Neurosurgical Review

, Volume 32, Issue 4, pp 417–424 | Cite as

Survival following stereotactic radiosurgery for newly diagnosed and recurrent glioblastoma multiforme: a multicenter experience

  • Alan T. Villavicencio
  • Sigita Burneikienė
  • Pantaleo Romanelli
  • Laura Fariselli
  • Lee McNeely
  • John D. Lipani
  • Steven D. Chang
  • E. Lee Nelson
  • Melinda McIntyre
  • Giovanni Broggi
  • John R. AdlerJr.
Original Article


Despite decades of clinical trials investigating new treatment modalities for glioblastoma multiforme (GBM), there have been no significant treatment advances since the 1980s. Reported median survival times for patients with GBM treated with current modalities generally range from 9 to 19 months. The purpose of the current study is to retrospectively review the ability of CyberKnife® (Accuray Incorporated, Sunnyvale, CA, USA) radiosurgery to provide local tumor control of newly diagnosed or recurrent GBM. Twenty patients (43.5 %) underwent CyberKnife treatment at the time of the initial diagnosis and/or during the first 3 months of their initial clinical management. Twenty-six patients (56.5%) were treated at the time of tumor recurrence or progression. CyberKnife was performed in addition to the traditional therapy. The median survival from diagnosis for the patients treated with CyberKnife as an initial clinical therapy was 11.5 months (range, 2–33) compared to 21 months (range, 8–96) for the patients treated at the time of tumor recurrence/progression. This difference was statistically significant (Kaplan–Meier analysis, P = 0.0004). The median survival from the CyberKnife treatment was 9.5 months (range, 0.25–31 months) and 7 months (range, 1–34 months) for patients in the newly diagnosed and recurrent GBM groups (Kaplan–Meier analysis, P = 0.79), respectively. Cox proportional hazards survival regression analysis demonstrated that survival time did not correlate significantly with treatment parameters (D max, D min, number of fractions) or target volume. Survival time and recursive partitioning analysis class were not correlated (P = 0.07). Patients with more extensive surgical interventions survived longer (P = 0.008), especially those who underwent total tumor resection vs. biopsy (P = 0.004). There is no apparent survival advantage in using CyberKnife in initial management of glioblastoma patients, and it should be reserved for patients whose tumors recur or progress after conventional therapy.


Brain tumors Cyberknife radiosurgery Glioblastoma multiforme Multicenter study Stereotactic radiosurgery Survival 



This work was supported by the CyberKnife Society and Justin Parker Neurosurgical Research Fund.


