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1.
BMC Mol Cell Biol ; 22(1): 32, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078283

RESUMO

BACKGROUND: Endothelial healing after deployment of cardiovascular devices is particularly important in the context of clinical outcome. It is therefore of great interest to develop tools for a precise prediction of endothelial growth after injury in the process of implant deployment. For experimental investigation of re-endothelialization in vitro cell migration assays are routinely used. However, semi-automatic analyses of live cell images are often based on gray value distributions and are as such limited by image quality and user dependence. The rise of deep learning algorithms offers promising opportunities for application in medical image analysis. Here, we present an intelligent cell detection (iCD) approach for comprehensive assay analysis to obtain essential characteristics on cell and population scale. RESULTS: In an in vitro wound healing assay, we compared conventional analysis methods with our iCD approach. Therefore we determined cell density and cell velocity on cell scale and the movement of the cell layer as well as the gap closure between two cell monolayers on population scale. Our data demonstrate that cell density analysis based on deep learning algorithms is superior to an adaptive threshold method regarding robustness against image distortion. In addition, results on cell scale obtained with iCD are in agreement with manually velocity detection, while conventional methods, such as Cell Image Velocimetry (CIV), underestimate cell velocity by a factor of 0.5. Further, we found that iCD analysis of the monolayer movement gave results just as well as manual freehand detection, while conventional methods again shows more frayed leading edge detection compared to manual detection. Analysis of monolayer edge protrusion by ICD also produced results, which are close to manual estimation with an relative error of 11.7%. In comparison, the conventional Canny method gave a relative error of 76.4%. CONCLUSION: The results of our experiments indicate that deep learning algorithms such as our iCD have the ability to outperform conventional methods in the field of wound healing analysis. The combined analysis on cell and population scale using iCD is very well suited for timesaving and high quality wound healing analysis enabling the research community to gain detailed understanding of endothelial movement.


Assuntos
Rastreamento de Células/métodos , Aprendizado Profundo , Cicatrização , Endotélio Vascular/citologia , Humanos
2.
Eur Urol ; 80(1): 4-6, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33722419

RESUMO

Men with metastatic germ cell tumors undergoing chemotherapy are at high risk of venous thromboembolic events and low risk of bleeding. A central venous-access device should be avoided whenever possible. Thromboprophylaxis may be prescribed after balancing the risks and benefits for each individual patient.

3.
ESMO Open ; 5(Suppl 3)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669298

RESUMO

BACKGROUND: The coronavirus pandemic has provoked discussions among healthcare providers how to manage cancer patients when faced with the threat of severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) infection. Immune checkpoint inhibitor (ICI) containing regimens are standard of care in the majority of metastatic clear cell renal cell carcinoma (mccRCC) patients. It remains unclear whether therapies should be modified in response to the COVID-19 pandemic. METHODS: We performed an online survey among physicians involved in the treatment of mccRCC, and 41 experts responded. Questions focused on criteria relevant for treatment decision outside the pandemic and the modifications of systemic therapy during COVID-19. FINDINGS: For the majority of experts (73%), the combination of International metastatic renal cell carcinoma Database Consortium (IMDC) risk category and patient fitness are two important factors for decision-making. The main treatment choice in fit, favourable risk patients outside the pandemic is pembrolizumab/axitinib for 53%, avelumab/axitinib, sunitinib or pazopanib for 13% of experts each. During the pandemic, ICI-containing regimens are chosen less often in favour of a tyrosine kinase inhibitors (TKI) monotherapy, mainly sunitinib or pazopanib (35%).In fit, intermediate/poor-risk patients outside the pandemic, over 80% of experts choose ipilimumab/nivolumab, in contrast to only 41% of physicians during COVID-19, instead more TKI monotherapies are given. In patients responding to established therapies with ICI/ICI or ICI/TKI combinations, most participants modify treatment regimen by extending cycle length, holding one ICI or even both. CONCLUSION: mccRCC treatment modifications in light of the coronavirus pandemic are variable, with a shift from ICI/ICI to ICI/TKI or TKI monotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Neoplasias Renais/tratamento farmacológico , Pneumonia Viral/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Betacoronavirus , COVID-19 , Carcinoma de Células Renais/secundário , Tomada de Decisão Clínica , Infecções por Coronavirus/prevenção & controle , Humanos , Fatores Imunológicos/uso terapêutico , Neoplasias Renais/patologia , Oncologia/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Inibidores de Proteínas Quinases/uso terapêutico , SARS-CoV-2 , Urologia/estatística & dados numéricos
4.
Trials ; 21(1): 579, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32586393

