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Background The Domus study, a randomized controlled trial (RCT), evaluated the effect of home-based specialized palliative care (SPC) reinforced with a psychological intervention for the patient-caregiver dyad on increasing advanced cancer patients' time spent at home, as opposed to hospitalized, and the number of home deaths. As palliative care extends to include support for patients' families and may thus assist caregivers and decrease demands on them, in this study we evaluated a secondary outcome, caregiver burden.Material and Methods Patients with incurable cancer and their caregivers were randomized (1:1) to care as usual or home-based SPC. Caregiver burden was assessed using the Zarit Burden Interview (ZBI) at baseline and 2, 4, 8 weeks and 6 months after randomization. Intervention effects were assessed in mixed effects models.Results A total of 258 caregivers were enrolled. Eleven per cent of informal caregivers experienced severe caregiver burden at baseline. Caregiver burden increased significantly over time in both groups (p = 0.0003), but no significant effect of the intervention was seen on overall caregiver burden (p = 0.5046) or burden subscales measuring role and personal strain.Conclusion In line with the majority of previous RCTs, the Domus intervention was not able to significantly reduce caregiver burden. Future interventions should consider targeting only caregivers reporting the greatest caregiver burden.
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Neoplasias , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Sobrecarga do Cuidador , Intervenção Psicossocial , Cuidadores/psicologia , Neoplasias/terapia , Neoplasias/psicologia , Qualidade de VidaRESUMO
Urothelial carcinoma of the bladder is a highly aggressive disease characterised by a very heterogeneous clinical outcome. Despite cystectomy, patients still have a high recurrence risk and shortened survival. Urokinase-type plasminogen activator receptor (uPAR) is present in tumour tissue specimens from patients with urothelial carcinoma. The different uPAR forms in blood are strong prognostic markers in other cancer types. We investigate the presence of different uPAR forms in tumour tissue and test the hypothesis that preoperative plasma levels of the uPAR forms predict recurrence free survival, cancer specific survival, and overall survival in patients treated with cystectomy for urothelial carcinoma. Using Western blotting we analyse neoplasia and adjacent benign-appearing urothelium from randomly selected patients for the presence of intact and cleaved uPAR forms. Prospectively collected preoperative plasma samples from 107 patients who underwent radical cystectomy for urothelial carcinoma are analysed. The different uPAR forms are measured by time-resolved fluorescence immunoassays. uPAR in tumour tissue from patients with urothelial carcinoma is demonstrated in both an intact and cleaved form. The different uPAR forms in plasma are all significantly associated with both recurrence free survival, cancer specific survival, and overall survival, high concentrations predicting short survival. uPAR (I) has the strongest association with a HR of 2.56 for overall survival. In the multivariable survival analysis uPAR (I) is significantly associated with cancer specific survival and overall survival.
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BACKGROUND: While hospitals remain the most common place of death in many western countries, specialised palliative care (SPC) at home is an alternative to improve the quality of life for patients with incurable cancer. We evaluated the cost-effectiveness of a systematic fast-track transition process from oncological treatment to SPC enriched with a psychological intervention at home for patients with incurable cancer and their caregivers. METHODS: A full economic evaluation with a time horizon of six months was performed from a societal perspective within a randomised controlled trial, the DOMUS trial ( Clinicaltrials.gov : NCT01885637). The primary outcome of the health economic analysis was a incremental cost-effectiveness ratio (ICER), which is obtained by comparing costs required per gain in Quality-Adjusted Life Years (QALY). The costs included primary and secondary healthcare costs, cost of intervention and informal care from caregivers. Public transfers were analysed in seperate analysis. QALYs were measured using EORTC QLQ-C30 for patients and SF-36 for caregivers. Bootstrap simulations were performed to obtain the ICER estimate. RESULTS: In total, 321 patients (162 in intervention group, 159 in control group) and 235 caregivers (126 in intervention group, 109 in control group) completed the study. The intervention resulted in significantly higher QALYs for patients when compared to usual care (p-value = 0.026), while being more expensive as well. In the 6 months observation period, the average incremental cost of intervention compared to usual care was 2015 per patient (p value < 0.000). The mean incremental gain was 0.01678 QALY (p-value = 0.026). Thereby, the ICER was 118,292/QALY when adjusting for baseline costs and quality of life. For the caregivers, we found no significant differences in QALYs between the intervention and control group (p-value = 0.630). At a willingness to pay of 80,000 per QALY, the probability that the intervention is cost-effective lies at 15% in the base case scenario. CONCLUSION: This model of fast-track SPC enriched with a psychological intervention yields better QALYs than usual care with a large increase in costs. TRIAL REGISTRATION: The trial was prospectively registered 25.6.2013. Clinicaltrials.gov Identifier: NCT01885637 .
