CT Perfusion Imaging as an Early Biomarker of Differential Response to Stereotactic Radiosurgery in C 6 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 nonresponders was possible using CT perfusion imaging. Validation of CT perfusion indices for response assessment is necessary before clinical implementation. Citation: Yeung TPC, Kurdi M, Wang Y, Al-Khazraji B, Morrison L, et al. (2014) CT Perfusion Imaging as an Early Biomarker of Differential Response to Stereotactic Radiosurgery in C6 Rat Gliomas. PLoS ONE 9(10): e109781. doi:10.1371/journal.pone. 0109781 Editor: Qinghui Zhang, University of Nebraska Medical Center, United States of America Received July 7, 2014; Accepted September 2, 2014; Published October 17, 2014 Copyright: 2014 Yeung et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files. Funding: This project was funded by the Brain Tumour Foundation of Canada, the Canadian Institutes of Health Research (T.P.C.Y.), and the Canadian Institutes of Health Research Strategic Training Program in Cancer Research and Technology Transfer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The author Dr. Ting-Yim Lee licences CT Perfusion software to and receives funding from GE Healthcare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. * Email: timothy.pokchi. yeung@gmail.com