bluuebunny/crossref_metadata_2025_split huggingface dataset:
C-MYC, HER2, and HER3 expression in localized prostate cancer (PC) treated with radical radiotherapy: Modulation by statins use and correlation with time to progression.
Authors: Torrejon Davis Yuri , Suarez Cristina , Maldonado Xavier , Navarro Alejandra , Morales Rafael , Planas Jacques , Valverde Claudia María , Nuñez Isaac , de Torres Ines , Morote Juan , Hernandez-Losa Javier , Carles Joan 
Published: March 2020

e16045 Background: There has been growing interest in the activity of statins (St) in PC patients receiving definitive radiation therapy. The oncogene Ras can be inhibited by HMG-CoA reductase inhibitors that in turn are also able to downregulate Myc. The aim of this study was to correlate St use and progression with the c-Myc, HER2 and HER3 expression in PC treated with radical radiotherapy (RT) with concurrent androgen deprivation. Methods: A total of 85 patients diagnosed with localised PC between 2000 and 2005 were selected for the study. Inmunohistochemical assay on core biopsy of each patient was performed using monoclonal antibodies for c-Myc, HER2 and HER3. The expression was evaluated using a semiquantitative method (Hscore scale: 0 to 300). Clinical and pathological variables were compared between St users and non-users and correlated with expression of c-Myc, HER2 and HER3. St users were defined as patients who had been taking St for at least 2 years before the diagnosis of PC and during follow up. Time to progression (TTP) was analyzed. Results: Mean age was 71 (56-82) years. Median follow-up was 75 months after RT. Twenty-five patients (29.4%) were using St. No statistical differences were found between treatment groups regarding median age, risk category, clinical T stage, Gleason score or median radiation dose. Median Hscore value of c-Myc was 40 (5-210) for St users vs. 72.5 (5-280) for non-users (p = 0.01). Only 8.6% of the cases showed HER2 expression and in those staining was mild intense and focal. Moderate expression of HER3 was observed in 36 cases (41.8%) and no correlation with St users nor with TTP was demonstrated (p=0.8). At the time of analysis, only 13 pts (15.3%) had biochemical relapse (1 low risk, 3 intermediate, and 9 high risk). St use (46.2%) was significantly associated with improved TTP (55 vs. 36.2 months, p = 0.022). Conclusions: Our work implicates a correlation of St use with a significant lower c-Myc expression and improvement in TTP in all groups, regardless the risk. No correlation was reported between HER2 or HER3, TTP and St use.
Influence of concurrent medications on PSA doubling time (PSADT) in patients (pts) with nonmetastatic biochemically relapsed prostate cancer (BRPC M0) after local therapy (tx).
Authors: Mermershtain Wilmosh , Ish-Shalom Maya , Maimon Natalie , Gottfried Maya , Rouvinov Keren , Pili Roberto , Hammers Hans J. , Sinibaldi Victoria J. , Carducci Michael Anthony , Eisenberger Mario A. , Keizman Daniel 
Published: March 2020

e16051 Background: In patients with BRPC(M0) after local tx, the most important prognostic factor is probably the PSADT (high risk < 3, intermediate risk 3–8.9, low risk ≥9.0 months). Pre-clinical and clinical studies in several cancer types have shown that commonly prescribed medications may inhibit tumor growth. The effect of commonly prescribed medications on PSADT in pts with BRPC(M0) is poorly defined. Aims: To study the effect of commonly prescribed medications on PSADT in pts with BRPC (M0) after local tx. Methods: We reviewed the records of 156 BRPC(M0) pts enrolled in 1 prospective (Keizman, CCR 2010) and two retrospective (Keizman, prostate 2012; Mermershtain, EMUC 2011) studies, in 2 centers across 2 countries. The effect of clinicopathologic factors and the use of statins, aspirin, and angiotensin system inhibitors (ASIs; ACE-I and ARBs) on initial PSADT (from the time of first PSA relapse to the initiation of any systemic tx) was analyzed using the Mann-Whitney or Kruskal-Wallis tests and regression analyses. Results: In the whole patient cohort (n=156), median age was 62, prior local tx consisted of radical prostatectomy in128 pts and EBRT in 28, and median PSADT was 6.7 months (mos). Median PSADT in ASIs users (n=48) vs non users (n=108) was 7.85 vs 5.6 mos (p=0.011). In multivariate analysis, the use of ASIs and Gleason score were associated with median PSADT. The use of statins (n=58) or aspirin (n=72), primary tx modality, and time from primary tx to PSA relapse had no significant effect on median PSADT. PSADT risk grouping in ASIs users vs non users was low 48% vs 27%, intermediate 42% vs 49%, and high 10% vs 24% (p=0.02). In multivariate analysis, the use of ASIs, Gleason score, and prior ADT were associated with PSADT risk grouping. The use of statins or aspirin, primary tx modality, and time from primary tx to PSA relapse had no significant effect on PSADT risk grouping. Conclusions: The use of ASIs, Gleason score, and prior ADT may be associated with PSADT (median and risk grouping) of pts with BRPC (M0) after local tx. This should be investigated prospectively, and if validated, applied in clinical practice and clinical trials.
International prevalence of nonmetastatic (M0) castration-resistant prostate cancer (CRPC).
Authors: Liede Alexander , Arellano Jorge , Hechmati Guy , Bennett Brian , Wong Steven 
Published: March 2020

