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Pham T.,University of Connecticut | Deherrera M.,Edwards Group | Sun W.,University of Connecticut
Computer Methods in Biomechanics and Biomedical Engineering | Year: 2014

Recent clinical studies of the percutaneous transvenous mitral annuloplasty (PTMA) devices have shown a short-term reduction of mitral regurgitation after implantation. However, adverse events associated with the devices such as compression and perforation of vessel branches, device migration and fracture were reported. In this study, a finite element analysis was carried out to investigate the biomechanical interaction between the proximal anchor stent of a PTMA device and the coronary sinus (CS) vessel in three steps including: (i) the stent release and contact with the CS wall, (ii) the axial pull t the stent connector and (iii) the pressure inflation of the vessel wall. To investigate the impact of the material properties of tissues and stents on the interactive responses, the CS vessel was modelled with human and porcine material properties, and the proximal stent was modelled with two different Nitinol materials with one being stiffer than the other. The results indicated that the vessel wall stresses and contact forces imposed by the stents were much higher in the human model than the porcine model. However, the mechanical differences induced by the two stent types were relatively small. The softer stent exhibited a better fatigue safety factor when deployed in the human model than in the porcine model. These results underscored the importance of the CS tissue mechanical properties. Vessel wall stress and stent radial force obtained in the human model were higher than those obtained in the porcine model, which also brought up questions as to the validity of using the porcine model to assess device mechanical function. The quantification of these biomechanical interactions can offer scientific insight into the development and optimisation of the PTMA device design. © 2013 © 2013 Taylor & Francis.


Hartley A.,Edwards Group | Sanghera P.,Edwards Group | Kazi W.,Edwards Group | Mehanna H.,Coventry University | And 3 more authors.
Clinical Oncology | Year: 2011

Aims: There has been a resurgence in interest in radiobiological modelling in head and neck cancer. The aim of this study was to determine if currently used parameters accurately predict both tumour and toxicity outcomes. Materials and methods: Trials were identified from a recent meta-analysis of altered fractionation. The tumour biologically effective dose (tBED; α/β=10Gy, tk [onset time of accelerated repopulation]=22 days, tp [average doubling time during accelerated repopulation]=3 days, α=0.3Gy-1), acute mucosal biologically effective dose (amBED; α/β=10Gy, tk=7 days, tp=2.5 days, α=0.3Gy-1) and late mucosal biologically effective dose (lmBED; α/β=3Gy) were calculated for each arm of each trial. The correlation between the absolute percentage difference in BED between treatment arms and the observed percentage difference in local control, acute grade 3 mucositis and late grade 3 mucosal reaction was then assessed. Results: A strong correlation was observed between the percentage difference in tBED and the percentage difference in local control (P=0.006). A trend towards a correlation was seen between the percentage difference in amBED and the percentage difference in acute grade 3 mucositis (P=0.06). A significant correlation was observed between the percentage difference in lmBED and the percentage difference in grade 3 late mucosal toxicity (P=0.02). However, a 15% decrease in lmBED between control and experimental arms of the study was necessary for any sparing of late mucosal toxicity to be observed. Conclusions: Currently used parameters for tumour accurately predict outcomes in randomised trials of altered fractionation. Although the relationship may be more complex for late mucosal reaction, the presence of a correlation is noteworthy given the infrequent reporting or occurrence of this toxicity. In the future, radiobiological modelling with the addition of volumetric parameters will be highly relevant, given attempts to dose escalate with intensity-modulated radiotherapy in poor risk patients and de-escalate in patients with an excellent prognosis. © 2010 The Royal College of Radiologists.


Sanghera P.,Edwards Group | Rampling R.,Beatson West of Scotland Cancer Center | Haylock B.,Clatterbridge Center for Oncology | Jefferies S.,Addenbrookes Hospital | And 4 more authors.
Clinical Oncology | Year: 2012

Since postoperative radiotherapy plus concomitant temozolomide followed by adjuvant temozolomide has become standard treatment for glioblastoma, the phenomenon of early post-treatment enlargement of the imaged tumour volume, usually without clinical deterioration, has become widely recognised. The term pseudoprogression has been used to describe a poorly understood pathophysiological process. In this review, the pathophysiological concepts, relevance, diagnosis and management of patients with 'pseudoprogression' and 'pseudoresponse' are discussed. Guidelines are given with respect to radiological imaging modality, mode and frequency. Further biological and clinical insights into these phenomena require carefully designed prospective studies. © 2011 The Royal College of Radiologists.


