Radiation-induced CD8 T-lymphocyte Apoptosis as a Predictor of Breast Fibrosis After Radiotherapy: Results of the Prospective Multicenter French Trial

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TitreRadiation-induced CD8 T-lymphocyte Apoptosis as a Predictor of Breast Fibrosis After Radiotherapy: Results of the Prospective Multicenter French Trial
Type de publicationJournal Article
Year of Publication2015
AuteursAzria D, Riou O, Castan F, Nguyen TDat, Peignaux K, Lemanski C, Lagrange J-L, Kirova Y, Lartigau E, Belkacemi Y, Bourgier C, Rivera S, Noel G, Clippe S, Mornex F, Hennequin C, Kramar A, Gourgou S, Pelegrin A, Fenoglietto P, Ozsahin EMahmut
JournalEBIOMEDICINE
Volume2
Pagination1965-1973
Date PublishedDEC
Type of ArticleArticle
ISSN2352-3964
Mots-clésApoptosis, Breast fibrosis, lymphocyte, Prediction, radiotherapy
Résumé

{Background: Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf+) after adjuvant breast RT in a prospective multicenter trial. Methods: A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were recruited at ten centers. RILA was assessed before RT by flow cytometry. Impact of RILA on bf+(primary endpoint) or relapse was assessed using a competing risk method. Receiver-operator characteristic (ROC) curve analyses were also performed in intention to treat. This study is registered with ClinicalTrials. gov, number NCT00893035 and final analyses are presented here. Findings: Four hundred and fifty-six pts (90.8%) were included in the final analysis. One hundred and eight pts (23.7%) received whole breast and node irradiation. A boost dose of 10-16 Gy was delivered in 449 pts (98.5%). Adjuvant hormonotherapy was administered to 349 pts (76.5%). With a median follow-up of 38.6 months, grade >= 2 bf+ was observed in 64 pts (14%). A decreased incidence of grade >= 2 bf+ was observed for increasing values of RILA (p = 0.012). No grade 3 bf+ was observed for patients with RILA = 12%. The area under the ROC curve was 0.62. For cut-off values of RILA = 20% and b12%, sensitivity and specificity were 80% and 34%, 56% and 67%, respectively. Negative predictive value for grade >= 2 bf+ was equal to 91% for RILA >= 20% and positive predictive value was equal to 22% for RILA b12% where the overall prevalence of grade >= 2 bf+ was estimated at 14%. A significant decrease in the risk of grade >= 2 bf+ was found if patients had no adjuvant hormonotherapy (sHR= 0.31

DOI10.1016/j.ebiom.2015.10.024