Development and evaluation of a method for tumor growth simulation in virtual clinical trials of breast cancer screening.

Abstract

Purpose: Image-based analysis of breast tumor growth rate may optimize breast cancer screening and diagnosis by suggesting optimal screening intervals and guide the clinical discussion regarding personalized screening based on tumor aggressiveness. Simulation-based virtual clinical trials (VCTs) can be used to evaluate and optimize medical imaging systems and design clinical trials. This study aimed to simulate tumor growth over multiple screening rounds. Approach: This study evaluates a preliminary method for simulating tumor growth. Clinical data on tumor volume doubling time (TVDT) was used to fit a probability distribution ("clinical fit") of TVDTs. Simulated tumors with TVDTs sampled from the clinical fit were inserted into 30 virtual breasts ("simulated cohort") and used to simulate mammograms. Based on the TVDT, two successive screening rounds were simulated for each virtual breast. TVDTs from clinical and simulated mammograms were compared. Tumor sizes in the simulated mammograms were measured by a radiologist in three repeated sessions to estimate TVDT. Results: The mean TVDT was 297days (standard deviation, SD, 169days) in the clinical fit and 322days (SD, 217days) in the simulated cohort. The mean estimated TVDT was 340days (SD, 287days). No significant difference was found between the estimated TVDTs from simulated mammograms and clinical TVDT values ( ). No significant difference ( ) was observed in the reproducibility of the tumor size measurements between the two screening rounds. Conclusions: The proposed method for tumor growth simulation has demonstrated close agreement with clinical results, supporting potential use in VCTs of temporal breast imaging.