Journal of gastrointestinal oncology最新文献

{"title":"<i>MS4A3</i> as a potential prognostic biomarker for colon cancer: integrated analysis of expression patterns and immune cell infiltration.","authors":"Li Feng, Qin Hao, Jing Fan, Guizhen Gao, Xu Gao, Hongyang Zhang, Zhao Ruigetu, Yu Wu, Hao Yang, Zhenfei Wang","doi":"10.21037/jgo-2026-0374","DOIUrl":"10.21037/jgo-2026-0374","url":null,"abstract":"<p><strong>Background: </strong>Membrane Spanning 4-Domains A3 (<i>MS4A3</i>) has been confirmed to possess significant tumor-suppressive potential in various malignancies. However, its expression characteristics and clinical prognostic value in colon cancer (CC) still lack systematic and in-depth investigation. This study aimed to systematically investigate the expression pattern, prognostic value, immune microenvironment association, and biological function of <i>MS4A3</i> in CC through integrated bioinformatics analyses and experimental validation.</p><p><strong>Methods: </strong>This study utilized The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) cohort to screen for genes significantly associated with CC and combined multiple independent Gene Expression Omnibus (GEO) datasets to validate the expression patterns and prognostic significance of <i>MS4A3</i>. Key biological pathways were identified through gene set enrichment analysis (GSEA), and tumor immune infiltration characteristics were evaluated using the CIBERSORT algorithm. Additionally, the expression of <i>MS4A3</i> and its impacts on cellular functions were validated at the cellular level through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, Cell Counting Kit-8 (CCK-8), EdU, Transwell, and TUNEL assays.</p><p><strong>Results: </strong>Analysis of public datasets revealed that <i>MS4A3</i> is significantly downregulated in CC tissues, and its low expression is an independent risk factor for shortened overall survival (OS). GSEA indicated that <i>MS4A3</i> downregulation is closely associated with the aberrant activation of the pentose phosphate pathway. Immune infiltration analysis showed that low <i>MS4A3</i> expression is closely linked to the enrichment of M2 macrophages and neutrophils, as well as the upregulation of multiple immune checkpoint genes. <i>In vitro</i> experiments further confirmed that <i>MS4A3</i> was lowly expressed in CC cell lines. Its overexpression significantly inhibited CC cell viability, proliferation, migration, and invasion, while simultaneously promoting cell apoptosis.</p><p><strong>Conclusions: </strong><i>MS4A3</i> expression is significantly decreased in CC tissues and is significantly correlated with poor prognosis, suggesting that this gene may serve as a potential prognostic biomarker.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"232"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early hypoalbuminemia during zolbetuximab therapy in gastroesophageal adenocarcinoma: a retrospective observational study.","authors":"Fares Jamal, Cody Eslinger, Abdullah Alsulaiman, Tanios Bekaii-Saab, Hao Xie, Daniel Ahn, Jason S Starr, Jake Jochum, Nguyen H Tran, Mojun Zhu, Ben George, Caitlin B Conboy, Conor D J O'Donnell, Jamie Bering, Harry H Yoon, Mohamad Bassam Sonbol","doi":"10.21037/jgo-2026-0570","DOIUrl":"10.21037/jgo-2026-0570","url":null,"abstract":"<p><strong>Background: </strong>Zolbetuximab has improved survival in claudin 18.2 (CLDN18.2)-positive gastroesophageal adenocarcinoma (GEA). Hypoalbuminemia was reported in phase III trials. However, the timing, magnitude, and clinical phenotype of serum protein decline remain incompletely characterized. This study aimed to characterize changes in serum albumin and total protein during zolbetuximab therapy and their associated clinical findings.</p><p><strong>Methods: </strong>We performed a retrospective cohort study of patients with CLDN18.2-positive GEA treated with zolbetuximab at Mayo Clinic sites. The primary endpoint was percent change in serum albumin from baseline to the first post-treatment measurement following therapy initiation. Secondary endpoints included percent change in total protein, development of new edema or ascites not attributable to disease progression, and changes in albumin and total protein after treatment discontinuation.