Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Eur J Cancer. 2013 Oct;49(15):3202-9. doi: 10.1016/j.ejca.2013.06.024. Epub 2013 Jul 15.
Accelerated radiotherapy (AR) improves the poor prognosis associated with epidermal growth factor receptor (EGFR) overexpression frequently seen in head and neck carcinomas. Combining AR with carbogen and nicotinamide (ARCON) counteracts enhanced tumour cell proliferation- and hypoxia-related radioresistance. The purpose of this study was to investigate if EGFR expression levels are associated with response to ARCON in patients with carcinoma of the larynx. Patients (N=272) with advanced stage larynx carcinoma were randomised between AR alone and ARCON. Paraffin-embedded biopsies from these patients were processed for immunohistochemical staining of EGFR. EGFR fraction was quantitated by automated image analysis and related to clinical outcome. A large variation was observed in EGFR fraction between tumours with expression levels ranging from 0 to 0.93 (median fraction 0.4). No difference in 5-year locoregional control was found between low and high EGFR expressing tumours in the AR arm (69% versus 75%), which is in line with the established effect of AR in EGFR overexpressing tumours. There was, however, a significant association in the ARCON arm: patients with low EGFR levels had a better 5-year locoregional control (88% versus 72% p=0.02) and disease-specific survival (92% versus 77% p=0.01). ARCON improved locoregional control relative to AR only in patients with low EGFR expression (hazard ratio (HR) 0.34 p=0.009). In conclusion, only in tumours with a low EGFR fraction, adding hypoxia modification to AR has an additive beneficial effect on outcome. EGFR expression is a predictive biomarker for the selection of patients that will or will not respond to ARCON.
加速放疗 (AR) 改善了头颈部癌中常见的表皮生长因子受体 (EGFR) 过表达所带来的不良预后。将 AR 与卡泊芬净和烟酰胺 (ARCON) 联合使用可以对抗肿瘤细胞增殖和缺氧相关的放射抵抗。本研究旨在探讨 EGFR 表达水平是否与喉癌患者对 AROCON 的反应相关。将 272 例晚期喉癌患者随机分为 AR 单独治疗组和 AROCON 治疗组。对这些患者的石蜡包埋活检进行 EGFR 免疫组化染色。通过自动图像分析定量 EGFR 分数，并与临床结果相关联。观察到肿瘤之间的 EGFR 分数存在很大差异，表达水平从 0 到 0.93（中位数分数为 0.4）。在 AR 组中，低 EGFR 表达和高 EGFR 表达的肿瘤之间 5 年局部区域控制率没有差异（69%对 75%），这与 AR 在 EGFR 过表达肿瘤中的作用一致。然而，在 AROCON 组中存在显著关联：低 EGFR 水平的患者 5 年局部区域控制率更好（88%对 72%，p=0.02）和疾病特异性生存率更高（92%对 77%，p=0.01）。与仅接受 AR 治疗相比，ARCON 仅在 EGFR 表达水平低的患者中改善了局部区域控制（风险比 (HR) 0.34，p=0.009）。结论是，只有在 EGFR 分数低的肿瘤中，将缺氧修饰物添加到 AR 中才会对结果产生附加的有益影响。EGFR 表达是选择对 AROCON 有反应或无反应的患者的预测生物标志物。
