EBioMedicine (Dec 2015)

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

  • David Azria,
  • Olivier Riou,
  • Florence Castan,
  • Tan Dat Nguyen,
  • Karine Peignaux,
  • Claire Lemanski,
  • Jean-Léon Lagrange,
  • Youlia Kirova,
  • Eric Lartigau,
  • Yazid Belkacemi,
  • Céline Bourgier,
  • Sofia Rivera,
  • Georges Noël,
  • Sébastien Clippe,
  • Françoise Mornex,
  • Christophe Hennequin,
  • Andrew Kramar,
  • Sophie Gourgou,
  • André Pèlegrin,
  • Pascal Fenoglietto,
  • Esat Mahmut Ozsahin

DOI
https://doi.org/10.1016/j.ebiom.2015.10.024
Journal volume & issue
Vol. 2, no. 12
pp. 1965 – 1973

Abstract

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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)”.

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