Advanced technologies for radiobiology and clinical radiotherapy
Lead Research Organisation:
University of Liverpool
Department Name: Molecular and Clinical Cancer Medicine
Abstract
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Planned Impact
The long-term objective of the research programme is to transform the delivery of proton- and ion-beam therapy using a system that is:
* Automated and is capable of adjusting the dose delivered in real time based on measurements of the position of the patient, tumour, organs at risk, and the dose-deposition profile;
* Capable of delivering a range of ion species from protons to carbon ions over a wide variety of dose rates, up to and including those required for FLASH radiotherapy, in the same treatment session; and
* Has a footprint small enough that provision of the therapy can be distributed across the country.
The societal benefits of the substantial increase in access to advanced proton- and ion-beam therapy for effective cancer treatment that would result from the successful execution of this programme is clear.
To lay the foundations of the technological programme required to deliver the programme outlined above we have formed an multidisciplinary collaboration composed of clinical oncologists, medical and academic physicists, biologists, engineers, and industrialists. We propose to take a holisitic `system' approach to the delivery of the programme. This requires that various technological developments required to implement a full system are brought forward in parallel. The creation of a project team that has the diverse skill set and motivation to take the project forward to deliver the long-term goal is a clear priority. Further, the sustainable development of the programme from proof of concept to spin out will require staff with a breadth of experience across the disciplines. The series of meetings and networking events that will be scheduled as part of our proposal will further enhance the collaborative network which will deliver our overall aims and goals.
We will prove the principle of the laser-hybrid accelerator system within a facility dedicated and utilised for radiobiology research. This facility will enable further characterisation of the radiobiological effects of proton and ion beams, particularly at the molecular and cellular level, leading to a significant scientific impact. Specifically the collaborative team has expertise in examining the impact of ionising radiation on cell survival in different tumour models linked with effects on DNA damage and repair, which will be used to deliver the current proposal for increased scientific knowledge and gain. Overall, our proof-of-principle system has the potential to deliver a step up in clinical capability by improving the delivery and efficacy of particle-beam therapy for the benefit of cancer patients. As well as the societal impact that this will achieve, we will engage with industrial partners to place the UK in a unique position to generate substantial economic gains through the industrialisation of the novel techniques that this proposal will develop.
* Automated and is capable of adjusting the dose delivered in real time based on measurements of the position of the patient, tumour, organs at risk, and the dose-deposition profile;
* Capable of delivering a range of ion species from protons to carbon ions over a wide variety of dose rates, up to and including those required for FLASH radiotherapy, in the same treatment session; and
* Has a footprint small enough that provision of the therapy can be distributed across the country.
The societal benefits of the substantial increase in access to advanced proton- and ion-beam therapy for effective cancer treatment that would result from the successful execution of this programme is clear.
To lay the foundations of the technological programme required to deliver the programme outlined above we have formed an multidisciplinary collaboration composed of clinical oncologists, medical and academic physicists, biologists, engineers, and industrialists. We propose to take a holisitic `system' approach to the delivery of the programme. This requires that various technological developments required to implement a full system are brought forward in parallel. The creation of a project team that has the diverse skill set and motivation to take the project forward to deliver the long-term goal is a clear priority. Further, the sustainable development of the programme from proof of concept to spin out will require staff with a breadth of experience across the disciplines. The series of meetings and networking events that will be scheduled as part of our proposal will further enhance the collaborative network which will deliver our overall aims and goals.
We will prove the principle of the laser-hybrid accelerator system within a facility dedicated and utilised for radiobiology research. This facility will enable further characterisation of the radiobiological effects of proton and ion beams, particularly at the molecular and cellular level, leading to a significant scientific impact. Specifically the collaborative team has expertise in examining the impact of ionising radiation on cell survival in different tumour models linked with effects on DNA damage and repair, which will be used to deliver the current proposal for increased scientific knowledge and gain. Overall, our proof-of-principle system has the potential to deliver a step up in clinical capability by improving the delivery and efficacy of particle-beam therapy for the benefit of cancer patients. As well as the societal impact that this will achieve, we will engage with industrial partners to place the UK in a unique position to generate substantial economic gains through the industrialisation of the novel techniques that this proposal will develop.
People |
ORCID iD |
| Jason Luke Parsons (Principal Investigator) |
Publications
Aymar G
(2020)
LhARA: The Laser-hybrid Accelerator for Radiobiological Applications
in Frontiers in Physics
Hughes JR
(2020)
FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy.
