bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histopathologic correlation of PI-RADS V.2 lesions on 3T multiparametric prostate MRI.
Authors: Katz Aaron , Liu Corinne , Kosinski Kaitlin E. 
Published: February 2017

10 Background: Prostate Imaging Reporting and Data System (PIRADS) Version 2 was recently issued by The American College of Radiology. Each score, from 1 to 5, corresponds to the likelihood of clinically significant cancer. We aim to evaluate the correlation between a higher PIRADS score and the presence of high grade tumor on histopathology. Methods: 300 consecutive 3T Multiparametric Prostate MRI (MP-MRI) were identified from March 26, 2012, to June 29, 2015. We reviewed patient charts and a total of 102 patients underwent either a transrectal ultrasound guided (TRUS) biopsy or a total prostatectomy after the MP-MRI. Thirty-four patients were excluded due to prior radiation or cryoablation to the prostate, leaving 68 treatment-naive patients (44-84 years). MP-MRIs were re-interpreted utilizing the new PIRADS V.2 scoring system and correlated with pathology findings. Statistical comparisons were made using R (v.3.1.2) and Fisher’s exact test. Results: High grade (Gleason 8-10) tumors were found only in MP-MRI with a PIRADS score of 5 and a higher percentage of tumor is found in MP-MRI with PIRADS scores of 4 and 5 (80%) when compared to PIRADS scores of 2 and 3 (32%). Low grade (Gleason 6-7) tumors were also found in both PIRADS 4 and 5 categories. There was a significant relationship between a higher PIRADS score and a finding of cancer on pathology (p = 0.0003, OR=0.118, 95% CI 0.03-0.41). Conclusions: The PIRADS scoring system is a useful tool in suggesting the likelihood of clinically significant cancer, with high grade tumors found only in MP-MRI with a score of PIRADS 5. However, MP-MRI and PIRADS criteria alone are not sufficient for determining clinically significant prostate cancer since both high grade and low grade tumors were found in PIRADS 5 and 4 categories. Correlation with other clinical parameters and biopsy is required for confirmation. A larger scale study would be helpful for further delineation. [Table: see text]
Relationship of phosphodiesterase type 5 inhibitor to biochemical recurrence after definitive therapy for prostate cancer.
Authors: Leapman Michael S. , Cowan Janet E. , Nguyen Hao Gia , Porten Sima P. , Cooperberg Matthew R. , Carroll Peter 
Published: February 2017

119 Background: Phosphodiesterase type 5 inhibitors (PDE5i) are commonly utilized among men receiving definitive treatment for prostate cancer (PCa). Recently, contradictory clinical evidence regarding the association between biochemical recurrence (BCR) and receipt of PDE5i has been reported. We aimed to clarify this question among a multi-center, cohort of men with PCa. Methods: Participants enrolled in Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) at diagnosis and received radical prostatectomy, RP, or radiation therapy, RT (external beam radiation therapy or brachytherapy) without androgen deprivation therapy ≤ 6 months. We examined associations between clinical, Prostate Cancer Index Sexual Function score, SF (0-100 (best)), and pathological characteristics as well as baseline, time-dependent and ever-use of PDE5i (patient or physician reported) with risk of BCR using descriptive analyses, Kaplan-Meier method, and multivariate Cox proportional hazards models. Results: A total of 4,844 men were identified (3,847 RP, 997 RT.) Men received RP at median age 61 years (IQR 56-66), had a mean baseline SF score 62.4 (SD 26.7), were followed for a median of 77 months (IQR 36-117), and 3,089 (80%) were prescribed or reported use of PDE5i post-operatively. Patients treated with RT were older with a median age 69 years (IQR 63-74) and mean baseline SF score 46.6 (SD 29.5), were followed for a median of 91 months (IQR 53-125), and had lower rates of reported PDE5i usage (421 men, 42%). In Cox regression models baseline use (HR = 0.9 (95% CI 0.3-2.4) p = 0.83) and ever-usage (HR = 0.7 (0.5-1.1) p = 0.73) of PDE5i were not independently associated with BCR after RP. Time-dependent use (HR 1.3 (0.6, 2.7) p = 0.45) also was not associated with BCR after RP among men taking PDE5i medications. Baseline (HR = 4.6 (0.6-37.3) p = 0.14) and ever-usage (HR 0.6 (0.3-1.5) p = 0.30) also were not associated with BCR after RT. This study was limited by incomplete data on prescription compliance. Conclusions: PDE5i usage following RP or RT for PCa was not associated with BCR. PDE5i therapy should not be withheld due to concerns that it increases the risk of disease recurrence.
Inflammatory bowel disease in patients with prostate cancer treated with radiation.
Authors: Gestaut Matthew Maxwell , Swanson Gregory P. 
Published: February 2017

