There are five working groups endorsed by CRUK that aim to support sustainable multidisciplinary networking and collaboration in priority areas. Membership includes representatives from each of the seven CRUK RadNet centres and more widely to include other UK centres working on radiotherapy focussed research.
- Emerging Radiotherapy Technologies
- Radiotherapy Drug Combinations
- Radiotherapy Immuno-oncology
- Molecular Imaging and Radiotherapy
- AI & Computational
Manchester senior academics co-lead three of the working groups, and our early career researchers lead various sub-groups and are active participants in all. These groups provide an excellent opportunity to train and inspire the next generation of radiation researchers, and build capacity for the future.
The ambition of each working group is to develop new collaborations and lever external funding to undertake internationally leading science; and provide a route to foster collaborations with industry working in the radiotherapy field.
Emerging Radiotherapy Technologies Working Group
Chairs: Prof Karen Kirkby (Manchester) and Dr David Fernandez-Antoran (Cambridge)
This group aims to better identify and understand the mechanisms behind innovative and novel technological approaches to delivering radiotherapy. The group endeavours to recognise any gaps in experimental provision and use subgroups and collaborations with other initiatives, to take discovery science into the clinic.
The subgroups are focussed on
- FLASH and Spatially Fractionated Radiotherapy (SFRT)
- Particle therapy using protons and heavier ions.
Underpinned by a CRUK funded national FLASH infrastructure award, there are multiple collaborative efforts ongoing such as using innovative primary 3D cultures (epithelioids) developed in Cambridge to compare the effects of electron FLASH (in Oxford) with proton FLASH (in Manchester) over timescales from seconds to days to months and even up to one year later.
Other areas of scientific interest include looking at immunological responses to emerging radiotherapy technologies (FLASH & SFRT) and investigating drug-radiotherapy combinations when treating with SFRT and protons. This group supports the UK’s initiative with the Science & Technology Facilities Council (STFC) to develop a national Ion Therapy Research Facility.
Radiotherapy Drug Combinations Working Group
Co-Chairs: Prof Kaye Williams (Manchester) and Prof Anthony Chalmers (Glasgow),
The vision is to support researchers and laboratories across the UK, encouraging and enabling groups to work with each other and with industrial partners to generate robust preclinical evidence to underpin high quality clinical trials.
The five subgroups are focussed on:
- Cell death and resistance
- DNA damage response
- Tumour metabolism
- Tumour microenvironment
The group have rapidly built effective partnerships with a broad range of stakeholders and drawn support from multiple pharmaceutical and biotechnology companies.
A key feature of the approach of this working group is to identify research labs with complementary skills and models, and to offer a team-based approach to potential investors and partners.
The group facilitate extensive collaborations locally, nationally and internationally including:
- CRAIN (Phase 1b clinical trial); Clinical collaboration with Astex Pharmaceuticals;
- CONCORDE (Therapeutic index study to a live multi-centre multi-arm platform trial);
- Reducing neurotoxicity from brain irradiation with FLASH radiation and PARP inhibitors (Manchester, Oxford, Glasgow);
- Modulating Agents during RT (Strathclyde and Netherlands Cancer Institute);
- Targeting cholesterol for glioblastoma treatment (Strathclyde/Manchester).
Future research includes: Tumour metabolism (Seed funding submitted, in collaboration with the CRUK RadNet ERT Working Group); Tumour microenvironment (Multi-centre project “Challenges and practical solutions of using the SARRP platforms for murine irradiation” is underway).
Radiotherapy Immuno-oncology (RT-IO) Working Group
Chairs: Professor Tim Illidge (Manchester), Professor Alan Melcher (ICR)
The Group investigates the immune response to radiotherapy (RT) and the mechanisms underlying it. Particular areas of interest are the dynamics of immunological biomarkers I n blood, and the effect of RT on the tumour microenvironment. Supported by a CRUK RadNet infrastructure award, RadPath was set up to provide a new immune pathology network in the UK, working to establish the infrastructure to analyse blood and tumour samples from across the network, and to provide a comprehensive world-leading analysis of RT-induced immunological changes in pts treated with RT.
Two potentially world leading prospective studies, investigating RT induced dynamic immune biomarkers in real time during RT under the RADPATH network, and facilitating extensive collaborations locally and nationally, are the TIMM-RAD study (Led by Prof Tim Illidge, Manchester) investigating rectal cancer, cervix cancer lymphoma, head and neck cancer and non-melanoma skin cancer and the closely aligned CHIMERA study run by Royal Marsden/ ICR which investigates the immune response in standard of care RT for rectal, H&N, lung, cervix and bladder cancer.
It has been recognised for all the fantastic work by the following key achievements:
- CRUK Programme grant (£2.4M), which is focused on the immune response to radiotherapy in head and neck cancer;
- CRUK Programme grant (£1.8M), investigating the mechanisms of combining radiotherapy and immunotherapy to improve cancer outcomes;
- CRUK Accelerator grant to investigate local intratumoural immunoradiotherapy (LIRT) (£764.7K);
- NCI Radiation Oncology-Biology Integration Network (ROBIN) grant (£170.4k).
Future research includes: The SOTO study working to generate patient-derived organoids to assess treatment response and outcomes; A H&N study investigating the HPV TCR repertoire; The CORINTH trial (phase Ib/II trial of IMRT with pembrolizumab and anti PD-1 in HPV-induced late stage carcinoma of the anus); ARISOTLE (phase III radiotherapy +/- irinotecan for rectal cancer); Prof Tim Illidge (Manchester) will investigate the effect of radiotherapy on the gut microbiome in pelvic cancer patients.
Molecular Imaging and Radiotherapy Working Group
Chair: David Lewis, Beatson/University of Glasgow
Within the Working Group, four key areas for interdisciplinary collaboration have formed into distinct sub-groups, each with separate leadership: WSG1 – Bed Technology (‘MIGRATES’ – Multi-centre deployment of preclinical multi-modal imaging guided radiotherapy); WSG2 – (Image and Tissue Registration); WSG3 – (Standardisation and Dosimetry); WSG4 – ( Imaging Biomarkers).
It has also been recognized for all the fantastic work by the following key achievements: Successful in two applications to the RadNet Networking Fund; Held RadNet workshops at the European Molecular Imaging Meeting; The MIGRATES project received £89,954 through a RadNet Project Seed Funding Award in July 2021; Developed a standardised syngeneic cancer model of head and neck cancer; Devised a standardised radiotherapy protocol for use at all sites; Developed a new unique “team science” way of working in preclinical imaging research.
Future research includes: Delivering on all the subgroup projects including dissemination of the bed and registration pipeline, publications of a white paper for dosimetry and a standard preclinical model for radiotherapy biomarker assessment. For WSG3: Commissioned a review on mice phantoms and a mini audit on dosimetry and phantoms. For WSG4: To perform this standardised radiotherapy in the MOC model in all Centres and jointly evaluate response. This should form a universal platform for preclinical assessment of biomarkers, drug-combinations and emerging radiotherapy across RadNet.