RADIOGRAPHIC AND HISTOPATHOLOGIC OBSERVATIONS AFTER COMBINED EGFR INHIBITION AND HYPOFRACTIONATED STEREOTACTIC RADIOSURGERY IN PATIENTS WITH RECURRENT MALIGNANT GLIOMAS

Purpose: To describe the radiographic and histopathologic changes after stereotactic radiosurgery (SRS) and epidermal growth factor receptor inhibition in patients with recurrent malignant gliomas. Methods and Materials: A total of 15 patients with recurrent high-grade gliomas were treated on a prospective Phase 1 trial combining SRS and gefitinib. The SRS dose was escalated from 18 to 36 Gy in three fractions. The planning target volume was the T-1-weighted contrast-enhancing (T1C) lesion plus 2 mm. Gefitinib was given at 250 mg daily. Serial brain magnetic resonance imaging scans were analyzed to characterize the volumetric changes in the T1C and T-2 abnormalities after treatment. Two patients underwent resection for suspected recurrence. Results: The median pretreatment magnetic resonance imaging T1C and T-2 volume was 40.9 and 184.1 cm(3), respectively. The median post-SRS percentage of increases in the T1C volume at 1, 2-4, and 5-7 months was 8.9%, 41.3%, and 99.6%, respectively. The median percentage increase in the T-2 volume likewise showed a trend upward after SRS, from 18.0% at 1 month to 37.8% at 5-7 months. For the 2 patients who underwent resection after SRS for an increasing T1C volume, the histopathologic analysis revealed therapy-induced vascular injury and necrosis. One patient with an asymptomatic increase in the T1C volume after SRS was treated conservatively. After a peak T1C volume increase at 9 months, the T1C volume had declined to 50% of the maximal volume at 15 months. The patients with the most dramatic increase in T1C volume experienced the longest overall survival. Conclusion: Patients experienced a notable increase in magnetic resonance imaging T1C and T-2 volumes after the combination of SRS and epidermal growth factor receptor inhibition. The tissue changes were consistent with a potent treatment effect. (C) 2009 Elsevier Inc.