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 A.S. Arndt, Ken L.B. Brown, Trude Butterfass-Bahloul, Gabriele Calaminus, Michael Capra, Catharina Dhooge, Mikael Eriksson, Adrienne M. Flanagan, Godehard FriedelMark 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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)36-50
Number of pages15
JournalEuropean Journal of Cancer
Volume109
DOIs
StatePublished - Mar 1 2019

Fingerprint

Osteosarcoma
Cohort Studies
Confidence Intervals
Survival
Neoplasm Metastasis
Biopsy
Neoplasms
Drug Combinations
Rare Diseases
Skeleton
Methotrexate
Doxorubicin
Cisplatin
Disease-Free Survival
Young Adult
Multivariate Analysis
Survival Rate
Randomized Controlled Trials
Bone and Bones
Drug Therapy

Keywords

  • Chemotherapy
  • Cohort
  • Osteosarcoma
  • Outcomes
  • Surgery

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Survival and prognosis with osteosarcoma : outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. / 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; Arndt, Carola A.S.; Brown, Ken L.B.; Butterfass-Bahloul, Trude; Calaminus, Gabriele; Capra, Michael; Dhooge, Catharina; Eriksson, Mikael; Flanagan, Adrienne M.; Friedel, Godehard; Gebhardt, Mark C.; Gelderblom, Hans; Goldsby, Robert; Grier, Holcombe E.; Grimer, Robert; Hawkins, Douglas S.; Hecker-Nolting, Stefanie; Sundby Hall, Kirsten; Isakoff, Michael S.; Jovic, Gordana; Kühne, Thomas; Kager, Leo; von Kalle, Thekla; Kabickova, Edita; Lang, Susanna; Lau, Ching C.; Leavey, Patrick J.; Lessnick, Stephen L.; Mascarenhas, Leo; Mayer-Steinacker, Regine; Meyers, Paul A.; Nagarajan, Raj; Randall, R. Lor; Reichardt, Peter; Renard, Marleen; Rechnitzer, Catherine; Schwartz, Cindy L.; Strauss, Sandra; Teot, Lisa; Timmermann, Beate; Sydes, Matthew R.; Marina, Neyssa.

In: European Journal of Cancer, Vol. 109, 01.03.2019, p. 36-50.

Research output: Contribution to journalArticle

Smeland, S, Bielack, SS, Whelan, J, Bernstein, M, Hogendoorn, P, Krailo, MD, Gorlick, R, Janeway, KA, Ingleby, FC, Anninga, J, Antal, I, Arndt, CAS, Brown, KLB, Butterfass-Bahloul, T, Calaminus, G, Capra, M, Dhooge, C, Eriksson, M, Flanagan, AM, Friedel, G, Gebhardt, MC, Gelderblom, H, Goldsby, R, Grier, HE, Grimer, R, Hawkins, DS, Hecker-Nolting, S, Sundby Hall, K, Isakoff, MS, Jovic, G, Kühne, T, Kager, L, von Kalle, T, Kabickova, E, Lang, S, Lau, CC, Leavey, PJ, Lessnick, SL, Mascarenhas, L, Mayer-Steinacker, R, Meyers, PA, Nagarajan, R, Randall, RL, Reichardt, P, Renard, M, Rechnitzer, C, Schwartz, CL, Strauss, S, Teot, L, Timmermann, B, Sydes, MR & Marina, N 2019, 'Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort', European Journal of Cancer, vol. 109, pp. 36-50. https://doi.org/10.1016/j.ejca.2018.11.027
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 ; Arndt, Carola A.S. ; Brown, Ken L.B. ; Butterfass-Bahloul, Trude ; Calaminus, Gabriele ; Capra, Michael ; Dhooge, Catharina ; Eriksson, Mikael ; Flanagan, Adrienne M. ; Friedel, Godehard ; Gebhardt, Mark C. ; Gelderblom, Hans ; Goldsby, Robert ; Grier, Holcombe E. ; Grimer, Robert ; Hawkins, Douglas S. ; Hecker-Nolting, Stefanie ; Sundby Hall, Kirsten ; Isakoff, Michael S. ; Jovic, Gordana ; Kühne, Thomas ; Kager, Leo ; von Kalle, Thekla ; Kabickova, Edita ; Lang, Susanna ; Lau, Ching C. ; Leavey, Patrick J. ; Lessnick, Stephen L. ; Mascarenhas, Leo ; Mayer-Steinacker, Regine ; Meyers, Paul A. ; Nagarajan, Raj ; Randall, R. Lor ; Reichardt, Peter ; Renard, Marleen ; Rechnitzer, Catherine ; Schwartz, Cindy L. ; Strauss, Sandra ; Teot, Lisa ; Timmermann, Beate ; Sydes, Matthew R. ; Marina, Neyssa. / Survival and prognosis with osteosarcoma : outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. In: European Journal of Cancer. 2019 ; Vol. 109. pp. 36-50.
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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.",
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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 A.S.

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

PY - 2019/3/1

Y1 - 2019/3/1

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

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