ESMO Gastrointestinal Oncology最新文献

{"title":"Exploring the associations between colorectal polyps and type 2 diabetes mellitus in a colonoscopy clinic population","authors":"J.S. Kimber ,&nbsp;E. Symonds ,&nbsp;W. Uylaki ,&nbsp;M. Horsnell ,&nbsp;P.A. Drew ,&nbsp;E. Smith ,&nbsp;R.R. Mikaeel ,&nbsp;J.E. Hardingham ,&nbsp;Y. Tomita ,&nbsp;D. Jesudason ,&nbsp;P.J. Hewett ,&nbsp;W.J. Brooks ,&nbsp;J.P. Young ,&nbsp;T.J. Price","doi":"10.1016/j.esmogo.2024.100053","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100053","url":null,"abstract":"<div><h3>Introduction</h3><p>An association has consistently been reported between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC). CRC develops within premalignant polyps. The aim of this work was to examine the relationship between colorectal polyp subtypes and T2DM across the population, including in low- and non-screening age groups.</p></div><div><h3>Material and methods</h3><p>A cross-sectional study was carried out using an audit of a colonoscopy database and histopathology reports at a tertiary teaching hospital during 2016. Included were consecutive patients undergoing colonoscopy for a diverse range of indications. Univariable and multivariable analyses were carried out to assess the associations between T2DM, age, sex, indications for the procedure and different types of colorectal polyps.</p></div><div><h3>Results</h3><p>Data were extracted from colonoscopies in 1395 patients. Evidence of T2DM was observed in 257 (18%) patients. Any adenoma was present in 109 (42%) patients with T2DM compared with 256 (22%) patients with no evidence of T2DM [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.9-3.4, <em>P</em> &lt; 0.001]. In patients &lt;50 years of age, occult bleeding was associated with any adenoma (OR 3.1, 95% CI 1.2-7.8, <em>P</em> = 0.03) and advanced adenoma (OR 21, 95% CI 1.8-240, <em>P</em> = 0.02). A multinomial logistic regression determined that male sex, T2DM, blood in the stool and older age were all independently associated with the presence of any adenoma.</p></div><div><h3>Conclusions</h3><p>Adenomas were independently associated with T2DM. Given the consistent association between CRC and T2DM, these data suggest that a diagnosis of T2DM may warrant closer colorectal surveillance.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000141/pdfft?md5=2a20218256fcb2cf4bfb33d91004cea8&pid=1-s2.0-S2949819824000141-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140552258","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":"SAGA—a phase Ib/II single-arm, multicenter study of sacituzumab govitecan for patients with metastatic esophagogastric adenocarcinoma","authors":"B. Kobitzsch ,&nbsp;G. Stocker ,&nbsp;U.T. Hacker ,&nbsp;S. Junge ,&nbsp;C. Pauligk ,&nbsp;S.-E. Al-Batran ,&nbsp;T.O. Goetze ,&nbsp;F. Lordick","doi":"10.1016/j.esmogo.2024.100051","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100051","url":null,"abstract":"<div><h3>Background</h3><p>Treatment of metastatic and locally advanced unresectable esophagogastric adenocarcinoma (EGA) after first-line therapy has limited efficacy. Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) linking a TROP-2-directed antibody to the topoisomerase-I inhibitor SN-38. EGA has a high TROP-2 positivity rate and is sensitive to topoisomerase inhibition. Thus far, limited data on the efficacy and safety of SG in this patient population are available.</p></div><div><h3>Aim</h3><p>To evaluate the safety and efficacy of SG in patients with metastatic EGA who progressed under previous treatment. Objective response rate (ORR) is the primary endpoint.</p></div><div><h3>Trial design</h3><p>SAGA is a single-arm, non-randomized, open-label multicenter phase Ib/II study. Patients after prior treatment with a fluoropyrimidine-platinum-containing chemotherapy with or without targeted therapy or immunotherapy will be treated with SG intravenously at a dose of 10 mg/kg body weight on days 1 and 8 of a 21-day treatment cycle. After a run-in phase of 20 patients, safety and efficacy will be evaluated and the trial will proceed to a recruitment goal of 56 patients when at least two tumor responses are documented in the run-in phase. A hypothesis of an ORR of 16% is tested against a null hypothesis of an ORR of 5%.