Cancer-related research at the Cockcroft Institute (CI) is a collective endeavour spanning all stakeholder institutions, each contributing uniquely to the development of advanced radiation therapy techniques. The Institute’s commitment to improving cancer treatment integrates expertise in beam physics, accelerator design, and medical applications, fostering innovation in both existing and emerging treatment modalities. This article highlights some of the key publications of 2024 in this crucial area.
Improving access to radiotherapy in lower middle-income countries
Several experts from Lancaster University and STFC participate in the STELLA project (Smart Technology to Extend Lives with Linear Accelerators) which aims to use new technology to improve access to radiotherapy in lower middle-income countries (LMIC), particularly in Africa. The project is led by CERN and the International Cancer Expert Corps charity. The UK ITAR project (Innovative Technology for improving Access to Radiotherapy), led by Professor Graeme Burt, developed the conceptual design for STELLA.
The results of a survey on linac performance and repair experiences in several cancer centres across Africa was published in Medical Research Archives [1], a journal of the European Society of Medicine. The survey identified numerous modes of radiotherapy equipment failure causing treatment downtime in LMICs that can be overcome by improvements in the design of radiotherapy technology. The article stresses the need for increased staff training, improved broadband access, and increased annual national funding for radiotherapy.
Graeme Burt also participated in the Lancet Oncology Commission on Radiotherapy and Theranostics, which published its latest report in November [2]. The report builds on the 2015 Lancet Oncology Commission, focusing on expanding global access to radiotherapy and theranostics. It highlights the ongoing disparity in radiotherapy availability between high-income and low- and middle-income countries, particularly due to a lack of trained workforce and insufficient equipment, and proposes a series of actions to address these challenges.
Very high energy electron beams for radiotherapy
Over the last year, a team led by Professor Roger M. Jones from the University of Manchester has published three papers in Scientific Reports on the use of Very High Energy Electron (VHEE) beams for radiotherapy. One of the articles [3] focuses on the optimization of dose distributions using quadrupole magnets to focus the VHEE beam. This approach reduces dose to healthy tissue and enables targeted treatment. The study examines the current beam focusing capabilities at the CLEAR (CERN Linear Electron Accelerator for Research) facility for energies above 200 MeV and investigates a more optimal quadrupole setup through Monte Carlo simulations.
Another study [4] investigates the potential of VHEE for treating tumours in inhomogeneous regions like lung and prostate cancers. Using the ARES facility at DESY, Germany, 154 MeV electrons were delivered to prostate and lung cancer cells to assess their biological effectiveness. Cell survival was compared between the VHEE irradiated cells and those irradiated by conventional 300 kVp X-rays. The results showed similar damage to cells from both VHEE and X-rays, indicating comparable relative biological effectiveness between the two. This study demonstrated that VHEE can effectively kill cancer cells, offering significant potential advantages over conventional photon radiotherapy, such as improved dose distribution, faster treatment, and reduced side effects.
The third paper [5] investigates the “FLASH” effect, where ultra-high dose rate (UHDR) irradiation using VHEE spares healthy tissue. The biological model employed was pBR322 plasmid DNA to measure DNA damage under different dose rates: conventional (0.08 Gy/s), intermediate (96 Gy/s), and UHDR (2×10⁹ Gy/s) at the CERN CLEAR facility. Results showed that UHDR irradiation significantly reduced DNA damage compared to conventional dose rates. The study is the first to report FLASH sparing with VHEE, demonstrating that UHDR with VHEE reduces DNA damage in a plasmid model, confirming the potential of VHEE for future radiotherapy applications.
Beam dynamics study for proton radiotherapy linac
Drs Robert Apsimon and Matt Southerby from Lancaster University carried out a beam dynamics study for a proton radiotherapy linac [6]. The paper presents a self-consistent framework for analyzing transverse beam dynamics in a proton linac, incorporating acceleration effects into the study. Two focusing schemes are developed: the FODO-like scheme and the minimum aperture scheme. The FODO-like scheme uses a single quadrupole per cavity and ensures a constant beam size along the lattice by minimizing the beam size at the cavity entrance/exit, accounting for adiabatic damping due to RF cavities. The minimum aperture scheme matches the beam ellipse to the cavity’s acceptance ellipse, optimizing the aperture size for a given cavity length. A simple RF cavity map approximation is used to model energy changes along the lattice, assuming longitudinal acceleration.
