Skip to main content

Advertisement

SpringerLink
Log in

Long-term results of the Spanish Protocol SO-95 for the treatment of non-metastatic high-grade osteosarcoma of the extremities in children

  • Research Articles
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Introduction

The long-term results of the Spanish Study Protocol SEOP-SO-95 for treatment of localised osteosarcoma of the extremities in children were evaluated.

Patients and methods

One hundred consecutive patients under 18 years of age from 22 institutions were enrolled from January 1995 to December 2000. Immunohistochemical expression of p53, HER/erbB-2 and P-glycoprotein were retrospectively studied in 27 patients. Treatment consisted of: preoperative chemotherapy with doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue and ifosfamide for 14 weeks; surgery of primary tumour in week 16; postoperative chemotherapy with the above-mentioned drugs for 25 weeks.

Results

With a median follow-up of 124 months (range 84–158 months), 69 patients (69%) were continuously event-free survivors; the 10-year probability of event-free survival (EFS) was 62%. Conservative surgery was performed in 85% of patients. Twenty-six patients had local recurrence or distant relapse. The median time to recurrence/relapse was 27 months (range 17–93 months). The local recurrence rate was 7% (7 of the 100 patients); 4 had wide surgical margins, 2 marginal and 1 intralesional. Four patients died as a result of chemotherapy-related toxicity and 1 developed a second neoplasia (acute myeloid leukaemia). p53 expression and HER2/erbB-2 expression showed no effect on survival or EFS.

Conclusions

This therapeutic protocol achieved good oncologic and orthopaedic results. We observed a significant treatment-related toxicity.

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

  1. Longhi A, Errani C, De Paolis M et al (2006) Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev 32:423–436

    Article  PubMed  Google Scholar 

  2. Bielack S, Carrle D, Jost L (2007) Osteosarcoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 18[Suppl2]:i77–i78

    Google Scholar 

  3. Bielack S, Kempf-Bielack B, Delling G et al (2002) Prognostic factors in high-grade osteosarcoma of the extremities and trunk: an analysis of 1702 patients treated with neoadjuvant Cooperative Osteosarcoma Study Group Protocols. J Clin Oncol 69:776–790

    Article  Google Scholar 

  4. Glaser DB, Lane JM, Huvos AG et al (1992) Survival, prognosis and therapeutic response in osteogenic sarcoma. The Memorial Hospital experience. Cancer 69:698–708

    Article  Google Scholar 

  5. Bacci G, Ferrari S, Bertoni F et al (2000) Longterm outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the Instituto Ortopedico Rizzoli according to the Osteosarcoma-2 protocol: an updated report. J Clin Oncol 18:4016–4027

    PubMed  CAS  Google Scholar 

  6. Goorin AM, Schwartzentruber DJ, Devidas V et al (2003) Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol 21:1574–1580

    Article  PubMed  CAS  Google Scholar 

  7. Ferrari S, Smeland S, Mercuri M et al (2005) 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 23:8845–8852

    Article  PubMed  Google Scholar 

  8. (2008) Registro Nacional de Tumores Infantiles. Estadisticas 1980-2007. Universidad de Valencia

  9. Huvos AG (1991) Bone tumors: diagnosis, treatment and prognosis, 2nd Edn. Saunders, Philadelphia, PA

    Google Scholar 

  10. Meyer WH, Pratt CB, Poquette CA et al (2001) Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children’s Research Hospital OS-91 trial. J Clin Oncol 19:171–182

    PubMed  CAS  Google Scholar 

  11. Fuchs N, Bielack S, Epler D et al (1998) Longterm 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 9:893–899

    Article  PubMed  CAS  Google Scholar 

  12. Winkler K, Bielack SS, Delling G et al (1993) Treatment of osteosarcoma: experience of the Cooperative Group Osteosarcoma Study (COSS). Cancer Treat Res 62:269–277

    PubMed  CAS  Google Scholar 

  13. Brösjo O (1999) Surgical procedure and local recurrence in 223 patients treated 1982–1997 according to two osteosarcoma chemotherapy protocols. The Scandinavian Sarcoma Group Experience. Clin Orthop Relat Res 285:58–61

    Google Scholar 

  14. Petrilli AS, de Camargo B, Fiho VO et al (2006) Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: prognostic factors and impact on survival. J Clin Oncol 24:1161–1167

    Article  PubMed  Google Scholar 

  15. Lindner NJ, Ramm O, Hillmann A et al (1999) Limb salvage and outcome of osteosarcoma. The University of Muenster experience. Clin Orthop Relat Res 8:3–9

    Google Scholar 

  16. Sluga M, Windhager R, Lang S et al (1999) Local and systemic control after ablative and limb salvage surgery in patients with osteosarcoma. Clin Orthop Relat Res 358:120–127

