Publications
200 results found
Gilbert DC, Duong T, Sydes M, et al., 2018, Transdermal oestradiol as a method of androgen suppression for prostate cancer within the STAMPEDE trial platform, BJU International, Vol: 121, Pages: 680-683, ISSN: 1464-4096
Androgen deprivation therapy (ADT) remains a cornerstone of the management of prostate cancer. The addition of ADT to radiotherapy improves disease-free and overall survival in the locally advanced setting and ADT forms the backbone onto which additional treatments may be added (either initially at first presentation or sequentially at disease progression). ADT is most commonly achieved with Gonadotrophin Releasing Hormone analogues (GnRHa) that act through the hypothalamic-pituitary-gonadal axis to prevent testicular production of testosterone. However, the therapeutic benefits of ADT are partially offset by its side-effects which include long-term This article is protected by copyright. All rights reserved.
Challapalli A, Edwards SM, Abel P, et al., 2018, Evaluating the prevalence and predictive factors of vasomotor and psychological symptoms in prostate cancer patients receiving hormonal therapy: Results from a single institution experience, CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY, Vol: 10, Pages: 29-35
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- Citations: 5
Shah ISA, Wilson HCP, Abel PD, 2017, Cardiovascular toxicities of systemic treatments of prostate cancer: oestrogen to the rescue?, Nature Reviews Urology, Vol: 14, ISSN: 1759-4812
MacLennan S, Williamson PR, Bekema H, et al., 2017, A core outcome set for localised prostate cancer effectiveness trials., BJU International, Vol: 120, Pages: E64-E79, ISSN: 1464-4096
OBJECTIVE: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio; which is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. PATIENTS, SUBJECTS AND METHODS: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 patients with prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs; cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and eight patients. RESULTS: The final COS included 19 outcomes. In all, 12 apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, and sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side-effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. CONCLUSION: We have established a COS for trials of effectiveness in localised prostate
Gilbert DC, Duong T, Kynaston HG, et al., 2016, Quality of life outcomes from the PATCH trial evaluating LHRH agonists versus transdermal oestradiol for androgen suppression in advanced prostate cancer, BJU International, Vol: 119, Pages: 667-675, ISSN: 1464-4096
OBJECTIVES: To compare quality of life (QoL) outcomes at 6 months between men with advanced prostate cancer (PCa) receiving either transdermal oestradiol (tE2) or LHRH agonists (LHRHa) for androgen deprivation therapy (ADT). PATIENTS AND METHODS: Men with locally advanced or metastatic PCa participating in an ongoing randomised, multi-centre UK trial comparing tE2 versus LHRHa for ADT were enrolled into a QoL sub-study. tE2 was delivered via 3 or 4 transcutaneous patches containing 100mcg of oestradiol/24 hours. LHRHa was administered as per local practice. Patients completed questionnaires based on EORTC QLQ-C30 with prostate-specific module QLQ PR25. The primary outcome measure was global QoL score at 6 months, compared between randomised arms. RESULTS: 727 men were enrolled between August 2007 and 5 October 2015 (412 tE2, 315 LHRHa) with QoL questionnaires completed at both baseline and 6 months. Baseline clinical characteristics were similar between arms: median age 74 years (interquartile range [IQR] 68-79), median PSA 44 ng/ml (IQR 19-119), and 40% (294/727) had metastatic disease. At 6 months, patients on tE2 reported higher global QoL than LHRHa (mean difference +4.2, 95% CI 1.2 to 7.1, p=0.006), less fatigue and improved physical function. Men in the tE2 arm were less likely to experience hot flushes (8% vs 46%), and report a lack of sexual interest (59% vs 74%) and sexual activity, but had higher rates of significant gynecomastia (37% vs 5%). The higher incidence of hot flushes among LHRHa patients appear to account for both the reduced global QoL and increased fatigue in the LHRHa arm compared to tE2 arm. CONCLUSION: Patients receiving tE2 for ADT had better 6-month self-reported QoL outcomes compared to those on LHRHa, but increased likelihood of gynecomastia. The ongoing trial will evaluate clinical efficacy, and longer term QoL. These findings are also potentially relevant for short-term neoadjuvant ADT. This article is protected by copyright. All righ
Symes DR, Najmudin Z, Cole JM, et al., 2016, High-resolution tomographic imaging using coherent hard x-rays from compact laser driven accelerators, Compact EUV & X-ray Light Sources 2016, Publisher: OSA Publishing
Extremely bright coherent femtosecond x-ray pulses are generated in compact laserdriven electron accelerators. Micro-tomography obtained with the Gemini laser indicates the usefulness of these sources in research and clinical applications.