</p></div><div><h3>Trial identifiers</h3><p>EU CT 2023-505257-40-00, NCT06123468, AIO-STO-0123/ass., IKF-t065</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000128/pdfft?md5=f81390f6ca11d95e982766109924f98a&pid=1-s2.0-S2949819824000128-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140549617","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":"Palliative and supportive care underutilization for patients with locally advanced pancreatic cancer: review of the NCDB☆","authors":"C.G. Cann ,&nbsp;C. Shen ,&nbsp;M. LaPelusa ,&nbsp;D. Cardin ,&nbsp;J. Berlin ,&nbsp;R. Agarwal ,&nbsp;C. Eng","doi":"10.1016/j.esmogo.2024.100049","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100049","url":null,"abstract":"<div><h3>Background</h3><p>Nearly one-third of patients with newly diagnosed pancreatic cancer present with locally advanced disease (LAPC), with 25% eligible for surgical resection, lending to a poor 5-year overall survival of 16.2%. Given the significant morbidity and mortality associated with LAPC, timely integration of palliative and supportive care (SC) into the treatment care plan is vital. The purpose of this study was to investigate the utilization of SC in patients with LAPC and identify the demographic and socioeconomic factors that influence its application.</p></div><div><h3>Patients and methods</h3><p>A retrospective database analysis of the National Cancer Database (NCDB) was carried out. Data regarding patients diagnosed with stage II-III LAPC between 2004 and 2018 were used. Analyses included tumor characteristics, demographics, socioeconomic parameters, and trends in utilization of SC.</p></div><div><h3>Results</h3><p>A total of 111 964 patients were included [stage II (72.3%); stage III (27.6%)]. Only 7.72% received SC despite 67% of patients receiving cancer-directed treatment at an academic or integrated network cancer program, 84% living in or near a metro area, and 60% living ≤20 miles of their primary treatment center. Rates of SC utilization remained &lt;8% and &lt;12% in stage II and III disease, respectively, throughout the two decades.</p></div><div><h3>Conclusions</h3><p>SC has been underutilized in the LAPC population over the past two decades, despite the increase in data supporting early integration of palliative care and the potential sociodemographic areas of unmet need. Future work should focus on evaluating practice patterns across cancer centers and the potential positive impact of early SC integration on both survival and quality-of-life outcomes for patients with LAPC.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000104/pdfft?md5=a14f6ed69e3577001eafae6699246017&pid=1-s2.0-S2949819824000104-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140180142","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":"Exploring the differences in the tumor microenvironment and immuno-oncologic targets in pancreatic ductal adenocarcinomas (PDAC) according to KRAS mutational status","authors":"E.B. Faber ,&nbsp;Y. Baca ,&nbsp;J. Xiu ,&nbsp;P. Walker ,&nbsp;G. Manji ,&nbsp;S. Gholami ,&nbsp;A. Saeed ,&nbsp;A. Prakash ,&nbsp;G.P. Botta ,&nbsp;D. Sohal ,&nbsp;H.J. Lenz ,&nbsp;A.F. Shields ,&nbsp;C. Nabhan ,&nbsp;W. El-Deiry ,&nbsp;A. Seeber ,&nbsp;V. Chiu ,&nbsp;J. Hwang ,&nbsp;E. Lou","doi":"10.1016/j.esmogo.2024.100042","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100042","url":null,"abstract":"<div><h3>Background</h3><p>The majority of pancreatic ductal adenocarcinomas (PDACs) are driven by mutant (mt) <em>KRAS</em>. How mt <em>KRAS</em> and co-driver mutations affect the immune cell (IC) landscape of PDAC remains uncertain. Herein, we characterize the types of IC in the PDAC tumor microenvironment (TME) and the prevalence of immuno-oncologic (IO) biomarkers by genomic and transcriptomic analysis in the context of <em>KRAS</em> status.</p></div><div><h3>Materials and methods</h3><p>4142 PDAC and 3727 colorectal cancer (CRC) cases with <em>KRAS</em> mt were analyzed using next-generation DNA sequencing, immunohistochemistry, and whole-transcriptome RNA sequencing. Microsatellite instability and deficiency in mismatch repair (MSI-H/dMMR) and tumor mutational burden (TMB) were also assessed.</p></div><div><h3>Results</h3><p>We found <em>KRAS</em> mt in 81% of PDAC, with the most common variant being <em>G12D</em> in PDAC, and fewer cases of <em>KRAS</em> mt were co-expressed with the predictive IO marker MSI-H/dMMR than <em>KRAS-</em>wild-type (wt). However, <em>KRAS</em>^{<em>G12D</em>}, <em>KRAS</em>^{<em>G12V</em>}, and <em>KRAS</em>^<em>Q61</em> mutations had significantly lower TMB than <em>KRAS</em> wt tumors in PDAC. The IC environment of <em>KRAS</em> mt PDAC showed significant differences in nearly all IC types; a similar pattern was observed in CRC but was less pronounced.