bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning algorithm improves identification of men with low-risk prostate cancer using PSMA-targeted 99mTc-MIP-1404 SPECT/CT.
Authors: Meyer Alexa , Stambler Nancy , Sjöstrand Karl , Richter Jens , Allaf Mohamad , Rowe Steven P. , Wong Vivien , Anand Aseem , Gorin Michael A. 
Published: May 2019

e16572 Background: Previous work has shown that the degree of expression of prostate-specific membrane antigen (PSMA) correlates with prostate cancer (PCa) grade and stage. We evaluated the additive value of a deep learning algorithm (PSMA-AI) of a PSMA-targeted small molecule SPECT/CT imaging agent (99mTc-MIP-1404) to identify men with low risk PCa who are potential active surveillance candidates. Methods: A secondary analysis of a phase III trial (NCT02615067) of men with PCa who underwent 99mTc-MIP-1404 SPECT/CT was conducted. Patients with a biopsy Gleason score (GS) of ≤6, clinical stage ≤T2, and prostate specific antigen (PSA) < 10 ng/mL who underwent radical prostatectomy (RP) following SPECT/CT were included in the present analysis. SPECT/CT images were retrospectively analyzed by PSMA-AI, which was developed and locked prior to analysis. PSMA-AI calculated the uptake of 99mTc-MIP-1404 against the background reference (TBR). The automated TBR of 14 was used as a threshold for PSMA-AI calls of positive disease. Multivariable logistic regression analysis was used to develop a base model for identifying men with occult GS ≥7 PCa in the RP specimen. This model included PSA density, % positive biopsy cores, and clinical stage. The diagnostic performance of this model was then compared to a second model that incorporated PSMA-AI calls. Results: In total, 87 patients enrolled in the original trial contributed to the analysis. The base model indicated that PSA density and % positive cores were significantly associated with occult GS ≥7 PCa (p < 0.05), but clinical stage was not (p = 0.23). The predictive ability of the model resulted in an area under the curve (AUC) of 0.73. Upon adding PSMA-AI calls, the AUC increased to 0.77. PSMA-AI calls (p = 0.045), pre-surgery PSA density (0.019) and % positive core (p < 0.004) remained statistically significant. PSMA-AI calls increased the positive predictive value from 70% to 77% and the negative predictive value from 57% to 74%. Conclusions: The addition of PSMA-AI calls demonstrated a significant improvement over known predictors for identifying men with occult GS ≥7 PCa, who are inappropriate candidates for active surveillance. Clinical trial information: NCT02615067.
PMEPA1 gene isoforms to indicate disease progression in solid tumors.
Authors: Sharad Shashwat , Sztupinszki ZsÃ£Â³fia , Szallasi Zoltan , Rosner Inger L. , Srivastava Shiv , Dobi Albert , Cullen Jennifer , Li Hua 
Published: May 2019

e16580 Background: Dysfuncitons of androgen and TGF-β signaling play important roles in prostate tumorigenesis. PMEPA1 gene has been defined as an androgen and TGF-β responsive gene which inhibits androgen and TGF-β signaling via negative feed-back loops. Our previous data has established that PMEPA1 distinct isoforms ( PMEPA1-a and PMEPA1-b) with disparities within N-terminus protein sequences navigate different androgen/TGF-β signaling regulations. In this study, the roles of PMEPA1 isoforms in disease progressions were investigated in solid tumors of prostate (CaP), breast, lung and colon. Methods: RNA seq data from total 2479 solid tumor samples in the TCGA dataset were used to study the correlation between expressions of PMEPA1 isoforms and disease progression including Gleason score, pathology stages, progression free survival rate (PFS) and overall survival rate (OS). The cohort is composed of 482 prostate, 1049 breast, 499 lung and 449 colon cancer patients. Results: In CaP, the TCGA data analysis showed that lower transcript level of PMEPA1-b isoform associated with higher Gleason scores and lower progression free survival rate (PFS) (P = 0.014) and worse overall survival rate (OS) (P < 0.01). The ratio of mRNA levels of PMEPA1-a versus PMEPA-b indicated higher Gleason score, lower PFS rate (P = 0.0063) and worse OS rate (P = 0.0042). In contrast, higher expression of both PMEPA1-a and PMEPA- b associated with lower PFS (P = 0.023 and 0.028, respectively) in breast cancer. And the enhanced ratio of PMEPA1-a/ b was also found to indicate lower PFS (P = 0.016) and worse OS (P = 0.016) in breast cancer. Similarly, the increased transcript levels of PMEPA1-a and PMEPA1-b isoforms significantly associated with lower PFS and worse OS rates in lung and colon cancer. The expression of PMEPA1 isoforms was not found to associate with pathology stages of diseases. Conclusions: Our data establish the biomarker potential of PMEPA1 gene isoforms ( a and b) indicating more aggressive disease progressions in 4 solid tumors, further underscoring the PMEPA1 isoform specific biological functions to differentiate regulation of androgen and TGF-β signaling in cancer cells.
