ESMO Gastrointestinal Oncology最新文献

{"title":"Temporal dynamics of CLDN18.2 expression following zolbetuximab treatment in advanced gastric cancer","authors":"K. Yamamoto ,&nbsp;I. Nakayama ,&nbsp;N. Sakamoto ,&nbsp;Y. Matsubara ,&nbsp;Y. Miyashita ,&nbsp;A. Kobayashi ,&nbsp;U. Okazaki ,&nbsp;D. Okemoto ,&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;T. Yoshino ,&nbsp;T. Kuwata ,&nbsp;K. Shitara","doi":"10.1016/j.esmogo.2025.100206","DOIUrl":"10.1016/j.esmogo.2025.100206","url":null,"abstract":"<div><h3>Background</h3><div>Zolbetuximab plus chemotherapy is the standard of care for unresectable advanced gastric cancer that is human epidermal growth factor receptor 2-negative and claudin-18 isoform 2 (CLDN18.2)-positive (2+/3+ staining intensity in ≥75% of tumor cells). The dynamics of CLDN18.2 expression after zolbetuximab remain poorly understood.</div></div><div><h3>Materials and methods</h3><div>Using immunohistochemistry, we retrospectively assessed CLDN18.2 expression in tumor samples from CLDN18.2-positive advanced gastric cancer collected before and after zolbetuximab-containing chemotherapy. Expression levels were evaluated based on the proportion of cells with ≥2+ staining intensity using multiple cut-off values (75%, 40%, and 25%).</div></div><div><h3>Results</h3><div>Among 65 patients who received zolbetuximab-containing therapy, CLDN18.2 status was assessable at both baseline and disease progression in 15 patients. At disease progression, 53.3% of cases converted to CLDN18.2-negative. CLDN18.2 positivity was retained in 66.7% and 73.3% of patients when applying 40% and 25% cut-off levels, respectively.</div></div><div><h3>Conclusions</h3><div>CLDN18.2 expression above the ≥75% cut-off declined after zolbetuximab, but lower-level expression was often preserved, supporting the potential for subsequent targeted therapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653305","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":"Dietary and lifestyle inflammation scores in relation to colon cancer recurrence in subgroups of patients based on common molecular tumour characteristics","authors":"E. Wesselink ,&nbsp;D.E. Kok ,&nbsp;K.C. Smit ,&nbsp;A.-S. van Lanen ,&nbsp;J.W.G. Derksen ,&nbsp;M. Koopman ,&nbsp;M. Ligtenberg ,&nbsp;I.D. Nagtegaal ,&nbsp;P.D.M. Rombout ,&nbsp;J.H.W. de Wilt ,&nbsp;E. Kampman ,&nbsp;A.M. May ,&nbsp;F.J.B. van Duijnhoven","doi":"10.1016/j.esmogo.2025.100202","DOIUrl":"10.1016/j.esmogo.2025.100202","url":null,"abstract":"<div><h3>Background</h3><div>The aim of this study was to investigate associations between the inflammatory potential of diet and lifestyle in relation to colon cancer recurrence in subgroups of patients based on molecular tumour characteristics that also influence the inflammatory tumour microenvironment.</div></div><div><h3>Patients and methods</h3><div>A nested case-control study was implemented in two prospective cohort studies of colon cancer patients. Participants who developed a recurrence were included as cases (<em>n</em> = 167). Matched controls (<em>n</em> = 668) were selected based on incidence density sampling. Lifestyle factors were assessed at diagnosis using self-administered questionnaires and dietary intake was assessed using a food frequency questionnaire. The dietary inflammation score (DIS) and the lifestyle inflammation score (LIS) were constructed. High-throughput next-generation sequencing of tumour tissue was used for mutation and microsatellite instability (MSI) analysis. Associations between the DIS and LIS and recurrence were assessed with conditional logistic regression analyses in all patients, as well as in subgroups based on MSI. For patients with microsatellite stable (MSS) tumours, further stratification based on mutation status of <em>KRAS, BRAF, PIK3CA, TP53</em> and <em>APC</em> was performed.