RTOG 0617 是针对不可切除III A/IIIB期非小细胞肺癌患者的III期随机试验，比较了标准剂量（60Gy）和高剂量（74Gy）放射治疗和化疗，加或不加曲妥昔单抗的效果。虽然该研究结果为阴性，但基于之前的证据表明，具有KRAS变异体，一种遗传性生殖突变，有益于曲妥昔单抗治疗的患者，我们评估了RTOG 0617中的KRAS变异体患者。从RTOG 0617收集的328/496（66%）名患者纳入了这个分析。对于事件发生时间结果，我们使用分层log-rank检验和多变量Cox回归模型。对于二元结果，我们使用Cochran-Mantel-Haenzel检验和多变量logistic回归模型。所有统计检验是双侧的，当p值<0.05时被认为是显著的。 共有17.1%（56/328）名患者具有KRAS变异体，KRAS变异体患者和非变异体患者的总体生存率相似。然而，只有在KRAS变异体患者中才观察到曲妥昔单抗的时间依赖性效应 - 在第一年内，接受曲妥昔单抗治疗的患者的死亡风险更高（HR = 3.37，95％CI：1.13-10.10，p = 0.030），而在第一年至第四年期间，死亡风险较低（HR = 0.33，95％CI：0.11-0.97，p = 0.043）。相反，在非变异体患者中，曲妥昔单抗的加入明显增加了局部失败的风险（HR = 1.59，95％CI：1.11-2.28，p = 0.012）。 尽管KRAS变异体患者未获得总体生存优势，但曲妥昔单抗对这个基因亚组的患者可能有潜在影响。相反，曲妥昔单抗似乎对非变异体患者有害。这些发现进一步支持了在研究将全身药物加入放射治疗时进行基因患者选择的重要性。

RTOG 0617 was a Phase III randomized trial for patients with unresectable stage IIIA/IIIB non-small-cell lung cancer comparing standard-dose (60Gy) versus high-dose (74Gy) radiotherapy and chemotherapy, plus or minus cetuximab. Although the study was negative, based on prior evidence that patients with the KRAS-variant, an inherited germline mutation, benefit from cetuximab, we evaluated KRAS-variant patients in RTOG 0617.From RTOG 0617 328/496 (66%) of patients were included in this analysis. For time-to-event outcomes, stratified log-rank tests and multivariable Cox regression models were used. For binary outcomes, Cochran-Mantel-Haenzel tests and multivariable logistic regression models were used. All statistical tests were two-sided, and a p-value <0.05 was considered significant.A total of 17.1% (56/328) of patients had the KRAS-variant, and overall survival rates were similar between KRAS-variant and non-variant patients. However, there was a time-dependent effect of cetuximab seen only in KRAS-variant patients - while the hazard of death was higher in cetuximab treated patients within year one (HR=3.37, 95% CI: 1.13-10.10, p=0.030), death was lower from year one to four (HR=0.33, 95% CI: 0.11-0.97, p=0.043). In contrast, in non-variant patients, the addition of cetuximab significantly increased local failure (HR=1.59, 95% CI: 1.11-2.28, p=0.012).Although an overall survival advantage was not achieved in KRAS-variant patients, there is potential impact of cetuximab for this genetic subset of patients. In contrast, cetuximab seems to harm non-variant patients. These findings further support the importance of genetic patient selection in trials studying the addition of systemic agents to radiotherapy.