{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T20:18:56Z","timestamp":1780517936837,"version":"3.54.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Local treatment of pelvic Ewing Sarcoma (EWS) is czhallenging due to complex anatomy and potential complications. Local therapy may be deferred to maintain chemotherapy dose-intensity, but the impact of this delay on outcomes remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods <\/jats:title>\n            <jats:p>A systematic review using the PICO model evaluated whether delayed local therapy affects long-term outcomes in localized pelvic EWS. Ovid Medline, Ovid Embase, and Cochrane Central databases were searched through June 2024. Studies were screened by two independent reviewers for quantitative and qualitative data extraction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of 1849 studies screened, eight eligible studies including 2618 patients were identified; none were pelvic-specific. When specified, 1\u201318% had pelvic primaries. All studies were retrospective with substantial heterogeneity in endpoints. Seven of eight studies indicated delayed local therapy was associated with reduced event-free survival (EFS) and\/or overall survival (OS). In the largest study (Lin et al.) of 1319 EWS patients, delayed local therapy\u2009&gt;\u200916 weeks was associated with significantly reduced OS (HR 1.41, CI 1.11\u20131.80, <jats:italic>p<\/jats:italic>\u2009=\u20090.005).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p> This systematic review highlights the importance of multidisciplinary coordinated care during initial chemotherapy to optimize local therapy timing, which may impact outcomes. Further studies are needed to assess timing significance, particularly for pelvic EWS.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00432-025-06286-8","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T16:58:45Z","timestamp":1756313925000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A systematic review on the impact of delayed local therapy in patients with Ewing sarcoma of the pelvis"],"prefix":"10.1007","volume":"151","author":[{"given":"Shook Fe","family":"Yap","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natacha","family":"Omer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Bhadri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Lewin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Nicholls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Carkeet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Orme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Winstanley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smaro","family":"Lazarakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Mar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Cayrol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"6286_CR1","doi-asserted-by":"crossref","unstructured":"Gr\u00fcnewald TGP, Cidre-Aranaz F, Surdez D, Tomazou EM, De \u00c1lava E, Kovar H et al (2018) Ewing sarcoma. Vol. 4, Nature Reviews Disease Primers. Nature Publishing Group","DOI":"10.1038\/s41572-018-0003-x"},{"key":"6286_CR2","doi-asserted-by":"crossref","unstructured":"Brown JM, Rakoczy K, Tokson JH, Jones KB, Groundland JS (2022) Ewing sarcoma of the pelvis: clinical features and overall survival. Cancer Treat Res Commun. ;33","DOI":"10.1016\/j.ctarc.2022.100634"},{"issue":"1","key":"6286_CR3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.clon.2012.07.010","volume":"25","author":"T B\u00f6lling","year":"2013","unstructured":"B\u00f6lling T, Hardes J, Dirksen U (2013) Management of bone tumours in paediatric oncology. Clin Oncol 25(1):19\u201326","journal-title":"Clin Oncol"},{"key":"6286_CR4","doi-asserted-by":"crossref","unstructured":"Leavey PJ, Laack NN, Krailo MD, Buxton A, Lor R, Dubois R et al (2021) SG,. Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children\u2019s Oncology Group Report. J Clin Oncol [Internet]. ;39:4029\u201338.","DOI":"10.1200\/JCO.21.00358"},{"key":"6286_CR5","doi-asserted-by":"crossref","unstructured":"Capanna R, Toni A, Sudanese A, Mcdonald D, Baccp G, Campanaccp M (1990) Ewing\u2019s sarcoma of the pelvis. Vol. 14, International Orthopaedics (SICOT)","DOI":"10.1007\/BF00183366"},{"issue":"10362","key":"6286_CR6","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/S0140-6736(22)01790-1","volume":"400","author":"B Brennan","year":"2022","unstructured":"Brennan B, Kirton L, Marec-B\u00e9rard P, Gaspar N, Laurence V, Mart\u00edn-Broto J et al (2022) Comparison of two chemotherapy regimens in patients with newly diagnosed ewing sarcoma (EE2012): an open-label, randomised, phase 3 trial. Lancet 400(10362):1513\u20131521","journal-title":"Lancet"},{"key":"6286_CR7","doi-asserted-by":"publisher","unstructured":"Dubois SG, Krailo MD, Gebhardt MC, Donaldson SS, Marcus KJ, Dormans J et al Comparative Evaluation of Local Control Strategies in Localized Ewing Sarcoma of Bone A Report From the Children\u2019s Oncology Group. Available from: https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/https:\/\/doi.org\/10.1002\/cncr.29065","DOI":"10.1002\/cncr.29065"},{"key":"6286_CR8","doi-asserted-by":"crossref","unstructured":"Cotterill SJ, Ahrens S, Paulussen M, J\u00fcrgens HF, Vo\u00fbte PA, Gadner H et al (2000) Prognostic factors in ewing\u2019s tumor of bone: analysis of 975 patients from the European intergroup cooperative ewing\u2019s sarcoma study group. 18, J Clin Oncol","DOI":"10.1200\/JCO.2000.18.17.3108"},{"key":"6286_CR9","doi-asserted-by":"crossref","unstructured":"Anderton J, Moroz V, Marec-B\u00e9rard P, Gaspar N, Laurence V, Mart\u00edn-Broto J et al (2020) International randomised controlled trial for the treatment of newly diagnosed EWING sarcoma family of tumours - EURO EWING 2012 protocol. Trials. ;21(1)","DOI":"10.1186\/s13063-019-4026-8"},{"key":"6286_CR10","doi-asserted-by":"publisher","unstructured":"Riggi N, Suv\u00e0 ML, Stamenkovic I, Ewing\u2019s DL (eds) (2021) New England Journal of Medicine [Internet]. ;384(2):154\u201364. Available from: http:\/\/www.nejm.org\/doi\/https:\/\/doi.org\/10.1056\/NEJMra2028910","DOI":"10.1056\/NEJMra2028910"},{"key":"6286_CR11","doi-asserted-by":"crossref","unstructured":"Z\u00f6llner SK, Amatruda JF, Bauer S, Collaud S, de \u00c1lava E, Dubois SG et al (2021) Ewing sarcoma\u2014diagnosis, treatment, clinical challenges and future perspectives, vol 10. Journal of Clinical Medicine. MDPI","DOI":"10.3390\/jcm10081685"},{"issue":"4","key":"6286_CR12","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1093\/annonc\/mdm521","volume":"19","author":"C Rodr\u00edguez-Galindo","year":"2008","unstructured":"Rodr\u00edguez-Galindo C, Navid F, Liu T, Billups CA, Rao BN, Krasin MJ (2008) Prognostic factors for local and distant control in ewing sarcoma family of tumors. Ann Oncol 19(4):814\u2013820","journal-title":"Ann Oncol"},{"key":"6286_CR13","doi-asserted-by":"publisher","unstructured":"Guder WK, Hardes J, Nottrott M, Steffen AJ, Dirksen U, Streitb\u00fcrger A Pelvic Ewing sarcoma: a retrospective outcome analysis of 104 patients who underwent pelvic tumor resection at a single supra-regional center. Available from: https:\/\/doi.org\/10.1186\/s13018-020-02028-3","DOI":"10.1186\/s13018-020-02028-3"},{"key":"6286_CR14","doi-asserted-by":"crossref","unstructured":"Ahmed SK, Robinson SI, Arndt CAS, Petersen IA, Haddock MG, Rose PS et al (2017) Pelvis ewing sarcoma: local control and survival in the modern era. Pediatr Blood Cancer. ;64(9)","DOI":"10.1002\/pbc.26504"},{"issue":"4","key":"6286_CR15","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1002\/(SICI)1097-0142(19990215)85:4<869::AID-CNCR14>3.0.CO;2-8","volume":"85","author":"C Hoffmann","year":"1999","unstructured":"Hoffmann C, Ahrens S, Dunst J, Hillmann A, Winkelmann W, Craft A et al (1999) Pelvic ewing sarcoma. A retrospective analysis of 241 cases. Cancer 85(4):869\u2013877","journal-title":"Cancer"},{"key":"6286_CR16","doi-asserted-by":"publisher","unstructured":"Xie X, Zeng Z, Yao H, Jin Q, Bian Y, Lv D et al Comparison of local control and survival outcomes between surgical and non-surgical local therapy on pelvic Ewing\u2019s sarcoma patients: a meta-analysis. [cited 2024 Aug 30]; Available from: https:\/\/doi.org\/10.21037\/tcr-20-1222","DOI":"10.21037\/tcr-20-1222"},{"key":"6286_CR17","doi-asserted-by":"crossref","unstructured":"Carrie