ESMO Gastrointestinal Oncology最新文献

{"title":"The outcomes of elderly patients with localized squamous-cell carcinoma of the anal canal treated with chemoradiation","authors":"M.P.G. Camandaroba,&nbsp;S. Aguiar Jr.,&nbsp;V. Souza e Silva,&nbsp;R.P. Riechelmann","doi":"10.1016/j.esmogo.2025.100282","DOIUrl":"10.1016/j.esmogo.2025.100282","url":null,"abstract":"<div><h3>Background</h3><div>Squamous-cell carcinoma of the anal canal (SCCA) is a rare gastrointestinal malignancy, and its incidence is increasing among the aging population. This study aims to examine treatment efficacy and toxicity in elderly patients and to compare treatment outcomes between elderly and non-elderly patients to inform optimal management strategies for SCCA in older adults.</div></div><div><h3>Patients and methods</h3><div>This retrospective study evaluates clinical outcomes in elderly (≥70 years) versus non-elderly (&lt;70 years) patients with localized SCCA treated with definitive chemoradiotherapy or radiotherapy alone. The primary endpoints were overall survival (OS) and disease-free survival (DFS), whereas secondary endpoints were cancer-specific survival (CSS), complete response rates and grade 3 or 4 toxicity profiles. Statistical analyses were conducted using descriptive statistics, Kaplan–Meier methods, and Cox proportional hazards models.</div></div><div><h3>Results</h3><div>The study analyzed 269 patients. Elderly patients had a median age of 77.3 (range 70-83) years and presented with a higher burden of comorbidities and a lower prevalence of human immunodeficiency virus. No significant differences in treatment types or toxicity rates were observed between the groups. The median DFS for elderly patients was 103 months versus 128 months for non-elderly patients (<em>P</em> = 0.43). CSS rates were comparable, showing a rate of 83% at five years for the elderly compared with 85% for non-elderly patients (<em>P</em> = 0.74). Cox regression analyses revealed that cancer stage and treatment completion were significant predictors of DFS and OS.</div></div><div><h3>Conclusion</h3><div>This study highlights that while elderly patients with SCCA experience similar survival outcomes to their younger counterparts, age-related factors and comorbidities require careful management to optimize treatment efficacy while minimizing toxicity.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100282"},"PeriodicalIF":0.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926897","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":"Corrigendum to “Feasibility of stereotactic radiotherapy with pembrolizumab in patients with deficient mismatch repair/microsatellite unstable metastatic colorectal cancer”","authors":"A. Gandini ,&nbsp;V. Martelli ,&nbsp;L. Belgioia ,&nbsp;S. Puglisi ,&nbsp;M. Cremante ,&nbsp;V. Murianni ,&nbsp;A. Damassi ,&nbsp;C. Pirrone ,&nbsp;F. Catalano ,&nbsp;M. Grassi ,&nbsp;L. Trevisan ,&nbsp;S. Vagge ,&nbsp;V. Andretta ,&nbsp;S. Mammoliti ,&nbsp;D. Comandini ,&nbsp;G. Fornarini ,&nbsp;A. Pessino ,&nbsp;A. Pastorino ,&nbsp;S. Sciallero ,&nbsp;A. Puccini ,&nbsp;A.F. Sobrero","doi":"10.1016/j.esmogo.2025.100279","DOIUrl":"10.1016/j.esmogo.2025.100279","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100279"},"PeriodicalIF":0.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926896","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":"Clinical outcomes of carbon-ion radiotherapy for residual or recurrent hepatocellular carcinoma after transarterial chemoembolization","authors":"Y. Sekiguchi ,&nbsp;K. Shibuya ,&nbsp;S. Tomogane ,&nbsp;Y. Miyasaka ,&nbsp;S. Kakizaki ,&nbsp;M. Okamoto ,&nbsp;K. Araki ,&nbsp;K. Shirabe ,&nbsp;T. Ohno","doi":"10.1016/j.esmogo.2025.100280","DOIUrl":"10.1016/j.esmogo.2025.100280","url":null,"abstract":"<div><h3>Background</h3><div>Transarterial chemoembolization (TACE) or embolization (TAE) for hepatocellular carcinoma (HCC) is often followed by an incomplete response or local recurrence, necessitating effective salvage therapies. Carbon-ion radiotherapy (CIRT) offers potential radiobiological advantages for treating TACE-refractory tumors. This study aimed to evaluate the efficacy and safety of CIRT for residual or recurrent HCC after TACE/TAE.