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1.
Int J Cancer ; 152(4): 761-768, 2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36196483

RESUMEN

Trabectedin is a marine-derived anticancer drug approved for the treatment of patients with advanced soft-tissue sarcomas (STS). Here, we aimed to analyze its use in a large cohort of STS patients treated in Italy in a real-world setting. Data on STS patients treated with trabectedin in Italy were prospectively collected from January 2013 to December 2019 by the national drug regulator, the Italian Medicines Agency (AIFA). Time-to-off-treatment (TToT) was defined as the time between the initial prescription of trabectedin and the date of treatment discontinuation for any cause. The impact of the different baseline covariates, including the initial prescribed dose of trabectedin, on TToT was evaluated using an accelerated failure time (AFT) models with log-logistic distribution. In total, we analyzed data from 2633 sarcoma patients and 14 950 individual cycles of trabectedin. The median number of cycles of trabectedin received per patient was 3 (interquartile range 2-7). The labeled 1.5 mg/sqm dose was used in 27.3% of all first prescriptions. Overall, the median TToT was 93 days. In the final AFT model, the variables significantly associated to longer TToT were female gender (+13% increase in TToT); ECOG performance status 0 (+50%); histological diagnosis of leiomyosarcoma (+22%), well-differentiated/dedifferentiated liposarcoma (+72%) or myxoid liposarcoma (+61%); receiving treatment in a high-volume center (+23%). In this large real-world cohort of STS patients treated with trabectedin, our findings support the use of trabectedin in STS patients, in particular in leiomyosarcoma and liposarcoma patients, and highlight the role of treatment center volume in their management.


Asunto(s)
Leiomiosarcoma , Liposarcoma Mixoide , Sarcoma , Neoplasias de los Tejidos Blandos , Tetrahidroisoquinolinas , Humanos , Adulto , Femenino , Masculino , Trabectedina/efectos adversos , Leiomiosarcoma/patología , Antineoplásicos Alquilantes/uso terapéutico , Dioxoles/uso terapéutico , Tetrahidroisoquinolinas/uso terapéutico , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Liposarcoma Mixoide/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Sistema de Registros
2.
Cancer ; 128(7): 1439-1448, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35026050

RESUMEN

BACKGROUND: To report on a retrospective case-series analysis of weekly cisplatin (wCDDP) as a single agent or combined with imatinib (wCDDP/I) in patients with advanced chordoma treated within the Italian Rare Cancer Network. METHODS: Adult patients with a diagnosis of advanced, brachyury-positive chordoma, treated from April 2007 to October 2020 with wCDDP or wCDDP/I were retrospectively identified. Imatinib was withheld at the same time as wCDDP. Response according to Response Evaluation Criteria in Solid Tumors, overall survival (OS), and progression-free survival (PFS) were analyzed. RESULTS: Thirty-three consecutive patients were identified (wCDDP as front-line n = 8 [24.2%]; wCDDP as a further line n = 25 [75.8%]; prior imatinib n = 25 [75.8%]; evidence of progression before starting wCDDP n = 33). Of 32 patients evaluable for response (wCDDP, n = 22 [68.8%]; wCDDP/I, n = 10 [31.3%]), best response was stable disease (SD) in 27 patients (84.3%) and progression in 5 patients (15.6%). At a median follow-up of 54 months, the median OS (m-OS) was 30.3 months (interquartile range [IQR], 18.1-56.6), the m-PFS was 8.0 months (IQR, 5.1-17.0), the 6-month PFS rate was 65.2%, and the 12-month PFS rate was 30.3%. Of 22 patients who received wCDDP, the best response was SD in 18 patients (81.8%) and progression in 4 patients (18.2%), and the m-PFS was 8.0 months (IQR, 5.1-17.0 months). Of 10 patients who received treatment with wCDDP/I, the best response was SD in 9 patients (90%) and progression in 1 patient (10%), and the m-PFS was 9.3 months (IQR, 4.9-26.5 months). CONCLUSIONS: This series suggests that wCDDP, both as a single agent and combined with imatinib, has antitumor activity in chordoma. Although no dimensional responses were observed, 65% and 30% of previously progressive patients were progression-free at 6 and 12 months, respectively. A prospective study is warranted.


Asunto(s)
Cordoma , Cisplatino , Adulto , Cordoma/tratamiento farmacológico , Supervivencia sin Enfermedad , Humanos , Mesilato de Imatinib/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento
3.
Cancer ; 128(10): 1958-1966, 2022 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-35201621

RESUMEN

BACKGROUND: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. METHODS: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m2 /d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp- patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. RESULTS: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp-, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp- patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). CONCLUSIONS: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/uso terapéutico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Niño , Supervivencia sin Enfermedad , Extremidades/patología , Humanos , Ifosfamida , Italia , Metotrexato , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Osteosarcoma/cirugía , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
4.
Eur J Public Health ; 32(6): 852-857, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36374643

RESUMEN

BACKGROUND: As a system of European Reference Networks (ERNs) emerges, the differences in quality of care for patients with rare cancers may increase at national level. We aimed to elucidate the processes and healthcare planning principles through which the reference centres (RCs) for rare cancers are embedded in national health systems. METHODS: We used a multiple case-study design based on the experiences of Czechia, Finland, France, Italy, Lithuania and Spain. Using sarcoma as an example of rare cancer, 52 semi-structured interviews were conducted during on-site visits, including a multidisciplinary group of professionals, Ministry of Health professionals, patient representatives and European policymakers. RESULTS: The comparative analysis showed substantial heterogeneity in the processes for formalizing RCs' status and in their levels of integration in the different health systems, but two models (centre-based and the network-based) can be envisaged at national level. RCs for rare cancers were legally established only in France and Spain. Expert clinicians cooperate in a structured way, using network mechanisms, in France and Italy, and these countries, plus Finland and Lithuania, had a referral system to facilitate patients' access from non-expert centres to RCs. Seven key healthcare planning principles in instituting RCs at the national level were identified. CONCLUSIONS: The conditions governing patient access to treatment centres-whether RCs or not-are decided at the national level. It is advisable to progressively align the European and national levels so that the RCs that participate in the ERNs also play a significant role at the national level.


Asunto(s)
Neoplasias , Humanos , España , Italia , Derivación y Consulta , Francia
5.
BMC Med Ethics ; 23(1): 67, 2022 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-35773683

RESUMEN

BACKGROUND: Clinical Ethics Support Services (CESS) have been established to support healthcare professionals in addressing ethically sensitive issues in clinical practice and, in many countries, they are under development. In the context of growing CESS, exploring how healthcare professionals experience and address clinical ethics issues in their daily practice represents a fundamental step to understand their potential needs. This is even more relevant in the context of extremely sensitive diseases, such as cancer. On this basis, we carried out a qualitative study conducting in-depth semi-structured interviews with stakeholders of a major comprehensive cancer centre in Italy, with the twofold aim of investigating what ethical issues arise in the context of clinical oncology and how they are addressed, as well as stakeholders' expectations about a potential CESS to be implemented within the Institution. METHODS: The study was conducted within the theoretical framework of Grounded Theory. Participants were healthcare professionals and other key stakeholders working within the cancer centre. The semi-structured interview aimed at exploring common ethical aspects of oncology, investigating stakeholders' professional experience in dealing with clinical ethics issues, their expectations and requests regarding ethics support services. Transcripts of the interviews were coded and analysed according to the principles of Grounded Theory. RESULTS: Twenty-one stakeholders were interviewed. Our analysis showed a wide consensus on the identification of ethically relevant issues, above all those concerning communication, end-of-life, and resource allocation. The absence of institutional tools or strategies to address and manage ethical issues at the patient bedside emerged, and this is reflected in the widespread request for their development in the future. The ideal support service should be fast and flexible in order to adapt to different needs and clinical cases. CONCLUSIONS: The interviewees showed a limited degree of 'ethical awareness': despite having reported many issues in clinical practice, they could hardly identify and describe the ethical aspects, while  complaining about a lack of ethical resources in their management. To build a truly effective support service, it therefore seems appropriate to take such context into consideration and address the emerged needs. Ethical sensitivity seems to be key and it becomes even more relevant in critical clinical areas, such as the therapeutic pathways of terminally ill patients.


