European Journal of Cancer最新文献

{"title":"Elevated serum magnesium levels prompt favourable outcomes in cancer patients treated with immune checkpoint blockers","authors":"Sait Kitapli, Ali Alkan, Ozgur Tanriverdi","doi":"10.1016/j.ejca.2024.115188","DOIUrl":"10.1016/j.ejca.2024.115188","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115188"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter Re: Elevated serum magnesium levels prompt favourable outcomes in cancer patients treated with immune checkpoint blockers","authors":"Ziyi Wang, Zihan Wang","doi":"10.1016/j.ejca.2024.115187","DOIUrl":"10.1016/j.ejca.2024.115187","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115187"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized monitoring for immune checkpoint inhibitor induced myocarditis using high-sensitivity troponin-T","authors":"Dirk Tomsitz ,&nbsp;Ulrich Grabmaier ,&nbsp;Judith Spiro ,&nbsp;Leo Nicolai ,&nbsp;Lars E. French ,&nbsp;Steffen Massberg ,&nbsp;Lucie Heinzerling","doi":"10.1016/j.ejca.2024.115186","DOIUrl":"10.1016/j.ejca.2024.115186","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitor (ICI)-induced Myocarditis (irMyocarditis) is a rare adverse event with a high mortality rate of 40–50 % and which is mostly not diagnosed until clinical symptoms emerge.</div></div><div><h3>Objectives</h3><div>This study aims to screen patients for irMyocarditis using high-sensitivity cardiac troponin-T (hs-TnT) before and regularly during therapy with ICI.</div></div><div><h3>Methods</h3><div>A cohort of 280 cancer patients were prospectively screened for levels of hs-TnT at baseline and prior to every ICI infusion. In case of elevation of hs-TnT, patients were referred for further work-up.</div></div><div><h3>Results</h3><div>In total, 196 patients exhibited a baseline hs-TnT ≤ 14 ng/l (99th percentile concentration for general population; group A) and 84 patients a hs-TnT &gt; 14 ng/l at baseline (group B). An increase of hs-TnT during ICI-treatment was observed in 56 out of 196 (27.6 %) and 56 out of 84 patients (66.7 %) in group A and B. Cardiovascular assessment was performed in 11.2 % and 27.4 % of patients, respectively, and 4.1 % and 9.5 % of patients were diagnosed with irMyocarditis and treated with corticosteroids. No fatalities occurred in any of the 16 irMyocarditis patients. Defining a threshold with the highest sensitivity and maximum specificity in receiver-operating characteristics curves, identified a limit of 22 ng/l (group A) and 60 ng/l (group B) hs-TnT, associated with a sensitivity of 100 % in both and a specificity of 91.0 % and 89.6 %, respectively, to detect irMyocarditis.</div></div><div><h3>Conclusion</h3><div>Screening of hs-TnT can identify irMyocarditis early and lead to reduction of MACE and mortality risk through interruption of ICI-treatment and prompt therapy with corticosteroids.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115186"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extensive molecular profiling of KRAS wild-type as compared to KRAS mutated pancreatic ductal adenocarcinoma on 318 patients","authors":"Jeanne Lena ,&nbsp;Mélissa Alamé ,&nbsp;Antoine Italiano ,&nbsp;Isabelle Soubeyran ,&nbsp;Laura Blouin ,&nbsp;Emmanuel Khalifa ,&nbsp;Sophie Cousin ,&nbsp;Simon Pernot ,&nbsp;Lola-Jade Palmieri","doi":"10.1016/j.ejca.2024.115197","DOIUrl":"10.1016/j.ejca.2024.115197","url":null,"abstract":"<div><h3>Purpose</h3><div>Molecular profiling is increasingly implemented to guide treatment of advanced pancreatic ductal adenocarcinoma (PDAC), especially when for clinical trials enrollment. This study aimed to describe actionable alterations detected in KRAS mutated (KRASm) versus KRAS wild-type (KRASwt) PDAC, the latter group being considered enriched in molecular alterations.