Abstract
The Bone Tumor Center of the “Istituto Ortopedico Rizzoli” was established in 1955 with the aim of studying and treating the musculoskeletal tumors. Between 1959 and 2006, 1245 patients with high grade nonmetastatic osteosarcoma of the extremity were treated at our Institute. Most of them were enrolled in study protocols.
In the “prechemotherapy era”, the cure rate was 11%, with an amputation rate of 90%. Our first experience with adjuvant chemotherapy was in 1972. A total of 223 patients received adjuvant chemotherapy, with a disease-free survival (DFS) ranging from 45% to 53%, according to the chemotherapy protocol used. With the introduction of neoadjuvant chemotherapy, the resection rate increased and reached 94%, when high dose fosfamide was added to standard doses of methotrexate, cisplatin, and adriamycin.
In the last few years, the results of treatment of nonmetastatic osteosarcoma of the extremity have reached a plateau (64% five-year DFS), and strategies of dose intensification are not able to improve the prognosis. Not only new active drugs, but also different approaches to the disease, are needed.
In this regard, we are now investigating tumor microenvironment-targeted agents and chemotherapy protocols based on prospective biological stratification of patients.
Collaborative projects with international groups and institutions are crucial for this rare disease.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Campanacci M, Bacci G, Bertoni F, Picci P, Minutillo A, Franceschi C. The treatment of osteosarcoma of the extremities: twenty years experience at the Istituto Ortopedico Rizzoli. Cancer. 1981;48:533-542.
Uribe-Botero G, Russel WO, Sutow WW, Martin RG. Primary osteosarcoma of bone: clinicopathological investigation of 243 cases, with necroscopy studies in 54. Am J Clin Pathol. 1977;67:427-435.
Marcove RC, Mike V, Hajek JV, Levin AG, Hutter RV. Osteogenic sarcoma below the age of twenty-one. A review of one hundred and forty five cases. J Bone Joint Surg Am. 1970;52:411-423.
Gaffney R, Unni KK, Sim FH, Slezak JM, Esther RJ, Bolander ME. Follow-up study of long-term survivors of osteosarcoma in the prechemotherapy era. Hum Pathol. 2006;37:1009-1014.
Cade S. Osteogenic sarcoma: a study based on 133 patients. J R Coll Surg Edinb. 1955;1:79-111.
Jenkin RD, Allt WE, Fitzpatrick PJ. Osteosarcoma. An assessment of management with particular reference to primary irradiation and selective delayed amputation. Cancer. 1972;30:393-400.
Marcove RC, Miké V, Huvos AG, Southam CM, Levin AG. Vaccine trials for osteogenic sarcoma. A preliminary report. CA Cancer J Clin. 1973;23:74-80.
Jaffe N. Recent advances in the chemotherapy of metastatic osteogenic sarcoma. Cancer. 1972;30:1627-1631.
Cortes EP, Holland JF, Wang JJ, et al. Doxorubicin in disseminated osteosarcoma. JAMA. 1972;221:1132-1138.
Bacci G, Gherlinzoni F, Picci P, et al. Adriamycin-methotrexate high dose versus adriamycin-methotrexate moderate dose as adjuvant chemotherapy for osteosarcoma of the extremities: a randomized study. Eur J Cancer Clin Oncol. 1986;22:1337-1345.
Bacci G, Picci P, Ruggieri P, et al. Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities. The Istituto Rizzoli Experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses) and intraarterial cisplatin. Cancer. 1990;65:2539-2553.
Rosen G, Marcove RC, Caparros B, Nirenberg A, Kosloff C, Huvos AG. Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery. Cancer. 1979;43:2163-2177.
Rosen G, Caparros B, Huvos AG, et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982;49:1221-1230.
Ferrari S, Bacci G, Picci P, et al. Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy. Ann Oncol. 1997;8:765-771.
Bacci G, Ferrari S, Bertoni F, et al. 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. J Clin Oncol. 2000;18:4016-4027.
Ferrari S, Mercuri M, Picci P, et al. Nonmetastatic osteosarcoma of the extremity: results of a neoadjuvant chemotherapy protocol (IOR/OS-3) with high-dose methotrexate, intra-arterial or intravenous cisplatin, doxorubicin, and salvage chemotherapy based on histologic tumor response. Tumori. 1999;85:458-464.
Winkler K, Bielack S, Delling G, et al. Effect of intra-arterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86). Cancer. 1990;66:1703-1710.
Bacci G, Ferrari S, Longhi A, et al. Neoadjuvant chemotherapy for high grade osteosarcoma of the extremities: long-term results for patients treated according to the Rizzoli IOR/OS-3b protocol. J Chemother. 2001;13:93-99.
Bacci G, Briccoli A, Ferrari S, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli’s 4th protocol. Eur J Cancer. 2001;37:2030-2039.
