TY - JOUR
T1 - Survival and prognosis with osteosarcoma
T2 - outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort
AU - Smeland, Sigbjørn
AU - Bielack, Stefan S.
AU - Whelan, Jeremy
AU - Bernstein, Mark
AU - Hogendoorn, Pancras
AU - Krailo, Mark D.
AU - Gorlick, Richard
AU - Janeway, Katherine A.
AU - Ingleby, Fiona C.
AU - Anninga, Jakob
AU - Antal, Imre
AU - Arndt, Carola
AU - Brown, Ken L.B.
AU - Butterfass-Bahloul, Trude
AU - Calaminus, Gabriele
AU - Capra, Michael
AU - Dhooge, Catharina
AU - Eriksson, Mikael
AU - Flanagan, Adrienne M.
AU - Friedel, Godehard
AU - Gebhardt, Mark C.
AU - Gelderblom, Hans
AU - Goldsby, Robert
AU - Grier, Holcombe E.
AU - Grimer, Robert
AU - Hawkins, Douglas S.
AU - Hecker-Nolting, Stefanie
AU - Sundby Hall, Kirsten
AU - Isakoff, Michael S.
AU - Jovic, Gordana
AU - Kühne, Thomas
AU - Kager, Leo
AU - von Kalle, Thekla
AU - Kabickova, Edita
AU - Lang, Susanna
AU - Lau, Ching C.
AU - Leavey, Patrick J.
AU - Lessnick, Stephen L.
AU - Mascarenhas, Leo
AU - Mayer-Steinacker, Regine
AU - Meyers, Paul A.
AU - Nagarajan, Raj
AU - Randall, R. Lor
AU - Reichardt, Peter
AU - Renard, Marleen
AU - Rechnitzer, Catherine
AU - Schwartz, Cindy L.
AU - Strauss, Sandra
AU - Teot, Lisa
AU - Timmermann, Beate
AU - Sydes, Matthew R.
AU - Marina, Neyssa
N1 - Funding Information:
Additional funding to the University of Muenster Centre for Clinical Trials, site of the EURAMOS Intergroup Safety Desk: Federal Ministry of Education and Research , Germany, BMBF 01KN1105 .
Funding Information:
Dr. Bielack reports grants from Deutsche Krebshilfe , Deutsche Forschungsgemeinschaft and European Science Foundation during the conduct of the study and personal fees from Lilly , Bayer , Pfizer , Novartis , Isofol and Clinigen , outside the submitted work. P.R. reports grants and personal fees from Novartis and personal fees from Pfizer , Bayer , PharmaMar , Amgen , AstraZeneca , Clinigen , Lilly and Deciphera , outside the submitted work. Dr Teot reports work under consideration for publication and COG subcontractor fees for pathology review, outside the submitted work. Dr Gebhardt reports other support from Clinical Orthopaedics and Related Research and other fees from Up-to-date, outside of the submitted work. Dr Meyers reports stock or other ownership in Amgen, Bayer, Dupont, Henry Schein, Jazz Pharmaceuticals, Mednax, Novartis, Procter and Gamble and Sigma–Aldrich; honoraria from France Foundation and personal fees from Takeda Pharmaceuticals , Medison and InterMune , outside the submitted work. Dr. Lessnick serves as a member of the Scientific Advisory Board for Salarius Pharmaceuticals, a company involved in cancer therapy development outside of the submitted work. Dr. Butterfass-Bahloul reports grants from the Federal Ministry of Education and Research , Germany, other support from European Science Foundation (ESF) under the EUROCORES Program European Clinical Trials (ECT), other from Deutsche Forschungsgemeinschaft (DFG) , during the conduct of the study. Dr. Marina reports other from Five Prime Therapeutics, outside the submitted work.
Funding Information:
The study sponsor was the UK Medical Research Council in Europe and the U.S. National Cancer Institute in North America and Australia. Each trial group organised local coordination elements; central coordination and analysis was led from MRC Clinical Trials Unit at UCL. Neither the sponsors nor the funders of the trial had a role in trial design, data analysis or data interpretation.Additional funding to the University of Muenster Centre for Clinical Trials, site of the EURAMOS Intergroup Safety Desk: Federal Ministry of Education and Research, Germany, BMBF 01KN1105.Dr. Bielack reports grants from Deutsche Krebshilfe, Deutsche Forschungsgemeinschaft and European Science Foundation during the conduct of the study and personal fees from Lilly, Bayer, Pfizer, Novartis, Isofol and Clinigen, outside the submitted work. P.R. reports grants and personal fees from Novartis and personal fees from Pfizer, Bayer, PharmaMar, Amgen, AstraZeneca, Clinigen, Lilly and Deciphera, outside the submitted work. Dr Teot reports work under consideration for publication and COG subcontractor fees for pathology review, outside the submitted work. Dr Gebhardt reports other support from Clinical Orthopaedics and Related Research and other fees from Up-to-date, outside of the submitted work. Dr Meyers reports stock or other ownership in Amgen, Bayer, Dupont, Henry Schein, Jazz Pharmaceuticals, Mednax, Novartis, Procter and Gamble and Sigma–Aldrich; honoraria from France Foundation and personal fees from Takeda Pharmaceuticals, Medison and InterMune, outside the submitted work. Dr. Lessnick serves as a member of the Scientific Advisory Board for Salarius Pharmaceuticals, a company involved in cancer therapy development outside of the submitted work. Dr. Butterfass-Bahloul reports grants from the Federal Ministry of Education and Research, Germany, other support from European Science Foundation (ESF) under the EUROCORES Program European Clinical Trials (ECT), other from Deutsche Forschungsgemeinschaft (DFG), during the conduct of the study. Dr. Marina reports other from Five Prime Therapeutics, outside the submitted work.
Publisher Copyright:
© 2018 The Authors
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - Chemotherapy
KW - Cohort
KW - Osteosarcoma
KW - Outcomes
KW - Surgery
UR - http://www.scopus.com/inward/record.url?scp=85060337012&partnerID=8YFLogxK
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U2 - 10.1016/j.ejca.2018.11.027
DO - 10.1016/j.ejca.2018.11.027
M3 - Article
C2 - 30685685
AN - SCOPUS:85060337012
SN - 0959-8049
VL - 109
SP - 36
EP - 50
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -