bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA22: Financial well-being and health: Definitions and measurement issues
Authors: Tucker-Seeley Reginald 
Published: February 2019

Abstract
The cost of cancer care is rising faster than other diseases, and the financial hardship that cancer imposes on families may exacerbate racial/ethnic and socioeconomic disparities in outcomes throughout survivorship. Discussions about the financial burden of cancer care have increased in recent years in the academic literature and popular press, and several terms have been used to describe this burden. Yet, the discussion oftentimes conflates the lack of material resources to cover medical expenses, the potential psychosocial distress accompanying the lack/reduction in financial resources, and the behavioral coping responses to address the lack /reduction in financial resources. Many health care professionals report feeling unprepared to address family financial well-being in the context of health care delivery, and research suggests that most individuals report low levels of financial self-efficacy even outside the context of managing a chronic disease. We currently lack reliable and valid measures to adequately assess the material, psychosocial, and behavioral aspects of household financial well-being prior to, during, and following cancer care. The dearth in assessment tools of financial well-being in the cancer context impedes efforts to identify modifiable intervention targets of the financial burden of cancer care to ensure that families do not succumb to financial ruin as they manage a chronic disease and navigate the health care system.
Citation Format: Reginald Tucker-Seeley. Financial well-being and health: Definitions and measurement issues [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 IA22.
Abstract IA29: Overcoming barriers to screening in rural areas: No bus, no taxi, no services
Authors: Thompson Beti , Carosso Elizabeth , Briant Kathy , Ibarra Genoveva 
Published: February 2019

Abstract
Background: Cancer screening in rural areas is hampered by numerous barriers; among these are systemic factors such as access to care in the rural area, lack of culturally appropriate physicians, and lack of screening systems. These barriers are often accompanied by structural impediments such as lack of transportation to distant clinics and screening settings, lack of child care, and inconvenient times for appointments. New and innovative approaches to dealing with rural populations are needed to overcome some of these barriers. In Eastern Washington State, the many rural areas are served by a Federally Qualified Health Center (FQHC) system. A number of their clinics are spread throughout the region, and we collaborated with them to work on two innovative cancer prevention strategies in the rural area.
Methods: Using a giant inflatable colon, we brought fecal occult blood test (FOBT) kits to 300 individuals who were over the age of 50 at regularly scheduled health fairs in the area. Individuals went through a brief educational tour of the colon, then received the kits, which were returned to us via mail or drop-off. A local hospital analyzed the kits and results were returned to participants. In a second study, women who were nonadherent with Pap testing were identified by the FQHC; after HIPAA consent, they were randomized to receive one of three intervention arms: a usual care arm, a video arm, or a promotora outreach arm. Adherence after seven months was assessed via medical records.
Results: For the colon study, we received a return rate of 75.6%. Of these, seven were abnormal and those participants received free or low-cost colonoscopies. For the cervical cancer study, the rates of adherence after seven months were 34% (usual care), 38.7% (video arm), and 53.4% (promotora outreach). In both studies, knowledge and intention to be screened were significantly increased.
Discussion: Rural areas suffer unique barriers to obtaining cancer prevention screening. Our approach of “meet the people where they are” has been positive in increasing screening rates. Whether it is participation at local community health fairs or collaboration with an FQHC, it is clear that “going to the people” is a method that works. More emphasis should be put on such methods in rural areas.
Citation Format: Beti Thompson, Elizabeth Carosso, Kathy Briant, Genoveva Ibarra. Overcoming barriers to screening in rural areas: No bus, no taxi, no services [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 IA29.
Abstract IA37: Intersectional approaches to studying the interaction of multiple and multilevel social determinants on cancer health disparities
Authors: Gomez Scarlett Lin 
Published: February 2019

Abstract
Social determinants of health are the characteristics and conditions that determine where and how people live, work, and play. Social determinants of health exist at multiple levels and can range from individual characteristics such as gender, education, and income, to local environmental conditions such as social and built environments, to societal influences such as health care policies and racial residential segregation. These characteristics can impact cancer outcomes across the continuum, from risk to death. Moreover, these characteristics are often highly correlated and can interact to influence disparate cancer outcomes above and beyond their individual health effects. The intersectional approach considers the impact on health and health equity of intersecting social positions and processes. To date, the intersectional approach has primarily been applied to qualitative research. This educational presentation will describe the concept of intersectionality, and explore approaches to apply the intersectional approach to cancer health disparities research questions at a population level.
Citation Format: Scarlett Lin Gomez. Intersectional approaches to studying the interaction of multiple and multilevel social determinants on cancer 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 IA37.
Abstract PR03: Somatic mutations and ancestry markers in Hispanic lung cancer patients
Authors: Cress William D. , Gimbrone Nicholas T. , Sarcar Bhaswati , Gordian Edna , Rivera Jason I. , Lopez Christian , Teer Jamie K. , Welsh Eric A. , Chiappori Alberto A. , Schabath Matthew B. , Reuther Gary W. , Santiago-Cardona Pedro G. 
Published: February 2019

