ESMO Gastrointestinal Oncology最新文献

{"title":"Concomitant proton pump inhibitors and capecitabine-based chemoradiotherapy in rectal cancer: an ancillary study from the PRODIGE 23 trial","authors":"M. Bridoux ,&nbsp;E. Aymes ,&nbsp;T. Conroy ,&nbsp;S. Gourgou ,&nbsp;A. Carnot ,&nbsp;C. Borg ,&nbsp;M.-C. Le Deley ,&nbsp;A. Turpin","doi":"10.1016/j.esmogo.2024.100119","DOIUrl":"10.1016/j.esmogo.2024.100119","url":null,"abstract":"<div><h3>Background</h3><div>Approximately one in five cancer patients use proton pump inhibitors (PPIs). In this work, we studied the effect of PPI co-medication during neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer (LARC) based on the phase III PRODIGE 23 trial.</div></div><div><h3>Materials and methods</h3><div>We gathered data on PPI exposure for patients from the PRODIGE 23 trial. PPI exposure was defined as PPI use during capecitabine treatment, either during CRT or as adjuvant therapy. The oncological outcomes included recurrence-free survival (RFS), overall survival (OS), cumulative incidence of metastatic recurrence, and pathological response to preoperative treatment. The association of PPI use with RFS, metastatic recurrence, and histological complete response was evaluated using univariate and multivariate Cox models.</div></div><div><h3>Results</h3><div>We analyzed data from 332 patients [165 in the NAC group with mFOLFIRINOX, capecitabine-based (CAP50) CRT, and surgery, and 167 in the standard-of-care control arm with CAP50 CRT and surgery]. Thirty-eight patients were co-administered a PPI during capecitabine administration. After a median follow-up of 49.4 months, the 3-year RFS rates were 74.1% [95% confidence interval (CI) 68.6% to 78.8%] and 68.4% (95% CI 51.2% to 80.7%) in the non-PPI and PPI groups, respectively, with no significant differences (<em>P</em> = 0.16). The 3-year OS rates were 91.2% (95% CI 87.2% to 93.9%) and 83% (95% CI 65.7% to 92%) in the non-PPI group and PPI groups, respectively, with no significant differences (<em>P</em> = 0.38). We observed no difference in the pathological complete response rate between both groups.</div></div><div><h3>Conclusions</h3><div>We observed no significant association between PPI exposure and survival or pathological response of patients receiving capecitabine-based CRT for LARC, supporting earlier research findings.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100119"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160881","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":"PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone","authors":"M. Sachdeva ,&nbsp;J.J. Zhao ,&nbsp;K.X. Zhu ,&nbsp;D.T.W. Yap ,&nbsp;N.Z.H. Wong ,&nbsp;N.B. Kumarakulasinghe ,&nbsp;J. Tey ,&nbsp;R. Sundar","doi":"10.1016/j.esmogo.2024.100109","DOIUrl":"10.1016/j.esmogo.2024.100109","url":null,"abstract":"<div><h3>Background</h3><div>Programmed death-ligand 1 (PD-L1) expression is a well-established positive predictive biomarker for response to immunotherapy in advanced esophageal squamous-cell carcinoma (aESCC). However, the association between PD-L1 and response to chemotherapy alone remains unclear. This study aims to determine the prognostic significance of PD-L1 expression in patients treated with first-line chemotherapy alone in aESCC.</div></div><div><h3>Materials and methods</h3><div>First-line phase III randomized trials that included PD-L1 expression as a biomarker in aESCC were extracted after a systematic search. A graphical reconstructive algorithm was used to estimate time-to-event outcomes from reported Kaplan–Meier (KM) plots and, where unavailable, KMSubtraction was utilized to derive KM plots of unreported PD-L1 subgroups. Thereafter, an individual patient data meta-analysis was conducted. Survival analyses for overall survival (OS) and progression-free survival (PFS) were conducted with Cox proportional hazards models with a shared-frailty term incorporated to account for interstudy differences.</div></div><div><h3>Results</h3><div>Chemotherapy arms from five randomized phase III trials—CheckMate-648, ESCORT-1st, KEYNOTE-590, RATIONALE-306 and ORIENT-15—comprising 1517 patients were included in the OS analysis. Compared with PD-L1-low-expressing tumors, patients with PD-L1-high-expressing tumors were at a significantly higher risk of mortality [hazard ratio (HR) 1.153, 95% confidence interval (CI) 1.018-1.305, <em>P</em> = 0.025]. Three trials—CheckMate-648, ESCORT-1st and ORIENT-15—comprising 949 patients treated with chemotherapy alone were included in the PFS analysis. Patients with PD-L1-high-expressing tumors had a non-significant increased risk of tumor progression (HR 1.076, 95% CI 0.923 –1.253, <em>P</em> = 0.349).