ESMO Gastrointestinal Oncology最新文献

{"title":"Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients","authors":"R. Naddaf ,&nbsp;H. Shmilovich ,&nbsp;S. Carasso ,&nbsp;R. Keshet-David ,&nbsp;R. Herren ,&nbsp;T. Gefen ,&nbsp;T. Goshen-Lago ,&nbsp;Y. Zwang ,&nbsp;I. Livyatan ,&nbsp;N. Shental ,&nbsp;O. Haberfeld ,&nbsp;R. Straussman ,&nbsp;S.R. Markar ,&nbsp;M. Nilsson ,&nbsp;H. Kashtan ,&nbsp;I. Ben-Aharon ,&nbsp;N. Geva-Zatorsky","doi":"10.1016/j.esmogo.2025.100172","DOIUrl":"10.1016/j.esmogo.2025.100172","url":null,"abstract":"<div><h3>Background</h3><div>Despite continuous improvement in long-term survival after esophagectomy, potential serious post-operative complications, such as anastomotic leaks (ALs), still occur. Several risk factors for ALs have been proposed, including environmental factors. Our main objective was to examine the correlation of esophageal tumor microbiome composition and functional profile with ALs. Additionally, we analyzed the microbiome of esophageal tumors and their potential correlation with clinical features of the patients.</div></div><div><h3>Materials and methods</h3><div>Surgical specimens of esophageal tumors and adjacent normal tissues were collected from consecutive patients who underwent an esophagectomy. Formalin-fixed paraffin-embedded (FFPE) tissue samples were processed using 16S ribosomal DNA multiple fragments amplicon sequencing to characterize bacterial microbiome composition. The tumor and normal tissue microbiome and bacterial functional profile were analyzed based on the clinical outcome of ALs.</div></div><div><h3>Results</h3><div>Out of 60 patients who met the inclusion criteria, 52 (86.7%) patients had both normal adjacent tissue (NAT) and tumor (T) FFPE samples included with sufficient bacterial DNA extracted for analysis. A total of 28% of participants had esophageal ALs. Proportion tests [<em>P</em> &lt; 0.05, false discovery rate (FDR) &lt; 0.25] revealed operational taxonomic units (OTUs) significantly present in T samples as opposed to NAT samples, as well as significantly present OTUs in patients with AL as opposed to patients without AL complication.</div></div><div><h3>Conclusions</h3><div>In this study, we provide a profile of the understudied esophageal microbiome and its connection to ALs. Our results can provide potential clues on how to avoid ALs by considering a patient’s personal microbiome when providing perioperative care.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100172"},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089166","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 for overall survival in advanced digestive neuroendocrine carcinoma treated with first-line cisplatin-based chemotherapy: a post hoc analysis of JCOG1213","authors":"H. Hirano ,&nbsp;K. Hirata ,&nbsp;Y. Honma ,&nbsp;C. Morizane ,&nbsp;N. Machida ,&nbsp;K. Kato ,&nbsp;T. Okusaka ,&nbsp;N. Boku ,&nbsp;S. Sekine ,&nbsp;N. Hiraoka ,&nbsp;J. Mizusawa ,&nbsp;Y. Sano ,&nbsp;Y. Shibuya ,&nbsp;M. Takahashi ,&nbsp;N. Fujimori ,&nbsp;M. Nomura ,&nbsp;Y. Doki ,&nbsp;M. Ueno ,&nbsp;T. Yoshikawa ,&nbsp;H. Takeuchi","doi":"10.1016/j.esmogo.2025.100178","DOIUrl":"10.1016/j.esmogo.2025.100178","url":null,"abstract":"<div><h3>Background</h3><div>There is no consensus on prognostic factors for advanced digestive neuroendocrine carcinoma (ADNEC). JCOG1213 was a phase III randomized trial that demonstrated equivalent overall survival (OS) between cisplatin plus etoposide and cisplatin plus irinotecan as first-line chemotherapy for ADNEC. We aimed to retrospectively explore prognostic factors for OS in patients with ADNEC using data from JCOG1213.</div></div><div><h3>Patients and methods</h3><div>The patients included in this <em>post hoc</em> analysis had ADNEC (2019 World Health Organization classification system) that was histologically confirmed by a central pathological review whose records included all clinical data required for multivariable analysis using a Cox proportional hazards model.