Abstract P3-12-18: Radiation-induced CD8 T-lymphocyte apoptosis as a predictor of late toxicity after radiotherapy: Results of the prospective multicenter French trial
Authors: Hennequin C , Azria D , Riou O , Castan F , Coelho M , Nguyen TD , Peignaux K , Lemanski C , Lagrange J-L , Kirova Y , Lartigau E , Belkacemi Y , Bourgier C , Noel G , Clippe S , Mornex F , Kramar A , Pèlegrin A , Ozsahin M 
Published: May 2016

Abstract
Purpose/Objective(s): We and others showed in retrospective and monocentric studies that radiation-induced CD8-lymphocyte apoptosis (RILA) can significantly predict differences in late toxicity between individuals and can be used as a rapid screening for potential hyper-reactive patients to radiation therapy (RT). We present here the clinical results of the prospective multicenter French trial (NCT00893035) evaluating the predictive role of RILA as a predictor of late effects after RT.
Materials/Methods: A total of 502 consenting breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were included by 10 French centers. Lymphocytes apoptosis was assessed before RT by associated condensation of DNA. The incidence of late toxicities was obtained using CTCAEv3.0 grading scale. Complication-free survival (CFS) and complication-relapse-free survival (CRFS) curves were estimated by the Kaplan-Meier method. The log-rank test was used to identify significant categorical variables for each of the survival curves. Cox model was used for multivariate analysis.
Results: Four hundred and fifty-four pts (90.4%) were included in the final analysis (clinical, biological and dosimetric data available). One hundred and eight pts (24%) received both whole breast (WB) and nodal irradiation (NI). A boost dose of 10-16 Gy was given in 448 pts (99%). Adjuvant hormonotherapy (tamoxifen or aromatase inhibitor) was delivered to 346 pts (76%). Three categories of absolute change in the percent CD8 cells in apoptosis before and after exposure to 8-Gy in vitro RT were constructed around the 33 percent quantiles, &lt;12%, 12-20%, and &gt;20%. In a median follow-up period of 38.5 months, grade 2 and 3 late fibrosis was observed in 54 (12%) and 3 (0.7%) pts, respectively. A decreased percentage of grade 2 or more late toxicity was observed for increasing values of CD8 apoptosis (p=0.001). No grade 3 late toxicity was observed for patients with RILA ≥12%. The 3-year CFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 79% (95% confidence interval [CI]: 72–85%), 90% (95% CI: 84–94%), and 93% (95% CI: 87–96%) for CD8 &lt;12%, 12–20%, and &gt;20%, respectively (p=0.001). Similar results were observed for the CRFS rates (p&lt;0.001). In multivariate analyses, prognostic factors for CFS were RILA&lt;12% (p=0.001), smoking history (p&lt;0.001), and adjuvant hormonal treatment (p=0.008). Negative predictive value for grade 2 or more toxicity was equal to 83% for CD8 &gt;20% and positive predictive value was equal to 22% for CD8 &lt;12% where the overall prevalence of grade 2 or more late side effects was estimated at 14%.
Conclusion: RILA significantly predicts differences in radiation-induced late toxicity between individuals. This study validates the use of RILA as a rapid screening for potential hyper-reactive pts to radiotherapy.
Citation Format: Hennequin C, Azria D, Riou O, Castan F, Coelho M, Nguyen TD, Peignaux K, Lemanski C, Lagrange J-L, Kirova Y, Lartigau E, Belkacemi Y, Bourgier C, Noel G, Clippe S, Mornex F, Kramar A, Pèlegrin A, Ozsahin M. Radiation-induced CD8 T-lymphocyte apoptosis as a predictor of late toxicity after radiotherapy: Results of the prospective multicenter French trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-18.