ESMO Gastrointestinal Oncology最新文献

{"title":"Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial","authors":"S. De Dosso ,&nbsp;D. Christoforidis ,&nbsp;E. Merlo ,&nbsp;A. Vannelli ,&nbsp;S. Popeskou ,&nbsp;P. Gaffuri ,&nbsp;G. Lollo ,&nbsp;L. Ambrosiani ,&nbsp;F. Radaelli ,&nbsp;M. Frattini ,&nbsp;M. Marengo ,&nbsp;K. Galetti ,&nbsp;G. Iezzi","doi":"10.1016/j.esmogo.2025.100169","DOIUrl":"10.1016/j.esmogo.2025.100169","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) is one of the most prevalent tumour types and a leading cause of cancer-related mortality worldwide. Surgery represents the primary therapeutic option, while advanced cases are typically managed with established chemotherapy protocols, which exhibit variable response rates. Recently, the gut microbiota has been implicated in chemoresistance. Notably, <em>Fusobacterium nucleatum</em>, a commensal bacterium found in the oral cavity, is enriched in CRC tissues and has been shown in experimental models to promote CRC cell proliferation and diminish tumour responsiveness to 5-fluorouracil. Though the administration of metronidazole has effectively reduced <em>F. nucleatum</em> load and overall tumour growth in animal models, its efficacy in decreasing <em>F. nucleatum</em> loads in human CRC has yet to be verified.</div></div><div><h3>Aim</h3><div>This proof-of-concept trial aims to determine the effectiveness of metronidazole in reducing the <em>F. nucleatum</em> load in tissues and its potential detrimental effects on tumour cells and the tumour microenvironment.</div></div><div><h3>Trial design</h3><div>Forty patients newly diagnosed with CRC, for whom surgical resection is planned, will receive metronidazole for 10 days before surgery, which must be scheduled within 3 days following the last administration. Patients who do not receive the treatment for at least 7 days will be deemed ineligible for the study and will be replaced. <em>Fusobacterium nucleatum</em> abundance will be assessed through specific quantitative PCR analysis on genomic DNA extracted from diagnostic biopsies and excised tissues, with comparative analysis.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100169"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825954","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":"European screening platform for EORTC clinical trials in advanced colorectal cancer ‘SPECTAcolor’","authors":"G. Folprecht ,&nbsp;M. Morfouace ,&nbsp;M. Collienne ,&nbsp;R. Salazar ,&nbsp;A. Stein ,&nbsp;E. Elez ,&nbsp;A.D. Wagner ,&nbsp;D. Arnold ,&nbsp;C.H. Kohne ,&nbsp;M. Ducreux ,&nbsp;F. Lordick ,&nbsp;B. Borelli ,&nbsp;A. Stevovic ,&nbsp;T. Gorlia ,&nbsp;E. Fontana ,&nbsp;D. Aust ,&nbsp;V. Golfinopoulos ,&nbsp;M. Moehler ,&nbsp;S. Tejpar","doi":"10.1016/j.esmogo.2025.100168","DOIUrl":"10.1016/j.esmogo.2025.100168","url":null,"abstract":"<div><h3>Background</h3><div>The European Organisation for Research and Treatment of Cancer (EORTC) has established the Screening Platform for Efficient Clinical Trial Access for COLORectal Patients (SPECTAcolor), which provides centralized molecular testing to screen patients for and facilitate enrollment in molecular-based therapeutic trials.</div></div><div><h3>Materials and methods</h3><div>Patients with advanced or metastatic colorectal malignancies were recruited in 11 European countries. Patients’ paraffin-embedded material was tested for <em>KRAS</em><em>, NRAS, BRAF</em>, and <em>PI3K</em> microsatellite instability-high (MSI-H) (not routine at the time of recruitment) and later by a 300-gene next-generation sequencing panel. RNA profiling was carried out in a subset of patients. Results were reported to the centers and patients were followed up for their clinical outcome.