</div></div><div><h3>Results</h3><div>Among 170 patients enrolled in JCOG1213, a total of 129 patients with ADNEC were included in this analysis. Multivariable analysis identified elevated serum lactate dehydrogenase (LDH; &gt;222 IU/l) as a significantly unfavorable prognostic factor for OS [hazard ratio (HR) 1.721, 95% confidence interval (CI) 1.144-2.589, <em>P</em> = 0.0092]. OS of patients with elevated serum LDH was shorter than that of patients without elevated serum LDH [median 9.5 months (95% CI 8.1-10.7 months) versus 15.6 months (95% CI 11.4-19.7 months); HR 1.799, 95% CI 1.242-2.604, <em>P</em> = 0.0019]. There were no distinct differences either in objective response rates or progression-free survival between patients with and without elevated serum LDH.</div></div><div><h3>Conclusion</h3><div>Serum LDH may serve as a simple, non-invasive, and clinically informative biomarker for prognostic evaluation in patients with ADNEC undergoing first-line platinum-based chemotherapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100178"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068437","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":"The clinical utility of an mGPS and SII combined score in patients with advanced gastric cancer treated with nivolumab monotherapy","authors":"S. Udagawa,&nbsp;A. Ooki,&nbsp;H. Osumi,&nbsp;K. Yoshino,&nbsp;M. Tamba,&nbsp;K. Shimozaki,&nbsp;S. Fukuoka,&nbsp;T. Wakatsuki,&nbsp;M. Ogura,&nbsp;E. Shinozaki,&nbsp;K. Chin,&nbsp;K. Yamaguchi","doi":"10.1016/j.esmogo.2025.100177","DOIUrl":"10.1016/j.esmogo.2025.100177","url":null,"abstract":"<div><h3>Background</h3><div>Several nutritional and inflammatory indices can predict the efficacy of immune checkpoint inhibitors and the prognosis in various cancers. However, indices that are useful for patients with advanced gastric cancer (AGC) remain unclear.</div></div><div><h3>Materials and methods</h3><div>This retrospective study was conducted at a single cancer center. Patients with AGC who received nivolumab as a third- or later-line treatment between June 2017 and May 2023 were selected. The association between nutritional and inflammatory indices and clinical outcomes was analyzed.</div></div><div><h3>Results</h3><div>In total, 277 patients were analyzed. Multivariate analysis revealed that several indices were significantly associated with time to treatment failure (TTF) and overall survival (OS) after adjustment for clinicopathological factors. The modified Glasgow prognostic score (mGPS) and systemic immune-inflammation index (SII) were identified as the most promising indices. A combined score (CS) developed by summing the SII and mGPS was associated with a shorter TTF and OS in CS 1 or 2 than in CS 0 [TTF: hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.04-1.87, <em>P</em> = 0.03 for CS 1 and HR 2.04, 95% CI 1.49-2.80, <em>P</em> &lt; 0.01 for CS 2; OS: HR 1.45, 95% CI 1.08-1.96, <em>P</em> &lt; 0.01 for CS 1 and HR 2.81, 95% CI 2.06-3.82, <em>P</em> &lt; 0.01 for CS 2]. CS 2 had a positive predictive value of 78.1% for detecting the first progressive disease. The clinical significance of CS was also confirmed in the first-line cohort.</div></div><div><h3>Conclusion</h3><div>CS may be useful for predicting treatment efficacy and prognosis in nivolumab-treated patients with AGC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100177"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary discussion in upper GI tumours: management of a patient with a locally advanced Siewert II gastroesophageal junctional adenocarcinoma","authors":"A. Petrillo ,&nbsp;T. Fleitas-Kanonnikoff ,&nbsp;M. Nilsson ,&nbsp;T. Leong ,&nbsp;H.W.M. van Laarhoven","doi":"10.1016/j.esmogo.2025.100176","DOIUrl":"10.1016/j.esmogo.2025.100176","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100176"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary discussion on upper GI tumours: management of a patient with a middle-third locally advanced squamous-cell carcinoma","authors":"A. Petrillo ,&nbsp;T. Fleitas-Kanonnikoff ,&nbsp;M. Nilsson ,&nbsp;T. Leong ,&nbsp;H.W.M. van Laarhoven","doi":"10.1016/j.esmogo.2025.100175","DOIUrl":"10.1016/j.esmogo.2025.100175","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100175"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world