Skip to main content
SpringerLink
Log in

Intraarterial Chemotherapy for Extremity Osteosarcoma and MFH in Adults

  • Symposium: Selected Papers Presented at the 2007 Meeting of the Musculoskeletal Tumor Society
  • Published:
Clinical Orthopaedics and Related Research

Abstract

The neoadjuvant treatment of osteosarcoma using intravenous agents has resulted in survival rates of 55% to 77% [3, 5, 6, 20, 22, 35]. We designed a neoadjuvant chemotherapy protocol using combined intraarterial and intravenous agents to treat high-grade osteosarcoma and malignant fibrous histiocytoma of bone in an attempt to improve survival. We report the results of treating 53 adults (age 18–77 years) diagnosed with nonmetastatic extremity osteosarcoma or malignant fibrous histiocytoma. Preoperative chemotherapy consisted of intravenous doxorubicin followed by intraarterial cisplatinum administered repetitively every 3 weeks for three to five cycles, depending on tumor response assessed by serial arteriography. Dose and duration of cisplatin were adjusted for tumor size. After resection, good responders (90% or greater necrosis) underwent treatment with the same agents and poor responders were treated with alternative agents for longer duration. Minimum followup was 24 months (mean, 111 months; range, 24–235 months). Estimated Kaplan-Meier survival at 10 years was 82% and event-free survival was 79%. Forty-one patients (77%) had a good histologic response and 92% (49 of 53) underwent limb-sparing procedures. Local recurrence occurred in two patients (4%). These results compared favorably with those reported in the current literature.

Level of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A–C
Fig. 2A–C

Similar content being viewed by others

References

  1. Bacci G, Ferrari S, Bertoni F, Ruggieri P, Picci P, Longhi A, Casadei R, Fabbri N, Forni C, Versari M, Campanacci M. 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.

    PubMed  CAS  Google Scholar 

  2. Bacci G, Ferrari S, Forni C, Mercuri M, Picci P, Bertoni F, Capanna R, Manfrini M, Donati D, Brach Del Prever A, Baldini N. The effect of intra-arterial versus intravenous cisplatinum in the neoadjuvant treatment of osteosarcoma of the limbs: the experience at the Rizzoli Institute. Chir Organi Mov. 1996;81:369–382.

    PubMed  CAS  Google Scholar 

  3. Bacci G, Ferrari S, Longhi A, Forni C, Bertoni F, Fabbri N, Zavatta M, Versari M. 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.

    PubMed  CAS  Google Scholar 

  4. Bacci G, Ferrari S, Mercuri M, Longhi A, Capanna R, Tienghi A, Brach del Prever A, Comandone A, Cesari M, Bernini G, Picci P. Neoadjuvant chemotherapy for extremity osteosarcoma: preliminary results of the Rizzoli’s 4th study. Acta Oncol. 1998;37:41–48.

    Article  PubMed  CAS  Google Scholar 

  5. Bacci G, Forni C, Longhi A, Ferrari S, Mercuri M, Bertoni F, Serra M, Briccoli A, Balladelli A, Picci P. 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.

    Article  PubMed  Google Scholar 

  6. Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy. Fifteen year experience in 789 patients treated at a single institution. Cancer. 2006;106:1154–1161.

    Article  PubMed  Google Scholar 

  7. Benjamin RS, Chawla SP, Carrasco CH, Raymond AK, Murray JA, Armen T, Patel S, Wallace S, Ayala A, Papadopoulos NE, et al. Preoperative chemotherapy for osteosarcoma with intravenous adriamycin and intra-arterial cisplatinum. Ann Oncol. 1992;3(Suppl 2):S3–S6.

    PubMed  Google Scholar 

  8. Bentzen SM, Poulsen HS, Kaae S, Jensen OM, Johansen H, Mouridsen HT, Daugaard S, Arnoldi C. Prognostic factors in osteosarcomas: a progression analysis. Cancer. 1988;62:194–202.

    Article  PubMed  CAS  Google Scholar 

  9. Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jürgens H, Winkler K. 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. 2002;20:776–790.

    Article  PubMed  Google Scholar 

  10. Brosjö O. Surgical procedure and local recurrence in 223 patients treated 1982–1997 according to two osteosarcoma chemotherapy protocols. The Scandinavian Sarcoma Group experience. Acta Orthop Scand. 1999;285(Suppl):58–61.

    Google Scholar 

  11. Carrasco CH, Charnsangavej C, Raymond AK, Richli WR, Wallace S, Chawla SP, Ayala AG, Murray JA, Benjamin RS. Osteosarcoma: angiographic assessment of response to preoperative chemotherapy. Radiology. 1989;170:839–842.

    PubMed  CAS  Google Scholar 

  12. Cores EP, Holland JF, Wang JJ, Sinks LF. Doxorubicin in disseminated osteosarcoma. JAMA. 1972;221:1132–1138.

    Article  PubMed  CAS  Google Scholar 

  13. Cullen JW, Jamroz BA, Stevens SL, Madsen W, Hinshaw I, Wilkins RM, Cullen P, Camozzi AB, Fink K, Peck SD, Kelly CM. The value of serial arteriography in osteosarcoma: delivery of chemotherapy, determination of therapy duration and prediction of necrosis. J Vasc Interv Radiol. 2005;16:1107–1119.

    PubMed  Google Scholar 

  14. Dahlin DC, Coventry MB. Osteogenic sarcoma. A study of six hundred cases. J Bone Joint Surg Am. 1967;49:101–110.

    PubMed  CAS  Google Scholar 

  15. Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteosarcoma: a critical review. J Clin Oncol. 1994;12:423–431.

    PubMed  CAS  Google Scholar 

  16. Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard D. A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res. 1993;286:241–246.

    PubMed  Google Scholar 

  17. Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. 1980;153:106–120.

    PubMed  Google Scholar 

  18. Ettinger LJ, Douglass HO, Higby DJ. Adjuvant Adriamycin and Cis-diamminedichloroplatinum (cis-platinum) in primary osteosarcoma. Cancer. 1981;47:248–254.

    Article  PubMed  CAS  Google Scholar 

  19. Ferrari S, Bacci G, Picci P, Mercuri M, Briccoli A, Pinto D, Gasbarrini A, Tienghi A, Brach del Prever A. 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.

    Article  PubMed  CAS  Google Scholar 

  20. Ferrari S, Bertoni F, Mercuri M, Picci P, Giacomini S, Longhi A, Bacci G. 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.

    Article  PubMed  CAS  Google Scholar 

  21. Ferrari S, Mercuri M, Picci P, Bertoni F, Brach del Prever A, Tienghi A, Mancini A, Longhi A, Rimondini S, Donati D, Manfrini M, Ruggieri P, Biagini R, Bacci G. 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.

    PubMed  CAS  Google Scholar 

  22. Ferrari S, Smeland S, Mercuri M, Bertoni F, Longhi A, Ruggieri P, Alvegard TA, Picci P, Capanna R, Bernini G, Müller C, Tienghi A, Wiebe T, Comandone A, Böhling T, Del Prever AB, Brosjö O, Bacci G, Saeter G. Italian and Scandinavian Sarcoma Groups. Neoadjuvant chemotherapy with high-dose ifosfamide, high-dose methotrexate, Cisplatin, and doxorubicin for patients with localized ostesarcoma of the extremity. A joint study by the Italian and Scandinavian Sarcoma Groups. J Clin Oncol. 2005;23:8845–8852.

    Article  PubMed  Google Scholar 

  23. Franzius C, Scluk J, Brinkschmidt C, Jurgens H, Schober O. Evaluation of chemotherapy response in primary bone tumors with F-18 FDG positron emission tomography compared with histologically assessed tumor necrosis. Clin Nucl Med. 2000;25:874–881.

    Article  PubMed  CAS  Google Scholar 

  24. Fuchs N, Bielack SS, Epler D, Bieling P, Delling G, Körholz D, Graf N, Heise U, Jürgens H, Kotz R, Salzer-Kuntschik M, Weinel P, Werner M, Winkler K. 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. 1998;9:893–899.

    Article  PubMed  CAS  Google Scholar 

  25. Honegger HP, Cserhati MD, Exner GU, von Hochstetter A, Groscurth P. Zürich experience with preoperative, high dose methotrexate-containing chemotherapy in patients with extremity osteosarcomas (OSA). Ann Oncol. 1991;2:489–494.

    PubMed  CAS  Google Scholar 

  26. Huvos AG, Rosen G, Marcove RC. Primary osteogenic sarcoma: pathologic aspects in 10 patients after treatment with chemotherapy, en bloc resection, and prosthetic bone replacement. Arch Pathol Lab Med. 1977;101:14–18.

    PubMed  CAS  Google Scholar 

  27. Jaffe N, Knapp J, Chuang VP, Wallace S, Ayala A, Murray J, Cangir A, Wang A, Benjamin RS. Osteosarcoma. Intra-arterial treatment of the primary tumor with cis-diamminedichloroplatinum II (CDP); angiographic, pathologic, and pharmacologic studies. Cancer. 1983;51:402–407.

    Article  PubMed  CAS  Google Scholar 

  28. Jaffe N, Raymond AK, Ayala A, Carrasco CH, Wallace S, Robertson R, Griffiths M, Wang YM. Effect of cumulative courses of intra-arterial cis-diamminedichloroplatinum II on the primary tumor in osteosarcoma. Cancer. 1989;63:63–67.

    Article  PubMed  CAS  Google Scholar 

  29. Jaffe N, Robertson R, Ayala A, Wallace S, Chuang V, Anzai T, Cangir A, Wang YM, Chen T. Comparison of cis-diamminedichloroplatinum II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma. J Clin Oncol. 1985;3:1101–1104.

    PubMed  CAS  Google Scholar 

  30. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–481.

    Article  Google Scholar 

  31. Kawai A, Sugihara S, Kunisada T, Uchida Y, Inoue H. Imaging assessment of the response of bone tumors to preoperative chemotherapy. Clin Orthop Relat Res. 1997;337:216–225.

    Article  PubMed  Google Scholar 

  32. Knop J, Delling G, Heise U, Wingler K. Scintigraphic evaluation of tumor regression during preoperative chemotherapy of osteosarcoma. Correlation of 99 mTc-methylene diphosphonate parametric imaging with surgical histopathology. Skeletal Radiol. 1990;19:165–172.

    Article  PubMed  CAS  Google Scholar 

  33. Kunisada T, Ozaki T, Kawai A. Imaging assessment of the responses of osteosarcoma patients to preoperative chemotherapy: angiography compared with thallium-201 scintigraphy. Cancer. 1999;86:949–956.

    Article  PubMed  CAS  Google Scholar 

  34. Lang P, Grampp S, Vahlensieck M. Primary bone tumors: value of MR angiography for preoperative planning and monitoring response to chemotherapy. AJR Am J Roentgenol. 1995;165:135–142.

    PubMed  CAS  Google Scholar 

  35. Lewis IJ, Nooij MA, Whelan J, Sydes MR, Grimer R, Hogendoorn PC, Memon MA, Weeden S, Uscinska BM, van Glabbeke M, Kirkpatrick A, Hauben EI, Craft AW, Taminiau AH. MRC BO06 and EORTC 80931 collaborators; European Osteosarcoma Intergroup. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy. A randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst. 2007;99:112–128.

    Article  PubMed  CAS  Google Scholar 

  36. Mankin HJ, Hornicek FJ, Rosenberg AE, Harmon DC, Gebhardt MC. Survival data for 648 patients with osteosarcoma treated at one institution. Clin Orthop Relat Res. 2004;429:286–291.

    Article  PubMed  Google Scholar 

  37. Mavligit GM, Benjamin RS, Patt YZ. Intra-arterial cis-platinum for patients with inoperable skeletal tumors. Cancer. 1981;48:1–4.

    Article  PubMed  CAS  Google Scholar 

  38. Mercuri M, Capanna R, Manfrini M, Bacci G, Picci P, Ruggieri P, Ferruzzi A, Ferraro A, Donati D, Biagini R, de Maio M, Cazzola A, Campanacci M. The management of malignant bone tumors in children and adolescents. Clin Orthop Relat Res. 1991;264:156–168.

    PubMed  Google Scholar 

  39. Mirra JJ, Picci P, Gold RH. Bone Tumors: Clinical, Radiologic, and Pathologic Correlations. Vol 1. Philadelphia, PA: Lea & Febiger; 1989:255–344, 766–794.

  40. Nair N, Ali G, Green AA. Response of osteosarcoma to chemotherapy. Evaluation with F-18 FDG-PET scans. Clin Positron Imaging. 2000;3:79–83.

    Article  PubMed  Google Scholar 

  41. Nitschke R, Starling KA, Vats T, Bryan H. Cis-diamminedichloroplatinum (NSC 119875) in childhood malignancies: A Southwest Oncology Group Study. Med Pediatr Oncol. 1978;4:127–132.

    Article  PubMed  CAS  Google Scholar 

  42. Provisor AJ, Ettinger LJ, Nachman JB, Krailo MD, Makley JT, Yunis EJ, Huvos AG, Betcher DL, Baum ES, Kisker CT, Miser JS. Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy. A report from the Children’s Cancer Group. J Clin Oncol. 1997;15:76–84.

