bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO-131: Inter-tumoral heterogeneity of progressive disease in melanoma patients treated with pembrolizumab
Authors: Topp Brian , Kumar Rukmini , Mayawala Kapil , de Alwis Dinesh , Hellmann Matt D. , Snyder Alexandra 
Published: December 2020

Abstract
Introduction: In clinical trials of patients treated with pembrolizumab, RECIST-defined progressive disease (PD) is often assumed to reflect generalized lack or loss of efficacy. However, mixed lesion-level responses within a given patient may reflect more clinically and immunobiologically-relevant heterogeneity than has been previously appreciated. To examine the heterogeneity and clinical impact of progressive disease, we characterized the patient-level and lesion-level responses in 511 patients with melanoma treated with pembrolizumab. Methods: Of 655 patients with melanoma treated with pembrolizumab in KEYNOTE-001 (NCT01295827), 511 patients had at least two scans and qualified for analysis. Patients were categorized as primary progression (RECIST-defined PD at first scan) or secondary progression (RECIST-defined PD as second scan or beyond). The percent change in diameter of overall and individual target lesions were examined, as well as patterns and timing of progression in non-target and new lesions. Results: Of 511 patients, 308 (60%) developed progression at some point during the study (primary progression 211/308, 69%; secondary progression 97/308, 31%). Of patients with primary progression, 105 (50%) had increased tumor burden (&gt;20% sum growth), while 90 (43%) had stable tumor burden (-30-+20% sum change) and 16 (8%) had decreased tumor burden (&gt;-30% sum decrease). Lesion-level heterogeneity was substantial, with 167 (79%) of patients having at least one shrinking metastasis despite primary progression. In patients with secondary progression, timing of onset was variable (median 56 weeks, +/- 35 weeks). Only 15% of patients with acquired resistance, (5% of patients with PD), displayed rebound of all lesions. The remaining patients displayed rebound of a subset of lesions (38%) and/or appearance of new metastatic lesions (46%). Lesion-level responses that have been achieved often persisted at/after onset of secondary progression. Conclusions: Patterns of progression to pembrolizumab are heterogeneous. In primary progression, there is evidence of some lesion-level benefit in the majority of patients. In secondary progression, many lesions demonstrate continued benefit despite isolated/oligo sites of progression. Consideration of these patterns may inform optimal treatment strategies. Lesion-specific analysis of biomarkers may be necessary to improve correlative analyses and response prediction.
Citation Format: Brian Topp, Rukmini Kumar, Kapil Mayawala, Dinesh de Alwis, Matt D. Hellmann, Alexandra Snyder. Inter-tumoral heterogeneity of progressive disease in melanoma patients treated with pembrolizumab [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-131.
Abstract PO-133: Breast tumors maintain a reservoir of subclonal diversity during primary expansion
Authors: Minussi Darlan Conterno , Nicholson Michael , Ye Hanghui , Davis Alexander , Wang Kaile , Sei Emi , Du Haowei , Rabbani Mashiat , Peng Cheng , Hu Min , Bai Shanshan , McDonald Thomas , Schalck Aislyn , Casasent Anna , Barrera Angelica , Chen Hui , Lim Bora , Arun Banu , Meric-Bernstam Funda , Michor Franziska , Navin Nicholas 
Published: December 2020

Abstract
Our knowledge of copy number evolution during the expansion of primary breast tumors is limited. To investigate this process, we developed a single-cell, single-molecule DNA sequencing method and performed copy number analysis of 13,808 single cells from six triple-negative breast cancers (TNBCs) and two breast cancer cell lines. Our data shows that breast tumors and cell lines are comprised of a large milieu (17-26) of subclones that are organized into a few (4-8) major superclones. Phylogenetic analysis and mathematical modeling show that copy number evolution was ongoing during the expansion of the primary tumor, after the initial punctuated burst of genomic instability. By expanding single daughter cells in culture, we show that cancer cells re-diversify their genomes and do not retain isogenic properties. These data elucidate modes of evolution and show that TNBCs maintain a vast reservoir of subclonal copy number diversity during the expansion of the primary tumor mass.
Citation Format: Darlan Conterno Minussi, Michael Nicholson, Hanghui Ye, Alexander Davis, Kaile Wang, Emi Sei, Haowei Du, Mashiat Rabbani, Cheng Peng, Min Hu, Shanshan Bai, Thomas McDonald, Aislyn Schalck, Anna Casasent, Angelica Barrera, Hui Chen, Bora Lim, Banu Arun, Funda Meric-Bernstam, Franziska Michor, Nicholas Navin. Breast tumors maintain a reservoir of subclonal diversity during primary expansion [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-133.
Abstract PR05: Mapping the tumor and microenvironmental evolution underlying DCIS progression through multiplexed ion beam imaging
Authors: Risom Tyler , Rivero Belen , Liu Candace , Baranski Alex , Strand Siri , Greenwald Noah , McCaffrey Erin , Varma Sushama , Keren Leeat , Srivastava Sucheta , Zhu Chunfang , Vennam Sujay , Hwang Shelley , Colditz Graham , Bendall Sean , West Robert , Angelo Michael 
Published: December 2020

