ESMO Gastrointestinal Oncology最新文献

{"title":"Multidisciplinary discussion in upper GI tumours: management of a patient with a locally advanced Siewert II gastroesophageal junctional adenocarcinoma","authors":"A. Petrillo , T. Fleitas-Kanonnikoff , M. Nilsson , T. Leong , H.W.M. van Laarhoven","doi":"10.1016/j.esmogo.2025.100176","DOIUrl":"10.1016/j.esmogo.2025.100176","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100176"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917547","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":"Multidisciplinary discussion on upper GI tumours: management of a patient with a middle-third locally advanced squamous-cell carcinoma","authors":"A. Petrillo , T. Fleitas-Kanonnikoff , M. Nilsson , T. Leong , H.W.M. van Laarhoven","doi":"10.1016/j.esmogo.2025.100175","DOIUrl":"10.1016/j.esmogo.2025.100175","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100175"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917546","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":"Real-world clinical impact of first-line immune checkpoint inhibitor-based therapy in advanced esophageal squamous cell carcinoma","authors":"M. Tamba ,&nbsp;K. Chin ,&nbsp;H. Osumi ,&nbsp;M. Ogura ,&nbsp;S. Fukuoka ,&nbsp;S. Udagawa ,&nbsp;K. Shimozaki ,&nbsp;K. Yoshino ,&nbsp;T. Wakatsuki ,&nbsp;E. Shinozaki ,&nbsp;K. Yamaguchi ,&nbsp;A. Ooki","doi":"10.1016/j.esmogo.2025.100171","DOIUrl":"10.1016/j.esmogo.2025.100171","url":null,"abstract":"<div><h3>Background</h3><div>Chemotherapy (chemo) combined with an immune checkpoint inhibitor (ICI) or dual ICI therapy with nivolumab and ipilimumab (nivo + ipi) is the standard first-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC). In this study, we evaluated real-world clinical outcomes for first-line ICI-based therapy and explored its prognostic factors.</div></div><div><h3>Patients and methods</h3><div>This single-center retrospective study included patients with ESCC who received ICI-based therapy between January 2021 and July 2024.</div></div><div><h3>Results</h3><div>In total, 92 patients received either ICI + chemo (<em>n</em> = 60) or nivo + ipi (<em>n</em> = 32). The median progression-free survival and overall survival (OS) were 5.0 and 16.0 months for ICI + chemo and 3.5 and 16.9 months for nivo + ipi, respectively. Of the 70 patients with measurable lesions, early tumor shrinkage (ETS) was achieved in 37% for ICI + chemo and 33% for nivo + ipi. ETS was significantly associated with a lower performance status and neutrophil-to-lymphocyte ratios, but not with the treatment regimen or programmed death-ligand 1 (PD-L1) status. Patients who achieved ETS showed significant tumor reduction and a durable response. ETS was an independent predictor of favorable OS (hazard ratio 0.34, 95% confidence interval 0.11-0.88, <em>P</em> = 0.04), whereas neither the treatment regimen nor the PD-L1 status influenced OS. Immune-related adverse events of grade ≥3 occurred in 12% of patients.</div></div><div><h3>Conclusions</h3><div>First-line immunotherapy is effective and safe for the treatment of patients with ESCC. Rapid and deep tumor shrinkage may serve as an early predictive biomarker for longer survival.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100171"},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912631","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":"Total neoadjuvant therapy in early-onset versus average-onset locally advanced rectal cancer: patient characteristics and tolerance of therapy☆","authors":"M.L. Conces ,&nbsp;N. Tursun ,&nbsp;I. Ozgur ,&nbsp;S. Yilmaz ,&nbsp;D. Elamin ,&nbsp;S. Patil ,&nbsp;Y. Bouferraa ,&nbsp;E. Gorgun ,&nbsp;D. Liska ,&nbsp;E. Weinstein ,&nbsp;S.D. Kamath ,&nbsp;S.R. Steele ,&nbsp;A.A. Khorana ,&nbsp;B. Laderian ,&nbsp;T.T. Jayakrishnan ,&nbsp;K.G. Nair ,&nbsp;S.R. Amarnath ,&nbsp;E.H. Balagamwala ,&nbsp;B.N. Estfan ,&nbsp;H. Kessler ,&nbsp;S.S. Krishnamurthi","doi":"10.1016/j.esmogo.2025.100170","DOIUrl":"10.1016/j.esmogo.2025.100170","url":null,"abstract":"<div><h3>Background</h3><div>Patients with early-onset (EO, age &lt;50 years) compared with average onset (AO, age ≥50 years) colorectal cancer have significantly higher rates of gastrointestinal toxicity with fluoropyrimidine and oxaliplatin therapy in the metastatic and adjuvant settings. Limited data exist regarding tolerance of total neoadjuvant therapy (TNT) when treating younger patients with locally advanced rectal cancer (LARC) despite the rising incidence of EO rectal cancer.</div></div><div><h3>Materials and methods</h3><div>Data were abstracted from a retrospective database of patients with LARC treated with TNT from 1 January 2015 through 28 April 2021. Characteristics compared between EO and AO patients were demographic features, baseline characteristics of tumor, treatment delivery, antiemetic use, and toxicities.</div></div><div><h3>Results</h3><div>Of 115 patients (39 EO, 76 AO), female patients constituted 51% of EO patients and 34% of AO patients (<em>P</em> = 0.077). No differences were found in race, ethnicity, clinical stage, dose of radiation or chemotherapy received, and antiemetic premedications and prescriptions. EO patients (versus AO patients) had more nausea (59% versus 28%, <em>P</em> = 0.001), fatigue (72% versus 47%, <em>P</em> = 0.013), and proctitis (28% versus 13%, <em>P</em> = 0.048) during chemoradiation and more nausea (69% versus 42%, <em>P</em> = 0.006) and stomatitis (21% versus 3.9%, <em>P</em> = 0.007) during chemotherapy. After adjusting for sex, EO patients were still at a greater odds of nausea compared with AO during chemoradiation (odds ratio 3.45, 95% confidence interval 1.51-7.69, <em>P</em> = 0.004) and chemotherapy (odds ratio 2.85, 95% confidence interval 1.28-6.67, <em>P</em> = 0.012).</div></div><div><h3>Conclusions</h3><div>Patients with EO, compared with AO, LARC receiving TNT appear to have higher rates of nausea and should be considered for enhanced antiemetic regimens.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100170"},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881728","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":"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":"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}