</div></div><div><h3>Results</h3><div>Recruitment began in September 2013. The molecular screening program was completed at the end of 2015. A total of &gt;1000 patients were prospectively recruited into SPECTAcolor. Molecular and complete clinical/follow-up data are available for 845 metastatic colorectal cancer (CRC) patients. The simple κ coefficient for the agreement between local and central testing for <em>KRAS</em>, <em>NRAS</em>, and <em>BRAF</em> was 0.82-0.95, and the κ for MSI-H was 0.55. The median overall survival was 56.6 months. Patients with <em>BRCA</em>, <em>FGFR</em>, and <em>HER2</em> alterations had a trend toward shorter survival.</div></div><div><h3>Conclusion</h3><div>SPECTAcolor demonstrated that recruitment to an academic screening platform is feasible and that central (quality-assured) testing may remain necessary even for commonly tested markers. SPECTAcolor has generated a clinical and molecular dataset with associated samples for &gt;800 CRC patients for future academic research such as biomarker validation. Linking screening platforms to therapeutic trials and ensuring sustainability remain challenging.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100168"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma","authors":"J.W. Valle ,&nbsp;G.K. Abou-Alfa ,&nbsp;R.K. Kelley ,&nbsp;M.A. Lowery ,&nbsp;R.T. Shroff ,&nbsp;Y. Bian ,&nbsp;G. Saint-Hilary ,&nbsp;H. Liu ,&nbsp;Z. Teng ,&nbsp;Z. Hua ,&nbsp;C. Gliser ,&nbsp;A. Vogel ,&nbsp;M.M. Javle","doi":"10.1016/j.esmogo.2025.100159","DOIUrl":"10.1016/j.esmogo.2025.100159","url":null,"abstract":"<div><h3>Background</h3><div>Quantitative drug benefit–risk assessment (BRA) helps assess the magnitude of benefit and risk of new cancer therapies. This BRA aimed to summarize the evidence for the benefits and risks of ivosidenib versus placebo for the treatment of previously treated, locally advanced or metastatic mutant isocitrate dehydrogenase-1 cholangiocarcinoma using data from the pivotal phase III ClarIDHy study.</div></div><div><h3>Materials and methods</h3><div>Cholangiocarcinoma experts determined relevant key benefit and risk criteria for ivosidenib and placebo to create a value tree and determined scales and weights. Multi-Criteria Decision Analysis modelling approaches were then applied to the ClarIDHy data to estimate the probability that the benefit–risk profile of ivosidenib was better than that of placebo.</div></div><div><h3>Results</h3><div>A total of 187 patients were randomly assigned to ivosidenib 500 mg (<em>n</em> = 126) or placebo (<em>n</em> = 61). The primary analysis [Scale Loss Score (SLoS) model] showed a 95.24% probability for the benefit–risk profile favoring ivosidenib versus placebo. Sensitivity analyses applying the SLoS model to alternative sets, and the linear and product models to the main and alternative sets, of benefit and risk criteria in the value tree also showed consistently high probability for the benefit–risk profile favoring ivosidenib versus placebo for all endpoints evaluated (SLoS model: &gt;95%; linear model: &gt;99%; product model: &gt;94%). Similarly, the random weights analysis favored ivosidenib with all evaluated weights and results converging quickly towards the main analysis results.</div></div><div><h3>Conclusions</h3><div>These results provide comprehensive evidence that ivosidenib is an effective treatment with a tolerable safety profile for this aggressive disease, supporting previous data (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> NCT02989857).</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus statement on the use of systemic therapies in pancreatic ductal adenocarcinoma in Asia","authors":"D.-Y. Oh ,&nbsp;B. Shen ,&nbsp;S. Satoi ,&nbsp;J. Zhou ,&nbsp;K.