Next-generation sequencing of primary prostate cancer tumors to reveal actionable opportunities for clinical management.
Authors: Crona Daniel James , Drier Anthony , Zhu Jing Daisy , Bell Emily Fox , Sketch Margaret Rose , Boland Alexandra , Garrett Amy , Wang Lin , Mitchell Khalis , Tomlins Scott A. , Dees Elizabeth Claire , Godley Paul Alphonso , Dunn Mary , Rose Tracy L , Basch Ethan M. , Milowsky Matthew I. , Whang Young E. 
Published: May 2019

e16582 Background: The Strata Trial (NCT03061305) is a multi-institutional precision oncology collaboration structured as an observational protocol that aims to match patients to genomically guided therapies. Methods: Selected University of North Carolina (UNC) metastatic prostate cancer (mPC) patients were enrolled on this IRB-approved study. Formalin fixed paraffin-embedded primary tumor specimens, without matched germline controls, were sent for targeted next generation sequencing (NGS) to detect actionable variants, including: mutations in 87 genes, copy number variations in 31 genes, gene fusions in 46 gene drivers, and microsatellite instability (MSI) status. mPC-related genes of specific interest included: AR, ATM, BRCA1/2, ERG, MSH2, MSH6, PTEN, RB1, and TP53. Results: Of the 108 cases sequenced, 6 (6%) failed testing. Of the 102 mPC patients with sequence data, the median age was 69 (47-86), 60 (59%) were white, 35 (34%) were black, 1 (1%) was Asian, and 6 (6%) declined to identify race. NGS data revealed 122 variants in 27 genes: 73 patients (71%) had at least one variant. Among those 73 patients, 38 (52%) had only 1 variant, 24 (33%) had 2 variants, 8 (11%) had 3 variants, and 3 (4%) had 4 variants. TMPRSS2-ERG fusions occurred most frequently (51%), followed by TP53 variants (38%), and PTEN variants (16%). Only 8% of patients had variants in DNA damage repair genes, including ATM (3%), BRCA2 (3%) and MSH2 (2%). Two patients with MSI high tumors were treated with pembrolizumab, while 4 patients with deep BRCA2 or ATM deletions were eligible for trials of PARP inhibition. Conclusions: Our UNC experience shows that a high proportion of primary prostate cancer tumors from mPC patients have genomic variants, and two patients were treated based on these data. Limited actionability may reflect the landscape of currently FDA approved mPC treatments available clinical trials, or due to short duration of follow-up after enrollment on the Strata Trial.
27-year patterns in high-risk prostate cancer treatment in a racially diverse, equal-access health care setting.
