Advanced Gastric Cancer Research Articles (Page 1)

E-cadherin expression and tumor-stroma ratio as prognostic biomarkers of peritoneal recurrence in advanced gastric cancer: a digital image analysis-based stratification study

Background Less than half of the human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) patients respond to trastuzumab plus chemotherapy, and the outcomes are unsatisfactory. Understanding the underlying mechanisms remains crucial for identifying patients who are more likely to benefit from treatment. Patients and methods We performed targeted DNA sequencing on paired pre-treatment and progressive tumour tissues from 22 HER2-positive advanced GC patients undergoing first-line treatment with trastuzumab and chemotherapy. Clinicopathological and genomic characteristics were assessed for the correlation with clinical outcomes. Results A performance status (PS) of 0–1 was associated with improved progression-free survival (PFS) and overall survival (OS) than a PS of 2. Poorly differentiated tumours exhibited shorter PFS than moderate or moderate-poor ones. Pre-treatment amplification of MYC or TOP2A gene was association with increased PFS, and suggested a potential benefit for OS. Patients with higher tumour mutation burden (TMB) experienced significantly worse PFS, while higher chromosome instability (CIN) appeared to be correlated with longer PFS. Compared to non-responders, responders had a higher CIN but similar TMB and intratumoural heterogeneity (ITH). PS and MYC amplification emerged as independent factors related to PFS according to multivariate survival analysis. Additionally, after treatment, TMB significantly increased in non-responders, while CIN significantly decreased in responders. Conclusions Pre-treatment MYC amplification and PS were independently associated with clinical outcomes in HER2-positive advanced GC patients treated with first-line trastuzumab plus chemotherapy. Dynamic post-treatment changes in TMB and CIS provide valuable insights into the relationship between therapeutic response and distinct evolutionary trajectories.

This study compared the efficacy and safety of S-1 + oxaliplatin (SOX) plus sintilimab, albumin-bound paclitaxel + oxaliplatin (P-SOX), and docetaxel + oxaliplatin + 5-fluorouracil (DOF) as neoadjuvant regimens for advanced gastric cancer. We retrospectively analyzed 289 patients who received neoadjuvant and adjuvant chemotherapy followed by standard D2 radical gastrectomy (SOX + sintilimab, n = 81; P-SOX, n = 128; DOF, n = 80). Patients were randomly divided 7 : 3 into training and validation sets. Short-term efficacy, long-term outcomes, and adverse events were evaluated, and predictors of progression-free survival (PFS) were explored. The objective response rate of SOX + sintilimab was 91.36% by tumor regression grade (TRG) and 70.37% by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), numerically higher than P-SOX (88.38 and 59.20%) and DOF (86.25 and 57.50%) without significance (TRG, P = 0.587; RECIST 1.1, P = 0.178). Median overall survival (OS) was 32 months [95% confidence interval (CI): 30.00-not reached] with SOX + sintilimab, superior to P-SOX (28 months; 95% CI: 26.00-31.00) and DOF (26 months; 95% CI: 23.00- 32.00) (P = 0.007). Median PFS was 30 months (95% CI: 27.00-33.00) for SOX + sintilimab, 25 months (95% CI: 22.00-26.00) for P-SOX, and 22.5 months (95% CI: 19.00-26.00) for DOF (P = 0.096). Common adverse events included grade 1-2 gastrointestinal reactions, peripheral neurotoxicity, and alopecia, with good tolerability. SOX plus sintilimab achieved the most favorable OS with comparable safety.

Background Advanced gastric cancer has a devastating prognosis, However, the optimal treatment for gastric cancer patients with multiple liver metastases(GCLM) remains yet to be fully elucidated. Cryoablation is a novel therapeutic approach that has the potential to induce tumor necrosis and elicit anti-tumor immune responses. Case presentation A 44-year-old male was diagnosed with advanced gastric adenocarcinoma. Despite undergoing multiple lines of systemic therapy and repeated locoregional treatments, the patient exhibited rapid tumor progression. Subsequent treatment with PD-1 inhibitors demonstrated limited efficacy. However, following the innovative application of cryoablation to eradicate a more significant lesion within the liver metastases, the patient achieved a partial response and experienced 15 months of progression-free survival (PFS) with the combined use of PD-1 inhibitors and chemotherapy at the time of this report. Conclusion Cryoablation combined with immunotherapy may provide potential benefits for specific patients and offer a meaningful therapeutic strategy for patients with advanced gastric cancer and liver metastases, which is worthy of further research.