</div></div><div><h3>Results</h3><div>A more pro-inflammatory diet was not associated with risk of recurrence [incidence rate ratio (IRR) 1.04, 95% confidence interval (CI) 0.96-1.12]. Persons who have a more pro-inflammatory lifestyle may have an increased recurrence risk (IRR 1.21, 95% CI 0.97-1.52), which was most pronounced for persons with MSS and <em>KRAS</em> or <em>PIK3CA</em> wildtype tumours (IRR 1.31, 95% CI 0.90-1.90 and IRR 1.30, 95% CI 0.98-1.71, respectively).</div></div><div><h3>Conclusion</h3><div>Our results suggest that associations between the LIS and recurrence might differ based on molecular tumour characteristics.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100202"},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653304","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":"Analysis of fruquintinib in patients with metastatic colorectal cancer who were enrolled in Spain: results from the global FRESCO-2 study","authors":"R. Garcia-Carbonero ,&nbsp;E. Elez ,&nbsp;P. García-Alfonso ,&nbsp;A. Cubillo Gracían ,&nbsp;R. López López ,&nbsp;P. Jimenez-Fonseca ,&nbsp;M.L. Limón Mirón ,&nbsp;A. Dasari ,&nbsp;S. Lonardi ,&nbsp;H. Zhu ,&nbsp;L. Chen ,&nbsp;Z. Yang ,&nbsp;W.R. Schelman ,&nbsp;J. Tabernero","doi":"10.1016/j.esmogo.2025.100205","DOIUrl":"10.1016/j.esmogo.2025.100205","url":null,"abstract":"<div><h3>Background</h3><div>In the phase III FRESCO-2 study, overall survival (OS) was significantly improved with fruquintinib plus best supportive care (BSC) versus placebo plus BSC in patients with refractory metastatic colorectal cancer (mCRC). Here, we present data from a FRESCO-2 subanalysis of patients enrolled in Spain.</div></div><div><h3>Patients and methods</h3><div>In FRESCO-2, patients had received all standard chemotherapies, anti-vascular endothelial growth factor and anti-epidermal growth factor receptor therapies, if indicated, and had progressed on or were intolerant to trifluridine/tipiracil (TAS-102) and/or regorafenib. Patients were randomized 2 : 1 to receive fruquintinib 5 mg orally or matching placebo once daily for 21 days in 28-day cycles, plus BSC. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), safety, and health-related quality of life.</div></div><div><h3>Results</h3><div>Of the 180 patients enrolled across 16 sites in Spain (26% of the global study population), 116 received fruquintinib and 64 received placebo. Baseline characteristics were balanced between arms. Patients treated with fruquintinib versus placebo had a median OS of 7.6 versus 4.6 months [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.44-0.91] and a median PFS of 3.7 versus 1.8 months (HR 0.24, 95% CI 0.17-0.36). Grade ≥3 treatment-emergent adverse events were reported in 60% versus 47% of patients treated with fruquintinib versus placebo. Median time to deterioration to an Eastern Cooperative Oncology Group performance status of two or more or death was 5.1 versus 2.9 months (HR 0.59, 95% CI 0.42-0.84) with fruquintinib versus placebo.</div></div><div><h3>Conclusions</h3><div>Results were consistent with the global FRESCO-2 study population, therefore supporting fruquintinib as a new treatment option for patients with refractory mCRC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100205"},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632383","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":"Tumor microbiome differences in early-onset versus average-onset pancreatic adenocarcinoma☆","authors":"T. Jayakrishnan ,&nbsp;N. Sangwan ,&nbsp;K.G. Nair ,&nbsp;S.D. Kamath ,&nbsp;M.H. Patel ,&nbsp;D. Joyce ,&nbsp;M. Walsh ,&nbsp;R. Simon ,&nbsp;D. Vadehra ,&nbsp;R.V. Iyer ,&nbsp;C. Fountzilas ,&nbsp;A.A. Khorana","doi":"10.1016/j.esmogo.2025.100194","DOIUrl":"10.1016/j.esmogo.2025.100194","url":null,"abstract":"<div><h3>Background</h3><div>Compelling evidence supports the biomarker potential of microbiome in pancreatic adenocarcinoma. Given the knowledge gap on the characteristics and significance of microbiome in early-onset pancreatic ductal adenocarcinoma (eoPDAC, age &lt;50 years), we aimed to evaluate microbiome profiles in resected specimens from individuals with eoPDAC and average-onset PDAC (aoPDAC, age &gt;50 years).