Authors: Rocco Nicholas R , Santomauro Michael G , Robertson Audry H , Kuo Huai-Ching , Brand Timothy C. , Chen Yongmei , Musser John E , Porter Christopher R. , Rosner Inger L. , Gable Preston , Cullen Jennifer , Stroup Sean P 
Published: May 2019

e16583 Background: Despite the significant stage migration of prostate cancer (CaP), a large proportion of patients harbor high-risk disease. Few CaP series provide long term outcomes with the ability to assess disparities in diverse populations. We examined 27-year outcomes among men treated for high risk CaP in a large, racially diverse, equal access system. Methods: A retrospective cohort study was conducted of patients enrolled into the Center for Prostate Disease Research (CPDR) Multi-Center National Database from 1990-2017. There were 2,241 CaP patients who were NCCN-defined high risk, had a self-reported race of Caucasian (CA) or African American (AA), and had a primary treatment of hormonal therapy (HT), radical prostatectomy (RP), radiation therapy (RT) or no treatment (NoTX). Demographic and clinico-pathological variables were evaluated and stratified by race and treatment. Primary study outcomes included temporal patterns in race-specific treatment intensity and type(s). Secondary outcomes included biochemical recurrence (BCR)-free survival (BRFS) and distant metastasis-free survival (DMFS). Unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis were used. Results: Mean patient age at CaP diagnosis and follow-up time were 68.1 years and 7.8 years, respectively. AAs made up 26.9% of the study cohort. Median prostate specific antigen level was 20.9 ng/mL (IQR: 7.8 - 35.0). 52% of patients had a biopsy Gleason score of 8 or greater. 714 (31.9%) underwent RP, 966 (43.1%) underwent RT, 288 (12.9%) received primary HT, and 273 (12.2%) had NoTX. A decreasing trend of HT, with stable rates of RP and RT, was observed. Median time to BCR after RP and RT was 1.3 and 3.1 years, respectively. After RP and RT, 51.2% and 39.3% experienced BCR while 10.9% and 12.7% experienced distant metastasis, respectively. There were no significant racial differences in treatment intensity, treatment type, BRFS or DMFS. Conclusions: In this longitudinal series, there was racial comparability for all study outcomes. Moreover, in this high-risk patient series with long-term follow up (median = 6.9 years), nearly 50% did not experience BCR, and only 1 in 10 men developed metastasis.
Comparative effectiveness of surgery versus external beam radiation with/without brachytherapy in intermediate and high-risk localized prostate cancer.
Authors: Yin Ming , Monk Paul , Mortazavi Amir , Joshi Monika , Folefac Edmund , Clinton Steven K. 
Published: May 2019

e16602 Background: Radical prostatectomy (RP) and definitive radiation with androgen deprivation therapy (ADT) are both standard of care options for intermediate and high-risk localized prostate cancer (PCa). It remains controversial if the two modalities produce equivalent outcomes because the PROTECT trial (2016) and three recent retrospective studies (2018) drew inconsistent conclusions. Methods: The Surveillance, Epidemiology and End Results (SEER) database was queried from 2004 to 2015 for localized PCa (TxN0M0) who received upfront surgery or who were recommended for surgery but instead received external beam radiation (EBRT) with or without brachytherapy boost to control selection bias. The Kaplan-Meier method was used to generate overall survival (OS) curves and the Cox regression analysis was performed to compare survival outcomes. Results: A total of 175,349 patients were eligible with a median age of 62 years old (age range: 26 to 99). 167,234 patients had upfront surgery and 8,115 patients had upfront radiotherapy, including 7,099 EBRT and 1,016 EBRT with brachytherapy. Overall, upfront surgery was associated with a better OS, compared with patients who received radiotherapy (all patients: adjusted HR [adjHR], 0.79; 95% CI, 0.74–0.83, P < 0.001). The survival benefit is more pronounced in patients of intermediate-risk group (adjHR, 0.61; 95% CI, 0.57–0.66, P < 0.001; N = 112,816), and remains significant in patients of high-risk group (adjHR, 0.91; 95% CI, 0.84–0.98, P = 0.02; N = 62,533). However, in elderly high-risk PCa patients (age ≥ 70), surgery was associated with a significantly inferior OS, compared with radiotherapy (adjHR, 1.16; 95% CI, 1.06–1.28, P = 0.002). Conclusions: Compared with upfront radiation therapy, definitive surgery was associated with overall survival benefit in intermediate- and high-risk localized PCa, except patients with old age and high-risk features, who should be considered for radiation therapy.
