Validation of a Radiosensitivity Molecular Signature in Breast Cancer
Validation of a Radiosensitivity Molecular Signature in Breast Cancer
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DOI：
10.1158/1078-0432.ccr-12-0891
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发表时间：
2012-09-15
影响因子：
11.5
通讯作者：
Torres-Roca, Javier F.
中科院分区：
文献类型：
--
作者：
Eschrich, Steven A.;Fulp, William J.;Torres-Roca, Javier F.
目的：之前，我们开发了一种放射敏感性分子特征[放射敏感性指数（RSI）]，并在118例患者的3个独立数据集（直肠、食管和头颈部）中进行了临床验证。在这里，我们在放疗（RT）治疗的乳腺癌患者中检测RSI。实验设计：RSI在2个先前发表的乳腺癌数据集中进行了测试。患者在卡罗林斯卡大学医院（n = 159）和伊拉斯谟医疗中心（n = 344）接受治疗。RSI应用如前所述。结果：我们在接受rt治疗的患者中检测了RSI （Karolinska）。与放射耐药（RR）患者相比，预测放射敏感（RS）患者的5年无复发生存率提高（95%对75%，P = 0.0212），但未经RT治疗的RS/RR患者之间没有差异（71%对77%，P 0.6744），与RSI是RT特异性的（相互作用项RSI x RT， P = 0.05）一致。同样，在Erasmus数据集中，接受RT治疗的RS患者的5年无远处转移生存率优于RR患者（77%对64%，P = 0.0409），但未接受RT治疗的患者无差异（RS对RR， 80%对81%，P = 0.9425）。多变量分析显示，RSI是rt治疗患者中最强的变量（Karolinska, HR 5.53, P = 0.0987; Erasmus, HR = 1.64, P = 0.0758），而在反向选择（去除a = 0.10）中，RSI是最终模型中唯一剩余的变量。最后，RSI是rt治疗ER+患者预后的独立预测因子（Erasmus，多变量分析，HR = 2.64, P = 0.0085）。结论：RSI在2个独立的乳腺癌数据集中得到了验证，总计503例患者。包括先前的数据，RSI在5个独立队列（621例患者）中得到验证，据我们所知，它代表了放射肿瘤学中最广泛验证的分子特征。临床癌症研究；十八(18);5134 - 43。(c) 2012年AACR。
Purpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients.Experimental Design: RSI was tested in 2 previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n = 159) and Erasmus Medical Center (n = 344). RSI was applied as previously described.Results: We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5-year relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, P = 0.0212), but there was no difference between RS/RR patients treated without RT (71% vs. 77%, P 0.6744), consistent with RSI being RT-specific (interaction term RSI x RT, P = 0.05). Similarly, in the Erasmus dataset, RT-treated RS patients had an improved 5-year distant metastasis-free survival over RR patients (77% vs. 64%, P = 0.0409), but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, P = 0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, HR 5.53, P = 0.0987, Erasmus, HR = 1.64, P = 0.0758) and in backward selection (removal a of 0.10), RSI was the only variable remaining in the final model. Finally, RSI is an independent predictor of outcome in RT-treated ER+ patients (Erasmus, multivariable analysis, HR = 2.64, P = 0.0085).Conclusions: RSI is validated in 2 independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in 5 independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology. Clin Cancer Res; 18(18); 5134-43. (c) 2012 AACR.