Abstract
Introduction: Hispanics are projected to constitute 23% of the U.S. population by 2050. However, large-scale sequencing projects, such as The Cancer Genome Atlas (TCGA), provide little information on this ethnic population. In fact, only seven out of over 500 lung adenocarcinoma tumors sequenced in the TCGA database are reported to be Hispanic. To address the lack of genomic data from Hispanic/Latino patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from these patients.
Methods: This retrospective observational study examined lung cancer tumor samples from 163 Hispanic/Latino patients, and tumor-derived DNA was subjected to targeted-exome sequencing (&gt;1000 genes, including EGFR, KRAS, STK11, and TP53) and ancestry analysis. Mutation frequencies in this Hispanic/Latino cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients. Novel mutations in EGFR were functionally characterized, and mutation rates were correlated with ancestry, patient sex, smoking status, and tumor histology.
Results: Among adenocarcinomas (n=120) in the Hispanic/Latino cohort, 31% had EGFR mutations versus 17% in the NHW control group (p &lt; 0.001). The EGFR mutations in Hispanic/Latino patients included well-characterized activating mutations, such as L858R, and uncharacterized EGFR variants. A rare exon 19 mutation, W731R, was identified that conferred resistance to both erlotinib and AZD9291. KRAS (20% vs. 38%; p=0.002) and STK11 (8% vs. 16%; p=0.065) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% vs. 40%; p=0.355) in Hispanic/Latino and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p=0.009) and may influence the rate of EGFR, KRAS, and STK11 mutations.
Conclusions: Driver mutations in Hispanic/Latino lung adenocarcinoma patients differ in frequency from those in NHWs associated with their Indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the Hispanic/Latino population.
Citation Format: William D. Cress, Nicholas T. Gimbrone, Bhaswati Sarcar, Edna Gordian, Jason I. Rivera, Christian Lopez, Jamie K. Teer, Eric A. Welsh, Alberto A. Chiappori, Matthew B. Schabath, Gary W. Reuther, Pedro G. Santiago-Cardona. Somatic mutations and ancestry markers in Hispanic lung cancer patients [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 PR03.
Abstract A30: Gene regulatory mechanisms governing invasive mucinous adenocarcinoma of the lung (IMA)
Authors: Guo Minzhe , Tomoshige Koichi , Fink-Baldauf Iris , Maeda Yutaka 
Published: February 2019

Abstract
Background: Invasive mucinous adenocarcinoma of the lung (IMA) comprises 5-10% of lung adenocarcinoma. IMA is pathologically characterized as lung tumor cells with goblet cell morphology containing abundant intracytoplasmic mucin. Recent advances using next-generation sequencing technology revealed driver oncogenes (e.g., KRAS mutation and NRG1 fusions) and a gene expression signature (e.g., NKX2-1 negative and SPDEF positive) inducing IMA. However, the genetic mechanism governing the pathogenesis of IMA is not fully understood. Here, we report the mechanism of the gene regulatory network regulating mucins and immune checkpoints in IMA.
Methods: Using lentiviral vectors expressing the anti-mucous transcription factor NKX2-1 (also known as TTF-1) and the pro-mucous transcription factor SPDEF, we assessed their functions in regulating the expression of mucins and immune checkpoints in multiple lung cancer cell lines. Using ChIP-seq datasets, we further identified genome-wide binding sites of NKX2-1 and SPDEF in A549 lung carcinoma cells that carry a KRAS mutation and produce mucins. We further deleted such binding sites in the genome using CRISPR/Cas9 to assess the function of the sites.
Results: NKX2-1 influenced the expression of immune checkpoints, including PD-L1, and mucin-related genes, including MUC5AC and SPDEF. Notably, NKX2-1 bound to the same noncoding region upstream of MUC5AC as SPDEF. The genomic deletion study using CRISPR/Cas9 indicated that both NKX2-1 and SPDEF bound to the enhancer region (but not the silencer region) of MUC5AC, suggesting that NKX2-1 suppresses mucin gene expression by blocking the activity of the enhancer region but not by recruiting a co-repressor complex such as HDAC to the region.
Conclusion: Transcription factors NKX2-1 and SPDEF function as yin and yang to affect the pathogenesis of IMA.
Citation Format: Minzhe Guo, Koichi Tomoshige, Iris Fink-Baldauf, Yutaka Maeda. Gene regulatory mechanisms governing invasive mucinous adenocarcinoma of the lung (IMA) [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A30.
Abstract IA02: The role of aneuploidy during tumorigenesis
Authors: Davoli Teresa 
Published: February 2019

