{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:16:38Z","timestamp":1791771398547,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Prognostic factors have been well described for osteosarcoma, but analyses evaluating the further course of long\u2010term survivors are lacking. We used the large database of the Cooperative Osteosarcoma Study Group (COSS) to perform such an analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>The COSS database 1980\u201004\/2019 was searched for 5\u2010year survivors of primary high\u2010grade central osteosarcoma of the extremities or trunk. Identified patients were analyzed for their further survival outcomes, assessing potentially prognostic and predictive factors already evident at initial disease presentation and treatment as well as their disease course during the first 5\u2009years of follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two thousand and nine former eligible patients were identified (median age at initial diagnosis 15.1 (2.5\u201363.0) years; male vs. female 1149 (57.2%) vs. 860 (42.8%); extremities vs. trunk 1927 (95.9%) vs. 82 (4.1%); extremity primaries &lt;1\/3 vs. \u22651\/3 of the involved bone 997 (67.8%) vs. 474 (32.2%) (456 unknown); localized vs. primary metastatic 1881 (93.6%) vs. 128 (6.4%); osteosarcoma as a secondary malignancy 41\/2009 (2.0%)). Therapy starting by chemotherapy versus primary surgery 1860 (92.6%) versus 149 (7.4%); definitive tumor surgery by limb salvage versus ablative 1347 (67.0%) versus 659 (1 no surgery, 2 unknown); tumor response to preoperative chemotherapy documented for 1765 (94.9%) patients receiving neoadjuvant chemotherapy, good (&lt;10% viable tumor) versus poor 1130 (64.0%) versus 635 (36.0%), local radiotherapy documented for 19 (0.9%) tumors. Recurrence during preceding 5\u2009years no versus yes 1681 (83.7%) versus 328 (16.3%).<\/jats:p>\n                    <jats:p>\n                      Median follow\u2010up starting 5\u2009years after initial diagnosis 6.1 (0.002\u201332.2) years; 1815 survivors and 194 deaths. Overall survival after another 5\/10\/15\/20\u2009years 91.7%\/88.9%\/85.8%\/83.4% for all patients; 97.5%\/95.2%\/92.4%\/89.9% if in remission years 1\u20135 versus 62.7%\/57.3%\/53.0%\/51.2% if recurrence year 1\u20135 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Significant predictors of survival for all patients age at diagnosis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.038), tumor site (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.030), having experienced the osteosarcoma as secondary malignancy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), tumor response to preoperative chemotherapy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Multivariate Cox regression testing possible for 1759 (87.6%) patients with complete dataset: Having had a recurrence in years 1\u20135 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), older age at diagnosis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009), and osteosarcoma as secondary malignancy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.013) retained significance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Highly important predictors of death such as the extent of tumor response to chemotherapy no longer remain valid after 5\u2010year survival. The individual history of malignancies and their outcomes seems to gain pivotal importance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This benchmark analysis clearly defined risk factors for the further course of 5\u2010year survivors from osteosarcoma. It argues for large disease\u2010oriented databases as well as for very long follow\u2010up periods. Novel findings will most likely require innovative statistical models to analyze such cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.6893","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T07:28:56Z","timestamp":1706513336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Beyond 5\u2010year survival. A report from the Cooperative Osteosarcoma Study Group (\n                    <scp>COSS<\/scp>\n                    )"],"prefix":"10.1002","volume":"13","author":[{"given":"Julia S.","family":"Fernandes","sequence":"first","affiliation":[{"name":"P\u00e4diatrie 5 (Onkologie, H\u00e4matologie, Immunologie), Stuttgart Cancer Center, Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin Klinikum Stuttgart\u2013Olgahospital  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4045-5838","authenticated-orcid":false,"given":"Claudia","family":"Blattmann","sequence":"additional","affiliation":[{"name":"P\u00e4diatrie 5 (Onkologie, H\u00e4matologie, Immunologie), Stuttgart Cancer Center, Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin Klinikum Stuttgart\u2013Olgahospital  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1815-138X","authenticated-orcid":false,"given":"Stefanie","family":"Hecker\u2010Nolting","sequence":"additional","affiliation":[{"name":"P\u00e4diatrie 5 (Onkologie, H\u00e4matologie, Immunologie), Stuttgart Cancer Center, Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin Klinikum Stuttgart\u2013Olgahospital  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4954-6488","authenticated-orcid":false,"given":"Leo","family":"Kager","sequence":"additional","affiliation":[{"name":"St. Anna Kinderspital, Universit\u00e4tsklinik f\u00fcr Kinder\u2010 und Jugendheilkunde der Medizinischen Universit\u00e4t Wien  Vienna Austria"},{"name":"St. Anna Children's Cancer Research Institute  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kevric","sequence":"additional","affiliation":[{"name":"P\u00e4diatrie 5 (Onkologie, H\u00e4matologie, Immunologie), Stuttgart Cancer Center, Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin Klinikum Stuttgart\u2013Olgahospital  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4460-8830","authenticated-orcid":false,"given":"Vanessa","family":"Mettmann","sequence":"additional","affiliation":[{"name":"P\u00e4diatrie 5 (Onkologie, H\u00e4matologie, Immunologie), Stuttgart Cancer Center, Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin Klinikum Stuttgart\u2013Olgahospital  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Sorg","sequence":"additional","affiliation":[{"name":"P\u00e4diatrie 5 (Onkologie, H\u00e4matologie, Immunologie), Stuttgart Cancer Center, Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin Klinikum Stuttgart\u2013Olgahospital  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4494-6741","authenticated-orcid":false,"given":"Marc","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Hochschule Aalen  Aalen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2144-3153","authenticated-orcid":false,"given":"Stefan S.","family":"Bielack","sequence":"additional","affiliation":[{"name":"P\u00e4diatrie 5 (Onkologie, H\u00e4matologie, Immunologie), Stuttgart Cancer Center, Zentrum f\u00fcr Kinder\u2010, Jugend\u2010 und Frauenmedizin Klinikum Stuttgart\u2013Olgahospital  Stuttgart Germany"},{"name":"Klinik f\u00fcr Kinder\u2010 und Jugendmedizin, P\u00e4diatrische H\u00e4matologie und Onkologie Universit\u00e4tsklinikum M\u00fcnster  M\u00fcnster 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