Osteosarcoma
Osteosarcoma is the most common bone cancer, mostly in teenagers. Chemotherapy plus surgery cures about two-thirds when it has not spread, but survival has not improved in 30 years and no new drug has worked in a large trial.
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.
State of the art today
- 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.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 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.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
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.
Same chemotherapy with resection of all metastases (thoracotomy) when feasible; survival ~25-30%.
Surgical resection of recurrence; ifosfamide ± etoposide, gemcitabine-docetaxel; regorafenib or cabozantinib; clinical trials (CAR-T, ADCs).
Carbon-ion or proton radiotherapy for craniofacial and pelvic tumours; Sm-153 or Ra-223 for bone-forming metastases (investigational).
Subtypes & biomarkers
top- Conventional high-grade (osteoblastic, chondroblastic, fibroblastic)
- Telangiectatic
- Small cell
- Low-grade central and parosteal (surgery alone)
- Periosteal (intermediate grade)
- Secondary (Paget, post-radiation)
- 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)
Target prevalence in this cancer
- 1970Amputation alone cures <20%; lung metastases the rule
- 1972High-dose methotrexate with leucovorin rescue (Jaffe) and adriamycin (Cortes) show activity
- 1979Rosen's T-10: neoadjuvant chemotherapy and limb salvage
- 1986Randomised proof that adjuvant chemotherapy cures (Link, NEJM; MIOS)
- 2008INT-0133: mifamurtide improves overall survival; EU approval 2009
- 2016EURAMOS-1: no benefit from intensifying for poor responders or interferon for good responders
- 2019Regorafenib (SARC024, REGOBONE) and cabozantinib (CABONE) show activity at relapse
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.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- via CAR-T cell therapy
- via Proton therapy
- via Carbon-ion therapy, Proton therapy
- via Proton therapy
- via Carbon-ion therapy
- via Proton therapy
- via Carbon-ion therapy
- via Proton therapy
- via CAR-T cell therapy
- via CAR-T cell therapy, Carbon-ion therapy, Proton therapy
- via CAR-T cell therapy, Carbon-ion therapy, Proton therapy
- via this cancer, CAR-T cell therapy, Proton therapy
- via CAR-T cell therapy, Proton therapy
- via CAR-T cell therapy, Proton therapy
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia CAR-T cell therapy, Proton therapy
- Cleveland Clinic Abu DhabiAbu Dhabi, AEvia CAR-T cell therapy, Proton therapy
- European Society for Radiotherapy and OncologyBrussels, BEvia Carbon-ion therapy, Proton therapy
- via CAR-T cell therapy, Proton therapy
- via CAR-T cell therapy, Proton therapy
- National Cancer Centre SingaporeSingapore, SGvia CAR-T cell therapy, Proton therapy
- Nationwide Children's HospitalColumbus, OH, USvia this cancer, CAR-T cell therapy
- via CAR-T cell therapy, Proton therapy
- Ruijin Hospital, Shanghai Jiao Tong UniversityShanghai, CNvia CAR-T cell therapy, Proton therapy
- Taipei Veterans General HospitalTaipei, TWvia CAR-T cell therapy, Carbon-ion therapy
- Texas Children's Cancer and Hematology CenterHouston, TX, USvia this cancer, CAR-T cell therapy
- via CAR-T cell therapy, Proton therapy
- via CAR-T cell therapy, Proton therapy
- Aarhus University HospitalAarhus, DKvia Proton therapy
- via CAR-T cell therapy
- Advanced Research Projects Agency for HealthWashington, DC, USvia CAR-T cell therapy
- All India Institute of Medical Sciences, New DelhiNew Delhi, INvia CAR-T cell therapy
- American Society for Radiation OncologyArlington, VA, USvia Proton therapy
- American Society of HematologyWashington, DC, USvia CAR-T cell therapy
- Apollo Hospitals (Apollo Cancer Centres)Chennai, INvia Proton therapy
- via CAR-T cell therapy
- via Proton therapy
- Central Drugs Standard Control OrganizationNew Delhi, INvia CAR-T cell therapy
- Centre Antoine LacassagneNice, FRvia Proton therapy
- Chan Zuckerberg BiohubSan Francisco, USvia CAR-T cell therapy
- Chang Gung Memorial HospitalTaoyuan, TWvia Proton therapy
- Children's Oncology Group (COG)Monrovia, CA, USvia this cancer
- Chinese PLA General HospitalBeijing, CNvia CAR-T cell therapy
- Christian Medical College, VelloreVellore, INvia CAR-T cell therapy
- via CAR-T cell therapy
- City of Hope Orange CountyIrvine, CA, USvia CAR-T cell therapy
- via CAR-T cell therapy
- Dan L Duncan Comprehensive Cancer Center, Baylor College of MedicineHouston, TX, USNCI comprehensivevia CAR-T cell therapy
- Erasmus MC Cancer InstituteRotterdam, NLvia Proton therapy
- European Hematology AssociationThe Hague, NLvia CAR-T cell therapy
- European Medicines AgencyAmsterdam, NLvia CAR-T cell therapy
- via CAR-T cell therapy
- Geneva University Hospitals (HUG)Geneva, CHvia CAR-T cell therapy
- via Docetaxel
- via CAR-T cell therapy
- Gunma University Heavy Ion Medical CenterMaebashi, JPvia Carbon-ion therapy
