Abstract 5594: Association of circulating cell-free DNA and prostate cancer risk groups in patients undergoing proton therapy
Authors: Bass Andrew , Velasquez Johnny , Rajaei Moein , Bryant Curtis , Mendenhall Nancy , Ricks-Santi Luisel J. 
Published: April 2023

Abstract
Even after radiation treatment, prostate cancer (PCa) patients receiving radiotherapy (RT) are still at risk for disease progression and recurrence. Predicting outcomes associated with cancer treatment is critical to PCa survivorship given that the 5-year survival rates for local and regional stage PCa is nearly 100%. Radiogenomics is a promising field of research focused on identifying genomic markers that can provide clinically useful prognostic predictions regarding radiation response and can potentially serve as the basis for personalized RT where cancer management is tailored to fit each individual patient. Circulating cell-free (ccfDNA) DNA has been found to 1) be associated with radiation sensitivity or toxicity, 2) relapse or recurrence, and 3) risk for the development of metastases before, during or following photon RT. Proton therapy, alternative to photon therapy, is a promising treatment that can reduce excess radiation dose and, in turn, the risk for adverse events. However, few studies have been done to determine if ccfDNA can predict response in proton radiation, which purports superior dose distribution, avoiding healthy tissues, minimizing the exit dose, and potentially reducing overall toxicity. The overall aim of this study is to determine if the quantity of ccfDNA is associated with PCa risk groups. We hypothesized that PCa patients within the highest risk group have quantitatively increased levels of ccfDNA compared to those in low and intermediate risk groups. This study leveraged the University of Florida Health Proton Therapy Institute Outcomes Tracking Protocol biobank of PCa patients with plasma and serum collected before, during and after proton RT. Isolation of ccfDNA at baseline, during treatment, and following treatment was undertaken and ccfDNA quantities were compared among patients in the low, intermediate and high risk groups using ANOVA. Our results indicate that the quantity difference between baseline and day 14 of treatment (p=0.055), 2 weeks post-treatment (p=0.54), and 4 weeks post-treatment (p=0.002) was associated with risk group. There was trend towards increasing ccfDNA quantity, as risk group increased; however, there was no correlation between risk group and treatment times using the Pearson correlation. Our results were consistent in that high ccfDNA quantity was associated with PCa risk. This is the first study determining the application of ccfDNA quantity on prostate cancer outcomes in patients undergoing proton RT. Identifying the determinants of radiation-related adverse outcomes will help inform impending predictive genomic technologies and improve cancer-related outcomes and survivorship.
Citation Format: Andrew Bass, Johnny Velasquez, Moein Rajaei, Curtis Bryant, Nancy Mendenhall, Luisel J. Ricks-Santi. Association of circulating cell-free DNA and prostate cancer risk groups in patients undergoing proton therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5594.