bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B078: Expression of activated STAT3 in the epithelial cells of hormone-naïve prostate cancer
Authors: Krzyzanowska Agnieszka , Don-Doncow Nicholas , Marginean Felicia-Elena , Watson William , Hellsten Rebecka , Bjartell Anders 
Published: February 2019

Abstract
Introduction: The Signal Transducer and Activator of Transcription 3 (STAT3) pathway is thought to be phosphorylated (pSTAT3) and constitutively activated in prostate cancer (PCa). Previous results from our laboratory showed high pSTAT3 levels in PCa metastases. In the present study we investigated the expression of pSTAT3 in tissue microarrays of two cohorts of localized hormone-naïve PCa patients and correlated it with disease outcome.
Methods: The expression of pSTAT3 in the nuclei of epithelial cells of prostatic glands was examined in two TMAs of paraffin-embedded prostatic tissue. The TMAs consisted of tissue originated from hormone-naïve radical prostatectomy patients from two different sites: Malmö (n=300) and Dublin (n=99).
Results: In the Malmö cohort, the average expression levels of pSTAT3 in the epithelial cells of benign glands were significantly higher than in the cancerous glands. Patients with low pSTAT3 levels in the epithelial cells of the cancerous glands showed reduced times to biochemical recurrence, compared to those with higher levels; however, adding the pSTAT3 expression data to Gleason score or pathologic T stage did not improve their prognostic values. The results for the Dublin cohort showed similar trends.
Conclusions: Low pSTAT3 expression in epithelial cells of cancerous prostatic glands in hormone-naïve PCa was associated with faster disease progression; however, pSTAT3 is unlikely to be a good biomarker in the early stages of PCa.
Citation Format: Agnieszka Krzyzanowska, Nicholas Don-Doncow, Felicia-Elena Marginean, William Watson, Rebecka Hellsten, Anders Bjartell. Expression of activated STAT3 in the epithelial cells of hormone-naïve prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B078.
Abstract B093: Development and validation of a novel automated Gleason grade and molecular profile that define a highly predictive prostate cancer progression algorithm-based test
Authors: Donovan Michael Joseph , Fernandez Gerardo , Scott Richard , Zeineh Jack , Koll Giovanni , Khan Faisal , Gladoun Nataliya , Charytonowicz Elizabeth , Tewari Ash , Cordon-Cardo Carlos 
Published: February 2019

Abstract
Background: Postoperative risk assessment remains an important variable in the treatment of prostate cancer. We aimed to develop and validate a tissue-based on-slide prognostic risk model test to identify which patients would benefit most from early intervention.
Methods: Prospectively designed retrospective study utilizing 892 patients, post radical prostatectomy, followed for a median of 8 years. We constructed a matched 50:50 training and test cohort to identify compound features using protein multiplex immunofluorescence combined with novel morphometry generated by advanced image analysis and machine learning tools. The primary endpoint was the development of a postoperative clinical failure (CF) including PSA rise post-adjuvant treatment, or metastasis or prostate cancer specific mortality. Time to event C-index and Kaplan-Meier were used to assess accuracy.
Results: The Precise postop model in training (n=306) selected 4 compound imaging features and one clinical variable to predict CF with a performance C-index of 0.82, [95%CI: 0.76-0.86], HR:6.7, [95%CI: 3.59-12.45], p &lt;0.00001. Of importance, the derived androgen receptor/Ki67/morphometric imaging features successfully replaced the subjective clinical Gleason grading in the final model. In validation, increasing Precise postop scores predicted shortened time to disease progression (n=284) with a C-index 0.77 [95%CI: 0.72-0.81], HR=5.4, [95%CI: 2.74-10.52], p &lt;0.00001.
Conclusion: Patients with high Precise postop scores had a higher likelihood of having disease progression within 8 years with a reduced durable response to androgen-deprivation therapy. The Precise postop algorithm-based model guided by machine learning replaces subjective Gleason grading with novel image features that combine morphometry with biologic attributes that more accurately reflect disease potential.
Citation Format: Michael Joseph Donovan, Gerardo Fernandez, Richard Scott, Jack Zeineh, Giovanni Koll, Faisal Khan, Nataliya Gladoun, Elizabeth Charytonowicz, Ash Tewari, Carlos Cordon-Cardo. Development and validation of a novel automated Gleason grade and molecular profile that define a highly predictive prostate cancer progression algorithm-based test [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B093.
Abstract IA05: Emerging therapeutic strategies for androgen indifferent prostate cancer
Authors: Beltran Himisha 
Published: February 2019

