Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
1.
J Med Internet Res ; 24(9): e35675, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36103220

RESUMO

A digital twin (DT), originally defined as a virtual representation of a physical asset, system, or process, is a new concept in health care. A DT in health care is not a single technology but a domain-adapted multimodal modeling approach incorporating the acquisition, management, analysis, prediction, and interpretation of data, aiming to improve medical decision-making. However, there are many challenges and barriers that must be overcome before a DT can be used in health care. In this viewpoint paper, we build on the current literature, address these challenges, and describe a dynamic DT in health care for optimizing individual patient health care journeys, specifically for women at risk for cardiovascular complications in the preconception and pregnancy periods and across the life course. We describe how we can commit multiple domains to developing this DT. With our cross-domain definition of the DT, we aim to define future goals, trade-offs, and methods that will guide the development of the dynamic DT and implementation strategies in health care.


Assuntos
Acontecimentos que Mudam a Vida , Assistência ao Paciente , Feminino , Humanos , Gravidez , Tecnologia
2.
J Surg Oncol ; 123(4): 1050-1056, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33332599

RESUMO

BACKGROUND AND OBJECTIVES: A dynamic prediction model for patients with soft tissue sarcoma of the extremities was previously developed to predict updated overall survival probabilities throughout patient follow-up. This study updates and externally validates the dynamic model. METHODS: Data from 3826 patients with high-grade extremity soft tissue sarcoma, treated surgically with curative intent were used to update the dynamic PERsonalised SARcoma Care (PERSARC) model. Patients were added to the model development cohort and grade was included in the model. External validation was performed with data from 1111 patients treated at a single tertiary center. RESULTS: Calibration plots show good model calibration. Dynamic C-indices suggest that the model can discriminate between high- and low-risk patients. The dynamic C-indices at 0, 1, 2, 3, 4, and 5 years after surgery were equal to 0.697, 0.790, 0.822, 0.818, 0.812, and 0.827, respectively. CONCLUSION: Results from the external validation show that the dynamic PERSARC model is reliable in predicting the probability of surviving an additional 5 years from a specific prediction time point during follow-up. The model combines patient-, treatment-specific and time-dependent variables such as local recurrence and distant metastasis to provide accurate survival predictions throughout follow-up and is available through the PERSARC app.


Assuntos
Extremidades/patologia , Modelos Estatísticos , Recidiva Local de Neoplasia/mortalidade , Nomogramas , Sarcoma/mortalidade , Extremidades/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/cirurgia , Taxa de Sobrevida
3.
Lancet Oncol ; 20(6): 877-886, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31029509

