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Birtle A.,Rosemere Cancer Center
Expert Review of Anticancer Therapy | Year: 2013

Recently, licensed and emerging treatments for metastatic castrate-resistant prostate cancer are transforming the prognosis for men whose disease has already progressed during or after docetaxel-based chemotherapy. Two agents (cabazitaxel and abiraterone) are already accessible to prescribers, having shown survival benefits versus their comparators in randomized controlled trials, and other agents are showing promising results. A future in which metastatic castrate-resistant prostate cancer can be managed as a 'chronic disease' looks tantalizingly close. The challenge for clinicians will be to use these treatments rationally, in a way that optimizes each individual patient's chances of prolonged survival. © 2013 2013 Expert Reviews Ltd. Source


Bezecny P.,Rosemere Cancer Center
Medical Oncology | Year: 2014

Epigenetic mechanisms are increasingly recognized as a major factor contributing to pathogenesis of cancer including glioblastoma, the most common and most malignant primary brain tumour in adults. Enzymatic modifications of histone proteins regulating gene expression are being exploited for therapeutic drug targeting. Over the last decade, numerous studies have shown promising results with histone deacetylase (HDAC) inhibitors in various malignancies. This article provides a brief overview of mechanism of anti-cancer effect and pharmacology of HDAC inhibitors and summarizes results from pre-clinical and clinical studies in glioblastoma. It analyses experience with HDAC inhibitors as single agents as well as in combination with targeted agents, cytotoxic chemotherapy and radiotherapy. Hallmark features of glioblastoma, such as uncontrolled cellular proliferation, invasion, angiogenesis and resistance to apoptosis, have been shown to be targeted by HDAC inhibitors in experiments with glioblastoma cell lines. Vorinostat is the most advanced HDAC inhibitor that entered clinical trials in glioblastoma, showing activity in recurrent disease. Multiple phase II trials with vorinostat in combination with targeted agents, temozolomide and radiotherapy are currently recruiting. While the results from pre-clinical studies are encouraging, early clinical trials showed only modest benefit and the value of HDAC inhibitors for clinical practice will need to be confirmed in larger prospective trials. Further research in epigenetic mechanisms driving glioblastoma pathogenesis and identification of molecular subtypes of glioblastoma is needed. This will hopefully lead to better selection of patients who will benefit from treatment with HDAC inhibitors. © Springer Science+Business Media 2014. Source


Hill G.,Rosemere Cancer Center | Thompson G.,Sheffield Hallam University | Willis S.,Sheffield Hallam University | Hodgson D.,Sheffield Hallam University
Radiography | Year: 2014

Aim: There is currently a drive within cancer services to incorporate user involvement in delivery and education, as such the aim of this article is to investigate the potential role of service users in pre-registration education and how this could impact on radiotherapy programmes. Method: Key databases were searched for terms: patient participation, service user involvement, health care education, student assessment, patient involvement, pre-registration education and training. Suitable literature was reviewed and references within all articles and documents were investigated to ensure as broad and an inclusive search possible. Results: There is little published literature indicating user involvement in radiotherapy education but many studies in nursing, medicine and other allied health professions indicate a rationale for user involvement. Discussion: There are benefits of involving service users, i.e. gaining insight from patients and carers perspectives, challenges stereotypes and assumptions. Disadvantages include the quality of the feedback from users in assessment, resources required, and the ethical considerations. Conclusion: Inclusion of service users in radiotherapy education is recommended in line with cancer care policy, they provide a unique perspective to learning and involvement should be encouraged. © 2013 The College of Radiographers. Source


Paramasivan S.,University of Bristol | Huddart R.,The Institute of Cancer Research | Hall E.,The Institute of Cancer Research | Lewis R.,The Institute of Cancer Research | And 3 more authors.
Trials | Year: 2011

