Professor Andrew Nisbet
Professor Andrew Nisbet was appointed Head of Medical Physics at the Royal Surrey County Hospital NHS Foundation Trust and Professor of Medical Physics at Surrey University in 2006. He graduated in Physics at the University of Edinburgh before completing an MSc in Medical Physics at the University of Aberdeen and subsequently a PhD from the same University. Prior to taking up appointment in Guildford he was Head of Radiotherapy Physics within the Medical Physics Department at the Oxford Radcliffe Hospitals NHS Trust.
The Department of Medical Physics includes the Regional Radiation Protection Service, Radiotherapy Physics, Radiopharmacy & Nuclear Medicine Physics, Scientific Computing, Technical Services and the Department also hosts the National Coordinating Centre for the Physics of Mammography on behalf of the NHS Breast Screening Programme.
Professor Nisbet has been a member of the Technology Subgroup of the National Radiotherapy Advisory Group, which produced an influential report on planning future radiotherapy services in England. He is an expert in the implementation of advanced radiotherapy techniques and the assessment of risk from such treatments. He has worked closely with the National Physical Laboratory in providing national recommendations on the measurement of dose for radiotherapy. He has been a consultant for the International Atomic Energy Agency producing guidelines for the on-site auditing of radiotherapy departments and has sat on the Panel of Scientific Experts for a European Union funded grant with the objectives of performing an EU-wide study on the implementation of Medical Exposure Directive requirements aimed at the reduction of the probability and the magnitude of accidents in radiotherapy and developing guidelines on a risk analysis of accidental and unintended exposures in external beam radiotherapy and, therefore, improving patient safety.
As Principal or co-Investigator he has held grants in excess of £6m. As Head of the Medical Physics Department and Co-Investigator he has been involved in two CRUK / EPSRC /MRC/ NIHR Cancer Imaging Programme Grants investigating the optimisation of digital technology for mammographic screening. He has helped develop the dosimetric methodology for determining cardiac dose from breast radiotherapy employed in a major international epidemiological study funded by the European Union, for which he was Partner and lead medical physicist, and which has recently published its results in the New England Journal of Medicine. He has been a co-investigator on a Department of Health funded grant examining the adaption of medical imaging systems for body monitoring in the event of a radiological incident. He has also been PI for two NIHR invention for innovation grants, in collaboration with the National Physical Laboratory, developing a novel superconducting quantum interference device (SQUID) based microbolometer for the measurement of radiobiological effect from particle therapy beams.
He has supervised 12 PhD, 3 MD and numerous MSc postgraduate students and has published over 80 papers in peer reviewed journals. He is currently primary or co-supervisor to a further 8 PhD students and 1 MD fellow.
optical fibres for application in interface radiation dosimetry, Applied Radiation and Isotopes 70 (7) pp. 1436-1441
TL dosimeters to measure photoelectron dose enhancement resulting from the use of a moderate to high-Z target (an iodinated contrast media) irradiated by 90kVp X-rays. We imagine its application in a novel radiation synovectomy technique, modelled by a phantom containing a reservoir of I
molecules at the interface of which the doped silica dosimeters are located. Measurements outside of the iodine photoelectron range are provided for using a stepped-design that allows insertion of the fibres within the phantom. Monte Carlo simulation (MCNPX) is used for verification. At the phantom medium I
-interface additional photoelectron generation is observed, ~60% above that in the absence of the I
, simulations providing agreement to within 3%. Percentage depth doses measured away from the iodine contrast medium reservoir are bounded by published PDDs at 80kVp and 100kVp. © 2011 Elsevier Ltd.
0.166). Conclusion: The choice to treat using IMRT at 15 MV should not be excluded, but should be based on risk versus benefit, considering the age and life expectancy of the patient together with the relative risk of radiation-induced cancer and NTCPs.
through Monte Carlo simulations and thermal
analysis for use in particle therapy.,
therapy beams, which are used in combination with the quantity absorbed dose in
radiotherapy, together with the increase in the number of particle therapy centres
worldwide necessitate a better understating of the biological effect of such modalities.