Asunto(s)
Ética Clínica , Motivación , Personal de Salud , Humanos , Oncología Médica , Investigación Cualitativa
6.
Genomics ; 113(5): 3439-3448, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34339817

RESUMEN

Myxoid liposarcoma (MLPS) is a rare soft-tissue sarcoma characterised by the expression of FUS-DDIT3 chimera. Trabectedin has shown significant clinical anti-tumour activity against MLPS. To characterise the molecular mechanism of trabectedin sensitivity and of resistance against it, we integrated genomic and transcriptomic data from treated mice bearing ML017 or ML017/ET, two patient-derived MLPS xenograft models, sensitive to and resistant against trabectedin, respectively. Longitudinal RNA-Seq analysis of ML017 showed that trabectedin acts mainly as a transcriptional regulator: 15 days after the third dose trabectedin modulates the transcription of 4883 genes involved in processes that sustain adipocyte differentiation. No such differences were observed in ML017/ET. Genomic analysis showed that prolonged treatment causes losses in 4p15.2, 4p16.3 and 17q21.3 cytobands leading to acquired-resistance against the drug. The results dissect the complex mechanism of action of trabectedin and provide the basis for novel combinatorial approaches for the treatment of MLPS that could overcome drug-resistance.


Asunto(s)
Liposarcoma Mixoide , Adulto , Animales , Modelos Animales de Enfermedad , Humanos , Liposarcoma Mixoide/tratamiento farmacológico , Liposarcoma Mixoide/genética , Liposarcoma Mixoide/patología , Ratones , Trabectedina/uso terapéutico
7.
Cancer ; 127(4): 569-576, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33107985

RESUMEN

BACKGROUND: The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network. METHODS: From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method. RESULTS: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction. CONCLUSIONS: The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Hemangioendotelioma Epitelioide/tratamiento farmacológico , Péptidos y Proteínas de Señalización Intracelular/genética , Sirolimus/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Progresión de la Enfermedad , Femenino , Hemangioendotelioma Epitelioide/epidemiología , Hemangioendotelioma Epitelioide/genética , Hemangioendotelioma Epitelioide/patología , Humanos , Italia/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Sirolimus/efectos adversos , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ
8.
Cancer ; 127(16): 2934-2942, 2021 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-33910263

RESUMEN

BACKGROUND: Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies. METHODS: The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan. RESULTS: It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately ≤1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types. CONCLUSIONS: Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.


Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Tejido Conectivo/patología , Consenso , Humanos , Incidencia , Estudios Prospectivos , Sarcoma/diagnóstico , Sarcoma/epidemiología , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/epidemiología
9.
Lancet Oncol ; 21(3): 456-466, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32066540

RESUMEN

BACKGROUND: Solitary fibrous tumour is an ultra-rare sarcoma, which encompasses different clinicopathological subgroups. The dedifferentiated subgroup shows an aggressive course with resistance to pazopanib, whereas in the malignant subgroup, pazopanib shows higher activity than in previous studies with chemotherapy. We designed a trial to test pazopanib activity in two different cohorts of solitary fibrous tumour: the malignant-dedifferentiated cohort, which was previously published, and the typical cohort, which is presented here. METHODS: In this single-arm, phase 2 trial, adult patients (aged ≥18 years) diagnosed with confirmed metastatic or unresectable typical solitary fibrous tumour of any location, who had progressed in the previous 6 months (by Choi criteria or Response Evaluation Criteria in Solid Tumors [RECIST]) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were enrolled at 11 tertiary hospitals in Italy, France, and Spain. Patients received pazopanib 800 mg once daily, taken orally, until progression, unacceptable toxicity, withdrawal of consent, non-compliance, or a delay in pazopanib administration of longer than 3 weeks. The primary endpoint was proportion of patients achieving an overall response measured by Choi criteria in patients who received at least 1 month of treatment with at least one radiological assessment. All patients who received at least one dose of the study drug were included in the safety analyses. This study is registered in ClinicalTrials.gov, NCT02066285, and with the European Clinical Trials Database, EudraCT 2013-005456-15. FINDINGS: From June 26, 2014, to Dec 13, 2018, of 40 patients who were assessed, 34 patients were enrolled and 31 patients were included in the response analysis. Median follow-up was 18 months (IQR 14-34), and 18 (58%) of 31 patients had a partial response, 12 (39%) had stable disease, and one (3%) showed progressive disease according to Choi criteria and central review. The proportion of overall response based on Choi criteria was 58% (95% CI 34-69). There were no deaths caused by toxicity, and the most frequent adverse events were diarrhoea (18 [53%] of 34 patients), fatigue (17 [50%]), and hypertension (17 [50%]). INTERPRETATION: To our knowledge, this is the first prospective trial of pazopanib for advanced typical solitary fibrous tumour. The manageable toxicity and activity shown by pazopanib in this cohort suggest that this drug could be considered as first-line treatment for advanced typical solitary fibrous tumour. FUNDING: Spanish Group for Research on Sarcomas (GEIS), Italian Sarcoma Group (ISG), French Sarcoma Group (FSG), GlaxoSmithKline, and Novartis.


