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Feldman-Stewart D.,Queens University | Capirci C.,Azienda ULSS 18 | Brennenstuhl S.,Queens University | Tong C.,Queens University | And 12 more authors.
Medical Decision Making

Purpose: To describe decisional roles of patients with early-stage prostate cancer in 9 countries and to compare the information they rated important for decision making (DM). Method: A survey of recently treated patients was conducted in Canada, Italy, England, Germany, Poland, Portugal, Netherlands, Spain, and Turkey. Participants indicated their decisional role in their actual decision and the role they would prefer now. Each participant also rated (essential/desired/no opinion/avoid) the importance of obtaining answers, between diagnosis and treatment decision, to each of 92 questions. For each essential/desired question, participants specified all purposes for that information (to help them: understand/decide/plan/not sure/other). Results: A total of 659 patients participated with country-specific response rates between 58%-77%. Between 83%-96% of each country's participants recalled actually taking an active decisional role and, in most countries, that increased slightly if they were to make the decision today; there were no significant differences among countries. There was a small reliable difference in the mean number of questions rated essential for DM across countries. More striking, however, was the wide variability within each country: no question was rated essential for DM by even 50% of its participants but almost every question was rated essential by some. Conclusions: Almost all participants from each country want to participate in their treatment decisions. Although there are country-specific differences in the amount of information required, wide variation within each country suggests that information that patients feel is essential or desired for DM should be addressed on an individual basis in all countries. Source

Barnett G.C.,University of Cambridge | Barnett G.C.,Strangeways Research Laboratories | Elliott R.M.,Christie Hospital | Alsner J.,Aarhus University Hospital | And 20 more authors.
Radiotherapy and Oncology

Background and purpose: Reported associations between risk of radiation-induced normal tissue injury and single nucleotide polymorphisms (SNPs) in TGFB1, encoding the pro-fibrotic cytokine transforming growth factor-beta 1 (TGF-β1), remain controversial. To overcome publication bias, the international Radiogenomics Consortium collected and analysed individual patient level data from both published and unpublished studies. Materials and methods: TGFB1 SNP rs1800469 c.-1347T>C (previously known as C-509T) genotype, treatment-related data, and clinically-assessed fibrosis (measured at least 2 years after therapy) were available in 2782 participants from 11 cohorts. All received adjuvant breast radiotherapy. Associations between late fibrosis or overall toxicity, reported by STAT (Standardised Total Average Toxicity) score, and rs1800469 genotype were assessed. Results: No statistically significant associations between either fibrosis or overall toxicity and rs1800469 genotype were observed with univariate or multivariate regression analysis. The multivariate odds ratio (OR), obtained from meta-analysis, for an increase in late fibrosis grade with each additional rare allele of rs1800469 was 0.98 (95% Confidence Interval (CI) 0.85-1.11). This CI is sufficiently narrow to rule out any clinically relevant effect on toxicity risk in carriers vs. non-carriers with a high probability. Conclusion: This meta-analysis has not confirmed previous reports of association between fibrosis or overall toxicity and rs1800469 genotype in breast cancer patients. It has demonstrated successful collaboration within the Radiogenomics Consortium. © 2012 Elsevier Ireland Ltd. All rights reserved. Source

Leach M.O.,Institute of Cancer Research and Royal Marsden | Morgan B.,Institute of Cancer Research and Royal Marsden | Tofts P.S.,University of Sussex | Buckley D.L.,University of Leeds | And 26 more authors.
European Radiology

Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and withconsistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCEMRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. Key Points ̇ Tumour vascular function is key to tumour development and treatment ̇ Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function ̇ Thus DCE-MRI with pharmacokinetic models can assess novel treatments ̇ Many recent developments are advancing the accuracy of and information from DCE-MRI ̇ Establishing common methodology across multiple centres is challenging and requires accepted guidelines. © European Society of Radiology 2012. Source

Moore A.S.,Queensland Childrens Medical Research Institute | Moore A.S.,Institute of Cancer Research and Royal Marsden | Kearns P.R.,University of Birmingham | Knapper S.,University of Cardiff | And 2 more authors.

Significant improvements in survival for children with acute myeloid leukaemia (AML) have been made over the past three decades, with overall survival rates now approximately 60-70%. However, these gains can be largely attributed to more intensive use of conventional cytotoxics made possible by advances in supportive care, and although over 90% of children achieve remission with frontline therapy, approximately one third in current protocols relapse. Furthermore, late effects of therapy cause significant morbidity for many survivors. Novel therapies are therefore desperately needed. Early-phase paediatric trials of several new agents such as clofarabine, sorafenib and gemtuzumab ozogamicin have shown encouraging results in recent years. Due to the relatively low incidence of AML in childhood, the success of paediatric early-phase clinical trials is largely dependent upon collaborative clinical trial design by international cooperative study groups. Successfully incorporating novel therapies into frontline therapy remains a challenge, but the potential for significant improvement in the duration and quality of survival for children with AML is high. © 2013 Macmillan Publishers Limited. Source

Desouza N.M.,Institute of Cancer Research and Royal Marsden | Desouza N.M.,MRI Unit | Orton M.,Institute of Cancer Research and Royal Marsden | Downey K.,Institute of Cancer Research and Royal Marsden | And 4 more authors.
Journal of Magnetic Resonance Imaging

Purpose To investigate the clinical utility of the reverse gradient algorithm in correcting distortions in diffusion-weighted images of the cervix and for increasing diagnostic performance. Materials and Methods Forty-one patients ages 25-72 years (mean 40 ± 11 years) with suspected or early stage cervical cancer were imaged at 3T using an endovaginal coil. T2-weighted (W) and diffusion-weighted images with right and left phase-encode gradient directions were obtained coronal to the cervix (b = 0, 100, 300, 500, 800 s mm-2). Differences in angle of the endocervical canal to the x-axis between T2W and right-gradient, left-gradient, and corrected images were measured. Uncorrected and corrected images were assessed for diagnostic performance when viewed together with T2W images by two independent observers against subsequent histology. Results The angles of the endocervical canal relative to the x-axis were significantly different between the T2W images and the right-gradient images (P = 0.007), approached significance for left-gradient images (P = 0.055), and were not significantly different after correction (P = 0.95). Corrected images enabled a definitive diagnosis in 34% (n = 14) of patients classified as equivocal on uncorrected images. Tumor volume in this subset was 0.18 ± 0.44 cm3 (mean ± SD; sensitivity of detection 100% [8/8], specificity 50% [3/6] for an experienced observer). Correction did not improve diagnostic performance for the less-experienced observer. Conclusion Distortion-corrected diffusion-weighted images improved correspondence with T2W images and diagnostic performance in a third of cases. © 2015 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. Source

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