Abstract 674: Clinical testing of the novel predictive biomarker for monitoring adverse reactions to radiation therapy
Authors: Okunieff Paul , Peletskaya Elena , Swarts Steven , Du Jinwei , Pastor Larry , Powell Michael , Zhang Aiguo 
Published: August 2018

Abstract
Introduction: RadToxTM is a unique, first generation patented technology that measures acute tissue damage following first radiation exposure, using only a few microliters of blood. The assay can be used both for research and clinical testing of plasma samples for patients undergoing radiation therapy.
Methodology: To evaluate the clinical utility of RadToxTM test, cfDNA measurements for 54 cancer patients were obtained from prospectively collected plasma samples at different times before and during radiation therapy for prostate cancer. RadToxTM data comparison between patients receiving x-ray (greater exposure of non-target tissue) versus proton (more focused intergral dose). Peak levels of RadTox, (minus pre-irradiation levels) during the first 7 days after starting radiation were significantly higher in the x-ray group (49.4 vs 25.8 ng/mL, p&lt;0.05). Similarly, average levels (5 daily post-irradiation RadToxTM levels corrected for pretreatment levels during that first week were also significantly higher in the x-ray group (26.0 vs 12.8 ng/mL, p&lt;0.05). Based on the clearance kinetics of RadToxTM measured in non-human primates with total body irradiation from previous work, the peak in cfDNA level was predicted to occur approximately 48 hr after the first dose of radiation. We analyzed RadToxTM data looking only at the 2nd day RadToxTM measurements from the 54 patient plasma sample sets (minus the pre-irradiation values from each patient). The average increase in RadToxTM was 14.8 ± 4.0 ng/mL in the proton group and 32.2 ± 11.8 ng/mL in the x-ray group 48 hr after the first dose of radiation (P=0.018). Three patterns of changes were seen among the patients. Many patients had little change in their RadToxTM during the first week of radiation. These have preliminarily been termed “low risk” and defined to have a peak/pre RadToxTM ratio of &lt;1.5. Most patients had a slow rise of their RadToxTM, and thus are termed “average risk” with a peak/pre ratio of ≤2. A few patients (≈3 of 54) had larger increases in their RadToxTM ratio, and are being considered “high risk”. Correlation of these RadToxTM data with objective short and medium term toxicity data are in progress.
Conclusion: RadToxTM was successfully tested against the “gold standard” predictor of toxicity - dose volume histography. A few patients, ≈6%, had very high RadToxTM levels, and may prove to be the subset of patients with greater treatment induced toxicity. Extended long-term follow-up of patient bowel and urinary function is underway. Follow-up data and future studies will allow us to determine if RadToxTM can stratify patients into toxicity-risk groupings and allow oncologists to develop safer cancer treatments.
Citation Format: Paul Okunieff, Elena Peletskaya, Steven Swarts, Jinwei Du, Larry Pastor, Michael Powell, Aiguo Zhang. Clinical testing of the novel predictive biomarker for monitoring adverse reactions to radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 674.