The Impact of Different Timing Schedules on Prostate HDR-Mono-Brachytherapy. A TCP Modeling Investigation

SIMPLE SUMMARY: Reported clinical data on high dose rate mono brachytherapy of prostate cancer carried out using two different treatment regimens are analyzed in this study. The analysis is based on a mechanistic tumor control probability model, which accounts for a possible increase in the tumor radio-sensitivity during treatment. The aim of the study was to verify a hypothesis that the clinically observed better performance of the longer treatment regimen (28 days vs. 14 days) might be due to a state of initial hypoxia and its ensued overcoming by re-oxygenation and, hence, re-sensitization of the prostate cancer. The performed investigation confirmed the assumption of initially hypoxic stage of the tumor followed by its re-sensitization, thus providing a foundation for the use of prolonged schedules for low- to intermediate-risk prostate cancer treatment. ABSTRACT: Background: Mechanistic TCP (tumor control probability) models exist that account for possible re-sensitization of an initially hypoxic tumor during treatment. This phenomenon potentially explains the better outcome of a 28-day vs 14-day treatment schedule of HDR (high dose rate) brachytherapy of low- to intermediate-risk prostate cancer as recently reported. Methods: A TCP model accounting for tumor re-sensitization developed earlier is used to analyze the reported clinical data. In order to analyze clinical data using individual TCP model, TCP distributions are constructed assuming inter-individual spread in radio-sensitivity. Results: Population radio-sensitivity parameter values are found that result in TCP population values which are close to the reported ones. Using the estimated population parameters, two hypothetical regimens are investigated that are shorter than the ones used clinically. The impact of the re-sensitization rate on the calculated treatment outcome is also investigated as is the anti-hypothesis that there is no re-sensitization during treatment. Conclusions: The carried out investigation shows that the observed clinical data cannot be described without assuming an initially hypoxic state of the tumor followed by re-oxygenation and, hence, re-sensitization. This phenomenon explains the better outcome of the prolonged treatment schedule compared to shorter regimens based on the fact that prostate cancer is a slowly repopulating tumor.