{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:33:47Z","timestamp":1761676427557},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T00:00:00Z","timestamp":1467849600000},"content-version":"vor","delay-in-days":67,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31170914","31370944"],"award-info":[{"award-number":["31170914","31370944"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The purpose of this study was to present our clinical experience of treating multifocal osteosarcoma (<jats:styled-content style=\"fixed-case\">MFOS<\/jats:styled-content>) in our center and gain more insight into the biology of this rare condition; in particular, to address with the help of precision genomic medicine the issue of whether the multiple osteosarcoma (OS) lesions in such patients are multi\u2010centric or originate from one primary lesion and metastasize to other sites. Finally, we aimed to identify particular gene phenotypes and mutations that differentiate MFOS from OS with only one tumor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical data of patients <jats:styled-content style=\"fixed-case\">with MFOS<\/jats:styled-content> treated at our center between <jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>une 2007 and <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content>ctober 2014 were collected and analyzed retrospectively. High throughput sequencing of the whole exome of normal tissue and multiple lesions had been performed on samples from two patients (<jats:styled-content style=\"fixed-case\">HJF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">JZ)<\/jats:styled-content> diagnosed in 2014. To explore the particular gene phenotype and clinical significance of <jats:styled-content style=\"fixed-case\">MFOS<\/jats:styled-content>, these sequencing results were analyzed and compared with those from patients with osteosarcoma in a single site. Seven patients with <jats:styled-content style=\"fixed-case\">MFOS<\/jats:styled-content> (three male and four female; average age 19.71 \u00b1 3.35 years were enrolled in this study. Two of these patients declined treatment and died after 4 and 6 months, respectively. The remaining patients received standard treatment comprising neoadjuvant chemotherapy, surgery and chemotherapy. The chemotherapy regimen was lobaplatin (45 mg\/m<jats:sup>2<\/jats:sup>), doxorubicin (60 mg\/m<jats:sup>2<\/jats:sup>) and ifosfamide (12 g\/m<jats:sup>2<\/jats:sup>). Patients were followed up every 3 months after completing treatment and evaluated by the <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>nneking and Response Evaluation Criteria in Solid Tumors scoring systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Up to the last follow\u2010up on 1 <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>ecember 2015, three patients were still alive. The event\u2010free survival ranged from 4 to 144 weeks (median, 50.14 weeks), the mean (\u00b1<jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>) being 55.45 \u00b1 45.47 weeks. Overall survival ranged from 16 to 388 weeks (median, 89 weeks; mean \u00b1 <jats:styled-content style=\"fixed-case\">SD,<\/jats:styled-content> 118.7 \u00b1 147.7 weeks). The rates of mutation of the targeted drug\u2010related genes were 133.5% \u00b1 3.0% in the proximal tibia lesion and 113.1% \u00b1 1.9% in the distal femur of patient <jats:styled-content style=\"fixed-case\">HJF<\/jats:styled-content> (<jats:italic>P<\/jats:italic> &lt; 0.01) and 136.1% \u00b1 10.8% in the proximal tibial lesion and 122.3% \u00b1 5.5% in the proximal humerus of patient <jats:styled-content style=\"fixed-case\">JZ<\/jats:styled-content> (<jats:italic>P<\/jats:italic> = 0.0335). Furthermore, there were several anti\u2010oncogenes in the somatic copy number variation lists analyzed from the two patients, especially <jats:styled-content style=\"fixed-case\">TP53<\/jats:styled-content>. However, no kataegis was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Early and radical surgery accompanied by appropriate chemotherapy is the optimal means of treating <jats:styled-content style=\"fixed-case\">MFOS<\/jats:styled-content>. These patients may benefit from precision genomic medicine.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.12249","type":"journal-article","created":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T11:04:11Z","timestamp":1467889451000},"page":"129-138","source":"Crossref","is-referenced-by-count":1,"title":["Preliminary Application of Precision Genomic Medicine Detecting Gene Variation in Patients with Multifocal Osteosarcoma"],"prefix":"10.1111","volume":"8","author":[{"given":"Hao\u2010qiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Xijing Hospital Forth Military Medical University  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Xijing Hospital Forth Military Medical University  Xi'an 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