bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening of BRCA2 mutated men for detection of prostate cancer: Preliminary results from a national high volume cancer center.
Authors: Zuradelli Monica , Buffi Nicolo' , Bianchi Paolo , Ripamonti Carla Barbara , Barile Monica , Casale Paolo , Saita Alberto , Lughezzani Giovanni , Hurle Rodolfo , Lo Iacono Nadia , Guazzoni Giorgio Ferruccio , Lazzeri Massimo , Santoro Armando 
Published: May 2019

e16567 Background: Up to 10% of cases of Prostate Cancer (PCa) are hereditary. Germline pathogenic mutations in BRCA2 gene confer the highest risk (2.5 to 8.6 fold in men ≤ 65 yr). Beyond periodic Prostate Specific Antigen (PSA) dosage and digital rectal examination (DRE), a targeted screening for carriers is still undefined. Prostate Health Index (PHI), a combination of the tPSA, fPSA and proPSA tests, may be a more accurate biomarker than PSA only to detect PCa. We evaluated how to better screen BRCA2 mutated men for PCa. Methods: We reviewed the genealogical trees of all women tested positive for germline BRCA2 pathogenic mutation at our clinic. We offered targeted BRCA2 mutational analysis to all first/second degree relative men between 40 and 69 yr. A targeted screening program (annual PSA and PHI dosages and DRE) was proposed to all men tested positive. In case of PSA and/or PHI values out of range ( > 4ng/ml and > 20, respectively) we proceeded with a multiparametric Magnetic Resonance Imaging (mpMRI) and fusion biopsy of suspected lesions. Results: From June 2008 to October 2018 610 breast/ovarian cancer patients had BRCA test: 35 (5.7%) tested positive for BRCA1 pathogenic mutation, 32 (5.2%) for BRCA2 pathogenic mutation. From October 2017 90 relatives were checked for the familial mutation and 24 (27%) (12 women, 12 men) tested positive for BRCA2 mutation. All the 12 men (median age 48 yr, IQR 44 to 60) accepted to join our screening program. During the first year all men had negative DRE. Median PSA was 0.70 (IQR 0.43 to 1.02), median PHI was 17.56 (IQR 11.85 to 24.06). One patient with out of range PHI value already had mpMRI resulted negative. During the second year 4 men underwent screening so far: they had negative DRE. Median PSA was 0.57 (IQR 0.38-0.77), median PHI was 16.88 (IQR 11.87-21.90). Two men had PHI out of range and will undergo mpMRI. Conclusions: An accurate review of the genealogical trees of breast/ovarian cancer BRCA2 mutated patients allows to identify male relatives potentially carriers of the same mutation. These men have a high lifetime risk of PCa and require an appropriate screening, currently absent. Our approach may be leveraged as proof of concept of selection and screening program in carriers of BRCA2 mutations.
The effect of E2F7 expression in prostate cancer on apoptosis and cell cycle of prostate cancer cells.
Authors: Wang Ying 
Published: May 2019

e16568 Background: Prostate cancer (PCa) is a leading cause of illness and death among men in the United States and Western Europe. However, the molecular mechanisms by which PCa developed has not been fully illustrated. Methods: Here, the expression of E2F7 in PCa was examined using IHC method and western blotting assay, and the expression of miR-30c was measured using qRT-PCR method. The cell cycle and apoptosis was determined by FACS. Cell Counting Kit-8 was used to testify cell proliferation. miR-30c mimics, miR-30c inhibitors and E2F7 siRNA transfections were performed to study the loss- and gain-function. Duel-luciferase reporter assay was performed to verify that E2F7 was one of the potential targets of miR-30c. Results: It was found that E2F7 was overexpressed in PCa cells and tissues compared with normal ones. Inhibition of E2F7 in PCa cells led to significant decreased proliferation rates, increased G1 phase percentage, and higher apoptosis rates of PCa. Duel-luciferase reporter assay showed that E2F7 was one of the targets of miR-30c. Moreover, introduction of miR-30c resulted in decreased proliferation rates, increased G1 phase percentage, and higher apoptosis rates of PCa cells while miR-30c inhibitor led to lower apoptosis rates of PCa cells. Conclusions: In conclusion, our study demonstrated that E2F7 may play a tumorigenesis promoting role of PCa cells, and that E2F7 was regulated via miR-30c, indicating that E2F7 and miR-30c might be viable therapeutic targets for PCa.
Determination of AR-V7 in plasma in patients with metastatic prostate cancer using capillary Nano-immunoassay.
Authors: Virseda Alvaro , Garcia Juan Luis , Marcos Asensio Sara , Garcia Garcia Javier , Herrero POLO Manuel , Cigarral Garcia Belen , Misiewicz-Krzeminska Irena , Gonzalez Rogelio , Garcia Rocio , Cruz-Hernández Juan J. , Veiga Francisco Gomez 
Published: May 2019

