To enhance urothelial carcinoma (UC) prognosis, clinicians combine surgery with intraoperative (ICT), neoadjuvant (NACT), or adjuvant chemotherapy (ACT); however, studies on their individual and combined effects vary. Furthermore, studies on the combined use of ACT and NACT are scarce.

This study aimed to assess the impact of these chemotherapy regimens on UC prognosis, particularly the effectiveness of ACT + NACT, using the Surveillance, Epidemiology, and End Results (SEER) database.

We analyzed 45,211 UC cases from 2019 to 2021, focusing on renal, ureter, bladder, prostate, and urethra UC. Cox model-adjusted survival curves and multivariable Cox regression were performed using SPSS and R software.

Compared with ACT, NACT alone did not significantly impact survival (hazard ratio [HR] 0.834, 95% confidence interval [CI] 0.392-1.774, p = 0.638), whereas ACT + NACT (HR 0.389, 95% CI 0.169-0.895, p = 0.026) and ICT + ACT + NACT (HR 0.466, 95% CI 0.246-0.883, p = 0.019) positively affected UC prognosis. However, when compared with the combination of ACT + NACT, the combination of ICT + ACT + NACT did not show a statistically significant effect (HR 1.198, 95% CI 0.427-3.362, p = 0.731). Compared with no chemotherapy, ACT reduced renal UC survival (HR 1.430, 95% CI 1.105-1.850, p = 0.007) but improved ureter (HR 0.460, 95% CI 0.232-0.915, p = 0.027) and bladder UC survival (HR 0.605, 95% CI 0.466-0.785, p < 0.001).

Prognosis after chemotherapy varied depending on different tumor locations. ACT reduced the prognosis of renal UC patients but elevated the prognosis of ureter UC and bladder UC patients. Distinct chemotherapy protocols have also yielded varying prognostic outcomes. For UC patients, the combination of ACT + NACT merits consideration in order to achieve better prognostic outcomes than the use of ACT or NACT alone. The adoption of ICT for UC patients may not be necessary.

Gastric cancer ranks fifth as the most common cancer and third as the leading cause of death worldwide. Risk factors include advancing age, low-fiber diets, high salt intake and Helicobacter pylori infection. Diagnosis relies on histological examination following endoscopic biopsy with staging accomplished through various imaging modalities. Early gastric cancer is primarily managed via endoscopic resection, while non-early operable cases typically undergo surgery. Advanced cases are addressed through sequential chemotherapy lines, with initial treatment usually comprising a platinum and fluoropyrimidine combination. Linitis plastica (LP) is a rare, aggressive form of gastric cancer characterized by diffuse infiltration of the gastric wall, resulting in poor outcomes even after curative resection. The absence of a standardized definition contributes to uncertainty regarding the precise incidence of these tumors. LP is often diagnosed at advanced stages, with a reported median survival rate of approximately 4%-29%, despite "curative resection". Its distinctive biological behavior includes perineural invasion, nodal metastasis, and peritoneal dissemination. The bleak prognosis for LP patients partly stems from delayed diagnosis and its aggressive biological nature, posing significant challenges for clinical management. Currently, no specialized treatment strategy exists for LP, and clinical approaches typically align with those used for general gastric cancer treatment. Surgical resection is the primary treatment, but the optimal surgical approach remains contentious. Recent studies have investigated the efficacy of neoadjuvant chemotherapy and radiotherapy in improving survival outcomes for LP patients. However, controversies persist regarding the role of adjuvant chemotherapy and postoperative radiotherapy. LP requires a multidisciplinary approach and personalized treatment strategies tailored to each patient's condition. Further research is needed to elucidate optimal therapeutic interventions and improve outcomes for LP patients.

Coagulation status is closely related to the progression of malignant tumors. In the era of neoadjuvant immunochemotherapy (NICT), the prognostic utility of coagulation indicators in patients with locally advanced gastric cancer (LAGC) undergoing new treatments remains to be determined.

To determine whether hypercoagulation is an effective prognostic indicator in patients with LAGC who underwent radical resection after NICT.

A retrospective analysis of clinical data from 104 patients with LAGC, who underwent radical resection after NICT between 2020 and 2023, was performed. D-dimer and fibrinogen concentrations were measured one week before NICT, and again one week before surgery, to analyze the association between these two indicators and their combined indices [non-hypercoagulation (D-dimer and fibrinogen concentrations within the upper limit of normal) vs hypercoagulation (D-dimer or fibrinogen concentrations above the upper limit of normal)] with prognosis. After radical resection, patients were followed-up periodically. The median follow-up duration was 21 months.

Data collected after NICT revealed that the three-year overall survival (OS) and disease-free survival (DFS) rates the non-hypercoagulation group were significantly better than those in the hypercoagulation group [94.4% vs 78.0% (P = 0.019) and 87.0% vs 68.0% (P = 0.027), respectively]. Multivariate analysis indicated that hypercoagulation after NICT was an independent factor for poor postoperative OS [hazard ratio (HR) 4.436, P = 0.023] and DFS (HR 2.551, P = 0.039). Pre-NICT data demonstrated no statistically significant difference in three-year OS between the non-hypercoagulation and hypercoagulation groups (88.3% vs 84.1%, respectively; P = 0.443).

Hypercoagulation after NICT is an effective prognostic indicator in patients with LAGC undergoing radical gastrectomy.

Based on the phase 3 PRODIGY study, neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) have emerged as a viable treatment option for Asian patients with resectable locally advanced gastric cancer (LAGC). This phase 2 study evaluated the efficacy and safety of combining neoadjuvant durvalumab with DOS, followed by surgery and adjuvant durvalumab plus S-1 chemotherapy, for resectable LAGC.

Patients with LAGC with cT2/3N+or cT4Nany tumors were enrolled in this study. Patients with proficient mismatch repair protein (pMMR) tumors received three cycles of neoadjuvant durvalumab plus DOS, administered every 3 weeks, followed by surgery and adjuvant S-1 plus durvalumab (main study arm). The primary endpoints were the rate of pathologic complete regression (pCR) and safety. An exploratory arm evaluated patients with deficient mismatch repair protein (dMMR) tumors, who received three cycles of neoadjuvant durvalumab and tremelimumab, followed by surgery and adjuvant durvalumab.

In the main study arm, 50 pMMR patients were enrolled, and received at least one dose of neoadjuvant treatment. The median age was 63 years, with 72.0% being men. 18 and 32 patients presented with clinical stage II and III tumors, respectively. 49 (98.0%) underwent surgery, with 45 achieving R0 resection. A pCR rate of 30.0% was observed, meeting the prespecified primary efficacy endpoint. With a median follow-up of 21.8 months, the 3-year progression-free survival and overall survival rates were 69.9% and 88.1%, respectively. 10% of patients experienced predefined unacceptable severe toxicities, including febrile neutropenia (n=3) and persistent G4 neutropenia (n=2) lasting more than 7 days, thereby meeting the primary safety endpoint. Nine patients with dMMR tumors were enrolled in the exploratory arm. All nine underwent surgery, with a pCR rate of 22.2%.

This study met its primary efficacy and safety endpoints. The combination of neoadjuvant durvalumab plus DOS, followed by surgery and adjuvant durvalumab plus S-1 chemotherapy, warrants further investigation in a phase 3 trial for Asian patients with LAGC.

04221555.

To report the latest systematic review and meta-analysis of randomized controlled trials (RCT) to compare perioperative versus adjuvant chemotherapy for resectable gastric cancer.

We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April, 2024 for RCT which compared perioperative versus adjuvant chemotherapy for resectable gastric cancer. Outcomes measured were overall survival (OS) and progression-free survival (PFS).

5 RCTs including 2,735 patients were included for meta-analysis. Meta-analysis revealed a significant longer PFS in the neoadjuvant chemotherapy (NAC) group (HR: 0.77; 95% CI: 0.69, 0.85; P<0.00001) compared with adjuvant chemotherapy (AC) group. Subgroup analysis found that there was still a significant superiority of NAC in female (HR: 0.53; 95% CI: 0.40, 0.70; P<0.0001) and cN+ (HR: 0.77; 95% CI: 0.67, 0.89; P=0.0005) patients, while the superiority disappeared in male (HR: 0.87; 95% CI: 0.74, 1.01; P=0.07) and cN- patients (HR: 0.91; 95% CI: 0.46, 1.78; P=0.77). In addition, meta-analysis observed a trend towards improved OS with NAC (HR: 0.86; 95% CI: 0.70, 1.07; P = 0.17), and sensitivity analysis demonstrated instability in OS.

NAC can significantly prolong PFS in patients with resectable gastric cancer compared to AC, and the benefit is more significant in women and cN+ patients. Besides, our analysis indicated that NAC has a potential to improve OS compared with AC.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024546165.

Perioperative chemotherapy combined with D2 radical gastrectomy has been proven to be the standard treatment for local advanced gastric cancer. However, tumor regression grading (TRG) is the only neoadjuvant chemotherapy (NACT) response evaluation criterion recommended by the NCCN guideline for gastric cancer (GC). Given TRG's limitations, we aim to explore a better comprehensive response evaluation method in this study.

Clinical information of 96 GC patients who received NACT was collected prospectively. Clinicopathological variables predictive of the response to NACT were identified by comparing the pre- and post-NACT examination results. The correlations between the response mode and long-term survival rate were assessed.

Univariate Cox regression analysis showed that CT-based evaluation of the primary lesion thickness (CT-thickness) and tumor markers (TMs) were significantly associated with prognosis. The comprehensive evaluation method, including CT-thickness, TRG, and TMs, was constructed and proved to have a higher Harrell's C index. Significant differences in overall survival (OS) and recurrence-free survival (RFS) were observed between responders and non-responders distinguished by the comprehensive evaluation method.

The combination of CT-thickness, TRG, and TMs could be used to construct a pragmatic NACT efficacy evaluation method with both high sensitivity and specificity, which could facilitate clinical decision-making, NACT-related clinical research conduction, and efficacy predictive biomarker exploration.

Patients with clinical T2N0 (cT2N0) gastric adenocarcinoma are recommended to undergo either perioperative chemotherapy or upfront resection. If T2N0 disease is pathologically confirmed, patients may be observed without chemotherapy. These guidelines create the possibility of both systemic therapy overuse and underuse depending on clinical staging accuracy. Our objectives were to define factors associated with upstaging after upfront resection and describe the association between postoperative chemotherapy and survival.