Abstract
Since Boveri’s postulates in 1914, aneuploidy has been recognized as a hallmark of human cancer; however, no comprehensive theory exists to explain its patterns and its role in tumor evolution. We have developed Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method for the prediction of tumor suppressor genes (TSG) and oncogenes (OG) through the analysis of the pattern of somatic mutations in cancer. By integrating our prediction of TSGs and OGs with information of copy number alterations, we found that the distribution on chromosomes and the potency of TSGs and OGs can predict the frequency of arm-level and chromosome-level deletions and amplification (Davoli et al., 2013). We propose that it is the decrease or increase in the gene dosage of TSG and OG genes in deletion and amplification to determine the recurrent patterns of aneuploidy selected during tumor evolution. More recently, we have performed gene expression analysis on tumor samples, comparing tumors with different levels of aneuploidy (Davoli et al., 2017). We have found that tumors with high levels of aneuploidy show increased markers of proliferation as well as a strong decrease in infiltrating immune cells, especially CD8+ T cells. Notably, we show that aneuploidy predicts patients’ survival in two clinical trails of immunotherapy in cancer patients. Compared to neoantigen load, aneuploidy represents an independent and stronger predictor of survival. A combined score including aneuploidy and neoantigen load allows superior prediction of survival after immunotherapy. We are now investigating the mechanism by which aneuploidy affects cancer immune evasion. I will present novel data suggesting that aneuploidy may play a role in inhibiting and dysregulating antigen processing and presentation in tumor cells. Overall, our data indicate that aneuploidy is a driver event in human tumorigenesis.
Citation Format: Teresa Davo4li. The role of aneuploidy during tumorigenesis [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA02.
Abstract IA05: Early steps in lung oncogenesis
Authors: Janes Samuel M. 
Published: February 2019

Abstract
Lung cancer is the biggest cancer killer of men and women, and there has been no improvement in survival over the last 50 years. To reduce the mortality of lung cancer, we need to both detect and treat it earlier, ideally at a preinvasive cancer stage before progression into full-blown invasive cancer. This would allow us to initiate treatment in a timely manner, increasing the chances of cure and saving lives. Lung cancers arise from preinvasive lesions but, interestingly, not all these lesions progress to cancer. We believe that understanding the differences between the lesions that progress to invasive cancer and those that disappear will direct us to the key proteins and genes that are mis-expressed, or inappropriately switched on or off, that lead to invasive cancer formation. My talk will outline studies that shed new understanding on how lung cancer develops and identify novel biological markers that accurately predict whether a lesion will eventually grow into a cancer. This, I hope, will enable targeting potential therapies to those patients with lesions that are likely to progress and identify the key genes and proteins associated with cancer development, thereby opening the possibility of developing chemoprophylactic therapeutic approaches to prohibit cancer development.
Citation Format: Samuel M. Janes. Early steps in lung oncogenesis [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA05.
Abstract IA07: Influence of cancer initiation on tumor progression in SCLC
Authors: Yang Dian , Winslow Monte M. , Sage Julien 
Published: February 2019

Abstract
The vast majority of cancer patients die from metastatic disease, but the molecular and cellular mechanisms that drive metastatic progression often remain poorly understood. Small cell lung cancer (SCLC) is a neuroendocrine form of lung cancer and one of the most metastatic and lethal cancers. Most SCLC patients are usually first diagnosed when they already have metastatic disease, and SCLC tumors are thus thought to acquire metastatic ability early in the course of tumor development. However, how early events shape the evolution and metastatic progression of SCLC is largely unknown. We will present evidence, using genetically engineered mouse models of SCLC, that distinct mechanisms drive metastatic progression depending on the cell of origin. In one mouse model, we found that tumors gain metastatic ability through amplification of the transcription factor Nfib; this amplification is accompanied by a striking opening of the chromatin at many sites in the genome. In the second model, metastatic progression is not associated with Nfib-driven chromatin alterations. Gene expression profiling studies reveal distinct mechanisms of metastatic progression in the two groups, as well as markers predictive of the two metastatic paths. Our data indicate that Nfib-independent metastases arise from pulmonary neuroendocrine cells. These observations demonstrate that the identity of tumor-initiating cells can determine the molecular mechanisms of tumor evolution.
Citation Format: Dian Yang, Monte M. Winslow, Julien Sage. Influence of cancer initiation on tumor progression in SCLC [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA07.
Abstract IA18: Evolution of acquired resistance in EGFR mutant NSCLC
Authors: Hata Aaron N. 
Published: February 2019

Abstract
Lung cancers harboring activating EGFR mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors; however, acquired drug resistance inevitably develops. Although genetic mechanisms of acquired resistance have been well characterized, less is known about how resistant clones evolve during treatment. Emerging data are beginning to illuminate the complex interplay of genetic clonal heterogeneity, adaptive signaling changes, epigenetic plasticity, and microenvironment factors that shapes the evolution of acquired resistance. Novel therapeutic strategies that specifically target these processes may prevent or delay the development of drug resistance.
Citation Format: Aaron N. Hata. Evolution of acquired resistance in EGFR mutant NSCLC [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA18.
Abstract IA20: Immunotherapy: Biomarkers and checkpoint blockade in NSCLC
Authors: Carbone David P. , Sharpnack Michael , He Kai 
Published: February 2019

Abstract
Immunotherapy approaches targeting the PD-1 pathway have shown some clinical benefits in a fraction of patients with lung cancer, but expression of PD-L1 has proved to be an imperfect biomarker of efficacy. Recent studies have shown that tumor mutation burden (TMB) is also correlated with outcome and that it appears to be independent of PD-L1. TMB, however, only indirectly measures the number of neoantigenic peptides presented on tumor cell surface class I MHC, and predicted MHC matches may be an even better predictor of benefit. In addition, mutations in genes such as LKB1 may modulate the immune response, and mutations in the antigen presentation pathway may block it altogether. Mutations in DNA repair pathway genes may increase the number of potential neoantigens. Analysis of non-PD-1 pathway immunomodulators, immune cell infiltration, microenvironmental and microbiomic context, together with in-depth analysis of tumor somatic genomics, could lead to better patient selection for immunotherapy.
Citation Format: David P. Carbone, Michael Sharpnack, Kai He. Immunotherapy: Biomarkers and checkpoint blockade in NSCLC [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA20.
Abstract IA23: Allele-specific HLA loss and immune escape in lung cancer evolution
Authors: McGranahan Nicholas , Rosenthal Rachel , Hiley Crispin T. , Rowan Andrew J. , Watkins Thomas B.K. , Wilson Gareth A. , Birkbak Nicolai J. , Veeriah Selvaraju , Loo Peter Van , Herrero Javier , Swanton Charles 
Published: February 2019

Abstract
In order to avoid immune predation, particularly in response to immunotherapy, tumors must acquire mechanisms to evade immune detection or withstand its activity. Disruption of human leukocyte antigen (HLA), which may lead to reduced neoantigen presentation, has been proposed as an immune escape strategy in many cancers, including lung cancer. A high proportion of cancer types have been found to downregulate HLA expression, potentially leading to the evasion of T cell-mediated destruction (Hicklin, 1999; Garrido, 2017) with reduced HLA expression associating with decreased overall survival and tumor progression (Mehta, 2008). Another irreversible means of HLA disruption is via loss of heterozygosity (LOH) at the HLA locus (Koopman, 2000). However, to date, the diversity of the HLA locus has impeded copy number analysis and determination of HLA loss. To investigate the prevalence, timing, and importance of HLA disruption, we developed LOHHLA (Loss Of Heterozygosity in Human Leukocyte Antigen), a computational tool to determine HLA allele-specific copy number from sequencing data. Supporting the notion that loss of antigen presentation may play an important role in immune evasion during tumor evolution, HLA LOH was identified in 40% of the NSCLC samples analyzed, frequently as a late event in tumor evolution and associated with a high subclonal neoantigen burden, increase in immune infiltration, and PD-L1 positivity. Characterizing HLA haplotype specific copy number with LOHHLA refines neoantigen prediction and may have implications for immunotherapeutic approaches targeting neoantigens.
Citation Format: Nicholas McGranahan, Rachel Rosenthal, Crispin T. Hiley, Andrew J. Rowan, Thomas B.K. Watkins, Gareth A. Wilson, Nicolai J. Birkbak, Selvaraju Veeriah, Peter Van Loo, Javier Herrero, Charles Swanton. Allele-specific HLA loss and immune escape in lung cancer evolution [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA23.