This study aimed to assess the diagnostic accuracy of multidetector contrast-enhanced computerised tomography (MDCT) and to establish a correlation between radiological and histopathological staging in upfront resected localised gastric cancers (GC).

All consecutive patients of resectable, localised GC who underwent upfront elective resection between 2010 and 2022 were included. The initial clinical staging determined during multidisciplinary meetings was compared with the pathological stage obtained after surgery. Subsequently, a retrospective, blinded review was conducted to assign a revised clinical staging, and accuracy was correlated.

The analysis of 138 patients revealed varying accuracy of MDCT in determining the T stage (66.9% for T1/T2, 64.6% for T3, and 87.2% for T4) and N stage (60.8% for N0, 63.7% for N1, and 83.2% for N2). The accuracy for stage group ranged from 71 to 78.65%. There was weak agreement observed between the T, N, and overall stage on clinicopathological correlation. However, a blinded radiology review by oncoradiologists resulted in improved accuracy, particularly in T1/T2 disease, and also improved pathological stage correlation.

Although MDCT is a valuable initial staging tool for gastric cancer, we found weak agreement between the clinical and the pathological stages in upfront resected gastric cancers. By implementing an expert radiology review and standardising scanning and reporting protocols, we can significantly improve the accuracy and correlation of MDCT with pathology, even for T1/T2 disease. This may help in better selecting patients for upfront surgery versus perioperative chemotherapy, especially in resource-constrained settings.

Since the FLOT4 gastric cancer (GC) trial, the use of adjuvant chemotherapy has been perceived as limited and its added value questioned. We wanted to objectify this perception and reassess the value of adjuvant chemotherapy in a real-world setting.

In our retrospective cohort study we analyzed real-world data from 147 patients with GC or cancer of the gastroesophageal junction (AEG) who received perioperative FLOT. Data originated from clinical care at the university hospital, local hospitals and medical practices. Clinicopathologic data, survival outcomes, and targetable biomarkers were analyzed.

Median overall survival (OS) and tumor specific survival (TSS) were 19.4 ± 2.9 and 19.9 ± 3.1 months, respectively. 84.4% completed all cycles of neoadjuvant chemotherapy. The pathological complete response rate was 11.8%. Adjuvant chemotherapy was initiated in only 42.9%. Survival rates of patients with marked tumor regression (TRG1) were not improved by adjuvant chemotherapy. Conversely, patients with partial histopathologic response (TRG2) showed a marked trend and those with minimal histopathologic response (TRG3) showed a significantly longer survival with any number of adjuvant chemotherapy cycles (OS: 22.3 ± 2.6 months versus 8.7 ± 2.4 months, p = 0.005; TSS: 22.3 ± 4.5 months versus 8.7 ± 2.4 months, p = 0.016). Targetable biomarkers PD-L1, Claudin 18.2, HER2 and microsatellite instability were detected in 53.4%, 26.2%, 7.8%, and 3.9% of the TRG2/3 patient subset, respectively.

In the real-world setting, adjuvant chemotherapy proved to be a critical turning point of the FLOT regimen. It should be sought-even in a reduced form-in patients with TRG2/3.

There is a clinical need to identify early predictors for response to neoadjuvant chemotherapy (NAC) in patients with gastric and gastroesophageal junction cancer (GC and GEJC). Radiomics involves extracting quantitative features from medical images. This study aimed to apply radiomics to build prediction models for the response to NAC.

All consecutive patients with non-metastatic GC and GEJC undergoing NAC and surgical resection in an Italian high-volume referral center between 2005 and 2021 were considered eligible. In patients selected, the CT scans performed upon staging were reviewed to segment the tumor and extract radiomic features using MODDICOM. The primary endpoint was to develop and validate radiomic-based predictive models to identify major responders (MR: tumor regression grade TRG 1-2) and non-responders (NR: TRG 4-5) to NAC. Following an initial feature selection, radiomic and combined radiomic-clinicopathologic prediction models were built for the MR or NR status based on logistic regressions. Internal validation was performed for each model. Radiomic models (in the entire case series and according to NAC regimens) were evaluated using the receiver operating characteristic area under the curve (AUC), sensitivity, and negative predictive value (NPV).

The study included 77 patients undergoing NAC and subsequent tumor resection. The MR prediction model after all types of NAC (AUC of 0.876, CI 95% 0.786 - 0.966, sensitivity 83%, and NPV 96%) was based on a statistical feature. The models predicting NR among patients undergoing epirubicin with cisplatin and fluorouracil (ECF), epirubicin with oxaliplatin and capecitabin (EOX), or fluorouracil with oxaliplatin and docetaxel (FLOT) (AUC 0.760, CI 95% 0.639-0.882), oxaliplatin-based chemotherapy (AUC 0.810, CI 95% 0.692-0.928), and FLOT (AUC 0.907, CI 95% 0.818 - 0.995) were based on statistical, morphological and textural features.

The developed radiomic models resulted promising in predicting the response to different neoadjuvant chemotherapy strategies. Once further implemented on larger datasets, they could be valuable and cost-effective instruments to target multimodal treatment in patients with GC.

Neoadjuvant therapy (NAT) is increasingly used in locally advanced gastric cancer (LAGC), but a significant proportion of patients respond poorly, causing adverse outcomes. Few studies have specifically examined the prognosis of this subgroup. This study aimed to analyze survival and recurrence in poor responders to guide follow-up and treatment strategies.