  1. 1.
    Adler JR Jr, Murphy MJ, Chang SD, Hancock SL (1999) Image-guided robotic radiosurgery. Neurosurgery 44:1299–1306 discussion 1306–1297PubMedCrossRefGoogle Scholar
  2. 2.
    Ammirati M, Galicich JH, Arbit E, Liao Y (1987) Reoperation in the treatment of recurrent intracranial malignant gliomas. Neurosurgery 21:607–614PubMedCrossRefGoogle Scholar
  3. 3.
    Burger PC, Heinz ER, Shibata T, Kleihues P (1988) Topographic anatomy and CT correlations in the untreated glioblastoma multiforme. J Neurosurg 68:698–704PubMedCrossRefGoogle Scholar
  4. 4.
    Burger PC, Dubois PJ, Schold SC Jr, Smith KR Jr, Odom GL, Crafts DC, Giangaspero F (1983) Computerized tomographic and pathologic studies of the untreated, quiescent, and recurrent glioblastoma multiforme. J Neurosurg 58:159–169PubMedCrossRefGoogle Scholar
  5. 5.
    Chan AA, Lau A, Pirzkall A, Chang SM, Verhey LJ, Larson D, McDermott MW, Dillon WP, Nelson SJ (2004) Proton magnetic resonance spectroscopy imaging in the evaluation of patients undergoing gamma knife surgery for grade IV glioma. J Neurosurg 101:467–475PubMedCrossRefGoogle Scholar
  6. 6.
    Chang CN, Chen WC, Wei KC, Ng SH, Ho YS, Huang DY, Lee SP, Hong JH (2003) High-dose-rate stereotactic brachytherapy for patients with newly diagnosed glioblastoma multiformes. J Neurooncol 61:45–55PubMedCrossRefGoogle Scholar
  7. 7.
    Chang SD, Adler JR (2001) Robotics and radiosurgery—the cyberknife. Stereotact Funct Neurosurg 76:204–208PubMedCrossRefGoogle Scholar
  8. 8.
    Cho KH, Hall WA, Gerbi BJ, Higgins PD, McGuire WA, Clark HB (1999) Single dose versus fractionated stereotactic radiotherapy for recurrent high-grade gliomas. Int J Radiat Oncol Biol Phys 45:1133–1141PubMedCrossRefGoogle Scholar
  9. 9.
    Ciric I, Vick NA, Mikhael MA, Cozzens J, Eller T, Walsh A (1990) Aggressive surgery for malignant supratentorial gliomas. Clin Neurosurg 36:375–383PubMedGoogle Scholar
  10. 10.
    Collins SP, Coppa ND, Zhang Y, Collins BT, McRae DA, Jean WC (2006) CyberKnife(R) radiosurgery in the treatment of complex skull base tumors: analysis of treatment planning parameters. Radiat Oncol 1:46PubMedCrossRefGoogle Scholar
  11. 11.
    Curran WJ Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE, Nelson DF (1993) Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst 85:704–710PubMedCrossRefGoogle Scholar
  12. 12.
    Deorah S, Lynch CF, Sibenaller ZA, Ryken TC (2006) Trends in brain cancer incidence and survival in the United States: surveillance, epidemiology, and end results program, 1973 to 2001. Neurosurg Focus 20:E1PubMedCrossRefGoogle Scholar
  13. 13.
    Fiveash JB, Spencer SA (2003) Role of radiation therapy and radiosurgery in glioblastoma multiforme. Cancer J 9:222–229PubMedCrossRefGoogle Scholar
  14. 14.
    Gannett D, Stea B, Lulu B, Adair T, Verdi C, Hamilton A (1995) Stereotactic radiosurgery as an adjunct to surgery and external beam radiotherapy in the treatment of patients with malignant gliomas. Int J Radiat Oncol Biol Phys 33:461–468PubMedGoogle Scholar
  15. 15.
    Halperin EC, Bentel G, Heinz ER, Burger PC (1989) Radiation therapy treatment planning in supratentorial glioblastoma multiforme: an analysis based on post mortem topographic anatomy with CT correlations. Int J Radiat Oncol Biol Phys 17:1347–1350PubMedGoogle Scholar
  16. 16.
    Hentschel SJ, Sawaya R (2003) Optimizing outcomes with maximal surgical resection of malignant gliomas. Cancer Control 10:109–114PubMedGoogle Scholar
  17. 17.
    Hochberg FH, Pruitt A (1980) Assumptions in the radiotherapy of glioblastoma. Neurology 30:907–911PubMedGoogle Scholar