RESUMO

BACKGROUND: Diffuse-type tenosynovial giant-cell tumour is a rare, locally aggressive, and difficult-to-treat soft tissue tumour. Clinical and surgical outcomes depend on multiple factors, including preoperative diagnostic assessment, the localisation and extent of disease, and possibly the choice of treatment modalities by orthopaedic surgeons. We did a retrospective cohort study to characterise global surgical treatment protocols, and assess surgical outcomes, complications, and functional results in patients with diffuse-type tenosynovial giant-cell tumours. METHODS: In this international, multicentre, retrospective cohort study, we included consecutive patients treated in 31 sarcoma reference centres between Jan 1, 1990, and Dec 31, 2017. Eligible patients were of any age and had histologically proven diffuse-type tenosynovial giant-cell tumour of large joints. Patient data were retrieved from the local databases of participating centres. Patients with localised-type tenosynovial giant-cell tumour were excluded. In the analysis, we only included patients with complete core criteria data regarding admission status, date of treatment, type of treatment at participating centre, and first local recurrence after treatment. We used a non-parametric method to estimate recurrence-free survival at 3, 5, and 10 years after initial surgical resection in a tertiary centre. We used a multivariate Cox regression model to estimate the effect of risk factors. We also present subgroup analyses of disease status at presentation (primary vs recurrent disease) and recurrence-free survival by surgery type (open surgery vs arthroscopic synovectomy), and prespecified risk factors were tested in a univariate and multivariable analyses, with an endpoint of first local recurrence after treatment in a tertiary centre. FINDINGS: Data collection for these analyses occurred between January, 2016, and May, 2018. We received the records of 1192 patients, of which 966 (81%) were surgically treated and had complete information on core criteria. 445 patients were admitted with therapy-naive disease of the knee and were primarily treated in a tertiary centre. Since patients with wait and see treatment do not have a starting date of treatment, these patients were excluded in the calculation of median follow-up time for all patients. For this calculation we used time of surgery as a starting date. 758 (64%) of 1192 patients had knee involvement and 628 (54%) of 1163 patients with complete data on type of surgery had one-staged open synovectomy. At a median follow-up of 54 months (IQR 27-97), recurrent disease developed in 425 (44%) of all 966 surgically treated cases, and recurrence-free survival was 62% (95% CI 59-65) at 3 years, 55% (51-58) at 5 years, and 40% (35-45) at 10 years. Surgical complications were reported in 105 (12%) of 906 patients who had complete data on surgical complications. Pain improved after surgical treatment in 255 (59%) of 434 patients and swelling improved in 328 (72%) of 453 patients who had complete data. INTERPRETATION: This study of patients with diffuse-type tenosynovial giant-cell tumour provides a comprehensive and up-to-date disease overview, assessing the clinical profile and management of the disease in multiple specialised referral centres. Surgical treatment of diffuse-type tenosynovial giant cell tumours is not a definitive treatment for every patient because it involves a high risk for local recurrent disease and a relatively high risk for postoperative complications. After surgical treatment in treatment-naive patients, risk factors for recurrent disease in individual patients were not identified in what we believe is the largest cohort to date. FUNDING: Daiichi Sankyo.


Assuntos
Tumor de Células Gigantes de Bainha Tendinosa/cirurgia , Recidiva Local de Neoplasia/cirurgia , Sinovectomia/mortalidade , Sinovite Pigmentada Vilonodular/cirurgia , Adulto , Feminino , Seguimentos , Tumor de Células Gigantes de Bainha Tendinosa/patologia , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Sinovite Pigmentada Vilonodular/patologia , Resultado do Tratamento
4.
Stat Med ; 38(2): 269-288, 2019 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-30338563

RESUMO

Survival analysis is used in the medical field to identify the effect of predictive variables on time to a specific event. Generally, not all variation of survival time can be explained by observed covariates. The effect of unobserved variables on the risk of a patient is called frailty. In multicenter studies, the unobserved center effect can induce frailty on its patients, which can lead to selection bias over time when ignored. For this reason, it is common practice in multicenter studies to include a random frailty term modeling center effect. In a more complex event structure, more than one type of event is possible. Independent frailty variables representing center effect can be incorporated in the model for each competing event. However, in the medical context, events representing disease progression are likely related and correlation is missed when assuming frailties to be independent. In this work, an additive gamma frailty model to account for correlation between frailties in a competing risks model is proposed, to model frailties at center level. Correlation indicates a common center effect on both events and measures how closely the risks are related. Estimation of the model using the expectation-maximization algorithm is illustrated. The model is applied to a data set from a multicenter clinical trial on breast cancer from the European Organisation for Research and Treatment of Cancer (EORTC trial 10854). Hospitals are compared by employing empirical Bayes estimates methodology together with corresponding confidence intervals.


Assuntos
Fragilidade/epidemiologia , Hospitais/estatística & dados numéricos , Modelos Estatísticos , Adulto , Teorema de Bayes , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Fragilidade/complicações , Fragilidade/mortalidade , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/métodos , Fatores de Risco , Viés de Seleção , Análise de Sobrevida
5.
Eur Heart J Digit Health ; 4(6): 444-454, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38045440