This multicenter retrospective study included patients with LAGC who received NAT. Tumor regression was graded following the Becker system, defining TRG 2-3 as poor response. Outcomes were assessed for overall survival (OS), recurrence-free survival (RFS), and recurrence patterns.

648 patients were included: 341 with TRG 2 and 307 with TRG 3. In the entire cohort, the 3-year OS and RFS were 54.6% and 55.2%, respectively. Recurrence occurred in 299 patients, with the following recurrence patterns: distant metastasis (26.1%, n = 78), peritoneal metastasis (21.1%, n = 63), locoregional recurrence (18.7%, n = 56), and multiple-site recurrence (18.4%, n = 55). Liver metastasis was significantly higher in the TRG 3 group than in the TRG 2 group (14.1% versus 5.3%, P = 0.010). ypN+ was the most significant independent risk factor for recurrence (OR = 2.73, 95% CI 1.83-4.08, P < 0.001); an increasing number of positive lymph nodes led to higher 3-year cumulative mortality in patients. Despite poor response to NAT, completing over four adjuvant chemotherapy cycles was associated with improved survival outcomes.

Poor NAT responders in LAGC have high recurrence rates, particularly in the first year post-surgery, with ypN+ status being the strongest predictor of recurrence. Completing over four cycles of AC was associated with survival improvement in this group.

Gastric cancer (GC) is a prevalent digestive system tumor, the fifth most diagnosed cancer worldwide, and a leading cause of cancer deaths. GC is distinguished by its pronounced heterogeneity and a dynamically evolving tumor microenvironment (TME). The lack of accurate disease models complicates the understanding of its mechanisms and impedes the discovery of novel drugs. A growing body of evidence suggests that GC organoids, developed using organoid culture technology, preserve the genetic, phenotypic, and behavioral characteristics. GC organoids hold significant potential for predicting treatment responses in individual patients. This review provides a comprehensive overview of the current clinical treatment strategies for GC, as well as the history, construction and clinical applications of organoids. The focus is on the role of organoids in simulating the TME to explore mechanisms of immune evasion and intratumoral microbiota in GC, as well as their applications in guiding clinical drug therapy and facilitating novel drug screening. Furthermore, we summarize the limitations of GC organoid models and underscore the need for continued technological advancements to benefit both basic and translational oncological research.

The safety and feasibility of laparoscopic surgery for T4b gastric cancer with transverse colon or mesocolon invasion remain insufficiently characterized. This study aimed to compare the surgical outcomes of laparoscopic and open gastrectomy in individuals with T4b gastric cancer involving these anatomical structures.

A retrospective cohort study was conducted across two centers, including 53 individuals with T4b gastric cancer involving the transverse colon or mesocolon who underwent curative-intent surgery between January 2011 and December 2019. Participants were divided into two groups based on the surgical approach: laparoscopic surgery (n = 32) and open surgery (n = 21). Perioperative outcomes, postoperative complications, and survival outcomes were evaluated and compared.

Baseline characteristics were comparable between the groups. The laparoscopic approach demonstrated significantly reduced intraoperative blood loss compared to open surgery (92.5 ± 101.9 mL vs. 147.6 ± 76.6 mL, p = 0.039). No significant differences were observed in operating time (187.8 ± 52.7 vs. 185.9 ± 52.3 min, p = 0.896), R0 resection rates (93.8% vs. 90.5%, p = 0.659), lymph node yield, or length of postoperative hospital stay. The incidence of postoperative complications was similar between the groups (10.3% vs. 10.5%, p = 0.986). Additionally, mean overall survival (31.4 vs. 27.2 months, p = 0.506) and progression-free survival (26.1 vs. 23.5 months, p = 0.573) did not differ significantly.

Laparoscopic gastrectomy with combined resection appears to be a feasible and safe alternative to open surgery for selected individuals with T4b gastric cancer involving the transverse colon or mesocolon. This approach achieves similar perioperative and long-term clinical outcomes compared to open surgery.

Effective treatment of locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer remains a challenge.

To compare the efficacy and safety of atezolizumab plus trastuzumab plus capecitabine and oxaliplatin chemotherapy (XELOX) vs trastuzumab plus XELOX in Chinese patients with locally advanced human epidermal growth factor receptor 2 (ERBB2; formerly HER2)-positive GC or adenocarcinoma of the GEJ.

This was an open-label phase 2 randomized clinical trial conducted at 8 study sites in China. Patient recruitment started on February 25, 2021, and this study is ongoing as participants are still being actively followed up. Chinese patients eligible for surgery with locally advanced ERBB2-positive GC or adenocarcinoma of the GEJ were included. Data were analyzed from March 2021 to October 2023.

Eligible patients were enrolled and randomly assigned 1:1 to perioperative treatment with either atezolizumab plus trastuzumab plus XELOX (arm A) or trastuzumab plus XELOX (arm B) for 3 neoadjuvant cycles (3 weeks per cycle) and 5 adjuvant cycles.

The primary efficacy end point was the pathological complete response (pCR) rate following completion of neoadjuvant therapy and surgery.

