P J Hoskin

The Hillingdon Hospitals NHS Foundation Trust, अक्सब्रिज, England, United Kingdom

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Publications (337)1900.41 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To validate the feasibility and use of dose points to characterize the bladder wall dose distribution and investigate potential impact of the applicator position in cervical cancer brachytherapy.
    Brachytherapy 12/2014; · 1.99 Impact Factor
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    ABSTRACT: Aims Stereotactic body radiotherapy (SBRT) combines image-guided radiotherapy with hypofractionation, both of which will probably result in improvements in patient outcomes in prostate cancer. Most clinical experience with this technique resides in North America. Here we present the first UK cohort to receive SBRT for prostate cancer. Materials and methods Fifty-one prostate cancer patients (10 low risk, 35 intermediate risk and 6 high risk) were treated with 36.25 Gy in five fractions over 1–2 weeks and gold seed image guidance. All patients had toxicity International Prostate Symptom score (IPSS) and Radiation Therapy Oncology Group) recorded prospectively and prostate-specific antigen was measured 3–6 monthly during follow-up. Results The median IPSS was 6, 11, 8 and 5 at baseline, 1–3 weeks, 4–6 weeks and 7–12 weeks after treatment. Radiation Therapy Oncology Group genitourinary and gastrointestinal toxicity of grade 2 was seen in 22% and 14%, respectively, at 1–3 weeks after treatment; no patient had grade 3+ toxicity at this time point, although two patients had grade 3 urinary frequency recorded during treatment. The median follow-up for the 42 patients who did not receive androgen deprivation was 14.5 months. Prostate-specific antigen at 13–18 months after treatment was 1.3 ng/ml. Conclusion Prostate SBRT is a promising treatment for organ-confined prostate cancer and is currently being investigated in a UK-led phase III trial.
    Clinical Oncology 12/2014; · 2.83 Impact Factor
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    ABSTRACT: To evaluate dosimetric parameters related to urethral strictures following high dose-rate brachytherapy (HDRBT) alone for prostate cancer. Ten strictures were identified in 213 patients treated with HDRBT alone receiving 34Gy in four fractions, 36Gy in four fractions, 31.5Gy in 3 fractions or 26Gy in 2 fractions. A matched-pair analysis used 2 controls for each case matched for dose fractionation schedule, pre-treatment IPSS score, number of needles used and clinical target volume. The urethra was divided into membranous urethra and inferior, mid and superior thirds of the prostatic urethra. Stricture rates were 3% in the 34Gy group, 4% in the 36Gy group, 6% in the 31.5Gy group and 4% in the 26Gy group. The median time to stricture formation was 26months (range 8-40). The dosimetric parameters investigated were not statistically different between cases and controls. No correlation was seen between stricture rate and fractionation schedule. Urethral stricture is an infrequent complication of prostate HDRBT when used to deliver high doses as sole treatment, with an overall incidence in this cohort of 10/213 (4.7%). In a matched pair analysis no association with dose schedule or urethral dosimetry was identified, but the small number of events limits definitive conclusions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 12/2014; 113(3):410-3. · 4.86 Impact Factor
  • Peter J Hoskin, Indrani S Bhattacharya
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    ABSTRACT: The purpose of modern radiotherapy is to deliver a precise high dose of radiation which will result in reproductive death of the cells. Radiation should transverse within the tumour volume whilst minimising damage to surrounding normal tissue. Overall 40% of cancers which are cured will have received radiotherapy. Current state of the art treatment will incorporate cross-sectional imaging and multiple high energy X-ray beams in processes called intensity modulated radiotherapy and image guided radiotherapy. Brachytherapy enables very high radiation doses to be delivered by the direct passage of a radiation source through or within the tumour volume and similar results can be achieved using rotational stereotactic X-ray beam techniques. Protons have the characteristics of particle beams which deposit their energy in a finite fixed peak at depth in tissue with no dose beyond this point - the Bragg peak. This has advantages in certain sites such as the spine adjacent to the spinal cord and particularly in children when the overall volume of tissue receiving radiation can be minimised. © 2014 Royal College of Physicians.