- Hadassah Medical CenterJerusalem, ILvia CAR-T cell therapy
- Henan Cancer HospitalZhengzhou, CNvia CAR-T cell therapy
- Hokkaido University HospitalSapporo, JPvia Proton therapy
- Hospital Clínic de Barcelona / IDIBAPSBarcelona, ESvia CAR-T cell therapy
- via CAR-T cell therapy
- Hospital Universitario 12 de OctubreMadrid, ESvia CAR-T cell therapy
- via CAR-T cell therapy
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensivevia Cisplatin
- via CAR-T cell therapy
- Institut Paoli-CalmettesMarseille, FRvia CAR-T cell therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- IRCCS Ospedale San RaffaeleMilan, ITvia CAR-T cell therapy
- via CAR-T cell therapy
- Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CAvia CAR-T cell therapy
- Leiden University Medical CenterLeiden, NLvia Proton therapy
- LYSA – The Lymphoma Study AssociationPierre-Bénite (Lyon), FRvia CAR-T cell therapy
- via Proton therapy
- via Proton therapy
- National Cancer Center Hospital EastKashiwa, Chiba, JPvia Proton therapy
- National Cancer Center KoreaGoyang, KRvia Proton therapy
- via CAR-T cell therapy
- National Taiwan University HospitalTaipei, TWvia Proton therapy
- via CAR-T cell therapy
- NCI Center for Cancer Research (intramural programme)Bethesda, MD, USvia CAR-T cell therapy
- via Proton therapy
- Northwell Health Cancer InstituteNew Hyde Park, NY, USvia CAR-T cell therapy
- via Proton therapy
- via Proton therapy
- Peking University Cancer HospitalBeijing, CNvia CAR-T cell therapy
- via Carbon-ion therapy
- Rigshospitalet – Copenhagen University HospitalCopenhagen, DKvia CAR-T cell therapy
- Royal Adelaide HospitalAdelaide, AUvia Proton therapy
- via CAR-T cell therapy
- Seoul St. Mary's HospitalSeoul, KRvia CAR-T cell therapy
- via Proton therapy
- Sheba Medical CenterRamat Gan, ILvia CAR-T cell therapy
- Shizuoka Cancer CenterNagaizumi, Shizuoka, JPvia Proton therapy
- via CAR-T cell therapy
- Siriraj Hospital, Mahidol UniversityBangkok, THvia CAR-T cell therapy
- Society for Immunotherapy of CancerMilwaukee, WI, USvia CAR-T cell therapy
- via Proton therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- University Cancer Center Frankfurt (UCT)Frankfurt am Main, DEvia CAR-T cell therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- via Proton therapy
- University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensivevia Proton therapy
- via Proton therapy
- UZ Leuven / Leuven Cancer InstituteLeuven, BEvia Proton therapy
- via Proton therapy
- Zhejiang Cancer HospitalHangzhou, CNvia Proton therapy
Questions to ask
topQuestions to ask your oncologist about Osteosarcoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Histologic necrosis after neoadjuvant chemotherapy, Alkaline phosphatase and LDH, Metastases at diagnosis, Germline TP53 / RB1 / RECQL4, GD2, HER2, B7-H3 expression), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Conventional high-grade, Telangiectatic, Small cell.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Localised high-grade
- For my situation (localised high-grade), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Methotrexate, Doxorubicin, Cisplatin or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic at diagnosis
- For my situation (metastatic at diagnosis), which of the standard options do you recommend and why?Why: Guideline options include: Same chemotherapy with resection of all metastases (thoracotomy) when feasible; survival ~25-30%.
- Am I a candidate for Methotrexate, Doxorubicin, Cisplatin or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Relapsed
- For my situation (relapsed), which of the standard options do you recommend and why?Why: Guideline options include: Surgical resection of recurrence; ifosfamide ± etoposide, gemcitabine-docetaxel; regorafenib or cabozantinib; clinical trials (CAR-T, ADCs).
- Am I a candidate for Ifosfamide, Etoposide, Regorafenib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Unresectable / axial
- For my situation (unresectable / axial), which of the standard options do you recommend and why?Why: Guideline options include: Carbon-ion or proton radiotherapy for craniofacial and pelvic tumours; Sm-153 or Ra-223 for bone-forming metastases (investigational).
- Am I a candidate for Radium-223 dichloride, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Regorafenib, Cabozantinib, CAR-T cell therapy, Radium-223 dichloride?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “No survival improvement since the 1980s; metastatic and relapsed disease ~20-30% survival”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “No recurrent druggable driver; genomic chaos”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
15targets
9drugs
11companies
5institutions
4pathways
2terms
3collections
2people
2Latest papers
topQuery for this cancer: (TITLE:"Osteosarcoma" OR ABSTRACT:"Osteosarcoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Osteosarcoma, not a curated reading list.
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