State-of-the-art approach for bone sarcomas

  • Andreas F. MavrogenisEmail author
  • Andrea Angelini
  • Christos Vottis
  • Emanuela Palmerini
  • Eugenio Rimondi
  • Giuseppe Rossi
  • Panayiotis J. Papagelopoulos
  • Pietro Ruggieri
Expert's Opinion (General Review)


Bone sarcomas are a variety of non-epithelial, malignant neoplasms of bone. The most common bone sarcomas are osteosarcoma, Ewing’s sarcoma, and chondrosarcoma. The approach to a patient with a suspected bone sarcoma from initial examination to the histological diagnosis and classification is staging. Staging is of critical importance, in order to classify different treatment options and point out which combination of them is more suitable depending on the severity of the tumor in every individual patient. Staging should include medical history, physical and imaging examination, and biopsy. This article presents the current approach for staging, principles of biopsy, tumor classification, treatment, and follow-up of patients with bone sarcomas.


Bone sarcoma Staging Biopsy Surgery Chemotherapy Radiation therapy 


Conflict of interest

None of the authors have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work.


  1. 1.
    Calabrò T, Mavrogenis AF, Ruggieri P (2011) Osteoblastic osteosarcoma in monostotic Paget’s disease. Musculoskelet Surg 95(1):37–40PubMedGoogle Scholar
  2. 2.
    Mavrogenis AF, Abati CN, Romagnoli C, Ruggieri P (2012) Similar survival but better function for patients after limb salvage versus amputation for distal tibia osteosarcoma. Clin Orthop Relat Res 470(6):1735–1748PubMedCentralPubMedGoogle Scholar
  3. 3.
    Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O (2007) Mesenchymal stem cell features of Ewing tumors. Cancer Cell 11(5):421–429PubMedGoogle Scholar
  4. 4.
    Bielack SS, Carrle D (2008) State-of-the-art approach in selective curable tumors: bone sarcoma. Ann Oncol 19(Suppl 7):vii155–vii160PubMedGoogle Scholar
  5. 5.
    ESMO/European Sarcoma Network Working Group (2012) Bone sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii100–vii109Google Scholar
  6. 6.
    Grimer RJ, Briggs TWR (2010) Earlier diagnosis of bone and soft-tissue tumors. J Bone Joint Surg Br 92-B:1489–1492Google Scholar
  7. 7.
    Meyer JS, Nadel HR, Marina N et al (2008) Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children’s Oncology Group Bone Tumor Committee. Pediatr Blood Cancer 51:163–170PubMedGoogle Scholar
  8. 8.
    Lietman SA, Joyce MJ (2010) Bone sarcomas: overview of management, with a focus on surgical treatment considerations. Clevel Clin J Med 77(Suppl 1):S8–S12Google Scholar
  9. 9.
    Bramer JA, van Linge JH, Grimer RJ et al (2009) Prognostic factors in localized extremity osteosarcoma: a systematic review. Eur J Surg Oncol 35:1030–1036PubMedGoogle Scholar
  10. 10.
    Leavey PJ, Collier AB (2008) Ewing sarcoma: prognostic criteria, outcomes and future treatment. Expert Rev Anticancer Ther 8:617–624PubMedGoogle Scholar
  11. 11.
    Enneking WF (1982) The issue of the biopsy. J Bone Joint Surg Am 64:1119–1120Google Scholar
  12. 12.
    Andreou D, Bielack SS, Carrle D et al (2011) 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 22(5):1228–1235PubMedGoogle Scholar
  13. 13.
    van den Berg H, Slaar A, Kroon HM et al (2008) Results of diagnostic review in pediatric bone tumors and tumor-like lesions. J Pediatr Orthop 28:561–564PubMedGoogle Scholar
  14. 14.
    Mankin HJ, Lange TA, Spanier SS (1982) The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J Bone Joint Surg Am 64:1121–1127PubMedGoogle Scholar
  15. 15.
