ESMO Gastrointestinal Oncology最新文献

{"title":"Revisiting cholesterol metabolism in hepatocellular carcinoma: a hidden driver of systemic therapy response","authors":"L.M. Stoffels ,&nbsp;E.S. Espinoza Rodriguez ,&nbsp;J. Theys ,&nbsp;R. Shiri-Sverdlov","doi":"10.1016/j.esmogo.2025.100284","DOIUrl":"10.1016/j.esmogo.2025.100284","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related mortality worldwide and poses a substantial challenge in the field of oncology. The majority of patients are diagnosed at advanced stages of the disease, where systemic therapies remain the primary treatment modality. These interventions, however, are frequently constrained by limited efficacy and considerable adverse effects, highlighting the pressing need for more precise and effective therapeutic strategies. Emerging evidence has identified cholesterol as a critical factor in HCC pathogenesis, influencing key processes such as tumor initiation, cellular proliferation, immune dysregulation, and metastatic progression. Moreover, disruptions in cholesterol metabolism have been increasingly implicated in resistance to systemic treatments. This review provides a concise overview of therapeutic approaches targeting cholesterol in HCC and examines the influence of cholesterol metabolism on the efficacy of systemic therapies, particularly those currently considered standard of care. Finally, we discuss existing challenges and propose future directions for integrating cholesterol-lowering strategies to enhance treatment outcomes in patients with HCC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100284"},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-system outcomes after adopting yttrium-90 radioembolization with personalized dosimetry as the primary treatment approach for unresectable, solitary hepatocellular carcinoma","authors":"A. Zamani ,&nbsp;K. Núñez ,&nbsp;T. Sandow ,&nbsp;J. Gimenez ,&nbsp;A. Cohen ,&nbsp;P. Thevenot","doi":"10.1016/j.esmogo.2026.100309","DOIUrl":"10.1016/j.esmogo.2026.100309","url":null,"abstract":"<div><h3>Background</h3><div>Yittrium-90 (⁹⁰Y) radioembolization has emerged as a secondary treatment option for early- to intermediate-stage hepatocellular carcinoma (HCC) in the Barcelona Clinic Liver Cancer (BCLC) Staging and Treatment Algorithm. Several trials have recently shown that ⁹⁰Y is a safe and effective primary treatment option for BCLC stages A and B. In this study, the outcomes for three treatment centers within a single health system with experience utilizing ⁹⁰Y as a definitive treatment option for early-stage HCC (BCLC-A) were analyzed in the context of results reported by the DOSISPHERE-01 and TARGET clinical trials.</div></div><div><h3>Materials and methods</h3><div>The cohort was derived from multiple treatment centers within a single health system that utilized ⁹⁰Y as the primary option for BCLC-A solitary, unresectable HCC &gt;3 cm and as a secondary option for HCC &lt;3 cm, both with an Eastern Cooperative Oncology Group score of 0-1 and Child–Pugh A5-B9 (<em>n</em> = 171, 2018-2024). The study outcomes included first-cycle objective response (OR) and complete response (CR) rates, target time to retreatment (tTTR), time to BCLC-C progression, progression-free survival (PFS), and overall survival (OS).</div></div><div><h3>Results</h3><div>Patients were enrolled between 2018 and 2024 (<em>n</em> = 171). OS rates at 1 and 3 years were 94% and 73%, with 1- and 3-year PFS rates of 89% and 61%, respectively. Response to first-cycle ⁹⁰Y could be assessed in 166 patients. The overall OR rate was 98% (163/166), with 71% (118/166) achieving a target CR. Patients who obtained a target CR had reduced progression rates at 1 year (2% versus 16%) and 3 years (21% versus 62%) compared with incomplete responders. The median tTTR in patients who achieved a target CR was 48 months, with 1- and 2-year retreatment rates of 9% and 24%, respectively.</div></div><div><h3>Conclusion</h3><div>First-cycle ⁹⁰Y radioembolization with personalized dosimetry is an effective treatment option for early-stage, solitary HCC that yields high, sustained response rates.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100309"},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advancements in radiotherapy for hepatocellular carcinoma","authors":"L.L. Chan ,&nbsp;K.S.H. Chok ,&nbsp;A.Y.H. Ip ,&nbsp;D.M.C. Poon ,&nbsp;S.L. Chan","doi":"10.1016/j.esmogo.2026.100308","DOIUrl":"10.1016/j.esmogo.2026.100308","url":null,"abstract":"<div><div>Radiotherapy has traditionally been uncommonly used for hepatocellular carcinoma (HCC) due to concerns of radiation-induced liver damage. However, advancements including stereotactic body radiotherapy have improved target localization and reduced toxicity, leading to its inclusion as a locoregional therapy in recent international guidelines. Newer technologies, such as MR-Linac and particle radiotherapy, have further improved the therapeutic ratio of radiotherapy, showing early promising results. The increasing application of radiotherapy in HCC has led to broadening of its indication to bridging to transplant and palliation. Beyond being a standalone treatment, radiotherapy is increasingly being combined with systemic therapies to enhance treatment response and survival rates. This combination is particularly relevant for patients with portal vein tumour thrombosis, as other locoregional therapies are often unsuitable for them. Furthermore, with the evolving concepts of oligometastatic and oligoprogressive HCC, radiotherapy is being explored as a promising approach to manage these conditions, especially as HCC patients experience longer survival with the introduction of immunotherapy. In this review, we provide an overview of these recent advancements in radiotherapy for HCC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100308"},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BevRam-GC01 study protocol: a phase I trial of bevacizumab plus ramucirumab and paclitaxel in advanced gastric cancer","authors":"T. Wakatsuki ,&nbsp;T. Mashima ,&nbsp;N. Miyazaki ,&nbsp;H. Osumi ,&nbsp;S. Fukuoka ,&nbsp;A. Ooki ,&nbsp;K. Shimozaki ,&nbsp;M. Ogura ,&nbsp;K. Yoshino ,&nbsp;S. Udagawa ,&nbsp;E. Shinozaki ,&nbsp;K. Chin ,&nbsp;N. Ishida ,&nbsp;H. Seimiya ,&nbsp;K. Yamaguchi","doi":"10.1016/j.esmogo.2025.100299","DOIUrl":"10.1016/j.esmogo.2025.100299","url":null,"abstract":"<div><h3>Background</h3><div>Plasma vascular endothelial growth factor-A (VEGF-A) concentrations markedly increased immediately after ramucirumab administration, and the high VEGF-A concentrations were significantly associated with worse outcomes in advanced gastric cancer. In a preclinical study, combination therapy with anti-VEGF-A and anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibodies showed superior tumor suppression compared with monotherapy, suggesting dual VEGF-A/VEGFR2 blockade may be a promising therapeutic strategy.</div></div><div><h3>Design</h3><div>The BevRam-GC01 trial is a phase I trial evaluating the tolerability and safety of bevacizumab biosimilar (5 or 10 mg/kg) plus ramucirumab (8 mg/kg) and paclitaxel (80 mg/m²) in patients with advanced gastric cancer refractory to first-line fluoropyrimidine–platinum chemotherapy. The study includes a safety part and an expansion part, in which, after confirming tolerability, patients will be randomized into three arms, including a control group, to obtain proof of concept and determine the optimal BEV-BS dose. Primary endpoints are dose-limiting toxicities in the safety part and adverse events in the expansion part. Key secondary endpoints include objective response rate and day 8 free VEGF-A suppression rate. Biomarker analysis will clarify the synergistic and complementary effects of anti-VEGFR2 and anti-VEGF-A antibodies on tumor biology, including angiogenesis, proliferation, and antitumor immunity, through multi-omics analysis and immune monitoring.