Dosimetric analysis of radiation therapy oncology group 0321: the importance of urethral dose

Radiation Therapy Oncology Group 0321 is the first multi-institutional cooperative group high-dose-rate (HDR) prostate brachytherapy trial with complete digital brachytherapy dosimetry data. This is a descriptive report of the data and an analysis of toxicity.

Patients are treated with external beam radiation therapy at 45 Gy and 1 HDR implant with 19 Gy in 2 fractions. Implants are done with transrectal ultrasound guidance, and computed tomography (CT)-compatible nonmetallic catheters. HDR planning is done on ≤3-mm-thick CT slices. The "mean DVH" (dose-volume histogram) of the planning target volume (PTV), implanted volume (IP), and organs at risk are calculated. This includes the mean and standard deviation (SD) of the volume at 10-percentage-point intervals from 10% to 200% of the prescribed dose. The conformal index (COIN), homogeneity index (HI), catheters per implant, and patients per institution are calculated. Multivariate analysis and hazard ratios calculation of all the variables against reported grade ≥2 (G2+) genitourinary (GU) adverse events (Common Terminology Criteria for Adverse Events, version 3) are performed.

Dosimetry data are based on 122 eligible patients from 14 institutions. The mean of PTV, IP, catheters per implant, and patients per institution are 54 cc, 63 cc, 19 and 9, respectively. The mean of %V100PTV, V80Bladder, V80Rectum, and V120Urethra were 94%, 0.40 cc, 0.15 cc, and 0.25 cc, respectively. There are too few G2+ gastrointestinal adverse event (GI AE) for correlative analysis; thus, the analysis has been performed on the more common G2+ GU AE. There are positive correlations noted between both acute and late G2+ GU AE and urethral dose at multiple levels. Positive correlations with late AE are seen with PTV and IP at high-dose levels. A negative correlation is seen between HI and acute AE. A higher patient accrual rate is associated with a lower rate of G2+ acute and late AE.

Higher urethral dose, larger high-dose volumes, and lower dose homogeneity are associated with greater toxicities. A mean dose-volume histogram comparison at all dose levels should be used for quality control and future research comparison.