Patients with cT2N0 gastric adenocarcinoma were identified using the National Cancer Database. Factors associated with upstaging were assessed by logistic regression. Survival was assessed using Kaplan-Meier and Cox proportional hazard analyses.

Of 4,076 patients undergoing upfront resection for cT2N0 gastric cancer, 1,933 (47.4%) were pathologically upstaged. Patients were more likely to be upstaged if they had >3.0-cm (adjusted odds ratio [aOR] 2.31, 95% confidence interval [CI] 1.97-2.70; P < .001) or poorly differentiated tumors (aOR 2.22, 95% CI 1.89-2.60; P < .001). Patients were less likely to be upstaged if they had distal tumors (aOR 0.77, 95% CI 0.64-0.93; P = .006). Of those pathologically upstaged (n = 1,933), 1,111 (57.4%) received adjuvant chemotherapy that was associated with improved survival (HR 0.55, 95% CI 0.47-0.63; P < .001). Among those not upstaged (n = 2,143), 247 (11.5%) received adjuvant chemotherapy that was not associated with improved survival (HR 0.92, 95% CI 0.70-1.21; P = .54).

Pathologic upstaging after upfront resection in patients with cT2N0 gastric cancer is associated with patient and tumor characteristics. Adjuvant chemotherapy is associated with improved survival only in the patients upstaged at surgery. An upfront surgical approach may be preferred in select patients, especially if avoiding chemotherapy is desired.

The multicentre RESOLVE trial examined the efficacy of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in gastric or gastro-oesophageal junction cancer. Initial analyses did not encompass overall survival owing to the immature data. This paper provides an updated analysis of the survival data from the RESOLVE trial.

In this randomised, open-label, phase 3 study, participants aged 18 years or older with cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma who were feasible for D2 lymphadenectomy and had a Karnofsky performance score of 70 or higher were enrolled. Participants were randomly assigned in a 1:1:1 ratio via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral capecitabine 1000 mg/m2 twice a day on days 1-14, adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40-60 mg twice a day on days 1-14), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy. The primary endpoint, assessed in the modified intention-to-treat population, was 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-CapOx and the non-inferiority (hazard ratio [HR] non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx, and has been reported previously. This final report focuses on the secondary endpoint of 5-year overall survival, also assessed in the modified intention-to-treat population. Other secondary endpoints-R0 resection rate and safety-were not updated in this analysis. The study is registered at ClinicalTrials.gov, NCT01534546, and is complete.

Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were enrolled and randomly assigned, of whom 1022 participants were included in the modified intention-to-treat population: 345 (259 male, 86 female) in the adjuvant-CapOx group, 340 (238 male, 102 female) in the adjuvant-SOX group, and 337 (271 male, 66 female) in the perioperative-SOX group. As of April 7, 2022, the median duration of follow-up was 62·8 months (IQR 52·0-75·1). The 5-year overall survival rates were 52·1% (95% CI 46·3-57·5) for the adjuvant-CapOx group, 61·0% (55·3-66·2) for the adjuvant-SOX group, and 60·0% (54·2-65·3), for the perioperative-SOX group. Overall survival was significantly prolonged with perioperative-SOX (HR 0·79; 95% CI 0·62-1·00, p=0·049) and adjuvant-SOX (HR 0·77, 0·61-0·98, p=0·033), compared with adjuvant-CapOx.

Consistent with the initial analysis of 3-year disease-free survival, the extended 5-year overall survival analysis from the RESOLVE trial confirmed the survival advantage of perioperative-SOX and adjuvant-SOX compared with the standard adjuvant-CapOx regimen. The SOX regimen, given perioperatively or as an adjuvant treatment, emerges as a potential standard treatment modality for locally advanced gastric or gastro-oesophageal junction cancer management in Asian patients.

The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, the Beijing Natural Science Foundation, National Natural Science Foundation of China, the Beijing Natural Science Foundation, Taiho, Hengrui Pharmaceutical and Sanofi-Aventis.

For the Chinese translation of the abstract see Supplementary Materials section.

Pathological regression grade after chemotherapy evaluated by surgically resected specimens is closely related with prognosis. Since usefulness of measuring the area of the residual tumor (ART) has been reported, this study aimed to evaluate the utility of ART in predicting the prognosis of patients with gastric cancer (GC) who received preoperative chemotherapy.

This single-center retrospective study examined the relationship between ART and survival outcomes. We included 92 patients who underwent preoperative chemotherapy followed by radical surgery for GC. Digital images were used to measure the ART in the largest pathological slice of each patient's surgical tumor specimen. We simply subclassified the patients as either ART-0 (< 0.1 mm2 or carcinoma in situ) or non-ART-0 to compare the prognoses.

Significant differences were noted in overall survival and recurrence-free survival (RFS) between ART-0 (n = 19) and non-ART-0 (n = 73). The survival curves were similar to those of major pathological response (MPR) (n = 24) or non-MPR (n = 68), which are commonly used as surrogate endpoint presently. Multivariate analysis revealed ART and ypN independent prognostic factors for RFS. Survival curves stratified using ART and ypN to indicate risk grades (low-, moderate-, or high-) were not significantly different from those stratified using the other three existing pathological regression grade systems and ypN.

