Gastric Cancer最新文献

{"title":"Clinical impact of CT-defined sarcopenia on long-term oncological outcomes in gastric cancer: validation of muscle mass cut-offs established according to EWGSOP recommendations.","authors":"Jasmin Hasanovic, Paul Friedrich Esslinger, Veronika Lummer, Heiner Nebelung, Leo Misera, Ralf-Thorsten Hoffmann, Johanna Kirchberg, Marius Distler, Jürgen Weitz, Daniel E Stange, Felix Merboth","doi":"10.1007/s10120-026-01796-x","DOIUrl":"https://doi.org/10.1007/s10120-026-01796-x","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is an important prognostic factor in gastrointestinal malignancies, but CT-based definitions vary. This study evaluated recently published computed tomography (CT)-based cut-offs for skeletal muscle index (SMI) and psoas muscle thickness normalized to height (PMTH), derived from a young, presumably healthy reference population according to recommendations of the European Working Group on Sarcopenia in Older People (EWGSOP), in patients undergoing surgery for gastric cancer.</p><p><strong>Methods: </strong>This retrospective, single-center cohort study included patients who underwent surgery for gastric cancer between 2013 and 2018. Preoperative CT was used to assess SMI and PMTH. The recently published reference cut-offs were compared with the established definitions of Prado et al. (SMI) and Gu et al. (PMTH). Overall survival (OS) and recurrence-free survival (RFS) were the primary and secondary endpoints, respectively.</p><p><strong>Results: </strong>Data from 212 patients with complete 5-year follow-up were analyzed. The reference cut-offs significantly discriminated OS and RFS (SMI, both p < 0.001; PMTH, both p = 0.002), whereas the established cut-offs showed weaker or no discrimination. Patients with both low SMI and low PMTH had the worst OS and RFS (both p < 0.001). Combined low SMI and low PMTH was associated with worse OS in univariable analysis (HR 2.57, 95% CI 1.54-4.30, p < 0.001) and remained independently associated in multivariable analysis (HR 1.83, 95% CI 1.01-3.30; p = 0.046).</p><p><strong>Conclusions: </strong>The recently published CT-based reference cut-offs for SMI and PMTH provided consistent prognostic stratification after gastric cancer resection, and their combined use identified patients with particularly poor long-term survival.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: An observational study of the effectiveness and safety of nivolumab plus chemotherapy for untreated advanced or recurrent gastric cancer in Japanese real-world settings: the G-KNIGHT study.","authors":"Shigenori Kadowaki, Tomoyuki Otsuka, Keiko Minashi, Shinichi Nishina, Hiroshi Yabusaki, Chiaki Inagaki, Tomohiro Nishina, Hisateru Yasui, Hiroshi Matsuoka, Nozomu Machida, Masahiro Tsuda, Fumio Nagashima, Hisashi Hosaka, Junichi Matsubara, Hiroyuki Arai, Satoshi Ida, Yuya Kimijima, Yuko Matsuda, Manabu Muto, Kei Muro","doi":"10.1007/s10120-026-01772-5","DOIUrl":"10.1007/s10120-026-01772-5","url":null,"abstract":"","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1179-1180"},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of long-term outcomes of robotic gastrectomy and laparoscopic gastrectomy using the modified age-adjusted Charlson Comorbidity Index.","authors":"Kyota Takahashi, Keiichi Fujiya, Masanori Terashima, Akifumi Notsu, Yusuke Koseki, Kenichiro Furukawa, Yutaka Tanizawa, Etsuro Bando","doi":"10.1007/s10120-026-01758-3","DOIUrl":"10.1007/s10120-026-01758-3","url":null,"abstract":"<p><strong>Background: </strong>The modified age-adjusted Charlson Comorbidity Index (mACCI) is associated with postoperative complications and long-term survival after gastrectomy. However, whether robotic gastrectomy (RG) provides clinical advantages over laparoscopic gastrectomy (LG) in high-risk patients remains unclear. This study evaluated short- and long-term outcomes of RG compared with LG according to mACCI.</p><p><strong>Methods: </strong>A total of 1501 patients who underwent minimally invasive gastrectomy for clinical stage I-II gastric cancer between 2012 and 2021 were retrospectively analyzed. Patients were stratified by mACCI (< 4 and ≥ 4), and propensity score matching was performed within each stratum. Short-term outcomes, overall survival (OS), recurrence-free survival (RFS), and cumulative incidence of other-cause and gastric cancer-specific death were assessed.