Dose-Response Prediction for SBRT of Prostate Cancer Based on Measured Cell Survival Curves Using a Unified Multi-Activation Model

Abstract

<h3>Purpose/Objective(s)</h3> Hypofractionated external beam radiotherapy with 10 to 30 fractions (fx) and stereotactic body radiation therapy (SBRT) for prostate cancer (PC) have similar rates of cancer control and toxicity at 5 years as compared to conventional treatment. There is a lack of a radiobiological modeling from lab experiments to guide this transition. By assuming a unified multi-activation (UMA) model of lab-measured radiosensitivity (RS) of the cell lines to the entire dose range, we explored the clinical dose-response, modeling tumor-control probability (TCP) and normal-tissue complication probability (NTCP). <h3>Materials/Methods</h3> Published cell survival curves (CSC) with experimental error bars for PC of 5 DU145 CSCs, 3 CP3 CSCs, 6 LNCaP + 2 LnCaP with BCL2 overexpressed or down-regulated CSCs, 3 wild-type (WT)-22RV1 CSCs, 3 post-radiation radioresistant (RR)-22RV1 CSCs, 2 hypoxia-22RV1 CSCs, 3 urothelial HCV-29 CSCs and 4 large intestine (LI) or small intestine (SI) stem cell and organoid CSCs were fitted with a UMA model by using a logit transformation and c²-regression to obtain the model parameters of g and n and their deviations. Cell survival at any fractional dose (=total dose/fx) and TCP and NTCP for the total number of cancer cells or normal tissue cells corresponding to a grade of toxicity were analytically determined from the parameters. <h3>Results</h3> All of the CSCs had been excellently fitted with R² > 0.95 and Q-factor > 0.2 excepting for two in-vivo LI/SI crypt CSCs each with an outline point. We identified radiobiological parameters and predicted TCP/NTCP curves and listed the data for the 8Gyx5 SBRT of PC in Table 1 that are comparable with the results listed in the HyTEC papers. The 0% TCP to RR or hypoxia PC and 100% NTCP to SI are similar to conventional EBRT. The Dg reflects the major uncertainties in the lab-measured RS. D50, the total dose at 50% TCP or NTCP, correlated with RS and number of cells. Cell heterogeneity greatly changed RS and shapes of TCP and NTCP curves. <h3>Conclusion</h3> These findings may be useful for the design and evaluation of new clinical treatment schemes in PC translating lab work into clinical application.