ART-based pathological assessment is a simple and useful method for predicting the prognosis in patients with GC who underwent radical surgery after chemotherapy.

Immune checkpoint inhibitors combined with chemotherapy have shown promising efficacy in treating gastric or gastroesophageal junction (G/GEJ) adenocarcinoma in the neoadjuvant setting. This phase II trial (NCT05715632) aimed to investigate the efficacy and safety of perioperative camrelizumab plus XELOX in patients with locally advanced G/GEJ adenocarcinoma. Treatment-naive patients with cT3-4aN1-3 M0 resectable locally advanced G/GEJ adenocarcinoma were recruited to receive camrelizumab (200 mg, intravenously) on Day 1 combined with XELOX (oxaliplatin at 130 mg/m2 on Day 1 and capecitabine at 1000 mg/m2 on Days 1-14) every 3 weeks for four cycles, followed by surgery and adjuvant camrelizumab combined with XELOX every 3 weeks for four cycles. The primary endpoint was the pathological complete response (pCR; ypT0N0) rate. From September 2020 to January 2023, 46 patients were enrolled, and all patients completed neoadjuvant therapy. Among them, 43 underwent D2 resection. In the intention-to-treat population, pCR was achieved in nine patients (19.6%, 95% confidence interval [CI]: 9.9%-34.4%), and the major pathological response was achieved in 25 patients (54.3%, 95% CI: 39.2%-68.8%). The objective response rate was 69.6%, of which 12 patients achieved a complete response and 20 patients achieved a partial response. The 1-year event-free survival and disease-free survival rates were both 93.1%. Treatment-related adverse events (TRAEs) occurred in 42 (91.3%) patients, and grade 3 TRAEs occurred in nine (19.6%) patients. No grades 4-5 TRAEs were observed. Perioperative camrelizumab combined with XELOX showed promising pathological response with an acceptable safety profile in patients with resectable locally advanced G/GEJ adenocarcinoma.

The nationwide registry of the Japanese Gastric Cancer Association contains data related to the efficacy of adjuvant chemotherapy and prognostic factors across this patient population; elderly patients with advanced resectable gastric cancer are especially prevalent. Here, we analyzed data from 34,931 patients, who were treated between 2011 and 2013 at 421 hospitals in Japan. Although adjuvant chemotherapy was effective overall, 75 years or older elderly patients had a worse prognosis compared to younger patients. The most administered adjuvant chemotherapy was S-1 monotherapy. Adjuvant S-1 monotherapy was also effective for patients with pT1N2, pT1N3, and pT3N0 stage II tumors, as well as patients with other stage II and III malignancies. Independent prognostic factors for poor overall and relapse-free survival in patients at both stage II and stage III were age 75 or older, male, preoperative Eastern Cooperative Oncology Group performance status (ECOG-PS) 1 or more, preoperative renal dysfunction, undifferentiated adenocarcinoma, undergoing total gastrectomy, open laparotomy, no adjuvant chemotherapy, D1 lymphadenectomy, residual tumor R1 or R2, and Clavien-Dindo classification grade II or higher. Age 75 or older, renal dysfunction, ECOG-PS 1 and total gastrectomy were also significant risk factors for postoperative complications and lower compliance with adjuvant chemotherapy. Our analysis also revealed that adjuvant chemotherapy after resection of cancer of gastric remnant and postoperative chemotherapy against CY1 gastric cancer were also effective. We conclude that adjuvant chemotherapy is effective for all stage II and III patients including age 75 or older gastric cancer patients, in addition to distal gastrectomy, proximal gastrectomy, and pylorus-preserving surgery to avoid total gastrectomy may improve surgical outcomes and quality of life for elderly patients.

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

This study aims to compare the efficacy between neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy vs . chemotherapy, and neoadjuvant triplet vs . doublet chemotherapeutic regimens in locally advanced gastric/esophagogastric junction cancer (LAGC).

We included LAGC patients from 47 hospitals in China's National Cancer Information Database (NCID) from January 2019 to December 2022. Using propensity score matching (PSM), we retrospectively analyzed the efficacy between neoadjuvant ICIs plus chemotherapy vs . chemotherapy alone, and neoadjuvant triplet vs . doublet chemotherapeutic regimens. The primary study result was the pathologic complete response (pCR) rate. The secondary study results were disease-free survival (DFS) and overall survival (OS).

A total of 1205 LAGC patients were included. After PSM, the ICIs plus chemotherapy and the chemotherapy cohorts had 184 patients each, while the doublet and triplet chemotherapy cohorts had 246 patients each. The pCR rate (14.13% vs . 7.61%, χ2 = 4.039, P = 0.044), and the 2-year (77.60% vs . 61.02%, HR = 0.67, 95% con-fidence interval [CI] 0.43-0.98, P = 0.048) and 3-year (70.55% vs . 61.02%, HR = 0.58, 95% CI 0.32-0.93, P = 0.048) DFS rates in the ICIs plus chemotherapy cohort were improved compared to those in the chemotherapy cohort. No significant increase was observed in the OS rates at both 1 year and 2 years. The pCR rates, DFS rates at 1-3 years, and OS rates at 1-2 years did not differ significantly between the doublet and triplet cohorts, respectively. No differences were observed in postoperative complications between any of the group comparisons.