RESUMO

BACKGROUND: Multiple therapies exist for patients with metastatic castration-resistant prostate cancer (mCRPC). However, their improvement on progression-free survival (PFS) remains modest, potentially explained by tumor molecular heterogeneity. Several prognostic molecular biomarkers have been identified for mCRPC that may have predictive potential to guide treatment selection and prolong PFS. We designed a platform trial to test this hypothesis. METHODS: The Prostate-Biomarker (ProBio) study is a multi-center, outcome-adaptive, multi-arm, biomarker-driven platform trial for tailoring treatment decisions for men with mCRPC. Treatment decisions in the experimental arms are based on biomarker signatures defined as mutations in certain genes/pathways suggested in the scientific literature to be important for treatment response in mCRPC. The biomarker signatures are determined by targeted sequencing of circulating tumor and germline DNA using a panel specifically designed for mCRPC. DISCUSSION: Patients are stratified based on the sequencing results and randomized to either current clinical practice (control), where the treating physician decides treatment, or to molecularly driven treatment selection based on the biomarker profile. Outcome-adaptive randomization is implemented to early identify promising treatments for a biomarker signature. Biomarker signature-treatment combinations graduate from the platform when they demonstrate 85% probability of improving PFS compared to the control arm. Graduated combinations are further evaluated in a seamless confirmatory trial with fixed randomization. The platform design allows for new drugs and biomarkers to be introduced in the study. CONCLUSIONS: The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03903835. Date of registration: April 4, 2019. Status: Recruiting.


Assuntos
Biomarcadores Tumorais/genética , Medicina de Precisão , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/terapia , Ensaios Clínicos Fase III como Assunto , Análise Mutacional de DNA , Mutação em Linhagem Germinativa , Humanos , Masculino , Estudos Multicêntricos como Assunto , Metástase Neoplásica , Intervalo Livre de Progressão , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Laryngoscope ; 130(9): E515-E521, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32065408

RESUMO

OBJECTIVES: Cisplatin-related hearing loss (HL) is claimed to progress after treatment. This controlled longitudinal study with extended follow-up investigates HL in testicular cancer survivors (TCSs) after cisplatin-based chemotherapy (CBCT). STUDY DESIGN: Controlled longitudinal study. METHODS: Eighty-two TCSs treated with CBCT between 1980 and 1994 in Norway participated in two surveys (S1/S3), including pure-tone audiograms (0.125-8 kHz) and self-reported HL, 12 and 31 years after treatment, respectively. Hearing thresholds were age-adjusted based on age-matched hearing thresholds from the general population (controls). Hearing loss was defined as thresholds >20 dB at any frequency. RESULTS: Between the two surveys, the prevalence of high-frequency HL (4, 6, and 8 kHz) increased from 73% to 94% but approached those of the aging general population after age adjustment. In TCSs aged >40 years at first survey, HL at the subsequent survey equaled that of controls. Self-reported HL increased from seven (9%) at S1 to 20 (26%) at S3. At S1, age-adjusted HL was identified in all (seven) TCSs reporting decreased hearing whereas at S3, hearing thresholds did not differ from controls in seven out of 20 patients reporting HL. CONCLUSION: CBCT-related ototoxicity causes high-frequency HL, but in contrast to reports from follow-up studies from the first post-treatment decade, no major progression was found beyond the first post-treatment decade for frequencies 0.125-8 kHz. Importantly, with extended follow-up, hearing thresholds of patients approach those of the general population, possibly due to a less-than-additive effect with age-related hearing loss (ARHL) in CBCT-treated patients. Age-and sex-matching is strongly advised in long-term follow-up of CBCT-related ototoxicity. Specificity for detecting ototoxicity with self-reported questionnaires decreases with extended follow-up. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:E515-E523, 2020.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Perda Auditiva de Alta Frequência/epidemiologia , Ototoxicidade/epidemiologia , Presbiacusia/epidemiologia , Neoplasias Testiculares/tratamento farmacológico , Adulto , Idoso , Envelhecimento , Audiometria de Tons Puros , Limiar Auditivo , Sobreviventes de Câncer/estatística & dados numéricos , Seguimentos , Audição , Perda Auditiva de Alta Frequência/induzido quimicamente , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Ototoxicidade/etiologia , Presbiacusia/etiologia , Autorrelato , Neoplasias Testiculares/fisiopatologia
6.
Eur Urol Oncol ; 2(3): 265-273, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31200840

RESUMO

CONTEXT: The centralization of cancer care is associated with better clinical outcomes and may be a method for optimizing value-based health care systems. OBJECTIVE: To systematically review the literature regarding the impact of centralization of care on clinical outcomes for genitourinary malignancies. EVIDENCE ACQUISITION: A systematic review was conducted using Ovid and MEDLINE to identify studies between 1970 and 2018 reporting on the centralization of care for genitourinary malignancies. Prospective and retrospective studies were screened. EVIDENCE SYNTHESIS: There were no published randomized control trials (RCTs) on the centralization of care for genitourinary malignancies. Twenty-two retrospective studies met inclusion criteria. Centralization of radical cystectomy was the most studied. Care for bladder cancer, prostate cancer, penile cancer, testicular cancer, and renal cancer was reportedly associated with better morbidity and survival outcomes for patients treated at high-volume centers. However, evidence of better outcomes for centralization of care remains limited for penile, renal, and testicular cancers owing to the paucity of data and/or the lower incidence of these genitourinary malignancies. CONCLUSIONS: Care for genitourinary malignancies by high-volume providers was associated with greater utilization of cancer surgery, lower morbidity, and better survival outcomes. Centralization of care was most appropriate for complex procedures such as radical cystectomy when interpreted in the context of survival outcomes. Further research is needed to address the impact of centralizing care for all urologic malignancies with consideration of the associated costs and patient-reported measures, including quality of life and patient experience. PATIENT SUMMARY: We explored the evidence for moving major operations into larger centers. We focused on surgery for cancers of the bladder, prostate, testicle, penis, and kidney, and found that larger-volume hospitals had better survival outcomes and fewer complications when compared to smaller hospitals. The difference may be greatest for complex major surgeries such as radical cystectomy.


Assuntos
Atenção à Saúde/organização & administração , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Neoplasias Urogenitais/terapia , Institutos de Câncer , Cistectomia/estatística & dados numéricos , Cistectomia/tendências , Atenção à Saúde/tendências , Mortalidade Hospitalar , Humanos , Tempo de Internação , Resultado do Tratamento , Neoplasias Urogenitais/mortalidade
7.
J Gynecol Oncol ; 30(4): e56, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31074244