Abstract
Ductal Carcinoma in Situ (DCIS) is a pre-invasive lesion that accounts for nearly 20% of new breast cancer diagnoses. Of these cases, about half will progress to invasive breast cancer (IBC) within ten years. However, because diagnostic criteria for delineating low risk lesions from those likely to progress to IBC have not been identified, many patients are receiving unnecessary chemotherapy and surgery that can result in therapy-related morbidity and death. With this in mind, we used Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF) and RNA-seq laser-capture microdissection (SMART-3SEQ) to construct a comprehensive spatial atlas describing the structure, function, and cellular composition of DCIS. MIBI-TOF and SMART-3SEQ were used to compare lesions from patients that later developed IBC with those from age- and history matched DCIS controls without recurrence. Using a 37-marker staining panel to interrogate 137 lesions, we identified 30 distinct cell populations of the epithelial, stromal, and immune lineages that were arranged in recurrent cellular microenvironments specific for DCIS or invasive disease. We observe a coordinated shift in the immune and stromal compartments as invasive disease arises, including an expansion of immune cell diversity and transition to reactive stromal phenotypes in synchronous DCIS + IBC, which was distinct from the macrophage-dominant microenvironment of recurrent IBC. Single-cell segmentation using a deep learning model was combined with pixel-level coexpression analysis to determine how thickness, continuity, and phenotype of ductal myoepithelium changes as tumors progress from a pre-invasive state. These data were incorporated into a comprehensive model which was subsequently used to identify a subset of features that correlate with disease-free survival following DCIS tumor resection. Taken together, these features represent important prognostic metrics that can be used to separate pre-invasive from indolent DCIS tumors, and allow for tailored therapy that improves patient outcomes and quality of life in this disease.
Citation Format: Tyler Risom, Belen Rivero, Candace Liu, Alex Baranski, Siri Strand, Noah Greenwald, Erin McCaffrey, Sushama Varma, Leeat Keren, Sucheta Srivastava, Chunfang Zhu, Sujay Vennam, Shelley Hwang, Graham Colditz, Sean Bendall, Robert West, Michael Angelo. Mapping the tumor and microenvironmental evolution underlying DCIS progression through multiplexed ion beam imaging [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PR05.
Abstract IA10: The Prevent Anal Cancer Study: the assessment of novel opportunities for anal cancer screening during COVID-19
Authors: Nyitray Alan G. 
Published: December 2020

Abstract
Cervical cancer screening began 70 years ago in high-resource settings and it has substantially lowered cervical cancer incidence in those settings; even so, incidence remains very high in many low and middle-income settings. As screening for other human papillomavirus-associated cancers is considered, self-screening approaches may lower some barriers to screening including cost, reluctance to access clinics, and examination embarrassment. The Prevent Anal Cancer (PAC) Study is recruiting men who have sex with men (MSM) and transgender people who have sex with men, aged ≥25 years in three cities in the United States (Chicago, Houston, and Milwaukee) to test anal self-exams and compliance with home-based self-swabbing. The PAC Study is comprised of two randomized clinical trials: NCT03489707 and NCT04090060. It is recruiting 1200 HIV+ and HIV- persons through 2023: 400 in Milwaukee to test home-based self-swabbing and 400 each in Chicago and Houston to test anal self-exams (ASEs). The Milwaukee cohort will evaluate compliance with annual home-based self-swabbing vs clinic-based HPV DNA specimen collection and determine factors associated with annual screening compliance; estimate the influence that home-based vs clinic-based screening has on the uptake of high-resolution anoscopy; estimate the association between high-risk HPV persistence and anal high-grade squamous intraepithelial lesions (HSIL); and estimate the association between HPV-16/host DNA methylation and anal HSIL. The Chicago/Houston cohort will be taught about anal anatomy, pathology, and the procedure for an ASE. The primary objective is to compare the participant’s ASE result with the clinician’s gold-standard Digital Anal Rectal Exam (DARE) to determine concordance, sensitivity and specificity. A secondary objective uses mathematical modeling to estimate the cost-effectiveness, impact on survival and health-related quality-of-life of ASE and DARE. Enrollment in both studies was suspended due to COVID-19. Due to concerns about potential COVID-19-related confounding of key associations, a 437-person online cohort of the same target populations was enrolled to assess COVID-19 impact over 5 longitudinal surveys. This presentation will provide an overview of anal cancer incidence, the PAC Study protocols, how COVID-19 may impact the studies’ results, and data collected to date to assess that impact. This study is supported by grants from the National Cancer Institute, National Institutes of Health (US).
Citation Format: Alan G. Nyitray. The Prevent Anal Cancer Study: the assessment of novel opportunities for anal cancer screening during COVID-19 [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA10.
Abstract IA33: The immunogenomic landscape of primary prostate cancer in African-American men
Authors: Lotan Tamara L. 
Published: December 2020