</div></div><div><h3>Conclusions</h3><div>Our study found PD-L1 expression is a negative predictor of OS in aESCC treated with first-line chemotherapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100109"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143159539","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":"Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis","authors":"Y.-Y. Su ,&nbsp;M.-Y. Lin ,&nbsp;S.M. Cheng ,&nbsp;W.-L. Chang ,&nbsp;C.-W. Hsu ,&nbsp;C.-M. Yeh ,&nbsp;C.-C. Yu ,&nbsp;Y.-C. Hou ,&nbsp;C.-J. Huang ,&nbsp;Y.-S. Liu ,&nbsp;Y.-J. Chao ,&nbsp;D.-Y. Hwang ,&nbsp;Y.S. Shan ,&nbsp;L.-T. Chen","doi":"10.1016/j.esmogo.2024.100113","DOIUrl":"10.1016/j.esmogo.2024.100113","url":null,"abstract":"<div><h3>Background</h3><div>Single-cell RNA sequencing (scRNA-seq) is a powerful tool which can unveil regulatory connections between genes and cells. However, due to the high demand for tissue quality, most scRNA-seq for pancreatic cancer is carried out by surgical specimen. This study (NCT05767697) aims to gain practical experience in carrying out scRNA-seq using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB).</div></div><div><h3>Materials and methods</h3><div>With a within-subjects design, two punctures from the same lesion, with a negative pressure of 5 ml (suction group) and without applying suction (non-suction group), were evaluated. Each biopsy sample was separated into three parts: white tissue, red material, and buffer for living cell counting. scRNA-seq was carried out according to the manufacturer’s protocol. The pancreatic adenocarcinoma dataset in The Cancer Genome Atlas (TCGA) was used as external validation.</div></div><div><h3>Results</h3><div>A total of 20 patients with 40 specimens were enrolled. The suction group achieved a success rate of 80% (16/20), which was significantly higher than the 10% (2/20) success rate in the non-suction group (<em>P</em> &lt; 0.001). scRNA-seq data were generated for four patients, including two early stage and two late stage. Overall, 15 major cell subtypes, including 4 cancer subclones, were identified across early and late stages. Analysis of differentially expressed genes identified an aggressive subclone highlighted by ubiquitin-conjugating enzyme E2 C (UBE2C) high expression, commonly in late stage. The TCGA dataset also demonstrated that UBE2C high-expression pancreatic cancer had a poor prognosis.</div></div><div><h3>Conclusions</h3><div>EUS-FNB with a negative pressure of 5 ml is feasible for scRNA-seq in clinical practice. A UBE2C high-expression subclone correlates with a poor prognosis, potentially becoming a new therapeutic target in future studies.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100113"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160896","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":"Evaluating trastuzumab deruxtecan in patients with gastrooesophageal adenocarcinoma who are ctDNA and HER2 positive: DECIPHER","authors":"E. Smyth ,&nbsp;D. Griffiths ,&nbsp;K. Cozens ,&nbsp;S. Ewings ,&nbsp;R. Waugh ,&nbsp;R.C. Turkington ,&nbsp;K. Foley ,&nbsp;R. Roy ,&nbsp;S. Ngan ,&nbsp;R. Owen ,&nbsp;D. Chuter ,&nbsp;C. Steele ,&nbsp;G. Griffiths","doi":"10.1016/j.esmogo.2024.100114","DOIUrl":"10.1016/j.esmogo.2024.100114","url":null,"abstract":"<div><div>Operable gastrooesophageal adenocarcinoma (GOA) is treated with multimodality therapy which is curative in &lt;50% of patients. Patients in the UK with operable GOA are treated with chemotherapy before and following surgery. Patients who have circulating tumour DNA (ctDNA) present after surgery have worse survival than ctDNA-negative patients. Trastuzumab deruxtecan (T-DXd), a novel human epidermal growth factor receptor 2 (HER2)-targeting antibody–drug conjugate is an effective drug in multiple tumour types and has been licensed to treat advanced HER2-positive GOA that has progressed after chemotherapy and trastuzumab and is European Society for Medical Oncology (ESMO) Guideline recommended. Evaluation of T-DXd in operable but micrometastatic GOA is an attractive option. DECIPHER is a multicentre, phase II trial testing the efficacy of T-DXd in reducing micrometastatic disease burden in HER2-positive GOA patients who are ctDNA positive after neoadjuvant chemotherapy and surgery. Patients will have their resection specimen and plasma analysed to confirm HER2 and ctDNA status post-operatively. Twenty-five ctDNA- and HER2-positive patients will be treated with 6.4 mg/kg T-DXd intravenously every 21 days for a maximum of eight cycles. Study follow-up visits will take place for a maximum of 2 years after treatment, with survival follow-up until the end of the study.