15 Background: Inflammatory bowel disease (IBD) has long been considered a risk factor for increased bowel toxicity from radiation therapy (RT); however, minimal evidence exists for patients with prostate cancer (PC) and IBD. Methods: The tumor registry was queried for patients with both IBD and PC from 2000-2010. A chart review was conducted for patients who received RT for PC. All patients carried the diagnosis IBD as defined by either Crohn’s disease or ulcerative colitis. RT specifics and radiation toxicity (acute and late) data were collected. Results: Eighteen patients met the inclusion criteria for PC and IBD diagnoses with radiation therapy treatment. Twelve were treated with external beam radiation therapy (EBRT), and 6 were treated with low dose rate (LDR) brachytherapy. Average length of follow-up was 12 years (median 9.54, range 0.42-19.9). Most patients had well controlled baseline bowel function on medical management. Twenty-two percent were in remission from IBD without any form of treatment; 56% were actively taking 5-ASA; 17% were prescribed prednisone; and 6% were taking Remicade. Sixty percent of patients (9/15) reported grade 0 (G0) diarrhea at baseline prior to radiation therapy. Forty percent (6/15) suffered grade 1 (G1) diarrhea at baseline. No baseline proctitis existed. Two patients reported ostomy prior to radiation. Following radiation treatment, 78% (14/18) of patients experienced G0 diarrhea while 22% (4/18) reported G1 diarrhea. No patients suffered from greater than G1 diarrhea. Sixty-seven percent (12/18), 17% (3/18) and 17% (3/18) of patients experienced G0, G1, and G2 proctitis, respectively. No patients suffered post-radiation stricture formation. All patients with G2 proctitis following RT received 3dCRT. Conclusions: No available published data explores RT for patients with PC and IBD. This retrospective review offers valuable insight into appropriate counseling for a rare patient subset. EBRT was associated with improvement in late G1 diarrhea rates. Grade 2 proctitis was only encountered among 3dCRT patients. No post-radiation stricture or ostomy placements occurred. Our findings suggest that IBD patients experience minimal toxicity with IMRT-based radiation therapy.
Digital health application for real-time patient-reported outcomes during prostate radiotherapy.
Authors: Yang Daniel Xiao , Thea Jackson , An Yi , Yu James B. 
Published: February 2017

157 Background: The use of digital health technology, including mobile applications, in the clinical setting is becoming increasingly more prevalent. Such technology is currently being explored as clinical research tools. While the side effects of prostate radiotherapy are well documented after treatment, there remains a paucity of data on patient-reported outcomes and changes in quality of life (QOL) during the treatment period. Therefore, mobile applications represent a practical platform to enable patient reporting in real-time during prostate radiotherapy. Methods: Using an existing open source code framework (Apple ResearchKit), we developed a novel mobile application that enables prostate cancer patients to report, either during or immediately following daily radiation treatment, changes in urinary, bowel, sexual, and hormonal QOL domains. The mobile application utilizes validated questions from the Expanded Prostate Index Composite for Clinical Practice (EPIC-CP) Survey, and allows for survey responses to be tracked over time throughout the treatment period and at routine follow up. Results: For the initial phase of our study, we are currently piloting the mobile application at a single institution with a goal of accruing 50 patients. Study results will be compared to data from traditional surveys, which are available at follow-up but impracticable for real-time symptom reporting. By ASCO 2016 Genitourinary Cancers Symposium, we plan to begin the second phase of our study where any patient can enroll online through a mobile software distribution platform (Apple App Store). Conclusions: We demonstrate the feasibility of using a mobile application to enable patients to report quality of life changes in real-time during prostate radiotherapy. Moreover, our application facilitates clinical trials where patient data collection can be automated and completed at scale. Future prospective studies are planned to evaluate validity of clinical trial data gathered through such methodology.
Biallelic inactivation of BRCA2 in metastatic castration-resistant prostate cancer and platinum sensitivity.
Authors: Cheng Heather H. , Pritchard Colin C. , Nelson Peter , Montgomery Robert B. 
Published: February 2017