</div></div><div><h3>Patients and methods</h3><div>We retrospectively analyzed 99 patients (106 lesions) treated with CIRT between 2010 and 2021. Eligible patients had residual or recurrent HCC after 52.8-60.0 Gy [relative biological effectiveness (RBE)] in 4 fractions, or 60.0 Gy (RBE) in 12 fractions for tumors near critical structures. Efficacy endpoints were local control (LC), overall survival (OS), and progression-free survival (PFS). Toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0, and liver function was monitored using Child–Pugh and albumin–bilirubin (ALBI) scores.</div></div><div><h3>Results</h3><div>At a median follow-up of 38 months, the 3-year OS, PFS, and LC rates were 70.3%, 34.8%, and 90.7%, respectively. On multivariate analysis, larger tumor size (≥3.5 cm) and poorer baseline liver function (modified ALBI grade ≥2b) were significant predictors of worse OS. The treatment was well tolerated; severe (grade ≥3) late toxicities were rare, including two cases of encephalopathy. There was no statistically significant deterioration in Child–Pugh or ALBI scores following treatment.</div></div><div><h3>Conclusions</h3><div>CIRT is a safe and effective salvage therapy for TACE-refractory HCC, offering excellent LC, favorable survival outcomes, and preserved liver function.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926804","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":"A review of established and new developments in local therapies for liver cancer","authors":"P. Seda ,&nbsp;R. Abbey ,&nbsp;L. Peng ,&nbsp;I. Ezeaku ,&nbsp;S.T. Laroia ,&nbsp;H. Aziz","doi":"10.1016/j.esmogo.2025.100283","DOIUrl":"10.1016/j.esmogo.2025.100283","url":null,"abstract":"<div><div>Liver cancer, especially hepatocellular carcinoma (HCC), which accounts for ∼75%-85% of primary liver cancers, remains a major global health challenge. Because of its high incidence, late diagnosis, and limited curative options, local therapies have become increasingly popular for the multidisciplinary management of HCC, especially in early and intermediate Barcelona Clinic Liver Cancer stages or in medically inoperable patients. This review examines a landscape of local treatment modalities for HCC encompassing radiofrequency ablation, microwave ablation, cryoablation, irreversible electroporation, histotripsy, transarterial chemoembolization, transarterial radioembolization, and stereotactic body radiotherapy. We also highlight their respective advantages and disadvantages, compare their survival outcomes, and identify current gaps in the literature, including the need for further comparisons between safety profiles and efficacy, and the growing landscape that is using different local therapies in a sequential or combinatorial fashion. Emphasis is placed on treatment decisions tailored to tumor burden, liver function, and patient-specific considerations. Expanding access to advanced local therapies in resource-limited settings remains a global priority.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100283"},"PeriodicalIF":0.