Radionuclide theragnostics is a fast-growing field with a multitude of promising emerging applications in cancer therapy and beyond. However, image-guided treatments with radiotherapeutics have so far been restricted to qualitative evaluation of imaging data to assess the suitability of patients for a course of treatment.
A ‘next generation’ approach to theragnostics will enable personalised dosimetry-based treatment planning based on the image data acquired (‘molecular radiotherapy’). This will entail multimodality imaging for pre-therapy treatment planning and for staging and monitoring response, the standardisation of data acquisition and processing to facilitate multi- centre data collation, and bio-kinetic modelling to extract the maximum information from data and to inform further treatments.
However, the realisation of the potential offered by theragnostics requires multi-centre, multi-national, and multi-disciplinary collaboration, as a full range of expertise is seldom available in single centres.
The RATIONALE network is a timely and much-needed effort to promote the full potential of the theragnostic approach to the treatment of cancer with radiotherapeutics by:
- Fostering collaborative research and training between experts and clinical centres to facilitate knowledge transfer.
- Supporting the optimisation and standardisation of data acquisition to allow data pooling to facilitate research and evidence creation.
- Bridging gaps between stakeholders and supporting communication between cross-speciality experts.
- Promoting multi-disciplinary theragnostic initiatives for the development of personalised treatments.
Challenges in Radionuclide Theragnostics
Within the RATIONALE network, the following major challenges and barriers to the progression of radionuclide theragnostics will be addressed:
Challenge 1 - Disconnected knowledge
Within the European nuclear medicine community, a substantial level of knowledge and experience exists in the theragnostics value chain. Leading experts are active throughout Europe in medical imaging, patient-specific dosimetry, pharmacokinetics as well as radiobiological modelling, radio-chemistry/pharmacy and clinical nuclear medicine. Unfortunately, not all aspects of expertise are available at single centres. For example, experts in diagnostic nuclear medicine imaging are not involved in therapeutic applications and centres specialized in radionuclide therapy may possess expertise in dosimetry while lacking in-depth imaging expertise. Furthermore, experts are active in only a small number of large university hospitals, mostly located in Western Europe, but are rarely found in smaller institutions and are frequently missing entirely in some ITCs. Support is required to facilitate collaboration and communication between the various disciplines involved (Fig 1).
Challenge 2 – Limited knowledge transfer and education
Education is key for the successful application of theragnostics and progress in theragnostic research. Unfortunately, the quality of education in theragnostic procedures is highly heterogeneous across Europe and can be sub-standard in local training programmes as specialists are not available locally. Educational programmes are frequently skewed towards local expertise while disregarding other important topics needed for theragnostics. The lack of expertise and substandard teaching is particularly evident in ITCs. Even in Western Europe, comprehensive education in MRT and theragnostics can be limited or even missing. A general lack of specific and high-level education leads to a limited interest of students towards theragnostics and hampers the career path of Young Researchers and Innovators (YRIs) in the field.
Challenge 3 - Lack of standardisation
To date, imaging technologies, imaging procedures, data formats, image analysis and dosimetry methods and software can vary widely across vendors and implementations. These variabilities hamper accurate and precise calculation of individual patient absorbed doses and therapy planning. Therefore, a clear understanding of the sources of these variabilities is needed to allow the comparison of results obtained in different centres/clinical studies. Moreover, the exchange of data and comparability of study results are hampered by the lack of standardisation – including standardised format for data reporting and quality control standards. Harmonisation of procedures to allow reproducible multicentre studies is urgently needed.
Challenge 4 – Available and reliable dosimetry
So far, clinical dosimetry has been mostly performed using ad hoc software, depending on locally available resources. The advent of commercial software gave a new impetus to the field by providing the community with relatively expensive but FDA/EMA compliant medical devices for clinical use. However, in light of the available bandwidth of software tools, benchmarking of these software solutions is required. Phantom experiments and activity measurements can only address a limited area of the clinical dosimetry workflow. Digital tools are needed to benchmark software solutions. In addition, the benchmarking of dosimetry solutions needs to consider the human, methodological and technological requirements, to appraise the feasibility of clinical dosimetry in a widely variable clinical context.
Challenge 5 - Demand for treatment personalization
Today, MRTs usually follow predefined dosing schemes. However, such a standard dosing scheme may not be optimal for individual patients and experience shows that depending on the pathology, radio-pharmaceutical, and the intended purpose of the therapeutic application, a range of image or non-image based indices may be required to optimize the clinical procedure and predict the outcome. Thus, there is an increased demand for solutions to personalize radiopharmaceutical administered activity and predict therapy outcomes based on patient-specific information including imaging and dosimetry.
Challenge 6 - Low numbers of patients at individual sites
Challenge 6 - Low numbers of patients at individual sites
The quality and validity of scientific studies in theragnostics suffer from a comparably small number of datasets. This impedes their validity to demonstrate the clinical relevance of the findings. To promote the fast translation of novel theragnostic procedures into clinical practice, the development of multi-disciplinary networks and multi-centric and multinational joint research is needed. However, in addition to the lack of standardisation, multi-national collaborations pose additional legal and ethical challenges towards data sharing between partners that can be addressed only through commonly accepted standards and governance models.
Research Coordination Objectives
RATIONALE aims to advance theragnostic research and clinical adoption by connecting different research and clinical groups, establishing a much-needed theragnostic network and promoting and facilitating transnational research initiatives. This objective stems also from the ongoing clinical and research engagements of the Action members. The Action defines the Research Coordination Objective (RCOs) as follows:
- RCO1. Disseminate tangible knowledge on theragnostic endeavors to relevant stakeholders, to better coordinate the research in the field, to avoid unintended duplication and to focus on research gaps.
- RCO2. Standardise therapeutic and imaging approaches for theragnostic applications between centres to facilitate data comparability and collaborative research through the provision of harmonization recommendations.
- RCO3. Stimulate the development of personalized theragnostic approaches by using the know-how and expertise of the network through documented and publicized internal/external communication and evidence generation.
- RCO4. Lead evaluation of theragnostic procedures for novel applications in cancer management through clinically driven Working Groups (WGs) inside the consortium and in engagement with professional organizations.
- RCO5. Ensure compliance with research ethics standards and personal data safety requirements in theragnostic research and develop workflows for data sharing in view of local and European legal requirements. (KPI5: guideline document on practical data sharing published)
Capacity-Building Objectives
RATIONALE aims to build a sustainable professional network based on personal contacts to facilitate knowledge transfer and cooperative research. One major part of these is the propagation of knowledge through inter-/national training activities and individual exchange between participating institutions. Thus, the Action defines the following Capacity-Building Objectives (CBOs):
- CBO1. To establish a sustainable network of diverse expertise from scientific, academic, industrial, governmental organizations and national initiatives and provide a platform for knowledge transfer between stakeholders involved in radionuclide theragnostics applications and research.
- CBO2. To provide excellent interdisciplinary training for PhD students and YRIs, particularly from participating ITCs, and develop openly available educational materials on theragnostic procedures to enable a state-of-the-art education irrespective of the local expertise.
- CBO3. To integrate comprehensive theragnostics education into local curricula and researcher training.
- CBO4. To support collaborations by setting up communication channels and establishing a knowledge transfer platform including information on locally available techniques and (local) legal requirements for collaborations and data sharing.
- CBO5. To make patient-specific dosimetry accessible to theragnostic centres through designing generally applicable workflows and benchmarking schemes based on open software and through the dissemination of necessary know-how.
- CBO6. To reflect on ethical issues and divergent legislation in the process of development and clinical implementation of radionuclide theragnostics.