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100299"},"PeriodicalIF":0.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative outcomes with low-dose and standard-dose immune checkpoint inhibitors in microsatellite stable advanced gastric/gastroesophageal adenocarcinoma☆","authors":"A. Ramaswamy ,&nbsp;V. Shenoy ,&nbsp;A. Bahl ,&nbsp;A. Rauthan ,&nbsp;V.M. Krishna ,&nbsp;V. Talwar ,&nbsp;V. Agarwala ,&nbsp;A. Kapoor ,&nbsp;R. Pinninti ,&nbsp;M. Sharma ,&nbsp;S.J. Rajappa ,&nbsp;N. Rohatgi ,&nbsp;A. Khan ,&nbsp;A. Jain ,&nbsp;U. Batra ,&nbsp;R.K. Kaushal ,&nbsp;M.V. Chandrakanth ,&nbsp;B. Sansar ,&nbsp;A. Gupta ,&nbsp;P. Bhargava ,&nbsp;V. Ostwal","doi":"10.1016/j.esmogo.2026.100302","DOIUrl":"10.1016/j.esmogo.2026.100302","url":null,"abstract":"<div><h3>Background</h3><div>The combination of chemotherapy and immune checkpoint inhibitors (ICIs) is usually considered standard in advanced gastric/gastroesophageal adenocarcinoma (GC) with combined positive score (CPS) 6≥5.</div></div><div><h3>Methods</h3><div>Data of patients with microsatellite stable advanced GCs receiving chemotherapy combined with ICIs between August 2021 and February 2024 were collated from eight institutions in India. The primary endpoint was to compare median overall survival between patients receiving standard-dose ICIs (SD-ICIs) and low-dose ICIs (LD-ICIs) as first-line treatment when CPS ≥5.</div></div><div><h3>Results</h3><div>Data of 288 patients were collated, of whom 256 patients had adequate data for analysis. A CPS ≥5 was seen in 161 patients (63%). Nivolumab was used in a majority of patients (75%). After propensity matching for age, 124 patients (62 patients receiving LD-ICIs and SD-ICIs, each) were available for analysis. With a median follow-up of 9.8 months [95% confidence interval (CI) 7.6-12.1 months], there was no difference in median overall survival between patients receiving LD-ICIs and SD-ICIs (16.8 months, 95% CI 7.59-25.97 months versus 16.1 months, 95% CI 10.3 months-not reached, <em>P</em> = 0.95). There was also no difference in median time to treatment failure between patients receiving LD-ICIs and SD-ICIs (6.83 months, 95% CI 4.65-9.01 months versus 7.78 months, 95% CI 6.04-9.56 months, <em>P</em> = 0.31).</div></div><div><h3>Conclusions</h3><div>LD-ICIs can be evaluated in combination with chemotherapy in patients with advanced GC and CPS ≥5 where standard dosing is not feasible, pending evidence from prospective trials.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100302"},"PeriodicalIF":0.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline and dynamic cytokines as biomarkers for immune checkpoint and anti-VEGF therapy in advanced hepatocellular carcinoma","authors":"H.C. Wilbur ,&nbsp;L.X. Zhao ,&nbsp;M. Nakazawa ,&nbsp;C. Kao ,&nbsp;J.D. Gordan ,&nbsp;T.P. Gade ,&nbsp;L. Cope ,&nbsp;L.T. Kagohara ,&nbsp;D. Zabransky ,&nbsp;W.J. Ho ,&nbsp;M. Baretti ,&nbsp;M. Yarchoan","doi":"10.1016/j.esmogo.2025.100273","DOIUrl":"10.1016/j.esmogo.2025.100273","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs), or the combination of ICIs and vascular endothelial growth factor (VEGF) inhibitors, are the preferred treatments for advanced hepatocellular carcinoma (HCC). However, the immunomodulatory effects of anti-VEGF therapy in HCC remain poorly understood. Predictive biomarkers are needed to guide therapy selection.</div></div><div><h3>Patients and methods</h3><div>We prospectively analyzed circulating cytokines in patients with advanced HCC receiving ICIs with or without anti-VEGF inhibitor therapy as standard of care. Serum samples were collected at baseline and ∼2 months after treatment initiation. A 32-cytokine Luminex panel was used to assess systemic immune changes. We examined associations between treatment group, cytokine dynamics, and clinical outcomes.