bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of isolated local failures following stereotactic body radiation therapy for low to intermediate risk prostate cancer.
Authors: Drescher Nicolette , Aghdam Nima , Danner Malika , Ayoob Marilyn , Yung Thomas M. , Lei Siyuan , Collins Brian Timothy , Lischalk Jonathan , Dritschilo Anatoly , Suy Simeng , Kumar Deepak , Lynch John J. , Collins Sean P. 
Published: March 2019

66 Background: SBRT is a safe and effective treatment option for patients with low to intermediate risk prostate cancer (PCa). SBRT delivers high biologically effective doses resulting in very low PSA nadirs. Strategies to diagnose and confirm salvageable isolated local failures (ILF) are needed. This study aims to examine the incidence and approach to management of ILF after SBRT in a large single institution cohort. Methods: All patients with low or intermediate risk PCa treated with SBRT at our institution were eligible for this study. Treatment was delivered using the robotic SBRT with doses of 35-36.25 Gy in five fractions. ILF were diagnosed using mpMRI and/or biopsy prompted by PSA rise after achieving long-term nadir. Choice of salvage therapy and post-salvage PSA were ascertained on follow up. Results: Between December, 2008 to August, 2018, 998 men with low to intermediate risk prostate cancer were eligible for analysis. Twenty patients (low risk, n = 4; intermediate risk, n = 16) were found to have ILF on either MRI (n = 15) and/or biopsy (n = 17). Three patients with MRI-identified ILF elected active surveillance in lieu of biopsy. Median pre-treatment PSA was 7.5 ng/ml. Median time to diagnosis of ILF was 72 months (37-96 months) with median PSA at the time of ILF of 2.3 ng/ml (1.1-10 ng/ml). Median PSA doubling time was 17 months (5-22 months). Thirteen patients with biopsy proven ILF proceeded with salvage therapy (cryotherapy n = 12, HIFU n = 1). Of 12 patients who underwent cryotherapy, 8 had a post-treatment PSA of < 0.1ng/ml, two patient’s results were unavailable, one patient had a PSA nadir of 0.7 ng/ml and one patient had yet to undergo post-salvage PSA test at the time of this report. Conclusions: The incidence of ILF is rare in our series. Diagnosis and management of ILF post-SBRT continues to evolve in the era of successful salvage therapy. Our report suggests an important role for early utilization of MRI and confirmatory biopsy at relatively low PSA levels and long PSA doubling time. Additionally, undetectable PSA post-salvage therapy supports early treatment after identifying ILF. Larger trials are needed for refinement of patient selection and most appropriate salvage modality.
Role of magnetic resonance imaging-transrectal ultrasound fusion targeted biopsy in the detection of prostate cancer in biopsy-naïve men: A literature based meta-analysis of randomized trials.
Authors: Tu Xiang , Liu Zhenhua , Qiu Shi , Xu He , Li Jiakun , Liao Xinyang , Jin Kun , Bao Yige , Yang Lu , Wei Qiang 
Published: March 2019

70 Background: Magnetic Resonance Imaging-Transrectal Ultrasound (MRI/TRUS) fusion targeted biopsy (TB) has been demonstrated to increase detection rates (DRs) of prostate cancer (PCa) in repeat-biopsy setting. However, its role in biopsy-naïve men remains controversial. We performed a meta-analysis based on well-designed randomized controlled trials (RCTs) to compare the diagnostic accuracy of MRI/TRUS fusion TB and systematic biopsy (SB) in the detection of PCa in biopsy-naïve men. Methods: A systematic review of PubMed (Medline), Embase, Ovid and the Cochrane Library up to 1st October, 2018 was conducted. The statistical analyses were performed with Revman 5.3. We compared the diagnostic accuracy between the intervention group (assisted with fusion TB) and the control group (SB only) by calculating the risk ratio (RR) with 95% confidence intervals (CIs) of overall PCa and clinically significant PCa (csPCa) DRs. Subgroup analysis was performed to highlight the independent role of MRI/TRUS fusion TB alone or combining fusion TB and SB together in the detection of PCa. Results: Six RCTs with 2187 participants were evaluated for the DRs of overall PCa. Pooled analysis revealed slight higher DRs of 62.7% (687/1095) in the intervention group compared with that of 41.3% (451/1092) in the control group (RR 1.40, 95% CI: 1.00-1.95). Four studies with 962 participants were evaluated for the DRs of csPCa. There is a trend favoring the intervention group which detected more csPCa (42.8%, 206/481) compared with SB in the control group (31.6%, 152/481) but with no significant difference (RR 1.36, 95% CI: 0.95-1.95). Subgroup analysis revealed fusion TB alone with less biopsy cores may equal the DRs of csPCa compared with SB alone (RR 1.24, 95% CI: 0.79-1.93). However, the DRs of overall PCa when combining MRI/TRUS fusion TB and SB was comparable to that applying SB alone (RR 1.48, 95% CI: 0.99-2.22). Conclusions: MRI/TRUS fusion TB may obtain similar csPCa DRs with less biopsy cores. But currently there was no enough evidence showing fusion TB can help significantly improve overall PCa or csPCa DRs compared with SB alone in biopsy-naïve men.
Racial disparities in survivorship care adherence among Medicare beneficiaries with prostate cancer.
Authors: Parikh Ravi Bharat , Chhatre Sumedha , Malkowicz S. Bruce , Li Bingnan , Jayadevappa Ravishankar 
Published: March 2019

