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BACKGROUND: Few prospective studies have compared poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors to chemotherapy for the treatment of BRCA1-mutated or BRCA2-mutated ovarian carcinoma. We aimed to assess rucaparib versus platinum-based and non-platinum-based chemotherapy in this setting. METHODS: In this open-label, randomised, controlled, phase 3 study (ARIEL4), conducted in 64 hospitals and cancer centres across 12 countries (Brazil, Canada, Czech Republic, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, the UK, and the USA), we recruited patients aged 18 years and older with BRCA1-mutated or BRCA2-mutated ovarian carcinoma, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and who had received two or more previous chemotherapy regimens. Eligible patients were randomly assigned (2:1), using an interactive response technology and block randomisation (block size of six) and stratified by progression-free interval after the most recent platinum-containing therapy, to oral rucaparib (600 mg twice daily) or chemotherapy (administered per institutional guidelines). Patients assigned to the chemotherapy group with platinum-resistant or partially platinum-sensitive disease were given paclitaxel (starting dose 60-80 mg/m2 on days 1, 8, and 15); those with fully platinum-sensitive disease received platinum-based chemotherapy (single-agent cisplatin or carboplatin, or platinum-doublet chemotherapy). Patients were treated in 21-day or 28-day cycles. The primary endpoint was investigator-assessed progression-free survival, assessed in the efficacy population (all randomly assigned patients with deleterious BRCA1 or BRCA2 mutations without reversion mutations), and then in the intention-to-treat population (all randomly assigned patients). Safety was assessed in all patients who received at least one dose of assigned study treatment. This study is registered with ClinicalTrials.gov, NCT02855944; enrolment is complete, and the study is ongoing. FINDINGS: Between March 1, 2017, and Sept 24, 2020, 930 patients were screened, of whom 349 eligible patients were randomly assigned to rucaparib (n=233) or chemotherapy (n=116). Median age was 58 years (IQR 52-64) and 332 (95%) patients were White. As of data cutoff (Sept 30, 2020), median follow-up was 25·0 months (IQR 13·8-32·5). In the efficacy population (220 patients in the rucaparib group; 105 in the chemotherapy group), median progression-free survival was 7·4 months (95% CI 7·3-9·1) in the rucaparib group versus 5·7 months (5·5-7·3) in the chemotherapy group (hazard ratio [HR] 0·64 [95% CI 0·49-0·84]; p=0·0010). In the intention-to-treat population (233 in the rucaparib group; 116 in the chemotherapy group), median progression-free survival was 7·4 months (95% CI 6·7-7·9) in the rucaparib group versus 5·7 months (5·5-6·7) in the chemotherapy group (HR 0·67 [95% CI 0·52-0·86]; p=0·0017). Most treatment-emergent adverse events were grade 1 or 2. The most common grade 3 or worse treatment-emergent adverse event was anaemia or decreased haemoglobin (in 52 [22%] of 232 patients in the rucaparib group vs six [5%] of 113 in the chemotherapy group). Serious treatment-emergent adverse events occurred in 62 (27%) patients in the rucaparib group versus 13 (12%) in the chemotherapy group; serious adverse events considered related to treatment by the investigator occurred in 32 (14%) patients in the rucaparib group and six (5%) in the chemotherapy group. Three deaths were considered to be potentially related to rucaparib (one due to cardiac disorder, one due to myelodysplastic syndrome, and one with an unconfirmed cause). INTERPRETATION: Results from the ARIEL4 study support rucaparib as an alternative treatment option to chemotherapy for patients with relapsed, BRCA1-mutated or BRCA2-mutated ovarian carcinoma. FUNDING: Clovis Oncology.