Combining paclitaxel with antiangiogenic agents has demonstrated improved efficacy as second-line treatment for advanced gastric cancer. Surufatinib, a multi-kinase inhibitor with antiangiogenic and immunomodulatory properties, has exhibited synergistic effects with chemotherapy in preclinical studies. This single-arm phase 2 trial enrolled patients aged 18-75 with HER2-negative unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma who had failed first-line therapy. All received surufatinib 250mg once daily plus paclitaxel 150mg/m2 every 3 weeks for up to 6 cycles, followed by maintenance surufatinib until progression, intolerable toxicity, or withdrawal. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Thirty-five patients were enrolled. Among 32 tumor response-evaluable patients, the ORR and DCR were 25.0% (95% confidence interval [CI]: 11.5, 43.4) and 87.5% (95% CI: 71.0, 96.5), respectively. Median PFS was 5.7 (95% CI: 4.7, 6.9) months and median OS was 10.8 (95% CI: 7.0, 17.2) months. In 26 patients with prior immunotherapy exposure, the median OS was 14.4 (95% CI: 8.5, not estimable) months. Overall, treatment-related adverse events of grade ≥ 3 occurred in 19 (54.3%) patients, with neutropenia (40.0%), leukopenia (34.3%), and hypertension (11.4%) being the most commonly observed. Surufatinib plus paclitaxel showed promising efficacy and manageable safety as second-line treatment for advanced gastric cancer, especially in patients who had failed prior immunotherapy. ChiCTR2200063336, registered in the Chinese Clinical Trial Registry on September 5, 2022.

A Cascaded Segmentation-Classification Deep Learning Framework for Preoperative Prediction of Occult Peritoneal Metastasis and Early Recurrence in Advanced Gastric Cancer.

End-to-end deep learning model with multi-channel and attention mechanisms for multi-class diagnosis in CT-T staging of advanced gastric cancer.

Yiqi Huayu Jiedu decoction enhances pathological response in neoadjuvant chemotherapy-treated gastric cancer patients: A prospective, randomized controlled trial.

ABSTRACTBackgroundImmunotherapy has become a new standard treatment for advanced gastric cancer (aGC). However, current biomarkers are insufficient for accurately identifying true responders, emphasizing the need for novel biomarkers.MethodsBetween December, 2020, and October, 2023, we recruited 91 consecutive aGC patients (49 in the discovery and 42 in the validation cohorts). Plasma samples were collected at baseline and after two cycles of immunotherapy. We conducted small RNA (sRNA) next‐generation sequencing on 140 samples. Additionally, we investigated previously reported potential biomarkers, including PD‐L1 combined positive score (CPS), inflammation scores, and serological tumor biomarkers.ResultsIn the discovery cohort, we identified two pre‐treatment sRNAs significantly associated with response to immunotherapy: high levels of hsa‐miR‐3916 (p = 0.020) and low levels of hsa‐miR‐181d‐5p (p = 0.046), confirmed in the validation cohort (p = 0.011 and p = 0.013, respectively). The AUCs for predicting response using these two sRNAs were 0.77 (95% CI; 0.62–0.93) and 0.83 (95% CI; 0.71–0.96), respectively. When integrating PD‐L1 CPS with these two sRNAs, the AUCs were 0.82 (95% CI; 0.68–0.96) and 0.83 (95% CI; 0.70–0.97) for the discovery and validation cohorts, respectively. Furthermore, when combining PD‐L1 CPS and serological tumor biomarkers with these two sRNAs, the AUCs were 0.89 (95% CI; 0.79–1.00) and 0.83 (95% CI; 0.70–0.96) for the discovery and validation cohorts, respectively. After combination immunotherapy, responders exhibited decreased levels of hsa‐miR‐320c (p = 0.006) and increased levels of hsa‐miR‐26b‐5p (p = 0.007). Additionally, patients with decreased hsa‐miR‐320c demonstrated a trend towards improved PFS (median: 9.17 vs. 3.03 months, p < 0.001) and OS (median: 16.43 vs. 10.23 months, p = 0.115).ConclusionThese findings provide valuable insights into the sRNA features associated with response to combination immunotherapy in aGC patients and suggest potential biomarkers useful for selecting patients likely to benefit from immunotherapy.

