bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate-specific membrane antigen (PSMA) PET-CT guided radiotherapy in oligometastatic prostate cancer.
Authors: Engels Benedikt , Guler Ozan Cem , Onal Cem , De Ridder Mark 
Published: March 2017

213 Background: Metastases-directed therapy by metastasectomy or radiotherapy (RT) might delay disease progression and postpone systemic treatment in patients with oligometastatic prostate cancer. Here, we evaluated retrospectively the efficacy and toxicity of 68Ga prostate-specific membrane antigen (PSMA) PET-CT guided radiotherapy (RT) in the treatment of oligometastatic prostate cancer. Methods: A total of 23 prostate cancer patients with biochemical relapse, of which 13 castration-sensitive and 10 castration-resistant, were treated with intensity-modulated and image-guided RT (IMRT-IGRT) on ≤ 3 metastases detected by 68Ga PSMA PET-CT. Androgen deprivation therapy was continued in castration-resistant patients. Local control (LC), progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Results: A total of 38 metastases were treated. Involved sites were pelvic bone (n = 16), pelvic lymph nodes (n = 11), para-aortic lymph nodes (n = 6), ribs (n = 3) and vertebral body (n = 2). The median PSA prior to RT was 1.06 ng/ml (range 0.10 – 29.0 ng/ml). A median dose of 43.5 Gy (range, 30-64 Gy) was delivered by IMRT-IGRT in 12-27 fractions. At a median follow-up of 7 months (range, 2-17 months), 19 patients (83%) are in remission. Four patients (17%) developed distant recurrence. The actuarial 1-year LC, PFS and OS rates were 100%, 51% (95% CI 8-83%) and 100%. Castration-sensitive patients displayed a statistically significantly superior PFS on univariate analysis as compared to castration-resistant patients (1-year PFS 67% vs 0%, p < 0.01). One patient experienced grade 2 acute gastro-intestinal toxicity. No grade 3 or more toxic events were observed. Conclusions: By providing optimal LC, low toxicity and a promising PFS in castration-sensitive patients, the current retrospective study illustrated that 68Ga PSMA PET-CT guided RT may be an attractive treatment option in patients with oligometastatic prostate cancer. Validation by randomized trials is eagerly awaited.
Diagnostic characteristics of men harboring lethal prostate cancer: A population-based analysis.
Authors: Thomas Helgstrand John , Klemann Nina , Toft Birgitte Grønkaer , Vainer Ben , Brasso Klaus , Iversen Peter , Røder Martin Andreas 
Published: March 2017

217 Background: Prostate specific antigen (PSA) based screening increases the number of men diagnosed with early localized prostate cancer (PCa). Further, curatively intended therapies have been demonstrated to reduce PCa mortality in randomized trials. However, controversy exists, and the overall impact on PCa mortality is less clear. Men who eventually die from PCa may constitute a subgroup with either adverse histopathological characteristics and/or clinically advanced disease at diagnosis. However, the clinical characteristics at diagnosis for men who eventually die from PCa are largely unknown. We retrieved clinical characteristics of all men dying from PCa in Denmark in an 18-year period. Methods: All men who died of PCa during the period 1995 to 2013 were identified in the Danish Causes of Death Registry. Age, Gleason score (GS), tumor stage classification, and PSA were retrieved from the Danish Prostate Cancer Registry (DaPCaR). For validation, manual revision of patient charts was performed. Patients were divided into three clinical phenotypes: distant metastatic disease, locally advanced/N+ disease, and localized disease. Patients with localized disease were further grouped according to GS and PSA. Results: A total of 19,487 men died of PCa in the period 1995-2013. In total, 46.7%, 16.8% and 25.1% of men presented with distant metastatic disease, locally advanced/N+ disease or localized disease, respectively. Among men with localized disease, 85.1% had GS ≥ 7 and only 2.1% (0.5% of all men dying from PCa) only, presented with low risk (PSA < 20 and GS ≤ 6) localized disease at the time of diagnosis. Conclusions: The majority of men (63.5%) who died from PCa had either locally advanced/N+ or M+ disease at diagnosis. Among men with localized PCa at diagnosis, the majority of men subsequently dying from PCa had either PSA > 20 ng/ml and/or adverse histopathological characteristics with Gleason score ≥ 7. A total of 94.5% of patients dying from PCa had either metastatic, locally advanced/N+, and/or GS ≥ 7 disease. Patients with localized disease, PSA < 20 ng/ml and GS ≤ 6 amounted for only 0.5% of all patients dying from PCa.