</p><p><strong>Results: </strong>Twenty-four patients were included. Serum albumin declined in all patients, and total protein declined in 23/24 (95.8%) immediately following treatment initiation. After the first cycle, median albumin decreased by 0.9 g/dL (22.5%), and total protein decreased by 1.5 g/dL (23.7%) from baseline. Ten patients (41.7%) developed new edema and 6 (25%) developed ascites, with 8 (33.3%) requiring diuretics and/or paracentesis, without radiographic disease progression. Renal and hepatic laboratory parameters remained stable, and urinalysis did not demonstrate nephrotic-range (grade 3+) proteinuria.</p><p><strong>Conclusions: </strong>Zolbetuximab therapy is associated with an early decline in serum albumin and total protein in real-world practice, frequently accompanied by edema or ascites and not explained by renal, hepatic, or progressive disease factors. These findings may reflect a treatment-related gastrointestinal protein-losing process and support close laboratory monitoring and supportive management during therapy. Further studies are warranted to clarify mechanism and clinical impact.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"210"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadonilimab plus chemotherapy in PD-L1-low gastroesophageal cancer: a bispecific opportunity?","authors":"Sohiel Deshpande, Daniel Lin","doi":"10.21037/jgo-2026-0692","DOIUrl":"10.21037/jgo-2026-0692","url":null,"abstract":"","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"281"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-operative management of rectal adenocarcinoma in a safety-net system: a decade of real-world outcomes outside watch-and-wait eligibility.","authors":"Ashley N Chavana, Piyush Pathak, Caleb Stewart, Laurynn Garcia, Alfredo Echeverria, Eric Silberfein, Cary Hsu, Benjamin Musher, Alexander N Hanania","doi":"10.21037/jgo-2026-0491","DOIUrl":"10.21037/jgo-2026-0491","url":null,"abstract":"<p><p>Recent guidelines increasingly support watch-and-wait (W&W) strategies for locally advanced rectal cancer (LARC) following favorable response to neoadjuvant therapy. However, these strategies have largely been validated in highly selected trial populations and require intensive surveillance that may be difficult to implement in underserved settings. Limited data exist on outcomes among patients affected by adverse social determinants of health, particularly in safety-net hospital systems. We evaluated outcomes of patients with LARC in an underserved setting who were managed non-operatively out of necessity, rather than according to W&W guidelines. Most of the presented cohort would not have met eligibility criteria for contemporary W&W trials and received care that largely predated widespread adoption of W&W, allowing assessment of whether comparable outcomes are achievable in a higher-risk, real-world population. This retrospective study included patients with LARC managed non-operatively with definitive intent at a single safety-net hospital system over a decade. All patients received radiotherapy and systemic chemotherapy. Clinical characteristics, treatment details, and oncologic outcomes were abstracted. Forty-nine patients were identified with a median follow-up of 25 months (range, 8-90 months). The cohort was 55% male and racially/ethnically diverse (63% Hispanic, 20% White, 12% Black). Most patients (69%) were uninsured. Reasons for non-operative management included patient preference (49%), suspicion of low-burden metastatic or non-regional nodal disease (35%), and medical comorbidities (16%). The majority (76%) received long-course chemoradiotherapy (50-55 Gy with concurrent capecitabine); the remainder received short-course radiotherapy (25 Gy/5 fractions). Local failure did not differ significantly between regimens (P=0.51). Two-year local control, progression-free survival, and overall survival were 59%, 43%, and 67%, respectively. Eighteen patients (37%) achieved an initial complete or near-complete clinical response, of whom 5 developed local recurrence. Distant-only metastasis was the most common recurrence pattern. Despite inclusion of higher-risk patients who would not meet standard W&W criteria, radiotherapy-based non-operative management achieved meaningful local control, with regrowth rates among responders comparable to prospective trials. These findings support the feasibility of organ-preserving approaches in safety-net populations even when adherence to W&W surveillance protocols remains challenging.