Neoadjuvant ICIs plus chemotherapy improved the pCR rate and 2-3 years DFS rates of LAGC compared to chemotherapy alone, but whether short-term benefit could translate into long-term efficacy is unclear. The triplet regimen was not superior to the doublet regimen in terms of efficacy. The safety after surgery was similar between either ICIs plus chemotherapy and chemotherapy or the triplet and the doublet regimen.

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.

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the fourth leading cause of cancer-related mortality. The survival of GC patients is significantly affected by the timing of diagnosis, as late-stage detection drastically reduces survival rates. This study investigates treatment modalities, survival outcomes, and mortality factors of GC patients in Najran, Saudi Arabia.

A retrospective analysis was conducted involving 121 patients diagnosed with GC treated at King Khaled Hospital in Najran from January 1, 2014, to December 31, 2022. Clinical and pathological parameters, treatment interventions, and survival outcomes were extracted and analyzed from medical records. The Kaplan-Meier method created survival curves and assessed survival probabilities over time. Univariate and multivariate Cox regression analyses identified independent factors associated with mortality risk, calculating hazard ratios (HR) and 95% confidence intervals (CI) to evaluate associations.

 The median age of the patients was 64 years, with 70 (57.9%) being over 60 years old. The cohort included 86 males (71.1%) and 35 females (28.9%), resulting in a male-to-female ratio of 2.5:1. Notably, 24 patients (19.8%) were underweight, 49 patients (40.5%) had hypertension, and 33 patients (27.3%) had diabetes. Helicobacter pylori infection was present in 18 patients (14.9%). Human epidermal growth factor receptor-2 (HER2) status was negative in 38 patients (31.4%). Elevated levels of carcinoembryonic antigen (CEA ≥ 5 ng/ml) and CA19-9 (≥ 37 U/mL) were noted in 51 patients (42.1%) and 50 patients (41.3%), respectively. Surgical intervention was performed on 72 patients (59.5%), while 49 patients (40.5%) were deemed non-resectable. Among the surgical cohort, neoadjuvant therapy was administered to 36 patients (30%), while others underwent initial or staged surgeries. Pathological findings predominantly showed 95 cases (78.5%) of intestinal-type adenocarcinomas compared to 26 cases (21.5%) of diffuse type. The most common TNM (tumor, node, metastasis) stage was IV (50 patients, 41.3%), followed by stage III (25 patients, 20.7%). During a follow-up of 41.3 ± 38.8 months, 96 patients (79.3%) were alive, while 25 patients (20.7%) had died. The median survival time was 28 months (95% CI: 20-51 months). The one-year, three-year, and five-year survival rates were 68.2% (82 patients), 42.8% (52 patients), and 37.4% (45 patients), respectively. Increased mortality was significantly associated with female gender (HR: 3.12; 95% CI: 1.56-6.24; p = 0.0013), stage IV disease (HR: 1.92; 95% CI: 1.01-3.66; p = 0.0481), and elevated CEA levels (HR: 1.95; 95% CI: 1.08-3.53; p = 0.0277). In contrast, neoadjuvant chemotherapy was linked to reduced mortality (HR: 0.55; 95% CI: 0.31-0.97; p = 0.0374).

The findings of this study indicate a five-year survival rate of 37.4% (95% CI: 29.3-47.8%) among GC patients in Najran. Notably, female gender, advanced disease stage, and elevated CEA levels emerged as significant predictors of increased mortality. Conversely, the administration of neoadjuvant chemotherapy was associated with a reduced mortality risk. These results emphasize the critical need for personalized treatment strategies and robust risk assessments to improve patient outcomes, particularly high-risk ones.

Gastric cancer is prevalent worldwide and is a leading cause of cancer-related death. Patients with GC often present at advanced stages at diagnosis. Patients with locally advanced diseases experience poor survival rates with surgery alone. Multimodality therapy, including peri-operative therapy and adjuvant therapy, has improved outcomes. However, there is no consensus on the optimal treatment approach. Molecular characteristics of GC may help guide treatment choices and studies are currently underway to evaluate other treatment modalities including immunotherapy and targeted therapy.

Helicobacter pylori (H. pylori) infection may affect the efficacy of immunotherapy and adjuvant chemotherapy in gastric cancer patients. However, the role of H. pylori infection in neoadjuvant chemotherapy in patients with locally advanced gastric cancer (LAGC) remains unclear. This study investigated the effect of H. pylori infection on neoadjuvant chemotherapy and prognosis of patients with LAGC.

This retrospective study utilized data from patients with LAGC who underwent neoadjuvant chemotherapy and surgical treatment at the Sixth Affiliated Hospital of Sun Yat-sen University from January 1, 2010, to January 31, 2021. Patients were grouped according to their H. pylori infection status. The responses of the two groups to neoadjuvant chemotherapy and oncological outcomes were then compared.