C, Mascard E, Gomez F, Habrand JL, Alapetite C, Oberlin O et al (1999) Nonmetastatic pelvic ewing sarcoma: report of the French society of pediatric oncology. Med Pediatr Oncol. ;33(5)","DOI":"10.1002\/(SICI)1096-911X(199911)33:5<444::AID-MPO2>3.0.CO;2-D"},{"issue":"2","key":"6286_CR18","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1097\/CORR.0000000000000962","volume":"478","author":"D Andreou","year":"2020","unstructured":"Andreou D, Ranft A, Gosheger G, Timmermann B, Ladenstein R, Hartmann W et al (2020) Which factors are associated with local control and survival of patients with localized pelvic ewing\u2019s sarcoma?? A retrospective analysis of data from the Euro-EWING99 trial. Clin Orthop Relat Res 478(2):290\u2013302","journal-title":"Clin Orthop Relat Res"},{"issue":"10","key":"6286_CR19","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.1016\/j.ejso.2021.05.027","volume":"47","author":"JR Lex","year":"2021","unstructured":"Lex JR, Kurisunkal V, Kaneuchi Y, Fujiwara T, Sherriff J, Wigley C et al (2021) Pelvic ewing sarcoma: should all patients receive pre-operative radiotherapy, or should it be delivered selectively? Eur J Surg Oncol 47(10):2618\u20132626","journal-title":"Eur J Surg Oncol"},{"key":"6286_CR20","unstructured":"Covidence Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org"},{"key":"6286_CR21","unstructured":"NHMRC. Additional levels of evidence and grades for recommendations for developers of guideline. Stage 2 consultation. Early 2008 - end June 2009 [Internet] (2008) Available from: www.nhmrc.gov.au\/publications\/synopses\/cp65syn.htm"},{"key":"6286_CR22","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","volume":"25","author":"A Stang","year":"2010","unstructured":"Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603\u2013605","journal-title":"Eur J Epidemiol"},{"issue":"13","key":"6286_CR23","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1002\/cncr.25144","volume":"116","author":"AA Gupta","year":"2010","unstructured":"Gupta AA, Pappo A, Saunders N, Hopyan S, Ferguson P, Wunder J et al (2010) Clinical outcome of children and adults with localized ewing sarcoma: impact of chemotherapy dose and timing of local therapy. Cancer 116(13):3189\u20133194","journal-title":"Cancer"},{"issue":"8","key":"6286_CR24","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1002\/pbc.24926","volume":"61","author":"B Abou Ali","year":"2014","unstructured":"Abou Ali B, Nader R, Tamim H, Eid T, Boulos F, Khoury N et al (2014) Outcome of ewing sarcoma in a multidisciplinary setting in Lebanon. Pediatr Blood Cancer 61(8):1472\u20131475","journal-title":"Pediatr Blood Cancer"},{"issue":"4","key":"6286_CR25","doi-asserted-by":"publisher","first-page":"194","DOI":"10.4103\/2278-330X.195344","volume":"5","author":"S Nasaka","year":"2016","unstructured":"Nasaka S, Gundeti S, Ganta R, Arigela R, Linga V, Maddali L (2016) Impact of treatment protocol on outcome of localized ewing\u2019s sarcoma. South Asian J Cancer 5(4):194\u2013195","journal-title":"South Asian J Cancer"},{"key":"6286_CR26","doi-asserted-by":"crossref","unstructured":"Lin TA, Ludmir EB, Liao KP, McAleer MF, Bishop AJ, Grosshans D et al (2020) Relationship between treatment center case volume and survival for localized ewing sarcoma: the role of radiotherapy timing. Pediatr Blood Cancer. ;67(11)","DOI":"10.1002\/pbc.28685"},{"issue":"1","key":"6286_CR27","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.ijrobp.2018.12.032","volume":"104","author":"TA Lin","year":"2019","unstructured":"Lin TA, Ludmir EB, Liao KP, McAleer MF, Grosshans DR, McGovern SL et al (2019) Timing of local therapy affects survival in ewing sarcoma. Int J Radiat Oncol Biol Phys 104(1):127\u2013136","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"6286_CR28","doi-asserted-by":"crossref","unstructured":"Parambil BC, Vora T, Sankaran H, Prasad M, Bakshi A, Puri A et al (2020) Outcomes with nondose-dense chemotherapy for ewing sarcoma: A practical approach for the developing world. Pediatr Blood