  18. 18.
    Hsieh PC, Chandler JP, Bhangoo S, Panagiotopoulos K, Kalapurakal JA, Marymont MH, Cozzens JW, Levy RM, Salehi S (2005) Adjuvant gamma knife stereotactic radiosurgery at the time of tumor progression potentially improves survival for patients with glioblastoma multiforme. Neurosurgery 57:684–692 discussion 684–692PubMedCrossRefGoogle Scholar
  19. 19.
    Hulshof MC, Koot RW, Schimmel EC, Dekker F, Bosch DA, Gonzalez Gonzalez D (2001) Prognostic factors in glioblastoma multiforme. 10 years experience of a single institution. Strahlenther Onkol 177:283–290PubMedCrossRefGoogle Scholar
  20. 20.
    Kelly PJ, Daumas-Duport C, Scheithauer BW, Kall BA, Kispert DB (1987) Stereotactic histologic correlations of computed tomography- and magnetic resonance imaging-defined abnormalities in patients with glial neoplasms. Mayo Clin Proc 62:450–459PubMedGoogle Scholar
  21. 21.
    Kondziolka D, Flickinger JC, Bissonette DJ, Bozik M, Lunsford LD (1997) Survival benefit of stereotactic radiosurgery for patients with malignant glial neoplasms. Neurosurgery 41:776–783 discussion 783–775PubMedCrossRefGoogle Scholar
  22. 22.
    Lunsford LD, Martinez AJ, Latchaw RE (1986) Magnetic resonance imaging does not define tumor boundaries. Acta Radiol Suppl 369:154–156PubMedGoogle Scholar
  23. 23.
    Mahajan A, McCutcheon IE, Suki D, Chang EL, Hassenbusch SJ, Weinberg JS, Shiu A, Maor MH, Woo SY (2005) Case-control study of stereotactic radiosurgery for recurrent glioblastoma multiforme. J Neurosurg 103:210–217PubMedCrossRefGoogle Scholar
  24. 24.
    Masciopinto JE, Levin AB, Mehta MP, Rhode BS (1995) Stereotactic radiosurgery for glioblastoma: a final report of 31 patients. J Neurosurg 82:530–535PubMedGoogle Scholar
  25. 25.
    McDermott MW, Berger MS, Kunwar S, Parsa AT, Sneed PK, Larson DA (2004) Stereotactic radiosurgery and interstitial brachytherapy for glial neoplasms. J Neurooncol 69:83–100PubMedCrossRefGoogle Scholar
  26. 26.
    Miwa K, Shinoda J, Yano H, Okumura A, Iwama T, Nakashima T, Sakai N (2004) Discrepancy between lesion distributions on methionine PET and MR images in patients with glioblastoma multiforme: insight from a PET and MR fusion image study. J Neurol Neurosurg Psychiatry 75:1457–1462PubMedCrossRefGoogle Scholar
  27. 27.
    Nieder C, Grosu AL, Astner S, Molls M (2005) Treatment of unresectable glioblastoma multiforme. Anticancer Res 25:4605–4610PubMedGoogle Scholar
  28. 28.
    Nieder C, Andratschke N, Wiedenmann N, Busch R, Grosu AL, Molls M (2004) Radiotherapy for high-grade gliomas. Does altered fractionation improve the outcome? Strahlenther Onkol 180:401–407PubMedCrossRefGoogle Scholar
  29. 29.
    Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartmann C, McLaughlin ME, Batchelor TT, Black PM, von Deimling A, Pomeroy SL, Golub TR, Louis DN (2003) Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 63:1602–1607PubMedGoogle Scholar
  30. 30.
    Nwokedi EC, DiBiase SJ, Jabbour S, Herman J, Amin P, Chin LS (2002) Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme. Neurosurgery 50:41–46 discussion 46–47PubMedCrossRefGoogle Scholar
  31. 31.
    Patwardhan RV, Shorter C, Willis BK, Reddy P, Smith D, Caldito GC, Nanda A (2004) Survival trends in elderly patients with glioblastoma multiforme: resective surgery, radiation, and chemotherapy. Surg Neurol 62:207–213 discussion 214–205PubMedCrossRefGoogle Scholar
  32. 32.
    Rich JN, Hans C, Jones B, Iversen ES, McLendon RE, Rasheed BK, Dobra A, Dressman HK, Bigner DD, Nevins JR, West M (2005) Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res 65:4051–4058PubMedCrossRefGoogle Scholar
