Osteosarcoma: The COSS Experience

  • Stefan Bielack
  • Herbert Jürgens
  • Gernot Jundt
  • Matthias Kevric
  • Thomas Kühne
  • Peter Reichardt
  • Andreas Zoubek
  • Mathias Werner
  • Winfried Winkelmann
  • Rainer Kotz
Part of the Cancer Treatment and Research book series (CTAR, volume 152)


COSS, the interdisciplinary Cooperative German–Austrian–Swiss Osteosarcoma Study Group, was founded in 1977 and has since registered some 3,500 bone sarcoma patients from over 200 institutions. For the purpose of the Pediatric and Adolescent Osteosarcoma Conference in Houston, March 2008, the outcomes of 2,464 consecutive patients with high-grade central osteosarcoma, who had been diagnosed between 1980 and 2005 and had been treated on neoadjuvant COSS protocols, were reviewed. Intended treatment had included surgery and multidrug chemotherapy, with high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide being used in most protocols. After a median follow-up of 7.31 years for 1,654 survivors, 5- and 10-year survival estimates were 0.748/0.695 for 2,017 patients with localized extremity tumors and 0.369/0.317 for 444 patients with axial tumors or/and primary metastases, respectively. Tumor response to preoperative chemotherapy was of independent prognostic significance. Over the years, there was a major shift from amputation towards limb-salvage. This development was least evident for patients below the age of 10. While survival expectancies improved from the first to the second half of the recruitment period, no further improvement was evident within the latter period. In the manuscript, the results described above are discussed based on the findings of the previous analyses of our group.


Induction Chemotherapy Poor Responder Secondary Malignancy Good Responder Primary Metastatic Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank all the patients who contributed to the COSS studies, and acknowledge the physicians, nurses, data managers, and support staff of the collaborating centers for their active participation, and the Deutsches Kinderkrebsregister for the exchange of follow-up information and data on secondary malignancies. We particularly appreciate the dedicated work of the staff of the COSS study center and of the members of the COSS reference panels. The COSS studies on which these analyses are based received support from Deutsche Krebshilfe, Bundesministerium für Forschung und Technologie, and Fördergemeinschaft Kinderkrebszentrum Hamburg.