A total of 239 patients were included in the analysis, and the baseline characteristics of the H. pylori-positive (n = 51) and H. pylori-negative (n = 188) groups were comparable. Further analysis revealed that H. pylori infection was significantly associated with the major pathological response (P = 0.009). Multivariate analysis showed that factors related to major pathological response included; age ≤ 50 (OR: 0.423, 95% CI: 0.194-0.925), H. pylori infection (OR: 0.396, 95% CI: 0.183-0.854), pathological stage T 3/4 (OR: 0.524, 95% CI: 0.288-0.954), and CA12-5 > 35 U/mL (OR: 0.345, 95% CI: 0.132-0.904). Both overall survival (OS) and disease-free survival (DFS) rates were poorer in the H. pylori-positive group than in the H. pylori-negative group (OS: Log-Rank P = 0.035; DFS: Log-Rank P = 0.029).

This cohort study indicated that H. pylori infection may be associated with tumor response to neoadjuvant chemotherapy and survival outcomes in patients with LAGC.

This study reviews the findings of a recent study by Li et al, which demonstrated that perioperative chemotherapy benefits patients with diffuse-type gastric cancer compared to surgery alone. Despite potential biases, the study supports the inclusion of perioperative chemotherapy in treatment guidelines. Neoadjuvant and adjuvant chemotherapy may also provide similar survival outcomes, allowing for flexible treatment planning.

Immunotherapy has become a prevalent strategy in the neoadjuvant treatment of advanced gastric cancer (AGC). This study investigates the predictive value of computed tomography (CT)-derived body composition parameters on the efficacy of neoadjuvant immunotherapy for AGC.

Data on 103 patients with resectable AGC who received neoadjuvant immunotherapy combined with chemotherapy at a teaching hospital between March 2020 and August 2022 were collected. Body composition parameters, including the subcutaneous adipose index (SAI), visceral adipose index (VAI), and skeletal muscle index (SMI), were calculated from pretreatment CT images. Logistic regression and Cox proportional hazards models assessed the impact of these parameters on pathological responses and survival outcomes following treatment.

Of the patients, 34 (33.0%) achieved a major pathological response (MPR). Higher SAI, VAI, and SMI values were significantly linked to an increased likelihood of achieving MPR (p < 0.05). Multivariate regression analysis revealed that only SAI independently predicted MPR (OR 1.042, 95% CI 1.009-1.077, p = 0.013). Furthermore, patients with a high SAI had significantly improved 2-year overall survival (76.9% vs. 54.9%, log-rank p = 0.012) and 2-year event-free survival (71.2% vs. 51.0%, log-rank p = 0.022) compared to those with low SAI. The survival benefit associated with high SAI was partly due to its higher MPR rate (mediating proportion: 37.5%, 95% CI: 12%-110%).

Pretreatment SAI independently correlates with MPR and better oncological outcomes in patients with AGC receiving neoadjuvant immunotherapy.

No consensus exists on the optimal therapy for resectable gastric cancer (GC) and gastroesophageal junction (GEJ) tumors, including the effectiveness of chemoradiotherapy versus perioperative chemotherapy (PC). Our study aimed to compare overall survival (OS) outcomes associated with the recommended treatment modalities for GC and GEJ tumors and evaluate treatment trends from 2010 to 2020. A national registry cohort identified patients with ≥ cT2 nonmetastatic GC and GEJ cancer. Treatment modalities were classified as neoadjuvant chemotherapy (NC), neoadjuvant chemoradiotherapy (NCR), PC, adjuvant chemotherapy (AC), and adjuvant chemoradiation (ACR). Kaplan-Meier curve and multivariable Cox regression models evaluated factors associated with OS. A cohort of 7665 patients were included. Patients who received PC had the highest OS (median 86.80 months, 95% CI 73.40-NE), while chemoradiotherapy in the neoadjuvant and adjuvant settings had worse OS than PC and NC (NCR median 47.15 months, 95% CI 44.58-52.27, and ACR median 52.67 months, 95%CI 42.78-63.93). The Cox proportional hazards model showed that NCR and NC had worse survival than PC (HR 1.74, 95% CI 1.50-2.02, p < 0.001 and HR 1.26, 95% CI 1.10-1.44, p = 0.0008, respectively). Additionally, the most utilized modality during 2020 was NC (35.8%), followed by PC (28.0%) and NCR (24.9%). The utilization of PC and NC had the most substantial rise between 2010 and 2020, increasing by 11.0%. The study demonstrates the association of PC with improved OS outcomes for nonmetastatic GC and GEJ tumors. Therapies combining radiation with chemotherapy and extended lymph node dissection correlated with a worse prognosis compared to PC and NC. Despite the association with improved outcomes, national data reveals low utilization rates for PC.

Gastric cancer (GC) remains a leading cause of morbidity and mortality worldwide. The current standard of care involves neoadjuvant chemotherapy (NACT) followed by radical gastrectomy. This study aims to evaluate the efficacy of neoadjuvant therapy with PD-1/PD-L1 inhibitors in comparison to chemotherapy alone for patients with locally advanced gastric cancer (LAGC).