clinical impact of first-line immune checkpoint inhibitor-based therapy in advanced esophageal squamous cell carcinoma","authors":"M. Tamba ,&nbsp;K. Chin ,&nbsp;H. Osumi ,&nbsp;M. Ogura ,&nbsp;S. Fukuoka ,&nbsp;S. Udagawa ,&nbsp;K. Shimozaki ,&nbsp;K. Yoshino ,&nbsp;T. Wakatsuki ,&nbsp;E. Shinozaki ,&nbsp;K. Yamaguchi ,&nbsp;A. Ooki","doi":"10.1016/j.esmogo.2025.100171","DOIUrl":"10.1016/j.esmogo.2025.100171","url":null,"abstract":"<div><h3>Background</h3><div>Chemotherapy (chemo) combined with an immune checkpoint inhibitor (ICI) or dual ICI therapy with nivolumab and ipilimumab (nivo + ipi) is the standard first-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC). In this study, we evaluated real-world clinical outcomes for first-line ICI-based therapy and explored its prognostic factors.</div></div><div><h3>Patients and methods</h3><div>This single-center retrospective study included patients with ESCC who received ICI-based therapy between January 2021 and July 2024.</div></div><div><h3>Results</h3><div>In total, 92 patients received either ICI + chemo (<em>n</em> = 60) or nivo + ipi (<em>n</em> = 32). The median progression-free survival and overall survival (OS) were 5.0 and 16.0 months for ICI + chemo and 3.5 and 16.9 months for nivo + ipi, respectively. Of the 70 patients with measurable lesions, early tumor shrinkage (ETS) was achieved in 37% for ICI + chemo and 33% for nivo + ipi. ETS was significantly associated with a lower performance status and neutrophil-to-lymphocyte ratios, but not with the treatment regimen or programmed death-ligand 1 (PD-L1) status. Patients who achieved ETS showed significant tumor reduction and a durable response. ETS was an independent predictor of favorable OS (hazard ratio 0.34, 95% confidence interval 0.11-0.88, <em>P</em> = 0.04), whereas neither the treatment regimen nor the PD-L1 status influenced OS. Immune-related adverse events of grade ≥3 occurred in 12% of patients.</div></div><div><h3>Conclusions</h3><div>First-line immunotherapy is effective and safe for the treatment of patients with ESCC. Rapid and deep tumor shrinkage may serve as an early predictive biomarker for longer survival.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100171"},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total neoadjuvant therapy in early-onset versus average-onset locally advanced rectal cancer: patient characteristics and tolerance of therapy☆","authors":"M.L. Conces ,&nbsp;N. Tursun ,&nbsp;I. Ozgur ,&nbsp;S. Yilmaz ,&nbsp;D. Elamin ,&nbsp;S. Patil ,&nbsp;Y. Bouferraa ,&nbsp;E. Gorgun ,&nbsp;D. Liska ,&nbsp;E. Weinstein ,&nbsp;S.D. Kamath ,&nbsp;S.R. Steele ,&nbsp;A.A. Khorana ,&nbsp;B. Laderian ,&nbsp;T.T. Jayakrishnan ,&nbsp;K.G. Nair ,&nbsp;S.R. Amarnath ,&nbsp;E.H. Balagamwala ,&nbsp;B.N. Estfan ,&nbsp;H. Kessler ,&nbsp;S.S. Krishnamurthi","doi":"10.1016/j.esmogo.2025.100170","DOIUrl":"10.1016/j.esmogo.2025.100170","url":null,"abstract":"<div><h3>Background</h3><div>Patients with early-onset (EO, age &lt;50 years) compared with average onset (AO, age ≥50 years) colorectal cancer have significantly higher rates of gastrointestinal toxicity with fluoropyrimidine and oxaliplatin therapy in the metastatic and adjuvant settings. Limited data exist regarding tolerance of total neoadjuvant therapy (TNT) when treating younger patients with locally advanced rectal cancer (LARC) despite the rising incidence of EO rectal cancer.</div></div><div><h3>Materials and methods</h3><div>Data were abstracted from a retrospective database of patients with LARC treated with TNT from 1 January 2015 through 28 April 2021. Characteristics compared between EO and AO patients were demographic features, baseline characteristics of tumor, treatment delivery, antiemetic use, and toxicities.