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Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Adolescente , Proteína BRCA1/genética , Proteína BRCA2/genética , Humanos , Indóis , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Estudos ProspectivosRESUMO
BACKGROUND: Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with InS. METHODS: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2-positive InS who were treated with anthracycline-based regimens, gemcitabine-based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence-free survival (RFS), progression-free survival (PFS) and overall survival were computed by Kaplan-Meier method. RESULTS: Seventy-two patients were included (66 anthracycline-based regimens; 26 gemcitabine-based regimens; 12 pazopanib). In the anthracycline-based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real-world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline-related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. CONCLUSION: This retrospective series shows the activity of anthracycline-based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Cardíacas/tratamento farmacológico , Sarcoma/tratamento farmacológico , Túnica Íntima/efeitos dos fármacos , Adulto , Idoso , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiotoxicidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/patologia , Humanos , Indazóis , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-mdm2/genética , Pirimidinas/administração & dosagem , Sarcoma/genética , Sarcoma/patologia , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Túnica Íntima/patologia , GencitabinaRESUMO
Importance: Patients with advanced soft tissue sarcoma (STS) have a median overall survival of less than 2 years. In a phase 2 study, an overall survival benefit in this population was observed with the addition of olaratumab to doxorubicin over doxorubicin alone. Objective: To determine the efficacy of doxorubicin plus olaratumab in patients with advanced/metastatic STS. Design, Setting, and Participants: ANNOUNCE was a confirmatory, phase 3, double-blind, randomized trial conducted at 110 sites in 25 countries from September 2015 to December 2018; the final date of follow-up was December 5, 2018. Eligible patients were anthracycline-naive adults with unresectable locally advanced or metastatic STS, an Eastern Cooperative Oncology Group performance status of 0 to 1, and cardiac ejection fraction of 50% or greater. Interventions: Patients were randomized 1:1 to receive doxorubicin, 75 mg/m2 (day 1), combined with olaratumab (n = 258), 20 mg/kg in cycle 1 and 15 mg/kg in subsequent cycles, or placebo (n = 251) on days 1 and 8 for up to 8 21-day cycles, followed by olaratumab/placebo monotherapy. Main Outcomes and Measures: Dual primary end points were overall survival with doxorubicin plus olaratumab vs doxorubicin plus placebo in total STS and leiomyosarcoma (LMS) populations. Results: Among the 509 patients randomized (mean age, 56.9 years; 58.2% women; 46.0% with LMS), all were included in the primary analysis and had a median length of follow-up of 31 months. No statistically significant difference in overall survival was observed between the doxorubicin plus olaratumab group vs the doxorubicin plus placebo group in either population (total STS: hazard ratio, 1.05 [95% CI, 0.84-1.30], P = .69, median overall survival, 20.4 months vs 19.7 months; LMS: hazard ratio, 0.95 [95% CI, 0.69-1.31], P = .76, median overall survival, 21.6 months vs 21.9 months). Adverse events of grade 3 or greater reported in 15% or more of total patients with STS were neutropenia (46.3% vs 49.0%), leukopenia (23.3% vs 23.7%), and febrile neutropenia (17.5% vs 16.5%). Conclusions and Relevance: In this phase 3 clinical trial of patients with advanced STS, treatment with doxorubicin plus olaratumab vs doxorubicin plus placebo resulted in no significant difference in overall survival. The findings did not confirm the overall survival benefit observed in the phase 2 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02451943.
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Antibióticos Antineoplásicos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/administração & dosagem , Sarcoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Método Duplo-Cego , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/uso terapêutico , Modelos de Riscos Proporcionais , Sarcoma/mortalidade , Sarcoma/secundário , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Alveolar soft part sarcoma (ASPS) is an exceedingly rare and orphan disease, without active drugs approved in the front line. Pazopanib and trabectedin are licensed for sarcoma treatment from second-line, but very little and contradictory data are available on their activity in ASPS. Lacking ongoing and/or planned clinical trials, we conducted a multi-institutional study involving the reference sites for sarcoma in Europe, U.S., and Japan, within the World Sarcoma Network, to investigate the efficacy of pazopanib and trabectedin. MATERIALS AND METHODS: From May 2007, 14 of the 27 centers that were asked to retrospectively review their databases had identified 44 advanced ASPS patients treated with pazopanib and/or trabectedin. Response was evaluated by Response Evaluation Criteria in Solid Tumors 1.1. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. RESULTS: Among 30 patients who received pazopanib, 18 were pretreated (13 with other antiangiogenics). Response was evaluable in 29/30 patients. Best responses were 1 complete response, 7 partial response (PR), 17 stable disease (SD), and 4 progressions. At a 19-month median follow-up, median PFS was 13.6 months (range: 1.6-32.2+), with 59% of patients progression-free at 1 year. Median OS was not reached.Among 23 patients treated with trabectedin, all were pretreated and evaluable for response. Best responses were 1 PR, 13 SD, and 9 progressions. At a 27-month median follow-up, median PFS was 3.7 months (range: 0.7-109), with 13% of patients progression-free at 1 year. Median OS was 9.1 months. CONCLUSION: The value of pazopanib in advanced ASPS is confirmed, with durable responses, whereas the value of trabectedin appears limited. These results are relevant to defining the best approach to advanced ASPS. IMPLICATIONS FOR PRACTICE: This retrospective study, conducted among the world reference centers for treatment of sarcoma, confirms the value of pazopanib in patients with advanced alveolar soft part sarcoma (ASPS), with dimensional and durable responses, whereas trabectedin shows a limited activity. Alveolar soft part sarcoma is resistant to conventional cytotoxic chemotherapy. Pazopanib and trabectedin are licensed for treatment of sarcoma from second line; in the lack of prospective clinical trials, these results are relevant to defining ASPS best management and strongly support initiatives aimed at obtaining the approval of pazopanib in the front line of the disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sarcoma Alveolar de Partes Moles/tratamento farmacológico , Adulto , Feminino , Seguimentos , Humanos , Indazóis , Masculino , Pessoa de Meia-Idade , Prognóstico , Pirimidinas/administração & dosagem , Estudos Retrospectivos , Sarcoma Alveolar de Partes Moles/patologia , Sulfonamidas/administração & dosagem , Taxa de Sobrevida , Trabectedina/administração & dosagemRESUMO
BACKGROUND AND OBJECTIVES: While treatment-induced tissue necrosis is a well-documented predictor of patient survival in malignant bone tumors, its prognostic value in soft tissue sarcomas is controversial. A prior study from our institution did not find a prognostic value to tumor necrosis. We analyze a more extensive database of high-grade soft tissue sarcomas treated with neoadjuvant chemotherapy, radiation therapy, or both to re-evaluate if the degree of tumor necrosis alone can be used as a predictive factor for local recurrence, metastasis, and disease-specific survival. METHODS: Two hundred and seven patients with high-grade extremity soft tissue sarcoma received neoadjuvant chemotherapy and/or radiation therapy and wide excision. Tumor treatment response was determined by histopathologic analysis, and patients were followed for local recurrence, metastasis, or death. RESULTS: Tumor necrosis ≥ 90% correlates with improved disease-free survival with univariate analysis, but this does not reach statistical significance on multivariate analysis. Age and tumor volume were found to be the only independent predictors of disease-free survival on multivariate analysis. CONCLUSIONS: There is insufficient evidence to support the use of necrosis to prognosticate survival and alter chemoradiation regimens in high grade soft tissue sarcomas of the extremity. Larger studies are needed to definitively address the prognostic value of necrosis. LEVEL OF EVIDENCE: Level II, Prognostic
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Terapia Neoadjuvante , Sarcoma/mortalidade , Sarcoma/patologia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Fatores Etários , Quimioterapia Adjuvante , Intervalo Livre de Doença , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Necrose , Recidiva Local de Neoplasia , Prognóstico , Radioterapia Adjuvante , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapiaRESUMO
Infections are major cause of morbidity and mortality in patients with multiple myeloma. Current treatment landscape of newly-diagnosed multiple myeloma includes different classes of drugs, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, all of which are characterized by specific risk and pattern of infectious complications. Additionally, autologous and allogeneic hematopoietic cell transplantation, widely used in the treatment of multiple myeloma, are complex procedures, carrying a significant risk of complications, and mainly infections. Finally, novel treatment modalities such as bispecific T-cell engagers and chimeric antigen receptor T-lymphocytes have been changing the paradigm of myeloma treatment in relapsed-refractory setting. These agents due to unique mechanism of action carry distinct pattern of infectious complications. In this review, an attempt has been made to summarize the incidence, risk factors, and patterns of infections during different stages of myeloma treatment including novel treatment modalities, and to provide evidence underlying the current concept of infectious disease prophylaxis in this category of patients.
