Skip to main content
SpringerLink
Log in

Management of osteosarcoma

  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Improving cure rates for osteosarcoma continues to be a major challenge. The clinical management of individual patients is exacting and requires a skilled, experienced team including a surgeon, pathologist, oncologist, and radiologist, with support from specialist nurses and rehabilitation teams. Outcomes from treatment have improved little in 20 years and remain disappointing. Chemotherapy for osteosarcoma is among the most grueling of any given for solid tumors, and treatment of the primary tumor is associated with permanent disability of some degree in a significant proportion of patients. New systemic treatments remain beyond the horizon. In recognition of these difficulties, an international cooperation has begun with the opening of a randomized trial, European and American Osteosarcoma (EURAMOS) 1, in Europe and the United States. This study heralds a new era of clinical investigation into osteosarcoma, with the promise of valuable biologic insights and rapid evaluation of investigational strategies. Osteosarcoma should always be treated under the guidance of a specialist team, and we recommend that whenever possible, patients be offered entry into EURAMOS 1 or other well-designed clinical trials.

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

Similar content being viewed by others

References and Recommended Reading

  1. Virtanen A, Pukkala E, Auvinen A:Incidence of bone and soft tissue sarcoma after radiotherapy:a cohort study of 295,712 Finnish cancer patients. Int J Cancer 2006, 118:1017–1021. An informative report on potential etiologic factors for osteosarcoma.

    Article  PubMed  CAS  Google Scholar 

  2. Merletti F, Richiardi L, Bertoni F et al.:Occupational factors and risk of adult bone sarcomas:a multicentric case-control study in Europe. Int J Cancer 2006, 118:721–727.

    Article  PubMed  CAS  Google Scholar 

  3. Friedman MA, Carter SK:The therapy of osteogenic sarcoma:current status and thoughts for the future. J Surg Oncol 1972, 4:482–510.

    Article  PubMed  CAS  Google Scholar 

  4. Cortes EP, Holland JF, Wang JJ, et al.:Amputation and adriamycin in primary osteosarcoma. N Engl J Med 1974, 291:998–1000.

    Article  PubMed  CAS  Google Scholar 

  5. Jaffe N, Frei EI, Traggis D:Adjuvant methotrexate citrovorum factor treatment of osteogenic sarcoma. N Engl J Med 1974, 291:996–997.

    Article  Google Scholar 

  6. Rosen G, Tan C, Sanmaneechai A, et al.:The rationale for multiple drug chemotherapy in the treatment of osteogenic sarcoma. Cancer 1975, 35:936–945.

    Article  PubMed  CAS  Google Scholar 

  7. Rosen G, Murphy ML, Huvos AG, et al.:Chemotherapy, en bloc resection, and prosthetic bone replacement in the treatment of osteogenic sarcoma. Cancer 1976, 37:1–11.

    Article  PubMed  CAS  Google Scholar 

  8. Rosen G, Marcove RC, Caparros B, et al.:Primary osteogenic sarcoma:the rationale for preoperative chemotherapy and delayed surgery. Cancer 1979, 43:2163–2177.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. Meyers PA, Heller G, Healey J, et al.:Chemotherapy for nonmetastatic osteogenic sarcoma:the Memorial Sloan-Kettering experience. J Clin Oncol 1992, 10:5–15.

    PubMed  CAS  Google Scholar 

  11. Saeter G, Alvegard TA, Elomaa I, et al.:Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effects of preoperative chemotherapy with single-agent high-dose methotrexate:a Scandinavian Sarcoma Group study. J Clin Oncol 1991, 9:1766–1775.

    PubMed  CAS  Google Scholar 

  12. Provisor AJ, Ettinger LJ, Nachman JB, et al.: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 

  13. Winkler K, Beron G, Delling G, et al.:Neoadjuvant chemotherapy of osteosarcoma:results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol 1988, 6:329–337.

    PubMed  CAS  Google Scholar 

  14. 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 1998, 9:893–899.

    Article  PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. Bacci G, Picci P, Ferrari S, et al.:Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin. Cancer 1993, 72:3227–3238.

