{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T02:31:41Z","timestamp":1782527501408,"version":"3.54.5"},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016037","name":"Fondation Gustave Roussy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016037","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018001","name":"Soci\u00e9t\u00e9 Fran\u00e7aise de Lutte Contre les Cancers et les Leuc\u00e9mies de l'Enfant et de l'Adolescent","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Maintenance treatment with vinorelbine and oral cyclophosphamide (oral\u2010CPM) improves outcome of nonmetastatic high\u2010risk (HR) and very\u2010high risk (VHR) rhabdomyosarcoma (RMS) patients. However, gonadal toxicity of maintenance was not yet investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The authors focused their analysis on male gonadal toxicity in HR\/VHR groups of RMS2005 trial, in France. In the HR group, patients were randomized to receive or not receive 6 months of maintenance (after nine or four IVADo] + five IVA). In the VHR group, patients received 6 months of maintenance (after four IVADo + five IVA). Exocrine gonadal dysfunction (EGD) was defined as followed: follicle\u2010stimulating hormone level &gt;10 IU\/L and\/or inhibin\u2010B &lt;80 pg\/mL and\/or oligoasthenozoospermia\/azoospermia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 86 eligible 5\u2010year RMS survivors \u226512 years old, 49 had available gonadal evaluation (median age at diagnosis\u00a0=\u00a06.4 years, median age at evaluation\u00a0=\u00a0\u00a018.7 years, 41 HR\/8 VHR). Twenty\u2010six (53%) received oral\u2010CPM (median cumulative dose\u00a0=\u00a04.2 g\/m<jats:sup>2<\/jats:sup>, range\u00a0=\u00a00.7\u20139.0). EGD was reported in 18 of 49 (37%). Exposure to oral\u2010CPM (odds ratio [OR], 5.45; 95% confidence interval [CI], 1.30\u201322.92, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.021) and older age at diagnosis (compared to 0\u20135 years, OR<jats:sub>5\u201310 years<\/jats:sub>, 9.61; 95% CI, 1.49\u201362.15 and OR<jats:sub>&gt;10 years<\/jats:sub>, 14.10; 95% CI, 1.89\u2013105.33, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.025) were significantly associated with EGD. Higher cumulative dose of oral\u2010CPM (&gt;4.5 g\/m<jats:sup>2<\/jats:sup>) tended to be more toxic (compared to nonexposure, OR<jats:sub>\u22644.5 g\/m2<\/jats:sub>, 2.95; 95% CI,\u00a00.78\u201311.09 and OR<jats:sub>&gt;4.5 g\/m2<\/jats:sub>, 7.20; 95% CI, 1.01\u201351.39, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.094).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Oral\u2010CPM induces additional gonadal damage to the ifosfamide\u2010based induction regimen. Fertility preservation could be considered in patients exposed to maintenance, especially those &gt;5 years old and exposed to \u226512 months of oral\u2010CPM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35918","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T06:50:48Z","timestamp":1748415048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of maintenance treatment on male gonadal function in patients treated for localized rhabdomyosarcoma in RMS2005 trial in France"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3936-5595","authenticated-orcid":false,"given":"Lea","family":"Rossillon","sequence":"first","affiliation":[{"name":"Department of Children and Adolescents Oncology Gustave Roussy  Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Thomas\u2010Teinturier","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diebetology Bic\u00eatre Hospital, Assistance Publique H\u00f4pitaux de Paris, University Paris\u2010Saclay  Le Kremlin Bic\u00eatre France"},{"name":"INSERM U1018 CESP, Radiation Epidemiology Team, Paris\u2010Saclay University, Gustave Roussy Cancer Campus  Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-139X","authenticated-orcid":false,"given":"Daniel","family":"Orbach","sequence":"additional","affiliation":[{"name":"SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, PSL University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Dominique","family":"Tabone","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato\u2010Oncology Armand\u2010Trousseau Sorbonne University Hospital Assistance Publique H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5928-7320","authenticated-orcid":false,"given":"Amandine","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology Institut d'H\u00e9matologie et d'Oncologie P\u00e9diatrique  Lyon France"},{"name":"INSERMU1290, RESHAPE  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Ansoborlo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology CHU Bordeaux  Bordeaux 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