Cancers represent a significant global health burden, affecting millions of individuals each year

Background: Gastric cancer is a serious health issue both globally and in Kazakhstan. Worldwide, gastric cancer ranks fifth in incidence, with the highest rates reported in East Asia, the Andes of South America, and Eastern Europe, while the lowest rates are reported in North America, Northern Europe, Africa, and Southeast Asia. Over 70% of the cases occur in resource-limited countries. In Kazakhstan, gastric cancer ranks third in morbidity and second in mortality, representing a serious clinical and social problem. Annually, 1600 deaths from malignant gastric neoplasms are registered. Peritoneal metastasis is considered one of the most severe complications of gastric cancer and has long been regarded as its terminal stage. The average life expectancy of patients with peritoneal metastasis is only 3-6 months, reflecting a high mortality rate and the limited efficacy of current treatments. Objective: We hypothesize that the prophylactic use of pressurized intraperitoneal aerosol chemotherapy (PIPAC) may reduce the incidence of peritoneal metastasis. The aim of this study is to evaluate the incidence of peritoneal metastasis following prophylactic PIPAC in patients with gastric cancer. The primary goal of this research is to evaluate whether adding prophylactic PIPAC to standard treatment before neoadjuvant chemotherapy can reduce the incidence of peritoneal metastasis in patients with locally advanced gastric cancer. Methods: This study is a single-center nonrandomized controlled trial with a planned enrollment of 160 patients. All participants will be included in one of the 2 groups: intervention group (PIPAC + perioperative chemotherapy + gastrectomy with D2 lymphadenectomy) or control group (perioperative chemotherapy + gastrectomy with D2 lymphadenectomy). The primary end point is the incidence of peritoneal metastasis, and the secondary end points are overall survival, recurrence-free survival, treatment-related adverse events, and personal satisfaction. Results: As of September 2025, this study is funded and recruiting; 102 participants have already been enrolled. Recruitment is planned to be performed between January 2025 and December 2026. No interim analyses have been performed; primary results are planned for Q1 2027. The manuscript is expected to be published by Q4 2027. Conclusions: Compared to standard chemotherapy, PIPAC has been reported to significantly improve survival rates in patients with peritoneal metastasis of gastric origin. We suggest that the neoadjuvant use of PIPAC may reduce the incidence of peritoneal metastasis and improve long-term survival outcomes. The results of our study will provide key information on the practicality and viability of PIPAC as a prophylactic technique for preventing the progression of gastric cancer. Trial Registration: ClinicalTrials.gov NCT06784765; https://clinicaltrials.gov/study/NCT06784765 International Registered Report Identifier (IRRID): PRR1-10.2196/78053

BACKGROUND Gastric cancer is a serious health issue both globally and in Kazakhstan. Worldwide, gastric cancer ranks fifth in incidence, with the highest rates reported in East Asia, the Andes of South America, and Eastern Europe, while the lowest rates are reported in North America, Northern Europe, Africa, and Southeast Asia. Over 70% of the cases occur in resource-limited countries. In Kazakhstan, gastric cancer ranks third in morbidity and second in mortality, representing a serious clinical and social problem. Annually, 1600 deaths from malignant gastric neoplasms are registered. Peritoneal metastasis is considered one of the most severe complications of gastric cancer and has long been regarded as its terminal stage. The average life expectancy of patients with peritoneal metastasis is only 3-6 months, reflecting a high mortality rate and the limited efficacy of current treatments. OBJECTIVE We hypothesize that the prophylactic use of pressurized intraperitoneal aerosol chemotherapy (PIPAC) may reduce the incidence of peritoneal metastasis. The aim of this study is to evaluate the incidence of peritoneal metastasis following prophylactic PIPAC in patients with gastric cancer. The primary goal of this research is to evaluate whether adding prophylactic PIPAC to standard treatment before neoadjuvant chemotherapy can reduce the incidence of peritoneal metastasis in patients with locally advanced gastric cancer. METHODS This study is a single-center nonrandomized controlled trial with a planned enrollment of 160 patients. All participants will be included in one of the 2 groups: intervention group (PIPAC + perioperative chemotherapy + gastrectomy with D2 lymphadenectomy) or control group (perioperative chemotherapy + gastrectomy with D2 lymphadenectomy). The primary end point is the incidence of peritoneal metastasis, and the secondary end points are overall survival, recurrence-free survival, treatment-related adverse events, and personal satisfaction. RESULTS As of September 2025, this study is funded and recruiting; 102 participants have already been enrolled. Recruitment is planned to be performed between January 2025 and December 2026. No interim analyses have been performed; primary results are planned for Q1 2027. The manuscript is expected to be published by Q4 2027. CONCLUSIONS Compared to standard chemotherapy, PIPAC has been reported to significantly improve survival rates in patients with peritoneal metastasis of gastric origin. We suggest that the neoadjuvant use of PIPAC may reduce the incidence of peritoneal metastasis and improve long-term survival outcomes. The results of our study will provide key information on the practicality and viability of PIPAC as a prophylactic technique for preventing the progression of gastric cancer. CLINICALTRIAL ClinicalTrials.gov NCT06784765; https://clinicaltrials.gov/study/NCT06784765 INTERNATIONAL REGISTERED REPORT PRR1-10.2196/78053

