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Journal of Clinical Oncology, Vol 22, No 24 (December 15), 2004: pp. 5017 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.04.234
Metastatic Osteosarcoma: A Curable Advanced MalignancyEvanston Northwestern Healthcare, Evanston, and Northwestern University, The Feinberg School of Medicine, Chicago, IL To the Editor: Kager et al1 should be congratulated on their careful delineation of the presentation and outcome of patients with primary metastatic osteosarcoma treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. The conclusions in this study are similar to those recently published in the Journal of Clinical Oncology by Tsuchiya et al.2 Both studies showed that osteosarcoma presenting as a primary metastatic malignancy is a curable disease in nearly 20% of patients. Several points deserve comment. First, the authors note that patients with skip metastases as their only manifestation of metastatic presentation, do quite well, with an overall long-term survival of greater than 50%. This stands in distinction from the classic teachings that skip metastases portend a poor prognosis. This finding may merit a separate publication to stand alone so that the opportunity is not lost to disseminate this important prognostic information as well as details of the therapeutic course leading to such an outcome. Additionally, in the study by Kager et al,1 patients with more than five metastases had only a 3% 5-year event-free survival, yet their 5-year overall survival was 19%. Despite recurrence, this overall survival rate should encourage us to recommend that patients have resection of multiple metastases. A useful univariate for study would have been the date on study or protocol used. Because computed tomography scanning became an important tool while the reported Cooperative Osteosarcoma Study studies were in progress, an expected stage migration may have occurred with metastatic disease presenting with smaller pulmonary metastases. Whether these patients fare better than those with more advanced pulmonary metastasis would be useful information. Notably, in this series, 69 patients (34%) presented with bone metastases. In an analysis by the same group presented at the 2003 American Society of Clinical Oncology meeting,3 only 17% of patients had bone metastases later as a manifestation of recurrence. One could ask why there was a difference when the same patient population was accrued. It is likely that skip metastases account for a portion of these patients. However, eliminating skip metastases still leaves 22% of patients with bony metastases. A possible explanation may relate to the greater use of bone scan at diagnosis but not at the time of recognition of pulmonary metastatic disease without bone pain. This point may be useful in that patients planning to undergo pulmonary metastasectomy should also undergo bone scan or positron emission tomography scan to detect bony metastases that may alter plans for thoracotomy. This study may also support the hypothesis that advanced disease is not inherently more chemotherapy-resistant than localized disease. In patients who received chemotherapy and had complete metastasectomy, 58% (Fig 5) of patients at most demonstrated chemotherapy resistance (those with a surgical complete response who subsequently died). This number closely matches that seen with primary disease, knowing that approximately 20% of patients have no microscopic metastases based on natural history studies. This would imply that perhaps the only reason to treat patients with chemotherapy early is to prevent the development of unresectable metastatic disease, as opposed to preventing chemotherapy-resistant micrometastases. Two small errors are noted. First, Table 1 notes that the 5-year overall survival for patients with extremity tumors is 54%, and this should be, I believe, 34%. Second, on page 2,017 in the top paragraph on the right, skip lesions were observed in only 1.4% of patients; I believe this was actually 12% (24 of 202 patients). Author's Disclosures of Potential Conflicts of Interest The author 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. Tsuchiya H, Kanazawa Y, Abdel-Wanis ME, et al: Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma: The Japanese Musculoskeletal Oncology Group Study. J Clin Oncol 20:3470-3477, 2002 3. 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)
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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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