-P. Kim ,&nbsp;S.P. Choo ,&nbsp;S.M. Woo ,&nbsp;S.L. Chan ,&nbsp;L. Shen ,&nbsp;M. Ikeda","doi":"10.1016/j.esmogo.2025.100158","DOIUrl":"10.1016/j.esmogo.2025.100158","url":null,"abstract":"<div><div>Systemic therapies, primarily cytotoxic chemotherapies, are the mainstay treatment option for pancreatic ductal adenocarcinoma (PDAC) alongside surgery. Several guidelines exist for managing PDAC within Asia, but recommendations for systemic therapies can differ significantly. Consequently, geographical areas across Asia not covered by international or regional guidelines often have disparate care for PDAC patients. To address this, we utilised the Delphi method to establish a collective opinion on the optimal use of systemic therapies for PDAC patients in Asia. Fourteen comprehensive consensus recommendations are reported. For resectable/localised and borderline resectable disease, recommendations were developed on specific chemotherapeutic regimens for adjuvant and neoadjuvant settings and best practice monitoring. Recommendations on downstaging/conversion therapy and therapy options were developed for locally advanced disease. In metastatic disease, recommendations for first- and second-line therapy options were developed, covering overall treatment strategy and best supportive care. In addition, consensus recommendations for molecular and genomic testing in PDAC were developed. To our knowledge, we report the first consensus statement on the optimal use of systemic therapies in PDAC for a broad, cross-border Asian population. These expert recommendations may serve as a starting point to improve the standardisation of treatment practices and care for PDAC patients within Asia.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100158"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for second primary tumors in the aerodigestive tract in non-Asian populations with head and neck cancer – systematic review and meta-analysis","authors":"A.D.I. Maan ,&nbsp;S.E.M. van de Ven ,&nbsp;S. Keereweer ,&nbsp;R. Cornelissen ,&nbsp;P.D. Siersema ,&nbsp;A.D. Koch","doi":"10.1016/j.esmogo.2025.100167","DOIUrl":"10.1016/j.esmogo.2025.100167","url":null,"abstract":"<div><h3>Background</h3><div>Patients diagnosed with a primary tumor in the esophagus, lungs, or head and neck are at an increased risk for developing second primary tumors (SPTs) in these regions. Most studies on SPT prevalence focus on Asian populations, with limited data available for non-Asian groups, leaving the utility of screening unclear. This review aims to assess the yield of screening for SPTs in non-Asian populations following a primary tumor in these regions.</div></div><div><h3>Patients and methods</h3><div>A systematic literature search was conducted to identify studies on screening for esophageal, lung, or head and neck SPTs after a primary tumor diagnosis in any of these sites. The primary outcome was the prevalence by screening of all diagnosed SPTs in the esophagus, head and neck or lungs.</div></div><div><h3>Results</h3><div>Due to limited data on screening for SPTs after esophageal or lung tumors, this review focused solely on screening after primary head and neck tumors. A total of 26 studies with 8071 patients from non-Asian countries were included. The pooled prevalence for all SPTs was 5.4% [95% confidence interval (CI) 4.1% to 7.2%]. The pooled prevalence for esophageal SPTs individually was 5.3% (95% CI 3.7% to 7.7%), for head and neck SPTs 4.6% (95% CI 1.0% to 18.1%) and for lung SPTs 4.0% (95% CI 2.6% to 6.2%). Most SPTs were detected in combination with an index hypopharynx carcinoma (60.0%). The proportion of synchronous (45.3%) and metachronous (54.7%) SPTs was similar.</div></div><div><h3>Conclusion</h3><div>Endoscopic screening for esophageal SPTs in non-Asian countries should be considered, especially in patients with a primary hypopharynx carcinoma.