RESUMO

OBJECTIVE: In this study, we evaluated the toxicity and clinical efficacy of nivolumab, a programmed cell death protein 1 (PD-1) inhibitor, on patients with platinum resistant ovarian cancer. METHODS: Every second week, 18 patients with platinum resistance ovarian cancer received nivolumab until disease progression occurred. We assessed toxicity, disease control rate, progression free survival (PFS) and overall survival (OS). Radiological response evaluation according to irRECIST was performed every 12th week, while clinical evaluation was done every second week. RESULTS: The disease control rate was 44% (95% confidence interval [CI]=19-87) as 8 showed stable disease, 6 showed progressive disease and 4 died before the first radiological response evaluation. The median OS was 30 weeks (95% CI=14-42; range, 3-95), and PFS was 15 weeks (95% CI=13-17). The median follow-up time was 30 weeks (range, 3-123). The rate of grade 2-5 adverse events was 28% (5 out of 18). Two patients (11%) developed grade 2 and 3 adverse events, respectively, while no grade 4 events were observed. One patient died from intestinal perforation, believed to be caused by concomitant bevacizumab rather than nivolumab. CONCLUSION: This study shows few adverse events, and promising clinical efficacy when using nivolumab for ovarian cancer.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Nivolumabe/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Administração Intravenosa , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/mortalidade , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/mortalidade , Platina/imunologia , Platina/uso terapêutico , Estudos Prospectivos
8.
Acta Oncol ; 57(10): 1392-1400, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29775128

RESUMO

BACKGROUND: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs. MATERIAL AND METHODS: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment. Information about second cancers after SII was retrieved from the Norwegian Cancer Registry. RESULTS: A larger Pt decline from SI to SII was associated with a decreased risk of a second cancer diagnosis (HR 0.78, 95% CI 0.62-0.99 per 10 ng/L/year), and worsening of paresthesias in hands (OR 1.98, 95% CI 1.09-3.59 per 10 ng/L/year) and tinnitus (OR 1.51, 95% CI 1.01-2.27 per 10 ng/L/year). CONCLUSION: In summary, we found a significant association between a larger Pt decline and a reduced risk of second cancers and deterioration of paresthesias in hands and tinnitus.


Assuntos
Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Cisplatino/efeitos adversos , Platina/sangue , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Idoso , Cisplatino/farmacocinética , Perda Auditiva/induzido quimicamente , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/mortalidade , Adulto Jovem
10.
Eur Urol ; 73(3): 394-405, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29100813

RESUMO

CONTEXT: Patients with clinical stage I (CS I) seminoma testis with large primary tumours and/or rete testis invasion (RTI) might have an increased risk of relapse. In recent years, these risk factors have frequently been employed to decide on adjuvant treatment. OBJECTIVE: To systematically review the literature on tumour size and RTI as risk factors for relapse in CS I seminoma testis patients under surveillance. EVIDENCE ACQUISITION: Relevant databases including Medline, Embase, and the Cochrane Library were searched up to November 2016. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The primary outcome was the rate of relapse and relapse-free survival (RFS). The risk of bias was assessed by the Quality in Prognosis Studies tool. EVIDENCE SYNTHESIS: After assessing 3068 abstracts and 80 full-text articles, 20 studies met the inclusion criteria. Although evidence to justify a cut-off of 4cm for size was lacking, it was the most frequently studied. The reported hazard ratio (HR) for the RFS for tumours >4cm was 1.59-2.8. Accordingly, the reported 5-yr RFS ranged from 86.6% to 95.5% and from 73.0% to 82.6% for patients having tumours ≤4 and >4cm, respectively. For tumours with RTI present, the reported HR was 1.4-1.7. The 5-yr RFS ranged from 86.0% to 92.0% and 74.9% to 79.5% for patients without versus those with RTI present, respectively. A meta-analysis was considered inappropriate due to data heterogeneity. CONCLUSIONS: Primary tumour size and RTI are associated with the risk of relapse in CS I seminoma testis patients during surveillance. However, in the presence of either risk factor, the vast majority of patients are cured by orchiectomy alone and will not relapse. Furthermore, the evidence on the prognostic value of size and RTI has significant limitations, so prudency is warranted on their routine use in clinical practice. PATIENT SUMMARY: Primary testicular tumour size and rete testis invasion are considered to be important prognostic factors for the risk of relapse in patients with clinical stage I seminoma testis. We systematically reviewed all the literature on the prognostic value of these two postulated risk factors. The outcome is that the prognostic power of these factors in the published literature is too low to advocate their routine use in clinical practice and to drive the choice on adjuvant treatment in clinical stage I seminoma testis patients.

