Neurosurgical Review

, Volume 35, Issue 2, pp 171–183 | Cite as

Chordomas of the skull base and cervical spine: clinical outcomes associated with a multimodal surgical resection combined with proton-beam radiation in 40 patients

  • Muneyoshi Yasuda
  • Damien Bresson
  • Salvatore Chibbaro
  • Jan F. Cornelius
  • Marc Polivka
  • Loic Feuvret
  • Masakazu Takayasu
  • Bernard George
Original Article


Previous studies of chordoma have focused on either surgery, radiotherapy, or particular tumor locations. This paper reviewed the outcomes of surgery and proton radiotherapy with various tumor locations. Between 2001 and 2008, 40 patients with chordomas of the skull base and cervical spine had surgery at our hospital. Most patients received proton therapy. Their clinical course was reviewed. Age, sex, tumor location, timing of surgery, extent of resection, and chondroid appearance were evaluated in regard to the progression-free survival (PFS) and overall survival (OS). The primary surgery (PS) group was analyzed independently. The extensive resection rate was 42.5%. Permanent neurological morbidity was seen in 3.8%. Radiotherapy was performed in 75% and the mean dose was 68.9 cobalt gray equivalents. The median follow-up was 56.5 months. The 5-year PFS and OS rates were 70% and 83.4%, respectively. Metastasis was seen in 12.5%. The tumor location at the cranio-cervical junction (CCJ) was associated with a lower PFS (P = 0.007). In the PS group, a younger age and the CCJ location were related to a lower PFS (P = 0.008 and P < 0.001, respectively). The CCJ location was also related to a lower OS (P = 0.043) and it was more common in young patients (P = 0.002). Among the survivors, the median of the last Karnofsky Performance Scale score was 80 with 25.7% of patients experiencing an increase and 11.4% experiencing a decrease. Multimodal surgery and proton therapy thus improved the chordoma treatment. The CCJ location and a younger age are risks for disease progression.


Chordoma Endoscope Proton Skull base Spine 



We sincerely express our gratitude to Dr. Akiko Tamakoshi at the Department of Public Health in Aichi Medical University for technical support in statistical analysis and Dr. Giuseppe Mirone, Ms. Karin Aouabed, Ms. Aline Le Borne, and Ms. Haruko Kobayashi for technical support in writing this paper.


The authors report no conflicts of interest concerning the materials or methods used in this study or the findings specified in this paper.