Single agent of apatinib in patients with recurrent or refractory cervical cancer: A real-world multicenter retrospective study.
Authors: Li Ning , Wang Ziyi , Wang Jing , Wu Lingying 
Published: May 2019

e17011 Background: Few effective treatment strategy has been established for patients with recurrent or refractory cervical cancer. The present study evaluates the efficacy and safety of apatinib single agent in Chinese patients with recurrent or refractory cervical cancer. Methods: Records of patients with cervical cancer treated from October 1, 2016 to December 31, 2017 in Cancer Hospital, Chinese Academy of Medical Sciences and Hunan Cancer Hospital were reviewed. Patients who met the following criteria were included: 1) patients had pathologically confirmed cervical cancer; 2) patients who experienced progression within 6 months or during previous treatment; 3) patients were given 250 mg apatinib daily for the present recurrence; 4) medical records were complete for evaluation of efficacy and toxicity. Tumor response was determined according to RECIST 1.1. The toxicity was determined according to CTCAE 4.0. SPSS 20.0 was adopted for statistic analysis. The primary endpoint was progression-free survival (PFS). Results: Twenty-nine patients were enrolled in our retrospective study. The clinical characteristics were shown in table 1. Thirteen patients (44.8%) had persistent disease and the other 16 patients (55.2%) had recurrent disease less than 6 months after the last treatment. Up to February 1, 2018, the median follow-up time was 8 months. Five (17.2%) patients achieved partial response, and 11 (37.9%) achieved stable disease, representing a disease control rate of 55.1%. The median PFS was 4 months (1-16 months). Nine patients were still on medication. The reasons of discontinued intervention were disease progression (80.0%, 16/20), toxicity (10.0%, 2/20) and other events unrelated with apatinib (10.0%, 2/20). Common adverse events were hypertension (G1, 65.5%), mucositis (G1, 55.2%), hand-foot syndrome (G1-2, 44.8%) and proteinuria (G1-2, 20.7%). Grade 3 proteinuria occurred in 1 patient (3.4%,). Conclusions: Apatinib single agent might be an effective and tolerable choice for patients with recurrent or refractory cervical cancer. Further study is warranted.[Table: see text]
Uterine corpus invasion as a risk factor in patients with early-stage cervical carcinoma receiving radical surgery.
Authors: Li Yifan , Li Ning , Wu Lingying 
Published: May 2019

e17012 Background: To explore whether pathologically verified uterine corpus invasion (UCI) is a risk factor for patients with early-stage (IB1-IIA2) cervical carcinoma receiving radical surgery. Methods: A mathed-case comparison of early-stage cervical carcinoma patients with pathologically verified UCI to patients without UCI on a 1:1 ratio was conducted. High risk factors (lymph node metastasis, paremetrial invasion, vaginal margin invasion) and intermediate risk factors (lymphovascular space invasion (LVSI) and deep stromal invasion) were completely matched between UCI and non-UCI groups. Kaplan-Meier and Log-rank test were applied for univariate analysis, and COX proportional hazard regression models were used for multivariate analysis. Results: 1320 consecutive patients with cervical carcinoma received surgery in our centerfrom Jan. 1st2009 to Dec 31st2014. 79 (5.98%) cases with UCI were identified. Median follow-up time was 43 months. There were 22 cases with recurrence. In UCI group, the recurrence rate was 20.3% (16/79), and in non-UCI group the recurrence rate was 7.6% (6/79). On univariate analysis, SCC, neoadjuvant chemotherapy (NACT), lymph node metastasis, parametrial invasion, LVSI, deep stromal invasion, vaginal invasion and UCI were significantly associated with disease free survival (DFS). After multivariate analysis, UCI ( p= 0.02, RR3.832, 95% CI1.235-11.893)and lymph node metastasis ( p= 0.042, RR 2.890, 95% CI1.038-8.045) were still independent risk factors for deceased DFS. Conclusions: Pathologically verified uterine corpus invasion might be an independent risk factor for decreased DFS in patients with early-stage cervical carcinoma receiving radical surgery.
