Background: Early noninvasive screening of patients who would benefit from neoadjuvant chemotherapy (NCT) is essential for personalized treatment of locally advanced gastric cancer (LAGC). The aim of this study was to identify a radioclinical signatures from pretreatment oversampled CT images to predict the response to NCT and prognosis of LAGC patients. Methods: LAGC patients were retrospectively recruited from six hospitals from January 2008 to December 2021. An SE-ResNet50-based chemotherapy response prediction system was developed from pretreatment CT images preprocessed with an imaging oversampling method (i.e., DeepSMOTE). Then, the Deep learning (DL) signature and clinic-based features were fed into the deep learning radioclinical signature (DLCS). The predictive performance of the model was evaluated based on discrimination, calibration and clinical usefulness. An additional model was built to predict overall survival (OS) and explore the survival benefit of the proposed DL signature and clinicopathological characteristics. Result: A total of 1060 LAGC patients were recruited from six hospitals, the training cohort (TC) and internal validation cohort (IVC) patients were randomly selected from center I. An external validation cohort (EVC) of 265 patients from 5 other centers was also included. The DLCS exhibited excellent performance in predicting the response to NCT in the IVC (AUC, 0.86) and EVC (AUC, 0.82), with good calibration in all cohorts (P>0.05). Moreover, the DLCS model outperformed the clinical model (P<0.05). Additionally, we found that the DL signature could serve as an independent factor for prognosis (HR, 0.828, P=0.004). The C-index, iAUC, and IBS for the OS model were 0.64, 1.24 and 0.71 in the test set. Conclusion: We proposed a DLCS model that combined imaging features with clinical risk factors to accurately predict tumor response and identify the risk of OS in LAGC patients priors to NCT that can then be used to guide personalized treatment plans with the help of computerized tumor-level characterization.

Objectives: To evaluate the efficacy of SOX combined with a programmed cell death protein-1 (PD-1) inhibitor compared with SOX alone in the perioperative management of locally advanced gastric cancer and to explore biomarkers that may predict response to anti-PD-1 therapy. Methods: Data of patients with clinical stage T3–4aN0–3M0 (IIb–III) gastric cancer were reviewed to create a primary database. Patients treated with perioperative SOX combined with sintilimab were included in Group A, while those treated with SOX alone were included in Group B. After one-to-one propensity score matching, pathological response and short-term survival outcomes were compared between the two groups. In addition, potential efficacy-related biomarkers were analyzed. Results: Between January 2018 and December 2022, a total of 150 patients were included in the analysis, with 75 patients in each group. The rates of pathological complete response (21.3% vs. 4.0%; P = 0.001) and major pathological response (45.3% vs. 22.7%; P = 0.003) in Group A were statistically higher than those in Group B. There was no significant difference in 1-year overall survival (92.8% vs. 92.0%; P = 0.392) and disease-free survival (88.9% vs. 88.0%; P = 0.357) between the two groups. Subgroup analysis of Group A showed that the pathological complete response (40.6% vs. 8.6%; P = 0.002) and major pathological response (65.6% vs. 28.6%; P = 0.002) rates were significantly higher in programmed death ligand-1-positive patients with a combined positive score of ≥ 5. A pathological complete response was achieved in 42.9% patients (3/7) with mismatch repair deficiency. For the two patients confirmed as Epstein-Barr virus-positive, one patient achieved a pathological complete response and the other achieved a major pathological response. Conclusions: The adoption of SOX combined with a PD-1 inhibitor may improve the pathological response rate of patients with locally advanced gastric cancer, especially those with programmed death ligand-1 combined positive score ≥ 5, Epstein–Barr virus-positivity and mismatch repair deficiency. However, further prospective studies are still warranted to confirm the long-term survival benefit.

Background: Patients with peritoneal metastasis (PM) from gastric cancer (GC) exhibit poor prognosis. Chemoimmunotherapy offers promising clinical benefits; however, its efficacy and predictive biomarkers in a conversion therapy setting remain unclear. The authors aimed to retrospectively evaluate chemoimmunotherapy efficacy in a conversion therapy setting for GC patients with PM and establish a prediction model for assessing clinical benefits. Materials and methods: A retrospective evaluation of clinical outcomes encompassed 55 GC patients with PM who underwent chemoimmunotherapy in a conversion therapy setting. Baseline PM specimens were collected for genomic and transcriptomic profiling. Clinicopathological factors, gene signatures, and tumor immune microenvironment were evaluated to identify predictive markers and develop a prediction model. Results: Chemoimmunotherapy achieved a 41.8% objective response rate and 72.4% R0 resection rate in GC patients with PM. Patients with conversion surgery showed better overall survival (OS) than those without the surgery (median OS: not reached vs 7.82 m, P<0.0001). Responders to chemoimmunotherapy showed higher ERBB2 and ERBB3 mutation frequencies, CTLA4 and HLA-DQB1 expression, and CD8+ T cell infiltration, but lower CDH1 mutation and naïve CD4+ T cell infiltration, compared to nonresponders. A prediction model was established integrating CDH1 and ERBB3 mutations, HLA-DQB1 expression, and naïve CD4+ T cell infiltration (AUC=0.918), which were further tested using an independent external cohort (AUC=0.785). Conclusion: This exploratory study comprehensively evaluated clinicopathological, genomic, and immune features and developed a novel prediction model, providing a rational basis for the selection of GC patients with PM for chemoimmunotherapy-involved conversion therapy.

