bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton therapy for prostate cancer: An analysis of rectal toxicity outcomes at University of Florida Proton Therapy Institute (UFPTI).
Authors: Colaco Rovel J. , Hoppe Bradford S. , Henderson Randal H. , Nichols Romaine Charles , Morris Christopher G. , Bryant Curtis , Li Zuofeng , Mendenhall William M. , Mendenhall Nancy Price 
Published: February 2017

161 Background: We aimed to characterize gastrointestinal effects of proton therapy (PT) in patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients on investigational protocols (IP) versus outcome tracking protocols (OTP). Methods: 1,290 patients treated consecutively with PT between August 2006 and June 2010 were studied. Pre-existing potential risk factors for RB (hemorrhoids, diabetes, aspirin, other anticoagulants) were recorded. Common terminology criteria for adverse events (CTCAE version 4.0) were used to grade toxicity. Median follow up was 3.5 years. Results: The majority (94.6%) of Grade 2 or higher gastrointestinal toxicity (GR2+) events after PT were rectal bleeding. GR1 RB occurred in 390 (30.2%) of patients, including those requiring no prescription intervention (82.6%) and those placed on a vitamin A regimen (16.3%). GR2 RB occurred in 14.7% of patients, including patients requiring prescription rectal suppositories (9.5%), cautery (4.9%), or hyperbaric oxygen (0.3%). Grade 3 (GR3) occurred in 0.8% of patients, including those requiring transfusion (0.6%) or colostomy (0.1%). Multivariate analyses showed that pretreatment daily aspirin (p=0.03), other anticoagulation (p=0.001), and the volume of rectum exposed to radiation dose levels (V70) (<.0001) were associated with an increased risk of Gr2+RB. Patients treated on investigational protocols (IP) had similar toxicity rates as those treated on an outcomes tracking protocol (OTP). Reduced rectal toxicity was noted in latter years of the study, which correlated with changes in treatment technique, pretreatment evaluation, and post-treatment supportive care regimens. Conclusions: PT was associated with low rates of GI toxicity, the most common toxicity being transient RB. GR2+RB is strongly associated with patient use of aspirin, other anti-coagulation and radiation dose volume parameters.
EpCAM expression in lymph node and bone metastases of prostate carcinoma: A pilot study.
Authors: Hoving Hilde , Campos Karen , De Jong Igle 
Published: February 2017

165 Background: Correct staging of prostate carcinoma has huge treatment implications since metastasized prostate carcinoma cannot be treated curatively. Nowadays, skeletal scintigraphy is the mainstay for the assessment for bone metastases despite its poor sensitivity. Lymph node metastases can be diagnosed accurately with Computed Tomography. However, the gold standard is a pelvic lymph node dissection. A non-invasive diagnostic modality, that can assess both lymph node and bone metastases simultaneously, is preferred. In this retrospective pilot study expression of epithelial cell adhesion molecule (EpCAM) was investigated in lymph node metastases, normal lymph nodes, and bone metastases of prostate carcinoma. Furthermore, EpCAM expression was correlated to clinicopathological parameters. Methods: Lymph node metastases (n = 22) and matched normal lymph nodes (n = 22) were available in 17 patients who underwent a pelvic lymph node dissection because of suspicion of nodal involvement on CT. Bone metastases (n = 24) were available in 24 patients who underwent surgery to confirm the disease or to treat skeletal related events. Immunohistochemistry was performed to determine EpCAM expression. Two researchers, blinded to clinical data, scored the immunoreactivity according to Allred. Sensitivity and specificity of EpCAM immunoreactivity in lymph node and bone metastases was calculated. Fisher’s Exact Test was used to correlate EpCAM expression to the clinicopathological parameters Gleason score, prior radiotherapy and prior hormonal treatment. Results: Sensitivity and specificity of EpCAM expression was 100% in lymph nodes. In bone metastases sensitivity was 92%. No correlation between EpCAM expression and clinicopathological parameters was found. Conclusions: Molecular imaging of EpCAM is promising for prostate carcinoma staging, due to the high sensitivity and specificity in lymph node metastases and the high sensitivity in bone metastases. Even in poorly differentiated metastases and after hormonal treatment and radiotherapy, EpCAM was expressed.
Perceptions of radiation oncologists and urologists on the type of evidence that informs and changes the clinical practice of prostate cancer.
Authors: Delpe Sophia D , Shah Nilay , Tilburt Jon Charles , Karnes R. Jeffrey , Nguyen Paul Linh , Shuch Brian , Gross Cary , Schulam Peter , Yu James B. , Ziegenfuss Jeanette , Kim Simon 
Published: February 2017