RESUMO

Aims: Risk assessment tools are needed for timely identification of patients with heart failure (HF) with reduced ejection fraction (HFrEF) who are at high risk of adverse events. In this study, we aim to derive a small set out of 4210 repeatedly measured proteins, which, along with clinical characteristics and established biomarkers, carry optimal prognostic capacity for adverse events, in patients with HFrEF. Methods and results: In 382 patients, we performed repeated blood sampling (median follow-up: 2.1 years) and applied an aptamer-based multiplex proteomic approach. We used machine learning to select the optimal set of predictors for the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization). The association between repeated measures of selected proteins and PEP was investigated by multivariable joint models. Internal validation (cross-validated c-index) and external validation (Henry Ford HF PharmacoGenomic Registry cohort) were performed. Nine proteins were selected in addition to the MAGGIC risk score, N-terminal pro-hormone B-type natriuretic peptide, and troponin T: suppression of tumourigenicity 2, tryptophanyl-tRNA synthetase cytoplasmic, histone H2A Type 3, angiotensinogen, deltex-1, thrombospondin-4, ADAMTS-like protein 2, anthrax toxin receptor 1, and cathepsin D. N-terminal pro-hormone B-type natriuretic peptide and angiotensinogen showed the strongest associations [hazard ratio (95% confidence interval): 1.96 (1.17-3.40) and 0.66 (0.49-0.88), respectively]. The multivariable model yielded a c-index of 0.85 upon internal validation and c-indices up to 0.80 upon external validation. The c-index was higher than that of a model containing established risk factors (P = 0.021). Conclusion: Nine serially measured proteins captured the most essential prognostic information for the occurrence of adverse events in patients with HFrEF, and provided incremental value for HF prognostication beyond established risk factors. These proteins could be used for dynamic, individual risk assessment in a prospective setting. These findings also illustrate the potential value of relatively 'novel' biomarkers for prognostication. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01851538?term=nCT01851538&draw=2&rank=1 24.

6.
Eur J Cancer ; 165: 71-80, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35219025

RESUMO

OBJECTIVE: The aim of the study is to assess the effect of perioperative chemotherapy (CTX) in patients with grade II-III extremity soft tissue sarcoma (eSTS) on overall survival (OS) and evaluate whether the PERSARC prediction tool could identify patients with eSTS more likely to benefit from CTX. METHODS: Patients (18-70 years) with primary high-grade eSTS surgically treated with curative intent were included in the retrospective cohort study. The effect of any perioperative CTX and anthracycline + ifosfamide (AI)-based CTX on OS was investigated in three PERSARC-risk groups (high/intermediate/low). The PERSARC-risk groups were defined by the 33% and 66% quantile of the predicted 5-year OS of the study population equal to a 5-year OS of 65.8% and 79.8%, respectively. The effect of CTX on OS was investigated with weighted Kaplan-Meier curves and multivariable Cox models with an interaction between risk group and CTX. RESULTS: This study included 5683 patients. The weighted Kaplan-Meier curves did not demonstrate a beneficial effect of any CTX and AI-based CTX on OS in the overall population. However, in the high PERSARC-risk group the 5-year OS of AI-based CTX was significantly better than no CTX (69.8% vs 59.0%, respectively, p = 0.004) (HR 0.66, 95%CI 0.53-0.83). CONCLUSIONS: This study demonstrated a beneficial effect of AI-based CTX on OS in a selected group of high-risk patients with an absolute survival benefit of 11% as stratified by the PERSARC prediction tool. However, no beneficial effect of CTX on OS was found in the overall population of patients with primary high-grade eSTS younger than 70 years.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Extremidades/cirurgia , Humanos , Ifosfamida/uso terapêutico , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/cirurgia
7.
Cancers (Basel) ; 13(3)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513855

RESUMO

Age is a known prognostic factor for many sarcoma subtypes, however in the literature there are limited data on the different risk profiles of different age groups for osteosarcoma survival. This study aims to provide an overview of survival in patients with high-grade osteosarcoma in different age groups and prognostic variables for survival and local control among the entire cohort. In this single center retrospective cohort study, 402 patients with skeletal high-grade osteosarcoma were diagnosed and treated with curative intent between 1978 and 2017 at the Leiden University Medical Center (LUMC). Prognostic factors for survival were analyzed using a Cox proportional hazard model. In this study poor overall survival (OS) and event-free survival (EFS) were associated with increasing age. Age groups, tumor size, poor histopathological response, distant metastasis (DM) at presentation and local recurrence (LR) were important independent prognostic factors influencing OS and EFS. Differences in outcome among different age groups can be partially explained by patient and treatment characteristics.

