Radiographic and histopathologic observations after combined EGFR inhibition and hypofractionated stereotactic radiosurgery in patients with recurrent malignant gliomas.

Abstract

To describe the radiographic and histopathologic changes after stereotactic radiosurgery (SRS) and epidermal growth factor receptor inhibition in patients with recurrent malignant gliomas. A total of 15 patients with recurrent high-grade gliomas were treated on a prospective Phase I 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 (T(1)C) 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 T(1)C and T(2) abnormalities after treatment. Two patients underwent resection for suspected recurrence. The median pretreatment magnetic resonance imaging T(1)C and T(2) volume was 40.9 and 184.1 cm(3), respectively. The median post-SRS percentage of increases in the T(1)C 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 T(1)C volume, the histopathologic analysis revealed therapy-induced vascular injury and necrosis. One patient with an asymptomatic increase in the T(1)C volume after SRS was treated conservatively. After a peak T(1)C volume increase at 9 months, the T(1)C volume had declined to 50% of the maximal volume at 15 months. The patients with the most dramatic increase in T(1)C volume experienced the longest overall survival. Patients experienced a notable increase in magnetic resonance imaging T(1)C 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.