Originally published as JCO Early Release 10.1200/JCO.2008.16.2305 on December 15 2008

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Second and Subsequent Recurrences of Osteosarcoma: Presentation, Treatment, and Outcomes of 249 Consecutive Cooperative Osteosarcoma Study Group Patients

From the Klinikum Stuttgart, Olgahospital, Klinik für Kinder und Jugendmedizin, Pädiatrie 5 (Onkologie, Hämatologie, Immunologie) and Pädiatrie 1 (Allgemeine Pädiatrie, Rheumatologie, Neurologie, Allergologie/Pulmologie, Gastroenterologie), Stuttgart; Universitätsklinikum Münster, Klinik und Poliklinik für Kinder und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Münster; Krankenhaus Groβhansdorf, Zentrum für Pneumologie und Thoraxchirurgie, Groβhansdorf; Klinik Schillerhöhe, Zentrum für Pneumologie und Thoraxchirurgie, Gerlingen; Universitätsklinikum Hamburg-Eppendorf, Universitätsklinik und Poliklinik für Kinder und Jugendmedizin, Abteilung für Pädiatrische Radiologie; Radiologische Privat-Praxis Raboisen; Universitätsklinikum Hamburg-Eppendorf, Ambulanzzentrum GmbH des UKE, Bereich Strahlentherapie, Hamburg, Germany; Universitätsspital beider Basel, Institut für Pathologie; Universitätskinderspital beider Basel, Onkologie/Hämatologie, Basel, Switzerland; and St. Anna Kinderspital, Vienna, Austria.

Corresponding author: Stefan S. Bielack, MD, Cooperative Osteosarkomstudiengruppe, Klinikum Stuttgart – Olgahospital, Pädiatrie 5 (Onkologie, Hämatologie, Immunologie), Bismarckstr 8, D-70176 Stuttgart, Germany; e-mail: coss{at}olgahospital-stuttgart.de.

Purpose To evaluate patient and tumor characteristics, treatment, and outcomes in a large cohort of unselected patients with second and subsequent recurrences of osteosarcoma.

Patients and Methods Two hundred forty-nine consecutive patients who had originally received combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group protocols and went on to develop a total of 409 second and subsequent osteosarcoma recurrences were analyzed for patient-, tumor-, and treatment-related factors and outcomes.

Results Five-year overall and event-free survival rates were 16% and 9% for 249 second, 14% and 0% for 93 third, 13% and 6% for 38 fourth, and 18% and 0% for 14 fifth recurrences, respectively. The proportion of recurrences confined to the lungs decreased and the proportion of those with chest wall involvement increased with increasing numbers of recurrences. The duration of relapse-free intervals and the number of lesions at recurrence correlated with outcomes. While only one of 205 patients with rerecurrence survived past 5 years without surgical remission, 5-year overall and event-free survival rates were 32% and 18% for 119 second, 26% and 0% for 45 third, 28% and 13% for 20 fourth, and 53% and 0% for five fifth recurrences, respectively, in which a renewed surgical remission was achieved. The use of chemotherapy correlated with longer survival in patients without surgical remissions.

Conclusion To our knowledge, this is the first report of survival estimates derived from large cohorts of unselected patients with second and subsequent osteosarcoma recurrences. It confirms the overwhelming importance of surgical clearance. Prognostic indicators after rerecurrences resemble those known from first recurrence. The exact role of re-treatment with chemotherapy, particularly in the adjuvant situation, remains to be defined.

Supported by Deutsche Krebshilfe, Bundesministerium für Forschung und Technologie, and Fördergemeinschaft Kinderkrebszentrum Hamburg.

Presented in part at the 18th Annual Meeting of the European Musculo-Skeletal Oncology Society, May 25-27, 2005, Trieste, Italy, and the Sarcoma Meeting Stuttgart 2005, June 15-17, 2005, Stuttgart, Germany.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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