</div></div><div><h3>Materials and methods</h3><div>We carried out shotgun metagenomic sequencing in resected specimens from individuals with eoPDAC (<em>n</em> = 24) and aoPDAC (<em>n</em> = 20). Statistical tests included Wilcoxon test, permutational analysis of variance, multiomic classifier modeling, differential abundance analysis, and linear regression. All <em>P</em> values were adjusted for multiple testing and <em>P</em> &lt; 0.05 was considered statistically significant.</div></div><div><h3>Results</h3><div>We successfully sequenced several bacteria and fungi in the tumor specimens from 44 individuals with resected PDAC (24 eoPDAC and 20 aoPDAC). The alpha diversity of the bacterial microbiome was higher in eoPDAC tumor tissue compared with aoPDAC (<em>P</em> = 0.04). In contrast, the fungal mycobiome’s alpha diversity was higher for aoPDAC tumor tissue (<em>P</em> = 0.02). Key organisms with differential abundance between tumor tissue from individuals with eoPDAC and aoPDAC included <em>Bacillus</em>, <em>Candida</em>, <em>Collimonas</em>, <em>Cupriavidus</em>, <em>Enterobacter</em>, <em>Escherichia</em>, <em>Klebsiella</em>, <em>Malasseiza</em>, <em>Mucilaginibacter</em>, <em>Neisseria</em>, and <em>Sphingomonas</em>. Higher bacterial diversity in tumor tissue was associated with better overall survival for individuals with eoPDAC (R = 0.26, <em>P</em> = 0.02).</div></div><div><h3>Conclusions</h3><div>Shotgun metagenomic sequencing identified bacterial microbiome and fungal mycobiome in tumors from individuals with eoPDAC and aoPDAC. We observed significant differences in alpha and beta diversity and relative abundances of organisms suggesting distinct microbiome signatures. Microbiome associations with survival were observed in eoPDAC indicating unique potential as prognostic biomarker.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100194"},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570721","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":"Systemic adjuvant and perioperative chemotherapy following curative-intent liver metastasectomy in colorectal cancer—is it justified?","authors":"R.D. Peixoto ,&nbsp;J.M. Loree ,&nbsp;T.A. Miranda ,&nbsp;J.P. Solar Vasconcelos ,&nbsp;D.J. Renouf ,&nbsp;J.M. Davies ,&nbsp;K. Gill ,&nbsp;S. Gill ,&nbsp;V. Poon ,&nbsp;C. Metcalf ,&nbsp;M. Chahal ,&nbsp;M.S. Bleszynski ,&nbsp;M. Segedi ,&nbsp;P.T.W. Kim ,&nbsp;H.J. Lim","doi":"10.1016/j.esmogo.2025.100190","DOIUrl":"10.1016/j.esmogo.2025.100190","url":null,"abstract":"<div><div>Colorectal liver metastases (CRLM) pose a significant challenge in oncological care, with surgical resection offering the best chance for long-term survival. Despite curative-intent liver metastasectomy, recurrence rates remain high, underscoring the need for effective adjuvant therapies. While adjuvant chemotherapy (AC) improves disease-free survival (DFS), evidence supporting its overall survival (OS) benefit is limited. This manuscript critically evaluates the role of AC following CRLM resection, with a focus on patient-specific factors influencing treatment outcomes across distinct clinical scenarios. The lack of stratification by molecular biomarkers in prior trials highlights a critical gap in current evidence. Future research should integrate biomarker-driven approaches, leverage circulating tumor DNA (ctDNA) for treatment stratification, and explore novel therapies, including immunotherapies and targeted agents, in both perioperative and adjuvant settings.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100190"},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514246","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":"Novel blood signature for HCC screening","authors":"K.-M. Chueng ,&nbsp;K.-N. Kwok ,&nbsp;S.J.-L. Lam ,&nbsp;H.-S. Lam ,&nbsp;S.-M. Yip ,&nbsp;S. Lam ,&nbsp;O.-P. Chiu ,&nbsp;A.K.-Y. Chan ,&nbsp;H.H.-W. Liu ,&nbsp;S.K.-K. Ng ,&nbsp;L. Sutanto ,&nbsp;J.C.K. Yung ,&nbsp;H.