e16574 Background: Liquid biopsy has the potential to provide information about cancers without invasive biopsy, using circulating biomarkers. The aim of present study was determinate the presence of androgen receptor splice variant 7 (AR-V7) in plasma using capillary nano-immunoassay in metastasis PCa and correlation with clinical and analytical data. Methods: Whole blood (10 ml) was collected and processed in EDTA tubes. Previously to determinate the presence of ARV-7 in plasma Capillary Electrophoresis Immunoassay or SimpleWestern analyses were performed using the WES™ machine. With this technique, proteins are separated by size, immobilised and probed with specific antibodies. The primary antibody used was Anti-Androgen Receptor antibody. Results: The study included 31 patients with diagnostic of PCa metatasic . Clinical characteristics of the patients were described in the table. AR-V7 signal was detected in 11 cases (36%). Twenty samples (64%) were considered as negative. The most of patients with expression positive for AR-V7, showed a Gleason score ≥ 8 (64% of cases). In AR-V7+, hemoglobine and dehydrogenase lactate levels were statistically significant (p < 0,05) respect to ARV7-. So, in AR-V7+ patients showed increased of FA and Albumin. Conclusions: Assessing the presence of AR-V7 in plasma from PC patients is feasible by a novel capillary nano-immunoassay. AR-V7 was observed in 36% of the PCA metastasic. These findings lay the foundations for liquid biopsy as a means of obtaining biological data in a more convenient way for the patient.[Table: see text]
Shared-decision making in prostate cancer with clinical decision-support.
Authors: Rocha Hermano Alexandre Lima , Dankwa-Mullan Irene , Juacaba Sergio Ferreira , Willis Van , Arriaga Yull Edwin , Jackson Gretchen Purcell , Meneleu Pedro 
Published: May 2019

e16576 Background: Shared decision-making is the process of deliberately interacting with patients who wish to make informed value-based choices, when there are no indicated best treatment options. Given the wide variation in prostate cancer treatment options, clinical decision-support systems (CDSS) may effectively support treatment decisions for patients with challenging risk-benefit profiles. However, limited data are available regarding CDSS in shared decision making. This study aimed to assess the alignment of CDSS therapeutic options with treatment received through a shared decision process. Methods: We identified patients with prostate cancer (Gleason Groups 1-5) who were engaged in shared treatment decision making, (from August–September 2018) at the Instituto do Câncer do Ceará, Brazil. IBM Watson for Oncology (WfO), a CDSS was used for the study. Treatment decisions were compared with WfO options (active surveillance, clinical trial, chemotherapy [CT], hormone therapy [HT], radiation [RT], brachytherapy [brachy], surgery and systemic therapy with GnRH suppression) and categorized as concordant (equivalent), partially concordant (a partial match), or discordant. Results: Concordance between WfO and shared treatment decisions was observed in 54% (26/48) of patients, partial concordance in 15% (7/48) and discordance in 31% (15/48). Most frequent treatments were RT+HT combination therapy (25%) and prostatectomy (21%). 8/15 (53%) discordant cases were due to patient preference for treatment over active surveillance. Patient preference for treatment over active surveillance was the most common reason (53%) for discordance. Conclusions: Variation in prostate cancer treatment exists. CDSS therapy options may be useful in quantifying and modifying unwarranted variations in prostate cancer treatment. Future studies are important for understanding reasons for variations. [Table: see text]
Longitudinal prostate cancer outcomes in a racially diverse cohort of military heath care beneficiaries: 1990-2017.
Authors: Cullen Jennifer , Oehrlein Nathan , Streicher Samantha , Kuo Huai-Ching , Chen Yongmei , Rice Kevin R. , Lu-Yao Grace L. , Rosner Inger L. 
Published: May 2019