72 Background: African-American men with prostate cancer have higher cancer-related and all-cause mortality than their Caucasian counterparts. Differences in adherence to guideline-based survivorship care may contribute to these disparities. Methods: Using the SEER-Medicare database, we conducted a retrospective cohort study of men ≥66 years old treated for localized prostate cancer between 2008 and 2011 who had at least two visits with a specialist or primary care physician after diagnosis. Patients were followed until 2013. We calculated rates of bone mineral density screening (among men treated with androgen deprivation therapy) and colorectal cancer screening after diagnosis, stratified by race and provider seen. We analyzed the association between continuity of care (CoC) and adherence to colorectal cancer screening after calculating a CoC index. Results: Among 107262 men with localized prostate cancer, adherence to colorectal cancer and bone mineral density screening was higher for Non-Hispanic White and Hispanic men compared to African-American men (Table). Adherence to screening was slightly higher for men who followed with primary care physicians compared to specialists. After adjusting for relevant covariates and number of providers, higher CoC with primary care physicians was associated with improved adherence to colorectal screening among Non-Hispanic Whites (OR = 1.25, 95% CI = 1.11-1.40), African-Americans (OR = 1.39, CI = 1.05-1.84) and Hispanics (OR = 2.74, CI = 1.27-5.90). However, higher CoC with specialists was significantly associated with colon cancer screening only among African Americans (OR 1.59, 95% CI 1.25-2.04). Conclusions: Among a large cohort of men with localized prostate cancer, the association between CoC and guideline-based survivorship care varied by type of provider and by racial and ethnic group. [Table: see text]
Plasma citrulline levels as a biomarker for bowel toxicity in prostate stereotactic radiotherapy with or without pelvic nodal radiation.
Authors: Fairmichael Ciaran , Redmond Kelly M. , Lyons Ciara , Stevenson Sarah R. , Osman Sarah O. , McGarry Conor K. , Irvine Denise M. , Mitchell Darren M. , King Raymond B. , Hounsell Alan R. , O'Sullivan Joe M. , Waugh David J. , Jain Suneil 
Published: March 2019