Cancer. ;67(11)","DOI":"10.1002\/pbc.28604"},{"issue":"7","key":"6286_CR29","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1080\/08880018.2020.1772912","volume":"37","author":"S Totadri","year":"2020","unstructured":"Totadri S, Bansal D, Rao KLN, Jain R, Saxena AK, Kapoor R et al (2020) Challenges in the management of localized ewing sarcoma in a developing country. Pediatr Hematol Oncol 37(7):610\u2013619","journal-title":"Pediatr Hematol Oncol"},{"key":"6286_CR30","doi-asserted-by":"crossref","unstructured":"Heesen P, Ranft A, Bhadri V, Brichard B, Collaud S, Cyprova S et al (2023) Association between local treatment modalities and event-free survival, overall survival, and local recurrence in patients with localised ewing sarcoma. Report from the ewing 2008 trial. Eur J Cancer. ;192","DOI":"10.1016\/j.ejca.2023.113260"},{"issue":"2","key":"6286_CR31","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.rpor.2020.02.001","volume":"25","author":"S Salah","year":"2020","unstructured":"Salah S, Halalsheh H, Abuhijla F, Ismael T, Yaser S, Shehadeh A et al (2020) The impact of local control timing in ewing sarcoma. Rep Practical Oncol Radiotherapy 25(2):255\u2013259","journal-title":"Rep Practical Oncol Radiotherapy"},{"issue":"33","key":"6286_CR32","doi-asserted-by":"publisher","first-page":"4148","DOI":"10.1200\/JCO.2011.41.5703","volume":"30","author":"RB Womer","year":"2012","unstructured":"Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE et al (2012) Randomized controlled trial of Interval-Compressed chemotherapy for the treatment of localized ewing sarcoma: A report from the children\u2019s oncology group. J Clin Oncol 30(33):4148\u20134154","journal-title":"J Clin Oncol"},{"key":"6286_CR33","doi-asserted-by":"crossref","unstructured":"Dunst J, Schuck A (2004) Role of Radiotherapy in Ewing Tumors. In: Pediatric Blood and Cancer. pp. 465\u201370","DOI":"10.1002\/pbc.10446"},{"issue":"4","key":"6286_CR34","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/0360-3016(95)00016-R","volume":"32","author":"J Dunst","year":"1995","unstructured":"Dunst J, J\u00fcrgens H, Sauer R, Pape H, Paulussen M, Winkelmann W et al (1995) Radiation therapy in ewing\u2019s sarcoma: an update of the CESS 86 trial. Int J Radiat Oncol Biol Phys 32(4):919\u2013930","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"7","key":"6286_CR35","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/S0959-8049(00)00028-9","volume":"36","author":"I Elomaa","year":"2000","unstructured":"Elomaa I, Blomqvist CP, Saeter G, \u00c5kerman M, Stenwig E, Wiebe T et al (2000) Five-year results in ewing\u2019s sarcoma. The Scandinavian sarcoma group experience with the SSG IX protocol. Eur J Cancer 36(7):875\u2013880","journal-title":"Eur J Cancer"},{"issue":"27","key":"6286_CR36","doi-asserted-by":"publisher","first-page":"4385","DOI":"10.1200\/JCO.2008.16.5720","volume":"26","author":"M Paulussen","year":"2008","unstructured":"Paulussen M, Craft AW, Lewis I, Hackshaw A, Douglas C, Dunst J et al (2008) Results of the EICESS-92 study: two randomized trials of ewing\u2019s sarcoma treatment - Cyclophosphamide compared with Ifosfamide in standard-risk patients and assessment of benefit of Etoposide added to standard treatment in high-risk patients. J Clin Oncol 26(27):4385\u20134393","journal-title":"J Clin Oncol"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06286-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-025-06286-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06286-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T04:35:39Z","timestamp":1757478939000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-025-06286-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,27]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["6286"],"URL":"https:\/\/doi.org\/10.1007\/s00432-025-06286-8","relation":{},"ISSN":["1432-1335"],"issn-type":[{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,27]]},"assertion":[{"value":"13 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Ethical approval and consent to participate"}},{"value":"All authors have consented to submission of this manuscript for publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Consent for publication"}}],"article-number":"237"}}