A Longitudinal Study of Individual Radiation Responses in Pediatric Patients Treated with Proton and Photon Radiotherapy, and Interventional Cardiology: Rationale and Research Protocol of the HARMONIC Project

Author:

Andreassi Maria Grazia1ORCID,Haddy Nadia2,Harms-Ringdahl Mats3,Campolo Jonica4ORCID,Borghini Andrea1ORCID,Chevalier François56ORCID,Schwenk Jochen M.7ORCID,Fresneau Brice89ORCID,Bolle Stephanie10,Fuentes Manuel11ORCID,Haghdoost Siamak356ORCID

Affiliation:

1. CNR National Research Council Institute of Clinical Physiology, 56125 Pisa, Italy

2. Radiation Epidemiology Team, Center for Research in Epidemiology and Population Health, INSERM U1018, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France

3. Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden

4. CNR National Research Council Institute of Clinical Physiology, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy

5. UMR6252 CIMAP, CEA-CNRS-ENSICAEN-University of Caen Normandy, 14000 Caen, France

6. Advanced Resource Center for HADrontherapy in Europe (ARCHADE), 14000 Caen, France

7. Affinity Proteomics, SciLifeLab, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH—Royal Institute of Technology, 10044 Stockholm, Sweden

8. Department of Children and Adolescents Oncology, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France

9. Cancer and Radiation Team, Center for Research in Epidemiology and Population Health, INSERM U1018, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France

10. Department of Radiation Therapy, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France

11. Deparment of Medicine and General Service of Cytometry, Proteomics Unit, Cancer Research Centre-IBMCC, CSIC-USAL, IBSAL, Campus Miguel de Unamuno s/n, University of Salamanca-CSIC, 37007 Salamanca, Spain

Abstract

The Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy (photon and proton) in Pediatrics (HARMONIC) is a five-year project funded by the European Commission that aimed to improve the understanding of the long-term ionizing radiation (IR) risks for pediatric patients. In this paper, we provide a detailed overview of the rationale, design, and methods for the biological aspect of the project with objectives to provide a mechanistic understanding of the molecular pathways involved in the IR response and to identify potential predictive biomarkers of individual response involved in long-term health risks. Biological samples will be collected at three time points: before the first exposure, at the end of the exposure, and one year after the exposure. The average whole-body dose, the dose to the target organ, and the dose to some important out-of-field organs will be estimated. State-of-the-art analytical methods will be used to assess the levels of a set of known biomarkers and also explore high-resolution approaches of proteomics and miRNA transcriptomes to provide an integrated assessment. By using bioinformatics and systems biology, biological pathways and novel pathways involved in the response to IR exposure will be deciphered.

Funder

Euratom research and training program

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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