The HollandPTC R&D Programme focuses on a variety of topics within the fields of biology, physics & technology, and applied clinical research. The programme is further divided into 6 roadmaps:

Radiobiology
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 the development of predictive and prognostic biomarkers that can be used for individualising radiation dose prescription and to increase the therapeutic window.

Technology for the next generation of proton therapy
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 tools for high-precision treatment planning and delivery, 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.

Imaging for biology-guided adaptive proton therapy
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 for the quantitative assessment of tumour response and healthy tissue damage. In particular, to identify patients who, during treatment, may require extra dose to the tumour or need extra protection of the healthy tissue.

Implementation and evaluation of new technology
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 strongly embedded in the clinic and clinical data is widely utilised for research. Furthermore, there is 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.

Predictive modelling, big data analytics, decision making, health economics
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, development of both doctor and patient decision support systems, and cost-effectiveness of photon and proton therapy. HollandPTC has a comprehensive research database that includes clinical data, treatment data and patient follow-up data including patient reported outcome measures. With this database patient selection can be improved by identifying the prognostic factor for early and late side effects for proton and photon treatment. Furthermore, cost-effectiveness analysis will be carried out to evaluate the societal costs of proton therapy.

Clinical trials
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 (RCT’s). As such, this roadmap contributes to the justification of the use of proton therapy.