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Skip Metastases in Osteosarcoma: Experience of the Cooperative Osteosarcoma Study Group

Leo Kager, Andreas Zoubek, Ulrike Kastner, Beate Kempf-Bielack, Jenny Potratz, Rainer Kotz, G. Ulrich Exner, Christiane Franzius, Susanna Lang, Rainer Maas, Heribert Jürgens, Helmut Gadner, Stefan Bielack

From the St Anna Children's Hospital; Departments of Pathology and Orthopedics, University Hospital Vienna, Vienna, Austria; Department of Orthopedics, University Hospital Zürich, Zürich, Switzerland; Diagnostic Radiology, Hamburg; Department of Nuclear Medicine, University Hospital Muenster; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster; and Olgahospital, Pediatrics 5–Oncology, Hematology, Immunology, Stuttgart, Germany

Address reprint requests to Stefan Bielack, MD, Olgahospital, Pediatrics 5, Bismarckstr 8, D-70176 Stuttgart, Germany; e-mail: coss{at}olgahospital-stuttgart.de

PURPOSE: The outlook for patients with osteosarcoma who present with synchronous regional bone metastases (skip metastases), either in the primary bone site or transarticular, is considered to be extremely poor. This study was conducted to further investigate the prognostic implication of skip metastases in osteosarcoma.

PATIENTS AND METHODS: The authors retrospectively analyzed the collected data of 1,765 consecutive patients with newly diagnosed high-grade osteosarcoma of bone who were registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies and identified 24 patients (1.4%) with unequivocally proven skip metastases. All 24 patients were treated by an aggressive surgical approach coupled with polychemotherapy. Demographic, diagnostic, tumor, and treatment-related variables and response and survival data were analyzed.

RESULTS: Skip metastases were identified preoperatively in 11 of 24 patients by bone scan, eight of 22 patients by plain x-ray, 15 of 18 patients by magnetic resonance imaging, and five of 10 patients by computed tomography. A complete surgical remission (CSR) of all clinically detectable tumor sites was achieved in 22 of 24 patients during front-line therapy. With a median follow-up time of 4.4 years (8 years for survivors) from diagnosis, 12 patients were alive, all of whom were in continuous CSR. Survival did correlate with location of skip metastases and histologic response to neoadjuvant chemotherapy.

CONCLUSION: Synchronous regional bone metastases are rare in osteosarcoma, and preoperative detection relies on appropriate diagnostic imaging. Aggressive multimodal therapy holds the promise to achieve prolonged survival, especially in patients in whom these metastases occur within the same bone as the primary lesion and whose tumors respond well to chemotherapy.

Supported by Deutsche Krebshilfe and Forschungsinstitut fuer krebskranke Kinder, St Anna Kinderspital (Vienna, Austria).

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 Sarcoma Meeting Stuttgart, Stuttgart, Germany, June 15-17, 2005.

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

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