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Neoplasias/terapia , Cuidados Paliativos/economia , Fatores de Tempo , Cuidado Transicional/economia , Idoso , Cuidadores/economia , Cuidadores/psicologia , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/psicologia , Cuidados Paliativos/métodos , Inquéritos e Questionários , Cuidado Transicional/normas , Cuidado Transicional/estatística & dados numéricosRESUMO
OBJECTIVES: To assess the effect of a systematic, fast-track transition from oncological treatment to specialised palliative care at home on symptom burden, to explore intervention mechanisms through patient and intervention provider characteristics and to assess long-term survival and place of death. MEASURES: The effect of a systematic, fast-track transition from oncological treatment to specialised palliative care at home on patient symptom burden was studied in the Domus randomised clinical trial. Participants had incurable cancer and limited treatment options. The intervention was provided by specialised palliative home teams (SPT) based in hospice or hospital and was enriched with a psychological intervention for patient and caregiver dyad. Symptom burden was measured with Edmonton Symptom Assessment System (ESAS-r) at baseline, 8 weeks and 6 months follow-up and analysed with mixed models. Survival and place of death was analysed with Kaplan-Meier and Fisher's exact tests. RESULTS: The study included 322 patients. Tiredness was significantly improved for the Domus intervention group at 6 months while the other nine symptom outcomes were not significantly different from the control group. Exploring the efficacy of intervention provider demonstrated significant differences in favour of the hospice SPT on four symptoms and total symptom score. Patients with children responded more favourably to the intervention. The long-term follow-up demonstrated no differences between the intervention and the control groups regarding survival or home deaths. CONCLUSIONS: The Domus intervention may reduce tiredness. Moreover, the intervention provider and having children might play a role concerning intervention efficacy. The intervention did not affect survival or home deaths. TRIAL REGISTRATION NUMBER: NCT01885637.
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Serviços de Assistência Domiciliar , Oncologia/métodos , Neoplasias/terapia , Cuidados Paliativos/métodos , Transferência de Pacientes/métodos , Adulto , Cuidadores/psicologia , Criança , Fadiga/etiologia , Fadiga/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de SaúdeRESUMO
LESSONS LEARNED: First trial to report safety and activity of the microtubule inhibitor vinflunine plus the tyrosine kinase inhibitor sorafenib in post-platinum metastatic urothelial cancer (mUC) patients.A recommended phase II dose was identified for the treatment combination of vinflunine plus sorafenib, with main adverse events including fatigue, febrile neutropenia, neutropenia, hypertension, and hyponatremia.An overall response rate of 41% to second-line vinflunine plus sorafenib treatment in patients with platinum-resistant mUC was confirmed. BACKGROUND: Platinum-progressive metastatic urothelial carcinoma (mUC) is a clinical challenge. The tyrosine kinase inhibitor sorafenib has demonstrated varied activity in mUC. This trial was designed to examine safety and activity of vinflunine plus sorafenib in mUC. METHODS: In addition to standard dose of vinflunine (320 or 280 mg/m2), patients received sorafenib (400, 600, or 800 mg/day), in a 3 + 3 dose-escalation phase I design. RESULTS: Twenty-two patients (median age 62.5 years) were included. Five patients received vinflunine 320 mg/m2 and 17 received 280 mg/m2. The maximum tolerated dose (MTD) of sorafenib with vinflunine 280 mg/m2 was 600 mg, and with vinflunine 320 mg/m2 it was not determined, owing to toxicity. Adverse events (AEs) grades 3 + 4 consisted of neutropenia (6 patients), febrile neutropenia (5), and hyponatremia (5). The overall response rate (ORR) in the efficacy-evaluable patients was 41% (7 of 17), all partial responses evaluated by RECIST version 1.1. Median overall survival (OS) was 7.0 months (1.8-41.7). CONCLUSION: The defined recommended phase II dose (RPTD) was vinflunine 280 mg/m2 plus sorafenib 400 mg. Sorafenib was too toxic in combination