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"270"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognosis of patients with gastrointestinal stromal tumors harboring the KIT exon 11 mutation: a retrospective cohort study.","authors":"Chunhui Shou, Weili Yang, Xiaodong Wang, Qi Zhang, Jiren Yu, Tingbo Liang","doi":"10.21037/jgo-2026-0409","DOIUrl":"10.21037/jgo-2026-0409","url":null,"abstract":"<p><strong>Background: </strong>The different pathogenic variant locations of KIT are associated with variable outcomes in patients with gastrointestinal stromal tumors (GISTs). The aim of this study was to investigate the prognosis and optimal duration of adjuvant imatinib treatment in patients with GISTs with the KIT exon 11 mutation.</p><p><strong>Methods: </strong>Patients who received surgical resection between January 2004 and December 2023 for primary GISTs with the KIT exon 11 mutation were retrospectively reviewed. The association of genotype and imatinib treatment with the prognosis of patients was analyzed.</p><p><strong>Results: </strong>Among the 647 patients included in the study, 155 different mutations were detected, and the most frequently mutated codons were 557-560. The common mutation types were deletion (n=233, 36.0%), substitution (n=222, 34.3%), and insertion-deletion (indel; n=132, 20.4%). GISTs with deletion or indel mutations were associated with more high-risk disease as compared to other mutations (43.0% <i>vs.</i> 31.2%; P=0.002). The median follow-up time was 55 (range, 12-255) months, and the 5-year disease-free survival (DFS) rate of the entire cohort was 83.4%. Adjuvant imatinib treatment significantly improved the DFS compared with surgery only in patients with intermediate-risk disease (5-year DFS rate: 96.4% <i>vs.</i> 91.7%) and high-risk disease (5-year DFS rate: 76.4% <i>vs.</i> 28.6%), respectively. Prolonged duration of adjuvant imatinib treatment was associated with better prognosis for high-risk patients (log-rank P<0.001). After the variables in the Cox model were adjusted, mutation type and adjuvant imatinib treatment were the independent predictors of prognosis.</p><p><strong>Conclusions: </strong>The deletion and indel mutations of KIT exon 11 may be unfavorable prognostic factors for patients with GIST. Prolongation of adjuvant imatinib treatment to 5 years may provide greater benefit to patients with high-risk GISTs harboring KIT exon 11 mutations.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"214"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trajectory identification of high-risk subgroups after colorectal cancer surgery in patients with minimal residual disease: a single-center longitudinal study.","authors":"Yahan Zhang, Lei Liang, Ruize Zhou, Shirong Wu, Yicheng Zhou, Jinjin Luo, Yujian Zeng, Ning Xu, Zhengqi Wen","doi":"10.21037/jgo-2026-0476","DOIUrl":"10.21037/jgo-2026-0476","url":null,"abstract":"<p><strong>Background: </strong>Postoperative recurrence and distant metastasis are crucial for long-term survival in colorectal cancer (CRC) patients. Minimal residual disease (MRD) after surgery is linked to these outcomes, with a negative MRD usually suggesting low risk. However, some patients still face recurrence or metastasis. This study assessed the prognostic significance of circulating tumor DNA (ctDNA)-MRD in CRC and identified high-risk subgroups through analysis of its longitudinal trajectory.</p><p><strong>Methods: </strong>This study analyzed clinical data from (n=124) stage II-III CRC patients who underwent ctDNA-MRD testing at The First Affiliated Hospital of Kunming Medical University between January 2017 and December 2024. Patients were categorized into four groups based on postoperative ctDNA-MRD status and recurrence: true negative (TN), false negative (FN), true positive (TP), and false positive (FP). Utilizing the longitudinal trajectory results of ctDNA-MRD, in conjunction with prognostic data, we aimed to delineate the characteristics of high-risk subgroups among CRC patients.