Asunto(s)
Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Tumores Fibrosos Solitarios/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Anciano , Femenino , Estudios de Seguimiento , Humanos , Indazoles , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Prospectivos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tumores Fibrosos Solitarios/patología , Tasa de Supervivencia
10.
Cancer ; 126(1): 98-104, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31536651

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Cardíacas/tratamiento farmacológico , Sarcoma/tratamiento farmacológico , Túnica Íntima/efectos de los fármacos , Adulto , Anciano , Antraciclinas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cardiotoxicidad , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/patología , Humanos , Indazoles , Masculino , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Proteínas Proto-Oncogénicas c-mdm2/genética , Pirimidinas/administración & dosificación , Sarcoma/genética , Sarcoma/patología , Sulfonamidas/administración & dosificación , Resultado del Tratamiento , Túnica Íntima/patología , Gemcitabina
11.
J Pathol ; 249(1): 90-101, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31020999

RESUMEN

Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma histotype with uncertain differentiation. EMC is hallmarked by the rearrangement of the NR4A3 gene, which in most cases fuses with EWSR1 or TAF15. TAF15-translocated EMC seem to feature a more aggressive course compared to EWSR1-positive EMCs, but whether the type of NR4A3 chimera impinges upon EMC biology is still largely undefined. To gain insights on this issue, a series of EMC samples (7 EWSR1-NR4A3 and 5 TAF15-NR4A3) were transcriptionally profiled. Our study unveiled that the two EMC variants display a distinct transcriptional profile and that the axon guidance pathway is a major discriminant. In particular, class 4-6 semaphorins and axonal guidance cues endowed with pro-tumorigenic activity were more expressed in TAF15-NR4A3 tumors; vice versa, class 3 semaphorins, considered to convey growth inhibitory signals, were more abundant in EWSR1-NR4A3 EMC. Intriguingly, the dichotomy in axon guidance signaling observed in the two tumor variants was recapitulated in in vitro cell models engineered to ectopically express EWSR1-NR4A3 or TAF15-NR4A3. Moreover, TAF15-NR4A3 cells displayed a more pronounced tumorigenic potential, as assessed by anchorage-independent growth. Overall, our results indicate that the type of NR4A3 chimera dictates an axon guidance switch and impacts on tumor cell biology. These findings may provide a framework for interpretation of the different clinical-pathological features of the two EMC variants and lay down the bases for the development of novel patient stratification criteria and therapeutic approaches. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Asunto(s)
Orientación del Axón , Axones/metabolismo , Biomarcadores de Tumor/metabolismo , Condrosarcoma/metabolismo , Proteínas de Unión al ADN/metabolismo , Neoplasias de los Tejidos Conjuntivo y Blando/metabolismo , Proteínas de Fusión Oncogénica/metabolismo , Receptores de Esteroides/metabolismo , Receptores de Hormona Tiroidea/metabolismo , Factores Asociados con la Proteína de Unión a TATA/metabolismo , Transactivadores/metabolismo , Adulto , Anciano , Axones/patología , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Condrosarcoma/genética , Condrosarcoma/patología , Proteínas de Unión al ADN/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Fusión Génica , Predisposición Genética a la Enfermedad , Humanos , Italia , Masculino , Persona de Mediana Edad , Neoplasias de los Tejidos Conjuntivo y Blando/genética , Neoplasias de los Tejidos Conjuntivo y Blando/patología , Proteínas de Fusión Oncogénica/genética , Fenotipo , Receptores de Esteroides/genética , Receptores de Hormona Tiroidea/genética , Semaforinas/genética , Semaforinas/metabolismo , Factores Asociados con la Proteína de Unión a TATA/genética , Transactivadores/genética , Transcriptoma , Translocación Genética
12.
Lancet Oncol ; 20(1): 134-144, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30578023