e16581 Background: Prostate cancer (PCa) incidence and mortality disproportionately burden African American (AA) men compared to Caucasian American (CA) men. An interplay of biological, social, and health care factors is blamed for this disparity. However, a recent multi-center study of the Veterans Affairs population found no differences in cancer progression, disease specific survival, or overall survival for AA versus CA men. This study examines a large, racially diverse military health care beneficiary cohort, enrolled over 25+ years, to examine the roles of race and comorbidity on metastasis-free and overall survival. Methods: The Center for Prostate Disease Research (CPDR) multi-center national database was the source of study subjects. Eligible patients included all men who underwent radical prostatectomy (RP) as primary treatment for PCa between January 1, 1990 to December 31, 2017. Comprehensive demographic, clinical, treatment, and outcomes data were collected on all enrollees. Unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis with adjustment for key clinical and pathologic factors were used to examine BCR-free, metastasis-free, and overall survival as a function of patient self-reported race (AA vs. CA). Results: There were 7,135 eligible men, among whom 22% self-reported as AA. Median age at RP and follow-up were 62 and 6.9 years, respectively. A total of 1521 BCR events, 210 metastasis events, and 879 deaths occurred. Compared to CA men, AA men were younger at diagnosis (59.4 vs. 62.7 years, p < 0.05) with higher median PSA (5.8 vs. 5.5 ng/mL, p < 0.05); however, NCCN risk strata, as well as clinical and pathologic stage and grade were distributed comparably across race. Despite slightly poorer BCR-free survival for AA men in both unadjusted and adjusted analysis, there were no statistically significant differences in 5-, 10-, and 15-year probabilities for metastasis-free or overall survival. Conclusions: In this racially diverse equal-access health care setting, this longitudinal cohort study revealed no differences in distant metastasis or overall survival between AA and CA men. Future work will examine molecular signatures of metastatic cancer.
Cancer driver genes in prostate cancer from young men.
Authors: Maistro Simone , Xavier Camila dos Santos , Serio Pedro Adolpho MP , Katayama Maria Lucia Hirata , Roela Rosimeire Aparecida , Koike Folgueira Maria A. A. 
Published: May 2019

e16586 Background: Although prostate carcinoma is the most frequent cancer in older man, it is a rare disease in young adults. Search for global knowledge of the cancer genome is of great importance for diagnosis and/or treatment of these patients. Our goal was to identify the mutation profile of prostate carcinoma from young adults aged ≤49 years, using in silico tools. Methods: In silico analysis of somatic variants derived from exome or genome sequencing, deposited in the COSMIC or CBIOPORTAL database or in published manuscripts was performed. Data was searched for cancer driver genes catalogued in Cancer Gene Census (CGC) or Candidate Cancer Gene Database rank A or B (CCGD) and DNA repair genes. Results: 46 prostate adenocarcinoma samples from patients aged between 23-49 years (median 44.5) were included. A median of 15 variants per patient (minimum: 2 and maximum: 343) was detected. The most frequent events were C to T transitions, representing a median percentage of 39% of the substitutions. A total of 160 genes were affected by pathogenic mutations (splice site, nonsense, frame shift ins, frame shift del, nonstop, in frame del). Ten tumors presented pathogenic variants in at least one cancer driver (CGC); 3 tumors presented SNVs in two CGC. The most frequently altered cancer causing genes (CGC) were MUC16 (17%); TP53 (8%), SPOP (8%), XPC, SYNE1, IDH1, CDMD3, ANAPC1, AHNAK (6%). Seven tumors presented pathogenic variants in at least one in driver candidate from CCGD rank A, and 3 tumors in CCGD rank B. Single nucleotide variants affecting genes involved in DNA repair were found in 35% samples and one tumor presented variants in genes involved in BER, NER, FA, DDC and HRR. Variants in TP53 and XPC wer3e detected in 3 tumors. Conclusions: In prostate carcinoma from young men a wide range of cancer causing genes may be altered, including MUC16 and TP53. Variants in DNA repair genes may be found in 35% of the samples.
The impact of simultaneous dose escalation VMAT to the focal lesion micro boost of localized prostate cancer.
Authors: Ahmed Radwa Fawzy Saleh , Abdel Malek Raafat Ragaie , Metwaly Mohamed , Abdel Aziz Omar , Al sirafy Samy , Seleem Ahmed 
Published: May 2019

