Introduction: Peritoneal metastasis (PM) is the most common site of recurrence following curative resection for advanced gastric cancer (GC). Along with disease progression, it can lead to complications such as intestinal obstruction, hydronephrosis, obstructive jaundice, and ascites, significantly impairing the patient's quality of life. Therefore, peritoneal metastasis is considered a critical target for treatment. In general, these patients are treated with systemic chemotherapy; however, the therapeutic effect is often limited due to the anticancer agents' poor penetration into the peritoneal cavity. We aim to identify factors associated with the best overall survival (OS) in GC patients with peritoneal metastasis. Methods: Patients with advanced GC who were diagnosed as having macroscopic PM or positive peritoneal cytology by staging laparoscopy were enrolled. We introduced intraperitoneal Paclitaxel (IP-PTX) combined with S-1 plus oxaliplatin (SOX). Gastrectomy with lymph node dissection was performed as conversion surgery when the PM showed an excellent response. Results: Ninety-six patients received IP-PTX + SOX, with a median of 16 courses. The 1- and 5-year OS rates were 70.2% and 24.5%, respectively, with a mean survival time (MST) of 20.0 months. No chemotherapy-related mortality was observed. Conversion surgery was performed in 44 patients (45.8%), with a 1-year OS rate of 100%. Conclusions: Combination chemotherapy using the IP-PTX + SOX regimen is highly effective and is recommended as induction chemotherapy for patients with PM from GC. Conversion gastrectomy should be considered following an excellent response, particularly in patients with peritoneal cancer index (PCI) scores below 20.

Peritoneal dissemination portends a dismal prognosis in patients with gastric adenocarcinoma in the context of limited effective treatments. The underlying cellular processes that drive gastric peritoneal carcinomatosis remain unclear, limiting the application of novel targeted therapies. In this comprehensive review, we aimed to identify and summarize all existing context-dependent molecular mechanisms that have been implicated in peritoneal dissemination and peritoneal carcinomatosis establishment from primary gastric adenocarcinoma. We applied a multilevel examination including data from in vivo murine models using human gastric cancer cell lines, in vitro technique-based studies, ex vivo models, and genomic/proteomic and molecular profiling analyses to report on various aspects of gastric cancer peritoneal metastasis biology. Mechanisms promoting peritoneal dissemination were grouped into three main functional categories: (1) intrinsic cancer cell biology, (2) cancer cell-peritoneal surface adhesion, and (3) peritoneal tumor microenvironment. We identified significant overlap among the three categories, indicating a complex interplay between multiple molecular mechanisms. By interrupting these pathways, peritoneal-directed therapies have the potential to improve quality and length of life in patients with high-risk primary gastric cancer.

Claudin 18 isoform 2 (CLDN18.2) is a potential therapeutic target in gastric cancer (GC). However, combining chemotherapy with anti-CLDN18.2 antibodies has shown limited efficacy in CLDN18.2-positive GC, and chemotherapy-induced changes in the tumor microenvironment (TME) remain unclear.

This study analyzed 37 GC samples, including 11 CLDN18.2-positive cases, using single-cell RNA sequencing and multiplex immunofluorescence to assess chemotherapy-driven TME changes in CLDN18.2-positive GC.

In chemotherapy-treated CLDN18.2-positive GC, cytotoxic natural killer (NK) cells displayed antibody-dependent cytotoxicity (ADCC)-related genes at lower levels than in untreated CLDN18.2-positive GC, while regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) showed TGFB1 expression at higher levels. Additionally, NK cells, Tregs, and TAMs were more abundant in chemotherapy-treated than untreated CLDN18.2-positive GC. These chemotherapy-induced changes were absent in CLDN18.2-negative GC. Cell-cell interaction analysis identified unique interactions in chemotherapy-treated CLDN18.2-positive GC, including CCL5-CCR5 signaling between cytotoxic NK cells (Sender) and effector Tregs (Receptor) and TGFB1-TGFBR signaling between effector Tregs (Sender) and TAMs (Receptor). Cytotoxic NK cells expressed CCL5 at higher levels, CCR5-positive Tregs were more prevalent, and TAMs exhibited higher TGF-β receptor signature scores in chemotherapy-treated than untreated CLDN18.2-positive GC.

Our findings indicate that chemotherapy can drive immunosuppressive TME modifications specific to CLDN18.2-positive GC.

Gastric cancer (GC) commonly presents in advanced stages with metastatic spread to the peritoneal cavity, and outcomes associated with gastric cancer with peritoneal metastasis (GCPM) continue to carry a dismal prognosis. Persistent challenges in the detection of peritoneal metastasis (PM) have resulted in a relative paucity of high-quality data to inform management decisions. Several consensus groups have published recommendations to guide management, including most recently the National Comprehensive Cancer Network guidelines, which now include cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a potential treatment modality in select patients with GCPM. Multiple clinical trials have investigated the use of CRS/HIPEC and other peritoneal-directed therapies, such as intraperitoneal chemotherapy (IPC) and pressurized intraperitoneal aerosolized chemotherapy (PIPAC). As high-volume centers work to incorporate such therapies into their practice, ongoing clinical trials are aimed at understanding their efficacy. Recent findings have improved understanding of the mechanisms and pathophysiology underlying GCPM while the discovery of novel targets offers potential for drug development and therapeutic strategies to overcome treatment resistance. This review highlights recent advancements and addresses the persistent challenges in managing GCPM while also offering a comprehensive summary of current guidelines and treatment strategies.

Trastuzumab deruxtecan (T-DXd) has been approved for the treatment of human epidermal growth factor receptor-2 (HER2)-positive gastric cancer and other indications in several countries and is considered moderately or highly emetogenic. The management of nausea and vomiting associated with T-DXd treatment has not been fully evaluated and the effectiveness of conventional prophylaxis remains unknown.

This open-label, randomized, multicenter, phase 2 study aimed to investigate the optimal antiemetic therapy for Japanese patients with gastric cancer undergoing T-DXd treatment. Patients were randomized to a doublet regimen group (dexamethasone and palonosetron) or triplet regimen group (aprepitant, dexamethasone, and palonosetron) at a ratio of one to one, stratified by sex, gastrectomy status, and study institution. Both antiemetic treatments were administered from day 1 before T-DXd administration, and emetic events and nausea were observed for 21 days. The primary endpoint was the antiemetic complete response (CR) rate to assess control for emetic events based on voluntary patient-reported outcomes (PROs) during cycle 1 (1-21 days).

