{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:12:05Z","timestamp":1793394725880,"version":"4.5.0"},"reference-count":39,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"28","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Outcome of patients with localized osteosarcoma is challenging. The role of mifamurtide is still a matter of debate. Two prospective trials were carried out in Italy (ISG\/OS-2) and Spain (GEIS-33) with mifamurtide in ABCB1\/P-glycoprotein (Pgp)\u2013positive patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>Patients age \u226440 years with localized extremity high-grade osteosarcoma were eligible. Analysis of Pgp expression from diagnostic biopsy was centralized. Patients received two cycles of preoperative methotrexate, doxorubicin, and cisplatinum (MAP) before surgery. Postoperatively, in case of Pgp overexpression (Pgp-positive), mifamurtide was added, combined with doxorubicin (one cycle) and four consecutive cycles of high-dose ifosfamide (HDIFO) for patients with poor histologic response, or with MAP in case of good response. Patients who were Pgp-negative received MAP postoperatively. We present the merged analysis of ISG\/OS-2 and GEIS-33 trial, an observational study with same inclusion criteria and treatment of ISG\/OS-2. The primary endpoint was 5-year event-free survival (EFS) according to the use of mifamurtide. Secondary endpoint was overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      From March 2013 to April 2018, 398 patients were analyzed. The median age was 14 years (range, 4-40), male\/female: 238\/160 (1.48\/1.0); 211 of 398 (53%) tumors were Pgp-positive, and 204 of 398 (51.3%) patients received mifamurtide. With a median follow-up of 70 months (IQR, 49-90 months), the 5-year EFS and OS were 65.2% (95% CI, 60.1 to 69.8) and 74.8% (95% CI, 69.8 to 79.0), respectively, with superior EFS for patients undergoing mifamurtide and chemotherapy as compared with EFS of patients undergoing chemotherapy alone (5-year EFS 71.4%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      58.3%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0139) not confirmed at multivariable analysis (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0593).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>In this merged analysis with a risk-adapted strategy for nonmetastatic osteosarcoma, the group with unfavorable prognoses, identified by Pgp expression, performed well when mifamurtide, combined with HDIFO in case of poor response, was administered after surgery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00210","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T19:59:07Z","timestamp":1755547147000},"page":"3113-3122","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Is There a Role for Mifamurtide in Nonmetastatic High-Grade Osteosarcoma? Results From the Italian Sarcoma Group (ISG\/OS-2) and Spanish Sarcoma Group (GEIS-33) Trials"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct01459484","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04383288","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-6705","authenticated-orcid":true,"given":"Emanuela","family":"Palmerini","sequence":"first","affiliation":[{"name":"Osteoncology, Bone and Soft Tissue Sarcomas, and Innovative Therapies Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy"},{"name":"Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Meazza","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Tamburini","sequence":"additional","affiliation":[{"name":"Department of Pediatric Onco-Hematology, AOU Meyer\u2014IRCCS, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4305-950X","authenticated-orcid":true,"given":"Catalina","family":"M\u00e1rquez-Vega","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Unit, Hospital Infantil Universitario Virgen del Roc\u00edo, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4462-5523","authenticated-orcid":true,"given":"Gianni","family":"Bisogno","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9257-900X","authenticated-orcid":false,"given":"Franca","family":"Fagioli","sequence":"additional","affiliation":[{"name":"S.C. Oncoematologia Pediatrica\u2014Regina Margherita Children's Hospital, A.O.U. Citt\u00e0 della Salute e della Scienza di Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Ferraresi","sequence":"additional","affiliation":[{"name":"Sarcomas and Rare Tumors Departmental Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Maria","family":"Milano","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Gene and Cellular Therapy, IRCCS Ospedale Pediatrico Bambino Ges\u00f9, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5452-431X","authenticated-orcid":true,"given":"Luca","family":"Coccoli","sequence":"additional","affiliation":[{"name":"Pediatric Onco-Hematology Unit, S. 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