Abstract
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.
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Winkler K, Beron G, Schellong G, et al. Kooperative Osteosarkomstudie COSS-77: Ergebnisse nach über 4 Jahren. Klin Pädiatr. 1982;194:251-256.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Kaatsch P, Spix C, et al.: Jahresbericht 2005: Deutsches Kinderkrebsregister. Mainz, Germany, Johannes-Gutenberg-Universität, Institut für Medizinische Statistik und Information; 2006
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.
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.
Salzer-Kuntschik M, Brand G, Delling G. Bestimmung des morphologischen Regressionsgrades nach Chemotherapie bei malignen Knochentumoren. Pathologie. 1983;4:135-141.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457-481.
Mantel M. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50:163-170.
Cox DR. Regression models and life-tables [with discussion]. J R Stat Soc [B]. 1972;34:187-220.
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.
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.
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.
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.
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.
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.
Abudu A, Grimer RJ, Tillman R, et al. The use of prostheses in skeletally immature patients. Orthop Clin North Am. 2006;37:75-84.
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.
Kotz RI, Windhager R, Dominkus M, Robioneck B, Müller-Daniels H. A self-extending paediatric leg implant. Nature. 2000;406:143-144.
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.
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.
Friedman MA, Carter SK. The therapy of osteogenic sarcoma: current status and thoughts for the future. J Surg Oncol. 1972;4:482-510.
Jaffe N, Frei E. Osteogenic sarcoma: advances in treatment. CA Cancer J Clin. 1976;26:351-359.
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.
Bielack SS, Machatschek JN, Flege S, Jürgens H. Delaying surgery with chemotherapy for osteosarcoma of the extremities. Expert Opin Pharmacother. 2004;5:1243-1256.
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.
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.
Acknowledgements
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.
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Bielack, S. et al. (2009). Osteosarcoma: The COSS Experience. In: Jaffe, N., Bruland, O., Bielack, S. (eds) Pediatric and Adolescent Osteosarcoma. Cancer Treatment and Research, vol 152. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-0284-9_15
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DOI: https://doi.org/10.1007/978-1-4419-0284-9_15
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