Dominique Elias

The peritoneum is one of the most frequent sites of recurrent gastric carcinoma after curative treatment, despite the administration of pre- and/or postoperative systemic chemotherapy. Indeed, the prognosis of peritoneal carcinomatosis from gastric carcinoma continues to be poor, with a median survival of less than one year with systemic chemotherapy. Whereas the prognosis of peritoneal carcinomatosis from colorectal cancer has changed with the development of locally administered hyperthermic intraperitoneal chemotherapy (HIPEC), survival results following carcinomatosis from gastric cancer remain disappointing, yielding a 5-year survival rate of less than 20%. Innovative surgical therapies such as intraperitoneal immunotherapy therefore need to be developed for the immediate postoperative period after complete cytoreductive surgery. In a recent randomised study, a clinical effect was obtained after intraperitoneal infusion of catumaxomab in patients with malignant ascites, notably from gastric carcinoma. Catumaxomab, a nonhumanized chimeric antibody, is characterized by its unique ability to bind to three different types of cells: tumour cells expressing the epithelial cell adhesion molecule (EpCAM), T lymphocytes (CD3) and also accessory cells (Fcγ receptor). Because the peritoneum is an immunocompetent organ and up to 90% of gastric carcinomas express EpCAM, intraperitoneal infusion of catumaxomab after complete resection of all macroscopic disease (as defined in the treatment of carcinomatosis from colorectal cancer) could therefore efficiently treat microscopic residual disease. The aim of this randomized phase II study is to assess 2-year overall survival after complete resection of limited carcinomatosis synchronous with gastric carcinoma, followed by an intraperitoneal infusion of catumaxomab with different total doses administered in each of the 2 arms. Close monitoring of peri-opertive mortality, morbidity and early surgical re-intervention will be done with stopping rules. Besides this analysis, translational research will be conducted to determine immunological markers of catumaxomab efficacy and to correlate these markers with clinical efficacy.

The decision to perform optimal surgery when peritoneal metastases (PM) are associated with liver metastases (LM) is extremely complex. No guidelines exist. The purpose of this study was to present a simple and useful statistical tool that generates a graphical calculator (nomogram) to help the clinician rapidly estimate individualized patient-specific survival before undergoing optimal surgery. An analysis of 287 patients with liver metastasis (LM), 119 patients with peritoneal metastasis (PM), and 37 patients with LM + PM, who underwent optimal surgery plus chemotherapy between 1995 and 2010 was performed. A minimal number of parameters were taken into account to obtain a nomogram that would be very simple to use. With the overall tumor load as the main prognostic factor, we included the number of lesions for LM and the peritoneal carcinomatosis score (PCI) for PM. The Cox model was used to generate the nomogram. The 5-year overall survival was, respectively, 38.5, 36.5, and 26.4 % in the LM group, the PM group, and the LM + PM group. The summation of 3 parameters (the number of LM, the PCI, and the type of surgery [liver resection, HIPEC, or both]), makes it easy to calculate a score that graphically corresponds to an estimation of survival after optimal surgery (nomogram). It can be used for LM alone, PM alone, or both. A graphic nomogram that is simple to calculate and easy to use enables us to rapidly appreciate the prognosis of patients according to the number of LM, the PCI, or both. This nomogram must be validated in prospective studies in other tertiary centers.