    Clinical medicine (London, England) 12/2014; 14 Suppl 6:s61-5. · 1.69 Impact Factor
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    ABSTRACT: Primary results from the phase 3 ALSYMPCA trial showed that radium-223 dichloride (radium-223), a targeted α-emitter, improved overall survival compared with placebo and was well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases. We did a prespecified subgroup analysis from ALSYMPCA to assess the effect of previous docetaxel use on the efficacy and safety of radium-223. In the phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care were randomly assigned (2:1) via an interactive voice response system to receive six injections of radium-223 (50 kBq/kg intravenously) or matching placebo, with one injection given every 4 weeks. Patients had either received previous docetaxel treatment or were unsuitable for or declined docetaxel; previous docetaxel use (yes or no) was a trial stratification factor. We investigated the effect of previous docetaxel use on radium-223 treatment for the primary endpoint of overall survival, the main secondary efficacy endpoints, and safety. Efficacy analyses were done for the intention-to-treat population; safety analyses were done for the safety population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Randomisation took place between June 12, 2008, and Feb 1, 2011. 526 (57%) of 921 randomly assigned patients had received previous docetaxel treatment (352 in the radium-223 group and 174 in the placebo group) and 395 (43%) had not (262 in the radium-223 group and 133 in the placebo group). Radium-223 prolonged median overall survival compared with placebo, irrespective of previous docetaxel use (previous docetaxel use, hazard ratio [HR] 0·70, 95% CI 0·56-0·88; p=0·002; no previous docetaxel use, HR 0·69, 0·52-0·92; p=0·01). The benefit of radium-223 compared with placebo was seen in both docetaxel subgroups for most main secondary efficacy endpoints; risk for time to time to first symptomatic skeletal event was reduced with radium-223 versus placebo in patients with previous docetaxel use, but the difference was not significant in those with no previous docetaxel use. 322 (62%) of 518 patients previously treated with docetaxel had grade 3-4 adverse events, compared with 205 (54%) of 383 patients without docetaxel. Patients who had previously been treated with docetaxel had a higher incidence of grade 3-4 thrombocytopenia with radium-223 than with placebo (31 [9%] of 347 patients vs five [3%] of 171 patients), whereas the incidence was similar between treatment groups among patients with no previous docetaxel use (seven [3%] of 253 patients vs one [1%] of 130 patients). The incidences of grade 3-4 anaemia and neutropenia were similar between the radium-223 and placebo groups within both docetaxel subgroups. Radium-223 is effective and well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases, irrespective of previous docetaxel use. Algeta ASA and Bayer HealthCare Pharmaceuticals. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 11/2014; 15(12):1397-406. · 25.12 Impact Factor
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    ABSTRACT: We previously demonstrated that 48% of patients with pain at sites of previously irradiated bone metastases benefit from reirradiation. It is unknown whether alleviating pain also improves patient perception of quality of life (QOL).
    Journal of Clinical Oncology 10/2014; · 17.88 Impact Factor
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    ABSTRACT: This single-centre retrospective study evaluated combination external beam radiotherapy and high dose rate brachytherapy for patients in whom radical treatment was appropriate but comorbidity or frailty excluded this as an option.
    Clinical Oncology 10/2014; · 2.83 Impact Factor
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    ABSTRACT: Prostate cancer (PCa) is the second most common disease among men worldwide. It is important to know survival outcomes and prognostic factors for this disease. Recruitment for the largest therapeutic randomised controlled trial in PCa-the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial (STAMPEDE)-includes men with newly diagnosed metastatic PCa who are commencing long-term androgen deprivation therapy (ADT); the control arm provides valuable data for a prospective cohort.
    European Urology 10/2014; · 12.48 Impact Factor
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    ABSTRACT: To investigate the optimal distribution of sources using high dose rate brachytherapy to deliver a focal boost to a dominant lesion within the whole prostate gland based on multi-parametric magnetic resonance imaging (mpMRI).