Of the 60 enrolled patients, 58 were eligible for inclusion in this analysis (29 patients in each regimen group). The overall CR rates for the doublet and triplet regimens were 41.4% (12/29 patients) and 37.9% (11/29 patients), respectively, and neither regimen met the pre-specified threshold (> 18/29 patients). The CR rate in the acute phase (0-24 h) was 86.2% (25/29 patients) for both regimens, and the CR rates in the delayed phase (2-21 days) were 41.4% (12/29 patients) and 37.9% (11/29 patients) for the doublet and triplet regimens, respectively.

Given that the primary endpoint was not met, further research is needed to better characterize nausea and vomiting with T-DXd to tailor an anti-emetic regimen that suits the needs of the patients.

Gastric cancer is the fifth most common cancer globally and is associated with significant morbidity and mortality. Despite its alarming prevalence, limited comparative evidence exists on its treatment efficacy and prognosis across diverse China populations.

To address this, our study used a large-scale dataset from the National Cancer Information Database, including data from 220,304 patients from 53 leading hospitals across 27 provinces in China.

From 2017 to 2023, early-stage (Stages I-II) gastric cancer diagnoses increased to 35.63% of all cancer cases. Our study evaluated the neoadjuvant treatment strategies, adjuvant post-operative therapy, first- and second-line management for progressive stages, alongside current gastric cancer treatment guidelines in China. Notably, immunotherapy accounted for 16.17% and 23.28% of first- and second-line treatments for late-stage gastric cancers, and 14.56% and 5.00% for neoadjuvant and adjuvant therapies, respectively. Analysis of survival rates revealed that the 1-, 2-, 3-, 4-, and 5-year survival rates were 74.07%, 54.89%, 44.21%, 37.97%, and 33.53%, respectively. The 5-year survival rates across stages I-IV were 85.07%, 49.34%, 35.56%, and 13.15%, respectively.

These findings offer critical insights into the current state of gastric cancer treatment in China and can inform future initiatives to improve therapeutic outcomes for patients with gastric cancer.

The treatment of gastric cancer remains highly challenging, particularly in cases of unresectable locally advanced or metastatic disease. Although chemotherapy and immunotherapy have shown some efficacy in such patients, significant limitations persist in extending survival and enhancing safety. To address these challenges, we designed an innovative first-line quadruple conversion therapy regimen that integrates a programmed cell death protein 1 (PD-1) inhibitor with chemotherapy, and we successfully implemented this therapy regimen in the treatment of a patient with unresectable locally advanced gastric adenocarcinoma.

We report the case of a 55-year-old male who was diagnosed with unresectable locally advanced gastric adenocarcinoma and presented with intermittent epigastric pain and multiple lymph node metastases in the abdominal cavity, with the metastasis being notably large in size. The tumor tissue was negative for human epidermal growth factor receptor 2 by immunohistochemistry. Considering the patient's status, the multidisciplinary team decided to administer sintilimab in combination with albumin-bound paclitaxel (nab-paclitaxel), S-1, and oxaliplatin as a quadruple drug conversion therapy. After 4 cycles of conversion therapy, the patient's epigastric pain was significantly alleviated, his stool color normalized, the volume of the primary tumor and lymph node metastases was markedly reduced, and the tumor marker levels decreased to within the normal range. The patient subsequently underwent laparoscopic total gastrectomy with abdominal lymph node dissection, and postoperative pathological biopsy revealed a pathological complete response and R0 resection, after which the patient recovered to an excellent physical status.

To the best of our knowledge, this is the first reported case of unresectable locally advanced gastric adenocarcinoma successfully treated with quadruple therapy with a PD-1 inhibitor and chemotherapy as a first-line conversion regimen. This first-line conversion therapy with the quadruple regimen may be effective and safe for unresectable locally advanced gastric adenocarcinoma.

We developed and refined an S-1 dosage formula based on renal function, sex, and body surface area (BSA) to achieve the target area under the concentration-time curve of 5-fluorouracil in two prospective pharmacokinetic studies. The clinical validity of the refined formula (BBT formula) was evaluated using data from the two phase III trials of fist-line chemotherapy including S-1 for advanced gastric cancer, which demonstrated that overall survival and progression-free survival tended to be shorter in patients whose S-1 standard dose, based on BSA alone, was lower than that determined using the BBT formula.

Chemo-naïve patients with HER2-negative advanced gastric or gastroesophageal junction cancer, whose standard S-1 dose is lower than that determined using the BBT formula, receive S-1 at an increased dose based on the BBT formula plus oxaliplatin (130 mg/m2) and nivolumab (360 mg/body). The primary endpoint is the incidence of dose-limiting toxicity in six patients in the phase I part and the proportion of patients requiring S-1 dose reduction in a total of 20 patients, expecting 30% and rejecting 50% with an alpha error of 0.1 and beta error of 0.2. The secondary endpoints are adverse events, relative dose intensity, response rate, disease control rate, progression-free survival, and overall survival. A correlation study is conducted to investigate the immune profiles associated with efficacy.

This phase I/II trial evaluates the safety and efficacy of S-1 at increased doses, determined by the BBT formula, in combination with oxaliplatin and nivolumab in patients with HER2-negative advanced gastric cancer, whose standard dose of S- 1 is lower than the dose recommended dose by the BBT formula.

This study was approved by the University of Tokyo Clinical Research Review Board (URL: https://www.ut-crescent.jp/patients/chiken_jisshi/ , review number: 2022529SP) and was initiated at 19 institutions in June 2023 (registered as jRCTs031230127).

Gastric cancer (GC) is one of the most common malignant tumors with poor survival. Although cisplatin is a first-line chemotherapy drug for GC, it still has the potential to develop drug resistance and side effects. Miltirone, extracted from Chinese herb Salvia miltiorrhiza Bunge, has been reported to significantly inhibit some types of cancer. However, its effects on GC have not been studied, the possible anti-tumor effects of miltirone in combination with cisplatin in GC patients have not been explored.

Human GC cell lines AGS, HGC27, MKN45 and MGC803 cells were treated with miltirone and cisplatin individually or combinatorially. Cell proliferation assay, flow cytometric assay, colony formation assay and Western blot were employed to evaluate the cytotoxic effects under these treatments. Wound healing and transwell assays were used to examine the effects of miltirone and/or cisplatin on GC cell migration and invasion. RNA-seq analysis was used to determine miltirone's potential target genes in AGS cells. GO analysis and molecular docking assay were used to determine the pathways affected by miltirone. Next, we examined changes in the selected pathway proteins. The in vivo animal model was verified the results of the in vitro experiments.

