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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Serval ID
serval:BIB_FAEEE27F5350
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Radiation-induced CD8 T-lymphocyte Apoptosis as a Predictor of Breast Fibrosis After Radiotherapy: Results of the Prospective Multicenter French Trial.
Journal
Ebiomedicine
Author(s)
Azria D., Riou O., Castan F., Nguyen T.D., Peignaux K., Lemanski C., Lagrange J.L., Kirova Y., Lartigau E., Belkacemi Y., Bourgier C., Rivera S., Noël G., Clippe S., Mornex F., Hennequin C., Kramar A., Gourgou S., Pèlegrin A., Fenoglietto P., Ozsahin E.M.
ISSN
2352-3964 (Electronic)
ISSN-L
2352-3964
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
2
Number
12
Pages
1965-1973
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Multicenter Study
Publication Status: epublish
Abstract
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 < 12%, 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 < 12% 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, p = 0.007) and presented a RILA ≥ 12% (sHR = 0.45, p = 0.002).
INTERPRETATION: RILA significantly predicts the risk of breast fibrosis. This study validates the use of RILA as a rapid screening test before RT delivery and will change definitely our daily clinical practice in radiation oncology.
FUNDING: The French National Cancer Institute (INCa) through the "Program Hospitalier de Recherche Clinique (PHRC)".
Keywords
Adult, Aged, Aged, 80 and over, Apoptosis/radiation effects, Biomarkers, Tumor, Breast Neoplasms/complications, Breast Neoplasms/diagnosis, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Female, Fibrocystic Breast Disease/diagnosis, Fibrocystic Breast Disease/epidemiology, Fibrosis, Humans, Incidence, Middle Aged, Neoplasm Grading, Neoplasm Staging, Prognosis, Proportional Hazards Models, Radiotherapy, Adjuvant/adverse effects, Recurrence, Risk Factors
Pubmed
Web of science
Open Access
Yes
Create date
20/02/2016 15:55
Last modification date
20/08/2019 16:26
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