8.
BMJ Open ; 10(10): e036376, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046463

RESUMO

OBJECTIVES: This study aimed at developing a dynamic prediction model for patients with Ewing sarcoma (ES) to provide predictions at different follow-up times. During follow-up, disease-related information becomes available, which has an impact on a patient's prognosis. Many prediction models include predictors available at baseline and do not consider the evolution of disease over time. SETTING: In the analysis, 979 patients with ES from the Gesellschaft für Pädiatrische Onkologie und Hämatologie registry, who underwent surgery and treatment between 1999 and 2009, were included. DESIGN: A dynamic prediction model was developed to predict updated 5-year survival probabilities from different prediction time points during follow-up. Time-dependent variables, such as local recurrence (LR) and distant metastasis (DM), as well as covariates measured at baseline, were included in the model. The time effects of covariates were investigated by using interaction terms between each variable and time. RESULTS: Developing LR, DM in the lungs (DMp) or extrapulmonary DM (DMo) has a strong effect on the probability of surviving an additional 5 years with HRs and 95% CIs equal to 20.881 (14.365 to 30.353), 6.759 (4.465 to 10.230) and 17.532 (13.210 to 23.268), respectively. The effects of primary tumour location, postoperative radiotherapy (PORT), histological response and disease extent at diagnosis on survival were found to change over time. The HR of PORT versus no PORT at the time of surgery is equal to 0.774 (0.594 to 1.008). One year after surgery, the HR is equal to 1.091 (0.851 to 1.397). CONCLUSIONS: The time-varying effects of several baseline variables, as well as the strong impact of time-dependent variables, show the importance of including updated information collected during follow-up in the prediction model to provide accurate predictions of survival.


Assuntos
Sarcoma de Ewing , Humanos , Recidiva Local de Neoplasia , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Sarcoma de Ewing/terapia , Análise de Sobrevida
9.
Eur J Cancer ; 141: 128-136, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33137588

RESUMO

PURPOSE: No studies extensively compared the young adults (YA, 18-39 years), middle-aged (40-69 years), and elderly (≥70 years) population with primary high-grade extremity soft tissue sarcoma (eSTS). This study aimed to determine whether the known effect of age on overall survival (OS) and disease progression can be explained by differences in tumour characteristics and treatment protocol among the YA, middle-aged and elderly population in patients with primary high-grade eSTS treated with curative intent. METHODS: In this retrospective multicentre study, inclusion criteria were patients with primary high-grade eSTS of 18 years and older, surgically treated with curative intent between 2000 and 2016. Cox proportional hazard models and a multistate model were used to determine the association of age on OS and disease progression. RESULTS: A total of 6260 patients were included in this study. YA presented more often after 'whoops'-surgery or for reresection due to residual disease, and with more deep-seated tumours. Elderly patients presented more often with grade III and larger (≥10 cm) tumours. After adjustment for the imbalance in tumour and treatment characteristics the hazard ratio for OS of the middle-aged population is 1.47 (95% confidence interval [CI]: 1.23-1.76) and 3.13 (95% CI: 2.59-3.78) in the elderly population, compared with YA. DISCUSSION: The effect of age on OS could only partially be explained by the imbalance in the tumour characteristics and treatment variables. The threefold higher risk of elderly could, at least partially, be explained by a higher other-cause mortality. The results might also be explained by a different tumour behaviour or suboptimal treatment in elderly compared with the younger population.