-L. Leung ,&nbsp;P.Y.-M. Woo ,&nbsp;H.H.-Y. Yiu ,&nbsp;D.C.C. Lam","doi":"10.1016/j.esmogo.2025.100185","DOIUrl":"10.1016/j.esmogo.2025.100185","url":null,"abstract":"<div><h3>Background</h3><div>Alpha-fetoprotein is commonly used for hepatocellular carcinoma (HCC) screening in at-risk populations, but its effectiveness is limited. Routine blood tests offer insights into cancer-related conditions and improve detection in other cancers. This study explores the postulated changes in routine blood tests of HCC patients, allowing the development of routine blood-based artificial intelligence for early HCC detection.</div></div><div><h3>Patients and methods</h3><div>This population-based retrospective study analyzed patient records from 2000 to 2018 from the Hong Kong Hospital Authority Data Collaboration Laboratory. Patients with chronic liver disease (CLD), both with and without HCC, were identified using ICD codes, antiviral drug history, virology tests, and radiology reports. Those with decompensated CLD were excluded. Routine blood tests included complete blood count, liver function test, renal function test, and clotting profiles, with records collected within 1 month before HCC diagnosis. Statistical analyses included descriptive statistics and the Mann–Whitney <em>U</em> (MWU) test.</div></div><div><h3>Results</h3><div>The cohort comprised 223 862 patients, including 31 149 with HCC (13.9%). Statistical analysis revealed a distinct blood signature for HCC patients, characterized by significant liver function derangement (elevated alanine aminotransferase, alkaline phosphatase, bilirubin, aspartate aminotransferase; decreased albumin), signs of systemic inflammation (lower lymphocyte count, red cell distribution width), bleeding tendencies (prolonged prothrombin time, activated partial thromboplastin time; low platelet count), and indications of cachexia (lower albumin, creatinine, urea)—all statistically significant (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>This study presents a novel blood signature for HCC detection based on extensive clinical data. The unique spectral characteristics effectively differentiate HCC from CLD controls, supporting the potential for machine learning models in HCC detection.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100185"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306795","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":"Managing adverse events in patients with metastatic colorectal cancer receiving trifluridine/tipiracil in combination with bevacizumab","authors":"M. Fakih ,&nbsp;F. Ciardiello ,&nbsp;G.W. Prager ,&nbsp;E. Élez ,&nbsp;E. Calleja ,&nbsp;N. Caussé-Amellal ,&nbsp;J. Taieb ,&nbsp;E. Van Cutsem","doi":"10.1016/j.esmogo.2025.100191","DOIUrl":"10.1016/j.esmogo.2025.100191","url":null,"abstract":"<div><div>For patients with metastatic colorectal cancer (mCRC) that is refractory to standard chemotherapy, a recommended standard-of-care treatment in the third-line setting is trifluridine/tipiracil (FTD/TPI) alone or in combination with bevacizumab; other treatment options include fruquintinib or regorafenib. The safety profiles of FTD/TPI and bevacizumab as individual agents are well characterized. Common adverse events (AEs) associated with FTD/TPI include neutropenia, anemia, nausea, and diarrhea, and AEs frequently observed with bevacizumab include hypertension, proteinuria, hemorrhage, venous thromboembolism, and gastrointestinal perforation. Approval of the combination of FTD/TPI plus bevacizumab for the treatment of patients with refractory mCRC in the United States and Europe was based on results from the phase III SUNLIGHT trial. There is clinical value in developing a specific set of recommendations for the prevention or management of the key AEs associated with the combination regimen to inform clinical care and improve patient benefit. In this review, we summarize the safety profile of combination treatment with FTD/TPI plus bevacizumab in patients with refractory mCRC who were enrolled in the SUNLIGHT trial, with a focus on the key AEs of neutropenia, anemia, nausea or vomiting, diarrhea, fatigue, hypertension, and hemorrhage. In addition, we provide recommendations for the management or prevention of these key AEs in clinical practice, based on published literature and expert opinions on effective strategies.