ObjectivesIn this study, we developed a multi-modal CT-based machine learning model to predict the response of gastric cancer (GC) patients to first-line chemotherapy combined with PD-1 inhibitors and performed external validation and multi-model comparisons.Materials and methodsWe retrospectively analyzed the clinical data of 348 patients with GC who underwent immunotherapy. The patients were categorized into an internal validation cohort (center A, n = 272) and an external validation cohort (center B, n = 76). Pre-treatment clinical and CT radiomics features were extracted to develop three models: a clinical model, a radiomics model and a clinical-radiomics model. The classifiers included logistic regression (LR), linear support vector classification (Linear SVC), support vector machine, and random forest.ResultsA total of 19 radiomics signatures and 5 clinical feature signatures were selected. In the radiomics model, the Linear SVC algorithm achieved an area under the receiver operating characteristic curve (AUC) of 0.88 and 0.76 in internal and external validation sets, respectively. In both the clinical model and the clinical-radiomics model, the LR algorithm demonstrated high and stable predictive performance in the internal (AUC = 0.89 and 0.94) and external validation datasets (AUC = 0.76 and 0.85). Among all models in the external validation dataset, the clinical-radiomics model utilizing LR outperformed all other classifiers.ConclusionsThe clinical-radiomics model, in combination with the LR algorithm, provides a reliable and effective method for predicting the early response of advanced GC patients treated with programmed cell death-1 (PD-1) inhibitors combined with chemotherapy.Critical relevance statementCT radiomics and laboratory parameters were used to evaluate early prediction of response to PD-1 inhibitors combined with chemotherapy in patients with advanced gastric cancer. This clinical-radiomics model provides a novel approach to predict immunotherapy efficacy and prognosis.Key PointsEvaluating the efficacy of PD-1 inhibitors combined with chemotherapy in advanced gastric cancer using only clinical data is limited.Only some patients with advanced gastric cancer treated with the PD-1 inhibitors combined with chemotherapy achieved complete regression.This clinical-radiomics model showed good performance for predicting gastric cancer response to chemotherapy combined with PD-1 inhibitors.Graphical

Advanced gastric cancer (GC) remains a significant global health burden with poor prognosis. Understanding organ-specific metastatic patterns and their prognostic implications is critical for optimizing patient management. This study leverages the Surveillance Epidemiology and End Results database to comprehensively analyze metastatic patterns in GC and develop a robust prognostic model. We analyzed data from 10,842 GC patients diagnosed between 2010 and 2014, focusing on metastases to the liver, lungs, bones, and brain. Metastatic patterns, prognostic outcomes, and risk factors were evaluated using multivariable logistic and Cox regression analyses. A nomogram was developed to predict overall survival. Liver metastases were the most common (40.5%), followed by lung (13.5%), bone (11.0%), and brain (1.7%). Dual-organ metastasis most frequently involved the liver and lungs. Patients with isolated liver metastases had a relatively better prognosis (hazard ratio = 1.29, 95% confidence interval = 1.23–1.36, P < .0001), while those with isolated bone metastases had the poorest outcomes (hazard ratio = 1.99, 95% confidence interval = 1.63–1.96, P < .0001). Prognosis was uniformly poor for patients with metastases to 2 or more organs. Key risk factors included male sex, older age, and poorly differentiated tumors. A nomogram incorporating these factors demonstrated strong predictive accuracy. This study provides a comprehensive analysis of organ-specific metastatic patterns in GC, highlighting the prognostic significance of metastatic sites. The developed nomogram offers a practical tool for clinicians to predict survival outcomes and tailor treatment strategies for advanced GC patients.