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100167"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-cell invigoration to cell-free DNA ratio associated with anti-PD-1 response in gastric or gastro-esophageal junction adenocarcinoma: VOYAGER trial","authors":"A. Makiyama ,&nbsp;Q. Hu ,&nbsp;T. Nagasaka ,&nbsp;H. Katsuya ,&nbsp;A. Nishioka ,&nbsp;I. Yasufuku ,&nbsp;T. Kashiwada ,&nbsp;Y. Shinohara ,&nbsp;S. Otsu ,&nbsp;M. Shimokawa ,&nbsp;H. Saeki ,&nbsp;H. Baba ,&nbsp;E. Oki","doi":"10.1016/j.esmogo.2025.100148","DOIUrl":"10.1016/j.esmogo.2025.100148","url":null,"abstract":"<div><h3>Background</h3><div>Previous melanoma research suggests that host immune status and tumor burden impact anti-programmed cell death protein 1 (PD-1) therapy efficacy, favoring patients with low tumor burden and minimal T-cell exhaustion.</div></div><div><h3>Patients and methods</h3><div>We conducted a phase II, multicenter, single-arm (VOYAGER) trial to assess early induction of nivolumab monotherapy as third-line or later treatment in patients with gastric adenocarcinoma showing response or stable disease as per RECIST v1.1 during prior chemotherapy. Biomarker analyses evaluated associations between nivolumab efficacy, T-cell activation, and cell-free DNA (cfDNA) as a tumor burden surrogate. Activated T cells (Ki67+ PD-1+ CD8+ T cells) were measured by flow cytometry of peripheral blood mononuclear cells.</div></div><div><h3>Results</h3><div>The study met its primary endpoint with a progression-free survival (PFS) rate at 6 months of 35.7% [80% confidence interval (CI) 26.4% to 45.1%]; median PFS and overall survival (OS) were 4.0 (95% CI 2.3-5.7) months and 10.9 (95% CI 9.9-16.0) months, respectively. No new safety signals were observed. Biomarker analyses revealed that baseline T-cell invigoration rate was associated with both response rate (RR) and prognosis. Baseline cfDNA also exhibited an association with prognosis, but not with RR. Moreover, the ratio of baseline T-cell invigoration to baseline cfDNA was strongly associated with RR (<em>P</em> &lt; 0.05) and prognosis (<em>P</em> &lt; 0.05) in third-line treatment of nivolumab.</div></div><div><h3>Conclusions</h3><div>This study not only demonstrated that early induction of nivolumab as a later-line regimen is an alternative strategy but also identified clinically available predictors for PD-1 blockade therapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100148"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility and impact of Lynch syndrome genetic testing in newly diagnosed colorectal cancer patients: a multicenter observational study in Greece","authors":"S. Manolakou ,&nbsp;N. Tsoukalas ,&nbsp;E. Saloustros ,&nbsp;T. Makatsoris ,&nbsp;I. Boukovinas ,&nbsp;A. Christopoulou ,&nbsp;A. Karampeazis ,&nbsp;I. Bompolaki ,&nbsp;I.-I. Varthalitis ,&nbsp;E. Voulgaris ,&nbsp;K. Ballasis ,&nbsp;A. Boutis ,&nbsp;E. Galani ,&nbsp;C. Kalofonos ,&nbsp;A. Koumarianou ,&nbsp;C. Kourousis ,&nbsp;P. Papakotoulas ,&nbsp;C. Papandreou ,&nbsp;E.-I. Perdikouri ,&nbsp;A. Andreadou ,&nbsp;Z. Saridaki","doi":"10.1016/j.esmogo.2025.100153","DOIUrl":"10.1016/j.esmogo.2025.100153","url":null,"abstract":"<div><h3>Background</h3><div>Lynch syndrome (LS) is an autosomal dominant disorder associated with a heightened risk of specific cancers, caused by germline mutations in the mismatch repair (MMR) system, which leads to microsatellite instability (MSI). MSI-positive colorectal cancer (CRC) patients have an increased likelihood of LS. Despite this, LS germline genetic testing is not reimbursed by the National Health Authorities in Greece. To address this gap, the Hellenic Society of Medical Oncology (HeSMO) initiated a national program to screen and diagnose CRC patients with LS.