  1. 1.
    Al Mefty O, Borba LA (1997) Skull base chordomas: a management challenge. J Neurosurg 86:182–189PubMedCrossRefGoogle Scholar
  2. 2.
    Almefty K, Pravdenkova S, Colli BO, Al Mefty O, Gokden M (2007) Chordoma and chondrosarcoma: similar, but quite different, skull base tumors. Cancer 110:2457–2467PubMedCrossRefGoogle Scholar
  3. 3.
    Austin Seymour M, Munzenrider J, Goitein M, Verhey L, Urie M, Gentry R et al (1989) Fractionated proton radiation therapy of chordoma and low-grade chondrosarcoma of the base of the skull. J Neurosurg 70:13–17PubMedCrossRefGoogle Scholar
  4. 4.
    Barrenechea IJ, Perin NI, Triana A, Lesser J, Costantino P, Sen C (2007) Surgical management of chordomas of the cervical spine. J Neurosurg Spine 6:398–406PubMedCrossRefGoogle Scholar
  5. 5.
    Benk V, Liebsch NJ, Munzenrider JE, Efird J, McManus P, Suit H (1995) Base of skull and cervical spine chordomas in children treated by high-dose irradiation. Int J Radiat Oncol Biol Phys 31:577–581PubMedCrossRefGoogle Scholar
  6. 6.
    Borba LA, Al Mefty O, Mrak RE, Suen J (1996) Cranial chordomas in children and adolescents. J Neurosurg 84:584–591PubMedCrossRefGoogle Scholar
  7. 7.
    Boriani S, Bandiera S, Biagini R, Bacchini P, Boriani L, Cappuccio M et al (2006) Chordoma of the mobile spine: fifty years of experience. Spine 31:493–503PubMedCrossRefGoogle Scholar
  8. 8.
    Carpentier A, Blanquet A, George B (2001) Suboccipital and cervical chordomas: radical resection with vertebral artery control. Neurosurg Focus 10:E4PubMedCrossRefGoogle Scholar
  9. 9.
    Casali PG, Messina A, Stacchiotti S, Tamborini E, Crippa F, Gronchi A et al (2004) Imatinib mesylate in chordoma. Cancer 101:2086–2097PubMedCrossRefGoogle Scholar
  10. 10.
    Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH (2007) Chordoma: the nonsarcoma primary bone tumor. Oncologist 12:1344–1350PubMedCrossRefGoogle Scholar
  11. 11.
    Cleaver O, Krieg PA (2001) Notochord patterning of the endoderm. Dev Biol 234:1–12PubMedCrossRefGoogle Scholar
  12. 12.
    Coffin CM, Swanson PE, Wick MR, Dehner LP (1993) Chordoma in childhood and adolescence. A clinicopathologic analysis of 12 cases. Arch Pathol Lab Med 117:927–933PubMedGoogle Scholar
  13. 13.
    Colli B, Al Mefty O (2001) Chordomas of the craniocervical junction: follow-up review and prognostic factors. J Neurosurg 95:933–943PubMedCrossRefGoogle Scholar
  14. 14.
    Colli BO, Al Mefty O (2001) Chordomas of the skull base: follow-up review and prognostic factors. Neurosurg Focus 10:E1PubMedCrossRefGoogle Scholar
  15. 15.
    Crockard HA, Steel T, Plowman N, Singh A, Crossman J, Revesz T et al (2001) A multidisciplinary team approach to skull base chordomas. J Neurosurg 95:175–183PubMedCrossRefGoogle Scholar
  16. 16.
    Debus J, Schulz Ertner D, Schad L, Essig M, Rhein B, Thillmann CO et al (2000) Stereotactic fractionated radiotherapy for chordomas and chondrosarcomas of the skull base. Int J Radiat Oncol Biol Phys 47:591–596PubMedCrossRefGoogle Scholar
  17. 17.
    Eriksson B, Gunterberg B, Kindblom LG (1981) Chordoma. A clinicopathologic and prognostic study of a Swedish national series. Acta Orthop Scand 52:49–58PubMedCrossRefGoogle Scholar
  18. 18.
    Fagundes MA, Hug EB, Liebsch NJ, Daly W, Efird J, Munzenrider JE (1995) Radiation therapy for chordomas of the base of skull and cervical spine: patterns of failure and outcome after relapse. Int J Radiat Oncol Biol Phys 33:579–584PubMedCrossRefGoogle Scholar
  19. 19.
    Feuvret L, Noel G, Weber DC, Pommier P, Ferrand R, De Marzi L et al (2007) A treatment planning comparison of combined photon–proton beams versus proton beams-only for the treatment of skull base tumors. Int J Radiat Oncol Biol Phys 69:944–954PubMedCrossRefGoogle Scholar
  20. 20.
    Forsyth PA, Cascino TL, Shaw EG, Scheithauer BW, O'Fallon JR, Dozier JC et al (1993) Intracranial chordomas: a clinicopathological and prognostic study of 51 cases. J Neurosurg 78:741–747PubMedCrossRefGoogle Scholar
  21. 21.
    Gay E, Sekhar LN, Rubinstein E, Wright DC, Sen C, Janecka IP et al (1995) Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients. Neurosurgery 36:887–896, discussion 896–897PubMedCrossRefGoogle Scholar
  22. 22.
    Habrand JL, Schneider R, Alapetite C, Feuvret L, Petras S, Datchary J et al (2008) Proton therapy in pediatric skull base and cervical canal low-grade bone malignancies. Int J Radiat Oncol Biol Phys 71:672–675PubMedCrossRefGoogle Scholar
