ESMO Gastrointestinal Oncology最新文献

{"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}

{"title":"Fibre, microbes and radiotherapy: unravelling the gut’s impact on radiotherapy in cancer","authors":"L. Twhigg ,&nbsp;H.M. Ng ,&nbsp;T. Glyn ,&nbsp;C. Wall ,&nbsp;R. Purcell","doi":"10.1016/j.esmogo.2025.100174","DOIUrl":"10.1016/j.esmogo.2025.100174","url":null,"abstract":"<div><div>The gut microbiome plays an integral role in many physiological functions, including immunity, metabolism, maintenance of membrane integrity and protection against pathogenic bacteria. Conversely, adverse changes in the gut microbiome—termed dysbiosis—have been linked to many diseases, including cancer. Dysbiosis can result from a range of endogenous and exogenous factors. Diet is one of the most important modulators of the gut microbiome; the indirect benefits of modulating the microbiome through diet interventions are beginning to be used in many disease settings. Beneficial microbes (commensals) can modulate the local and systemic immune environment through the production of metabolites, such as short-chain fatty acids (SCFAs). Commensal bacteria ferment dietary fibre to produce SCFAs, and increasing dietary fibre intake has been shown to both increase SCFA production in the colon and affect immune responses. Recent studies have shown that dietary fibre can increase tumour responses to immunotherapy and chemotherapy, but data on the effect of increased fibre and changes in the microbiome on radiotherapy are limited. In this article, we review the current evidence regarding dietary fibre interventions and modulation of the gut microbiome in improving outcomes in patients receiving pelvic radiotherapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100174"},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221506","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":"Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment","authors":"F. Rossari ,&nbsp;D. Lavacchi ,&nbsp;E. Alimenti ,&nbsp;C. Soldà ,&nbsp;F. Salani ,&nbsp;L. Esposito ,&nbsp;S. Foti ,&nbsp;S. Camera ,&nbsp;M. Persano ,&nbsp;F. Lo Prinzi ,&nbsp;F. Vitiello ,&nbsp;E. Pellegrini ,&nbsp;M. Bruccoleri ,&nbsp;M.D. Rizzato ,&nbsp;M. Caccese ,&nbsp;I.G. Rapposelli ,&nbsp;A. Guidolin ,&nbsp;A. De Rosa ,&nbsp;L. Antonuzzo ,&nbsp;G. Masi ,&nbsp;A. Casadei-Gardini","doi":"10.1016/j.esmogo.2025.100186","DOIUrl":"10.1016/j.esmogo.2025.100186","url":null,"abstract":"<div><h3>Background</h3><div>Atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) every 3 weeks (AtezBev) became a standard-of-care first-line treatment for advanced hepatocellular carcinoma (aHCC) following IMbrave150. However, real-world data suggest milder efficacy. Early bevacizumab interruption due to adverse events (AEs) is a frequent occurrence in real-world scenario associated with poor prognosis. Additionally, early bevacizumab dose/time modifications (eBEVmod) may negatively impact outcome.</div></div><div><h3>Materials and methods</h3><div>Data from AtezBev-treated aHCC patients (<em>n</em> = 100) in five Italian institutions were retrospectively analyzed. Cumulative bevacizumab dose (mg/kg) received in the first 3 months of treatment was analyzed by receiver operating characteristic (ROC) to identify a cut-off value to estimate survival and dichotomize the variable. Baseline clinical and laboratory characteristics were analyzed with uni-/multivariate models to explore potential differences on overall survival (OS), objective response rate (ORR) and disease control rate (DCR) based on eBEVmod. Progression-free survival (PFS) was a secondary endpoint.</div></div><div><h3>Results</h3><div>In the overall population, the median (m) follow-up was 11.4 months, mOS was 20.5 months, mPFS was 10.4 months, ORR was 31% and DCR was 75%. ROC on 3-month cumulative bevacizumab dose revealed an area under the curve of 0.74 (<em>P</em> = 0.001) and eBEVmod cut-off of &lt;45 mg/kg/3 months (i.e. 10.5 mg/kg/3 weeks) having 73% sensitivity and specificity in predicting death. Twenty-three percent of patients had eBEVmod (of which 39.1% had treatment delay, 39.1% discontinuation and 21.7% dose reduction), with no differences in baseline characteristics nor second-line treatments compared with non-eBEVmod, except for sex. eBEVmod patients had inferior ORR/DCR (14%/48% versus 36%/82%) and increased risk of death [hazard ratio (HR) 4.2, <em>P</em> = 0.0049], with a 12-month survival probability of 53.3% versus 77.4%. eBEVmod was an independent negative prognostic factor of survival at multivariate analysis (HR 3.3, <em>P</em> = 0.0125). Patients with eBEVmod also had a trend in worse PFS, although not statistically significant (mPFS 3.8 versus 12.6 months, HR 1.8, <em>P</em> = 0.0774).</div></div><div><h3>Conclusions</h3><div>eBEVmod is an independent unfavorable prognostic factor of response and survival in AtezBev-treated aHCC patients. Optimization of bevacizumab AE management to reduce eBEVmod may substantially improve treatment outcome in real-world practice.