ESMO Gastrointestinal Oncology最新文献

{"title":"Poor-prognosis young-onset colorectal cancer is defined by the mesenchymal subtype and can be predicted by integrating molecular and histopathological characteristics","authors":"J. Ke ,&nbsp;Y. Li ,&nbsp;L. Qi ,&nbsp;X. Li ,&nbsp;W. Wang ,&nbsp;S. Ten Hoorn ,&nbsp;Y. Zhu ,&nbsp;H. Huang ,&nbsp;F. Gao ,&nbsp;L. Vermeulen ,&nbsp;X. Wang","doi":"10.1016/j.esmogo.2025.100181","DOIUrl":"10.1016/j.esmogo.2025.100181","url":null,"abstract":"<div><h3>Background</h3><div>Young-onset colorectal cancer (CRC), affecting individuals &lt;50 years of age, presents a significant health threat worldwide. The molecular and clinical characteristics of young-onset CRC are poorly understood, complicating the development of effective biomarkers for precision oncology. This study aimed to dissect age-dependent molecular heterogeneity of CRC and establish a model for identifying high-risk young-onset patients.</div></div><div><h3>Methods</h3><div>We analyzed clinical data for 564 439 patient samples across three large cohorts. For molecular characterizations, a subset of 1874 patient samples was used. A deep learning framework was used to analyze hematoxylin–eosin-stained whole-slide images to quantify Shannon diversity indices (SDIs). Subsequently, a multivariate model, integrating SDI, microsatellite status and promoter methylation of miR-200s, was developed for predicting the consensus molecular subtype (CMS)4-mesenchymal subtype, followed by internal and external clinical validations.</div></div><div><h3>Results</h3><div>Young-onset CRC patients exhibited better overall survival but worse relapse-free survival and higher metastasis rates compared with late-onset cases. Molecular subtyping analysis found that young-onset CRC also comprises the same four subtypes (CMS1-4), but the prevalence differs from late-onset CRC. Stratified analysis suggested that the poor outcomes in young-onset CRC were due to higher prevalence of the CMS4-mesenchymal subtype. To predict CMS4, we established an effective risk-scoring model (area under the curve = 0.87) combining molecular and histological markers, with multiple independent validations.</div></div><div><h3>Conclusions</h3><div>CRC shows age-dependent molecular heterogeneity, with young-onset cases more frequently presenting the CMS4 subtype. To predict CMS4, we developed and validated a robust risk-scoring model integrating molecular and histological markers, offering a new translatable tool for more optimized management of young-onset patients.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibre, microbes and radiotherapy: unravelling the gut’s impact on radiotherapy in cancer","authors":"L. Twhigg ,&nbsp;H.M. Ng ,&nbsp;T. Glyn ,&nbsp;C. Wall ,&nbsp;R. Purcell","doi":"10.1016/j.esmogo.2025.100174","DOIUrl":"10.1016/j.esmogo.2025.100174","url":null,"abstract":"<div><div>The gut microbiome plays an integral role in many physiological functions, including immunity, metabolism, maintenance of membrane integrity and protection against pathogenic bacteria. Conversely, adverse changes in the gut microbiome—termed dysbiosis—have been linked to many diseases, including cancer. Dysbiosis can result from a range of endogenous and exogenous factors. Diet is one of the most important modulators of the gut microbiome; the indirect benefits of modulating the microbiome through diet interventions are beginning to be used in many disease settings. Beneficial microbes (commensals) can modulate the local and systemic immune environment through the production of metabolites, such as short-chain fatty acids (SCFAs). Commensal bacteria ferment dietary fibre to produce SCFAs, and increasing dietary fibre intake has been shown to both increase SCFA production in the colon and affect immune responses. Recent studies have shown that dietary fibre can increase tumour responses to immunotherapy and chemotherapy, but data on the effect of increased fibre and changes in the microbiome on