73 Background: Plasma levels of citrulline, an amino acid, are derived mainly from small bowel enterocytes. Decreased levels occur in a range of bowel conditions and citrulline has been proposed as a biomarker of bowel toxicity in pelvic radiotherapy. In a prospective study, we identify no correlation between plasma citrulline and toxicity in men receiving prostate stereotactic radiotherapy randomized to receive either pelvic nodal irradiation or not. Furthermore, citrulline levels were not significantly different between these two groups. Methods: As part of an approved clinical trial, men with intermediate to high risk prostate cancer were randomised 1:1 to prostate only or prostate + pelvic nodal radiotherapy, delivered with a rectal spacer gel in situ. The prostate and proximal seminal vesicles received 40 Gy in 5 fractions. Those randomised to the pelvic nodal arm also received 25 Gy in 5 fractions to pelvic nodes. Citrulline was measured at 10 points during treatment – consent, before fraction 1, 1 and 24 hours following fraction 1, prior to each fraction 2 – 5 and at 6 weeks’ and 3 months’ follow up. Bowel toxicity was measured by EPIC patient reported scores. Results: 16 men with follow up of at least 3 months (median 9, maximum 18 months) were analysed. Reported toxicity was significantly higher in the prostate and pelvis arm: 5 of 9 men showed a decrease in EPIC bowel domain summary score of 10 points or more compared to 0 of 7 in the prostate-only arm (p = 0.0337, two tailed Fisher’s exact test). No significant correlation between toxicity and citrulline levels was seen, nor did citrulline vary significantly between arms or fall as treatment progressed. Data analysis for a further 8 men already recruited to the study is ongoing. Conclusions: Toxicity was more commonly reported by men randomised to receive pelvic radiotherapy, suggesting that the small bowel irradiated in pelvic fields plays a role in bowel toxicity experienced during stereotactic radiotherapy. Citrulline levels showed no significant correlation with toxicity or radiation dose to small bowel. We propose that citrulline is not a useful biomarker of small bowel toxicity in this setting. Clinical trial information: NCT03253978.
Four-year outcomes of hypofractionated proton therapy for localized prostate cancer.
Authors: Grewal Amardeep S. , Schonewolf Caitlin , Both Stefan , Lam Sarah , Mazzoni Susan , Bekelman Justin E. , Christodouleas John Paul , Vapiwala Neha 
Published: March 2019

80 Background: Hypofractionated radiation therapy (HFRT) is an effective treatment for localized prostate cancer (LPC). This study was performed to determine the toxicity profile and biochemical-clinical failure (BCF) rates for patients with LPC treated with hypofractionated proton therapy (HFPT). Methods: Between 2010 and 2017, 184 men were enrolled on a trial of 70Gy in 28 fractions of HFPT for low to intermediate-risk LPC. Androgen suppression (AS) was allowed. Acute and late toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Urinary and erectile quality of life changes were captured using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) Questionnaire, respectively. Results: Median follow-up was 49.2 months. Enrolled patients had low-risk [LR] (n = 18), favorable intermediate-risk [FIR] (n = 78), and unfavorable intermediate-risk [UIR] (n = 88) disease. Twenty-six percent of patients received neoadjuvant and concurrent AS, with a median duration of 6 months. Four-year rates of BCF free survival were 95.7%, 94.4%, 98.7%, and 93.2% in the overall group and the LR, FIR, and UIR cohorts, respectively (p = .21). Overall survival at 4 years was 97.3%. No deaths were attributable to prostate cancer. Median IPSS before and 1 year post-HFPT were 6 and 7 for LR patients, 6 and 6 for FIR patients, and 8 and 7 for UIR patients. Median IIEF-5 before and 1 year post-HFPT were 21 and 18 for LR patients, 18 and 16.5 for FIR patients, and 15 and 10.5 for UIR patients. The incidence of acute grade 2 or higher gastrointestinal (GI) and urologic (GU) toxicities were 3.8% and 12.5%, respectively. One acute grade 3 GI toxicity was reported. The 4-year incidence of late grade 2 or higher GU and GI toxicity was 7.6% and 13.6%, respectively. One late grade 3 GI toxicity was reported. The predominant late grade 2 GI and GU toxicities were rectal bleeding and urinary frequency, respectively, accounting for 79% and 57% events. All late toxicities were transient. Conclusions: HFPT is associated with low rates of toxicity in the treatment of prostate cancer. Further analyses are warranted to assess long term toxicity and understand differences between proton and photon HFRT. Clinical trial information: NCT01352429.
Health literacy is a barrier to shared decision making in early prostate cancer (PCA) among African American (AA) men.
Authors: Martin-Doyle William , Filson Christopher Paul , Regan Susan , Trinh Quoc-Dien , Williams Sierra , Master Viraj A. , Kilbridge Kerry L. 
Published: March 2019

