CT Perfusion Imaging as an Early Biomarker of Differential Response to Stereotactic Radiosurgery in C6 Rat Gliomas

BACKGROUND The therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT) perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model. METHODS Rats with orthotopic C6 glioma tumors received either mock irradiation (controls, N = 8) or stereotactic radiosurgery (N = 25, 12 Gy in one fraction) delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute CT perfusion and histological changes, and 13 irradiated animals were used to study survival. Irradiated animals with survival >15 days were designated as responders while those with survival ≤15 days were non-responders. Longitudinal CT perfusion imaging was performed at baseline and regularly for eight weeks post-baseline. RESULTS Early signs of radiation-induced injury were observed on histology. There was an overall survival benefit following stereotactic radiosurgery when compared to the controls (log-rank P<0.04). Responders to stereotactic radiosurgery showed lower relative blood volume (rBV), and permeability-surface area (PS) product on day 7 post-stereotactic radiosurgery when compared to controls and non-responders (P<0.05). rBV and PS on day 7 showed correlations with overall survival (P<0.05), and were predictive of survival with 92% accuracy. CONCLUSIONS Response to stereotactic radiosurgery was heterogeneous, and early selection of responders and non-responders was possible using CT perfusion imaging. Validation of CT perfusion indices for response assessment is necessary before clinical implementation.