Abstract
The development of castration resistance in prostate cancer most commonly involves reactivation of androgen receptor (AR) signaling; this knowledge has informed the clinical development of potent AR-targeted agents now commonly used in the clinic. However, a subset of prostate cancers may evolve under therapeutic pressure of the AR towards non-AR driven, or “androgen indifferent,” disease. This has been associated with aggressive clinical features with repeat biopsies enriched with TP53 and RB1 genomic loss, overexpression of MYCN, epigenetic changes, and activation of alternative lineage programs such as neuronal and neuroendocrine pathways. One extreme manifestation is complete transformation to a small cell/neuroendocrine carcinoma with loss of AR expression. Although castration-resistant neuroendocrine prostate cancer evolves clonally from prostate adenocarcinoma likely through a trans-differentiation process, it acquires molecular alterations seen in other poorly differentiated neuroendocrine cancers. This talk will focus on emerging biomarker-driven therapeutic strategies for androgen-indifferent disease, including updates on targeting the N-myc/Aurora kinase A complex, the potential role for epigenetic therapies, and new data to inform ADC and immunotherapy development for this subset.
Citation Format: Himisha Beltran. Emerging therapeutic strategies for androgen indifferent prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA05.
Abstract IA09: Early, highly specific risk stratification for lethal prostate cancer using a prespecified statistical model based on four kallikrein markers in blood
Authors: Lilja Hans 
Published: February 2019

Abstract
Prostate-specific antigen (PSA) and human kallikrein-related peptidase 2 (hK2) are 237-aa single chain glycoproteins with uniquely different serine proteinase activity and products of two highly homologous primate-lineage specific, androgen receptor-regulated genes (KLK3 and KLK2) with abundant prostate-restricted expression. In blood from healthy middle-aged men not subject to PSA testing, million-fold lower levels of multiple noncatalytic forms of PSA and hK2 are very strongly associated with 20+ year- risk of metastasis or death from prostate cancer (PC), whereas prospective randomized trials in Europe show that early detection by systematic PSA testing reduces PC-specific deaths but remains controversial due to harm from overdiagnosis and overtreatment. Population-based findings of longer lead time at Gleason Grade Group ≥2 (GGG2) versus GGG1 at PC diagnosis provide evidence of grade progression over time. However, our estimates of a ≤6% risk of ≥GGG2-PC by a predefined statistical model based on four kallikrein markers in blood in middle-aged men with modestly elevated PSA is strongly associated with 15-20-year risk of PC death or metastasis below population average. By contrast, a smaller subset of these middle-aged men with modestly elevated PSA and a ≥6% four kallikrein risk-score have 15-20-year risk of PC death or metastasis that is multiple folds higher than the population average. Although evidence exists that mutations in germline DNA are associated with PC-death or metastasis, it is currently unclear how we could integrate these findings in programs aimed at early specific detection of lethal PC.
Citation Format: Hans Lilja. Early, highly specific risk stratification for lethal prostate cancer using a prespecified statistical model based on four kallikrein markers in blood [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA09.
Abstract IA11: Germline genetic testing in prostate cancer
Authors: Pritchard Colin C. 
Published: February 2019

Abstract
Recent studies have revealed a higher than expected frequency of germline autosomal dominant cancer predisposition gene mutations in men with high-risk and advanced prostate cancer. These mutations have important implications for risk-stratification and precision therapy, as well as for cancer risks in family members. This has led to relatively rapid adoption of germline panel genetic testing in clinical practice, and facilitated identification of cancer-free men who are mutation carriers at elevated risk for prostate cancer. This talk will cover the spectrum of germline cancer predisposition genes associated with prostate cancer, issues surrounding clinical genetic panel testing, and emerging data on how germline genetic information may be used to inform screening and risk.
Citation Format: Colin C. Pritchard. Germline genetic testing in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA11.
Abstract IA20: Lineage plasticity in antiandrogen resistance
Authors: Abida Wassim 
Published: February 2019

Abstract
Resistance to the novel androgen receptor (AR)-directed therapies enzalutamide and abiraterone acetate can evolve with an aggressive clinical phenotype and atypical histology, including neuroendocrine features. Genomic studies have also revealed enrichment in TP53 and RB1 alterations in advanced metastatic CRPC when compared with primary disease. In recent work, the Sawyers and Goodrich groups have independently shown that concurrent loss of TP53 and RB1 confers resistance to antiandrogen and lineage plasticity through upregulation of the transcription factor SOX2. These studies implicate key tumor suppressors in lineage switching in resistant prostate cancer, and suggest that antiandrogen resistance may be targeted by epigenetic agents in advanced disease.
Citation Format: Wassim Abida. Lineage plasticity in antiandrogen resistance [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA20.
Abstract IA24: Making immunotherapy work in prostate cancer
Authors: Gulley James L. 
Published: February 2019