Prior therapy and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC) in a hospital-based database.
Authors: Francini Edoardo , Gray Kathryn P. , Xie Wanling , Kantoff Philip W. , Harshman Lauren Christine , Taplin Mary-Ellen , Sweeney Christopher 
Published: March 2017

221 Background: Recent reports have shown that patients (pts) with low volume (LV) mHSPC and those who relapse after prior local therapy (PLT) have median overall survival (OS) longer than 5 years with androgen deprivation therapy (ADT) alone. Using data from our prospectively collected hospital-based database, we aimed to detail the outcomes of pts with mHSPC by combining PLT or de novo (DN) and LV or high volume (HV) of disease. Methods: A cohort of mHSPCpts treated with ADT between 1990 and 2013 was identified in the Dana-Farber Cancer Institute IRB approved database and categorized as DN or PLT and HV or LV, at time of ADT start. HV was defined as visceral metastases and/or ≥ 4 bone metastases (BM) with at least 1 BM beyond the pelvis and axis. The analysis endpoints included OS, defined as time from ADT start to death from all causes. Kaplan-Meier method estimated the time to events distribution with median (95% CI). Cox proportional hazards model evaluated patient and disease volume groups on disease outcomes and provided estimates of hazard ratio (95% CI) for the comparison by groups. Results: Of the 354 pts included and classified as LV or HV, 202 (57%) had PLT, while 152 (43%) presented with DN metastases. The distributions of the 4 groups are 38% (PLT/LV), 19% (PLT/HV), 14% (DN/LV) and 29% (DN/HV). Compared to pts in PLT/LV group, those in the other 3 cohorts had a significantly higher risk of death. In particular, a statistically significant gradient in OS was noted (Trend test P < 0.001) within the groups in favor of PLT, primarily, and LV, secondarily. Conclusions: Consistent with the results seen in clinical trials, our hospital database informs us that disease volume and history of PLT define 4 distinct subgroups with different outcomes. This classification can be routinely used for counseling pts and future clinical trial design including oligometastatic disease. [Table: see text]
Impact of resistance exercise on metabolic syndrome (MetS) parameters in men receiving androgen deprivation therapy (ADT) for prostate cancer.
Authors: Dorff Tanya B. , Gross Mitchell E. , Quinn David I. , Pinski Jacek K. , Schroeder E. Todd , Groshen Susan G. , Dieli-Conwright Christina Marie , Kiwata Jacqueline 
Published: March 2017

223 Background: Cardiovascular disease is the leading cause of death in men with prostate cancer. ADT is effective treatment, but can induce loss of skeletal muscle, plus increase central fat, lipids, and insulin resistance. These changes in MetS components may contribute to excess cardiac risk. We tested whether a resistance exercise program, designed to increase skeletal muscle mass, could offset adverse changes in MetS parameters during ADT. Methods: Men on ADT for at least 12 weeks were randomized to exercise (EX) or no exercise (NOEX). EX was supervised, periodized resistance training followed by stretching 3x/week for 12 weeks, 45 min/session. NOEX did home-based stretching 3x/week. Baseline and post-intervention measurements included weight, waist circumference, lean body mass, lipids, insulin, glucose, hsCRP. Quality of life (QOL) was evaluated with FACT-P and BFI, and muscle biopsies were obtained pre- and post-intervention. Mean of changes from baseline were compared between groups using ANCOVA. Results: 24 men (mean age 65; range 49-81) completed protocol with 100% compliance (n = 12 EX, n = 12 NOEX). Baseline PSA ranged from 0 – 8.1 ng/mL and did not change; subjects had been on ADT for a mean of 17 months (range 3-84). In multivariable analysis controlling for baseline muscle mass, age, and ADT duration, the mean change in waist circumference after 12 weeks was significantly different between EX (-2.05 cm +/- 2.82) and NOEX (+0.69 cm +/- 2.01) groups (p = 0.011, t-test). There were no significant differences for other parameters. However, consistent patterns were noted in: mean fasting glucose -4.59 mg/dL in EX compared with +1.12 mg/dL in NOEX (p = 0.21, t-test) and diastolic blood pressure -2.17 mmHg in EX vs +2.0 mmHg in NOEX (p = 0.27, t-test). In the EX group 5/12 had MetS at baseline which remained stable while the NOEX group increased from 2/12 with MetS at baseline to 3/12 post intervention. Analysis of QOL and muscle biopsies are ongoing. Conclusions: Supervised resistance exercise for 12 weeks is feasible and decreases waist circumference in men receiving ADT for prostate cancer. Longer follow-up may reveal additional impacts of resistance training on MetS. Clinical trial information: NCT01909440.