The present novel study is part of performance testing and development of a microcalorimeter
based on Superconducting QUantum Interference Devices (SQUIDs). Unlike
other microdosimetric detectors that are used for investigating the energy distribution,
this detector provides a direct measurement of energy deposition at the micrometer
scale, that can be used to improve our understanding of biological effects in particle
therapy application, radiation protection and environmental dosimetry. Temperature
rises of less than 1 ¼K are detectable and when combined with the low specific heat
capacity of the absorber at cryogenic temperature, extremely high energy deposition
sensitivity of approximately 0.4 eV can be achieved.
The detector consists of three layers: a Tissue Equivalent (TE) absorber, a SuperConducting
(SC) absorber and a silicon substrate. Ideally all energy would be deposited in
the TE absorber and the heat rise in the SC layer would arise due to heat conduction
from the TE layer. However, in practice direct particle absorption occurs in all three
layers and must be corrected for.
To investigate the thermal behavior within the detector, and quantify any possible
correction, particle tracks were simulated employing Geant4 (v9.6) Monte Carlo simulations.
The track information was then passed to the COMSOL Multiphysics (Finite
Element Method) software. The 3D heat transfer within each layer was then evaluated
in a time-dependent model. For a statistically reliable outcome, the simulations had to
be repeated for a large number of particles. An automated system has been developed
that couples Geant4 Monte Carlo output to COMSOL for determining the expected
distribution of proton tracks and their thermal contribution within the detector.
The percentage heat contribution from the TE absorber into the SC absorber was
determined for mono-energetic proton pencil beams of 3.8, 10, 62 and 230 MeV. The
corrected energy distribution is compared to the ideal energy distribution, exhibiting
their energy response, especially when intended for use in radiotherapy applications over a wide range
of energies (typically from X-rays generated at 80 kVp up to 25 MV photon and MeV electron beams). In
this paper, the energy response of glass beads (Mill Hill, Japan) is investigated for their TL response to kV
X-rays from an orthovoltage radiotherapy unit and also for MV photon and MeV electron beams from a
medical linear accelerator. The experimental findings show that for photon and electron beams, the TL
response of this particular glass bead, normalised to unity for 6 MV X-rays (TPR20/10¼0.670), decreases
to 0.9670.02 for 15 MV X-rays (TPR20/10¼0.761) and to 0.9570.01 for 20 MeV electron beams
(R50,D¼8.35 cm). This compares favourably with other TLD materials such as LiF and also alanine
dosimeters that are readout with an EPR system. For kV X-rays, the response increases to 4.5270.05 for
80 kV X-rays (HVL¼2.4 mm Al) which approaches 3 times that of LiF TLDs and 5 times that of alanine.
In conclusion, the particular glass beads, when used as a dosimeter material, show a relatively small
energy dependence over the megavoltage range of clinically relevant radiation qualities, being clearly
advantageous for accurate dosimetry. Conversely, the energy response is significant for photon beam
energies covering the kV range. In both circumstances, in dosimetric evaluations the energy response
needs to be taken into account.
Audit is imperative in delivering consistent and safe radiotherapy and the UK has a strong history of radiotherapy audit. The National Physical Laboratory (NPL) has undertaken audit measurements since 1994 and this work examines results from these audits.
Materials and Methods
This paper reviews audit results from 209 separate beams from 82 on-site visits to National Health Service (NHS) radiotherapy departments conducted between June 1994 and February 2015. Measurements were undertaken following the relevant UK code of practice. The accuracy of the implementation of absorbed dose calibration across the UK is quantified for MV photon, MeV electron and kV x-ray radiotherapy beams.
Over the measurement period the standard deviation of MV photon beam output has reduced from 0.8 % to 0.4 %. The switch from air kerma- to absorbed dose-based electron code of practice contributed to a reduction in the difference of electron beam output of 0.6 % (p Conclusions
The introduction of the 2003 electron code of practice based on absorbed dose to water decreased the difference between absolute dose measurements by the centre and NPL. The use of a single photon code of practice over the period of measurements has contributed to a reduction in measurement variation. Within the clinical setting, on-site audit visits have been shown to identify areas of improvement for determining and implementing absolute dose calibrations.