Shah SIA, Wilson HCP, Abel PD, 2016, First, do no harm, second, do some good, third, give choice and fourth, save cash: the 1, 2, 3 and 4 of transdermal oestradiol as androgen deprivation therapy ticks all the boxes, INTERNAL MEDICINE JOURNAL, Vol: 46, Pages: 241-243, ISSN: 1444-0903
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- Citations: 1
Langley RE, Kynaston HG, Alhasso AA, et al., 2015, A randomised comparison evaluating changes in bone mineral density in advanced prostate cancer: luteinising hormone-releasing hormone agonists versus transdermal oestradiol., European Urology, Vol: 69, Pages: 1016-1025, ISSN: 1421-993X
BACKGROUND: Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa. OBJECTIVE: To compare BMD change in men receiving either LHRHa or oestradiol patches (OP). DESIGN, SETTING, AND PARTICIPANTS: Men with locally advanced or metastatic PCa participating in the randomised UK Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) trial (allocation ratio of 1:2 for LHRHa:OP, 2006-2011; 1:1, thereafter) were recruited into a BMD study (2006-2012). Dual-energy x-ray absorptiometry scans were performed at baseline, 1 yr, and 2 yr. INTERVENTIONS: LHRHa as per local practice, OP (FemSeven 100μg/24h patches). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr change in lumbar spine (LS) BMD from baseline compared between randomised arms using analysis of covariance. RESULTS AND LIMITATIONS: A total of 74 eligible men (LHRHa 28, OP 46) participated from seven centres. Baseline clinical characteristics and 3-mo castration rates (testosterone ≤1.7 nmol/l, LHRHa 96% [26 of 27], OP 96% [43 of 45]) were similar between arms. Mean 1-yr change in LS BMD was -0.021g/cm(3) for patients randomised to the LHRHa arm (mean percentage change -1.4%) and +0.069g/cm(3) for the OP arm (+6.0%; p<0.001). Similar patterns were seen in hip and total body measurements. The largest difference between arms was at 2 yr for those remaining on allocated treatment only: LS BMD mean percentage change LHRHa -3.0% and OP +7.9% (p<0.001). CONCLUSIONS: Transdermal oestradiol as a single agent produces castration levels of testosterone while mitigating BMD loss. These early data provide further supporting evidence for the ongoing phase 3 trial. PATIENT SUMMARY: This study found that prostate cancer patients treated with transdermal oestradiol for ho
Coyle C, Mangar S, Abel P, et al., 2015, Erythema nodosum as a result of estrogen patch therapy for prostate cancer: a case report., J Med Case Rep, Vol: 9
INTRODUCTION: Erythema nodosum is often associated with a distressing symptomatology, including painful subcutaneous nodules, polyarthropathy, and significant fatigue. Whilst it is a well-documented side-effect of estrogen therapy in females, we describe what we believe to be the first report in the literature of erythema nodosum as a result of estrogen therapy in a male. CASE PRESENTATION: A 64-year-old Afro-Caribbean man with locally advanced carcinoma of the prostate agreed to participate in a randomized controlled trial comparing estrogen patches with luteinizing hormone-releasing hormone analogs to achieve androgen deprivation, and was allocated to the group receiving estrogen patches. One month later he presented with tender lesions on his shins and painful swelling of his ankles, wrists, and left shoulder. This was followed by progressive severe fatigue that required hospital admission, where he was diagnosed with erythema nodosum by a rheumatologist. Two months after discontinuing the estrogen patches the erythema nodosum, and associated symptoms, had fully resolved, and to date he remains well with no further recurrence. CONCLUSION: Trial results may establish transdermal estrogen as an alternative to luteinizing hormone-releasing hormone analogs in the management of prostate cancer, and has already been established as a therapy for male to female transsexuals. It is essential to record the toxicity profile of transdermal estrogen in men to ensure accurate safety information. This case report highlights a previously undocumented toxicity of estrogen therapy in men, of which oncologists, urologists, and endocrinologists need to be aware. Rheumatologists and dermatologists should add estrogen therapy to their differential diagnosis of men presenting with erythema nodosum.
