Northern Ireland Cancer Center

Belfast, United Kingdom

Northern Ireland Cancer Center

Belfast, United Kingdom
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Walls G.,Northern Ireland Cancer Center | Napier S.,Royal Group of Hospitals Trust | Stewart D.,Northern Ireland Cancer Center
Frontiers in Oncology | Year: 2014

Background: Orbital metastases are an uncommon finding, being present in just 9% deceased patients with metastatic cancer. Only a quarter of patients with choroidal metastases have bilateral disease. Parotid cancer is not a common form of head and neck malignancy. Bilateral multifocal metastases from adenocarcinoma ex pleomorphic of parotid gland have been documented just once before in the literature. We present a similar case where palliative EBRT was used to gain local control with minimal toxicity. Case Presentation: The case of a 45-year-old Caucasian gentleman who presented to his general practitioner with otalgia and weight loss. Imaging revealed a mass in the deep lobe of the left parotid gland, invading into the medial pterygoid muscle. PET-CT revealed locoregional and distant lymphatic involvement plus disseminated skeletal metastases. Lymph node examination revealed adenocarcinoma ex pleomorphic histology. Within weeks of this diagnosis, the patient developed rapidly progressive visual impairment. Ophthalmologists found multifocal uveal masses bilaterally. Palliative fractions of external beam radiotherapy were delivered to the orbits before combination chemotherapy. We discuss the patient's presentation, histopathology, and management, with support from the literature regarding applied and related therapies. Summary: In this rare presentation of disseminated malignancy affecting the choroid bilaterally, the authors demonstrate the application of palliative EBRT to good local effect. Given the nature of this treatment and that of the metastases, in the setting of incurable disease orbital morbidity is likely to occur again before the patient's death. Awareness of the initial symptoms is important to provide prompt care and maintain quality of life. © 2014 Walls, Napier and Stewart.


Vengalil S.,Northern Ireland Cancer Center | O'Sullivan J.M.,Northern Ireland Cancer Center | O'Sullivan J.M.,Queen's University of Belfast | Parker C.C.,Royal Marsden Hospital
Current Opinion in Supportive and Palliative Care | Year: 2012

Purpose of review Bone metastases in prostate cancer are often the cause of significant morbidity in patients with castrateresistant disease, and several studies have shown significant pain palliation with systemic radionuclide treatment. The purpose of this review is to discuss the place of radionuclides in the dynamic treatment landscape of metastatic prostate cancer in light of new evidence demonstrating benefit beyond palliation. Recent findings The recently reported ALSYMPCA trial, which was a multicentre, placebo-controlled, phase 3 randomized controlled trial in patients with symptomatic metastatic castrate-resistant prostate cancer (CRPC) has shown significant overall survival (OS) benefit in favour of Radium-223 (Alpharadin) treatment [median OS 14.0 vs. 11.2 months; P0.00185; hazard ratio 0.695; 95% confidence interval (CI) 0.552-0.875]. This situation led to early unblinding of the trial and patients on placebo arm being offered Radium-223 treatment. Summary It has been an exciting and challenging time for treatment of patients with metastatic CRPC with six new agents demonstrating OS benefit in phase 3 trials, in this setting since 2004. Further research should focus on appropriate sequencing and innovative strategies to use these therapeutic agents to maximize benefit for patients. In the case of radionuclides, novel strategies include repeated administration, dose intense regimens and combination with other agents. © 2012 Wolters Kluwer Health | Lippincott Williams &Wilkins.