</p><p><strong>Results: </strong>Among patients with mACCI ≥ 4, RG was associated with a lower incidence of postoperative complications than LG after matching (2.7% vs. 8.2%, P = 0.036), including pancreatic fistula (0% vs. 3.3%, P = 0.030). RG showed significantly improved OS (HR 0.485, 95% CI 0.271-0.868, P = 0.015) and RFS (HR 0.417, 95% CI 0.236-0.738, P = 0.003). Competing risk analysis demonstrated a lower incidence of other-cause death in the RG group, whereas gastric cancer-specific mortality did not differ. No significant differences were observed between approaches in patients with mACCI < 4.</p><p><strong>Conclusions: </strong>Robotic gastrectomy was associated with reduced postoperative complications and improved long-term outcomes in high-risk patients with substantial comorbidities. RG may represent a preferable surgical approach in this population.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1083-1091"},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hospital-based gastric cancer outcomes in the United States (2003-2022): racial and regional disparities.","authors":"Yasutoshi Shiratori, Neha Sharma, Syed Matthew Kodilinye, Carla Barberan Parraga, Fatima Khan, Ahmed E Salem, Sarah Meribout, Diana Cheung, Aaron Tokayer, Anthony Kalloo, Linda A Lee","doi":"10.1007/s10120-026-01765-4","DOIUrl":"10.1007/s10120-026-01765-4","url":null,"abstract":"<p><strong>Introduction: </strong>Racial disparities in gastric cancer (GC) outcomes have gained increasing attention in the United States, particularly given the large immigrant population from high-incidence regions.</p><p><strong>Methods: </strong>We analyzed a nationally representative hospital database (2003-2022) to identify patients with a primary diagnosis of gastric cancer. Outcomes included in-hospital mortality, surgical receipt, perioperative complications, length of stay, and home discharge. Multivariate logistic regression adjusting for sociodemographic and hospital factors estimated odds ratios (ORs) with 95% confidence intervals. Temporal trends and race-period interactions were analyzed to assess in-hospital mortality changes, with regional subgroup analyses evaluating geographic variation.</p><p><strong>Results: </strong>A total of 137,951 patients were included. GC admissions and in-hospital mortality declined by 82% and 60% over two decades; however, racial disparities persisted. Compared with White patients, Black (OR 1.17, 95% CI 1.11-1.25) and Native American patients (OR 1.14, 95% CI 1.04-1.26) had higher odds of in-hospital mortality. The Black-White mortality gap narrowed during 2013-2018 but widened after 2019, indicating temporal heterogeneity (P for interaction = 0.026). Black patients underwent surgery less frequently (OR 0.85), experienced more perioperative complications (OR 1.11), and were less often discharged home (OR 0.86). Regionally, mortality was higher among Black patients in the Northeast (OR 1.36) and South (OR 1.14), and among Asian (OR 1.35) and Native American patients (OR 1.47) in the West.</p><p><strong>Conclusions: </strong>Despite improvements in GC admissions and in-hospital mortality, clinically relevant racial and regional disparities in hospital-based outcomes persist, highlighting the need for targeted public health and health system strategies to achieve equitable care.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"940-948"},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline whole-exome sequencing identifies CTNND1 as a candidate gene for hereditary gastric cancer in a large Brazilian cohort.","authors":"Deivid Calebe de Souza, Thaliane Buranello, Dario Tenorio Tavares Neto, Janina Pontes Pisani, Giovanna Napolitano Pereira Ribeiro, Marcia Olandoski, David Schlesinger, João Paulo Kitajima, Danilo Vilela Viana, Maria Isabel Achatz","doi":"10.1007/s10120-026-01780-5","DOIUrl":"10.1007/s10120-026-01780-5","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is the fifth most commonly diagnosed cancer. Although 10% of cases show familial clustering, a monogenic hereditary cause is rarely observed. Little is known about the molecular profile of familial gastric cancer cases in Brazil. Thus, we aimed to characterize the germline genomic profile of patients with potentially hereditary gastric cancer in the Brazilian population.