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 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 T₁-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 T₂ abnormalities after treatment. Two patients underwent resection for suspected recurrence.

Results

The median pretreatment magnetic resonance imaging T₁C and T₂ volume was 40.9 and 184.1 cm³, 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 T₂ 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 T₂ volumes after the combination of SRS and epidermal growth factor receptor inhibition. The tissue changes were consistent with a potent treatment effect.

Stereotactic radiosurgery, SRS, Recurrent glioma, Malignant glioma, Radiotherapy