</div></div><div><h3>Materials and methods</h3><div>From 2017 to 2019, 151 newly diagnosed CRC patients in Greece were enrolled. MSI molecular analysis was carried out, followed by next-generation sequencing (NGS) germline testing in MSI patients without sporadic alterations to identify LS.</div></div><div><h3>Results</h3><div>Of the patients, 76 (51.7%) exhibited MMR deficiency, with their tumors more likely to have mucinous histology (<em>P</em> &lt; 0.001) and stage II disease (<em>P</em> = 0.015). Fourteen patients with MSH2, MSH6, or PMS2 deficiency directly underwent germline analysis, and all were positive for LS. Sixteen MSI patients (20.5%) had sporadic BRAFV600E mutations, and another 16 had MLH1 promoter hypermethylation. Of the remaining 32 patients tested for germline mutations, 8 were positive for LS, accounting for 15% of CRC patients—a 2.9-fold greater proportion than expected, according to historic records. Testing asymptomatic relatives identified two first-degree relatives with MSH2 mutations.</div></div><div><h3>Conclusions</h3><div>These findings underscore the critical need for CRC-adapted preventive oncology and support the implementation of a national LS screening program in Greece, aligned with international guidelines.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100153"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the potential of antibody–drug conjugates in gastrointestinal malignancies: beyond HER2 targets","authors":"P. Ntellas ,&nbsp;A. Athauda ,&nbsp;K. Sugiyama ,&nbsp;M.L. Le ,&nbsp;V. Crespi ,&nbsp;I. Chau","doi":"10.1016/j.esmogo.2025.100154","DOIUrl":"10.1016/j.esmogo.2025.100154","url":null,"abstract":"<div><div>Antibody–drug conjugates (ADCs) are an emerging class of targeted cancer therapeutics, combining the specificity of monoclonal antibodies with the potency of cytotoxic agents to deliver localized treatment while minimizing off-target effects. Recent advancements in ADC design focus on optimizing payloads, improving linker stability, and selecting effective target antigens. Additionally, innovative approaches such as small-molecule drug conjugates, immune-stimulating payloads, and bispecific or biparatopic antibodies are being explored to enhance specificity and efficacy. Despite challenges like neutralizing antibodies, toxicity, and variable efficacy, several ADCs have shown promise in patients with solid tumours. Particularly, in gastrointestinal cancers, ADCs targeting antigens such as claudin 18.2, c-MET, and CEACAM5 have demonstrated clinical activity offering potential alternatives to traditional human epidermal growth factor receptor 2 (HER2)-based therapies. Ongoing efforts to refine ADCs and explore novel formats offer significant potential to transform the treatment landscape of gastrointestinal cancers. This review examines the current state of ADC development for gastrointestinal malignancies, focusing on emerging targets and strategies beyond HER2.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100154"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GATA6 immunohistochemistry and prognosis after surgical resection of pancreatic adenocarcinoma: results from the ESPAC-4 trial","authors":"R.C. Grant ,&nbsp;K. Duan ,&nbsp;R. Jackson ,&nbsp;W. Greenhalf ,&nbsp;E. Costello-Goldring ,&nbsp;P. Ghaneh ,&nbsp;C. Halloran ,&nbsp;D. Palmer ,&nbsp;T. Hackert ,&nbsp;M. Büchler ,&nbsp;S. Hutchinson ,&nbsp;S. Ramotar ,&nbsp;A. Dodd ,&nbsp;J. Wilson ,&nbsp;F. Notta ,&nbsp;G. O’Kane ,&nbsp;J. Knox ,&nbsp;J. Neoptolemos ,&nbsp;S. Gallinger ,&nbsp;S.E. Fischer","doi":"10.1016/j.esmogo.2025.100138","DOIUrl":"10.1016/j.esmogo.2025.100138","url":null,"abstract":"<div><h3>Background</h3><div>No prognostic biomarker is currently used in clinical management of patients with surgically resected pancreatic cancer other than CA-19-9. In this study, we tested the prognostic value of GATA6 measured with immunohistochemistry and digital assistance.