Radiotherapy in lung adenocarcinoma with brain metastases: Effects of activating epidermal growth factor receptor mutations on clinical response
Radiotherapy in lung adenocarcinoma with brain metastases: Effects of activating epidermal growth factor receptor mutations on clinical response
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DOI：
10.1158/1078-0432.ccr-07-1468
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发表时间：
2008-01-01
影响因子：
11.5
通讯作者：
Yang, Pan-Chyr
中科院分区：
文献类型：
--
作者：
Gow, Chien-Hung;Chien, Chun-Ru;Yang, Pan-Chyr
目的：全脑放射治疗（WBRT）已被应用于肺腺癌脑转移瘤的不可手术治疗。最近，一项体外研究显示，与野生型相比，突变型表皮生长因子受体（EGFR）肺癌细胞系在电离辐射下的克隆存活率降低。为了阐明EGFR突变在放射治疗中的作用，我们评估了WBRT的临床反应和肺腺癌患者的生存率与脑metabolis.Experimental Design：这是一个回顾性分析63例肺腺癌脑转移瘤患者接受WBRT治疗的人口统计学数据，EGFR突变状态，WBRT反应和生存数据进行了收集。在WBRT开始后1个月评估临床应答。使用单变量和逻辑回归模型检验与临床应答相关的潜在预测因素。Log-rank检验和考克斯回归分析，以确定影响survival.Results的因素：临床反应WBRT观察29例（46%），与34名无反应患者（54%）。EGFR突变患者对WBRT的缓解率高于野生型患者（54% vs 24%; P = 0.045）。EGFR酪氨酸激酶抑制剂的施用（P = 0.034）和EGFR突变（P = 0.029）与WBRT应答独立相关。在考克斯回归分析中，WBRT应答者（P = 0.010）和无颅外转移（P = 0.002）与更好的生存率相关。EGFR突变和WBRT期间EGFR TKI的给药是肺腺癌脑转移患者WBRT反应的独立预测因素。
Purpose: Whole-brain radiation therapy (WBRT) has been applied to inoperable brain metastases in lung adenocarcinoma. Recently, an in vitro study showed reduced clonogenic survival of mutant epidermal growth factor receptor (EGFR) lung cancer cell lines in response to ionizing radiation compared with that of the wild type. To elucidate the role of EGFR mutations in radiation treatment, we evaluated the clinical response to WBRT and survival of lung adenocarcinoma patients with brain metastases.Experimental Design: This was a retrospective analysis of 63 patients with brain metastases from lung adenocarcinoma who were treated with WBRT Demographic data, EGFR mutation status, response to WBRT, and survival data were collected. Clinical response was assessed 1 month after the start of WBRT Univariate and logistic regression models were used to test potential predictive factors associated with clinical response. Log-rank test and Cox regression were analyzed to identify factors that affected survival.Results: Clinical response to WBRT was observed in 29 patients (46%), with 34 nonresponder patients (54%). Patients with EGFR mutations had higher response rates to WBRTcompared with those with the wild-type (54% versus 24%; P = 0.045). Both the administration of EGFR tyrosine kinase inhibitor (P = 0.034) and EGFR mutation (P = 0.029) were independently associated with response to WBRT In Cox regression analysis, WBRT responder (P = 0.010) and absence of extracranial metastases (P = 0.002) were associated with better survival.Conclusions: Both the EGFR mutations and the administration of EGFR TKI during WBRT were independent predictors of response to WBRT in brain metastases of lung adenocarcinoma.