Miltirone inhibited cell growth, migration, and invasion, as well as induced apoptosis in GC cells. In combinatorial treatments, miltirone synergistically enhanced cytotoxicity of cisplatin in GC cells. Moreover, the expression levels of 606 genes appeared to be significantly modulated by miltirone via RNA-seq analyses, and PI3K/AKT signaling pathway was found to refer to miltirone activity. Furthermore, miltirone together with cisplatin treatment significantly reduced the expression levels of p-PI3K, p-Akt, p-mTOR, while the total levels of PI3K and Akt remained unchanged. In addition, compared with the control group, the tumors growth was significantly suppressed in groups treated with the two agents alone or in combination, and even more so in the combination group in vivo.

Miltirone inhibited the proliferation of GC cells and significantly potentiates the anticancer activities of cisplatin by downregulating the PI3K/AKT signaling pathway. Combination therapy of miltirone and cisplatin represents a novel potential treatment of gastric cancer.

As adjuvant chemotherapy for stage III gastric cancer, the phase III (JACCRO GC-07) trial showed that docetaxel plus S-1 (DS) was superior to S-1 in terms of recurrence-free and overall survival. However, whether adding docetaxel to S-1 in the adjuvant setting affects survival after recurrence remains unclear. The optimal treatment strategy for patients who develop recurrence during or after DS has also been controversial.

We used results from JACCRO GC-07 to investigate post-recurrence survival (PRS) in patients who developed recurrence during or after completing adjuvant chemotherapy. PRS was compared between adjuvant groups and among post-recurrence chemotherapeutic regimens.

During 5 years of follow-up after surgery, 161 of 441 patients in the DS group and 216 of 452 patients in the S-1 group developed recurrence, with median PRS of 12.6 and 11.4 months, respectively (hazard ratio [HR] 0.98, 95 % confidence interval [CI] 0.79-1.22; p = 0.84). Among patients with recurrence, 115 patients in the DS group and 165 patients in the S-1 group received chemotherapy, and median PRS was 14.5 and 13.7 months, respectively (HR 1.04, 95 %CI 0.81-1.34; p = 0.76). Platinum-based chemotherapy resulted in longer PRS than non-platinum chemotherapy, regardless of the adjuvant chemotherapeutic regimen or time of recurrence.

PRS was similar between patients who received adjuvant chemotherapy with DS or with S-1 alone. PRS was also similar between groups of patients who received chemotherapy after recurrence. Platinum-based chemotherapy might be the optimal treatment for patients who develop recurrence after completing adjuvant DS, regardless of the time of recurrence.

Gastric cancer remains a prevalent malignancy worldwide, with peritoneal metastasis being the predominant form of recurrence and metastasis, which are clear predictors of prognosis. The aim of this comprehensive bibliometric analysis was to assess the current status of the research landscape and to identify impending trends in gastric cancer peritoneal metastasis (GCPM).

Relevant studies of GCPM were retrieved from the Web of Science Core Collection database. Qualified articles were screened based on the inclusion and exclusion criteria for further analysis. The selected publications were then subjected to bibliometric analysis utilizing VOSviewer software.

In total, 1,100 publications were included for analysis. The results revealed a consistent upward trend in the number of publications annually from 2000 to 2024, with an anticipated continuation of this growth in future research. The National Cancer Center Japan, emerged as the institution with the most publications and Professor Kodera and Annals of Surgical Oncology were identified as the most influential author and journal, respectively, in the domain of GCPM. In terms of international collaborations, the USA, Japan, and France were the most engaged countries. Yonemura was recognized as the most frequently cited author. Gastrectomy, systemic chemotherapy, and intraperitoneal therapy are the current research hotspots within this domain.

Research related to GCPM had rapidly increased over the past two decades. These findings identify the most influential countries, institutions, authors, journals, and academic collaboration networks, while also clarifying hotspots and future trends in GCPM research.

HER2-positive gastric cancer (GC), a unique molecular subtype, has garnered significant interest in recent years. Here, we review clinical trial data on advanced HER2-positive GC from the past 15 years. Trastuzumab plus standard chemotherapy remain the first-line treatment. The initial survival benefits conferred by immune checkpoint inhibitors plus trastuzumab and standard chemotherapy are encouraging. The combination of ramucirumab and mono-chemotherapy, as well as the antibody conjugated drug trastuzumab deruxtecan, is the recommended second-line regimen. Treatment with immune checkpoint inhibitors plus ramucirumab and mono-chemotherapy shows promise. Despite the limited treatment options for third line and beyond, development of novel therapeutic strategies is expected. Although clinical cure of advanced HER2-positive GC is unlikely, current clinical studies offer valuable insight into regimens that prolong survival.

Gemcitabine/cisplatin (GemCis) was the long-standing first-line treatment for advanced biliary tract cancers (BTCs). Following positive results from the TOPAZ-01 and KEYNOTE-966 trials, immune checkpoint inhibitors (ICIs) combined with chemotherapy are now the standard of care. We aim to compare the efficacy of first-line therapies for advanced BTCs.

Our systematic review included studies from five databases focusing on English-language articles published between January 2010 and June 2024. We included randomized clinical trials (RCTs) that featured GemCis in a treatment arm for treatment-naive adults with advanced BTCs. The primary endpoints were overall survival (OS) and progression-free survival. We conducted a one-stage meta-analysis using reconstructed survival data, Cox-based models, and restricted mean survival time (RMST).

After screening 8,797 studies, 17 RCTs were selected, involving a total of 4,584 patients. Of these, 2,140 (46.7%) received GemCis. The majority (68.9%) were diagnosed with intrahepatic or extrahepatic cholangiocarcinoma, and 80% had metastatic disease at the time of treatment. The pooled median OS in the GemCis group was 11.6 months (95% CI 11.3-12.2 months). GemCis plus pembrolizumab (hazard ratio [HR] 0.99, 95% CI 0.98-0.99; p <0.001), GemCis plus durvalumab (HR 0.98, 95% CI 0.97-0.99; p = 0.015), GemCis plus S-1 (HR 0.97 95% CI 0.95-0.99; p <0.001), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.98-0.99; p <0.001) demonstrated superior OS compared with GemCis alone. These combinations also showed increases in RMST by +1.1, +2.5, +2.8, and +2.1 months, respectively. In terms of progression-free survival, GemCis with ICIs (HR 0.91, 95% CI 0.78-0.94; p <0.001), GemCis plus S-1 (HR 0.98, 95% CI 0.96-0.99; p = 0.003), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.97-0.99; p <0.001) also demonstrated superiority, with corresponding RMST increases of +0.7, +1.9, and +2.5 months, respectively.