</div></div><div><h3>Results</h3><div>Among 56 enrolled patients, 35 patients were treated with ICIs only (ICI-only), and 21 patients were treated with ICIs plus the VEGF inhibitor bevacizumab (ICI + Bev). Demographic characteristics and treatment outcomes were generally balanced between the two groups. As compared with ICI-only, patients receiving ICI + Bev exhibited significantly reduced fold changes in multiple cytokines on treatment, including sCD40L, macrophage inflammatory protein-1β (MIP-1β), monokine induced by interferon-γ (MIG), and interleukin (IL)-1Ra, of which above-median circulating baseline levels of MIP-1β were associated with inferior clinical outcomes. In addition, patients with above-median circulating levels of IL-6 and IL-12p40 at baseline had longer progression-free survival with ICI + Bev versus ICI-only. Treatment-associated reductions in IL-1Ra, IL-8, IL-18, and VEGF-A were associated with favorable clinical outcomes.</div></div><div><h3>Conclusions</h3><div>In a highly exploratory analysis, myeloid-inflammatory signatures at baseline and treatment-associated reductions in key myeloid cytokines may identify patients most likely to benefit from adding Bev to ICI. Prospective validation of these markers in independent cohorts is warranted.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100273"},"PeriodicalIF":0.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and translational results from the phase II ABACO trial evaluating the activity of cabozantinib in pretreated patients with metastatic colorectal cancer","authors":"V. De Falco ,&nbsp;P.P. Vitiello ,&nbsp;D. Ciardiello ,&nbsp;G. Grasso ,&nbsp;E. Mariella ,&nbsp;G. Martini ,&nbsp;S. Napolitano ,&nbsp;C. Cardone ,&nbsp;G. Arrichiello ,&nbsp;E. Varriale ,&nbsp;M. Di Bisceglie ,&nbsp;T. Latiano ,&nbsp;E. Maiello ,&nbsp;A. Reginelli ,&nbsp;M.C. Brunese ,&nbsp;S. Cappabianca ,&nbsp;S. Del Tufo ,&nbsp;A. Orlando ,&nbsp;A. Nicastro ,&nbsp;F. Caraglia ,&nbsp;E. Martinelli","doi":"10.1016/j.esmogo.2026.100303","DOIUrl":"10.1016/j.esmogo.2026.100303","url":null,"abstract":"<div><h3>Background</h3><div>Angiogenesis is a key mechanism in metastatic colorectal cancer (mCRC). Novel agents targeting this pathway, like cabozantinib, are of great therapeutic need.</div></div><div><h3>Patients and methods</h3><div>We conducted an open-label, single-arm phase II trial to assess the antitumor activity of cabozantinib in patients with pretreated mCRC who had progressed following at least two prior lines of therapy. The primary endpoint was the progression-free survival (PFS) rate at 16 weeks, whereas secondary endpoints included median PFS, overall survival (OS), response rate, disease control rate, and safety. DNA- and RNA-based translational analyses were carried out on biological samples.</div></div><div><h3>Results</h3><div>From October 2019 to January 2023, 33 patients were treated with oral cabozantinib, 60 mg daily. The primary endpoint was met: 11/33 assessable patients (33%) were progression-free at 16 weeks. Median PFS was 2.27 months [95% confidence interval (CI) 1.71-3.65 months], median OS was 6.25 months (95% CI 3.81-10.26 months). Disease control rate was 45.5%. Cabozantinib was generally fairly tolerated. Exploratory analyses investigating the effect of clinical disease features on PFS showed no significant correlation. Comprehensive genomic profiling on 30 patients (tissues and plasma) suggested that absence of <em>TP53</em> mutations and tumor mutational burden (TMB) ≥4 mutations/Mb positively correlated with response (PFS &gt;16 weeks). Additionally, for a subset of 18 (54.5%) patients, RNA sequencing from archival formalin-fixed paraffin-embedded samples was carried out. Molecular subtypes 4 (CMS4) was the most represented transcriptional subtype (10/18 cases). To verify if other transcriptional features were associated with treatment benefit, for each sample we computed gene set variation analysis. For epithelial-mesenchymal transition (EMT) and angiogenesis gene sets, we identified a trend toward higher scores in tumors from patients with longer PFS.