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Solid Tumours

Poor prognosis osteosarcoma: new therapeutic approach

Bone Marrow Transplantation volume 41, pages S131–S134 (2008)Cite this article

Abstract

Over the past 30 years, a significant improvement in the prognosis of localized osteosarcoma of the extremities has been observed. Despite these results, approximately 30–40% of patients will relapse, mostly within the first 3 years from diagnosis. The prognosis of patients with recurrent disease or metastases at diagnosis is poor. To improve the survival in this patient population, several attempts have been made. An increased dose intensity of chemotherapy induces short lasting remission but does not increase the survival. In the era of targeted therapy, few drugs have been tested with dismal results. The use of biological agents endowed with immunomodulant activity (that is IL-2) or reduced-intensity allogeneic hemopoietic SCT has produced intriguing results that need further confirmation. In this context, an ongoing study explores the antitumor activity of specific T-cytotoxic lymphocytes.

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References

  1. Campanacci M . Bone Tumors, 2nd edn. Lippincott-Verlag: Bologna, Italy, 1999, pp 1418–1468.

    Book  Google Scholar 

  2. Bacci G, Ferrari S, Bertoni F, Ruggieri P, Picci P, Longhi A 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.

    Article  CAS  Google Scholar 

  3. Bielack S, Kempf-Bielack B, Schwenzer D, Birkfellner T, Delling G, Ewerbeck V et al. Neoadjuvant therapy for localized osteosarcoma of extremities. Results from the Cooperative Osteosarcoma Study Group COSS of 925 patients. Klin Padiatr 1999; 211: 260–270.

    Article  CAS  Google Scholar 

  4. Ferrari S, Briccoli A, Mercuri M, Bertoni F, Picci P, Tienghi A et al. Postrelapse survival in osteosarcoma of the extremities: prognostic factors for long-term survival. J Clin Oncol 2003; 21: 710–715.

    Article  Google Scholar 

  5. Voute PA, Souhami RL, Nooij M, Somers R, Cortes-Funes H, van der Eijken JW et al. A phase II study of cisplatin, ifosfamide and doxorubicin in operable primary, axial skeletal and metastatic osteosarcoma. European Osteosarcoma Intergroup (EOI). Ann Oncol 1999; 10: 1211–1218.

    Article  CAS  Google Scholar 

  6. Harris MB, Gieser P, Goorin AM, Ayala A, Shochat SJ, Ferguson WS et al. Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study. J Clin Oncol 1998; 16: 3641–3648.

    Article  CAS  Google Scholar 

  7. Longhi A, Fabbri N, Donati D, Capanna R, Briccoli A, Biagini R et al. Neoadjuvant chemotherapy for patients with synchronous multifocal osteosarcoma: results in eleven cases. J Chemother 2001; 13: 324–330.

    Article  CAS  Google Scholar 

  8. Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K 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.

    Article  Google Scholar 

  9. Bacci G, Ferrari S, Longhi A, Picci P, Mercuri M, Alvegard TA et al. 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.

    Article  CAS  Google Scholar 

  10. Fagioli F, Aglietta M, Tienghi A, Ferrari S, Brach del Prever A, Vassallo E et al. High-dose chemotherapy in the treatment of relapsed osteosarcoma: an Italian Sarcoma Group Study. J Clin Oncol 2002; 20: 2150–2156.

    Article  CAS  Google Scholar 

  11. Sauerbrey A, Bielack S, Kempf-Bielack B, Zoubek A, Paulussen M, Zintl F . High-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (ASCT) as salvage therapy for relapsed osteosarcoma. Bone Marrow Transplant 2001; 27: 933–937.

    Article  CAS  Google Scholar 

  12. Franzius C, Bielack S, Sciuk J, Vollet B, Jurgens H, Schober O . High-activity samarium-153-EDTMP therapy in unresectable osteosarcoma. Nuklearmedizin 1999; 38: 337–340.

    Article  CAS  Google Scholar 

  13. Anderson PM, Wiseman GA, Dispenzieri A, Arndt CA, Hartmann LC, Smithson WA 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  CAS  Google Scholar 

  14. Luksch R, Perotti D, Cefalo G, Gambacorti Passerini C, Massimino M, Spreafico F et al. Immunomodulation in a treatment program including pre- and post-operative interleukin-2 and chemotherapy for childhood osteosarcoma. Tumori 2003; 89: 263–268.

    Article  CAS  Google Scholar 

  15. Resnick IB, Shapira MY, Slavin S . Nonmyeloablative stem cell transplantation and cell therapy for malignant and non-malignant diseases. Transpl Immunol 2005; 14: 207–219.

    Article  CAS  Google Scholar 

  16. Fagioli F, Ricchiardi A, Carnevale-Schianca F . Nonmyeloablative allogeneic hemopoietic stem cell transplants. Haematologica 2002; 87: 13–19.