Contribution of mouse adrenal glands to intratumor androgens and growth of castration-resistant prostate cancer xenografts.
Authors: Mostaghel Elahe A. , Biehl Heather , Hernandez Susanna , Zhang Ailin , Bartlett Jon , Corey Eva , Penning Trevor M. , Oksala Riikka , True Lawrence D. , Nelson Peter 
Published: March 2017

224 Background: Historical studies using radioimmunoassay did not detect adrenal androgens in serum from castrate mice, and it is widely held that rodent adrenal glands do not make adrenal androgens due to lack of CYP17A expression. This contrasts with the clinical setting in which circulating adrenal androgens are significant and inhibition of adrenal CYP17A markedly decreases tissue androgens. Methods: We evaluated CYP17A (by methylation, transcript and protein) and androgens (by mass spectrometry) in adrenal glands of CB17-NOD/SCID mice. We determined the impact of adrenalectomy (ADX) on suppressing tumor androgens and growth in two patient derived xenografts (PDX) models of castration resistant prostate cancer (CRPC). Results: CYP17A is unmethylated, and transcript and protein are present in adrenals from intact and castrate mice. In castrate mice adrenal levels of DHEA (0.75 pg/mg), androstenedione (AED; 44pg/mg), T (12.5pg/mg) and DHT (4.7 pg/mg) are detectable and nearly 2 orders of magnitude higher than in kidney, liver or muscle (p < 0.05 for all). In castrate mice bearing LuCaP35 and LuCaP96 tumors, ADX suppressed tumor steroids at 21-30 days after ADX vs castration alone (LuCaP35: AED 0.05 vs 0.02 pg/mg, p = 0.005; T 0.64 vs 0.03 pg/mg p < 0.001; DHT 2.3 vs 0.23 pg/mg, p = 0.0003; LuCaP96: AED 0.06 vs 0.02 pg/mg p = 0.08; T 0.81 vs 0.03 pg/mg, p < 0.0001; DHT 1.3 vs 0.04 pg/mg, p = 0.002), and delayed time to tumor re-growth (median survival: LuCaP35 33 vs 179 days, p = 0.006; LuCaP96 25 vs 301 days, p = 0.0012). Whereas tumor recurrence in LuCaP96 was uniformly delayed, a subset of tumors in LuCaP35 showed more rapid regrowth after ADX (66 days vs undefined, p = 0.008), with a trend toward increased levels of tumor steroids (progesterone 0.25 vs 0.02 pg/mg, p = 0.07; T 0.14 vs 0.02, p = 0.04; DHT 0.36 vs 0.21, p = 0.17). Recurrent tumors variably showed induction of full length and truncated AR variants and/or induction of steroidogenic enzymes as potential mechanisms of resistance. Conclusions: Adrenally-derived steroids are produced in mice and contribute to tumor androgen levels and growth in PDX models. Mice are an appropriate model for evaluation of steroidogenesis inhibitors in CRPC xenograft studies
Family history, race, and prostate cancer.