</p><p><strong>Results: </strong>(I) In this study, ctDNA-MRD negativity and alpha-fetoprotein (AFP) <7 ng/mL were protective factors for progression-free survival (PFS), while pathology node (pN1), and pN2 stages were risk factors. For overall survival (OS), protective factors included MRD negativity, AFP <7 ng/mL, carcinoembryonic antigen (CEA) <5 ng/mL, carbohydrate antigen 125 (CA125) <24 U/mL, and neutrophil-lymphocyte ratio (NLR) <3.8. Risk factors were albumin (ALB) <39 g/L, pN1, and pN2 stages. (II) Longitudinal MRD trajectory analysis revealed that ctDNA-MRD signals consistently increased in recurrent patients but decreased or disappeared in non-recurrent patients. The mean variant allele frequency (VAF) value was highest in the ctDNA-MRD-positive recurrent group, significantly more than that in the ctDNA-MRD-negative non-recurrent and recurrent groups (P=0.047), though detection breadth was highest in the ctDNA-MRD-positive recurrent group without statistical significance (P=0.20). Overall, total VAF was higher in recurrent than non-recurrent groups across all subgroups, but not significantly (P=0.71).</p><p><strong>Conclusions: </strong>ctDNA-MRD status serves as a crucial prognostic indicator for patients with CRC. Longitudinal monitoring of ctDNA-MRD is more effective than single-point assessments in identifying CRC patients at high risk.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"225"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a nomogram for the non-invasive prediction of human epidermal growth factor receptor 2 expression in gastric adenocarcinoma: an ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography-based study.","authors":"Sijie Yang, Xiuqing Xue, Wen Jiang, Minyi Wang, Xinyi Zhang, Yu Chen, Dachuan Zhang, Qi Zhou, Yuetao Wang, Xiaoliang Shao","doi":"10.21037/jgo-2026-0345","DOIUrl":"10.21037/jgo-2026-0345","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is a major global malignancy, and human epidermal growth factor receptor 2 (HER2) expression serves as a critical biomarker for guiding targeted treatment. However, current invasive biopsy methods have inherent limitations. This study aimed to explore the association between preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) metabolic parameters and HER2 expression in gastric adenocarcinoma, and to develop a preliminary nomogram as an exploratory tool for non-invasive prediction.</p><p><strong>Methods: </strong>We retrospectively analyzed 231 gastric adenocarcinoma patients with preoperative ¹⁸F-FDG PET/CT. Tumor metabolic parameters were extracted following automated lesion segmentation using a threshold of 40% maximum standardized uptake value (SUV_max). Univariate and multivariate logistic regression identified independent predictors of HER2 status, which informed the construction of a visual nomogram. The model was evaluated with the area under the receiver operating characteristic curve for discrimination, calibration curves for goodness-of-fit, and decision curve analysis (DCA) for clinical net benefit.</p><p><strong>Results: </strong>Of the 231 gastric adenocarcinoma patients enrolled, 30 (13%) were HER2-positive. Univariate logistic regression indicated positive correlations between HER2 positivity and higher primary tumor SUV_max [odds ratio (OR) =1.04, 95% confidence interval (CI): 1.00-1.08, P=0.07] and SUV_mean (OR =1.07, 95% CI: 1.00-1.15, P=0.08). Multivariate analysis confirmed SUV_max, tumor location, and differentiation grade as independent predictors (all P<0.05). The combined nomogram attained an area under the curve (AUC) of 0.710 and a bootstrap-validated concordance index (C-index) of 0.686. Calibration analysis showed satisfactory predictive consistency, and DCA verified the clinical applicability of the model.</p><p><strong>Conclusions: </strong>¹⁸F‑FDG PET/CT metabolic parameters are associated with HER2 positivity among patients with gastric adenocarcinoma. The integrated nomogram incorporating both PET metrics and clinical factors holds promise for noninvasive HER2 prediction and can act as an exploratory predictive tool, though its clinical performance awaits additional validation.