Outcomes after combined modality therapy for EGFR-mutant and wild-type locally advanced NSCLC.
Outcomes after combined modality therapy for EGFR-mutant and wild-type locally advanced NSCLC.
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EGFR突变剂和野生型局部晚期NSCLC的合并方式治疗后的结果。
DOI：
10.1634/theoncologist.2011-0040
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Sequist LV
中科院分区：
文献类型：
--
作者：
Mak RH;Doran E;Muzikansky A;Kang J;Neal JW;Baldini EH;Choi NC;Willers H;Jackman DM;Sequist LV
表皮生长因子受体(EGFR)突变识别非小细胞肺癌(NSCLC)的一种独特的生物学亚型。EGFR突变的局部晚期非小细胞肺癌患者的治疗结果尚未得到很好的描述。我们对123例局部晚期NSCLC患者进行了包括胸部放射治疗(RT)在内的综合治疗，并对已知的EGFR突变状态的患者的结果进行了回顾分析。结果采用Kaplan-Meier分析、对数等级检验和多变量Cox回归模型进行比较。所有123名患者都接受了胸部放射治疗；25%的患者肿瘤有EGFR突变，94%的患者有III期疾病。总体而言，81%的患者在放疗的同时接受了化疗，55%的患者接受了手术切除。在中位随访时间为27.5个月的情况下，EGFR突变肿瘤患者的总存活率显著高于野生型肿瘤患者(2年估计：92.6%对69.0%；p=0.04)。两年无复发生存率(41.4%比35.8%；p=0.33)和远处复发率(63.7%比61.7%；p=0.39)没有显著差异。EGFR突变患者的2年局部复发率显著低于野生型患者(17.8%比41.7%；p=0.005)。多变量分析显示，EGFR突变基因型与降低LRR的风险相关(HR=0.44；95%CI，0.19-1.00；p=0.05)，但与OS无关，调整了手术和其他潜在混杂因素。我们观察到，接受RT治疗的局部晚期NSCLC的EGFR突变患者的LRR率低于EGFR野生型患者，这提出了EGFR突变可能增加对RT和/或化疗的敏感性的假设。联合治疗后突变状态与总存活率之间的关联不那么明显。我们的数据可作为未来前瞻性研究中EGFR基因分型结果的有用基线估计。
Epidermal growth factor receptor (EGFR) mutations identify a unique biological subtype of non-small cell lung cancer (NSCLC). Treatment outcomes for EGFR-mutant locally advanced NSCLC patients have not been well-described. We retrospectively examined outcomes after combined modality therapy including thoracic radiation therapy (RT) in 123 patients with locally advanced NSCLC and known EGFR mutation status. Outcomes were compared using Kaplan-Meier analysis, the log-rank test, and multivariate Cox regression models. All 123 patients underwent thoracic RT; 25% had tumors with EGFR mutations, and 94% had stage III disease. Overall 81% received chemotherapy concurrent with RT and 55% underwent surgical resection. With a median follow-up of 27.5 months, overall survival was significantly higher in patients with EGFR-mutant versus wild-type tumors (2-year estimate: 92.6% versus 69.0%; p=0.04). Two-year relapse-free survival (41.4% versus 35.8%; p=0.33) and distant recurrence rates (63.7% versus 61.7%; p=0.39) did not differ significantly by genotype. The 2-year locoregional recurrence rate (LRR) was significantly lower in EGFR-mutant versus wild-type patients (17.8% versus 41.7%; p=0.005). EGFR-mutant genotype was associated with decreased risk of LRR on multivariable analysis (HR=0.44; 95% CI, 0.19-1.00; p=0.05), but not OS, after adjusting for surgery and other potential confounders. We observed that EGFR-mutant patients with locally advanced NSCLC treated with RT had lower rates of LRR than EGFR wild-type patients, raising the hypothesis that EGFR mutations may confer sensitivity to RT and/or chemotherapy. The association between mutation status and overall survival after combined modality therapy was less robust. Our data may serve as a useful baseline estimate of outcomes by EGFR genotype for future prospective studies.
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