Objectives To evaluate the efficacy of combining PD-1 inhibitors with chemotherapy in conversion therapy for patients with stage IV gastric cancer and to determine the populations most likely to benefit from this regimen. Methods Data from patients with stage IV gastric cancer who received conversion therapy with PD-1 inhibitors combined with chemotherapy between January 2018 and December 2022 at multiple centers were retrospectively reviewed. Patients who underwent conversion surgery were categorized into a surgery group, while those who did not were placed into a palliative group. The survival outcomes between the two groups and the potential biomarkers that may predict the effectiveness of combining PD-1 inhibitors with chemotherapy were analyzed. Results A total of 105 patients were included in the analysis, with 48 patients in the surgery group and 57 patients in the palliative group, resulting in a conversion rate of 45.7%. R0 resection was performed in 40 patients (83.3%) in the surgery group. The median survival time (MST) was not reached in the surgery group, while it was 12.0 months in the palliative group (P < 0.001). There were significant differences in 1-year and 3-year overall survival (OS) between the two groups (1-year OS: 93.7% vs. 45.6%, P < 0.001; 3-year OS: 52.1% vs. 4.0%, P < 0.001). Subgroup analysis revealed that patients with PD-L1 CPS ≥ 1 had significantly higher overall response rates (62.5% vs. 38.5%, P = 0.016) and conversion rates (60.4% vs. 32.7%, P = 0.005). For patients with peritoneal metastasis, a significant survival benefit was observed in those who received HIPEC treatment compared to those who did not (MST: 18.0 months vs. 9.0 months, P = 0.039). The incidence of treatment-related adverse events was similar to previous observations, with no new safety signals identified. Conclusions The combination of PD-1 inhibitors with chemotherapy in conversion therapy is feasible for patients with stage IV gastric cancer. Individuals who exhibit improved responses to chemoimmunotherapy potentially experience survival benefits, particularly those with PD-L1 positivity.

TAF1L may play an important role in the occurrence and development of gastric cancer (GC), but the correlation between the expression of TAF1L and the clinicopathological factors and prognosis of GC is still unclear. A total of 1053 GC patients in Zhejiang Cancer Hospital between January 1st, 2018 to December 31th, 2019 were screened. Finally, 120 patients met the inclusion criteria. TAF1L expression was detected by immunohistochemistry, and the correlations of TAF1L in clinicopathological characteristics and prognosis were analyzed. TCGA GC dataset was used to perform further bioinformatics analysis. In this study, TAF1L expression was evaluated in 120 clinical samples of GC. TAF1L expression was higher in tumor tissues and was associated with tumor differentiation (p = 0.046), signet-ring cells (p = 0.043), dMMR status (p = 0.011), lympho-vascular invasion (p = 0.038), and neural invasion (p = 0.005) in our cohort. Cases with high expression of TAF1L presented worse mean OS than those with low expression (40.3 months vs. 51.8 months, p = 0.019), and the difference was also significant in HER2-positive cases (20.9 months vs. 51.2 months, p = 0.007) as well as pMMR cases (38.8 months vs. 51.6 months, p = 0.006). Multivariate Cox regression analysis showed that TAF1L (HR = 2.044, 95%CI = 1.007–4.147, p = 0.048) and HER2 status (HR = 2.383, 95%CI = 1.087–5.222, p = 0.030) were independent prognosis factors of these patients. In subgroup analysis, TAF1L was the independent prognostic risk factor in HER2-positive patients (HR = 6.736, 95%CI = 1.373–33.032, p = 0.019). and pMMR patients (HR = 2.291, 95%CI = 1.126–4.660, p = 0.022). Besides, HER2 status was the independent prognostic risk factor in TAF1L-H patients (HR = 4.832, 95%CI = 1.908–12.239, p = 0.001). TCGA dataset also indicated the higher expression of TAF1L in tumors than normal tissues (p < 0.001). High TAF1L expression is linked to worse survival in MSS (11.0 months vs. 35.0 months, p = 0.0046) groups, and is negatively associated with overall survival in HER2-positive cases (24.0 months vs. 57.0 months, p = 0.0039). TAF1L is closely related to the occurrence and development of GC. Our results suggested that TAF1L is a significant biomarker for predicting prognosis of GC and may play an important role in immunotherapy and targeted therapy.

Cutaneous metastases from gastric cancer are rare (<1%) and typically indicate advanced disease with poor prognosis. We report a unique case of a 53‐year‐old male presenting with an asymptomatic left temporal erythematous nodule, later diagnosed as metastatic gastric adenocarcinoma with signet‐ring cell features. Initial skin biopsy revealed adenocarcinoma (CDX2+/CK20+/CK7+), prompting gastrointestinal evaluation, which confirmed poorly differentiated gastric adenocarcinoma (30% signet‐ring cell component). The patient received neoadjuvant immunochemotherapy (paclitaxel+S‐1+sintilimab), followed by laparoscopic radical gastrectomy (D2 lymphadenectomy) and resection of the skin lesion. Postoperative pathology showed Becker grade 2 regression in the primary gastric tumor and Mandard grade 3 regression in the cutaneous metastasis. The surgical specimen showed metastasis in 20 of 65 lymph nodes and was staged ypT4aN3bM1 (AJCC 8th edition). Biomarker assessment demonstrated high Claudin18.2 expression (~90%) but low PD‐L1 expression (CPS ~1). Postoperative surveillance showed no radiographic local recurrence or distant metastasis through April 2025; however, leptomeningeal metastasis was confirmed by cerebrospinal fluid (CSF) cytology in May 2025. This case illustrates substantial early tumor regression with perioperative chemoimmunotherapy in an unusual metastatic presentation while also demonstrating that early response does not necessarily translate into durable disease control.