Highlights
- •Hyperthermic intraperitoneal chemotherapy has been proposed within various multimodality strategies for both the prevention and treatment of gastric cancer peritoneal carcinomatosis.
- •The present work aims to clarify the potential role of hyperthermic intraperitoneal chemotherapy in gastric cancer at different stages of peritoneal disease progression.
- •A survival advantage of 4 month is seen with the use of HIPEC as a prophylactic strategy.
Abstract
Importance
Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used within various multimodality
strategies for the prevention and treatment of gastric cancer peritoneal carcinomatosis.
Objective
To systematically evaluate the role of HIPEC in gastric cancer and clarify its effectiveness
at different stages of peritoneal disease progression.
Data sources
Medline and Embase databases between January 1, 1985 and June 1, 2016.
Study selection
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.
Data extraction and synthesis
A random-effects network meta-analysis.
Main outcomes and measures
The primary outcomes were overall survival and disease recurrence. Secondary outcomes
were overall complications, type of complications, and sites of recurrence.
Results
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.
Conclusions
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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
2012 G. Estimated cancer incidence, mortality and prevalence worldwide. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx; [Accessed 10 August 2016].
- Advanced gastric cancer: what we know and what we still have to learn.World J Gastroenterol. 2016; 22: 1139-1159
- The treatment of peritoneal carcinomatosis in advanced gastric cancer: state of the art.Int J Surg Oncol. 2014; 2014: 912418
- Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer.J Clin Oncol. 2003; 21: 3737-3743
- Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial.Gynecol Oncol. 2011; 122: 215-220
- Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C.Cancer. 1988; 61: 232-237
- Cochrane handbook for systematic reviews of interventions version 5.1.0.The Cochrane Collaboration, 2011 ([updated March 2011] Available from:)
- Methodological index for non-randomized studies (minors): development and validation of a new instrument.ANZ J Surg. 2003; 73: 712-716
- Laparoscopic versus open distal gastrectomy for gastric cancer: a meta-analysis of randomized controlled trials and high-quality nonrandomized studies.Ann Surg. 2012; 255: 446-456
- The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.Ann Intern Med. 2009; 151: W65-W94
- Meta-analysis in clinical trials revisited.Contemp Clin Trials. 2015; 45: 139-145
- Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188
- Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study.Hepatogastroenterology. 2001; 48: 1776-1782
- Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma.Cancer. 1999; 85: 529-534
- Effects of continuous hyperthermic peritoneal perfusion on prognosis of gastric cancer with serosal invasion.Eur J Surg. 1995; 161: 581-586
- Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of gastric cancer. Final results of a randomized controlled study.Cancer. 1994; 73: 2048-2052
- Continuous hyperthermic peritoneal perfusion for the prevention of peritoneal recurrence of gastric cancer: randomized controlled study.World J Surg. 1994; 18: 150-155
- Hyperthermic peritoneal perfusion combined with anticancer chemotherapy as prophylactic treatment of peritoneal recurrence of gastric cancer.Hepatogastroenterology. 1989; 36: 75-78
- Effect of neoadjuvant chemotherapy combined with hyperthermic intraperitoneal perfusion chemotherapy on advanced gastric cancer.Exp Ther Med. 2014; 7: 1083-1088
- Fibrin-sealant-delivered cisplatin chemotherapy versus cisplatin hyperthermic intraperitoneal perfusion chemotherapy for locally advanced gastric cancer without peritoneal metastases: a randomized phase-II clinical trial with a 40-month follow-up.Cell Biochem Biophys. 2015; 71: 1171-1180
- Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial.J Surg Oncol. 2014; 110: 275-284
- Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial.Ann Surg Oncol. 2011; 18: 1575-1581
- Prophylaxis with intraoperative chemohyperthermia against peritoneal recurrence of serosal invasion-positive gastric cancer.World J Surg. 1995; 19 (discussion 455): 450-454
- Intraoperative hyperthermic intraperitoneal chemotherapy as adjuvant chemotherapy for advanced gastric cancer patients with serosal invasion.J Chin Med Assoc. 2013; 76: 425-431
- Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer: evaluation by multivariate regression analysis.Oncology. 1999; 57: 106-114
- Hyperthermic intraperitoneal chemoperfusion in combined treatment of locally advanced and disseminated gastric cancer: results of a single-centre retrospective study.Int J Hyperth. 2014; 30: 159-165
