{"entity":{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","aka":[],"tldr":"Osteosarcoma is the most common bone cancer, mostly in teenagers. Chemotherapy plus surgery cures about two-thirds when it has not spread; because no new drug has beaten that chemotherapy in a large trial in 30 years, the next gains are being sought in cellular therapy against GD2, HER2 and B7-H3.","summary":"Osteosarcoma is a high-grade bone sarcoma with chaotic genomes (TP53 and RB1 loss, chromothripsis, no recurrent targetable driver), arising in the metaphyses of long bones during growth spurts and in older adults after Paget disease or radiation. Germline predisposition (Li-Fraumeni, hereditary retinoblastoma, Rothmund-Thomson) accounts for a meaningful fraction.\n\nStandard therapy since the 1980s is neoadjuvant MAP (high-dose methotrexate, doxorubicin, cisplatin), limb-salvage surgery, and adjuvant MAP; histologic response (≥90% necrosis) is prognostic but intensifying therapy for poor responders (EURAMOS-1: adding ifosfamide-etoposide) did not help, nor did interferon maintenance. Mifamurtide (liposomal MTP-PE) is approved in the EU (INT-0133) but not in the US. Lung metastases are resected whenever possible. Relapsed disease has ~20% survival; multikinase inhibitors (regorafenib in SARC024/REGOBONE, cabozantinib in CABONE, sorafenib) give short PFS gains. Novel approaches: GD2- and HER2-directed CAR-T, B7-H3 ADCs, radiopharmaceuticals (Ra-223, Sm-153), and biology from canine osteosarcoma.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Osteosarcoma","links":[{"label":"NCCN Guidelines: Bone Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418"},{"label":"EURAMOS-1 (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(16)30214-5"},{"label":"NCI PDQ: osteosarcoma","url":"https://www.cancer.gov/types/bone/patient/osteosarcoma-treatment-pdq"}],"tags":["gap-fill","paediatric","sarcoma","aya"],"related":["ewing-sarcoma","chondrosarcoma","chordoma","rhabdomyosarcoma","undifferentiated-pleomorphic-sarcoma"],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","limb-salvage-surgery","kinase-inhibitors","carbon-ion","proton-therapy","car-t","radioligand-therapy"],"targets":["gd2","her2","b7h3","tp53","vegf"],"drugs":["methotrexate","doxorubicin","cisplatin","ifosfamide","etoposide","mifamurtide","regorafenib","cabozantinib","docetaxel","radium-223"],"companies":["bayer","exelixis","takeda","childrens-oncology-group"],"institutions":[],"pathways":["p53-cell-cycle","vegf-angiogenesis"],"terms":["fnclcc-grade","limb-salvage-term","histological-response-induction"],"trials":["euramos-1","ccss","nct06935409","cabone","regobone","sarc028"],"people":["stefan-bielack"],"bottlenecks":[],"keyPapers":["paper-marina-lancet-oncol"],"journals":["journal-of-adolescent-and-young-adult-oncology"],"dependsOn":[],"notes":[],"group":"paediatric","burden":"The most common primary bone cancer; ~1,000 cases per year in the US with peaks in adolescence and over 60 (Paget disease, radiation); 5-year survival ~70% localised, ~25% metastatic.","subtypes":["Conventional high-grade (osteoblastic, chondroblastic, fibroblastic)","Telangiectatic","Small cell","Low-grade central and parosteal (surgery alone)","Periosteal (intermediate grade)","Secondary (Paget, post-radiation)"],"biomarkers":["Histologic necrosis after neoadjuvant chemotherapy (≥90% good response)","Alkaline phosphatase and LDH","Metastases at diagnosis (lung, bone)","Germline TP53 / RB1 / RECQL4","GD2, HER2, B7-H3 expression (trial eligibility)","ctDNA copy-number burden (prognostic, emerging)"],"standardOfCare":[{"setting":"Localised high-grade","approach":"Neoadjuvant MAP (methotrexate, doxorubicin, cisplatin) ×2 cycles, limb-salvage resection with wide margins (amputation if required), adjuvant MAP to ~29 weeks; mifamurtide added in EU.","refs":["methotrexate","doxorubicin","cisplatin","mifamurtide","limb-salvage-surgery"],"guideline":{"nccn":"Category 1 (MAP)","version":"NCCN Guidelines: Bone Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418"}},{"setting":"Metastatic at diagnosis","approach":"Same chemotherapy with resection of all metastases (thoracotomy) when feasible; survival ~25-30%.","refs":["methotrexate","doxorubicin","cisplatin","ifosfamide","etoposide"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Bone Cancer"}},{"setting":"Relapsed","approach":"Surgical resection of recurrence; ifosfamide ± etoposide, gemcitabine-docetaxel; regorafenib or cabozantinib; clinical trials (CAR-T, ADCs).","refs":["ifosfamide","etoposide","regorafenib","cabozantinib","docetaxel"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Bone Cancer"}},{"setting":"Unresectable / axial","approach":"Carbon-ion or proton radiotherapy for craniofacial and pelvic tumours; Sm-153 or Ra-223 for bone-forming metastases (investigational).","refs":["carbon-ion","proton-therapy","radium-223"]}],"stateOfArt":["MAP chemotherapy, unchanged since the 1980s, remains the standard; EURAMOS-1 (2,260 patients) closed the door on intensification.","Limb salvage is possible in >90% with expandable prostheses for growing children.","Multikinase inhibitors are the only agents with randomised evidence at relapse, and the gain is months.","Immunotherapy has largely failed (checkpoint inhibitors inactive); cellular therapy against GD2/HER2/B7-H3 is the active frontier."],"history":[{"year":1970,"title":"Amputation alone cures <20%; lung metastases the rule","refs":[]},{"year":1972,"title":"High-dose methotrexate with leucovorin rescue (Jaffe) and adriamycin (Cortes) show activity","refs":["methotrexate","doxorubicin"]},{"year":1979,"title":"Rosen's T-10: neoadjuvant chemotherapy and limb salvage","refs":["limb-salvage-surgery"]},{"year":1986,"title":"Randomised proof that adjuvant chemotherapy cures (Link, NEJM; MIOS)","refs":[]},{"year":2008,"title":"INT-0133: mifamurtide improves overall survival; EU approval 2009","refs":["mifamurtide"]},{"year":2016,"title":"EURAMOS-1: no benefit from intensifying for poor responders or interferon for good responders","refs":[]},{"year":2019,"title":"Regorafenib (SARC024, REGOBONE) and cabozantinib (CABONE) show activity at relapse","refs":["regorafenib","cabozantinib"]}],"pipeline":["regorafenib","cabozantinib","car-t","radium-223","b7h3","hs-20093","cobolimab","vactosertib"],"openProblems":["No survival improvement since the 1980s; metastatic and relapsed disease ~20-30% survival.","No recurrent druggable driver; genomic chaos.","Chemotherapy toxicity: cardiotoxicity, hearing loss, infertility, second cancers.","Rarity fragments trials; international cooperation (EURAMOS) needed for every question."],"parent":"sarcoma"},"route":"/cancers/osteosarcoma/","neighbours":{"cancer":[{"id":"adamantinoma","kind":"cancer","name":"Adamantinoma of bone","route":"/cancers/adamantinoma/"},{"id":"aya-cancers","kind":"cancer","name":"Adolescent and young adult cancers (ages 15 to 39)","route":"/cancers/aya-cancers/"},{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"chondrosarcoma","kind":"cancer","name":"Chondrosarcoma","route":"/cancers/chondrosarcoma/"},{"id":"chordoma","kind":"cancer","name":"Chordoma","route":"/cancers/chordoma/"},{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","route":"/cancers/ewing-sarcoma/"},{"id":"rhabdomyosarcoma","kind":"cancer","name":"Rhabdomyosarcoma","route":"/cancers/rhabdomyosarcoma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"undifferentiated-pleomorphic-sarcoma","kind":"cancer","name":"Undifferentiated