    Article  PubMed  CAS  Google Scholar 

  17. Bramwell VH, Burgers M, Sneath R, et al.:A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults:the first study of the European Osteosarcoma Intergroup. J Clin Oncol 1992, 10:1579–1591.

    PubMed  CAS  Google Scholar 

  18. Souhami RL, Craft AW, Van der Eijken JW, et al.:Randomised trial of two regimens of chemotherapy in operable osteosarcoma:a study of the European Osteosarcoma Intergroup. Lancet 1997, 350:911–917. A large multi-international randomized study that demonstrated no survival advantage for a multiagent T10-based chemotherapy regimen over a combination of doxorubicin and cisplatin alone.

    Article  PubMed  CAS  Google Scholar 

  19. Lewis IJ, Nooij M: Chemotherapy at standard or increased dose intensity in patients with operable osteosarcoma of the extremity; a randomised controlled trial conducted by the European Osteosarcoma Intergroup (ISRCTN 86294690). Abstract presented at the Annual Meeting of the American Society of Clinical Oncology. Chicago, IL; May 31–June 3, 2003. A large randomized trial comparing a dose-intense schedule of doxorubicin and cisplatin with a standard schedule. The final results will be published in full imminently.

  20. Meyers PA, Schwartz CL, Krailo M, et al.:Osteosarcoma:a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol 2005, 23:2004–2011. The largest randomized trial of chemotherapy in osteosarcoma. The results have caused debate as an absolute advantage for MTP-PE was not clearly demonstrated.

    Article  CAS  Google Scholar 

  21. Fidler IJ, Sone S, Fogler WE, Barnes ZL:Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide. Proc Natl Acad Sci U S A 1981, 78:1680–1684.

    Article  PubMed  CAS  Google Scholar 

  22. MacEwen EG, Kurzman ID, Rosenthal RC, et al.:Therapy for osteosarcoma in dogs with intravenous injection of liposome-encapsulated muramyl tripeptide. J Natl Cancer Inst 1989, 81:935–938.

    Article  PubMed  CAS  Google Scholar 

  23. Kleinerman ES, Jia SF, Griffin J, et al.:Phase II study of liposomal muramyl tripeptide in osteosarcoma:the cytokine cascade and monocyte activation following administration. J Clin Oncol 1992, 10:1310–1316.

    PubMed  CAS  Google Scholar 

  24. Kleinerman ES, Meyers PA, Raymond AK, et al.:Combination therapy with ifosfamide and liposomeencapsulated muramyl tripeptide:tolerability, toxicity, and immune stimulation. J Immunother Emphasis Tumor Immunol 1995, 17:181–193.

    PubMed  CAS  Google Scholar 

  25. Kleinerman ES:Biologic therapy for osteosarcoma using liposome-encapsulated muramyl tripeptide. Hematol Clin N Amer 1995, 9:927–938.

    CAS  Google Scholar 

  26. Romet-Lemonne JL, Mills B, Fridman WH, Munsell M:Prospectively planned analysis of data from a phase III study of liposomal muramyltripeptide phosphatidylethanolamine in the treatment of osteosarcoma. J Clin Oncol 2005, 23:6437–6438.

    Article  PubMed  Google Scholar 

  27. Huvos AG, Rosen G, Marcove RC:Primary osteogenic sarcoma:pathologic aspects in 20 patients after treatment with chemotherapy, en bloc resection, and prosthetic bone replacement. Arch Pathol Lab Med 1977, 101:14–18.

    PubMed  CAS  Google Scholar 

  28. 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 2003, 21:1574–1580. A small but important study investigating the timing of surgery for osteosarcoma. No advantage for neoadjuvant treatment was seen, but the amputation rate was unacceptably high by current standards.

    Article  PubMed  CAS  Google Scholar 

  29. Bacci G, Ferrari S, Longhi A, et al.:Preoperative therapy versus immediate surgery in nonmetastatic osteosarcoma. J Clin Oncol 2003, 21:4662–4663.

    Article  PubMed  CAS  Google Scholar 

  30. Bacci G, Picci P, Ferrari S, et al.:Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities:the recent experience at the Rizzoli Institute. Cancer Treat Res 1993, 62:299–308.

