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ARTICLES: Robert K. Heck, Jr., Terrance D. Peabody, and Michael A. Simon Staging of Primary Malignancies of Bone CA Cancer J Clin 2006; 56: 366-375 [Abstract] [Full text] [PDF]

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Prognosis and Treatment of Osteosarcoma Skip Metastases: Response to Bielack et al.

Robert K. Heck, MD, Terrance Peabody, MD, and Michael Simon, MD   (12 January 2007)

Skip metastases in osteosarcoma

Stefan Bielack, MD, Leo Kager and Andreas Zoubek   (12 January 2007)

Prognosis and Treatment of Osteosarcoma Skip Metastases: Response to Bielack et al. 12 January 2007
Robert K. Heck, MD, Assistant Professor Department of Orthopaedic Surgery, University of Tennessee-Campbell Clinic, Memphis, TN, Terrance Peabody, MD, and Michael Simon, MD Send letter to journal: Re: Prognosis and Treatment of Osteosarcoma Skip Metastases: Response to Bielack et al. rheck{at}campbellclinic.com Robert K. Heck, MD, et al.	We thank Dr. Kager, Dr. Zoubek, and Dr. Bielack for their letter as well as for their interest in our paper. We also congratulate them on their recently published manuscript reporting the results of their Cooperative Osteosarcoma Study Group (1) which demonstrates a better prognosis for patients with osteosarcoma skip metastases when compared with previously reported studies (2,3,4,5). As pointed out in their manuscript, however, the incidence of skip metastases in their study was substantially lower than in several other studies (1,2,3,5). The results of this retrospective, multicenter, multinational study, therefore, must be interpreted with some caution. Nevertheless, their study clearly demonstrates that some patients with osteosarcoma skip metastases can be treated successfully with multi-drug chemotherapy and surgery with wide margins. We agree that patients with osteosarcoma skip metastases should be treated aggressively. This fact is reflected in the treatment protocols at our respective institutions. In no way did we mean to suggest that these patients should be treated with “therapeutic nihilism.” We are attempting to point out that it is likely that individuals with skip metastases from high grade bone sarcomas have a worse prognosis than those without and possibly similar prognosis to those with pulmonary metastases. We think this point is reflected appropriately in the new AJCC staging system in which patients with skip metastases are grouped between patients with localized disease and those with distant metastases (6,7). We agree that this is based on imperfect non-randomized data. Like most articles on staging systems, our conclusions are based on the best information available from multiple non-randomized studies that include information based on this relatively rare event. What is needed is a staging system based on molecular events that lead to metastases and chemotherapy resistance. Hopefully, in the coming decades, anatomic staging will be replaced by biologic/molecular staging. Sincerely, Robert Heck, MD Terrance Peabody, MD Michael Simon, MD REFERENCES 1. Kager L, Zoubek A, Kastner U, et al. Skip Metastases in Osteosarcoma: Experience of the Cooperative Osteosarcoma Study Group. J Clin Oncol 2006;24:1535-1541. 2. Enneking WF, Kagan A. The implications of "skip" metastases in osteosarcoma. Clin Orthop Relat Res 1975;111:33-41. 3. Wuisman P, Enneking WF. Prognosis for patients who have osteosarcoma with skip metastasis. J Bone Joint Surg Am 1990;72:60-68. 4. Malawer MM, Dunham WK. Skip metastases in osteosarcoma: Recent experience. J Surg Oncol 1983;22:236-245. 5. Sajadi KR, Heck RK, Neel MD, et al. The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 2004;426:92-96. 6. Heck RK, Peabody TD, Simon MA. Staging of primary malignancies of bone. CA Cancer J Clin 2006;56:366-375. 7. Greene F, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual. 6th ed. New York: Springer; 2002.
Skip metastases in osteosarcoma 12 January 2007
Stefan Bielack, MD Olgahospital, Pediatrics 5, Bismarckstr 8, D-70176 Stuttgart, Germany, Leo Kager and Andreas Zoubek Send letter to journal: Re: Skip metastases in osteosarcoma coss{at}olgahospital-stuttgart.de Stefan Bielack, MD, et al.	Dear editor, Heck et al. (1) should be congratulated on their excellent article on the staging of primary malignancies of bone. One point, however, deserves comment and clarification. The authors state that "It is well established that osteosarcoma patients with skip metastases have a very poor prognosis" (2-5). It must, however, be noted that the studies cited to support this statement included either a sizeable number of patients from the prechemotherapy era, when prognosis was poor even for patients without skip metastases (2,3), or focused on small series of patients (4,5). The recently published results of our Cooperative Osteosarcoma Study Group (COSS) investigations provide good evidence that the outlook for patients with osteosarcoma and skip metastases have a reasonable potential for survival if treated by aggressive therapy including surgery with adequate margins and multidrug chemotherapy (6,7); and other reports support these findings (8,9). Taken together, our results strongly argue against therapeutic nihilism in patients with osteosarcoma who present with skip lesions. These patients should be treated according to the same principles as other osteosarcoma patients, as their prognosis may then be similar. Yours sincerely, Leo Kager, MD Andreas Zoubek, MD Stefan Bielack, MD Stuttgart and Vienna, Dec. 5, 2006. REFERENCES 1. Heck RK, Peabody TD, Simon MA. Staging of primary malignancies of bone. CA Cancer J Clin 2006;56:366-375. 2. Enneking WF, Kagan A. The implications of "skip" metastases in osteosarcoma. Clin Orthop Relat Res 1975;111:33-41. 3. Wuisman P, Enneking WF. Prognosis for patients who have osteosarcoma with skip metastasis. J Bone Joint Surg Am 1990;72:60-68. 4. Malawer MM, Dunham WK. Skip metastases in osteosarcoma: Recent experience. J Surg Oncol 1983;22:236-245. 5. Sajadi KR, Heck RK, Neel MD, et al. The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 2004;426:92-96. 6. Kager L, Zoubek A, Pötschger U, et al. Primary metastatic osteosarcoma: Presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 2003;21:2011-2018. 7. Kager L, Zoubek A, Kastner U, et al. Skip metastases in osteosarcoma: experience of the Cooperative Osteosarcoma Study Group. J Clin Oncol 2006;24:1535-1541. 8. Leavey PJ, Day MD, Booth T, et al. Skip metastasis in osteosarcoma. J Pediatr Hematol Oncol 2003;25:806-808. 9. Jaffe N, Pearson P, Eftekhari F, et al. Skip metastases in pediatric osteosarcoma. Proc Am Soc Clin Oncol 2002;21:277b (abstr 2925).