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"216"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of DNA damage response-related markers in esophageal squamous cell carcinoma using machine learning approaches.","authors":"Chao Huang, Yan-Jiao Zhang, Fan Zhang, Chun-Yue Gai, Zhen-Hua Li, Hui-Lai Lv, Shi-Wang Wen, Zi-Qiang Tian","doi":"10.21037/jgo-2026-0588","DOIUrl":"10.21037/jgo-2026-0588","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) lacks reliable prognostic biomarkers. Homologous recombination deficiency (HRD) has been implicated in genomic instability across multiple cancers, but its prognostic significance in ESCC remains unexplored. This study aimed to evaluate HRD score as a prognostic biomarker and develop a machine learning-based predictive model for ESCC.</p><p><strong>Methods: </strong>Transcriptomic and clinical data from 78 ESCC patients were obtained from The Cancer Genome Atlas (TCGA) and randomly split into training (70%) and test (30%) cohorts. Prognostic models were constructed using 112 machine learning algorithm combinations based on DNA damage response (DDR)-related genes. Gene set enrichment analysis (GSEA), somatic mutation profiling, and immune cell infiltration estimation via CIBERSORT were performed to characterize HRD-associated molecular features.</p><p><strong>Results: </strong>High HRD scores were significantly associated with poorer overall survival (P<0.05). Among 112 algorithm combinations, the survival support vector machine (Survival-SVM) model demonstrated optimal performance [training concordance index (C-index): 0.741; test C-index: 0.708], identifying six hub genes: <i>PARP1</i>, <i>MBD4</i>, <i>TELO2</i>, <i>NSMCE3</i>, <i>SMUG1</i>, and <i>BABAM1</i>. A nomogram incorporating risk score (RS) and clinical variables achieved strong predictive accuracy for 1- to 3-year survival [area under the curve (AUC) >0.7]. High-HRD tumors exhibited distinct mutational patterns (<i>TP53</i> and <i>TTN</i>) and enriched glutathione metabolism and cytochrome P450 pathways. Immune infiltration analysis revealed significant differences in plasma cell and neutrophil infiltration between risk groups (P<0.05), suggesting HRD-associated immune microenvironment remodeling.</p><p><strong>Conclusions: </strong>We developed a novel HRD-based prognostic model incorporating six DDR-related genes that demonstrates robust predictive performance in ESCC. HRD score is identified as an independent prognostic factor associated with genomic instability, immune microenvironment alterations, and clinical outcomes. These findings provide a theoretical basis for personalized treatment strategies, including potential applications of PARP inhibitors and immunotherapy in ESCC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"204"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of sintilimab-based neoadjuvant regimens in patients with resectable gastric or gastroesophageal junction adenocarcinoma: a single-arm systematic review and meta-analysis.","authors":"Tingting Nan, Siheng Lian, Xiaohong Wu, Ruina Cai, Yumei Cai, Yonglong Su, Xiaoyun Ye, Yuhong Huang, Jinbao Wei, Ruping Ni","doi":"10.21037/jgo-2026-0479","DOIUrl":"10.21037/jgo-2026-0479","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant immunotherapy has emerged as a research focus in the management of resectable gastric and gastroesophageal junction (G/GEJ) cancer. Sintilimab, a fully human anti-programmed death receptor-1 (PD-1) monoclonal antibody with high PD-1 affinity, demonstrates favorable antitumor activity, safety, accessibility, and cost-effectiveness, highlighting its potential in neoadjuvant settings. This single-arm meta-analysis aimed to provide pooled estimates of efficacy and safety by aggregating the rates of tumor response, R0 resection, survival, and toxicity of neoadjuvant sintilimab-based regimens in resectable G/GEJ adenocarcinoma.</p><p><strong>Methods: </strong>Original articles describing the safety and efficacy of sintilimab-based regimens for the neoadjuvant treatment of G/GEJ adenocarcinoma, published up to August 19, 2025, were retrieved from the Embase, PubMed/MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. STATA 16.0 was employed for data analysis.