Shah SIMRANA, Jin ANDI, Wilson HANNAHCP, et al., 2015, Novel Computed Tomography-based Metric Reliably Estimates bone Strength, Offering Potentially Meaningful Enhancement in Clinical Fracture Risk Prediction, European Journal of Medicine, Vol: 10, Pages: 214-220, ISSN: 2310-3434
Osteoporosis with resultant fractures is a major global health problem with huge socioeconomicimplications for patients, families and healthcare services. Areal (2D bone mineraldensity (BMD) assessment is commonly used for predicting such fracture risk, but is unreliable,estimating only about 50% of bone strength. By contrast, computed tomography (CT) basedtechniques could provide improved metrics for estimating bone strength such as bone volumefraction (BVF; a 3D volumetric measure of mineralised bone), enabling cheap, safe and reliablestrategies for clinical application, and to help divert resources to patients identified as most likelyto benefit, meeting an unmet need.Here we describe a novel method for measuring BVF at clinical-CT like low-resolution(550µm voxel size). Femoral heads (n=8) were micro-CT scanned ex-vivo. Micro-CT data weredowngraded in resolution from 30µm to 550µm voxel size and BVF calculated at high and lowresolution. Experimental mechanical testing was applied to measure ex vivo bone strength ofsamples. BVF measures collected at high-resolution showed high correlation (correlationcoefficient r2=0.95) with low-resolution data. Low-resolution BVF metrics showed high correlation(r2=0.96) with calculated sample strength. These results demonstrate that measuring BVF at lowresolution is feasible, which also predicts bone strength. Measures of BVF should be useful for clinically estimating bone strength and fracture risk. The method needs to be validated using clinical CT scans.
Wilson HCP, Abel PD, Shah SIA, 2015, Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study - how useful is the current clinical gold standard for fracture risk?, Clinical Interventions in Aging, Vol: 10, Pages: 1653-1655, ISSN: 1178-1998
Wilson H, Shah I, Abel P, et al., 2015, Contemporary hormone therapy with LHRH agonists for prostate cancer: avoiding osteoporosis and fracture, Central European Journal of Urology, Vol: 68, Pages: 165-168
Abel M, Ahmed H, Leen E, et al., 2015, Ultrasound-guided trans-rectal high intensity focused ultrasound (HIFU) for advanced cervical cancer ablation is feasible: a case report, Journal of Therapeutic Ultrasound, Vol: (2015) 3:21
Langley RE, Trinh D, Jovic G, et al., 2014, Bone density in men receiving androgen deprivation therapy for prostate cancer: A randomized comparison between transdermal estrogen and luteinising hormone-releasing hormone agonists., 50th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
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- Citations: 1
Langley RE, Truinh D, Jovic G, et al., 2014, Prostate Adenocarcinoma: TransCutaneons Hormones, PR09 (PATCH): A randomized controlled trial of transdemal estrogen patches versus luteinising hormone releasing hormone agonists in locally advanced and metastatic prostate cancer., 50th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Shah SIA, Cafferty FH, Langley RE, et al., 2014, Re: Androgen Deprivation Therapy: Impact on Quality of Life and Cardiovascular Health, JOURNAL OF SEXUAL MEDICINE, Vol: 11, Pages: 314-315, ISSN: 1743-6095
Shah S, Abel P, Duong T, et al., 2014, Parenteral oestrogen: Effective and safer than both oral oestrogen and contemporary androgen deprivation therapy for prostate cancer?, Scandinavian Journal of Urology, Vol: 2014 Early Online 1-2
Phillips I, Shah SIA, Duong T, et al., 2014, Androgen Deprivation Therapy and the Re-emergence of Parenteral Estrogen in Prostate Cancer., Oncol Hematol Rev, Vol: 10, Pages: 42-47, ISSN: 2052-3815
Androgen deprivation therapy (ADT) resulting in testosterone suppression is central to the management of prostate cancer (PC). As PC incidence increases, ADT is more frequently prescribed, and for longer periods of time as survival improves. Initial approaches to ADT included orchiectomy or oral estrogen (diethylstilbestrol [DES]). DES reduces PC-specific mortality, but causes substantial cardiovascular (CV) toxicity. Currently, luteinizing hormone-releasing hormone agonists (LHRHa) are mainly used; they produce low levels of both testosterone and estrogen (as estrogen in men results from the aromatization of testosterone), and many toxicities including osteoporosis, fractures, hot flashes, erectile dysfunction, muscle weakness, increased risk for diabetes, changes in body composition, and CV toxicity. An alternative approach is parenteral estrogen, it suppresses testosterone, appears to mitigate the CV complications of oral estrogen by avoiding first-pass hepatic metabolism, and avoids complications caused by estrogen deprivation. Recent research on the toxicity of ADT and the rationale for revisiting parenteral estrogen is discussed.