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747109","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":"This is not Lynch syndrome: lessons from misattributed diagnoses in constitutional mismatch repair deficiency","authors":"A.H. Mohammad ,&nbsp;E. Rohr ,&nbsp;A. Moise ,&nbsp;R.M. Abdulsalam ,&nbsp;W. Davalan ,&nbsp;A. Rizzolo ,&nbsp;A.S. Liberman ,&nbsp;C. Goudie ,&nbsp;L. Palma ,&nbsp;W.D. Foulkes","doi":"10.1016/j.esmogo.2024.100111","DOIUrl":"10.1016/j.esmogo.2024.100111","url":null,"abstract":"<div><h3>Background</h3><div>Underdiagnosis of constitutional mismatch repair deficiency (CMMRD) syndrome leads to suboptimal cancer surveillance and management of CMMRD patients. Assessing pitfalls that led to the misdiagnosis of CMMRD is important to improve care trajectories, and to highlight the importance of accurate molecular and pathology-based assessment of patients presenting with CMMRD-associated features.</div></div><div><h3>Materials and methods</h3><div>A retrospective chart review of two patients with molecularly confirmed CMMRD ascertained through the Medical Genetics service of the McGill University Health Centre (MUHC) was conducted to study the pathway and pitfalls to diagnosis. Records were reviewed and summarized as timelines to depict important events relating to diagnosis and management of CMMRD patients.</div></div><div><h3>Results</h3><div>Unfamiliarity with CMMRD contributed to a diagnosis delay and initiation of CMMRD-specific surveillance. Pitfalls along the diagnostic pathway included inaccurate clinical information relayed to pathologists, unfamiliarity with CMMRD-defining features on immunohistochemistry (IHC) analyses, IHC variability and unreliability, and lack of awareness of the pivotal role for medical genetics in the diagnosis of CMMRD.</div></div><div><h3>Conclusions</h3><div>Improved awareness of CMMRD in patients presenting with CMMRD-associated features can help guide IHC analysis and expedite referral to medical genetics for accurate molecular diagnosis. Consequently, timely CMMRD diagnosis improves surveillance and patient management and allows for appropriate genetic counseling for family members.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100111"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143147137","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":"PD-L1 as a response biomarker to chemotherapy plus immune checkpoint inhibitors in operable gastroesophageal adenocarcinoma: a meta-analysis of neoadjuvant clinical trials","authors":"A. Cammarota ,&nbsp;S.K. Kamarajah ,&nbsp;S. Markar ,&nbsp;E.C. Smyth","doi":"10.1016/j.esmogo.2024.100107","DOIUrl":"10.1016/j.esmogo.2024.100107","url":null,"abstract":"<div><h3>Background</h3><div>Perioperative chemoimmunotherapy [i.e. chemotherapy plus immune checkpoint inhibitor (ICI) (ChT–ICI)] is an investigational treatment for operable gastroesophageal adenocarcinoma (GEA) with unclear outcomes in an unselected population. We aimed to assess the cumulative treatment effect of ChT–ICI on pathological response rates, the surrogacy of pathological response rates on overall survival (OS), and the value of programmed death-ligand 1 (PD-L1) as a biomarker of response to ICIs in operable GEA.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of randomised clinical trials (RCTs) of ChT with or without ICIs with the primary outcome being pathological response rates [pathological complete response (pCR) and similar metrics]. A weighted linear regression model quantified the relationship between pathological response rates and OS using a determination coefficient (<em>R</em>²). A second meta-regression analysed the predictive effect of PD-L1 on pCR in trials of ICIs with ChT or chemoradiotherapy (CRT).</div></div><div><h3>Results</h3><div>A total of 18 records from 15 RCTs were included. Of 6624 patients, 5291 received ChT and 1333 ChT–ICI. ChT–ICI significantly improved pathological response rates [pooled odds ratio 3.18, 95% confidence interval (CI) 2.42-4.18, <em>P</em> &lt; 0.0001] compared with ChT (pooled odds ratio 1.66, 95% CI 1.33-2.07, <em>P</em> &lt; 0.0001). The correlation between pathological response and OS was low (<em>R</em>² = 0.12) but improved in recent trials (<em>R</em>² = 0.51) and those with ChT–biological agents, including ICIs (<em>R</em>² = 0.79). In the second analysis (11 studies, 633 patients), PD-L1 ≥5 was a significant predictor of response both individually (estimate: 0.73, 95% CI 0.28-1.18, <em>P</em> = 0.001) and after accounting for the backbone treatment (estimate: 0.80, 95% CI 0.28-1.33, <em>P</em> = 0.003).