Linac and Gamma Knife Radiosurgery in the Management of Relapsed Malignant Gliomas

Joseph R. Simpson1, K.M. Rich2, R.E. Drzymala3, D.F. Mullen3, D.B. Mansur3, G.P. Linette4, E.A. Filiput3, M.R. Chicoine2, A. Perry5

1Washington University in St. Louis 2Department of Neurosurgery,Washington University in Saint Louis, St Louis, MO, USA 3Department of Radioation Oncology, Washington University in Saint Louis, St Louis, MO, USA 4Department of Medical Oncology, Washington University in Saint Louis, St Louis, MO, USA 5Department of Pathology. Washington University in Saint Louis, St Louis, MO, USA

Keywords: glioblastoma multiforme, gamma knife, anaplastic astrocytoma, outcome, radiosurgery

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     Malignant gliomas remain largely refractory to radiation therapy in spite of many dose escalation attempts. Whole brain doses of 60 Gy fail to control even microscopic disease and the radiation tolerance of normal brain tissue has limited further dose and volume escalation. Meanwhile most recurrences occur within two centimeters of the original contrast-enhancing mass. 
     We sought to examine the role of radiosurgery in the treatment of relapsed malignant gliomas, where the site of failure to control disease had been demonstrated by a focal recurrence pattern. Might such treatment provide patient benefit?
     Between February, 1989 and June, 2009 126 selected patients with malignant gliomas were treated with stereotactic radiosurgery using a modified linear accelerator or a Leksell Gamma Knife device. The vast majority were treated for recurrent disease following surgery, > 60 Gy partial brain irradiation, and chemotherapy. Patients selected had a unifocal recurrence on MRI imaging with a maximum diameter of < 4.5 cm.
     We evaluated the clinical and imaging records of patients who had radiosurgery.
     The median survival for patients with recurrent anaplastic astrocytomas was 20 months, while that of patients with glioblastoma was 7 months. Toxicity was mild with no cases of symptomatic radionecrosis. In keeping with the apparent focal nature of recurrence, subsequent treatment failure occurred more often locally than at distant sites.
     This was a retrospective study.
     Patients with focal recurrence of malignant glioma may derive significant survival benefit from radiosurgery at relapse with little risk of significant toxicity, particularly with anaplastic astrocytoma. Improvements in overall survival for GBM remains limited by the non-focal nature of recurrence and the degree of radiotherapy and chemotherapy resistance generally encountered.
     The new Gamma Knife Extend device allows fractionated, frameless treatments and shows promise for treating patients with larger recurrences and earlier in the course of relapse.


Project Roles:

J. Simpson (), K. Rich (), R. Drzymala (), D. Mullen (), D. Mansur (), G. Linette (), E. Filiput (), M. Chicoine (), A. Perry ()