Introduction

The European Union has a long-term history of funding radioprotection research via the DG-ENER/Euratom. In this context, EURAMED (European Alliance for Medical Radiation Protection Research) plays a pivotal role by shaping research in the field of medical radiation protection research, thereby increasing the science base in medical radiation protection. By bringing together key stakeholders, including European Association of Nuclear Medicine (EANM), European Federation of Organizations for Medical Physics (EFOMP), European Federation of Radiographer Societies (EFRS), European Society of Radiology (ESR) and European Society for Radiotherapy and Oncology (ESTRO), EURAMED fosters collaborative, cross-disciplinary research.

The rocc-n-roll roadmap and SRA and their relevance for ESTRO

As part of Horizon 2020, EURAMED initiated the rocc-n-roll project in order to propose a strategy for medical radiation research in the coming decades. Based on the challenges identified by the international multidisciplinary project consortium, this resulted in the rocc-n-roll roadmap and strategic research agenda (SRA). With a patient centered view, both align with European health and digital innovation funding, and with efforts to advance personalized medicine using ionizing radiation in Europe. This roadmap and SRA aim to guide European policymakers, funders, and the scientific and clinical communities on key actions in research, infrastructure, education, and training for medical applications of ionising radiation. Prioritized actions focus on maximizing patient life expectancy and quality of life, integrating radiation protection into healthcare safety measures, and strengthening healthcare systems.

An important aim of the rocc-n-roll roadmap and SRA is to establish a clear and comprehensive position for radiation research that, beyond advising policy makers, will also serve as guidance for EURAMED representatives, when getting involved with European authorities in the execution of the proposed actions.

ESTRO, as a member of EURAMED, has been asked to get more involved in EURAMED activities. ESTRO does understand this approach as a chance to foster and promote radiation oncology research within the European framework. Therefore and within the scene set above, the present guidance document is intended to define ESTRO’s strategic priorities in radiation oncology research in regards to the EURAMED framework, the rocc-n-roll roadmap and SRA, particularly in the context of radiation safety, optimized cancer care, and collaborative research in Europe.

The main output of the EURAMED rocc-n-roll “Medical radiation protection roadmap” are eight “breakthroughs” identifying “research and technological developments that may substantially impact medical applications of IR”. Although only one breakthrough is termed “Improve/develop therapies” and radiation oncology is only one of three subtopics (the others being theranostics and interventional procedures), all eight breakthroughs are closely connected to our field of work and offer numerous opportunities for ESTRO to get involved in activities under the EURAMED framework.  The breakthroughs span all fields of expertise and interests of ESTRO and include technological aspects such as new treatment technologies (cf. breakthroug (BT) 2 of the rocc-n-roll roadmap), AI based methods and dosimetry, radiation biology and multimodal treatments with biologicals, strategies for evidence building and governance and communication aspects. For example, the title of BT 3 is Patient Radiation Protection and Benefit-Risk Ratio, which might at first sight not exactly resonate with radiation oncology. However, the subtopics listed are Radiation biology and patient dosimetry, and the vision statement and suggested actions are highly relevant for radiation oncology, including (among others) biological effects of dose and fractionation as well as new radiotherapy approaches such as FLASH and combination effects with systemic therapies.

Opportunities for research for the ESTRO community

General policy

The topics listed in the EURAMED rocc-n-roll roadmap and SRA correspond to research fields of researchers from all disciplines within radiation oncology. Beyond RO centered activities, ESTRO strongly supports the establishment of cross-discipline projects. Within radiation oncology, the ESTRO community is inherently interdisciplinary - bringing together radiation oncologists, medical physicists, RTTs and radiation biologists - joined by the common goal of improving patient care. EURAMED calls should therefore encourage interdisciplinary and interprofessional projects and should specifically support projects with a potential impact on clinical practice, such as improving treatment outcomes, including minimizing side-effects or technology-driven improvements in treatment quality and / or treatment efficiency. In the EURAMED context, studies on normal tissue effects at all levels from a biological, technical and clinical perspective are of particular importance.

