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Late urinary toxicity modeling after stereotactic body radiotherapy (SBRT) in the definitive treatment of localized prostate cancer.

ABSTRACT: Late urinary symptom flare has been shown to occur in a small subset of men treated with ultra- hypofractionated stereotactic body radiotherapy (SBRT) for prostate cancer. The purpose of this study was to use normal tissue complication probability modeling in an effort to derive SBRT specific dosimetric predictor's of late urinary flare.Two hundred and sixteen men were treated for localized prostate cancer using ultra- hypofractionated SBRT. A dose of 35-36.25 Gy in 5 fractions was delivered to the prostate and proximal seminal vesicles. Functional surveys were conducted before and after treatment to assess late toxicity. Phenomenologic NTCP models were fit to bladder DVHs and late urinary flare outcomes using maximum likelihood estimation.Twenty-nine patients experienced late urinary flare within two years of completion of treatment. Fitting of bladder DVH data to a Lyman NTCP model resulted in parameter estimates of m, TD50, and n of 0.19 (0-0.47), 38.7 Gy (31.1-46.4), and 0.13 (-0.14-0.41), respectively. Subsequent fit to a hottest volume probit model revealed a significant association of late urinary flare with dose to the hottest 12.7% of bladder volume. Multivariate analysis resulted in a final model that included patient age and hottest volume probit model predictions. Kaplan-Meier analysis demonstrated a two-year urinary flare free survival of 95.7% in patients 65 years or older with a bladder D12.7% of 33.5 Gy or less, compared to 74.5% in patients meeting none of these criteria.NTCP modeling of late urinary flare after ultra-hypofractionated prostate SBRT demonstrates a relatively small volume effect for dose to the bladder, suggesting that reduction of volume receiving elevated dose will result in decreased incidence of late urinary toxicity. Future studies will be needed to examine the impact of dose to other potential sources of late genitourinary toxicity.

SUBMITTER: Kole TP

PROVIDER: S-EPMC4986047 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Multiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our institutional prostate SBRT experience with SpaceOAR placement. METHODS:Fifty men with low- or intermediate-risk prostate cancer treated at a single institution with linear accelerator-based SBRT to 3625?cGy in 5 fractions, with or without androgen deprivation therapy (ADT) were included. All patients underwent SpaceOAR and fiducial marker placement followed by pre-treatment MRI. Toxicity assessments were conducted at least weekly while on treatment, 1?month after treatment, and every follow-up visit thereafter. Post-treatment PSA measurements were obtained 4?months after SBRT, followed by every 3-6?months thereafter. Acute toxicity was documented per RTOG criteria. RESULTS:Median follow up time was 20 (range 4-44) months. Median PSA at time of diagnosis was 7.4 (2.7-19.5) ng/ml. Eighteen men received 6?months of ADT for unfavorable intermediate risk disease. No PSA failures were recorded. Median PSA was 0.9?ng/mL at 20?months; 0.08 and 1.32?ng/mL in men who did and did not receive ADT, respectively. Mean prostate-rectum separation achieved with SpaceOAR was 9.6?±?4?mm at the prostate midgland. No grade???3 GU or GI toxicity was recorded. During treatment, 30% of men developed new grade 2 GU toxicity (urgency or dysuria). These symptoms were present in 30% of men at 1?month and in 12% of men at 1?year post-treatment. During treatment, GI toxicity was limited to grade 1 symptoms (16%), although 4% of men developed grade 2 symptoms during the first 4?weeks after SBRT. All GI symptoms were resolving by the 1?month post-treatment assessment and no acute or late rectal toxicity was reported >?1?month after treatment. CONCLUSIONS:Periprostatic hydrogel placement followed by prostate SBRT resulted in minimal GI toxicity, and favorable early oncologic outcomes. These results indicate that SBRT with periprostatic spacer is a well-tolerated, safe, and convenient treatment option for localized prostate cancer.

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Late urinary toxicity modeling after stereotactic body radiotherapy (SBRT) in the definitive treatment of localized prostate cancer.

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