167 Background: Physicians have a variety of resources available about the treatment of localized prostate cancer. Yet, it is largely unknown what resources and evidence radiation oncologists and urologists commonly use to inform patients and possibly alter clinical practice. In this national survey study, we assessed the types of resources prostate cancer specialists’ use and the level of evidence needed to change treatment recommendations in localized prostate cancer. Methods: From a random sample, 1,422 physicians were sent a mail survey assessing what type of information was used to guide prostate cancer treatment. The survey also queried what level of evidence could alter recommendations. Multivariable logistic regression models were used to identify for differences in physician characteristics for each outcome. Results: Survey response rates were similar for radiation oncologists and urologists (44% vs. 46%; p=0.46). Specialty-specific journals represented the most commonly used resource to inform the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to utilize medical journals (25% vs. 38.7%, OR: 0.50; p=0.01), cancer journals (21.7% vs. 50.8%, OR: 0.50; p<0.001), but more likely to rely on clinical guidelines (46.3% vs. 37.7%,OR: 1.6; p=0.006). Radiation oncologists and urologists both viewed RCT’s as the most likely source of evidence needed to change treatment recommendations (85% vs. 77%). Conclusions: Both specialties most commonly rely on their specialty-specific journals to inform their clinical practice and view RCT’s as the level of evidence needed to change treatment recommendations for localized prostate cancer. Radiation oncologists embraced greater diversity in literature, while urologists were more likely to use clinical guidelines. Utilizing this information may overcome barriers to the dissemination and adoption of new treatment paradigms for localized prostate cancer.
A population-based study of factors associated with post-prostatectomy radiation therapy utilization.
Authors: Maurice Matthew J. , Zhu Hui , Abouassaly Robert 
Published: February 2017

182 Background: Based on level one evidence, adjuvant radiation therapy (aRT) improves cancer control in post-prostatectomy patients with adverse pathologic features. We sought to evaluate its utilization and to identify factors affecting of its use. Methods: Using the National Cancer Database, a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, we identified men diagnosed with prostate cancer between 2004 and 2011 who were found to have pT3 disease or pT2 disease with positive margins following prostatectomy. We defined aRT as radiation to the prostate and/or pelvis 6 months or less after prostatectomy. We then used univariate and multivariate logistic regression models to assess potential patient and provider predictors of aRT use. Results: We evaluated 103,092 men who had either pT3 disease (81%) or pT2 with positive margins (19%). Of these, we identified 10,043 men (9.7%) who received aRT. Since 2004, there has been a steady decline in aRT usage with time (range, 11.5% to 7.8%). Compared to 2004, patients diagnosed in 2011 were significantly less likely to receive aRT (odds ratio [OR] 0.78, confidence interval [CI] 0.71-0.85, p<0.0001). Higher Gleason score and T stage were strongly associated with positive aRT utilization (p<0.0001), while increasing age was associated with decreased use (p<0.0001). Another strong predictor of aRT uptake was hospital type. Compared to patients treated at community hospitals, patients treated at comprehensive cancer centers or teaching hospitals were significantly less likely to receive aRT (OR 0.63, 0.58-0.68, p<0.0001 or OR 0.42, CI 0.39-0.46, p<0.0001, respectively). Charlson score and hospital location were significantly but weakly associated with aRT. Other demographic variables were not predictive of aRT. Conclusions: Post-prostatectomy aRT use is declining despite clear proof of its benefit. Consistent with the evidence, patients with risk factors for biochemical relapse (i.e. high Gleason score or T3 disease) and younger patients, who are more likely to benefit, are receiving aRT. Surprisingly, aRT use is lower at teaching hospitals, which may reflect higher usage of salvage radiation.
Factors associated with biopsy progression on active surveillance.
Authors: Welty Christopher J , Cowan Janet E. , Nguyen Hao , Shinohara Katsuto , Perez Nannette , Greene Kirsten L , Meng Maxwell V. , Cooperberg Matthew R. , Carroll Peter 
Published: February 2017

