Research program

To improve molecular mechanistic understanding of the proton-induced DNA damage response and to exploit this understanding to enhance the effectiveness of proton irradiation.

One of the requirements for further breakthroughs with proton therapy is to obtain a fundamental understanding of the proton- versus photon-induced DNA damage response. This increased understanding of the various mechanisms involved in the response to radiation also offers new prospects for developing predictive and prognostic biomarkers that can be used for individualising radiation dose prescription and increasing the therapeutic window.

To increase the precision of proton therapy by developing technology for high-precision image-guided and biology-guided online adaptive proton therapy.

This roadmap focuses on improving the delivery of the dose to the tumour with high precision while minimizing the dose to surrounding healthy tissue. This is realized by developing and implementing techniques including high-precision treatment planning and delivery tools, offline and online-adaptive proton therapy approaches, and real-time in-vivo quality assurance. Furthermore, the combination of physics- and technology-driven developments with the rapidly evolving advances in cancer biology is essential to continue improving proton therapy outcomes for the future.

To develop and pre-clinically and clinically validate quantitative imaging biomarkers for pre-treatment characterisation and response assessment of the tumour and healthy tissue.

This roadmap aims to help define and enhance the best possible proton dose distribution in the patient by applying the best available biological information. Biology-weighted imaging will be explored and (pre-clinically and clinically) validated to assess the physiology of the tumour as well as healthy tissue. This will pave the way for personalised dose prescription and personalised optimisation of the proton therapy treatment plan. Furthermore, it can also be used to quantitatively assess tumour response and healthy tissue damage. In particular, to identify patients who, during treatment, may require extra doses to the tumour or need extra protection of the healthy tissue.

To implement and evaluate technological innovations for proton therapy in clinical practice realising the next generation of proton therapy.

In general, radiotherapy research in the Netherlands is firmly embedded in the clinic and clinical data is widely utilised for research. Furthermore, there is a great willingness to apply research results in routine clinical practice. The aim of this roadmap is to implement and evaluate new technologies in clinical practice.

To develop knowledge on the optimal clinical indication of proton therapy, integrating patient’s characteristics and preferences, cost-effectiveness analysis and predictive modelling of benefits and complications for photon and proton therapy.

This roadmap covers the research on predictive modelling of clinical outcomes used for the model-based indications. It also includes big data analytics, doctor and patient decision support systems development, and photon and proton therapy cost-effectiveness. HollandPTC has a comprehensive research database that includes clinical data, treatment data and patient follow-up data including patient-reported outcome measures. This database can improve patient selection by identifying the prognostic factor for early and late proton and photon treatment side effects. Furthermore, a cost-effectiveness analysis will be carried out to evaluate the societal costs of proton therapy.

To provide level-I clinical evidence of the currently theoretical benefit of proton therapy compared to the best possible photon treatment currently available.

The research will aim to obtain level-I evidence regarding the benefits of proton therapy compared to state-of-the-art photon therapy and/or other treatment modalities by cohort studies and randomized controlled trials (RCTs). As such, this roadmap contributes to the justification of using proton therapy.

HollandPTC software