e16052 Background: CRPC represents a growing public health concern that has not been adequately quantified. In the absence of metastases, CRPC represents a transitional disease state defined by increases in prostate specific antigen (PSA) despite castration levels of androgens during androgen deprivation therapy (ADT). We developed a model to estimate M0 CRPC prevalence in selected countries. Methods: A patient-flow model was developed to estimate 5-year limited duration prevalence of prostate cancer (PC) and M0 PC in each country, each year (2008 to 2028) using age-specific incidence and survival data from population cancer registries from 28 countries in North (US, Canada, Mexico) and South America (Brazil), Europe (18 countries), Asia (5 countries), and Australia. The proportion of men with M0 PC treated with ADT was based on literature reports and survey research with physicians treating PC. PSA relapse rates from published literature were used to estimate CRPC among ADT treated. Results: PC prevalence is driven by size and aging of populations, with notable increases predicted within 15 years in regions other than US, Canada, and EU5 (table). The prevalence model, which utilized country-level data, indicates that M0 CRPC represents a relatively small proportion (2-8%) of the total PC population. Nonetheless, widespread screening and demographic changes dictate that the prevalence of CRPC will increase over the next 15 years, assuming current ADT rates. Conclusions: Incidence trends in PC are dependent on PSA screening, which is projected to lead to an increase in M0 PC and PC prevalence in most regions. The number of men treated with ADT and who ultimately develop CRPC will increase accordingly, as demonstrated in the model. [Table: see text]
Cell-free plasma DNA for the diagnosis and follow-up of prostate cancer patients.
Authors: Wroclawski Marcelo L. , Serpa Ary , Fonseca Fernando L. A. , Neto Oseas Castro Neves , Pompeo Antônio C. L. , Machado Marcos Tobias , Del Giglio Auro 
Published: March 2020

e16058 Background: Cell free plasma DNA (CF–pDNA) may have diagnostic and prognostic value in patients with Prostate Cancer (PCa). Methods: We included 133 men with PCa and 33 controls. PCa patients had blood drawn every 3 months for 2 years. CFpDNA was measured by spectrophotometry. Results: CF-pDNA had an area under the curve of 0.824 with a sensitivity of 66.2%, a specificity of 87.9% ,a positive and negative likelihood ratios of 5.46 and 0.39, respectively. There was no statistical significant correlation between CF-pDNA levels at study entry with PSA, Gleason score, stage and biochemical recurrence free survival(BRFS). However, with a mean follow up of 13.5 months, we observed significantly shorter BRFS for patients with at least one value above 140 ng/ mL of CF-pDNA during follow up (p= 0.048). Conclusions: CF-pDNA is a potentially valuable biomarker for PCa diagnosis and may have a prognostic role during follow-up of patients with PCa.
Investigator-initiated pilot study of bicalutamide and raloxifene in hormone-resistant prostate cancer.
Authors: Ho Thai Huu , Northfelt Donald W. , Nateras Rafael Nunez , Bryce Alan H. , Dueck Amylou C. , Castle Erik P. 
Published: March 2020

