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

Sigbjørn Smeland, Stefan S Bielack, Jeremy Whelan, Mark Bernstein, Pancras Hogendoorn, Mark D Krailo, Richard Gorlick, Katherine A Janeway, Fiona C Ingleby, Jakob Anninga, Imre Antal, Carola Arndt, Ken L B Brown, Trude Butterfass-Bahloul, Gabriele Calaminus, Michael Capra, Catharina Dhooge, Mikael Eriksson, Adrienne M Flanagan, Godehard Friedel, Mark C Gebhardt, Hans Gelderblom, Robert Goldsby, Holcombe E Grier, Robert Grimer, Douglas S Hawkins, Stefanie Hecker-Nolting, Kirsten Sundby Hall, Michael S Isakoff, Gordana Jovic, Thomas Kühne, Leo Kager, Thekla von Kalle, Edita Kabickova, Susanna Lang, Ching C Lau, Patrick J Leavey, Stephen L Lessnick, Leo Mascarenhas, Regine Mayer-Steinacker, Paul A Meyers, Raj Nagarajan, R Lor Randall, Peter Reichardt, Marleen Renard, Catherine Rechnitzer, Cindy L Schwartz, Sandra Strauss, Lisa Teot, Beate Timmermann, Matthew R Sydes, Neyssa Marina, Sigbjørn Smeland, Stefan S Bielack, Jeremy Whelan, Mark Bernstein, Pancras Hogendoorn, Mark D Krailo, Richard Gorlick, Katherine A Janeway, Fiona C Ingleby, Jakob Anninga, Imre Antal, Carola Arndt, Ken L B Brown, Trude Butterfass-Bahloul, Gabriele Calaminus, Michael Capra, Catharina Dhooge, Mikael Eriksson, Adrienne M Flanagan, Godehard Friedel, Mark C Gebhardt, Hans Gelderblom, Robert Goldsby, Holcombe E Grier, Robert Grimer, Douglas S Hawkins, Stefanie Hecker-Nolting, Kirsten Sundby Hall, Michael S Isakoff, Gordana Jovic, Thomas Kühne, Leo Kager, Thekla von Kalle, Edita Kabickova, Susanna Lang, Ching C Lau, Patrick J Leavey, Stephen L Lessnick, Leo Mascarenhas, Regine Mayer-Steinacker, Paul A Meyers, Raj Nagarajan, R Lor Randall, Peter Reichardt, Marleen Renard, Catherine Rechnitzer, Cindy L Schwartz, Sandra Strauss, Lisa Teot, Beate Timmermann, Matthew R Sydes, Neyssa Marina

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.

Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Flow diagram describing patient cohorts included in the ‘registration cohort’ and the ‘M0-CSR’ groups for analysis. CT, computed tomography; EFS, event-free survival; IQR, interquartile range; EURAMOS-1, European and American Osteosarcoma Study-1.
Fig. 2
Fig. 2
Kaplan–Meier plots for event-free survival and overall survival. (A) Full ‘registration cohort’. (B) Subset of ‘registration cohort’ patients with localised disease at registration (M0).M0 group includes patients with no metastases and possible metastases. (C) Subset of ‘registration cohort’ patients with metastatic disease at registration (M1). (D) ‘M0-CSR’ group, *Note that the number of patients at risk at the time of surgery is smaller for EFS than for OS because some patients had EFS event before surgery. EFS, event-free survival; OS, overall survival.
Fig. 3
Fig. 3
Hazard of event-free survival (EFS) from diagnostic biopsy for all ‘registration cohort’ patients, plotted by metastatic status at registration. Note: non-COG patients categorised at registration as having ‘possible’ metastases are included in the M0 category. Shaded area shows 95% CI around estimates. CI, confidence interval; COG, Children's Oncology Group.

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