radiotherapy are limited. In this article, we review the current evidence regarding dietary fibre interventions and modulation of the gut microbiome in improving outcomes in patients receiving pelvic radiotherapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100174"},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early bevacizumab dose and time modifications may affect efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma treatment","authors":"F. Rossari ,&nbsp;D. Lavacchi ,&nbsp;E. Alimenti ,&nbsp;C. Soldà ,&nbsp;F. Salani ,&nbsp;L. Esposito ,&nbsp;S. Foti ,&nbsp;S. Camera ,&nbsp;M. Persano ,&nbsp;F. Lo Prinzi ,&nbsp;F. Vitiello ,&nbsp;E. Pellegrini ,&nbsp;M. Bruccoleri ,&nbsp;M.D. Rizzato ,&nbsp;M. Caccese ,&nbsp;I.G. Rapposelli ,&nbsp;A. Guidolin ,&nbsp;A. De Rosa ,&nbsp;L. Antonuzzo ,&nbsp;G. Masi ,&nbsp;A. Casadei-Gardini","doi":"10.1016/j.esmogo.2025.100186","DOIUrl":"10.1016/j.esmogo.2025.100186","url":null,"abstract":"<div><h3>Background</h3><div>Atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) every 3 weeks (AtezBev) became a standard-of-care first-line treatment for advanced hepatocellular carcinoma (aHCC) following IMbrave150. However, real-world data suggest milder efficacy. Early bevacizumab interruption due to adverse events (AEs) is a frequent occurrence in real-world scenario associated with poor prognosis. Additionally, early bevacizumab dose/time modifications (eBEVmod) may negatively impact outcome.</div></div><div><h3>Materials and methods</h3><div>Data from AtezBev-treated aHCC patients (<em>n</em> = 100) in five Italian institutions were retrospectively analyzed. Cumulative bevacizumab dose (mg/kg) received in the first 3 months of treatment was analyzed by receiver operating characteristic (ROC) to identify a cut-off value to estimate survival and dichotomize the variable. Baseline clinical and laboratory characteristics were analyzed with uni-/multivariate models to explore potential differences on overall survival (OS), objective response rate (ORR) and disease control rate (DCR) based on eBEVmod. Progression-free survival (PFS) was a secondary endpoint.</div></div><div><h3>Results</h3><div>In the overall population, the median (m) follow-up was 11.4 months, mOS was 20.5 months, mPFS was 10.4 months, ORR was 31% and DCR was 75%. ROC on 3-month cumulative bevacizumab dose revealed an area under the curve of 0.74 (<em>P</em> = 0.001) and eBEVmod cut-off of &lt;45 mg/kg/3 months (i.e. 10.5 mg/kg/3 weeks) having 73% sensitivity and specificity in predicting death. Twenty-three percent of patients had eBEVmod (of which 39.1% had treatment delay, 39.1% discontinuation and 21.7% dose reduction), with no differences in baseline characteristics nor second-line treatments compared with non-eBEVmod, except for sex. eBEVmod patients had inferior ORR/DCR (14%/48% versus 36%/82%) and increased risk of death [hazard ratio (HR) 4.2, <em>P</em> = 0.0049], with a 12-month survival probability of 53.3% versus 77.4%. eBEVmod was an independent negative prognostic factor of survival at multivariate analysis (HR 3.3, <em>P</em> = 0.0125). Patients with eBEVmod also had a trend in worse PFS, although not statistically significant (mPFS 3.8 versus 12.6 months, HR 1.8, <em>P</em> = 0.0774).</div></div><div><h3>Conclusions</h3><div>eBEVmod is an independent unfavorable prognostic factor of response and survival in AtezBev-treated aHCC patients. Optimization of bevacizumab AE management to reduce eBEVmod may substantially improve treatment outcome in real-world practice.