    PubMed  CAS  Google Scholar 

  31. 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.

    PubMed  CAS  Google Scholar 

  32. Meyers PA, Gorlick R, Heller G, et al.:Intensification of preoperative chemotherapy for osteogenic sarcoma:results of the Memorial Sloan-Kettering (T12) protocol. J Clin Oncol 1998, 16:2452–2458.

    PubMed  CAS  Google Scholar 

  33. Ferrari S, Smeland S, Mercuri M, 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 2005, 23:8845–8852. Very intensive chemotherapy proved toxic and not obviously superior to standard schedules in this prospective but nonrandomized study.

    Article  PubMed  Google Scholar 

  34. The European and American Osteosarcoma Study Group: The EURAMOS I trial. Available at:http://www.euramos.org. Accessed August 9, 2006. Updated information is available about a major international trial between four osteosarcoma study groups.

  35. Einhorn S, Strander H:Is interferon tissue specific? Effect of human leukocyte and fibroblast interferons on the growth of lymphoblastoid and osteosarcoma cell lines. J Gen Virol 1977, 35:573–577.

    Article  PubMed  CAS  Google Scholar 

  36. Hofmann V, Groscurth P, Morant R, et al.:Effects of leukocyte interferon (E. coli) on human bone sarcoma growth in vitro and in the nude mouse. Eur J Cancer Clin Oncol 1985, 21:859–863.

    Article  PubMed  CAS  Google Scholar 

  37. Brosjo O:Osteosarcoma and interferon. Studies of human xenografts in the nude mouse. Acta Orthop Scand Suppl 1989, 229:1–36.

    PubMed  CAS  Google Scholar 

  38. Adamson A, Aparisi T, Brostrom LA:Interferon treatment of osteosarcoma. Pontificiae Acad Scient Scripta Varia 1979, 43:383–406.

    Google Scholar 

  39. Strander H, Bauer HC, Brosjo O, et al.:Long-term adjuvant interferon treatment of human osteosarcoma. A pilot study. Acta Oncol 1995, 34:877–880.

    PubMed  CAS  Google Scholar 

  40. Muller CR, Smeland S, Bauer HC, et al.:Interferonalpha as the only adjuvant treatment in high-grade osteosarcoma:long term results of the Karolinska Hospital series. Acta Oncol 2005, 44:475–480. Updated results of the most extensive clinical experience of interferon in osteosarcoma.

    Article  PubMed  CAS  Google Scholar 

  41. Manara MC, Serra M, Benini S, et al.:Effectiveness of type I interferons in the treatment of multidrug resistant osteosarcoma cells. Int J Oncol 2004, 24:365–372.

    PubMed  CAS  Google Scholar 

  42. Takaoka A, Hayakawa S, Yanai H, et al.:Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 2003, 424:516–523.

    Article  PubMed  CAS  Google Scholar 

  43. Stein U, Walther W, Shoemaker RH:Modulation of mdr1 expression by cytokines in human colon carcinoma cells:an approach for reversal of multidrug resistance. Br J Cancer 1996, 74:1384–1391.

    PubMed  CAS  Google Scholar 

  44. Pritchard-Jones K, Spendlove I, Wilton C, et al.:Immune responses to the 105AD7 human antiidiotypic vaccine after intensive chemotherapy, for osteosarcoma. Br J Cancer 2005, 92:1358–1365.

    Article  PubMed  CAS  Google Scholar 

  45. Anderson PM, Wiseman GA, Dispenzieri A, et al.:High-dose samarium-153 ethylene diamine tetramethylene phosphonate:low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol 2002, 20:189–196.

    Article  PubMed  CAS  Google Scholar 

  46. Franzius C, Schuck A, Bielack SS:High-dose samarium-153 ethylene diamine tetramethylene phosphonate:low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol 2002, 20:1953–1954.

    PubMed  Google Scholar 

  47. 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 2002, 20:776–790. A very valuable analysis of prognostic factors from a large database reporting on multicenter outcomes.