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Transplante de Células-Tronco Hematopoéticas , Infecções , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções/etiologia , Infecções/terapia , Fatores de RiscoRESUMO
Lipoma arborescens, described as lipomatous infiltration and distention of synovial villi resulting in a frond-like appearance, most frequently affects the suprapatellar recess of the knee. While there have been reports of this entity involving the upper extremity joints, bursa, and tendon sheaths, we present the first reported case of lipoma arborescens isolated to the biceps tendon sheath. We describe imaging and histologic findings with clinical correlation.
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Lipoma/complicações , Lipoma/patologia , Dor de Ombro/diagnóstico , Dor de Ombro/etiologia , Tendinopatia/complicações , Tendinopatia/patologia , Tendões/patologia , Braço/patologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: Ocular melanoma is a rare disease with a strong predilection for the liver. Systemic and locoregional treatments for metastatic ocular melanoma have had disappointing results, with an average survival of 5-7 months. Resection and/or radiofrequency ablation (RFA) of liver lesions were attempted to improve the patient outcomes. METHODS: Eight patients with liver metastasis from ocular melanoma underwent surgery and/or RFA at the University of Southern California, University Hospital from 1 January 2001 to 31 December 2009. Their charts were retrospectively reviewed. RESULTS: All patients had undergone eye enucleation as the primary treatment. Four patients had all metastatic liver lesions addressed: one patient underwent left lateral segmentectomy and three patients had combinations of left lateral segmentectomies, wedge resections and RFA of two to four lesions. Two patients underwent surgical biopsies for diagnosis, one patient was unresectable and one patient underwent RFA of a dominant lesion. The median survival was 36 months. The median survival of patients who underwent surgery alone or in conjunction with RFA to address all liver lesions was 46 months. CONCLUSIONS: There are few reports of RFA for metastatic ocular melanoma. RFA of liver lesions in addition to resection can perhaps lead to improved survival and may play a critical role in the future management of this disease.
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Ablação por Cateter , Neoplasias Oculares/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Melanoma/secundário , Melanoma/cirurgia , Idoso , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Ewing sarcoma is a primitive neuroectodermal tumor which seldom presents with primary disease in people over age 40 and outside of the appendicular or axial skeleton. We examine a case of primary thoracic Ewing Sarcoma diagnosed initially by CT-guided biopsy in a woman at the age of 74 years. The disease progressed after initial combined modality therapy consisting of neoadjuvant chemotherapy, surgical resection, and adjuvant radiation therapy and two additional courses of multiagent chemotherapy. After relapse of her disease, subsequent second- and third-line systemic agents which included chemotherapy and targeted agents were given with disease stabilization achieved now over 30 months from initial diagnosis. To our knowledge, this is the first report of a primary pulmonary Ewing sarcoma diagnosed in a patient greater than 70 years of age in whom multiple remissions have been achieved with tolerable toxicities.
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PARP inhibitors have recently emerged as a maintenance treatment option for metastatic pancreatic cancer patients with germline BRCA mutations. However, the possibility of PARP-inhibitor use as a standalone-targeted therapy for patients with various homologous repair pathway alterations remains mostly undetermined. Here we report a clinical case of a 56-year-old woman with pancreatic ductal adenocarcinoma harboring a somatic PALB2 mutation. Following disease progression after 10 cycles of FOLFIRINOX chemotherapy and two cycles of second-line gemcitabine, she was switched to talazoparib and achieved a complete clinical response after 25 months of treatment. The patient remains alive without clinical or radiological signs of disease progression three years after the start of talazoparib with no targeted therapy-related toxicities. This case highlights the role of broad molecular profiling as a window of opportunity to achieve a durable response for selected pancreatic cancer patients while pinpointing our gaps in understanding the whole picture of management of these patients since a new puzzle element represented by PARP inhibitors was introduced to clinical practice.
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Solid pseudopapillary neoplasm (SPN) of the pancreas is an extremely rare tumor, associated with favorable prognosis and long-term survival in patients with advanced disease. However, limited data exist on systemic therapy for such patients. Herein, we present a case of a young woman with a history of SPN, who progressed after multiple surgical resections and chemotherapy regimens. The immunohistochemistry (IHC) showed overexpression of estrogen receptors (ER) and progesterone receptors (PR) in tumor tissue. The patient started to receive tamoxifen and showed a durable response to endocrine therapy.