Despite incremental advancements, a breakthrough in advanced BTC treatment remains elusive. Further improvements in treatment efficacy may require biomarker identification to optimize combinational therapies for better patient selection.

This study analyzed recent RCTs, including KEYNOTE-966, TOPAZ-1, NIFE, and SWOG 1815, involving 4,584 patients with advanced biliary tract cancer. A meta-analysis of 17 treatment arms, using reconstructed survival data, confirmed the modest survival benefit of GemCis plus ICIs, supporting its guideline adoption. The findings, however, highlight the need for biomarker identification and better patient selection.

Locally advanced gastric cancer (LAGC) poses a significant surgical challenge. While laparoscopic gastrectomy (LG) offers potential advantages, its cost-effectiveness relative to open gastrectomy (OG) in China remains uncertain. To compare the cost-effectiveness of LG and OG for LAGC in China. A Markov model compared the cost-effectiveness of LG and OG for LAGC. Probabilities and utilities were derived from published literature. Direct medical costs were obtained from the First Hospital of Lanzhou University. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as the cost per quality-adjusted life-year (QALY) gained, using a willingness-to-pay threshold of ¥268,074/QALY. Sensitivity analyses assessed model robustness. Across 1-, 3-, and 5-year time horizons, OG had lower total costs and greater effectiveness than LG for LAGC. At 5 years, OG had a total cost of ¥128,259 and 7.20 QALYs versus LG's ¥136,668 and 7.18 QALYs; the ICER for OG was -¥474,758/QALY. OG dominated at the ¥268,074 willingness-to-pay threshold. Sensitivity analysis indicated that variations in LG and OG costs minimally influenced the cost-effectiveness. Probabilistic sensitivity analysis, performed across 10,000 iterations, consistently identified OG as the optimal strategy (100% of iterations). From a Chinese health economics perspective-a framework essential for informing national healthcare resource allocation-OG consistently demonstrated a superior cost-effectiveness compared with LG for LAGC across 1, 3, and 5 years. This longitudinal observation of sustained cost-effectiveness persisted despite the statistically insignificant differences in overall costs and effectiveness between the two procedures.

Although the emergence of immunotherapy has benefited patients with advanced gastric cancer (AGC), the magnitude of the benefit among real-world patients with HER2-negative AGC remains unclear.

The current study aimed to evaluate the treatment features across various immunotherapy approval periods and investigate the utility of immunotherapy for patients with HER2-negative AGC in daily practice.

Retrospective observational study.

We retrospectively evaluated the clinical outcomes of patients with HER2-negative AGC who received first-line platinum-based chemotherapy between 2011 and 2023 across different periods of immunotherapy approval in Japan: Group A (pre-immunotherapy approval): 2011-2017; Group B (approved for third-line treatment or later): 2018-2021; and Group C (approved for first-line treatment): 2022-2023.

A total of 949 patients were enrolled (n = 477, 344, and 128 for Groups A, B, and C, respectively). Patient characteristics were comparable between the three groups, except for the proportion of those aged ⩾75 years (p = 0.002), prior gastrectomy (p = 0.03), and liver metastases (p = 0.0005). The median overall survival (OS) was 16.2, 15.2, and 21.3 months in Groups A, B, and C, respectively, with no significant difference between the groups (log-rank p = 0.50). Patients who received first-line immunotherapy plus chemotherapy (n = 173) showed significantly better OS than did those who did not receive any immunotherapy-containing treatment from 2011 to 2017 (n = 382; hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.61-0.99; p = 0.04). Multivariate analysis showed that the use of first-line immunotherapy was not significantly associated with worse OS, whereas the use of any-line immunotherapy was significantly associated with prognosis (HR, 0.54; 95% CI, 0.47-0.63; p < 0.0001). The proportion of patients receiving any second-line treatment was comparable between the groups: 76%, 80%, and 71%, respectively.

Our study suggests that immunotherapy has a moderate impact on improving the survival of real-world patients with HER2-negative AGC, highlighting the need for appropriate treatment strategies, including efforts to identify biomarkers and the development of other agents.

Advanced gastric cancer with gastric outlet obstruction (GOO) causes malnutrition and medication adherence issues, leading to a poor prognosis. We developed a novel multimodal, less invasive treatment approach for gastric cancer patients with symptomatic GOO: laparoscopic stomach-partitioning gastrojejunostomy (LSPGJ) combined with neoadjuvant chemotherapy (NAC), followed by minimally invasive gastrectomy with reuse of gastrojejunostomy. This study is a retrospective analysis of the safety and feasibility of our treatment strategy.

In this single-institution retrospective study, we enrolled 54 patients (NAC group, n = 26; upfront gastrectomy group, n = 28) who achieved R0 resection through a minimally invasive approach between 2007 and 2020 and evaluated their short- and long-term outcomes.

After LSPGJ, the Gastric Outlet Obstruction Scoring System score significantly improved (p < 0.001). The median relative dose intensity of NAC was 88.2%. Regarding short-term outcomes, there were no differences in postoperative complications, length of postsurgical hospital stay, and adjuvant chemotherapy administration. Although overall survival and relapse-free survival showed trends toward improvement in the NAC group, these differences were not statistically significant. The cumulative incidence curve for recurrence in the NAC group was significantly lower than that of the upfront gastrectomy group (p = 0.041). Recurrence and hematogenous metastasis were significantly lower in the NAC group (p = 0.031 and 0.041, respectively) than in the upfront gastrectomy group. A forest plot revealed that NAC yielded favorable outcomes, particularly for patients with a body mass index (BMI) < 18.5 kg/m2, cT4, or cN1.

LSPGJ combined with NAC followed by minimally invasive gastrectomy was a safe and feasible treatment strategy for patients with advanced gastric cancer with symptomatic GOO. This procedure may contribute to the early recovery of oral intake and help maintain NAC dose intensity, potentially improving prognosis, particularly for patients with low BMI and advanced-stage disease.