84 Background: ASCO, AUA, ASTRO and SUO endorse shared decision making for men with localized PCa. We explored treatment decisions among providers and their AA patients (pts) in a prospective cohort study at Grady Memorial Hospital and the Atlanta Veterans Administration Hospital. Methods: Following their visit, 18 providers documented the PCa treatment options they had discussed with 124 newly diagnosed, early-stage, African American PCa pts. At a subsequent visit, prior to choosing their cancer treatment, pts were asked to name the options they had discussed with their provider. Demographics were collected. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM). Numeracy, comprehension of common PCa terms, and anatomic knowledge were assessed using published methods (Kilbridge K, et al. J Clin Oncol 27:2015-2021, 2009). Chi-square, t-tests and multivariate logistic regression were used to identify variables associated with correct understanding of treatment choices. Results: Just 23.4% of pts correctly understood their treatment options. In univariate analysis, only health literacy was statistically significantly associated with comprehension of PCa treatment options (p < 0.05). In a multivariate logistic model adjusting for age, education, income, numeracy, comprehension of common PCa terms, and anatomic knowledge; health literacy remained the only significant predictor of pts’ comprehension of their treatment choices (OR 3.8, 95% CI 1.2-11.9, p = 0.021). Even among the 49 pts with the highest level of health literacy, only 34.7% correctly understood their cancer treatment options (compared to 16.0% among low literacy patients). Conclusions: Successful shared decision making requires pts to understand their treatment choices. Information presented by healthcare providers may be overwhelming for newly diagnosed pts, particularly those with lower health literacy. Our study suggests that even pts with the highest level of health literacy may need additional support to understand their PCa treatment options.
Clinical and genetic determinants of toxicity and quality-of-life (QOL) outcomes for SBRT in Asian prostate cancer.
Authors: Tan Janice Ser Huey , Tan Sheena Xue Fei , Li Youquan , Tuan Jeffrey Kit Loong , Tan Terence Wee Kiat , Wang Michael Lian Chek , Tay Kae Jack , Lee Lui Shiong , Teh Jonathan Yi Hui , Chua Melvin Lee Kiang 
Published: March 2019

95 Background: There is limited data on clinical and patient-reported quality of life (PRO-QOL) outcomes after stereotactic body radiotherapy (SBRT) in Asian men with localised prostate cancer. Demographic differences with regard to PRO-QOL outcomes may be due to variation in germline genetics. We therefore conduct a single-institution prospective phase II trial of prostate SBRT in Asian men with intermediate-risk prostate cancers (IR-PCa). Additionally, we investigated association of dosimetric and genetic factors with outcomes. Methods: Patients with biopsy-proven NCCN-defined IR-PCa were recruited. SBRT was delivered at 36.25 Gy/5fr using a Linac-based RapidArc technique. Adverse events (AEs) were assessed with CTCAEv4.0 and IPSS; PRO-QOL assessed using the EPIC instrument at baseline, 1 and 2-year post-SBRT. Germline genetics were profiled by whole exome sequencing (30X). Results: 65 patients were recruited over the period of 2014-2016 (median follow-up = 30 mo). We observed 4 acute ≥G2 gastrointestinal (GI) events (3 fecal urgency, 1 diarrhea). Longitudinal assessment of acute genitourinary (GU) events by IPSS showed worsened symptoms that peaked at 1 wk post-SBRT (44.6% vs 6.2% at 1 mo for men reporting scale upgrade). There was no significant association between acute GU effects (by IPSS) and dosimetric parameters of the irradiated urethra and bladder. PRO-QOL scores demonstrated minimal change over time across all domains; however, sexual bother in the top 50th percentile subgroup at baseline indicated ≥20% worsening of scores for 10/32 (31%) at 12 mo and 5/12 (42%) at 24 mo; which was not associated with Dosemax to the penile bulb (P = 0.1). We observed a high frequency of germline mutations in DNA repair genes (N = 10; 15.4%), including two BRCA2 stop-gain and frameshift mutations. In particular, BRCA2 mutations were detected in 2 of 4 cases with ≥G2 GI effects, independent of rectal dose. Conclusions: While prostate SBRT is well tolerated in our Asian cohort, there appears to be demographic differences in sexual bother compared to Caucasian cohorts. Interestingly, we observed a higher than expected prevalence for germline mutations in DNA repair genes, which may predict treatment response. Clinical trial information: NCT02313298.
A 17-gene genomic prostate score as a predictor of adverse pathology for men on active surveillance.
Authors: Kornberg Zachary , Cooperberg Matthew R. , Cowan Janet E. , Simko Jeffry , Chan June M. , Tenggara Imelda , Carroll Peter 
Published: March 2019

