{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:06:19Z","timestamp":1790802379825,"version":"4.1.0"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Dutch Cancer Society","doi-asserted-by":"publisher","award":["DEV 2023-3\/15461"],"award-info":[{"award-number":["DEV 2023-3\/15461"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006244","name":"Stichting Kinderen Kankervrij","doi-asserted-by":"publisher","award":["project number 458 \\u201CPACT-ES: Personalised Approach to Chemotherapy Treatment for Ewing\\u2019s Sarcoma\\u201D"],"award-info":[{"award-number":["project number 458 \\u201CPACT-ES: Personalised Approach to Chemotherapy Treatment for Ewing\\u2019s Sarcoma\\u201D"]}],"id":[{"id":"10.13039\/501100006244","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","ejcancer.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Cancer"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.ejca.2026.117057","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T15:38:53Z","timestamp":1789573133000},"page":"117057","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Assessing the effect of chemotherapy dose reductions and time delay on event-free survival in Ewing Sarcoma: A retrospective analysis of the Euro Ewing 2012 trial"],"prefix":"10.1016","volume":"247","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5684-7513","authenticated-orcid":false,"given":"Yuan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Fiocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6255-6552","authenticated-orcid":false,"given":"Laura","family":"Kirton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-300X","authenticated-orcid":false,"given":"Piers","family":"Gaunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Brennan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes H.M.","family":"Merks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-9976","authenticated-orcid":false,"given":"Marta","family":"Spreafico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejca.2026.117057_bib1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1634\/theoncologist.11-5-503","article-title":"Ewing\u2019s sarcoma family of tumors: current management","volume":"11","author":"Bernstein","year":"2006","journal-title":"Oncologist"},{"key":"10.1016\/j.ejca.2026.117057_bib2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/MPH.0b013e31816e22f3","article-title":"Changes in incidence and survival of Ewing sarcoma patients over the past 3 decades: SEER data","volume":"30","author":"Esiashvili","year":"2008","journal-title":"J Pediatr Hematol Oncol"},{"key":"10.1016\/j.ejca.2026.117057_bib3","series-title":"Ewing sarcoma","author":"Durer","year":"2024"},{"key":"10.1016\/j.ejca.2026.117057_bib4","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.3390\/jcm10081685","article-title":"Ewing sarcoma\u2014diagnosis, treatment, clinical challenges and future perspectives","volume":"10","author":"Z\u00f6llner","year":"2021","journal-title":"J Clin Med"},{"key":"10.1016\/j.ejca.2026.117057_bib5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41572-018-0003-x","article-title":"Ewing sarcoma","volume":"4","author":"Gr\u00fcnewald","year":"2018","journal-title":"Nat Rev Dis Prim"},{"key":"10.1016\/j.ejca.2026.117057_bib6","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(22)01790-1","article-title":"Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012): an open-label, randomised, phase 3 trial","volume":"400","author":"Brennan","year":"2022","journal-title":"Lancet"},{"key":"10.1016\/j.ejca.2026.117057_bib7","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1200\/JCO.1990.8.12.1935","article-title":"The calculation of received dose intensity","volume":"8","author":"Hryniuk","year":"1990","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2026.117057_bib8","first-page":"4028","article-title":"Received dose and dose-intensity of chemotherapy and outcome in nonmetastatic extremity osteosarcoma","volume":"36","author":"Lewis","year":"2000","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2026.117057_bib9","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-022980","article-title":"Method to measure the mismatch between target and achieved received dose intensity of chemotherapy in cancer trials: a retrospective analysis of the MRC BO06 trial in osteosarcoma","volume":"9","author":"Lancia","year":"2019","journal-title":"BMJ Open"},{"key":"10.1016\/j.ejca.2026.117057_bib10","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00280-019-03797-3","article-title":"A novel method to address the association between received dose intensity and survival outcome: benefits of approaching treatment intensification at a more individualised level in a trial of the European Osteosarcoma Intergroup","volume":"83","author":"Lancia","year":"2019","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1016\/j.ejca.2026.117057_bib11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12874-024-02416-x","article-title":"Causal effect of chemotherapy received dose intensity on survival outcome: a retrospective study in osteosarcoma","volume":"24","author":"Spreafico","year":"2024","journal-title":"BMC Med Res Methodol"},{"key":"10.1016\/j.ejca.2026.117057_bib12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/ajco.13998","article-title":"Association of chemotherapy dose intensity and age with outcomes in patients with Ewing\u2019s family sarcoma","volume":"21","author":"Klingberg","year":"2025","journal-title":"Asia Pac J Clin Oncol"},{"key":"10.1016\/j.ejca.2026.117057_bib13","doi-asserted-by":"crossref","first-page":"11570","DOI":"10.1200\/JCO.2022.40.16_suppl.11570","article-title":"Dose intensity and outcomes of VDC\/IE chemotherapy for adolescent and adult patients with Ewing\u2019s family sarcoma","volume":"40","author":"Klingberg","year":"2022","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2026.117057_bib14","doi-asserted-by":"crossref","first-page":"11502","DOI":"10.1200\/JCO.2021.39.15_suppl.11502","article-title":"Association