  23. 23.
    Hasegawa T, Ishii D, Kida Y, Yoshimoto M, Koike J, Iizuka H (2007) Gamma knife surgery for skull base chordomas and chondrosarcomas. J Neurosurg 107:752–757PubMedCrossRefGoogle Scholar
  24. 24.
    Heffelfinger MJ, Dahlin DC, MacCarty CS, Beabout JW (1973) Chordomas and cartilaginous tumors at the skull base. Cancer 32:410–420PubMedCrossRefGoogle Scholar
  25. 25.
    Hoch BL, Nielsen GP, Liebsch NJ, Rosenberg AE (2006) Base of skull chordomas in children and adolescents: a clinicopathologic study of 73 cases. Am J Surg Pathol 30:811–818PubMedCrossRefGoogle Scholar
  26. 26.
    Horten BC, Montague SR (1976) Human ecchordosis physaliphora and chick embryonic notochord. A comparative electron microscopic study. Virchows Arch A Pathol Anat Histol 371:295–303PubMedCrossRefGoogle Scholar
  27. 27.
    Hug EB, Loredo LN, Slater JD, DeVries A, Grove RI, Schaefer RA et al (1999) Proton radiation therapy for chordomas and chondrosarcomas of the skull base. J Neurosurg 91:432–439PubMedCrossRefGoogle Scholar
  28. 28.
    Hug EB (2001) Review of skull base chordomas: prognostic factors and long-term results of proton-beam radiotherapy. Neurosurg Focus 10:E11PubMedCrossRefGoogle Scholar
  29. 29.
    Hunter CJ, Matyas JR, Duncan NA (2004) Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat 205:357–362PubMedCrossRefGoogle Scholar
  30. 30.
    Igaki H, Tokuuye K, Okumura T, Sugahara S, Kagei K, Hata M et al (2004) Clinical results of proton beam therapy for skull base chordoma. Int J Radiat Oncol Biol Phys 60:1120–1126PubMedCrossRefGoogle Scholar
  31. 31.
    Iwasa Y, Nakashima Y, Okajima H, Morishita S (1998) Sacral chordoma in early childhood: clinicopathological and immunohistochemical study. Pediatr Dev Pathol 1:420–426PubMedCrossRefGoogle Scholar
  32. 32.
    Kaneko Y, Sato Y, Iwaki T, Shin RW, Tateishi J, Fukui M (1991) Chordoma in early childhood: a clinicopathological study. Neurosurgery 29:442–446PubMedCrossRefGoogle Scholar
  33. 33.
    Lanzino G, Dumont AS, Lopes MB, Laws ER Jr (2001) Skull base chordomas: overview of disease, management options, and outcome. Neurosurg Focus 10:E12PubMedCrossRefGoogle Scholar
  34. 34.
    Martin JJ, Niranjan A, Kondziolka D, Flickinger JC, Lozanne KA, Lunsford LD (2007) Radiosurgery for chordomas and chondrosarcomas of the skull base. J Neurosurg 107:758–764PubMedCrossRefGoogle Scholar
  35. 35.
    McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM (2001) Chordoma: incidence and survival patterns in the United States, 1973–1995. Cancer Causes Control 12:1–11PubMedCrossRefGoogle Scholar
  36. 36.
    Mehnert F, Beschorner R, Kuker W, Hahn U, Nagele T (2004) Retroclival ecchordosis physaliphora: MR imaging and review of the literature. AJNR 25:1851–1855PubMedGoogle Scholar
  37. 37.
    Miralbell R, Lomax A, Russo M (1997) Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation. Int J Radiat Oncol Biol Phys 38:805–811PubMedCrossRefGoogle Scholar
  38. 38.
    Mirra J, Nelson S, Della Rocca C, Mertens F (2002) Chordoma. In: Fletcher CD, Unni K, Mertens F (eds) Pathology and genetics of tumours of soft tissue and bone. IARC Press, Lyon, pp 316–317Google Scholar
  39. 39.
    Mitchell A, Scheithauer BW, Unni KK, Forsyth PJ, Wold LE, McGivney DJ (1993) Chordoma and chondroid neoplasms of the spheno-occiput. An immunohistochemical study of 41 cases with prognostic and nosologic implications. Cancer 72:2943–2949PubMedCrossRefGoogle Scholar
  40. 40.
    Munzenrider JE, Liebsch NJ (1999) Proton therapy for tumors of the skull base. Strahlenther Onkol 175(Suppl 2):57–63PubMedCrossRefGoogle Scholar
  41. 41.
    Noel G, Habrand JL, Mammar H, Pontvert D, Haie Meder C, Hasboun D et al (2001) Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protontherapie D'Orsay experience. Int J Radiat Oncol Biol Phys 51:392–398PubMedGoogle Scholar
  42. 42.
    Noel G, Habrand JL, Jauffret E, de Crevoisier R, Dederke S, Mammar H et al (2003) Radiation therapy for chordoma and chondrosarcoma of the skull base and the cervical spine: prognostic factors and patterns of failure. Strahlenther Onkol 179:241–248PubMedCrossRefGoogle Scholar
  43. 43.
    Noel G, Feuvret L, Ferrand R, Boisserie G, Mazeron JJ, Habrand JL (2004) Radiotherapeutic factors in the management of cervical–basal chordomas and chondrosarcomas. Neurosurgery 55:1252–1260, discussion 1260–1262PubMedGoogle Scholar