pleomorphic sarcoma (UPS)","route":"/cancers/undifferentiated-pleomorphic-sarcoma/"}],"technology":[{"id":"rejuv-ayac-distinct-group","kind":"technology","name":"Adolescents and young adults: a group with its own cancers, its own gap and its own needs","route":"/technologies/rejuv-ayac-distinct-group/"},{"id":"biology-guided-radiotherapy","kind":"technology","name":"Biology-guided radiotherapy (RefleXion X1, SCINTIX)","route":"/technologies/biology-guided-radiotherapy/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"carbon-ion-synchrotrons","kind":"technology","name":"Carbon-ion synchrotrons and facilities","route":"/technologies/carbon-ion-synchrotrons/"},{"id":"carbon-ion","kind":"technology","name":"Carbon-ion therapy","route":"/technologies/carbon-ion/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"rejuv-paed-fertility-female","kind":"technology","name":"Fertility in girls and young women treated for cancer, including ovarian tissue freezing","route":"/technologies/rejuv-paed-fertility-female/"},{"id":"rejuv-paed-hearing","kind":"technology","name":"Hearing after platinum and cranial radiotherapy in a developing child","route":"/technologies/rejuv-paed-hearing/"},{"id":"hearing-after-platinum-chemotherapy","kind":"technology","name":"Hearing and tinnitus after platinum chemotherapy","route":"/technologies/hearing-after-platinum-chemotherapy/"},{"id":"rejuv-ayac-diagnostic-delay","kind":"technology","name":"How long it takes to diagnose cancer in a young person, and what the evidence actually says","route":"/technologies/rejuv-ayac-diagnostic-delay/"},{"id":"rejuv-paed-chronic-disease-burden","kind":"technology","name":"How much illness childhood cancer survivors carry, and at what age","route":"/technologies/rejuv-paed-chronic-disease-burden/"},{"id":"rejuv-paed-kidneys","kind":"technology","name":"Kidneys after cisplatin, ifosfamide, radiotherapy and nephrectomy in childhood","route":"/technologies/rejuv-paed-kidneys/"},{"id":"rejuv-recon-limb","kind":"technology","name":"Limb salvage, amputation, and the rehabilitation that follows either","route":"/technologies/rejuv-recon-limb/"},{"id":"limb-salvage-surgery","kind":"technology","name":"Limb-salvage surgery and endoprosthetic reconstruction","route":"/technologies/limb-salvage-surgery/"},{"id":"rejuv-mind-body-after-stoma-and-limb-loss","kind":"technology","name":"Living with a stoma, and living after an amputation","route":"/technologies/rejuv-mind-body-after-stoma-and-limb-loss/"},{"id":"sarcoma-methylation-classifier","kind":"technology","name":"Methylation classifier for sarcomas","route":"/technologies/sarcoma-methylation-classifier/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"},{"id":"rejuv-ayac-services","kind":"technology","name":"Services built for teenagers and young adults, and what the national evaluation found","route":"/technologies/rejuv-ayac-services/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"},{"id":"rejuv-rehab-assistive-devices","kind":"technology","name":"The devices that do the restoring, and who pays for them","route":"/technologies/rejuv-rehab-assistive-devices/"},{"id":"rejuv-paed-heart","kind":"technology","name":"The heart after anthracyclines and chest radiotherapy in childhood","route":"/technologies/rejuv-paed-heart/"},{"id":"x-ray-radiography-fluoroscopy","kind":"technology","name":"X-ray radiography and fluoroscopy","route":"/technologies/x-ray-radiography-fluoroscopy/"}],"target":[{"id":"aldh2","kind":"target","name":"ALDH2","route":"/targets/aldh2/"},{"id":"b7h3","kind":"target","name":"B7-H3","route":"/targets/b7h3/"},{"id":"cxcl10","kind":"target","name":"CXCL10","route":"/targets/cxcl10/"},{"id":"dhfr","kind":"target","name":"Dihydrofolate