TY - JOUR
T1 - Validation of a high performance functional assay for individual radiosensitivity in pediatric oncology
T2 - A prospective cohort study (ARPEGE)
AU - Bernier-chastagner, Valérie
AU - Hettal, Liza
AU - Gillon, Véronique
AU - Fernandes, Laurinda
AU - Huin-schohn, Cécile
AU - Vazel, Marion
AU - Tosti, Priscillia
AU - Salleron, Julia
AU - François, Aurélie
AU - Cérimèle, Elise
AU - Perreira, Sandrine
AU - Peiffert, Didier
AU - Chastagner, Pascal
AU - Vogin, Guillaume
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/7/6
Y1 - 2018/7/6
N2 - 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.
AB - 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.
KW - Biomarker
KW - Pediatric oncology
KW - Predictive assay
KW - Radiosensitivity
KW - Radiotherapy
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=85049603772&partnerID=8YFLogxK
U2 - 10.1186/s12885-018-4652-7
DO - 10.1186/s12885-018-4652-7
M3 - Article
C2 - 29976172
AN - SCOPUS:85049603772
SN - 1471-2407
VL - 18
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 719
ER -