Biweekly irinotecan plus cisplatin combination therapy (BIRIP) and irinotecan monotherapy (IRI) are both expectable second-line chemotherapy (SLC) options for treating advanced gastric cancer (AGC). Although many patients receiving SLC have undergone gastrectomy, the impact of gastrectomy on SLC remains unclear, and the impact of gastrectomy may vary from regimen to regimen.

A total of 290 eligible patients registered in two randomized phase III trials evaluating BIRIP (IRI, 60 mg/m2; CDDP, 30 mg/m2, q2w) or IRI (150 mg/m2, q2w) for patients with AGC was classified into the prior gastrectomy subgroup (PGG) or the no gastrectomy subgroup (NGG). We performed a subgroup analysis to evaluate the impact of gastrectomy on second-line BIRIP and IRI.

The BIRIP demonstrated significantly longer OS (11.1 vs. 6.8 months; HR 0.64; P = 0.026) and PFS (3.7 vs. 2.3 months; HR 0.54; P = 0.003) than the IRI, as well as better ORR (23.5% vs. 7.1%, P = 0.046) and DCR (74.5% vs. 47.6%, P = 0.010) in NGG. Although in PGG, the BIRIP failed to demonstrate differences in OS (13.8 vs. 13.8 months; HR 0.94; P = 0.722), PFS (4.9 vs. 4.5 months; HR 0.82; P = 0.194), ORR (18.3% vs. 20.5%) and DCR (70.4% vs. 65.1%). The incidence of grade 3 or worse adverse events did not differ except for a high incidence of anemia in the BIRIP group in PGG.

BIRIP was an effective treatment option that may improve survival outcomes among patients with AGC without previous gastrectomy.

UMIN000025367.

Gastric cancer is a significant global contributor to cancer-related mortality. Stage IV gastric cancer represents a significant percentage of patients in Western countries, with peritoneal dissemination being the most prevalent site. Peritoneal disease comprises two distinct entities, macroscopic (P1) and microscopic (P0CY1), which are associated with poor long-term survival rates. Although the present standard of treatment is palliative chemotherapy, a global controversy has arisen concerning specific patients with limited disease burden or conversion to negative lavage cytology following chemotherapy. Available approaches include systemic or intraperitoneal chemotherapy, upfront gastrectomy, and conversion surgery. This review consolidated the current evidence regarding multimodal management, indicating prolonged survival for this distinct subgroup of patients. Considering the complexity of peritoneal metastases, the potential of the multimodal approach unveils promising prospects for identifying the optimal treatment for this particular subset of stage IV patients and thus enhancing their survival outcomes.

Gastric cancer is the fifth most common malignancy and the fifth primary cause of death from cancer all over the world. Because of diagnosis of gastric cancer at advanced, incurable stages and limited response to treatment, the disease has an adverse prognosis and a low survival rate. Chemotherapy consisting of medications such as platinum and 5-Fluorouracil can be effective for patients with advanced stomach cancer. Nevertheless, drug resistance eventually leads to unsuccessful therapy and adverse outcomes for gastric cancer patients. Most therapy failures in gastric cancer patients undergoing chemotherapy are caused by the development of drug resistance. Several studies have shown that noncoding RNAs (ncRNAs) play important roles in the resistance of gastric cancer to chemotherapy drugs. The development of stomach cancer is greatly impacted by a number of ncRNAs, including microRNAs (e.g., miR-21, miR-27a), circular RNAs (e.g., CircPVT1), and long noncoding RNAs (e.g., HOTAIR). Because of their regulatory characteristics in certain genes implicated in the chemoresistant phenotype of gastric cancer, much evidence has demonstrated their function in the emergence and persistence of drug resistance. In the future, ncRNA-based treatment could represent a novel approach to treating drug resistance. Despite numerous studies on anticancer drug resistance mechanisms, it is still unclear how these mechanisms are regulated. In this review, we investigated the evolving function and molecular mechanisms of ncRNAs related to drug resistance, their function in controlling drug resistance in gastric cancer, and their potential to create targeted therapeutics for reducing drug resistance in gastric cancer.

Gastric cancer (GC) has benefited from treatment improvements such as minimally invasive surgery, molecular-targeted drugs, and immune check point inhibitors. However, the prognosis of advanced GC is still unfavorable. Minimally invasive pre-treatment detection of drug sensitivity (MI-PDDS) has increasing importance in view of improved chemotherapy. Gastric biopsy specimens are obtained with relative ease but have not been considered an appropriate source for generating cell lines because of their minute amounts. We therefore materialized the idea of MI-PDDS using biopsy-derived cell lines obtained from endoscopic biopsy specimens. Here, a cell line designated TCC-GC1-C1 was established from a biopsy specimen of a histologically confirmed adenocarcinoma of the stomach. The cell line showed the ability of forming spheroid with deeply stained nuclei and disturbed cellular morphology indicative of malignancy. Single-nucleotide polymorphism (SNP) genotyping of the cell line revealed a duplication of chromosome19q and a deletion of chromosome 8p. A drug screening test with 221 anticancer drugs showed that the cell line had high sensitivity to the proteasome inhibitor (Carfilzomib) and the fibroblast growth factor receptor inhibitor (Erdafitinib), with a low IC50 value of under 0.1 μM. Our MI-PDDS approach holds promise in making a treatment decision for advanced GC.

Differences in demographics, medical expertise, and patient healthcare resources across countries have led to significant variations in guidelines. In light of these differences, in this review, we aimed to explore and compare the most recent updates to gastric cancer treatment from five guidelines that are available in English. These English-version guidelines, which have been recently published and updated for journal publication, include those published in South Korea in 2024, Japan in 2021, China in 2023, the United States in 2024, and Europe in 2024. The South Korean and Japanese guidelines provide a higher proportion of content to endoscopic and surgical treatments, reflecting their focus on minimally invasive techniques, function-preserving surgeries, and systemic therapy. The Chinese guidelines provide recommendations addressing not only surgical approaches but also perioperative chemotherapy and palliative systemic therapy. Meanwhile, in the United States and European guidelines, a higher proportion of the content is dedicated to perioperative and palliative systemic therapy, aligning with their approaches to advanced-stage disease management. All guidelines address surgical and systemic chemotherapy treatments; however, the proportion and emphasis of content vary based on the patient distribution and treatment approaches specific to each country. With emerging research findings on gastric cancer treatment worldwide, the national guidelines are being progressively revised and updated. Understanding the commonalities and differences among national guidelines, along with the underlying evidence, can provide valuable insights into the treatment of gastric cancer.