Abstract
African-American (AA) men have a 1.5-fold higher incidence of prostate cancer (PCa) than non-Latino White (WH) men and are nearly 2.5 times more likely to die from their disease. These disparities are likely due to a combination of social, environmental, and biological factors. Discerning the biological determinants of aggressive PCa in AA men remains a critical and unmet need in cancer health disparities research. Although there have been several large-scale genome sequencing studies that identified unique molecular drivers in primary and metastatic PCa, these have included few AA patients, even fewer with potentially lethal PCa, and have generally lacked clinical outcome data. Work by our group and others demonstrates that the most common somatic genomic alterations in primary PCa (such as ERG rearrangement and PTEN deletion) occur at significantly different frequencies in AA and WH men, providing the first direct evidence for molecular differences between PCa arising in AA and WH patients. Similarly, gene expression studies by other groups have consistently found that various immune response pathways are more highly expressed in PCa arising in AA compared to WH patients. However to date, few studies have integrated somatic molecular subtype data with immune tumor microenvironment (TME) characterization across different populations. To begin to address these knowledge gaps, we have studied primary PCa tissues from a unique cohort comprising 200 self-identified AA and 200 WH patients, matched by grade and other clinical-pathologic parameters, with long-term follow-up for biochemical recurrence and metastasis. This cohort is unique in that it is highly enriched for high-risk disease and has now been profiled for somatic genomic, epigenomic, transcriptomic and tumor microenvironment landscapes, enabling one of the first integrative molecular portraits of AA PCa. We find that tumor infiltrating T-lymphocyte density is significantly correlated with underlying tumor molecular subtype and oncologic outcomes, but does not vary by racial ancestry. In contrast, using a combination of transcriptomic, methylation and quantitative immunohistochemical analyses, we demonstrate that tumor infiltrating B-lymphocyte density is significantly higher among AA compared to WH PCa patients, irrespective of molecular subtype, and trends towards improved outcomes.
Citation Format: Tamara L. Lotan. The immunogenomic landscape of primary prostate cancer in African-American men [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA33.
Abstract PO-001: Evaluating medication adherence and its predictors among breast cancer survivors on oral endocrine therapy in a large academic medical center
Authors: Mohan Anjana , Paranjpe Rutugandha , Hwang Grace , Opsomer Carine , Lu Kelvin , Abajue Uzo , Zaghloul Hanna , Abughosh Susan , Trivedi Meghana 
Published: December 2020

Abstract
Introduction: Adherence to oral endocrine therapy (OET) reduces recurrence risk for hormone receptor-positive breast cancer (HR+ BC). Refill data accessed through electronic health records (EHRs) may provide objective assessment of medication adherence. Our goal was to (1) determine feasibility of reviewing EHR to assess medication adherence, (2) evaluate 6-month OET adherence in HR+ BC patients, and (3) identify predictors of low adherence. Materials and methods: A single-center, retrospective study from May through December 2018 was conducted. Primary endpoint was adherence rate at 6-months. Chi-square and student’s t-test were used to compare adherent and non-adherent groups. Multivariable logistic regression models were used to assess predictors of adherence. Further, a subgroup analysis was further conducted among patients with stage 0 – III to assess the adherence in early-stage setting. Results: Of 492 patients, 338 patients were included in adherence analysis. Of 338 patients identified, 82% (n= 277) were adherent at 6 months. In the multivariable logistic model, race/ethnicity, type of endocrine therapy, and time on therapy were found to be significantly associated with adherence. Asian/Non-Hispanic and Caucasian/Hispanic patients were less likely to be adherent as compared to Caucasian/Non-Hispanics (Asian/Non-Hispanic OR 0.3; 95% CI 0.11-0.82, Caucasian/Hispanic OR 0.27; 95% CI 0.11-0.64). Patients on aromatase inhibitors were more likely to be adherent as compared to patients on tamoxifen (OR 2.06; 95% CI 1.02-4.14). Lastly, patients on OET for 3-5 years had lower adherence as compared to patients on OET for 2 years or less (OR 0.29; 95% CI 0.09-0.91). The subgroup analysis of patients with stage 0-III disease revealed similar findings that race/ethnicity and type of endocrine therapy were significant predictors of adherence. Conclusion: Accessing refill data through EHR was found to be feasible. Tamoxifen therapy, Asian/Non-Hispanic and Caucasian/Hispanic origin, and longer time on therapy predicted non-adherence in our patients.
Citation Format: Anjana Mohan, Rutugandha Paranjpe, Grace Hwang, Carine Opsomer, Kelvin Lu, Uzo Abajue, Hanna Zaghloul, Susan Abughosh, Meghana Trivedi. Evaluating medication adherence and its predictors among breast cancer survivors on oral endocrine therapy in a large academic medical center [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-001.
Abstract PO-010: Clustering of prostate cancer risk behaviors in West African men: The familial cohort study
Authors: Akinbule Oluwafunke , Oladoyinbo Catherine , Bolajoko Opeyemi 
Published: December 2020