</div></div><div><h3>Methods</h3><div>This prospective monocentric study included patients with locally advanced or metastatic PDAC who underwent next-generation sequencing (NGS) on liquid biopsy and/or tissue samples between 2015 and 2023, as part of the BIP academic study (NCT02534649). Actionable alterations were classified using the ESCAT (ESMO Scale for Clinical Actionability of molecular Targets).</div></div><div><h3>Results</h3><div>A total of 378 patients with a PDAC underwent NGS: 73 on tissue samples, 162 on liquid biopsies, and 143 on both tissue and liquid. Liquid biopsies had a 59.3 % performance (181 informative samples out of 305). Among 318 informative NGS samples, 273 (86 %) were <em>KRAS</em>m, and 45 (14 %) were <em>KRAS</em>wt. Median overall survival (OS) was 19.35 in <em>KRASwt</em> patients and 16.89 months for <em>KRAS</em>m patients (HR 0.67, 95 %CI (0.49–0.90), <em>p</em> = 0.02). ESCAT alterations were found in 15.7 % of total population, with 31.1 % in <em>KRAS</em>wt tumors and 13.2 % in <em>KRAS</em>m tumors. <em>BRCA1/2</em> mutations were identified in 7.5 % of the population, and one <em>NTRK</em> fusion was found in a <em>KRAS</em>wt PDAC. The molecular tumor board considered 71 patients (22.3 %) eligible for early-phase trials, with 14 treated with matched therapy.</div></div><div><h3>Conclusion</h3><div>Although actionable mutations were more frequent in <em>KRAS</em>wt tumors, 13.2 % of <em>KRAS</em>m PDAC harbored ESCAT alterations, emphasizing the importance of molecular profiling regardless of <em>KRAS</em> status.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115197"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies","authors":"Vincent Ribrag ,&nbsp;Lara Iglesias ,&nbsp;Filippo De Braud ,&nbsp;Brigette Ma ,&nbsp;Tomoya Yokota ,&nbsp;Thomas Zander ,&nbsp;Anna Spreafico ,&nbsp;Vivek Subbiah ,&nbsp;Anna L. Illert ,&nbsp;Daniel Tan ,&nbsp;Armando Santoro ,&nbsp;Pamela N. Munster ,&nbsp;Youko Suehiro ,&nbsp;Yongsheng Wang ,&nbsp;Dong-Mei Ji ,&nbsp;Shuqi Chen ,&nbsp;Karen Beltz ,&nbsp;Naoko Suenaga ,&nbsp;Thiruvamoor Ramkumar ,&nbsp;Fangjun Luo ,&nbsp;Zev A. Wainberg","doi":"10.1016/j.ejca.2024.115122","DOIUrl":"10.1016/j.ejca.2024.115122","url":null,"abstract":"<div><h3>Purpose</h3><div>MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.</div></div><div><h3>Methods</h3><div>MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles. Safety assessments included the nature of dose-limiting toxicities (DLTs) and the incidence and severity of adverse events (AEs) and serious AEs. The PK profile of MAK683 was assessed in sequential blood samples of cycles 1–6, and pharmacodynamic profiles were measured by H3K27me3 changes from baseline.</div></div><div><h3>Results</h3><div>Overall, 139 patients (clear cell carcinoma of the ovary [CCCO], 9 [6.5%]; castration-resistant prostate cancer [CRPC], 22 [15.8 %]; diffuse large B-cell lymphoma [DLBCL], 31 [22.3%]; epithelioid sarcoma [ES], 17 [12.2 %]; gastric cancer [GC], 37 [26.6 %]; nasopharyngeal carcinoma [NPC], 17 [12.2 %]; SWI/SNF-mutated sarcoma, 6 [4.3 %]) received MAK683. Median duration of exposure was 57 days (range: 4–1006). Fifteen patients experienced 22 DLTs including thrombocytopenia (4.9 %) and febrile neutropenia (3.3 %). MAK683-related AEs were reported in 98 patients (70.5 %); 43 patients had grade 3/4 drug-related AEs, including neutropenia, thrombocytopenia, and anemia. MAK683 was quickly absorbed, with peak plasma concentrations ranging from 0.975 to 4.08 h. Median progression-free survival was 1.9 months (90 % confidence interval [CI]: 1.8–2.3), and overall response rate was 5.8 % (90 % CI: 2.52–11.03 %). Clinical activity was observed in patients with advanced DLBCL and ES.