Investigating the feasibility of using low-cost commercially available silica beads as novel thermo-luminescence dosimeters (TLD) for postal dosimetry audit.
A mail-based dosimetry audit was designed to assess the positional and dosimetric accuracy of SABR-lung treatment delivery using alanine and EBT3-film, placed in a CIRS-anthropomorphic thorax phantom. In conjunction, the silica beads were dosimetrically characterised as TLDs and cross-calibrated against the alanine. A CT-scan of the phantom with pre-delineated volumes was sent to 20 RT centres and used to create a SABR plan using local current protocols and techniques. The silica beads were held in an insert, designed to match that of the alanine holder and ionisation chamber to give the same measurement length. The doses determined by the silica beads were compared to those measured by alanine, the local ionisation chamber, film and the TPS calculation.
The mean percentage difference between the doses measured by the silica beads and the calculated doses by the TPS was found to be 0.7% and differed by 0.6%, 0.7%, and 1.3% from the alanine, film and local ionisation chamber measurements respectively.
Results obtained with the silica beads agree well with those obtained from conventional detectors including alanine, film and ionisation chambers. This together with the waterproof and inert characteristics and minimal dose fading associated with silica bead TLDs confirm their potential as a postal dosimetry audit tool in both water and plastic phantoms which could withstand challenges of temperature and humidity variation, as well as postal service delays.
Radiotherapy requires tight control of the delivered dose. This should include the variation in beam output as this may directly affect treatment outcomes. This work provides results from a multi-centre analysis of routine beam output measurements.
Materials and Methods
A request for 6MV beam output data was submitted to all radiotherapy centres in the UK, covering the period January 2015 ? July 2015. An analysis of the received data was performed, grouping the data by manufacturer, machine age, and recording method to quantify any observed differences. Trends in beam output drift over time were assessed as well as inter-centre variability. Annual trends were calculated by linear extrapolation of the fitted data.
Data was received from 204 treatment machines across 52 centres. Results were normally distributed with mean of 0.0% (percentage deviation from initial calibration) and a 0.8% standard deviation, with 98.1% of results within ±2%. There were eight centres relying solely on paper records. Annual trends varied greatly between machines with a mean drift of +0.9%/year with 95th percentiles of +5.1%/year and -2.2%/year. For the machines of known age 25% were over ten years old, however there was no significant differences observed with machine age.
Machine beam output measurements were largely within ±2% of 1.00cGy/MU. Clear trends in measured output over time were seen, with some machines having large drifts which would result in additional burden to maintain within acceptable tolerances. This work may act as a baseline for future comparison of beam output measurements.
To define a method and investigate how the adjustment of scan parameters affected the image quality and Hounsfield units (HUs) on a CT scanner used for radiotherapy treatment planning. A lack of similar investigations in the literature may be a contributing factor in the apparent reluctance to optimise radiotherapy CT protocols.
A Catphan phantom was used to assess how image quality on a Toshiba Aquilion LB scanner changed with scan parameters. Acquisition and reconstruction field-of-view (FOV), collimation, image slice thickness, effective mAs per rotation and reconstruction algorithm were varied. Changes were assessed for HUs of different materials, high contrast spatial resolution (HCSR), contrast-noise ratio (CNR), HU uniformity, scan direction low contrast and CT dose-index.
CNR and HCSR varied most with reconstruction algorithm, reconstruction FOV and effective mAs. Collimation, but not image slice width, had a significant effect on CT dose-index with narrower collimation giving higher doses. Dose increased with effective mAs. Highest HU differences were seen when changing reconstruction algorithm: 56 HU for densities close to water and 117 HU for bone-like materials. Acquisition FOV affected the HUs but reconstruction FOV and effective mAs did not.
All the scan parameters investigated affected the image quality metrics. Reconstruction algorithm, reconstruction FOV, collimation and effective mAs were most important. Reconstruction algorithm and acquisition FOV had significant effect on HU. The methodology is applicable to radiotherapy CT scanners when investigating image quality optimisation, prior to assessing the impact of scan protocol changes on clinical CT images and treatment plans.