</div></div><div><h3>Conclusions</h3><div>Perioperative ChT–ICI improves pathological response rates in operable GEA and PD-L1 ≥5 is a significant biomarker of pCR, supporting stratification by PD-L1 and the design of biomarker-selected trials.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722394","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":"Practical management of oligometastatic gastric cancer","authors":"Y. Narita ,&nbsp;K. Muro ,&nbsp;D. Takahari","doi":"10.1016/j.esmogo.2024.100108","DOIUrl":"10.1016/j.esmogo.2024.100108","url":null,"abstract":"<div><div>Gastric cancer is one of the types of cancer with a high prevalence of morbidity. The frequency of esophagogastric junction cancer, 5-year survival rates, perioperative adjuvant therapy, and standard chemotherapeutic regimens for gastric cancer vary between Asian countries and the West. Although oligometastasis is considered an intermediate state between localized and systemic disease, no standardized definition regarding metastatic organ sites or international consensus in gastric cancer exists. Both local treatment, such as radical surgery and radiotherapy, and systemic chemotherapy can be employed for treating patients with gastric cancer with oligometastatic disease. Recently, evidence for oligometastatic gastric cancer has been accumulated, including findings from several clinical trials conducted in Asian and Western countries, focusing on both organ-specific and non-organ-specific oligometastatic gastric cancer. Here, we review the latest findings on oligometastasis in gastric cancer, including variations in treatment strategies between Western and Asian countries. Further investigation is needed to determine the most favorable practical management strategies for patients with metachronous oligometastasis in gastric cancer, including the use of molecular-targeted agents and immune checkpoint inhibitors. The results of ongoing trials may shed light on the optimal treatment approaches for oligometastatic disease.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100108"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704083","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":"Risk factor of severe diarrhea and enterocolitis induced by CAPOX: a retrospective multicenter study","authors":"A. Teixeira ,&nbsp;T. Felismino ,&nbsp;M.D. Donadio ,&nbsp;G. Catani ,&nbsp;A.L.M. da Silva ,&nbsp;R. Weschenfelder ,&nbsp;R.D. Peixoto ,&nbsp;J.M. O’Connor ,&nbsp;A.K. Coutinho ,&nbsp;R.P. Riechelmann","doi":"10.1016/j.esmogo.2024.100110","DOIUrl":"10.1016/j.esmogo.2024.100110","url":null,"abstract":"<div><h3>Background</h3><div>We have previously suggested that concurrent use of capecitabine plus oxaliplatin (CAPOX) and angiotensin receptor blockers (ARBs) significantly increased the risk of severe diarrhea and/or enterocolitis. We conducted a multicenter larger study to validate this finding, adjusting for other risk factors.</div></div><div><h3>Patients and methods</h3><div>This was a retrospective multicenter study of patients with colorectal cancer treated with at least one cycle of CAPOX. The primary endpoint was grade (G) ≥3 diarrhea and/or enterocolitis induced by CAPOX. Unadjusted and adjusted logistic regression models were used to evaluate risk factors for G ≥3 diarrhea and/or enterocolitis. <em>P</em> &lt; 0.05 was deemed significant.</div></div><div><h3>Results</h3><div>From April 2010 to December 2023, 362 patients were included. In univariate analyses, age ≥65 years, right-sided tumors, use of ARBs or angiotensin-converting enzyme inhibitors (ACEi), age-adjusted Charlson Comorbidity Index, and estimated glomerular filtration rate (eGFR) &lt;60 ml/min were associated with G ≥3 diarrhea and/or enterocolitis. In the multivariable analysis, age ≥65 years [odds ratio (OR) 2.71, 95% confidence interval (CI) 1.38-5.33, <em>P</em> = 0.004] and eGFR &lt;60 ml/min (OR 5.4, 95% CI 2.25-13.8, <em>P</em> &lt; 0.001), but not use of ARBs or ACEi, were significant.</div></div><div><h3>Conclusions</h3><div>Age ≥65 years and eGFR &lt;60 ml/min were independent risk factors for G ≥3 diarrhea/enterocolitis in patients treated with CAPOX. Concurrent use of ARBs or ACEi was not associated with G ≥3 diarrhea/enterocolitis.