Purpose: Our long-term goal is to evaluate early predictors of tumor radiation response. As a first step, the response of 9L orthotopic brain tumors were measured following MRI guided planning of stereotactic radiotherapy (SRS) in order to determine the dose to cure 50%, TCD50.
Methods: 118 Fischer-344 rats were implanted with 105 rat 9L cells in 10 µl using males and females. Tumors either grew untreated or were treated with 20 or 25 Gy to the 95% isodose as follows. Around 8 days post-implantation, rats were imaged with contrast enhanced MRI (MRI-CE) and irradiated using a Small Animal Radiation Research Platform (SARRP) from Xstrahl Inc. (Suwanee, GA) operating at 220 kV and 13 mA with an effective energy of ~70 keV and dose rate of ~2.5 Gy per minute. Rat orientations were assessed using cone-beam CT; tumor locations were co-registered using the MRI-CE images. Treatment planning using MuriPlan software from Xstrahl Inc. allowed delivery of four non-coplanar arcs with an identical isocenter. Rats were monitored daily for physical and behavioral abnormalities. Study endpoints were animal survival at 200 days with no weight loss exceeding 20% of maximum animal weight.
Results: The TCD50 was established from Kaplan-Meier survival analysis as between 20 and 25 Gy. Animals with large tumors assessed from MRI-CE on the day of treatment did not survive long, as expected. For example, tumors >150 mm³ correlated inversely with survival for animals treated with 25 Gy (Wilcoxon Rank Sum test). Cox Proportions-Hazards modeling did not suggest an effect of sex with the caveat of the wide confidence intervals.
Conclusion: The radiation response of orthotopic 9L tumors was characterized using clinically relevant treatment techniques. One future direction is to evaluate the predictive value of pre-treatment vascular measures (blood flow, vascular permeability, etc.) on radiation response.
Funding Support, Disclosures, and Conflict of Interest: Research reported in this publication was also supported by National Cancer Institute of the National Institutes of Health under award number R01-CA218596
Tumor Control, Modeling, Brain