19 Background: Active surveillance (AS) is a treatment strategy for prostate cancer (CaP) involving monitoring of men diagnosed with low-risk CaP to reduce overtreatment. We report factors associated with disease progression while on AS in a large, single institution cohort. Methods: We retrospectively reviewed the data of men enrolled in the University of California at San Francisco (UCSF) AS cohort between 1990 and 2012. Strict eligibility criteria were prostate-specific antigen (PSA) less than 10ng/ml, Stage less than cT3, Gleason grade 6 or less, 33% or less of biopsy cores positive, and 50% or less of any single biopsy core positive. Men who did not meet these criteria but elected AS were followed as well. Surveillance consisted of quarterly PSA testing, reimaging with TRUS at provider discretion, and annual prostate biopsy. Biopsy progression was defined as upgrade to at least Gleason 7 or increase in volume more than 33% cores. Factors associated with progression while on active surveillance were determined through multivariate Cox proportional hazards regression. Results: Of 1,009 men enrolled in AS at UCSF, 758 men have consented to participate in research to date and have been followed on AS for a median of 57 months. Of these, 518 (68%) met strict criteria for AS while 240 (32%) did not. The median number of repeat biopsies was three (IQR 2-4). At 5 years after diagnosis, 53% were progression-free and 40% of patients received local therapy. Overall survival was 94% among those not AS eligible and 100% among those AS eligible at 5 years. There were no CaP-related deaths. In multivariate analysis, only PSA density (PSAD) and later year of diagnosis were positively associated with the risk of both biopsy progression (HR 1.62, 95% CI 1.36-1.92, p<0.01 and HR 1.17, 95% CI 1.10-1.25, p<0.01, respectively) and receiving treatment (HR 1.39, 95% CI 1.20-1.60, p<0.01 and HR 1.18, 95% CI 1.14-1.23, p<0.01, respectively). White race was associated with receiving treatment (HR 1.92, 95% CI 1.35-2.74, p<0.01) but not with disease progression. Conclusions: The majority of men who enrolled in this active surveillance cohort remained on AS after a median follow up of 57 months. While higher PSAD was associated with biopsy progression, additional predictive tools would improve selection and counseling of men for AS.
Bother following stereotactic body radiation therapy for clinically localized prostate cancer.
Authors: Bhattasali Onita , Chen Leonard , Park Jee-Won , Kim Joy S. , Yung Thomas M. , Collins Brian Timothy , Suy Simeng , Lynch John , Dritschilo Anatoly , Collins Sean P. 
Published: February 2017

195 Background: Stereotactic body radiation therapy (SBRT) delivers high doses of radiation while minimizing radiation to adjacent normal tissues. Large fraction sizes may increase the risk of functional decrements. However, treatment-related bother may be more important to a patient than treatment-related dysfunction. Methods: Between August 2007 and July 2011, 228 hormone-naïve patients with clinically localized prostate cancer were treated with 35-36.25 Gy SBRT delivered using the CyberKnife Radiosurgical System (Accuray) in five fractions. Patients completed the validated Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire at baseline, one month post-treatment, every three months the first year, then every six months. EPIC scores for bother range from 0 to 100 with lower values representing increased interference or annoyance caused by limitations in function. Results: Two hundred twenty eight patients at a median age of 69 (range, age 44 to 90) received SBRT with a minimum follow-up of 24 months. Urinary bother increased transiently first at one month and again at 12 months before returning to pre-treatment scores at two years: 80.2 (baseline); 68.2 (one month); 79.8 (three months); 78.3 (six months); 74.5 (nine months); 71.1 (12 months); 75.8 (18 months); 78.3 (24 months). Bowel bother followed a similar pattern but with a more protracted late-stage decline: 91.4 (baseline); 76.0 (one month); 87.8 (three months); 88.4 (six months); 85.8 (nine months); 85.7 (12 months); 87.8 (18 months); 90.1 (24 months). Sexual bother progressively worsened over two years: 65.9 (baseline); 64.8 (three months); 63.0 (six months); 63.2 (12 months); 59.0 (18 months); 58.4 (24 months). Conclusions: SBRT for clinically localized prostate cancer was well tolerated. Treatment-related bother was comparable to conventionally fractionated radiation therapy and brachytherapy. Transient late increases in urinary and bowel bother were observed at one year. Sexual bother steadily increased during the first two years following treatment.
Circadian dysrhythm and advanced prostate cancer.
Authors: Mucci Lorelei A. , Markt Sarah , Sigurdardottir Lara , Lockley Steven W. , Fall Katja , Stampfer Meir J. , Gudnason Vilmundur , Kraft Peter , Rider Jennifer R , Czeisler Charles A , Valdimarsdottir Unnur Anna 
Published: February 2017

