Improved Irritative Voiding Symptoms 3 Years after Stereotactic Body Radiation Therapy for Prostate Cancer

Background: Irritative voiding symptoms are common in elderly men and following prostate radiotherapy. The impact of hypofractionated treatment on irritative voiding symptoms has not been determined. This study sought to evaluate urgency, frequency and nocturia following SBRT for prostate cancer. Methods: Patients treated with SBRT monotherapy for localized prostate cancer from August 2007 to July 2011 at Georgetown University Hospital were included in this study. Treatment was delivered using the CyberKnife® with doses of 35 Gy-36.25 Gy in 5 fractions. Patient-reported urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) before treatment and at 1, 3, 6, 9, 12 months post-treatment and every 6 months thereafter.Results: 204 patients at a median age of 69 years received SBRT with a median follow-up of 4.8 years. Prior to treatment, 50.0% of patients reported moderate to severe lower urinary track symptoms and 17.7% felt that urinary frequency was a moderate to big problem. The mean prostate volume was 39 cc and 8% had prior procedures for benign prostatic hyperplasia (BPH). A mean baseline IPSS-irritative score of 4.8 significantly increased to 6.5 at 1 month (p 8) at baseline, the mean IPSS-I decreased from a baseline score of 6.8 to 4.9 at three years post-SBRT. This decrease was both statistically (p < 0.0001) and clinically significant (MID = 1.45). Only 14.6% of patients felt that urinary frequency was a moderate to big problem at three years post-SBRT (p = 0.23).Conclusions: Treatment of prostate cance

PROCTITIS ONE WEEK AFTER STEREOTACTIC BODY RADIATION THERAPY FOR PROSTATE CANCER: IMPLICATIONS FOR CLINICAL TRIAL DESIGN

Background: Proctitis following prostate cancer radiation therapy is a primary determinant of quality of life (QOL). While previous studies have assessed acute rectal morbidity at 1 month after stereotactic body radiotherapy (SBRT), little data exist on the prevalence and severity of rectal morbidity within the first week following treatment. This study reports the acute bowel morbidity one week following prostate SBRT. Materials and methods: Between May 2013 and August 2014, 103 patients with clinically localized prostate cancer were treated with 35 to 36.25 Gy in five fractions using robotic SBRT delivered on a prospective clinical trial. Bowel toxicity was graded using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv.4). Bowel QOL was assessed using EPIC-26 questionnaire bowel domain at baseline, one week, one month, and three months. Time-dependent changes in bowel symptoms were statistically compared using the Wilcoxon signed-rank test. Clinically significant change was assessed by the minimally important difference (MID) in EPIC score. This was defined as a change of one-half standard deviation (SD) from the baseline score. Results: One hundred and three patients with a minimum of three months of follow-up were analyzed. The cumulative incidence of acute grade 2 GI toxicity was 23%. There were no acute ≥ grade 3 bowel toxicities. EPIC bowel summary scores maximally declined at 1 week after SBRT (-13.9, p<0.0001) before returning to baseline at three months after SBRT (+0.03, p=0.94). Prior to treatment, 4.9% of men reported that their bowel bother was a moderate to big problem. This increased to 28.4% (p<0.0001) one week after SBRT and returned to baseline at three months after SBRT (0.0%, p=0.66). Only the bowel summary and bowel bother score declines at 1 week met the MID threshold for clinically significant change. Conclusion: The rate and severity of acute proctitis following prostate SBRT peaked at one week after treatment and returned to baseline by 3 months. Toxicity assessment at one week can therefore minimize recall bias and should aid in the design of future clinical trials focused on accurately capturing and minimizing acute morbidity following SBRT

Urethrogram-directed Stereotactic Body Radiation Therapy (SBRT) for Clinically Localized Prostate Cancer in Patients with Contraindications to Magnetic Resonance Imaging

Purpose: Magnetic resonance imaging (MRI)-directed stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. For patients with contraindications to MRI, CT-urethrogram is an alternative imaging approach to identify the location of the prostatic apex to guide treatment. This study sought to evaluate the safety of urethrogram-directed SBRT for prostate cancer.Methods: Between February 2009 and January 2014, 31 men with clinically localized prostate cancer were treated definitively with urethrogram-directed SBRT with or without supplemental intensity modulated radiation therapy (IMRT) at Georgetown University Hospital. SBRT was delivered either as a primary treatment of 35-36.25 Gray (Gy) in 5 fractions or as a boost of 19.5 Gy in 3 fractions followed by supplemental conventionally fractionated intensity modulated radiation therapy (45-50.4 Gy). Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0).Results: The median patient age was 70 years with a median prostate volume of 38 cc. The median follow-up was 3.7 years. The patients were elderly (Median age = 70), and comorbidities were common (Carlson Comorbidity Index > 2 in 36%). 71% of patients utilized alpha agonists prior to treatment, and 9.7% had prior procedures for benign prostatic hyperplasia (BPH). The 3-year actuarial incidence rates of > Grade 3 GU toxicity and > Grade 2 GI toxicity were 3.2% and 9.7%, respectively. There were no Grade 4 or 5 toxicities.Conclusions: MRI is the preferred imaging modality to guide prostate SBRT treatment. However, urethrogram-directed SBRT is a safe alternative for the treatment of patients with prostate cancer who are unable to undergo MRI

