Validation of a high performance functional assay for individual radiosensitivity in pediatric oncology: A prospective cohort study (ARPEGE)

Valérie Bernier-chastagner, Liza Hettal, Véronique Gillon, Laurinda Fernandes, Cécile Huin-schohn, Marion Vazel, Priscillia Tosti, Julia Salleron, Aurélie François, Elise Cérimèle, Sandrine Perreira, Didier Peiffert, Pascal Chastagner, Guillaume Vogin*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)


Background: Approximately 900 children/adolescents are treated with radiotherapy (RT) every year in France. However, among the 80% of survivors, the cumulative incidence of long-term morbidity - including second malignancies - reach 73.4% thirty years after the cancer diagnosis. Identifying a priori the subjects at risk for RT sequelae is a major challenge of paediatric oncology. Individual radiosensitivity (IRS) of children/adolescents is unknown at this time, probably with large variability depending on the age when considering the changes in metabolic functions throughout growth. We previously retrospectively showed that unrepaired DNA double strand breaks (DSB) as well a delay in the nucleoshuttling of the pATM protein were common features to patients with RT toxicity. We aim to validate a high performance functional assay for IRS prospectively. Methods/design: ARPEGE is a prospective open-label, non-randomized multicentre cohort study. We will prospectively recruit 222 children/adolescents who require RT as part of their routine care and follow them during 15 years. Prior RT we will collect blood and skin samples to raise a primary dermal fibroblast line to carry out in blind the IRS assay. As a primary objective, we will determine its discriminating ability to predict the occurrence of unusual early skin, mucous or hematological toxicity. The primary endpoint is the measurement of residual double-strand breaks 24 h after ex vivo radiation assessed with indirect immunofluorescence (γH2AX marker). Secondary endpoints include the determination of pATM foci at 10 min and 1 h (pATM marker) and micronuclei at 24 h. In parallel toxicity including second malignancies will be reported according to NCI-CTCAE v4.0 reference scale three months of the completion of RT then periodically during 15 years. Confusion factors such as irradiated volume, skin phototype, previous chemotherapy regimen, smoking, comorbities (diabetes, immunodeficiency, chronic inflammatory disease.) will be reported. Discussion: ARPEGE would be the first study to document the distribution of IRS in the pediatric subpopulation. Screening hypersensitive patients would be a major step forward in the management of cancers, opening a way to personalized pediatric oncology.

Original languageEnglish
Article number719
JournalBMC Cancer
Issue number1
Publication statusPublished - 6 Jul 2018
Externally publishedYes


  • Biomarker
  • Pediatric oncology
  • Predictive assay
  • Radiosensitivity
  • Radiotherapy
  • Toxicity


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