RESUMEN

BACKGROUND: A solitary fibrous tumour is a rare soft-tissue tumour with three clinicopathological variants: typical, malignant, and dedifferentiated. Preclinical experiments and retrospective studies have shown different sensitivities of solitary fibrous tumour to chemotherapy and antiangiogenics. We therefore designed a trial to assess the activity of pazopanib in a cohort of patients with malignant or dedifferentiated solitary fibrous tumour. The clinical and translational results are presented here. METHODS: In this single-arm, phase 2 trial, adult patients (aged ≥ 18 years) with histologically confirmed metastatic or unresectable malignant or dedifferentiated solitary fibrous tumour at any location, who had progressed (by RECIST and Choi criteria) in the previous 6 months and had an ECOG performance status of 0-2, were enrolled at 16 third-level hospitals with expertise in sarcoma care in Spain, Italy, and France. Patients received pazopanib 800 mg once daily, taken orally without food, at least 1 h before or 2 h after a meal, until progression or intolerance. The primary endpoint of the study was overall response measured by Choi criteria in the subset of the intention-to-treat population (patients who received at least 1 month of treatment with at least one radiological assessment). All patients who received at least one dose of the study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02066285, and with the European Clinical Trials Database, EudraCT number 2013-005456-15. FINDINGS: From June 26, 2014, to Nov 24, 2016, of 40 patients assessed, 36 were enrolled (34 with malignant solitary fibrous tumour and two with dedifferentiated solitary fibrous tumour). Median follow-up was 27 months (IQR 16-31). Based on central radiology review, 18 (51%) of 35 evaluable patients had partial responses, nine (26%) had stable disease, and eight (23%) had progressive disease according to Choi criteria. Further enrolment of patients with dedifferentiated solitary fibrous tumour was stopped after detection of early and fast progressions in a planned interim analysis. 51% (95% CI 34-69) of 35 patients achieved an overall response according to Choi criteria. Ten (29%) of 35 patients died. There were no deaths related to adverse events and the most frequent grade 3 or higher adverse events were hypertension (11 [31%] of 36 patients), neutropenia (four [11%]), increased concentrations of alanine aminotransferase (four [11%]), and increased concentrations of bilirubin (three [8%]). INTERPRETATION: To our knowledge, this is the first trial of pazopanib for treatment of malignant solitary fibrous tumour showing activity in this patient group. The manageable toxicity profile and the activity shown by pazopanib suggests that this drug could be an option for systemic treatment of advanced malignant solitary fibrous tumour, and provides a benchmark for future trials. FUNDING: Spanish Group for Research on Sarcomas (GEIS), Italian Sarcoma Group (ISG), French Sarcoma Group (FSG), GlaxoSmithKline, and Novartis.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Tumores Fibrosos Solitarios/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Femenino , Humanos , Indazoles , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Neoplasias de los Tejidos Blandos/patología , Tumores Fibrosos Solitarios/patología , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Análisis de Supervivencia
13.
Ann Surg Oncol ; 26(11): 3535-3541, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31313035

RESUMEN

INTRODUCTION: Retroperitoneal sarcomas (RPS) lie in the retroperitoneal space and are covered by a peritoneal layer. However, some RPS have an intraperitoneal component (IPC), which invades into the peritoneal cavity. The significance of such a clinical presentation is unknown. METHODS: We retrospectively analyzed our prospectively maintained institutional database of RPS, along with intraoperative photographs taken to document the primary tumor extent at laparotomy. The effects of IPC on overall survival (OS), local recurrence (LR), and distant metastasis (DM) were evaluated. RESULTS: IPC was present in 81 of 493 patients (16.4%). It was significantly associated with older age (64 vs. 59, p = 0.008), gender (67% vs. 33% males, p = 0.005), and multifocality (11.1% vs. 0.5%; p < 0.0001). IPC was not associated with size or any specific histology, while it showed a weak association with high malignancy grade (40.7% vs. 28.6% in G3 tumors; p = 0.076). At a median follow-up of 32 months IPC was associated with worse 5-year OS (54% vs. 74%, p < 0.001) and crude cumulative incidence (CCI) of LR (5-year CCI of LR: 38% vs. 19%, p = 0.001), but not to CCI of DM. However, multivariable models showed that IPC's effect on OS (HR: 1.52, 95% CI 0.92-2.49, p = 0.1) and LR (HR: 1.34, 95% CI 0.8-2.26, p = 0.27) could be sufficiently explained by other known risk factors. CONCLUSIONS: IPC is associated with increased LR and decreased survival. However, the effect of IPC on prognosis is predominantly related to other tumor characteristics already included in published nomograms. IPC should not be a contraindication to a proper surgical resection.


