Half of the patients had T2 and half had Gleason 7 prostate cancer. They administered HDR in a single implant over 2 days in three fractions; four different dose schedules were evaluated (10, 10.5, 11, or 11.5 Gy). The 3- and 5-year Cobimetinib cell line biochemical control rates (nadir + 2) were 88% and 85%. There were no differences in toxicity between doses. Acute rectal toxicity was nearly all Grade 1 and acute Grade 3 urinary toxicity occurred in only 1 patient. Chronic Grade 3

urinary toxicity was <10% and no Grade 4 toxicities were recorded. The group from Offenbach Germany, lead by Zamboglou and Baltas, obtained excellent results in 718 patients using intraoperative TRUS treatment planning. The dose and fractionation schedule evolved over time (51). Protocol A (9.5 Gy × 4 in one implant), protocol B (9.5 Gy × 4

in two implants), and finally the current protocol C (11.5 Gy × 3 in three implants). The authors progressively included higher risk group cases so that for protocol C 57% of cases were intermediate- or high-risk compared with 27% in protocol A and 44% in protocol B. The median followup by protocol was 7.7 years for 141 patients (protocol A), 4.9 years for 351 patients (protocol B), and 2.1 years NLG919 ic50 for 226 patients (protocol C). The 3-year biochemical control for all patients was 95% and distant metastasis–free survival was 98%. The 5-year results were available for protocols A and B (9.5 Gy × 4). Biochemical control was 97% and 94%. There were no significant differences correlated with T score, PSA, Gleason Fluorometholone Acetate score, or risk group. Late Grade 3 GU and GI toxicities were 3.5% and 1.6%. Urinary strictures that required urethrotomy (Grade 3 GU toxicity) occurred in 1.8% and 2 patients required urinary diversion to manage urinary incontinence (Grade 4 GU toxicity). Although the followup is significantly less in protocol C, there were no apparent differences in tumor control or morbidity between

the three protocols. Ghilezan et al. (52) reported on an ultra-hypofractionated HDR monotherapy trial for low- and intermediate-risk prostate cancer that accrued 100 patients. The total dose was 24 Gy for the first 50 patients (one implant, two fractions, and 6 h interfraction interval) and 27 Gy in the next 50 patients. The median followup was 17 months. There were no differences in acute or chronic toxicities between the two doses. The maximum chronic GU and GI toxicities Grade 2 or higher were ≤5% with the exception of urinary frequency/urgency, which was 16%. These symptoms resolved by 6 months in most cases (0% for the 24 Gy and 4.8% for the 27 Gy). The program was changed to two implants 2–3 weeks apart to increase the time for normal tissue repair and to shorten the time of the procedure per day by removing the same day waiting between fractions.