New indications and combinations with protons
The new proton beam therapy will allow us to target tumour cells more accurately to reduce radiotherapy side-effects and improve quality-of-life
Proton beam therapy (PBT) is a type of advanced radiotherapy, with the potential of more precisely delivering a targeted dose of radiation to the tumour while improving the sparing of the surrounding healthy tissues and because the dose is delivered in the tumour there is no exit dose.
The first NHS proton therapy centre opened in Manchester in December 2018 and includes a research room, which allows research to be undertaken to keep the treatments offered to patients in the gantry rooms at the cutting edge.
At the moment, PBT is offered where existing clinical evidence suggests there is maximum benefit to patients and where tumours are difficult or impossible to treat by more conventional means.
In the future it is hoped to extend the indications and include tumour genomic subtypes or genetic information about the long-term risk of side effects that will identify the patients who will benefit most from PBT.
Through our research we are:
- Using mechanistic mathematical models to look at each step of the DNA damage and repair pathway to elucidate potential genetic variants that will identify patients who may benefit from PBT. These models can also be mapped on to treatment plans and provide additional information on normal tissue toxicity.
- Identifying genetic variants that increase risk of radiation side effects. In collaboration with our Cancer Prevention and Early Detection colleagues and using Manchester expertise in genomic medicine.
- Identifying patients with a high-genetic risk of late side effects following conventional radiotherapy, who might benefit from photon therapy.
- Exploring whether patient groups relating to our Musculoskeletal and Hearing Health research have increased risk of toxicity from radiotherapy.
- Establishing infrastructure for biobanking (storing blood and other samples) and data collection for UK proton therapy patients to support future research into risk stratification.
- Validating our research findings and establish first-in-man trials, in collaboration with other NIHR Biomedical Research Centre infrastructure and the NIHR Rare Diseases Translational Research Collaboration to facilitate studies in rare cancers.
Progress to date
- Mathematical modelling research incorporated in to research version of Eclipse treatment planning software and some of our models incorporated into NIH funded open source TOPAS n- Bio which gives the research an international dimension.
- First randomised clinical trial for PBT (TORPEDO) with CRUK launched, whilst working with CTRad to establish a national framework for UK PBT clinical trials.
- Establishing protocol for biobanking samples for UK PBT patients.
- Public engagement activities took place throughout British Science Week and the programme has also been involved in developing a play about protons and working with a glass blower to develop artistic representations of a proton beam.
- Proton beam therapy – The challenges of delivering high quality evidence of clinical benefit Clin Oncol (R Coll Radiol). 2018 May;30(5):280-284.
doi: 10.1016/j.clon.2018.02.031. Epub 2018 Mar 16
- In Silico Non-Homologous End Joining Following Ion Induced DNA Double Strand Breaks Predicts That Repair Fidelity Depends on Break Density Scientific Reports – Nature. DOI: 10.1038/s41598-018-21111-8
- Biologically augmented treatment planning in a research version of a clinical treatment planning system Eclipse to enable identification of patients with genetic variants who might benefit from photon therapy.
- Establishing infrastructure for biobanking (storing blood and other samples) and data collection for UK proton therapy patients when the clinical service starts in late 2018.
- In collaboration with CTRad working on a programme of national clinical trials to validate our research findings and establish first-in-man trials.
- Linking in with the targeting hypoxia and new radiotherapy-immunotherapy combinations programmes, where PBT may have particular applications to highly hypoxic tumours and stimulating an immune response.