# Osteosarcoma

Source: https://onco.cc/cancers/osteosarcoma/  
OnCo record `osteosarcoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Standard 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; paediatric; sarcoma; aya
- 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/osteosarcoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/osteosarcoma/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/osteosarcoma/#what-it-is [6 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/osteosarcoma/#finding-it [6 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/osteosarcoma/#treating-it [4 settings, 1 regimen, 4 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/osteosarcoma/#evidence [18 trials, 2 key papers, 7 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/osteosarcoma/#science [18 targets, 2 pathways, 6 preclinical models]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/osteosarcoma/where-you-are/ [7 centres]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/osteosarcoma/#living-with-it [17 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/osteosarcoma/coming/ [16 medicines, 18 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/osteosarcoma/data/ [119 connected records]

## Standard of care

- Localised high-grade: 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. ([Methotrexate](https://onco.cc/drugs/methotrexate/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Mifamurtide](https://onco.cc/drugs/mifamurtide/), [Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/))
- Metastatic at diagnosis: Same chemotherapy with resection of all metastases (thoracotomy) when feasible; survival ~25-30%. ([Methotrexate](https://onco.cc/drugs/methotrexate/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Etoposide](https://onco.cc/drugs/etoposide/))
- Relapsed: Surgical resection of recurrence; ifosfamide ± etoposide, gemcitabine-docetaxel; regorafenib or cabozantinib; clinical trials (CAR-T, ADCs). ([Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Etoposide](https://onco.cc/drugs/etoposide/), [Regorafenib](https://onco.cc/drugs/regorafenib/), [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Docetaxel](https://onco.cc/drugs/docetaxel/))
- Unresectable / axial: Carbon-ion or proton radiotherapy for craniofacial and pelvic tumours; Sm-153 or Ra-223 for bone-forming metastases (investigational). ([Carbon-ion therapy](https://onco.cc/technologies/carbon-ion/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Radium-223 dichloride](https://onco.cc/drugs/radium-223/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Osteosarcoma
- NCCN Guidelines: Bone Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418
- EURAMOS-1 (Lancet Oncol 2016): https://doi.org/10.1016/S1470-2045(16)30214-5
- NCI PDQ: osteosarcoma: https://www.cancer.gov/types/bone/patient/osteosarcoma-treatment-pdq