e16592 Background: Dose Escalation to the prostate is showing promising results of increasing local control. The study aims to assess biochemical failure free survival (BFF) after dose escalation to the prostate 78Gy with simultaneous integrated boost (SIB) 87Gy to the focal lesion. Genito-urinary (GU) & gastro-intestinal (GI) toxicity was assessed by comparing investigational toxicity score & patient outcome reports. Methods: Thirty intermediate & high risk localized prostate cancer patients were treated with dose escalated VMAT protocol of 78 Gy/35 fractions to prostate & 87Gy boost to focal lesion detected by baseline multi-parametric MRI & TRUS as well. Neo-adjuvant, Concurrent & adjuvant hormonal therapy was applied. Risk structures dose statistics were matched to modified Quantec with EQD2 equation. For each patient, daily online fiducial markers image guided verification was done. Toxicity profile was assessed by RTOG for subjective assessment and FACIT quality of life protocol for objective assessment during the radiotherapy course & follow up period. Results: About 80% of patients received the pre-determined protocol, however three patients received 76Gy to prostate & 84Gy to the focal lesion to comply with the risk structure constrains. At median follow up period of 18 months-BFF was 93.3 %. By the end of radiotherapy, 80% developed G3 GU toxicity while 30% developed G2 GI toxicity. Correlation between bladder V40 (≥or≤ 40%) & GU toxicity (≤ G3 vs G3) was of border line statistical significance (P = 0.05). After radiotherapy, GU toxicity dropped to 17.2% G2 & 13% G3 at the 3rd month while 0 % G3 afterwards. Three patients developed G4 rectal toxicity (bleeding per rectum); one at 9th month of ending treatment & two at 12th month; two of them needed cautery for angio-dysplasia as post radiation sequelae confirmed by colonoscopy. However, the correlation between V40 of the rectum ≥ 40% was significant with rectal toxicity (G0 vs G4) (P = 0.02). Comparing FACIT assessment during radiotherapy or in follow up showed no significant difference affecting the quality of life. Conclusions: Dose Escalation with SIB should be done using advanced technique like VMAT with image guidance. Re-validation of risk structure & rectal dose constrains should be considered especially for dose escalation ≥ 72Gy. Clinical trial information: NCT03384199.
Prostate image-guided transperineal elastic-registration biopsy, a new diagnostic tool to refine the risk-stratification of prostate cancer and improve therapeutic decisions.
Authors: Graff-Cailleaud Pierre , Covin Bertrand , Portalez Daniel , Aziza Richard , Khalifa Jonathan , Roumiguié Mathieu , Malavaud Bernard 
Published: May 2019

e16595 Background: To evaluate image-guided Transperineal Elastic-Registration biopsy (TPER-B) in the risk-stratification of low-to-intermediate risk prostate cancer detected by Transrectal-ultrasound biopsy (TRUS-B) when estimates of cancer grade and volume discorded with multiparametric Magnetic Resonance Imaging (MRI). Methods: All patients referred for active surveillance or organ-conservative management were collegially reviewed for consistency between TRUS-B results and MRI. Image-guided TPER-B of the index target (IT) defined as the largest Prostate Imaging-Reporting Data System-v2 ≥3 abnormality were organized for discordant cases. Pathology reported Gleason grade, maximum cancer core length (MCCL) and total CCL (TCCL). Results: Of 237 prostate cancer patients (1-7/2018), 42 required TPER-B for risk-stratification. Eight cores were obtained [Median&IQR: 8 (6-10)] including five (IQR: 4-6) in the IT. TPER-B of the IT yielded longer MCCL [Mean&(95%CI): 5.4(3.9-6.9) vs. 2.5mm(1.9-3.1), p = 0.002] and TCCL [16.7(10.6-22.8) vs. 3.9mm(3.1-4.8), p = 0.0001] than TRUS-B of the gland. On TPER-B cores, longer TCCL [Mean&(95%CI): 28.9mm(19.1-38.7) vs. 12.3mm(4.8-19.7), p = 0.02] were measured in Gleason score-7 than score-6 cancers (no cancers detected on IT TPER-B in 11 patients, all but one score 6 < 4mm on TRUS-B). TPER-B cores of the IT upgraded 16/42(38.1%) patients. 21/42(50.0%) met University College London-definition 1 (Gleason score≥4+3 and/or MCL≥6mm) and 27/42(64.3%) definition 2 (Gleason score≥3+4 and/or MCL≥4mm), which correlate to clinically significant cancers > 0.5mL and > 0.2mL, respectively. Allocation to higher risk groups than anticipated from TRUS-B spurred adaptation of treatment protocols (active surveillance n = 15, prostatectomy n = 11, ionizing radiation n = 13, pending n = 3). Conclusions: Image-guided TPER-B of the index target provided more cancer material for pathology. Subsequent re-evaluation of cancer volume and grade switched a majority of patients towards higher risk groups and treatments with curative intent.
Ten year treatment complication outcomes of radical prostatectomy versus external beam radiation therapy versus brachytherapy for 1,503 patients with intermediate risk prostate cancer.
Authors: Goy Barry W. , Burchette Raoul J. 
Published: May 2019

e16599 Background: To compare 10 year treatment complication outcomes of radical prostatectomy(RP) vs external beam radiation therapy(EBRT) vs brachytherapy(BT) for patients with intermediate risk prostate cancer(IRPC). Methods: A retrospective analysis was performed on 1,503 IRPC patients who underwent treatment from 2004 to 2007, using univariate comparisons. 819 underwent RP, 574 underwent EBRT, and 110 underwent BT using iodine-125. Urinary and rectal complications for RP were graded as severe if patients required ≥ 3 pads/diapers per day, required chronic use of condom catheter or penile clamp, daily self-catheterization, placement of sling or artificial urinary sphincter, or developed rectal fistula/incontinence. Complications for EBRT and BT were graded as severe if they were classified as grade 3 or 4 on the Radiation Therapy Oncology Group grading system for late effects. For erectile dysfunction, the prevalence of patients requiring injections, pumps or penile implants were calculated after a minimum of 1 year of follow up. Results: Median follow up was 10.0 years for RP, 9.6 for EBRT, and 9.8 for BT. Neoadjuvant androgen deprivation therapy was given in 0.6% for RP patients vs 58.9% of EBRT vs 12.7% of BT, p < 0.0001. Median age for RP vs EBRT vs BT was 62.1, 70.8, 65.3, p < 0.0001. The 10-year prevalence of severe urinary complications for RP vs EBRT vs BT was 10.1%, 12.5%, 4.6%, p = 0.04. The percentage of patients having a pre-treatment American Urological Association(AUA) urinary score for RP vs EBRT vs BT was 7.3%, 11.5%, 97.3%, p < 0.0001. The 10-year prevalence of severe rectal complications for RP vs EBRT vs BT was 0.5%, 1.6%, 0.0%, p = 0.06. The 10-year prevalence of erectile dysfunction devices for RP vs EBRT vs BT was 24.3%, 6.6%, 8.2%, p < 0.0001. Conclusions: After 10 years of follow-up, BT had the lowest rate of severe urinary complications, which may due to using the AUA score to avoid implanting those who had significant baseline obstructive voiding symptoms. EBRT had a higher rate of severe rectal complications. RP had the highest probability of undergoing treatment using erectile dysfunction devices, despite having younger patients.
Deep learning hybrid 3D/2D convolutional neural network for prostate MRI recognition.
Authors: Van Jasper , Yoon Choongheon , Glavis-Bloom Justin , Bardis Michelle , Ushinsky Alexander , Chow Daniel S. , Chang Peter , Houshyar Roozbeh , Chantaduly Chanon , Grant William A. , Fujimoto Dylann 
Published: May 2019

e16600 Background: Prostate cancer is the most common cancer of men in the United States, with over 200,000 new cases diagnosed in 2018. Multiparametric MRI of the prostate (mpMRI) has emerged as valuable adjunct for the detection and characterization of prostate cancer as well as for guidance of prostate biopsy. As mpMRI progresses towards widespread clinical use, major challenges have been identified, arising from the need to increase accuracy of mpMRI localization of prostate lesions, improve in lesion categorization, and decrease the time and technical complexity of mpMRI evaluation by radiologists or urologists. Deep learning convolutional neural networks (CNN) for image recognition are becoming a more common method of machine learning and show promise in evaluation of complex medical imaging. In this study we describe a deep learning approach for automatic localization and segmentation of prostates organ on clinically acquired mpMRIs. Methods: This IRB approved retrospective review included patients who had a prostate MRI between September 2014 and August 2018 and an MR-guided transrectal biopsy. For each mpMRI the prostate was manually segmented by a board-certified abdominal radiologist on T2 weighted sequence. A hybrid 3D/2D CNN based on U-Net architecture was developed and trained using these manually segmented images to perform automated organ segmentation. After training, the CNN was used to produce prostate segmentations autonomously on clinical mpMRI. Accuracy of the CNN was assessed by Sørensen–Dice coefficient and Pearson coefficient. Five-fold validation was performed. Results: The CNN was successfully trained and five-fold validation performed on 411 prostate mpMRIs. The Sørensen–Dice coefficient from the five-fold cross validation was 0.87 and the Pearson correlation coefficient for segmented volume was 0.99. Conclusions: These results demonstrate that a CNN can be developed and trained to automatically localize and volumetrically segment the prostate on clinical mpMRI with high accuracy. This study supports the potential for developing an automated deep learning CNN for organ segmentation to replace clinical manual segmentation. Future studies will look towards prostate lesion localization and categorization on mpMRI.