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Osteosarcoma

An Author Correction to this article was published on 30 December 2022

This article has been updated

Abstract

Osteosarcoma is the most common primary malignant tumour of the bone. Osteosarcoma incidence is bimodal, peaking at 18 and 60 years of age, and is slightly more common in males. The key pathophysiological mechanism involves several possible genetic drivers of disease linked to bone formation, causing malignant progression and metastasis. While there have been significant improvements in the outcome of patients with localized disease, with event-free survival outcomes exceeding 60%, in patients with metastatic disease, event-free survival outcomes remain poor at less than 30%. The suspicion of osteosarcoma based on radiographs still requires pathological evaluation of a bone biopsy specimen for definitive diagnosis and CT imaging of the chest should be performed to identify lung nodules. So far, population-based screening and surveillance strategies have not been implemented due to the rarity of osteosarcoma and the lack of reliable markers. Current screening focuses only on groups at high risk such as patients with genetic cancer predisposition syndromes. Management of osteosarcoma requires a multidisciplinary team of paediatric and medical oncologists, orthopaedic and general surgeons, pathologists, radiologists and specialist nurses. Survivors of osteosarcoma require specialized medical follow-up, as curative treatment consisting of chemotherapy and surgery has long-term adverse effects, which also affect the quality of life of patients. The development of osteosarcoma model systems and related research as well as the evaluation of new treatment approaches are ongoing to improve disease outcomes, especially for patients with metastases.

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Fig. 1: Anatomical distribution of a primary osteosarcoma tumour.
Fig. 2: Osteosarcoma incidence by age and sex.
Fig. 3: Model of osteosarcomagenesis: key role of oncogenetic drivers.
Fig. 4: Model of osteosarcomagenesis: local tumour microenvironment.
Fig. 5: Potential targets for osteosarcoma treatment.
Fig. 6: Osteoblastic osteosarcoma imaging.
Fig. 7: Osteosarcoma histology.
Fig. 8: Osteosarcoma treatment algorithm.
Fig. 9: Osteosarcoma MAP chemotherapy example.

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Acknowledgements

R.G. is supported as the H. Grant Taylor, M.D., W.W. Sutow, M.D. and Margaret P. Sullivan, M.D. Distinguished Chair in Paediatrics. J.G. and R.G. both acknowledge the support of the Foster Foundation, Swim Across America Inc., the Osteosarcoma Institute, the QuadW Foundation and the Barbara Epstein Foundation. A.M.F. is supported by the Tom Prince Cancer Trust, the Bone Cancer Research Trust, Sarcoma UK, the Cancer Research UK University College London Experimental Cancer Medicine Centre, the RNOH Research and Development Department, and the National Institute for Health Research, University College London Hospitals Biomedical Research Centre. H.C.B. acknowledges support by Triumph Over Kid Cancer Foundation (to Valerae Lewis), A Shelter for Cancer Families, formerly Amshwand Sarcoma Cancer Foundation (to the Sarcoma Medical Oncology Department at MD Anderson Cancer Center), QuadW Foundation (to the Sarcoma Oncology Group), and Cancer Prevention Research Institute of Texas. S.S. is funded in part by the National Institute for Health Research, University College London Hospitals Biomedical Research Centre. J.A.L. acknowledges the support of the Osteosarcoma Institute, the Rally Foundation, and the Make It Better (MIB) Agents. R.D.R. is supported by the National Institutes of Health/National Cancer Institute, the Osteosarcoma Institute, the Hyundai Hope on Wheels Foundation, the CancerFREE Kids Foundation, Steps for Sarcoma, and the St. Baldrick’s Foundation. D.H. acknowledges support from ICO Cancer Center, France (ref# “DorSarc-2018-ICO-DH”), Ouest Valorisation SATT (France) and the Bone Cancer Research Trust (UK). K.J. acknowledges support from Pan Mass Challenge and philanthropic funds supporting osteosarcoma research at Dana-Farber Cancer Institute. The work of S.B. is charitably supported by Förderkreis krebskranke Kinder Stuttgart e.V. We are very thankful to W.-L. Wang and A. Lazar of the Division of Pathology at MD Anderson Cancer Center for providing the histology figures as well as their descriptions.

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Since 2019, S.B. has been on Advisory Boards for Eli Lilly, Ipsen, Hoffmann La Roche, Bayer Healthcare, Boehringer Ingelheim, EISAI and MAP Biopharma. All other authors declare no competing interests.

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Beird, H.C., Bielack, S.S., Flanagan, A.M. et al. Osteosarcoma. Nat Rev Dis Primers 8, 77 (2022). https://doi.org/10.1038/s41572-022-00409-y

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