Authors: Schiff Joshua , Ledet Elisa M. , Ernst Emma M. , Garvey Cathryn E. , Cotogno Patrick , Sartor Oliver 
Published: March 2017

225 Background: African American (AA) race and family history (FH) of prostate cancer (PCa) increase the incidence and mortality of PCa. The goal of this study was to assess and compare FH in AA and Caucasian (C) men. Methods: During June 2015 through September 2016, 338 men with prostate cancer had FH collected at Tulane Cancer Center (C = 266 and AA = 72). A FH was defined as ≥ 1 1st degree relative with PCa and/or ≥ 2 affected 2nd/3rddegree relatives. Documented clinical factors were age at diagnosis (dx), Gleason score, incidence of radical prostatectomy (RP), and presence of metastases (at any time). Chi-square and Mann-Whitney U tests were performed to identify potential clinical correlates with regard to FH and race. Results: For demographics see table below. On average, men with a FH of PCa (n = 110) had a median age at dx of 59.6 as compared to those without a FH of PCa (n = 151) (median age at dx = 63.0). Overall FH patients (pts) were younger at dx (p = 0.00046). FH had a particularly impactful influence upon the age at dx for C men (p = 0.00086, 58 [n = 88] vs. 62.5 [n = 112]); statistics were limited for AA men. Gleason scores were not different between pts with or without a FH, and there was no relationship between Gleason score and race. Metastatic disease (mets) was detected in 23.97% of men (n = 93). C men with a FH of PCa (n = 40) were 1.55 times more likely to develop mets (p = 0.0352). AA data were limited so no comment can be made. No relationship was detected between the pts having undergone a RP and race, but pts with a FH of PCa (n = 61) were 1.39 times more likely to have undergone surgery (p = 0.016). Data by racial subsets were too limited to be conclusive. Conclusions: The study highlighted the significant impact that FH of PCa has upon age at dx and presence of mets. More AA data are needed to be conclusive. [Table: see text]
5-year patient-reported outcomes of bowel and urinary bother in the CHHiP trial (CRUK/06/016).
Authors: Dearnaley David P. , Mossop Helen , Syndikus Isabel , Khoo Vincent , Bloomfield DJ , Parker Chris C. , Logue John , Scrase Christopher D , Birtle Alison J. , Staffurth John , Malik Zafar , Panades Miguel , Eswar Chinnamani , Graham John , Russell J. Martin , Gao Annie , Wilkins Anna , Cruickshank Clare , Griffin Clare , Hall Emma 
Published: March 2017

23 Background: Hypofractionated radiotherapy (hRT) has been shown to be non-inferior to conventional fractionation (cRT) in the CHHiP trial. Clinician reported toxicity was low across all fractionation schedules at 5 years (y), as were patient reported outcomes (PRO) to 2y. Here we aim to confirm these findings with PRO data at 5y. Methods: The CHHiP trial randomised patients (pts) in a 1:1:1 ratio to cRT: 74Gy/37 fractions (f) or hRT: 60Gy/20f or 57Gy/19f. Overall bowel bother (BB) and urinary bother (UB) were assessed as single items of the UCLA-PCI and EPIC-50 instruments. PRO were completed before hormone therapy and RT (pRT). Late symptoms were assessed 6 monthly from 6-24 months and yearly to 5y. Differences in the distribution of scores were assessed using a chi2 trend test. Odds of an increase in bother were modelled using ordered logistic regression. Kaplan-Meier methods were used to estimate time to “small” or worse bother, with RT schedules compared using the log-rank test. Results: Between Oct, 2002 and Nov, 2009 2100 pts were recruited into the PRO sub-study (696 74Gy, 698 60Gy and 706 57Gy). Return rates at 5y were 355 (51%), 388 (56%) and 402 (57%) for the 74, 60 and 57Gy schedules respectively. Cross-sectional analyses at 5y showed no difference between groups (Table 1). The odds of an increase in BB from pRT to 5y for hRT compared to cRT were (Odds Ratio (OR) (99% CI), p-value): 60Gy: 0.78 (0.52-1.18), 0.12; 57Gy: 0.75 (0.50-1.12), 0.06, and for UB were: 60Gy: 1.00 (0.67-1.50), 1.00; 57Gy: 1.08 (0.72-1.61), 0.62. Time to first late “small” or worse BB was also similar across groups (Hazard ratio (HR) (99% CI), p-value): 60Gy: 1.08 (0.85-1.37), 0.42; 57Gy: 0.92 (0.71-1.18), 0.36 or UB: 60Gy: 0.93 (0.73-1.20), 0.48; 57Gy: 0.91 (0.71, 1.17), 0.34. Conclusions: After 5 years follow-up, cRT and hRT showed a similar low level of patient reported BB and UB. Clinical trial information: ISRCTN97182923. [Table: see text]
Prognostic value of neutrophil-to-lymphocyte ratio (NLR) in pts with metastatic castration-resistant prostate cancer (mCRPC) receiving a new agent (NA)- based third-line treatment: Final results from a multicenter Italian study.
