1. A Comparative Study of Biological Effects of VHEE, Protons and other Radiotherapy Modalities
Kristina Small
University of Manchester, Christie NHS Foundation Trust, Cockcroft Institute

2. Background and Overview
Project aim - to investigate the type and quantity of DNA damage caused due to irradiation of plasmid DNA by VHEE
Brief introduction to Very High-Energy Electron therapy and its advantages
Plasmid irradiation simulations using Geant4-DNA
Experimental plans at VELA/CLARA
Other activities during the year

3. VHEE – A Very Brief Overview
The aim of any radiotherapy treatment is to deliver the maximum radiation dose to cancer cells while minimising the dose to healthy surrounding cells
Currently, photon beams of energy up to 15 MV are used for the treatment of deep-seated tumours – however, high doses are delivered to surrounding healthy tissue
Recent developments in the design of high-gradient accelerating cavities have allowed exploration of VHEE therapy (50 – 250 MeV)

4. VHEE – Potential Advantages
Sufficient penetrative power to
reach deep-seated tumours –
200 MeV corresponds to ~30 cm
depth
Marked insensitivity to
inhomogeneities – unaffected by
regions of changing density
Improved dose delivery and
organ-at-risk sparing compared
with conventional photon therapy
FLASH therapy – rapid delivery
allows very high dose rates
(> 40 Gy)

5. Plasmid Irradiation Simulation
Plasmids are small, circular DNA
structures distinct from chromosomal
DNA. They have the advantage of being
unable to repair after irradiation, allowing
pure damage data to be measured
Geant4-DNA, a Monte Carlo particle
tracking code, is used to simulate early
biological damage at the cellular and
molecular level, specifically single- and
double-strand breaks
Simulation aims – firstly reproduce proton
irradiation results produced by the
PRECISE group
Secondly, adapt the code to allow
electron simulations and repeat
simulations with VHEE for comparison

6. Plasmid Irradiation Experiments
The VHEE plasmid simulations will form the basis of an experiment anticipated at the VELA/CLARA facility during the second quarter of 2018
Experiment aim – to quantify and compare the yield of single- and double-strand breaks resulting from irradiation of plasmid DNA by 10 – 50 MeV electrons over a range of doses up to 2000 Gy to previous proton data
Dry and wet samples will be irradiated to measure the contribution of direct and indirect effects to the total damage

7. Plasmid Irradiation Experiments
After irradiation, the plasmids will be analysed using a technique called Agarose Gel Electrophoresis to measure the relative amounts of super-coiled, open-circle and linear forms
The relative amounts of the three plasmid forms will be fitted to Cowan’s 1987 model for calculation of SSB and DSB yields
DNA molecules can be made
to move through an agarose gel
using an electric field
Larger molecules move through
the gel more slowly than smaller
molecules, with the differently-sized
molecules forming distinct bands on
the gel

8. Conferences, Schools and Outreach
March 2017 – Multi-Scale Monte-Carlo Modelling for Radiotherapy Sandpit (Manchester)
March 2017 – Sharing the Vision for World-Class Radiotherapy Symposium (Manchester)
June 2017 – Optimising Medical Accelerators School (Pavia, Italy)
July 2017 – Very High Energy Electron Therapy: Medical and Accelerator Physics Aspects towards Machine Realisation (Daresbury). Poster presentation
July 2017 – Volunteering with Erasmus summer school – ‘Diversity in the Culture of Physics’
November 2017 – Cockcroft Postgraduate Conference (1st place)

9. References
Vysin, L et al., Proton-induced direct and indirect damage of plasmid DNA, 2015, Radiat. Environ. Biophys. 54: 343 – 352
Leloup, C et al., Evaluation of lesion clustering in irradiated plasmid DNA, 2005, Int. J. Radiat. Biol. 81: 41 – 54
Bazalova-Carter, M. et al. Treatment planning for radiotherapy with very high-energy electron beams and comparison of VHEE and VMAT plans. Med. Phys. 42, 2615–2625 (2015)
Khan, V, ‘A Damped and Detuned Accelerating Structure for the Main Linacs of the Compact Linear Collider,’ University of Manchester, 2011
DesRosiers, C et al., ‘ MeV electron beams in radiation therapy,’ Phys. Med. Biol. 45, 1781–1805 (2000)

10. Merry Christmas!