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100186"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic factors and treatment response in HER2-positive gastric cancer patients receiving trastuzumab deruxtecan: secondary analysis of the EN-DEAVOR study","authors":"K. Nakanishi ,&nbsp;N. Sugimoto ,&nbsp;Y. Kodera ,&nbsp;H. Kawakami ,&nbsp;A. Makiyama ,&nbsp;H. Konishi ,&nbsp;S. Morita ,&nbsp;Y. Narita ,&nbsp;K. Minashi ,&nbsp;M. Imano ,&nbsp;R. Inamoto ,&nbsp;T. Nishina ,&nbsp;T. Kawakami ,&nbsp;M. Hagiwara ,&nbsp;H. Kume ,&nbsp;K. Yamaguchi ,&nbsp;W. Hashimoto ,&nbsp;K. Muro","doi":"10.1016/j.esmogo.2025.100184","DOIUrl":"10.1016/j.esmogo.2025.100184","url":null,"abstract":"<div><h3>Background</h3><div>EN-DEAVOR was a multi-institutional retrospective study evaluating the effectiveness and safety of trastuzumab deruxtecan (T-DXd) in gastric cancer patients. This secondary analysis investigated prognostic factors for real-world progression-free survival (rwPFS) and objective response rate (ORR) for T-DXd as third- or later-line treatment.</div></div><div><h3>Patients and methods</h3><div>Patients aged ≥20 years with histopathologically confirmed human epidermal growth factor receptor 2 (HER2)-positive unresectable advanced or recurrent gastric or gastroesophageal junction adenocarcinoma, who had worsened after chemotherapy, were included. Patients received T-DXd as third- or later-line therapy between September 2020 and September 2021. Univariate and multivariate analyses identified prognostic factors for rwPFS and ORR.</div></div><div><h3>Results</h3><div>Of the 307 patients, 75.6% were male and 69.1% were aged ≥65 years. The median duration of prior trastuzumab treatment was 6.5 months (range 0-81.5 months). Multivariate analysis showed HER2 immunohistochemistry (IHC) 3+ [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86], intestinal type lesions (HR 0.59, 95% CI 0.43-0.79), modified Glasgow Prognostic Score (mGPS) 0 and 1 (HR 0.71, 95% CI 0.53-0.95), and longer duration of prior trastuzumab treatment (≥ median) (HR 0.75, 95% CI 0.58-0.97) as positive prognostic factors for rwPFS. Longer prior trastuzumab treatment was also a positive prognostic factor for ORR (odds ratio 2.02, 95% CI 1.13-3.63).</div></div><div><h3>Conclusions</h3><div>Patients with clinical benefits from prolonged trastuzumab treatment are likely to benefit from T-DXd. Similarly, HER2 IHC 3+, intestinal type lesions, and better mGPS (0 or 1) are associated with longer rwPFS. However, T-DXd should not be withheld even in patients without these factors, as a median PFS of 3.42 months was observed in those with the shortest prior trastuzumab exposure.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100184"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controversies in upper GI oncology: role of radiotherapy in non-metastatic gastroesophageal adenocarcinoma","authors":"A. Petrillo ,&nbsp;M. Verheij ,&nbsp;T. Leong","doi":"10.1016/j.esmogo.2025.100188","DOIUrl":"10.1016/j.esmogo.2025.100188","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100188"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline genomic profiling of patients with early-onset colorectal cancer","authors":"G. Mauri ,&nbsp;M. Puzzono ,&nbsp;A. Mannucci ,&nbsp;F. Gaudioso ,&nbsp;H. Mittal ,&nbsp;L. Mosca ,&nbsp;V. Burgio ,&nbsp;S. Ghezzi ,&nbsp;M. Ronzoni ,&nbsp;S. Mariano ,&nbsp;R. Rosati ,&nbsp;L. Monti ,&nbsp;U. Cavallari ,&nbsp;A. Sartore-Bianchi ,&nbsp;S. Siena ,&nbsp;G.M. Cavestro","doi":"10.1016/j.esmogo.2025.100182","DOIUrl":"10.1016/j.esmogo.2025.100182","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of early-onset colorectal cancer (EO-CRC) is rising. While most cases of EO-CRC are sporadic, the prevalence of hereditary cancer predisposition syndromes remains a subject of debate. Moreover, genes not traditionally associated with EO-CRC development are rarely included in germline testing panels.</div></div><div><h3>Patients and methods</h3><div>Germline profiling data of patients with EO-CRC presenting to our clinics were collected at two Italian university institutions: IRCCS San Raffaele Scientific Institute and Grande Ospedale Metropolitano Niguarda. Multigene germline profiling analysis was carried out using next-generation sequencing and multiplex ligation probe amplification. Associations between germline alterations and clinicopathological variables were analyzed.