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926898","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":"Clinicopathologic correlates of claudin 18.2 expression in esophagogastric cancer at multiple expression levels","authors":"C.H. Maeng ,&nbsp;A. Alkashash ,&nbsp;A. Sy ,&nbsp;H. Barnes ,&nbsp;S. Bannon ,&nbsp;C. Simms ,&nbsp;M.R. Strickland ,&nbsp;J.N. Glickman ,&nbsp;S.J. Klempner","doi":"10.1016/j.esmogo.2025.100278","DOIUrl":"10.1016/j.esmogo.2025.100278","url":null,"abstract":"<div><h3>Background</h3><div>Claudin-18 isoform 2 (CLDN18.2) is a validated therapeutic target in gastric cancer (GC) and gastroesophageal junction cancer (GEJ). The approved antibody zolbetuximab requires higher expression levels (≥75% of tumor cells with 2-3+ membranous staining), yet broader thresholds are increasingly explored. Data on clinicopathologic correlates and biomarker overlap at lower cut-offs remain limited.</div></div><div><h3>Patients and methods</h3><div>We retrospectively analyzed patients with esophageal cancer (EC), GEJ, or GC who underwent CLDN18.2 immunohistochemistry at a single high-volume center (2023-2025). CLDN18.2 positivity was defined using three thresholds: (i) stringent (<em>75% threshold</em>: ≥75% of tumor cells with 2-3+ staining); (ii) broader (<em>H-score 25</em>; ≥1+ intensity in ≥25% of cells); and (iii) the lowest (<em>H-score 10</em>; ≥1+ intensity in ≥10% of cells). Associations between CLDN18.2 and clinicopathologic variables, including histology and standard biomarkers [human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and mismatch repair (MMR)], were assessed.</div></div><div><h3>Results</h3><div>In total, 149 patients were included: 43 EC (28.9%), 46 GEJ (30.9%), and 60 GC (40.3%). CLDN18.2 positivity rates were 48.3%, 71.1%, and 73.8% at the <em>75%</em>, <em>H-score 25</em>, and <em>H-score 10</em> thresholds, respectively. CLDN18.2 positivity significantly correlated with tumor location, highest in GC and followed by GEJ and EC across thresholds. At the lowest cut-off, positivity was 85.0% in GC, 69.6% in GEJ, and 62.8% in EC (<em>P</em> = 0.030). Histological subtypes were also associated across thresholds: poorly cohesive carcinoma (PCC) demonstrated significantly higher positivity than non-PCC. No significant associations were found with HER2, PD-L1 combined positive score, or MMR. Triple positivity for CLDN18.2, HER2, and PD-L1 was rare (≤5.5%).</div></div><div><h3>Conclusion</h3><div>CLDN18.2 expression in upper gastrointestinal cancers was significantly associated with gastric origin and PCC histology, independent of HER2 and PD-L1 status. Broadening the threshold for positivity identified nearly three-quarters of patients as CLDN18.2 positive, underscoring the impact of selection cut points on trial eligibility. These findings highlight the potential to expand patient access to CLDN18.2-targeted therapies using lower thresholds.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100278"},"PeriodicalIF":0.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926805","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":"Growth differentiation factor-15 (GDF-15) in localized pancreatic adenocarcinoma treated with multiagent chemotherapy: a biomarker analysis from the NEOLAP trial (AIO-PAK-0113)","authors":"B. Kimmel ,&nbsp;S.T. Löhnert ,&nbsp;F. Wedekink ,&nbsp;M. Günther ,&nbsp;S. Ormanns ,&nbsp;I. Hartlapp ,&nbsp;J. Siveke ,&nbsp;G. Siegler ,&nbsp;S. Boeck ,&nbsp;H. Algül ,&nbsp;U. Martens ,&nbsp;F. Kullmann ,&nbsp;T. Ettrich ,&nbsp;S. Held ,&nbsp;F. Anger ,&nbsp;C.-T. Germer ,&nbsp;V. Heinemann ,&nbsp;J. Wischhusen ,&nbsp;V. Kunzmann","doi":"10.1016/j.esmogo.2025.100274","DOIUrl":"10.1016/j.esmogo.2025.100274","url":null,"abstract":"<div><h3>Background</h3><div>The prognostic and predictive role of growth differentiation factor-15 (GDF-15) in localized, non-metastatic pancreatic ductal adenocarcinoma (PDAC) has not yet been explored.</div></div><div><h3>Patients and methods</h3><div>During the prospective randomized phase II NEOLAP-1 (AIO-PAK-0113) trial for patients with therapy-naive locally advanced (borderline or unresectable) PDAC, blood (<em>n</em> = 131) and tumor tissue samples (<em>n</em> = 39) were collected. Using paired baseline and post-induction chemotherapy (ICT) samples, circulating GDF-15 (cGDF-15) levels were quantified by enzyme-linked immunosorbent assay, and local GDF-15 tumor expression (tGDF-15) was assessed by immunohistochemistry.