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Journal of Clinical Oncology, Vol 22, No 24 (December 15), 2004: pp. 5017-5018 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.04.101
In Reply:
St Anna Children’s Hospital, Vienna, Austria We are grateful for Dr Brockstein's extraordinarily precise and comprehensive review of our recent reports on high-grade osteosarcoma1,2 and appreciate his suggestions on how current knowledge about the rare disease of primary metastatic osteosarcoma might be further enhanced by additional analyses of the Cooperative Osteosarcoma Study Group (COSS) data set. To begin, we agree that the results obtained in our patients with skip metastases merit a separate publication, and a manuscript is already in preparation. Our observation that many patients with skip metastases can achieve long-term survival stands in contrast to some previous reports that concluded that skip metastases herald a catastrophic outcome. It must be noted, however, that these earlier series included a sizeable number of patients from the prechemotherapy era, when prognosis was poor even for patients without skip metastases.3,4 Results reported in a more recent publication by Leavey et al5 support our observation that patients with high-grade osteosarcoma and skip metastases have a potential for survival if treated by surgery with adequate margins and multidrug chemotherapy. During the 20-year recruitment period of our study, diagnostic imaging improved considerably; therefore, it is possible that stage migration towards metastatic disease with smaller lesions and lower tumor burden may have occurred. Unfortunately, information concerning the size of metastases was not routinely collected in the COSS trials. In our study, we focused on patients with clearly defined metastatic disease (ie, proven histologically or by disease progression). Among these patients, 5-year event-free survival (20% v 19%, P = .71, log-rank test) and 5-year overall survival (31% v 28%, P = .27) did not differ between patients who were diagnosed before 1990 (n = 84) or after 1990 (n = 118). Dr Brockstein is correct in noting that, in the COSS experience, the relative proportion of bone involvement is higher among synchronous than among metachronous metastases.1,2 The reason for this difference is unknown. Because all COSS protocols required bone scans as well as appropriate imaging of the primary tumor site as part of diagnostic staging in case of pulmonary relapse, insufficient use of bone scans at relapse is an unlikely explanation. Our data indicate that advanced disease at diagnosis is not inherently more chemotherapy-resistant than localized disease, and we agree with Dr Brockstein that (neo)adjuvant chemotherapy holds promise to prevent the development of unresectable metastatic disease, which in turn portends a catastrophic outcome. However, it has to be noted that our analysis was restricted to patients with unequivocally proven metastatic disease and that patients whose evidence for primary spread was limited to diagnostic imaging were not included. Therefore, we cannot exclude that a minority of osteosarcoma metastases may be cured by chemotherapy alone. As noted by Dr Brockstein, 5-year overall survival for patients presenting with primary metastatic extremity osteosarcoma was erroneously given as 54% in Table 1 and should be 34%, as depicted in Figure 2. Skip lesions were observed in only 1.4% of patients (24 of 1,765 patients) with osteosarcoma, as stated. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Kager L, Zoubek A, Potschger U, et al: Primary metastatic osteosarcoma: Presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 21:2011-2018, 2003 2. Bielack SS, Kempf-Bielack B, Branscheid D, et al: Relapsed osteosarcoma: An analysis of 576 Cooperative Osteosarcoma Study Group (COSS) patients. Proc Am Soc Clin Oncol 22:822, 2003 (abstr 3305)
3. Wuisman P, Enneking WF: Prognosis for patients who have osteosarcoma with skip metastasis. J Bone Joint Surg Am 72:60-68, 1990 4. Enneking WF, Kagan A: "Skip" metastases in osteosarcoma. Cancer 36:2192-2205, 1975[Medline] 5. Leavey PJ, Day MD, Booth T, et al: Skip metastasis in osteosarcoma. J Pediatr Hematol Oncol 25:806-808, 2003[CrossRef][Medline]
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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