## Connected records

- cancers: [Adamantinoma of bone](https://onco.cc/cancers/adamantinoma/), [Adolescent and young adult cancers (ages 15 to 39)](https://onco.cc/cancers/aya-cancers/), [Childhood cancers (all types)](https://onco.cc/cancers/childhood-cancers/), [Chondrosarcoma](https://onco.cc/cancers/chondrosarcoma/), [Chordoma](https://onco.cc/cancers/chordoma/), [Ewing sarcoma](https://onco.cc/cancers/ewing-sarcoma/), [Rhabdomyosarcoma](https://onco.cc/cancers/rhabdomyosarcoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Undifferentiated pleomorphic sarcoma (UPS)](https://onco.cc/cancers/undifferentiated-pleomorphic-sarcoma/)
- technologies: [Biology-guided radiotherapy (RefleXion X1, SCINTIX)](https://onco.cc/technologies/biology-guided-radiotherapy/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Carbon-ion synchrotrons and facilities](https://onco.cc/technologies/carbon-ion-synchrotrons/), [Carbon-ion therapy](https://onco.cc/technologies/carbon-ion/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Limb-salvage surgery and endoprosthetic reconstruction](https://onco.cc/technologies/limb-salvage-surgery/), [Methylation classifier for sarcomas](https://onco.cc/technologies/sarcoma-methylation-classifier/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Radioligand therapy (beta emitters)](https://onco.cc/technologies/radioligand-therapy/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/), [X-ray radiography and fluoroscopy](https://onco.cc/technologies/x-ray-radiography-fluoroscopy/)
- targets: [ALDH2](https://onco.cc/targets/aldh2/), [B7-H3](https://onco.cc/targets/b7h3/), [CXCL10](https://onco.cc/targets/cxcl10/), [Dihydrofolate reductase (DHFR)](https://onco.cc/targets/dhfr/), [ERCC2](https://onco.cc/targets/ercc2/), [GD2 (disialoganglioside)](https://onco.cc/targets/gd2/), [HER2](https://onco.cc/targets/her2/), [RECQL4](https://onco.cc/targets/recql4/), [SQSTM1](https://onco.cc/targets/sqstm1/), [TP53](https://onco.cc/targets/tp53/), [VEGF / VEGFR](https://onco.cc/targets/vegf/), [ZNF217](https://onco.cc/targets/znf217/)
- drugs: [Aldoxorubicin](https://onco.cc/drugs/aldoxorubicin/), [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Cobolimab](https://onco.cc/drugs/cobolimab/), [Denosumab](https://onco.cc/drugs/denosumab/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Etoposide](https://onco.cc/drugs/etoposide/), [HS-20093](https://onco.cc/drugs/hs-20093/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Mifamurtide](https://onco.cc/drugs/mifamurtide/), [Radium-223 dichloride](https://onco.cc/drugs/radium-223/), [Regorafenib](https://onco.cc/drugs/regorafenib/), [Sodium thiosulfate (otoprotectant)](https://onco.cc/drugs/sodium-thiosulfate/), [Vactosertib](https://onco.cc/drugs/vactosertib/)
- companies: [Bayer](https://onco.cc/companies/bayer/), [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/), [Exelixis](https://onco.cc/companies/exelixis/), [French Sarcoma Group](https://onco.cc/companies/french-sarcoma-group/), [Gemini Therapeutics](https://onco.cc/companies/gemini-therapeutics/), [SARC (Sarcoma Alliance for Research through Collaboration)](https://onco.cc/companies/sarc/), [Takeda](https://onco.cc/companies/takeda/)
- pathways: [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/)
- terms: [Adolescent and young adult (AYA) oncology](https://onco.cc/terms/aya-oncology/), [FNCLCC grade (soft-tissue sarcoma)](https://onco.cc/terms/fnclcc-grade/), [Histological response to induction chemotherapy (osteosarcoma and Ewing sarcoma)](https://onco.cc/terms/histological-response-induction/), [Li-Fraumeni syndrome (germline TP53)](https://onco.cc/terms/li-fraumeni/), [Limb-salvage surgery](https://onco.cc/terms/limb-salvage-term/)
- trials: [A Eurosarc Study of Mifamurtide in Advanced Osteosarcoma (MEMOS)](https://onco.cc/trials/nct02441309/), [A Study of Cobolimab Plus Dostarlimab in Pediatric and Young Adult Participants With Cancer](https://onco.cc/trials/nct06521567/), [ARTEMIS-002: HS-20093 in Patients With Relapsed or Refractory Osteosarcoma and Other Sarcomas](https://onco.cc/trials/nct05830123/), [CABONE](https://onco.cc/trials/cabone/), [Childhood Cancer Survivor Study (CCSS)](https://onco.cc/trials/ccss/), [Combination of External Beam Radiotherapy With 153Sm-EDTMP to Treat High Risk Osteosarcoma](https://onco.cc/trials/nct01886105/), [Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma](https://onco.cc/trials/nct00112463/), [EURAMOS-1](https://onco.cc/trials/euramos-1/), [Evaluation of the Safety and Efficacy of Mifamurtide Versus Standard Treatment With Sorafenib in Patients With High-risk Osteosarcoma](https://onco.cc/trials/nct07787429/), [High Dose Methotrexate With Leucovorin Rescue With or Without Glucarpidase in Osteosarcoma](https://onco.cc/trials/nct00634322/), [Lu-TARGO (177Lu-TARGeted Osteosarcoma Therapy)](https://onco.cc/trials/nct07357519/), [Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients](https://onco.cc/trials/nct03643133/), [REGOBONE](https://onco.cc/trials/regobone/), [SARC028](https://onco.cc/trials/sarc028/), [SPEARHEAD-3 Pediatric Study](https://onco.cc/trials/nct05642455/), [Study of HS-20093 Versus Gemcitabine in Combination With Docetaxel in Treatment of Osteosarcoma After Previous Second-line Treatment Failure](https://onco.cc/trials/nct06935409/), [Study to Assess Safety and Efficacy of Vactosertib in Adolescents and Adults With Recurrent, Refractory or Progressive Osteosarcoma](https://onco.cc/trials/nct05588648/), [Will Glucarpidase After Methotrexate Treatment for Bone Sarcoma Lead to Fewer Side Effects and Reduce Chemotherapy Delays?](https://onco.cc/trials/nct02022358/)
- people: [Antoine Italiano](https://onco.cc/people/antoine-italiano/), [Emil "Tom" Frei III](https://onco.cc/people/emil-frei/), [Florence Duffaud](https://onco.cc/people/florence-duffaud/), [Robbie G. Majzner](https://onco.cc/people/robbie-majzner/), [Sant P. Chawla](https://onco.cc/people/sant-chawla/), [Sid Sijbrandij](https://onco.cc/people/sid-sijbrandij/), [Stefan S. Bielack](https://onco.cc/people/stefan-bielack/), [Terry Fox](https://onco.cc/people/terry-fox/), [Uta Dirksen](https://onco.cc/people/uta-dirksen/)
- key papers: [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](https://onco.cc/key-papers/paper-marina-lancet-oncol/), [The threat of medical misinformation: a case of ivermectin toxicity in a pediatric oncology patient](https://onco.cc/key-papers/paper-gilene-ivermectin-toxicity-paediatric-oncology-2025/)
- journals: [Journal of adolescent and young adult oncology](https://onco.cc/journals/journal-of-adolescent-and-young-adult-oncology/)
- collections: [Alex's Lemonade Stand Foundation (ALSF)](https://onco.cc/collections/alexs-lemonade-stand/), [St. Baldrick's Foundation](https://onco.cc/collections/st-baldricks/)
- institutions: [Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille](https://onco.cc/institutions/ap-hm-timone/), [Klinikum Stuttgart / Olgahospital](https://onco.cc/institutions/klinikum-stuttgart-olgahospital/), [Nationwide Children's Hospital](https://onco.cc/institutions/nationwide-childrens/), [Sarcoma Oncology Center](https://onco.cc/institutions/sarcoma-oncology-center/), [St. Jude Children's Research Hospital](https://onco.cc/institutions/st-jude/), [Terry Fox Foundation](https://onco.cc/institutions/terry-fox-foundation/), [Texas Children's Cancer and Hematology Center](https://onco.cc/institutions/texas-childrens/)

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JSON: https://onco.cc/api/v1/entities/osteosarcoma.json