164 Background: Predictive biomarkers are urgently needed in the treatment of metastatic castration-resistant prostate cancer (mCRPC), and the promise of precision medicine depends on understanding the molecular underpinnings of sensitivity to specific therapies. Methods: We identified three patients with mCRPC who achieved exceptional response to platinum chemotherapy after failing prior standard therapies. To identify associated molecular lesions, we retrospectively performed clinical targeted next generation sequencing (UW-OncoPlex) on metastatic and/or primary tumors. Results: Three of three patients were identified to have biallelic inactivation of BRCA2 (breast cancer 2, early onset), a tumor suppressor gene critical for homologous DNA repair and mutations of which are associated with hereditary breast and ovarian cancers. Two patients were subsequently confirmed to carry deleterious germline mutations in BRCA2, including one patient who was diagnosed at age 66 and lacked a significant family history of cancer. The third patient had somatic BRCA2 homozygous copy loss. Conclusions: Biallelic BRCA2 inactivation in mCRPC warrants further study as a predictive biomarker for sensitivity to platinum chemotherapy.
A phase II open-label trial of GTx-758 in men with castration-resistant prostate cancer: Final analysis of the primary endpoint.
Authors: Yu Evan Y. , Hancock Michael L. , Babicz Tamas , Tutrone Ronald F. , Ng Christopher , Belkoff Laurence H. , Aronson William J. , Papai Zsuzsanna , Geczi Lajos , Getzenberg Robert H. 
Published: February 2017

185 Background: Recently approved agents that target the androgen receptor pathway emphasize the importance of the persistent activity of the androgen receptor pathway in castration-resistant prostate cancer (CRPC). This raises the possibility that agents with distinct mechanisms of action may add value. GTx-758 is a selective ERα agonist that can increase SHBG and therefore reduce biologically active testosterone (T) levels. Reported here are the results, including the final primary endpoint analysis, from the 250 mg daily GTx-758 cohort of a phase II clinical trial in men on LHRH agonists that developed CRPC. Methods: This phase II open label trial (G200712, NCT01615120) treated men with high risk nmCRPC or mCRPC with T levels < 50 ng/dL who continued to receive their current form of ADT along with either 125 mg or 250 mg of GTx-758 daily, for at least 90 days. The primary endpoint was the proportion of men with a PSA decline ≥ 50% by day 90, while secondary endpoints included serum total and free T, sex hormone binding globulin (SHBG), bone turnover markers and hot flashes. Results: The 250 mg cohort (n = 39) has completed the time period for assessment of the primary endpoint. Ten of the 39 (26%) subjects exhibited a ≥ 50% decrease in PSA by Day 90, with 11/39 (28%) by Day 120, while 18/39 (46%) had PSA declines of ≥ 30%. Median SHBG levels increased 301% of baseline, confirming the principal mechanism of drug action. While on study, median free T decreases of 44% were observed across all subjects and 20/26 (77%) of the subjects with baseline serum free T levels > 0.7 pg/ml fell below this level. Therefore, 250 mg GTx-758 decreased free testosterone levels in an additive fashion to their existing LHRH therapy. The bone turnover biomarker, C-telopeptide, decreased in 79% of the subjects. 250 mg of GTx-758 has been generally well tolerated with two reported possibly drug related SAEs (VTE and MI). Conclusions: In this phase II trial, 250 mg daily GTx-758 has activity, likely mediated by lowering free T levels in patients with CRPC on LHRH therapy, and may provide amelioration of estrogen deficiency side effects associated with ADT. Clinical trial information: NCT01615120.
Radium-223 (Ra-223) re-treatment (Re-tx): First experience from an international, multicenter, prospective study in patients (Pts) with castration-resistant prostate cancer and bone metastases (mCRPC).
Authors: Sartor A. Oliver , Heinrich Daniel , Mariados Neil , Méndez-Vidal María José , Keizman Daniel , Thellenberg-Karlsson Camilla , Peer Avivit , Procopio Giuseppe , Frank Stephen Jay , Pulkkanen Kalevi , Severi Stefano , Trigo Perez Jose Manuel , Schwarzenberger Paul , Li Rui , Nordquist Luke T. 
Published: February 2017