</p></div><div><h3>Conclusions</h3><p>Therapeutic IO targets like programmed death-ligand 1 are enriched in pancreatic adenocarcinoma cases harboring specific targetable variants of <em>KRAS</em> mt PDAC. Better understanding of the TME could lead to tailored immunotherapeutic strategies to overcome these barriers in <em>KRAS</em> mt PDAC, possibly in combination with molecularly targeted treatment strategies.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"4 ","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000037/pdfft?md5=f0e1f32ee3f35620dbf89352bc9d864d&pid=1-s2.0-S2949819824000037-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137955","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":"Immunonutrition supplementation for resectable gastric cancer during standard neoadjuvant chemotherapy of FLOT. A proof-of-concept protocol: I-SUPPLY","authors":"V. Pusceddu ,&nbsp;C. Donisi ,&nbsp;A. Pretta ,&nbsp;F. Loi ,&nbsp;R. Badas ,&nbsp;P. Ziranu ,&nbsp;M. Puzzoni ,&nbsp;E. Lai ,&nbsp;S. Mariani ,&nbsp;E. Palmas ,&nbsp;M. Pozzari ,&nbsp;E. Cimbro ,&nbsp;A.P. D’Agata ,&nbsp;S. Pinto ,&nbsp;F. Coghe ,&nbsp;S. Bergamini ,&nbsp;D. Fanni ,&nbsp;G. Faa ,&nbsp;T. Yoshino ,&nbsp;M. Scartozzi","doi":"10.1016/j.esmogo.2023.100036","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.100036","url":null,"abstract":"<div><p>The ‘immune pattern’ of the esophagogastric junction and gastric cancer (GC) has been related to tumour progression and/or response to therapies. GC can be classified as immunogenic or immune-resistant based on the infiltration of the tumour microenvironment (TME) from different immune cells (ICs), the most significant of which are activated lymphocytes (a-Ly) CD8+ and CD4+. From the amount of a-Ly infiltration in TME, we can identify tumours with high Immunoscore (IS) which correlates with better prognosis in terms of disease-free survival and overall survival (OS). IC activation and consequent immunogenic TME requires high nutrient absorption and synthesis and accumulation of protein, lipid, and nucleotides. However, tumour cells (TCs) promote their own proliferation by stealing micronutrients to ICs, therefore leading to an immunosuppressive TME phenotype. This proof-of-concept protocol aims to assess whether a controlled enteral immune nutrition (EIN) supplementation can revert the TME in favour of ICs over TCs, in both auxotrophic and non-auxotrophic malignancies, witnessed by an increase in IS in surgical specimen over biopsy controls. Secondary endpoints are: (i) tumour regression grade assessment compared to historical data from FLOT4/AIO; (ii) combined proportion score ratio; (iii) relapse-free survival at 3 years and OS; and (iv) quality of life by the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ)-30.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819823000511/pdfft?md5=05db5c0c4240cb8caf9ef723b5d78681&pid=1-s2.0-S2949819823000511-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140122705","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":"Immune checkpoint expression and co-expression landscape in gastroesophageal adenocarcinoma","authors":"Y. Vedire ,&nbsp;S. Kalvapudi ,&nbsp;R.J. Seager ,&nbsp;R. Duve ,&nbsp;J. Conroy ,&nbsp;S. Pabla ,&nbsp;S. Mukherjee","doi":"10.1016/j.esmogo.2024.100045","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100045","url":null,"abstract":"<div><h3>Background</h3><p>Addition of immunotherapy to standard chemotherapy marginally improved outcomes in gastroesophageal adenocarcinoma (GEAC). Recently, dual immunotherapy has shown efficacy in melanoma and non-small-cell lung cancer over single checkpoint inhibition. We sought to decipher the expression landscape of commonly targeted immune checkpoints in GEAC with a particular attention to their co-expression with programmed death-ligand 1 (PD-L1).</p></div><div><h3>Materials and methods</h3><p>Targeted RNA sequencing was carried out on 65 metastatic GEAC tumors obtained from, and gene expression was measured for 394 immune transcripts. Co-expression analyses were conducted by calculating Pearson correlations for every possible pair of 15 checkpoint genes and clustering groups of similarly expressed genes. These analyses were validated using a 90-patient cohort identified from The Cancer Genome Atlas database.