    Radiotherapy and Oncology 09/2014; · 4.86 Impact Factor
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    ABSTRACT: Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been relatively small, and knowledge about these risks is limited.
    JNCI Journal of the National Cancer Institute 08/2014; 106(9). · 15.16 Impact Factor
  • Gillian Bedard, Peter Hoskin, Edward Chow
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    ABSTRACT: Introduction Radiation therapy has been shown to successfully palliate bone metastases. A number of systematic reviews and large clinical trials have reported response rates for initial treatment and retreatment. Objective To determine overall response rates of patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment. Methods Intent-to-treat and evaluable patient statistics from a systematic review of palliative radiotherapy trials for initial treatment of bone metastases and a randomized clinical trial of retreatment were pooled and analyzed to determine the overall response rates for patients receiving initial treatment and retreatment. Results In the intent-to-treat calculation, 71–73% of patients had an overall response to radiation treatment and in the evaluable patient population; 85–87% of patients did so. Response rates varied slightly whether patients underwent single or multiple fractions in initial treatment or retreatment. Conclusions Single and multiple fraction radiation treatment yielded very similar overall response rates. Patients treated with a single fraction for both initial and repeat radiation experience almost identical overall response to those patients treated with multiple fraction treatment. It is therefore recommended that patients with uncomplicated painful bone metastases be treated with a single 8 Gy fraction of radiation at both the initial treatment and retreatment.
    Radiotherapy and Oncology 07/2014; · 4.86 Impact Factor
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    ABSTRACT: Background To evaluate late urinary (GU) and gastrointestinal (GI) adverse events (AEs) and biochemical control of disease after high-dose rate brachytherapy (HDR-BT) in locally advanced prostate cancer. Patients and methods 227 consecutive patients were treated with 3 × 10.5 Gy (n = 109) or 2 × 13 Gy (n = 118) HDR-BT alone. Biochemical failure was assessed using the Phoenix definition of PSA nadir + 2 μg/l and late AEs using the RTOG scoring system and the International Prostate Symptom Score (IPSS). Results Kaplan–Meier estimates and prevalence of late events indicate that urinary, bowel and IPSS symptoms are higher after 31.5 Gy than after 26 Gy, however differences are significant only for Grade 1 and 2 urinary toxicity. Kaplan–Meier estimates of morbidity are consistently and considerably higher than time-point estimates of prevalence; which reflects the transient nature of most symptoms. At 3 years 93% and 97% of patients treated with 26 and 31.5 Gy, respectively, were free from biochemical relapse (p = 0.5) and 91% for the latter regimen at 5 years. In univariate and multivariate analysis risk-category was the only significant predictor of relapse (p < 0.03). Conclusion These HDR-BT schedules achieved high levels of biochemical control of disease in patients with advanced prostate cancer with few severe complications seen throughout the first 3 years.
    Radiotherapy and Oncology 07/2014; · 4.86 Impact Factor
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    ABSTRACT: Background:The addition of carbogen and nicotinamide (CON) to radiotherapy (RT) improves overall survival in invasive bladder cancer. We explored whether expression of the hypoxia marker hypoxia-inducible factor-1α (HIF-1α) alone or in combination with other markers predicted benefit from CON.Methods:A retrospective study was carried out using material from patients with high-grade invasive bladder carcinoma enrolled in the BCON phase III trial of RT alone or with CON (RT+CON). HIF-1α expression was studied in 137 tumours using tissue microarrays and immunohistochemistry. Data were available from other studies for carbonic anhydrase IX and glucose transporter 1 protein and gene expression and tumour necrosis.Results:Patients with high HIF-1α expression had improved 5-year local relapse-free survival with RT+CON (47%) compared with RT alone (21%; hazard ratio (HR) 0.48, 95% CI 0.26-0.8, P=0.02), no benefit was seen with low HIF-1α expression (HR 0.81, 95% CI 0.43-1.50, P=0.5). Combinations of markers including necrosis also predicted benefit but did not improve on prediction using necrosis alone.Conclusions:HIF-1α may be used to predict benefit from CON in patients with bladder cancer but does not improve on use of necrosis.British Journal of Cancer advance online publication, 17 June 2014; doi:10.1038/bjc.2014.315 www.bjcancer.com.