    Mavrogenis AF, Gambarotti M, Angelini A, Palmerini E, Staals EL, Ruggieri P, Papagelopoulos PJ (2012) Chondrosarcomas revisited. Orthopedics 35(3):e379–e390PubMedGoogle Scholar
  16. 16.
    Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F (2013) WHO classification of tumours of soft tissue and bone. IARC Press, LyonGoogle Scholar
  17. 17.
    Picci P, Vanel D, Briccoli A et al (2001) Computed tomography of pulmonary metastases from osteosarcoma: the less poor technique. A study of 51 patients with histological correlation. Ann Oncol 12:1601–1604PubMedGoogle Scholar
  18. 18.
    Benz MR, Tchekmedyian N, Eilber FC et al (2009) Utilization of positron emission tomography in the management of patients with sarcoma. Curr Opin Oncol 21:345–351PubMedGoogle Scholar
  19. 19.
    Moriceau G, Ory B, Mitrofan L, Riganti C, Blanchard F, Brion R, Charrier C, Battaglia S, Pilet P, Denis MG, Shultz LD, Mönkkönen J, Rédini F, Heymann D (2010) Zoledronic acid potentiates mTOR inhibition and abolishes the resistance of osteosarcoma cells to RAD001 (Everolimus): pivotal role of the prenylation process. Cancer Res 70(24):10329–10339PubMedCentralPubMedGoogle Scholar
  20. 20.
    Enneking WF (1986) A system of staging musculoskeletal neoplasms. Clin Orthop Relat Res 204:9–24PubMedGoogle Scholar
  21. 21.
    Jawad MU, Scully SP (2010) In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res 468(7):2000–2002PubMedCentralPubMedGoogle Scholar
  22. 22.
    Greene FL, Page DL, Fleming ID et al (eds) (2002) AJCC cancer staging manual. Springer, New York, pp 213–219Google Scholar
  23. 23.
    Campanacci M (1999) Bone and soft tissue tumors: clinical features, imaging, pathology and treatment. Springer, New York, pp 1–70Google Scholar
  24. 24.
    Malawer MM, Helman LJ, O’Sullivan B (2004) Sarcomas of bone. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology. Vol 2, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1794–1893Google Scholar
  25. 25.
    Odri GA, Dumoucel S, Picarda G, Battaglia S, Lamoureux F, Corradini N, Rousseau J, Tirode F, Laud K, Delattre O, Gouin F, Heymann D, Rédini F (2010) Zoledronic acid as a new adjuvant therapeutic strategy for Ewing’s sarcoma patients. Cancer Res 70(19):7610–7619PubMedGoogle Scholar
  26. 26.
    Lamoureux F, Richard P, Wittrant Y, Battaglia S, Pilet P, Trichet V, Blanchard F, Gouin F, Pitard B, Heymann D, Rédini F (2007) Therapeutic relevance of osteoprotegerin gene therapy in osteosarcoma: blockade of the vicious cycle between tumor cell proliferation and bone resorption. Cancer Res 67(15):7308–7318PubMedGoogle Scholar
  27. 27.
    Lamoureux F, Picarda G, Rousseau J, Gourden C, Battaglia S, Charrier C, Pitard B, Heymann D, Rédini F (2008) Therapeutic efficacy of soluble receptor activator of nuclear factor-kappa B-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma. Mol Cancer Ther 7(10):3389–3398PubMedCentralPubMedGoogle Scholar
  28. 28.
    Duan X, Jia SF, Koshkina N, Kleinerman ES (2006) Intranasal interleukin-12 gene therapy enhanced the activity of ifosfamide against osteosarcoma lung metastases. Cancer 106(6):1382–1388PubMedGoogle Scholar
  29. 29.
    Simon MA, Springfield DS (1998) Surgery for bone and soft-tissue tumors. Lippincott-Raven, PhiladelphiaGoogle Scholar
  30. 30.
    Mavrogenis AF, Pala E, Guerra G, Ruggieri P (2012) Post-radiation sarcomas. Clinical outcome of 52 patients. J Surg Oncol 105(6):570–576PubMedGoogle Scholar
  31. 31.
