limited. We conducted a post-marketing surveillance study to assess safety and efficacy of eribulin in STS patients stratified by subtype. METHODS: Japanese patients (n = 256) with advanced or metastatic STS receiving eribulin treatment were monitored for treatment status, adverse events, diagnostic imaging, and clinical outcomes at 3 months and 1 year. Interim analysis was performed. Patients will be monitored up to 2 years. RESULTS: Interim analysis included 3-month (n = 255), imaging (n = 226), and 1-year (n = 105) data. STS subtype distribution was normal. Median number of eribulin cycles was 3.0 (range: 1-17 cycles). Among patients with imaging data, best overall tumor response (12 weeks) was partial response, 7.5% (n = 17); stable disease, 34.5% (n = 78); and stable disease ≥11 weeks, 10.2% (n = 23). Overall response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) for all patients were 7.5%, 42.0% and 17.7%, respectively. ORR, DCR, and CBR were 10.3%, 32.0% and 16.5%, respectively, for patients with STS subtypes other than liposarcoma and leiomyosarcoma and included responses from patients with rare STS subtypes. Adverse drug reactions (ADRs) occurred in 211 (82.7%) patients (42 [16.5%] patients had serious ADRs), and none led to death. ADRs leading to drug withdrawal and dose reduction occurred in 27 (10.6%) and 55 (21.6%) patients, respectively. CONCLUSION: Eribulin was generally well tolerated and showed antitumor activity against STSs, including rare subtypes that currently have few treatment options. CLINICAL TRIAL NUMBER: NCT03058406 (ClinicalTrials.gov).


Assuntos
Furanos/uso terapêutico , Cetonas/uso terapêutico , Sarcoma/classificação , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/classificação , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Furanos/efeitos adversos , Humanos , Cetonas/efeitos adversos , Leiomiossarcoma/patologia , Lipossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Sarcoma/patologia , Resultado do Tratamento , Adulto Jovem
10.
BMC Cancer ; 19(1): 724, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331295

RESUMO

BACKGROUND: Soft tissue sarcoma (STS) comprises a family of rare, heterogeneous tumors of mesenchymal origin. Single-agent doxorubicin remains the first-line standard-of-care treatment for advanced and inoperable STS, but response rates are only around 15%. In 2016, phase Ib/II clinical trial results reported an overall survival benefit of 11.8 months when combining doxorubicin and the platelet-derived growth factor receptor alpha (PDGFRA)-directed antibody olaratumab compared to doxorubicin alone, without providing a scientific rationale for such unprecedented therapeutic effect. We decided to evaluate the efficacy of olaratumab in a panel of STS patient-derived xenografts (PDX). METHODS: NMRI nu/nu mice were bilaterally transplanted with tumor tissue of patient-derived xenograft models expressing PDGFRA, including models of leiomyosarcoma (UZLX-STS22), malignant peripheral nerve sheath tumor (UZLX-STS39), myxofibrosarcoma (UZLX-STS59) and undifferentiated pleomorphic sarcoma (UZLX-STS84). Mice were randomly divided into four different treatment groups: (1) control, (2) doxorubicin (3 mg/kg once weekly), (3) anti-PDGFRA [olaratumab (60 mg/kg twice weekly) + mouse anti-PDGFRA antibody 1E10 (20 mg/kg twice weekly)] and (4) the combination of doxorubicin and anti-PDGFRA (same dose/schedule as in the single treatment arms). Tumor volume, histopathology and Western blotting were used to assess treatment efficacy. RESULTS: Anti-PDGFRA treatment as a single agent did not reduce tumor growth and did not result in significant anti-proliferative or pro-apoptotic activity. Combining doxorubicin and anti-PDGFRA did not reduce tumor burden, though a mild inhibition of proliferation was observed in UZLX-STS39 and -STS59. A pro-apoptotic effect was observed in all models except UZLX-STS22. Antitumor effects on histology were not significantly different comparing doxorubicin and the combination treatment. Moreover, anti-PDGFRA treatment, both as a single agent as well as combined with doxorubicin, did not result in inhibition of the downstream MAPK and PI3K/AKT signaling pathways. CONCLUSIONS: We were not able to demonstrate significant antitumor effects of anti-PDGFRA treatment in selected STS PDX models, neither alone nor in combination with doxorubicin. This is in line with the very recent results of the phase III clinical trial NCT02451943 ANNOUNCE, which did not confirm the clinical benefit of olaratumab in combination with doxorubicin over single agent doxorubicin.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/imunologia , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Doxorrubicina/administração & dosagem , Quimioterapia Combinada , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Resultado do Tratamento , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Pediatr Blood Cancer ; 66(11): e27935, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31339226

RESUMO

Spindle cell and sclerosing rhabdomyosarcoma (ssRMS) is a rare variant of rhabdomyosarcoma, which includes three distinct subtypes. In infants, these tumors are commonly associated with recurring fusions involving VGLL2 or NCOA2 and have a favorable prognosis. We present four cases of ssRMS and 16 additional cases from the literature, which show that these patients present with localized disease and have an excellent prognosis regardless of surgical margin or lack of radiation therapy. Molecularly defined spindle cell rhabdomyosarcoma in infants is likely a biologically distinct entity which may not require the aggressive multimodal treatment used for other subtypes of rhabdomyosarcoma.


