{"entity":{"id":"osteosarcoma","kind":"indication","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":["ra-223","sm-153"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":["her2","b7h3"],"drugs":["cabozantinib","docetaxel","radium-223"],"companies":["bayer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"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":[],"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":[],"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":["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":["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":[]},{"year":1979,"title":"Rosen's T-10: neoadjuvant chemotherapy and limb salvage","refs":[]},{"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":[]},{"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":["cabozantinib"]}],"pipeline":["cabozantinib","radium-223","b7h3"],"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."]},"route":"/indications/osteosarcoma/","neighbours":{"isotope":[{"id":"ra-223","kind":"isotope","name":"Radium-223","route":"/isotopes/ra-223/"},{"id":"sm-153","kind":"isotope","name":"Samarium-153","route":"/isotopes/sm-153/"}],"technology":[{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"}],"target":[{"id":"b7h3","kind":"target","name":"B7-H3","route":"/targets/b7h3/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","route":"/drugs/cabozantinib/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"radium-223","kind":"drug","name":"Radium-223 dichloride","route":"/drugs/radium-223/"}],"company":[{"id":"bayer","kind":"company","name":"Bayer","route":"/companies/bayer/"}],"trial":[{"id":"nct07357519","kind":"trial","name":"Lu-TARGO (177Lu-TARGeted Osteosarcoma Therapy)","route":"/trials/nct07357519/"}]}}