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Wilmslow, United Kingdom

Routsis D.,University of Cambridge | Staffurth J.,University of Cardiff | Mackay R.,North Western Medical Physics
Clinical Oncology

A growing body of evidence as to the benefits of intensity-modulated radiotherapy (IMRT) has led to the recommendation for its adoption as a treatment option for cancer patients within the UK. Routine clinical implementation of this technology has been slow. One of the causal factors was identified as being the need to improve confidence by improving the understanding and technical skills for IMRT of clinical oncology staff. This report determines and describes the additional knowledge and skills required for IMRT practice for clinical oncologists, clinical scientists (radiotherapy physicists) and radiographers, derived from reviewing evidence from other nations' IMRT practices and adapting them to UK needs. This knowledge and skills specification can be used to inform IMRT educational curricula. Novel educational methods to maintain the required understanding and skills are also described. © 2010 The Royal College of Radiologists. Source

Donaldson S.B.,University of Manchester | West C.M.L.,University of Manchester | Davidson S.E.,The Christie | Carrington B.M.,The Christie | And 5 more authors.
Magnetic Resonance in Medicine

The Tofts tracer kinetic models are often used to analyze dynamic contrast-enhanced MRI data. They are derived from a general two-compartment exchange model (2CXM) but assume negligible plasma mean transit time. The 2CXM estimates tissue plasma perfusion and capillary permeability-surface area; the Tofts models estimate the transfer constant Ktrans, which reflects a combination of these two parameters. The aims of this study were to compare the 2CXM and Tofts models and report microvascular parameters in patients with cervical cancer. Thirty patients were scanned pretreatment using a dynamic contrast-enhanced MRI protocol with a 3 sec temporal resolution and a total scan duration of 4 min. Whole-tumor parameters were estimated with both models. The 2CXM provided superior fits to the data for all patients (all 30 P values < 0.005), and significantly different parameter estimates were obtained (P < 0.01). Ktrans (mean 5 0.35 ± 0.26 min21) did not equal absolute values of tissue plasma perfusion (mean 5 0.65 6 0.56 mL/mL/min) or permeability-surface area (mean 5 0.14 6 0.09 mL/mL/min) but correlated strongly with tissue plasma perfusion (r 5 0.944; P 5 0.01). Average plasma mean transit time, calculated with the 2CXM, was 22 ± 16 sec, suggesting the assumption of negligible plasma mean transit time is not appropriate in this dataset and the 2CXM is better suited for its analysis than the Tofts models. The results demonstrate the importance of selecting an appropriate tracer kinetic model in dynamic contrast-enhanced MRI. © 2010 Wiley-Liss, Inc. Source

Sebastian A.,University of Manchester | Allan E.,The Christie NHS Foundation Trust | Allan D.,North Western Medical Physics | Allan D.,University of Manchester | And 2 more authors.
Journal of Dermatological Science

Background: We recently reported use of photodynamic therapy (PDT) for treating keloid disease (KD). However, in view of high recurrence rates post any treatment modality, adjuvant therapies should be considered. Additionally, we previously demonstrated the effect of a novel electrical waveform, the degenerate wave (DW) on differential gene expression in keloid fibroblasts. Objective: In this study, we evaluated the in vitro cytotoxic effect of PDT at 5J/cm 2 and 10J/cm 2 of red light (633±3nm) using 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) with and without DW, on keloid fibroblasts compared to normal skin fibroblasts. Methods: The rate of intracellular photosensitizer (protoporphyrin IX, PPIX) generation and disintegration, reactive oxygen species (ROS) generation, LDH cytotoxicity, WST-1 cytoproliferation, apoptosis by Caspase-3 activation, mitochondrial membrane potential assessment by JC-1 aggregates, qRT-PCR, flow cytometry and In-Cell Western Blotting were performed. Results: PPIX accumulation and disintegration rate was higher in keloid than normal fibroblasts after incubation with MAL compared to ALA. Increased cytotoxicity and decreased cytoproliferation were observed for keloid fibroblasts after PDT. +. DW treatment compared to PDT alone. ROS generation, mitochondrial membrane depolarization, apoptosis (Caspase-3 activation) and collagens I and III gene down-regulation were higher in keloid compared to normal skin fibroblasts after MAL-PDT. +. DW treatment. An increase in the number of cells entering apoptosis and necrosis was observed after PDT. +. DW treatment by flow cytometry analysis. All positive findings were statistically significant (P<0.05). Conclusion: The cytotoxic effect of PDT on keloid fibroblasts can be enhanced significantly with addition of DW stimulation, indicating for the first time the utility of this potential combinational therapy. © 2011 Japanese Society for Investigative Dermatology. Source