    British Journal of Cancer 06/2014; · 4.82 Impact Factor
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    ABSTRACT: The aim of this study was to test the utility of AIMP3, an upstream regulator of DNA damage response following genotoxic stress, as a clinical biomarker in muscle-invasive bladder cancer (MIBC). AIMP3 was identified from a meta-analysis of a global gene-expression dataset. AIMP3 protein expression was determined by immunohistochemistry on a customised bladder cancer tissue-microarray (TMA). The mechanism of gene silencing was probed using methylation-specific PCR. The association between AIMP3 expression, Tp53 transactivity and genomic stability was analysed. In vitro AIMP3 translocation to the nucleus in response to ionising radiation was demonstrated using immunofluorescence. Radiosensitisation effects of siRNA-mediated AIMP3-knockdown were measured using colony forming assays. TMAs derived from patients enrolled in BCON, a Phase III multicentre radiotherapy trial in bladder cancer (ISRCTN45938399) were used to evaluate the association between AIMP3 expression and survival. The prognostic value of AIMP3 expression was determined in a TMA derived from patients treated by radical cystectomy. Loss of AIMP3 expression was frequent in MIBC and associated with impaired Tp53 transactivity and genomic instability. AIMP3-knockdown was associated with an increase in radioresistance. Loss of AIMP3 expression was associated with survival in MIBC patients following radiotherapy (HR = 0.53; 95% CI: 0.36 to 0.78, p=0.002) but was not prognostic in the cystectomy set. In conclusion, AIMP3 expression is lost in a subset of bladder cancers and is significantly predictive of survival following radiotherapy in MIBC patients. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 06/2014; · 6.20 Impact Factor
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    ABSTRACT: In this report, the Committee on Medical Aspects of Radiation in the Environment (COMARE) presents a comprehensive review of the radium contamination in the area around Dalgety Bay. This report covers the history of the site, the type and extent of the contamination, the recent investigations and the cancer epidemiology for the area. The report also considers the implications for other similarly contaminated sites.
    05/2014; Department of Health., ISBN: 978-0-85951-755-3
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    ABSTRACT: Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range α-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases.1 METHODS: In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2:1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751.
    The Lancet Oncology 05/2014; · 25.12 Impact Factor
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    ABSTRACT: Inoperable endometrial cancer may be treated with curative aim using radical radiotherapy alone. The radiation techniques are external beam radiotherapy (EBRT) alone, EBRT plus brachytherapy, and brachytherapy alone. Recently, high-dose rate (HDR) brachytherapy has been used instead of low-dose rate (LDR) brachytherapy. Image-Guided Brachytherapy (IGBT) enables sufficient coverage of the tumour and reduction of dose to the organs at risk thus increasing the therapeutic ratio of treatment. Local control rates with three-dimensional brachytherapy appear better than with conventional techniques (about 90-100%, and 70-90%, respectively).
