Desiderio Jacopo, Chao Joseph, Melstrom Laleh, Warner Susanne, Tozzi Federico, Fong Yuman, Parisi Amilcare, Woo Yanghee
Department of Surgery, City of Hope National Medical Centre, Duarte, CA, USA; Department of Digestive Surgery, St. Mary's Hospital, University of Perugia, Terni, Italy.
Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Centre, Duarte, CA, USA.
Eur J Cancer. 2017 Jul;79:1-14. doi: 10.1016/j.ejca.2017.03.030. Epub 2017 Apr 26.
Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used within various multimodality strategies for the prevention and treatment of gastric cancer peritoneal carcinomatosis.
To systematically evaluate the role of HIPEC in gastric cancer and clarify its effectiveness at different stages of peritoneal disease progression.
Medline and Embase databases between January 1, 1985 and June 1, 2016.
Randomised control trials and high-quality non-randomised control trials selected on a validated tool (methodological index for non-randomised studies) comparing HIPEC and standard oncological management for the treatment of advanced stage gastric cancer with and without peritoneal carcinomatosis were considered.
A random-effects network meta-analysis.
The primary outcomes were overall survival and disease recurrence. Secondary outcomes were overall complications, type of complications, and sites of recurrence.
A total of 11 RCTs and 21 non-randomised control trials (2520 patients) were included. For patients without the presence of peritoneal carcinomatosis (PC), the overall survival rates between the HIPEC and control groups at 3 or 5 years resulted in favour of the HIPEC group (risk ratio [RR] = 0.82, P = 0.01). No difference in the 3-year overall survival (RR = 0.99, P = 0.85) in but a prolonged median survival of 4 months in favour of the HIPEC group (WMD = 4.04, P < 0.001) was seen in patients with PC. HIPEC was associated with significantly higher risk of complications for both patients with PC (RR = 2.15, P < 0.01) and without (RR = 2.17, P < 0.01). This increased risk in the HIPEC group was related to systemic drugs toxicity. Anastomotic leakage rates were found to be similar between groups.
Our study demonstrates a survival advantage of the use of HIPEC as a prophylactic strategy and suggests that patients whose disease burden is limited to positive cytology and limited nodal involvement may benefit the most from HIPEC. For patients with extensive carcinomatosis, the completeness of cytoreductive surgery is a critical prognostic factor for survival. Future RCTs should better define patient selection criteria.
热灌注腹腔化疗（HIPEC）已被用于多种多模式策略中，以预防和治疗胃癌腹膜转移。
系统评价HIPEC在胃癌治疗中的作用，并阐明其在腹膜疾病进展不同阶段的有效性。
1985年1月1日至2016年6月1日期间的Medline和Embase数据库。
采用经过验证的工具（非随机研究方法学指数）筛选的随机对照试验和高质量非随机对照试验，比较HIPEC与标准肿瘤治疗方法对伴有或不伴有腹膜转移的晚期胃癌的治疗效果。
进行随机效应网络荟萃分析。
主要结局指标为总生存期和疾病复发。次要结局指标为总体并发症、并发症类型及复发部位。
共纳入11项随机对照试验和21项非随机对照试验（2520例患者）。对于无腹膜转移（PC）的患者，HIPEC组与对照组在3年或5年时的总生存率显示HIPEC组更具优势（风险比[RR]=0.82，P=0.01）。伴有PC的患者3年总生存率无差异（RR=0.99，P=0.85），但HIPEC组中位生存期延长4个月更具优势（加权均数差[WMD]=4.04，P<0.001）。HIPEC组伴有PC的患者（RR=2.15，P<0.01）和不伴有PC的患者（RR=2.17，P<0.01）发生并发症的风险均显著更高。HIPEC组这种风险增加与全身药物毒性有关。两组间吻合口漏发生率相似。
我们的研究表明，HIPEC作为一种预防性策略具有生存优势，提示疾病负担仅限于阳性细胞学检查和有限淋巴结受累的患者可能从HIPEC中获益最大。对于广泛转移的患者，细胞减灭术的彻底性是生存的关键预后因素。未来的随机对照试验应更好地明确患者选择标准。