Agnew C.E.,Northern Ireland Cancer Center | McGarry C.K.,Northern Ireland Cancer Center | McGarry C.K.,Queen's University of Belfast
Radiotherapy and Oncology | Year: 2016

Purpose To provide a tool to enable gamma analysis software algorithms to be included in a quality assurance (QA) program. Methods Four image sets were created comprising two geometric images to independently test the distance to agreement (DTA) and dose difference (DD) elements of the gamma algorithm, a clinical step and shoot IMRT field and a clinical VMAT arc. The images were analysed using global and local gamma analysis with 2 in-house and 8 commercially available software encompassing 15 software versions. The effect of image resolution on gamma pass rates was also investigated. Results All but one software accurately calculated the gamma passing rate for the geometric images. Variation in global gamma passing rates of 1% at 3%/3 mm and over 2% at 1%/1 mm was measured between software and software versions with analysis of appropriately sampled images. Conclusion This study provides a suite of test images and the gamma pass rates achieved for a selection of commercially available software. This image suite will enable validation of gamma analysis software within a QA program and provide a frame of reference by which to compare results reported in the literature from various manufacturers and software versions. © 2015 Elsevier Ireland Ltd. All rights reserved.


Prue G.,University of Ulster | Allen J.,University of Ulster | Gracey J.,University of Ulster | Rankin J.,Northern Ireland Cancer Center | Cramp F.,University of the West of England
Journal of Pain and Symptom Management | Year: 2010

Context: Research has indicated that individuals with gynecological cancer experience severe fatigue. Objectives: This longitudinal survey aimed to analyze the fatigue experienced over the course of one year by a gynecological cancer population, to determine if the fatigue was more severe than that reported by females without cancer, and to identify variables associated with cancer-related fatigue (CRF). Methods: Data were collected over a 12-month period before, during, and after anticancer treatment. Fatigue was assessed using the Multidimensional Fatigue Symptom Inventory-Short Form. Participants with cancer also completed the Rotterdam Symptom Checklist. Results: Sixty-five cancer patients (mean age = 57.4 years, standard deviation [SD] = 13.9) and 60 control subjects (mean age = 55.4 years, SD = 13.6) participated. Descriptive analysis and repeated measurements modeling indicated that the cancer participants reported worse fatigue than the noncancer individuals before, during, and after anticancer treatment (P < 0.001) and that the level of fatigue in persons with cancer changed with time (P = 0.02). A forward stepwise regression demonstrated that psychological distress level was the only independent predictor of CRF during anticancer treatment (P < 0.00), explaining 44% of the variance in fatigue. After treatment, both psychological distress level (P < 0.00) and physical symptom distress (P = 0.03) were independent predictors of fatigue, accounting for 81% of the variance. Conclusion: Psychological distress level is an important indicator of CRF in gynecological cancer. Interventions focused on the reduction of psychological distress may help alleviate CRF. © 2010 U.S. Cancer Pain Relief Committee.


Agnew A.,Northern Ireland Cancer Center | Agnew C.E.,Northern Ireland Cancer Center | Grattan M.W.D.,Northern Ireland Cancer Center | Hounsell A.R.,Northern Ireland Cancer Center | And 3 more authors.
Physics in Medicine and Biology | Year: 2014

This work investigated the differences between multileaf collimator (MLC) positioning accuracy determined using either log files or electronic portal imaging devices (EPID) and then assessed the possibility of reducing patient specific quality control (QC) via phantom-less methodologies. In-house software was developed, and validated, to track MLC positional accuracy with the rotational and static gantry picket fence tests using an integrated electronic portal image. This software was used to monitor MLC daily performance over a 1 year period for two Varian TrueBeam linear accelerators, with the results directly compared with MLC positions determined using leaf trajectory log files. This software was validated by introducing known shifts and collimator errors. Skewness of the MLCs was found to be 0.03 ± 0.06° (mean ±1 standard deviation (SD)) and was dependent on whether the collimator was rotated manually or automatically. Trajectory log files, analysed using in-house software, showed average MLC positioning errors with a magnitude of 0.004 ± 0.003 mm (rotational) and 0.004 ± 0.011 mm (static) across two TrueBeam units over 1 year (mean ±1 SD). These ranges, as indicated by the SD, were lower than the related average MLC positioning errors of 0.000 ± 0.025 mm (rotational) and 0.000 ± 0.039 mm (static) that were obtained using the in-house EPID based software. The range of EPID measured MLC positional errors was larger due to the inherent uncertainties of the procedure. Over the duration of the study, multiple MLC positional errors were detected using the EPID based software but these same errors were not detected using the trajectory log files. This work shows the importance of increasing linac specific QC when phantom-less methodologies, such as the use of log files, are used to reduce patient specific QC. Tolerances of 0.25 mm have been created for the MLC positional errors using the EPID-based automated picket fence test. The software allows diagnosis of any specific leaf that needs repair and gives an indication as to the course of action that is required. © 2014 Institute of Physics and Engineering in Medicine.


