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Farrugia D.,Gloucestershire Oncology Center | Reed N.,Beatson Oncology Center | Thakker R.V.,University of Oxford
British Journal of Cancer | Year: 2011

Background:This study sought to determine the safety of single agent capecitabine, a pro-drug of 5FU, in patients with metastatic non-pancreatic neuroendocrine tumours (NETs).Methods:Multicentre phase II, first-line study design. Oral capecitabine was administered on days 1-14 of 3-week cycles.Results:Treatment was safe and well tolerated. Common toxicities were diarrhoea and fatigue.Conclusion:The study provides evidence to support the use of capecitabine as a substitute for infusional 5FU in the management of NETs. © 2011 Cancer Research UK All rights reserved. Source


Haviland J.S.,The Institute of Cancer Research | Haviland J.S.,University of Southampton | Owen J.R.,Gloucestershire Oncology Center | Dewar J.A.,Ninewells Hospital | And 13 more authors.
The Lancet Oncology | Year: 2013

Background: 5-year results of the UK Standardisation of Breast Radiotherapy (START) trials suggested that lower total doses of radiotherapy delivered in fewer, larger doses (fractions) are at least as safe and effective as the historical standard regimen (50 Gy in 25 fractions) for women after primary surgery for early breast cancer. In this prespecified analysis, we report the 10-year follow-up of the START trials testing 13 fraction and 15 fraction regimens. Methods: From 1999 to 2002, women with completely excised invasive breast cancer (pT1-3a, pN0-1, M0) were enrolled from 35 UK radiotherapy centres. Patients were randomly assigned to a treatment regimen after primary surgery followed by chemotherapy and endocrine treatment (where prescribed). Randomisation was computer-generated and stratified by centre, type of primary surgery (breast-conservation surgery or mastectomy), and tumour bed boost radiotherapy. In START-A, a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 41·6 Gy or 39 Gy in 13 fractions over 5 weeks. In START-B, a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 40 Gy in 15 fractions over 3 weeks. Eligibility criteria included age older than 18 years and no immediate surgical reconstruction. Primary endpoints were local-regional tumour relapse and late normal tissue effects. Analysis was by intention to treat. Follow-up data are still being collected. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. Findings: START-A enrolled 2236 women. Median follow-up was 9·3 years (IQR 8·0-10·0), after which 139 local-regional relapses had occurred. 10-year rates of local-regional relapse did not differ significantly between the 41·6 Gy and 50 Gy regimen groups (6·3%, 95% CI 4·7-8·5 vs 7·4%, 5·5-10·0; hazard ratio [HR] 0·91, 95% CI 0·59-1·38; p=0·65) or the 39 Gy (8·8%, 95% CI 6·7-11·4) and 50 Gy regimen groups (HR 1·18, 95% CI 0·79-1·76; p=0·41). In START-A, moderate or marked breast induration, telangiectasia, and breast oedema were significantly less common normal tissue effects in the 39 Gy group than in the 50 Gy group. Normal tissue effects did not differ significantly between 41·6 Gy and 50 Gy groups. START-B enrolled 2215 women. Median follow-up was 9·9 years (IQR 7·5-10·1), after which 95 local-regional relapses had occurred. The proportion of patients with local-regional relapse at 10 years did not differ significantly between the 40 Gy group (4·3%, 95% CI 3·2-5·9) and the 50 Gy group (5·5%, 95% CI 4·2-7·2; HR 0·77, 95% CI 0·51-1·16; p=0·21). In START-B, breast shrinkage, telangiectasia, and breast oedema were significantly less common normal tissue effects in the 40 Gy group than in the 50 Gy group. Interpretation: Long-term follow-up confirms that appropriately dosed hypofractionated radiotherapy is safe and effective for patients with early breast cancer. The results support the continued use of 40 Gy in 15 fractions, which has already been adopted by most UK centres as the standard of care for women requiring adjuvant radiotherapy for invasive early breast cancer. Funding: Cancer Research UK, UK Medical Research Council, UK Department of Health. © 2013 Elsevier Ltd. Source