</div></div><div><h3>Conclusion</h3><div>Within the limitations of a single-arm phase II trial, cabozantinib demonstrates both safety and antitumor activity in mCRC. The observed correlation between specific molecular features, such as EMT activation and angiogenesis, and cabozantinib activity is hypothesis-generating and warrants further investigation.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100303"},"PeriodicalIF":0.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment attrition between lines of therapy and its impact on outcomes for well-differentiated neuroendocrine tumors in British Columbia","authors":"R. Fedrigo ,&nbsp;T. do Amaral Miranda ,&nbsp;R. D’Alpino Peioxoto ,&nbsp;S. Gill ,&nbsp;F. Benard ,&nbsp;D. Wilson ,&nbsp;P. Martineau ,&nbsp;I. Alberts ,&nbsp;J.P. Solar Vasconcelos ,&nbsp;J.M. Loree","doi":"10.1016/j.esmogo.2026.100305","DOIUrl":"10.1016/j.esmogo.2026.100305","url":null,"abstract":"<div><h3>Background</h3><div>Neuroendocrine neoplasms are uncommon malignancies with variable prognosis. With a growing number of available therapies and recent data supporting earlier initiation of radioligand therapy, we aimed to characterize attrition between lines of therapy to inform treatment sequencing and establish baseline assumptions for future health technology assessments.</div></div><div><h3>Patients and methods</h3><div>In this retrospective chart review, patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs) who received one or more systemic therapies from January 2010 to December 2023 were reviewed. The primary endpoint was attrition between treatment lines. Logistic regression model was used to identify predictors of attrition.</div></div><div><h3>Results</h3><div>Among 234 patients, 65 (28%) had pancreatic NETs (pNETs) and 169 (72%) had extra-pancreatic gastrointestinal NETs (ep-GI-NETs); median age at diagnosis was 65 years. Maximum number of treatment lines was six for pNETs and four for ep-GI-NETs. First-to-second-line attrition rates were 22% [95% confidence interval (CI) 13% to 36%] and 34% (95% CI 25% to 44%) for pNETs and ep-GI-NETs, respectively. Somatostatin analogs were the preferred first line in 194 patients (83%). Peptide receptor radionuclide therapy was administered to 13 pNETs (20%) and 42 ep-GI-NETs (25%). Median first-line progression-free survival (PFS) was 8.8 months and 26.1 months for pNETs and ep-GI-NETs, respectively. Patients treated in the latter cohort (2021-2023) had a lower risk of attrition compared with those in the earlier cohort (2010-2020) (odds ratio 0.38, 95% CI 0.14-0.94, <em>P</em> = 0.046).</div></div><div><h3>Conclusions</h3><div>Despite longer first-line PFS, patients with ep-GI-NETs faced higher attrition rates. These findings emphasize the need to prioritize the most effective therapies early during treatment sequencing to ensure patients are exposed to the most active agents.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100305"},"PeriodicalIF":0.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of nutritional risk screening on outcomes of first-line treatment in metastatic esophagogastric adenocarcinoma: a secondary analysis of the AIO-MATEO trial","authors":"R. Stelmach ,&nbsp;S. Lorenzen ,&nbsp;T.J. Ettrich ,&nbsp;F.R. Longo ,&nbsp;B. Chibaudel ,&nbsp;R. Greil ,&nbsp;M. Perwög ,&nbsp;J. Larcher-Steiner ,&nbsp;D. Jäger ,&nbsp;F. Lordick ,&nbsp;G. Stocker ,&nbsp;G.M. Haag","doi":"10.1016/j.esmogo.2025.100297","DOIUrl":"10.1016/j.esmogo.2025.100297","url":null,"abstract":"<div><h3>Background</h3><div>Malnutrition is common in patients with metastatic esophagogastric adenocarcinoma (EGA). However, the prognostic impact of nutritional risk screening (NRS) in advanced EGA remains underexplored. This preplanned analysis of the phase II AIO-MATEO trial evaluated the impact of NRS on clinical outcomes for patients with advanced EGA.