Yahya S.,Edwards Group | Zarkar A.,Edwards Group | Southgate E.,Edwards Group | Nightingale P.,University of Birmingham | Webster G.,Edwards Group
British Journal of Radiology | Year: 2013

Objective: We evaluated and compared a high-fibre diet leaflet, daily microenema and no preparation to establish how best to achieve consistent bowel preparation in prostate cancer patients being treated with radical radiotherapy. Methods: 3 cohorts of 10 patients had different dietary interventions: no bowel preparation, high-fibre diet information leaflet and daily microenemas. The available cone beam CT (CBCT) scans of each patient were used to quantify interfractional changes in rectal distension (measured using average cross-sectional area - CSA), prostate shifts relative to bony anatomy compared with that at CT planning scan and rates of geometric miss (i.e. shifts of >5mm). 85 CBCT scans were available in the pre-leaflet cohort, 89 scans in the post-leaflet, and 89 scans in the postenema group. Results: Mean rectal CSA in the post-enema group was reduced compared with both pre-leaflet (p=0.010) and post-leaflet values (p=0.031). The magnitude of observed mean prostate shifts was significantly reduced in the post-enema group compared with the pre-leaflet group (p=0.014). The proportion of scans showing geometric miss (i.e. shift ≥5mm) in the post-enema group (31%) was significantly lower than in the pre-leaflet (62%, p≤0.001) or post-leaflet groups (56%, p≤0.001). Conclusion: This study indicates microenema to be an effective measure to achieve reduction in rectal CSA, prostate shift and reduce geometric miss of >5mm. A further prospective randomised study is advocated to validate the results. Advances in knowledge: The use of microenema is effective in reducing prostate shift and rectal CSA, consequently decreasing the incidence of geographical miss. © 2013 The Authors.


PubMed | Mount Vernon Hospital, Edwards Group, University of Manchester, University of Nottingham and University College London
Type: | Journal: The British journal of radiology | Year: 2017

The HIPPO trial is a UK randomised phase II trial of Hippocampal Sparing (HS) versus Conventional Whole Brain Radiotherapy after surgical resection or radiosurgery in favourable prognosis patients with 1-4 brain metastases. Each participating centre completed a planning benchmark case as part of the dedicated radiotherapy trials quality assurance programme (RTQA), promoting the safe and effective delivery of HS Intensity Modulated Radiotherapy (IMRT) in a multi-centre trial setting.Submitted planning benchmark cases were reviewed using visualisation for radiotherapy software (VODCA) evaluating plan quality and compliance in relation to the HIPPO radiotherapy planning and delivery guidelines.Comparison of the planning benchmark data highlighted a plan specified using dose to medium as an outlier by comparison to those specified using dose to water. Further evaluation identified that the reported plan statistics for dose to medium were lower as a result of the dose calculated at regions of PTV inclusive of bony cranium being lower relative to brain.Specification of dose to water or medium remains a source of potential ambiguity and it is essential that as part of a multicentre trial consideration is given to reported differences, particularly in the presence of bone. Evaluation of planning benchmark data as part of a RTQA programme has highlighted an important feature of HS IMRT dosimetry dependent on dose being specified to water or medium, informing the development and undertaking of HS IMRT as part of the HIPPO trial. Advances in knowledge: The potential clinical impact of differences between dose to medium and dose to water are demonstrated for the first time, in the setting of HS WBRT.


Sherriff J.,Edwards Group
The British journal of radiology | Year: 2013

Different methods for contouring target volumes are currently in use in the UK when irradiating glioblastomas post operatively. Both one- and two-phase techniques are offered at different centres. 90% of relapses are recognised to occur locally when using radiotherapy alone. The objective of this evaluation was to determine the pattern of relapse following concomitant radiotherapy with temozolomide (RT-TMZ). A retrospective analysis of patients receiving RT-TMZ between 2006 and 2010 was performed. Outcome data including survival were calculated from the start of radiotherapy. Analysis of available serial cross-sectional imaging was performed from diagnosis to first relapse. The site of first relapse was defined by the relationship to primary disease. Central relapse was defined as progression of the primary enhancing mass or the appearance of a new enhancing nodule within 2 cm. 105 patients were identified as receiving RT-TMZ. 34 patients were not eligible for relapse analysis owing to either lack of progression or unsuitable imaging. Patterns of first relapse were as follows: 55 (77%) patients relapsed centrally within 2 cm of the original gadolinium-enhanced mass on MRI, 13 (18%) patients relapsed >4 cm from the original enhancement and 3 (4%) relapsed within the contralateral hemisphere. Central relapse remains the predominant pattern of failure following RT-TMZ. Single-phase conformal radiotherapy using a 2-cm margin from the original contrast-enhanced mass is appropriate for the majority of these patients. ADVANCES IN KNOWLEDGE: Central relapse remains the predominant pattern of failure following chemoradiotherapy for glioblastomas.