Abstract
Background: The risk of developing prostate cancer (CaP) is higher in Black Africans compared to non-Hispanic whites. Smoking, alcohol consumption, Unhealthy dietary behavior (consumption of high fat, sugar and salt diets) and chronic exposure to pesticides have been strongly associated with the risk of CaP. However, there is scarcity of information on clustering pattern of these risk behaviors among African men. Specific Aim(s)/Methods: Cross-sectional data of 500 West-African Black men representative from the Prostate Cancer Familial Cohort Study was analyzed. Two- step cluster analysis was used to identify cluster groups and multinomial logistic regression analysis was used to determine the association between behavioral risk factors and socio-demographic data. Results: The mean (95% CI) age and years spent in school were 47.93(47.05, 48.82) and 14.11(13.41, 14.80). The prevalence of smoking, alcohol drinking, chronic pesticide exposure and unhealthy diet was 26.2%, 44.7%, 39.0% and 82.4% respectively. Men of ages 35-34 years consumed High fat, sugar and salt (HFSS) diet most frequently. Most (96.6%) of the respondents were involved in at least one CaP risk behavior. Eleven clusters were identified in the clustering analysis, 3.4% had no risk, 24.4% had single risk behavior, 48.8% had double risk behaviors and 23.4% had multiple risk behaviors. Men with uncompleted college education were more likely to have multiple risk behaviors. Nigerian men were more likely to smoke or consume alcohol in addition to HFSS dietary intake.
Men with Chronic exposure to pesticide consuming HFSS diet and/or smoking were more likely to have low body mass index. Cameroon men were more likely to have chronic exposure to pesticide in addition to HFSS diet intake and/or smoking.
Conclusion: Policies and Behavior change interventions focused on double and multiple risk behaviors for CaP with consideration for socio-demoographic differences is essential for reducing the risk of CaP in Black men.
Citation Format: Oluwafunke Akinbule, Catherine Oladoyinbo, Opeyemi Bolajoko. Clustering of prostate cancer risk behaviors in West African men: The familial cohort study [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-010.
Abstract PO-027: A mixed-methods assessment of SDH screening tool and its contribution to health
Authors: Piña Sashiel , Scott Mary Alice , Thomas Rhianna , Tsabetaye McKayla , Kane Abigail , la Rosa Iván De , Chandler Kerianne , Ceballos Rachel 
Published: December 2020

Abstract
Inequities in social determinants of health (SDH) are major contributors to persistent health disparities across the cancer continuum. While screening tools to address patient non-medical social needs have been developed, little evidence of screening tool effectiveness or guidance on implementation is available. Our pilot study examines the use of a social needs screening tool in a high need primary health care setting in the U.S.-Mexico border region. A 4-item SDH screening tool assessed for food insecurity, lack of transportation, legal issues, or domestic violence. The study objective is to identify facilitators and barriers to appropriate referrals for social needs from the perspective of patients and providers. The PRECEDE-PROCEED model is used to guide intervention development. This study focuses on the PRECEDE (Pre- disposing, Reinforcing, and Enabling Constructs in Educational/Environmental Diagnosis and Evaluation) portion of the PRECEDE-PROCEED model to identify factors that impact the use of the developed SDH screening tool. Data collection uses a mixed-methods approach through the review of patient electronic medical records (EMR) and qualitative interviews of clinic patients, physicians, and staff. Data focuses on the factors influencing the use of the SDH screening tool, the subsequent social service referrals, as well as the associated rate of in-clinic SDH tool utilization through physician and patient reported use and EMR review. Data collection and analysis are currently ongoing. Themes identified during preliminary analyses include the importance of patient-physician relationships, barriers to SDH assessment during the clinical encounter, and potential policy and clinic-level facilitators to the screening tool’s implementation. The study findings will be applied to the development of an educational intervention targeting primary care residency programs. This intervention will improve the way providers address SDH needs of patients ensuring more wholistic patient care
Citation Format: Sashiel Piña, Mary Alice Scott, Rhianna Thomas, McKayla Tsabetaye, Abigail Kane, Iván De la Rosa, Kerianne Chandler, Rachel Ceballos. A mixed-methods assessment of SDH screening tool and its contribution to health [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-027.