Butterworth K.T.,Queen's University of Belfast | McGarry C.K.,Queen's University of Belfast | McGarry C.K.,Northern Ireland Cancer Center | Trainor C.,Queen's University of Belfast | And 5 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: To determine the in-field and out-of-field cell survival of cells irradiated with either primary field or scattered radiation in the presence and absence of intercellular communication. Methods and Materials: Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and primary fibroblast (AGO1552) cells following exposure to different field configurations delivered using a 6-MV photon beam produced with a Varian linear accelerator. Results: Nonuniform dose distributions were delivered using a multileaf collimator (MLC) in which half of the cell population was shielded. Clonogenic survival in the shielded region was significantly lower than that predicted from the linear quadratic model. In both cell lines, the out-of-field responses appeared to saturate at 40%-50% survival at a scattered dose of 0.70 Gy in DU-145 cells and 0.24 Gy in AGO1522 cells. There was an approximately eightfold difference in the initial slopes of the out-of-field response compared with the α-component of the uniform field response. In contrast, cells in the exposed part of the field showed increased survival. These observations were abrogated by direct physical inhibition of cellular communication and by the addition of the inducible nitric oxide synthase inhibitor aminoguanidine known to inhibit intercellular bystander effects. Additional studies showed the proportion of cells irradiated and dose delivered to the shielded and exposed regions of the field to impact on response. Conclusions: These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields with cellular communication between differentially irradiated cell populations playing an important role. Validation of these observations in additional cell models may facilitate the refinement of existing radiobiological models and the observations considered important determinants of cell survival. © 2011 Elsevier Inc.


Jain S.,Northern Ireland Cancer Center | Jain S.,Queen's University of Belfast | Hirst D.G.,Queen's University of Belfast | O'Sullivan J.M.,Northern Ireland Cancer Center | O'Sullivan J.M.,Queen's University of Belfast
British Journal of Radiology | Year: 2012

Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed. © 2012 The British Institute of Radiology.


Agnew C.E.,Northern Ireland Cancer Center | King R.B.,Northern Ireland Cancer Center | Hounsell A.R.,Northern Ireland Cancer Center | Hounsell A.R.,Queen's University of Belfast | And 2 more authors.
Physics in Medicine and Biology | Year: 2012

This study aims to evaluate the use of Varian radiotherapy dynamic treatment log (DynaLog) files to verify IMRT plan delivery as part of a routine quality assurance procedure. Delivery accuracy in terms of machine performance was quantified by multileaf collimator (MLC) position errors and fluence delivery accuracy for patients receiving intensity modulated radiation therapy (IMRT) treatment. The relationship between machine performance and plan complexity, quantified by the modulation complexity score (MCS) was also investigated. Actual MLC positions and delivered fraction of monitor units (MU), recorded every 50ms during IMRT delivery, were extracted from the DynaLog files. The planned MLC positions and fractional MU were taken from the record and verify system MLC control file. Planned and delivered beam data were compared to determine leaf position errors with and without the overshoot effect. Analysis was also performed on planned and actual fluence maps reconstructed from the MLC control file and delivered treatment log files respectively. This analysis was performed for all treatment fractions for 5 prostate, 5 prostate and pelvic node (PPN) and 5 head and neck (H & N) IMRT plans, totalling 82 IMRT fields in ∼5500 DynaLog files. The root mean square (RMS) leaf position errors without the overshoot effect were 0.09, 0.26, 0.19mm for the prostate, PPN and H & N plans respectively, which increased to 0.30, 0.39 and 0.30mm when the overshoot effect was considered. Average errors were not affected by the overshoot effect and were 0.05, 0.13 and 0.17mm for prostate, PPN and H & N plans respectively. The percentage of pixels passing fluence map gamma analysis at 3%/3mm was 99.94 ± 0.25%, which reduced to 91.62 ± 11.39% at 1%/1mm criterion. Leaf position errors, but not gamma passing rate, were directly related to plan complexity as determined by the MCS. Site specific confidence intervals for average leaf position errors were set at0.03-0.12mm for prostate and0.02-0.28mm for more complex PPN and H & N plans. For all treatment sites confidence intervals for RMS errors with the overshoot was set at 0-0.50mm and for the percentage of pixels passing a gamma analysis at 1%/1mm a confidence interval of 68.83% was set also for all treatment sites. This work demonstrates the successful implementation of treatment log files to validate IMRT deliveries and how dynamic log files can diagnose delivery errors not possible with phantom based QC. Machine performance was found to be directly related to plan complexity but this is not the dominant determinant of delivery accuracy. © 2012 Institute of Physics and Engineering in Medicine.