in International journal of molecular sciences
| Description | The aim of this award was to lay the technological foundations for the development of a laser-driven hybrid accelerator system (termed LhARA) delivering protons and other ions, which could be dedicated to the study of the biology at the molecular and cellular level. This is important in the development of a new ion beam facility that could be used to generate new strategies for the treatment of specific cancers using laser-generated ions. Through this funding, we successfully delivered a conceptual design report outlining LhARA, as well as utilising the proton beam therapy facility at the Clatterbridge Cancer Centre as a test bed for studying radiobiology. This work has now led to further funding (£2M) from UKRI where LhARA will now form a central part of the ion beam therapy research facility (ITRF), where the next generation of radiotherapy treatments for cancer will be developed. |
| Exploitation Route | This work is now being actively developed through additional (£2M) UKRI funding by a consortium with expertise in radiation biology, particle physics, and radiation oncology to develop the ion beam therapy research facility (ITRF) dedicated for radiobiology research. The future outcomes are our further understanding of the biology of laser-driven ions at the molecular and cellular level leading to an academic and scientific impact. Additionally, this increased scientific knowledge can eventually be translated for the benefit of cancer patients leading to more effective treatments and improved survival rates, as well as reductions in adverse treatment side effects, thus leading to a societal and healthcare impact. |
| Sectors | Education,Healthcare |
| URL | https://www.ukri.org/news/researching-a-new-generation-of-technology-to-treat-cancer/ |
| Description | Examining the impact of FLASH proton beam therapy |
| Amount | £30,000 (GBP) |
| Organisation | The Clatterbridge Cancer Centre NHS Foundation Trust |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2020 |
| End | 04/2022 |
| Description | Realizing the radiobiological impact of protons and high-LET particles in head and neck cancer and glioblastoma models |
| Amount | $1,770,799 (USD) |
| Funding ID | 1R01CA256854-01 |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 07/2021 |
| End | 04/2026 |
| Title | Method for quantifying levels of complex DNA damage in cells following irradiation |
| Description | We have established a specific method, entitled the Enzyme-Modified Neutral Comet (EMNC) assay, for quantitatively examining the levels of complex DNA damage (CDD) induced by ionising radiation. This is now a commonly used technique by Dr Jason Parsons and his Team to further our understanding of radiobiology within cultured cell lines. Specifically, the EMNC allows an assessment of CDD induced by ionising radiation of increasing linear energy transfer (LET), and have proven this can capture such sites in cultured cells following proton beam therapy. This will enable further investigations into the molecular and cellular biology of radiation-induced CDD, with the future goal of developing optimal strategies for the effective use of protons and other high-LET radiation in cancer treatment. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | The EMNC assay has only been reported this year, although we have previously used this methodology to further our understanding of the radiobiology of protons, as evidenced here (PMID: 30851349; 29413288). Further impact will no doubt be developed more in the future. |
| URL | https://www.mdpi.com/2409-9279/4/1/14 |
| Title | Research Laboratory Examining Proton Irradiation |
| Description | In association with our collaborators at the Clatterbridge Cancer Centre, we have established a research laboratory at the Centre (with generous funding of ~£40k) dedicated for examining the molecular and cellular effects of proton beam therapy. This is now heavily used by Dr Jason Parsons and his Team to further an understanding of the radiobiology of proton irradiation on cancer cells, although is open and indeed being utilised for collaborative radiobiology research particularly with other UK Centres (e.g. University of Birmingham, University of Oxford, University College London, and Imperial College London). The future goal is the development of optimal strategies for the effective use of protons in cancer treatment. This research is vital given that the Clatterbridge Cancer Centre currently houses the only accessible proton beam therapy facility, and now the only research laboratory, in the UK but that new proton facilities are now active in Manchester and London (from 2021). Therefore this facility is currently at the forefront of radiobiology research into proton beam therapy. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| Impact | The establishment of the new research laboratory at the Clatterbridge Cancer Centre is crucial in furthering our understanding of the radiobiology of proton beam therapy in cancer cells, and since this is currently the only such accessible and collaborative facility in the UK, we are at the forefront of research in this area. |
| Description | Collaboration with Clatterbridge Cancer Centre |
| Organisation | The Clatterbridge Cancer Centre NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | My research team and I have regular visits to Dr Andrzej Kacperek and the Eye Proton Therapy Team at the Clatterbridge Cancer Centre, Bebington, UK in order to perform cell irradiation experiments using the 60 MeV proton beam. We also have regular contact and discussion with our collaborators on experimental design, results and evaluation in order for the research to proceed effectively. |
| Collaborator Contribution | Our partners at the Clatterbridge Cancer Centre, including Dr Andrez Kacperek, assist in the dosimetry and delivery of proton beam irradiation of cells. They also advise on experimental design, and interpretation of results. |
| Impact | As a consequence of this collaboration, we have now established a radiobiology research laboratory at the Clatterbridge Cancer Centre (funded by the Centre to a cost of ~£40k) which is dedicated for further examining the cellular response to proton beam therapy, and majorly used by Dr Jason Parsons and his research team. This research laboratory, and indeed the proton beam facility itself, are currently the only facilities available in the UK for studying the effects of protons on cancer cells and crucial for the increased future use of proton beam therapy for cancer treatment. Also published research in three peer-reviewed manuscripts (PMID: 29413288; PMID: 30851349, PMID: 34277417). |
| Start Year | 2014 |
| Description | Collaboration with Imperial College London |