Bacci G, Ferrari S, Longhi A, et al. Italian Sarcoma Group/Scandinavian Sarcoma Group. High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: preliminary results of an Italian Sarcoma Group/Scandinavian Sarcoma Group pilot study. J Chemother. 2002;14:198-206.
Ferrari S, Smeland S, Mercuri M, et al. Italian and Scandinavian Sarcoma Groups. 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. 2005;23:8845-8852.
ISG/OS-1 Protocol at: www.controlled-trials.com/ISRCTN21335128.
Ferrari S, Bertoni F, Mercuri M, 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. 2001;12:1145-1150.
Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 2006;106:1154-1161.
Baldini N, Scotlandi K, Barbanti-Bròdano G, et al. Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med. 1995;333:1380-1385.
Baldini N, Scotlandi K, Serra M, et al. P-glycoprotein expression in osteosarcoma: a basis for risk-adapted adjuvant chemotherapy. J Orthop Res. 1999;17:629-632.
Serra M, Scotlandi K, Reverter-Branchat G, 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. 2003;21:536-542.
Gorlick R, Huvos AG, Heller G, et al. Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol. 1999;17:2781-2788.
Schwartz CL, Gorlick R, Teot L, et al. Children’s Oncology Group. Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children’s Oncology Group. J Clin Oncol. 2007;25:2057-2062.
Serra M, Picci P, Ferrari S, Bacci G. Prognostic value of P-glycoprotein in high-grade osteosarcoma. Comment on: J Clin Oncol. 2007;25:2057-2062.
Ferrari S, Bertoni F, Zanella L, et al. Evaluation of P-glycoprotein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high-grade osteosarcoma. Cancer. 2004;100:1936-1942.
Serra M, Pasello M, Manara MC, et al. Can P-glycoprotein status be used to stratify high-grade osteosarcoma patients? Results from the Italian/Scandinavian Sarcoma Group 1 treatment protocol. Int J Oncol. 2006;29:1459-1468.
Ferrari S, Briccoli A, Mercuri M, et al. Postrelapse survival in osteosarcoma of the extremities: prognostic factors for long-term survival. J Clin Oncol. 2003;21:710-715.
Fagioli F, Aglietta M, Tienghi A, et al. High-dose chemotherapy in the treatment of relapsed osteosarcoma: an Italian sarcoma group study. J Clin Oncol. 2002;20:2150-2156.
Bacci G, Forni C, Longhi A, et al. Local recurrence and local control of non-metastatic osteosarcoma of the extremities: a 27-year experience in a single institution. J Surg Oncol. 2007;96:118-123.
Bacci G, Briccoli A, Ferrari S, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli’s 4th protocol. Eur J Cancer. 2001;37:2030–2039.
Ferrari S, Briccoli A, Mercuri M, et al. Late relapse in osteosarcoma. J Pediatr Hematol Oncol. 2006;28:418-422.
Longhi A, Ferrari S, Bacci G, Specchia S. Long-term follow-up of patients with doxorubicin-induced cardiac toxicity after chemotherapy for osteosarcoma. Anticancer Drugs. 2007;18:737-744.
Ferrari S, Pieretti F, Verri E, et al. Prospective evaluation of renal function in pediatric and adult patients treated with high-dose ifosfamide, cisplatin and high-dose methotrexate. Anticancer Drugs. 2005;16:733-738.
Longhi A, Porcu E, Petracchi S, Versari M, Conticini L, Bacci G. Reproductive functions in female patients treated with adjuvant and neoadjuvant chemotherapy for localized osteosarcoma of the extremity. Cancer. 2000;89:1961-1965.
Longhi A, Macchiagodena M, Vitali G, Bacci G. Fertility in male patients treated with neoadjuvant chemotherapy for osteosarcoma. J Pediatr Hematol Oncol. 2003;25:292-296.
Bacci G, Ferrari C, Longhi A, et al. Second malignant neoplasm in patients with osteosarcoma of the extremities treated with adjuvant and neoadjuvant chemotherapy. J Pediatr Hematol Oncol. 2006;28:774-780.
Luciani F, Spada M, De Milito A, et al. Effect of proton pump inhibitor pre-treatment for resistance of solid tumor to cytotoxic drugs. J Natl Cancer Inst. 2004;96:1702-1713.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Ferrari, S. et al. (2009). The Treatment of Nonmetastatic High Grade Osteosarcoma of the Extremity: Review of the Italian Rizzoli Experience. Impact on the Future. In: Jaffe, N., Bruland, O., Bielack, S. (eds) Pediatric and Adolescent Osteosarcoma. Cancer Treatment and Research, vol 152. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-0284-9_14
Download citation
DOI: https://doi.org/10.1007/978-1-4419-0284-9_14
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4419-0283-2
Online ISBN: 978-1-4419-0284-9
eBook Packages: MedicineMedicine (R0)