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100191"},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296997","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":"Genomic heterogeneity and clinical implications in gastrointestinal neuroendocrine carcinoma: MYC and KRAS as predictive biomarkers","authors":"T. Ozato ,&nbsp;Y. Kono ,&nbsp;H. Yamamoto ,&nbsp;A. Hirasawa ,&nbsp;D. Ennishi ,&nbsp;S. Tomida ,&nbsp;S. Toyooka ,&nbsp;M. Otsuka","doi":"10.1016/j.esmogo.2025.100193","DOIUrl":"10.1016/j.esmogo.2025.100193","url":null,"abstract":"<div><h3>Background</h3><div>Gastrointestinal neuroendocrine carcinoma (GI-NEC) is a highly lethal malignancy with significant clinical and molecular heterogeneities. Given its rarity, large-scale studies are lacking, and research on its genomic landscape remains limited. Consequently, to date, no reliable biomarkers for treatment selection and prognosis have been identified. To address this gap in knowledge, we investigated the clinical impact of genomic features on GI-NEC.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 261 patients with advanced or recurrent GI-NEC using a nationwide comprehensive genomic profiling database. We analyzed the correlation between platinum-based chemotherapy and the clinical outcomes in 152 patients, focusing on time to treatment failure and overall survival. We integrated the sequencing data with clinical information to identify potential biomarkers predictive of chemotherapy efficacy and survival.</div></div><div><h3>Results</h3><div>In the GI-NECs analyzed, <em>TP53</em> (85.8%) and <em>RB1</em> (38.7%) were the most frequently mutated genes. Genetic alterations varied according to the primary tumor site, exhibiting co-occurring and mutually exclusive mutations. Notably, <em>RB1</em> deficiency and <em>CCNE1</em> amplification were mutually exclusive, particularly in esophageal and gastric NEC. <em>MYC</em> amplification was associated with a shorter time to treatment failure (<em>P</em> = 0.050), while <em>KRAS</em> alterations were significantly associated with a shorter overall survival (<em>P</em> = 0.001) in recurrent or unresectable GI-NECs.</div></div><div><h3>Conclusion</h3><div>This study underscored the clinical and genomic heterogeneity of GI-NEC and highlighted the need to integrate genomic and clinical data to achieve personalized medicine. <em>MYC</em> amplification and <em>KRAS</em> alterations may serve as valuable predictors of treatment response and prognosis in patients with GI-NEC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144261871","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":"WJOG18524G: a single-arm phase II study evaluating bemarituzumab combined with ramucirumab and paclitaxel in fibroblast growth factor receptor 2b (FGFR2b)-positive advanced gastric or gastroesophageal junction cancer (RAINBIRD)","authors":"K. Shimozaki ,&nbsp;K. Hirata ,&nbsp;H. Hayashi ,&nbsp;Y. Sato ,&nbsp;Y. Komatsu ,&nbsp;S. Taniguchi ,&nbsp;N. Takahashi ,&nbsp;K. Yamaguchi ,&nbsp;M. Furuta ,&nbsp;T. Kawakami ,&nbsp;Y. Narita ,&nbsp;T. Ando ,&nbsp;A. Makiyama ,&nbsp;S. Mitani ,&nbsp;T. Ogata ,&nbsp;N. Takegawa ,&nbsp;W. Okamoto ,&nbsp;T. Nishina ,&nbsp;M. Komoda ,&nbsp;A. Hosokawa ,&nbsp;K. Muro","doi":"10.1016/j.esmogo.2025.100189","DOIUrl":"10.1016/j.esmogo.2025.100189","url":null,"abstract":"<div><h3>Background</h3><div>Fibroblast growth factor receptor 2b (FGFR2)-overexpressing advanced gastric cancer (AGC) is associated with poor prognosis and limited treatment options. Bemarituzumab, which selectively binds to FGFR2b, is being investigated in combination with chemotherapy as a first-line treatment. Dual inhibition of the vascular endothelial growth factor–vascular endothelial growth factor receptor and FGF–FGFR pathways may improve the survival of FGFR2b-positive AGC through synergistic inhibition of angiogenesis and the downstream signals for tumor proliferation.