Theodorakou C.,North Western Medical Physics | Theodorakou C.,University of Manchester | Walker A.,University of Manchester | Horner K.,North Western Medical Physics | And 3 more authors.
British Journal of Radiology

Objectives: Cone beam CT (CBCT) is an emerging X-ray technology applied in dentomaxillofacial imaging. Previous published studies have estimated the effective dose and radiation risks using adult anthropomorphic phantoms for a wide range of CBCT units and imaging protocols. Methods: Measurements were made five dental CBCT units for a range of imaging protocols, using 10-year-old and adolescent phantoms and thermoluminescent dosimeters. The purpose of the study was to estimate paediatric organ and effective doses from dental CBCT. Results: The average effective doses to the 10-year-old and adolescent phantoms were 116 μSv and 79 μSv, respectively, which are similar to adult doses. The salivary glands received the highest organ dose and there was a fourfold increase in the thyroid dose of the 10-year-old relative to that of the adolescent because of its smaller size. The remainder tissues and salivary and thyroid glands contributed most significantly to the effective dose for a 10-year-old, whereas for an adolescent the remainder tissues and the salivary glands contributed the most significantly. It was found that the percentage attributable lifetime mortality risks were 0.002% and 0.001% for a 10-year-old and an adolescent patient, respectively, which are considerably higher than the risk to an adult having received the same doses. Conclusion: It is therefore imperative that dental CBCT examinations on children should be fully justified over conventional X-ray imaging and that dose optimisation by field of view collimation is particularly important in young children. © 2012 The British Institute of Radiology. Source

Ho K.F.,Academic Radiation Oncology | Marchant T.,North Western Medical Physics | Moore C.,North Western Medical Physics | Webster G.,North Western Medical Physics | And 6 more authors.
International Journal of Radiation Oncology Biology Physics

Purpose: Parotid-sparing head-and-neck intensity-modulated radiotherapy (IMRT) can reduce long-term xerostomia. However, patients frequently experience weight loss and tumor shrinkage during treatment. We evaluate the use of kilovoltage (kV) cone beam computed tomography (CBCT) for dose monitoring and examine if the dosimetric impact of such changes on the parotid and critical neural structures warrants replanning during treatment. Methods and materials: Ten patients with locally advanced oropharyngeal cancer were treated with contralateral parotid-sparing IMRT concurrently with platinum-based chemotherapy. Mean doses of 65 Gy and 54 Gy were delivered to clinical target volume (CTV)1 and CTV2, respectively, in 30 daily fractions. CBCT was prospectively acquired weekly. Each CBCT was coregistered with the planned isocenter. The spinal cord, brainstem, parotids, larynx, and oral cavity were outlined on each CBCT. Dose distributions were recalculated on the CBCT after correcting the gray scale to provide accurate Hounsfield calibration, using the original IMRT plan configuration. Results: Planned contralateral parotid mean doses were not significantly different to those delivered during treatment (p > 0.1). Ipsilateral and contralateral parotids showed a mean reduction in volume of 29.7% and 28.4%, respectively. There was no significant difference between planned and delivered maximum dose to the brainstem (p = 0.6) or spinal cord (p = 0.2), mean dose to larynx (p = 0.5) and oral cavity (p = 0.8). End-of-treatment mean weight loss was 7.5 kg (8.8% of baseline weight). Despite a ≥10% weight loss in 5 patients, there was no significant dosimetric change affecting the contralateral parotid and neural structures. Conclusions: Although patient weight loss and parotid volume shrinkage was observed, overall, there was no significant excess dose to the organs at risk. No replanning was felt necessary for this patient cohort, but a larger patient sample will be investigated to further confirm these results. Nevertheless, kilovoltage CBCT is a valuable tool for patient setup verification and monitoring of dosimetric variation during radiotherapy. © 2012 Elsevier Inc. Source

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