Assuntos
Rabdomiossarcoma Embrionário/congênito , Neoplasias de Tecidos Moles/congênito , Amputação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Extremidades/patologia , Feminino , Doenças do Pé/congênito , Doenças do Pé/tratamento farmacológico , Doenças do Pé/genética , Doenças do Pé/cirurgia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/genética , Doenças do Prematuro/cirurgia , Masculino , Proteínas de Fusão Oncogênica/genética , Indução de Remissão , Rabdomiossarcoma Embrionário/tratamento farmacológico , Rabdomiossarcoma Embrionário/genética , Rabdomiossarcoma Embrionário/cirurgia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/cirurgia , Coxa da Perna , Neoplasias Torácicas/congênito , Neoplasias Torácicas/tratamento farmacológico , Neoplasias Torácicas/genética , Neoplasias Torácicas/cirurgia , Parede Torácica/patologia , Vincristina/administração & dosagem
12.
Anticancer Res ; 39(7): 3553-3563, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262879

RESUMO

BACKGROUND/AIM: Trabectedin is a DNA-damaging agent and has been approved for the treatment of patients with advanced soft tissue sarcoma. Schlafen 11 (SLFN11) was identified as a dominant determinant of the response to DNA-damaging agents. The aim of the study was to clarify the association between SLFN11 expression and the antitumor activity of trabectedin. MATERIALS AND METHODS: The antitumor activity of trabectedin was evaluated under different expression levels of SLFN11 regulated by RNA interference and CRISPR-Cas9 systems, and the combined antitumor activity of ataxia telangiectasia and Rad3-related protein kinase (ATR) inhibitor and trabectedin in sarcoma cell lines using in vitro a cell viability assay and in vivo xenograft models. RESULTS: SLFN11-knockdown cell lines had a lower sensitivity to trabectedin, compared to parental cells. ATR inhibitor enhanced the antitumor activity of trabectedin in SLFN11-knockdown cells and in a SLFN11-knockout xenograft model. CONCLUSION: SLFN11 expression might be a key factor in the antitumor activity of trabectedin.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Proteínas Nucleares/metabolismo , Sarcoma/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Trabectedina/farmacologia , Animais , Antineoplásicos Alquilantes/uso terapêutico , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Nucleares/genética , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Trabectedina/uso terapêutico
13.
Anticancer Res ; 39(7): 3945-3947, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262925

RESUMO

BACKGROUND/AIM: Malignant melanoma is a rare disease in the pediatric population and there are no recommendations regarding its management in children, while the current standard of care in metastatic or unresectable melanoma in adult patients includes immunotherapy (anti-CTLA-4 and anti-PD-1 antibodies). Advances in the management of adults with melanoma offer the prospect of promising therapeutic options for children. CASE REPORT: We describe a case of a 7-year-old patient with recurrent metastatic melanoma, for whom pembrolizumab was used as an adjuvant therapy on compassionate use basis. CONCLUSION: Due to adverse events, the treatment was discontinued after 5 months of pembrolizumab, but with 12-months of follow-up, patient remains in complete remission.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Antirreumáticos/uso terapêutico , Artrite Juvenil/induzido quimicamente , Artrite Juvenil/tratamento farmacológico , Criança , Feminino , Humanos , Metotrexato/uso terapêutico , Esteroides/uso terapêutico , Resultado do Tratamento , Uveíte/induzido quimicamente
14.
BMC Cancer ; 19(1): 725, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337342