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704082","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":"Genetic and transcriptomic analyses of early-onset colon cancer (EOCC): a post hoc analysis of 2973 patients from two adjuvant randomized trials","authors":"A. Gandini ,&nbsp;C. Gallois ,&nbsp;H. Blons ,&nbsp;C. Mulot ,&nbsp;N. Agueeff ,&nbsp;C. Lepage ,&nbsp;R. Guimbaud ,&nbsp;L. Mineur ,&nbsp;J. Desramé ,&nbsp;B. Chibaudel ,&nbsp;A. de Reyniès ,&nbsp;T. André ,&nbsp;P. Laurent-Puig ,&nbsp;J. Taieb","doi":"10.1016/j.esmogo.2024.100106","DOIUrl":"10.1016/j.esmogo.2024.100106","url":null,"abstract":"<div><h3>Background</h3><div>Despite decreasing colon cancer (CC) incidence worldwide, an inverse trend is being registered since the late 1990s in people &lt;50 years old, possibly due to an increasing exposure to lifestyle-related risk factors/exposome. Early-onset CC (EOCC) typically manifests in more advanced stages and may harbor a distinct genetic profile. However, its prognosis remains controversial, and disease stratification through gene expression-based subtyping could potentially provide insight.</div></div><div><h3>Materials and methods</h3><div>We collected data from stage III CC patients enrolled in PETACC-8 and IDEA-France and we analyzed them according to a cut-off of 50 years of age, defining EOCC and late-onset CC (LOCC). Molecular analyses were carried out to evaluate mismatch repair deficiency (dMMR) and extended genetic profile. RNA-sequencing analyses were carried out to determine consensus molecular subtypes (CMS).</div></div><div><h3>Results</h3><div>A total of 2607 LOCC and 366 EOCC were included. When compared to LOCC, EOCC were in better general conditions and presented more advanced-stage diseases. EOCC were more often dMMR, CMS1, <em>RAS</em> wild-type, and mutated for <em>PTEN, CTNNB1, ERBB2,</em> and <em>DDR2</em>. Relapse-free survival (RFS) was similar in the two age groups (3-year rate 74% versus 76%), but differences were observed according to CMS. In CMS1, a better RFS was observed in mismatch repair-proficient (pMMR) EOCC versus LOCC (3-year rate 82% versus 63%, <em>P</em> = 0.041), while this was not observed in dMMR CMS1.</div></div><div><h3>Conclusions</h3><div>In conclusion, EOCCs are diagnosed in more advanced stages, are more often dMMR, harbor a specific genetic profile, and have similar RFS when compared to LOCC, even if the age effect on RFS appeared to vary among CMS groups.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143159961","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":"Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumours","authors":"M. Berndsen ,&nbsp;F. Puls ,&nbsp;A. Thornell ,&nbsp;Y. Arvidsson ,&nbsp;A. Muth ,&nbsp;S. Lindskog ,&nbsp;E. Elias","doi":"10.1016/j.esmogo.2024.100105","DOIUrl":"10.1016/j.esmogo.2024.100105","url":null,"abstract":"<div><h3>Background</h3><div>There are limited treatment options for patients with advanced or metastatic gastrointestinal stromal tumours (GISTs) that lack mutations targetable by tyrosine kinase inhibitors (TKIs) or that have developed resistance to TKIs. Gastrin-releasing peptide receptor (GRPR) theranostics may offer a viable option in GISTs. However, the expression of the GRPR in GIST has not been extensively studied.</div></div><div><h3>Materials and methods</h3><div>GRPR expression was evaluated using immunohistochemistry in two separate tissue microarrays from patients treated at Sahlgrenska University Hospital, one from the pre-TKI era (1983-2001) and the other from the post-TKI era (2014-2020). In total, 205 tumour samples were characterized as having low/none or moderate/high expression of the GRPR, and these were correlated with clinical characteristics and survival outcomes.</div></div><div><h3>Results</h3><div>In total, 80% of the tumour samples exhibited moderate or high expression of GRPR. GRPR expression was not associated with gender, age, tumour location, or risk group, as defined by the modified National Institutes of Health (NIH) consensus criteria. Neoadjuvant treatment with TKI was correlated with low/none GRPR expression (<em>P</em> = 0.04). In patients who underwent surgery with curative intent and did not receive neoadjuvant treatment, GRPR expression was not associated with survival outcomes.</div></div><div><h3>Conclusions</h3><div>This study is the first to investigate GRPR expression in a large cohort of GIST tumours. Our results demonstrate that most GIST tumours exhibit a moderate to high expression of the receptor, suggesting that GRPR theranostics could be a viable option for TKI-resistant GIST. Interestingly, tumours that were pretreated with TKI showed lower expression levels of GRPR, indicating a need for further studies to explore this finding.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100105"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578047","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}