Abstract
Immunotherapeutic approaches can only be successful when the immune system recognizes the tumor and generates a response that causes immune effector cells to seek out and destroy the tumor. Recent clinical advances in immunotherapy have capitalized on tumors that the immune system has developed an immune response to, but is prevented from killing by specific immune checkpoints that protect normal tissue from autoimmune attack. Tumor cells use these checkpoints to escape immune attack. However, many tumors, including the vast majority of prostate tumors, do not have an underlying immune response. A variety of modalities, some more efficient than others, can lead to immune recognition, but cannot be fully effective when used as monotherapies. Optimal clinical benefit will be achieved with rational combination therapies that generate a robust immune response and allow those generated effector cells to remain functional within the tumor microenvironment.
Citation Format: James L. Gulley. Making immunotherapy work in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA24.
Abstract A05: Genetic factors associated with racial disparities of liver cancer
Authors: Cui Zihan , Wang Zhe , Zhao Tingting , Sang Qingxiang Amy , Zhang Jinfeng 
Published: February 2019

Abstract
Liver cancer (hepatocellular carcinoma [HCC]) is a leading cause of cancer-related morbidity and mortality worldwide. Racial disparities in HCC have been well-known among several racial and ethnic groups in the U.S. The incidence rates (per 100,000/year) for non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanics (HISP), and Asian/Pacific Islanders (API) are 7.0, 15.7, 11.8, and 18.6, respectively. The 5-year survival rates (%) for the four population groups are 18.2, 15.1, 19.2, and 24.4, respectively. NHWs have the lowest incidence rates, while APIs have the highest 5-year survival rate among the four racial and ethnic groups. Previous studies have indicated that socioeconomic status, in general, is associated with HCC health disparity; however, they alone cannot fully explain the disparity between different racial and ethnic groups. Few studies have investigated the biologic factors that may be associated with the health disparity in HCC. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we have performed a comprehensive analysis of differentially expressed genes and pathways between Caucasian and Asian American liver cancer patients and identified hundreds of differentially expressed genes. We also identified a handful of genes that are differentially mutated between Caucasian American and Asian American HCC patients using the somatic mutation data from TCGA. We will discuss in details the differentially expressed genes and pathways, and their implications for the HCC health disparity. As far as we know, our study represents the largest-scale study on the biologic factors for HCC health disparity between Caucasian and Asian American liver cancer patients.
Note: This abstract was not presented at the conference.
Citation Format: Zihan Cui, Zhe Wang, Tingting Zhao, Qingxiang Amy Sang, Jinfeng Zhang. Genetic factors associated with racial disparities of liver cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A05.
Abstract A15: Challenges and successes in delivering a cancer survivorship support program among rural Latinas
Authors: Ceballos Rachel M. 
Published: February 2019

Abstract
Introduction: Rates of cancer survivorship are increasing for most cancers. However, Latina cancer survivors tend to experience lower quality of life and higher levels of distress following cancer compared to non-Latina Whites (NLW). While social support resources can alleviate the negative psychosocial impact of cancer sequelae, there are often limited resource availability and uptake among Latina cancer survivors.
Objective: This presentation will include descriptions of the qualitative and quantitative study design, recruitment strategies, cultural adaptations of the intervention, challenges, and successes in data collection and intervention delivery.
Methods: This study included a qualitative needs assessment of Latina survivors of breast and gynecologic cancers living in a rural region of Washington State, development of a 10-week Spanish-language survivor-support program, and a randomized control trial (RCT) whose effectiveness was evaluated with psychosocial and biologic outcomes. Intervention delivery and qualitative and quantitative data collection were conducted by promotores (lay health workers).
Conclusion: Challenges and successes of conducting the qualitative assessment, delivering the intervention, and data collection will be discussed. Future studies can build on the methodologic insight gained from this project.
Citation Format: Rachel M. Ceballos. Challenges and successes in delivering a cancer survivorship support program among rural Latinas [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A15.
Abstract A17: [Advocate Abstract:] Culturally sensitive outreach for clinical trials and research studies is key to addressing biologic contributors to health disparities
Authors: Holloway Jamie 
Published: February 2019

Abstract
Background: I will present a quick look at outcome disparities and some specific cases where there is a clear biologic basis for outcome disparities in cancer. It would also be relevant to look at some statistics of the racial makeup of participants in clinical trials.
Data: I will incorporate the survey results from a high school student (who will be listed as a coauthor) that will address attitudes toward clinical trial participation, stratified by race. I will also present some of the strategies that a team I am leading at Howard University hopes to employ as they use social media and local outreach to increase enrollment of African American patients in the MBC project.
Citation Format: Jamie Holloway. [Advocate Abstract:] Culturally sensitive outreach for clinical trials and research studies is key to addressing biologic contributors to health disparities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A17.
Abstract A51: Disparities in cervical cancer patients by race and histology
Authors: Huang Ying , Tarney Christopher , Tian Chunqiao , Bateman Nicholas , Conrads Thomas , Hamilton Chad , Maxwell George , Darcy Kathleen 
Published: February 2019

