bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer extracted features of gland morphology on H&E surgically resected tissue images as predictive of biochemical recurrence and rate of expression in African American compared to Caucasian American men.
Authors: Leo Patrick , Janaki Nafiseh , Thawani Rajat , Elliott Robin , Gupta Sanjay , Shih Natalie , Feldman Michael D , Madabhushi Anant 
Published: September 2018

e16559 Background: Prostate cancer (PCa) is 1.7 times more prevalent and 2.3 times more lethal in African American (AA) men than in Caucasian American (CA) men. Additionally there is a higher incidence (when controlling for relative population size) of more aggressive PCa in the AA compared to the CA population which has led a number of groups to investigate whether there are molecular differences in the disease phenotype between the two groups. In this work we investigate whether computer extracted features of glandular morphology from digitized pathology images of surgical specimens identified as predictive of biochemical recurrence are also differentially expressed between AA and CA patients. Methods: Two cohorts were gathered. Cohort 1 (C1) contained digitized whole mount Gleason 7 radical prostatectomy specimens (RPS) from 72 patients (46 CA, 26 AA). Cohort 2 (C2) comprising quarter and whole mount RPS from 145 patients (135 CA, 10 AA), who either had biochemical recurrence in 5 years (47) or did not (98). A pathologist annotated each image in both cohorts for a representative cancerous region. Glands were automatically segmented and 216 features describing gland arrangement, shape, and disorder were extracted from every image. Features were tested for significance by Wilcoxon rank sum test at p < .05. Results: 8 features of gland morphology were significantly different between AA and CA groups and also predictive of biochemical recurrence (Table). Conclusions: We identified 8 computer extracted features of gland morphology that were both differentially expressed between AA and CA men and predictive of biochemical recurrence, suggesting that there are histomorphometric differences in prostate cancer appearance between AA and CA men. [Table: see text]
First-in-human phase 1 PET study of CTT1057, a novel 18F-labeled imaging agent targeting prostate specific membrane antigen (PSMA) in prostate cancer.
Authors: Aggarwal Rahul Raj , Behr Spencer , Seo Youngho , Gao Kenneth , Rahanfar Vahid , Slater Jim , Blecha Joseph , Langton-Webster Beatrice , Berkman Clifford , Vanbrocklin Henry 
Published: September 2018

e16562 Background: Urea-based 68Ga-PSMA PET is increasingly being utilized for diagnostic purposes in prostate cancer; however high tracer uptake within the salivary gland and kidney may be dose-limiting upon translation to radiotherapy. We developed a novel 18F labeled agent, CTT1057, a PSMA inhibitor based on a phosphoramidate scaffold with nanomolar and irreversible binding affinity to PSMA and robust internalization, and performed a first-in-human imaging study. Methods: Patients (pts) with metastatic castration resistant prostate cancer (mCRPC) were eligible. 10 mCi (370 MBq) of CTT1057 was injected and whole body PET/MR imaging (SIGNA PET/MR, GE) was performed 60 min post-injection. SUVmean in normal organs was recorded by drawing a 1 cm3 volume-of-interest. SUVmax was determined for each PSMA-avid metastasis. 10 randomly selected, consecutive 68Ga-PSMA PET scans from an independent cohort were used for descriptive comparison. Results: 5 pts with mCRPC were enrolled, with average age of 66 years (range 35–85) and median PSA of 12.2 (range 0.73 – 157.7). 55 PSMA-avid metastases were seen, including 37 osseous (average SUVmax = 8.1 ± 4.4), 15 lymph node (SUVmax = 11.0 ± 6.1), and 3 pulmonary (SUVmax = 3.2 ± 0.6). 31 (83%) and 12 (32%) of the PSMA-avid osseous lesions were visible on CT and bone scan, respectively. The mean short axis diameter of PSMA-avid lymph nodes was 0.7 ± 0.4 cm. Tumor-to-background ratios (liver, muscle, blood pool) were 2.8 ± 2.3, 14.9 ± 11.6, and 3.2 ± 2.4, respectively. SUVmean in salivary gland and kidney were 3.6 ± 0.4 and 9.1 ± 0.8 for CTT1057 and 15.8 ± 2.7 and 35.9 ± 9.6 for 68Ga-PSMA, respectively. No tracer-related adverse events were observed and radiation dose estimates for organs and whole-body effective dose were within acceptable limits. Conclusions: 18F-labeled CTT1057 targeting PSMA, detected mCRPC lesions in the soft tissue and bone at greater sensitivity than conventional imaging. CTT1057 distribution of uptake was similar to urea-based PSMA imaging, with preliminary evidence of lower uptake in the salivary gland and kidney. Further clinical studies of the CTT1057 backbone as a diagnostic and therapeutic agent in mCRPC are warranted. Clinical trial information: NCT02916537.
SM88 in non-metastatic rising PSA-recurrent prostate cancer.
Authors: Del Priore Giuseppe , Sokol Gerald H. , Chen Wen-Tien , Tsao Che-Kai , Hoffman Steve 
Published: September 2018

e16567 Background: SM88 is a novel combination of substituted amino acid ( AA) and repurposed agents with non-toxic activity in a variety of cancers including prostate (PC). Non-metastatic biochemically recurrent PC (nmPC) is ideal for such a well-tolerated, non-androgen based treatment. We present biomarker activity including CTCs (circulating tumor cells) after completion of the Ib dose escalating pharmacokinetic portion of the SM88 development plan. Methods: Planned analysis of an ongoing prospective Phase Ib/II open label study of nmPC (PCWG3 definition). Subject 1 received the 1stdose level of AA, and others received 2x dose. All subjects also received a combination of low dose re-purposed CYP3a4 inducer, oxidative stress catalyst, and mTOR inhibitor. Results: Four subjects completed at least 1 cycle (28d) with all PK sampling as prespecified. Median age was 73(70-80); all had prior ADT that was discontinued 3-6 yrs earlier, and either had curative intent prostatectomy (n = 2) or RT (n = 2); Testosterone level was castrate in one after prior RT. CTCs fell (p < 0.01) to undetectable (n = 1) or by > 25% (n = 3) (see table) while PSA remained stable (PCWG3 criteria). Preliminary LDH, neutrophil/lymphocyte ratio (N:L), urinary NTx, bone specific AlkPhos (bAP) trends are in the table below. There were no drug related serious adverse events (2 grade: 1- pigmentation, 1- vasomotor). EORTC-QLQ30 and PR25 scores were either improved or stable. Conclusions: Treatment with SM88 in patients with nmPC in the completed phase Ib cohort was associated with CTC reduction, and stable biomarker trends including PSA and LDH. There was no significant toxicity or adverse patient reported outcomes. Based on these results, the dose escalation was stopped at the second level and a cohort expansion phase II initiated. A phase III RCT is planned for confirmation of these results. Clinical trial information: NCT02796898. [Table: see text]
Analysis of racial differences in histologic subtype and survival in renal cell carcinoma at an urban academic cancer center.
Authors: Wong Kevin , Shusterman Michael , Gartrell Benjamin Adam 
Published: September 2018

e16571 Background: Black patientswithrenal cell carcinoma (RCC) have a unique distribution of histological subtypes and historic worse survival compared to white patients. Little is known about RCC in Hispanics. We investigated histologic and survival differences between racial groups treated for RCC at the Montefiore-Einstein Cancer Center (MECC) in Bronx, NY. Methods: We included via the Cancer Registry 1010 patients who underwent RCC resection at MECC between 2000 and 2015. Demographics, clinical characteristics and pathology reports were collected. Logistic regression and Cox proportional hazards models were built to evaluate the association of histology and survival with clinically and statistically significant risk factors in Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic (H) patients. Results: 233 patients were NHW (23.1%), 383 NHB (37.9%), 174 H (17.2%), and 220 other race (21.8%). Median age was 61 (range 22, 91). 58% were male. Histology was 529 (52%) clear cell (CC), 255 (25%) papillary (P), 100 (10%) chromophobe, and 126 (12.5%) other. P was more common in NHB (60.5%) compared to NHW (17%) and less common in H (6.3%) patients (P < 0.0001). On multivariate logistic analysis, patients with P vs. CC were more likely to be NHB (OR 5.06; 95% CI 2.92, 8.76; P < 0.0001) and less likely to have a body mass index > 30 (BMI, OR 0.49; 95% CI 0.32, 0.76, P = 0.001) adjusting for age, race, gender, hypertension (HTN), and end stage renal disease (ESRD). Adjusting for above covariates there were no significant differences for C vs. CC. There was no difference in disease free survival (DFS) for NHB vs. NHW (HR 0.93; 95% CI 0.44, 1.94; P = 0.841) or H vs. NHW (HR 1.29; 95% CI 0.62, 2.71; P = 0.495) patients adjusting for age, gender, histology, ESRD, and BMI. There was no difference in overall survival (OS) for NHB vs. NHW (HR 0.97; 95% CI 0.57, 1.65; P = 0.908) or H vs. NHW (HR 1.37; 95% CI 0.79, 2.38; P = 0.256) patients adjusting for the same covariates. Conclusions: In this cohort of patients with RCC, P histology and lower BMI were significantly associated with NHB race. Unlike historic cohorts there was no significant difference in DFS or OS in NHB compared to NHW patients.
A new prostate cancer biopsy reporting system with prognostic potential.
Authors: Shah Paras Hemant , Olsson Carl A. , Paulucci David J , Elmasri Matthew , Vira Manish Arvind , Yaskiv Oksana , Kapoor Deepak A. 
Published: September 2018

e16572 Background: Presently, prostate biopsy (PBx) results typically report the highest Gleason Grade Group in the PBx as the single metric used to gauge the clinical aggressiveness of tumor and dictate treatment. However, using that single parameter alone limits the clinician by lack of consideration of the entire PBx. Intuitively we presumed that a PBx showing multiple cores of cancer would represent more aggressive disease. Herein, we propose the Weighted Gleason Grade Group (WGGG), a novel scoring system that synthesizes histopathologic data and cancer volume into a single numeric value representing the entire PBx, allowing the urologist to more accurately predict adverse pathologic outcomes of radical prostatectomy (RP). Methods: We studied 246 men who underwent RP after standard multi-core PBx. The highest Gleason score of each PBx was converted to its final GGG. The WGGG was calculated by summing the Gleason score of each positive core and normalized for a 12 core total. RP pathology was studied to determine adverse pathological outcomes, specifically, extraprostatic extension (EPE), positive surgical margins (PSM), seminal vesical invasion (SVI), pathological up-grading and any adverse feature. We then studied the ability of conventional GGG versus WGGG to have ‘predicted’ the risk of these adverse features comparing their respective receiver operating characteristic (ROC) areas under the curve (AUC) for each, as well as any adverse feature. Results: The AUC for the WGGG vs. GGG was significantly higher for predicting EPE (AUC 0.782 vs. 0.697, respectively; z = -3.29; p = .0009), PSM (AUC 0.644 vs. 0.563, respectively; z = -3.00; p = .0027), SVI (AUC 0.829 vs. 0.713, respectively; z = -3.05; p = .0023) and pathologic up-grading (AUC 0.584 vs. 0.349, respectively; z = -3.13; p = .002). Finally, the AUC for any adverse feature was 0.637 for WGGG versus 0.556 for GGG; z = -3.29; p = .001. Conclusions: The WGGG, by providing a metric reflecting the entirety of the PBx, is more informative than conventional single GGG alone in ‘predicting’ adverse pathologic outcomes on radical prostatectomy specimens. We are now studying if % cancer/ PBx core will improve WGGG performance.
Hypofractionated radiation therapy in low-risk prostate cancer: Outcome, toxicity, and sexual function.
Authors: Marinelli Luca , Reverberi Chiara , Osti Mattia Falchetto , De Sanctis Vitaliana , Giuliani Manuela , Tronnolone Lidia , Valeriani Maurizio 
Published: September 2018

e16575 Background: To evaluate efficacy, toxicity of image-guided hypofractionated radiotherapy (HFRT) in patients with low-risk prostate cancer. Methods: Eighty-five low-risk prostate cancer patients (Gleason score ≤6, clinical stage T1/T2a-b N0 M0, and PSA ≤10 ng/mL) were treated with HFRT from March 2007 to November 2015. All patients were staged with multi-parametric contrast-enhanced MRI. Clinical target volume (CTV) encompassed prostate with proximal seminal vescicles. Margin from CTV to PTV was 5 mm in all directions. Patients received a total dose of 60 Gy in 20 fractions with 3D-CRT. Daily cone beam CT (IGRT) was executed. RTOG/EORTC morbidity Scoring Scale was used for evaluate toxicities. Results: Median follow-up was 54 months (range 11-116 months). The actuarial 8-years Overall Survival was 97.1%. Eight-years Cancer Specific Survival was 100%, 8-years Biochemical Relapse Free Survival was 98.8%, no patients presented clinical local recurrence. Median of PSA at diagnosis was 3.27 ng/mL (range 1.69-9.98 ng/mL) and at the last follow-up was 0.39 ng/mL (range 0.01-2.26 ng/mL). Acute grade 1-2 gastrointestinal (GI) toxicity occurred in 13 patients (15.3%), grade 1-2 genitourinary (GU) toxicity in 33 cases (38.8%). Grade 3 GU toxicity occurred in 2 patients (2.4%). Grade 1-2 GI and GU late toxicities were observed in 4 (4.7 %) and 25 (29.4 %) patients, respectively. Sexual functionality was qualitatively evaluated, scoring 0 for absence, 1 for presence of erection but insufficient for intercourse, 2 for a sufficient one. Before RT, 4.7 % had score 0, 47.1% had score 1 and 48.2% had score 2. After RT, 34.1% of patients presented score 0, 51.8% score 1 and 14.1% score 2 (Chi-square p = 0,004). After treatment, patients with < 70 years presented score 0 in 4.7% of patients, score 1 in 20% and score 2 in 8.2%. Those with > 70 years, 29.4% presented score 0, 31.8% score 1 and 5.9% score 2 (Chi square p = 0.011). Conclusions: Long-term results of our study demonstrated that HFRT in low-risk prostate cancer is efficacy and well tolerated. HFRT significantly worsened sexual function, even if patients with age < 70 years had a higher probability to maintain any form of sexual function after therapy.
Effects of ALK1Fc treatment on prostate cancer cells interacting with bone and bone cells in bone metastasis models.
Authors: Kruithof-de Julio Marianna , Astrologo Letizia , Zoni Eugenio , Karkampouna Sofia , Gray Peter C , Klima Irena , Grosjean Joel , Goumans Marie Jose , Hawinkels Lukas J.A.C. , Van der Pluijm Gabri , ten Dijke Peter , Spahn Martin , Thalmann George N. 
Published: September 2018

e16576 Background: Prostate cancer is the second most common cancer in men worldwide. Lethality is normally associated with the consequences of metastasis rather than the primary tumor. In particular, bone is the most frequent site of metastasis and once prostate tumor cells are engrafted in the skeleton, curative therapy is no longer possible. Bone morphogenetic proteins (BMPs) play a critical role in bone physiology and pathology. However, little is known about the role of BMP9 and its signaling receptors, ALK1 and ALK2, in prostate cancer and bone metastasis. In this context, we investigate the impact of BMP9 on primary prostate cancer and derived bone metastasis. Methods: The human ALK1 extracellular domain (ECD) binds BMP9 and BMP10 with high affinity. In order to study the effect of BMP9 in vitro and in vivo we use a soluble chimeric protein, consisting of ALK1 ECD fused to human Fc (ALK1Fc), for preventing the activation of endogenous signaling. ALK1Fc sequesters BMP9 and BMP10, preserving the activation of ALK1 through other ligands. Results: We show that ALK1Fc reduces BMP9-mediated signaling and decreases proliferation of highly metastatic and tumor initiating human prostate cancer cells in vitro. In line with these observations, we demonstrate that ALK1Fc reduces tumor growth in vivo in an orthotopic transplantation model. The propensity of the primary prostate cancer to metastasize to the bone is also investigated. In particular, we report how the ALK1Fc influences the prostate cancer cells in vitro and in vivo when these are probed in different bone settings (co-culture with bone cells and intraosseous transplantation in mice). Conclusions: Our study provides the first demonstration that ALK1Fc inhibits prostate cancer cells growth identifying BMP9 as a putative therapeutic target and ALK1Fc as a potential therapy. All together, these findings justify the ongoing clinical development of drugs blocking ALK1 and ALK2 receptor activity.
Evaluation of PRUNE2 and PCA3 expression as metastasis predictors in Gleason 7 prostate cancer.
Authors: Lauer Richard C. , Barry Marc , Wu Jin , Lee Ji-Hyun , McCance Dennis J. , Du Ruofei , Rao Arpit , Dobroff Andrey S. , Dias-Neto Emmanuel , Chen Isan , Pasqualini Renata , Arap Wadih 
Published: September 2018

e16583 Background: There is an urgent need to differentiate from truly localized prostate cancer and micrometastatic disease. PCA3 is an FDA-approved biomarker for prostate cancer; however, it is not a predictor of metastasis behavior. We have recently identified PRUNE2 as an unrecognized tumor suppressor gene. Here we examined if the ratio of PRUNE2 and its corresponding dominant-negative oncogene PCA3 might serve as a better predictor of the metastatic potential of prostate cancer, compared to PCA3alone. Methods: We studied 105 prostate cancer patients who underwent a radical prostatectomy at UNM Hospital from 2001 to 2009. At the time of prostatectomy, these patients had a Gleason score of 7 and organ-confined disease. They had at least 5-year follow-up for disease recurrence, and 19 patients developed recurrent disease. PCA3 and PRUNE2 gene expression was quantified by qRT-PCR and normalized to housekeeping control genes. Each experiment was carried out in triplicates. The Wilcoxon rank sum test was used to evaluate whether or not the difference in gene expression of PRUNE2 or PCA3 or the gene expression ratio ( PRUNE2/ PCA3), between patients with and without recurrence, was significant. The association between the time to recurrence and expression levels of each single gene or ratio were also analyzed by the Kaplan-Meier method along with log-rank test and the COX PH modeling. Results: There was no significant difference in expression levels of PRUNE2, PCA3, or the ratio PRUNE2/ PCA3, between patients who developed recurrent disease relative to those who did not. Conclusions: PRUNE2 and PCA3 expression levels, as well as PRUNE2/ PCA3 ratio, did not predict the metastatic potential of Gleason 7 prostate cancer in our retrospective patient cohort. We postulated that the deregulation of the molecular axis of PRUNE2 and PCA3 might occur early in the development of prostate cancer. We are currently examining this mechanistic hypothesis in other studies. [Table: see text]
Biologic target volume delineation and the application of three-dimensional ultrasound image system in hypofractional radiotherapy for prostate cancer.
Authors: Wang Jie , Ma Jiabao , Lang Jin Yi 
Published: September 2018

e16585 Background: To investigate the value of magnetic resonance spectroscopy (MRS) and positron emission computed tomography (PET-CT) in biological target volume(BTV) delineation of prostate cancer using hypofractional intensity modulated radiotherapy (HF-IMRT) with simultaneously integrated boost(SIB), and the preliminary efficacy and adverse effects of 3D ultrasound (3DUS) guided imaging in the treatment of prostate cancer using HF-IMRT and SIB. Methods: Between August 2015 and May 2016, 13 patients diagnosed with mid-high risk prostate cancer were retrospectively enrolled. All the eligible patients had underwent MRI MRS and PET-CT(18F-FDG or 11C-CHO) examination before radiotherapy. 5 patients had explicit BTV by examinations mentioned above. Radiation oncologists fused 3DUS and CT images and delineated tumor target volume referring to MRS and PET-CT. The target volumes were named as GTVMRI BTVMRS BTVPET-CT respectively and the volume were recorded. 3DUS guided HF-IMRT were applied during the radiotherapy. Results: The volumes of GTVMRI BTVMRS BTVPET-CT among the 5 patients were different. The mean volume of GTVMRI BTVMRS and BTVPET-CT were 3.52±1.69cm3, 6.64±2.27cm3 and 5.47±2.60cm3,respectively. Significant difference was only observed between GTVMRI and BTVMRS( P = 0.046). Compared to GTVMRI, the average increasing volumes of BTVMRS and BTVPET-CT were 89.07% and 55.52%. The prescription dose and biological effective dose(BED) of BTVMRS were 70.09-73.45Gy and 129.06-135.54Gy. The prescription dose and BED of the whole prostate were 66.02-69.40Gy and 113.32-124.82Gy. The dose of bladder and rectum were within safe control. The prostate specific antigen (PSA) were significantly decreased after radiotherapy. No local recurrence or distant metastasis was observed. Conclusions: MRS and PET-CT can be applied to delineation of the BTV of prostate cancer. With the help of multi-modal image guidance, dose painting for prostate cancer is feasible. 3DUS guided HF-IMRT with SIB is an alternative for radiation oncologists based on BTVMRS. With shortened time and less cost, this technique is safe and non-radioactive compared to CBCT guidance.
Utility of 11C choline PET CT and MRI in relapsed prostate cancer (PC).
Authors: Tarter Thomas H , Esparaz Benjamin , Lieber David , Zorn Adam , Locke Jon , Muscato Mark , Rashid Thomas , Whisnant Mindy , Wade James Lloyd 
Published: September 2018

e16586 Background: Choline intracellular transport is upregulated in PC, and it is phosphorylated by choline kinase and becomes trapped within PC cells. 11 C Choline has t½ life of 20.4 minutes and emits positrons detectable by PET. Retrospective studies of 11 C choline PET CT in (PC) have been reported. In this original prospective study, we calculated the performance of 11C choline with whole body PET CT and pelvic PET MRI in patients (pts) with biochemical PC relapse. Methods: From November 2014- June 2016, 101 pts with biochemical PC relapse underwent 11C choline PET CT and pelvic PET MRI. Scans were read in blinded fashion. Tissue was obtained from area of 11 C Choline positivity and correlated with scan results. Results: Sixty-two pts (61%) were included in the analysis. 49 pts were excluded due to non-compliance with protocol. 11C choline PET CT and pelvic MRI showed a sensitivity of 92.5%, specificity of 45.5%, positive predictive value of 75.5%, and negative predictive value of 76.9%. Of 37 pts with positive 11C choline PET scans and confirmation of PC, 12 (32%) had positive 11C choline PET scans and negative CT and MRI scans; 7 (18%) had positive C11 choline and CT scans and negative MRI scans; 12 (32%) had positive 11C choline and MRI scans and negative CT scans, and 9 (24%) had positive 11C choline, CT and MRI scans. Mean PSA level in this group of 37 pts was 9.86 ng/mL (range 0.4 – 107.9 ng/mL), and 7 (19%) of the pts had PSA levels < 2 ng/mL. Conclusions: 11C choline PET improves detection of relapsed PC over CT and MRI scans. 11C choline PET pelvic MRI improves detection over 11C choline PET CT.