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Teaching pack: Osteosarcoma

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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.

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  1. Teaching pack · Cancer · paediatric

    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.

    Teaching pack: Osteosarcoma · OnCo, CC BY 4.0 · not medical advice1 / 9
  2. What it is

    In two paragraphs

    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.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    Localised high-gradeNeoadjuvant MAP (methotrexate, doxorubicin, cisplatin) ×2 cycles, limb-salvage resection with wide margins (amputation if required), adjuvant MAP to ~29 weeks; mifamurtide added in EU.NCCN Category 1 (MAP)
    Metastatic at diagnosisSame chemotherapy with resection of all metastases (thoracotomy) when feasible; survival ~25-30%.NCCN Category 2A
    RelapsedSurgical resection of recurrence; ifosfamide ± etoposide, gemcitabine-docetaxel; regorafenib or cabozantinib; clinical trials (CAR-T, ADCs).NCCN Category 2A
    Unresectable / axialCarbon-ion or proton radiotherapy for craniofacial and pelvic tumours; Sm-153 or Ra-223 for bone-forming metastases (investigational).not mapped
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  4. State of the art

    Where the field stands

    • 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.
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  5. History

    How we got here

    1. 1970Amputation alone cures <20%; lung metastases the rule
    2. 1972High-dose methotrexate with leucovorin rescue (Jaffe) and adriamycin (Cortes) show activity
    3. 1979Rosen's T-10: neoadjuvant chemotherapy and limb salvage
    4. 1986Randomised proof that adjuvant chemotherapy cures (Link, NEJM; MIOS)
    5. 2008INT-0133: mifamurtide improves overall survival; EU approval 2009
    6. 2016EURAMOS-1: no benefit from intensifying for poor responders or interferon for good responders
    7. 2019Regorafenib (SARC024, REGOBONE) and cabozantinib (CABONE) show activity at relapse
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  6. Pipeline

    What is coming

    • Regorafenib (product)
    • Cabozantinib (product)
    • CAR-T cell therapy (technology)
    • Radium-223 dichloride (product)
    • B7-H3 (target)
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  7. Open problems

    What nobody has solved

    • 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.
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  8. Quiz

    Check understanding

    1. What is CAR-T and which cancers is it approved for?
      Answer
      A patient's T cells are engineered with a synthetic receptor, multiplied, and returned. Approved CD19 products treat B-cell lymphomas and leukaemias; BCMA products treat multiple myeloma; the first solid-tumour approval (Claudin 18.2, gastric) is in China.
    2. What is in vivo CAR-T and why is it exciting?
      Answer
      Targeted lipid nanoparticles or viral vectors deliver CAR-encoding mRNA or DNA to T cells inside the patient, avoiding manufacturing, lymphodepletion, and wait time and allowing redosing; first-in-human data in 2025-26 show B-cell depletion. AbbVie bought Capstan for up to $2.1B.
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  9. Sources

    Read the primary sources

    • 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
    • Wikipedia: https://en.wikipedia.org/wiki/Osteosarcoma
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1418
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