11.
Onco Targets Ther ; 10: 371-385, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28144152

RESUMO

BACKGROUND: This population-wide retrospective, non-interventional registry study assessed changes in overall survival (OS) and factors influencing OS in Norwegian patients with renal cell carcinoma (RCC). METHODS: Two population-wide health registries were used to identify all RCC patients with (mRCC) or without metastases diagnosed before (2002-2005) and after (2006-2008 and 2009-2011) introduction of targeted therapies. Median OS was estimated using Kaplan-Meier method. Cox proportional hazards regression modeling was used to identify prognostic factors. RESULTS: Overall, 5,463 patients were diagnosed with RCC during 2002-2005 (n=1,898), 2006-2008 (n=1,631), and 2009-2011 (n=1,934); of these, 1,678 (31%) had mRCC. Patients diagnosed in 2009-2011 and 2006-2008 had significant (P<0.001) improvements in OS versus those diagnosed in 2002-2005: median OS, not reached and not reached versus 82.0 months in RCC; 14.0 and 12.0 months versus 9.0 months in mRCC. Similarly, OS improvements were seen in the primary and elderly (≥75 years) mRCC populations. Median OS was comparable (12 months) between clear cell and papillary mRCC, but it was longer (24.0 months) for chromophobe mRCC. Multivariate regression analyses showed that younger age, previous nephrectomy, and 1 or more prescriptions of targeted therapy were significantly associated with longer OS in mRCC patients. CONCLUSION: OS increased in RCC and mRCC patients in Norway between 2002 and 2011 following introduction of targeted therapies.

12.
World J Urol ; 35(8): 1161-1166, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27738807

RESUMO

INTRODUCTION: In 1979, the Copenhagen group around Dr. Skakkebaek introduced contralateral biopsy in patients with testicular germ cell tumour (GCT) as a means of early diagnosing a contralateral testicular tumour (Berthelsen et al. in Br Med J 2(6186):363-364, 1). Although the rationale of contralateral biopsies is based on much of scientific evidence, no issue regarding the management of GCTs has been more controversial than the issue of contralateral biopsies (Heidenreich in BJU Int 104(9 Pt B):1346-1350, 2; Grigor and Rorth in Eur Urol 23(1):129-135, 3). A poll conducted during the GCT Consensus Meeting in Berlin 2011 revealed that 43 % of 60 leading experts would not recommend a contralateral biopsy and only 13.7 % would do the biopsy in all cases with GCT (Beyer et al. in Ann Oncol 24(4):878-888, 4). Likewise, the European Association of Urology and the European Society of Medical Oncology offer only weak recommendations with respect to contralateral biopsies in their guidelines of testicular cancer (Albers et al. in Eur Urol 68(6):1054-1068, 5; Oldenburg et al. in Ann Oncol 24(Suppl 6):vi125-vi132, 6). CONCLUSION: This review summarizes contemporary knowledge regarding contralateral biopsies to provide professionals caring for GCT patients with sufficient information to decide for or against the procedure in clinical practice.


Assuntos
Biópsia/métodos , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Primárias Múltiplas/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Testiculares/patologia , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Testiculares/diagnóstico
13.
Urol Oncol ; 34(11): 487.e13-487.e20, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27523611