197 Background: Ra-223 tx for up to 6 injections (inj) is indicated for pts with symptomatic bone metastases. Ra-223 tx beyond 6 inj has not been previously reported. Herein we report the first safety and efficacy findings of Ra-223 re-tx from an international prospective trial in mCRPC pts. Methods: Pts with CRPC with ≥ 2 bone mets who completed 6 initial Ra-223 inj with no disease progression in bone and progressed after initial tx were potentially eligible for Ra-223 re-tx, provided that hematologic (heme) parameters were adequate. No concomitant cytotoxic agents were allowed; other agents were allowed at investigator discretion. Primary objective was safety. Exploratory objectives were time to radiographic bone progression, time to ALP progression, and radiographic progression-free survival (rPFS) based on MRI/CT and bone scans performed q 3 mo. Results: 44 pts had Ra-223 re-tx, 29 (66%) completed tx with all 6 inj; median (med) number inj = 6. Med time from initial Ra-223 tx = 6 mo. Besides prior Ra-223, all pts had ≥ 2 hormonal regimens; 45% had ≥ 1 chemotherapy regimen. 32 (73%) failed novel hormonal agents, eg, abiraterone and enzalutamide. Baseline characteristics were comparable to ALSYMPCA (Table). No new safety concerns were noted; incidence of tx-emergent adverse events (TEAEs) in re-tx pts was comparable to or lower than ALSYMPCA (Table). Only 2 re-tx pts had grade 3 heme TEAEs. Only 1 pt had radiographic bone progression; med time to ALP progression was not reached. Med rPFS = 9.9 mo. Conclusions: Ra-223 re-tx was well tolerated in this highly selected population, with minimal heme toxicity, and provided continued control of disease progression in bone. Clinical trial information: NCT01934790. [Table: see text] [Table: see text]
Second interim analysis (IA2) results from a phase II trial of TAK-385, an oral GnRH antagonist, in prostate cancer patients (pts).
Authors: Saad Fred , Bailen James L. , Pieczonka Christopher Michael , Saltzstein Daniel R. , Sieber Paul R. , Maclean David B. , Shi Hongliang , Faessel Helene M. , Shore Neal D. 
Published: February 2017

200 Background: Gonadotropin-releasing hormone (GnRH) antagonists achieve rapid decrease in testosterone (T) without transient T surge seen with GnRH agonists and thus may avoid clinical flare symptomatology. TAK-385 is an investigational, oral, non-peptide GnRH antagonist highly selective for the human GnRH receptor (IC50 0.12 nM). We report IA2 results from a phase 2, randomized, open label, parallel group study of TAK-385 in pts with advanced prostate cancer (NCT02083185). Methods: Pts aged ≥ 18 yrs with histologically confirmed prostate cancer, baseline T > 150 ng/dL and prostate-specific antigen (PSA) > 2 ng/mL, who were candidates for first-line androgen deprivation therapy, were randomized to receive oral TAK-385, 80 or 120 mg, once daily (QD) or leuprorelin (LEU) 22.5 mg subcutaneously every 12 wks, for 48 wks. The primary endpoint was effective castration rate of TAK-385 (T < 50 ng/dL) from wk 5–24. Secondary endpoints included: safety, pharmacokinetics (PK), and PSA. Results: At data cut-off, 75 pts had received TAK-385 (39 at 80 mg, 36 at 120 mg QD); 20 pts received LEU. Median age was 73 yrs with TAK-385 and 68.5 yrs with LEU; median treatment duration was 35.1 wks and 37.8 wks. After 3 days/4 wks/24 wks of treatment, median T was 36.9/10.6/8.9 ng/dL with TAK385 vs 648.1/13.0/11.5 ng/dL with LEU. T < 50 ng/dL was sustained over 5–24 wks in 92% vs 95% of pts (TAK-385 vs LEU). After 24 wks, PSA was reduced by 97.3% to a median of 0.1 ng/mL with TAK-385 vs 92.4% to 0.2 ng/mL with LEU. All-grade adverse events occurred in 91% vs 95% of pts (TAK-385 vs LEU); the most common were hot flush (59/60%), fatigue (21/15%), elevated alanine aminotransferase (9/10%), nasopharyngitis (8/5%), and elevated aspartate aminotransferase (5/10%). Initial analysis of pooled phase 1/2 data showed similar PK in the phase 2 pts and in previously studied healthy men, with dose-proportional plasma trough levels over > 6 mos. Conclusions: At IA2, the efficacy of TAK-385 was consistent with the GnRH antagonist mechanism of action and the safety profile was good. TAK-385 rapidly reduced T and sustained castration ( < 50 ng/dL) over 24 wks. Further investigation of TAK-385, as an option to injectable GnRH therapies, is warranted. Clinical trial information: NCT02083185.
Automated bone scan index as a quantitative imaging biomarker indicative of efficacy to enzalutamide in patients with metastatic castrate resistant prostate cancer (mCRPC).
Authors: Anand Aseem , Morris Michael J. , Larson Steven M. , Ohlsson Mattias , Joseffson Andreas , Helgstrand John Thomas , Edenbrandt Lars , Oturai Peter Sander , Roeder M. Andreas , Bjartell Anders 
Published: February 2017