Survival differences based on tumor size among stage 1B cervical cancer patients in Louisiana using revised FIGO staging system.
Authors: Nair Navya , Zhang Lu , Kuan-Celarier Anna , Wu Xiao-cheng , Jernigan Amelia 
Published: May 2019

e17017 Background: In the recently revised 2018 FIGO cervical cancer staging, stage IB is sub-classified into 3 classes based on tumor size. We aim to determine if larger tumor size confers worse survival outcomes in women with stage IB cervical cancer in Louisiana. Methods: Women with stage IB cervical cancer diagnosed between 2010 and 2016 were identified from the Louisiana Tumor Registry. Patients with positive pelvic or para-aortic lymph nodes and those with less than 30 days follow up were excluded. Subjects were classified into three groups based on tumor size: stage IB1 ( < 2cm), stage IB2 (≥ 2cm and < 4cm), and stage IB3 (≥ 4cm). Cox proportional hazards were used to estimate differences in overall (OS) and cause-specific survival (CSS). Covariates included age, race, insurance, census tract-poverty level, and marital status. Results: 198 patients were included with a median follow up time of 43.8 months. Mean age of patients in this cohort was 46.8 years. The subjects were well distributed between the groups: 79 (39.4%) stage IB1, 60 (30.3%) stage IB2, and 60 (30.3%) stage IB3. White women comprised a larger percentage of earlier stage tumors (79.5% 1B1 vs 68.3% 1B2 vs 53.3% 1B3, p < 0.01); Black women were overrepresented in later stage disease (45.0% IB3, 28.3% IB2, 20.5% IB1, p < 0.01). There were no significant differences between the three groups in age, insurance status, poverty level, or marital status. After adjusting for covariates, patients with stage 1B3 disease had worse survival than those with stage 1B1 disease in both OS [HR 6.01 (1.96,18.50)] and CSS [HR 24.31 (2.97,199.00)]. Patients with stage 1B2 disease had worse survival than those with 1B1 disease but this did not reach statistical significance: OS HR 1.88 (0.52,6.74); CSS HR 6.79 (0.77, 59.99). Kaplan-Meier curves of OS and CSS show significant survival differences between the three groups (p < 0.0001) with best outcomes in stage 1B1 and worst in stage 1B3 patients. Conclusions: This analysis of contemporary stage IB cervical cancer patients in Louisiana confirms that tumor size > 4cm confers worse clinical prognosis. Black women are overrepresented advanced stage IB disease. While patients with tumors 2-4cm did worse than those with tumors < 2cm, this did not reach statistical significance. This could be due to the limited sample size of our cohort.
ARID1A interacts with nonmuscle myosin IIA to regulate cancer cell motility.
Authors: Osagie Oloruntoba Ismail , Li Zhigui , Mi Shijun , Aguilan Jennifer T , Huang Gloria S. 