</div></div><div><h3>Conclusion</h3><div>Overall, MAK683 treatment was well tolerated, and clinical activity was observed in patients with advanced DLBCL and ES.</div></div><div><h3>Clinical Trial Information</h3><div><span><span>NCT02900651</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115122"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update on access to novel treatment for metastatic melanoma in Europe — A 2024 survey of the European melanoma registry and the European association of dermato-oncology","authors":"L. Kandolf ,&nbsp;P.A. Ascierto ,&nbsp;L. Bastholt ,&nbsp;I. Gavrilova ,&nbsp;J. Haanen ,&nbsp;A. Hauschild ,&nbsp;D. Herceg ,&nbsp;C. Hoeller ,&nbsp;A. Jalovcic Suljevic ,&nbsp;JI Kessels ,&nbsp;I. Krajsova ,&nbsp;M. Kukushkina ,&nbsp;A. Lallas ,&nbsp;P. Lorigan ,&nbsp;J. Mangana ,&nbsp;I. Marquez-Rodas ,&nbsp;L. Mazilu ,&nbsp;P. Mohr ,&nbsp;M. Bylaite-Bucinskiene ,&nbsp;J. Ocvirk ,&nbsp;C. Garbe","doi":"10.1016/j.ejca.2024.115124","DOIUrl":"10.1016/j.ejca.2024.115124","url":null,"abstract":"<div><div>Advances in cancer treatments have significantly improved their effectiveness, yet access to first-line therapies remains limited. A 2017 survey revealed that over 25 % of metastatic melanoma patients in Europe lacked access to recommended therapies. To address this, the European Association of Dermato-Oncology and the European Melanoma Registry conducted a follow-up study on the registration and reimbursement of first-line treatments.A web-based survey using LimeSurvey was distributed to melanoma experts across 27 European countries from February to April 2022 and updated from February to April 2024. The questionnaire covered the percentage of patients receiving recommended treatments, as well as treatment authorization and reimbursement dates for systemic and adjuvant therapies.There has been significant improvement in the registration and reimbursement of BRAFi/MEKi, anti-PD1, and anti-PD1/anti-CTLA4 therapies, increasing from 48 %, 63 %, and 37 % in 2017 to 96 %, 96 %, and 78 % in 2024, respectively. Despite these gains, restrictions persist. Anti-PD1/anti-CTLA4 combination immunotherapy is still not available without restrictions in 48 % of the surveyed countries. The nivolumab/relatlimab combination is licensed only for PDL-1-negative melanoma and reimbursed in seven countries of Europe. Tebentafusp is reimbursed in 15 countries and talimogene laherpervec in 5. In 2024, adjuvant treatments for stage III melanoma are reimbursed in 22 countries for dabrafenib/trametinib and 24 of 27 for anti-PD1 antibodies. Pembrolizumab and nivolumab are reimbursed in 15 and 8 countries, respectively, for stage IIB/IIC disease.While there have been improvements in the reimbursement of metastatic melanoma treatments in Europe, challenges and discrepancies remain. Further efforts at European and global levels are needed to harmonize and enhance access to cancer medicines.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115124"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry” [Eur. J. Cancer 212, 2024, 115056]","authors":"A. Özkan ,&nbsp;E. Kapiteijn ,&nbsp;F. van den Bos ,&nbsp;M.J.B. Aarts ,&nbsp;F.W.P.J. van den Berkmortel ,&nbsp;C.U. Blank ,&nbsp;M. Bloem ,&nbsp;W.A.M. Blokx ,&nbsp;M.J. Boers-Sonderen ,&nbsp;J.J. Bonenkamp ,&nbsp;A.J.M. van den Eertwegh ,&nbsp;J.W.B. de Groot ,&nbsp;J.B. Haanen ,&nbsp;C.E. Holtslag ,&nbsp;G.A.P. Hospers ,&nbsp;D. Piersma ,&nbsp;R.S. van Rijn ,&nbsp;A.M. Stevense-den Boer ,&nbsp;K.P.M. Suijkerbuijk ,&nbsp;A.A.M. van der Veldt ,&nbsp;N.A. de Glas","doi":"10.1016/j.ejca.2024.115194","DOIUrl":"10.1016/j.ejca.2024.115194","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115194"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of