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Bizarre parosteal osteochondromatous proliferation (BPOP) or Nora's lesion, is a rare benign surface-based bone lesion most commonly involving the tubular bones of hands and feet. We report an unusual case of BPOP affecting the distal ulna in a 22-year-old man who presented with a painless wrist mass following injury and was successfully treated with surgical resection. We focus on multi-modality imaging, histopathology, and differential diagnosis (including osteochondroma, florid reactive periostitis, myositis ossificans, and surface-type osteosarcoma), as well as a review of the literature regarding recent concepts on etiology and evolution, spectrum of imaging characteristics and diagnostic overlap, histopathology, as well as treatment options.
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Neoplasias Ósseas , Osteocondroma , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Proliferação de Células , Humanos , Masculino , Osteocondroma/diagnóstico por imagem , Osteocondroma/cirurgia , Ulna/diagnóstico por imagem , Ulna/cirurgia , Articulação do Punho , Adulto JovemRESUMO
BACKGROUND: This observational, retrospective effort across Europe, US, Australia, and Asia aimed to assess the activity of systemic therapies in EHE, an ultra-rare sarcoma, marked by WWTR1-CAMTA1 or YAP1-TFE3 fusions. METHODS: Twenty sarcoma reference centres contributed data. Patients with advanced EHE diagnosed from 2000 onwards and treated with systemic therapies, were selected. Local pathologic review and molecular confirmation were required. Radiological response was retrospectively assessed by local investigators according to RECIST. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. RESULTS: Overall, 73 patients were included; 21 had more than one treatment. Thirty-three patients received anthracyclines regimens, achieving 1 (3%) partial response (PR), 25 (76%) stable disease (SD), 7 (21%) progressive disease (PD). The median (m-) PFS and m-OS were 5.5 and 14.3 months respectively. Eleven patients received paclitaxel, achieving 1 (9%) PR, 6 (55%) SD, 4 (36%) PD. The m-PFS and m-OS were 2.9 and 18.6 months, respectively. Twelve patients received pazopanib, achieving 3 (25%) SD, 9 (75%) PD. The m-PFS and m-OS were.2.9 and 8.5 months, respectively. Fifteen patients received INF-α 2b, achieving 1 (7%) PR, 11 (73%) SD, 3 (20%) PD. The m-PFS and m-OS were 8.9 months and 64.3, respectively. Among 27 patients treated with other regimens, 1 PR (ifosfamide) and 9 SD (5 gemcitabine +docetaxel, 2 oral cyclophosphamide, 2 others) were reported. CONCLUSION: Systemic therapies available for advanced sarcomas have limited activity in EHE. The identification of new active compounds, especially for rapidly progressive cases, is acutely needed.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hemangioendotelioma Epitelioide/tratamento farmacológico , Sarcoma/tratamento farmacológico , Adulto , Feminino , Seguimentos , Hemangioendotelioma Epitelioide/patologia , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Taxa de SobrevidaRESUMO
BACKGROUND: Biopsy tissue can be obtained through a fine needle, a wider coring needle, or through an open surgical incision. Though much literature exists regarding the diagnostic yield of these techniques individually, none compare accuracy of diagnosis in the same mass. QUESTIONS/PURPOSES: We asked how the diagnostic accuracy of fine-needle aspiration, core biopsy, and open surgical biopsy compare in regard to identifying malignancy, establishing the exact diagnosis, and guiding the appropriate treatment of soft tissue masses. PATIENTS AND METHODS: We prospectively studied 57 patients with palpable extremity soft tissue masses, performing fine-needle aspiration, followed by core biopsy, followed by surgical biopsy of the same mass. RESULTS: Open surgical biopsy was 100% accurate on all accounts. With regard to determining malignancy, fine-needle aspiration and core biopsy had 79.17% and 79.2% sensitivity, 72.7% and 81.8% specificity, 67.9% and 76% positive predictive value, 82.8% and 84.4% negative predictive value, and an overall accuracy of 75.4% and 80.7%, respectively. In regard to determining exact diagnosis, fine-needle aspiration had a 33.3% accuracy and core biopsy had a 45.6% accuracy. With regard to eventual treatment, fine-needle aspiration was 38.6% accurate and core biopsy was 49.1% accurate. CONCLUSIONS: In soft tissue mass diagnosis, core biopsy is more accurate than fine-needle aspiration on all accounts, and open biopsy is more accurate than both in determining malignancy, establishing the exact diagnosis, and the guiding appropriate treatment.