</p><p><strong>Methods: </strong>DNA from peripheral blood or buccal swab was obtained for whole-exome sequencing of 126 patients with gastric cancer with suspected hereditary cancer predisposition syndrome from the Mendelics laboratory.</p><p><strong>Results: </strong>Results from our initial analyses using an exome-derived multigene panel showed that, among the 11 cases identified as having hereditary cancer predisposing syndrome, BRCA2 gene was the most frequently mutated (n = 3, 27.3%). Whole exome sequencing showed candidate genes, such as FBXO24 and CTNND1. Among the candidates, CTNND1 has emerging evidence of association with gastric cancer predisposition. Analysis of somatic data from The Cancer Genome Atlas showed that diffuse gastric tumors and signet ring cell adenocarcinomas with somatic mutations in CTNND1 exhibited high microsatellite instability and high mutation count. A rare germline variant identified in CTNND1 may expand understanding of hereditary gastric cancer predisposition.</p><p><strong>Conclusions: </strong>This is the first study to evaluate, through germline whole exome sequencing, candidate genes for gastric cancer predisposition in a large Brazilian population. The novel candidate genes identified may be associated with gastric cancer and have potential to improve surveillance and management of individuals at increased risk of developing this tumor.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"960-971"},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic origin of increased serum TFF3 in gastric cancer bearing subjects.","authors":"Komei Kuge, Junko Mukohyama, Yoshimi Yasukawa, Yuko Ishibashi, Hiroki Masuda, Tomohiko Yasuda, Yasukazu Ohmoto, Hideyuki Takeshima, Akihisa Matsuda, Hiroshi Yoshida, Yasuyuki Seto, James R Goldenring, Toshikazu Ushijima, Sachiyo Nomura","doi":"10.1007/s10120-026-01782-3","DOIUrl":"10.1007/s10120-026-01782-3","url":null,"abstract":"<p><strong>Background: </strong>Serum trefoil factor 3 (TFF3) has emerged as a promising biomarker for gastric cancer; however, its biological origin remains unclear.</p><p><strong>Methods: </strong>Gastric cancer was induced by Helicobacter pylori infection combined with N-methyl-N-nitrosourea (MNU), whereas a rat model was established using N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) alone. Serum TFF levels were measured by ELISA. Organ-specific TFF3 expression, cytokine profiles, STAT3 activation, and epigenetic regulation were analyzed using RT-PCR, immunohistochemistry, multiplex assays, Western blotting, and ChIP-qPCR.</p><p><strong>Results: </strong>Serum TFF1-3 levels were significantly elevated in gastric cancer-bearing mice, with TFF3 showing robust diagnostic performance. In rats, serum TFF3 levels remained unchanged after total gastrectomy. TFF3 expression was selectively upregulated in the liver, accompanied by STAT3 activation. Gastric IL-6 expression was increased, suggesting portal-mediated signaling to the liver. ChIP-qPCR demonstrated sustained enrichment of H3K27ac at the TFF3 locus following IL-6 stimulation.</p><p><strong>Conclusions: </strong>Increased serum TFF3 in gastric cancer originates from the liver and is associated with IL-6-STAT3 signaling. Persistent elevation after gastrectomy may be explained by epigenetic activation, supporting the biological basis of TFF3 as a surrogate marker.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1001-1014"},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catheter based intraperitoneal chemotherapy using taxane for peritoneal metastases from gastric cancer: from bench to bedside-a narrative review.","authors":"Joji Kitayama","doi":"10.1007/s10120-026-01767-2","DOIUrl":"10.1007/s10120-026-01767-2","url":null,"abstract":"<p><p>Peritoneal metastasis (PM) is the most common and clinically devastating mode of spread in Gastric Cancer. Despite advances in systemic therapy, outcomes for gastric cancer with peritoneal metastasis (GCPM) remain poor, largely because the distinctive biology of PM, including sparse vascularization and the peritoneal-plasma barrier, restricts drug delivery and promotes therapeutic resistance. To overcome these limitations, locoregional approaches such as cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced, but