Butterworth K.T.,Queen's University of Belfast | McMahon S.J.,Queen's University of Belfast | Hounsell A.R.,Queen's University of Belfast | Hounsell A.R.,Northern Ireland Cancer Center | And 3 more authors.
Clinical Oncology | Year: 2013

Classical radiation biology research has centred on nuclear DNA as the main target of radiation-induced damage. Over the past two decades, this has been challenged by a significant amount of scientific evidence clearly showing radiation-induced cell signalling effects to have important roles in mediating overall radiobiological response. These effects, generally termed radiation-induced bystander effects (RIBEs) have challenged the traditional DNA targeted theory in radiation biology and highlighted an important role for cells not directly traversed by radiation. The multiplicity of experimental systems and exposure conditions in which RIBEs have been observed has hindered precise definitions of these effects. However, RIBEs have recently been classified for different relevant human radiation exposure scenarios in an attempt to clarify their role invivo. Despite significant research efforts in this area, there is little direct evidence for their role in clinically relevant exposure scenarios. In this review, we explore the clinical relevance of RIBEs from classical experimental approaches through to novel models that have been used to further determine their potential implications in the clinic. © 2013 The Royal College of Radiologists.


King R.B.,Northern Ireland Cancer Center
Physics in medicine and biology | Year: 2013

Flattening filter free (FFF) linear accelerators allow for an increase in instantaneous dose-rate of the x-ray pulses by a factor of 2-6 over the conventional flattened output. As a result, radiobiological investigations are being carried out to determine the effect of these higher dose-rates on cell response. The studies reported thus far have presented conflicting results, highlighting the need for further investigation. To determine the radiobiological impact of the increased dose-rates from FFF exposures a Varian Truebeam medical linear accelerator was used to irradiate two human cancer cell lines in vitro, DU-145 prostate and H460 non-small cell lung, with both flattened and FFF 6 MV beams. The fluence profile of the FFF beam was modified using a custom-designed Nylon compensator to produce a similar dose profile to the flattened beam (6X) at the cell surface but at a higher instantaneous dose-rate. For both cell lines there appeared to be no significant change in cell survival. Curve fitting coefficients for DU145 cells irradiated with constant average dose-rates were 6X: α = 0.09 ± 0.03, β = 0.03 ± 0.01 and 6FFF: α = 0.14 ± 0.13, β = 0.03 ± 0.02 with a significance of p = 0.75. For H460 cells irradiated with the same instantaneous dose-rate but different average dose-rate the fit coefficients were 6FFF (low dose-rate): α = 0.21 ± 0.11, 0.07 ± 0.02 and 6FFF (high dose-rate): α = 0.21 ± 0.16, 0.07 ± 0.03, with p = 0.79. The results indicate that collective damage behaviour does not occur at the instantaneous dose-rates investigated here and that the use of either modality should result in the same clinical outcome, however this will require further validation in vivo.

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