head and neck cancer of unknown primary: A phase IV study by DAHANCA","authors":"Signe Bergliot Nielsen ,&nbsp;Nina Munk Lyhne ,&nbsp;Maria Andersen ,&nbsp;Christina Caroline Plaschke ,&nbsp;Anita Birgitte Gothelf ,&nbsp;Jørgen Johansen ,&nbsp;Christian Maare ,&nbsp;Mohammad Farhadi ,&nbsp;Christian Godballe ,&nbsp;Hanne Primdahl ,&nbsp;Anne Ivalu Sander Holm ,&nbsp;Jan Alsner ,&nbsp;Thomas Kjærgaard ,&nbsp;Jens Overgaard","doi":"10.1016/j.ejca.2024.115211","DOIUrl":"10.1016/j.ejca.2024.115211","url":null,"abstract":"<div><h3>Background</h3><div>Diagnostic and therapeutic management of patients with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remains a challenge. The aim of the present phase IV study was to assess adherence to the current Danish guidelines and evaluate the treatment outcome in HNSCCUP patients.</div></div><div><h3>Materials and methods</h3><div>Prospectively collected data in the DAHANCA database from patients treated between 2014 and 2020 was evaluated. The median follow-up was 6.7 years. Treatment included definitive neck dissection (dND), primary (chemo-)radiotherapy ((C-)RT), neck dissection (ND) followed by postoperative (C-)RT (ND + (C-)PORT). Outcome were reported as five-year estimates of loco-regional failure (LRF), ultimate LRF (ULRF), disease specific mortality (DSM), overall survival (OS), and toxicity scores ≥ 3.</div></div><div><h3>Results</h3><div>A total of 288 patients were treated, of which 254 (88 %) received treatment with curative intent and were eligible for adherence assessment. These were allocated to dND (n = 60), (C-)RT (n = 81) and ND + (C-)PORT (n = 113). The HPV/p16 status was known in 94 % of patients with 109 (43 %) positive cases. The 5-year LRF, DSM, and OS for patients treated with curative intent was 22 %, 15 % and 73 %, and in patients with p16 positive disease 16 %, 5 %, and 85 %. The overall guideline adherence was 76 % (192/254). In the adherent group the LRF, ULRF, DSM, and OS were 22 %, 11 %, 16 %, and 73 %, respectively.</div></div><div><h3>Conclusion</h3><div>The study revealed good treatment outcome measures in HNSCCUP patients subject to the Danish guidelines, comparable to other head and neck cancer patients. The observed guideline-deviations did not affect outcome.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115211"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcomas developed in patients with Lynch Syndrome are enriched in pleomorphic soft-tissue sarcomas and are sensitive to immunotherapy","authors":"F. Poumeaud ,&nbsp;T. Valentin ,&nbsp;N. Fares ,&nbsp;B. Segier ,&nbsp;S. Watson ,&nbsp;B. Verret ,&nbsp;C. Tlemsani ,&nbsp;N. Penel ,&nbsp;S. Lejeune ,&nbsp;N. Firmin ,&nbsp;A. Sabouret ,&nbsp;J.-C. Thery ,&nbsp;S. Bonvalot ,&nbsp;E. Cottereau ,&nbsp;E. Cauchin ,&nbsp;A. Lancon ,&nbsp;S. Nambot ,&nbsp;H. Zattara ,&nbsp;M. Coudert ,&nbsp;E. Fourme ,&nbsp;R. Guimbaud","doi":"10.1016/j.ejca.2024.115196","DOIUrl":"10.1016/j.ejca.2024.115196","url":null,"abstract":"<div><h3>Background</h3><div>Sarcomas do not belong to the Lynch Syndrome (LS)-tumour spectrum. A growing body literature has reported sarcomas in patients with LS. Clinical and tumour characteristics of these patients remain unknown.</div></div><div><h3>Patients and methods</h3><div>We set up the first national retrospective study, SarcLynch, describing the pathological and clinical characteristics of sarcomas developed in patients with LS. Patients were identified from two national networks and included from 23 centres in France.