Background: Recruitment to randomised controlled trials (RCTs) with very different treatment arms is often difficult. The ProtecT (Prostate testing for cancer and Treatment) study successfully used qualitative research methods to improve recruitment and these methods were replicated in five other RCTs facing recruitment difficulties. A similar qualitative recruitment investigation was undertaken in the SPARE (Selective bladder Preservation Against Radical Excision) feasibility study to explore reasons for low recruitment and attempt to improve recruitment rates by implementing changes suggested by qualitative findings.Methods: In Phase I of the investigation, reasons for low levels of recruitment were explored through content analysis of RCT documents, thematic analysis of interviews with trial staff and recruiters, and conversation analysis of audio-recordings of recruitment appointments. Findings were presented to the trial management group and a plan of action was agreed. In Phase II, changes to design and conduct were implemented, with training and feedback provided for recruitment staff.Results: Five key challenges to trial recruitment were identified in Phase I: (a) Investigators and recruiters had considerable difficulty articulating the trial design in simple terms; (b) The recruitment pathway was complicated, involving staff across different specialties/centres and communication often broke down; (c) Recruiters inadvertently used 'loaded' terminology such as 'gold standard' in study information, leading to unbalanced presentation; (d) Fewer eligible patients were identified than had been anticipated; (e) Strong treatment preferences were expressed by potential participants and trial staff in some centres. In Phase II, study information (patient information sheet and flowchart) was simplified, the recruitment pathway was focused around lead recruiters, and training sessions and 'tips' were provided for recruiters. Issues of patient eligibility were insurmountable, however, and the independent Trial Steering Committee advised closure of the SPARE trial in February 2010.Conclusions: The qualitative investigation identified the key aspects of trial design and conduct that were hindering recruitment, and a plan of action that was acceptable to trial investigators and recruiters was implemented. Qualitative investigations can thus be used to elucidate challenges to recruitment in trials with very different treatment arms, but require sufficient time to be undertaken successfully.Trial Registration: CRUK/07/011; ISRCTN61126465. © 2011 Paramasivan et al; licensee BioMed Central Ltd. Source


Langenhuijsen J.,Radboud University Nijmegen | Birtle A.,Rosemere Cancer Center | Klatte T.,Medical University of Vienna | Porpiglia F.,San Luigi Gonzaga Hospital | Timsit M.-O.,University of Paris Descartes
European Urology Focus | Year: 2016

Context: Controversy exists regarding the choice for surgical approach and the role of lymph node dissection (LND) in adrenocortical carcinoma (ACC) treatment. ACC surgery is increasingly advocated to be performed in specialist referral centres. Objective: To review systematically the evidence of oncologic outcomes for ACC surgery by open adrenalectomy (OA) or laparoscopic adrenalectomy (LA), and for concomitant LND. The influence of surgical volume is also analysed. Evidence acquisition: A systematic review of Ovid Medline, Embase, and the Cochrane Library was performed in June 2015 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Twenty-six publications were selected for inclusion in the analysis. Meta-analyses were performed when appropriate. Evidence synthesis: Included studies reported on oncologic outcomes after surgical treatment of ACC (11 studies), compared different surgical approaches (7 studies), evaluated the role of LND (3 studies), and analysed the effect of surgical volume on outcome (5 studies). From the available studies and the meta-analysis, no differences were found in the rate of positive surgical margins, disease-free survival, and overall survival between OA and LA in localised disease. In patients with histologically proven positive lymph nodes, a shorter time to recurrence was seen when no proper LND was performed. A trend for better recurrence-free survival and disease-specific survival after LND was found. In high-volume centres, more aggressive and open surgery was performed. In low-volume centres, higher local recurrence and distant metastases rates, and a shorter time to recurrence were seen. Our findings are limited due to the low level of evidence of selected studies, patient and disease heterogeneity, and heterogeneous surgeon populations. Conclusions: After adequate clinical staging for localised disease, LA is as effective and oncologically safe as OA, as long as oncologic principles are respected. LA should be performed by surgeons with extensive experience in laparoscopic adrenal surgery in high-volume centres. Patients with locally advanced disease and metastatic disease, for debulking purposes, should be operated on extensively with open surgery with adequate margins and concomitant LND to optimise staging, which may contribute to survival in locally advanced disease. Patient summary: Laparoscopic surgery for localised adrenocortical carcinoma is safe and effective when performed by expert surgeons in high-volume centres. Patients with more extensive tumours should be operated with open surgery; lymph node dissection is mainly applied to determine the stage of the disease. Laparoscopic surgery for localised adrenocortical carcinoma is safe and effective when performed by expert surgeons at high-volume centres. Patients with more extensive disease should be operated with open surgery, and lymph node dissection is indicated mainly for staging. © 2015 European Association of Urology. Source

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