RESUMO

BACKGROUND: The prognosis of patients with metastatic or advanced sarcomas is poor and there are few options for treatment. Several studies have shown that gemcitabine and docetaxel (GD) combination chemotherapy has antitumor activity against various subtypes of sarcoma. Recently, some studies have shown a favourable outcome for GD combination chemotherapy for relapsed high-grade osteosarcoma and spindle cell sarcoma of bone. If the effectiveness of GD is proven, this will result in new treatment options for advanced bone and soft tissue sarcomas (STS). The aim of this prospective Phase 2 study is to evaluate the efficacy and toxicity of the GD combination in patients with advanced bone sarcomas and STS. METHODS: This is a Phase 2, single-arm, open-label study to investigate the efficacy and safety of combination chemotherapy with GD for advanced bone sarcomas and STS and will enrol 20 patients. The patients will receive gemcitabine 900 mg/m2 on Days 1 and 8, and docetaxel 70 mg/m2 on Day 8 in 3-week cycles until disease progression or other evidence of treatment failure. The primary aim of this study is to analyse GD's effect on progression-free survival (PFS). The secondary objectives are to analyse treatment efficacy and safety in terms of response rate, tumour control rate, overall survival, and adverse event rate. The length of follow-up will be 5 years. DISCUSSION: This study will evaluate the efficacy and safety of combination therapy with gemcitabine and docetaxel for bone sarcomas and STS. If this combination proves to be acceptable, it could be used for as second, third, or later line therapy for patients with sarcomas (especially bone sarcomas). In the future, the role of various treatments, including GD therapy, will be clarified for specific subtypes of sarcoma. TRIAL REGISTRATION: This study was registered as UMIN000031004 (University Hospital Medical Information Network-Clinical Trial Registry: UMIN-CTR) on 1 March 1 2018 and with the Japan Registry of Clinical Trials (jRCT) as jRCTs051180042 on 30 January 2019. The posted information will be updated as needed to reflect protocol amendments and study progress.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Osteossarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Ensaios Clínicos Fase II como Assunto , Desoxicitidina/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Adulto Jovem
15.
Int J Clin Oncol ; 24(10): 1311-1319, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31197555

RESUMO

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.


Assuntos
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 Sobrevida
17.
Expert Opin Pharmacother ; 20(12): 1503-1515, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31136210

RESUMO

Introduction: Liposarcomas are a heterogeneous group of soft tissue tumors that arise from adipose tissue and are one of the most common soft tissue sarcomas found in adults. Liposarcomas are subclassified into four subtypes with distinct histologic and biologic features that influence their treatment and management. Areas covered: This manuscript reviews the key clinicopathologic and cytogenic characteristics of the liposarcoma histologic subtypes and summarizes the results of recent clinical trials, treatment options, and future directions in the pharmacotherapy for the management of liposarcoma. Expert opinion: Despite significant advancements in the management of this disease, the treatment of liposarcoma continues to be a challenge. Surgical resection remains the mainstay of treatment for localized disease; however, use of systemic therapies in conjunction with surgery may be considered in patients where tumor shrinkage could reduce surgical morbidity and in patients with high-risk of micrometastatic disease. Anthracycline-based chemotherapy regimens remain the standard first-line treatment for unresectable/metastatic liposarcoma. Trabectedin and eribulin are currently the two most promising and evidenced-based second-line treatment options for liposarcomas. However, multiple clinical trials dedicated to patients with liposarcoma evaluating novel targeted agents are ongoing. Every effort should be made to enroll patients with liposarcoma into histotype-specific clinical trials.


Assuntos
Antineoplásicos/classificação , Antineoplásicos/uso terapêutico , Drogas em Investigação/uso terapêutico , Lipossarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Antraciclinas/uso terapêutico , Descoberta de Drogas/métodos , Descoberta de Drogas/tendências , Furanos/uso terapêutico , Humanos , Cetonas/uso terapêutico , Lipossarcoma/epidemiologia , Lipossarcoma/patologia , Sarcoma/tratamento farmacológico , Sarcoma/epidemiologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/epidemiologia , Neoplasias de Tecidos Moles/patologia , Trabectedina/uso terapêutico
18.
Chirurg ; 90(6): 457-461, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31053897

RESUMO

BACKGROUND: Patients with localized high-risk soft tissue sarcoma are at high risk for both local recurrence and distant metastases despite optimal surgical treatment. OBJECTIVE: Importance of preoperative or postoperative chemotherapy and hyperthermia. METHODS: Evaluation and overview of published study results. RESULTS: Preoperative or postoperative radiotherapy is considered as standard for patients with localized high-risk soft tissue sarcoma. The results of two randomized studies on neoadjuvant chemotherapy showed a survival benefit. As both studies did not have a control arm without chemotherapy but in one case the superiority of anthracycline/ifosfamide-based chemotherapy in combination with hyperthermia over chemotherapy alone and in the other case the superiority of anthracycline/ifosfamide-based chemotherapy over histology-specific chemotherapy were shown, the formal proof of the superiority of this treatment is still missing. Stratifying the patients treated in the so far largest randomized adjuvant chemotherapy trial according to current risk criteria ( http://www.sarculator.com ) revealed a significant survival benefit for patients at high risk of recurrence. CONCLUSION: For high-risk soft tissue sarcomas, multimodal treatment strategies involving perioperative chemotherapy, radiotherapy and, if possible, hyperthermia should be considered in addition to tumor resection. Preoperative chemotherapy should be given preference over postoperative chemotherapy based on available data.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Ifosfamida , Recidiva Local de Neoplasia , Ensaios Clínicos Controlados Aleatórios como Assunto , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico
19.
Zhonghua Zhong Liu Za Zhi ; 41(4): 309-314, 2019 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-31014058

