The D10 for urethra predicted stricture development, but this correlated directly to the fractionation schedule. The other predictive factor, on multivariate MS-275 chemical structure analysis, was a prostate-specific antigen level lower than 10 ng/mL. These patients had a significantly lower stricture rate. This dose correlation has been reported by other groups. Sullivan et al. (13) reported on the late stricture risk in 474 patients treated with HDRB, either as a boost or as a monotherapy. The EBRT dose used was comparable

with ours, but the HDRB schedules consisted of 16–20 Gy/4 or 19.5 Gy/3. They found a 6-year rate of 11.2% for those who received an HDRB boost to EBRT. They also reported an increased stricture rate using a high-dose single-fraction HDRB with no EBRT. In this group, the actuarial 3-year rate was 15.3%. Pellizzon et al. (14) reported a series of 108 men with a median followup of 4 months who received EBRT and HDRB boost of 16–20 Gy/4. At 5 years, the actuarial stricture free rate was 86.2%. In both these series, the actuarial outcomes are comparable with ours for 18–20 Gy/3–4. In

contrast, many studies, using biologically similar schedules to ours either do not report strictures [15], [16], [17] and [18] or report only a crude rate of less than 12% [11], [13], [19], [20], [21] and [22]. For example, recently Hsu et al. (18) reported the preliminary results of Radiation Therapy Oncology Group 0321 study. One hundred twenty-nine patients underwent a 45 Gy EBRT with an HDRB boost of 19 Gy/2. Although

the followup frame is limited, they Omipalisib molecular weight reported actuarial late genitourinary toxicity of less than 3% at 18 months. However, they neither report strictures as oxyclozanide a separate toxicity nor is it clear that the data forms used would capture these episodes with certainty. We were able to document the site of stricture in the vast majority of patients. Consistent with the literature, 43 of 45 strictures were at, or below, the apex. Only 1 patient had an intraprostatic stricture and 1 had a bladder neck contracture. Sullivan et al. (13) reported almost identical pattern of stricture positions, with 35 of 38 strictures seen in the bulbomembranous urethra. The position of strictures, at or below the apex, is suggestive of dose sensitivity in this anatomic region. In a retrospective analysis, Mohammed et al. (11) found that the risk of stricture was significantly associated with a bulbomembranous urethral “hotspot.” In this current analysis, we have not measured dose in the bulbar/apex region. However, a higher urethral D10 correlated to the risk of stricture formation. Therefore, the acceptable maximum to the urethra has, as an absolute value, increased with each change in dose fractionation. If this maximal region is in the apex or bulbar region, any caudal needle movement may increase the stricture risk.