- Lack of efficacy of prophylactic continuous hyperthermic peritoneal perfusion on subsequent peritoneal recurrence and survival in patients with advanced gastric cancer.Surgery. 2002; 131: 521-528
- Efficacy and safety of intraoperative peritoneal hyperthermic chemotherapy for advanced gastric cancer patients with serosal invasion. A long-term follow-up study.Dig Surg. 2006; 23: 93-102
- Continuous hyperthermic peritoneal perfusion for peritoneal dissemination of gastric cancer.Hepatogastroenterology. 1998; 45: 2079-2086
- Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer.Ann Surg. 1990; 212: 592-596
- Improved mortality rate of gastric carcinoma patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic chemoperfusion combined with surgery.Cancer. 1997; 79: 884-891
- Costs and clinical outcome of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from gastric cancer.Acta Oncol. 2012; 51: 112-121
- Peritoneal carcinomatosis in patients with gastric cancer, and the role for surgical resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy.Am J Surg. 2014; 207: 78-83
- Therapeutic outcomes of continuous hyperthermic peritoneal perfusion against advanced gastric cancer with peritoneal carcinomatosis.Hepatogastroenterology. 2006; 53: 473-478
- Surgical resection with hyperthermic intraperitoneal chemotherapy for gastric cancer patients with peritoneal dissemination.J Surg Oncol. 2010; 102: 361-365
- Clinical study of cisplatin hyperthermic intraperitoneal perfusion chemotherapy in combination with docetaxel, 5-fluorouracil and leucovorin intravenous chemotherapy for the treatment of advanced-stage gastric carcinoma.Hepatogastroenterology. 2013; 60: 989-994
- Impact of intra-operative intraperitoneal chemotherapy on organ/space surgical site infection in patients with gastric cancer.J Hosp Infect. 2015; 91: 237-243
- Effectiveness of continuous hyperthermic peritoneal perfusion for the peritoneal dissemination of gastric cancer.Gan To Kagaku Ryoho. 2002; 29: 2168-2173
- Clinical result of intraperitoneal hyperthermic chemoperfusion for gastric cancer with serosal invasion to prevent peritoneal recurrence.Gan To Kagaku Ryoho. 1998; 25: 1436-1438
- Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for advanced gastric cancer.J Gastrointest Surg. 2004; 8: 454-463
- Clinical evaluation of intraperitoneal hyperthermic perfusion in far-advanced gastric cancer.Gan To Kagaku Ryoho. 1989; 16: 2726-2729
- Clinical evaluation of intra-peritoneal hyperthermic perfusion under hypothermic general anesthesia for advanced gastric cancer.Gan To Kagaku Ryoho. 1991; 18: 1804-1807
- Survival time and prevention of side effects of intraperitoneal hyperthermic perfusion with mitomycin C combined with surgery for patients with advanced gastric cancer.Cancer Treat Res. 1996; 81: 169-176
- Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.Nat Med. 2015; 21: 449-456
- Prognostic and therapeutic values of peritoneal cytology in gastric cancer.Acta Cytol. 1978; 22: 225-229
- Relationship between the cytologic characteristics of intraperitoneal free cancer cells and the prognosis in patients with gastric cancer.Acta Cytol. 1990; 34: 437-442
- Relation between clinical and histologic outcome of intraperitoneal hyperthermic perfusion for patients with gastric cancer and peritoneal metastasis.Oncology. 1993; 50: 338-343
- Histologic changes induced by intraperitoneal chemotherapy with 5-fluorouracil and mitomycin C in patients with peritoneal carcinomatosis from cystadenocarcinoma of the colon or appendix.Cancer. 1990; 65: 1495-1501
- Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by complete resection and intraperitoneal chemotherapy.Cancer. 2001; 92: 71-76
- Intraperitoneal chemo-hyperthermia with mitomycin C for gastric cancer patients with peritoneal carcinomatosis.Anticancer Res. 1999; 19: 1375-1382
- Indications for early postoperative intraperitoneal chemotherapy of advanced gastric cancer: results of a prospective randomized trial.World J Surg. 2001; 25: 985-990
- Intraperitoneal chemohyperthermia: rationale, technique, indications, and results.Surg Oncol Clin N Am. 2001; 10 ([xi]): 915-933
- Long-term survival is improved by an extended lymph node dissection in potentially curable gastric cancer.Hepatogastroenterology. 2002; 49: 1167-1171
- Prospective morbidity and mortality assessment of cytoreductive surgery plus perioperative intraperitoneal chemotherapy to treat peritoneal dissemination of appendiceal mucinous malignancy.Ann Surg Oncol. 2006; 13: 635-644
- GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study.BMC Cancer. 2014; 14: 183
- Extensive intraoperative peritoneal lavage as a standard prophylactic strategy for peritoneal recurrence in patients with gastric carcinoma.Ann Surg. 2009; 250: 242-246
Article info
Publication history
Published online: April 26, 2017
Accepted:
March 26,
2017
Received in revised form:
March 9,
2017
Received:
December 15,
2016
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.