199 Background: The circadian rhythm regulates diverse biologic pathways including tumor oncogenes, metabolism, and cell proliferation. Dysregulation of the circadian rhythm arises from faulty input signals such as exposure to light at night, variability in core circadian rhythm genes, and variation in outputs that regulate circadian behavior including melatonin. There is compelling biologic rationale, but little human data, on circadian dysrhythm and advanced prostate cancer. Methods: We undertook an integrative molecular epidemiology study of circadian dysrhythm and advanced prostate cancer among men in the Icelandic AGES-Reykjavik cohort and the U.S. Health Professionals Follow-up Study, which allowed integration of questionnaire data, biorepositories, and long-term follow-up. We characterized circadian dysrhythm using complimentary approaches: information on sleep problems from questionnaires, prediagnostic melatonin (6-sulfatoxymelatonin) measured on first morning void urine samples, and genetic variation across twelve circadian clock genes. We used multivariable regression models to estimate relative risks (RR) and 95% confidence intervals (CI) of associations with advanced prostate cancer, adjusted for potential confounders. Results: Twenty percent of men reported sleep problems. Men who had trouble falling asleep (RR = 2.1; 95% CI 0.7-6.2) and staying asleep (RR=3.2, 95% CI 1.1-9.7) had an increased risk of developing advanced prostate cancer. Men with sleep problems had significantly lower melatonin levels compared to those without. Low melatonin levels were associated with a statistically significant 4-fold higher risk of advanced prostate cancer compared to those with high levels (95% CI: 1.25-10.0). Variant alleles in two SNPs in cryptochrome (CRY1), involved in generating and maintaining circadian rhythms, were significantly associated with risk of advanced prostate cancer in both cohorts, with a gene-level p-value<0.01. Conclusions: Our results suggest there are multiple nodes in the circadian rhythm that are associated with an increased risk of advanced prostate cancer. As such, there is the potential for complimentary strategies to target circadian disruption and reduce the risk of advanced prostate cancer.
Response to androgen signaling (AS)-directed therapy after treatment with abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Post hoc analysis of study COU-AA-302.
Authors: Smith Matthew R. , Matheny Shannon , Saad Fred , Rathkopf Dana E. , Mulders Peter F.A. , De Bono Johann Sebastian , Small Eric Jay , Shore Neal D. , Fizazi Karim , Kheoh Thian San , Li Jinhui , Todd Mary Beth , Griffin Thomas W. , Yu Margaret K. , Ryan Charles J. 
Published: February 2017

21 Background: In study COU-AA-302 of men with mCRPC and no prior chemotherapy, AA plus prednisone (hereafter AA) significantly increased radiographic progression-free survival. There is limited information about response to subsequent AS-directed therapies following AA. In this post hoc analysis of pts who received AA during study COU-AA-302, we evaluated clinical response to subsequent AA or enzalutamide (ENZ). Methods: In COU-AA-302, 546 pts were randomized and received AA. Subsequent response and discontinuation data from 88 pts receiving AS-directed therapy after study were collected retrospectively, source verified, and entered into the database. Median time to prostate-specific antigen (PSA) progression with 95% confidence intervals was estimated using the Kaplan-Meier method. Results: As of May 2013, following AA on study, 55 pts received subsequent AA and 33 received subsequent ENZ. 69% (38/55) of pts in the AA then AA group and 67% (22/33) pts in the AA then ENZ group received intervening chemotherapy. Baseline patient characteristics were similar across both groups and to the overall COU-AA-302 population. Median (range) exposure to subsequent therapy was 4 (1-20) months for AA and 5 (1-12) months for ENZ. Response to subsequent AA or ENZ is summarized in the Table. Conclusions: In this post hoc analysis, pts previously treated with AA experienced modest clinical response on subsequent treatment with either AA or ENZ. These data support further studies of subsequent AS-targeted drugs following treatment with AA for mCRPC. Clinical trial information: NCT00887198. [Table: see text]
Whole pelvic irradiation for prostate cancer patients with a biochemical relapse following radical prostatectomy: The era of robot-assisted minimally invasive surgery.
Authors: Kim Jae-Sung , Kang Hyun-Cheol , Byun Seok-Soo , Lee Sang Eun 
Published: February 2017