</div></div><div><h3>Patients and methods</h3><div>One hundred and ninety-three patients with resected pancreatic ductal adenocarcinoma from the ESPAC-4 trial of adjuvant gemcitabine and capecitabine were included. Two pathologists independently assessed GATA6 protein expression by immunohistochemistry in tissue microarray cores, manually and with digital assistance. Overall survival was compared across GATA6 levels using multivariate Cox proportional hazard regressions, with exploratory analyses evaluating recurrence-free survival and differential treatment effects.</div></div><div><h3>Results</h3><div>Interobserver concordance improved with digitally assisted scoring (kappa 0.72 versus 0.25, <em>P</em> &lt; 0.001). Median overall survival was 24.3 months [95% confidence interval (CI) 19.2-32.1 months] with low GATA6 expression versus 35.2 months (95% CI 29.9-53.0 months) with high GATA6 expression (adjusted hazard ratio 1.60, 95% CI 1.08-2.38, <em>P =</em> 0.02). Similar results were observed for recurrence-free survival (adjusted hazard ratio 1.45, 95% CI 0.99-2.14, <em>P =</em> 0.06). GATA6 expression was not associated with differential treatment effects.</div></div><div><h3>Conclusions</h3><div>GATA6 expression measured by immunohistochemistry with digital assistance was a prognostic biomarker among people with pancreatic adenocarcinoma treated with surgical resection and adjuvant chemotherapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrahepatic cholangiocarcinoma trends and treatment lines: real-world evidence from the French National Hospital Discharge database","authors":"M. Delaye ,&nbsp;B. Grenier ,&nbsp;A. Lièvre ,&nbsp;C. Neuzillet","doi":"10.1016/j.esmogo.2025.100152","DOIUrl":"10.1016/j.esmogo.2025.100152","url":null,"abstract":"<div><h3>Background</h3><div>Little is known about the therapeutic trajectory of patients treated in hospitals for intrahepatic cholangiocarcinoma (iCCA) and patterns of care in daily clinical practice.</div></div><div><h3>Patients and methods</h3><div>An observational retrospective study was conducted on the French National Hospital Discharge Database. All patients with a new diagnosis of iCCA who had a first hospital stay (S1) from January 2016 to December 2021 were included. They were followed up until December 2021, or in-hospital death, whichever occurred first. Crude annual hospitalization rates were computed. Treatment lines were identified with an artificial intelligence algorithm [Analysis of Treatment Lines using Alignment of Sequences (ATLAS)]. A multistate model was used to compute the transition rates between lines.</div></div><div><h3>Results</h3><div>Overall, 13 491 patients were included and the mean (standard deviation) follow-up duration was 13.1 months (17.9 months). The median age at S1 was 72.0 years and 55.9% were male. Nearly 20.7% were admitted via emergency services for S1, and 32.1% had metastases. Between 2016 and 2021, the crude annual rate of new iCCA cases increased from 3.08 [95% confidence interval (CI) 2.94-3.24] in 2016 (<em>n</em> = 1598) to 4.12 (95% CI 3.95-4.29) per 100 000 adult person-years in 2021 (<em>n</em> = 2188). Among 4855 patients receiving first-line systemic therapy (L1), 37.7% (95% CI 36.0% to 39.3%) received a second-line 2 (L2) during the follow-up. The median time between the start of L1 and the beginning of L2 was 7.0 months.</div></div><div><h3>Conclusions</h3><div>This study provides up-to-date national real-world data on iCCA, revealing an increasing burden year by year in France, a poor outcome of patients with iCCA on L1 systemic therapy, and the low proportion of patients receiving an L2.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}