Comment on “Prognostic Factors in High-Grade Osteosarcoma of the Extremities or Trunk: An Analysis of 1,702 Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols”

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.12.2910 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12065572 Comment on “Prognostic Factors in High-Grade Osteosarcoma of the Extremities or Trunk: An Analysis of 1,702 Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols” Stefano FerrarixStefano FerrariSearch for articles by this author , Mario MercurixMario MercuriSearch for articles by this author , Gaetano BaccixGaetano BacciSearch for articles by this author Stefan S. BielackxStefan S. BielackSearch for articles by this author , Heribert JürgensxHeribert JürgensSearch for articles by this author Show More Istituto Ortopedico Rizzoli, Bologna, ItalyCooperative Osteosarcoma Study Group, University Children’s Hospital Muenster, Münster, Germany https://doi.org/10.1200/JCO.2002.20.12.2910 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15062002In Reply:We agree with Drs Ferrari et al that the choice of systemic therapy is likely to influence response to preoperative treatment and survival. All Cooperative Osteosarcoma Study Group (COSS) protocols active since 1980 have called for intensive pre- and postoperative chemotherapy. In fact, all studies since 1986 have included the same four agents: doxorubicin, high-dose methotrexate, cisplatin, and ifosfamide.1 We therefore believe that it was well justified to combine all of these studies into an analysis of prognostic factors, as reported in our article.2Our result that response to preoperative chemotherapy is of utmost prognostic importance in osteosarcoma is in agreement with almost all published trials. Ferrari et al’s recent observation that this might not be the case if poor responders to an ifosfamide-free preoperative regimen are treated with ifosfamide postoperatively3 is highly unusual and warrants verification in a prospective, randomized trial. Several European and American groups are currently discussing a common study in which such a strategy may be evaluated.Ferrari et al point to what they believe is a “relatively low” rate of conservative surgery (55%) in our report and compare this to 87% in a cohort of 763 patients from the Istituto Ortopedico Rizzoli. This comparison, as performed, is not correct. All of the Rizzoli patients, but only approximately half of the patients from the COSS cohort, were treated in 1990 or later. We have pointed out in our article that the use of ablative surgery (defined as amputation, disarticulation, or rotation plasty) decreased from 60% (455 of 757) in the 1980s to 31% (265 of 844) in the 1990s.2 It must be stressed that it is not limb salvage per se, which is the goal of osteosarcoma surgery, but rather the achievement of adequate surgical margins with preservation of a functional limb. In terms of function, rotation plasties could well be included among the conservative procedures. If they were counted as such, the overall rate of conservative surgery in our cohort was not 55%, but 71% (1,141 of 1,601). The corresponding figure for the 1990s is 84% (705 of 844), very similar to the 87% from Ferrari’s cohort. Ferrari et al are, however, correct in pointing out that centralization is likely to lead to an increased use of conservative procedures. The institution at which surgery was actually performed (not necessarily corresponding to the institution registering the patient) was reported for 1,439 of our patients. Two thirds of these patients (n = 959) were operated on in the 15 largest surgical centers (more than 20 documented procedures each). When looking at the total recruitment period, their rates of amputation/disarticulation, rotation plasty, and resection were 22% (n = 212), 21% (n = 197), and 57% (n = 550). The remaining third of patients (n = 480) were operated on at a variety of institutions which each averaged less than one operation per year. There, the corresponding figures were 42% (n = 202), 11% (n = 54), and 47% (n = 224).Unlike Ferrari et al imply, it is certainly not the COSS strategy to promote the distribution of patients with rare tumors to numerous centers. Nevertheless, it is the aim of the group to recruit nationwide and hence to contribute to improved standards of care. Still, we would like to point out that the majority of patients in the COSS studies are registered from and are seen in a limited number of institutions. Regarding the reported series of 1,702, 69% were registered from the 28 largest centers, which each contributed more than 20 patients (21% of the participating institutions). The remaining 105 smaller institutions (79%) entered fewer than one third of all patients.In order to ensure a uniformly high standard of care despite multiple institutions, the COSS as well as the other pediatric oncology trial groups established under the auspices of the Society of Pediatric Oncology and Hematology of the German-speaking countries perform a task that extends far beyond mere data collection and handling. Participating institutions can rely on panels of experts including oncologists, radiologists, pathologists, orthopedic surgeons, and members of other subspecialties to offer counsel and assistance in all aspects of local and systemic therapy. This structure guarantees that advice based on the cumulative experience and expertise of the respective group is available for each and every individual patient. Thus, the group as a whole provides the “multidisciplinary vision” which is essential in cancer therapy.1. Bielack S, Kempf-Bielack B, Schwenzer D, et al: Neoadjuvante Therapie des lokalisierten Osteosarkoms der Extremitäten: Erfahrungen der Cooperativen Osteosarkomstudiengruppe COSS an 925 Patienten. Klin Pädiatr 211:: 260,1999-270, Crossref, Medline, Google Scholar2. Bielack S, Kempf-Bielack B, Delling G, et al: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1,702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 20:: 776,2002-790, Link, Google Scholar3. Ferrari S, Bertoni F, Picci P, et al: Predictive factors of disease-free survival for non-metastatic osteosarcoma of the extremity: An analysis of 300 patients treated at the Rizzoli Institute. Ann Oncol 12:: 1145,2001-1150, Crossref, Medline, Google Scholar