Published: May 2019

e17036 Background: ARID1A (BAF250A), a member of the SWI/SNF chromatin remodeling complex, is one of the most frequently mutated genes in human cancer. Here we report the discovery of a novel protein-protein interaction between ARID1A and the actin-binding motor protein, non-muscle myosin IIA (NM IIA) encoded by the myosin heavy chain 9 ( MYH9). Methods: The ARID1A immunoprecipitated protein complex was separated by gel electrophoresis followed by analysis of the peptide digested gel bands by C18-Reversed Phase chromatography using an Ultimate 3000 RSLCnano System (Thermo Scientific) equipped with an Acclaim PepMap C18 column (Thermo Scientific) and connected to a TriVersa NanoMate nanoelectrospray source (Advion) and a linear ion trap LTQ-XL mass spectrometer (Thermo Scientific). Protein identification was performed by Mascot search engine v. 2.5.1 (Matrix Science) against NCBI Homo sapiens database. Scaffold software v. 4.5.1 (Proteome Software Inc.) was used to validate the MS/MS peptide and protein identification based on 99% protein and 95% peptide probabilities. Immunoprecipitation and immunoblotting were done to evaluate the protein-protein interaction in ARID1A-wild type cell lines. Isogenic engineered cell lines, ES2 shRNA-control or shRNA- ARID1A stable transfection , and HCT116 control or ARID1A knockout by CRISPR-Cas9 (Horizon Discovery) were used to evaluate the effect of ARID1A loss on NM IIA expression and phosphorylation, and on cell migration by in vitro scratch assay with time lapse imaging. Results: Scaffold analysis of peptide spectra identified NM IIA with > 99% probability in the ARID1A immunopurified protein complex. In the ARID1A wildtype cell lines ES2 and KLE, endogenous NM IIA co-immunoprecipitated with ARID1A and vice versa. ES2 sh ARID1A cells had decreased total and phosphorylated NM IIA expression, and impaired cell migration compared to control cells. Similarly, HCT116 ARID1A homozygous knockout cells had impaired cell migration compared with HCT116 control cells. Conclusions: We report for the first time that ARID1A interacts with NM IIA to regulate cancer cell motility. Further investigation is ongoing to elucidate the significance of this newly identified function of ARID1A.
Multiple genetic alterations to predict the clinical outcome for bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study.
Authors: Du Nan , Gao Jie , Li Fang , Liu Zihao , Chen Huoming , Liao Guoqing , Meng Jichang , Zhao Hui , Huang Mengli , Wang Qing , Cai Shangli 
Published: May 2019

e17037 Background: Bevacizumab(BV) plus chemotherapy is widely used in patients with advanced ovarian cancer(OC). However, there was not predict biomakers to determined the use of BV-based treatment in OC currently.Therefore, exploring the predict biomarkers for BV is imperative. Methods: Tumor issues of advanced OC treated with BV plus chemotherapy were used for next generation sequencing (NGS) with a 150-gene targeted panel. The correlation between Progression-Free Survival (PFS) and genes or clinicopathology features was analyzed by Kaplan-Meier or Cox regression. For multivariate Cox regression, all factors with a p-value < 0.05 in univariate Cox regression were included. The potential predictive genes would be analyzed with VEGF-related signatures by using 374 OC mRNA data from The Cancer Genome Atlas (TCGA).Statistical analysis was performed using GraphPad Prism and SPSS. Results: 62 Chinese advanced OC patients treated with BV-base therapy were enrolled in this study from May 2015 to March 2018.The median PFS of these patients was 5.7 months , while ORR and DCR rate was 14.5% and 96.8%, repecitively.Patients with EGFR or HER2 alterations had poorer PFS compared with wild-type (EGFR,4.2 months vs. 7.4 months,p = 0.019;HER2,3.8 months vs. 7.3 months, p = 0.045), while MYC amplification patients got better PFS than MYC wild-type patients(17.4 months vs. 6.0 months,p = 0.049). However, in multivariate Cox regression anlysis, EGFR and HER2 were significantly correlated with PFS(P < 0.001 and p = 0.016,respectively),and MYC amplification seemed to have a positive trend(p = 0.052).Moreover,patients with HER2 alterations has a poorer OS(p = 0.008).The VEGF-related signatures analysis results indicated EGFR variants may upregulated VEGFA expression to induced resistant of BV,while downregulation of HIF was significantly correlated with MYC amplification,which was beneficial to efficacy of BV.HER2 alterations has not correlated with VEGF pathways,suggesting HER2 was a poor prognosis of OC instead of an negative predictor of BV. Conclusions: NGS is an effective method to reveal the potential predictor for BV plus chemotherapy in advanced ovarian cancer, and the patients with EGFR or HER2 alterations should consider alternative regimens such as anti-EGFR or anti-HER2 target therapy instead of BV-based regimens.