Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON, Canada; Division of Gynecologic Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON, Canada.
Gynecol Oncol. 2020 Jul;158(1):218-228. doi: 10.1016/j.ygyno.2020.03.034. Epub 2020 May 6.
Heated intraperitoneal chemotherapy (HIPEC) has not been universally adopted at the time of interval cytoreductive surgery for primary epithelial ovarian cancer (EOC) despite evidence of a 12-month overall survival (OS) benefit in a recent landmark randomized trial. We performed a systematic review and meta-analysis to assess oncologic outcomes and perioperative morbidity following HIPEC among primary EOC patients.
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to August 2019, for observational and randomized studies of primary EOC patients undergoing HIPEC. We assessed risk of bias using the Institute of Health Economics Quality Appraisal Checklist for single-arm cohort studies, Newcastle-Ottawa Scale for comparative cohort studies, and Cochrane Collaboration's Tool for randomized trials. We qualitatively summarized survival outcomes and calculated the pooled proportion of 30-day grade III-IV morbidity and postoperative death.
We identified 35 articles including 2252 primary EOC patients; one study was a randomized trial, and only six studies included a comparator group of surgery alone. The timing, temperature, and chemotherapeutic agents used for HIPEC differed across studies. Reported OS was highly variable (3-year OS range: 46-77%); three comparative cohort studies and the sole randomized trial reported statistically significant survival benefits for HIPEC over surgery alone, while two comparative cohort studies did not. The pooled proportions for grade III-IV morbidity and postoperative death at 30 days were 34% (95% CI 20-52) and 0% (95% CI 0-5) respectively.
One randomized trial suggests that HIPEC at time of interval cytoreductive surgery should be considered in patients with primary EOC. However, there is significant heterogeneity in literature with respect to an appropriate HIPEC regimen, short- and long-term outcomes. High-quality prospective randomized trials are urgently needed to clarify the role of HIPEC in the first-line treatment of primary EOC.
尽管最近一项具有里程碑意义的随机试验表明，在间隔性细胞减灭术时进行加热腹腔内化疗（HIPEC）可使上皮性卵巢癌（EOC）患者的总生存期（OS）延长 12 个月，但该方法尚未在原发性 EOC 患者的间隔性细胞减灭术中得到普遍应用。我们进行了一项系统评价和荟萃分析，以评估原发性 EOC 患者接受 HIPEC 后的肿瘤学结果和围手术期发病率。
我们检索了 MEDLINE、EMBASE、Cochrane 对照试验中心注册库和 Cochrane 系统评价数据库，从建库至 2019 年 8 月，以评估接受 HIPEC 的原发性 EOC 患者的观察性和随机研究。我们使用单臂队列研究的卫生经济学研究所质量评估清单、比较队列研究的纽卡斯尔-渥太华量表和 Cochrane 协作的随机试验工具来评估偏倚风险。我们定性总结了生存结果，并计算了 30 天内 3 级-4 级发病率和术后死亡率的汇总比例。
我们共确定了 35 篇文章，包括 2252 名原发性 EOC 患者；其中一项研究为随机试验，仅有 6 项研究包括单独手术的对照组。HIPEC 的时间、温度和化疗药物在不同的研究中有所不同。报道的 OS 差异很大（3 年 OS 范围：46%-77%）；三项比较队列研究和唯一的随机试验报告了 HIPEC 与单独手术相比具有统计学显著的生存优势，而两项比较队列研究则没有。30 天内 3 级-4 级发病率和术后死亡率的汇总比例分别为 34%（95%CI 20%-52%）和 0%（95%CI 0%-5%）。
一项随机试验表明，在原发性 EOC 患者中，间隔性细胞减灭术时进行 HIPEC 应被考虑。然而，文献中关于合适的 HIPEC 方案、短期和长期结果存在显著异质性。迫切需要高质量的前瞻性随机试验来阐明 HIPEC 在原发性 EOC 一线治疗中的作用。