  33. 33.
    Roberge D, Souhami L (2003) Stereotactic radiosurgery in the management of intracranial gliomas. Technol Cancer Res Treat 2:117–125PubMedGoogle Scholar
  34. 34.
    Salcman M (1980) Survival in glioblastoma: historical perspective. Neurosurgery 7:435–439PubMedCrossRefGoogle Scholar
  35. 35.
    Sarkaria JN, Mehta MP, Loeffler JS, Buatti JM, Chappell RJ, Levin AB, Alexander E III, Friedman WA, Kinsella TJ (1995) Radiosurgery in the initial management of malignant gliomas: survival comparison with the RTOG recursive partitioning analysis. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 32:931–941PubMedCrossRefGoogle Scholar
  36. 36.
    Sathornsumetee S, Rich JN (2006) New treatment strategies for malignant gliomas. Expert Rev Anticancer Ther 6:1087–1104PubMedCrossRefGoogle Scholar
  37. 37.
    Scott CB, Scarantino C, Urtasun R, Movsas B, Jones CU, Simpson JR, Fischbach AJ, Curran WJ Jr (1998) Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06. Int J Radiat Oncol Biol Phys 40:51–55PubMedCrossRefGoogle Scholar
  38. 38.
    Shrieve DC, Alexander E III, Black PM, Wen PY, Fine HA, Kooy HM, Loeffler JS (1999) Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome. J Neurosurg 90:72–77PubMedCrossRefGoogle Scholar
  39. 39.
    Silbergeld DL, Rostomily RC, Alvord EC Jr (1991) The cause of death in patients with glioblastoma is multifactorial: clinical factors and autopsy findings in 117 cases of supratentorial glioblastoma in adults. J Neurooncol 10:179–185PubMedCrossRefGoogle Scholar
  40. 40.
    Simon M, Ludwig M, Fimmers R, Mahlberg R, Muller-Erkwoh A, Koster G, Schramm J (2006) Variant of the CHEK2 gene as a prognostic marker in glioblastoma multiforme. Neurosurgery 59:1078–1085 discussion 1085PubMedGoogle Scholar
  41. 41.
    Souhami L, Seiferheld W, Brachman D, Podgorsak EB, Werner-Wasik M, Lustig R, Schultz CJ, Sause W, Okunieff P, Buckner J, Zamorano L, Mehta MP, Curran WJ Jr (2004) Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys 60:853–860PubMedGoogle Scholar
  42. 42.
    Stieber VW, Bourland JD, Tome WA, Mehta MP (2003) Gentlemen (and ladies), choose your weapons: Gamma knife vs. linear accelerator radiosurgery. Technol Cancer Res Treat 2:79–86PubMedGoogle Scholar
  43. 43.
    Vordermark D, Kolbl O, Ruprecht K, Vince GH, Bratengeier K, Flentje M (2005) Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma. BMC Cancer 5:55PubMedCrossRefGoogle Scholar
  44. 44.
    Wallner KE, Galicich JH, Krol G, Arbit E, Malkin MG (1989) Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys 16:1405–1409PubMedGoogle Scholar
  45. 45.
    Yu C, Jozsef G, Apuzzo ML, Petrovich Z (2003) Dosimetric comparison of CyberKnife with other radiosurgical modalities for an ellipsoidal target. Neurosurgery 53:1155–1162 discussion 1162–1153PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Alan T. Villavicencio
    • 1
  • Sigita Burneikienė
    • 1
  • Pantaleo Romanelli
    • 2
    • 3
  • Laura Fariselli
    • 4
  • Lee McNeely
    • 5
  • John D. Lipani
    • 2
  • Steven D. Chang
    • 2
  • E. Lee Nelson
    • 1
  • Melinda McIntyre
    • 5
  • Giovanni Broggi
    • 4
  • John R. AdlerJr.
    • 2
  1. 1.Boulder Neurosurgical AssociatesBoulderUSA
  2. 2.Department of Neurosurgery, School of MedicineStanford UniversityStanfordUSA
  3. 3.Department of NeurosurgeryNeuromed IRCCSPozilliItaly
  4. 4.Department of NeurosurgeryBesta Neurological InstituteMilanItaly
  5. 5.Rocky Mountain CyberKnife CenterBoulderUSA

Personalised recommendations