Prognostic Analysis of Prophylactic Hyperthermic Intraperitoneal Chemotherapy for Advanced Gastric Cancer: a Propensity Score-Matched Analysis.

PURPOSE: To investigate the efficacy of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (AGC). METHODS: We included 198 patients treated from December 2016 to January 2019; of these patients, the 132 who had clinical T4 gastric cancer were divided into a hyperthermic intraperitoneal chemotherapy group (HIPEC group) and a radical gastrectomy and D2 lymph node dissection group (control group). Because this study was retrospective, we used propensity score matching (PSM) to reduce selectivity bias; we then assessed risk factors for recurrence and compared prognosis in terms of survival in the gastrectomy and prophylactic HIPEC groups. RESULTS: Prophylactic HIPEC reduced the risk of postoperative peritoneal metastasis (PM: 27.5% vs. 10.5%, P = 0.015) and did not increase the risk of postoperative complications, but there was no significant difference in the effect on hepatic metastases or other distant metastases. Risk factors for recurrence included pT4 staging and positive lymph node metastases. Both disease-free survival (DFS: HR 0.592; 95% CI 0.354-0.990; P = 0.042) and peritoneal recurrence-free survival (PFS: HR 0.314; 95% CI 0.127-0.774; P = 0.008) were better in the prophylactic HIPEC group than in the gastrectomy-only group. In addition, there was no difference in the prognosis of patients between the two groups of raltitrexed (RT) and paclitaxel (PTX) for perfusion dosing. CONCLUSION: Our study showed that prophylactic HIPEC could prevent postoperative PM in patients with AGC and did not increase the incidence of postoperative complications. However, it was not found to be effective in the prevention of other metastases, such as hepatic metastases.

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals.

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients.