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Methotrexate Free Chemotherapy and Limb Salvage Surgery for Paediatric Osteosarcoma in India

  • Symposium - Musculoskeletal Oncology
  • Published:
Indian Journal of Orthopaedics Aims and scope Submit manuscript

Abstract

Background

Osteosarcoma (OS) is the most common primary malignant tumor of bone. The survival of OS patients has steadily improved from <20% in the early 20th century to around 70% with current treatment. There are very few studies in pediatric OS from India analyzing various aspects of the disease. This study focuses on the clinical profile, treatment options, and their complications and survival outcomes in pediatric osteosarcoma (OS) patients.

Materials and Methods

This was a retrospective observational study which included pediatric patients <14 years of age, with newly diagnosed OS confirmed by histological diagnosis. Medical records of all patients were reviewed for clinical profile, treatment data, surgical management, and treatment complications. Patients alive at the end of treatment were followed up and overall (OAS) and disease-free survival (DFS) were analyzed.

Results

Sixty-two patients were diagnosed with OS during the study of whom 55 opted for treatment. Cisplatin, adriamycin, and ifosfamide (PAI) was offered as chemotherapy and was completed as planned in the majority of patients. Limb salvage surgery was performed in most patients (87%, n = 40). The local recurrence occurred in 7 patients. The 3 years overall survival for the cohort was 54.6% ± 7.8% and DFS was 43.4% ± 7.9%, with females and those with the localized disease having a significantly better DFS.

Conclusions

High dose methotrexate free chemotherapy can give good OAS in localized disease and LSS is feasible in most of the pediatric OS patients. However the modest DFS even for localized disease with PAI chemotherapy and extremely poor outcomes in the metastatic OS, demand further research and innovations in systemic therapy to improve outcomes.

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References

  1. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res 2009;152:3–13.

    Article  Google Scholar 

  2. Tiwari A, Jain S, Mehta S, Kumar R, Kapoor G, Kumar K, et al. Limb salvage surgery for osteosarcoma: Early results in Indian patients. Indian J Orthop 2014;48:266–72.

    Article  Google Scholar 

  3. 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 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002;20:776–90.

    Article  Google Scholar 

  4. Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A. Picci P, et al. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer 2006;106:1154–61.

    Article  Google Scholar 

  5. Kager L, Zoubek A, Pötschger U, Kastner U, Flege S. Kempf-Bielack B, et al. Primary metastatic osteosarcoma: Presentation and outcome of patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2003;21:2011–8.

    Article  Google Scholar 

  6. Luetke A, Meyers PA, Lewis I, Juergens H. Osteosarcoma treatment – Where do we stand? A state of the art review. Cancer Treat Rev 2014;40:523–32.

    Article  Google Scholar 

  7. Daw NC, Neel MD, Rao BN, Billups CA, Wu J, Jenkins JJ, et al. Frontline treatment of localized osteosarcoma without methotrexate: Results of the St. Jude children’s research hospital OS99 trial. Cancer 2011;117:2770–8.

    Article  Google Scholar 

  8. Machak GN, Tkachev SI, Solovyev YN, Sinyukov PA, Ivanov SM, Kochergina NV, et al. Neoadjuvant chemotherapy and local radiotherapy for high-grade osteosarcoma of the extremities. Mayo Clin Proc 2003;78:147–55.

    Article  Google Scholar 

  9. Geller DS, Gorlick R. Osteosarcoma: A review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol 2010;8:705–18.

    PubMed  Google Scholar 

  10. Simon MA, Aschliman MA, Thomas N, Mankin HJ. Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur 1986. J Bone Joint Surg Am 2005;87:2822.

    Article  Google Scholar 

  11. Davidson AW, Hong A, McCarthy SW, Stalley PD. En-bloc resection, extracorporeal irradiation, and re-implantation in limb salvage for bony malignancies. J Bone Joint Surg Br 2005;87:851–7.

    Article  CAS  Google Scholar 

  12. Gulia A, Puri A, Agarwal MG, Laskar S, Reddy K. Diaphyseal reconstruction with extrcorporeal irradiated autogenous tumor bone. Orthop Proc 2012;94-B Suppl 14:30.

  13. Mei J, Zhu XZ, Wang ZY, Cai XS. Functional outcomes and quality of life in patients with osteosarcoma treated with amputation versus limb-salvage surgery: A systematic review and meta-analysis. Arch Orthop Trauma Surg 2014;134:1507–16.

    Article  Google Scholar 

  14. Eiser C, Darlington AS, Stride CB, Grimer R. Quality of life implications as a consequence of surgery: Limb salvage, primary and secondary amputation. Sarcoma 2001;5:189–95.

    Article  CAS  Google Scholar 

  15. Nagarajan R, Kamruzzaman A, Ness KK, Marchese VG, Sklar C, Mertens A, et al. Twenty years of followup of survivors of childhood osteosarcoma: A report from the childhood cancer survivor study. Cancer 2011;117:625–34.

    Article  Google Scholar 

  16. Grimer RJ, Carter SR, Tillman RM, Abudu S, Jeys L. Osteosarcoma with poor necrosis and close margins – Amputation or limb salvage? J Bone Joint Surg Br 2012;94-B Suppl 14:45.

  17. Andreou D, Bielack SS, Carrie D, Kevric M, Kotz R, Winkelmann W, et al. The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery. An analysis of 1355 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. Ann Oncol 2011;22:1228–35.

    Article  CAS  Google Scholar 

  18. Renard AJ, Veth RP, Schreuder HW, Schraffordt Koops H, van Horn J, Keller A, et al. Revisions of endoprosthetic reconstructions after limb salvage in musculoskeletal oncology. Arch Orthop Trauma Surg 1998;117:125–31.

    Article  CAS  Google Scholar 

  19. Mavrogenis AF, Abati CN, Romagnoli C, Ruggieri P. Similar survival but better function for patients after limb salvage versus amputation for distal tibia osteosarcoma. Clin Orthop Relat Res 2012;470:1735–48.

    Article  Google Scholar 

  20. Kempf-Bielack B, Bielack SS, Jiirgens H, Branscheid D, Berdel WE, Exner GU, et al. Osteosarcoma relapse after combined modality therapy: An analysis of unselected patients in the cooperative osteosarcoma study group (COSS). J Clin Oncol 2005;23:559–68.

    Article  Google Scholar 

  21. Berner K, Hall KS, Monge OR, Weedon-Fekjier H, Zaikova O, Bruland ØS, et al. Prognostic factors and treatment results of high-grade osteosarcoma in Norway: A scope beyond the “classical” patient. Sarcoma 2015;2015:516843.

    PubMed  PubMed Central  Google Scholar 

  22. Bacci G, Longhi A, Ferrari S, Lari S, Manfrini M, Donati D, et al. Prognostic significance of serum alkaline phosphatase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: Recent experience at Rizzoli institute. Oncol Rep 2002;9:171–5.

    PubMed  Google Scholar 

  23. Eselgrim M, Grunert H, Kühne T, Zoubek A, Kevric M, Burger H, et al. Dose intensity of chemotherapy for osteosarcoma and outcome in the cooperative osteosarcoma study group (COSS) trials. Pediatr Blood Cancer 2006;47:42–50.

    Article  Google Scholar 

  24. Errani C, Longhi A, Rossi G, Rimondi E, Biazzo A, Toscano A, et al. Palliative therapy for osteosarcoma. Expert Rev Anticancer Ther 2011;11:217–27.

    Article  Google Scholar 

  25. Jawad MU, Cheung MC, Clarke J, Koniaris LG, Scully SP. Osteosarcoma: Improvement in survival limited to high-grade patients only. J Cancer Res Clin Oncol 2011;137:597–607.

    Article  Google Scholar 

  26. Meyers PA, Gorlick R, Heller G, Casper E, Lane J, Huvos AG. et al. Intensification of preoperative chemotherapy for osteogenic sarcoma: Results of the memorial Sloan-Kettering (T12) protocol. J Clin Oncol 1998;16:2452–8.

    Article  CAS  Google Scholar 

  27. Imran H, Enders F, Krailo M, Sim F, Okuno S, Hawkins D, et al. Effect of time to resumption of chemotherapy after definitive surgery on prognosis for non-metastatic osteosarcoma. J Bone Joint Surg Am 2009;91:604–12.

    Article  Google Scholar 

  28. Scully SP, Ghert MA, Zurakowski D, Thompson RC, Gebhardt MC. Pathologic fracture in osteosarcoma: Prognostic importance and treatment implications. J Bone Joint Surg Am 2002;84-A: 49–57.

    Article  Google Scholar 

  29. Salunke AA, Chen Y, Tan JH, Chen X, Khin LW, Puhaindran ME, et al. Does a pathological fracture affect the prognosis in patients with osteosarcoma of the extremities? a systematic review and meta-analysis. Bone Joint J 2014;96-B:1396–403.

    Article  CAS  Google Scholar 

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Correspondence to Reghu Kesavapillai Sukumaran.

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Sukumaran, R.K., Rajeshwari, B., Sugath, S. et al. Methotrexate Free Chemotherapy and Limb Salvage Surgery for Paediatric Osteosarcoma in India. IJOO 52, 58–64 (2018). https://doi.org/10.4103/ortho.IJOrtho_195_17

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  • DOI: https://doi.org/10.4103/ortho.IJOrtho_195_17

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