表皮生长因子受体突变型非小细胞肺癌患者：更易发生骨和脑转移？
EGFR mutated non-small cell lung cancer patients: more prone to development of bone and brain metastases?
机构信息
Department of Pulmonary Diseases, Maastricht University Medical Center+, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
Department of Pulmonary Diseases, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
出版信息
Lung Cancer. 2014 Apr;84(1):86-91. doi: 10.1016/j.lungcan.2014.01.006. Epub 2014 Jan 23.
OBJECTIVES
Both bone and brain are frequent sites of metastasis in non-small cell lung cancer (NSCLC). Conflicting data exist whether EGFR mutant (+) patients are more prone to develop brain metastases or have a better outcome with brain metastases compared to EGFR/KRAS wildtype (WT) or KRAS+ patients. For bone metastases this has not been studied.
METHODS
In this retrospective case-control study all EGFR+ (exons 19 and 21) patients diagnosed at two pathology departments were selected (2004/2008 to 2012). For every EGFR+ patient a consecutive KRAS+ and WT patient with metastatic NSCLC (mNSCLC) was identified. Patients with another malignancy within 2 years of mNSCLC diagnosis were excluded. Data regarding age, gender, performance score, histology, treatment, bone/brain metastases diagnosis, skeletal related events (SRE) and subsequent survival were collected.
RESULTS
189 patients were included: 62 EGFR+, 65 KRAS+, 62 WT. 32%, 35% and 40%, respectively, had brain metastases (p=0.645). Mean time to brain metastases was 20.8 [± 12.0], 10.8 [± 9.8], 16.4 [± 10.2] months (EGFR+-KRAS+, p = 0.020, EGFR+-WT, p = 0.321). Median post brain metastases survival was 12.1 [5.0-19.1], 7.6 [1.2-14.0], 10.7 [1.5-19.8] months (p = 0.674). 60%, 52% and 50% had metastatic bone disease (p=0.528). Mean time to development of metastatic bone disease was 13.4 [± 10.6], 23.3 [± 19.4], 16.4 [± 9.6] months (p = 0.201). Median post metastatic bone disease survival was 15.0 [10.6-20.3], 9.0 [5.2-12.9], 3.2 [0.0-6.9] months (p = 0.010). Time to 1st SRE was not significantly different.
CONCLUSIONS
Incidence of brain and bone metastases was not different between EGFR+, KRAS+ and WT patients. Post brain metastases survival, time from mNSCLC diagnosis to metastatic bone disease and 1st SRE did not differ either. Post metastatic bone disease survival was significantly longer in EGFR+ patients. Although prevention of SRE's is important for all patients, the latter finding calls for a separate study for SRE preventing agents in EGFR+ patients.
目的
非小细胞肺癌（NSCLC）常发生骨和脑转移。目前尚存在争议，即与 EGFR/KRAS 野生型（WT）或 KRAS+患者相比，EGFR 突变（+）患者是否更容易发生脑转移，或发生脑转移后结局更好。对于骨转移，目前尚未进行相关研究。
方法
本回顾性病例对照研究纳入了在两个病理科诊断为 EGFR+（外显子 19 和 21）的所有患者（2004/2008 年至 2012 年）。对于每例 EGFR+患者，均选择了连续的 EGFR/KRAS+和 WT 转移性 NSCLC（mNSCLC）患者。排除 mNSCLC 诊断后 2 年内患有其他恶性肿瘤的患者。收集了患者的年龄、性别、体能状态评分、组织学、治疗、骨/脑转移诊断、骨骼相关事件（SRE）和随后的生存情况。
结果
共纳入 189 例患者：62 例 EGFR+，65 例 KRAS+，62 例 WT。分别有 32%、35%和 40%（p=0.645）发生脑转移。脑转移的中位时间分别为 20.8 [± 12.0]、10.8 [± 9.8]、16.4 [± 10.2] 个月（EGFR+-KRAS+，p = 0.020，EGFR+-WT，p = 0.321）。脑转移后的中位生存时间分别为 12.1 [5.0-19.1]、7.6 [1.2-14.0]、10.7 [1.5-19.8] 个月（p = 0.674）。分别有 60%、52%和 50%发生了骨转移（p=0.528）。骨转移的中位时间分别为 13.4 [± 10.6]、23.3 [± 19.4]、16.4 [± 9.6] 个月（p = 0.201）。骨转移后的中位生存时间分别为 15.0 [10.6-20.3]、9.0 [5.2-12.9]、3.2 [0.0-6.9] 个月（p = 0.010）。首次 SRE 的时间无显著差异。
结论
EGFR+、KRAS+和 WT 患者的脑转移和骨转移发生率无差异。脑转移后的生存时间、从 mNSCLC 诊断到发生骨转移的时间以及首次 SRE 时间也无差异。EGFR+患者发生骨转移后的生存时间显著更长。虽然预防 SRE 对所有患者都很重要，但这一发现需要对 EGFR+患者的 SRE 预防药物进行单独研究。
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