Predictors of Acute Urinary Flare Following Stereotactic Body Radiation Therapy (SBRT) in the Definitive Treatment of Localized Prostate Cancer

S180 responders at the third time point due to tumor regression. For partial responders, the mean change in Ktrans and Kep in the tumor at 3-4 months after treatment relative to the second time point was 45% and 100%, respectively. The corresponding change in nodal masses was -7% and -18%, respectively. Conclusion: The DCE-MRI pharmacokinetic parameters from primary tumor and nodal masses showed different trends between responders and partial responders group at different time points. These preliminary results suggest that pharmacokinetic parameters not only from different areas, but also those at different time points, can be used as a marker for prediction and early detection of response to concurrent chemoradiation therapy in head and neck cancer. Author Disclosure: Y. Liu: None. T. Diwanji: None. B. Zhang: None. J. Zhuo: None. R. Gullapalli: None. R. Morales: None. W.D. D’Souza: None.

1056 Treating Glioblastoma Multiforme as a Chronic Disease: Mathematical Dose Fractionation Schedule Optimization and Modeling With Cancer Stem Cell Dynamics V.Y. Yu, D. Nguyen, F. Pajonk, T.B. Kaprealian, P.A. Kupelian, M.L. Steinberg, D. Low, and K. Sheng; University of California, Los Angeles, Los Angeles, CA Purpose/Objective(s): Previously developed ordinary differential equations (ODE) that model the dynamic interaction and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC) have predicted and possibly explained the definitive GBM treatment failure with conventional, hypo or accelerated fractionation schedules. In this study, we used this approach to explore the feasibility of improving GBM treatment outcome via optimization of the fractionation with the option of protracted treatment schedules. Materials/Methods: The ODE dynamics system was formulated into a non-convex optimization problem with the objective to minimize remaining tumor cells 500 days from the onset of radiation therapy, while maintaining the maximal normal tissue biological effective dose (BED) of 100 Gy. The GBM growth and radiation therapy cell killing parameters are shown in Table 1, where the radiological parameters of the CSC and DCC compartments were determined via curve fitting based on published GBM cell survival data. Optimization of the dose fractions were performed with varying regular time schedules that span over one year, including daily (weekdays), weekly, biweekly, and monthly to explore the potential in delaying recurrence with a chronic treatment scenario. The recurrence time points were determined as the time at which the total cell numbers regrow to 109cells and compared against the standard treatment schedule of 2 GyX30. Results: For the daily, weekly, biweekly, and monthly time schedules, the recurrence time points were found to be 659, 615, 593 and 570 days, respectively, significantly delayed compared with the standard schedule recurrence time of 418 days. For all time schedules, the optimal dose fraction size progression was at a low and relatively constant value in the beginning and a gradual increase to more aggressive fractions at the end of the treatment course. For the daily, weekly, biweekly, and monthly time schedules the optimized dose fraction ranges were [0.26 1.9], [1.03 4.87], [1.67 6.31] and [2.77 7.84] Gy, respectively. Conclusion: Chronic radiation therapy treatment schedules have been explored through modeling and optimization of a dual compartment cancer stem cell dynamics model that predicts definitive treatment failure in GBM. It has been shown that the optimized prolonged treatment schedule may significantly delay GBM recurrence up to 241 days compared to the standard treatment schedule. The logistically more practical weekly, biweekly or monthly treatments may also provide considerable recurrence delay benefit. This study indicates a completely new direction of GBM treatment by using significantly lower overall dose rates that resemble maintenance chemotherapy of the disease.

International Journal of Radiation Oncology  Biology  Physics ePoster Abstracts 1056; Table 1

CSC and DCC Simulation Parameters

Potential Doubling time (days)

CSC fraction

aCSC

bCSC

aDCC bDCC tissue a/b

3.9

50%

0.01

1.8e-7

0.12

Normal

0.03

3

Author Disclosure: V.Y. Yu: None. D. Nguyen: None. F. Pajonk: None. T.B. Kaprealian: None. P.A. Kupelian: None. M.L. Steinberg: None. D. Low: None. K. Sheng: None.

1057 Predictors of Acute Urinary Flare Following Stereotactic Body Radiation Therapy (SBRT) in the Definitive Treatment of Localized Prostate Cancer M.C. Repka, T.P. Kole, B. Wu, S. Lei, S. Suy, A. Dritschilo, and S.P. Collins; Georgetown University Hospital, Washington, DC Purpose/Objective(s): Clinical studies have demonstrated an association between genitourinary toxicity and dose to critical genitourinary structures in patients treated with brachytherapy and external beam radiation therapy (EBRT) for prostate cancer. The purpose of this study was to identify patient related and dosimetric predictors of acute urinary flare in a prospective cohort of patients undergoing stereotactic body radiation therapy (SBRT) for localized prostate cancer. Materials/Methods: One hundred three men were treated definitively for localized prostate cancer using robotic SBRT on a prospective institutional protocol. The planning target volume (PTV) consisted of the prostate and proximal seminal vesicles as defined on non-contrast CT and fused T2 MRI with a 3 mm margin at the prostate-bladder interface. Inverse plans were generated with a prescription dose (PD) of 35 to 36.25 Gy in 5 fractions to the PTV using 6 MV photons. Patients who were not already using alpha-receptor antagonists were prophylactically treated with tamsulosin. Patient surveys including the International Prostate Symptom Score (IPSS) were conducted before and one week following the completion of SBRT. Cumulative and differential dose-volume histograms (DVHs) were created for the bladder, bladder wall, bladder neck, and prostatic urethra. Acute urinary flare was defined as an increase in IPSS of 5 points or more with an absolute score of at least 15 points. Results: Twenty-one point four percent of patients experienced acute urinary flare one week following completion of prostate SBRT. Dosevolume cut-off analysis was performed in order to identify statistically significant predictors of acute urinary flare. Univariate regression analysis of patient-related and dosimetric parameters demonstrated that prostatic volume and bladder wall D15.5% were significant predictors of acute urinary flare. Multivariate regression analysis confirmed both prostatic volume and bladder wall D15.5% as significant independent predictors of urinary flare, with a median split prostate volume of 36 cm3 resulting in an 11.8% versus 37.2% incidence of acute flare and a median split dose to the hottest 15.5% of bladder wall of 32.6 Gy resulting in a 9.8% versus 34.6% incidence of acute flare. No dosimetric parameters of the bladder, bladder neck, or prostatic urethra were significantly associated with increased toxicity. Conclusion: Dose-volume histogram analysis of acute urinary toxicity identified that the bladder wall D15.5%, in addition to prostate volume, is a significant predictor of acute urinary flare in patients treated with SBRT for prostate cancer. The consequential effects of acute urinary flare in this prospective cohort of patients treated with prostate SBRT in terms of late urinary toxicity warrants further investigation. Author Disclosure: M.C. Repka: None. T.P. Kole: None. B. Wu: None. S. Lei: None. S. Suy: None. A. Dritschilo: None. S.P. Collins: Consultant; Accuray.

1058 Mean-clustered ADC Metrics for Assessing Treatment Response in Glioblastoma A. Chu, T. Yanagihara, K. Cauley, and T.J. Wang; Columbia University Medical Center, New York, NY