with vinflunine 320 mg/m2. The ORR of 41% to this second-line combination treatment of mUC is noteworthy and supports further trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Sorafenibe/efeitos adversos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Hiponatremia/induzido quimicamente , Hiponatremia/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Sorafenibe/administração & dosagem , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: Specialized palliative care (SPC) interventions increasingly include patient-caregiver dyads, but their effects on dyadic coping are unknown. We investigated whether an SPC and dyadic psychological intervention increased aspects of dyadic coping in patients with advanced cancer and their caregivers, whether dyad characteristics moderated effects and whether aspects of dyadic coping mediated significant intervention effects on caregivers' anxiety and depression. METHODS: We randomized 258 patients with incurable cancer and their caregivers to care as usual or accelerated transition from oncological treatment to home-based SPC and dyadic psychological support. In secondary outcome analyses, using mixed-effects models, we estimated intervention effects and 95% confidence intervals (CIs) for communication of stress and common coping, and moderation by dyad type and demographics. In path analyses, we investigated whether stress communication and common coping mediated intervention effects on caregivers' symptoms of anxiety and depression. (Clinicaltrials.gov NCT01885637). RESULTS: The intervention significantly increased common coping in patients and caregivers in couples (estimated difference, 0.68; 95% CI, 0.11 to 1.24) and stress communication by partner caregivers (0.97; 0.24 to 1.24). We found some support for different intervention effects for spouses and other dyads, but no evidence of mediation. CONCLUSIONS: Specialized palliative care and dyadic psychological intervention may affect aspects of dyadic coping. Common coping and stress communication did not mediate the previously found significant intervention effects on caregiver anxiety and depression, indicating that other mechanisms may have been central in the intervention.
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Cuidadores/psicologia , Neoplasias/psicologia , Cuidados Paliativos/psicologia , Adaptação Psicológica , Adulto , Idoso , Ansiedade/psicologia , Depressão/psicologia , Feminino , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Serviços de Assistência Domiciliar/normas , Enfermagem de Cuidados Paliativos na Terminalidade da Vida/normas , Enfermagem Oncológica/normas , Cuidados Paliativos/normas , Guias de Prática Clínica como Assunto , Cuidado Transicional/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de VidaRESUMO
BACKGROUND: Specialised palliative care trials often fail to address intervention effects on caregiver anxiety and depression, particularly in bereavement. We evaluate effects of specialised palliative care and dyadic psychological intervention on caregiver anxiety and depression in a randomised controlled trial (RCT). METHODS: Patients with incurable cancer and limited antineoplastic treatment options and their caregivers, recruited from a university hospital oncology department, were randomised (1:1) to care as usual or accelerated transition from oncological treatment to home-based specialised palliative care. We assessed caregivers' symptoms of anxiety and depression with the Symptom Checklist-92 up to six months after randomisation and 19 months into bereavement, and estimated intervention effects in mixed effects models. RESULTS: The 'Domus' trial enrolled 258 caregivers. The intervention significantly attenuated increases in caregivers' symptoms of anxiety overall (estimated difference, -0.12; 95% confidence interval, -0.22 to -0.01, p = 0.0266), and symptoms of depression at eight weeks (-0.17; -0.33 to -0.02; p = 0.0314), six months (-0.27; -0.49 to -0.05; p = 0.0165), and in bereavement at two weeks (-0.28; -0.52 to -0.03; p = 0.0295) and two months (-0.24; -0.48 to -0.01; p = 0.0448). CONCLUSIONS: This first RCT evaluating specialised palliative care with dyadic psychological support significantly attenuated caregiver anxiety and depression before and during bereavement. (Clinicaltrials.gov: NCT01885637).