The systemic inflammatory response index (SIRI) is calculated via the following formula: SIRI = monocyte count × neutrophil count/lymphocyte count. The value of the SIRI in predicting the prognosis of gastric cancer (GC) remains controversial. This study revealed the precise effect of the SIRI in predicting GC prognosis through a meta-analysis.

The ability of the SIRI to predict GC prognosis was evaluated by calculating combined hazard ratios (HRs) and 95% confidence intervals (CIs). Furthermore, the combined odds ratios (ORs) and 95% CIs were determined to analyze the associations between the SIRI and the clinicopathological characteristics of patients with GC.

Seven publications on a total of 1763 cases were included in this study. The SIRI threshold was between 0.58 and 1.35, and the median value was 0.85. Our pooled findings revealed that a higher SIRI was significantly linked with poor overall survival (OS) (HR = 1.87, 95% CI = 1.59-2.20, p < 0.001) and disease-free survival (DFS; HR = 1.88, 95% CI = 1.50-2.36, p < 0.001) in GC patients. However, the SIRI did not exhibit a significant association with sex (OR = 1.98, 95% CI = 0.82-4.75, p = 0.126), surgery type (OR = 0.96, 95% CI = 0.61-1.51, p = 0.847), tumor differentiation (OR = 0.75, 95% CI = 0.54-1.06, p = 0.099), or TNM stage (OR = 1.25, 95% CI = 0.34-4.62, p = 0.743) in patients with GC.

An elevated SIRI was significantly associated with unfavorable OS and DFS in patients with GC. Thus, the SIRI is a reliable biomarker for predicting GC prognosis in clinical practice.

Accurately extrapolating survival beyond trial follow-up is essential in a health technology assessment where model choice often substantially impacts estimates of clinical and cost effectiveness. Evidence suggests standard parametric models often provide poor fits to long-term data from immuno-oncology trials. Palmer et al. developed an algorithm to aid the selection of more flexible survival models for these interventions. We assess the usability of the algorithm, identify areas for improvement and evaluate whether it effectively identifies models capable of accurate extrapolation.

We applied the Palmer algorithm to the CheckMate-649 trial, which investigated nivolumab plus chemotherapy versus chemotherapy alone in patients with gastroesophageal adenocarcinoma. We evaluated the algorithm's performance by comparing survival estimates from identified models using the 12-month data cut to survival observed in the 48-month data cut.

The Palmer algorithm offers a systematic procedure for model selection, encouraging detailed analyses and ensuring that crucial stages in the selection process are not overlooked. In our study, a range of models were identified as potentially appropriate for extrapolating survival, but only flexible parametric non-mixture cure models provided extrapolations that were plausible and accurately predicted subsequently observed survival. The algorithm could be improved with minor additions around the specification of hazard plots and setting out plausibility criteria.

The Palmer algorithm provides a systematic framework for identifying suitable survival models, and for defining plausibility criteria for extrapolation validity. Using the algorithm ensures that model selection is based on explicit justification and evidence, which could reduce discordance in health technology appraisals.

Gastric cancer with liver metastases (GCLM) is a challenging condition that significantly reduces long-term survival rates, but recent advancements in surgical techniques have shown promise. This study aims to comprehensively evaluate the impact of surgical resection on survival rates in GCLM patients.

We conducted a population-based analysis utilizing the SEER database for patients diagnosed with GCLM between 2010 and 2015. Overall survival (OS) was compared between patients who underwent cancer-directed surgery (CDS) and those who did not. The overlap weighting method based on lasso regression with penalty factors was employed to minimize selection bias. Survival outcomes were compared using Kaplan-Meier curves and Cox proportional hazards models, with subgroup analyses to further explore the effects of surgery among patients.

A total of 3694 patients with GCLM were identified. Of those, 354 (9.58%) patients underwent CDS. After propensity score adjustment, The median OS was significantly higher in the surgical resection group (12 months, 95% confidence interval (CI) 11-16) compared to the nonresection group (6 months, 95% CI: 5-6). Cox regression analysis revealed a substantial improvement in OS for the surgical resection group, with a hazard ratio (HR) of 0.562 (95% CI: 0.482-0.656), including patients with adverse conditions.

The analysis demonstrated a clear association between surgical resection and enhanced OS in GCLM patients. Nevertheless, further research endeavors should be undertaken to identify specific prognostic factors that aid in the selection of optimal candidates for surgical resection.

Potential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study.

Patients with synchronous or metachronous LMGC received 2-4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis.

Seventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1-71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9-34.0) and 34.9 % (95 % CI 22.2-50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1-3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16-6.35), P = 0.022; pN1-3: HR 9.11 (95 % CI, 1.22-68.2), P = 0.031).

R0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis.

UMIN 000011445 (https://www.umin.ac.jp/ctr/).

Prostate cancer is an androgen-dependent malignancy that presents a marked treatment challenge, particularly after progression to the castration-resistant stage. Traditional treatments such as androgen deprivation therapy often lead to resistance, necessitating novel therapeutic approaches. Previous studies have indicated that some of the azolato-bridged dinuclear platinum(II) complexes (general formula: [{cis-Pt(NH3)2}2(μ-OH)(μ-azolato)]X2, where azolato = pyrazolato, 1,2,3-triazolato, or tetrazolato and X = nitrate or perchlorate) inhibit androgen receptor (AR) signaling. Therefore, here we investigated the potential of 14 such complexes as agents for the treatment of prostate cancer by examining their antiproliferative activity in the human prostate adenocarcinoma cell line LNCaP. Several of the complexes, particularly 5-H-Y ([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2), effectively inhibited LNCaP cell growth, even at low concentrations, by direct modulation of AR signaling, and by binding to DNA and inducing apoptosis, which is a common mechanism of action of Pt-based drugs such as cisplatin (cis-diamminedichloridoplatinum(II)). Comparative analysis with cisplatin revealed superior inhibitory effects of these complexes. Further investigation revealed that 5-H-Y suppressed mRNA expression of genes downstream from AR and induced apoptosis, particularly in cells overexpressing AR, highlighting its potential as an AR antagonist. Thus, we provide here insights into the mechanisms underlying the antiproliferative effects of azolato-bridged complexes in prostate cancer.