</div></div><div><h3>Patients and methods</h3><div>Patients enrolled in the MATEO trial (exploring S-1 maintenance therapy) with an available baseline NRS before induction chemotherapy were included. Patients were stratified by their baseline NRS score (&lt;3 versus ≥3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier and Cox regression methods.</div></div><div><h3>Results</h3><div>Of the 136 patients, 86 had an NRS score &lt;3 and 50 had an NRS score ≥3 at baseline. Baseline median European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) global health score was lower for the NRS ≥3 group (37.5 versus 58.3). Nutritional interventions were more frequent in the NRS ≥3 group (45.8% versus 10.6%; <em>P</em> &lt; 0.001). Patients with NRS ≥3 had inferior median PFS (4.9 months versus 6.9 months; <em>P</em> = 0.025) and OS (8.2 months versus 13.2 months; <em>P</em> = 0.003). Patients whose NRS score improved during induction chemotherapy showed superior median PFS (7.4 months versus 4.1 months; <em>P</em> = 0.085) and OS (20.1 months versus 8.0 months; <em>P</em> = 0.054) compared with those without improvement. No significant differences in overall toxicity were observed.</div></div><div><h3>Conclusions</h3><div>Baseline NRS is a significant predictor of outcome in patients with metastatic EGA. Our findings underscore the importance of routinely assessing the nutritional status of patients with metastatic EGA and intervening early.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100297"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of claudin 18.2 expression on the efficacy of trastuzumab deruxtecan in patients with HER2-positive gastric or gastroesophageal junction cancer","authors":"D. Okemoto ,&nbsp;I. Nakayama ,&nbsp;A. Jubashi ,&nbsp;N. Sakamoto ,&nbsp;M. Okunaka ,&nbsp;Y. Matsubara ,&nbsp;Y. Miyashita ,&nbsp;A. Kobayashi ,&nbsp;U. Okazaki ,&nbsp;K. Yamamoto ,&nbsp;K. Seguchi ,&nbsp;T. Hosokai ,&nbsp;T. Ogura ,&nbsp;S. Mishima ,&nbsp;D. Kotani ,&nbsp;A. Kawazoe ,&nbsp;T. Hashimoto ,&nbsp;Y. Kuboki ,&nbsp;H. Bando ,&nbsp;T. Kojima ,&nbsp;K. Shitara","doi":"10.1016/j.esmogo.2025.100300","DOIUrl":"10.1016/j.esmogo.2025.100300","url":null,"abstract":"<div><h3>Background</h3><div>Human epidermal growth factor receptor 2 (HER2) and claudin 18.2 (CLDN18.2) are key therapeutic targets in metastatic gastric and gastroesophageal junction cancer (mGC/GEJC). Trastuzumab deruxtecan (T-DXd) is standard care for previously treated HER2-positive mGC/GEJC, but the prognostic impact of CLDN18.2 remains unclear.</div></div><div><h3>Patients and methods</h3><div>We retrospectively reviewed patients with HER2-positive mGC/GEJC treated with T-DXd at National Cancer Center Hospital East until February 2025. T-DXd outcomes were compared between CLDN18.2-positive (≥2+ in ≥75% of tumor cells) and -negative patients in two cohorts: those with HER2 positivity before first-line therapy (overall cohort) and those maintaining HER2 positivity immediately before T-DXd (remaining HER2 cohort). CLDN18.2 expression was evaluated at any time before T-DXd administration.</div></div><div><h3>Results</h3><div>Eighty-seven patients were included in the overall cohort and 30 in the remaining HER2 cohort. In the overall cohort, progression-free survival (PFS) was shorter in CLDN18.2-positive patients [3.9 versus 5.3 months; hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.04-3.34, <em>P</em> = 0.036], with an adjusted HR of 1.82 (95% CI 1.02-3.28, <em>P</em> = 0.047). Overall survival (OS) showed a shorter trend (8.6 versus 11.2 months, HR 1.36, 95% CI 0.76-2.45, <em>P</em> = 0.30). In the remaining HER2 cohort, CLDN18.2-positive patients had shorter PFS (3.2 versus 8.0 months, HR 3.40, 95% CI 1.38-8.40, <em>P</em> = 0.008) and OS (7.1 versus 12.9 months, HR 2.44, 95% CI 1.04-5.74, <em>P</em> = 0.041).</div></div><div><h3>Conclusions</h3><div>CLDN18.2 positivity may attenuate the efficacy of T-DXd in HER2-positive mGC/GEJC, supporting the rationale for dual blockade of CLDN18.2 and HER2.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100300"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}