210 Background: We hypothesized that the addition of whole pelvic radiotherapy (WPRT) might improve biochemical outcome in salvage radiotherapy (RT) for biochemical failure (BCF), especially in patients with postoperative high-risk features after radical prostatectomy (RP) being good candidates beneficial from WPRT. Methods: From August 2004 to April 2012, 180 patients who experienced BCF after RP were treated with salvage RT. The primary end point was the biochemical relapse-free survival (bRFS) defined as no prostate-specific antigen (PSA) failure and no additional salvage treatments. Patients were stratified into theee groups; prostate bed radiotherapy (PBRT) alone (n = 52), PBRT with hormone (n = 85), and WPRT with hormone (n = 43). The effects of WPRT combined with hormone was measured in the high-risk patients defined as pN1 stage or inadequate pelvic lymph node dissection (harvested lymph nodes number of less than four). Toxicity from treatment was recorded when genitourinary or gastrointestinal (GI) events occurred. Results: The median follow-up was 43 months (8 to 103 months). The independent predictors for poor bRFS were time to PSA failure less than or equal to 1 year, PSA at salvage greater than 1 ng/mL, PSA doubling time less than 6 months, and PBRT alone group. The risk of BCF after salvage RT was significantly higher in PBRT alone group in comparison to that of WPRT with hormone group (hazard ratio [HR], 3.9; 95% CI, 1.8-8.3, p <0.001), but the outcomes of PBRT with hormone was not statistically different from that of WPRT with hormone (p = 0.67). The advantage of WPRT and hormone over PBRT alone was only observed in the high-risk patients (HR, 5.7; 95% CI, 1.8-17.7, p = 0.003), and not in other patients (HR, 3.2; 95% CI, 0.7-14.9. p = 0.14). Patient treated with WPRT had more greater than or equal to grade 2 late GI toxicity than those having PBRT (17% vs. 5%, p= 0.01). Conclusions: Patients with postoperative high risk features could benefit from WPRT and hormone therapy for postoperative BCF. The additional toxicity by WPRT and long-term outcomes warrant further investigations.
Spironolactone: A selective androgen receptor modulator in castration-resistant prostate cancer.
Authors: Barthelemy Philippe , Erdmann Eva , Duclos Brigitte , Bergerat Jean Pierre , Kurtz Jean-Emmanuel , Ceraline Jocelyn 
Published: February 2017

212 Background: Spironolactone is an effective drug to treat arterial hypertension as well as fluid retention and hypokalemia. Recently, some data suggested that spironolactone might induce progression in castration-resistant prostate cancer (CRPC) patients treated by abiraterone acetate, a recently approved selective CYP17 inhibitor. Nevertheless, no biological data are available to explain these clinical observations. The purpose of this study was to identify the potential underlying molecular mechanism. Methods: Effect of spironolactone with or without Abiraterone acetate (AA) on androgen receptor (AR) was assessed on LNCaP cells in this study. We performed a yeast-based functional assay with different levels of spironolactone with and without AA. The nuclear localization and activation of androgen receptor (AR) were detected by immunofluorescence and luciferase assays. Results: Results from the yeast-based functional assay show that the wild type androgen receptor is activated by high concentrations of spironolactone in an androgen-depleted environment. Moreover, spironolactone-induced AR transcriptional activity is downregulated by different AR antagonists as well as high concentrations of AA. These results suggest that spironolactone is possibly a potential AR modulator. Luciferase reporter assays showed that AR transcriptional activity in LNCaP cells was upregulated by spironolactone as well. Finally, AR immunoreactivity was almost nuclear in spironolactone-exposed cells. Taken together, these results suggest that spironolactone is a selective androgen receptor modulator. Conclusions: Spironolactone is a selective androgen receptor modulator and should be used with caution in routine practice in patient with metastatic prostate cancer treated by hormonotherapy especially AA.