PurposeThis research conducts a comparison of Totally Robotic Total Gastrectomy (TRTG) and Robot-Assisted Total Gastrectomy (RATG) to evaluate their relative outcomes in patients with advanced gastric cancer, providing evidence to guide individualized surgical strategy selection.MethodsWe retrospectively gathered clinical data from patients who underwent either TRTG or RATG between January 2015 and December 2021, totaling 204 participants. After applying Propensity Score Matching (PSM), the matched cohort consisted of 118 patients, with 59 individuals in each of the TRTG and RATG groups. The study then compared the short-term and long-term outcomes between these two groups.ResultsPost-matching, there were no significant baseline differences between the groups. Surgery duration and anastomosis duration were both longer in the TRTG group than in the RATG group. However, TRTG was associated with significantly reduced intraoperative blood loss, shorter times to postoperative mobilization, flatus, and eating, decreased hospital stay, smaller incision sizes, and lower postoperative stress responses compared to RATG. The RATG group harvested a higher number of lymph nodes. No significant differences were observed between the two groups regarding postoperative complications, proximal and distal margins, nerve invasion, vascular cancer thrombus, postoperative drainage output, and hospitalization costs. The three-year overall survival and disease-free survival rates were similar between both groups.ConclusionsTRTG offers a safer and more advantageous surgical option regarding short-term outcomes compared to RATG and may be considered a preferable choice for total gastrectomy.

FGFR2-IIIc isoform detection reveals prognostic prevalence and a functional link to mesenchymal transition in gastric and gastroesophageal junction cancer.

Chest computed tomography of trastuzumab-deruxtecan (T-DXd)-related interstitial lung disease: Key points for radiologists.

Background Antibody-drug conjugates (ADCs) are an emerging therapy for HER2-positive advanced gastric cancer (AGC), yet their comparative efficacy and safety remain unclear. This systematic review and meta-analysis aimed to evaluate the clinical outcomes of different ADCs in this patient population. Methods A systematic search of PubMed, Embase, Cochrane, and Scopus databases was performed to identify relevant studies. The primary endpoint was the pooled overall response rate (ORR), analyzed using a random-effects model. Safety, subgroup analyses, and publication bias were also assessed. Results Twelve studies comprising 1041 patients were included. The pooled ORR across all ADCs was 33.4% (95% CI, 26.3%–41.3%). Efficacy varied substantially among agents: trastuzumab deruxtecan (T-DXd) and DP303c demonstrated the highest ORRs (42.5% and 42.9%, respectively), whereas others, such as Trastuzumab emtansine (T-DM1), showed lower efficacy (20.6%). ORR was not significantly affected by prior treatment lines (P = 0.6559) or cohort type (P = 0.7185). The most common adverse events included nausea (47.7%), with grade ≥3 anemia (21.1%) and neutropenia (15.1%) being the most frequent severe toxicities. Conclusions The efficacy of ADCs in HER2-positive AGC is highly variable. T-DXd and DP303c appear to be the most active agents, underscoring the critical importance of specific drug selection. Managing toxicities such as anemia and neutropenia is essential for optimizing treatment. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420250653886 , identifier PROSPERO CRD420250653886.

Abstract Peritoneal metastasis is a common form of metastasis in advanced gastric cancer, often associated with poor prognosis. The distinctive biological characteristics of peritoneal metastasis have resulted in the limited efficacy of conventional treatments, including systemic chemotherapy and cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC). Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method administered via laparoscopy, offering several advantages, including a lower drug dosage, a more extensive and uniform drug distribution, and deeper drug penetration compared to HIPEC. As an innovative treatment for advanced gastric cancer with peritoneal metastases, PIPAC has attached increasing attention from researchers globally. A significant number of research centers around the globe are currently engaged in investigating this technique. In this study, a comprehensive review of prospective studies on PIPAC for advanced gastric cancer with peritoneal metastasis, conducted since 2012, is presented. This review includes four completed studies and seven ongoing studies. Published results demonstrate promising feasibility, safety, and efficacy for PIPAC. However, further large-scale, prospective, randomized controlled clinical trials are necessary to compare treatment regimens and fully establish the safety and short- and long-term efficacy of PIPAC. Additionally, future studies should further clarify the indications and contraindications for PIPAC in treating advanced gastric cancer with peritoneal metastasis.

