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Journal of Clinical Oncology, Vol 22, No 12 (June 15), 2004: pp. 2511-2513 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.045
In Reply:Department of Musculoskeletal Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy In reply to the comments on our letter,1 we accept the rectification of the total number of patients being 1,702 instead of 480; nonetheless, Bielack et al should have also specified that this number includes not only the patients with nonmetastatic osteosarcoma of the extremities who entered the neoadjuvant Cooperative Osteosarcoma Study Group (COSS) studies,2 but also patients with tumors located in clavicle, scapula, rib, spine, and pelvis; patients presenting with metastases; patients not treated with surgery; and patients whose local treatment is unknown! We would like to underline that since the heart of matter was the high number of amputations performed in the study by Goorin et al (Pediatric Oncology Group Study POG-8651),3 in our letter,1 we evaluated only patients with nonmetatastatic osteosarcoma of the extremities treated by surgery. Besides this preamble, there are some points we wish to answer to. First, even if we evaluate all the 1,702 patients treated by the COSS group, the significance of our conclusion remains the same: in fact, since these patients were treated in the 133 participating institutions, the mean number of cases treated by each institution was less than 13 (1,702 ÷ 133 = 12.8). The COSS studies considered2 were performed throughout a 19-year period (from 1980 to 1998), so the mean number of patients treated by a single institution was 0.7 per year (ie, approximately one case every 2 years). Second, Bielack et al also pointed out that two-thirds (ie, 1,134) of all definitive operative procedures were performed in only 15 centers. We therefore guess that the remaining 567 patients underwent surgery in the other 118 centers, meaning that each center treated 4.8 patients during the 19-year period (ie, approximately one patient every 4 years)—a rate not so different from that which was reported in our letter.1 On the basis of these data, we believe that it is possible to assume that at least one of three patients received surgery in institutions having little experience with treating osteosarcoma of the extremities. Even if we consider the 1,134 patients treated in the 15 specialized centers, the number of cases per year remains low, with two exceptions. In fact, two other COSS groups' articles4,5 report that the total numbers of patients treated in Vienna and in Muenster were 136 and 130, respectively; so it follows that the other 13 centers treated a very small number of patients—approximately three cases per year. Third, as regards the rate of amputations in the COSS studies, Bielack et al state that the percentage we reported (60%) is not correct, since it only refers to patients treated before 1990,6 and that after that year the rate of limb salvages was significantly higher: 69%. This percentage is considerably lower than those achieved during the same period at our institution (89% for the 676 patients treated between 1990 and 2000) and in other centers (G. Roussy, 80%7; Memorial Sloan-Kettering, 80%8; Debrè Hospital, 93%9). Considering all COSS studies2 regardless of the year of treatment, we actually noticed that limb salvages were performed only in the 45% of patients with extremity tumors, and if we further focus on the studies about the cases treated in Vienna4 and Muenster5 that were published separately, we learn that they performed limb salvages for 79 (61%) of 130 patients, and for 84 (62%) of 136 patients, respectively. So we deduce that in the other centers that percentage was 42% (562 of 1,329). This difference is statistically significant (P < .0001). Moreover, even if we only consider patients of the COSS studies treated after 1990, we see that the rate of amputations is considerably lower in Vienna and Munster4,5 than in the other COSS institutions (5% v 16%). In accordance with these data, it should be extremely interesting for us to know rates of conservative surgery, local recurrence, and final outcome according to the numbers of patients treated in Vienna and Muenster versus the other 13 specialized centers, versus all other institutions participating in the COSS studies. Fourth, as regards the interest of Bielack et al in knowing the importance of surgical volume for musculoskeletal sarcoma surgery, we are not able to answer properly, since in our institution, all bone tumors are surgically treated in a single ward with five surgeons. Nonetheless, the head of this surgical team (M. Campanacci, MD, until 1998; currently, M. Mercuri, MD) is always responsible for the decision about the type of surgery to perform after discussion with the team and the medical staff involved (ie, chemotherapists and radiotherapists, in addition to surgeons). We also wish to take this opportunity to make clear that we do not intend to criticize the work (which is excellent overall) from the COSS group, with whom we have collaborated. Nonetheless, we want to confirm that, with regard to such a rare disease like osteosarcoma, we believe surgery to be better performed in a small number of well-trained institutions. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Bacci G, Ferrari S, Longhi A, et al: Preoperative therapy versus immediate surgery in nonmetastatic osteosarcoma. J Clin Oncol 21:4662–4663, 2003
2. Bielack SS, Kempf-Bielack B, Delling G, et al: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 20:776–790, 2002
3. Goorin AM, Schwartzentruber DJ, Devidas M, et al: Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol 21:1574–1580, 2003 4. Sluga M, Windhager R, Lang S, et al: Local and systemic control after ablative and limb sparing surgery in patients with osteosarcoma. Clin Orthop 358:120–127, 1999 5. Lindner NJ, Ramm O, Hillmann A, et al: Limb salvage and outcome of osteosarcoma: The University of Muenster experience. Clin Orthop 358:83–89, 1999
6. Fuchs N, Bielack SS, Epler D, et al: Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group's protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol 9:893–899, 1998 7. Kalifa C, Razafindrakoto H, Vassal G, et al: Chemotherapy in osteogenic sarcoma: The experience of the pediatric department of the Gustave Roussy Institute, in Humphrey GB (ed): Osteosarcoma in Adolescent and Young Adults. Boston, MA, Kluwer Academic Publishers, 1993 8. Meyers PA, Heller G, Healey J, et al: Chemotherapy for nonmetastatic osteogenic sarcoma: The Memorial Sloan-Kettering experience. J Clin Oncol 10:5–15, 1992[Abstract] 9. Delepine N, Delepine G, Desbois JC: A monocentric therapy study: An approach to optimize the results of the treatment of osteosarcoma by protocols based upon HDMTX, associated with systematic conservative surgery, in Humphrey GB (ed): Osteosarcoma in Adolescent and Young Adults. Boston, MA, Kluwer Academic Publishers, 1993
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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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