226 Background: The automated BSI (auto-BSI) is a computerized means of quantitatively expressing tumor burden in bone. Following the analytical validation of auto-BSI, we are now clinically qualifying the tool as a response biomarker in mCRPC. In the present study, we assess the association of auto-BSI and that of PSA with overall survival (OS) in mCRPC patients (pts) being treated with enzalutamide. Methods: All mCRPC pts who initiated enzalutamide treatment at Skåne Hospital, Sweden and at Rigshospitalet, Denmark, with a minimum of one year follow-up, were eligible for the study. Eligible mCRPC pts with baseline (BL) bone scan available before starting enzalutamide were enrolled in the study. PSA, hemoglobin (Hgb) and alkaline phosphatase (ALP) were obtained at BL. Treatment follow-up PSA and auto-BSI were obtained at week-12. auto-BSI was obtained using the analytically validated EXIN boneBSIversion 2.0. Cox regression and concordance index (c-index) were used to evaluate the association with OS. Results: 80 mCRPC pts with BL bone scans were enrolled in the study. Treatment follow-up bone scans were available from 62 pts. Univariate analysis demonstrated that auto-BSI, PSA, ALP and Hgb at BL were associated with OS (p < 0.0001). In the multivariate analysis, only auto-BSI and HgB were significantly associated with OS. The auto-BSI showed the highest c-index in prediction of OS (c-index 0.72, SE 0.03). Adding auto-BSI to the BL covariate model significantly improved the discrimination from c-index 0.67 to 0.72 (p < 0.05). At treatment follow-up, the univariate analysis of the change in auto-BSI and the percent change in PSA were strongly associated with OS with c-index 0.76 and 0.72 (SE 0.05), respectively. In bivariate analysis, the change in auto-BSI remained strongly associated with OS (p < 0.0001) whereas the percent change in PSA appeared to be less so (p = 0.07). Conclusions: Auto-BSI and its change demonstrated an independent and a strong association with OS in mCRPC pts being treated with enzalutamide. The study serve as a foundation for prospective validation of auto-BSI as an imaging biomarker indicative of efficacy to enzalutamide.
Evaluating abiraterone responses in African Americans with metastatic CRPC.
Authors: Stolten Michael D. , Ledet Elisa M. , Guccione Jeffrey R. , Feibus Allison H. , Lewis Brian E. , Silberstein Jonathan L. , Sartor A. Oliver 
Published: February 2017

244 Background: A disparity between African American (AA) and other racial groups is documented in prostate cancer incidence and mortality. For metastatic CRPC, abiraterone (Abi) showed improvement in overall survival and gained FDA approval. However, Phase III trials enrolled mostly Caucasian (CA) patients. Documentation of Abi response rates in AA men is scant. Further characterization of Abi responses in AA men was the objective of this study. Methods: Age at diagnosis, prior enzalutamide (Enza) and/or docetaxel (Doc), and duration of Abi treatment were assessed. Baseline values at Abi initiation for alkaline phosphatase (ALP), hemoglobin (Hgb), and lactate dehydrogenase (LDH) were recorded. PSA values at baseline and throughout treatment were also logged. The velocity of PSA decline was determined by the PSA half-life (PSAHL) based on time to nadir. PCWG2 criteria were used to define PSA response and progression. Results: This was a single institution, retrospective cohort of 103 patients with mCRPC treated with Abi (n = 24 AA; n = 79 CA). Median age at diagnosis was 61.8 years and 62.4 years for AA and CA respectively. Prior Enza/Doc was 4.2%/33.3% for AA and 6.3%/29.1% for CA. Median duration of Abi therapy in AA was 207 days and 253 days for CA; neither median age or duration were statistically distinct. Median AA baseline ALP, Hgb, LDH, and PSA was 136 (range (r) = 59-653), 11.8 (r = 8.9-15.4), 256 (r = 157-401), and 59.9 (r = 4.8-1658) respectively. Median CA baseline ALP, Hgb, LDH, and PSA were 88 (r = 51-1600), 12.4 (r = 8.4-15.0), 204 (r = 100-528), and 40.6 (r = 2.5-2890) respectively. The difference in baseline lab values between AA and CA were insignificant. No statistical difference was seen in median PSAHL (AA = 55 days; CA = 64 days), or PSA decline of > 30% (AA = 50%; CA = 52%), > 50% (AA = 46%; CA = 39%), or > 90% (AA = 21%; CA = 14%). Finally, neither the median time to nadir (AA = 119 days; CA = 137 days) or progression (AA = 157 days; CA = 131 days) were significantly different. Conclusions: Comparison between AA men and CA men in mCRPC patients being treated with Abi showed no statistical difference in response rates, duration of response, or time to progression. Prospective, multi-institutional studies are needed to further assess these findings.