放疗后乳腺癌纤维化的预测因子：放疗诱导的 CD8+T 淋巴细胞凋亡：前瞻性多中心法国研究结果。
Radiation-induced CD8 T-lymphocyte Apoptosis as a Predictor of Breast Fibrosis After Radiotherapy: Results of the Prospective Multicenter French Trial.
机构信息
Montpellier Cancer Institute (ICM), Montpellier Cancer Research Institute (IRCM), University of Montpellier, Montpellier, France.
Institut Jean Godinot, Reims, France.
出版信息
EBioMedicine. 2015 Oct 25;2(12):1965-73. doi: 10.1016/j.ebiom.2015.10.024. eCollection 2015 Dec.
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)".
背景
单中心队列研究表明，辐射诱导的 CD8 T 淋巴细胞凋亡（RILA）可预测根治性放疗后晚期毒性。我们在一项前瞻性多中心试验中评估了 RILA 作为辅助乳房放疗后乳房纤维化（bf +）预测因子的作用。
方法
共招募了 10 个中心的 502 名接受保乳手术和辅助放疗的乳腺癌患者（pts）。在放疗前通过流式细胞术评估 RILA。使用竞争风险方法评估 RILA 对 bf +（主要终点）或复发的影响。还在意向治疗中进行了接收者操作特征（ROC）曲线分析。这项研究在 ClinicalTrials.gov 注册，编号为 NCT00893035，此处呈现最终分析结果。
发现
共有 456 名 pts（90.8%）纳入最终分析。108 名 pts（23.7%）接受全乳房和淋巴结照射。449 名 pts（98.5%）接受了 10-16 Gy 的增量剂量。349 名 pts（76.5%）接受了辅助激素治疗。中位随访 38.6 个月，64 名 pts（14%）观察到≥2 级 bf +。RILA 值增加时，观察到≥2 级 bf +的发生率降低（p = 0.012）。对于 RILA≥12%的患者，未观察到 3 级 bf +。ROC 曲线下面积为 0.62。对于 RILA≥20%和<12%的截断值，敏感性和特异性分别为 80%和 34%、56%和 67%。RILA≥20%的阴性预测值为 91%，RILA<12%的阳性预测值为 22%，其中≥2 级 bf +的总体患病率估计为 14%。如果患者未接受辅助激素治疗（sHR = 0.31，p = 0.007）且存在 RILA≥12%（sHR = 0.45，p = 0.002），则发现≥2 级 bf +的风险显著降低。
结论
RILA 可显著预测乳房纤维化的风险。这项研究验证了 RILA 作为放疗前快速筛选试验的使用，并将改变我们在放射肿瘤学中的日常临床实践。
资助
法国国家癌症研究所（INCa）通过“医院临床研究计划（PHRC）”。
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