</div></div><div><h3>Results</h3><div>Of 115 patients (39 EO, 76 AO), female patients constituted 51% of EO patients and 34% of AO patients (<em>P</em> = 0.077). No differences were found in race, ethnicity, clinical stage, dose of radiation or chemotherapy received, and antiemetic premedications and prescriptions. EO patients (versus AO patients) had more nausea (59% versus 28%, <em>P</em> = 0.001), fatigue (72% versus 47%, <em>P</em> = 0.013), and proctitis (28% versus 13%, <em>P</em> = 0.048) during chemoradiation and more nausea (69% versus 42%, <em>P</em> = 0.006) and stomatitis (21% versus 3.9%, <em>P</em> = 0.007) during chemotherapy. After adjusting for sex, EO patients were still at a greater odds of nausea compared with AO during chemoradiation (odds ratio 3.45, 95% confidence interval 1.51-7.69, <em>P</em> = 0.004) and chemotherapy (odds ratio 2.85, 95% confidence interval 1.28-6.67, <em>P</em> = 0.012).</div></div><div><h3>Conclusions</h3><div>Patients with EO, compared with AO, LARC receiving TNT appear to have higher rates of nausea and should be considered for enhanced antiemetic regimens.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100170"},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative metronidazole treatment to evaluate its efficacy in reducing Fusobacterium nucleatum colonisation in colorectal cancer patients: a proof-of-concept trial","authors":"S. De Dosso ,&nbsp;D. Christoforidis ,&nbsp;E. Merlo ,&nbsp;A. Vannelli ,&nbsp;S. Popeskou ,&nbsp;P. Gaffuri ,&nbsp;G. Lollo ,&nbsp;L. Ambrosiani ,&nbsp;F. Radaelli ,&nbsp;M. Frattini ,&nbsp;M. Marengo ,&nbsp;K. Galetti ,&nbsp;G. Iezzi","doi":"10.1016/j.esmogo.2025.100169","DOIUrl":"10.1016/j.esmogo.2025.100169","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) is one of the most prevalent tumour types and a leading cause of cancer-related mortality worldwide. Surgery represents the primary therapeutic option, while advanced cases are typically managed with established chemotherapy protocols, which exhibit variable response rates. Recently, the gut microbiota has been implicated in chemoresistance. Notably, <em>Fusobacterium nucleatum</em>, a commensal bacterium found in the oral cavity, is enriched in CRC tissues and has been shown in experimental models to promote CRC cell proliferation and diminish tumour responsiveness to 5-fluorouracil. Though the administration of metronidazole has effectively reduced <em>F. nucleatum</em> load and overall tumour growth in animal models, its efficacy in decreasing <em>F. nucleatum</em> loads in human CRC has yet to be verified.</div></div><div><h3>Aim</h3><div>This proof-of-concept trial aims to determine the effectiveness of metronidazole in reducing the <em>F. nucleatum</em> load in tissues and its potential detrimental effects on tumour cells and the tumour microenvironment.</div></div><div><h3>Trial design</h3><div>Forty patients newly diagnosed with CRC, for whom surgical resection is planned, will receive metronidazole for 10 days before surgery, which must be scheduled within 3 days following the last administration. Patients who do not receive the treatment for at least 7 days will be deemed ineligible for the study and will be replaced. <em>Fusobacterium nucleatum</em> abundance will be assessed through specific quantitative PCR analysis on genomic DNA extracted from diagnostic biopsies and excised tissues, with comparative analysis.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100169"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European screening platform for EORTC clinical trials in advanced colorectal cancer ‘SPECTAcolor’","authors":"G. Folprecht ,&nbsp;M. Morfouace ,&nbsp;M. Collienne ,&nbsp;R. Salazar ,&nbsp;A. Stein ,&nbsp;E. Elez ,&nbsp;A.D. Wagner ,&nbsp;D. Arnold ,&nbsp;C.H. Kohne ,&nbsp;M. Ducreux ,&nbsp;F. Lordick ,&nbsp;B. Borelli ,&nbsp;A. Stevovic ,&nbsp;T. Gorlia ,&nbsp;E. Fontana ,&nbsp;D. Aust ,&nbsp;V. Golfinopoulos ,&nbsp;M. Moehler ,&nbsp;S. Tejpar","doi":"10.1016/j.esmogo.2025.100168","DOIUrl":"10.1016/j.esmogo.2025.100168","url":null,"abstract":"<div><h3>Background</h3><div>The European Organisation for Research and Treatment of Cancer (EORTC) has established the Screening Platform for Efficient Clinical Trial Access for COLORectal Patients (SPECTAcolor), which provides centralized molecular testing to screen patients for and facilitate enrollment in molecular-based therapeutic trials.