P J Hoskin

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

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Publications (312)1914.3 Total impact

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    ABSTRACT: To determine the optimal single-dose radiotherapy schedule for pain from bone metastases in a multi-centre, international, randomised trial. 651 patients were randomised to either 8Gy (n=325) or 4Gy (n=326) radiotherapy. Pain at 4, 8, 12, 24 and 52weeks was assessed using a Categorical Scale (CS) and a Visual Analogue Scale (VAS). The primary endpoint was response at 4weeks. There was no significant difference in patient demographics and other co-variates. The complete response (CR) rate and ORR (complete or partial response) for all follow-up times were higher after 8Gy (p=0.02). The Kaplan-Meier actuarial rate (categorical scale) at 4weeks for ORR was 80% after 8Gy compared to 68% after 4Gy (p=0.0015). 117 re-treatments were given of which 72 were in the 4Gy group and 45 in 8Gy arm (p=0.01). There was a marked consistent difference in pain relief at all time points in favour of 8Gy. These data reinforce the case for single dose 8Gy radiotherapy to be recommended for metastatic bone pain in all healthcare settings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 05/2015; DOI:10.1016/j.radonc.2015.05.008 · 4.86 Impact Factor
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    ABSTRACT: It is unclear whether patients with early-stage Hodgkin's lymphoma and negative findings on positron-emission tomography (PET) after three cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) require radiotherapy. Patients with newly diagnosed stage IA or stage IIA Hodgkin's lymphoma received three cycles of ABVD and then underwent PET scanning. Patients with negative PET findings were randomly assigned to receive involved-field radiotherapy or no further treatment; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy. This trial assessing the noninferiority of no further treatment was designed to exclude a difference in the 3-year progression-free survival rate of 7 or more percentage points from the assumed 95% progression-free survival rate in the radiotherapy group. A total of 602 patients (53.3% male; median age, 34 years) were recruited, and 571 patients underwent PET scanning. The PET findings were negative in 426 of these patients (74.6%), 420 of whom were randomly assigned to a study group (209 to the radiotherapy group and 211 to no further therapy). At a median of 60 months of follow-up, there had been 8 instances of disease progression in the radiotherapy group, and 8 patients had died (3 with disease progression, 1 of whom died from Hodgkin's lymphoma); there had been 20 instances of disease progression in the group with no further therapy, and 4 patients had died (2 with disease progression and none from Hodgkin's lymphoma). In the radiotherapy group, 5 of the deaths occurred in patients who received no radiotherapy. The 3-year progression-free survival rate was 94.6% (95% confidence interval [CI], 91.5 to 97.7) in the radiotherapy group and 90.8% (95% CI, 86.9 to 94.8) in the group that received no further therapy, with an absolute risk difference of -3.8 percentage points (95% CI, -8.8 to 1.3). The results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival. Nevertheless, patients in this study with early-stage Hodgkin's lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy. (Funded by Leukaemia and Lymphoma Research and others; RAPID ClinicalTrials.gov number, NCT00943423.).
    New England Journal of Medicine 04/2015; 372(17):1598-607. DOI:10.1056/NEJMoa1408648 · 54.42 Impact Factor
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    ABSTRACT: The NCIC CTG Symptom Control.20 randomized trial (SC.20) confirmed the effectiveness of re-irradiation to painful bone metastases. This companion study correlates urinary markers of osteoclast activity with response to re-irradiation, survival and skeletal related events (SREs). Pain response was assessed using the International Consensus Endpoints. Urinary markers of bone turnover-pyridinoline (PYD), deoxypyridinoline (DPD), N-telopeptide (NTX), Alpha and Beta cross-laps of C-telopeptide (CTX)-before and 1month after re-irradiation were correlated to response to re-irradiation and then to both, either or none of the initial and re-irradiation: frequent responders (response to both); eventual responders (response to re-irradiation only); eventual non-responders (response to initial radiation only), and absolute non-responders (no response to both). Significant differences between 40 responders and 69 non-responders to re-irradiation existed for PYD (p=0.03) and DPD (p=0.04) at baseline. When patients were categorized as frequent responders (N=34), eventual responders (6), eventual non-responders (59) and absolute non-responders (10), the mean values of all markers in the absolute non-responders at baseline and the follow-up were about double those for the other three groups with statistically significant difference for DPD (p=0.03) at baseline. Absolute non-responders had the worst survival. The few occurrences of the SREs did not allow meaningful comparisons among the groups. There were significant differences between responders and non-responders to re-irradiation for PYD and DPD at baseline. The urinary markers in the absolute non-responders were markedly elevated at both baseline and follow-up with a statistically significant difference for DPD at baseline. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 03/2015; 115(1). DOI:10.1016/j.radonc.2015.02.025 · 4.86 Impact Factor
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    I.S. Bhattacharya, P.J. Hoskin