Shah SIA, Langley RE, Cafferty FH, et al., 2013, Fracture after androgen deprivation therapy among men with a high baseline risk of skeletal complications, BJU INTERNATIONAL, Vol: 112, Pages: E431-E432, ISSN: 1464-4096
Langley R, Cafferty FH, Abel PD, 2013, Extending the case for oestradiol in androgen-sensitive prostate cancer Reply, LANCET ONCOLOGY, Vol: 14, Pages: E253-E253, ISSN: 1470-2045
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- Citations: 1
Gale-Grant O, Gatter M, Abel P, 2013, Developing ideas of professionalism., Clin Teach, Vol: 10, Pages: 165-169
BACKGROUND: Professionalism is widely acknowledged as being central to medical practice, and is taught at most UK medical schools. The impact of this teaching in the context of competing influences on a student's developing view of themselves as professional is, however, unclear. We explored the understanding of professionalism in third-year medical students who have recently completed this element of their formal teaching, and related this understanding to previously unexplored wider influences placed upon them during their development. METHODS: A questionnaire consisting of two closed questions and two open questions was distributed via e-mail to third-year students at Imperial College School of Medicine, London. The closed questions explored both beliefs about what constitutes medical professionalism and preferences for the teaching of professionalism. The open questions explored the contexts within which students believed their understanding of professionalism was derived. Content analysis of text-based questions was performed. RESULTS AND DISCUSSION: The most commonly cited aspects of professionalism by students in this study were confidentiality, good medical knowledge and practical skill. Students also cited promptness, hygiene and appearance as being important, although these factors are rarely cited in the literature. Students cited role models, the media and parents as the three most important influences on their view of professionalism. These merit further consideration in future research and course design. Most students agreed that professionalism should be taught at medical school, but that this would be best achieved within a clinical setting. The favoured model for acquisition of views on professionalism was observation of doctors rather than formal teaching.
Shah SIA, Abel PD, Langley RE, et al., 2013, Comment on 'Endocrine therapy in prostate cancer: time for re-appraisal of risks, benefits and cost-effectiveness?', BRITISH JOURNAL OF CANCER, Vol: 108, Pages: 2192-2193, ISSN: 0007-0920
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- Citations: 1
Langley RE, Cafferty FH, Alhasso AA, et al., 2013, Cardiovascular outcomes in patients with locally advanced and metastatic prostate cancer treated with luteinising-hormone-releasing-hormone agonists or transdermal oestrogen: the randomised, phase 2 MRC PATCH trial (PR09), LANCET ONCOLOGY, Vol: 14, Pages: 306-316, ISSN: 1470-2045
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- Citations: 69
Cafferty FH, Langley RE, Abel PD, 2013, Use of transdermal estrogen in the management of advanced prostate cancer, UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, Vol: 31, Pages: 279-279, ISSN: 1078-1439
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- Citations: 1
Malietzis G, Monzon L, Hand J, et al., 2013, High-intensity focused ultrasound: advances in technology and experimental trials support enhanced utility of focused ultrasound surgery in oncology, Br J Radiol, Vol: 86, ISSN: 1748-880X
High-intensity focused ultrasound (HIFU) is a rapidly maturing technology with diverse clinical applications. In the field of oncology, the use of HIFU to non-invasively cause tissue necrosis in a defined target, a technique known as focused ultrasound surgery (FUS), has considerable potential for tumour ablation. In this article, we outline the development and underlying principles of HIFU, overview the limitations and commercially available equipment for FUS, then summarise some of the recent technological advances and experimental clinical trials that we predict will have a positive impact on extending the role of FUS in cancer therapy.