Acute Urinary Morbidity Following Stereotactic Body Radiation Therapy for Prostate Cancer with Prophylactic Alpha-Adrenergic Antagonist and Urethral Dose Reduction

Background: Stereotactic body radiation therapy (SBRT) delivers high doses of radiation to the prostate while minimizing radiation to adjacent critical organs. Large fraction sizes may increase urinary morbidity due to unavoidable treatment of the prostatic urethra. This study reports rates of acute urinary morbidity following SBRT for localized prostate cancer with prophylactic alpha-adrenergic antagonist utilization and urethral dose reduction (UDR).Methods: From April 2013 to September 2014, 102 patients with clinically localized prostate cancer were treated with robotic SBRT to a total dose of 35-36.25 Gy in 5 fractions. UDR was employed to limit the maximum point dose of the prostatic urethra to 40 Gy. Prophylactic alpha-adrenergic antagonists were initiated five days prior to SBRT and continued until resolution of urinary symptoms. Quality of life (QoL) was assessed before and after treatment using the American Urological Association Symptom Score (AUA) and the Expanded Prostate Cancer Index Composite-26 (EPIC-26). Clinical significance was assessed using a minimally important difference (MID) of one half standard deviation change from baseline.Results: 102 patients underwent definitive prostate SBRT with UDR and were followed for 3 months. No patient experienced acute urinary retention requiring catheterization. A mean baseline AUA symptom score of 9.06 significantly increased to 11.83 one-week post-SBRT (p = 0.0024) and 11.84 one-month post-SBRT (p = 0.0023) but returned to baseline by 3 months. A mean baseline EPIC-26 irritative/obstructive score of 87.7 decreased to 74.1 one-week post-SBRT (p < 0.0001) and 77.8 one-month post-SBRT (p < 0.0001) but returned to baseline at 3 months. EPIC-26 irritative/obstructive score changes were clinically significant, exceeding the MID of 6.0. At baseline, 8.9% of men described their urinary function as a moderate to big problem, and that proportion increased to 37.6% one week following completion of SBRT before returning to baseline by three months.Conclusions: SBRT for localized prostate cancer with utilization of prophylactic alpha-adrenergic antagonist and UDR was well tolerated as determined by acute urinary function and bother, and symptoms were comparable to those observed following conventionally fractionated external beam radiation therapy (EBRT). Longer follow-up is required to assess long-term toxicity and efficacy following SBRT with UDR

Stereotactic Body Radiation Therapy for Prostate Cancer: What is the Appropriate Patient-Reported Outcome for Clinical Trial Design?

Purpose: Stereotactic body radiation therapy (SBRT) is increasingly utilized as primary treatment for clinically localized prostate cancer. Consensus regarding the appropriate patient-reported outcome (PRO) endpoints for clinical trials for early stage prostate cancer RT is lacking. To aid in trial design, this study presents PROs over 36 months following SBRT for clinically localized prostate cancer. Methods: 174 hormone-naïve patients were treated with 35-36.25 Gy SBRT in 5 fractions. Patients completed the EPIC-26 questionnaire at baseline and all follow-ups; the proportion of patients developing a clinically significant decline in each EPIC domain was determined. The minimally important difference (MID) was defined as a change of one-half SD from the baseline. Per RTOG 0938, we examined the percentage of patients who reported decline in EPIC urinary summary score of >2 points and EPIC bowel summary score of >5 points from baseline to one year. Results: 174 patients received SBRT with minimum follow-up of 36 months. The proportion of patients reporting a clinically significant decline in EPIC urinary/bowel scores was 34%/30%, 40%/32.2%, and 32.8%/21.5% at 6, 12, and 36 months. The percentage of patients reporting decline in the EPIC urinary summary score of >2 points was 43.2%, 51.6% and 41.8% at 6, 12, and 36 months. The percentage of patients reporting decline in EPIC bowel domain summary score of >5 points was 29.6% 29% and 22.4% at 6, 12, and 36 months. Conclusion: Our treatment protocol meets the RTOG 0938 criteria for advancing to a Phase III trial compared to conventionally fractionated RT. Between 12-36 months, the proportion of patients reporting decrease in both EPIC urinary and bowel scores declined, suggesting late improvement in these domains. Further investigation is needed to elucidate 1) which domains bear the greatest influence on post-treatment QOL, and 2) at what time point PRO endpoint(s) should be assessed

Dark Matter Physics with Wide Field Spectroscopic Surveys

International audienceThis white paper summarizes the astronomical observations for next decade to probe the particle properties of dark matter, and concludes that a 10m class wide-field, high-multiplex spectroscopic survey facility is required for the next decade to definitively search for deviations from the cold collisionless dark matter model