Surgery with Hyperthermic Intraperitoneal Chemotherapy After Response to Induction Chemotherapy in Patients with Peritoneal Metastasis of Gastric Cancer

Background: Gastric cancer (GC) with peritoneal metastases (PM) has a dismal prognosis and to date only a few management options have been reported. Of those, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after induction bidirectional intraperitoneal and systemic chemotherapy (BIPSC) appear as a promising treatment option for these patients. Outcome data including safety and efficacy of CRS with radical Gastrectomy and HIPEC after response to combination of laparoscopic HIPEC (LHIPEC) with BIPSC as an induction therapy in patients with PM of GC was evaluated in this retrospective observational study.

Methods: Diagnostic Laparoscopy was performed in 53 patients with PM of GC who admitted to the Center for Treatment of Peritoneal Surface Malignancies, Istanbul, between 2013 and 2016. Peritoneal cancer index (PCI), ascites status and cytology were determined. The patients underwent LHIPEC and then, BIPSC induction chemotherapy using intraperitoneal docetaxel (30 mg/m) and cisplatin (30 mg/m) and intravenous Docetaxel/Cisplatin/5-Fluorouracil (DCF) for 3 cycles. In selected patients, CRS with radical gastrectomy and HIPEC were performed after the response to induction therapy. BIPSC was continued for 3 more cycles with a dose reduction in an adjuvant setting.

Results: All LHIPEC procedures were uneventful with Grade 1-2 side effects (11/53, 20,8%). As a response to induction chemotherapy PCI was reduced from 19.6±8 (range, 6-39) to 13.6±9.8 (range, 1-39) (P<0.001). Ascites was detected in 55% (29 out of 53) and cytology was positive in 51% (27 out of 53) of the patients before induction chemotherapy. Ascites was completely abolished and all cytology became negative. Then, 34 of 53 (64.15%) patients underwent CRS with radical gastrectomy and HIPEC. CC0/1 resection was achieved in 22 (64.70%) of patients (P<0.05). The median survival time was 18.9±13.4 (95% CI: 15.2-22.6 months. Combined surgery and HIPEC related mortality occurred in 1 out of 34 patients (2.9%) due to developed diffuse intravascular coagulation at postoperative day 2. Grade 2 operative complications included biliary fistula in one, and duodenal stump leakage in two patients (8.7%). All of the fistula closed with conservative management. The median survival time was 18.9±13.4 months and the median progression-free survival time was 15.6±12.9 with 1-, 2-, and 5-year survival rates of 82.4%, 59% and 17.6% in patients with PM of GC. Multivariate analysis identified high peritoneal cancer index (P=0.000) and complete resection (P<0.05) as independent predictors for better progression-free and overall survival.

Conclusions: The best outcomes can be expected with optimal cytoreduction and limited peritoneal dissemination in response to induction chemotherapy. Knowledgeable selection of patients with PM of GC is essential to perform surgery with HIPEC safely with acceptable mortality and morbidity.