e16065 Background: Estrogens, in addition to androgen may contribute to the progression of prostate cancer.The combination of bicalutamide, a non-steroidal anti-androgen, and raloxifene, a selective estrogen receptor modulator, has a synergistic effect on cell death of prostate cancer cell lines such as DU145 and PC3. We investigated the safety of combined treatment of bicalutamide and raloxifene on quality of life in patients affected by hormone-resistant prostate cancer. Methods: Eligibility requirements included metastatic hormone-resistant prostate cancer, Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received the combination of bicalutamide, 50 mg, and raloxifene, 60 mg, daily in 28 day cycles for a maximum of 6 cycles. The primary endpoint was to describe the adverse event profile of combined treatment with bicalutamide and raloxifene. The secondary endpoint was to describe the quality of life of patients receiving the combination. Adverse events were graded by the investigator using the NCI Common Terminology Criteria for Adverse Events version 4.0 and the quality of life was assessed by the patient using aLinear Analog Scale Assessment (scale of 0-100). Serum levels of estradiol and testosterone were monitored during treatment. Results: Eighteen evaluable patients were included in the statistical analysis after an initial run-in safety cohort of six patients. Two patients completed 6 cycles per protocol, the remaining sixteen patients were taken off protocol after disease progression. Patients completed a median of 2 cycles. There were no grade 4 events and grade 3 adverse events consisted of hypertension (5.6%) and back pain (5.6%). Erectile dysfunction (grade 1) was the most common adverse event (77.8%). Patient assessment of quality of life (mental, physical, social, emotional, spiritual) did not reveal any statistically different changes after 2 cycles of treatment. An analysis of testosterone and estradiol levels will be reported. Conclusions: We conclude that combination of bicalutamide and raloxifene is well-tolerated. The combination of androgen and estrogen receptor blockade warrants further study for efficacy in hormone-resistant prostate cancer. Clinical trial information: NCT01050842.
How does stereotactic body radiotherapy compare to standard external beam radiotherapy or low-dose rate brachytherapy for low-risk prostate cancer?
Authors: Sethukavalan Perakaa , Cheung Patrick , Morton Gerard , D'Alimonte Laura , Deabreu Andrea , Mamedov Alexandre , Zhang Liying , Chung Hans T. , Nam Robert , Loblaw D. Andrew 
Published: March 2020

e16070 Background: Stereotactic body radiotherapy (SBRT) is an emerging radiotherapy technique that appears to be efficacious, well tolerated and convenient. However, outcomes for patients treated with SBRT are unknown compared to more conventional radiation options for patients with prostate cancer. The purpose of this study is to evaluate and compare late toxicities and biochemical disease-free survival (bDFS) of low risk prostate cancer patients treated SBRT (35Gy/5 fractions), standard external beam radiotherapy (STND; median 76Gy/38 fractions) or low-dose brachytherapy (LDR; iodine-125, 145Gy) at the Odette Cancer Centre. Methods: Consecutive patients with low risk prostate cancer treated with radiation from 2006-2008 were analyzed. Patients treated with SBRT were part of a phase 2 prospective clinical trial; patients treated with STND or LDR had data abstracted from medical charts retrospectively. Patients treated with neoadjuvant androgen deprivation therapy were excluded from biochemical analyses. Univariate (UVA) and multivariate analyses (MVA) of Cox proportional hazard model were conducted to identify significant covariates predicting bDFS. Results: A total of 357 low-risk prostate cancer patients were identified (84 SBRT, 81 STND and 192 LDR). The median follow-up was 57, 62, and 59 months, respectively. At baseline, 85% of patients were T1c, 15% T2a; 100% had GS 6; median PSA 5.9 ng/ml. There were more patients in the STND and LDR cohort who had T2a disease (6%, 21% and 16%, p= 0.013) and the mean PSA was higher in the STND cohort (6.08, 6.69, and 6.02, p=0.017). Patients who received LDR experienced more late hematuria (0%, 1.23% and 11.98%, p<0.0001); otherwise there were no significant differences in late toxicities observed. There were no significant differences in bDFS (97.4% vs 96.9% vs 97.2% at 60 months, p=0.94). There were no covariates identified predicting bDFS on UVA or MVA, including treatment type. Conclusions: SBRT, STND and LDR show equivalent effectiveness and both external beam techniques showed less hematuria than LDR. However, SBRT and LDR are more convenient and less costly than STND. Further prospective studies of SBRT are ongoing.
Skeletal-related events (SRE) and bone-targeted agents for metastatic prostate cancer: Are we changing outcomes?
Authors: Moretto Patricia , Hutton Brian , Kuchuk Iryna , Canil Christina M. , Ng Terry L. , Addison Christina L. , Clemons Mark J. 
Published: March 2020