RESUMO

OBJECTIVE: To evaluate the associations between long-term serum levels of platinum (se-Pt) and neurotoxicity and ototoxicity (NTX), endocrine gonadal function (endocrine-GF), and cardiovascular disease (CVD) in testicular cancer survivors. MATERIAL AND METHODS: A total of 292 cisplatin-treated testicular cancer survivors (1980-1994) participated in a national follow-up study (2007-2008). Se-Pt was quantified by inductively coupled plasma mass spectrometry, and categorized in quartiles. Symptoms of NTX were assessed with scale for chemotherapy-induced neurotoxicity (SCIN), with each symptom in 4 categories and total SCIN score categorized in quartiles. Endocrine-GF was categorized according to cutoff values for the 25, 50, and 75 percentiles of luteinizing hormone (LH) and testosterone within each decadal age group established from a control group. CVD was defined as ischemic heart disease, stroke, or artery occlusion. Associations between se-Pt levels and NTX, endocrine-GF, or risk for CVD, were analyzed with ordinal logistic regression and Cox regression, respectively. RESULTS: Median follow-up was 19 years (range: 13-28). In ordinal regression analyses, increasing quartiles of se-Pt were significantly associated with increasing quartiles of SCIN (P for trend = 0.05), increased tinnitus (P<0.001), and increased hearing impairment (P = 0.04). The association remained significant for tinnitus when adjusting for cisplatin dose. Increasing LH quartiles was associated with increasing se-Pt quartiles (P = 0.04). No association between se-Pt in quartiles and CVD was established. CONCLUSION: Median 19 years after treatment, increasing quartiles of se-Pt are associated with increasing SCIN score, tinnitus, hearing impairment, and increasing LH levels. However, these associations remained significant only for tinnitus and LH when adjusting for administered cisplatin dose.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sobreviventes de Câncer , Doenças Cardiovasculares/epidemiologia , Cisplatino/efeitos adversos , Perda Auditiva/induzido quimicamente , Hormônio Luteinizante/sangue , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Neoplasias Testiculares/tratamento farmacológico , Zumbido/induzido quimicamente , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/sangue , Terapia Combinada , Comorbidade , Etoposídeo/administração & dosagem , Seguimentos , Perda Auditiva/epidemiologia , Humanos , Hipogonadismo/epidemiologia , Hipogonadismo/etiologia , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Orquiectomia , Doenças do Sistema Nervoso Periférico/epidemiologia , Inquéritos e Questionários , Neoplasias Testiculares/cirurgia , Zumbido/epidemiologia , Vimblastina/administração & dosagem , Adulto Jovem
14.
J Clin Oncol ; 34(23): 2687-9, 2016 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-27382103
15.
J Cancer Res Clin Oncol ; 142(9): 1979-94, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27424191

RESUMO

BACKGROUND: Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines. METHODS: In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array. RESULTS: Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT. CONCLUSION: Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.


Assuntos
Antineoplásicos , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Taxoides/farmacologia , Neoplasias Testiculares/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Paclitaxel/farmacologia , Neoplasias Testiculares/patologia
16.
J Cancer Surviv ; 10(5): 842-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26920871

RESUMO

PURPOSE: The purpose of this research is to study the prevalence of posttraumatic stress disorder (PTSD) and variables associated with PTSD in Norwegian long-term testicular cancer survivors (TCSs) both cross-sectionally and longitudinally. METHODS: At a mean of 11 years after diagnosis, 1418 TCSs responded to a mailed questionnaire, and at a mean of 19 years after diagnosis, 1046 of them responded again to a modified questionnaire. Posttraumatic symptoms related to testicular cancer were self-rated with the Impact of Event Scale (IES) at the 11-year study only. An IES total score ≥35 defined Full PTSD, and a score 26-34 identified Partial PTSD, and the combination of Full and Partial PTSD defined Probable PTSD. RESULTS: At the 11-year study, 4.5 % had Full PTSD, 6.4 % had Partial PTSD, and 10.9 % Probable had PTSD. At both studies, socio-demographic variables, somatic health, anxiety/depression, chronic fatigue, and neurotoxic adverse effects were significantly associated with Probable PTSD in bivariate analyses. Probable anxiety disorder, poor self-rated health, and neurotoxicity remained significant with Probable PTSD in multivariate analyses at the 11-year study. In bivariate analyses, probable PTSD at that time significantly predicted socio-demographic variables, somatic health, anxiety/depression, chronic fatigue, and neurotoxicity among participants of the 19-year study, but only probable anxiety disorder remained significant in multivariable analysis. CONCLUSIONS: In spite of excellent prognosis, 10.9 % of long-term testicular cancer survivors had Probable PTSD at a mean of 11 years after diagnosis. Probable PTSD was significantly associated with a broad range of problems both at that time and was predictive of considerable problems at a mean of 19 year postdiagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Among long-term testicular cancer survivors, 10.9 % have Probable PTSD with many associated problems, and therefore health personnel should explore stress symptoms at follow-up since efficient treatments are available.