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Ansiedade/terapia , Cuidadores/psicologia , Depressão/terapia , Serviços de Assistência Domiciliar/organização & administração , Cuidados Paliativos/organização & administração , Psicoterapia/métodos , Idoso , Feminino , Serviços de Assistência Domiciliar/normas , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/normasRESUMO
ABSTRACTObjective:Patients with incurable cancer and their informal caregivers have numerous psychological and psychosocial needs. Many of these patients wish to receive their care and die at home. Few home-based specialized palliative care (SPC) interventions systematically integrate psychological support. We present a psychological intervention for patient-caregiver dyads developed for an ongoing randomized controlled trial (RCT) of home-based SPC, known as Domus, as well as the results of an assessment of its acceptability and feasibility. METHOD: The Domus model of SPC for patients with incurable cancer and their caregivers offered systematic psychological assessment and dyadic intervention as part of interdisciplinary care. Through accelerated transition to SPC, the aim of the model was to enhance patients' chances of receiving care and dying at home. Integration of psychological support sought to facilitate this goal by alleviating distress in patients and caregivers. Psychologists provided needs-based sessions based on existential-phenomenological therapy. Feasibility and acceptability were investigated by examining enrollment, nonparticipation, and completion of psychological sessions. RESULTS: Enrollment in the RCT and uptake of the psychological intervention indicated that it was feasible and acceptable to patients and caregivers. The strengths of the intervention included its focus on dyads, psychological distress, and existential concerns, as well as interdisciplinary collaboration and psychological interventions offered according to need. Its main limitation was a lack of an intervention for other family members. SIGNIFICANCE OF RESULTS: Our results show that psychological intervention can be systematically integrated into SPC and that it appears feasible to provide dyadic needs-based sessions with an existential therapeutic approach. The Domus RCT will provide evidence of the efficacy of a novel model of multidisciplinary SPC.
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Cuidadores/psicologia , Serviços de Assistência Domiciliar/tendências , Pacientes/psicologia , Estresse Psicológico/terapia , Protocolos Clínicos/normas , Humanos , Neoplasias/psicologia , Neoplasias/terapia , Estresse Psicológico/psicologiaRESUMO
CONTEXT: Avoidable hospital admissions are important negative indicators of quality of end-of-life care. Specialized palliative care (SPC) may support patients remaining at home. OBJECTIVES: Therefore, the purpose of this study was to investigate if SPC at home could prevent hospital admissions in patients with incurable cancer. METHODS: These are secondary results of Domus: a randomized controlled trial of accelerated transition to SPC with psychological intervention at home (Clinicaltrials.gov: NCT01885637). Participants were patients with incurable cancer and limited antineoplastic treatment options and their caregivers. They were included from the Department of Oncology, Rigshospitalet, Denmark, between 2013 and 2016. The control group received usual care. Outcomes were hospital admissions, causes thereof, and patient and caregiver perceptions of place of care (home, hospital, etc.) at baseline, four weeks, eight weeks, and six months. RESULTS: During the study, 340 patients were randomized and 322 were included in modified intention-to-treat analyses. Overall, there were no significant differences in hospital admissions between the groups. The intervention group had more admissions triggered by worsened general health (22% vs. 16%, P = 0.0436) or unmanageable home situation (8% vs. 4%, P = 0.0119). After diagnostics, admissions were more often caused by clinical symptoms of cancer without progression in the intervention group (11% vs. 7%, P = 0.0493). The two groups did not differ significantly in overall potentially avoidable admissions. Both groups felt mostly safe about their place of care. CONCLUSION: The intervention did not prevent hospital admissions. Likely, any intervention effects were outweighed by increased identification of problems in the intervention group leading to hospital admissions. Overall, patients and caregivers felt safe in their current place of care.