e16074 Background: Bone-targeted agents (BTA) have been extensively studied in patients (pts) with prostate cancer (PC) and bone metastases (BM). Relatively little is known about the impact of BTAs on skeletal morbidity in the non-trial setting. We evaluated the impact BTAs on SRE and survival at a large Canadian cancer centre. Methods: Electronic heath records were reviewed for PC pts referred for further management from January 2008-June 2012. Demographic, clinical, and treatment data including: date of CRPC, occurrence of SRE, and BTA use were collected and analyzed. Results: A total of 141 pt charts were examined and were included in the analysis. Median age was 74 years (IQR 63-82), and 95% were stage IV at time of referral. Consequences of BMs included:101 pts had at least one SRE (72%), 58 (40%) pts had ≥1 SRE and 39% were hospitalised due to an SRE. Median overall survival from diagnosis of BM was 35.4 months (m) (IQR 16.1-65.9). Overall, 74 pts (52%) developed castration resistant PC (CRPC). In the CRPC group, the use of imaging to assess BM was highly variable, ranging from only once (12%) to every 1-2 m (4%), however the mode was every 3-5 m (43%). Sixty one percent (45/74) received a BTA, primarilyzoledronic acid (ZA). Despite having CRPC and BM, 39% never received a BTA, mainly because it was not offered (64%), or due to patient’s refusal (29%). Median time from diagnosis of CRPC to start of BTA was 1 month. Sixty-nine percent of pts had BTA discontinued, mainly due to progression of disease and pts deterioration. Osteonecrosis of the jaw occurred in 4% (2/45). In 39 pts (53%) the first SRE occurred prior to CRPC diagnosis, and 62 pts (84%) had at least 1 SRE after CRPC diagnosis. Forty seven percent (21/45) had a new SRE after starting BTA. Conclusions: BM have significant consequences for pts with PC irrespective of hormone sensitivity. Even for pts with CRPC the use of BTAs is highly variable. This reflects physician’s belief in the efficacy of BTAs, tailored by the expected benefits to each pt according to performance status and extent of disease. Interestingly in the CRPC group 53% have had an SRE prior to CRPC diagnosis. Strategies to optimise the care of pts with BM are clearly warranted.
Utilization and cancer detection by U.S. prostate biopsies (2005-2011).
Authors: Olsson Carl A. , Kapoor Deepak A. , Anderson Ann E. , Mendrinos Savvas E. , Bostwick David G. 
Published: March 2020

e16076 Background: To assess the positive biopsy rate and core sampling pattern in patients undergoing prostate biopsy in the US at a national reference laboratory and pathology laboratories integrated into urology group practices and analyze the relationship between positive biopsy rates and number of specimen vials per biopsy (v/b). Methods: For the years 2005-11, we collected pathology data from a national reference laboratory (NRL) including number of urologists and urology practices referring samples, total specimen vials submitted per prostate biopsy, and final diagnosis for each case. The diagnoses were categorized as benign, malignant, prostatic intraepithelial neoplasia or atypical small acinar proliferation. Over the same period, similar data was gathered from urology practices with in-house laboratories performing global pathology services (urology practice labs, UPL) identified by a member survey of the Large Urology Group Practice Association. For each year studied, positive biopsy rate and number of specimen vials/biopsy were calculated in aggregate and separately for each site of service. Results: From 2005-11, 437,937 biopsies were submitted in 4,230,129 vials (9.4 v/b); overall positive biopsy rate was 40.3%, identical at both the NRL and UPL (p=0.97). Nationally, the number of specimen vials/biopsy increased sharply from a mean of 8.8 during 2005-8 to 10.3 from 2009-11 (difference 1.5 v/b, p=0.03). For the most recent 3 year period (2009-11), there was no significant difference between the NRL (10.0 v/b) and UPL (10.6 v/b) (p=0.08). Positive biopsy rate correlated strongly (p<0.01) with number of specimen vials/biopsy. Conclusions: The positive prostate biopsy rate of 40.3% is identical across sites of service. Although there was a national trend towards increased specimen vials/biopsy from 2005-11, from 2009-11 there was no significant difference in specimen vials/biopsy across sites of service. Increased cancer detection rate correlated significantly with increased number of specimens examined. Segregation of prostate biopsy cores into 10-12 unique specimen vials has been adopted by urologists across sites of service and can be considered the de facto national standard of care.
Clinical outcome (CO) and predictive factors (PRE) evaluation of a cohort of castration resistant prostate cancer (CRPC) patients (pts) treated with abiraterone acetate (AA) in a named patient program (NPP): Preliminary results from a retrospective study.
Authors: Veccia Antonello , Fratino Lucia , Basso Umberto , Donini Maddalena , D'Angelo Alessandro , Massari Francesco , Procopio Giuseppe , Gasparro Donatello , Verderame Francesco , Messina Caterina , Zustovich Fable , Iacovelli Roberto , Fraccon Anna Paola , Pappagallo Giovanni L. , Maines Francesca , Caffo Orazio , Galligioni Enzo 
Published: March 2020

