Discipline: Mathematics and Statistics
Subcategory: Cancer Research
Room: Exhibit Hall
Alexandria Johnson - University of South Florida
Co-Author(s): Renee Brady-Nicholls, H. Lee Moffitt Cancer Center, Tampa, Florida
Background: Black men have the highest prostate cancer (PCa) mortality across all US population groups. We hypothesize that this may be the result of limited health care access, poverty, and low participation from black men in clinical trials. We use a simple mathematical model to investigate differences in PSA dynamics between black and white men undergoing androgen deprivation therapy (ADT).Methods: The model was calibrated to longitudinal PSA data from 57 PCa patients (N = 47 white, N = 10 black) receiving androgen deprivation therapy (ADT). To compensate for the lack of data for black patients, propensity score matching was used to select 15 white patients that were most alike to the 10 black patients based on their Eastern Cooperative Oncology Group (ECOG) score, age, and tumor burden. Using a previously developed model of stem cell, non-stem, and prostate-specific antigen (PSA) dynamics, parameter analysis and leave-one-out process was used to determine which parameters should be uniform among all patients and which should be patient-specific, and to determine if any parameters showed a significant difference.Results: The leave-one-out analysis found that having a uniform ADT cytotoxicity resulted in the best Akaike Information Criteria score for both black and white patients. Parameter analysis found a significant difference in the ADT cytotoxicity value between the black and white patients. Nested optimization was subsequently used to determine race-specific uniform cytotoxicity rates, while the remaining patient-specific parameters were determined. Statistical analysis found that black patients had a significantly higher stem cell self-renewal rate than the white patients. We hypothesize that this is primarily responsible for earlier progression in black patients.Conclusions: Our results suggest that PSA stem cell self-renewal is the parameter driving dynamic PSA differences between white and black patients. This valuable information can be used in the future to design race-specific treatment modalities to maximally delay time to progression.
Funder Acknowledgement(s): Funding was provided by:1. National Cancer Institute for Grant P20 CA202920-01A1, Southeast Partnership for Improving Research and Training in Cancer Health-Disparities (SPIRIT-CHD).2. NIH/NCI 1R21CA234787-01A1 “Predicting patient-specific responses to personalize ADT for prostate cancer.
Faculty Advisor: Renee Brady-Nicholls, Renee.Brady@moffitt.org
Role: Every part of the research except creating the model equations.