{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:03:06Z","timestamp":1791385386395,"version":"4.3.3"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T00:00:00Z","timestamp":1604102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: The evidence on high-dose ifosfamide (HD-IFO) use in patients with relapsed osteosarcoma is limited. We performed a retrospective study to analyze HD-IFO activity. Methods: Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +\/\u2212 ifosfamide (MAP+\/\u2212I)] with measurable disease according to RECIST1.1 were eligible to ifosfamide (3 g\/m2\/day) continuous infusion (c.i.) days 1\u20135 q21d. RECIST1.1 overall response rate (ORR) (complete response (CR) + partial response (PR)), progression-free survival at 6-month (6m-PFS), duration of response (DOR), and 2-year overall survival (2y-OS) were assessed. PARP1 expression and gene mutations were tested by immunohistochemistry and next-generation sequencing. Results: 51 patients were included. ORR was 20% (1 CR + 9 PR). Median DOR was 5 months (95%CI 2\u20137). Median PFS, 6m-PFS, OS, and 2y-OS were 6 months (95%CI 4\u20139), 51%, 15 months (10\u201319), and 30%, respectively. A second surgical complete remission (CR2) was achieved in 26 (51%) patients. After multivariate analysis, previous use of ifosfamide (HR 2.007, p = 0.034) and CR2 (HR 0.126, p &lt; 0.001) showed a significant correlation with PFS and OS, respectively. No significant correlation was found between outcomes and PARP1 or gene mutations. Conclusions: HD-IFO should be considered as the standard first-line treatment option in relapsed osteosarcoma and control arm of future trial in this setting.<\/jats:p>","DOI":"10.3390\/cells9112389","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T21:39:56Z","timestamp":1604180396000},"page":"2389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["High Dose Ifosfamide in Relapsed and Unresectable High-Grade Osteosarcoma Patients: A Retrospective Series"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-6705","authenticated-orcid":false,"given":"Emanuela","family":"Palmerini","sequence":"first","affiliation":[{"name":"Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9704-3290","authenticated-orcid":false,"given":"Elisabetta","family":"Setola","sequence":"additional","affiliation":[{"name":"Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5515-569X","authenticated-orcid":false,"given":"Giovanni","family":"Grignani","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS. St. Provinciale 142, Km 3.95, 10060 Candiolo, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3294-8819","authenticated-orcid":false,"given":"Lorenzo","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS. St. Provinciale 142, Km 3.95, 10060 Candiolo, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Comandone","sequence":"additional","affiliation":[{"name":"Ospedale San Giovanni Bosco, 10154 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Righi","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Longhi","sequence":"additional","affiliation":[{"name":"Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Cesari","sequence":"additional","affiliation":[{"name":"Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Paioli","sequence":"additional","affiliation":[{"name":"Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Hakim","sequence":"additional","affiliation":[{"name":"Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Pierini","sequence":"additional","affiliation":[{"name":"Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Marchesi","sequence":"additional","affiliation":[{"name":"Italian Sarcoma Group, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Vanel","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5073-8618","authenticated-orcid":false,"given":"Ymera","family":"Pignochino","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS. St. Provinciale 142, Km 3.95, 10060 Candiolo, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide Maria","family":"Donati","sequence":"additional","affiliation":[{"name":"Orthopedic Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8519-4101","authenticated-orcid":false,"given":"Piero","family":"Picci","sequence":"additional","affiliation":[{"name":"Italian Sarcoma Group, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Campanacci, M. 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