Authors: Caffo Orazio , Bria Emilio , De Giorgi Ugo , Tucci Marcello , Galli Luca , Fratino Lucia , Rossetti Sabrina , Iacovelli Roberto , Lo Re Giovanni , Mosillo Claudia , Gasparro Donatello , Guglielmini Pamela , Damiani Azzurra , Procopio Giuseppe , De Lisi Delia , Ortega Cinzia , Scagliarini Sarah , Donini Maddalena , Sperduti Isabella , Basso Umberto 
Published: March 2017

230 Background: High NLR has been reported to be a poor prognostic indicator in both first and second mCRPC lines, while no information is available concerning this issue in pts treated in third line therapy. The present study is aimed to assess the possible relationship between third line clinical outcomes and NLR in a series of mCRPC pts treated with a NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] after the failure of docetaxel (DOC) and another NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. Cox regression analysis was used to assess the independent prognostic value of a series of pretreatment covariates, in terms of overall survival (OS), comprising NLR. Results: A consecutive series of 476 mCRPC pts with bone (86%), nodal (56%) or visceral (15%) mets, was collected. All pts received a NA-based third line: 135 received AA, 221 CABA and 120 ENZ. Data on NLR were available for 398 pts (84%). In the univariate analyses, the NLR as a discrete variable dichotomized according to the Maximally Selected Log-Rank statistics (optimal cut-off: 3.66), was significantly associated with both OS and progression free survival (PFS), calculated from the third line start (p < 0.0001). At the multivariate analysis, NLR, performance status, pain, hemoglobin, alkaline phosphatase, treatment with AA and with CABA were independent prognostic factors for PFS, while NLR, performance status, hemoglobin, PSA, and lactate dehydrogenase were independent prognostic factors for OS . In Kaplan-Meier analysis, the median OS from the start of third-line was higher (14.2 vs 9.3 mos) in pts with NLR ≤ 3.1 compared to those with NLR > 3.1 (log-rank; P < 0.0001). Similarly, the median PFS was 5.5 and 3.8 (log-rank; P < 0.0001) in pts with NLR ≤ 3.66 and > 3.66, respectively. Conclusions: Our results, observed in the largest cohort of mCRCP pts treated with NA-based third line after DOC and another NA, confirms that NLR is an independent factor for PFS and OS also in this population.
Association of cfDNA androgen receptor amplifications with BRAF alterations in mCRPC.