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    ABSTRACT: Stereotactic body radiotherapy (SBRT) can deliver high radiation doses to small volumes with very tight margins, which has significant advantages when treating tumours close to the spinal cord or at sites of retreatment. When treating spinal tumours, meticulous quality control is essential with effective immobilisation, as dose gradients at the edge of the spinal cord will be steep and excessive movements can be catastrophic. A range of dose-fractionation schedules have been used from single doses of 15-24 Gy to fractionated schedules delivering 15-35 Gy in three to five fractions. Indications include solitary or up to three vertebral metastases and primary tumours, in particular chordomas or bone sarcomas. Pain relief from metastatic disease is seen in over 80%, with similar rates of objective local control. Local control can be achieved in primary tumours of the spine in up to 95% and similar response rates are seen in non-spinal bone metastases. Toxicity rates are low, even in series that have delivered re-irradiation with myelopathy in <1%, although later vertebral fracture may occur. Further prospective studies are required to formally evaluate patient selection and optimal dose and fractionation alongside an evaluation of cost-effectiveness. Copyright © 2015. Published by Elsevier Ltd.
    Clinical Oncology 02/2015; 7(5). DOI:10.1016/j.clon.2015.01.030 · 2.83 Impact Factor
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    ABSTRACT: Objectives: A review of SBRT for oligometastases defined as three or fewer sites of isolated metastatic disease. The aim was to identify local control, overall survival (OS) and progression free survival (PFS) of patients receiving SBRT for OM disease. Methods: Data was analysed for SBRT delivered between 1/9/10-31/3/14. End points included local control, progression free survival, overall survival and toxicity. Results: 76 patients received SBRT. Median age was 60 (31-89) years. 44 were male. Median follow-up was 12.3(0.2-36.9) months. Major primary tumour sites included colorectal (38%), breast (18%) and prostate (12%). Treatment sites included lymph nodes (42%), bone and spine (29%) and soft tissue (29%). 42% were previously treated with conventional radiotherapy. 45% were disease free after SBRT. 4% had local relapse, 45% had distant relapse, 6% had local and distant relapse. Local control was 89%. OS was 84.4% at 1 year and 63.2% at 2 years. PFS was 49.1% at 1 year and 26.2% at 2 years. Toxicities included duodenal ulcer and biliary stricture formation. Conclusion: SBRT can achieve durable control of OM lesions and results in minimal radiation-induced morbidity. Advances in knowledge: This cohort is one of the largest reported to date and contributes to the field of SBRT in oligometastases which is emerging as an important research area. It is the only study reported from the UK and uses a uniform technique throughout. The efficacy and low toxicity with durable control of local disease with this approach is shown setting the foundations for future randomised studies.
    British Journal of Radiology 02/2015; 88(1048):20140712. DOI:10.1259/bjr.20140712 · 1.53 Impact Factor
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    ABSTRACT: PURPOSE: 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. METHODS AND MATERIALS: One hundred twenty-eight optimized MRI plans were evaluated. The International Commission of Radiation Units and Measurements (ICRU-38) point doses (Brow), surrogate for bladder base doses, were compared with D-2cc. Vaginal source to superior-anterior border of the symphysis distances were measured and compared within two groups, namely Group 1-B-ICRU/D-2cc >= 1 and Group 2-B-ICRU/D-2cc <1. Additionally, points at 1.5 and 2 cm cranial to the B-ICRU, parallel to the tandem and the body axis were analyzed. RESULTS: Thirty-seven percent of the patients had the ratio B-ICRU/D-2cc of 1 or higher, with the 2cc subvolume at the bladder base (Group 1). In 63%, B-ICRU/D-2cc, ratio was lower than 1 and the 2cc, cranial to the bladder base (Group 2). Median vaginal source-to-superior anterior border of the symphysis line distance was -2 cm (range, -3.7 to + 1.2 cm) in Group 1 and +1.8 cm (range, -2 to +4.8 cm) in Group 2 (+ cranial/- caudal direction). There was a high correlation between vaginal sources near the symphysis and the 2cc subvolume at the bladder base. The additional points provided no added value. CONCLUSIONS: Location of the 2cc subvolume varies in cervical cancer brachytherapy. Maximum doses are at the bladder base if vaginal sources are also in the vicinity of the bladder base indicated by B-ICRU/D-2cc ratio of 1 or higher. Such variation should be considered in dose-effect analyses and intercomparisons, as the same D-2cc at different bladder locations may correlate with different morbidity profiles and severity Reporting D-2cc and B-ICRU doses together therefore remains essential.
    Brachytherapy 12/2014; 14(2). DOI:10.1016/j.brachy.2014.11.006 · 1.99 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. DOI:10.1016/j.radonc.2014.10.007 · 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(Suppl_6):s61-5. DOI:10.7861/clinmedicine.14-6-s61 · 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. DOI:10.1016/S1470-2045(14)70474-7 · 24.73 Impact Factor
