1. Comparison of Toxicity Profiles Associated with Three High-Dose-Rate Brachytherapy Treatment Schedules for Favorable-Risk Prostate Cancer Maha Saada Jawad, M.D. 1, Joshua T. Dilworth, M.D., Ph.D. 1, Hong Ye, M.S. 1, Michelle Wallace, B.S.N., O.C.N. 1, Alvaro Martinez, M.D., F.A.C.R. 2, Peter Y. Chen, M.D., F.A.C.R 1, Gary S. Gustafson, M.D. 1, Daniel J. Krauss, M.D. 1 1 Department of Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, MI 2 Michigan HealthCare Professionals/21 st Century Oncology, Farmington Hills, MI

2. Key Points There is a trend to progressively hypofractionating radiation treatments for prostate cancer in the context of both EBRT and interstitial brachytherapy At our institution, we have moved from 4 to 2 to 1 fraction of HDR brachytherapy as monotherapy for favorable-risk prostate cancer (≤ T2b, Gleason ≤ 7, pre-RT PSA ≤ 18) Here, we report the acute and chronic GU and GI toxicity profiles associated with 3 HDR brachytherapy regimens, using 4 and 2 fractions (38 Gy/4 fx vs 24 Gy/2 fx vs 27 Gy/2 fx)

3. Patient Characteristics All (n=494) 38/4 (n=319) 24/2 (n=79) 27/2 (n=96) p value Age (yrs) (Median, Range) 63, 40-83 62, 40-81 64, 48-81 65, 47-80 0.09 Follow-up (yrs) (Median) 4.1 5.5 3.5 2.9 <0.001 NCCN Group Low-risk Intermediate-risk 68% 32% 73% 27% 61% 39% 58% 42% 0.01 Clin stage T1a-T1c T2a-T2b 80% 20% 77% 23% 82% 18% 92% 8% 0.004 Gleason ≤ 6 7 71% 29% 77% 23% 62% 38% 60% 40% 0.002 Pre-Treatment PSA < 10 ng/mL 10-18 ng/mL 96% 4% 96% 4% 96% 4% 96% 4% 0.99 Pre-Treatment HT Yes No 14% 86% 19% 81% 5% 95% 3% 97% <0.001

4. Overall Acute & Chronic Toxicity Acute Chronic ToxicityGrade 1Grade 2Grade 3Grade 1Grade 2Grade 3 Frequency/Urgency40%14%2%37%20%1% Dysuria23%6%<1%19%7%1.5% Urinary Retention16%7%<1%23%4%1% Incontinence3%1.5%<1%8%2%<1% Hematuria3%1.5%0%5%7%<1% Diarrhea9%1%0%8%1%0% Rectal Pain/Tenesmus4%<1%0%5%0.5%0% Rectal Bleeding3%0% 7%2%0% Proctitis<1% 0%2%1%0% Acute grade 1 hematuria was higher with 38 Gy vs 27 Gy (5% vs 0%, p=0.004) but not statistically different from 24 Gy; no differences in grade 2/3 hematuria Chronic grade 1 retention was higher with 27 Gy (41%) vs both 24 Gy (17%, p=0.002) and 38 Gy (19%, p<0.001); no differences in grade 2/3 retention All other acute and chronic GU and GI toxicities were similar between the 3 groups

5. Conclusions These data confirm similar and well-tolerated GU and GI toxicity profiles for the three dose regimens Low rates of grade 2, minimal grade 3, and no grade 4/5 toxicity All results were similar when excluding patients who received hormonal therapy Given the favorable side effect profiles reported, further hypofractionation and/or dose escalation may be feasible