</div></div><div><h3>Results</h3><div>A total of 130 patients with EO-CRC were screened. The median age at EO-CRC diagnosis was 42 years (range 22-49 years). Germline pathogenic or likely pathogenic variants (PVs/LPVs) associated with hereditary cancer predisposition syndromes were identified in 23 (18%) patients, while germline variants of unknown significance were found in 47 (36%) patients. No alterations in high-penetrance genes associated with cancer susceptibility were observed in 67 (52%) patients. No patients with microsatellite stable <em>BRAF</em>-mutant (<em>n</em> = 5) or signet ring cell CRC (<em>n</em> = 2) exhibited germline PVs/LPVs. No clinicopathological features were significantly enriched in hereditary compared with sporadic EO-CRC. Germline PVs in <em>FLCN</em> and <em>SDHAF2</em> were identified in two patients with EO-CRC.</div></div><div><h3>Conclusions</h3><div>While most EO-CRC cases are sporadic, approximately one-fifth arises within the context of hereditary cancer predisposition syndromes. As <em>FLCN</em> and <em>SDH</em> are not currently included in the current guidelines for EO-CRC, PVs/LPVs in these genes may be underestimated. To better understand their significance, we recommend including their assessment in all patients with EO-CRC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDM2 amplification in a real-world cohort of patients with biliary tract cancer from the Spanish RETUD gastrointestinal registry","authors":"A.J. Muñoz Martín ,&nbsp;F. Castet ,&nbsp;J. Soto Alsar ,&nbsp;J. Adeva ,&nbsp;P. Peinado ,&nbsp;B. Graña ,&nbsp;I. Alés Díaz ,&nbsp;R.M. Rodríguez-Alonso ,&nbsp;M. Lobo de Mena ,&nbsp;R. Vera ,&nbsp;I. Ruiz de Mena ,&nbsp;S. Aguilar ,&nbsp;S. Vega ,&nbsp;L. Ortega Morán ,&nbsp;T. Macarulla","doi":"10.1016/j.esmogo.2025.100187","DOIUrl":"10.1016/j.esmogo.2025.100187","url":null,"abstract":"<div><h3>Background</h3><div>Antagonist of mouse double minute 2 homolog (<em>MDM2</em>) represents a novel therapeutic strategy in biliary tract cancer (BTC). We aimed to characterize the epidemiology of <em>MDM2</em> amplifications in patients with BTC, associations of <em>MDM2</em> with other genetic alterations, and survival outcomes.</div></div><div><h3>Materials and methods</h3><div>A real-world cohort of patients diagnosed with BTC (1 January 2017 to 31 December 2022) was evaluated (RETUD NCT06711211). Next-generation sequencing (NGS) testing was carried out. Demographic and clinical characteristics, molecular profile, treatments, and effectiveness [overall response rate (ORR) and survival outcomes] were assessed. Progression-free survival (PFS), overall survival (OS), and ORR were estimated for patients receiving first-line therapy, using the Kaplan–Meier method. Descriptive analyses were used to assess demographic, clinical, and molecular features.</div></div><div><h3>Results</h3><div>A total of 301 patients were included. <em>MDM2</em> amplification was reported in 19 patients (6.3%); two of them (10.5%) had <em>TP53</em> mutations. Most patients (63.2%; 12/19) with <em>MDM2</em> amplification had intrahepatic tumors. However, <em>MDM2</em> amplification was more frequent in patients with gall-bladder carcinoma (12.9%; 4/31). Patients with/without <em>MDM2</em> amplification receiving first-line therapy [cisplatin and gemcitabine (CisGem)] showed a median OS [95% confidence interval (CI)] of 18.4 months (12.3-19.9 months) and 17.8 months (12.3-19.9 months, <em>P</em> = 0.247), a median PFS (95% CI) of 5.3 months (2.7-8.9 months) and 6.0 months (5.3-6.8 months, <em>P</em> = 0.423), and an ORR of 21.4% and 29.6% (<em>P</em> = 0.762), respectively.</div></div><div><h3>Conclusions</h3><div>Incidence of <em>MDM2</em> amplification was similar to that described in other BTC cohorts. Comparable results in demographic/clinical characteristics, molecular profile, and survival outcomes between patients with/without <em>MDM2</em> amplification was observed.