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表皮生长因子受体突变状态和表皮生长因子受体酪氨酸激酶抑制剂对非小细胞肺腺癌脑转移立体定向放射外科疗效的影响:133 例连续患者的回顾性分析。

Impacts of EGFR-mutation status and EGFR-TKI on the efficacy of stereotactic radiosurgery for brain metastases from non-small cell lung adenocarcinoma: A retrospective analysis of 133 consecutive patients.

机构信息

Division of Radiation Oncology, Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto-city, Nagano-prefecture, Japan.

Division of Radiation Oncology, Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto-city, Nagano-prefecture, Japan.

出版信息

Lung Cancer. 2018 May;119:120-126. doi: 10.1016/j.lungcan.2018.03.013. Epub 2018 Mar 14.

Abstract

OBJECTIVES

Recent advances in target therapies have prolonged overall survival (OS) for patients with epidermal growth factor receptor (EGFR)-mutant lung cancer. The impact of EGFR mutations on stereotactic radiosurgery (SRS) for brain metastases (BM) has yet to be determined. The present study sought to evaluate the efficacy and limitations of SRS, administered with EGFR-tyrosine kinase inhibitors (TKI), for BM from EGFR-mutant lung adenocarcinoma.

MATERIALS AND METHODS

This retrospective observational study analyzed data from patients with BM arising from EGFR-mutant lung adenocarcinoma who received upfront Gamma Knife SRS between December 2010 and April 2016. OS and distant and local intracranial disease control rates were calculated. The prognostic factors for each event were also determined.

RESULTS

One hundred thirty-three consecutive patients (47 males/86 females) were eligible. The median age was 69 years, and the median Karnofsky performance status (KPS) was 90. Sixty-six patients (50%) had no history of EGFR-TKI use at the time of SRS. EGFR-TKI were administered to 85% of EGFR-TKI naïve patients after SRS. One- and 2-year OS rates were 74% and 52%, respectively. One- and 2-year distant BM recurrence rates (per patient) after SRS were 34% and 53%, respectively. One- and 2-year rates of local tumor control (per lesion) were 97% and 95%, respectively. Multivariate proportional hazards analyses showed that being EGFR-TKI naïve was associated with longer OS (HR: 0.42, P < 0.001), a lower distant intracranial recurrence rate (HR: 0.61, P = 0.037) and a higher local tumor control rate (HR: 0.28, P = 0.001).

CONCLUSIONS

The present study demonstrated the upfront SRS strategy to offer a minimally invasive and effective treatment option for EGFR-mutant lung adenocarcinoma patients with limited BM. EGFR-TKI naïve patients were found to be a distinct subgroup for which a longer survival time and durable intracranial disease control can be expected.

摘要

目的

针对表皮生长因子受体(EGFR)突变型肺癌患者,靶向治疗的最新进展延长了总生存期(OS)。EGFR 突变对脑转移瘤(BM)立体定向放射外科(SRS)的影响仍有待确定。本研究旨在评估 EGFR 酪氨酸激酶抑制剂(TKI)联合 SRS 治疗 EGFR 突变型肺腺癌脑转移瘤的疗效和局限性。

材料与方法

本回顾性观察性研究分析了 2010 年 12 月至 2016 年 4 月期间接受伽玛刀 SRS 治疗的 EGFR 突变型肺腺癌脑转移瘤患者的数据。计算了 OS 和远处及局部颅内疾病控制率。还确定了每种事件的预后因素。

结果

共有 133 例连续患者(47 例男性/86 例女性)符合条件。中位年龄为 69 岁,中位卡氏功能状态评分(KPS)为 90。66 例(50%)在 SRS 时无 EGFR-TKI 应用史。SRS 后 85%的 EGFR-TKI 初治患者接受了 EGFR-TKI 治疗。SRS 后 1 年和 2 年的 OS 率分别为 74%和 52%。SRS 后 1 年和 2 年的远处脑转移瘤复发率(每位患者)分别为 34%和 53%。SRS 后 1 年和 2 年的局部肿瘤控制率(每个病灶)分别为 97%和 95%。多变量比例风险分析表明,EGFR-TKI 初治与更长的 OS 相关(HR:0.42,P<0.001)、更低的远处颅内复发率(HR:0.61,P=0.037)和更高的局部肿瘤控制率(HR:0.28,P=0.001)。

结论

本研究表明,对于 EGFR 突变型肺腺癌伴有限脑转移瘤的患者,SRS 策略为其提供了一种微创且有效的治疗选择。EGFR-TKI 初治患者是一个明显的亚组,他们可以预期更长的生存时间和持久的颅内疾病控制。

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