Department of Thoracic Oncology, University Hospital Heidelberg and Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Röntgenstr. 1, 69126, Heidelberg, Germany.
Department of Pathology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Med Oncol. 2018 Jun 15;35(7):106. doi: 10.1007/s12032-018-1169-5.
Prior studies have demonstrated an association between excision repair cross-complementation group 1 (ERCC1) expression level and outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. The aim of this study was to assess the impact of ERCC1 on survival for patients with stage IIIB/IV non-squamous NSCLC (NS-NSCLC) enrolled in the INNOVATIONS trial, thus receiving as treatment either erlotinib/bevacizumab (EB) or cisplatin/gemcitabine/bevacizumab (PGB). We retrospectively analyzed tumor tissue of 72 patients using immunohistochemistry to assess the expression of ERCC1. The distribution between treatment arms was equal (36 patients each). Two different H scores were calculated and correlated with survival. In ERCC1-positive patients, no significant difference in terms of progression-free survival (PFS) between treatment arms has been detected. ERCC1-negative patients benefited from PGB compared to EB arm (H score: HR = 0.377, 95% CI [0.167-0.849], p = 0.0151; modified H score: HR = 0.484, 95% CI [0.234-1.004], p = 0.0468). With respect to the scoring system, in the EB-arm, a significant superior PFS turned out in ERCC1-positive patients when employing the H-score (HR = 0.430, 95% CI [0.188-0.981], p = 0.0397; median 4.9 vs. 3.9 months), but not with the modified H-score. Our findings support the hypothesis that NS-NSCLC displaying a low ERCC1 expression might benefit from cisplatin-based chemotherapy. High expression indicated better PFS in the EB arm supporting the prognostic impact. However, as impact of ERCC1-assessment even might depend on scoring systems differences, the need in standardization of assessment methodology is emphasized.
先前的研究表明，切除修复交叉互补基因 1（ERCC1）表达水平与接受铂类化疗的晚期非小细胞肺癌（NSCLC）患者的结局有关。本研究旨在评估 ERCC1 对 INNOVATIONS 试验中入组的 IIIB/IV 期非鳞状 NSCLC（NS-NSCLC）患者生存的影响，这些患者接受厄洛替尼/贝伐单抗（EB）或顺铂/吉西他滨/贝伐单抗（PGB）治疗。我们使用免疫组织化学法对 72 例患者的肿瘤组织进行了回顾性分析，以评估 ERCC1 的表达。治疗组之间的分布是相等的（每组 36 例）。计算了两种不同的 H 评分并与生存相关联。在 ERCC1 阳性患者中，未检测到治疗组之间无进展生存期（PFS）的显著差异。与 EB 组相比，ERCC1 阴性患者从 PGB 治疗中获益（H 评分：HR=0.377，95%CI[0.167-0.849]，p=0.0151；改良 H 评分：HR=0.484，95%CI[0.234-1.004]，p=0.0468）。就评分系统而言，在 EB 组中，当使用 H 评分时，ERCC1 阳性患者的 PFS 显著提高（HR=0.430，95%CI[0.188-0.981]，p=0.0397；中位 4.9 个月 vs. 3.9 个月），而改良 H 评分则不然。我们的研究结果支持这样的假设，即表达低水平 ERCC1 的 NS-NSCLC 可能受益于基于顺铂的化疗。高表达在 EB 组中提示 PFS 更好，支持预后影响。然而，由于 ERCC1 评估的影响甚至可能取决于评分系统的差异，因此强调需要标准化评估方法。