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100187"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147176","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":"Intra-arterial hepatic chemotherapy in metastatic colorectal cancer: differences between oxaliplatin-naive versus oxaliplatin-pretreated patients","authors":"E. El Rawadi ,&nbsp;B. Bonnet ,&nbsp;L. Pierotti ,&nbsp;V. Boige ,&nbsp;L. Tselikas ,&nbsp;C. Smolenschi ,&nbsp;M. Valéry ,&nbsp;T. Pudlarz ,&nbsp;A. Fuerea ,&nbsp;T. De Baere ,&nbsp;A. Tarabay ,&nbsp;M. Gelli ,&nbsp;E. Fernandez-de-Sevilla ,&nbsp;D. Malka ,&nbsp;A. Hollebecque ,&nbsp;M. Ducreux ,&nbsp;A. Boilève","doi":"10.1016/j.esmogo.2025.100173","DOIUrl":"10.1016/j.esmogo.2025.100173","url":null,"abstract":"<div><h3>Background</h3><div>Oxaliplatin-based hepatic arterial infusions (HAI) combined with intravenous therapy is a therapeutic option for colorectal cancer with liver-only metastasis, notably in the palliative setting, either initially or after failure of systemic chemotherapy. Our study aimed to assess efficacy and tolerance between oxaliplatin-naive patients and oxaliplatin-pretreated patients.</div></div><div><h3>Methods</h3><div>Between 2008 and 2022, single-center consecutive patients presenting with liver metastasis secondary to colorectal cancer who received at least one cycle of HAI-oxaliplatin combined with systemic therapy were included.</div></div><div><h3>Results</h3><div>The oxaliplatin-naive arm included 63 patients (median age 58 years) and the pretreated arm included 244 patients (median age 53 years). Patient characteristics were well balanced between the groups. All patients in the oxaliplatin-naive arm received HAI-oxaliplatin while 13% of the pretreated patients received HAI-FOLFIRINOX. After a median follow-up of 36 months, median progression-free survival was 14 months in the oxaliplatin-naive group (range 11.8-24 months) and 10.1 months in the pretreated group (range 9.4-12.5 months) (<em>P</em> = 0.016). The objective response rate was 66.7% and the disease control rate was 79.4% in the oxaliplatin-naive group, versus 32.4% and 77.5% (<em>P</em> &lt; 0.001) in the pretreated group. Grade 3-4 toxicities were comparable between the two groups, including neuropathy. Secondary resection/ablation rate was 22.2% in oxaliplatin-naive patients and 17.6% in pretreated patients.</div></div><div><h3>Conclusion</h3><div>Oxaliplatin use as an intra-arterial hepatic infusion is feasible and efficient after previous systemic oxaliplatin; it showed significant response rates without increased toxicities. It can provide alternative treatments and spare late-setting drugs such as regorafenib and tipiracil–trifluridine for a further palliative intent treatment.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100173"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138210","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":"Long-term outcome after perioperative chemotherapy and surgery for gastro-esophageal adenocarcinoma","authors":"S. Shim ,&nbsp;A.C. Larsen ,&nbsp;L. Bæksgaard ,&nbsp;P. Pfeiffer ,&nbsp;M. Nordsmark ,&nbsp;J.R. Sørensen ,&nbsp;A.K. Motavaf ,&nbsp;M. Ladekarl","doi":"10.1016/j.esmogo.2025.100183","DOIUrl":"10.1016/j.esmogo.2025.100183","url":null,"abstract":"<div><h3>Background</h3><div>The long-term fate of patients treated for resectable gastro-esophageal adenocarcinoma with perioperative chemotherapy outside randomized clinical trials (RCTs) is poorly described. In this national cohort, we report on outcomes after 12 years.</div></div><div><h3>Materials and methods</h3><div>Baseline clinicopathological factors and blood tests were collected in 285 patients treated from May 2008 to June 2010, and postsurgical factors were collected in the 202 patients that were radically resected. Response to preoperative chemotherapy was assessed by postsurgical restaging. Additional information on second cancers, comorbidities, and competing causes of death was obtained.