</p><p><strong>Results: </strong>A total of 693 patients from 13 studies were included. Neoadjuvant sintilimab plus chemotherapy achieved pooled pathologic complete response (pCR) and major pathologic response (MPR) rates of 24% and 50%, respectively. Subgroup analyses showed higher pCR and MPR in prospective <i>vs.</i> retrospective studies. Patients with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥5 showed significantly better pCR (41% <i>vs.</i> 18%, P=0.02) and MPR (69% <i>vs.</i> 36%, P=0.002) rates than those with CPS <5. Microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) status was correlated with higher pCR (51% <i>vs.</i> 20%, P=0.01). Secondary outcomes included objective response rate (ORR) (75%), disease control rate (DCR) (99%), and R0 resection rate (99%). One-year disease-free survival (DFS) and overall survival (OS) were 90% and 98%; 2-year event-free survival (EFS) and OS were 67% and 83%. Common treatment-related adverse events (TRAEs) included nausea, alopecia, and hematological toxicities. Among grade ≥3 TRAEs, only lymphopenia had an incidence exceeding 10% (18%).</p><p><strong>Conclusions: </strong>The pooled results indicate that the sintilimab-based neoadjuvant regimen offers promising efficacy and tolerability in G/GEJ adenocarcinoma. Subgroup analyses suggest higher pathological response in patients with PD-L1 CPS≥5 or MSI-H/dMMR. However, these exploratory findings require randomized controlled trials (RCTs) validation.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"208"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world efficacy and safety of fruquintinib plus PD-1 inhibitors with or without radiotherapy in refractory metastatic colorectal cancer: a single-center retrospective cohort study.","authors":"An Yi, Lihong He, Xin Liu, Zhuoyu He, Jin Liu, Bin Li, Huaiwen Zhang, Yan Liu, Chunling Jiang","doi":"10.21037/jgo-2026-0430","DOIUrl":"10.21037/jgo-2026-0430","url":null,"abstract":"<p><strong>Background: </strong>Patients with microsatellite-stable (MSS) refractory metastatic colorectal cancer (mCRC) derive little benefit from immune checkpoint inhibitors. Whether fruquintinib and localized radiotherapy improve outcomes when combined with programmed death-1 (PD-1) inhibitors remains uncertain in routine practice.This study aimed to evaluate and compare the real-world efficacy and safety of fruquintinib monotherapy (FM), fruquintinib plus a PD-1 inhibitor (FP), and the trimodal combination of fruquintinib, a PD-1 inhibitor, and concurrent radiotherapy (FPR) in refractory mCRC.</p><p><strong>Methods: </strong>This single-center retrospective cohort study included 145 heavily pretreated patients with mCRC who had progressed after at least two systemic treatment lines. Propensity score matching (PSM) was used to address baseline imbalances among the three groups. Tumor response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) every two to three treatment cycles according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.</p><p><strong>Results: </strong>Among the pre-matched cohort (n=145), baseline characteristics were significantly imbalanced across groups regarding brain, lymph node, and bone metastases. After 1:1:1 PSM (n=16 per group), all baseline characteristics achieved statistical balance (P>0.05). Post-PSM analysis demonstrated that both the FP (median PFS: 5.0 months; P=0.04) and FPR groups (median PFS: 7.2 months; P=0.002) significantly prolonged PFS compared with the FM group (median PFS: 3.5 months). The FPR cohort achieved a numerically highest disease control rate (87.5% <i>vs.</i> 62.5% for FM/FP; P=0.20). Multivariable Cox regression confirmed combination therapy as an independent predictor of favorable PFS (P=0.004). Median OS did not differ significantly among the matched arms (P=0.62). Grade 3-4 toxicities were infrequent and comparable across all groups (P>0.05).</p><p><strong>Conclusions: </strong>Fruquintinib combined with a PD-1 inhibitor, with or without concurrent radiotherapy, was associated with significantly longer PFS than fruquintinib alone in refractory mCRC, while maintaining a manageable safety profile. These findings provide preliminary real-world support for fruquintinib-based combination strategies, but prospective validation is required.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"230"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}