OPTIma: Optimising Proton Therapy through Imaging

Over 350,000 cancer cases are diagnosed annually in the UK with some 40% of patients receiving radiotherapy as part of their curative treatment. Most radiotherapy treatments employ external x-ray beams generated by linacs. However, there is a growing interest in the use of high-energy proton beams for radiotherapy. Within the UK, two NHS centres and several private ones will open in the next few years. Proton Beam Therapy is most useful for tumours in the head/neck region, some brain tumours, tumours near to organs at risk and childhood cancers.

Protons lose their energy in a very different way to x-rays (photons) as they have a finite range in tissue with most of their energy being deposited near the end of this range. So protons can target a tumour with a focused dose with less exposure of healthy tissue to radiation. The challenge is, clearly, predicting accurately where the protons will deposit the bulk of their energy - in the target tumour and not in neighbouring healthy tissue. Treatment planning is currently based on x-ray CT imagery but this gives rise to unavoidable uncertainties in translating from images based on low energy x-rays to the ranges of high energy protons. The answer is to use the same radiation type to treat and to image - the concept of the 'same ruler'. Imaging with protons has proved difficult as it is necessary to track individuals protons as they pass through a patient or phantom and record the corresponding residual energy of each proton. Our previous project, PRaVDA, laid the foundations of this for a broad beam of protons. Current Proton Beam Therapy facilities use small diameter beams that are electromagnetically scanned over the target region. This implies a radically different instrument concept and design, but based on our experience with PRaVDA. The philosophy is to provide a robust, turn-key (as far as feasible for a cutting-edge instrument) that can be exploited by a wider community.

This project will provide a national facility in the unique Research Room at The Christie Proton Beam Therapy Centre, Manchester, for exploring proton imaging with a state-of-the-art scanning pencil-beam delivery system. This will open up to the research community a new medical imaging modality - charged-particle imaging in radiotherapy.

The main project aims are:

Explore the capabilities of proton CT and radiography in reducing range uncertainties to a level that do not influence optimum treatment planning.

Develop algorithms for complex biological samples that provide in a computationally efficient manner satisfactory and quantifiable imagery.

Combining different modes of proton CT and other imagery (x-ray CT, PET, etc) to provide more clinical information and improved imagery.

Providing a facility and a methodology for the accurate calibration of phantoms for other proton therapy centres.

Understanding how proton CT can be successfully integrated in treatment workflows from planning to in and between treatment monitoring.

Further the development of proton imaging for gantry systems and encourage commercial exploitation.

The ultimate and most important beneficiaries are the cancer patients who will have improved outcomes from their proton therapy treatment. It is, by its very nature, difficult to quantify these benefits or the number of patients involved. With more accurate planning through the use of proton CT with greatly reduced margins then it will be feasible to use the sharp distal edge falloff in producing treatment plans rather than having to rely so heavily on the less sharp lateral edges. One example of an aggressive cancer, affecting children and young people, that could become much more amenable to radiotherapy is brain stem glioma. As previously stated, tumour types and locations that would benefit from proton therapy are tumours in the head and neck region, tumours adjacent to critical organs, some types of brain tumour and nearly all childhood cancers. There is some hope that advances in proton therapy may be allow the successful treatment of non-small cell lung cancer - a cancer type that has shown little progress in survival rates over many years. These advantages come from reducing range errors in planning less than 1%, but there are other advances of proton CT - reduce or eliminate CT artefacts due to metal/dental implants, lower diagnostic dose compared to x-ray CT (by a factor of ~3) and its use for patient alignment verification before treatment.

Providing a research facility with the ability to conduct extended experiments and trials will benefit not only the academic aspects of radiotherapy but also its use in practice. It is important that any future system should meet the clinical needs and integrate well with the workflow of a fully operational facility. Installing a unique facility is a state-of-the-art proton beam therapy centre attached to a world leading cancer hospital will be a fertile environment for involvement with not just the national but the international clinical and research communities.

Providing a methodology and a resource for the accurate calibration of phantoms will enhance the QA at proton therapy sites worldwide, especially in association with NPL's solid reputation in this field. If such a service is provided, it would enhance the use of all proton therapy sites worldwide.

The long term goal is, of course, to demonstrate the advantages of proton therapy so that it becomes commercially viable to develop systems that could be installed on existing and future delivery systems. There are some five major manufacturers of proton therapy facilities with the two largest being Varian Medical Systems and IBA. The Christie Centre employs a Varian system and we have good contacts with IBA (most of the private providers the UK use IBA systems). Though we have demonstrated the ability of proton CT to yield very useful clinical data. the field is not at the appropriate TRL for commercial involvement and investment. The normal development route would be a VC funded new company working in association with a leading manufacturer to develop and de-risk prototype systems and commence the regulatory processes.