reductase (DHFR)","route":"/targets/dhfr/"},{"id":"ercc2","kind":"target","name":"ERCC2","route":"/targets/ercc2/"},{"id":"gd2","kind":"target","name":"GD2 (disialoganglioside)","route":"/targets/gd2/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"recql4","kind":"target","name":"RECQL4","route":"/targets/recql4/"},{"id":"sqstm1","kind":"target","name":"SQSTM1","route":"/targets/sqstm1/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"},{"id":"znf217","kind":"target","name":"ZNF217","route":"/targets/znf217/"}],"drug":[{"id":"aldoxorubicin","kind":"drug","name":"Aldoxorubicin","route":"/drugs/aldoxorubicin/"},{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","route":"/drugs/cabozantinib/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"cobolimab","kind":"drug","name":"Cobolimab","route":"/drugs/cobolimab/"},{"id":"denosumab","kind":"drug","name":"Denosumab","route":"/drugs/denosumab/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"hs-20093","kind":"drug","name":"HS-20093","route":"/drugs/hs-20093/"},{"id":"ifosfamide","kind":"drug","name":"Ifosfamide","route":"/drugs/ifosfamide/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"mifamurtide","kind":"drug","name":"Mifamurtide","route":"/drugs/mifamurtide/"},{"id":"radium-223","kind":"drug","name":"Radium-223 dichloride","route":"/drugs/radium-223/"},{"id":"regorafenib","kind":"drug","name":"Regorafenib","route":"/drugs/regorafenib/"},{"id":"sodium-thiosulfate","kind":"drug","name":"Sodium thiosulfate (otoprotectant)","route":"/drugs/sodium-thiosulfate/"},{"id":"vactosertib","kind":"drug","name":"Vactosertib","route":"/drugs/vactosertib/"}],"company":[{"id":"bayer","kind":"company","name":"Bayer","route":"/companies/bayer/"},{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"},{"id":"exelixis","kind":"company","name":"Exelixis","route":"/companies/exelixis/"},{"id":"french-sarcoma-group","kind":"company","name":"French Sarcoma Group","route":"/companies/french-sarcoma-group/"},{"id":"gemini-therapeutics","kind":"company","name":"Gemini Therapeutics","route":"/companies/gemini-therapeutics/"},{"id":"sarc","kind":"company","name":"SARC (Sarcoma Alliance for Research through Collaboration)","route":"/companies/sarc/"},{"id":"takeda","kind":"company","name":"Takeda","route":"/companies/takeda/"}],"pathway":[{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"},{"id":"vegf-angiogenesis","kind":"pathway","name":"VEGF angiogenesis","route":"/pathways/vegf-angiogenesis/"}],"term":[{"id":"aya-oncology","kind":"term","name":"Adolescent and young adult (AYA) oncology","route":"/terms/aya-oncology/"},{"id":"fnclcc-grade","kind":"term","name":"FNCLCC grade (soft-tissue sarcoma)","route":"/terms/fnclcc-grade/"},{"id":"histological-response-induction","kind":"term","name":"Histological response to induction chemotherapy (osteosarcoma and Ewing sarcoma)","route":"/terms/histological-response-induction/"},{"id":"li-fraumeni","kind":"term","name":"Li-Fraumeni syndrome (germline TP53)","route":"/terms/li-fraumeni/"},{"id":"limb-salvage-term","kind":"term","name":"Limb-salvage surgery","route":"/terms/limb-salvage-term/"}],"trial":[{"id":"nct02441309","kind":"trial","name":"A Eurosarc Study of Mifamurtide in Advanced Osteosarcoma (MEMOS)","route":"/trials/nct02441309/"},{"id":"nct06521567","kind":"trial","name":"A Study of Cobolimab Plus Dostarlimab in Pediatric and Young Adult Participants With Cancer","route":"/trials/nct06521567/"},{"id":"nct05830123","kind":"trial","name":"ARTEMIS-002: HS-20093 in Patients With Relapsed or Refractory Osteosarcoma and Other