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Biópsia por Agulha Fina , Biópsia/métodos , Neoplasias de Tecidos Moles/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , California , Extremidades , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/cirurgia , Adulto JovemRESUMO
BACKGROUND: Fascia-wrapped diced cartilage grafts have become a useful tool in modern rhinoplasty surgery. Unfortunately, fascial harvest is associated with donor site morbidity; therefore, a nonautologous alternative to fascia would be ideal. Decellularized porcine mesothelium (PM), Meso BioMatrix™, is an acellular scaffold that could potentially fill this need. To determine if PM could serve as an acceptable alternative, we histologically compared diced cartilage grafts wrapped in fascia versus PM. METHODS: Human rib cartilage and temporoparietal fascia were obtained under an IRB-approved protocol. Cartilage was diced into 0.5 mm pieces and implanted in subcutaneous pockets in nude rats. Implanted materials included cartilage alone, cartilage wrapped in fascia, cartilage wrapped in PM, fascia alone, or PM alone. Specimens were harvested at 8 weeks and stained with hematoxylin and eosin, Masson's trichrome, Safranin-O, and Verhoeff's stain to assess cartilage viability, architecture, and regenerative potential. RESULTS: Unwrapped diced cartilage showed the highest cartilage viability, but was associated with loss of contour and dispersion of the cartilage pieces. Meso BioMatrix-wrapped grafts maintained contour and cartilage pieces had not dispersed; however, there was a significantly lower number of nucleated lacunae and a greater amount of basophilia than both fascia-wrapped cartilage and unwrapped cartilage. There was no significant difference in cartilage resorption between fascia-wrapped cartilage and Meso BioMatrix-wrapped cartilage or in the proteoglycan or collagen content between all groups. CONCLUSION: Off-the-shelf decellularized PM was associated with lower cartilage viability than unprocessed fascial allograft. No cartilage piece dispersion, fibrosis, resorption, or a foreign body reaction to Meso BioMatrix was observed. PM, although not equivalent to autologous tissue, may be utilized to achieve acceptable clinical results and be a viable alternative that limits donor side morbidity. This experimental study supports further clinical investigation of this material in rhinoplasty procedures.
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Cartilagem/transplante , Rinoplastia/métodos , Animais , Epitélio , Fáscia , Humanos , Próteses e Implantes , Ratos , Ratos Nus , Suínos , Transplante AutólogoRESUMO
BACKGROUND: Carpometacarpal joint osteoarthritis affects 8 to 12 percent of the general population. Surgical management provides symptomatic relief for 78 percent of patients who fail conservative therapy, but little consensus exists regarding which surgical procedure provides superior patient outcomes. Recent human trials substituted exogenous acellular dermal matrices in the bone space, but there are no quantitative histologic data on the outcome of acellular dermal matrices in this environment. The authors aimed to quantify the revascularization and recellularization of acellular dermal matrices in the joint space using a rabbit model. METHODS: Bilateral lunate carpal bones were surgically removed in New Zealand rabbits. Acellular dermal matrix and autologous tissue were implanted in place of the lunate of the right and left wrists, respectively. Acellular dermal matrix was also implanted subcutaneously as a nonjoint control. Histologic and immunofluorescence analysis was performed after collection at 0, 6, and 12 weeks. RESULTS: Quantitative analysis of anti-α-smooth muscle actin and CD31 immunofluorescence revealed a sequential and comparable increase of vascular lumens in joint space and subcutaneous acellular dermal matrices. In contrast, autologous tissue implanted in the joint space did not have a similar increase in α-smooth muscle actin-positive or CD31-positive lumens. Semiquantitative analysis revealed increased cellularity in both autologous and acellular dermal matrix wrist implants at each time point, whereas average cellularity of subcutaneous acellular dermal matrix peaked at 6 weeks and regressed by 12 weeks. Trichrome and Sirius red staining revealed abundant collagen at all time points. CONCLUSION: The trapeziectomy joint space supports both cellular and vascular ingrowth into human acellular dermal matrix.