  1. 1.
    Winkler K, Beron G, Schellong G, et al. Kooperative Osteosarkomstudie COSS-77: Ergebnisse nach über 4 Jahren. Klin Pädiatr. 1982;194:251-256.CrossRefPubMedGoogle Scholar
  2. 2.
    Winkler K, Beron G, Kotz R, et al. Neoadjuvant chemotherapy for osteogenic sarcoma: results of a cooperative German/Austrian study. J Clin Oncol. 1984;2:617-623.PubMedGoogle Scholar
  3. 3.
    Winkler K, Beron G, Delling G, et al. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988;6:329-337.PubMedGoogle Scholar
  4. 4.
    Bielack S, Beck J, Delling G, et al. Neoadjuvant chemotherapy of osteosarcoma. Results of the cooperative studies COSS-80 and COSS-82 after 7 and 5 years. Klin Padiatr. 1989;201:275-284.CrossRefPubMedGoogle Scholar
  5. 5.
    Winkler K, Bielack S, Delling G, et al. Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (Study COSS-86). Cancer. 1990;66:1703-1710.CrossRefPubMedGoogle Scholar
  6. 6.
    Bielack S, Wulff B, Delling G, et al. Osteosarcoma of the trunk treated by multimodal therapy: experience of the cooperative osteosarcoma study group COSS. Med Pediatr Oncol. 1995;24:6-12.CrossRefPubMedGoogle Scholar
  7. 7.
    Fuchs N, Bielack S, Epler D, et al. Long-term results of the co-operative German–Austrian–Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol. 1998;9:893-899.CrossRefPubMedGoogle Scholar
  8. 8.
    Bielack S, Kempf-Bielack B, Schwenzer D, et al. Neoadjuvante Therapie des lokalisierten Osteosarkoms der Extremitäten. Erfahrungen der Cooperativen Osteosarkomstudiengruppe COSS an 925 Patienten. Klin Padiatr. 1999a;211:260-270.PubMedGoogle Scholar
  9. 9.
    Bielack SS, Kempf-Bielack B, Heise U, Schwenzer D, Winkler K. Combined modality treatment for osteosarcoma occurring as a second malignant disease. J Clin Oncol. 1999;17:1164-1174.PubMedGoogle Scholar
  10. 10.
    Bielack SS, Kempf-Bielack B, Delling G, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 2002;20:776-790.CrossRefPubMedGoogle Scholar
  11. 11.
    Ozaki T, Flege S, Liljenqvist U, et al. Osteosarcoma of the spine: experience of the Cooperative Osteosarcoma Study Group (COSS). Cancer. 2002;94:1069-1077.CrossRefPubMedGoogle Scholar
  12. 12.
    Ozaki T, Flege S, Kevric M, et al. Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 2003;21:334-341.CrossRefPubMedGoogle Scholar
  13. 13.
    Kager L, Zoubek A, Pötschger U, et al. Primary metastatic osteosarcoma: presentation and outcome of 202 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols. J Clin Oncol. 2003;21:2011-2018.CrossRefPubMedGoogle Scholar
  14. 14.
    Kaatsch P, Spix C, et al.: Jahresbericht 2005: Deutsches Kinderkrebsregister. Mainz, Germany, Johannes-Gutenberg-Universität, Institut für Medizinische Statistik und Information; 2006Google Scholar
  15. 15.
    Jaffe N, Paed D, Farber S, et al. Favorable response of metastatic osteogenic sarcoma to pulse high-dose methotrexate with citrovorum rescue and radiation therapy. Cancer. 1973;31:1367-1373.CrossRefPubMedGoogle Scholar
  16. 16.
    Jaffe N, Frei E 3rd, Traggis D, Bishop Y. Adjuvant methotrexate and citrovorum-factor treatment of osteogenic sarcoma. N Engl J Med. 1974;291:994-997.CrossRefPubMedGoogle Scholar
  17. 17.
    Salzer-Kuntschik M, Brand G, Delling G. Bestimmung des morphologischen Regressionsgrades nach Chemotherapie bei malignen Knochentumoren. Pathologie. 1983;4:135-141.Google Scholar
  18. 18.
    Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457-481.CrossRefGoogle Scholar
  19. 19.
    Mantel M. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50:163-170.PubMedGoogle Scholar
  20. 20.
    Cox DR. Regression models and life-tables [with discussion]. J R Stat Soc [B]. 1972;34:187-220.Google Scholar
  21. 21.
    Jasnau S, Meyer U, Potratz J, et al. Craniofacial osteosarcoma Experience of the cooperative German–Austrian–Swiss osteosarcoma study group. Oral Oncol. 2008;44:286-294.CrossRefPubMedGoogle Scholar
  22. 22.
    Kager L, Zoubek A, Kastner U, et al. Skip metastases in osteosarcoma: experience of the Cooperative Osteosarcoma Study Group. J Clin Oncol. 2006;24:1535-1541.CrossRefPubMedGoogle Scholar
  23. 23.
    Kempf-Bielack B, Bielack SS, Jürgens H, et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 2005;23:559-568.CrossRefPubMedGoogle Scholar
  24. 24.
    Picci P, Sangiorgi L, Rougraff BT, et al. The relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol. 1994;12:2699-2705.PubMedGoogle Scholar
  25. 25.
    Bielack S, Kempf-Bielack B, Winkler K. Osteosarcoma: relationship of response to preoperative chemotherapy and type of surgery to local recurrence. J Clin Oncol. 1996;15:683-684.Google Scholar
  26. 26.
    Hillmann A, Hoffmann C, Gosheger G, Krakau H, Winkelmann W. Malignant tumor of the distal part of the femur or the proximal part of the tibia: endoprosthetic replacement or rotationplasty. Functional outcome and quality-of-life measurements. J Bone Joint Surg Am. 1999;81:462-468.CrossRefPubMedGoogle Scholar
  27. 27.
    Abudu A, Grimer RJ, Tillman R, et al. The use of prostheses in skeletally immature patients. Orthop Clin North Am. 2006;37:75-84.CrossRefPubMedGoogle Scholar
  28. 28.
    Hardes J, Gebert C, Hillmann A, et al. Die Möglichkeiten und Grenzen der Umkehrplastik im operativen Behandlungsplan der primär malignen Knochentumoren. Orthopäde. 2003;32:965-970.CrossRefPubMedGoogle Scholar
  29. 29.
    Kotz RI, Windhager R, Dominkus M, Robioneck B, Müller-Daniels H. A self-extending paediatric leg implant. Nature. 2000;406:143-144.CrossRefPubMedGoogle Scholar
  30. 30.
    Krepler P, Dominkus M, Toma CD, Kotz R. Endoprosthesis management of the extremities of children after resection of primary malignant bone tumors. Orthopade. 2003;32:1013-1019.CrossRefPubMedGoogle Scholar
  31. 31.
    Bielack S, Erttmann R, Winkler K, Landbeck G. Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy. Eur J Cancer Clin Oncol. 1989;25:873-882.CrossRefPubMedGoogle Scholar
  32. 32.
    Friedman MA, Carter SK. The therapy of osteogenic sarcoma: current status and thoughts for the future. J Surg Oncol. 1972;4:482-510.CrossRefPubMedGoogle Scholar
  33. 33.
    Jaffe N, Frei E. Osteogenic sarcoma: advances in treatment. CA Cancer J Clin. 1976;26:351-359.CrossRefPubMedGoogle Scholar
  34. 34.
    Link MP, Goorin AM, Miser AW, et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremities. N Engl J Med. 1986;314:1600-1606.CrossRefPubMedGoogle Scholar
  35. 35.
    Bielack SS, Machatschek JN, Flege S, Jürgens H. Delaying surgery with chemotherapy for osteosarcoma of the extremities. Expert Opin Pharmacother. 2004;5:1243-1256.CrossRefPubMedGoogle Scholar
  36. 36.
    Stiller CA, Bielack SS, Jundt G, Steliarova-Foucher E. Bone tumours in European children and adolescents, 1978–1997. Report from the Automated Childhood Cancer Information System project. Eur J Cancer. 2006;42:2124-2135.CrossRefPubMedGoogle Scholar
  37. 37.
    Bielack S, Kempf-Bielack B, Branscheid D, et al. Second and subsequent recurrences of osteosarcoma: Presentation, treatment, and outcomes of 249 consecutive Cooperative Osteosarcoma Study Group patients. J Clin Oncol. 2009;27:557–65.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Stefan Bielack
    • 1
  • Herbert Jürgens
  • Gernot Jundt
  • Matthias Kevric
  • Thomas Kühne
  • Peter Reichardt
  • Andreas Zoubek
  • Mathias Werner
  • Winfried Winkelmann
  • Rainer Kotz
  1. 1.Pädiatrie 5 (Onkologie, Hämatologie,Immunologie)Klinikum Stuttgart, Zentrum für Kinder- und Jugendmedizin - OlgahospitalStuttgartGermany

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