    Mavrogenis AF, Angelini A, Pala E, Calabro T, Bianchi G, Casadei R, Ruggieri P (2011) Radiation-induced sarcomas. J Long Term Eff Med Implants 21(3):233–240PubMedGoogle Scholar
  32. 32.
    Picci P, Sangiorgi L, Rougraff BT et al (1994) Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol 12:2699–2705PubMedGoogle Scholar
  33. 33.
    Blakely ML, Spurbeck WW, Pappo AS et al (1999) The impact of margin of resection on outcome in pediatric non-rhabdomyosarcoma soft tissue sarcoma. J Pediatr Surg 34:672–675PubMedGoogle Scholar
  34. 34.
    Davis AM, Kandel RA, Wunder JS et al (1997) The impact of residual disease on local recurrence in patients treated by initial unplanned resection for soft tissue sarcoma of the extremity. J Surg Oncol 66:81–87PubMedGoogle Scholar
  35. 35.
    Gupta GR, Yasko AW, Lewis VO et al (2009) Risk of local recurrence after deltoid-sparing resection for osteosarcoma of the proximal humerus. Cancer 115:3767–3773PubMedGoogle Scholar
  36. 36.
    Chandrasekar CR, Wafa H, Grimer RJ, Carter SR, Tillman RM, Abudu A (2008) The effect of an unplanned excision of a soft-tissue sarcoma on prognosis. J Bone Joint Surg Br 90:203–208PubMedGoogle Scholar
  37. 37.
    Mavrogenis AF, Angelini A, Drago G, Merlino B, Ruggieri P (2013) Survival analysis of patients with chondrosarcomas of the pelvis. J Surg Oncol 108(1):19–27PubMedGoogle Scholar
  38. 38.
    World Health Organisation (1980) International classification of impairments, disabilities, and handicaps. World Health Organisation, GenevaGoogle Scholar
  39. 39.
    Frink SJ, Rutledge J, Lewis VO, Lin PP, Yasko AW (2005) Favorable long-term results of prosthetic arthroplasty of the knee for distal femur neoplasms. Clin Orthop Relat Res 438:65–70PubMedGoogle Scholar
  40. 40.
    Sim IW, Tse LF, Ek ET, Powell GJ, Choong PF (2007) Salvaging the limb salvage: management of complications following endoprosthetic reconstruction for tumours around the knee. Eur J Surg Oncol 33(6):796–802PubMedGoogle Scholar
  41. 41.
    Heisel C, Breusch SJ, Schmid G, Bernd L (2004) Lower limb salvage surgery with MUTARS endoprostheses: 2 to 7 year results. Acta Orthop Belg 70(2):142–147PubMedGoogle Scholar
  42. 42.
    O’Sullivan B, Davis AM, Turcotte R et al (2002) Preoperative versus postoperative radiotherapy in soft tissue reconstruction of the limbs: a randomized trial. Lancet 359:2235–2241PubMedGoogle Scholar
  43. 43.
    Ruggieri P, Mavrogenis AF, Mercuri M (2011) Quality of life following limb salvage surgery for bone sarcomas. Expert Rev Pharmacoecon Outcomes Res 11(1):59–73PubMedGoogle Scholar
  44. 44.
    Ruggieri P, Mavrogenis AF, Casadei R, Errani C, Angelini A, Calabrò T, Pala E, Mercuri M (2010) Protocol of surgical treatment of long bone pathological fractures. Injury 41(11):1161–1167PubMedGoogle Scholar
  45. 45.
    Scully SP, Ghert MA, Zurakowski D et al (2002) Pathologic fracture in osteosarcoma: prognostic importance and treatment implications. J Bone Joint Surg Am 84A(1):49–57Google Scholar
  46. 46.
    Scully SP, Temple HT, O’Keefe RJ et al (1996) The surgical treatment of patients with osteosarcoma who sustain a pathologic fracture. Clin Orthop Relat Res 324:227–232PubMedGoogle Scholar
  47. 47.
    Papagelopoulos PJ, Mavrogenis AF, Savvidou OD, Benetos IS, Galanis EC, Soucacos PN (2008) Pathological fractures in primary bone sarcomas. Injury 39(4):395–403PubMedGoogle Scholar
  48. 48.
    Ruggieri P, Mavrogenis AF, Casadei R, Errani C, Angelini A, Calabrò T, Pala E, Mercuri M (2010) Protocol of surgical treatment of long bone pathological fractures. Injury 41(11):1161–1167PubMedGoogle Scholar
  49. 49.
    Mavrogenis AF, Pala E, Angelini A, Ferraro A, Ruggieri P (2013) Proximal tibial resections and reconstructions: clinical outcome of 225 patients. J Surg Oncol 107(4):335–342PubMedGoogle Scholar
  50. 50.
    Mavrogenis AF, Angelini A, Pala E, Sakellariou VI, Ruggieri P, Papagelopoulos PJ (2012) Reconstruction of the extensor mechanism after major knee resection. Orthopedics 35(5):e672–e680PubMedGoogle Scholar
  51. 51.
    Ruggieri P, Mavrogenis AF, Pala E, Abdel-Mota’al M, Mercuri M (2012) Long term results of fixed-hinge megaprostheses in limb salvage for malignancy. Knee 19(5):543–549PubMedGoogle Scholar
  52. 52.
    Ruggieri P, Mavrogenis AF, Guerra G, Mercuri M (2011) Preliminary results after reconstruction of bony defects of the proximal humerus with an allograft-resurfacing composite. J Bone Joint Surg Br 93(8):1098–1103PubMedGoogle Scholar
  53. 53.
    Canadell J, Forriol F, Cara JA (1994) Removal of metaphyseal bone tumours with preservation of the epiphysis. Physeal distraction before excision. J Bone Joint Surg Br 76:127–132PubMedGoogle Scholar
  54. 54.
    Mavrogenis AF, Soultanis K, Patapis P, Guerra G, Fabbri N, Ruggieri P, Papagelopoulos PJ (2012) Pelvic resections. Orthopedics 35(2):e232–e243PubMedGoogle Scholar
  55. 55.
    Enneking WF, Dunham WK (1978) Resection and reconstruction for primary neoplasms involving the innominate bone. J Bone Joint Surg Am 60(6):731–746PubMedGoogle Scholar
  56. 56.
    Conrad EU III, Springfield D, Peabody TD (1998) Pelvis. In: Simon MA, Springfield D (eds) Surgery for bone and soft-tissue tumors. Lippincott-Raven Publishers, Philadelphia, pp 323–341Google Scholar
  57. 57.
    Fuchs B, Yaszemski MJ, Sim FH (2002) Combined posterior pelvis and lumbar spine resection for sarcoma. Clin Orthop Relat Res 397:12–18PubMedGoogle Scholar
  58. 58.
    Mavrogenis AF, Soultanis K, Patapis P, Papagelopoulos PJ (2011) Anterior thigh flap extended hemipelvectomy and spinoiliac arthrodesis. Surg Oncol 20(4):e215–e221PubMedGoogle Scholar
  59. 59.
    Senchenkov A, Moran SL, Petty PM, Knoetgen J 3rd, Clay RP, Bite U et al (2008) Predictors of complications and outcomes of external hemipelvectomy wounds: account of 160 consecutive cases. Ann Surg Oncol 15:355–363PubMedGoogle Scholar
  60. 60.
    Campanacci M, Capanna R (1991) Pelvic resections: the Rizzoli Institute experience. Orthop Clin North Am 22(1):65–86PubMedGoogle Scholar
  61. 61.
    Karakousis C, Sugarbaker PH (2001) Sacrectomy. In: Malawer MM, Sugarbaker PH (eds) Musculoskeletal cancer surgery. Kluwer Academic Publishers, Dordrecht, The Netherlands, pp 413–422Google Scholar
  62. 62.