Assuntos
Transtornos de Estresse Pós-Traumáticos/etiologia , Sobreviventes/psicologia , Neoplasias Testiculares/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Prevalência , Prognóstico , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Inquéritos e Questionários , Neoplasias Testiculares/complicações , Neoplasias Testiculares/terapia
17.
Oncologist ; 20(9): 1028-35, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26240132

RESUMO

BACKGROUND: With the advent of targeted therapies, many treatment options in the first-line setting of metastatic clear cell renal cell carcinoma (mccRCC) have emerged. Guidelines and randomized trial reports usually do not elucidate the decision criteria for the different treatment options. In order to extract the decision criteria for the optimal therapy for patients, we performed an analysis of treatment algorithms from experts in the field. MATERIALS AND METHODS: Treatment algorithms for the treatment of mccRCC from experts of 11 institutions were obtained, and decision trees were deduced. Treatment options were identified and a list of unified decision criteria determined. The final decision trees were analyzed with a methodology based on diagnostic nodes, which allows for an automated cross-comparison of decision trees. The most common treatment recommendations were determined, and areas of discordance were identified. RESULTS: The analysis revealed heterogeneity in most clinical scenarios. The recommendations selected for first-line treatment of mccRCC included sunitinib, pazopanib, temsirolimus, interferon-α combined with bevacizumab, high-dose interleukin-2, sorafenib, axitinib, everolimus, and best supportive care. The criteria relevant for treatment decisions were performance status, Memorial Sloan Kettering Cancer Center risk group, only or mainly lung metastases, cardiac insufficiency, hepatic insufficiency, age, and "zugzwang" (composite of multiple, related criteria). CONCLUSION: In the present study, we used diagnostic nodes to compare treatment algorithms in the first-line treatment of mccRCC. The results illustrate the heterogeneity of the decision criteria and treatment strategies for mccRCC and how available data are interpreted and implemented differently among experts. IMPLICATIONS FOR PRACTICE: The data provided in the present report should not be considered to serve as treatment recommendations for the management of treatment-naïve patients with multiple metastases from metastatic clear cell renal cell carcinoma outside a clinical trial; however, the data highlight the different treatment options and the criteria used to select them. The diversity in decision making and how results from phase III trials can be interpreted and implemented differently in daily practice are demonstrated.


Assuntos
Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/diagnóstico , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Árvores de Decisões , Diagnóstico por Computador/métodos , Humanos , Neoplasias Renais/patologia , Metástase Neoplásica
18.
Eur Urol ; 68(6): 1054-68, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26297604

RESUMO

CONTEXT: This is an update of the previous European Association of Urology testis cancer guidelines published in 2011, which included major changes in the diagnosis and treatment of germ cell tumours. OBJECTIVE: To summarise latest developments in the treatment of this rare disease. Recommendations have been agreed within a multidisciplinary working group consisting of urologists, medical oncologists, and radiation oncologists. EVIDENCE ACQUISITION: A semi-structured literature search up to February 2015 was performed to update the recommendations. In addition, this document was subjected to double-blind peer review before publication. EVIDENCE SYNTHESIS: This publication focuses on the most important changes in treatment recommendations for clinical stage I disease and the updated recommendations for follow-up. CONCLUSIONS: Most changes in the recommendations will lead to an overall reduction in treatment burden for patients with germ cell tumours. In advanced stages, treatment intensification is clearly defined to further improve overall survival rates. PATIENT SUMMARY: This is an update of a previously published version of the European Association of Urology guidelines for testis cancer, and includes new recommendations for clinical stage I disease and revision of the follow-up recommendations. Patients should be fully informed of all the treatment options available to them.


Assuntos
Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Árvores de Decisões , Humanos , Masculino , Estadiamento de Neoplasias
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