Chua M.L.K.,Public Health England | Somaiah N.,Public Health England | Bourne S.,Public Health England | Daley F.,Public Health England | And 10 more authors.
Radiotherapy and Oncology | Year: 2011

Purpose: The aim of this study was to compare inter-individual and inter-cell type variation in DNA double-strand break (DSB) repair following in vivo irradiation of human skin. Materials and methods: Duplicate 4 mm core biopsies of irradiated and unirradiated skin were collected from 35 patients 24 h after 4 Gy exposure using 6 MeV electrons. Residual DSB were quantified by scoring 53BP1 foci in dermal fibroblasts, endothelial cells, superficial keratinocytes and basal epidermal cells. Results: Coefficients of inter-individual variation for levels of residual foci 24 h after in vivo irradiation of skin were 39.9% in dermal fibroblasts, 44.3% in endothelial cells, 32.9% in superficial keratinocytes and 46.4% in basal epidermal cells (p < 0.001, ANOVA). In contrast, the coefficient of inter-cell type variation for residual foci levels was only 11.3% in human skin between the different epidermal and dermal cells (p = 0.034, ANOVA). Foci levels between the different skin cell types were correlated (Pearson's R = 0.855-0.955, p < 0.001). Conclusions: Patient-specific factors appear to be more important than cell type-specific factors in determining residual foci levels following in vivo irradiation of human skin. © 2011 Elsevier Ireland Ltd. All rights reserved. Source


Martin S.,Section of Academic Radiotherapy | Sydenham M.,Institute of Cancer Research | Haviland J.,Institute of Cancer Research | A'Hern R.,Institute of Cancer Research | And 3 more authors.
Radiotherapy and Oncology | Year: 2010

Purpose: To test for association between single nucleotide polymorphisms at the TGFβ1 locus and the risk of late normal tissue injury following whole breast radiotherapy. Methods: A retrospective study compared the number of variant alleles at -509 and codons 10 and 25 of the TGFβ1 locus in women followed up in two prospective clinical trials who developed either marked radiotherapy adverse effects or no adverse effects after matching on fractionation schedule, breast size, surgical deficit, chemotherapy and length of follow up. Results: Median follow up in the two trials was 7.4 (maximum 15) years and 5.3 (maximum 5.3) years. 1237/1716 (72%) women with photographic assessments of radiotherapy adverse effects were alive and well, and 147/1237 (12%) potential cases with the most marked change in photographic change in breast appearance were matched to potential controls recording no change. In an unmatched analysis of 82 cases and 108 controls, no significant difference in the number of genetic variants was observed. Conclusions: No association was detected between sequence variations at the TGFβ1 locus and the risk of late adverse effects of breast radiotherapy. © 2010 Elsevier Ireland Ltd. All rights reserved. Source


Benstead K.,Gloucestershire Oncology Center | Palmieri C.,University of Liverpool | Brewster A.,Velindre Hospital | Gilson D.,Leeds Cancer Center | Jenkins P.,Gloucestershire Oncology Center
Clinical Oncology | Year: 2015

Aims: To develop a consensus on the minimum competences in non-surgical oncology that medical students need to acquire in order to be safe Foundation Year 1 (F1) doctors. Materials and methods: A two-round Delphi survey was conducted by e-mail with an expert panel of 24 consultant oncologists who had expressed an interest in undergraduate education. Results: The response rate to round 1, which asked panellists to list the competences they thought were important, was 50%. The competences they generated contained 86 different concepts. These were categorised according to the learning outcomes in Tomorrow's Doctors. The panellists were then asked to rate the importance of each proposed competence between 1 and 9 on a Likert scale to give a measure of the perceived importance and consensus. The panellists generated competences in all the main categories of learning outcomes in Tomorrow's Doctors. The scores were highest and the consensus greatest for those competences related to the doctor as a practitioner and the doctor as a professional. Conclusion: The Delphi survey was an effective method of obtaining the judgement of an expert panel and in measuring the degree of consensus. The results of the survey were valuable in informing the design of a UK non-surgical oncology curriculum. © 2015 The Royal College of Radiologists. Source

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