Abstract
Introduction: The incidence and mortality of cervical cancer in the United States has decreased over the last four decades given screening and vaccination programs. Nevertheless, this statement cannot be generalized among all races. We investigated cancer-related mortality (CRM) and non-cancer related mortality (NCM) for cervical cancer patients among racial groups.
Methods: Women diagnosed with cervical cancer from 1990-2014 were identified from the Surveillance, Epidemiology and End Results database. Racial disparities in survival for non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic (HSP), and Asian/Pacific Islander (API) patients were compared using a competing risk model that accounted for both CRM and NCM. Analyses were particularly performed by histologic subtype for squamous cell carcinoma (SCC) vs. adenocarcinoma and adenosquamous carcinoma (AC/ASC).
Results: 62,887 cervical patients were analyzed: 34,520 (54.8%) NHW, 8,650 (13.8%) NHB, 13,937 (22.2%) HSP, and 5,780 (9.2%) API. From 1990 to 2014, the proportion of SCC has decreased, while the proportion of AC/ASC has increased among all racial groups with the exception of NHB patients who saw a smaller increase in AC/ASC (P&lt;.0001). NHB patients were more likely to be diagnosed at advanced stages, and upon adjusting for known prognostic factors, NHB patients had the worst CRM and NCM among all racial groups (P&lt;.0001). HSP patients had better CRM for both SCC and AC/ASC (P&lt;.0001), whereas API patients had worse CRM for AC/ASC (P&lt;.0001) when compared to NHW patients.
Conclusions: Both CRM and NCM significantly vary among racial groups, with the worst survival being seen in NHB patients.
Citation Format: Ying Huang, Christopher Tarney, Chunqiao Tian, Nicholas Bateman, Thomas Conrads, Chad Hamilton, George Maxwell, Kathleen Darcy. Disparities in cervical cancer patients by race and histology [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A51.
Abstract A58: Racial disparities in head and neck cancers in an urban hospital
Authors: Zeigler-Johnson Charnita , Keith Scott , Guiles Frances , Cognetti David , Bar-Ad Voichita , Axelrod Rita 
Published: February 2019

Abstract
Introduction: Although head and neck cancer incidence rates are higher for white residents in Philadelphia, PA, related mortality rates are highest for black residents. It is not clear how clinical factors and risk factors like HPV and smoking contribute to these disparities. The goal of this study is to determine which factors are associated with advanced head and neck cancers in a diverse sample of patients from a Philadelphia hospital.
Methods: Cancer registry data from Thomas Jefferson University (957 beds, Philadelphia, PA) were used to obtain clinical records from 922 head and neck cancer patients diagnosed from 2011-2015. One patient of other race was removed from these analyses. We examined advanced cancer among the primary racial groups represented in our hospital population. Chi-square tests were used to examine differences in categorical variables. The Kruskal-Wallis test was used to compare continuous variables. Logistic and Cox regression models were designed to examine independent associations with advanced disease and time to mortality. Covariates included age, race, tumor stage, HPV status, smoking status, gender, and treatment type.
Results: Our sample included 921 patients (788 white, 96 black, 37 Asian). Our descriptive analysis showed that among the three groups, blacks were more likely to be female (p=0.033). Positive HPV status was most prevalent for white patients (p=0.004). Oral and nasopharyngeal cancers were most common among Asians, and oropharyngeal cancers were most common among whites. In univariate analysis, black patients were most likely to die from their cancer. Multivariable analyses showed that current smoking (compared to never smoking) was associated with T3/T4 stage at diagnosis (OR=6.85, 95% CI=1.11-42.2). Time to death was significantly shorter for older individuals (HR=1.02 95% CI=1.01-1.05), current smokers (HR=2.24, 95% CI=1.25-4.00) and patients receiving radiation only (HR=7.70, 95% CI=1.38-42.95). Positive HPV status was protective (HR=0.29, 95% CI=0.19-0.44). No significant race effects were observed in these models.
Conclusions: The results of this study suggest that race is not independently associated with head and neck cancer or associated mortality. These results also suggest that some risk factors for head and neck cancer and related outcomes may be modified by educational and behavioral interventions.
Citation Format: Charnita Zeigler-Johnson, Scott Keith, Frances Guiles, David Cognetti, Voichita Bar-Ad, Rita Axelrod. Racial disparities in head and neck cancers in an urban hospital [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A58.