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Serviços de Assistência Domiciliar , Hospitalização , Neoplasias/terapia , Cuidados Paliativos , Assistência Terminal , Idoso , Cuidadores , Feminino , Humanos , Masculino , Neoplasias/psicologia , Assistência Terminal/métodosRESUMO
BACKGROUND: The optimal treatment strategy for patients with clinical stage I (CS-1) seminoma is controversial. The objective of the current study was to evaluate the outcomes for patients considered to be at high risk of disease recurrence with a tumor size ≥6 cm. Patients were treated with either adjuvant radiotherapy (RT) or followed with surveillance. METHODS: From the Danish Testicular Cancer database, the authors identified 473 patients with CS-1 seminoma with a tumor size ≥6 cm. Of these, 254 patients underwent adjuvant RT and 219 were followed with surveillance. Cumulative incidence function was applied to estimate the risk of disease recurrence, risk of second malignant neoplasm, and risk of receiving >1 line of treatment. Survival of the 2 groups was compared with the log-rank test and Cox model including age at diagnosis. RESULTS: No significant differences were found with regard to overall survival or risk of a second malignant neoplasm. Patients undergoing adjuvant RT received more treatments per patient than patients followed with surveillance, but there was no significant difference noted with regard to the risk of receiving >1 line of treatment. The 10-year cumulative incidence of disease recurrence was 32% versus 2.8%, respectively, for patients followed with surveillance and adjuvant RT. In patients followed with surveillance who developed disease recurrence, there was a high incidence of second recurrences after RT. CONCLUSIONS: The 10-year overall survival was found to be similar irrespective of primary treatment. Adjuvant RT was found to effectively reduce the rate of disease recurrence but resulted in the overtreatment of approximately two-thirds of the patients. The high incidence of second disease recurrences after RT in the patients followed with surveillance needs be addressed in future studies. Cancer 2017;123:1212-1218. © 2016 American Cancer Society.
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Seminoma/epidemiologia , Seminoma/radioterapia , Adolescente , Adulto , Criança , Dinamarca/epidemiologia , Seguimentos , Humanos , Masculino , Estadiamento de Neoplasias , Vigilância da População , Radioterapia Adjuvante/métodos , Fatores de Risco , Seminoma/mortalidade , Seminoma/patologia , Resultado do Tratamento , Carga Tumoral , Adulto JovemRESUMO
BACKGROUND: Comprehensive data on late relapse (LR) and very LR (VLR) in patients with clinical stage I (CS-1) testicular cancer followed on surveillance are missing. These data are essential for planning optimal follow-up. OBJECTIVE: Assess incidence and outcome of LR (>2 yr) and VLR (>5 yr) in a large cohort of CS-1 surveillance patients, and examine differences in the clinical characteristics of patients with early relapse (ER), LR, and VLR. DESIGN, SETTING, AND PARTICIPANTS: CS-1 surveillance patients diagnosed between 1984 and 2007 were identified from the retrospective Danish Testicular Cancer (DaTeCa) database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We estimated survival and relapse probabilities and compared the results using log-rank tests and Cox regression analyses. We compared differences in patient characteristics by using χ(2), Fisher exact, and Mann-Whitney tests. RESULTS AND LIMITATIONS: Our study included 3366 (2000 seminoma and 1366 nonseminoma) patients. Median follow-up was 15 yr. Five-year conditional risk of LR was 5.0% and 2.1% for seminoma and nonseminoma patients, respectively. There were no significant differences in disease-specific or overall survival when comparing the LR(VLR) and ER patients by log-rank, but Cox regression adjusted for age showed a significant effect of time to relapse on survival for seminoma patients. Apart from significantly more ER nonseminoma patients with elevated human chorionic gonadotropin at relapse, there were no significant differences in patient characteristics at orchiectomy or relapse. Limitations include retrospective design and exclusion of patients who had been offered adjuvant therapy. CONCLUSIONS: The risk of VLR is minimal, and the patients carry a good prognosis. Patient characteristics of CS-1 surveillance patients with LR(VLR) do not differ significantly from patients with ER. PATIENT SUMMARY: We compared stage I testicular cancer surveillance patients with early relapse (ER) versus late relapse (LR; >2 yr). LR patients as a group did no worse than ER patients, although increased time to relapse was negatively associated with survival for seminoma patients.