We conducted a systematic search of PubMed, Web of Science, and Embase to identify studies examining the addition of PD-1/PD-L1 inhibitors to neoadjuvant therapy for LAGC. Odds ratios (OR) were calculated for binary outcomes, such as pathological complete response (pCR), with corresponding 95% confidence intervals (CI).

Seven studies were included, encompassing a total of 1772 patients. Baseline median age ranged from 31 to 75 years. Most patients had an ECOG performance status score of 0 (942 patients), while 294 had an ECOG score of 1. The estimated pCR (OR 5.94, 95% CI 3.98-8.87; p < 0.000001) significantly favored the PD-1/PD-L1 inhibitors combined with chemotherapy over chemotherapy alone. Additionally, the incidence of certain adverse events increased significantly in the intervention group, including any-grade hypothyroidism (OR 4.55, 95% CI 2.27-9.10; p = 0.000019) and rash (OR 1.74, 95% CI 1.10-2.76; p = 0.017). Conversely, the control group showed a statistically significant lower incidence of grade ≥ 3 fatigue (OR 2.80, 95% CI 1.15-6.85; p = 0.024) compared to the intervention group.

This systematic review and meta-analysis indicate that the addition of PD-1/PD-L1 inhibitors to neoadjuvant chemotherapy is associated with a higher pathological complete response rate compared to chemotherapy alone in patients with locally advanced gastric cancer.

This study aims to evaluate the effectiveness and safety of prophylactic hyperthermic intraperitoneal chemotherapy (P-HIPEC) in patients with locally advanced gastric cancer (AGC) after laparoscopic radical gastrectomy. Additionally, it explores how the frequency and timing of P-HIPEC influence treatment outcomes.

A retrospective analysis was conducted on 227 patients with locally AGC who underwent laparoscopic surgery at Maoming People's Hospital from January 2016 to December 2022. Patients were stratified into the HIPEC group (n=101) and the non-HIPEC group (n=126), based on whether they received postoperative P-HIPEC. Propensity score matching (PSM) was used to adjust for baseline characteristics, facilitating a comparative analysis of survival outcomes, postoperative complications and recurrence patterns. Cox regression analysis was performed to identify prognostic factors. Furthermore, the impact of varying P-HIPEC frequencies and initiation timings was evaluated.

No significant differences in overall survival (OS) or postoperative complication rates were observed between the two groups in the original and PSM cohorts. But the disease-free survival (DFS) of the HIPEC group was significantly higher than that of the non-HIPEC group (HR 0.569; 95% CI 0.362-0.894; p = 0.013) in the PSM cohort, with 1-year, 3-year, and 5-year DFS rates showing notable improvement (77.9% vs. 69.7%, 60.1% vs. 43.0%, and 46.2% vs. 25.5%). The incidence of isolated peritoneal metastasis (PM) was significantly lower in the HIPEC group (5.3% vs. 17.3%, p = 0.039). Multivariate Cox regression analysis identified P-HIPEC as an independent protective factor for DFS. Further analysis indicated that neither the number of P-HIPEC sessions had a significant impact on OS (p = 0.388) or DFS (p = 0.735), nor did the timing of P-HIPEC initiation affect OS (p = 0.620) or DFS (p = 0.488). Likewise, different P-HIPEC frequencies or initiation timings had no significant impact on postoperative complication rates or recurrence patterns.

P-HIPEC effectively reduces the risk of postoperative PM and improves DFS in patients with locally AGC without increasing postoperative complications. However, it does not significantly impact OS. Additionally, variations in the frequency and timing of P-HIPEC initiation do not significantly affect survival outcomes, postoperative complications, or recurrence patterns.

The prognosis of advanced gastric cancer (GC) with extensive lymph node (LN) metastasis treated with surgery alone remains poor. We conducted a multicenter phase II study to evaluate the efficacy and safety of perioperative capecitabine plus oxaliplatin (CapeOx) therapy in patients with advanced GC with extensive LN metastases.

Patients with histologically proven HER2-negative or unknown gastric adenocarcinoma with paraaortic LN (PALN) metastases and/or bulky LN metastases located at the celiac axis, common hepatic artery, and/or splenic artery were included in the study. Patients received three cycles of preoperative CapeOx every 3 weeks, followed by five cycles of postoperative CapeOx after gastrectomy with D2 or D2 + including PALN dissection. The primary endpoint was the response rate (RR) according to the RECIST v1.0 criteria.

Thirty patients from 14 institutions were enrolled from September 2017 to June 2022. Complete response, partial response, stable disease, and progressive disease occurred in zero, 20, eight, and one patient, respectively. One patient was not evaluated. The RR was 66.7% (90% confidence interval, 50.1-80.7%; one-sided P = 0.049). The preoperative chemotherapy completion rate and the curative resection rate were 96.7% and 93.3%, respectively. The minor (grade ≥ 1b) pathological RR was 66.7%. Grade 3 adverse events of preoperative chemotherapy included neutropenia in 3.3%, anemia in 6.7%, and anorexia in 10.0%. One treatment-related death occurred due to postoperative complications.

Preoperative CapeOx chemotherapy showed a favorable RR, curative resection rate, and acceptable adverse events in patients with advanced GC with extensive LN metastasis.

UMIN000028749 and jRCTs051180186.

Gastric cancer patients receiving neoadjuvant chemotherapy (NACT) are more vulnerable to perioperative stress. Enhanced recovery after surgery (ERAS) is widely used in surgical patients aiming at reducing stress responses. However, whether this approach is safe and feasible for gastric cancer patients received minimally invasive radical gastrectomy after NACT remained determined. So, the objective of this study is to investigate the effects of ERAS for this special group of gastric cancer patients.

The data of gastric cancer patients who underwent minimally invasive radical gastrectomy after NACT were collected. Patients were divided into an ERAS group and a conventional group based on whether they received perioperative ERAS management. Propensity score matching was conducted to eliminate bias. Pre- and postoperative inflammatory and nutritional marker levels, postoperative complications, recovery indices and 3-year OS and RFS were observed.

A total of 252 patients were analyzed after 1:1 PSM, including 126 patients in the ERAS group and 126 in the conventional group. The results showed that the implementation of ERAS significantly reduced the levels of novel inflammatory indicators, improve nutritional status and accelerate postoperative recovery. We found that the 3-year OS (72.2 % vs. 66.7 %) and RFS (67.5 % vs. 61.9 %) in the ERAS group showed an improvement trend compared to those in the traditional group, especially for stage III patients, although these differences were not significant.

The perioperative ERAS program is safe and feasible for gastric cancer patients received minimally invasive radical gastrectomy after NACT.

Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023.

The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys.

Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023. Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014. The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023. However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively.

The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

The Korean Laparoendoscopic Gastrointestinal Surgery Study Group (KLASS) trial series represents a comprehensive body of surgical clinical trials and studies focused on laparoscopic techniques in the treatment of gastric cancer. These trials, conducted and overseen by the KLASS, began with KLASS 01 in 2006 and have progressed to their 14th series as of December 2024. To date, approximately 36 papers, including pivotal publications, have been featured in high-impact journals, significantly advancing the field of gastric cancer treatment. Their findings have been incorporated into gastric cancer treatment guidelines in Korea, Japan, and China, underscoring their influence and clinical relevance. I take immense pride in being part of this remarkable journey, alongside esteemed seniors, colleagues, and numerous clinical researchers who initiated KLASS in 2004. This paper aims to review the studies conducted within the KLASS series to date and provide insights insight into the ongoing the ongoing research initiatives being developed by this esteemed group on their behalf.

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.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area. Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version. Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

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.

Lymphovascular invasion (LVI) has been identified as a prognostic factor in various cancers, but its significance in node-negative gastric cancer remains unclear. Gastric cancer prognosis is notably affected by lymph node metastasis, with LVI potentially indicating metastatic spread.

A retrospective review was conducted on 5,699 patients who underwent curative radical gastrectomy for gastric cancer between 1989 and 2018. The median follow-up duration was 62 months (0-362 months). Overall, disease-specific, and disease-free survival were compared based on LVI status and stratified by T stage. Additionally, patients with stage IIA or T2N0 were further evaluated to clarify the clinical significance of LVI in the T2N0 group.

The T2N0 LVI-positive group exhibited significantly poor prognosis than those in the T2N0 LVI-negative group, with no significant differences observed on comparing the T2N0 LVI-positive group with the T2N1 LVI-negative or LVI-positive groups. Furthermore, although the T2N0 LVI-negative group demonstrated better prognosis compared to the IIA group, the T2N0 LVI-positive group exhibited worse survival. In addition, LVI positivity was an independent risk factor for overall survival in T2N0 patients.

LVI in node-negative gastric cancer has clinical significance as a prognostic indicator, indicating an increased risk of disease recurrence and poor survival especially in T2 cohort. This indicates an increased likelihood of lymph node involvement and may influence treatment decisions and follow-up strategies.

Neoadjuvant chemotherapy has been demonstrated to be effective and recommended as the standard treatment option in patients with locally advanced gastric or gastro-oesophageal junction (G/GOJ) cancer. In this study, we will explore the efficacy and safety of chemotherapy combined with cadonilimab, a programmed death-1/cytotoxic T lymphocyte-associated antigen-4 bispecific antibody, in neoadjuvant therapy for locally advanced G/GOJ adenocarcinoma.

This is a single-centre, single-arm, open-label, phase II trial that will enrol 37 patients in total. Eligible patients will be registered and receive three cycles of oxaliplatin and S-1 (SOX) regimen in combination with cadonilimab. Radical D2 (D2 lymphadenectomy) gastrectomy will be performed within 4 weeks after the last administration of chemotherapy plus cadonilimab. The primary endpoint is the pathological complete response rate. Secondary endpoints are R0 resection rate, major pathological response, 2-year disease-free survival rate, 2-year overall survival rate and safety. The first participant was recruited on 1 September 2023 and the enrolment will be completed in July 2025.

Written informed consent will be required from and provided by all the patients enrolled. The study protocol (V.3.0, 28 April 2023) has been approved by the independent ethics committee of West China Hospital, Sichuan University (approval number: 2023526) and conducted under the Declaration of Helsinki. The results of the study may provide more evidence for neoadjuvant immunotherapy combined with chemotherapy in locally advanced G/GOJ adenocarcinoma.

ClinicalTrials.gov, NCT05948449.