Optimization of proton beam therapy systems
Professor Robert Appleby, from the University of Manchester published a couple of papers on the optimisation of proton beam therapy systems. The first article [7] presents the design of a large momentum acceptance arc for applications such as cancer therapy and muon accelerators, aiming to improve the energy layer switching time in hadron therapy. A “closed-dispersion arc” with fixed-field accelerator optics is proposed to overcome the current limitations of small momentum acceptance (<±1%). The design, developed for protons at 0.5 – 3.0 MeV (±42% momentum acceptance), uses permanent magnet Halbach arrays with minimal multipole errors and zero dispersion at both ends of the beamline. The beamline design has been tested for robustness against realistic errors. This study demonstrates that such an arc can achieve large momentum acceptance, with plans to scale it up for medical use in the future.
The second article [8], evaluates the delivery time of proton arc therapy (PAT) plans, focusing on the high-energy layer switching times that may affect clinical feasibility. The authors apply an emulator to model the delivery of “sawtooth” PAT plans on an existing cyclotron-based system. They find that PAT plans, using this approach, consistently require longer delivery times compared to static intensity modulated proton therapy. Additionally, continuous gantry rotation is identified as the optimal delivery method for PAT on such systems. The study concludes that the simplified sawtooth PAT planning approach may be clinically unfeasible without further advancements in existing clinical technologies.
Advancements in online dosimetry and beam monitoring
Building on its leadership role in the Optimization of Medical Accelerators (OMA) network, the University of Liverpool team under Professor Carsten P Welsch continues to drive innovation in online dosimetry and real-time beam monitoring, critical for ensuring precision and safety in advanced radiotherapy. They were invited to present this important work at the International Beam Instrumentation Conference (IBIC2024) in Beijing, China and published an article about their studies [9].
Laser-hybrid accelerator for radiobiological applications
LhARA (Laser-hybrid Accelerator for Radiobiological Applications) is another medical accelerator project with strong participation from the Cockcroft Institute and its partners. As an integral part of the Ion Therapy Research Facility (ITFR) project, LhARA aims to design and develop a hybrid accelerator structure to harness the unique properties of laser driven ion beams for radiobiological research and applications.
Professor Paul McKenna and his team at the University of Strathclyde play a leading role in advancing laser-driven ion sources and related technology and applications. Dr Ross Gray co-leads a LhARA work package that includes ion source development. In a recent Communications Physics paper [10], the group has introduced a machine learning (deep neural network) based synthetic diagnostic of laser-accelerated ions to predict the energy spectrum based on measured laser and plasma input parameters. This non-destructive ion diagnostic enables high-repetition laser operations with the approach extendable to a fully surrogate model for predicting realistic ion beam properties, unlocking potential for diverse applications including radiation therapy.
The group has also contributed to research published in Nature Communications [11], demonstrating the generation of multi-MeV proton beams from a fast-replenishing, ambient-temperature liquid sheet. The proton beams, generated at 5 Hz repetition rate using only 190 mJ of laser energy, exhibit exceptionally low divergence and a hundred-fold increase in flux compared to those from solid targets. Coupled with the high shot-to-shot stability of this source, this represents a crucial step towards practical applications.
In another study [12], the Strathclyde group and collaborators present a compact scintillating fiber imaging spectrometer designed for characterizing proton beams in high-power laser facilities. Prototype tests and simulations demonstrate its ability to accurately reconstruct multi-component proton beam profiles while remaining resistant to electromagnetic pulses. This advancement will help to accelerate the development of laser-driven proton beams for applications such as radiation therapy.
A unified approach to cancer research
Rather than isolated projects, these here-presented activities represent a unified, strategic drive across the Cockcroft Institute. The interplay between VHEE and proton therapy research, infrastructure development for global radiotherapy access, and advancements in online dosimetry exemplifies a collaborative effort to revolutionize cancer treatment. By leveraging expertise from all partner institutions, CI continues to shape the future of accelerator-based medical applications, ensuring that innovations reach both high-tech treatment centres and underserved regions worldwide.
References:
[1] Tackling the radiotherapy shortage in Sub-Saharan Africa by gathering and using data from Lower-Middle-Income and High-Income Countries’ facilities for designing a future robust radiotherapy facility
Dosanjh, Manjit; Ige, Taofeeq A.; Bateman, Joseph; Jenkins, Alexander; Angal-Kalinin, Deepa; Burt, Graeme; McIntosh, Peter; Coleman, C. Norman; O’Brien, Donna; Pistenmaa, David; Wendling, Eugenia
MEDICAL RESEARCH ARCHIVES 12(8) (2024)
https://doi.org/10.18103/mra.v12i8.5530
[2] Radiotherapy and theranostics: a Lancet Oncology Commission
Abdel-Wahab, May et al.
LANCET ONCOLOGY 25(11), e545-e580 (NOV 2024)
https://doi.org/10.1016/S1470-2045(24)00407-8
[3] CERN-based experiments and Monte-Carlo studies on focused dose delivery with very high energy electron (VHEE) beams for radiotherapy applications
Whitmore, L.; Mackay, R. I.; van Herk, M.; Korysko, P.; Farabolini, W.; Malyzhenkov, A.; Corsini, R.; Jones, R. M.