their broader use remains limited by invasiveness, patient selection challenges, and variable survival benefits. In this setting, catheter-based normothermic intraperitoneal chemotherapy (CBIP) has emerged as a practical and scalable strategy, particularly in East Asia. By enabling repeated intraperitoneal administration through an implanted port, CBIP provides sustained regional drug exposure with minimal procedural burden and can be readily combined with systemic therapy. Among available agents, Paclitaxel and Docetaxel are especially suitable because of their prolonged peritoneal retention and low systemic absorption. Accordingly, taxane-based CBIP represents a biologically rational and clinically feasible platform for GCPM. In this review, we summarize its pharmacologic basis, clinical evidence, and future innovations in drug formulation and delivery that may further improve outcomes in this highly challenging disease.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"904-919"},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of oncological outcomes between robotic and laparoscopic surgeries for gastric cancer: a multi-institutional cohort study in Japan.","authors":"Haruku Fujita, Tatsuto Nishigori, Yoshito Yamashita, Hisahiro Hosogi, Seiichiro Kanaya, Michihiro Yamamoto, Yosuke Kinjo, Masato Kondo, Hiroaki Hata, Hironori Kawada, Koichi Matsuo, Atsushi Itami, Kenjiro Hirai, Yuichiro Kawamura, Dai Manaka, Sanae Nakajima, Hiroshi Okabe, Kosuke Toda, Eiji Tanaka, Tetsuo Ito, Akira Miki, Kiyotaka Kawaguchi, Ryosuke Mizuno, Masazumi Sakaguchi, Shintaro Okumura, Shigeo Hisamori, Shigeru Tsunoda, Koya Hida, Kentaro Ueno, Shiro Tanaka, Kazutaka Obama","doi":"10.1007/s10120-026-01761-8","DOIUrl":"10.1007/s10120-026-01761-8","url":null,"abstract":"<p><strong>Background: </strong>The oncological safety and benefits of robotic gastrectomy (RG) in daily clinical practice remain unknown. This study aimed to compare 3-year outcomes between RG and laparoscopic gastrectomy (LG) for gastric cancer.</p><p><strong>Methods: </strong>This multi-institutional retrospective cohort study was conducted in 19 Japanese hospitals and included patients with gastric cancer who underwent minimally invasive gastrectomy between January 2017 and December 2020. To balance baseline characteristics between patients who underwent RG and LG, 1:2 propensity score matching was conducted using 28 variables. The primary endpoint was 3-year relapse-free survival (RFS), with non-inferiority defined as the upper limit of 95% confidence interval (CI) for a hazard ratio (HR) of <1.33.</p><p><strong>Results: </strong>In this study, 3181 patients were included. After propensity score matching, 676 and 1352 patients from the RG and LG groups, respectively, were included in the analysis. In the matched cohort, RG was associated with longer operation time and less blood loss, whereas postoperative complications were comparable between the groups. Three-year RFS rate was 84.1% in the RG group and 84.3% in the LG group (HR, 1.02; 95% CI, 0.81-1.29; p = 0.873), indicating that RG met the criterion for non-inferiority to LG. The 3-year overall survival rate was 90.6% and 89.2% in the RG and LG groups, respectively (HR, 0.86; 95% CI, 0.64-1.17; p = 0.340). Subgroup analysis revealed that RG was associated with significantly better RFS in patients with pathological T4 disease (HR, 0.68; 95% CI, 0.47-0.99; p = 0.049).</p><p><strong>Conclusions: </strong>RG was not inferior to LG with respect to oncological outcomes.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1101-1114"},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline IL-6 independently predicts severe immune-related toxicity and poor survival in advanced gastric cancer treated with immunotherapy.","authors":"Wanrong Liu, Hui Tang, Ningning Li, Wei Qiu, Xiaoyuan Li, Lin Zhao","doi":"10.1007/s10120-026-01744-9","DOIUrl":"10.1007/s10120-026-01744-9","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) improve survival in advanced gastric cancer (GC), yet predicting therapeutic benefit versus toxicity remains challenging. Elevated interleukin-6 (IL-6) is linked to poor prognosis, but whether it simultaneously influences immune-related adverse events (irAEs) and how this relationship impacts survival remains unclear.