High-throughput Pre-clinical Platform for Proton Therapy Research
Lead Research Organisation:
University of Manchester
Department Name: School of Medical Sciences
Abstract
Research in FLASH (ultra high dose rate radiotherapy) was ignited in 2014 by a paper by Vincent Fauvadon at Institute Curie, which showed reduced side-effects without compromise to efficacy of tumour treatment. This discovery has impelled an international research interest in FLASH. However the radiobiological mechanisms of FLASH are still not understood, and discovery is challenged by conflicting results limiting clinical implementation. The reduced side-effects promise of FLASH is critically important for proton therapy. In the UK, a high proportion of patients treated with proton therapy are children, where side effects can have a significant impact on their development, cognition and quality of life.
This proposal will create a proton-FLASH in vivo research capability for the first time in the UK. There is an urgent need for highly repeatable research on proton-FLASH to bridge the gap between discovery science and clinical trials. This proposal will address this need, enabling research in FLASH and across a range of important themes in proton therapy. We are working with XStrahl, a UK company and world leader in the field, to develop an automation solution to enable high-throughput experiments which will transform the statistical significance which can be achieved in these experiments.
The platform will also enable a capability to address emerging themes to keep UK proton therapy research at the cutting edge.
Spatially Fractionated Radiotherapy is an emerging theme where new evidence also suggests a possibility of fewer side effects, and is highly likely to be an important theme of radiotherapy research in the future. Whilst there may be some overlap in the mechanisms of FLASH and SFRT, what these are and how to optimise them is unknown. This proposal will enable the UK to contribute and lead in this research.
The NHS vision for proton therapy always included a research capability. The Proton Research Room in Manchester was funded by the Christie Charity largely from public donations. Since 2019, when the first proton beam was delivered in the Research Room, we have started developing collaborations and have an active programme of research. We now plan to expand this into a national resource for proton therapy. The equipment requested in this proposal adds an in vivo capability which provides the missing component in the continuum of research from discovery science to the clinic.
This proposal will create a proton-FLASH in vivo research capability for the first time in the UK. There is an urgent need for highly repeatable research on proton-FLASH to bridge the gap between discovery science and clinical trials. This proposal will address this need, enabling research in FLASH and across a range of important themes in proton therapy. We are working with XStrahl, a UK company and world leader in the field, to develop an automation solution to enable high-throughput experiments which will transform the statistical significance which can be achieved in these experiments.
The platform will also enable a capability to address emerging themes to keep UK proton therapy research at the cutting edge.
Spatially Fractionated Radiotherapy is an emerging theme where new evidence also suggests a possibility of fewer side effects, and is highly likely to be an important theme of radiotherapy research in the future. Whilst there may be some overlap in the mechanisms of FLASH and SFRT, what these are and how to optimise them is unknown. This proposal will enable the UK to contribute and lead in this research.
The NHS vision for proton therapy always included a research capability. The Proton Research Room in Manchester was funded by the Christie Charity largely from public donations. Since 2019, when the first proton beam was delivered in the Research Room, we have started developing collaborations and have an active programme of research. We now plan to expand this into a national resource for proton therapy. The equipment requested in this proposal adds an in vivo capability which provides the missing component in the continuum of research from discovery science to the clinic.
Technical Summary
We request funding to purchase a Small Animal Radiation Research Platform (SARRP) from XStrahl, and a FANUC 7-axis robot. The SARRP will integrate with our pre-clinical proton research beamline funded by CRUK RadNET. This new facility will extend and enhance the the Christie Proton Research Room by adding a preclinical capability alongside our existing in vitro research. The XStrahl SARRP is the industry leading platform for pre-clinical radiation research and will be adapted specifically for proton irradiation. This will enable in-situ photon imaging to precisely mimic the way patients are treated clinically. We will integrate an automation solution using a FANUC robotic arm (where we already have significant experience) to enable high throughput and highly repeatable research with accurate dosimetry at conventional and ultra high dose rate (FLASH). The design will also enable investigation in the emerging theme of spatially fractionated radiotherapy. This will be the first and only facility in the UK for pre-clinical research with protons and will operate as a national facility.
Proton beam-time is a valuable resource (>£1000 per hour), which is accessed for research between the hours of 11pm and 3am. To realise the most effective use of beamtime, and ensure that the equipment has the capacity to serve the UK community, development of automation is essential. This will ensure high repeatability and dosimetry for experiments whilst achieving the high-throughput required.
Proton beam-time is a valuable resource (>£1000 per hour), which is accessed for research between the hours of 11pm and 3am. To realise the most effective use of beamtime, and ensure that the equipment has the capacity to serve the UK community, development of automation is essential. This will ensure high repeatability and dosimetry for experiments whilst achieving the high-throughput required.