</div></div><div><h3>Results</h3><div>Overall survival (OS) at 5 and 10 years was 31.9% and 24.2%, respectively. Multivariate analysis (MA) showed prognostic value of clinical T- and N-stage, dysphagia, and Charlson Comorbidity Index. Elevated leucocytes and lactate dehydrogenase, and low lymphocytes were additional adverse prognostic factors. Ten-year incidence rate of second cancers was 10.1%.</div><div>OS at 5 and 10 years from radical surgery was 43.1% and 32.1%, respectively. MA showed prognostic value of postneoadjuvant pathological (yp) Union for International Cancer Control (UICC) stage and downstaging. However, downstaging was strongly correlated with clinical stage. At the 5-year landmark, marginally significant trends toward a favorable recurrence-free survival were associated with ypT0 and age &lt;70 years, but only 3.4% experienced late recurrences. Postoperative complications caused a quarter of deaths in the half of radically resected patients who died without recurrence.</div></div><div><h3>Conclusions</h3><div>Five-year OS was 4%-6% points inferior to RCTs. Pretreatment white blood cell counts, but not postoperative, could supplement clinical prognostic factors. Downstaging by preoperative chemotherapy was prognostic but correlated strongly with pretreatment clinical stage.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100183"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-onset enriches the identification of actionable alterations in patients with KRAS wild-type pancreatic ductal adenocarcinoma","authors":"E. Scarlato ,&nbsp;S. Casalino ,&nbsp;L. Mendo ,&nbsp;A. Sordo ,&nbsp;V. De Vita ,&nbsp;E. San Lorenzo ,&nbsp;A. Quinzii ,&nbsp;C. Zecchetto ,&nbsp;G. Butturini ,&nbsp;D. Melisi","doi":"10.1016/j.esmogo.2025.100179","DOIUrl":"10.1016/j.esmogo.2025.100179","url":null,"abstract":"<div><h3>Background</h3><div>Approximately 10% of pancreatic ductal adenocarcinoma (PDAC) cases are <em>KRAS</em> wild-type (<em>KRAS</em>-wt). Among these, only a small subgroup harbors druggable genomic alterations, raising the question of when to apply broader next-generation DNA sequencing testing. Early-onset (EO) PDAC is increasing globally, with recent evidence suggesting an enrichment of <em>KRAS</em>-wt cases in younger patients.</div></div><div><h3>Patients and methods</h3><div>This retrospective observational study analyzed secondary data from a predefined database. Genomic alterations were identified using FoundationOne CDx or Liquid gene panels in patients who had failed standard treatments. Cases were classified by <em>KRAS</em> status, and <em>KRAS</em>-wt patients were stratified into EO (≤52.5 years) and late-onset (LO) (&gt;52.5 years) groups. Alterations were evaluated according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESMO ESCAT).</div></div><div><h3>Results</h3><div>Next-generation sequencing was carried out on 224 PDAC and 10 pancreatic acinar cell carcinoma (PACC) patients. Within PDAC patients, 23.2% (52/224) were <em>KRAS</em>-wt. Actionable TIER I-III alterations were more frequent in <em>KRAS</em>-wt cases (23.1% versus 11.6%, <em>P</em> = 0.04), with gene fusion events exclusively found in <em>KRAS</em>-wt (9.6% versus 0%, <em>P</em> = 0.0006). Among <em>KRAS</em>-wt PDACs, significantly higher frequencies of druggable TIER I-III were identified across EO-PDAC (6 versus 6, or 54.5% versus 14.6%, <em>P</em> = 0.006). Notably, actionable gene fusions were found to be significantly enriched in <em>KRAS</em>-wt EO-PDACs compared with LO counterparts (4 versus 1, or 36.4% versus 2.4%, <em>P</em> = 0.005).</div></div><div><h3>Conclusions</h3><div><em>KRAS</em>-wt PDAC diagnosed at a younger age more frequently harbors actionable mutations, highlighting the importance of comprehensive genomic profiling to guide targeted therapeutic interventions in this patient population.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100179"},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089167","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}