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Efeitos Adversos de Longa Duração , Orquiectomia , Seminoma , Neoplasias Testiculares , Adulto , Idoso , Gonadotropina Coriônica/análise , Dinamarca/epidemiologia , Humanos , Incidência , Efeitos Adversos de Longa Duração/epidemiologia , Efeitos Adversos de Longa Duração/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Orquiectomia/efeitos adversos , Orquiectomia/métodos , Orquiectomia/estatística & dados numéricos , Recidiva , Estudos Retrospectivos , Seminoma/mortalidade , Seminoma/patologia , Análise de Sobrevida , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologiaRESUMO
PURPOSE: The purposes of the present study were to classify the palliative care population (PCP) in a comprehensive cancer centre by using information on antineoplastic treatment options and to analyse associations between socio-demographic factors, cancer diagnoses, treatment characteristics and receiving specialist palliative care (SPC). METHODS: This is a cross-sectional screening study of patients with cancer in the Department of Oncology, Rigshospitalet, Copenhagen University Hospital for 6 months. Patients were assessed to be included in the DOMUS study: a randomised controlled trial of accelerated transition to SPC at home (NCT01885637). The PCP was classified as patients with incurable cancer and limited or no antineoplastic treatment options. Patients with performance status 2-4 were further classified as the essential palliative care population (EPCP). RESULTS: During the study period, 3717 patients with cancer were assessed. The PCP comprised 513 patients yielding a prevalence of 14 %. The EPCP comprised 256 patients (7 %). The EPCP was older, more likely inpatients, had a higher comorbidity burden and 38 % received SPC. Women, patients without caregivers and patients with breast cancer were more likely to receive SPC. CONCLUSIONS: By using objective criteria from clinical data and systematic screening, the observed prevalence of the PCP of 14 % may be generalisable to comprehensive cancer centres with similar composition of cancer diagnoses.
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Institutos de Câncer/estatística & dados numéricos , Estudos Transversais/métodos , Cuidados Paliativos/classificação , Idoso , Cuidadores , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-IdadeRESUMO
The objective of the present study was to confirm the expression and localisation pattern of the urokinase-type plasminogen activator receptor (uPAR) focusing on its possible clinical relevance in patients with urothelial neoplasia of the bladder. uPAR is a central molecule in tissue remodelling during cancer invasion and metastasis and is an established prognostic marker in various cancer diseases other than bladder cancer. Formalin-fixed and paraffin-embedded tumour-tissue blocks from 186 patients treated with radical cystectomy were analysed. uPAR expression was scored as either negative or positive as well as by the actual score. Separate scores were obtained for cancer cells, macrophages and myofibroblasts at the invasive front and in tumour core. We were able to confirm, in an independent patient cohort, the tissue expression and localisation pattern of uPAR as investigated by Immunohistochemistry as well as a significant association between uPAR positivity and increasing tumour stage and tumour grade. This demonstrates the robustness of our previous and current findings. In addition the association between uPAR positive myofibroblasts and poor survival was reproduced. The highest hazard ratios for survival were seen for uPAR positive myofibroblasts both at the invasive front and in tumour core. Evaluating uPAR expression by the actual score showed a significant association between uPAR positive myofibroblasts in tumour core and an increased risk of cancer specific mortality. Our investigations have generated new and valuable biological information about the cell types being involved in tumour invasion and progression through the plasminogen activation system.