e16078 Background: AA provided a survival advantage compared to placebo, in pts who had received docetaxel for CRPC. Before the regulatory authority approval, AA was made available in Italy through a NPP supervised by the local ethic committees. The present retrospective study is aimed to assess PRE and CO in an unselected CRPC population which received AA by NPP. Methods: We retrospectively reviewed the clinical records of all pts treated with AA by NPP in our Institutions. For each pt we have recorded the pre and post-AA clinical history, the treatment details and outcomes. We have assessed the ability of a series of selected 22 clinical factors to predict AA response through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: To date we have collected a consecutive series of 136 pts from 13 Italian hospitals. The median age was 72 yrs (range 52-87). The median baseline PSA was 154 ng/ml (range 0.33->100.000); 80% and 16.7% of the pts showed bone and measurable lesions respectively. The median duration of AA treatment was 15 wks (range 1-73); 59 treatments are ongoing. Grade 3-4 toxicities were anemia (5 pts), nausea (1 pt), fatigue (4 pts), bone pain (3 pts), and hypokaliemia (1 pt). A PSA reduction > 50% was observed in 37.5% of the pts. Having a performance status (PS) 0-1 [(exp(beta) 4.541; p= 0.018], a previous ormonotherapy lasting >40 months [(exp(beta) 3.299; p= 0.020], baseline hemoglobin >12 g/dl [(exp(beta) 2.595; p= 0.074], no visceral organ involvement [(exp(beta) 1.929; p= 0.097] resulted to be independently predictive of a PSA reduction > 50%. The median PFS and OS were 5 mos and 14 mos, respectively; the 1-year PFS and OS rates were 25.7% and 53%, respectively. Conclusions: Our preliminary results have confirmed the efficacy of AA in second line CRPC outside clinical trials. Pts with good PS, with good hemoglobin levels, with long-lasting hormosensitivity, and without visceral organ involvement have higher probability to achieve a biochemical response to AA.
Effect of suppression of bcl-2 with antisense oligonucleotides on p53 expression.
Authors: Guinan Patrick , Rubenstein Marvin , Hollowell Courtney M.P. 
Published: March 2020

e16085 Background: In theory gene therapy is specific but difficulties are encounted in practice. Tumors express altered patterns of expression and regulatory pathways provide many targets. However the actual activity of most genes are similar to normal. Resistance develops because pathways are complex, regulated by stimulatory and inhibitory factors, each affected by therapy. Tumors alter dependence on targeted gene products for growth by relying upon others, through compensation. Antisense oligos have targeted regulatory proteins in both in vivo and in vitro prostate cancer models. Cells treated with antisense directed against bcl-2 compensated by suppressing caspase-3 (an apoptosis promoter) and enhancing androgen receptor (AR), (co-activating) p300 and IL-6 expression. This suggests that in LNCaP a progression to increased androgen sensitivity accompanies bcl-2 suppression with a pattern of co-activation associated with more advanced prostate tumors. Methods: We evaluated mono- and bispecific oligos which targeted and equally suppressed bcl-2 expression in LNCaP cells. To further evaluate compensatory mechanisms related to tumor resistance we evaluated the level of the suppressor gene p53 employing RT-PCR and agarose gel quantification. Bands representing pcr product were photographed, converted to black and white and assessed by MIPAV software. Results: Comparable amounts of RNA from LNCaP cells treated with either mono- or bispecific oligos directed against bcl-2 (and EGFR in the bispecifics) were evaluated by RT-PCR using primers directed against p53. When background intensity was subtracted, the relative intensity of all bands corresponding to p53 and representing cells treated with MR4, MR24 and MR42 (compared to controls) were respectively increased 47.5% ± 42.3 (p = 0.02), 86.5% ± 35.3 (p = 0.00013) and 58.0% ± 42.0 (p = 0.0077). These results were pooled from both duplicate PCR runs and gels, and indicate each oligo targeting bcl-2 significantly enhanced p53 expression. Conclusions: Inhibition of bcl-2 activity mediated via antisense oligos enhances suppressor gene p53 expression. In contrast to the effects noted above, p53 enhancement would appear beneficial.