Chalkley A.,Edwards Group
The British journal of radiology | Year: 2014

To evaluate a new commercial PTW-60019 microDiamond (PTW, Freiburg, Germany) synthetic single-crystal diamond detector for relative dosimetry measurements on a clinical CyberKnife™ VSI (Accuray Inc., Sunnyvale, CA) system. Relative output factors (ROFs) were measured for collimator diameters from 5 to 60 mm, and compared with diode [PTW-60017, PTW-60018 and IBA Dosimetry (Schwarzenbruck, Germany) SFD] and ionization chamber (PTW-31014 PinPoint and PTW-31010 Semiflex) measurements. Beam profiles were measured at a range of depths, and collimator sizes, with the detector stem oriented both parallel and perpendicular to the central axis (CAX). Percentage depth-dose (PDD) curves were obtained for the 60-mm collimator and compared with natural Diamond Detector (PTW-60003) and ionization chamber curves to evaluate energy dependence. Penumbral broadening was noted on profile measurements made with the microDiamond oriented with the stem parallel to the CAX, in comparison with diodes. Oriented perpendicular to the CAX, the profile penumbra was sharper, but stem effects could not be ruled out. The PDD measurements were within 0.5% of ionization chamber measurements, indicating insignificant dose-rate dependence. The ROF for the microDiamond fell between diode and ionization chamber results. Published Monte Carlo-derived CyberKnife-specific factors were applied to the PTW-60017, PTW-60018 and PTW-31014 ROFs, and the microDiamond factors agreed within 2.0% of the mean of these. Over a range of small field relative dosimetry measurements, the microDiamond detector shows excellent spatial resolution, dose-rate independence and water equivalence. The microDiamond is a suitable tool for commissioning stereotactic systems.


Sherriff J.M.,Edwards Group | Ogunremi B.,Queen Elizabeth Hospital | Colley S.,Queen Elizabeth Hospital | Sanghera P.,Edwards Group | Hartley A.,Edwards Group
British Journal of Radiology | Year: 2012

Objectives: Positron emission tomography with CT (PET/CT) scanning is increasingly being used in head and neck cancer to assess response after radical concomitant chemoradiotherapy. The purpose of this study was to assess the use of PET/CT following chemoradiotherapy at our institution. Methods: All patients receiving radical chemoradiotherapy for head and neck cancer over a 9-year period were retrospectively identified. Outcome data including local control and overall survival were collected for all patients. The negative predictive value of PET/CT for local recurrence was calculated. Of those with a reported positive PET/CT scan the maximum standardised uptake values were compared with the incidence of local recurrence. Results: 92 patients were identified having a post-treatment PET/CT from a total of 301 patients receiving radical concomitant chemoradiotherapy. Median time from completion of chemoradiotherapy to PET/CT scan was 3 (range 2-8) months. Median follow-up in surviving patients was 19 and 25 months in the PET/CT and non-PET/CT groups, respectively. The negative predictive value for local recurrence was 91.8%. The median maximum standardised uptake values were 10.2 (range 3.1-33) and 6.89 (range 3.1-30) in those with local recurrence and with no local recurrence, respectively. Conclusions: Post-chemoradiotherapy PET/CT may aid subsequent management decisions. Patients with a negative PET/CT scan after radical chemoradiotherapy have a 91.8% chance of remaining free of local recurrence 19 months post-treatment. A higher maximum standardised uptake value on the post-chemoradiotherapy PET/CT may predict subsequent local recurrence and warrants further investigation. Advances in knowledge: Post-chemoradiotherapy PET/CT imaging aids subsequent management decisions. © 2012 The British Institute of Radiology.


Chalkley A.,Edwards Group | Heyes G.,Edwards Group
British Journal of Radiology | Year: 2014

Objective: To evaluate a new commercial PTW-60019 microDiamond™ (PTW, Freiburg, Germany) synthetic single-crystal diamond detector for relative dosimetry measurements on a clinical CyberKnife™ VSI (Accuray Inc., Sunnyvale, CA) system.Methods: Relative output factors (ROFs) were measured for collimator diameters from 5 to 60mm, and compared with diode [PTW-60017, PTW-60018 and IBA Dosimetry (Schwarzenbruck, Germany) SFD] and ionization chamber (PTW-31014 PinPoint® and PTW-31010 Semiflex) measurements. Beam profiles were measured at a range of depths, and collimator sizes, with the detector stem oriented both parallel and perpendicular to the central axis (CAX). Percentage depth-dose (PDD) curves were obtained for the 60-mm collimator and compared with natural Diamond Detector (PTW-60003) and ionization chamber curves to evaluate energy dependence.Results: Penumbral broadening was noted on profile measurements made with the microDiamond oriented with the stem parallel to the CAX, in comparison with diodes. Oriented perpendicular to the CAX, the profile penumbra was sharper, but stem effects could not be ruled out. The PDD measurements were within 0.5% of ionization chamber measurements, indicating insignificant dose-rate dependence. The ROF for the micro-Diamond fell between diode and ionization chamber results. Published Monte Carlo-derived CyberKnifespecific factors were applied to the PTW-60017, PTW-60018 and PTW-31014 ROFs, and the micro-Diamond factors agreed within 2.0% of the mean of these.Conclusion: Over a range of small field relative dosimetry measurements, the microDiamond detector shows excellent spatial resolution, dose-rate independence and water equivalence.Advances in knowledge: The microDiamond is a suitable tool for commissioning stereotactic systems. © 2014 The Authors.


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