Prediction of radiotherapy toxicity: 20 years of COPERNIC radiosensitivity diagnosis procedure

Abstract

Purpose

Since 2004, in the frame of the care pathway, our Research Unit has replied to the demand of expertise of radiation oncologists about the individual radiosensitivity of some of their patients. This procedure, called COPERNIC, is based on a skin biopsy and the radiation-induced nucleoshuttling of the ATM protein (the RIANS model), a major actor of DNA break repair and signaling. In 2016, with the first 117 COPERNIC fibroblast lines, we obtained a significant correlation between the maximum number of the nuclear ATM foci, pATM_max, and the CTCAE severity grade of the post-radiotherapy tissue reactions. In this study, we propose to verify the validity of our previous findings with a new COPERNIC data subset obtained in the 2014–2024 period.

Materials and methods

We applied a standard immunofluorescence technique to quiescent COPERNIC fibroblasts to assess, after 2 Gy, the level of micronuclei, γH2AX and pATM foci. The 117 COPERNIC data published in 2016 were considered as the reference data subset. A new COPERNIC data subset composed of 133 fibroblast cell lines was considered as the validating data subset.

Results

Our data showed that spontaneous or residual micronuclei levels, and residual γH2AX foci levels cannot predict CTCAE grades. Conversely, the linear formula linking the maximal number of pATM foci and the corresponding CTCAE grade and obtained in 2016 from the reference data subset fitted well the validating data.

Conclusions

The maximal number of pATM foci appears to be one of the most reliable biomarkers for predicting post-radiotherapy radiotoxicity.