| Organisation | Imperial College London |
| Department | Department of Physics |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My Group and I are providing our expertise in radiation biology to Prof Ken Long and the The Laser hybrid Accelerator for Radiobiological Applications (LhARA) consortium at Imperial College London, UK. We have been providing our expertise into the development of a radiobiology research facility as part of the LhARA project, and also guidance on the future progress of the initiative. |
| Collaborator Contribution | Our collaborator, Prof Ken Long, leads on the collaborative LhARA project aiming to establish a laser accelerator facility for in vitro and in vivo radiobiology research. Therefore Prof Long provides his intellectual input into the development of the laser accelerator, and in designing the future direction of the project. |
| Impact | No outputs or outcomes have yet resulted. This collaboration, however, is multidisciplinary involving the respective Groups with expertise in physics (Prof Long) and radiation biology (Dr Parsons). |
| Start Year | 2019 |
| Description | Collaboration with University of Birmingham |
| Organisation | University of Birmingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My postdoctoral research scientist (Dr Jonathan Hughes) employed on the STFC grant had regular visits to the University of Birmingham, UK in order to discuss with colleagues there about establishment of radiobiology facilities in association with the Birmingham cyclotron. These were to be specifically designed to enable the progress of ultra-high dose rate (FLASH) proton radiobiology research. Myself and Dr Hughes also had regular contact and discussions with our collaborators, including Prof Stuart Green, Prof Tzany Kokalova-Wheldon, Dr Tony Price and Dr Ben Phoenix, to discuss the effective development of the facilities and of the associated research. |
| Collaborator Contribution | Our partners, led by Prof Stuart Green, Prof Tzany Kokalova-Wheldon, Dr Tony Price and Dr Ben Phoenix, assisted in access to the Birmingham cyclotron for FLASH proton irradiation, but also providing space for us to build and establish radiobiology facilities on site. Our collaborators have also been actively involved in the discussion of experimental setup for proton irradiations, and to plan the future direction of the work.. |
| Impact | No outputs or outcomes have resulted as yet. |
| Start Year | 2019 |
| Description | Collaboration with University of Oxford |
| Organisation | University of Oxford |
| Department | Department of Oncology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | The STFC grant has enabled myself and my postdoctoral research scientist (Dr Jonathan Hughes) to engage with Prof Kristoffer Petersson the University of Oxford, UK regarding collaborative research into ultra-high dose rate (FLASH) radiotherapy. Myself and Dr Hughes have had regular contact and discussions with Prof Petersson to develop research into examining the radiobiology of both FLASH electrons and protons. |
| Collaborator Contribution | Our partner, Prof Kristoffer Petersson, is one of the world leaders investigating ultra-high dose rate (FLASH) radiotherapy having trained in the renowned Lausanne Group led by Prof Vozenin. He has provided significant intellectual support into our proposed radiobiology research into FLASH protons, which no doubt will be developed further. |
| Impact | Published a review on FLASH protons (PMID: 32899466). |
| Start Year | 2019 |
| Description | Collaboration with University of Oxford |
| Organisation | University of Oxford |
| Department | Department of Oncology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My postdoctoral research scientist (Dr Rachel Carter) employed on the MRC Award had regular visits to the CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, UK in order to perform irradiation experiments (using high-LET alpha particles) in collaboration with Dr Mark Hill. Myself and Dr Carter also had regular contact and discussions with our collaborators, including both Dr Mark Hill and Prof Peter O'Neill, which also involved Institute visits every 6 months to discuss the effective progress of the research. |
| Collaborator Contribution | Our partners, led by Dr Mark Hill and his Postdoctoral Research Scientist Dr Jamie Thompson, assist in the dosimetry and delivery of alpha particle irradiation to cells using their laboratory facilities. Prof Peter O'Neill has been advising on design of irradiation studies, as well as on in vitro biochemical experiments using mononucleosome substrates. Both were also actively involved in the evaluation and discussion of results, and to plan the future direction of the work.. |
| Impact | Published research in three peer-reviewed manuscripts (PMID: 29413288; PMID: 30851349, PMID: 34277417). Also published one expert review (PMID: 36902352). |
| Start Year | 2014 |
| Description | Invited seminar speaker |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Other audiences |
| Results and Impact | Invited seminar speaker at the Physics of Cancer Conference, Liverpool, UK. The seminar covered the radiobiology of proton beam therapy, and the associations with complex DNA damage and the cellular DNA damage response. This is important for our understanding of the molecular and cellular responses to DNA damage induced by proton beam therapy, and for the identification and development of optimal strategies utilising this radiotherapy modality for cancer treatment. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited seminar speaker |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Other audiences |
| Results and Impact | Invited seminar speaker at the Institute of Physics-Ultra-high dose rate: Transforming Radiotherapy in a FLASH, London, UK. The seminar covered our research on the the radiobiology of protons versus photons in head and neck tumour cell models and how to optimise the radiotherapy response through targeting DNA damage and repair. This also covered our very preliminary research examining the radiobiology of protons delivered at ultra-high dose rates (FLASH). |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://iop.eventsair.com/udr2022 |
| Description | Invited seminar speaker |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Invited seminar speaker at the Liverpool Cancer Research Institute Scientific Symposium, Liverpool, UK. The seminar covered the radiobiology of proton beam therapy versus photon radiotherapy in head and neck cancer models, but also strategies to optimise radiation-induced tumour cell killing through targeting the DNA damage response that can be translated clinically. |
| Year(s) Of Engagement Activity | 2021 |