Parikh Neil R, Likhacheva Anna, Pinnix Chelsea, Allen Pamela K, Prabhu Sujit S, Guha-Thakurta Nandita, Welsh James W, Brown Paul D, Chang Eric L
Department of Radiation Oncology, MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 97, Houston, TX 77030, USA.
Department of Neurosurgery, MD Anderson Cancer Center, 1400 Holcombe Blvd., Room FC7.2000, Unit 442, Houston, TX 77030, USA.
J Radiosurg SBRT. 2015;3(3):171-178.
Determine whether EGFR and KRAS mutations carry prognostic significance in non-small cell lung cancer (NSCLC) patients with brain metastases treated with stereotactic radiosurgery.
Ninety-four NSCLC patients with brain metastases initially treated with stereotactic radiosurgery were retrospectively reviewed. Both EGFR and KRAS mutation status were recorded in 67 patients: EGFR+/KRAS- status in 9 patients, EGFR-/KRAS+ in 15 patients, and EGFR-/KRAS- in 43 patients. Survival was determined using the Kaplan-Meier method. Cox regression was used to assess the effects of patient factors on overall survival, local control, and distant brain control - all from time of brain metastasis diagnosis.
Median overall survival from time of brain metastasis diagnosis was 30.6 months for EGFR+/KRAS- patients, 9.8 months for EGFR-/KRAS+ patients, and 19.1 months for EGFR-/KRAS- patients (p=0.094). Local control at 2 years was 100% for EGFR+/KRAS- patients, 66.7% for EGFR-/KRAS+ patients, and 97.2% for EGFR-/KRAS- patients (p=0.399). Distant brain control at 12 months was achieved in 66.7% of EGFR+/KRAS- patients, 30.0% of EGFR-/KRAS+ patients, and 73.7% of EGFR-/KRAS- patients (p=0.039). On multivariate analysis, the most important predictors of mortality were baseline DS-GPA>2 (HR=0.27; p=0.001), EGFR mutation positivity (HR=0.30; p=0.054), and KRAS mutation positivity (HR=2.12; p=0.056); the most important predictors of distant brain failure were KRAS status (HR=4.44; p=0.004) and extracranial disease (HR=3.28; p=0.058); there was no statistically significant multivariate model identified for local control.
In NSCLC patients with brain metastases, KRAS mutations portend higher rates of distant brain failure. Our data also suggests that EGFR portends better overall survival and KRAS portends worse overall survival, though this still needs to be verified by a larger study.
确定表皮生长因子受体（EGFR）和 Kirsten 大鼠肉瘤病毒癌基因（KRAS）突变在接受立体定向放射外科治疗的非小细胞肺癌（NSCLC）脑转移患者中是否具有预后意义。
回顾性分析了 94 例最初接受立体定向放射外科治疗的 NSCLC 脑转移患者。记录了 67 例患者的 EGFR 和 KRAS 突变状态：9 例为 EGFR+/KRAS-状态，15 例为 EGFR-/KRAS+，43 例为 EGFR-/KRAS-。采用 Kaplan-Meier 方法确定生存率。使用 Cox 回归评估患者因素对总生存期、局部控制和远处脑转移控制的影响——均从脑转移诊断时间开始计算。
从脑转移诊断时间起，EGFR+/KRAS-患者的中位总生存期为 30.6 个月，EGFR-/KRAS+患者为 9.8 个月，EGFR-/KRAS-患者为 19.1 个月（p = 0.094）。EGFR+/KRAS-患者 2 年时的局部控制率为 100%，EGFR-/KRAS+患者为 66.7%，EGFR-/KRAS-患者为 97.2%（p = 0.399）。EGFR+/KRAS-患者 12 个月时的远处脑转移控制率为 66.7%，EGFR-/KRAS+患者为 30.0%，EGFR-/KRAS-患者为 73.7%（p = 0.039）。多因素分析显示，死亡的最重要预测因素是基线诊断评分-分级预后评估（DS-GPA）>2（风险比[HR]=0.27；p = 0.001）、EGFR 突变阳性（HR = 0.30；p = 0.054）和 KRAS 突变阳性（HR = 2.12；p = 0.056）；远处脑转移失败的最重要预测因素是 KRAS 状态（HR = 4.44；p = 0.004）和颅外疾病（HR = 3.28；p = 0.058）；未发现用于局部控制的具有统计学意义的多因素模型。
在 NSCLC 脑转移患者中，KRAS 突变预示着更高的远处脑转移失败率。我们的数据还表明，EGFR 预示着更好的总生存期，KRAS 预示着更差的总生存期，不过这仍需更大规模的研究来验证。