RESUMO

Objective: To compare the clinical efficacy and drug safety between oral apatinib combined with conventional chemotherapy and conventional chemotherapy alone for the treatment of osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis. Methods: Thirty-three osteosarcoma and soft tissue sarcoma patients with pulmonary metastasis who were treated in the Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University from January 2015 to December 2017 were enrolled in this study. Patients with osteosarcoma received methotrexate, adriamycin (ADM), cisplatin (CDDP), ifosfamide (IFO) sequential regimen; patients with soft tissue sarcoma were treated with IFO and ADM regimen. Eighteen of these patients received an additional oral dose of apatinib. The patients were followed up regularly for changes in primary tumors and metastases, adverse reactions and prognosis. Results: Before treatment, the maximum diameter of pulmonary metastases in patients of apatinib group and routine treatment group were (4.46±1.70) cm and (4.53±2.00) cm, respectively, without significant difference (P=0.909). After treatment, the maximum diameter of pulmonary metastases in patients of apatinib group was (1.46±1.39) cm, significantly smaller than (3.02±1.20) cm of routine treatment group (P=0.002). After treatment, the maximum diameter of the primary lesions in the apatinib group and the conventional treatment group median decreased 0.31 cm and 0.12 cm, respectively, without significant difference (P=0.542). After treatment, the maximum diameter of the lung metastases in the apatinib group median decreased 0.59 cm, significantly more than 0.18 cm of the conventional treatment group (P=0.027). The median progression-free survival (PFS) was 9.4 months in the 33 patients. The median PFS was 9.6 months and 8.3 months in the apatinib group and the conventional treatment group, respectively, without significant difference (P=0.593). Specific adverse reactions both occurred in apatinib group and routine treatment group, mainly including oral mucosal reactions and digestive tract reactions (including nausea, vomiting and diarrhea). Conclusions: Apatinib can effectively reduce the volume of primary and metastatic lesions in patients with bone and soft tissue sarcoma accompanied by lung metastasis without reducing the survival rate or causing uncontrollable adverse reactions. The safety and clinical efficacy of apatinib are significant.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Pulmonares/secundário , Osteossarcoma/tratamento farmacológico , Osteossarcoma/secundário , Piridinas/uso terapêutico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Neoplasias Ósseas/patologia , Criança , China , Humanos , Sarcoma/tratamento farmacológico , Sarcoma/secundário , Neoplasias de Tecidos Moles/patologia , Resultado do Tratamento
20.
Am J Clin Oncol ; 42(5): 426-431, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30913092

RESUMO

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) comprise a rare, aggressive subtype of soft tissue sarcoma. While surgery is the mainstay of therapy for this disease, the role of neoadjuvant therapy remains undefined. METHODS: This study reviewed patients 16 years of age and older who underwent surgical treatment for MPNST between 1974 and 2012 at the authors' institution. Univariate and multivariate analyses were performed of clinicopathologic and treatment variables predictive of disease-specific survival (DSS) and disease-free survival. RESULTS: Eighty-eight patients with primary localized MPNST underwent surgical treatment between 1974 and 2012 at our institution. Of these, 38 (43%) underwent neoadjuvant chemotherapy and had tissue available for analysis. Neoadjuvant radiation was given to 25 patients (68%). The median follow-up time for survivors was 12.5 years (range, 4 to 27 y). Nine patients (23%) had underlying MPNST. With a cutoff of ≥90% pathologic necrosis and/or fibrosis defining response, we identified 14 responders (36%). On univariate analysis, patient age, tumor size, and pathologic response were significantly associated with DSS (P=0.015, 0.011, and 0.030, respectively). CONCLUSIONS: Although the impact of neoadjuvant chemotherapy on the outcome of primary localized MPNST patients continues to be debated, this study shows that a pathologic response to therapy is associated with a significant improvement in DSS. The challenge moving forward is to determine upfront which patients will be "responders" to standard systemic therapy and which patients should be considered for newer investigational agents as part of a clinical trial.


Assuntos
Terapia Neoadjuvante , Neoplasias da Bainha Neural/tratamento farmacológico , Neoplasias da Bainha Neural/patologia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/patologia , Centros Médicos Acadêmicos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , California , Estudos de Coortes , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias da Bainha Neural/mortalidade , Neoplasias da Bainha Neural/cirurgia , Procedimentos Ortopédicos/métodos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/cirurgia , Análise de Sobrevida , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA