Gynecological Department, Charité Medizinische Universität Berlin, Campus Virchow Klinikum, Berlin, Germany,
Ann Surg Oncol. 2014 Mar;21(3):955-62. doi: 10.1245/s10434-013-3347-1. Epub 2013 Nov 12.
Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression-free survival (PFS).
Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher's exact test, Kendall's tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan-Meier method.
At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601-0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68-75.25; and p = 0.044, HR 3.33, 95 % CI 1.03-10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22-42.19 and p = 0.036, OR 10.18, 95 % CI 1.16-88.69, respectively).
HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results.
上皮性卵巢癌（EOC）仍然是妇科恶性肿瘤死亡的主要原因。在原发性 EOC 中，肿瘤减灭术的彻底性和铂类药物反应是总生存（OS）的最重要预后因素。在复发的情况下，细胞减灭术的作用尚不清楚。一个关键问题是预测术前具有最佳手术结局的亚组患者。本研究的目的是分析 HE4 在上皮性卵巢癌患者首次复发时对手术结果和铂类药物反应的预测作用。次要目的是 HE4 对 OS 和无进展生存期（PFS）的预后作用。
73 名上皮性卵巢癌患者在二次细胞减灭术前采集血浆。共有 66.7%的患者行全子宫及双侧附件切除术；86.3%的患者对铂类药物治疗有反应。HE4 采用酶联免疫吸附试验检测。统计分析采用卡方检验、Fisher 确切检验、Kendall's tau b 检验和 Mann-Whitney U 检验。根据 Kaplan-Meier 方法估计 OS、PFS 率及相应的 95%置信区间（CI）。
当 HE4 截断值为 250 pMk 时，预测完全肉眼肿瘤清除的敏感性为 52%，特异性为 93.8%（p=0.001，95%CI 0.601-0.861）。血浆 HE4 浓度与铂类药物反应是 OS 的唯一独立预后因素（p<0.001，风险比[HR]18.77，95%CI 4.68-75.25；p=0.044，HR 3.33，95%CI 1.03-10.7）。与腹水一起，HE4 是手术结局的唯一独立预测因素（p=0.029，优势比[OR]7.2，95%CI 1.22-42.19；p=0.036，OR 10.18，95%CI 1.16-88.69）。
HE4 是复发性上皮性卵巢癌患者手术结局和 OS 的独立预测标志物。需要更大的人群研究来验证这些结果。