</div></div><div><h3>Results</h3><div>Eighty-one patients participated in the SarcLynch study. Sixty-seven (83 %) tumours were soft-tissue sarcomas (STS) and 14 (17 %) bone sarcomas. Among STS, 59 (88 %) showed a pleomorphic component, with undifferentiated pleomorphic sarcoma (UPS) (36 %) and pleomorphic rhabdomyosarcoma (pRMS) (21 %) being the most represented subtypes. Sarcoma was the first neoplastic event in 32 patients (40 %). Thirty-two patients (40 %) were carriers of <em>MSH2</em> germline pathogenic variants. Among patients who underwent an assessment of deficient mismatch repair (dMMR) by immunohistochemistry and/or molecular biology status, 75 % were dMMR by immunohistochemistry and 45 % were microsatellite instability high (MSI-H). Eight patients received immune checkpoint inhibitors and 4 (50 %) exhibited an objective response with 3 complete radiological response including 1 patient with pathological complete response. Duration of response ranged from 6 to 20 months.</div></div><div><h3>Conclusions</h3><div>SarcLynch, the largest multicentric series describing sarcomas developed in patients with LS, revealed an enrichment in patients with pleomorphic sarcomas – especially UPS and pRMS. This finding strongly supports screening for MMR status evaluation in these rare histotypes both for oncogenetic screening and therapeutic interest. Considering an objective response rate of 50 %, access to immunotherapy should be considered in these tumours.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115196"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiome and immune checkpoint inhibitor toxicity","authors":"Rik J. Verheijden ,&nbsp;Mick J.M. van Eijs ,&nbsp;Fernanda L. Paganelli ,&nbsp;Marco C. Viveen ,&nbsp;Malbert R.C. Rogers ,&nbsp;Janetta Top ,&nbsp;Anne M. May ,&nbsp;Janneke H.H.M. van de Wijgert ,&nbsp;Karijn P.M. Suijkerbuijk ,&nbsp;on behalf of the UNICIT-consortium","doi":"10.1016/j.ejca.2025.115221","DOIUrl":"10.1016/j.ejca.2025.115221","url":null,"abstract":"<div><h3>Background</h3><div>Multiple studies have suggested that gut microbiome may influence immune checkpoint inhibitor (ICI) efficacy, but its association with immune-related adverse events (irAEs) is less well studied. In this prospective cohort study, we assessed whether gut microbiome composition at start, or changes during ICI, are associated with severe irAEs.</div></div><div><h3>Methods</h3><div>Stool samples of cancer patients treated with anti-PD-1 ± anti-CTLA-4 were analyzed using 16S rRNA gene sequencing and metagenomic shotgun sequencing. Differences in alpha and beta diversity between patients with and without severe irAE were assessed, as well as differential relative abundance (RA) of taxa, MetaCyc pathways, and seven prespecified literature-based bacterial groups including pathobionts and Ruminococcaceae.</div></div><div><h3>Findings</h3><div>We analyzed 497 samples of 195 patients before and soon after starting ICI, at severe irAE onset and after starting immunosuppression. Mean RA of the pathobionts group was significantly higher in patients who developed a severe irAE (8.2 %) compared to those who did not (4.8 %; odds ratio 1.40; 95 %CI 1.07–1.87) at baseline, and also early during ICI treatment and at severe irAE onset. A significantly stronger decrease in RA of Ruminococcaceae after starting ICI was observed in patients who developed a severe irAE compared to those who did not. RAs of Ruminococcaceae, the genus <em>Ruminococcus</em>, and the species <em>R. bromii</em> and <em>R. callidus</em> were significantly lower at severe irAE onset compared to other time points.</div></div><div><h3>Interpretation</h3><div>Gut microbiome dysbiosis signaled by higher RA of pathobionts and decrease in RA of Ruminococcaceae may predispose to severe irAEs.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115221"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}