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Osteosarcoma Relapse After Combined Modality Therapy: An Analysis of Unselected Patients in the Cooperative Osteosarcoma Study Group (COSS)

From the Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie; Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A; Universitätsklinikum Münster, Klinik und Poliklinik für Thorax-, Herz- und Gefäßchirurgie, Münster; Krankenhaus Großhansdorf, Zentrum für Pneumologie und Thoraxchirurgie, Großhansdorf; Universitätsklinikum Düsseldorf, Klinik für Kinder-Onkologie, -Hämatologie und -Immunologie, Düsseldorf; Universitätsklinikum Hamburg-Eppendorf, Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin, Abteilung für Pädiatrische Radiologie; Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Pädiatrische Hämatologie und Onkologie; Radiologische Privat-Praxis Raboisen; Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Radiologie, Abteilung für Strahlentherapie und Radioonkologie, Hamburg; Zentrum für Kinderheilkunde und Jugendmedizin des Klinikums der Johann Wolfgang Goethe-Universität, Klinik für Kinderheilkunde III, Pädiatrische Onkologie, Hämatologie und Hämostaseologie, Frankfurt; Olgahospital Stuttgart, Pädiatrie 5 (Onkologie, Hämatologie und Immunologie), Stuttgart, Germany; Orthopädische Universitätsklinik Balgrist, Zürich; Kantonsspital Basel, Institut für Pathologie, Basel, Switzerland; Universitätsklinik für Orthopädie, Allgemeines Krankenhaus Wien, Vienna; St Anna Kinderspital, Vienna, Austria

Address reprint requests to Beate Kempf-Bielack, Cooperative Osteosarkomstudiengruppe (COSS), Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Albert-Schweitzer-Str 33, D-48149 Münster, Germany; e-mail: coss{at}uni-muenster.de

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma.

PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients).

RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy.

CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.

Supported in part by Deutsche Krebshilfe.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003, and at the 36th Congress of the International Society of Paediatric Oncology, Oslo, Norway, September 16-19, 2004.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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