    PubMed  Google Scholar 

  17. Fagioli F, Berger M, Brach del Prever A, Lioji S, Aglietta M, Ferrari S et al. Regression of metastatic osteosarcoma following non-myeloablative stem cell transplantation. A case report. Haematologica 2003; 88: ECR16.

    PubMed  Google Scholar 

  18. Carnevale-Schianca F, Cignetti A, Capaldi A, Vitaggio K, Vallario A, Ricchiardi A et al. Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD. Blood 2006; 107: 3795–3803.

    Article  CAS  Google Scholar 

  19. Goi K, Sugita K, Tezuka T, Sato H, Uno K, Inukai T et al. A successful case of allogeneic bone marrow transplantation for osteosarcoma with multiple metastases of lung and bone. Bone Marrow Transplant 2006; 37: 115–116.

    Article  CAS  Google Scholar 

  20. Kounami S, Nakayama K, Yoshiyama M, Yoshimasu T, Aoyagi N, Yoshikawa N . Non-myeloablative allogenic peripheral blood stem cell transplantation in a patient with refractory osteosarcoma. Pediatr Transplant 2005; 9: 342–345.

    Article  Google Scholar 

  21. Seibel N, Krailo M, Sato J . Phase II window of topotecan in newly diagnosed metastatic osteosarcoma CCG 7943. Proceedings of the ASCO, May 12–15, 2001, San Francisco, CA, (abstract 1509).

  22. Okuno S, Ryan LM, Edmonson JH, Priebat DA, Blum RH . Phase II trial of gemcitabine in patients with advanced sarcomas (E1797): a trial of the Eastern Cooperative Oncology Group. Cancer 2003; 97: 1969–1973.

    Article  CAS  Google Scholar 

  23. Leu KM, Ostruszka LJ, Shewach D, Zalupski M, Sondak V, Biermann JS et al. Laboratory and clinical evidence of synergistic cytotoxicity of sequential treatment with gemcitabine followed by docetaxel in the treatment of sarcoma. J Clin Oncol 2004; 22: 1706–1712.

    Article  CAS  Google Scholar 

  24. Laverdiere C, Kolb EA, Supko JG, Gorlick R, Meyers PA, Maki RG et al. Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma. Cancer 2003; 98: 832–840.

    Article  CAS  Google Scholar 

  25. Muller CR, Smeland S, Bauer HC, Saeter G, Strander H . Interferon-alpha as the only adjuvant treatment in high-grade osteosarcoma: long term results of the Karolinska Hospital series. Acta Oncol 2005; 44: 475–480.

    Article  Google Scholar 

  26. Hoffman TK, Muller-Berghaus J, Ferris RJ, Johnson JT, Storkus WJ, Whiteside TL . Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck. Clin Cancer Res 2002; 8: 1787–1793.

    Google Scholar 

  27. Della Bella S, Gennaro M, Vaccari M, Ferraris C, Nicola S, Riva A et al. Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 2003; 89: 1463–1472.

    Article  CAS  Google Scholar 

  28. Gabrilovich D . Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 2004; 4: 941–952.

    Article  CAS  Google Scholar 

  29. Bollard CM, Savoldo B, Rooney CM, Heslop HE . Adoptive T-cell therapy for EBV-associated post-transplant lymphoproliferative disease. Acta Haematol 2003; 110: 139.

    Article  Google Scholar 

  30. Pardoll D . T-cells take aim at cancer. Proc Natl Acad Sci USA 2002; 99: 15840.

    Article  CAS  Google Scholar 

  31. Montagna D, Schiavo R, Gibelli N, Pedrazzoli P, Tonelli R, Pagani S et al. Ex-vivo generation and expansion of anti-tumor cytotoxic T-cell lines derived from patients or their HLA-identical sibling. Int J Cancer 2004; 110: 76–86.

    Article  CAS  Google Scholar 

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Acknowledgements

This study has been partially supported by the Gigi Ghirotti Association and by Compagnia di S Paolo, Torino, Italy.

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Authors and Affiliations

  1. Stem Cell Transplantation and Cellular Therapy Unit, Regina Margherita Children's Hospital, Turin, Italy

    F Fagioli, E Biasin, O M Mereuta, M Muraro & E Madon

  2. Department of Pediatric Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori di Milano, Milan, Italy

    R Luksch

  3. Division of Chemotherapy, Istituti Ortopedici Rizzoli, University of Bologna, Bologna, Italy

    S Ferrari

  4. Department of Clinical Oncology, IRCC, University of Turin, Turin, Italy

    M Aglietta

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  1. F Fagioli
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  6. S Ferrari
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Correspondence to F Fagioli.

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None of the authors declared any financial interests.

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Fagioli, F., Biasin, E., Mereuta, O. et al. Poor prognosis osteosarcoma: new therapeutic approach. Bone Marrow Transplant 41 (Suppl 2), S131–S134 (2008). https://doi.org/10.1038/bmt.2008.71

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