</p></div><div><h3>Results</h3><p>The clinical cohort was primarily male (86.2%), Caucasian (93.9%), and had positive PD-L1 status (63.1%). The correlation matrix delineated two clusters of co-expression with the first including PD-L1, programmed cell death protein 1 (<em>PD-1</em>), cytotoxic T-lymphocyte associated protein 4 (<em>CTLA-4</em>), lymphocyte-activation gene 3 (<em>LAG3</em>), and indoleamine 2,3-dioxygenase-1 (<em>IDO1</em>) and the second included programmed cell death 1 ligand 2 (<em>PD-L2</em>), T-cell immunoglobulin and mucin domain-containing protein 3 (<em>TIM3</em>), and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (<em>TIGIT</em>) genes. <em>LAG3</em> and <em>IDO1</em> genes showed strong co-expression with PD-L1 in both cohorts and PD-L1-positive and -negative subgroups. Interestingly, <em>CD8</em> showed strong co-expression with <em>CTLA-4</em>, <em>PD-1</em>, <em>LAG3</em>, and <em>TIGIT</em>.</p></div><div><h3>Conclusions</h3><p>We show that immune checkpoints are often co-expressed in GEAC, suggesting possible common underlying mechanisms for checkpoint expression. Strong correlation between checkpoints like <em>LAG3</em>, <em>TIM3</em>, and <em>IDO1</em> with <em>PD-1</em>/<em>PD-L1</em> axis in GEAC argues for developing dual checkpoint inhibition therapy in this patient population. Future preclinical and clinical studies are needed to evaluate the efficacy and safety of these potential immunotherapy combinations.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000062/pdfft?md5=0b211870fd4caac7b45c24c7698672cb&pid=1-s2.0-S2949819824000062-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140042193","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":"Advances in the management of hepatobiliary and pancreatic malignancies: highlights from the ESMO Annual Meeting 2023 by the EORTC GI Tract Cancer Group","authors":"C. Fulgenzi ,&nbsp;I. Garajová ,&nbsp;M. Moehler ,&nbsp;M.P. Lutz ,&nbsp;E. Smyth ,&nbsp;L. Rimassa ,&nbsp;C. Neuzillet ,&nbsp;A. Lamarca","doi":"10.1016/j.esmogo.2023.100039","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.100039","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100039"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819823000547/pdfft?md5=3eeecdcaaec3ebf5ebf44929fe4681bc&pid=1-s2.0-S2949819823000547-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140187659","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":"Integration of genomic aberrations to predict clinical outcomes for patients with gastroesophageal adenocarcinoma receiving neoadjuvant chemotherapy","authors":"E.C. Smyth ,&nbsp;D. Watson ,&nbsp;M.P. Castro ,&nbsp;B. Nutzinger ,&nbsp;S. Kapoor ,&nbsp;S. Rajagopalan ,&nbsp;C. Cheah ,&nbsp;P.R. Nair ,&nbsp;A. Alam ,&nbsp;G. Devonshire ,&nbsp;N. Grehan ,&nbsp;R.P. Suseela ,&nbsp;A. Tyagi ,&nbsp;A.K. Agrawal ,&nbsp;M. Sauban ,&nbsp;A. Pampana ,&nbsp;A. Ghosh ,&nbsp;Y. Ullal ,&nbsp;Y. Narvekar ,&nbsp;M.D. Macpherson ,&nbsp;R.C. Fitzgerald","doi":"10.1016/j.esmogo.2023.08.009","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.08.009","url":null,"abstract":"<div><h3>Background</h3><p>Esophageal cancer [esophagogastric adenocarcinoma (OGA)] shows heterogeneity at the molecular level, leading to lower efficacy rates and highlighting the need for personalized treatment strategies. We have developed a computational model that uses both mechanistic and statistical approaches to integrate a patient’s genomic aberrations, revealing signaling pathway dysregulation and variable drug response. The model output, Therapy Response Index (TRI), has been used to predict therapeutic outcomes in this study.</p></div><div><h3>Design</h3><p>TRI’s ability to predict patient outcomes was retrospectively evaluated in a prospectively collected cohort of patients with operable OGA from the UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium receiving neoadjuvant chemotherapy. Stratified random sampling was used to split the data into training and validation subsets. Multivariate Cox proportional hazard and proportional odds models were used to predict survival and pathological response as a function of TRI and clinical thresholds compared with clinical factors.