This inter-comparison exercise was performed to demonstrate the variability of
quantitative SPECT/CT imaging for lutetium-177 (177Lu) in current clinical practice.
Our aim was to assess the feasibility of using international inter-comparison exercises
as a means to ensure consistency between clinical sites whilst enabling the sites to
use their own choice of quantitative imaging protocols, specific to their systems.
Dual-compartment concentric spherical sources of accurately known activity
concentrations were prepared and sent to seven European clinical sites. The site staff
were not aware of the true volumes or activity within the sources - they performed
SPECT/CT imaging of the source, positioned within a water-filled phantom, using their
own choice of parameters and reported their estimate of the activities within the
The volumes reported by the participants for the inner section of the source were all
within 29% of the true value, and within 60% of the true value for the outer section. The
activities reported by the participants for the inner section of the source were all within
20% of the true value, whilst those reported for the outer section were up to 83%
different to the true value.
A variety of calibration and segmentation methods were used by the participants for
this exercise which demonstrated the variability of quantitative imaging across clinical
sites. . This paper presents a method to assess consistency between sites using
different calibration and segmentation methods.
comparison, irradiation exposures were also carried
out on 5 mm length of Ge-doped optical fibres that
have been widely investigated for their TL properties
The dose response was linear for the investigated
dose range of 1 to 2500 cGy, with an R2 correlation
coefficient of > 0.999 and reproducibility of 1.7%.
The results suggest the potential for use of glass
beads as TL dosimeters in radiotherapy.
2014a,b,c, 2015a,b), detailed study of TL variation is required for the products from various manufacturers.
Investigation is made for glass beads from four manufacturers from four countries: China (Rocaille), Japan (Mill Hill), Indonesia (TOHO") and Czech Republic (Czech). Sample composition was determined using an energy-dispersive X-ray unit coupled to a scanning electron microscope. Values of mass attenuation coefficient, ¼/Á, as a function of photon energy were then calculated for photons of energy 1 keV to 10 MeV, using the National Institute of Standards and Technology XCOM program. Radiation and energy response were determined using X-rays generated at accelerating potentials from 80 kVp to 6 MV (TPR20/10¼0.670).
All bead types showed TL to be linear with dose (R240.999). Glow curve dosimetric peaks reached a
maximum value at 300 °C for the Toho and 290 °C for the Czech and Mill Hill products but was between
200?250 °C for the Rocaille product. Radiation sensitivity following mass normalisation varied within an
order of magnitude; Toho samples showed the greatest and Rocaille the least sensitivity. For the Toho,
Czech, Rocaille and Mill Hill samples the energy responses at 80 kVp were 5.0, 4.0, 3.6 and 3.3 times that
obtained at 6 MV. All four glass bead types offer potential use as TL dosimeters over doses commonly
applied in radiotherapy. Energy response variation was o1% at 6 MV but significant variation was found
for photon beam energies covering the kV range; careful characterisation is required if use at this range is
ení technické v Praze Fakulta jaderná a fyzikáln? in~enýrská
1 cm, 2 cm × 2 cm, 3 cm × 3 cm, 4 cm × 4 cm, and 10 cm × 10 cm have been investigated using commercially available silica-based fibres and glass beads (GB) as TL dosimeters and a Varian linear accelerator operating at 6, 10 and 15 MV. Ge-doped SiO2 fibres have previously been shown by this group to offer a viable system for use as dosimeters. The fibres and GB, offer good spatial resolution ( 2 mm respectively), large dynamic dose range (with linearity from tens of mGy up to well in excess of many tens of Gy), a non-hygroscopic nature and low cost. The
main aim of this present work is to investigate the use of Ge-doped optical fibres and GBs as thermoluminescence dosimeters in small photon fields for different photon beam energies, comparing the measurements against Gafchromic films, hospital commissioning data obtained from small
ionisation chambers and photon diodes and Monte Carlo simulations with FLUKA and BEAMnrc.