For the ESTRO community, the EURAMED rocc-n-roll roadmap and SRA are of particular importance, as they can and should support aspects that are crucial for making radiation oncology future-proof, but are not or not easily funded by other funding mechanisms or agencies. Specifically, ESTRO should advocate within EURAMED for the increased support for projects in the clinical implementation of new treatment technologies to better overcome the so-called “Death Valley of translational research”, the phase between initial proof-of-principle feasibility studies and the clinical readiness of the technology for implementation in real-world clinical settings. In particular, the rising standards and costs of the associated processes to comply with the Medical Device Regulation (MDR) need to be explicitly fundable as part of research projects. This needs to be recognized in calls and funding rules. Furthermore, increasing the involvement of patients, both as stakeholders in clinical trials and in decision making about their own treatment, is important to ESTRO. Therefore, the ESTRO engagement within EURAMED should aim at either initiating and supporting dedicated calls or including these aspects in more general calls.
 

Topics of special interest for radiation oncology to be supported by ESTRO representatives within EURAMED

Structural support for Clinical Evidence building

There are many emerging technologies in radiotherapy (particle therapy, FLASH, image guided radiotherapy with MRI, adaptive radiotherapy, etc.) that may change the dose distribution and consequently the balance between oncological outcome and toxicity. To demonstrate effectiveness of the new treatments and learn about dose effects on normal tissue, the funding of clinical trials and particularly trial registries is crucial. Currently this is a limiting factor. The radiotherapy industry is not in the position to fund trials to the extent that pharma can, because of the fundamental difference in business model: innovations in equipment are not directly linked to one specific treatment and alternative innovations can circumvent patents quite easily. Thus, industry can’t monetize these inventions to the extent that is common in pharma (BT 2, 3 and 5, 6).

Although randomized controlled trials are considered the highest standard for building clinical evidence for the assessment of new technologies, in radiation oncology other study designs can also be appropriate. In particular data registries, prospectively collecting real-world data can be a valuable source for investigating dose effects on normal tissues. Importantly, such data registries need to include both clinical outcome data and technical data such as medical images (CT, PET, MRI) and dose distributions, to assess the local effects of dose on tissues. This requires an infrastructure suitable to handle these types of data elements.

Improving Radiobiological understanding

Pre-clinical, translational research is aiming to improve patient treatment with radiotherapy through knowledge of biological parameters. This is with a focus on either increasing tumor response, sparing the normal tissue or both. The emerging technologies mentioned above are on different levels in the translational pipeline, and solid pre-clinical data is needed to gain enough knowledge and understanding of the underlying biological mechanisms for a safe clinical translation. This is particularly the case for adaptative Radiotherapy, FLASH, Spatial Fractionated Radiotherapy (SFRT), and combination treatments of RT and nuclear medicine. Some of these modalities are already included in clinical trials, but pre-clinical research could facilitate a broader clinical implementation.

In addition to these new modalities, there is also a changing use of the radiotherapy regimes, with an increased use of re-irradiation (a second course of radiotherapy for cancer patients), hypofractionation and combination therapies with targeted drugs and immunotherapy. We are unlikely to ever fully understand the fractionation effects and tissue recovery, or fundamentally expand our understanding of key radiobiological factors from clinical data alone. This is, amongst others, due to the considerable heterogeneity in patient cohorts, which makes it challenging to extract individual radiobiological parameters in data analysis. Well-designed pre-clinical studies will allow this and will create clear synergy with ongoing clinical work. The hypotheses arising from pre-clinical studies can guide the design of future clinical protocols and treatments (BT 2,3).

Conclusion

Overall, it is of high interest for ESTRO to be actively involved in the EURAMED framework. Beyond networking with the other medical societies involved in radiation research, there shall be opportunities along the rocc-n-roll SRA and roadmap to shape future EU calls in order to create support for clinical, technological and biological research in the context of radiation oncology.

The topics listed above shall give an impression of topics of interest. However, it is of utmost importance, that ESTRO representatives also watch the developments in the field, bring them up within the framework, take care of dead ends and aim at early support of “rising stars” in order to exploit opportunities best.

By the ESTRO Working Group on Priorities of ESTRO for engagement within the EURAMED framework: Yavuz Anacak, Ege University School of Medicine (TR); Franziska Eckert, Medical University of Vienna (AT); Ursula Nestle, Kliniken Maria Hilf GmbH (DE); Francois Paris, National Institute of Health and Medical Research, Inserm (FR); Christian Richter, OncoRay (DE); Brita Singers Sorensen, Aarhus University (DK); Uulke van der Heide, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NL).