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Derme Acelular , Artroplastia/métodos , Articulações Carpometacarpais/cirurgia , Regeneração Tecidual Guiada/métodos , Osso Semilunar/cirurgia , Trapézio/cirurgia , Animais , Humanos , Coelhos , Distribuição AleatóriaRESUMO
Importance: Epithelioid sarcoma (ES) is an exceedingly rare malignant neoplasm with distinctive pathologic, molecular, and clinical features as well as the potential to respond to new targeted drugs. Little is known on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in this disease. Objective: To report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with advanced ES. Design, Setting, and Participants: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis of patients with locally advanced/metastatic ES diagnosed between 1990 and 2016. Local pathological review was performed in all cases to confirm diagnosis according to most recent criteria. Exposures: All patients included in the study received anthracycline-based regimens, gemcitabine-based regimens, or pazopanib. Main Outcome and Measures: Response was assessed by RECIST. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. Classic and proximal subtypes were defined based on morphology (according to 2013 World Health Organization guidelines). Results: Overall, 115 patients were included, 80 (70%) were men and 35 (30%) were women, with a median age of 32 years (range, 15-77 years). Of the 115 patients with ES, 85 were treated with anthracycline-based regimens, 41 with gemcitabine-based regimens, and 18 with pazopanib. Twenty-four received more than 1 treatment. Median follow-up was 34 months. Response rate for anthracycline-based regimens was 22%, with a median PFS of 6 months. One complete response (CR) was reported. A trend toward a higher response rate was noticed in morphological proximal type (26%) vs classic type (19%) and in proximal vs distal primary site (26% vs 18%). The response rate for gemcitabine-based regimens was 27%, with 2 CR and a median PFS of 4 months. In this group, a trend toward a higher response rate was reported in classic vs proximal morphological type (30% vs 22%) and in distal vs proximal primary site (40% vs 14%). In the pazopanib group, no objective responses were seen, and median PFS was 3 months. Conclusions and Relevance: This is the largest retrospective series of systemic therapy in ES. We confirm a moderate activity of anthracycline-based and gemcitabine-based regimens in ES, with a similar response rate and PFS in both groups. The value of pazopanib was low. These data may serve as a benchmark for trials of novel agents in ES.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sarcoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Antraciclinas/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Indazóis , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pirimidinas/administração & dosagem , Indução de Remissão , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Sulfonamidas/administração & dosagem , Adulto Jovem , GencitabinaRESUMO
We report the first case of calcifying fibrous pseudotumor (CFPT) to arise in the posterior mediastinum with encapsulation of the thoracic duct. This exceedingly rare lesion was incidentally discovered in an asymptomatic young woman and treated with surgical resection, requiring ligation and excision of the thoracic duct. There has been no evidence of tumor recurrence or postoperative complication.
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Doenças do Mediastino/patologia , Ducto Torácico/patologia , Adulto , Calcinose/patologia , Feminino , Fibrose/patologia , Humanos , Imageamento por Ressonância Magnética , Doenças do Mediastino/diagnóstico por imagem , Mediastino/patologia , Ducto Torácico/cirurgia , Tomografia Computadorizada por Raios XRESUMO
AIMS: To evaluate an immunohistochemical panel differentiating endometrial stromal sarcoma (ESS) from uterine leiomyosarcoma (ULMS) and leiomyoma (LM). METHODS: 94 cases (28 ESS, 41 ULMS, 25 LM) were retrieved and arrayed. 10 immunomarkers (estrogen receptor (ER), progesterone receptor (PR), CD10, smooth muscle actin, desmin, h-caldesmon, transgelin, GEM, ASC1, stathmin1) were used. A predictive model was constructed and examined by receiver operating characteristics curve analysis to determine area under the curve (AUC). RESULTS: The combination of ER(+)/PR(+)/CD10(+)/GEM(-)/h-caldesmon(-)/transgelin(-) can predict ESS versus ULMS with AUC predictive value of 0.872 (95% CI 0.784 to 0.961, p<0.0001). The combination of ER(+)/PR(+)/CD10(+)/h-caldesmon(-)/transgelin(-) can predict low grade (LG) ESS from 'LG' ULMS with AUC predictive value of 0.914 (95% CI 0.832 to 0.995, p<0.0001). Finally, ULMS and ESS, including the LGs, were more likely to be stathmin1(+) than LM. CONCLUSIONS: Due to the different clinical course and management, adding novel antibodies (GEM, transgelin) to the well established immunohistochemistry panel seemed to be useful in distinguishing ESS from ULMS and LG ESS from 'LG' ULMS. Finally, stathmin1 expression could be of value in differentiating LM from uterine sarcomas.
