Nancy P. Mendenhall, MD: 2015 North Jefferson St; menden@shands.ufl.edu; 904-588-1800

1. The Value of Dose Constraints in Minimizing Rectal Toxicity in Patients Receiving Radiation Therapy for Prostate Cancer: Three-Year Analysis of Toxicity Outcomes in 2 Prospective Trials of Image-guided Proton Therapy for Early- and Intermediate-Risk Prostate Cancer Nancy P Mendenhall, MD; Zuofeng Li, DSc; Bradford S Hoppe, MD; Robert B Marcus, Jr, MD; William M Mendenhall, MD; R Charles Nichols, MD; Christopher G Morris, MS; Christopher R Williams, MD; Joseph Costa, DO; Randal Henderson, MD University of Florida Proton Therapy Institute, Jacksonville, Florida Conclusions Outcomes at 3 years with image-guided proton therapy in doses up to 82 CGE, based on organ-constraints and the techniques used in this study, continue to suggest high efficacy and minimal toxicity. There appears to be a very steep dose response for manifestation of rectal injury and the volume of rectum receiving doses between 70 and 75 CGE. The correlation noted between grade 2+ rectal bleeding and /or proctitis and various dose-volume parameters may be useful in designing dose-volume constraint goals for organs at risk in future clinical trials. Figure 1. Probability of Grade 2+ rectal bleeding with dose-volume histogram parameters Nancy P. Mendenhall, MD: 2015 North Jefferson St; menden@shands.ufl.edu; 904-588-1800 Introduction Results The purpose of this study was to assess the usefulness of dose-volume constraints for minimizing the risk of rectal toxicity with image-guided proton therapy for early- and intermediate-risk prostate cancer. One of 89 low-risk and 1 of 82 intermediate-risk patients had disease progression. Three-year biochemical progression-free survival (bPFS) and overall survival rates for the combined group are 99% and 95%, respectively. Only 2 patients developed grade 3+ gastrointestinal toxicities: both were on anti-coagulation and both events resolved after intervention and did not recur. The prevalence and cumulative incidence of all grade 2+ gastrointestinal toxicity at 3 years were 7.1% and 14.1%, respectively. The majority of events were rectal bleeding with or without proctitis. Multivariate analyses showed significant correlation between grade 2+ rectal bleeding and/or proctitis and the percent of rectum receiving doses ranging from 30 CGE to 75 CGE (V30, p=0.0475; V70, p=0.0199; and V75, p=0.0152). Figure 1 shows the relationship between the probability of grade 2+ rectal bleeding and the % of rectum receiving 30, 70, or 75 CGE. Methods One hundred seventy-one prostate cancer patients accrued to prospective institutional review board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low–risk disease or dose escalation from 78 to 82 CGE for intermediate-risk disease. Minimum potential follow-up was 3 years. Toxicity rates were correlated with clinical factors and prospectively calculated dose volume relationships to organs at risk.