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Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Ativador de Plasminogênio Tipo Uroquinase/análise , Estudos Retrospectivos , Bexiga Urinária/química , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/patologia , Urotélio/química , Urotélio/metabolismo , Urotélio/patologiaAssuntos
Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Embrionárias de Células Germinativas/terapia , Orquiectomia , Seminoma/diagnóstico , Seminoma/patologia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/terapia , Humanos , MasculinoRESUMO
OBJECTIVES: To evaluate the expression-and localization pattern of the urokinase-type plasminogen activator receptor (uPAR), focusing on its clinical implications in patients with urothelial neoplasia of the bladder treated with radical cystectomy. uPAR is a central molecule in tissue remodeling during cancer invasion and metastasis and is an established prognostic marker in cancer. The expression and localization of uPAR and its prognostic significance is only limitedly investigated in urothelial bladder neoplasia. MATERIALS AND METHODS: The expression-and localization pattern of uPAR was investigated in formalin-fixed paraffin-embedded tumor tissue from 149 patients treated with radical cystectomy between 1988 and 2005. uPAR expression was determined by immunohistochemistry and scored as either negative or positive. Separate values were obtained for cancer cells, macrophages, and myofibroblasts at the invasive front and tumor core, respectively. Statistical analyses were performed to evaluate the association of uPAR localization and score with clinicopathologic covariates and survival. RESULTS: uPAR positivity was seen in 122/137 (89%) and 118/149 (74%) of the neoplasias at the invasive front and tumor core, respectively. uPAR was primarily expressed by myofibroblasts and macrophages in the surrounding stroma as well as some cancer cells. A significant association between uPAR positivity and T-stage as well as grade was found for all 3 cell types in tumor core (P ≤ 0.04 for all comparisons). In univariate analysis, the uPAR positive group had a shorter survival than the uPAR negative group (hazard ratio = 2.39; 95% CI: 1.15-5.01; P = 0.020). CONCLUSIONS: The expression of uPAR is a possible prognostic marker that could be useful in identification of patients with aggressive, highly invasive tumors that could benefit from additional chemotherapy or more intensive follow-up after cystectomy.
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Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/patologia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/biossíntese , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Receptores de Ativador de Plasminogênio Tipo Uroquinase/análise , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
PURPOSE: To describe treatment results in a large cohort with stage I nonseminoma germ cell cancer (NSGCC) treated in a surveillance program. PATIENTS AND METHODS: From January 1, 1984, to December 31, 2007, 1,226 patients with stage I NSGCC, including high-risk patients with vascular invasion, were observed in a surveillance program. RESULTS: The relapse rate after orchiectomy alone was 30.6% at 5 years. Presence of vascular invasion together with embryonal carcinoma and rete testis invasion in the testicular primary identified a group with a relapse risk of 50%. Without risk factors, the relapse risk was 12%. Eighty percent of relapses were diagnosed within the first year after orchiectomy. The median time to relapse was 5 months (range, 1 to 308 months). Early relapses were mainly detected by increase in tumor markers, and late relapses were detected by computed tomography scans. Relapses after 5 years were seen in 0.5% of the whole cohort or in 1.6% of relapsing patients. The majority of relapses (94.4%) belonged to the good prognostic group according to the International Germ Cell Cancer Collaborative Group classification. The disease-specific survival at 15 years was 99.1%. CONCLUSION: A surveillance policy for patients with stage I NSGCC is a safe approach associated with an excellent cure rate and an overall low treatment burden despite a high relapse rate in a small group of patients. We recommend surveillance for patients with stage I NSGCC with immediate systemic treatment at relapse. Clearly defined risk factors for relapse are presented if an option of risk-adapted treatment is preferred.
Assuntos
Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia , Neoplasias Testiculares/cirurgia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Dinamarca , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/secundário , Orquiectomia/efeitos adversos , Orquiectomia/mortalidade , Vigilância da População , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Neoplasias Testiculares/sangue , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The focus of Specialized Palliative Care (SPC) is to improve care for patients with incurable diseases and their families, which includes the opportunity to make their own choice of place of care and ultimately place of death. The Danish Palliative Care Trial (DOMUS) aims to investigate whether an accelerated transition process from oncological treatment to continuing SPC at home for patients with incurable cancer results in more patients reaching their preferred place of care and death. The SPC in this trial is enriched with a manualized psychological intervention. METHODS/DESIGN: DOMUS is a controlled randomized clinical trial with a balanced parallel-group randomization (1:1). The planned sample size is 340 in- and outpatients treated at the Department of Oncology at Copenhagen University Hospital. Patients are randomly assigned either to: a) standard care plus SPC enriched with a standardized psychological intervention for patients and caregivers at home or b) standard care alone. Inclusion criteria are incurable cancer with no or limited antineoplastic treatment options. DISCUSSION: Programs that facilitate transition from hospital treatment to SPC at home for patients with incurable cancer can be a powerful tool to improve patients' quality of life and support family/caregivers during the disease trajectory. The present study offers a model for achieving optimal delivery of palliative care in the patient's preferred place of care and attempt to clarify challenges. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01885637.