Materials and Methods: Three patient data sets with different lung tumour sizes were selected: T1=6cc, T2=31cc and T3=60cc. Each was planned in Eclipse for SABR using 3DCRT, sliding window IMRT and VMAT,
creating 9 treatment plans which were then delivered to a dynamic thorax phantom. The phantom was programmed to move at a typical patient breathing amplitude of 15mm with a period of 5 seconds and
Varian linacs were used for the delivery. EBT3 Gafchromic film was used in coronal and sagittal planes for measuring dose distributions. Static phantom measurements were compared with the TPS calculated plans to
establish agreement between expected and measured dose distributions without motion, using the software OmniPro I'mRT. Comparisons of static and dynamic phantom measurements followed. Global gamma analysis
was used to carry out a relative comparison between the three delivery techniques. Five regions of the gamma index map (Middle, Proximal Left, Proximal Right, Distal Left, Distal Right) were analysed to quantify the
differences along the axis of motion. The criteria used for the gamma analysis were 3%/3mm, with a threshold of 20%.
Results: The setup and delivery accuracy was confirmed by the agreement between planned and static delivered dose distributions. The average percentage of pixels passing was 100% (T1),100% (T2) and 98.46%
(T3). The comparison of films with and without motion gave lower percentages of pixels passing, ranging between 33.68 - 59.94% (T1), 47.86 - 61.77% (T2) and 43.44 - 64.32% (T3). Comparison of the delivery
technique, showed passing rates of 33.63 - 52.25% (3DCRT), 43.44 - 64.52% (IMRT) and 46.58- 56.08% (VMAT). Analysis of the five regions for all delivery techniques gave averages of 93.76% (Middle), 58.7%
(Proximal) and 12.8% (Distal). For 3DCRT results were 87.08% (Middle), 46.52% (Proximal) and 12.54% (Distal), for IMRT were 96.45%, 69.20%, 14.14% and for VMAT 97.75%, 60.39% and 11.71%, respectively.
Conclusions: The results are indicative of the intra-fractional respiratory motion-induced dosimetric inaccuracies caused in three SABR delivery techniques.On average, the impact is greatest in the distal regions,
significant in the proximal regions, whereas the middle region is less susceptible to these effects. No noticeable difference was observedbetween coronal and sagittal planes. The results also suggest that the effect of motion is greater in the proximal regions for 3DCRT in relation to the other techniques, particularly with smaller tumour sizes.
security, with many potential uses limited by system cost and/or detector dimensions.
Current X-ray detector sensitivities are limited by the bulk X-ray attenuation of the
materials and consequently necessitate thick crystals (~ 1 mm ? 1 cm), resulting in rigid
structure, high operational voltages and high cost. Here we present a disruptive,
flexible, low cost, broad-band, and high sensitivity direct X-ray transduction technology
produced by embedding high atomic number bismuth oxide nanoparticles in an organic
bulk heterojunction. These hybrid detectors demonstrate sensitivities of 1712 µC mGy-1
cm-3 for ?soft? X-rays and ~30 and 58 µC mGy-1 cm-3 under 6 and 15 MV ?hard? X-rays
generated from a medical linear accelerator; strongly competing with the current solid state detectors, all achieved at low bias voltages (-10 V) and low power, enabling
detector operation powered by coin cell batteries.
This study tested the hypothesis that shows advanced image analysis can differentiate fit and unfit patients for radical radiotherapy from standard radiotherapy planning imaging, when compared to formal lung function tests (FEV1, Forced Expiratory Volume in 1 second) and TLCO (Transfer Factor of Carbon Monoxide).
An apical region of interest (ROI) of lung parenchyma was extracted from a standard radiotherapy planning CT scan. Software using a grey level co-occurrence matrix (GLCM) assigned an entropy score to each voxel, based on its similarity to the voxels around it. Density and entropy scores were compared between a cohort of fit patients (defined as FEV1 and TLCO above 50% predicted value) and unfit patients (FEV1 or TLCO below 50% predicted).
29 fit and 32 unfit patients were included. Mean and median density and mean and median entropy were significantly different between fit and unfit patients (p= 0.0021, 0.0019, 0.0357 and 0.0363 respectively, 2 sided t-test).
Density and entropy assessment can differentiate between fit and unfit patients for radical radiotherapy, using standard CT imaging.