    The British journal of radiology 05/2014; · 2.11 Impact Factor
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    British Journal of Haematology 04/2014; · 4.94 Impact Factor
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    ABSTRACT: Follicular lymphoma has been shown to be highly radiosensitive with responses to doses as low as 4 Gy in two fractions. This trial was designed to explore the dose response for follicular lymphoma comparing 4 Gy in two fractions with 24 Gy in 12 fractions METHODS: FORT is a prospective randomised, unblinded, phase 3 non-inferiority study comparing radiotherapy given as 4 Gy in two fractions with a standard dose of 24 Gy in 12 fractions. Entry criteria included all patients aged over 18 years, having local radiotherapy for radical or palliative local control, with follicular lymphoma or marginal zone lymphoma, who had received no previous treatment for at least 1 month before. The primary outcome was time to local progression analysed on an intention-to-treat basis. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Radiotherapy target sites were randomised (1:1) with minimisation stratified by histology (follicular lymphoma vs marginal zone lymphoma), treatment intent (palliative or curative) and centre. This trial is registered with ClinicalTrials.gov number, NCT00310167. 299 sites were randomly assigned to 24 Gy and 315 sites to 4 Gy between April 7, 2006, and June 8, 2011, at 43 centres in the UK. After a median follow-up of 26 months (range 0·39-75·4), 91 local progressions had been recorded (21 in the 24 Gy group and 70 in the 4 Gy group). Time to local progression with 4 Gy was not non-inferior to 24 Gy (hazard ratio 3·42, 95% CI 2·09-5·55, p<0·0001). Eight (3%) of 282 patients in the 24 Gy group and four (1%) of 300 in the 4 Gy group had acute grade 3-4 toxic effects. Four (1%) patients in the 24 Gy group and four (1%) patients in the 4 Gy group had late toxic effects. Mucositis was the most common event in the 24 Gy group (two patients with acute mucositis and two with late mucositis; all grade 3) and was not reported in the 4 Gy group. The most common acute effect was pain at the site of irradiation (two patients in the 4 Gy group, one patient in the 24 Gy group; all grade 3), and the most common late effect was fatigue (two patients in the 4 Gy group, one patient in the 24 Gy group; all grade 3). 24 Gy in 12 fractions is the more effective radiation schedule for indolent lymphoma and should be regarded as the standard of care. However, 4 Gy remains a useful alternative for palliative treatment. Cancer Research UK.
    The Lancet Oncology 02/2014; · 25.12 Impact Factor
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    ABSTRACT: The development of a radiation induced second primary cancer (SPC) is one the most serious long term consequences of successful cancer treatment. This review aims to evaluate SPC in prostate cancer (PCa) patients treated with radiotherapy, and assess whether radiation technique influences SPC. A systematic review of the literature was performed to identify studies examining SPC in irradiated PCa patients. This identified 19 registry publications, 21 institutional series and 7 other studies. There is marked heterogeneity in published studies. An increased risk of radiation-induced SPC has been identified in several studies, particularly those with longer durations of follow-up. The risk of radiation-induced SPC appears small, in the range of 1 in 220 to 1 in 290 over all durations of follow-up, and may increase to 1 in 70 for patients followed up for more than 10 years, based on studies which include patients treated with older radiation techniques (i.e. non-conformal, large field). To date there are insufficient clinical data to draw firm conclusions about the impact of more modern techniques such as IMRT and brachytherapy on SPC risk, although limited evidence is encouraging. In conclusion, despite heterogeneity between studies, an increased risk of SPC following radiation for PCa has been identified in several studies, and this risk appears to increase over time. This must be borne in mind when considering which patients to irradiate and which techniques to employ.
    Radiotherapy and Oncology 02/2014; · 4.86 Impact Factor

Publication Stats

6k Citations
1,900.41 Total Impact Points

Institutions

  • 1994–2014
    • The Hillingdon Hospitals NHS Foundation Trust
      अक्सब्रिज, England, United Kingdom
  • 2013
    • University of Toronto
      • Department of Radiation Oncology
      Toronto, Ontario, Canada
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2006–2013
    • East Coast Community Healthcare CIC
      Beccles, England, United Kingdom
    • University of Hamburg
      • Department of Radiotherapy and Radio-Oncology
      Hamburg, Hamburg, Germany
  • 2006–2011
    • Institute of Cancer Research
      • Division of Genetics and Epidemiology
      Londinium, England, United Kingdom
  • 2009
    • Bank of Cyprus Oncology Center
      Lefkoşa, Lefkosia, Cyprus
    • The Ohio State University
      • Department of Radiology
      Columbus, OH, United States
  • 2007–2008
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
    • Tata Memorial Centre
      Mumbai, Mahārāshtra, India
    • Europe Hospitals
      Bruxelles, Brussels Capital Region, Belgium
  • 2005
    • University College London
      • Department of Haematology
      Londinium, England, United Kingdom
  • 2003
    • Guy's and St Thomas' NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2002
    • Sarcoma Oncology Center
      Santa Monica, California, United States