Introduction.Gastric cancer remains a major public health burden in Kazakhstan. Perioperative FLOT is the standard for locally advanced, resectable disease, yet real-world evidence from Central Asia -particularly on treatment exposure, pathological response, toxicity, and costs has been limited.Objective.This study aimed to evaluate real-world outcomes and economic aspects of perioperative FLOT chemotherapy in resectable gastric cancer in Kazakhstan.Methods.We conducted a retrospective single-center cohort study of patients with resectable gastric adenocarcinoma treated with perioperative chemotherapy at the National Research Oncology Center (Astana) between 2020 and 2024. Clinical data (baseline characteristics, chemotherapy delivery, adverse events), surgical outcomes, histopathologic tumor regression, and regimen-level costs were extracted from medical records and national tariff documents.Results.Seventy-four patients (mean age 57.4 years; 71.6% male) were analyzed. Neoadjuvant FLOT was completed in 86.5% (four cycles in 81.1%); total gastrectomy was performed in 74.3%, and R0 margins were achieved in 82.4%. Histopathologic regression was observed in a substantial proportion, although complete responses were uncommon and residual locally advanced and/or node-positive disease remained frequent. Most patients-initiated adjuvant chemotherapy. During neoadjuvant therapy, toxicities were recorded in 62.1%, with grade 3-4 neutropenia in 18.9% and hospitalizations in 12.2%. Economic analysis showed XELOX had the lowestdirect costs; versus XELOX, FOLFOX and FLOT were approximately 13% and 31% higher, respectively, with the widest variability for FLOT amid national tariff volatility.Conclusions.Perioperative FLOT is feasible in routine practice, yielding frequent R0 resection and meaningful regression, though complete responses are uncommon. Given higher direct costs and tariff volatility, priorities include aligning reimbursement with real-world expenditures and evaluating biomarker-guided, supportive-care–optimized approaches in prospective multicenter studies. Keywords:gastric cancer,perioperative chemotherapy,FLOT,pathological response,real-world evidence,health economics,Kazakhstan.

Pathological lymph-node status after neoadjuvant treatment and surgery (ypN) is prognostic in gastric cancer but unavailable before resection. We developed a pilot prediction model to estimate ypN risk from seven variables recorded before radical surgery in patients treated within a single-center PIPAC program; the timing of blood counts relative to neoadjuvant treatment could not be established. Of 62 patients, 47 with recorded ypN were analyzed (18 ypN-positive). Predictors were clinical T and N stage, tumor grade, age, body-mass index, white-cell count, and platelet count. Ridge logistic regression (primary), random forest, and Firth logistic regression were evaluated by cross-validation. Out-of-fold AUCs were 0.701 (95% confidence interval 0.539-0.851), 0.667 (0.488-0.831), and 0.703 (0.532-0.851), respectively; Brier scores were 0.227, 0.227, and 0.222 (prevalence-only reference 0.236). Performance was modest and imprecise; because the predictor panel was selected using the same cross-validation, estimates may be optimistic. These findings are an exploratory signal requiring independent validation.