In total, 42 patients were screened and randomly assigned to arm A (n = 21) or arm B (n = 21). The median (range) ages were 61 (33-72) years and 65 (49-72) years in arm A and arm B, respectively, and 39 patients (93%) were male. The pCR rate was significantly higher in arm A (8 [38%]) than arm B (3 [14%]; difference, 23.8%; 90% CI, 1.3-44.7). Age younger than 65 years, male sex, and intestinal Lauren classification were significantly associated with a better pCR rate in arm A. Median event-free survival, disease-free survival, and overall survival were not reached. Based on the same way of interpretation, major pathologic response should be statistically significantly different between the 2 arms, while other outcome measures remained not significantly different. The incidence of treatment-emergent adverse events was 100% (21 of 21) and 100% (21 of 21) in arms A and B, respectively; grade 3 or higher TEAEs, 57% (12 of 21) and 67% (14 of 21), respectively; and serious TEAEs, 29% (6 of 21) and 10% (2 of 21), respectively.

In this randomized clinical trial, add-on atezolizumab to trastuzumab plus XELOX therapy demonstrated promising efficacy in this patient population, and no new safety concerns were raised.

ClinicalTrials.gov Identifier: NCT04661150.

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.

Background: Medical care structures differ between urban and rural areas. Clinical cancer registries can depict real-world care through detailed data analysis, identifying potential regional disparities and contributing to improvements in healthcare. Methods: Data from the Brandenburg-Berlin Clinical-Epidemiological Cancer Registry for the years of diagnosis 2017-2022 were analyzed to assess the epidemiology and real-world care of gastric cancer, including cardia. Brandenburg was compared to Berlin regarding perioperative treatment regimens. The resulting survival benefits were assessed using Kaplan-Meier and Cox regression models. Results: For the years of diagnosis 2017 to 2022, 5805 cases of gastric carcinoma were documented in the cancer registry. Survival data showed no significant differences between Berlin and Brandenburg. Preoperative therapy for cT3/cT4N0 tumors was significantly more common in Berlin (72%) than in Brandenburg (68%). Perioperative therapy was associated with a survival benefit for stages T3-/T4N+ but not for stages T1N+ or T2. The lower proportion of pre-treated T3/T4N+ patients in rural Brandenburg did not result in a significant survival difference. Conclusions: The data provide a comprehensive representation of the current state of gastric cancer care in these two regions. Gastric cancer treatment outcomes, in terms of survival, are comparable between the rural region of Brandenburg and the urban center of Berlin.

Many patients respond poorly to neoadjuvant chemotherapy (NACT), negatively affecting the surgical success rate. Identifying effective biomarkers and understanding the potential resistance mechanisms are urgently needed. Data of 18 patients with advanced stomach cancer who were treated with NACT categorized according to tumor regression grade into major histological response (MJHR) and nonhistological response (NHR) groups were retrospectively analyzed. Genomic signatures associated with the response to NACT were identified using whole-exome and RNA sequencing. Extraction of molecular signatures revealed increased deficient mismatch repair signature and tumor mutation levels in the NHR group. Compared to the MJHR group, the NHR group was also characterized by a greater number of copy number alterations (p = 0.08), which was further confirmed by RNA sequencing, and upregulation of aurora kinase A (AURKA) (p = 0.05) and cyclin-dependent kinase 6 (CDK6) (p = 0.049). Western blot analysis and immunohistochemical analyses further confirmed high CDK6 (p < 0.01/p < 0.0001) and AURKA (p < 0.01/p < 0.001) expression levels in the NHR group. Finally, palbociclib, an inhibitor of CDK4/6, effectively inhibited the proliferation (p < 0.05) and induced apoptosis of oxaliplatin-resistant gastric cancer cells (p < 0.01) in vitro. These findings support the potential value of AURKA and CDK6 amplification, as well as their effects on the tumor microenvironment, in predicting poor outcomes of NACT in patients with locally advanced gastric cancer. Thus, CDK4/6 inhibitors could be used to treat NACT-resistant patients with gastric cancer.

With the annual increase in the incidence and mortality rates of gastric cancer, it has gradually become one of the significant threats to human health. Approximately 90% of gastric cancer patients are diagnosed with adenocarcinoma. Although the 5-year survival rate for early-stage gastric cancer can exceed 90%, due to its concealed symptoms, less than half of the patients are eligible for radical surgical treatment upon diagnosis. For gastric cancer patients receiving palliative treatment, the current expected survival time is only about one year. In China, the majority of gastric cancer patients, accounting for about 80% of the total, are in the locally advanced stage. For these patients, radical surgery remains the primary treatment option; however, surgery alone is often inadequate in controlling tumor progression. In the pivotal MAGIC study, the recurrence rate was as high as 75%, and similar results were obtained in the French ACCORD07-FFCD9703 study. Numerous clinical trials are currently exploring preoperative neoadjuvant therapy for patients with locally advanced gastric cancer. Data indicates that preoperative neoadjuvant therapy can not only reduce the size of the local tumor but also shrink surrounding lymph nodes, thereby downstaging the tumor and improving the R0 resection rate. Additionally, it can decrease tumor cell activity and eliminate potential micrometastases. The emergence of various immunotherapies has ushered in a new era for neoadjuvant treatment options for gastric cancer.

The FLOT regimen, a combination of fluorouracil, leucovorin, oxaliplatin, and docetaxel, is a standard treatment for gastric and esophagogastric junction cancers, but concerns exist about its potential renal toxicity. The exact prevalence and severity of renal toxicity need to be well documented, and this knowledge gap could impact the optimal use of the FLOT regimen in clinical practice. We aimed to evaluate the renal toxicity profile of the FLOT regimen with a specific focus on acute kidney disease (AKD) onset in a real-life setting and explore associated risk factors.

We conducted a multicenter retrospective study involving 96 patients treated with preoperatory FLOT. The incidence of AKD and potential risk factors were identified.

AKD occurred in 3 patients (incidence rate of 0.0122 cases/month of follow-up). Oral antidiabetic agents and prostate hypertrophy emerged as significant predictors of AKD.

AKD is uncommon in patients treated with the preoperatory FLOT regimen. Our findings highlight the importance of diligent renal function monitoring and appropriate preventive strategies in patients undergoing FLOT treatment. These results encourage the conduction of further studies and clinical experience in larger populations and patients with lower baseline estimated glomerular filtration rate.

We investigated the safety and efficacy of laparoscopic gastrectomy (LG) in patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy (NAC).

This study included 247 consecutive patients with advanced gastric cancer who underwent NAC followed by gastrectomy between 2007 and 2017 at one of six institutions. The patients were divided into the open gastrectomy (OG) and LG groups. The short- and long-term outcomes in both groups were investigated after propensity score matching.

After propensity score matching, 72 pairs of patients were selected. The baseline characteristics were not significantly different after matching. Compared with the OG group, the LG group had a significantly longer operative time (360 vs. 305 min, P = 0.002) and less intraoperative blood loss (271 vs. 652 mL, P < 0.001). The LG group had more harvested lymph nodes than the OG group (57.4 vs. 45.1, P < 0.001). The frequency of Clavien-Dindo grade ≥ 2 postoperative complications was not significantly different (26% vs. 22%, P = 0.698). The interval between surgery and postoperative chemotherapy was significantly shorter in the LG group (48.7 vs. 68.6 days, P = 0.048). The 5-year overall survival rates in the OG and LG groups were 54.4% and 53.5%, respectively. The overall survival was similar between the two groups (P = 0.773). No significant differences were observed between the two groups in terms of the type of recurrence, including lymph node, hematogenous, and peritoneal recurrences (P = 1.000, P = 1.000, and P = 0.686, respectively).

Based on both short- and long-term results, LG is a potential therapeutic option for patients with gastric cancer who undergo NAC.

Many patients with locally advanced gastro-oesophageal cancers are unable to complete adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, raising questions about its therapeutic utility. The aim of this study was to examine whether pathological response to neoadjuvant FLOT can guide its adjuvant use.

Patients with non-metastatic gastro-oesophageal adenocarcinoma who received neoadjuvant FLOT and underwent surgery from 1 January 2017 to 1 January 2022 from 43 hospitals across 12 countries were analysed. Pathological response was assessed using tumour regression grading systems, trichotomized into minimal responders (MR; worst category), complete responders (CR; pCR), and partial responders (PR; between MR and CR). Survival outcomes of patients who did and did not receive adjuvant FLOT were compared using Kaplan-Meier, Cox regression, propensity score matched, and sensitivity analysis.

A total of 1887 patients (459 MR, 221 CR, and 1207 PR) were evaluated. The median follow-up was 25.5 (interquartile range 15.0-39.1) months. In the MR group, there was no difference in disease-free survival (DFS; HR 1.03 (95% c.i. 0.78 to 1.36), P = 0.836) between those who did and did not receive adjuvant FLOT. Whilst there was a difference in non-adjusted OS, this became statistically non-significant after adjusting for baseline characteristics (HR 0.96 (95% c.i. 0.70 to 1.30), P = 0.801). In the CR group, there was no difference in DFS (HR 0.88 (95% c.i. 0.41 to 1.85), P = 0.724) or OS (HR 0.69 (95% c.i. 0.31 to 1.54), P = 0.343) between those who did and did not receive adjuvant FLOT. In the PR group, adjuvant FLOT conferred a significant DFS (HR 0.68 (95% c.i. 0.55 to 0.86), P < 0.001) and OS (HR 0.55 (95% c.i. 0.44 to 0.69), P < 0.001) benefit.

Pathological response to neoadjuvant FLOT may guide the use of adjuvant FLOT, enabling personalized approaches to treatment.

Gastric cancer is a major cause of cancer mortality, with poorer prognosis in the presence of peritoneal metastases as low as 2.8-9 months. Systemic therapy has a limited role. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. This study evaluates survival of patients with gastric cancer and peritoneal metastases (GCPM) undergoing CRS and HIPEC at an Australian centre.

A retrospective analysis was conducted on a prospectively collected database of patients who underwent CRS and HIPEC for GCPM from January 2009 to December 2023. Data included demographics, perioperative factors, histopathology and survival.

Twenty-four patients were identified, with median postoperative overall survival of 11.7 months (95% CI 8.6-34.2 months). Most patients had poorly differentiated adenocarcinoma (n = 23, 96%), with 14 (58%) exhibiting signet cell pathology. 62% (n = 15) received preoperative chemotherapy. Median PCI was 5, with a CC score of 0 in 96% of patients (n = 23). Clavien-Dindo III/IV morbidity was noted in 8 patients (33%) with no perioperative mortality. No survival differences were found between those with signet cell pathology and those without (10.6 vs. 11.7 months, p = 0.83), nor between those receiving preoperative chemotherapy and those who did not (11.7 vs. 10.6 months, p = 0.60). Age, sex, PCI, CC and tumour markers demonstrated correlations with survival in linear regression, but no individual factor significantly influenced outcomes.

CRS and HIPEC for low volume GCPM should be considered in select patients.

To systematically evaluate the efficacy and safety of combination therapy with toripalimab in the treatment of advanced gastric cancer (GC).

We conducted a thorough search for relevant studies in PubMed, Embase, Cochrane Library, and Web of Science. Effect estimates were computed utilizing Stata software (version 14.0) and either random or fixed effects models, as applicable. A subgroup analysis was undertaken to assess the effect of various combination therapies on overall response rate (ORR). Begg and Egger's tests were employed to assess publication bias.

The study consisted of 8 trials, which included 277 participants with advanced gastric cancer. The overall ORR was 41.4% (95% CI, 32.4%-50.3%), with a disease control rate (DCR) of 83.6% (95% CI, 74.6%-92.7%), a median overall survival (mOS) of 11.0 months (95% CI, 9.6-12.4), and a median progression-free survival (mPFS) of 4.2 months (95% CI, 2.5-6.0) for the combination therapy with toripalimab. Subgroup analysis revealed that the combination of toripalimab and chemotherapy achieved a greater ORR compared to the non-chemotherapy group, with ORR rates of 49.8% (95% CI, 42.2%-57.4%) and 31.9% (95% CI, 26.7%-37.1%), respectively. The combination therapy with toripalimab led to adverse events (AEs) of any grade at 94.0% of cases (95% CI, 89.5%-98.5%) and grade 3 AEs at 32.4% (95% CI, 17.8%-47.1%). The sensitivity analysis indicated that no single study affected the overall results.

Combination therapy of toripalimab can improve clinical efficacy, although with increased but manageable toxicity. Additional clinical trials are required to assess comprehensively the efficacy and safety of alternative toripalimab regimens. The review agreement has been recorded with PROSPERO (CRD42024585696).

Treatment with cadonilimab and chemotherapy has shown promise as a first-line treatment for gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, its application in neoadjuvant settings has not yet been documented.

This multicenter, phase 2 trial (ChiCTR2200066893) was conducted at four hospitals across China. Treatment-naive patients with locally advanced G/GEJ adenocarcinoma (cT3/4, N+, M0) and who were human epidermal growth factor receptor 2 negative received 3-cycle or 4-cycle neoadjuvant treatment of cadonilimab plus FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy, followed by gastrectomy and 4-cycle adjuvant FLOT chemotherapy. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included major pathological response (MPR), overall response rate (ORR), disease control rate (DCR), R0 resection rate, downstaging rate, and safety.

Between December 23, 2022, and December 15, 2023, 32 of 38 patients completed the scheduled treatment, achieving an R0 resection rate of 100% (32/32). The pCR rate was 21.1% (8/38, 90% confidence interval [CI]: 9.7-32.4), and the MPR rate was 44.7% (17/38, 90% CI: 30.9-58.5). Radiological evaluations were available for 28 of 38 patients by blinded independent central review. The ORR was 60.7% (17/28, 90% CI: 44.7-76.7), and the DCR was 100.0% (28/28, 90% CI: 100.0-100.0). Tumor downstaging occurred in 71.9% of patients (23/32), with consistent efficacy across all populations observed in the subgroup analysis. Grade 3 adverse events occurred in 31.6% of patients without severe safety issues.

Neoadjuvant cadonilimab plus FLOT chemotherapy treatment exhibits promising efficacy with manageable toxicities in locally advanced G/GEJ adenocarcinoma, providing preliminary evidence for further investigation.

This study was funded by Akeso Biopharma.

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.

This study aimed to evaluate the clinical significance of four-dimensional dynamic ventilation CT (4DCT) for assessing resectability in borderline resectable locally advanced esophageal cancer (BR-LAEC) and confirmed the pathological validity of the 4DCT results in surgery without prior treatment.

We retrospectively reviewed 128 patients (107 men; median age, 68 [range, 43-89] years) diagnosed with BR-LAEC on initial conventional CT (i-CT). These patients were initially classified into three categories: BR1 (closer to resectable), BR2 (resectability not assessable), or BR3 (closer to unresectable). Subsequent 4DCT reclassified patients as either resectable or unresectable within 1 week of i-CT. We analyzed the diagnostic shift induced by 4DCT. Additionally, 18 patients who underwent surgery without prior treatment were evaluated using 4DCT and pathological outcomes.

4DCT reclassified patients with BR-LAEC as resectable (57.0%; 73/128) and unresectable (43.0%; 55/128). Of 53 patients initially classified as BR1, 32.1% (17/53) were reclassified as unresectable, and of 47 patients initially classified as BR3, 46.8% (22/47) were reclassified as resectable. Among 28 patients initially classified as BR2, 53.6% (15/27) were reclassified as resectable and 46.4% (13/27) as unresectable. In the surgery-only cohort of 18 patients, 9 were initially classified as BR1 and 9 as BR2, and all were reclassified as resectable. These patients were pathologically confirmed to have resectable disease.

4DCT may provide information complementary to that provided by initial conventional CT in assessing resectability among patients with BR-LAEC, and could be a useful adjunct tool for guiding clinical decisions in this patient population.

BACKGROUND: Early recurrence after esophagectomy is often used as a surrogate for aggressive tumor biology and treatment failure. However, there is no standardized definition of early recurrence, and predictors for early recurrence are unknown. Therefore, we aimed to define an evidence-based cutoff to discriminate early and late recurrence and assess the influence of neoadjuvant treatment modalities for patients with esophageal or gastroesophageal-junction adenocarcinoma (EAC).

This dual-center retrospective cohort study included patients who underwent esophagectomy for stage II-III EAC after neoadjuvant treatment with chemotherapy using 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) or radiochemotherapy according to the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study (CROSS) protocol from 2012 to 2022. The optimal cutoff for early versus late recurrence was calculated by using the most significant difference in survival after recurrence (SAR). Multivariable logistic regression was used to identify variables associated with early recurrence.

Of 334 included patients, 160 (47.9%) were diagnosed with recurrence. Most patients had systemic (60.5%) or multiple sites of recurrence (21.1%), whereas local-only recurrence (9.2%) and carcinomatosis (9.2%) were rare. The optimal interval between surgery and recurrence for distinguishing early and late recurrence was 18 months (median SAR: 9.1 versus 17.8 months, p = 0.039) with only 24% of recurrences diagnosed after the calculated cutoff. Advanced pathologic tumor infiltration (ypT3-4, p = 0.006), nodal positivity (p = 0.013), poor treatment response (>10% residual tumor, p = 0.015), and no adjuvant treatment (p = 0.048) predicted early recurrence.

Early recurrence can be defined as recurrent disease within 18 months. Hallmarks for early recurrence are poor response to neoadjuvant therapy with persisting advanced disease. In those patients, adjuvant therapy and closer follow-up should be considered.

Lymphatic route is the main pathway for gastric cancer (GC) spread, and lymph node (LN) involvement is a major prognostic factor after curative resection. The aim of this study was to assess the outcomes of specific LN station dissection.

Patients with locally advanced (cT2-4N0-3M0) GC who underwent multimodal treatment between 2013 and 2023 were included in the study. Patients who had not undergone gastrectomy, had early (cT1) or metastatic GC, who had undergone multiorgan resections, palliative care, had died before the end of curative-intent planned treatment, or had incomplete clinical or pathological information were excluded. The primary endpoint was the development of serious complications, and the secondary outcome was OS.

Mulivariable analysis revealed, that among patients who received neoadjuvant chemotherapy (NAC), it was observed that station 10 lymphadenectomy was associated with a higher risk of serious postoperative complications. (27.6 % vs 8.7 %; OR = 3.28) Among the no-NAC group, it was observed that station 13 lymphadenectomy was associated with a higher risk of serious postoperative complications. (57.1 % vs 13.2 %; OR = 6.96). Among the NAC group, a lower risk of death was observed in patients with station 8 (HR = 0.53) or 11 lymphadenectomy (HR = 0.53).

While D2 lymphadenectomy remains crucial, particularly in in high-volume, experienced GC centers, the necessity of a more extensive D2+ lymphadenectomy is not supported by our findings. Moreover, we aimed to highlight the importance of tailored surgical approaches and emphasize the significance of LN station dissection in influencing both short-term complications and long-term survival outcomes.

In the Western hemisphere, nonmetastatic locally advanced esophageal carcinoma is mostly treated in multimodal therapy protocols according to current therapy guidelines. In squamous cell carcinoma of the esophagus, neoadjuvant chemoradiation is the favorable option. Unimodal surgical and chemoradiation treatment alternatives show inferior results on this entity. For locally advanced adenocarcinoma of the esophagus perioperative chemotherapy and neoadjuvant chemoradiation have been competing treatment approaches in the recent past. Both are evidence based (class I evidence) and superior compared to unimodal surgery. However, the latest results of head-to-head comparative therapy studies show superior overall survival results for the FLOT regimen of perioperative chemotherapy. Furthermore, immunotherapy and targeted therapy with monoclonal antibodies have become a strong focus of current clinical research. Nivolumab as well as trastuzumab are already an important part of the current standard therapies. In both entities - SCC and AC - a significant quota of patients shows a locoregional complete remission of the tumor in the specimen after modern neoadjuvant therapy and surgical resection. The addition of immunotherapy and targeted therapy to neoadjuvant therapy further increases complete remission rates in defined subgroups according to the results of current studies. Currently, three prospective randomized trials are ongoing on the subject of future possibilities for organ-preserving concepts in case of complete clinical remission ("surgery as needed," "watch and wait"). It is to be expected for the future that curative short-term and long-term treatment results in locally advanced esophageal carcinoma will significantly improve, particularly due to the additional possibilities of immunotherapy and organ-preserving therapy concepts in postneoadjuvant complete remission.

Neoadjuvant chemoradiotherapy in patients with esophageal- and gastroesophageal junction cancer induces tumor regression. In approximately one fourth of patients, this leads to a pathological complete response in the resection specimen. Hence, active surveillance may be an alternative strategy in patients without residual disease after neoadjuvant chemoradiotherapy. Previous studies have shown that the combination of esophagogastroduodenoscopy with bite-on-bite biopsies, endoscopic ultrasound with fine needle aspiration of suspected lymph nodes, and a PET-CT-scan can be considered adequate for the detection of residual disease. So far, it has been unclear whether active surveillance with surgery as needed is a safe treatment option and leads to non-inferior overall survival compared to standard esophagectomy after neoadjuvant chemoradiotherapy. This review will discuss the current status of active surveillance for esophageal and junctional cancer.

Half of the patients with esophageal cancer, cancer of the gastro-esophageal junction and gastric cancer present metastasis at the time of diagnosis. In addition, even patients originally thought to be free of metastasis will present metachronous metastasis in the course of the disease. These patients are considered incurable and current standard of care for metastatic esophageal, gastro-esophageal junction and gastric cancers is a systemic therapy without curative intention. However, patients presenting only a low metastatic load are now defined as oligometastatic disease and should benefit from an aggressive, multimodal therapy. We present here a review of recent publications investigating multimodal therapies for oligometastatic disease and showing that a systemic therapy combined with a resection of the primary tumor together with metastasis is associated with a better prognosis than a systemic therapy alone. We also give a precise focus on esophageal squamous cell carcinomas and adenocarcinomas of the gastro-esophageal junction and of the stomach. Interestingly, patients with oligometastatic cancer of the esophago-gastric junction can even be treated in curative intention with such a multimodal therapy as we present here in a short case report. In conclusion, new therapeutic strategies including multimodal approaches for oligometastatic disease have shown promising results in the last years and ongoing randomized prospective trials will provide us the evidence to include them in future European guidelines.

In Nigeria, gastric cancer is the 10th most common and 9th most deadly malignancy. The limited availability of robust data makes further characterizing it challenging. The objective of this study was to assess the presentation, and management of gastric cancer in Nigeria using an institutional cancer registry.

We reviewed a prospective database of patients diagnosed with any gastric cancer at a single tertiary referral center over 15 years (2007-2022). Patients with suspected gastric cancer were surveyed for sociodemographics and then added to the institutional gastric cancer registry. Thereafter, periodic chart review and phone call was used to obtain investigation results, and survival data, respectively. Only patients with complete histopathology were included in analysis.

138 patients met inclusion criteria (mean age 55.3 years, 68.8% male). Patients typically presented with weight loss (119, 86.2%) and anorexia (92, 66.7%). Blood work (132, 95.7%) and ultrasound (80, 57.9%) were the most common investigations. Most fully staged patients presented with metastatic disease (39, 90.2%). Patients underwent at least one treatment modality (109, 79.0%), and most 54 (49.5%) underwent both chemotherapy and surgery. Patients undergoing surgery usually had resection of their tumor (58, 67.4%). The median time of follow-up was 45.6 months, and 51.4% (71) of patients were dead at that time point.

Our gastric cancer database identified that most patients present with advanced disease and are undergoing at least one treatment modality. The next steps include initiatives to strengthen the quality of registry data, identify high-risk patients, and provide timely treatment.

Despite the introduction of multimodal treatment regimens, the prognosis of gastric cancer peritoneal metastasis (GCPM) remains poor. To establish efficient therapies, a deeper understanding of pathophysiological mechanisms in the development of GCPM is necessary and this requires adequate functional models. Therefore, we established a three-dimensional model to study tumor adhesion, invasion and growth.

A co-culture of peritoneal mesothelial cells with fibroblasts and collagen I was cultivated to further seed human gastric cancer cell lines on the surface. Different imaging techniques (optical microscopy, immunohistochemistry, scanning (SEM) and transmission (TEM) electron microscopy) served as tools to proof the sustainability of the model.

We demonstrated the feasibility of creating a robust GCPM model. We showed that the model is reproducible under various conditions (6-, 12-, and 24-wells) and pre-analytical processing is possible. The imaging was feasible and allowed the comparison of morphological changes on the GCPM model to normal human peritoneum.

We established a reproducible and robust organotypic model of GCPM which can be used to generate deeper knowledge on the pathophysiology of GCPM and might serve as a platform for testing different chemotherapy schemes in order to establish a personalized treatment for patients with GCPM.

Gastric cancer (GC) is one of the most common causes of cancer-related death worldwide. As a novel form of programmed cell death, disulfidptosis is characterized by excessive cysteine accumulation, disulfide stress and actin destruction. There is evidence that targeting disulfidptosis is a promising anticancer strategy. Further improvement of GC risk stratification based on disulfidptosis has positive clinical significance.

We analyzed the expression levels of disulfidptosis-associated genes (DPAGs) in normal and GC tissues and characterized the molecular subtypes of GC patients. Based on the characteristics of DPAG subtypes, differentially expressed prognosis-related genes were selected by LASSO-univariate Cox analysis and multivariate Cox analysis analyzed to establish a prognostic model. Using single-cell sequencing analysis reveals the cell subpopulation for GC. The function of the selected target in GC was verified by in vitro experimental means, including siRNA, qRT-PCR, Western blot, CCK-8, and Transwell assay.

DPAG score was verified to be an independent prognostic factor of GC and was significantly associated with poor prognosis of gastric cancer. Subsequent studies on subgroup immunoinfiltration characteristics, drug sensitivity analysis, immunotherapy response and somatic mutation characteristics of DPAG score comprehensively confirmed the potential guiding significance of DPAG score for individualized treatment of gastric cancer patients. Single-cell sequencing analysis revealed the expression characteristics of DPAG-related prognostic signatures across cell subpopulations. In vitro experiments showed APC11, as one of the selected DPAGs, was highly expressed in gastric cancer, and knockdown of APC11 could significantly inhibit the proliferation and migration of GC cells, demonstrating the reliability of bioinformatics results.

The results of this study provide a new perspective for exploring the role of disulfidptosis in the occurrence and development of GC.

Gastric cancer has a high mortality rate. Therapeutic management must be multidisciplinary to offer the patient the best, personalized strategy.

We performed an observational study to evaluate the pathological response, survival and nutritional status in patients with resectable gastric cancer and candidates for perioperative chemotherapy with the fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen versus other regimens. The primary endpoints were pathological response rate, care continuity rate and survival outcomes. A total of 96 patients attending the Hospital "Policlinico San Matteo" in Pavia (Italy) between January 2012 and August 2022 were selected for the study.

Regarding pathological response rates, the best rate (TRG-0) was recorded in the FLOT group with a percentage of 6.2% compared with 4.7% in the NO-FLOT arm (p=0.052). The highest failure rate to complete the post-operative phase was 75% in the NO-FLOT group and only 25% in the FLOT group (p=0.007). Survival outcomes were better in the FLOT group with a median disease-free survival of 30 versus 22.2 months (p=0.586).

Despite the limitations, the results obtained were consistent with the medical literature and confirmed the effectiveness of the FLOT chemotherapy in real life. Nevertheless, some questions remain: the application in elderly patients, the addition of immunotherapy in patients with microsatellite instability or with high PD-L1 levels, comparison with chemoradiotherapy in junctional cancers and real cure rates. The FLOT regimen has revolutionized the treatment of resectable gastric cancer, but caution is needed before considering it an absolute standard of care.

Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC), and diffuse (dif-GC) gastric cancer.

Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery alone (SAvalidation) and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS).

In the SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a 5-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, P = .52 and P = .011), but worse than int-GC (55% and 42%, P = .11 and P < .001). In the CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-) complete response) compared with int-GC (26% and 35%) and dif-GC (10% and 28%, P < .001 and P = .005). The 5-year RS in the CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared with dif-GC (35% and 38%, P = .004 and P < .001).

Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.

The pre-treatment waiting interval of gastric cancer patients receiving neoadjuvant chemotherapy (nCT) followed by gastrectomy includes pre-nCT (diagnosis to nCT) and preoperative (diagnosis to surgery) waiting intervals. This study aimed to investigate the impact of these two distinct intervals on short-term postoperative outcomes.

Patients (cT1-4aN0-3M0) who underwent nCT plus gastrectomy were included using the Dutch national DUCA-database. Multivariate logistic regression was used to determine the impact of the two waiting intervals upon short-term postoperative outcomes: pre-nCT waiting intervals (≤5, 5-8 and 8-12 weeks) and preoperative waiting intervals (≤17, 17-22, and >22 weeks).

Between 2010 and 2021, 1242 patients were included. Compared to the pre-nCT waiting interval ≤5 weeks, the longer intervals (5-8 and 8-12 weeks) were not associated with worse 30-day mortality (p-value = 0.707; p-value = 0.900), overall complications (p-value = 0.733; p-value = 0.453), pulmonary complications (p-value = 0.250; p-value = 0.238), gastrointestinal complications (p-value = 0.396; p-value = 0.992), re-interventions (p-value = 0.407; p-value = 0.072) and 30-day readmission (p-value = 0.992; p-value = 0.664). Compared to the preoperative waiting interval ≤17 weeks, the longer intervals (17-22 and > 22 weeks) were also not associated with worse 30-day mortality (p-value = 0.926; p-value = 0.732), overall complications (p-value = 0.286; p-value = 0.510), pulmonary complications (p-value = 0.912; p-value = 0.351), gastrointestinal complications (p-value = 0.765; p-value = 0.882), re-interventions (p-value = 0.617; p-value = 0.800) and 30-day readmission (p-value = 0.592; p-value = 0.782).

A longer pre-nCT or preoperative waiting interval is not associated with worse short-term postoperative outcomes in Western gastric cancer patients undergoing nCT plus gastrectomy.

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 (GC) is a heterogeneous tumor with various molecular changes. An active search for molecular markers is crucial to determine the effectiveness of drug treatment and prognosis of the disease. Several biomarkers have the greatest clinical significance: HER2, MSI / dMMR, PD-L1 (CPS), EBV and Claudin 18.

To study the frequency of HER2, MSI / dMMR and PD-L1 (CPS) in patients with operable GC depending on the tumor type according to P. Lauren.

The study included 600 patients with GC who underwent radical surgical treatment at the N.N. Blokhin National Medical Research Center of Oncology from 2018 to 2023.

In the study, the proportion of diffuse GC was 21.5% (120/600). HER2 overexpression was found in 5.2% (5/96) of cases with diffuse GC, 20.4% (37/181) of cases with intestinal GC, 10.1% (7/69) of cases with mixed GC (p=0.0029). The incidence of MSI was 3.3% (4/120) of cases with diffuse GC, 11.2% (28/251) of cases with intestinal GC, 7.3% (7/97) of cases with mixed GC (p=0.0378). PD-L1 expression (CPS> 1) was found in 42.3% (11/26) of cases with diffuse GC, 59.4% (35/59) of cases with intestinal GC, 27.3% (9/33) of cases with mixed GC (p=0.006). In poorly cohesive/signet ring cell cancer MSI occurred in 2.5% (2/79) of cases; HER2 overexpression - in 2.9% (2/68) of cases; PD-L1 (CPS> 1) - in 42.1% (8/19) of cases.

Our study demonstrated that in diffuse and poorly cohesive/signet ring cell GC the frequency of occurrence of the above clinically significant tumor biomarkers is lower compared to intestinal/mixed GC.