</div></div><div><h3>Materials and methods</h3><div>Patients with advanced or metastatic colorectal malignancies were recruited in 11 European countries. Patients’ paraffin-embedded material was tested for <em>KRAS</em><em>, NRAS, BRAF</em>, and <em>PI3K</em> microsatellite instability-high (MSI-H) (not routine at the time of recruitment) and later by a 300-gene next-generation sequencing panel. RNA profiling was carried out in a subset of patients. Results were reported to the centers and patients were followed up for their clinical outcome.</div></div><div><h3>Results</h3><div>Recruitment began in September 2013. The molecular screening program was completed at the end of 2015. A total of &gt;1000 patients were prospectively recruited into SPECTAcolor. Molecular and complete clinical/follow-up data are available for 845 metastatic colorectal cancer (CRC) patients. The simple κ coefficient for the agreement between local and central testing for <em>KRAS</em>, <em>NRAS</em>, and <em>BRAF</em> was 0.82-0.95, and the κ for MSI-H was 0.55. The median overall survival was 56.6 months. Patients with <em>BRCA</em>, <em>FGFR</em>, and <em>HER2</em> alterations had a trend toward shorter survival.</div></div><div><h3>Conclusion</h3><div>SPECTAcolor demonstrated that recruitment to an academic screening platform is feasible and that central (quality-assured) testing may remain necessary even for commonly tested markers. SPECTAcolor has generated a clinical and molecular dataset with associated samples for &gt;800 CRC patients for future academic research such as biomarker validation. Linking screening platforms to therapeutic trials and ensuring sustainability remain challenging.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100168"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative benefit–risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma","authors":"J.W. Valle ,&nbsp;G.K. Abou-Alfa ,&nbsp;R.K. Kelley ,&nbsp;M.A. Lowery ,&nbsp;R.T. Shroff ,&nbsp;Y. Bian ,&nbsp;G. Saint-Hilary ,&nbsp;H. Liu ,&nbsp;Z. Teng ,&nbsp;Z. Hua ,&nbsp;C. Gliser ,&nbsp;A. Vogel ,&nbsp;M.M. Javle","doi":"10.1016/j.esmogo.2025.100159","DOIUrl":"10.1016/j.esmogo.2025.100159","url":null,"abstract":"<div><h3>Background</h3><div>Quantitative drug benefit–risk assessment (BRA) helps assess the magnitude of benefit and risk of new cancer therapies. This BRA aimed to summarize the evidence for the benefits and risks of ivosidenib versus placebo for the treatment of previously treated, locally advanced or metastatic mutant isocitrate dehydrogenase-1 cholangiocarcinoma using data from the pivotal phase III ClarIDHy study.</div></div><div><h3>Materials and methods</h3><div>Cholangiocarcinoma experts determined relevant key benefit and risk criteria for ivosidenib and placebo to create a value tree and determined scales and weights. Multi-Criteria Decision Analysis modelling approaches were then applied to the ClarIDHy data to estimate the probability that the benefit–risk profile of ivosidenib was better than that of placebo.</div></div><div><h3>Results</h3><div>A total of 187 patients were randomly assigned to ivosidenib 500 mg (<em>n</em> = 126) or placebo (<em>n</em> = 61). The primary analysis [Scale Loss Score (SLoS) model] showed a 95.24% probability for the benefit–risk profile favoring ivosidenib versus placebo. Sensitivity analyses applying the SLoS model to alternative sets, and the linear and product models to the main and alternative sets, of benefit and risk criteria in the value tree also showed consistently high probability for the benefit–risk profile favoring ivosidenib versus placebo for all endpoints evaluated (SLoS model: &gt;95%; linear model: &gt;99%; product model: &gt;94%). Similarly, the random weights analysis favored ivosidenib with all evaluated weights and results converging quickly towards the main analysis results.</div></div><div><h3>Conclusions</h3><div>These results provide comprehensive evidence that ivosidenib is an effective treatment with a tolerable safety profile for this aggressive disease, supporting previous data (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> NCT02989857).</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"8 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}