    Article  PubMed  Google Scholar 

  17. Bacci G, Forni C, Longhi A et al (2007) Local recurrence and local control of non-metastatic osteosarcoma of the extremities: a 27-year experience in a single institution. J Surg Oncol 96:118–123

    Article  PubMed  Google Scholar 

  18. Kaste SC, Liu T, Billups CA et al (2004) Tumor size as a predictor of outcome in pediatric nonmetastatic osteosarcoma. Pediatr Blood Cancer 43:723–728

    Article  PubMed  Google Scholar 

  19. Jun AL, Min SK, Dong HK et al (2008) Relative tumor burden predicts metastasis-free survival in pediatric osteosarcoma. Pediatr Blood Cancer 50:195–200

    Article  Google Scholar 

  20. Papai Z, Feja CN, Hanna EN et al (1997) p53 overexpression as an indicator of overall survival and response to treatment in osteosarcomas. Pathol Oncol Res 3:15–19

    Article  PubMed  Google Scholar 

  21. Onda M, Matsuda S, Higaki S et al (1996) ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer 77:71–78

    Article  PubMed  CAS  Google Scholar 

  22. Toguchida J, Yamaguchi T, Ritchie B et al (1992) Mutation spectrum of p53 gene in bone and soft tissue sarcomas. Cancer Res 52:6194–6199

    PubMed  CAS  Google Scholar 

  23. Wunder JS, Gokgoz N, Parkes R et al (2005) TP53 mutations and outcome in osteosarcoma: a prospective, multicenter study. J Clin Oncol 23:1483–1490

    Article  PubMed  CAS  Google Scholar 

  24. Baldini N, Scotlandi K, Barbanti-Brodano G et al (1995) Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med 333:1380–1385

    Article  PubMed  CAS  Google Scholar 

  25. Serra M, Maurici D, Scotlandi K et al (1999) Relationship between P-glycoprotein expression and p53 status in high-grade osteosarcoma. Int J Oncol 14:301–307

    PubMed  CAS  Google Scholar 

  26. Meyers PA, Gorlic R, Heller G et al (1998) Intensification of preoperative chemotherapy for osteogenic sarcoma: results of the Memorial-Sloan-Kettering (T-12) protocol. J Clin Oncol 16:2452–2458

    PubMed  CAS  Google Scholar 

  27. Reddel RR, Kefford RF, Grant JM et al (1982) Ototoxicity in patients receiving cisplatin: importance of dose and method of drug administration. Cancer Treat Rep 66:19–23

    PubMed  CAS  Google Scholar 

  28. Pratt CB, Meyer WH, Luo X et al (1997) Second malignant neoplasms occurring in survivors of osteosarcoma. Cancer 80:60–65

    Article  Google Scholar 

  29. Aung L, Gorlik RG, Shi W et al (2002) Second malignant neoplasms in long-term survivors of osteosarcoma: Memorial Sloan-Kettering Cancer Center experience. Cancer 95:1728–1734

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Servicio de Pediatría, Hospital Ramón y Cajal-Universidad de Alcalá, Ctra. de Colmenar Viejo km. 9,100, ES-28034, Madrid, Spain

    Arturo Muñoz, Guillermo Ocete & María Soledad Maldonado

  2. Hospital Virgen del Rocío, Sevilla, Spain

    José Alfaro & Manuel Ruiz del Portal

  3. Hospital San Pablo, Barcelona, Spain

    Nuria Pardo

  4. Hospital La Paz, Madrid, Spain

    Purificación García-Miguel & Jorge de las Heras

  5. Hospital Niño Jesús, Madrid, Spain

    Víctor Quintero

  6. Hospital Valle de Hebrón, Barcelona, Spain

    Luis Gros

  7. Hospital 12 de Octubre, Madrid, Spain

    Carmen Melero

  8. Hospital Central de Asturias, Oviedo, Asturias, Spain

    María Jesús Antuña

  9. Esplugues de Llobregat, Hospital San Juan de Dios, Barcelona, Spain

    Ramón Huguet

Authors
  1. Arturo Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José Alfaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nuria Pardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Purificación García-Miguel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Víctor Quintero
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luis Gros
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carmen Melero
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. María Jesús Antuña
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Guillermo Ocete
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jorge de las Heras
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Manuel Ruiz del Portal
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ramón Huguet
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. María Soledad Maldonado
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arturo Muñoz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Muñoz, A., Alfaro, J., Pardo, N. et al. Long-term results of the Spanish Protocol SO-95 for the treatment of non-metastatic high-grade osteosarcoma of the extremities in children. Clin Transl Oncol 11, 387–392 (2009). https://doi.org/10.1007/s12094-009-0373-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-009-0373-3

Keywords

Search

Navigation