</div></div><div><h3>Design</h3><div>The WJOG18524G trial (RAINBIRD) is a single-arm, multicenter phase II trial to evaluate the safety and efficacy of bemarituzumab in combination with paclitaxel plus ramucirumab in patients with FGFR2b-positive AGC who are intolerant or refractory to first-line fluoropyrimidine-based chemotherapy. The main inclusion criteria are unresectable or metastatic FGFR2b-positive gastric adenocarcinoma, refractoriness or intolerance to fluoropyrimidine-based chemotherapy, measurable lesions, and performance status of 0 or 1. The primary endpoint is the objective response rate, which is assessed by a blinded independent central review. Translational research is planned to explore the predictive biomarkers and mechanisms of resistance to bemarituzumab by sequencing tumor DNA (PleSSiSion-Neo) and circulating tumor DNA (Guardant360), which are collected at multiple time points.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100189"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241892","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":"Poor-prognosis young-onset colorectal cancer is defined by the mesenchymal subtype and can be predicted by integrating molecular and histopathological characteristics","authors":"J. Ke ,&nbsp;Y. Li ,&nbsp;L. Qi ,&nbsp;X. Li ,&nbsp;W. Wang ,&nbsp;S. Ten Hoorn ,&nbsp;Y. Zhu ,&nbsp;H. Huang ,&nbsp;F. Gao ,&nbsp;L. Vermeulen ,&nbsp;X. Wang","doi":"10.1016/j.esmogo.2025.100181","DOIUrl":"10.1016/j.esmogo.2025.100181","url":null,"abstract":"<div><h3>Background</h3><div>Young-onset colorectal cancer (CRC), affecting individuals &lt;50 years of age, presents a significant health threat worldwide. The molecular and clinical characteristics of young-onset CRC are poorly understood, complicating the development of effective biomarkers for precision oncology. This study aimed to dissect age-dependent molecular heterogeneity of CRC and establish a model for identifying high-risk young-onset patients.</div></div><div><h3>Methods</h3><div>We analyzed clinical data for 564 439 patient samples across three large cohorts. For molecular characterizations, a subset of 1874 patient samples was used. A deep learning framework was used to analyze hematoxylin–eosin-stained whole-slide images to quantify Shannon diversity indices (SDIs). Subsequently, a multivariate model, integrating SDI, microsatellite status and promoter methylation of miR-200s, was developed for predicting the consensus molecular subtype (CMS)4-mesenchymal subtype, followed by internal and external clinical validations.</div></div><div><h3>Results</h3><div>Young-onset CRC patients exhibited better overall survival but worse relapse-free survival and higher metastasis rates compared with late-onset cases. Molecular subtyping analysis found that young-onset CRC also comprises the same four subtypes (CMS1-4), but the prevalence differs from late-onset CRC. Stratified analysis suggested that the poor outcomes in young-onset CRC were due to higher prevalence of the CMS4-mesenchymal subtype. To predict CMS4, we established an effective risk-scoring model (area under the curve = 0.87) combining molecular and histological markers, with multiple independent validations.</div></div><div><h3>Conclusions</h3><div>CRC shows age-dependent molecular heterogeneity, with young-onset cases more frequently presenting the CMS4 subtype. To predict CMS4, we developed and validated a robust risk-scoring model integrating molecular and histological markers, offering a new translatable tool for more optimized management of young-onset patients.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241893","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}