    PubMed  CAS  Google Scholar 

  43. Quintana J, Beresi V, DelPozo H, Latorre JJ, Henriquez A, Chamas N, Diaz V, Geldres V, Sepulveda L, Macho L, Dolz G. Intra-arterial cisplatin given prior to surgery in osteosarcoma: grade of necrosis and size of tumor as major prognostic factors. Am J Pediatr Hematol Oncol. 1991;13:269–273.

    Article  PubMed  CAS  Google Scholar 

  44. Rha SY, Chung HC, Gong SJ, Shim KY, Ahn JB, Yang WI, Shin KH, Yoo NC, Kim JH, Roh JK, Lee CI, Kim BS. Combined preoperative chemotherapy with intra-arterial Cisplatin and continuous intravenous Adriamycin for high grade osteosarcoma. Oncol Rep. 1999;6:631–637.

    PubMed  CAS  Google Scholar 

  45. Rosen G, Caparros B, Nirenberg A. The successful management of metastatic osteogenic sarcoma: A model for the treatment of primary osteogenic sarcoma. In: van Oosterom AT, Muggia FM, Cleton FJ, eds. Therapeutic Progress in Ovarian Cancer, Testicular Cancer and the Sarcomas. Boston, MA: Leiden University Press; 1979:349–366.

  46. 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;43:2163–2192.

    Article  PubMed  CAS  Google Scholar 

  47. Schulte M, Brecht-Krauss D, Werner M. Evaluation of neoadjuvant therapy response of osteogenic sarcoma using FDG-PET. J Nucl Med. 1999;40:1637–1643.

    PubMed  CAS  Google Scholar 

  48. Stewart DJ, Benjamin RS, Zimmerman S, Caprioli RM, Wallace S, Chuang V, Calvo D 3rd, Samuels M, Bonura J, Loo TL. Clinical pharmacology of intra-arterial cis-diamminedichloroplatinum (II). Cancer Res. 1983;43:917–920.

    PubMed  CAS  Google Scholar 

  49. Uchida A, Myoui A, Araki N, Yoshikawa H, Shinto Y, Ueda T. Neoadjuvant chemotherapy for pediatric osteosarcoma patients. Cancer. 1997;79:411–415.

    Article  PubMed  CAS  Google Scholar 

  50. Wilkins RM, Cullen JW, Camozzi AB, Jamroz BA, Odom L. Improved survival in primary nonmetastatic pediatric osteosarcoma of the extremity. Clin Orthop Relat Res. 2005;438:128–136.

    Article  PubMed  CAS  Google Scholar 

  51. Wilkins RM, Cullen JW, Odom L, Jamroz BA, Cullen PM, Fink K, Peck SD, Stevens SL, Kelly CM, Camozzi AB. Superior survival in treatment of primary nonmetastatic pediatric osteosarcoma of the extremity. Ann Surg Oncol. 2003;10:498–507.

    Article  PubMed  Google Scholar 

  52. Winkler K, Bielack S, Delling G, Salzer-Kuntschik M, Kotz R, Greenshaw C, Jürgens H, Ritter J, Kusnierz-Glaz C, Erttmann R, Gadicke G, Graf N, Ladenstein R, Leyvraz S, Mertens R, Weinel P. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Lorrie Odom, Rocky Mountain Pediatric Hematology Oncology; Dr. Brandt Jamroz, interventional radiologist; Dr. Sanford Peck, pathologist; and the departments of audiology, rehabilitation, and cardiology at Presbyterian/St Luke’s Medical Center. We are especially grateful to Dr. John Cullen for his help in designing the protocol and his continued commitment toward research in pediatric oncology.

Author information

Authors and Affiliations

  1. The Denver Clinic for Extremities at Risk, Presbyterian/St Luke’s Medical Center, 1601 E. 19th Avenue, Suite 3250, Denver, CO, 80218, USA

    Ronald R. Hugate MD, Ross M. Wilkins MD, Cynthia M. Kelly MD, Walt Madsen MD, Ioana Hinshaw MD & Anne B. Camozzi BA

Authors
  1. Ronald R. Hugate MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ross M. Wilkins MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cynthia M. Kelly MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Walt Madsen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ioana Hinshaw MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anne B. Camozzi BA
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald R. Hugate MD.

Additional information

Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

About this article

Cite this article

Hugate, R.R., Wilkins, R.M., Kelly, C.M. et al. Intraarterial Chemotherapy for Extremity Osteosarcoma and MFH in Adults. Clin Orthop Relat Res 466, 1292–1301 (2008). https://doi.org/10.1007/s11999-008-0252-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11999-008-0252-1

Keywords

Search

Navigation