Effect of Large Prostate Volume on Efficacy and Toxicity of Moderately Hypofractionated Radiation Therapy in Patients With Prostate Cancer.

Purpose: To evaluate the effect of prostate volume on outcomes after moderately hypofractionated radiation therapy (mHFRT) for prostate cancer. Methods and Materials: Prostate cancer patients treated with mHFRT at a Veteran's Affairs Medical Center from August 20, 2008, to January 31, 2018, were identified. Patients were placed into a large prostate planning target volume (LPTV) cohort if their prostate PTV was in the highest quartile. Acute/late genitourinary (GU) and gastrointestinal toxicity events among patients with and without LPTV were compared. Multivariable analyses estimated the effect of factors on toxicity. Overall survival, biochemical recurrence-free survival, and freedom from late GU/gastrointestinal toxicity of patients with and without LPTV were estimated via Kaplan-Meier. Results: Four hundred and seventy-two patients were included. Ninety-three percent received 70 Gy in 2.5 Gy fractions; 75% received androgen deprivation therapy. Median follow-up was 69 months. Patients with LPTV (PTV >138.4 cm3) had a higher late 2 + GU toxicity compared with those without (59% vs 48%, P = .03). Earlier time to late 2 + GU toxicity was associated with LPTV (hazard ratio 1.36; 95% confidence interval [CI], 1.00-1.86; P = .047), androgen deprivation therapy use (hazard ratio 1.60; 95% CI, 1.13-2.27; P = .01), and higher baseline American Urologic Association symptom score (odds ratio 1.03; 95% CI, 1.02-1.05; P < .001). At 2 years, freedom from late 2 + GU toxicity was 46% (95% CI, 47%-54%) for those with LPTV versus 61% (95% CI, 55%-65%) for those without (P = .04). Late grade 3 GU toxicity was 7% for those with LPTV and 4% for those without. No differences in overall survival or biochemical recurrence-free survival were observed between patients with or without LPTV. Conclusions: LPTV did not affect efficacy of mHFRT for prostate cancer; however, it was associated with increased risk and earlier onset of late grade 2 + GU toxicity.

Effects of Feeding Varying Levels of DL-Methionine on Live Performance and Yield of Broiler Chickens.

This study was designed to evaluate the effects of dietary supplemental DL-methionine (MET) on live performance and meat yield for broilers raised to a common weight. A total of 1552 one-day old Ross 708, sexed broilers were randomly distributed to 32 pens resulting in eight treatments (TRT) of four replicates with 44 male or 53 female/pen. A randomized complete block with a 2 × 4 (sex × 4 MET levels 0, 0.5, 1, and 2 g/kg) factorial arrangement of TRT was used. A common weight of 2400 g was approached by day 46 (1 and 2 g MET/kg feed) and day 48 (0 and 0.5 g MET/kg feed). Supplementation of MET at 1, and 2 g/kg had a lower (p < 0.01) feed conversion ratio (FCR) at day 46/48 than broilers fed 0.5 g MET/kg. Broilers without supplemental MET had the worst (p < 0.01) feed conversion and average daily gain (ADG) at day 46/48. Birds fed 0 g MET/kg of feed had lower (p < 0.05) whole eviscerated carcass without giblets (WOG), yield than birds fed 2 g MET/kg of feed. Additionally, birds fed 0 g MET/kg of feed had lower (p < 0.05) breast fillet and tender percent yields than birds fed supplemental MET. Elimination of MET from organic broiler diets resulted in reduced ADG, breast fillet yield and feed efficiency of meat yield of broilers raised to day 46/48. Reduction in MET supplementation below current levels reduced the efficiency of meat production of organic broilers raised to day 46/48.

Association of Presalvage Radiotherapy PSA Levels After Prostatectomy With Outcomes of Long-term Antiandrogen Therapy in Men With Prostate Cancer.