Gastric cancer with macroscopic peritoneal metastases represents a major therapeutic challenge and is associated with a poor prognosis. This review aims to evaluate the efficacy and safety of new treatment modalities. A systematic search of PubMed was conducted to identify studies published between January 2014 and April 2024. Inclusion criteria were trials investigating novel therapies for gastric cancer with peritoneal metastases. Data on treatment efficacy, survival outcomes, and side effects were extracted.

Molecular-targeted drugs and immune checkpoint inhibitors have been developed for various malignant diseases, thereby improving clinical outcomes. However, these drugs are expensive, and few studies have assessed their actual use and costs in Japan. This study aimed to survey the use and costs of first-line chemotherapy for advanced/recurrent gastric cancer (AGC) in real-world settings.

The survey included patients with human epidermal growth factor receptor type2 (HER2)-negative AGC who initiated first-line chemotherapy from January 2022 to December 2022 at the participating 92 institutions in the Japan Clinical Oncology Group. Data on the regimens were collected using Google Forms. A regimen that costs >500 000 Japanese yen (JPY) per month was defined as expensive.

Data on chemotherapy regimens were collected from 2173 patients at all 92 institutions between March 2023 and May 2023. We analyzed 2113 patients who underwent the chemotherapy with recommended regimens and conditionally recommended regimens according to the Japanese Gastric Cancer Treatment Guidelines sixth edition. The expensive regimens were triplet chemotherapy with fluoropyrimidine (S-1 or capecitabine or 5-fluorouracil/levofolinate), oxaliplatin, and nivolumab. Their monthly costs ranged from 767 648 to 771 046 JPY. Nivolumab-containing regimens cost more than 20 times the price of conventional chemotherapy with fluoropyrimidine and oxaliplatin. These regimens were used in 1416 (67%) of 2113 patients: in 71% of patients aged ≤74 years and in 59% of patients aged ≥75 years.

The regimens with >20-fold cost of conventional chemotherapy were used as first-line chemotherapy in two-thirds of patients and more than half even in the elderly population with HER2-negative AGC. This finding is important for future health economic studies on drug cost-efficacy.

Chemotherapy tolerance weakened efficacy of chemotherapy drugs in the treating gastric cancer (GC). Banxiaxiexin decoction (BXXXD) was widely used in digestive diseases for thousands of years in Traditional Chinese medicine (TCM). In order to better treat GC, three other herbs were added to BXXXD to create a new prescription named Modified Banxiaxiexin decoction (MBXXXD). Although MBXXXD potentially treated GC by improving chemotherapy tolerance, the possible mechanisms were still unknown.

To explore the therapeutic effect of MBXXXD on GC patients and explore the possible anti-cancer mechanism.

A randomized controlled trial (n = 146) was conducted to evaluate the clinical efficacy between MBXXXD + chemotherapy (n = 73) and placebo + chemotherapy (n = 73) in GC patients by testing overall survival, progression free survival, clinical symptoms, quality of life score, tumor markers, T cell subpopulation, and adverse reactions. Network pharmacology was conducted to discover the potential mechanism of MBXXXD in treating GC. Metabolic activity assay, cell clone colony formation and mitochondrial apoptosis were detected in human GC cell lines including AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD. Multiple pathways including P53, AKT, IκB, P65, P38, ERK, JNK p-AKT, p-P65, p-P38, p-ERK and p-JNK in AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy were also detected.

MBXXXD + chemotherapy promoted overall survival and progression free survival, improved clinical symptoms and quality of life score, increased T4 lymphocyte ratio and T8 lymphocyte ratio as well as T4/T8 lymphocyte ratio, and alleviated adverse reactions in GC patients. Network pharmacology predicted multiple targets and pathways of MBXXXD in treating GC including apoptosis, P53 pathway, AKT pathway, MAPK pathway. MBXXXD inhibited cell viability, decreased cell clone colony formation, and promoted mitochondrial apoptosis by producing reactive oxygen species (ROS), promoting mitochondrial permeability transition pore (MPTP) and the cleavage of pro-caspase-3 and pro-caspase-9, and decreasing mito-tracker red Chloromethyl-X-rosamine (CMXRos) in AGS cell, KNM-45 cell and SGC7901 cell. MBXXXD up-regulated the expression of P53 and IκB, and down-regulated the expression of p-AKT, p-P65, p-P38, p-ERK, p-JNK, AKT, P65, P38, ERK and JNK AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy.

MBXXXD benefitted chemotherapy for GC by regulating multiple targets and pathways.

Nonresectable gastric cancer develops rapidly; thus, monitoring disease progression especially in patients receiving nivolumab as late-line therapy is important. Biomarkers may facilitate the evaluation of nivolumab treatment response. Herein, we assessed the utility of serum-based inflammatory indicators for evaluating tumor response to nivolumab.

This multicenter retrospective cohort study included 111 patients treated with nivolumab monotherapy for nonresectable advanced or recurrent gastric cancer from October 2017 to October 2021. We measured changes in the C-reactive protein (CRP)-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in serum from baseline to after the fourth administration of nivolumab. Furthermore, we calculated the area under the receiver operating characteristic curves (AUC ROCs) for CAR, PLR, and NLR to identify the optimal cutoff values for treatment response. We also investigated the relationship between clinicopathologic factors and disease control (complete response, partial response, and stable disease) using the chi-squared test.

The overall response rate (complete and partial response) was 11.7%, and the disease control rate was 44.1%. The median overall survival (OS) was 14.0 (95% CI 10.7‒19.2) months, and the median progression-free survival (PFS) was 4.1 (95% CI 3.0‒5.9) months. The AUC ROCs for CAR, PLR, and NLR before nivolumab monotherapy for patients with progressive disease (PD) were 0.574 (95% CI, 0.461‒0.687), 0.528 (95% CI, 0.418‒0.637), and 0.511 (95% CI, 0.401‒0.620), respectively. The values for changes in CAR, PLR, and NLR were 0.766 (95% CI, 0.666‒0.865), 0.707 (95% CI, 0.607‒0.807), and 0.660 (95% CI 0.556‒0.765), respectively. The cutoff values for the treatment response were 3.0, 1.3, and 1.4 for CAR, PLR, and NLR, respectively. The PFS and OS were significantly longer when the treatment response values for changes in CAR, PLR, and NLR were below these cutoff values (CAR: OS, p < 0.0001 and PFS, p < 0.0001; PLR: OS, p = 0.0289 and PFS, p = 0.0302; and NLR: OS, p = 0.0077 and PFS, p = 0.0044).

Measurement of the changes in CAR, PLR, and NLR could provide a simple, prompt, noninvasive method to evaluate response to nivolumab monotherapy.

