In the latest issue of the International Journal of Molecular Sciences, HARMONIC researchers provide a detailed overview of the rationale, design and methods for understanding how radiotherapy affects our body and which biomarkers can be used to predict long-term health risks.

Radiotherapy has saved the lives of countless young cancer patients. However, exposure to radiation at a young age may have adverse health effects that may not appear until years or decades later, such as the development of other unrelated cancers, or cardiac and vascular disorders. “Unless we have a better understanding of the biological mechanisms that lead to these long-term health effects, we can do little to prevent them,” says Siamak Haghdoost, researcher at Stockholm University and University of Caen and leader of the HARMONIC work package on biology, in close collaboration with Maria Grazzia Andreassi (Italy) and Nadia Haddy (France).

Linking individual biological samples and dose information

To conduct the study, Haghdoost and his team are collecting blood and saliva samples from each participant at three different times: before they are exposed to the radiation, immediately after exposure, and one year after exposure. The participants include cancer patients treated with proton and photon therapy, as well as patients undergoing X-ray procedures for heart defects.

For each patient, the team will determine the type and amount of radiation absorbed by the whole body, as well as the dose received by the target organ and other organs that were not directly exposed to the radiation. They will then use advanced analytical methods to examine the levels of specific biomarkers that are already known to be associated with radiation-induced adverse health effects. They will also use cutting-edge techniques such as proteomics (the study of proteins) and miRNA transcriptomics (the study of small RNA molecules) to gain a comprehensive understanding of the biological effects of radiation. Finally, they will use bioinformatics and systems biology to make sense of the huge amount of data.

“We hope that these approaches will allow us to identify new biological pathways involved in the body’s response to radiation exposure, as well as potential predictive biomarkers that can identify patients at high risk of late health effects due to the radiation,” says Haghdoost. This could help clinicians to provide the most appropriate treatment for each individual patient.



Andreassi MG, Haddy N, Harms-Ringdahl M et al. 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. Int J Mol Sci. 2023 May 8;24(9):8416. doi: 10.3390/ijms24098416.