  44. 44.
    Noel G, Feuvret L, Calugaru V, Dhermain F, Mammar H, Haie Meder C et al (2005) Chordomas of the base of the skull and upper cervical spine. One hundred patients irradiated by a 3D conformal technique combining photon and proton beams. Acta oncol 44:700–708PubMedCrossRefGoogle Scholar
  45. 45.
    O'Connell JX, Renard LG, Liebsch NJ, Efird JT, Munzenrider JE, Rosenberg AE (1994) Base of skull chordoma. A correlative study of histologic and clinical features of 62 cases. Cancer 74:2261–2267PubMedCrossRefGoogle Scholar
  46. 46.
    Pallini R, Maira G, Pierconti F, Falchetti ML, Alvino E, Cimino Reale G et al (2003) Chordoma of the skull base: predictors of tumor recurrence. J Neurosurg 98:812–822PubMedCrossRefGoogle Scholar
  47. 47.
    Pamir MN, Kilic T, Ture U, Ozek MM (2004) Multimodality management of 26 skull-base chordomas with 4-year mean follow-up: experience at a single institution. Acta Neurochir Wien 146:343–354PubMedCrossRefGoogle Scholar
  48. 48.
    Pearlman AW, Friedman M (1970) Radical radiation therapy of chordoma. Acta oncol 108:332–341Google Scholar
  49. 49.
    Raffel C, Wright DC, Gutin PH, Wilson CB (1985) Cranial chordomas: clinical presentation and results of operative and radiation therapy in twenty-six patients. Neurosurgery 17:703–710PubMedCrossRefGoogle Scholar
  50. 50.
    Rich TA, Schiller A, Suit HD, Mankin HJ (1985) Clinical and pathologic review of 48 cases of chordoma. Cancer 56:182–187PubMedCrossRefGoogle Scholar
  51. 51.
    Samii A, Gerganov VM, Herold C, Hayashi N, Naka T, Mirzayan MJ et al (2007) Chordomas of the skull base: surgical management and outcome. J Neurosurg 107:319–324PubMedCrossRefGoogle Scholar
  52. 52.
    Schonegger K, Gelpi E, Prayer D, Dieckmann K, Matula C, Hassler M et al (2005) Recurrent and metastatic clivus chordoma: systemic palliative therapy retards disease progression. Anticancer Drugs 16:1139–1143PubMedCrossRefGoogle Scholar
  53. 53.
    Sekhar LN, Pranatartiharan R, Chanda A, Wright DC (2001) Chordomas and chondrosarcomas of the skull base: results and complications of surgical management. Neurosurg Focus 10:E2PubMedCrossRefGoogle Scholar
  54. 54.
    Sen C, Triana A (2001) Cranial chordomas: results of radical excision. Neurosurg Focus 10:E3PubMedCrossRefGoogle Scholar
  55. 55.
    Suit HD, Goitein M, Munzenrider J, Verhey L, Davis KR, Koehler A et al (1982) Definitive radiation therapy for chordoma and chondrosarcoma of base of skull and cervical spine. J Neurosurg 56:377–385PubMedCrossRefGoogle Scholar
  56. 56.
    Tamaki N, Nagashima T, Ehara K, Motooka Y, Barua KK (2001) Surgical approaches and strategies for skull base chordomas. Neurosurg Focus 10:E9PubMedCrossRefGoogle Scholar
  57. 57.
    Torres MA, Chang EL, Mahajan A, Lege DG, Riley BA, Zhang X et al (2009) Optimal treatment planning for skull base chordoma: photons, protons, or a combination of both? Int J Radiat Oncol Biol Phys 74:1033–1039PubMedCrossRefGoogle Scholar
  58. 58.
    Tzortzidis F, Elahi F, Wright D, Natarajan SK, Sekhar LN (2006) Patient outcome at long-term follow-up after aggressive microsurgical resection of cranial base chordomas. Neurosurgery 59:230–237PubMedCrossRefGoogle Scholar
  59. 59.
    Wei J, Sandison GA, Hsi WC, Ringor M, Lu X (2006) Dosimetric impact of a CT metal artefact suppression algorithm for proton, electron and photon therapies. Acta oncol 51:5183–5197Google Scholar
  60. 60.
    Yoneoka Y, Tsumanuma I, Fukuda M, Tamura T, Morii K, Tanaka R et al (2008) Cranial base chordoma—long term outcome and review of the literature. Acta Neurochir (Wien) 150:773–778CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Muneyoshi Yasuda
    • 1
    • 5
  • Damien Bresson
    • 1
  • Salvatore Chibbaro
    • 1
  • Jan F. Cornelius
    • 1
  • Marc Polivka
    • 2
  • Loic Feuvret
    • 3
    • 4
  • Masakazu Takayasu
    • 5
  • Bernard George
    • 1
  1. 1.Department of NeurosurgeryLariboisiere Hospital (AP-HP)ParisFrance
  2. 2.Department of PathologyLariboisiere Hospital (AP-HP)ParisFrance
  3. 3.Department of RadiotherapyPitie Salpetriere Hospital (AP-HP)ParisFrance
  4. 4.Institute CurieProtontherapy Center of OrsayOrsayFrance
  5. 5.Department of NeurosurgeryAichi Medical UniversityNagakuteJapan

Personalised recommendations