Authors: Ledet Elisa M. , Schiff Joshua , Cotogno Patrick , Manogue Charlotte , Ernst Emma M. , Lewis Brian E. , Sartor Oliver 
Published: March 2017

234 Background: Cell free DNA (cfDNA) present in plasma of cancer pts can reflect tumoral alterations. Genomic alterations in cfDNA alter prognosis and abiraterone/enzalutamide resistance in mCRPC. The goal of this evaluation was to characterize AR amplifications (Amps) and various somatic point mutations (Muts) detected in mCRPC cfDNA and to relate those changes to other common alterations in the cfDNA landscape. Methods: A heterogenous group of 46 mCRPC patients (pts) with evidence of clinical progression from Tulane Cancer Center underwent cfDNA analysis using Guardant360 test (Guardant Health, Redwood City, CA). This evaluation included full exonic coverage of 70 genes and amplifications in 18 genes. Mutations reported herein include both known pathogenic mutations as well as mutations uncharacterized for functional importance. Results: 69.5% (n = 32) of the mCRPC pts evaluated had an AR alteration. Of the pts with AR alterations, 46.8% (n = 16) had AR Amps, 43.7% (n = 14) had AR Muts, and only 6.25% (n = 2) had both. In this cohort, AR alterations were the most commonly observed aberration. In addition to amplifications, 12 different AR Muts were detected. AR Muts included: T878A (n = 9), H875Y (n = 5), W742C (n = 4), AR L702H (n = 3), and others. To better understand the relationship between AR alteration and other commonly detected cfDNA aberrations, association between BRAF (35.5%), TP53 (46.7%), and MYC (22.2%) alterations and AR were assessed. Among these genes, TP53 alterations were all Muts and MYC alterations were all Amps. BRAF alterations were predominantly Amps (N = 15) though Muts were also detected (N = 6). Neither TP53 Muts or MYC Amps were significantly associated with AR alterations. On the other hand, BRAF alterations were significantly associated with AR Amps (p = 0.041); 60% (9/15) pts with AR Amps also had BRAF alteration (Odds ratio = 7.71, 95% CI 1.284- 46.366). Conclusions: AR alterations in cfDNA impact both disease progression and response to therapy. Co-segregation of AR and BRAF alterations may have significant prognostic and therapeutic implications. Further research and larger sample size is needed to further elucidate associations between the common somatic alterations detected in mCRPC.
Tissue-based analytics provide the next generation of prostate cancer risk models.
Authors: Donovan Michael , Scott Richard , Khan Faisal m , Zeineh Jack , Koll Giovanni , Gladoun Nataliya , Charytonowicz Elizabeth , Fernandez Gerardo 
Published: March 2017

236 Background: Quantitative analysis of formalin-fixed paraffin-embedded (FFPE) prostate samples post radical-prostatectomy (RP) can help guide management of post-operative prostate cancer (PCa) patients. We have previously published on the results of our systems (precise) pathology platform which includes integration of clinical data with immunofluorescent (IF) morphology and biomarkers to predict disease progression in post-RP patients. We extended this approach by developing quantitative image features that further refine risk discrimination by directly competing with Gleason through the incorporation of biological attributes. Methods: Tissue microarrays representing a 892 RP population from Roswell Park Cancer Institute and the Henry Ford Hospital, with median 8 years follow-up were stained with a multiplex IF assay incorporating CK18 (epithelial cells), CK5/6 (basal cells), AMACR, the Androgen Receptor (AR), and Ki67. Images were captured with a Nikon i90 microscope / CRI multiplex camera and a Bayesian probabilistic approach was used to derive micro-anatomic quantitative image attributes. We generated a 50:50 balanced training / test cohort and optimized feature construction using clinical variables. Multivariate models were produced on the 324 training set to predict disease progression (i.e. clinical failure) which included a PSA rise post-adjuvant therapy, metastasis or death from PCa. The concordance index (CI), sensitivity and specificity were used to assess performance of the model. Results: A multivariate training model yielded a CI of 0.80, sensitivity 85% and specificity 74% with a hazard ratio of 9.8. By comparison a clinical only model produced a CI of 0.77, sensitivity 80% and specificity 73%, with a hazard ratio of 6. The IF model consisted of 3 features including pathologic stage and two imaging features that combine morphometry integrated with levels of AR and Ki67. Neither the Gleason score nor PSA were selected. Conclusions: Tissue-based models which incorporate objective and biological attributes accurately predict disease progression. Once validated, such approaches may replace the subjective Gleason grading system and provide an additional tool for pathologists when assigning risk.