A Monte Carlo simulation tool to analyze breast cancer trial outcomes: application to FAST-Forward trial

BACKGROUND: FAST-Forward trial has established the characteristics of 5-fraction breast cancer treatments that produce the same local cancer control as the standard 15-fraction schedule, while maintaining its safety level. Aim: To adapt a Monte Carlo simulation tool, previously used to study the surgery-to-radiotherapy delay effect on head and neck tumor control, to simulate breast cancer trials and apply it to reproduce FAST-Forward trial outcomes. Methods: The updated Monte Carlo tool incorporates the linear-quadratic model for estimating the cell survival fraction for different dose fractions, as well as a component that simulates tumor bed boost. Model parameters have been evaluated for the three FAST-Forward trial arms. Results: The importance of the number of patients in the samples and the role played by the tumor bed boost have been studied. Sample size is a key factor, as the actual number of patients in the trial generates uncertainties that may explain the paradox that the 26 Gy regimen may be more effective in terms of tumor control than the 27 Gy regimen. The boost model implemented has showed up as a consistent and robust procedure to simulate the empirical situation. Conclusions: The Monte Carlo tool provides a good description of the trends observed in the trial, making it a very powerful tool for investigating the characteristics of any treatment regimen. The actual number of patients in the FAST-Forward trial appears to be insufficient to draw general conclusions about the capabilities of each of the arms studied.