</div></div><div><h3>Results</h3><div>Lower baseline cGDF-15 levels (≤0.8 ng/ml) were significantly associated with increased median overall survival [21.92 (95% CI 19.73-24.16) versus 12.68 [95% confidence interval (CI) 10.56-14.81] months, <em>P</em> &lt; 0.001, and significantly higher secondary R0 resection rates (36.5% versus 13.9%, <em>P</em> = 0.0051). In contrast to CA 19-9, cGDF-15 levels significantly increased after ICT [median 1.0 ng/ml [interquartile range (IQR) 0.62-1.5 ng/ml] at baseline versus median 2.37 ng/ml (IQR 1.32-4.43 ng/ml) at week 16], especially after treatment using platinum-based agents. In initial tumor specimens, GDF-15 expression was rare and predominantly confined to tumor cells. tGDF-15 correlated with high cGDF-15 levels at baseline [median 1.8 ng/ml (1.13-2.34 ng/ml) in positive tumor specimens, versus 0.76 ng/ml (0.55-1.17 ng/ml) in negative tumor specimens; <em>P</em> = 0.0087]. Similarly to cGDF-15, tGDF-15 expression increased after ICT (from 10% to 41% positive tumor specimens).</div></div><div><h3>Conclusions</h3><div>High cGDF-15 levels at baseline are a negative prognostic and predictive biomarker in localized, non-metastatic PDAC. Considering that GDF-15 is further up-regulated by neoadjuvant multiagent chemotherapy, our data, together with recent findings on clinical effects of GDF-15, provide a strong rationale for upfront therapeutic GDF-15 blockade in localized PDAC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100274"},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791900","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":"Impact of diabetes mellitus on treatment efficacy in patients with advanced pancreatic cancer: the Italian, multicenter, observational PANCAKE study","authors":"P. Andena ,&nbsp;G. Tine ,&nbsp;F. Nichetti ,&nbsp;A. Pretta ,&nbsp;L. Bartalini ,&nbsp;S. Ljevar ,&nbsp;A. Michelotti ,&nbsp;L. Salvatore ,&nbsp;M. Prisciandaro ,&nbsp;A. Franza ,&nbsp;G. Grelli ,&nbsp;P. Ziranu ,&nbsp;M. Bensi ,&nbsp;V. Mazzaferro ,&nbsp;J. Coppa ,&nbsp;C. Sciortino ,&nbsp;G. Zapelloni ,&nbsp;C. Pircher ,&nbsp;S.K. Garattini ,&nbsp;C. Vivaldi ,&nbsp;M. Niger","doi":"10.1016/j.esmogo.2025.100276","DOIUrl":"10.1016/j.esmogo.2025.100276","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) is a known risk factor for pancreatic ductal adenocarcinoma (PDAC). Preclinical evidence suggests higher glucose levels may enhance chemotherapy injury to PDAC cells. Clinical evidence of DM’s impact in patients with PDAC receiving palliative treatment remains conflicting, however.</div></div><div><h3>Materials and methods</h3><div>PANCAKE, an Italian multicenter observational study, assessed the impact of DM and blood glucose levels on progression-free survival during first-line treatment and overall survival (OS) in patients with advanced PDAC.</div></div><div><h3>Results</h3><div>Among 663 patients with available baseline and on-treatment glycemic values, DM was confirmed in 193 patients (29.1%). Pre-existing DM was associated with a modest but significant OS benefit [median OS 11.6 versus 10.3 months, adjusted hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.67-0.99; <em>P</em> = 0.036]. This benefit was significantly associated with the chemotherapy regimen: it was observed only in patients treated with first-line gemcitabine–nab-paclitaxel, but not with FOLFIRINOX. A longitudinal, Bayesian joint modelling approach accounting for the concomitant use of glucose-lowering medications confirmed a statistically significant, but clinically modest prognostic effect of glycemic trends, as a 10 mg/dl-point increase from baseline blood glucose values resulted associated with a 4% reduction in the risk of death (HR for OS 0.9967, 95% CI 0.9939-0.9995).