Advances in knowledge
This study shows that a novel intervention can generate further data from standard CT imaging. This data could be combined with existing studies to form a multi-organ patient fitness assessment from a single CT scan.
The accuracy of delivered dose depends directly upon initial beam calibration and subsequent maintenance of this beam output. The uncertainty associated with these measurements and its impact on clinical outcomes is not well documented. This work gives an evidence based approach to determining this variation and its clinical impact.
This work will quantify for the first time the variations present in the routine maintenance of beam output on a national scale. The novel application of these dosimetric uncertainties to radiobiological models is then employed to predict the variation in clinical outcome due to the quantified dosimetric variations for specific clinical cases, including both tumour control and associated treatment complications on both individual and patient populations.
The linear-quadratic and Lyman Kutcher Burman models have been implemented to allow flexibility in the modelling of individual patient doses on a fraction by fraction basis. The variation in delivered doses due to beam output variations is seen to be normally distributed with a standard deviation of 0.7%. These variations may lead to a typical patient experiencing a range in treatment outcome probabilities of over 10% for cancers with a steep dose response curve such as head and neck in both the case of an individual patient and for a patient population.
The precise control of beam output is shown to be a major factor in the overall uncertainty for dose delivery in modern treatment techniques. With reductions in other uncertainties in radiotherapy treatments, now may be the time to consider reduction of tolerance levels to allow optimal patient treatment and outcomes.
The clinical introduction of magnetic resonance imaging guided radiotherapy has
prompted consideration of the potential impact of the static magnetic field on biological
responses to radiation. This review provides an introduction to the mechanisms of
biological interaction of radiation and magnetic fields individually, in addition to a
description of the magnetic field effects on megavoltage photon beams at the
macroscale, microscale and nanoscale arising from the Lorentz force on secondary
A relatively small number of scientific studies have measured the impact of combined
static magnetic fields and ionising radiation on biological endpoints of relevance to
radiotherapy. Approximately half of these investigations found that static magnetic
fields in combination with ionising radiation produced a significantly different outcome
compared with ionising radiation alone. MRI strength static magnetic fields appear to
modestly influence the radiation response via a mechanism distinct from modification
to the dose distribution. This review intends to serve as a reference for future biological
studies, such that understanding of static magnetic field plus ionising radiation
synergism may be improved, and if necessary, accounted for in magnetic resonance
imaging guided radiotherapy treatment planning.
The experimental work described in this thesis uses a second order TA technique to analyse CT (Computer Tomography) imaging data from patients with NSCLC. The software developed as part of this project uses a voxel by voxel analysis of CT imaging, by comparing grey levels using grey level co-occurrence matrices (GLCMs).
Three approaches (themes 1-3) were explored. The first approach shows that TA can help differentiate between tumour and Radiation Induced Lung Injury (RILI) after Stereotactic Ablative Body Radiotherapy (SABR) in early stage lung cancer. The second approach suggests that assessing muscle loss on diagnostic imaging can help predict outcome in advanced NSCLC. The third and final approach uses TA to generate a functional assessment of lung function. TA is able to differentiate between patients who are fit or unfit for radical radiotherapy, based on TA of lung tissue on CT imaging, rather than formal lung function tests.
TA technique described in this thesis is a novel intervention in gaining functional data from CT imaging. It is particularly attractive as the analysis is generated from routine oncological imaging. As a result these tools have the potential to be cost effective and could be integrated into a standard radiology workflow.
This thesis looks at methods of increasing the dose delivered to the tumour whilst reducing the dose to the organs at risk. The methods used to achieve this are the use of a bladder scanner to reduce internal organ movement, the use of a plan of the day strategy, the use of interstitial needles for brachytherapy and the use of texture analysis to predict those patients who are not going to achieve a complete response to chemoradiotherapy.
The final chapter starts to explore the question of whether immunotherapy in the form of immune checkpoint blockade drugs could potentially be of benefit in cervical cancer. The tumour microenvironment was assessed before and during chemoradiotherapy by looking at tumour infiltrating lymphocyte populations and the expression of PD-1 and PD-L1. These were also studied in the peripheral blood.