Assuntos
Sarcoma/epidemiologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/epidemiologia , Neoplasias de Tecidos Moles/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
BMJ Open ; 7(2): e012930, 2017 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-28196946

RESUMO

OBJECTIVES: This study investigates the effect of surgical margins and radiotherapy, in the presence of individual baseline characteristics, on survival in a large population of high-grade soft tissue sarcoma of the extremities using a multistate model. DESIGN: A retrospective multicentre cohort study. SETTING: 4 tertiary referral centres for orthopaedic oncology. PARTICIPANTS: 687 patients with primary, non-disseminated, high-grade sarcoma only, receiving surgical treatment with curative intent between 2000 and 2010 were included. MAIN OUTCOME MEASURES: The risk to progress from 'alive without disease' (ANED) after surgery to 'local recurrence' (LR) or 'distant metastasis (DM)/death'. The effect of surgical margins and (neo)adjuvant radiotherapy on LR and overall survival was evaluated taking patients' and tumour characteristics into account. RESULTS: The multistate model underlined that wide surgical margins and the use of neoadjuvant radiotherapy decreased the risk of LR but have little effect on survival. The main prognostic risk factors for transition ANED to LR are tumour size (HR 1.06; 95% CI 1.01 to 1.11 (size in cm)) and (neo)adjuvant radiotherapy. The HRs for patients treated with adjuvant or no radiotherapy compared with neoadjuvant radiotherapy are equal to 4.36 (95% CI 1.34 to 14.24) and 14.20 (95% CI 4.14 to 48.75), respectively. Surgical resection margins had a protective effect for the occurrence of LR with HRs equal to 0.61 (95% CI 0.33 to 1.12), and 0.16 (95% CI 0.07 to 0.41) for margins between 0 and 2 mm and wider than 2 mm, respectively. For transition ANED to distant metastases/Death, age (HR 1.64 (95% CI 0.95 to 2.85) and 1.90 (95% CI 1.09 to 3.29) for 25-50 years and >50 years, respectively) and tumour size (1.06 (95% CI 1.04 to 1.08)) were prognostic factors. CONCLUSIONS: This paper underlined the alternating effect of surgical margins and the use of neoadjuvant radiotherapy on oncological outcomes between patients with different baseline characteristics. The multistate model incorporates this essential information of a specific patient's history, tumour characteristics and adjuvant treatment modalities and allows a more comprehensive prediction of future events.


Assuntos
Modelos Estatísticos , Recidiva Local de Neoplasia/prevenção & controle , Sarcoma/terapia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Sarcoma/secundário , Taxa de Sobrevida , Carga Tumoral
12.
Eur J Cancer ; 83: 313-323, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28797949

RESUMO

BACKGROUND: To support shared decision-making, we developed the first prediction model for patients with primary soft-tissue sarcomas of the extremities (ESTS) which takes into account treatment modalities, including applied radiotherapy (RT) and achieved surgical margins. The PERsonalised SARcoma Care (PERSARC) model, predicts overall survival (OS) and the probability of local recurrence (LR) at 3, 5 and 10 years. AIM: Development and validation, by internal validation, of the PERSARC prediction model. METHODS: The cohort used to develop the model consists of 766 ESTS patients who underwent surgery, between 2000 and 2014, at five specialised international sarcoma centres. To assess the effect of prognostic factors on OS and on the cumulative incidence of LR (CILR), a multivariate Cox proportional hazard regression and the Fine and Gray model were estimated. Predictive performance was investigated by using internal cross validation (CV) and calibration. The discriminative ability of the model was determined with the C-index. RESULTS: Multivariate Cox regression revealed that age and tumour size had a significant effect on OS. More importantly, patients who received RT showed better outcomes, in terms of OS and CILR, than those treated with surgery alone. Internal validation of the model showed good calibration and discrimination, with a C-index of 0.677 and 0.696 for OS and CILR, respectively. CONCLUSIONS: The PERSARC model is the first to incorporate known clinical risk factors with the use of different treatments and surgical outcome measures. The developed model is internally validated to provide a reliable prediction of post-operative OS and CILR for patients with primary high-grade ESTS. LEVEL OF SIGNIFICANCE: level III.


Assuntos
Técnicas de Apoio para a Decisão , Psicoterapia Centrada na Pessoa/métodos , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Fatores Etários , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Sarcoma/epidemiologia , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/epidemiologia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Análise de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA