bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cabazitaxel in metastatic castrate resistant prostate cancer (mCRPC) in the era of enzalutamide (ENZA) and abiraterone acetate (AA).
Authors: Body Amy , Pranavan Gane , Malik Laeeq 
Published: September 2018

e16517 Background: The concurrent development of cabazitaxel, AA, ENZA, and radium-223 has recently increased the number of therapeutic options for mCRPC. Cabazitaxel is currently approved for mCRPC patients who have previously received docetaxel. There are no data on the activity of cabazitaxel in patients who had previously progressed on docetaxel and either ENZA or AA. We examined the efficacy and tolerability of cabazitaxel in patients who progressed on docetaxel and either AA or ENZA. Methods: We searched our databases for all mCRPC patients who had received cabazitaxel up to July 2016. We reviewed medical records to collect information on tolerability, treatment sequencing and treatment outcomes. These data were analysed descriptively using Excel 2010. Results: Of 30 patients screened, only 20 patients received cabazitaxel after progressing on docetaxel and either ENZA or AA. The median age at the time of treatment was 70.8 years. All except one patient had Zubrod performance status (PS) ≥1. All patients had ≥4 sites of metastatic disease, 20% had liver or lung metastases. About 11/20 (55%) individuals had previously received ENZA (median duration 5.8 months) and 12/20 (60%) received AA (median duration 10 months). The median number of cabazitaxel administered was 6 cycles. Only 3/20 (15%) completed 10 cycles. The most common reasons for treatment discontinuation were progressive disease (35.3%) and toxicity (23.5%). The dose of cabazitaxel was reduced at baseline in most patients due to poor PS. PSA response occurred in one-third of patients while stable disease (clinical+radiological) was seen in 40% patients. The median progression free survival (PFS) was 4 months and overall survival measured 4.6 months. About 20% had ≥6 months PFS. After progression, only one-fourth went on to receive further systemic therapy. The most common toxicities were anaemia (100%), neutropenia (65%), fatigue (65%), peripheral neuropathy (35%) and diarrhoea (25%). Conclusions: Within limitations of a small retrospective study, cabazitaxel showed very modest antitumour activity in this cohort of mCRPC patients with significant tumour burden and prior exposure to docetaxel and biological agents.
The effect of corticosteroid (Cs) use during docetaxel (D) treatment on overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Gyergyay Fruzsina , Budai Barna , Biro Krisztina , Kuronya Zsofia , Nagyivanyi Krisztian , Vajdics Timea , Oreskovich Anna , Geczi Lajos 
Published: September 2018

e16522 Background: Cs are commonly used in the treatment of mCRPC, because of their inhibitory effects on the secretion of ACTH and their palliative effects. Inhibition of ACTH results in downregulation of adrenal androgens. Cs may have a cytotoxic effect on prostate cancer cells, mediated in part by the downregulation of androgen receptors and the activation of glucocorticoid receptor-mediated signaling and downstream antiangiogenic activity. The rationale for adding Cs to D chemotherapy is for the management of symptoms and adverse events rather than for improving responses. D (without Cs) + ADT (androgen-deprivation therapy) vs ADT alone in castration-sensitive prostate cancer has resulted in significant increase in survival (NEJM, 2015). Cs has been reported to adversely influence OS during enzalutamide (NEJM, 2012). In the COU-AA-301 trial Cs use at baseline was an independent prognostic factor in multivariate analysis, but not in a stepwise selection model (JCO, 2013). Methods: We performed a retrospective analysis of 117 mCRPC pts treated with D. All pts had standard Cs premedication before D and 74 pts received prednisone 5 mg po BID, but 43 pts didn’t get continuous Cs therapy. Kaplan-Meier estimates and Cox regression model were used. Results: Pts characteristics were as follows: median age 66 yrs (range 48-81), Gleason score ≤6: 22pts, ≥7: 61pts. (34 NA). Altogether 1015 cycles of D were given, median 8 (range 2-27). Subsequent therapies were as follows: Abiraterone Acetate (AA) (75), Mitoxantrone (46), Xofigo (5), other chemotherapies (7), none (21). Pts receiving Cs had an inferior OS in all subgroups, although none was significant (Table). Only the Gleason score was an independent prognostic factor in multivariate analysis. Conclusions: Our data suggest, that D therapy withouth Cs is at least as effective as the combination. More data is neccesary to support the suspicion of negative influence of Cs on OS. Thus unnecesarry Cs treatment might be ommited. [Table: see text]
Apatinib in combination with hypofractionation radiotherapy in bone metastatic prostate cancer: Results from a pilot, multicenter study.
Authors: Zeng Ming , Zhao Feng , Tian Wei 
Published: September 2018

e16523 Background: To study safety and efficacy of apatinib, a vascular endothelial growth factor receptor-2 (VEGF2) inhibitor, in combination with radiotherapy in patients with bone metastatic prostate cancer (BMPC), based on potential synergistic antitumor activities of apatinib and Radiation Therapy (RT). Methods: In a dose escalation study, 18 patients (6/cohort) received apatinib at 250 mg every other day, 250 mg or 500 mg daily. The 250 mg daily cohort was expanded to 19 patients in combination with RT (6 Gy/fraction, 5 fraction in total), comparing with the RT alone cohort with 10 patients. Evaluations included adverse events (AEs), prostate specific antigen (PSA) levels, radiographic evaluation and pain relief. Results: In the dose escalation patients, common apatinib-related AEs (arAEs) were fatigue (11, 61%), anorexia 10, 55%), hand foot syndrome (9, 50%), proteinuria (8, 44%), and HTN (8, 44%). Grade 3 arAEs included HTN, proteinuria, and liver dysfunction. No treatment-related death occurred. In the apatinib plus RT cohort, AEs were increased comparing to either apatinib alone or RT alone; The combination cohort showed improvement in pain control. Conclusions: In BMPC patients, apatinib at less than 500 mg daily dose as mono-therapy had tolerable toxicity, consistent with previous reports in patients with other tumors. Apatinib at dose of 250mg daily combining with RT improved pain control while the overall AEs were manageable. Further studies are needed in large sample size trials. Clinical trial information: NCT02998242.
Is chemical/surgical castration necessary during docetaxel chemotherapy for castration-resistant prostate cancer?
Authors: Watanabe Masahito , Kanao Kent , Muramatsu Hiroyuki , Morinaga Shingo , Kajikawa Keishi , Kobayashi Ikuo , Nishikawa Genya , Kato Yoshiharu , Nakamura Kogenta , Sumitomo Makoto 
Published: September 2018

e16530 Background: Docetaxel is the standard treatment for castration-resistant prostate cancer (CRPC). However, the role of chemical/surgical castration during docetaxel chemotherapy is unclear. The purpose of this study was to analyze the impact of castration during docetaxel chemotherapy. Methods: Data from 43 patients diagnosed with CRPC and treated at our institute with docetaxel chemotherapy, from January 2007 to September 2016, were analyzed retrospectively. They were divided into two groups according to the continuation of chemical castration during docetaxel chemotherapy: a continuation group and a discontinued group. Patients’ background data (age and serum prostate-specific antigen [PSA] level), PSA decline, progression-free survival, and overall survival were compared between the two groups. Results: The continuation group included 19 patients, and the discontinued group included 24 patients. Castration included surgical castration (15.8%), use of a luteinizing hormone-releasing hormone (LH-RH) agonist (68.4%), and use of an LH-RH antagonist (15.8%). There were no significant differences in patient age (73.5 years vs. 73.5 years; p = 0.878) and baseline serum PSA levels (14.25 ng/ml vs. 31.1 ng/ml, p = 0.745) between the two groups at the start of chemotherapy. PSA declines of ≥50% were observed in 7/14 patients and in 9/20 patients, respectively. There were no significant differences between the two groups with respect to the median progression-free survival (5.7 months vs. 9.9 months, p = 0.406) and overall survival. (52.1 months vs. 44.1 months, p = 0.776). Conclusions: Continuing chemical/surgical castration during docetaxel chemotherapy did not affect progression and prognosis of CRPC. Our results might suggest that chemical castration is not necessary during docetaxel chemotherapy.
Results of a phase II trial of selinexor, an oral selective inhibitor of nuclear export (SINE), in patients with metastatic castration resistant prostate cancer (mCRPC) refractory to abiraterone or enzalutamide.
Authors: Wei Xiao , Siegel Adam Phillip , Aggarwal Rahul Raj , Lin Amy M. , Friedlander Terence W. , Fong Lawrence , Paraganlija Mirela , Chang Emily , Zhang Li , Ryan Charles J. 
Published: September 2018

e16533 Background: Patients (pts) with abiraterone (abi) or enza (enza) refractory mCRPC typically have limited treatment options. Selinexor is a first in class SINE that specifically inhibits the nuclear export protein Exportin-1 (XPO-1) which is overexpressed in prostate cancer (PCa), leading to cytoplasmic mislocalization of tumor suppressor proteins. In preclinical models of PCa, selinexor reduced tumor growth and decreased the incidence of bone metastasis. Methods: Eligibility criteria included progressive mCRPC with primary or acquired resistance to abi, enza, or their combination. Prior chemotherapy for mCRPC was not allowed. All pts must have > 1 bone metastasis. The primary objective was radiographic progression free survival (rPFS). Results: Fourteen pts were enrolled between Oct 2014 and Oct 2016. The median age was 72 years (range 56-79) and median baseline PSA was 73.8 ng/mL (range 12.8-686.9). Eleven pts (79%) had both prior abi and enza. The initial selinexor dose was 65 mg/m2 on Day 1 (D1) and Day 3 (D3) weekly. For toxicity concerns, after the first 2 pts, dose was reduced to 60 mg on D1 and D3 for the first 3 wks followed by a 1-wk rest period (28-day cycle). All pts received ondansetron and olanzapine to prevent nausea and anorexia. The median treatment duration was 3 cycles (range 1-12), and median follow-up was 4 months. One pt (7.1%) had > 50% PSA decline, 5 pts (35.7%) had > 30% PSA decline, and 7 pts (50%) had any PSA decline. Of 10 pts evaluable, 9 pts had stable disease as best radiographic response, and 1 pt had progressive disease on the first radiographic evaluation. The median rPFS was 3.6 months (95% CI 2.1-not reached). The most common AEs of any severity were anorexia (86%), nausea (64%), weight loss (50%), fatigue (50%), thrombocytopenia (50%), anemia (36%), and vomiting (36%). Grade 3/4 AEs included nausea (14%), vomiting (14%), anemia (14%), anorexia (7%), weight loss (7%), thrombocytopenia (7%) and neutropenia (7%). Conclusions: Selinexor demonstrated limited clinical activity in mCRPC. Toxicity, in particular anorexia and weight loss, hinders further development in this pt population. Clinical trial information: NCT02215161.
Treatment outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) and cardiovascular disorders or diabetes: The Prostate Cancer Registry.
Authors: Lumen Nicolaas , Chowdhury Simon , Birtle Alison J. , Bjartell Anders , Costa Luis , Feyerabend Susan , Galli Luca , Kalinka-Warzocha Ewa , Kramer Gero , Maroto Pablo , Matveev Vsevolod B , Paiss Thomas , Pisconti Salvatore , Spaeth Dominique , Veiga Francisco Gomez , Antoni Laurent , Klumper Edwin , Wapenaar Robert , Thoret-Bauchet Florence , Lee Emma 
Published: September 2018

e16537 Background: The Prostate Cancer Registry is a prospective study of >3000 men with mCRPC in routine care. These patients (pts) have a high level of comorbidities which are often underrepresented in RCTs. Methods: Data were collected from pts with mCRPC irrespective of treatment (tx). Outcomes in pts with comorbidities were assessed. Results: At study entry, 16.6% of pts had a cardiac disorder, 9.7% hypertension only, 17.7% diabetes. Characteristics, first txs and outcomes are shown in the table below. Conclusions: In this real-life setting, AAP, ENZ, or DOC tx was feasible in pts with cardiac disorders, hypertension or diabetes; proportions treated with each drug were similar to the overall mCRPC population. Regardless of tx PFS was shorter than TTP, which may reflect the impact of pts’ comorbidities in real life. Pts with cardiac disorders had poorer outcomes vs the overall population. Clinical trial information: NCT02236637. [Table: see text]
Costs of skeletal-related events (SREs) in patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with oral therapies.
Authors: Engel-Nitz Nicole , Behl Ajay S. , Blauer-Peterson Cori , Li Sophia S , Dawson Nancy Ann 
Published: September 2018

e16539 Background: SREs are associated with increased mortality and costs for mCRPC patients. The impact of mCRPC oral therapies on SREs is not well understood in the real world. This study examined the occurrence of and health care costs associated with SREs among mCRPC patients treated with abiraterone acetate + prednisone (ABI) or enzalutamide (ENZ). Methods: A retrospective study of a large national health claims database identified patients initiated on ABI or ENZ from 9/2012- 6/2015. Patients included had: ≥1 claim with prostate cancer diagnosis (ICD-9-CM 185.x) from 6 mo. pre- to 30 days post-index; ≥6 mo. pre- + ≥3 mo. post-index health plan enrollment. Index was date initiated on first oral therapy (ABI/ENZ). SREs (spinal cord compression, radiation to bone, pathological fracture, bone surgery) were assessed and health care cost calculated for patients with/without SREs in baseline/follow-up. Descriptive analyses and Cox proportional hazards examined SREs; generalized linear models assessed costs. Models adjusted for ABI/ENZ, age, region, baseline comorbidities, bone/brain/visceral metastases, docetaxel, and statin use. Results: The table below summarizes unadjusted results. Total all-cause per patient per month (PPPM) costs of 1,516 patients were highest for those with follow-up SREs. A significant difference in cost exists when comparing across all groups. Among patients without baseline SREs, adjusted analysis found greater hazards of follow-up SREs for baseline bone metastases (HR: 1.62, P = 0.003), baseline visceral metastases (HR: 1.68, P < 0.001), prior docetaxel (HR: 1.46, P = 0.004), and ENZ (vs. ABI) as first treatment (HR: 1.35, P = 0.013). Patients with follow-up SREs (with/without baseline SREs) had 19% higher adjusted costs compared to those without baseline or follow-up SREs (P < 0.001 each). Conclusions: SREs were common among mCRPC patients and associated with a significant financial burden. [Table: see text]
Pathogen identification in prostate cancer biopsies using transcriptome sequencing.
Authors: Shah Carisa M , Bareja Rohan , Elemento Olivier 
Published: September 2018

e16545 Background: Tumor biopsies may frequently be associated with microbial species due to proximity with microbial communities or due to contamination during tissue processing. We examined sequencing data from tumor biopsies to explore the tumor-associated microbiome in prostate cancer. Methods: Patients were enrolled in a prospective Precision Medicine study to evaluate genomic alterations based on freshly obtained tissue biopsies. Total RNA was prepared for RNA sequencing using the standard Illumina mRNA sample preparation protocol. Paired-end RNA-sequencing at read lengths of 50 or 51 bp was performed with the HiSeq 2000 (Illumina). A total of ~268 million paired-end reads were generated, corresponding to 27 billion bases. Kraken and FusionCatcher were used to identify the metagenome that maps to microbial species. R was used to analyze the microbial pathogens and to create a heatmap of microbial abundance. We focused our analysis on prostate cancer. Results: From 1/30/2013 to 12/16/15, 83 patients with urothelial cancers were identified, of which 32 patients with prostate cancer (n = 23 from primary tumor, n = 9 metastatic prostate cancer) were sequenced. Of the 9 metastatic samples, 5 were metastatic prostate cancer to bone, 4 were other metastases. A giant cell tumor of bone was used as a control. The metagenome was identified and mapped to the Kraken pathogen database. 43 unique pathogens characterized the microbiome associated with prostate cancer, including Streptomyces species, Acinetobacter baumannii, Enterobacteriaceae, and Corynebacterium species. The most prevalent species in prostate cancer bone metastases were also the most prevalent in primary prostate tumors. Prostate cancer bone metastases clustered separately from the primary prostate cancer samples, the other metastases, and primary bone cancer. Conclusions: We have identified a putative microbiome signature associated with prostate cancer. Prostate cancer bone metastases appear to cluster separately from prostate cancer, suggesting a non-random association with microbial communities. Ongoing work is looking to (1) validate microbial association using orthogonal analyses and (2) determine the exact origin of the signature.
Detection of HRD gene mutations and copy number changes in cfDNA from prostate cancer patients.
Authors: Raymond Chris , Hernandez Jenny , Brobey Reynolds , Wang Yue , Potts Kristy , Garg Kavita , Lim Lee , DiPasquo Dan , Li Mark , Dehghani Mehdi , Amato Robert J. 
Published: September 2018

e16546 Background: Recent genomic surveys of prostate cancer have identified somatic mutations in metastatic castration-resistant prostate cancer (mCRPC). In this study, we examined mCRPC patients for AR aberrations and mutations in the HRD (homologous recombination DNA-repair) pathway which may confer platinum or PARP inhibitor sensitivity. Methods: A novel targeted-hybrid-capture NGS assay capable of identifying deleterious mutations, copy number amplification and gene copy loss, was applied to circulating, cell-free DNA (cfDNA) extracted from plasma samples from 20 mCRPC patients. Samples were collected between 3/2010 – 10/2015 and stored at -20C. The gene panel used in the assay included AR and several genes in the HRD pathway — ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, NBN, PALB2, and RAD51. Sequencing libraries created with the cfDNA extracted from 2.8-4 mLs of plasma had an average unique read coverage depth of 2282 genome equivalents (range 445 – 5136, median 2181). Results: Somatic variations were observed in 17 of the 20 samples analyzed. Copy number variation (CNV) was observed in 11 samples. AR amplification, linked to resistance to abiraterone and enzalutamide, was observed in 30% (6) of samples. Canonical AR ligand binding domain mutations, such as T787A and L702H were also detected. ATM, BRCA1, BRCA2, HDAC2, and FANCA gene deletions were also detected, as well as frameshift, nonsense, and other deleterious mutations in HRD genes. Significant CNV in multiple genes was observed in at least 5 patient samples. Mutations were detected across the entire collection date range, speaking to the robustness of cfDNA. Conclusions: Non-invasive tumor mCRPC genotyping appears to be feasible. The ability to detect HRD gene alterations suggests cfDNA testing may be suitable for the detection of HRD pathway defects and overall genome instability.
Computer extracted nuclear features from tumor and benign regions of Feulgen and H&E images to help predict recurrence in prostate cancer patients following radical prostatectomy.
Authors: Gawlik Anna , Lee George , Feldman Michael D , Zhu Guangjing , Veltri Robert W. , Madabhushi Anant 
Published: September 2018

e16556 Background: Following radical prostatectomy, around 30% of prostate cancer (PCa) patients experience biochemical recurrence (BCR). H&E highlights nuclear morphology and Feulgen reflects nuclear DNA content, a feature linked to PCa presence and aggressiveness. In this work we sought to explore whether computer extracted measurements of tumor morphology and tumor adjacent benign regions on H&E and Feulgen tissue images could predict BCR. Methods: We used 108 patients (59 BCR and 49 non-recurrence (NR)) and each patient had 242 QH features calculated from both the tumor and benign region of stained TMA core images. Feature selection was performed on a training set (30 BCR, 24 NR) to select the 10 most discriminating tumor and tumor adjacent benign features of each stain. A random forest classifier was trained with features so identified and validated on a test set (29 BCR, 25 NR) to predict BCR. Predictions were displayed using Kaplan-Meier analysis and area under the ROC curve (AUC). Results: The most discriminating feature from the tumor regions of the H&E stain was Fourier descriptors of nuclear shape and from the Feulgen stain was texture intensity while from the benign regions it was invariant moments of nuclear shape and texture contrast energy. Combining the significant features from tumor and tumor adjacent benign regions from H&E and Feulgen resulted in the highest accuracy and a statistically significant difference (p < 0.05) via a log-rank test (Table 1). Gleason score did not show statistically significant differences and had the lowest AUC. Conclusions: Combining nuclear morphology and DNA related features of the tumor and tumor adjacent benign regions enabled accurate prediction of BCR. With additional multi-site validation, the combined H&E + Feulgen classifier could allow better risk stratification and post-surgical patient management. [Table: see text]
Accounting for improved prostate cancer mortality outcomes in Haitian men: A histological analysis.
Authors: Thoreson Nick , Rand Alexander , Sarita-Reyes Carmen , Soliman Mahmoud , Li Lei , Qureshi Muhammad M. , Gignac Gretchen , Hirsch Ariel 
Published: September 2018

e16557 Background: In a previous wide-ranging study on the outcomes of prostate cancer patients at a safety-net hospital, we discovered significantly improved mortality outcomes for Haitian Creole prostate cancer patients compared to all other languages spoken, including black English speakers, with p = 0.017 [Rand, AE, et al., Clin Genitourin Cancer. (6):455-60 (2014)]. In order to assess any molecular indications that could be contributing to this finding, we performed a histological analysis of prostate cancer specimens, comparing black English-speaking patients to Haitian Creole patients. Methods: We sampled prostatectomies from 34 black English-speaking patients and 38 black Haitian Creole-speaking patients, taken between December 2011 and June 2015. In addition to primary and secondary Gleason scores, extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymphovascular invasion (LVI), and perineural invasion (PNI), we observed any small amounts of grade 5 tissue present for the tertiary Gleason score. Finally, we analyzed the presence of acute and chronic inflammation and inflammatory severity. A chi square analysis was used to compare the categories between the Haitian and non-Haitian sets, with a probability less than 0.05 considered statistically significant. Results: While the null hypothesis was confirmed for primary, secondary, and total Gleason scores, 23.7% of the Haitian samples had a tertiary Gleason score of 5, compared to only 6.3% of non-Haitian samples (p = 0.046). The two populations exhibited similar rates of EPE (p = 0.719), SVI (p = 0.884), and PNI (p = 0.597), with no LVI apparent in any sample. No significant trends were noted in acute vs. chronic inflammation (p = 0.402) or severity of inflammation (p = 0.601). Conclusions: Samples taken from Haitian Creole-speaking patients had a significantly higher rate of grade 5 tertiary Gleason tissue than the non-Haitian patient samples. The presence of a tertiary Gleason score indicates a higher risk of metastasis, yet the Haitian samples do not reveal a greater rate of extraprostatic invasion. Further studies investigating underlying health factors among Haitian patients might be useful in accounting for improved patient outcomes.