This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bacci, G. Articles by Campanacci, M. Search for Related Content PubMed PubMed Citation Articles by Bacci, G. Articles by Campanacci, M. Social Bookmarking                            What's this?

Long-Term Outcome for Patients With Nonmetastatic Osteosarcoma of the Extremity Treated at the Istituto Ortopedico Rizzoli According to the Istituto Ortopedico Rizzoli/Osteosarcoma-2 Protocol: An Updated Report

From the Service of Chemotherapy, Laboratory of Pathology, Fifth Service of Orthopedic Surgery, and Laboratory of Oncologic Research, Department of Musculoskeletal Oncology, I.F. Goidanich of the Istituto Ortopedico Rizzoli, Bologna, Italy.

Address reprint requests to Gaetano Bacci, MD, Sezione di Chemioterapia, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna, Italy; email gaetano.bacci{at}ior.it

PURPOSE: To provide an estimate of long-term prognosis for patients with osteosarcoma of the extremity treated in a single institution with neoadjuvant chemotherapy and observed for at least 10 years.

PATIENTS AND METHODS: Patients with nonmetastatic osteosarcoma of the extremity were preoperatively treated with high-dose methotrexate, cisplatin, and doxorubicin (ADM). Postoperatively, good responders (90% or more tumor necrosis) received the same three drugs used before surgery, whereas poor responders (less than 90% tumor necrosis) received ifosfamide and etoposide in addition to those three drugs.

RESULTS: For the 164 patients who entered the study between September 1986 and December 1989, surgery was a limb salvage in 136 cases (82%) and a good histologic response was observed in 117 patients (71%). At a follow-up ranging from 10 to 13 years (median, 11.5 years), 101 patients (61%) remained continuously free of disease, 61 relapsed, and two died of ADM-induced cardiotoxicity. There were no differences in prognosis between good and poor responding patients. ADM-induced cardiotoxicity (six patients), male infertility (10 of the 12 assessable patients), and second malignancies (seven patients) were the major complications of chemotherapy. Despite the large number of limb salvages performed, only four local recurrences (2.4%) were registered.

CONCLUSION: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with nonmetastatic osteosarcoma of the extremity and amputation may be avoided in more than 80% of them. Because local or systemic relapses, myocardiopathies, and second malignancies are possible even 5 years or more after the beginning of treatment, a long-term follow-up is recommended for these patients.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. J. Messerschmitt, R. M. Garcia, F. W. Abdul-Karim, E. M. Greenfield, and P. J. Getty Osteosarcoma J. Am. Acad. Ortho. Surg., August 1, 2009; 17(8): 515 - 527. [Abstract] [Full Text] [PDF]

				S. Avnet, L. Sciacca, M. Salerno, G. Gancitano, M. F. Cassarino, A. Longhi, M. Zakikhani, J. M. Carboni, M. Gottardis, A. Giunti, et al. Insulin Receptor Isoform A and Insulin-like Growth Factor II as Additional Treatment Targets in Human Osteosarcoma Cancer Res., March 15, 2009; 69(6): 2443 - 2452. [Abstract] [Full Text] [PDF]

				C. M. Costelloe, H. A. Macapinlac, J. E. Madewell, N. E. Fitzgerald, O. R. Mawlawi, E. M. Rohren, A. K. Raymond, V. O. Lewis, P. M. Anderson, R. L. Bassett Jr., et al. 18F-FDG PET/CT as an Indicator of Progression-Free and Overall Survival in Osteosarcoma J. Nucl. Med., March 1, 2009; 50(3): 340 - 347. [Abstract] [Full Text] [PDF]

				T. YONEMOTO, T. ISHII, Y. TAKEUCHI, Y. HAGIWARA, S. IWATA, and S.-I. TATEZAKI Recently Intensified Chemotherapy for High-grade Osteosarcoma May Affect Fertility in Long-term Male Survivors Anticancer Res, February 1, 2009; 29(2): 763 - 767. [Abstract] [Full Text] [PDF]

				L. H. Aksnes, H. C. F. Bauer, N. L. Jebsen, G. Folleras, C. Allert, G. S. Haugen, and K. S. Hall Limb-sparing surgery preserves more function than amputation: A SCANDINAVIAN SARCOMA GROUP STUDY OF 118 PATIENTS J Bone Joint Surg Br, June 1, 2008; 90-B(6): 786 - 794. [Abstract] [Full Text] [PDF]

				S. L. Spunt, S. X. Skapek, and C. M. Coffin Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcomas Oncologist, June 1, 2008; 13(6): 668 - 678. [Abstract] [Full Text] [PDF]

				P. Zhang, Y. Yang, P. A. Zweidler-McKay, and D. P.M. Hughes Critical Role of Notch Signaling in Osteosarcoma Invasion and Metastasis Clin. Cancer Res., May 15, 2008; 14(10): 2962 - 2969. [Abstract] [Full Text] [PDF]

