Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

The peritoneum is a common site of metastasis in advanced gastric cancer (GC). Diagnostic laparoscopy is now routinely performed as part of disease staging, leading to an earlier diagnosis of synchronous peritoneal metastasis (PM). The biology of GCPM is unique and aggressive, leading to a dismal prognosis. These tumors tend to be resistant to traditional systemic therapy, and yet, this remains the current standard-of-care recommended by most international clinical guidelines. As this is an area of unmet clinical need, several translational studies and clinical trials have focused on addressing this specific disease state. Advances in genomic sequencing and molecular profiling have revealed several promising therapeutic targets and elucidated novel biology, particularly on the role of the surrounding tumor microenvironment in GCPM. Peritoneal-specific clinical trials are being designed with a combination of locoregional therapeutic strategies with systemic therapy. In this review, we summarize the new knowledge of cancer biology, advances in surgical techniques, and emergence of novel therapies as an integrated strategy emerges to address GCPM as a distinct clinical entity. 

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.21.02745?role=tab

Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis

Advances in the management of peritoneal malignancies

Despite promising results, the effectiveness of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer with peritoneal carcinomatosis (GCPC) has not been systematically evaluated. The aim of this systematic review is to compare the survival, complications and risk of recurrence between CRS + HIPEC versus CRS alone in GCPC. A systematic review was performed in MEDLINE and Web of Science according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Primary studies with patients with GCPC older than 18 years were included. Methodological Index for Non-randomized Studies (MINORS) criteria were used to assess the quality of the studies. We performed random-effects meta-analysis of risk ratios (RR). We assessed heterogeneity using the I2 statistic. Five studies were included in the qualitative and four in the quantitative analysis. The overall survival (OS) rate after 1 year was 3.65 times higher for CRS + HIPEC than CRS alone [RR = 3.65, 95% confidence interval (95% CI) = 1.01–13.26, I2 = 73%]. The OS rate after 5 years was more than three times higher for CRS + HIPEC than for CRS alone (RR = 3.25, 95% CI = 1.28–8.26, I2 = 8%). No significant differences between CRS + HIPEC and CRS alone related to complications were found (RR = 1.05, 95% CI = 0.83–1.33, I2 = 0%). The risk of peritoneal recurrence was significantly lower for CRS + HIPEC than for CRS alone (RR = 0.23, 95% CI = 0.11–0.48, I2 = 40%). The results may be associated with some information or indication bias. Results should be analysed cautiously given the detected heterogeneity and limitations of included studies. However, treatment with CRS + HIPEC seems to increase the survival of patients with GCPC, more than treatment with CRS alone, decrease the risk of peritoneal recurrence and not be associated with more complications. 

/pdf/impact-of-cytoreductive-surgery-with-hyperthermic-1wydydhj.pdf

Impact of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Gastric Cancer with Peritoneal Carcinomatosis: A Systematic Review and Meta-analysis

Abstract Objectives Peritoneal carcinomatosis is the most frequent site of metastases in patients with gastric cancer. Current standard treatment is palliative systemic chemotherapy with very poor prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) resulted in long-term benefits in selected patients. Among patients with peritoneal carcinomatosis, a distinctive subset is oligometastatic disease which is characterized by low metastatic burden. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a recent technique of intraperitoneal chemotherapy used in combination with systemic chemotherapy with promising results. Methods PIPAC VER-One is a prospective, randomized, multicenter phase III clinical trial that aims to evaluate the effectiveness of the use of PIPAC in combination with systemic chemotherapy in patients with gastric cancer and synchronous positive peritoneal cytology and/or limited peritoneal metastases (peritoneal cancer index [PCI] ≤6). Patients will be randomized into two arms: arm A (control) treated with standard systemic chemotherapy and arm B (experimental) treated with a bidirectional scheme including PIPAC and systemic chemotherapy. Results Primary endpoint is the secondary resectability rate. Secondary endpoints are: overall survival (OS), pregression-free survival (PFS), disease-free survival (DFS), histological response assessed both on primary tumor and peritoneal lesions, quality of life (QoL), complication rate (CTCAE v5), and incremental cost-effectiveness ratios (ICER). Conclusions The role of PIPAC in multimodal treatment for oligometastatic gastric cancer will be investigated in this trial.

/pdf/pressurized-intraperitoneal-aerosol-chemotherapy-pipac-in-2038t313.pdf

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in multimodal therapy for patients with oligometastatic peritoneal gastric cancer: a randomized multicenter phase III trial PIPAC VEROne

BACKGROUND The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.

Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study).

A Lintis

Papers

Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study).