Immune checkpoint inhibitors (ICIs) have improved treatment outcomes for gastric cancer. However, immune-related adverse events (irAEs) pose a major challenge. This study aimed to identify predictive factors for irAE occurrence in patients with advanced or recurrent gastric cancer treated with nivolumab. We retrospectively analyzed information of 115 patients with advanced or recurrent gastric cancer treated with nivolumab monotherapy or in combination with chemotherapy. Patient characteristics and laboratory data, including complete blood counts, and clinical outcomes were analyzed. Optimal cutoffs for potential predictive factors were determined using ROC curve analysis. irAEs developed in 21 patients, with a median onset time of 124days after treatment initiation. Patients with an eosinophil proportion ≥ 4% showed higher irAE rates compared to those with < 4%. Multivariate analysis identified eosinophil proportion ≥ 4% (odds ratio 5.0) and neutrophil-to-lymphocyte ratio < 1.9 (odds ratio 4.6) as independent predictors of irAE occurrence. Patients with an elevated eosinophil proportion had higher levels throughout the treatment than those without irAEs at baseline, two months, and three months after treatment initiation. Patients with eosinophil proportions ≥ 4% demonstrated better overall survival and a tendency toward improved progression-free survival. Elevated eosinophil proportion before ICI treatment was a predictor of irAE occurrence and was associated with improved survival in patients with advanced or recurrent gastric cancer. This readily available clinical parameter may help identify patients more likely to benefit from ICI therapy, while enabling closer monitoring of potential irAEs.

ABSTRACT Aim Laparoscopic and endoscopic cooperative surgery (LECS) is a minimally invasive procedure that preserves gastric function and reduces complications. Although widely applied for gastrointestinal stromal tumors, its role in gastric cancer remains uncertain. We prospectively evaluated LECS as an alternative for elderly gastric cancer patients who declined conventional gastrectomy. Methods This single‐center prospective study enrolled 20 patients aged 75–89 years with gastric cancer ≤ 5 cm. All patients underwent Inverted‐LECS using the Crown method. The primary endpoint was surgery‐related morbidity (Clavien–Dindo ≥ III). Secondary endpoints were operative outcomes, margin status, quality of life (QOL), and survival. Results Median age was 82 years, and 80% were cT1. No intraoperative complications or conversions occurred. Surgical morbidity ≥ Grade III was 0%. Delayed gastric emptying occurred in 25%, all Grade II. Resection margins were negative in 80%, including all pathologically early cancers. At 3 months, body weight and fat‐free mass were preserved, physical function scores recovered to baseline, and mental function improved. Ninety‐day mortality was 0%. With a median follow‐up of 32 months, disease progression occurred in six patients, mainly with advanced disease or positive margins. One‐ and 3‐year overall survival rates were 95% and 76.2%, and disease‐specific survival 95% and 90%. Conclusions LECS was technically safe and feasible for elderly gastric cancer patients ineligible for gastrectomy. However, because oncological curability cannot be assured in advanced gastric cancer or high‐grade lymph node metastasis, careful selection and informed consent are essential. LECS may serve as a functional‐preserving alternative to observation or palliative treatment.

Retraction Note: Effect of neoadjuvant chemotherapy combined with arterial chemoembolization on short-term clinical outcome of locally advanced gastric cancer

This retrospective study analyzed the effectiveness of Inetetamab combined with an immunochemotherapy regimen as first-line treatment in two cases of advanced gastric cancer with human epidermal growth factor receptor 2 (HER2) expression. Both patients were elderly males diagnosed with gastric cancer presenting with distant metastasis at initial diagnosis. They were treated with a combination of Inetetamab, Tislelizumab, and the XELOX regimen (Inetetamab 300mg administered on Day 1; Tislelizumab 200mg administered on Day 1; Oxaliplatin 150mg administered on Day 2; Capecitabine 1.5g orally twice daily on Days 1-14; repeated every 3 weeks per cycle). Efficacy evaluation revealed that both patients achieved a partial response (PR). They attained progression-free survival (PFS) durations of 10 to 12 months. Treatment was well-tolerated through-out, with no occurrence of grade 3–4 adverse events. This therapeutic regimen provided significant survival benefits for these patients with advanced, multiply metastatic, HER2-positive gastric cancer. The findings of this study suggest a novel first-line treatment strategy for advanced gastric cancer, potentially improving treatment efficacy and quality of life for HER2-positive gastric cancer patients. Nevertheless, further clinical trials are warranted to validate the efficacy and safety of this treatment approach.