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INfraStructure in Proton International REsearch

Periodic Reporting for period 1 - INSPIRE (INfraStructure in Proton International REsearch)

Reporting period: 2018-03-01 to 2019-08-31

Proton Beam Therapy (PBT) is a type of advanced radiotherapy capable of delivering and conforming a targeted dose of radiation to the tumour while causing minimal damage to the surrounding healthy tissue. The INSPIRE project brings together 17 European centres to form the first highly specialised research infrastructure for high-energy PBT.

There are still research challenges to be addressed within PBT which could yield better treatments and outcomes for patients. It is imperative that this research is done within an environment of rigorous quality assurance (QA) and intercomparibility.


1.Develop a new infrastructure
2.Enable researchers to access this infrastructure and conduct state of the art research
3.Provide training for the next generation
4.Facilitate knowledge exchange and share best practice
5.Develop joint research activities that will improve facilities within the infrastructure
6.Develop joint research activities where technological challenges exist to improve European competitiveness
7.Develop an innovation pipeline
8.Conduct research within the principles of responsible research and innovation

The activities of INSPIRE are grouped into 3 areas: Networking Activities (NA), Transnational Access (TNA) and Joint Research Activities (JRA) and arranged into 10 interconnecting Work Packages (WP). WP1 Project Management; NA include WP2 Access Gateway, QA and Standards; WP3 Training users and inspiring the Next Generation; WP4 Communication and Dissemination; WP5 Innovation and Sustainability WP5. WP6 Trans-National Access. JRA comprises of 4 WPs: WP7 Radiobiology; WP8 Patient selection and data sharing; WP9 Mathematical simulation and modelling for proton therapy and WP10 Dosimetry, robustness and uncertainties.

The consortium is made up of internationally leading research and clinical facilities, industry partners and SME.
During RP1, time has been spent on:
•Budget and continuous progress monitoring against the Tasks, Milestones and Deliverables described in the Grant Agreement
•Coordinated full consortium and WP meetings (face to face 01/03/2018 and 09/06/2019; teleconference 10/10/2018 and 28/05/2019)
•Developed an online Access Gateway for TNA, communicating the project to the outside world and access to INSPIRE’s Innovation Gateway
•Undertook a quality assurance audit (QAA) across all TNA providers to define common standards and protocols; a more detailed QA study on radiobiology and further European audits are planned
•Organised training events, conferences and workshops for INSPIRE researchers and the wider scientific community (PTCOG58 and BiGART
•Engaged with European Initiatives including ESTRO task force EPTN
•Developed a Knowledge Hub (online and face to face information days) to communicate information about PBT
•Facilitated Discipline Hops, Technical Secondments and Summer Placements within PBT
•Developed a data management plan
•Developed an Open Access gateway to provide access to the research outputs of INSPIRE, software and data
•Coordinated outreach activities (Open Nights, videos and fact sheets)
•Promoted INSPIRE at National and International Scientific Meetings
•Sponsored places on training courses e.g. PSI Winter School, IC PBT School, Christie Summer School
•UMCG and IBA have developed a database for NTCP to help to select patients for PBT
•Varian are developing detector technology to integrate in to their clinical delivery system for Flash dosimetry
•17 TNA projects have been submitted; 3 projects are under review and 14 have been approved – 3 of which are underway. The projects come from 8 EU states (1 external to Europe)
•IC, SKANDION, UNIMAN and CHRISTIE are developing systems for precise positioning and irradiation of biological samples
•NPI-CAS, LSMU, AU and TUD have studied the biological effects of protons in vitro and in vivo. GSI is developing protocols and setups for irradiating gel-based 3D cultures to enable RBE measurements for more realistic conditions
•GSI, UNIMAN, CHRISTIE and SKANDION are developing models to improve the outcome of treatment of poorly oxygenated tumours and to better understand hypoxia-induced radioresistance mechanisms
•UNAMUR, IFJ PAN, and NPI-CAS are studying the effects of radio-sensitisation with drugs and nanoparticles
•UMCG have defined models for the selection process of head and neck, lung cancer and breast cancer patients for protons. These have been implemented in National Indication Protocol for Proton Therapy in the Netherlands
•UNIMAN/CHRISTIE Malthus model has been used to look at national referral patterns for PBT to identify regions of under referral and can simulate future demand
•PSI are developing methods for automated treatment planning to be assessed with the aim of providing ‘expert system’ proton planning
•GSI/UNIMAN are looking at how the results from WP7 can be integrated in to biologically optimised probabilistic treatment plans, taking variations in RBE and OER into account
•AU, CHRISTIE, SKANDION and GSI are studying the effects of including variable RBE for cancer patients into treatment planning while TUD and CHRISTIE evaluate the impact of spot scanning and organ motion
•IFJ-PAN is modelling spatial distribution of biological effectiveness for realistic proton beam treatment plans
•TUD is setting up a model environment of PBS nozzle in treatment and experimental rooms with Monte Carlo interface TOPAS
•A PBS delivery simulator is being established at AU and validated against actual treatment deliveries
•IFJ-PAN demonstrated that elements prepared with 3D printers for modification of proton beams produce less scattered radiation and are safe for patients
•UNIMAN/CHRISTIE are studying the development of phantoms containing tissue equivalent materials to look at the variation in RBE along the Bragg peak while NPI-CAS use track-etched detectors with other dosimetric quantities
•NPI-CAS is studying detectors for the measurement of the secondary radiation field at patient level to estimate the risk of secondary tumours at specific organs (WP8) while SKANDION study theoretical Monte Carlo modelling of secondary dose assessment
•UNIMAN/CHRISTIE are looking at LaBr3 scintillator detector technology for prompt gamma-ray detection to address range verification in PBT, using a multi-detector approach with 16 detector units to develop a reconstruction algorithm capable of determining the gamma-ray origin in 3 dimensions
•UNAMUR used GEANT4 to model the radiation characteristics of a proton therapy centre and irradiate tumours in silico
A new technology that has the potential to transform radiotherapy included in INSPIRE’s JRA is called Flash. In Flash, a higher dose is delivered very rapidly, typically >40Gy per second. Flash is revolutionary because it appears to spare normal tissues while maintaining tumour control. Varian have developed technology for Flash dosimetry and a prototype will be tested in AU (WP5 and WP10). PSI is working on Flash treatment planning (WP10) while UNIMAN, CHRISTIE, IC and GSI are conducting experiments and simulations (WP7 and WP9) to understand the mechanisms for Flash. TNA providers are developing their capability to deliver Flash and INSPIRE is working with the EU EMPIR project UHDpulse to develop workshops and collaborations. If successful, FLASH will radically change cancer therapy – a key societal change brought about in part, through INSPIRE.