Department of Obstetrics and Gynaecology, Centre for Gynaecologic Oncology Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
Eur J Cancer. 2013 Oct;49(15):3191-201. doi: 10.1016/j.ejca.2013.06.013. Epub 2013 Jul 11.
To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy.
We used data of the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial in which 670 patients were randomly assigned to primary surgery or neoadjuvant chemotherapy. The primary outcome was overall survival. Ten baseline clinical and pathological characteristics were selected as potential biomarkers. Using Subpopulation Treatment Effect Pattern Plots (STEPP), biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection. We also combined selected biomarkers to form a multimarker treatment selection rule.
The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment, in terms of five-year survival (p for interaction: 0.008 and 0.016, respectively). Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours >45 mm benefited more from neoadjuvant chemotherapy. In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective. We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage, the potential five-year survival rate in the population of treated patients would be 27.3% (95% confidence interval (CI) 21.9-33.0), 7.8% higher than if all were treated with primary surgery, and 5.6% higher if all were treated with neoadjuvant chemotherapy.
Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial, we found in this exploratory analysis that patients with stage IIIC and less extensive metastatic tumours had higher survival with primary surgery, while patients with stage IV disease and large metastatic tumours had higher survival with neoadjuvant chemotherapy. For patients who did not meet these criteria, both treatment options led to comparable survival rates.
为了探究是否可以通过晚期卵巢癌患者的基线特征生物标志物来识别更受益于初次手术或新辅助化疗的亚组患者。
我们使用欧洲癌症研究与治疗组织（EORTC）55971 试验的数据，该试验中 670 名患者被随机分配至初次手术或新辅助化疗组。主要结局为总生存。选择 10 个基线临床和病理特征作为潜在的生物标志物。使用亚组治疗效果模式图（STEPP），与治疗具有统计学显著定性相加交互作用的标志物被认为对治疗选择具有潜在信息价值。我们还将选定的标志物组合起来形成一个多标志物治疗选择规则。
最大转移瘤大小和临床分期与治疗获益的程度（五年生存率）显著相关（交互作用的 p 值分别为 0.008 和 0.016）。肿瘤最大直径 ⩽45 mm 的 IIIC 期患者从初次手术中获益更多，而肿瘤最大直径 >45 mm 的 IV 期患者则从新辅助化疗中获益更多。肿瘤最大直径较大的 IIIC 期患者和转移灶较少的 IV 期患者，两种治疗方法同样有效。我们估计，根据最大转移瘤和临床分期选择治疗方法，治疗患者人群的潜在五年生存率为 27.3%（95%置信区间（CI）21.9-33.0），比所有患者均接受初次手术治疗时高 7.8%，比所有患者均接受新辅助化疗时高 5.6%。
尽管在 EORTC 55971 试验中，接受初次手术和新辅助化疗的卵巢癌患者总体生存情况相当，但我们在这项探索性分析中发现，肿瘤最大直径较小且转移灶范围较小的 IIIC 期患者接受初次手术治疗时生存率更高，而肿瘤最大直径较大且转移灶范围较大的 IV 期患者接受新辅助化疗时生存率更高。对于不符合这些标准的患者，两种治疗选择导致的生存率相似。