				A. Spreafico, S. Schenone, T. Serchi, M. Orlandini, A. Angelucci, D. Magrini, G. Bernardini, G. Collodel, A. Di Stefano, C. Tintori, et al. Antiproliferative and proapoptotic activities of new pyrazolo[3,4-d]pyrimidine derivative Src kinase inhibitors in human osteosarcoma cells FASEB J, May 1, 2008; 22(5): 1560 - 1571. [Abstract] [Full Text] [PDF]

				R. K. Heck Jr., T. D. Peabody, and M. A. Simon Staging of Primary Malignancies of Bone CA Cancer J Clin, November 1, 2006; 56(6): 366 - 375. [Abstract] [Full Text] [PDF]

				A. S. Petrilli, B. de Camargo, V. O. Filho, P. Bruniera, A. L. Brunetto, R. Jesus-Garcia, O. P. Camargo, W. Pena, P. Pericles, A. Davi, et al. Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: Prognostic Factors and Impact on Survival J. Clin. Oncol., March 1, 2006; 24(7): 1161 - 1168. [Abstract] [Full Text] [PDF]

				S. Ferrari, S. Smeland, M. Mercuri, F. Bertoni, A. Longhi, P. Ruggieri, T. A. Alvegard, P. Picci, R. Capanna, G. Bernini, et al. Neoadjuvant Chemotherapy With High-Dose Ifosfamide, High-Dose Methotrexate, Cisplatin, and Doxorubicin for Patients With Localized Osteosarcoma of the Extremity: A Joint Study by the Italian and Scandinavian Sarcoma Groups J. Clin. Oncol., December 1, 2005; 23(34): 8845 - 8852. [Abstract] [Full Text] [PDF]

				P. M. Anderson, G. A. Wiseman, L. Erlandson, V. Rodriguez, B. Trotz, S. A. Dubansky, and K. Albritton Gemcitabine Radiosensitization after High-Dose Samarium for Osteoblastic Osteosarcoma Clin. Cancer Res., October 1, 2005; 11(19): 6895 - 6900. [Abstract] [Full Text] [PDF]

				D. P. M. Hughes, D. G. Thomas, T. J. Giordano, L. H. Baker, and K. T. McDonagh Cell Surface Expression of Epidermal Growth Factor Receptor and Her-2 with Nuclear Expression of Her-4 in Primary Osteosarcoma Cancer Res., March 15, 2004; 64(6): 2047 - 2053. [Abstract] [Full Text] [PDF]

				M. Serra, G. Reverter-Branchat, D. Maurici, S. Benini, J.-N. Shen, T. Chano, C.-M. Hattinger, M.-C. Manara, M. Pasello, K. Scotlandi, et al. Analysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells Ann. Onc., January 1, 2004; 15(1): 151 - 160. [Abstract] [Full Text] [PDF]

				H. R. Dhaini, D. G. Thomas, T. J. Giordano, T. D. Johnson, J. S. Biermann, K. Leu, P. F. Hollenberg, and L. H. Baker Cytochrome P450 CYP3A4/5 Expression as a Biomarker of Outcome in Osteosarcoma J. Clin. Oncol., July 1, 2003; 21(13): 2481 - 2485. [Abstract] [Full Text] [PDF]

				P. Prolo, F. Chiappelli, G. Bernard, M. Fiala, A. Ibarra, M.L. Sartori, A. Dovio, and A. Angeli Neuroendocrine-Immune Surveillance of Osteosarcoma: Emerging Hypothesis Journal of Dental Research, June 1, 2003; 82(6): 417 - 421. [Abstract] [Full Text] [PDF]

				A M Wikstrom, L Hovi, L Dunkel, and U M Saarinen-Pihkala Restoration of ovarian function after chemotherapy for osteosarcoma Arch. Dis. Child., May 1, 2003; 88(5): 428 - 431. [Abstract] [Full Text] [PDF]

				M. Serra, K. Scotlandi, G. Reverter-Branchat, S. Ferrari, M. C. Manara, S. Benini, M. Incaprera, F. Bertoni, M. Mercuri, A. Briccoli, et al. Value of P-Glycoprotein and Clinicopathologic Factors as the Basis for New Treatment Strategies in High-Grade Osteosarcoma of the Extremities J. Clin. Oncol., February 1, 2003; 21(3): 536 - 542. [Abstract] [Full Text] [PDF]

				G. N. Machak, S. I. Tkachev, Y. N. Solovyev, P. A. Sinyukov, S. M. Ivanov, N. V. Kochergina, A. D. Ryjkov, V. V. Tepliakov, B. Y. Bokhian, and V. V. Glebovskaya Neoadjuvant Chemotherapy and Local Radiotherapy for High-Grade Osteosarcoma of the Extremities Mayo Clin. Proc., February 1, 2003; 78(2): 147 - 155. [Abstract] [PDF]

				D. G. Thomas, T. J. Giordano, D. Sanders, J. S. Biermann, and L. Baker Absence of HER2/neu Gene Expression in Osteosarcoma and Skeletal Ewing's Sarcoma Clin. Cancer Res., March 1, 2002; 8(3): 788 - 793. [Abstract] [Full Text] [PDF]