    Article  Google Scholar 

  48. Jaffe N, Carrasco H, Raymond K, et al.:Can cure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery? Cancer 2002, 95:2202–2210.

    Article  PubMed  Google Scholar 

  49. Machak GN, Tkachev SI, Solovyev YN, et al.:Neoadjuvant chemotherapy and local radiotherapy for high-grade osteosarcoma of the extremities. Mayo Clin Proc 2003, 78:147–155.

    Article  PubMed  Google Scholar 

  50. DeLaney TF, Park L, Goldberg SI, et al.:Radiotherapy for local control of osteosarcoma. Int J Radiat Oncol Biol Phys 2005, 61:492–498.

    Article  PubMed  Google Scholar 

  51. Wu F, Wang ZB, Chen WZ, et al.:Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China:an overview. Ultrason Sonochem 2004, 11:149–154.

    Article  PubMed  CAS  Google Scholar 

  52. Smith RB, Apostolakis LW, Karnell LH, et al.:National Cancer Data Base report on osteosarcoma of the head and neck. Cancer 2003, 98:1670–1680. A large series of craniofacial osteosarcoma that details valuable prognostic factors.

    Article  PubMed  Google Scholar 

  53. Strauss SJ, McTiernan A, Whelan JS:Late relapse of osteosarcoma:implications for follow-up and screening. Pediatr Blood Cancer 2004, 43:692–697.

    Article  PubMed  Google Scholar 

  54. Chou AJ, Merola PR, Wexler LH, et al.:Treatment of osteosarcoma at first recurrence after contemporary therapy:the Memorial Sloan-Kettering Cancer Center experience. Cancer 2005, 104:2214–2221.

    Article  PubMed  Google Scholar 

  55. Bacci G, Briccoli A, Longhi A, et al.:Treatment and outcome of recurrent osteosarcoma:experience at Rizzoli in 235 patients initially treated with neoadjuvant chemotherapy. Acta Oncol 2005, 44:748–755.

    Article  PubMed  CAS  Google Scholar 

  56. Kempf-Bielack B, Bielack SS, Jurgens H, et al.:Osteosarcoma relapse after combined modality therapy:an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol 2005, 23:559–568. Important series detailing outcomes after relapse following optimal first-line therapy.

    Article  PubMed  Google Scholar 

  57. Hauben EI, Bielack S, Grimer R, et al.:Clinico-histologic parameters of osteosarcoma patients with late relapse. Eur J Cancer 2006, 42:460–466.

    Article  PubMed  CAS  Google Scholar 

  58. Widemann BC, Balis FM, Kempf-Bielack B, et al.:Highdose methotrexate-induced nephrotoxicity in patients with osteosarcoma. Cancer 2004, 100:2222–2232.

    Article  PubMed  CAS  Google Scholar 

  59. Patel SR, Papadopoulos NE, Plager C, et al.:Phase II study of paclitaxel in patients with previously treated osteosarcoma and its variants. Cancer 1996, 78:741–744.

    Article  PubMed  CAS  Google Scholar 

  60. McTiernan A, Whelan J:A phase II study of docetaxel for the treatment of recurrent osteosarcoma. Sarcoma 2004, 8:71–76.

    CAS  PubMed  Google Scholar 

  61. Laverdiere C, Kolb EA, Supko JG, et al.:Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma. Cancer 2003, 98:832–840.

    Article  PubMed  CAS  Google Scholar 

  62. Winkler K, Baron G, Kotz R, et al.:Neoadjuvant chemotherapy for osteogenic sarcoma:results of a cooperative German/Austrian study. J Clin Oncol 1984, 2:617–624.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, University College Hospital, 250 Euston Road, NW1 2PG, London, UK

    Jeremy Whelan MD

Authors
  1. Jeremy Whelan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Beatrice Seddon PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martha Perisoglou MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Whelan, J., Seddon, B. & Perisoglou, M. Management of osteosarcoma. Curr. Treat. Options in Oncol. 7, 444–455 (2006). https://doi.org/10.1007/s11864-006-0020-y

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-006-0020-y

Keywords

Search

Navigation