    Rose PS, Yaszemski MJ, Dekutoski MB, Shives TC, Sim FH (2009) Classification of spinopelvic resections: oncologic and reconstructive implications. International society of limb salvage meeting, BostonGoogle Scholar
  63. 63.
    Kollender Y, Shabat S, Bickels J et al (2000) Internal hemipelvectomy for bone sarcomas in children and young adults: surgical considerations. Eur J Surg Oncol 26(4):398–404PubMedGoogle Scholar
  64. 64.
    Ruggieri P, Mavrogenis AF, Pala E, Romantini M, Manfrini M, Mercuri M (2013) Outcome of expandable prostheses in children. J Pediatr Orthop 33(3):244–253PubMedGoogle Scholar
  65. 65.
    Mavrogenis AF, Papagelopoulos PJ, Coll-Mesa L, Pala E, Colangeli M, Manfrini M, Ruggieri P (2012) Expandable tumor prostheses in children. J BUON 17(1):9–15PubMedGoogle Scholar
  66. 66.
    Neel MD, Wilkins RM, Rao BN et al (2003) Early multicenter experience with a noninvasive expandable prosthesis. Clin Orthop Relat Res 415:72–81PubMedGoogle Scholar
  67. 67.
    Yoshida Y, Iwata S, Ueda T et al (2008) Current state of extendable prostheses for the lower limb in Japan. Surg Oncol 17:65–71PubMedGoogle Scholar
  68. 68.
    Belthur MV, Grimer RJ, Suneja R et al (2003) Extensible endoprostheses for bone tumors of the proximal femur in children. J Pediatr Orthop 23:230–235PubMedGoogle Scholar
  69. 69.
    Henderson ER, Pepper AM, Marulanda GA et al (2010) What is the emotional acceptance after limb salvage with an expandable prosthesis? Clin Orthop Relat Res 468:2933–2938PubMedCentralPubMedGoogle Scholar
  70. 70.
    Eckardt JJ, Safran MR, Eilber FR et al (1993) Expandable endoprosthetic reconstruction of the skeletally immature after malignant bone tumor resection. Clin Orthop Relat Res 297:188–202PubMedGoogle Scholar
  71. 71.
    Schindler OS, Cannon SR, Briggs TW et al (1998) Use of extendable total femoral replacements in children with malignant bone tumors. Clin Orthop Relat Res 357:157–170PubMedGoogle Scholar
  72. 72.
    Wilkins RM, Soubeiran A (2001) The Phenix expandable prosthesis: early American experience. Clin Orthop Relat Res 382:51–58PubMedGoogle Scholar
  73. 73.
    Saghieh S, Abboud MR, Muwakkit SA et al (2010) Seven-year experience of using repiphysis expandable prosthesis in children with bone tumors. Pediatr Blood Cancer 55:457–463PubMedGoogle Scholar
  74. 74.
    Cheong D, Letson GD (2011) Computer-assisted navigation and musculoskeletal sarcoma surgery. Cancer Control 18(3):171–176PubMedGoogle Scholar
  75. 75.
    Dorr LD, Deshmane P (2009) Precision surgery. Orthopedics 32(9). doi: 10.3928/01477447-20090728-26
  76. 76.
    Mavrogenis AF, Savvidou OD, Mimidis G, Papanastasiou J, Koulalis D, Demertzis N, Papagelopoulos PJ (2013) Computer-assisted navigation in orthopedic surgery. Orthopedics 36(8):631–642PubMedGoogle Scholar
  77. 77.
    Arndt CA, Crist WM (1999) Common musculoskeletal tumors of childhood and adolescence. N Engl J Med 341:342–352PubMedGoogle Scholar
  78. 78.
    Bielack SS, Machatschek JN, Flege S, Jurgens H (2004) Delaying surgery with chemotherapy for osteosarcoma of the extremities. Expert Opin Pharmacother 5:1243–1256PubMedGoogle Scholar
  79. 79.
    Bernstein M, Kovar H, Paulussen M et al (2006) Ewing’s sarcoma family of tumors: current management. Oncologist 11:503–519PubMedGoogle Scholar
  80. 80.