Asunto(s)
Recurrencia Local de Neoplasia/patología , Neoplasias Peritoneales/patología , Neoplasias Retroperitoneales/patología , Sarcoma/patología , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/cirugía , Neoplasias Peritoneales/cirugía , Pronóstico , Estudios Prospectivos , Neoplasias Retroperitoneales/cirugía , Estudios Retrospectivos , Factores de Riesgo , Sarcoma/cirugía , Tasa de Supervivencia
14.
J Surg Oncol ; 120(2): 256-261, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31066052

RESUMEN

BACKGROUND: The aim was to describe complicated tumor response (CTR) to tyrosine-kinase inhibitors (TKI) in gastrointestinal stromal tumors (GIST) patients. METHODS: From 2001 to 2017, data from patients with metastatic (group A) or locally advanced (group B) GIST who received TKI at our institution were collected. We defined CTR as bleeding, abscess, or perforation as surgical complications of TKI. Patients who had progressive disease were excluded. Clinical characteristics were assessed, and time of occurrence and mortality rate recorded. RESULTS: Among 470 patients, 30 developed CTR (6.4%), 26 in group A (6.8%) and four in group B (4.5%) (P = 0.43). Bleeding, abscess, and perforation, respectively, were observed in 17 (56.7%), 8 (26.7%), and 5 (16.7%) patients. A conservative approach was possible in 17 (56.7%) cases; four (13.3%) patients received percutaneous drainage, while nine (30%) underwent emergency surgery. The overall rate of mortality was 13.3%. CTR occurred after 1.6 months (median time) from the imatinib mesylate onset in group B and 14 months in group A. CONCLUSIONS: While the risk of CTR in early metastatic patients is virtually nil, patients with locally advanced disease should be monitored carefully. CTR as a consequence of TKI therapy do not prevent patients receiving a potentially curative surgery.


Asunto(s)
Neoplasias Gastrointestinales/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Mesilato de Imatinib/efectos adversos , Complicaciones Posoperatorias/terapia , Inhibidores de Proteínas Quinasas/efectos adversos , Sunitinib/efectos adversos , Antineoplásicos/efectos adversos , Femenino , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos
15.
J Surg Oncol ; 119(3): 318-323, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30554403

RESUMEN

BACKGROUND: Patients with retroperitoneal sarcoma (RPSs) who undergo primary inadequate surgery before referral to specialized sarcoma centers may be considered for completion surgery (CS). We wanted to compare the outcome of these patients to those who underwent primary adequate surgery (PAS) at a single referral institution. METHODS: We identified 34 patients who were referred for CS after primary inadequate surgery. Using a propensity score based on validated RPS outcome risk factors, we managed to match 28 patients to patients with PAS. RESULTS: Median time lag between the first and second operation in CS patients was 5 months (2-15). Surgical extent was similar among groups (median number of organs resected = 3; P = 0.08), and macroscopically complete excision was achieved in all patients. The rate of severe complications did not differ between the groups (1 of 28 vs 3 of 28, respectively; P = 0.35) and no perioperative mortality was documented. Median follow-up was 43.5 months. Patients in the CS group had similar local recurrence-free survival (mean, 92.1 ± 9.7 vs 99.8 ± 12.4; P = 0.85) and relapse-free survival (mean, 88.7 ± 9.8 vs 80.9 ± 12.3; P = 0.3) to those with PAS. CONCLUSIONS: CS has short- and long-term outcomes comparable to PAS. While primary surgery should always be carried out at a referral institution, some of the patients who undergo an initial incomplete resection at a non specialist center can still be offered a salvage procedure at a referral institution with comparable results.


Asunto(s)
Recurrencia Local de Neoplasia/mortalidad , Neoplasia Residual/mortalidad , Puntaje de Propensión , Reoperación/mortalidad , Neoplasias Retroperitoneales/mortalidad , Terapia Recuperativa , Sarcoma/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasia Residual/patología , Neoplasia Residual/cirugía , Pronóstico , Estudios Prospectivos , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/cirugía , Sarcoma/patología , Sarcoma/cirugía , Tasa de Supervivencia
16.
Cancer ; 124(20): 4056-4063, 2018 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-30216418