</div></div><div><h3>Conclusions</h3><div>DM and higher blood glucose levels show a statistically significant, though clinically modest, impact on the OS of patients affected by advanced PDAC, which may be differential according to the chemotherapy regimen. This evidence lays the foundations to guide future studies on pharmacological and dietary approaches targeting tumor metabolism in this setting.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100276"},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791901","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":"Highlights in oesophagogastric cancers from ESMO congress 2025","authors":"A. Petrillo ,&nbsp;F. Pietrantonio ,&nbsp;T. Fleitas-Kanonnikoff","doi":"10.1016/j.esmogo.2025.100275","DOIUrl":"10.1016/j.esmogo.2025.100275","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100275"},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791902","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":"ESMO podcast on upper GI cancers: highlights in hepatocellular carcinoma and pancreatic cancer from ESMO 2025","authors":"J. Dekervel ,&nbsp;A. Vogel ,&nbsp;E. O’Reilly","doi":"10.1016/j.esmogo.2025.100277","DOIUrl":"10.1016/j.esmogo.2025.100277","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100277"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145738835","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":"An open label phase II study of total neoadjuvant therapy (TNT) consisting of FLOT with pembrolizumab and short radiation for patients with locally advanced gastroesophageal junction adenocarcinoma (EPOC2301)","authors":"K. Sato ,&nbsp;I. Nakayama ,&nbsp;M. Yura ,&nbsp;A. Sato ,&nbsp;M. Suzuki ,&nbsp;T. Kadota ,&nbsp;M. Nakamura ,&nbsp;N. Sakamoto ,&nbsp;T. Hashimoto ,&nbsp;S. Sakashita ,&nbsp;M. Wakabayashi ,&nbsp;H. Shoji ,&nbsp;T. Hayashi ,&nbsp;H. Daiko ,&nbsp;K. Kato ,&nbsp;T. Yoshino ,&nbsp;T. Yano ,&nbsp;T. Fujita ,&nbsp;T. Kinoshita ,&nbsp;K. Shitara","doi":"10.1016/j.esmogo.2025.100267","DOIUrl":"10.1016/j.esmogo.2025.100267","url":null,"abstract":"<div><h3>Background</h3><div>Durvalumab combined with fluorouracil, leucovorin, oxaliplatin, and docetaxel (D-FLOT) has demonstrated significant improvement in event-free survival (EFS) among patients with resectable gastric and gastroesophageal junction adenocarcinoma (GEJA) and is expected to become a new standard of care. Nevertheless, surgical resection remains requisite and is associated with substantial morbidity and deterioration in quality of life for GEJA. Given that D-FLOT achieves a pathological complete response in ∼20% of patients, intensification of total neoadjuvant therapy with short-course radiation (SRT) could further increase clinical CR (cCR) rates and facilitate non-operative management (NOM) in selected GEJA patients.</div></div><div><h3>Trial design</h3><div>EPOC2301 is a single-arm, phase II study evaluating the efficacy and safety of pembrolizumab with FLOT plus SRT as total neoadjuvant therapy for resectable GEJA. Patients receive two cycles of FLOT and one dose of pembrolizumab, followed by 25 Gy radiotherapy, then two more cycles of FLOT and one dose of pembrolizumab. Response is assessed by computed tomography, positron emission tomography-computed tomography, endoscopy with bite-on-bite biopsy, and whole-genome circulating tumor DNA analysis. Patients achieving cCR or near-cCR continue NOM with pembrolizumab and FLOT, whereas those without adequate response undergo surgery followed by adjuvant pembrolizumab and FLOT. The primary endpoint is 3-year EFS.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100267"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693513","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}