    Grimer RJ, Cannon SR, Taminiau AM et al (2003) Osteosarcoma over the age of forty. Eur J Cancer 39:157–163PubMedGoogle Scholar
  81. 81.
    Scurr M, Judson I (2006) How to treat the Ewing’s family of sarcomas in adult patients. Oncologist 11:65–72PubMedGoogle Scholar
  82. 82.
    Bacci G, Picci P, Ferrari S et al (1998) Neoadjuvant chemotherapy for Ewing’s sarcoma of bone: no benefit observed after adding ifosfamide and etoposide to vincristine, actinomycin, cyclophosphamide, and doxorubicin in the maintenance phase—results of two sequential studies. Cancer 82:1174–1183PubMedGoogle Scholar
  83. 83.
    Paulussen M, Ahrens S, Dunst J et al (2001) Localized Ewing tumor of bone: final results of the cooperative Ewing’s Sarcoma Study CESS 86. J Clin Oncol 19:1818–1829PubMedGoogle Scholar
  84. 84.
    Grier HE, Krailo MD, Tarbell NJ et al (2003) Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 348:694–701PubMedGoogle Scholar
  85. 85.
    Ozaki T, Flege S, Kevric M et al (2003) Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group. J Clin Oncol 21:334–341PubMedGoogle Scholar
  86. 86.
    DeLaney TF, Park L, Goldberg SI et al (2005) Radiotherapy for local control of osteosarcoma. Int J Radiat Oncol Biol Phys 61:492–498PubMedGoogle Scholar
  87. 87.
    Patel S, DeLaney TF (2008) Advanced-technology radiation therapy for bone sarcomas. Cancer Control 15(1):21–37PubMedGoogle Scholar
  88. 88.
    Hug EB (2001) Review of skull base chordomas: prognostic factors and long-term results of proton-beam radiotherapy. Neurosurg Focus 10:E11PubMedGoogle Scholar
  89. 89.
    Munzenrider JE, Liebsch NJ (1999) Proton therapy for tumors of the skull base. Strahlenther Onkol 175(suppl 2):57–63PubMedGoogle Scholar
  90. 90.
    Ewing J (1972) Classics in oncology. Diffuse endothelioma of bone. James Ewing. Proceedings of the New York Pathological Society, 1921. CA Cancer J Clin 22: 95–98Google Scholar
  91. 91.
    Sailer SL (1997) The role of radiation therapy in localized Ewing’s sarcoma. Semin Radiat Oncol 7:225–235PubMedGoogle Scholar
  92. 92.
    Park L, Delaney TF, Liebsch NJ et al (2006) Sacral chordomas: impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor. Int J Radiat Oncol Biol Phys 65:1514–1521PubMedGoogle Scholar
  93. 93.
    Lee CT, Bilton SD, Famiglietti RM et al (2005) Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques? Int J Radiat Oncol Biol Phys 63:362–372PubMedGoogle Scholar
  94. 94.
    DeLaney TF, Liebsch NJ, Spiro IJ et al (2006) Proton radiotherapy for spine and paraspinal sarcomas. Int J Radiat Oncol Biol Phys 66:S115–S116Google Scholar
  95. 95.
    Yock T, Schneider R, Friedmann A et al (2005) Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a dosimetric comparison with photons. Int J Radiat Oncol Biol Phys 63:1161–1168PubMedGoogle Scholar
  96. 96.
    Ozaki T, Hillmann A, Rübe C et al (1997) The impact of intraoperative brachytherapy on surgery of Ewing’s sarcoma. J Cancer Res Clin Oncol 123:53–56PubMedGoogle Scholar
  97. 97.
    Linstadt DE, Castro JR, Phillips TL (1991) Neon ion radiotherapy: results of the phase I/II clinical trial. Int J Radiat Oncol Biol Phys 20:761–769PubMedGoogle Scholar
  98. 98.