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    ABSTRACT: Purpose 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). Patients and Methods We used the database of a randomized trial comparing radiation treatment dose fractionation schedules to evaluate whether response, determined using the International Consensus Endpoint (ICE) and Brief Pain Inventory pain score (BPI-PS), is associated with patient perception of benefit, as measured using the European Organisation for Resesarch and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and functional interference scale of the BPI (BPI-FI). Evaluable patients completed baseline and 2-month follow-up assessments. Results Among 850 randomly assigned patients, 528 were evaluable for response using the ICE and 605 using the BPI-PS. Using the ICE, 253 patients experienced a response and 275 did not. Responding patients had superior scores on all items of the BPI-FI (ie, general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life) and improved QOL, as determined by scores on the EORTC QLQ-C30 scales of physical, role, emotional and social functioning, global QOL, fatigue, pain, and appetite. Similar results were obtained using the BPI-PS; observed improvements were typically of lesser magnitude. Conclusion Patients responding to reirradiation of painful bone metastases experience superior QOL scores and less functional interference associated with pain. Patients should be offered re-treatment for painful bone metastases in the hope of reducing pain severity as well as improving QOL and pain interference. (C) 2014 by American Society of Clinical Oncology
    Journal of Clinical Oncology 10/2014; 32(34). DOI:10.1200/JCO.2014.57.6264 · 17.88 Impact Factor
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    ABSTRACT: Aims: 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. Materials and methods: In total, 59 patients were selected for a combined approach and treated between October 2000 and October 2011; 68% were male. The median age was 77 years (range 53-88 years); 66% had adenocarcinoma, 31% squamous cell carcinoma. Tumour stage: I: 20%, II: 43%, III: 32% and IV: 3%. External beam radiotherapy doses of either 27 Gy/six fractions or 30 Gy/10 fractions were delivered, followed by high dose rate brachytherapy at doses of either 10 or 15 Gy utilising an iridium 192 source at 1 cm. Results: The median overall survival of all treated patients was 12.3 months; 1, 2 and 3 year survival rates were 51, 19 and 7%, respectively. Patients with stage I disease had a median survival of 16 months compared with 10 months for patients with stage III disease (P = 0.036). The pretreatment dysphagia score was associated with survival (P = 0.021). Conclusions: This study shows the value of a purely radiation-based approach in a selected population. Treatment is deliverable with excellent compliance and the median survival compares favourably with unselected patients treated palliatively in our institution.
    Clinical Oncology 10/2014; 27(1). DOI:10.1016/j.clon.2014.09.001 · 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; 66(6). DOI:10.1016/j.eururo.2014.09.032 · 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; 113(1). DOI:10.1016/j.radonc.2014.09.001 · 4.86 Impact Factor
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    ABSTRACT: Background 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. Methods Nonsurgical menopause risk was analyzed in 2127 women treated for HL in England and Wales at ages younger than 36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were estimated using Cox regression, modified Poisson regression, and competing risks. All statistical tests were two-sided. Results During follow-up, 605 patients underwent nonsurgical menopause before age 40 years. Risk of premature menopause increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not statistically significantly raised after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Menopause generally occurred sooner after ovarian radiotherapy (62.5% within five years of >= 5 Gy treatment) and BEAM (50.9% within five years) than after alkylating chemotherapy (24.2% within five years of >= 6 cycles), and after treatment at older than at younger ages. Cumulative risk of menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely supradiaphragmatic radiotherapy. Tables of individualized risk information for patients by future period, treatment type, dose and age are provided. Conclusions Patients treated with HL need to plan intended pregnancies using personalized information on their risk of menopause by different future time points.
    JNCI Journal of the National Cancer Institute 08/2014; 106(9). DOI:10.1093/jnci/dju207 · 15.16 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; 112(1). DOI:10.1016/j.radonc.2014.06.007 · 4.86 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 07/2014; DOI:10.1002/ijc.29022 · 5.01 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; 112(1). DOI:10.1016/j.radonc.2014.06.015 · 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; 111(3). DOI:10.1038/bjc.2014.315 · 4.82 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; 15(7). DOI:10.1016/S1470-2045(14)70183-4 · 24.73 Impact Factor

Publication Stats

7k Citations
1,914.30 Total Impact Points

Institutions

  • 1994–2014
    • The Hillingdon Hospitals NHS Foundation Trust
      अक्सब्रिज, England, United Kingdom
  • 2013
    • Sunnybrook Health Sciences Centre
      • Department of Radiation Oncology
      Toronto, Ontario, Canada
  • 2006–2013
    • East Coast Community Healthcare CIC
      Beccles, England, United Kingdom
    • The University of Sheffield
      Sheffield, England, United Kingdom
  • 2012
    • University College London
      Londinium, England, United Kingdom
    • Cancer Treatment Centre
      Anaheim, California, United States
  • 2011
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2007–2011
    • Institute of Cancer Research
      • Division of Genetics and Epidemiology
      Londinium, England, United Kingdom
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada
  • 2010
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
  • 2009
    • Nottingham University Hospitals NHS Trust
      Nottigham, England, United Kingdom
    • Middlesex University, UK
      Londinium, England, United Kingdom
  • 2006–2007
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 1994–2006
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2005
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 1999
    • Mount Vernon College
      Mount Vernon, New York, United States