title: Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study.
abstract: OBJECTIVE
  This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT).
  
  
  METHODS
  Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (> or = 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9-60 months). Six patients remained alive for 3 to 60 months.
  
  
  CONCLUSIONS
  The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.
authors.affiliation: Department of Radiation Medicine, University of Kentucky Medical Center, Lexington 40536-0293, USA. wilregi@pop.uky.edu
authors.forename: W F
authors.initials: WF
authors.lastname: Regine
authors.forename: R A
authors.initials: RA
authors.lastname: Patchell
authors.forename: J M
authors.initials: JM
authors.lastname: Strottmann
authors.forename: A
authors.initials: A
authors.lastname: Meigooni
authors.forename: M
authors.initials: M
authors.lastname: Sanders
authors.forename: B
authors.initials: B
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery; D012086:Reoperation