    Kamada T, Tsujii H, Tsuji H et al (2002) Efficacy and safety of carbon ion radiotherapy in bone and soft tissue sarcomas. J Clin Oncol 20:4466–4471PubMedGoogle Scholar
  99. 99.
    Schulz-Ertner D, Nikoghosyan A, Thilmann C et al (2004) Results of carbon ion radiotherapy in 152 patients. Int J Radiat Oncol Biol Phys 58:631–640PubMedGoogle Scholar
  100. 100.
    Anderson PM, Wiseman GA, Dispenzieri A et al (2002) High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol 20:189–196PubMedGoogle Scholar
  101. 101.
    Anderson PM, Wiseman GA, Erlandson L et al (2005) Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma. Clin Cancer Res 11(19 Pt 1):6895–6900PubMedGoogle Scholar
  102. 102.
    Kager L, Zoubek A, Potschger U et al (2003) Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 21:2011–2018PubMedGoogle Scholar
  103. 103.
    Paulussen M, Ahrens S, Burdach S et al (1998) Primary metastatic (stage IV) Ewing tumor: survival analysis of 171 patients from the EICESS studies. European Intergroup Cooperative Ewing Sarcoma Studies. Ann Oncol 9:275–281PubMedGoogle Scholar
  104. 104.
    Kempf-Bielack B, Bielack SS, Jürgens H et al (2005) Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol 20:559–568Google Scholar
  105. 105.
    Briccoli A, Rocca M, Ferrari S et al (2004) Surgery for lung metastases in Ewing’s sarcoma of bone. Eur J Surg Oncol 30:63–67PubMedGoogle Scholar
  106. 106.
    Fröhlich B, Ahrens S, Burdach S, Klingebiel T, Ladenstein R, Paulussen M, Zoubek A, Jürgens H (1999) High-dosage chemotherapy in primary metastasized and relapsed Ewing’s sarcoma. Klin Padiatr 211(4):284–290PubMedGoogle Scholar
  107. 107.
    Mavrogenis AF, Pala E, Romantini M, Guerra G, Romagnoli C, Maccauro G, Ruggieri P (2011) Side effects of radiation in musculoskeletal oncology: clinical evaluation of radiation-induced fractures. Int J Immunopathol Pharmacol 24(1 Suppl 2):29–37PubMedGoogle Scholar
  108. 108.
    Mavrogenis AF, Papagelopoulos PJ, Romantini M, Angelini A, Ruggieri P (2010) Side effects of chemotherapy in musculoskeletal oncology. J Long Term Eff Med Implants 20(1):1–12PubMedGoogle Scholar
  109. 109.
    Mavrogenis AF, Papagelopoulos PJ, Romantini M, Guerra G, Ruggieri P (2009) Side effects of radiation in musculoskeletal oncology. J Long Term Eff Med Implants 19(4):287–304PubMedGoogle Scholar
  110. 110.
    Casadei R, Mavrogenis AF, De Paolis M, Ruggieri P (2013) Two-stage, combined, three-level en bloc spondylectomy for a recurrent post-radiation sarcoma of the lumbar spine. Eur J Orthop Surg Traumatol 23(Suppl 1):93–100Google Scholar

Copyright information

© Springer-Verlag France 2014

Authors and Affiliations

  • Andreas F. Mavrogenis
    • 1
    Email author
  • Andrea Angelini
    • 2
  • Christos Vottis
    • 1
  • Emanuela Palmerini
    • 4
  • Eugenio Rimondi
    • 3
  • Giuseppe Rossi
    • 3
  • Panayiotis J. Papagelopoulos
    • 1
  • Pietro Ruggieri
    • 2
  1. 1.First Department of Orthopaedics, ATTIKON University HospitalAthens University Medical SchoolAthensGreece
  2. 2.Department of OrthopaedicsIstituto Ortopedico RizzoliBolognaItaly
  3. 3.Department of Radiology and Interventional RadiologyIstituto Ortopedico RizzoliBolognaItaly
  4. 4.Department of Medical OncologyIstituto Ortopedico RizzoliBolognaItaly

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