Yeung Timothy Pok Chi, Kurdi Maher, Wang Yong, Al-Khazraji Baraa, Morrison Laura, Hoffman Lisa, Jackson Dwayne, Crukley Cathie, Lee Ting-Yim, Bauman Glenn, Yartsev Slav
Department of Medical Biophysics, Western University, London, Ontario, Canada; Robarts Research Institute, Western University, London, Ontario, Canada; London Regional Cancer Program, London, Ontario, Canada.
Department of Pathology, Western University, London, Ontario, Canada; Department of Pathology, King Abdulaziz University, Jeddah, Makkah, Saudi Arabia.
PLoS One. 2014 Oct 17;9(10):e109781. doi: 10.1371/journal.pone.0109781. eCollection 2014.
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.
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.
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.
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.
立体定向放射外科治疗胶质母细胞瘤的疗效尚不清楚，需要一种有效的生物标志物来识别可能从该治疗中获益的患者。本研究在恶性大鼠胶质瘤模型中，研究了计算机断层扫描（CT）灌注成像作为立体定向放射外科治疗反应的早期成像生物标志物的疗效。
原位C6胶质瘤大鼠接受模拟照射（对照组，N = 8）或螺旋断层放疗进行的立体定向放射外科治疗（N = 25，单次剂量12 Gy）。12只接受照射的动物在立体定向放射外科治疗后4天处死，以评估急性CT灌注和组织学变化，13只接受照射的动物用于研究生存情况。生存时间>15天的照射动物被指定为反应者，而生存时间≤15天的为无反应者。在基线时进行纵向CT灌注成像，并在基线后定期进行8周。
组织学观察到放射损伤的早期迹象。与对照组相比，立体定向放射外科治疗后总体生存有获益（对数秩检验P<0.04）。与对照组和无反应者相比，立体定向放射外科治疗的反应者在立体定向放射外科治疗后第7天显示出较低的相对血容量（rBV）和通透表面积（PS）乘积（P<0.05）。第7天的rBV和PS与总体生存相关（P<0.05），并以92%的准确率预测生存情况。
立体定向放射外科治疗的反应存在异质性，使用CT灌注成像可以早期区分反应者和无反应者。在临床应用前，有必要对用于反应评估的CT灌注指标进行验证。