Sarcomas","route":"/trials/nct05830123/"},{"id":"cabone","kind":"trial","name":"CABONE","route":"/trials/cabone/"},{"id":"ccss","kind":"trial","name":"Childhood Cancer Survivor Study (CCSS)","route":"/trials/ccss/"},{"id":"nct01886105","kind":"trial","name":"Combination of External Beam Radiotherapy With 153Sm-EDTMP to Treat High Risk Osteosarcoma","route":"/trials/nct01886105/"},{"id":"nct00112463","kind":"trial","name":"Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma","route":"/trials/nct00112463/"},{"id":"euramos-1","kind":"trial","name":"EURAMOS-1","route":"/trials/euramos-1/"},{"id":"nct07787429","kind":"trial","name":"Evaluation of the Safety and Efficacy of Mifamurtide Versus Standard Treatment With Sorafenib in Patients With High-risk Osteosarcoma","route":"/trials/nct07787429/"},{"id":"nct00634322","kind":"trial","name":"High Dose Methotrexate With Leucovorin Rescue With or Without Glucarpidase in Osteosarcoma","route":"/trials/nct00634322/"},{"id":"nct07357519","kind":"trial","name":"Lu-TARGO (177Lu-TARGeted Osteosarcoma Therapy)","route":"/trials/nct07357519/"},{"id":"nct03643133","kind":"trial","name":"Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma 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Italiano","route":"/people/antoine-italiano/"},{"id":"emil-frei","kind":"person","name":"Emil \"Tom\" Frei III","route":"/people/emil-frei/"},{"id":"florence-duffaud","kind":"person","name":"Florence Duffaud","route":"/people/florence-duffaud/"},{"id":"robbie-majzner","kind":"person","name":"Robbie G. 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Bielack","route":"/people/stefan-bielack/"},{"id":"terry-fox","kind":"person","name":"Terry Fox","route":"/people/terry-fox/"},{"id":"uta-dirksen","kind":"person","name":"Uta Dirksen","route":"/people/uta-dirksen/"}],"paper":[{"id":"paper-marina-lancet-oncol","kind":"paper","name":"Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial","route":"/key-papers/paper-marina-lancet-oncol/"},{"id":"paper-gilene-ivermectin-toxicity-paediatric-oncology-2025","kind":"paper","name":"The threat of medical misinformation: a case of ivermectin toxicity in a pediatric oncology patient","route":"/key-papers/paper-gilene-ivermectin-toxicity-paediatric-oncology-2025/"}],"journal":[{"id":"journal-of-adolescent-and-young-adult-oncology","kind":"journal","name":"Journal of adolescent and young adult oncology","route":"/journals/journal-of-adolescent-and-young-adult-oncology/"}],"collection":[{"id":"alexs-lemonade-stand","kind":"collection","name":"Alex's Lemonade Stand Foundation (ALSF)","route":"/collections/alexs-lemonade-stand/"},{"id":"st-baldricks","kind":"collection","name":"St. Baldrick's Foundation","route":"/collections/st-baldricks/"}],"institution":[{"id":"ap-hm-timone","kind":"institution","name":"Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille","route":"/institutions/ap-hm-timone/"},{"id":"klinikum-stuttgart-olgahospital","kind":"institution","name":"Klinikum Stuttgart / Olgahospital","route":"/institutions/klinikum-stuttgart-olgahospital/"},{"id":"nationwide-childrens","kind":"institution","name":"Nationwide Children's Hospital","route":"/institutions/nationwide-childrens/"},{"id":"sarcoma-oncology-center","kind":"institution","name":"Sarcoma Oncology Center","route":"/institutions/sarcoma-oncology-center/"},{"id":"st-jude","kind":"institution","name":"St. Jude Children's Research Hospital","route":"/institutions/st-jude/"},{"id":"terry-fox-foundation","kind":"institution","name":"Terry Fox Foundation","route":"/institutions/terry-fox-foundation/"},{"id":"texas-childrens","kind":"institution","name":"Texas Children's Cancer and Hematology Center","route":"/institutions/texas-childrens/"}]}}