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100186"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189475","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":"Prognostic factors and treatment response in HER2-positive gastric cancer patients receiving trastuzumab deruxtecan: secondary analysis of the EN-DEAVOR study","authors":"K. Nakanishi ,&nbsp;N. Sugimoto ,&nbsp;Y. Kodera ,&nbsp;H. Kawakami ,&nbsp;A. Makiyama ,&nbsp;H. Konishi ,&nbsp;S. Morita ,&nbsp;Y. Narita ,&nbsp;K. Minashi ,&nbsp;M. Imano ,&nbsp;R. Inamoto ,&nbsp;T. Nishina ,&nbsp;T. Kawakami ,&nbsp;M. Hagiwara ,&nbsp;H. Kume ,&nbsp;K. Yamaguchi ,&nbsp;W. Hashimoto ,&nbsp;K. Muro","doi":"10.1016/j.esmogo.2025.100184","DOIUrl":"10.1016/j.esmogo.2025.100184","url":null,"abstract":"<div><h3>Background</h3><div>EN-DEAVOR was a multi-institutional retrospective study evaluating the effectiveness and safety of trastuzumab deruxtecan (T-DXd) in gastric cancer patients. This secondary analysis investigated prognostic factors for real-world progression-free survival (rwPFS) and objective response rate (ORR) for T-DXd as third- or later-line treatment.</div></div><div><h3>Patients and methods</h3><div>Patients aged ≥20 years with histopathologically confirmed human epidermal growth factor receptor 2 (HER2)-positive unresectable advanced or recurrent gastric or gastroesophageal junction adenocarcinoma, who had worsened after chemotherapy, were included. Patients received T-DXd as third- or later-line therapy between September 2020 and September 2021. Univariate and multivariate analyses identified prognostic factors for rwPFS and ORR.</div></div><div><h3>Results</h3><div>Of the 307 patients, 75.6% were male and 69.1% were aged ≥65 years. The median duration of prior trastuzumab treatment was 6.5 months (range 0-81.5 months). Multivariate analysis showed HER2 immunohistochemistry (IHC) 3+ [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86], intestinal type lesions (HR 0.59, 95% CI 0.43-0.79), modified Glasgow Prognostic Score (mGPS) 0 and 1 (HR 0.71, 95% CI 0.53-0.95), and longer duration of prior trastuzumab treatment (≥ median) (HR 0.75, 95% CI 0.58-0.97) as positive prognostic factors for rwPFS. Longer prior trastuzumab treatment was also a positive prognostic factor for ORR (odds ratio 2.02, 95% CI 1.13-3.63).</div></div><div><h3>Conclusions</h3><div>Patients with clinical benefits from prolonged trastuzumab treatment are likely to benefit from T-DXd. Similarly, HER2 IHC 3+, intestinal type lesions, and better mGPS (0 or 1) are associated with longer rwPFS. However, T-DXd should not be withheld even in patients without these factors, as a median PFS of 3.42 months was observed in those with the shortest prior trastuzumab exposure.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100184"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147175","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":"Controversies in upper GI oncology: role of radiotherapy in non-metastatic gastroesophageal adenocarcinoma","authors":"A. Petrillo ,&nbsp;M. Verheij ,&nbsp;T. Leong","doi":"10.1016/j.esmogo.2025.100188","DOIUrl":"10.1016/j.esmogo.2025.100188","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100188"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147178","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":"Germline genomic profiling of patients with early-onset colorectal cancer","authors":"G. Mauri ,&nbsp;M. Puzzono ,&nbsp;A. Mannucci ,&nbsp;F. Gaudioso ,&nbsp;H. Mittal ,&nbsp;L. Mosca ,&nbsp;V. Burgio ,&nbsp;S. Ghezzi ,&nbsp;M. Ronzoni ,&nbsp;S. Mariano ,&nbsp;R. Rosati ,&nbsp;L. Monti ,&nbsp;U. Cavallari ,&nbsp;A. Sartore-Bianchi ,&nbsp;S. Siena ,&nbsp;G.M. Cavestro","doi":"10.1016/j.esmogo.2025.100182","DOIUrl":"10.1016/j.esmogo.2025.100182","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of early-onset colorectal cancer (EO-CRC) is rising. While most cases of EO-CRC are sporadic, the prevalence of hereditary cancer predisposition syndromes remains a subject of debate. Moreover, genes not traditionally associated with EO-CRC development are rarely included in germline testing panels.</div></div><div><h3>Patients and methods</h3><div>Germline profiling data of patients with EO-CRC presenting to our clinics were collected at two Italian university institutions: IRCCS San Raffaele Scientific Institute and Grande Ospedale Metropolitano Niguarda. Multigene germline profiling analysis was carried out using next-generation sequencing and multiplex ligation probe amplification. Associations between germline alterations and clinicopathological variables were analyzed.</div></div><div><h3>Results</h3><div>A total of 130 patients with EO-CRC were screened. The median age at EO-CRC diagnosis was 42 years (range 22-49 years). Germline pathogenic or likely pathogenic variants (PVs/LPVs) associated with hereditary cancer predisposition syndromes were identified in 23 (18%) patients, while germline variants of unknown significance were found in 47 (36%) patients. No alterations in high-penetrance genes associated with cancer susceptibility were observed in 67 (52%) patients. No patients with microsatellite stable <em>BRAF</em>-mutant (<em>n</em> = 5) or signet ring cell CRC (<em>n</em> = 2) exhibited germline PVs/LPVs. No clinicopathological features were significantly enriched in hereditary compared with sporadic EO-CRC. Germline PVs in <em>FLCN</em> and <em>SDHAF2</em> were identified in two patients with EO-CRC.</div></div><div><h3>Conclusions</h3><div>While most EO-CRC cases are sporadic, approximately one-fifth arises within the context of hereditary cancer predisposition syndromes. As <em>FLCN</em> and <em>SDH</em> are not currently included in the current guidelines for EO-CRC, PVs/LPVs in these genes may be underestimated. To better understand their significance, we recommend including their assessment in all patients with EO-CRC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147177","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}