Importance: In men with recurrent prostate cancer, addition of long-term antiandrogen therapy to salvage radiotherapy (SRT) was associated with overall survival (OS) in the NRG/RTOG 9601 study. However, hormone therapy has associated morbidity, and there are no validated predictive biomarkers to identify which patients derive most benefit from treatment. Objective: To examine the role of pre-SRT prostate-specific antigen (PSA) levels to personalize hormone therapy use with SRT. Interventions: Men were randomized to SRT plus high-dose nonsteroidal antiandrogen (bicalutamide, 150 mg/d) or placebo for 2 years. Design, Setting, and Participants: In this secondary analysis of the multicenter RTOG 9601 double-blind, placebo-controlled randomized clinical trial conducted from 1998 to 2003 by a multinational cooperative group, men with a positive surgical margin or pathologic T3 disease after radical prostatectomy with pre-SRT PSA of 0.2 to 4.0 ng/mL were included. Analysis was performed between March 4, 2019, and December 20, 2019. Main Outcomes and Measures: The primary outcome was overall survival (OS). Secondary end points included distant metastasis (DM), other-cause mortality (OCM), and grades 3 to 5 cardiac and neurologic toxic effects. Subgroup analyses were performed using the protocol-specified PSA stratification variable (1.5 ng/mL) and additional PSA cut points, including test for interaction. Competing risk analyses were performed for DM and other-cause mortality (OCM). Results: Overall, 760 men with PSA elevation after radical prostatectomy for prostate cancer were included. The median (range) age of particpants was 65 (40-83) years. Antiandrogen assignment was associated with an OS benefit in the PSA stratum greater than 1.5 ng/mL (n = 118) with a 25% 12-year absolute benefit (hazard ratio [HR], 0.45; 95% CI, 0.25-0.81), but not in the PSA of 1.5 ng/mL or less stratum (n = 642) (1% 12-year absolute difference; HR, 0.87; 95% CI, 0.66-1.16). In a subanalysis of men with PSA of 0.61 to 1.5 (n = 253), there was an OS benefit associated with antiandrogen assignment (HR, 0.61; 95% CI, 0.39-0.94). In those receiving early SRT (PSA ≤0.6 ng/mL, n = 389), there was no improvement in OS (HR, 1.16; 95% CI, 0.79-1.70), an increased OCM hazard (subdistribution HR, 1.94; 95% CI, 1.17-3.20; P = .01), and an increased odds of late grades 3 to 5 cardiac and neurologic toxic effects (odds ratio, 3.57; 95% CI, 1.09-15.97; P = .05). Conclusions and Relevance: These results suggest that pre-SRT PSA level may be a prognostic biomarker for outcomes of antiandrogen treatment with SRT. In patients receiving late SRT (PSA >0.6 ng/mL, hormone therapy was associated with improved outcomes. In men receiving early SRT (PSA ≤0.6 ng/mL), long-term antiandrogen treatment was not associated with improved OS. Future randomized clinical trials are needed to determine hormonal therapy benefit in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT00002874.

Nonuniform Planning Target Volume Margins for Prostate Bed on the Basis of Surgical Clips on Daily Cone Beam Computed Tomography.

PURPOSE: We hypothesized that the interfraction motions of the superior and inferior prostate beds differ and therefore require different margins. In this study, we used daily cone beam computed tomography (CBCT) to evaluate the motion of postprostatectomy surgical clips (separated to superior and inferior portions) within the planning target volume (PTV) to derive data-driven PTV margins. METHODS AND MATERIALS: Our study cohort included consecutive patients with identifiable surgical clips undergoing prostate bed irradiation with daily CBCT image guidance. We identified and contoured the clips within the PTV on the planning computed tomography and CBCT scans. All CBCT scans were registered to the planning computed tomography scan on the basis of pelvic bony structures. The superior border of the pubic symphysis was used to mark the division between the superior and inferior portions. RESULTS: Eleven patients with 263 CBCT scans were included in the cohort. In the left-right direction, the global mean M, systematic error Σ, and residue error σ were 0.02, 0.03, and 0.16 cm, respectively, for superior clips, and 0.00, 0.03, and 0.03 cm, respectively, for inferior clips. In the anterior-posterior direction, the corresponding values were M = 0.01, Σ = 0.25, and σ= 0.37, respectively, for superior, and M = 0.08, Σ= 0.13, σ= 0.15, respectively, for inferior. In the superior-inferior direction, the values were M =-0.06, Σ= 0.23, and σ= 0.27, respectively, for superior, and M =-0.01, Σ= 0.21, σ= 0.20, respectively, for inferior. The results of the 2-tailed F tests showed that the anterior-posterior motion is statistically different between the superior and inferior portions in the anterior-posterior direction. There is no statistical difference in the superior-inferior and lateral directions. Therefore, we propose a set of nonuniform PTV margins (based on the formula 2.5 Σ+ 0.7σ) as 0.2 cm for all prostate beds in the left-right direction, 0.7 cm for all in superior-inferior, and 0.9 to 0.4 for superior-inferior in the anterior-posterior direction. CONCLUSIONS: The difference in motion between the superior and inferior portions of the prostate bed is statistically insignificant in the left-right and superior-inferior directions, but statistically significant in the anterior-posterior direction, which warrants a nonuniform PTV margin scheme.

Radioactive sources embedded in suture are associated with improved postimplant dosimetry in men treated with prostate brachytherapy.

BACKGROUND AND PURPOSE: Reports using the retropubic and transperineal technique of prostate brachytherapy suggest that adequate radiation doses are required for good clinical results with I-125. After 3 years of using loose sources (LS), radioactive sources embedded in suture (SES) were introduced into our prostate brachytherapy technique. The purpose of the present report is to determine whether dosimetric quantifiers of implant adequacy were affected by the use of SES. MATERIALS AND METHODS: Between September 1999 and April 2000, 20 patients were treated with prostate brachytherapy alone with a preplanned, preloaded needle technique using LS. Between May 2000 and February 2001, 20 patients were treated with prostate brachytherapy alone with a preplanned, preloaded needle technique using SES. Dosimetric quantifiers (DQ) of implant adequacy were calculated using a computed tomography scan performed 1 month following prostate brachytherapy. DQ were compared between patients treated with LS and patients treated with SES. RESULTS: The demographic characteristics were similar for each group. Men treated with SES had slightly smaller prostate glands compared to men treated with LS. The mean total activity and activity per seed were similar for each group but the activity per unit volume was slightly higher for the SES group. Patients treated with SES were found to have significantly improved DQ compared to patients treated with LS. The mean V100 for patients treated with SES was 94.10% compared to 86.54% in those patients treated with LS (P<0.001). CONCLUSIONS: In our experience using preplanning and preloaded needles, the use of SES is associated with improved postimplant DQ.