OPTIma: Optimising Proton Therapy through Imaging

Lead Research Organisation: University of Lincoln
Department Name: School of Computer Science

Abstract

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.

Planned Impact

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.

Publications

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Esposito M (2018) A large area CMOS Active Pixel Sensor for imaging in proton therapy in Journal of Instrumentation

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Esposito M (2018) PRaVDA: The first solid-state system for proton computed tomography. in Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)

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Granado-González M (2022) A novel range telescope concept for proton CT. in Physics in medicine and biology

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Heritage S (2023) An Update to the Malthus Model for Radiotherapy Utilisation in England. in Clinical oncology (Royal College of Radiologists (Great Britain))

 
Description The system build has been delayed by global shortages in electronic services and components. However, custom silicon strip sensors have been designed, manufactured and characterised. A new custom integrated circuit for the read-out of 128 strip sensor channels has be fabricated and currently undergoing tests. The complete data acquisition system has been designed and build is underway. Complete date for all custom boards executed August 2023. The system is capable of tracking up to 7 protons per cyclotron bunch and and an expected improvement of about 60 times in acquisition time for a complete proton CT compared to other systems. A novel calorimeter, to residual the residual energies of individual protons that have passed through patient, is under construction. This calorimeter will be able to produce the energy of each proton in a bunch. Patent proration in progress
Exploitation Route The system, after initial tests at the OncoRay facility, Dresden, will be installed at the NHS Christie Proton Beam Therapy Centre, Manchester, as a national research facility. The University is actively seeking translation routes for our patent portfolio.
Sectors Healthcare

 
Description Currently there about 100 Proton Beam Therapy (PBT) facilities in operation with a further 60 planned or under construction. Approximately 50% of cancer patients cases require external beam radiotherapy for curative purposes. Most radiotherapy delivered by external x-ray beams from over 300 linacs across the UK. PBT today represents <1% of radiotherapy treatments, based on expert reports, at least 20% of patients would benefit from PBT. Proton CT would allow for lower dose imaging during treatment . Proton CT has potential when used in combination with x-ray CT to provide more details allowing for optimum treatment plans to be executed as well as robust plans . This means in real terms that treatments that might have not been possible before as they were too risky being near a critical structure ( eg optic nerve) are now possible. There is huge scope for individual treatment plans to be developed using the OPTIma system and a patients individual physiological makeup can be uniquely characterised by real measurements in place of inferred calibration based on X-ray CT images. This again will lead to greater scope in treatment planning. Challenges overcome to achieve impact Clinical buy in - For any development to be taken up and hence successful there has to be a perceived need . We work closely with the medical physics teams at both The Christie and University Hospital Birmingham and ensure that we are answering not only real problems but also in a way that is useful within a clinical workflow. Manufacturer acceptance - Research in isolation without being mindful of implementation often yields disappointing results. We have developed relationships with current proton CT prototype manufacturers who have or are currently working towards industrial uptake and they have shared openly their lessons learnt. Care has been taken to develop with these in mind. We have opened discussion with Varian surrounding the project, but it will be possible once we have the equipment installed to take these initial discussions to the next level. Development of novel readout custom integrated circuit (ASIC) is potentially leading to the provision of off-the-shelf sensor systems using lion strip sensors by ISDI Ltd
First Year Of Impact 2021
Sector Electronics
Impact Types Economic

 
Description University of Lincoln Core Equipment 2020
Amount £455,056 (GBP)
Funding ID EP/V035398/1 
Organisation University of Lincoln 
Sector Academic/University
Country United Kingdom
Start 11/2020 
End 04/2022
 
Description Cosylab 
Organisation Cosylab
Country Slovenia 
Sector Academic/University 
PI Contribution Joint development proton CT instrumentation and publicity drive
Collaborator Contribution Provision, by long-term loan, of multi-anode PMT assemblies
Impact Development activities still progressing
Start Year 2019
 
Title Proton Calorimeter 
Description An energy determining apparatus for determining the individual energy of one or more particles of hadron radiation has a main axis for aligning with a general direction of incident particles . The apparatus comprises a two-dimensional array of scintillator elements configured to emit a quantity of light in response to energy of one or more incident particles of hadron radiation passing through, or along, that scintillator element . Each of the scintillator elements is an elongate element with a longitudinal axis extending parallel to the main axis . An array of detectors convert the light from the scintillator elements into electrical signals. A processor is configured to determine a total quantity of light corresponding to energy of a single particle based on outputs of the array of detectors. 
IP Reference 2017288.8 
Protection Patent application published
Year Protection Granted 2019
Licensed No
Impact Experimental work cuurently under development ; patent placed inorder to protect IP . An alternate technique is also under consideration and assessment for IP protection.
 
Description 53rd SSRMP 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Carla Winterhalter presented The importance of the Monte Carlo physics settings for simulations
in proton therapy. the talk was important to connect with other groups and keep our presence as a proton CT group active whilst in the development phase of our equipment
Year(s) Of Engagement Activity 2019
URL https://ssrpm.ch/event/53rd-ssrmp-annual-meeting/
 
Description 5th Annual Loma Linda workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Important knowldge sharing between OPTIma group and Loma Linda two important players in the development of CT and integrated imaging for proton therapy . Michela Esposito and Carla Winterhalter visited the meeting and presented on behalf of OPTIma
Year(s) Of Engagement Activity 2019
URL http://ionimaging.org/llu2019-overview/
 
Description 6Th Annual Loma Linda workshop ( virtual ) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral Presentations and abstracts - keeping up to date on thinking and important connection whilst groups cannot meet face to face .
Year(s) Of Engagement Activity 2020
URL http://ionimaging.org/llu2020-overview/
 
Description CRUK AACR - 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Poster presentation of the outline of OPTIma to an audience of diverse nature
Year(s) Of Engagement Activity 2019
URL https://www.cancerresearchuk.org/funding-for-researchers/research-events-and-conferences/cruk-aacr-j...
 
Description INFN - Italian Institute for Nuclear physics, Naples, Italy, 20-21 November 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Paper and talk - Photon counting detectors for medical imaging.
Year(s) Of Engagement Activity 2018
 
Description Ion Imaging Workshop - PTCOG58 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact One day workshop on ion imaging for clinical applications. Organised by PI, approximately 90 attendees
Year(s) Of Engagement Activity 2019
URL http://www.ionimaging.org/ws2019-overview/
 
Description Joint KT and EP Detector Seminar- Cern 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Nigel Allinson gave an update to the diverse group on the trials and tribulations of developing a proton CT system
Year(s) Of Engagement Activity 2020
URL https://indico.cern.ch/event/976430/
 
Description PRaVDA to OPTIma The trials and tribulations of Proton CT 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Seminar to connect recent research with commerce and end-users
Year(s) Of Engagement Activity 2020
 
Description Workshop on accelerator technology for particle therapy 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This workshop brought together leaders in the fields of particle therapy and accelerator physics to present and discuss emerging technologies and techniques for the application of particle accelerators for the treatment of cancer.
Year(s) Of Engagement Activity 2020
URL https://www.iopconferences.org/iop/frontend/reg/thome.csp?pageID=988134&eventID=1575