97 Background: The OncotypeDX Genomic Prostate Score (GPS) test is a RNA expression assay that can be performed on needle-core biopsies from men with prostate cancer (PCa). GPS has previously been validated as a predictor of adverse pathology in men with low-risk prostate cancer who undergo primary radical prostatectomy (RP). We sought to determine whether GPS was associated with increased risk of adverse pathology for men enrolled on active surveillance (AS) who undergo delayed RP. Methods: Of 1,662 men enrolled on AS at the University of California San Francisco (UCSF) who consented for prospective data collection, we evaluated 215 men on AS with Gleason score (GS) 3+3 and GS 3+4 PCa who underwent GPS testing at diagnostic or confirmatory biopsy (ie. within 1 year). Patients had at least 6 biopsy cores sampled and ≤ 33% positive cores, stage T1 or T2 disease, PSA < 20, and clinical Cancer of the Prostate Risk Assessment (CAPRA) score < 6. The primary outcome was adverse pathology at delayed RP, defined as GS ≥ 4+3, stage ≥ pT3a or pN1. We performed Cox proportional hazards regression, and inverse probability censored weights (IPCW) models to evaluate association between GPS and adverse pathology, adjusting for CAPRA score. Results: 72 percent (N=154) of the cohort had GS 3+3, and 28 percent (N=61) had GS 3+4. 83 percent of men (N=179) were low risk, and 17 percent of men (N=36) were intermediate risk by CAPRA scoring. Median GPS was 26.4 (interquartile range [IQR]: 18.8, 34.6). Median time from diagnosis to RP was 23 months (IQR: 15, 40). 121 men had adverse pathology on delayed RP at a median time of 27 months (IQR 16, 43) to prostatectomy. In a Cox-proportional hazards regression adjusted for CAPRA, GPS was associated with increased risk of adverse pathology at delayed RP (Hazard Ratio [HR] per 5 units: 1.12, 95 Confidence Interval [CI]: 1.05, 1.20, p < 0.01). CAPRA score was not associated with adverse pathology (p=0.09). IPCW model findings were very similar to Cox results. Conclusions: In patients who undergo RP after a relatively short period of AS, a higher GPS is associated with increased risk for adverse pathology on delayed RP.
Impact of testosterone replacement therapy after radiation therapy on prostate cancer outcomes.
Authors: Sarkar Reith , Parsons J Kellogg , Einck John Paul , Mundt Arno James , Kader A. Karim , Kane Christopher J. , Riviere Paul , McKay Rana R. , Murphy James Don , Rose Brent Shane 
Published: March 2019

99 Background: Currently there is little data to guide the use of testosterone replacement therapy in prostate cancer patients who have received radiation therapy (RT). We sought to evaluate the impact of post-RT testosterone replacement on prostate cancer outcomes in a large national cohort. Methods: We conducted a population-based cohort study using the Veterans Affairs Informatics and Computing Infrastructure. We identified node-negative and non-metastatic prostate cancer patients diagnosed between 2001-2015 treated with RT. We excluded patients for missing covariate and follow-up data. Receipt of testosterone was coded as a time-dependent covariate. Other covariates included: age, Charlson Comorbidity index, diagnosis year, body mass index, race, PSA, clinical T/N/M stage, Gleason score, and receipt of hormone therapy. We evaluated prostate cancer-specific survival, overall survival, and biochemical recurrence free survival using multivariable Cox regression. Results: Our cohort included 41,544 patients, of whom 544 (1.3%) received testosterone replacement after RT. There were no differences in Charlson comorbidity, clinical T stage, median pre-treatment PSA or Gleason score between treatment groups. Testosterone patients were more likely to be of younger age, non-black, have a lower median post-treatment PSA nadir (0.1 vs. 0.2; p < 0.001), have higher BMI, and have used hormone therapy (46.7% vs 40.3%; p = 0.003). Median duration of ADT usage was equivalent between treatment groups (testosterone: 185 days vs. non-testosterone: 186 days, p = 0.77). The median time from RT to TRT was 3.52 years. After controlling for differences in covariates between treatment groups, we found no difference in prostate cancer specific mortality (HR 1.02; 95% CI 0.62-1.67; p = 0.95), overall survival (HR 1.02; 95% CI 0.84-1.24; p = 0.86), non-cancer mortality (HR 1.02; 95% CI 0.82-1.27; p = 0.86) biochemical recurrence free survival (HR 1.07; 95% CI 0.90-1.28; p = 0.45). Conclusions: Our results suggest that testosterone replacement is safe in prostate cancer patients who have received RT. Prospective data are required to confirm the safety of post-RT testosterone replacement.