Karavitakis M, Ahmed HU, Abel PD, et al., 2012, Trends in pathologic outcomes after introduction of active surveillance in the UK: Implication for focal therapy, PROSTATE, Vol: 72, Pages: 1464-1468, ISSN: 0270-4137
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- Citations: 4
Gauthier TP, Muhammad A, Wasan HS, et al., 2012, Reproducibility of Quantitative Assessment of Altered Hepatic Hemodynamics With Dynamic Contrast-Enhanced Ultrasound, JOURNAL OF ULTRASOUND IN MEDICINE, Vol: 31, Pages: 1413-1420, ISSN: 0278-4297
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- Citations: 8
Karavitakis M, Ahmed HU, Abel PD, et al., 2012, Anatomically versus biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy., Ther Adv Urol, Vol: 4, Pages: 155-160
OBJECTIVES: Since tumor focality in prostate cancer continues to be considered a major limitation for focal prostate therapy, in this study we attempted to compare the pathological features and the proportion of patients with anatomically unifocal versus biologically unifocal tumors (i.e. multifocal prostate cancer in which the secondary nonindex elements are small, low grade and clinically insignificant) who were suitable for focal therapy. METHODS: Ninety-five consecutive whole mount laparoscopic radical prostatectomy samples underwent pathological assessment (from January 2007 to November 2009). Tumor focality, laterality, Gleason score and volume of individual foci, total tumor volume, pathological stage and surgical margin status were assessed. The index lesion was defined as the largest by volume. Patients suitable for focal ablation were defined as having tumors that were unifocal, organ confined, with a Gleason score (GS) up to 7 prostate cancer, or multifocal, organ confined, GS up to 7 prostate cancer, with one large index lesion and the remaining foci demonstrating features of clinically insignificant disease (total tumor volume of all secondary foci ≤0.5 cm(3) with GS ≤ 6). RESULTS: Patients with biologically unifocal cancer had significantly lower total tumor volume (3.26 versus 7.28 cm(3); p < 0.001), index lesion volume (2.9 versus 7.16 cm(3); p < 0.001), rates of seminal vesicle invasion (4% versus 34%; p < 0.001), rates of positive surgical margins (22.4% versus 52.1%; p < 0.001) and rates of 4+3 GS tumors (10.2% versus 29.1%; p = 0.018). The proportion of patients suitable for focal therapy was higher in the biologically unifocal versus anatomically unifocal cancer group, although without reaching statistical significance (65.3% versus 45.8%; p = 0.11). CONCLUSIONS: Patients with biologically unifocal tumors have better pathological outcome than those with anatomically unifocal disease. At present the assumption that multifocality
Karavitakis M, Ahmed HU, Abel PD, et al., 2012, Margin Status After Laparoscopic Radical Prostatectomy and the Index Lesion: Implications for Preoperative Evaluation of Tumor Focality in Prostate Cancer, JOURNAL OF ENDOUROLOGY, Vol: 26, Pages: 503-508, ISSN: 0892-7790
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- Citations: 19
Karavitakis M, Ahmed HU, Abel PD, et al., 2012, Evolution of the pathological outcomes after radical prostatectomy with increasing use of active surveillance in the UK: Implication for focal therapy, EUROPEAN UROLOGY SUPPLEMENTS, Vol: 11, Pages: E20-U330, ISSN: 1569-9056
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