RESUMEN

BACKGROUND: We present the results of an academic phase 2 study on imatinib plus everolimus in patients who have progressive advanced chordoma. METHODS: In January 2011, 43 adult chordoma patients were enrolled in the study and received imatinib 400 mg/day and everolimus 2.5 mg/day until progression or limiting toxicity. Eligible patients had progressed in the 6 months before study entry. PDGFRB, S6, and 4EBP1 expression and phosphorylation were evaluated by way of immunohistochemistry and/or western blotting. The primary endpoint was the overall response rate (ORR) according to Choi criteria. Secondary endpoints were RECIST 1.1 response, progression-free survival (PFS), overall survival (OS), correlation between S6/4EBP1 phosphorylation and response. RESULTS: Thirteen of 43 patients were pretreated with imatinib. Among 40 of the 43 patients who were evaluable by Choi criteria, the best responses were 9 with partial response (ORR, 20.9%), 24 with stable disease (SD) (ORR, 55.8%), and 7 with progressive disease (ORR, 16.3%). Forty-two patients were evaluable by RECIST criteria, with 1 partial response (ORR, 2.3%), 37 stable disease (ORR, 86%), and 4 progressive disease (ORR, 9.3%). The median PFS according to Choi criteria was 11.5 months (range, 4.6-17.6 months), and 58.8% and 48.1% of patients were progression-free at 9 and 12 months, respectively. The median PFS by RECIST criteria was 14 months; the median OS was 47.1 months. When assessable, S6/4EBP1 was phosphorylated in a high and moderate/low proportion of tumor cells in responsive and nonresponsive patients, respectively. Toxicity caused a temporary and definitive treatment discontinuation in 60.5% and 30.2% of patients, respectively. CONCLUSIONS: Imatinib plus everolimus showed a limited activity in progressing advanced chordoma. Interestingly, the amount of tumor cells activated for mammalian target of rapamycin effectors correlated with the response. Toxicity was not negligible.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Cordoma/tratamiento farmacológico , Everolimus/administración & dosificación , Mesilato de Imatinib/administración & dosificación , Adulto , Anciano , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Cordoma/mortalidad , Cordoma/patología , Progresión de la Enfermedad , Everolimus/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Mesilato de Imatinib/efectos adversos , Masculino , Persona de Mediana Edad , Sarcoma/tratamiento farmacológico , Sarcoma/mortalidad , Sarcoma/patología , Neoplasias de la Base del Cráneo/tratamiento farmacológico , Neoplasias de la Base del Cráneo/mortalidad , Neoplasias de la Base del Cráneo/patología , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/patología , Análisis de Supervivencia
17.
Ann Surg ; 267(5): 959-964, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28394870

RESUMEN

OBJECTIVE: To investigate the safety of radical resection for retroperitoneal sarcoma (RPS). BACKGROUND: The surgical management of RPS frequently involves complex multivisceral resection. Improved oncologic outcomes have been demonstrated with this approach compared to marginal excision, but the safety of radical resection has not been shown in a large study population. METHODS: The Transatlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaborative of sarcoma centers. A combined experience of 1007 consecutive resections for primary RPS from January 2002 to December 2011 was studied retrospectively with respect to adverse events. A weighted organ score was devised to account for differences in surgical complexity. Univariate and multivariate logistic regression analyses were performed to investigate associations between adverse events and number and patterns of organs resected. Associations between adverse events and overall survival, local recurrence, and distant metastases were investigated. RESULTS: Severe postoperative adverse events (Clavien-Dindo ≥3) occurred in 165 patients (16.4%) and 18 patients (1.8%) died within 30 days. Significant predictors of severe adverse events were age (P = 0.003), transfusion requirements (P < 0.001), and resected organ score (P = 0.042). Resections involving pancreaticoduodenectomy, major vascular resection, and splenectomy/pancreatectomy were found to entail higher operative risk (odds ratio >1.5). There was no impact of postoperative adverse events on overall survival, local recurrence, or distant metastases. CONCLUSIONS: A radical surgical approach to RPS is safe when carried out at a specialist sarcoma center. High-risk resections should be carefully considered on an individual basis and weighed against anticipated disease biology. There appears to be no association between surgical morbidity and long-term oncologic outcomes.