SCIENTIFIC REPORTS 14(1), 11120 (MAY 2024)
https://doi.org/10.1038/s41598-024-60997-5
[4] First in vitro measurement of VHEE relative biological effectiveness (RBE) in lung and prostate cancer cells using the ARES linac at DESY
Wanstall, Hannah C.; Burkart, Florian; Dinter, Hannes; Kellermeier, Max; Kuropka, Willi; Mayet, Frank; Vinatier, Thomas; Santina, Elham; Chadwick, Amy L.; Merchant, Michael J.; Henthorn, Nicholas T.; Koepke, Michael; Stacey, Blae; Jaster-Merz, Sonja; Jones, Roger M.
SCIENTIFIC REPORTS 14(1), 10957 (MAY 2024)
https://doi.org/10.1038/s41598-024-60585-7
[5] VHEE FLASH sparing effect measured at CLEAR, CERN with DNA damage of pBR322 plasmid as a biological endpoint
Wanstall, Hannah C.; Korysko, Pierre; Farabolini, Wilfred; Corsini, Roberto; Bateman, Joseph J.; Rieker, Vilde; Hemming, Abigail; Henthorn, Nicholas T.; Merchant, Michael J.; Santina, Elham; Chadwick, Amy L.; Robertson, Cameron; Malyzhenkov, Alexander; Jones, Roger M.
SCIENTIFIC REPORTS 14(1), 14803 (JUN 2024)
https://doi.org/10.1038/s41598-024-65055-8
[6] Beam dynamics framework incorporating acceleration to define the minimum aperture in two focusing schemes for proton radiotherapy linac
Southerby, M.; Apsimon, R.
PHYSICAL REVIEW ACCELERATORS AND BEAMS 27(6), 064401 (JUN 2024) https://doi.org/10.1103/PhysRevAccelBeams.27.064401
[7] Design of a large energy acceptance beamline using fixed field accelerator optics
Steinberg, A. F.; Appleby, R. B.; Yap, J. S. L.; Sheehy, S. L.
PHYSICAL REVIEW ACCELERATORS AND BEAMS 27(7), 071601 (JUL 2024) https://doi.org/10.1103/PhysRevAccelBeams.27.071601
[8] Emulating the Delivery of Sawtooth Proton Arc Therapy Plans on a Cyclotron-Based Proton Beam Therapy System
Burford-Eyre, Samuel; Aitkenhead, Adam; Aylward, Jack D.; Henthorn, Nicholas T.; Ingram, Samuel P.; Mackay, Ranald; Manger, Samuel; Merchant, Michael J.; Sitch, Peter; Warmenhoven, John-William; Appleby, Robert B.
CANCERS 16(19), 3315 (OCT 2024)
https://doi.org/10.3390/cancers16193315
[9] First proof-of-concept transverse beam profile measurements with gas jet in-vivo dose profiler for medical accelerators
N. Kumar, W. Butcher, M. Patel, F. Thesni M.P., and C.P. Welsch
Proc IBIC2024, Beijing, China (2024)
https://doi.org/10.18429/JACoW-IBIC2024-WEBC3
[10] A neural network-based synthetic diagnostic of laser-accelerated proton energy spectra McQueen, Christopher J. G.; Wilson, Robbie; Frazer, Timothy P.; King, Martin; Alderton, Matthew; Bacon, Ewan F. J.; Dolier, Ewan J.; Dzelzainis, Thomas; Patel, Jesel K.; P. Peat, Maia; Torrance, Ben C.; Gray, Ross J.; McKenna, Paul
COMMUNICATIONS PHYSICS 8(1), 66 (FEB 2025)
https://doi.org/10.1038/s42005-025-01984-8
[11] Stable laser-acceleration of high-flux proton beams with plasma collimation
Streeter, M. J. V. et al.
NATURE COMMUNICATIONS 16(1), 1004 (JAN 2025)
https://doi.org/10.1038/s41467-025-56248-4
[12] A scintillating fiber imaging spectrometer for active characterization of laser-driven proton beams
Patel, J. K.; Armstrong, C. D.; Wilson, R.; Alderton, M.; Dolier, E. J.; Frazer, T. P.; Horne, A.; Lofrese, A.; Peat, M.; Woodward, M.; Zielbauer, B.; Clarke, R. J.; Deas, R.; Rajeev, P. P.; Gray, R. J.; McKenna, P.
HIGH POWER LASER SCIENCE AND ENGINEERING 12, e70 (DEC 2024)
https://doi.org/10.1017/hpl.2024.62