</p></div><div><h3>Results</h3><p>A total of 270 patients with OGA were selected who had 50× whole genome sequencing carried out on tissue derived from either biopsy or resection. Patients were treated with chemotherapy drugs or regimens according to UK clinical guidelines. The association of TRI with overall survival (OS) was significant above and beyond standard clinical factors (<em>P</em> = 0.0012). A significant association was also observed with disease-free survival (DFS; <em>P</em> = 0.0288). A TRI optimized for tumor regression grade also displayed a significant association (<em>P</em> = 0.0011).</p></div><div><h3>Conclusions</h3><p>TRI was predictive of OS and DFS beyond clinical factors. These positive results suggest the potential utility of personalized biosimulation-informed therapy selection and that further assessment in prospective clinical studies is warranted.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819823000109/pdfft?md5=c47bbdcdc5f341df1a7eb134067306ed&pid=1-s2.0-S2949819823000109-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140188243","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":"ItaLynch: an ongoing Italian study to evaluate the feasibility of mainstreaming the diagnosis of Lynch syndrome in colorectal cancer patients","authors":"A. Puccini ,&nbsp;F. Grillo ,&nbsp;M. Fassan ,&nbsp;S. Lonardi ,&nbsp;M. Genuardi ,&nbsp;R. Cannizzaro ,&nbsp;G.M. Cavestro ,&nbsp;F. Marmorino ,&nbsp;V. Conca ,&nbsp;L. Salvatore ,&nbsp;F. Bergamo ,&nbsp;F. Tosi ,&nbsp;F. Morano ,&nbsp;V. Daprà ,&nbsp;C. Molica ,&nbsp;D. Barana ,&nbsp;A. Guglielmi ,&nbsp;C. Signorelli ,&nbsp;M. D’Amico ,&nbsp;F. Zoratto ,&nbsp;S. Sciallero","doi":"10.1016/j.esmogo.2024.100044","DOIUrl":"https://doi.org/10.1016/j.esmogo.2024.100044","url":null,"abstract":"<div><h3>Background</h3><p>International guidelines recommend universal screening for Lynch syndrome (LS) through somatic DNA mismatch repair deficiency (dMMR) testing in all colorectal cancers (CRCs). However, LS remains largely underdiagnosed. Mainstreaming LS diagnosis through oncologist-driven genetic testing could increase detection rates, thus extending the benefits of precision prevention to patients with LS and their families. We aim to evaluate the feasibility of the mainstreaming diagnostic algorithm for LS.</p></div><div><h3>Patients and methods</h3><p>ItaLynch is an ongoing, prospective, observational, multicenter, multidisciplinary, Italian study in patients with dMMR CRC. Being descriptive in nature, it does not attempt to test any specific, <em>a priori</em>, hypothesis. Patients with dMMR CRC are selected by universal screening by immunohistochemistry (IHC). In <em>MLH1</em>-deficient patients, reflex testing for <em>BRAF</em>^{<em>V600E</em>} and, when appropriate, for <em>MLH1</em> promoter hypermethylation is carried out. For all dMMR CRC, a ‘Lynch Alert’ is added to the pathology report: positive when a patient is at high risk for LS, due to reflex testing results or to loss of non-MLH1 proteins. Conversely, a ‘Lynch Alert’ is negative when the patient is likely to be a nonhereditary case (i.e. MLH1 loss and <em>BRAF</em>^{<em>V600E</em>} or <em>MLH1</em> promoter hypermethylation). In patients with a positive ‘Lynch Alert’, after providing a brief explanation about the risks and benefits of genetic testing, the oncologist asks patients for their consent to mainstream genetic testing. Thus a blood sample is drawn for constitutional variants of the MMR genes. Carriers of a germline variant are then referred to post-test genetic counseling. Referral to clinical genetic services is also advised for patients with clinical suspect criteria.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000050/pdfft?md5=a9e317b1ef518a3ffe5057441a898300&pid=1-s2.0-S2949819824000050-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030362","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":"Highlights from the ESMO Annual Meeting 2023 – EORTC GI Tract Group picks from the colorectal and anal cancer track","authors":"R. Fazio ,&nbsp;D. Arnold ,&nbsp;G. Folprecht ,&nbsp;M.G. Guren ,&nbsp;T. Koessler ,&nbsp;L. Wyrwicz ,&nbsp;F. Sclafani","doi":"10.1016/j.esmogo.2023.100038","DOIUrl":"https://doi.org/10.1016/j.esmogo.2023.100038","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"3 ","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819823000535/pdfft?md5=4662bfb0403b8bf79cb9010db6e2a9fd&pid=1-s2.0-S2949819823000535-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140188245","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}