Asunto(s)
Márgenes de Escisión , Pancreaticoduodenectomía , Neoplasias Retroperitoneales/cirugía , Sarcoma/cirugía , Esplenectomía , Anciano , Canadá/epidemiología , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Periodo Posoperatorio , Neoplasias Retroperitoneales/epidemiología , Estudios Retrospectivos , Sarcoma/epidemiología , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiología
18.
Oncologist ; 23(1): 62-70, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28754721

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sarcoma de Parte Blanda Alveolar/tratamiento farmacológico , Adulto , Femenino , Estudios de Seguimiento , Humanos , Indazoles , Masculino , Persona de Mediana Edad , Pronóstico , Pirimidinas/administración & dosificación , Estudios Retrospectivos , Sarcoma de Parte Blanda Alveolar/patología , Sulfonamidas/administración & dosificación , Tasa de Supervivencia , Trabectedina/administración & dosificación
19.
Ann Surg Oncol ; 25(6): 1536-1543, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29470819

RESUMEN

BACKGROUND: Established practice for the management of soft tissue sarcoma (STS) of the extremity and trunk wall combines perioperative radiotherapy (RT) with limb-preserving surgery. OBJECTIVE: The aim of this study was to explore whether high-quality surgery at high-volume centers may offer equivalent local control in selected cases, when RT needs to be avoided. METHODS: All consecutive adult cases of primary, high-risk STSs treated in a high-volume reference center over a 12-year timeframe were included, and, on retrospective analysis, were divided into two groups. Group A received RT with surgery, and Group B received surgery alone. The primary endpoint was local recurrence-free survival (LRFS). RESULTS: Overall, 390 patients were included (318 in Group A and 72 in Group B), with a median follow-up of 53 months. The main reasons for avoiding RT were patient choice and technical considerations (vascular bypass or flap reconstruction). No difference in R0 resection was seen between the groups (79% vs. 70%; p = 0.18), but Group A had more G3 tumors (80.5% vs. 68%; p = 0.021). No difference in 5-year LRFS was evident (84% vs. 81%; p = 0.16). CONCLUSIONS: LRFS did not differ between patients with high-risk STSs receiving perioperative RT and those treated with surgery alone. The study was retrospective and omission of RT was largely uncontrolled with inherent bias. Nonetheless, data suggest that in experienced centers, the omission of RT did not diminish local disease outcome. Future studies on a selective approach to RT administration are awaited.


Asunto(s)
Recurrencia Local de Neoplasia , Sarcoma/radioterapia , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía , Adulto , Anciano , Instituciones Oncológicas , Supervivencia sin Enfermedad , Extremidades , Femenino , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Clasificación del Tumor , Radioterapia Adyuvante , Estudios Retrospectivos , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Tasa de Supervivencia , Torso , Carga Tumoral
20.
J Magn Reson Imaging ; 47(3): 829-840, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28653477

RESUMEN

PURPOSE: To assess the feasibility of grading soft tissue sarcomas (STSs) using MRI features (radiomics). MATERIALS AND METHODS: MRI (echo planar SE, 1.5T) from 19 patients with STSs and a known histological grading, were retrospectively analyzed. The apparent diffusion coefficient (ADC) maps, obtained by diffusion-weighted imaging acquisitions, were analyzed through 65 radiomic features, intensity-based (first order statistics, FOS) and texture (gray level co-occurrence matrix, GLCM; and gray level run length matrix, GLRLM) features. Feature selection (sequential forward floating search) and classification (k-nearest neighbor classifier) were performed to distinguish intermediate- from high-grade STSs. Classification was performed using the three different sub-groups of features separately as well as all the features together. The entire dataset was divided in three subsets: the training, validation and test set, containing, respectively, 60, 30, and 10% of the data. RESULTS: Intermediate-grade lesions had a higher and less disperse ADC values compared with high-grade ones: most of FOS related to intensity are higher for the intermediate-grade STSs, while FOS related to signal variability were higher in the high grade (e.g., the feature variance is 2.6*105 ± 0.9*105 versus 3.3*105 ± 1.6*105 , P = 0.3). The GLCM features related to entropy and dissimilarity were higher in the high-grade. When performing classification, the best accuracy is obtained with a maximum of three features for each subgroup, FOS features being those leading to the best classification (validation set: FOS accuracy 0.90 ± 0.11, area under the curve [AUC] 0.85 ± 0.16; test set: FOS accuracy 0.88 ± 0.25, AUC 0.87 ± 0.34). CONCLUSION: Good accuracy and AUC could be obtained using only few Radiomic features, belonging to the FOS class. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:829-840.


Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Interpretación de Imagen Asistida por Computador/métodos , Sarcoma/diagnóstico por imagen , Sarcoma/patología , Adulto , Anciano , Diagnóstico Diferencial , Imagen Eco-Planar/métodos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto Joven
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