"leading Edge" Gamma Knife Stereotactic Radiosurgery For Patients With Recurrent Glioblastoma Multiforme: An Update

Keywords: glioblastoma multiforme, image guidance, gamma knife, technique, recurrent disease

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       Glioblastoma multiforme (GBM) spreads along predictable white matter pathways, has a predominantly local pattern of recurrence, and responds uniquely to high-dose radiation. Astrocytes migrate down white matter pathways by projecting invadopodia and expressing proteins capable of breaking down surrounding extracellular matrix. Laboratory data show that large single fraction doses of radiation are more effective than low doses at interfering with the migratory ability of dedifferentiated astrocytes. RTOG 93-05 addressed the radiosurgical treatment of the enhancing nidus of GBM on MRI.
     Our hypothesis is that targeting the local white matter pathways of spread (the “Leading Edge”) may prove more effective in the treatment of GBM.
     Between 3/14/98 and 06/16/08, 41 patients with recurrent GBM, were treated to the FLAIR- or MR Spect-defined “leading edge” with Gamma Knife Radiosurgery (LEGRS). The median age was 56 years and 58% were male. 
     LEGRS took place a median of 4.3 months from original diagnosis, with a range from 2.8 to 24 months. Median Karnofsky performance status (KPS) was 80; all had a KPS > 70. An average volume of 39 cc of leading edge tissue was targeted, using a median dose of 10 Gy (range: 8-12) at the 50% isodose line.
     Median survival from time of recurrence and LEGRS is 12.6 months. With 24 patients deceased (77%), and median follow up of 27.8 months for the seven survivors, median overall survival from diagnosis is 19.3 months and 2 and 3-year survivals of 36% and 19.5% respectively. The rate of clinically significant radionecrosis was 7%.
     This is a retrospective study.
     These results compare favorably to those reported from phase II trials in recurrent malignant gliomas.
     LEGRS may be an effective salvage therapy for patients with recurrent GBM. A prospective multi-center study should follow. Up-front leading edge radiosurgery should also be considered for this disease.


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