</p><p><strong>Methods: </strong>We retrospectively analyzed 244 patients with advanced GC treated with ICIs. Predictors of high-grade irAEs were evaluated using Firth's penalized logistic regression to mitigate small-sample bias. Independent prognostic factors for overall survival (OS) were identified via multivariable Cox analysis and validated using propensity score matching (PSM). Causal mediation analysis was performed to assess whether the effect of IL-6 on OS was mediated through irAEs. Biological mechanisms were explored using TCGA-STAD transcriptomic data.</p><p><strong>Results: </strong>Baseline IL-6 was a strong independent predictor of high-grade irAEs (OR = 2.74, P < 0.001) and inferior OS (P = 0.019), a finding confirmed after PSM. Mediation analysis did not demonstrate a statistically significant mediating effect of irAEs on the relationship between IL-6 and survival. Bioinformatic validation linked high IL-6 expression to hyper-inflammatory signaling (TNF/IL-17 pathways) and immunosuppressive M2 macrophage infiltration.</p><p><strong>Conclusion: </strong>Baseline IL-6 was independently associated with both severe immune-related toxicity and inferior overall survival, suggesting that elevated systemic IL-6 reflects an adverse inflammatory state in which toxicity does not necessarily correspond to improved therapeutic outcomes. These findings support further evaluation of IL-6 in risk stratification and warrant prospective investigation into its potential therapeutic modulation in combination with ICIs.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"1053-1064"},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic management of resectable mismatch-repair deficient/microsatellite instability-high gastroesophageal adenocarcinoma: a real-world analysis from Austria.","authors":"Martin Korpan, Daniel Nothdurfter, Bernhard Doleschal, Lukas Weiss, Sophie Roider-Schur, Leopold Öhler, Ewald Wöll, Julia M Berger, Elisabeth S Bergen, Gerald W Prager, Behrang Mozayani, Anna S Berghoff, Matthias Preusser, Hannah C Puhr, Florian Huemer, Aysegül Ilhan-Mutlu","doi":"10.1007/s10120-026-01776-1","DOIUrl":"10.1007/s10120-026-01776-1","url":null,"abstract":"<p><strong>Background: </strong>Mismatch-repair deficient (dMMR)/microsatellite instability-high (MSI-H) gastroesophageal adenocarcinoma (GEA) is associated with favorable prognosis but limited benefit from perioperative chemotherapy. Although immune checkpoint inhibition (ICI)-based approaches have shown promising activity in early-phase studies, the optimal therapeutic combinations and the feasibility of non-operative management (NOM) in resectable disease remain unclear.</p><p><strong>Methods: </strong>This exploratory, retrospective, multicenter, real-world study included 55 patients with resectable dMMR/MSI-H GEA, who were divided into subgroups, characterized and compared according to treatment strategy (chemotherapy, chemoimmunotherapy, immunotherapy and initial resection). Pathological and clinical complete response (pCR, cCR), progression-free (PFS) and overall survival (OS) were evaluated.</p><p><strong>Results: </strong>Patients received chemotherapy (n=10), chemoimmunotherapy (n=16), immunotherapy (n=13), or initial resection without subsequent systemic treatment (n=16). Forty five (82%) patients had surgical resection. The pCR rate was 22% (n=2/9) in the chemotherapy, 27% (n=4/15) in the chemoimmunotherapy, and 100% (n=5/5) in the immunotherapy (i.e., doublet ICI) subgroup, respectively. The overall cCR rate in NOM patients was 33% (n=3/9), with rates of 37.5% (n=3/8) in the immunotherapy subgroup and 0% (n=0/1) in the chemoimmunotherapy subgroup. Complete response rates (pCR/cCR) were significantly associated with PD-L1 CPS ≥10 (p=0.027).</p><p><strong>Conclusion: </strong>This real-world study is, to our knowledge, the first to evaluate a broad spectrum of therapeutic combinations in patients with resectable MSI-H/dMMR GEA, showing meaningful antitumor activity, particularly with doublet ICI. Given the challenges of conducting randomized prospective trials in this setting, such real world data may support clinicians in guiding therapeutic decision-making.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"949-959"},"PeriodicalIF":6.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}