of treatment delays with an unfavorable outcome in patients with localized Ewing sarcoma: a retrospective analysis of data from the GPOH Euro-E.W.I.N.G.99 trial","volume":"39","author":"Dirksen","year":"2021","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2026.117057_bib15","series-title":"Causal inference: what if","author":"Hern\u00e1n","year":"2020"},{"key":"10.1016\/j.ejca.2026.117057_bib16","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4103\/2229-3485.83221","article-title":"Intention-to-treat concept: a review","volume":"2","author":"Gupta","year":"2011","journal-title":"Perspect Clin Res"},{"key":"10.1016\/j.ejca.2026.117057_bib17","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1001\/jama.2021.2825","article-title":"Interpreting the results of intention-to-treat, per-protocol, and as-treated analyses of clinical trials","volume":"326","author":"Smith","year":"2021","journal-title":"JAMA"},{"key":"10.1016\/j.ejca.2026.117057_bib18","article-title":"The estimands framework: a primer on the ICH E9(R1) addendum","volume":"384","author":"Kahan","year":"2024","journal-title":"BMJ"},{"key":"10.1016\/j.ejca.2026.117057_bib19","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/aje\/kwv254","article-title":"Using big data to emulate a target trial when a randomized trial is not available","volume":"183","author":"Hern\u00e1n","year":"2016","journal-title":"Am J Epidemiol"},{"key":"10.1016\/j.ejca.2026.117057_bib20","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1001\/jama.2022.21383","article-title":"Target trial emulation: a framework for causal inference from observational data","volume":"328","author":"Hern\u00e1n","year":"2022","journal-title":"JAMA"},{"key":"10.1016\/j.ejca.2026.117057_bib21","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1001\/jama.2025.13350","article-title":"Transparent reporting of observational studies emulating a target trial\u2013the TARGET statement","volume":"334","author":"Cashin","year":"2024","journal-title":"JAMA"},{"key":"10.1016\/j.ejca.2026.117057_bib22","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1177\/0962280218780619","article-title":"Marginal structural models with dose-delay joint-exposure for assessing variations to chemotherapy intensity","volume":"28","author":"Lancia","year":"2019","journal-title":"Stat Methods Med Res"},{"key":"10.1016\/j.ejca.2026.117057_bib23","series-title":"Euro Ewing 2012 (EE2012) protocol, version 5.0.","article-title":"Clinical Trials Unit","author":"Cancer Research UK","year":"2017"},{"key":"10.1016\/j.ejca.2026.117057_bib24","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13063-019-4026-8","article-title":"International randomised controlled trial for the treatment of newly diagnosed Ewing sarcoma family of tumours\u2013EURO EWING 2012 protocol","volume":"21","author":"Anderton","year":"2020","journal-title":"Trials"},{"issue":"3","key":"10.1016\/j.ejca.2026.117057_bib25","doi-asserted-by":"crossref","first-page":"e130","DOI":"10.1200\/JOP.2017.025411","article-title":"Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology\/Oncology Pharmacy Association","volume":"14","author":"Fahrenbruch","year":"2018","journal-title":"J Oncol Pract"},{"key":"10.1016\/j.ejca.2026.117057_bib26","unstructured":"National Cancer Institute. CTEP trial development and conduct. Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. 2010. https:\/\/dctd.cancer.gov\/research\/ctep-trials\/trial-development (accessed 6 Mar 2025)."},{"key":"10.1016\/j.ejca.2026.117057_bib27","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2021-053456","article-title":"Novel longitudinal Multiple Overall Toxicity (MOTox) score to quantify adverse events experienced by patients during chemotherapy treatment: a retrospective analysis of the MRC BO06 trial in osteosarcoma","volume":"11","author":"Spreafico","year":"2021","journal-title":"BMJ Open"},{"key":"10.1016\/j.ejca.2026.117057_bib28","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0197-2456(96)00075-X","article-title":"A note on quantifying follow-up in studies of failure time","volume":"17","author":"Schemper","year":"1996","journal-title":"Control Clin Trials"},{"key":"10.1016\/j.ejca.2026.117057_bib29","series-title":"Dynamic prediction in clinical survival analysis","article-title":"Boca Raton, FL","author":"van Houwelingen","year":"2011"},{"key":"10.1016\/j.ejca.2026.117057_bib30","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1214\/17-AOAS1101","article-title":"Covariate balancing propensity score for a continuous treatment: application to the efficacy of political advertisements","volume":"12","author":"Fong","year":"2018","journal-title":"Ann Appl Stat"},{"key":"10.1016\/j.ejca.2026.117057_bib31","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1200\/JCO.2014.55.2208","article-title":"Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis","volume":"32","author":"Uno","year":"2014","journal-title":"J Clin Oncol"}],"container-title":["European Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959804926008397?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959804926008397?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:32:22Z","timestamp":1790800342000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959804926008397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":31,"alternative-id":["S0959804926008397"],"URL":"https:\/\/doi.org\/10.1016\/j.ejca.2026.117057","relation":{},"ISSN":["0959-8049"],"issn-type":[{"value":"0959-8049","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Assessing the effect of chemotherapy dose reductions and time delay on event-free survival in Ewing Sarcoma: A retrospective analysis of the Euro Ewing 2012 trial","name":"articletitle","label":"Article Title"},{"value":"European Journal of Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejca.2026.117057","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"117057"}}