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Eur J Cancer. 2019 Mar;109:36-50. doi: 10.1016/j.ejca.2018.11.027. Epub 2019 Jan 25.

Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort.

Author information

1
SSG Oslo University Hospital and Scandinavian Sarcoma Group and Institute for Clinical Medicine, University of Oslo, Norway. Electronic address: ssm@ous-hf.no.
2
COSS Klinikum Stuttgart - Olgahospital Stuttgart, Germany.
3
EOI University College Hospital, London, UK.
4
COG IWK Health Center, Dalhousie University, Halifax, NS, Canada.
5
TMG Path Leiden University Medical Centre, Leiden, Netherlands.
6
COG Children's Oncology Group, Arcadia, CA, USA.
7
COG the University of Texas M D Anderson Cancer Center, Houston, TX, USA.
8
COG Dana-Farber Cancer Institute, Boston, MA, USA.
9
CDC MRC Clinical Trials Unit at UCL, London, UK.
10
EOI, Netherlands.
11
COSS Semmelweis Egyetem Budapest, Budapest, Hungary.
12
COG Mayo Clinic, Rochester, MN, USA.
13
COG University of British Columbia, Vancouver, BC, Canada.
14
EISD Centre for Clinical Trials, University Hospital Muenster, Muenster, Germany.
15
QLCC Pädiatrische Hämatologie und Onkologie, Universitätsklinikum Bonn, Bonn, Germany.
16
EOI Our Lady's Children's Hospital, Dublin, Ireland.
17
EOI University Hospital Ghent, Gent, Belgium.
18
SSG Lund University, Lund, Sweden.
19
EOI Royal National Orthopaedic Hospital, Stanmore; Cancer Institute, University College London, London, UK.
20
COSS Klinik Schillerhöhe - Thoraxchirurgie Gerlingen, Germany.
21
EOI Leiden University Medical Center, Leiden, the Netherlands.
22
COG UCSF Medical Center-Mission Bay, Pediatric Oncology, San Francisco, CA, USA.
23
EOI Royal Orthopaedic Hospital, Birmingham, UK.
24
COG University of Washington, Seattle, WA, USA.
25
SSG Oslo University Hospital, Oslo, Norway.
26
COG Connecticut Children's Medical Center, Hartford, CT, USA.
27
COSS Universitätsspital Basel, Basel, Switzerland.
28
COSS St. Anna Kinderspital /CCRI, Wien, Austria.
29
COSS University Hospital MOTOL, Praha, Czech Republic.
30
COSS Medizinische Universität Wien, Vienna, Austria.
31
COG Baylor College of Medicine, Houston, TX, USA.
32
COG Southwestern and Children's Medical Center, Dallas, TX, USA.
33
COG Nationwide Children's Hospital and the Ohio State University, Columbus, OH, USA.
34
COG Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
35
COSS Universitätsklinikum Ulm, Ulm, Germany.
36
COG Memorial Sloan Kettering Cancer Center, New York, NY, USA.
37
COG Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
38
COG Primary Childrens Hospital, The University of Utah, Salt Lake City, UT, USA.
39
COSS Helios Kliniken Berlin-Buch, Berlin, Germany.
40
EOI University Hospital Leuven, Leuven, Belgium.
41
SSG Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
42
COG Boston Children's Hospital, Boston, MA, USA.
43
COSS Universitätsklinikum Essen, Essen, Germany.
44
CDC MRC Clinical Trials Unit at UCL, London, UK. Electronic address: mrcctu.euramos@ucl.ac.uk.
45
COG Five Prime Therapeutics, Inc South San Francisco, CA, USA.

Abstract

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.

KEYWORDS:

Chemotherapy; Cohort; Osteosarcoma; Outcomes; Surgery

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