Association between EGFR-TKI resistance and efficacy of radiotherapy for brain metastases from EGFR-mutant lung adenocarcinoma.
Association between EGFR-TKI resistance and efficacy of radiotherapy for brain metastases from EGFR-mutant lung adenocarcinoma.
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发表时间：
2013-04
影响因子：
2
通讯作者：
H. Hirata;Katsumasa Nakamura;N. Kunitake;Y. Shioyama;Tomonari Sasaki;S. Ohga;Takeshi Nonoshita;T. Yoshitake;K. Asai;Kouji Inoue;A. Nagashima;M. Ono;H. Honda
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作者：
H. Hirata;Katsumasa Nakamura;N. Kunitake;Y. Shioyama;Tomonari Sasaki;S. Ohga;Takeshi Nonoshita;T. Yoshitake;K. Asai;Kouji Inoue;A. Nagashima;M. Ono;H. Honda
目的探讨表皮生长因子受体(EGFR)突变、对表皮生长因子受体酪氨酸激酶抑制剂(TKIs)获得性耐药的肺腺癌患者对放射治疗脑转移瘤的反应。患者和方法将47例患者分为三组：TKI-单纯EGFR突变组(n=11)、TKI耐药EGFR突变组(n=10)和EGFR-野生型组(n=26)。23例行立体定向放射治疗，24例行全脑放射治疗。结果耐药肿瘤患者放疗后3个月的有效率(11%)明显低于单纯肿瘤患者(82%，p=0.006)和野生型肿瘤患者(48%，p=0.1)。在单变量分析中，TKI耐药肿瘤患者的中枢神经系统无进展和总生存期显著短于TKI-naive患者(分别为p=0.018和p=0.005)。多变量分析显示，TKI抵抗是总体生存较差的独立预测因素(p=0.011)。结论TKIs获得性耐药可能与脑放疗疗效低下有关。
AIM To clarify how patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) respond to radiotherapy (RT) for brain metastases. PATIENTS AND METHODS Forty-seven patients were divided into the following three groups: a TKI-naïve group with EGFR mutation (n=11), a TKI-resistant group with EGFR mutation (n=10), and an EGFR-wild-type group (n=26). Patients received stereotactic RT (n=23) or whole-brain RT (n=24). RESULTS The response rate for patients with TKI-resistant tumor at three months after RT tended to be lower (11%) than that of those who were TKI-naïve (82%, p=0.006) and for patients with wild-type EGFR (48%, p=0.10). On univariate analysis, central nervous system progression-free and overall survival were significantly shorter for patients with TKI-resistant tumors than for those who were TKI-naïve (p=0.018 and p=0.005, respectively). Multivariate analysis showed that TKI resistance was an independent predictor of poorer overall survival (p=0.011). CONCLUSION Acquired resistance to TKIs appears to be associated with low efficacy of brain RT.