Targeted Radiotherapy Internal Dosimetry: A platform for individualized patient dosimetry and radiobiological assessment

Informations projet

TRIDOS

N° de convention de subvention: 839135

DOI

10.3030/839135

Projet clôturé

Date de signature de la CE 12 Avril 2019

Date de début 1 Mai 2019

Date de fin 30 Octobre 2021

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 172 932,48

Contribution de l’UE

€ 172 932,48

Coordonné par

FUNDACION PUBLICA GALEGA INSTITUTO DE INVESTIGACION SANITARIA DE SANTIAGO DE COMPOSTELA
Spain

Periodic Reporting for period 1 - TRIDOS (Targeted Radiotherapy Internal Dosimetry: A platform for individualized patient dosimetry and radiobiological assessment)

Période du rapport: 2019-05-01 au 2021-04-30

Résumé du contexte et des objectifs généraux du projet

Targeted radionuclide therapy (TRNT) is a growing type of radiotherapy in which radioactive compounds with high tumor affinity are administered to patients. Several limitations jeopardize the design of optimal treatments in this promising therapy. On one hand, the dose delivered to the patient depends on the anatomy of the patient and the biodistribution of the administered drug, which is greatly heterogeneous among individuals. Due to this complexity, internal dosimetry is far from the accuracy achieved in External radiotherapy (ERT). In addition, the biological effects of TRNT differ from those observed in ERT, due to the long-lived radionuclides employed. The reliable radiobiological models used to quantify ERT effectiveness and toxicity are therefore not directly extensible to TRNT. As a result, TRNT treatments are currently primarily based on the administration of empirical activities to patients. This limits the potential of TRNT, particularly in terms of therapy individualization. The action “Targeted Radiotherapy Internal Dosimetry: A platform for individualized patient dosimetry and radiobiological assessment” aimed to develop methods for the personalization of TRNT.

Cancer is the second leading cause of death worldwide, and its social and economic impact increases every year. Despite the major scientific and clinical advances in cancer treatment in the last decades, cancer remains a global complex health concern with limited therapies. Radiotherapy is one of the main clinical strategies used to treat cancer, being applied to approximately 50% of all cancer patients. By working on the development of personalized dosimetry and radiobiological modelling of TRNT, the products of this Marie Skłodowska-Curie Action (MSCA) provided promising tools for the devolpemnt of better cancer treatments, with direct impact on both the scientific community and the society.

The objectives of this project have been to develop methodologies for (a) accurate, individualized dosimetry, and (b) radiobiological assessment of TRNT, shifting from the current paradigm of empirical treatment to the era of personalized treatment. In addition, this MSCA Individual Fellowship aimed to consolidate my professional career as independent researcher.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The project was conducted through 4 work objectives. WO1 aimed to develop patient individualized dose calculation methods for radiopharmaceuticals. The study and development of radiobiological models for TRNT was addressed in WO2. WO3 focused in the implementation of a platform for the evaluation of internal dosimetry in TRNT patients. Finally, WO4 was to test the developed tools in patients with the purpose of clinical validation.

I could successfully complete the objectives of the project. We investigated and developed Monte Carlo based calculation methods and novel biokinetic models of drug biodistribution to determine patient individualized internal doses for TRNT. We developed a pharmacokinetic model for a promising theragnosis radioparmaceutical duo. Regarding radiobiological modelling, we developed a model of continuous radiation damage, adequate to describe the effects of TRNT and we checked that it adequately fits the evolution of tumor volumes for different cell lines after treatment. We also developed a mathematical model of thyroid response to 131I therapy, considering the dynamics of two tumor markers usually measured in the management of thyroid cancer treatment as important surrogates of treatment response. The products of the project were implemented in a software platform useful for the clinical practice, allowing easy handling and user interactivity. The dosimetry tool was tested on two cohorts of patients undergoing PET studies. The results of the project led to 6 publications in prestigious peer-reviewed scientific journals and I was corresponding author of an article published in 2020 in one of the top journals in the field.

Although affected by the limiting situation of the COVID-19 pandemic, during this MSCA Individual Fellowship our findings were presented in 4 renowned scientific conferences. I was invited as speaker to the workshop “Experimental Radiobiology: Physics meets Biology and Medicine” organised by the Heidelberg Center Latin America, and I won the young best presentation award at the 2019 International Conference on Medical Physics. My participation to international conferences also helped me to strengthen my professional network. Regarding communication to the general public, I developed educational materials about the medical uses of radiation and visited students of primary and secondary schools. Among other activities, I participated on the European Researchers’ Night 2021, broadcasting my research project and highlighting our findings. To fulfil my interest in technology transfer, I attended the webinar about the New European Regulatory Framework for Medical Devices organized by the training programme of the Atlantic KET MED Project, and the training on Industrial property organized by the Beneficiary institution, IDIS.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The dosimetry methodologies developed in this MSCA provide a viable and useful tool for patient individualized calculation of the dose associated to medical procedures involving radiopharmaceuticals, with higher accuracy than phantom-based methods. In addition, the radiobiological models developed in the project can assist in the interpretation of TRNT clinical data. These models are also useful to investigate treatment individualization strategies, aiming to improve the tumor control rates achieved with TRNT. This MSCA provided a framework to fulfill the guidelines set by the European Council directive 2013/59/Euratom, which hardened the criteria of previous European regulations and stated that TRNT treatments should be planned according to the radiation doses delivered to individual patients, as is the case for ERT. This will contribute to improve the safety standards and the quality of treatment in TNRT. The tools developed in the action will in this way favour the development of better cancer patient treatment.

Regarding my career advances, this MSCA allowed me to: i) extend my area of expertise, formerly limited to ERT, to the growing and promising field of TRNT, and ii) to work in a clinical enviroment, optimal to perform translational research in Medical Physics. This contributed to my consolidation as an expert in the field of radiotherapy and is the basis of the investigations I plan to further explore. I also fortified my management skills and reinforced my maturity to lead research projects, which will greatly impact my career as independent researcher.

Workflow of the TRIDOS dosimetric method and radiobiological evaluation