This study is registered with number K2023006.

The effectiveness of palliative gastrectomy for advanced GC remains a topic of debate. This study sought to establish whether palliative gastrectomy has an impact on prolonging survival.

We carried out systematic searches in PubMed, Cochrane Library, Web of Science, and the EMBASE databases from database inception to July 2023 to gather studies that examined the connection between palliative gastrectomy and the prognosis of advanced GC. The study employed overall survival as the primary outcome, with the hazard ratio serving as the selected parameter to gauge the association. Subgroup analyses were performed to delve into potential differences within the included studies, categorizing them by study region and sample size in order to examine possible sources of heterogeneity. The stability of individual studies was assessed through sensitivity analysis. The analysis included 20 articles, encompassing a total of 23,061 patients.

According to the meta-analysis results, patients who underwent palliative gastrectomy exhibited a noteworthy enhancement in overall survival (HR: 1.49; 95% CI: 1.12-1.99; P = 0.006) in comparison to those who did not receive this procedure. There was no association between the type of surgery and the length of hospital stay, as revealed by the analysis (HR = -0.02; 95% CI: -0.84-0.81; P = 0.970).

Based on this meta-analysis, patients with advanced gastric cancer who underwent palliative gastrectomy may experience an extended survival duration without a significant prolongation of their hospitalization.

Despite advances in systemic chemotherapy, patients with gastric cancer (GC) and peritoneal metastases (PMs) continue to have poor prognoses. Intraperitoneal (IP) administration of Paclitaxel (PTX) combined with systemic chemotherapy shows promise in treating PMs from GC. However, methods of drug administration need to be optimized to maximize efficacy. In this study, we utilized a mouse model with PMs derived from a human GC cell line, administering PTX either IP or intravenously (IV), and Carboplatin (CBDCA) IV 0, 1, and 4 days after PTX administration. The PMs were resected 30 min later, and concentrations of PTX and CBDCA in resected tumors were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results indicated that PTX concentrations were higher with IP administration than with IV administration, with significant differences observed on days 0 and 1. CBDCA concentrations 4 days post-IP PTX administration were higher than with simultaneous IV PTX administration. These findings suggest that IP PTX administration enhances CBDCA concentration in peritoneal tumors. Therefore, sequential IV administration of anti-cancer drugs appears more effective than simultaneous administration with IP PTX, a strategy that may improve prognoses for patients with PMs.

Bone marrow metastasis (BMM) of gastric cancer (GC), which is the most common cause of disseminated intravascular coagulation (DIC) among solid tumors, has a poor prognosis. Studies on prognostic improvement beyond one year in patients with GC with BMM are limited. This is the first report of a patient who survived over three years after 30 months of S-1 plus oxaliplatin (SOX) therapy for GC with BMM.

The patient was a 72-year-old woman who presented with anemia and high levels of alkaline phosphatase (ALP) and carbohydrate antigen 19-9 (CA19-9). Detailed examination led to the diagnosis with BMM of GC uncomplicated by DIC and the SOX regimen was initiated in November 2018. After six cycles, she was switched to S-1 monotherapy, and both ALP and CA19-9 levels reached normal by November 2019. However, computed tomography in April 2021 showed multiple bone metastases. Therefore, she was switched to paclitaxel-based therapy. In November 2021, the patient was further switched to nivolumab monotherapy, but she succumbed due to DIC in March 2022.

GCs with BMM are prone to DIC, and the SOX regimen, which includes S-1 with efficacy against micrometastases, may constitute a safe and effective treatment modality.

We aimed to summarize survival data from RCTs in patients with GO adenocarcinoma; estimate and explain worst-, typical-, and best-case-scenarios of survival time; and determine if simple multiples of median overall survival (mOS) could estimate these percentiles.

We systematically searched RCTs of systemic therapies for GO adenocarcinoma published 2000-2022. The following key percentiles were extracted from overall survival curves: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). We tested if these percentiles could be estimated by simple multiples of mOS: 0.25 of the median for the 90th percentile, 0.5 for the 75th, 2 for the 25th, and 3 for the 10th.

We identified 44 trials (22,447 participants). For first line chemotherapy and immunotherapy combined (CI) trials (n = 3) worst-to-best case survival time ranged from 4 months to not reached, compared to 3-30 months for other trials (n = 27) and 1-23 months for subsequent lines (n = 14). Simple multiples of mOS accurately estimated the following survival percentiles: 90th (n = 3/3 trials), 75th (n = 3/3), and 25th (n = 2/3) in first line CI trials. In other first line trials, the mOS accurately estimated the 90th survival percentile in n = 22/27 trials, 75th percentile in n = 26/27, 25th percentile in 27/27 trials, and 10th percentile in 22/27 trials. Simple multiples of the mOS accurately predicted the 90th, 75th, 25th, and 10th survival percentiles in the majority of trials of second and subsequent lines apart from chemotherapy and immunotherapy only trials.

We provide realistic, evidence-based prognostic information as scenarios for survival time which can inform clinical decision-making. Simple multiples of the mOS accurately estimated the percentiles for most groups.

Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects. The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to increase survival rates in these patients. Despite these advancements, debates persist regarding the magnitude of survival improvement attributed to this treatment modality. The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis, and it took a comparative analysis of patients exhibiting positive and negative cytological findings.

To compare the impact of HIPEC on survival in gastric cancer patients with peritoneal metastasis and positive or negative cytology.

Between April 2013 and March 2020, 84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts: HIPEC (20 patients with peritoneal metastasis), cytology-positive (23 patients without peritoneal nodules but with positive wash cytology), and cytology-negative (41 patients with advanced gastric cancer, no peritoneal nodules, and negative wash cytology). The HIPEC cohort underwent gastrectomy with HIPEC, while the cytology-positive and cytology-negative groups received gastrectomy alone. The demographic, pathological, and survival data of the groups were compared.

The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss. Nevertheless, the complication rates were consistent across all three groups. Median survival in the HIPEC group was 20.00 ± 4.89 months, with 1-year, 2-year, and 3-year overall survival rates of 73.90%, 28.70%, and 9.60%, respectively. These figures paralleled the survival rates of the cytology-positive group (52.20% at 1 year, 28.50% at 2 years, and 19.00% at 3 years). Notably, 47% of patients experienced peritoneal recurrence.

HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis, mirroring the outcomes in cytology-positive patients. However, peritoneal recurrence remained high.