Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort
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BACKGROUND: High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. The European and American Osteosarcoma Study (EURAMOS)-1 is a collaboration of four study groups aiming to improve outcomes of this rare disease by facilitating randomised controlled trials. METHODS: Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high-grade osteosarcoma in which case complete surgical resection at all sites was deemed to be possible. A three-drug combination with methotrexate, doxorubicin and cisplatin was defined as standard chemotherapy, and between April 2005 and June 2011, 2260 patients were registered. We report survival outcomes and prognostic factors in the full cohort of registered patients. RESULTS: For all registered patients at a median follow-up of 54 months (interquartile range: 38-73) from biopsy, 3-year and 5-year event-free survival were 59% (95% confidence interval [CI]: 57-61%) and 54% (95% CI: 52-56%), respectively. Multivariate analyses showed that the most adverse factors at diagnosis were pulmonary metastases (hazard ratio [HR] = 2.34, 95% CI: 1.95-2.81), non-pulmonary metastases (HR = 1.94, 95% CI: 1.38-2.73) or an axial skeleton tumour site (HR = 1.53, 95% CI: 1.10-2.13). The histological subtypes telangiectatic (HR = 0.52, 95% CI: 0.33-0.80) and unspecified conventional (HR = 0.67, 95% CI: 0.52-0.88) were associated with a favourable prognosis compared with chondroblastic subtype. The 3-year and 5-year overall survival from biopsy were 79% (95% CI: 77-81%) and 71% (95% CI: 68-73%), respectively. For patients with localised disease at presentation and in complete remission after surgery, having a poor histological response was associated with worse outcome after surgery (HR = 2.13, 95% CI: 1.76-2.58). In radically operated patients, there was no good evidence that axial tumour site was associated with worse outcome. CONCLUSIONS: In conclusion, data from >2000 patients registered to EURAMOS-1 demonstrated survival rates in concordance with institution- or group-level osteosarcoma trials. Further efforts are required to drive improvements for patients who can be identified to be at higher risk of adverse outcome. This trial reaffirms known prognostic factors, and owing to the large numbers of patients registered, it sheds light on some additional factors to consider.
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Multiple studies using combined neoadjuvant chemotherapy and surgery showed long-term disease-free survival rates of 60-70% in young patients with apparently localized disease.
“Multiple studies using a combined approach of neoadjuvant chemotherapy and surgery showed long-term, disease-free survival rates in the range of 60-70% in young patients with apparently localized disease 125 .”
From Osteosarcoma (2022) · cites this paper as [125]
Current treatment paradigms offer patients with newly diagnosed, resectable osteosarcoma long-term survival rates of 60-70%.
“Current treatment paradigms offer patients with newly diagnosed, resectable osteosarcoma long-term survival rates of 60-70% 125 .”
From Osteosarcoma (2022) · cites this paper as [125]
Local recurrence is rare; it accounted for only 7% of all events in almost 1,000 patients who had an event in EURAMOS-1.
“Local recurrence is rare; for example, it accounted for only 7% of all events in almost 1,000 patients who had an event in EURAMOS-1 (ref.125 ).”
From Osteosarcoma (2022) · cites this paper as [125]
One of the life-threatening late effects of chemotherapy is the development of secondary malignancies, such as therapy-related acute myelogenous leukaemia/myelodysplastic syndrome, central nervous system tumours or secondary solid tumours, which occur in ~3% of patients.
“One of the life-threatening late effects of chemotherapy is the development of secondary malignancies, such as therapy-related acute myelogenous leukaemia/myelodysplastic syndrome, central nervous system tumours or secondary solid tumours, which occur in ~3% of patients 125 .”
From Osteosarcoma (2022) · cites this paper as [125]
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- Authors
- Smeland, S., Bielack, S. S., Whelan, J., Bernstein, M., Hogendoorn, P., Krailo, M. D., Gorlick, R., Janeway, K. A., Ingleby, F. C., Anninga, J., Antal, I., Arndt, C., Brown, K. L. B., Butterfass-Bahloul, T., Calaminus, G., Capra, M., Dhooge, C., Eriksson, M., Flanagan, A. M., Friedel, G., Gebhardt, M. C., Gelderblom, H., Goldsby, R., Grier, H. E., Grimer, R., Hawkins, D. S., Hecker-Nolting, S., Sundby Hall, K., Isakoff, M. S., Jovic, G., Kühne, T., Kager, L., von Kalle, T., Kabickova, E., Lang, S., Lau, C. C., Leavey, P. J., Lessnick, S. L., Mascarenhas, L., Mayer-Steinacker, R., Meyers, P. A., Nagarajan, R., Randall, R. L., Reichardt, P., Renard, M., Rechnitzer, C., Schwartz, C. L., Strauss, S., Teot, L., Timmermann, B., Sydes, M. R., & Marina, N.
- Affiliations
- Oslo University Hospital (NO)
- Olgahospital (DE)
- University College Hospital (GB)
- Dalhousie University (CA)
- Leiden University (NL)
- Children's Oncology Group (US)
- The University of Texas MD Anderson Cancer Center (US)
- Dana-Farber Cancer Institute (US)
- MRC Clinical Trials Unit at UCL (GB)
- Semmelweis University (HU)
- Mayo Clinic (US)
- University of British Columbia (CA)
- University Hospital Bonn (DE)
- Ghent University Hospital (BE)
- Lund University (SE)
- Royal National Orthopaedic Hospital (GB)
- Klinik Schillerhöhe (DE)
- Leiden University Medical Center (NL)
- University of California San Francisco Medical Center (US)
- Royal Orthopaedic Hospital (GB)
- University of Washington (US)
- Connecticut Children's Medical Center (US)
- University Hospital of Basel (CH)
- St Anna Children's Hospital (AT)
- Medical University of Vienna (AT)
- Baylor College of Medicine (US)
- Children's Medical Center (US)
- Nationwide Children's Hospital (US)
- University of Southern California (US)
- Memorial Sloan Kettering Cancer Center (US)
- Primary Children's Hospital (US)
- Helios Kliniken (DE)
- KU Leuven (BE)
- University of Copenhagen (DK)
- Boston Children's Hospital (US)
- Essen University Hospital (DE)
- Five Prime Therapeutics (United States) (US)
- Corresponding author
- Smeland, Sigbjørn
- Sydes, Matthew R.
- ORCID
- Smeland, Sigbjørn
- Bielack, Stefan S.
- Whelan, Jeremy
- Bernstein, Mark
- Hogendoorn, Pancras
- Krailo, Mark D.
- Gorlick, Richard
- Janeway, Katherine A.
- Ingleby, Fiona C.
- Anninga, Jakob
- Antal, Imre
- Calaminus, Gabriele
- Capra, Michael
- Dhooge, Catharina
- Flanagan, Adrienne M.
- Friedel, Godehard
- Gelderblom, Hans
- Goldsby, Robert
- Grier, Holcombe E.
- Grimer, Robert
- Hawkins, Douglas S.
- Isakoff, Michael S.
- Jovic, Gordana
- Kühne, Thomas
- Kager, Leo
- Lau, Ching C.
- Leavey, Patrick J.
- Lessnick, Stephen L.
- Mascarenhas, Leo
- Meyers, Paul A.
- Randall, R.Lor
- Reichardt, Peter
- Rechnitzer, Catherine
- Schwartz, Cindy L.
- Strauss, Sandra
- Timmermann, Beate
- Sydes, Matthew R.
- Marina, Neyssa
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 109
- Pages
- 36-50
- ISSN
- 0959-8049 (ISSN-L)
- PMC
- PMC6506906
- OpenAlex
- W2913276036
- Cited by
- 704
- References
- 32
- Citations by year
- 2026: 70 · 2025: 123 · 2024: 129 · 2023: 110 · 2022: 107 · 2021: 92 · 2020: 55 · 2019: 16 · 2012: 1
- FWCI
- 50.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Journal of Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- UK Medical Research Council
- Federal Ministry of Education and Research (BMBF 01KN1105)
- Deutsche Krebshilfe
- Deutsche Forschungsgemeinschaft
- European Science Foundation
- Lilly
- Bayer
- Pfizer
- Novartis
- Isofol
- Clinigen
- PharmaMar
- Amgen
- AstraZeneca
- Deciphera
- Takeda Pharmaceuticals
- Medison
- InterMune
- European Science Foundation (ESF)
- Deutsche Forschungsgemeinschaft (DFG)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- osteosarcoma, high-grade osteosarcoma, survival outcomes, prognostic factors, event-free survival, overall survival, lung metastasis, histological subtypes, telangiectatic osteosarcoma, chondroblastic osteosarcoma
- MeSH terms
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols, Bone Neoplasms, Child, Cisplatin, Doxorubicin, Female, Follow-Up Studies, Humans, Male, Methotrexate, Neoplasm Metastasis, Prognosis, Osteosarcoma, Cohort Studies, Survival Rate
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