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Biomarcadores Tumorais/análise , Neoplasias do Endométrio/diagnóstico , Leiomioma/diagnóstico , Leiomiossarcoma/diagnóstico , Sarcoma do Estroma Endometrial/diagnóstico , Neoplasias Uterinas/diagnóstico , Área Sob a Curva , Diagnóstico Diferencial , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Leiomioma/metabolismo , Leiomiossarcoma/metabolismo , Curva ROC , Sarcoma do Estroma Endometrial/metabolismo , Análise Serial de Tecidos , Neoplasias Uterinas/metabolismoRESUMO
IMPORTANCE: Standard therapy for advanced soft-tissue sarcoma has not changed substantially in decades, and patient prognosis remains poor. Aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, showed clinical activity against advanced soft-tissue sarcoma in phase 1 studies. OBJECTIVE: To evaluate efficacy and safety of aldoxorubicin vs doxorubicin in patients with advanced soft-tissue sarcoma. DESIGN, SETTING, AND PARTICIPANTS: International, multicenter, phase 2b, open-label, randomized study at general community practices, private practices, or institutional practices. Between August 2012 and December 2013, 140 patients with previously untreated locally advanced, unresectable, or metastatic soft-tissue sarcoma were screened. INTERVENTIONS: Randomization (2:1) to aldoxorubicin 350 mg/m2 (dose equivalent to doxorubicin 260 mg/m2) or doxorubicin 75 mg/m2, administered once every 3 weeks for up to 6 cycles. MAIN OUTCOMES AND MEASURES: Primary end point was progression-free survival. Secondary end points were 6-month progression-free survival, overall survival, tumor response rate, and safety. All efficacy end points were evaluated by independent and local review. RESULTS: A total of 126 patients were randomized, and 123 received aldoxorubicin (n = 83) or doxorubicin (n = 40). Median (range) patient age was 54.0 (21-77 years); 42 (34%) had leiomyosarcoma. By independent review, median progression-free survival was significantly improved (5.6 [95% CI, 3.0-8.1] vs 2.7 [95% CI, 1.6-4.3] months; P = .02) with aldoxorubicin compared with doxorubicin, as was the rate of 6-month progression-free survival (46% and 23%; P = .02). Median overall survival was 15.8 (95% CI, 13.0 to not available) months with aldoxorubicin and 14.3 (95% CI, 8.6-20.6) months with doxorubicin (P = .21). Overall tumor response rate (by Response Evaluation Criteria in Solid Tumors, version 1.1) by independent review was higher with aldoxorubicin than with doxorubicin (25% [20 patients, all partial response] vs 0%). Grade 3 or 4 neutropenia was more frequent with aldoxorubicin than with doxorubicin (24 [29%] vs 5 [12%]), but not grade 3 or 4 febrile neutropenia (12 [14%] vs 7 [18%]). No acute cardiotoxic effects were observed with either treatment, although left ventricular ejection fraction less than 50% occurred in 3 of 40 patients receiving doxorubicin. CONCLUSIONS AND RELEVANCE: Single-agent aldoxorubicin therapy showed superior efficacy over doxorubicin by prolonging progression-free survival and improving rates of 6-month progression-free survival and tumor response. Aldoxorubicin therapy exhibited manageable adverse effects, without unexpected events, and without evidence of acute cardiotoxicity. Further investigation of aldoxorubicin therapy in advanced soft-tissue sarcoma is warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01514188.