bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO-196: Oral cancer disparity among African Americans
Authors: Bhuiyan Shabnam
Published: December 2020

Introduction: Oral cancer caused thousands of deaths every year. The rate of oral cancer death is higher due to the late-stage discovery of oral cancer. Cancer health disparity is prevalent in indifferent racial/ethnic groups. African Americans are the primary victim of cancer health disparity. Here we directed a comprehensive review of available literature to observe the oral cancer disparity in African Americans.

Method: We used various databases such as PubMed, Google scholar, and TMC (Texas Medical Center) library in July 2020. Software used to establish literature are EndNote and Zotero software. Search terms and methods used are [Oral Cancer] AND [African Americans], [Cancer Disparity] AND [African Americans], and [Oral Cancer] AND[Racial Disparity]. We found several articles that match our criteria.

After reviewing the text, a table has been generated to conclude the articles. Result: Studies show varied results. Some studies showed a higher rate of oral cancer in African Americans, and some studies show a lack of knowledge of oral cancer in African Americans. Some studies also show the decline of oral cancer in African Americans. Discussion: Studies regarding oral cancer in African Americans focus on a different topic. There should be more studies that deal with one consistent question so that we can see the cancer disparity in this population. Cancer researchers should be informed about these issues of research gap in oral cancer so that they can make an appropriate decision where to allocate funding during their investigation.

Citation Format: Shabnam Bhuiyan. Oral cancer disparity among African Americans [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-196.
Abstract PO-215: Diabetes and the quality of adjuvant therapy in Medicaid-insured women with breast cancer
Authors: Wang Yun , Lian Min , Liu Ying
Published: December 2020

Introduction. Diabetes is associated with poorer prognosis among breast cancer patients. It remains uncertain about the impact of comorbid diabetes on breast cancer treatments, especially among low-income women. Methods. Using the linked Missouri Cancer Registry and Medicaid claims data, we identified 3,761 women aged 18–64 diagnosed with stage 0-III breast cancer from 2007 to 2016. We estimated odds ratios (ORs) of the adherence and quality of adjuvant therapy, including the uptake, timely initiation (<30 days of diagnosis (neo-adjuvant), <120 days after diagnosis (adjuvant), or 90 days after surgery(adjuvant)), and completion of radiation therapy (≥25 sessions) and chemotherapy (recommended regimen-specific durations), as well as adherence (medication possession rate≥80%) and persistence (<90-consecutive-days’ prescription) of endocrine therapy, for diabetic women compared with non-diabetic women, using multivariate logistic regression models adjusted for sociodemographic and clinical factors. Results. Overall, 20.7% of women had diabetes prior to breast cancer, 66.1% received radiation therapy, 72.6% with invasive breast cancer initiated chemotherapy, and 71.5% with hormone receptor- positive tumors received endocrine therapy. Diabetic women were less likely than non-diabetic women to utilize radiation therapy (odd ratio (OR) =0.83, 95% confidence interval (CI) 0.69-0.99) and chemotherapy (OR=0.75, 95% CI 0.59-0.96).

Among patients receiving chemotherapy, diabetes was associated with a lower likelihood of completion of chemotherapy (OR=0.79 (95% CI=0.62-0.996). Diabetic women initiated radiation therapy in a more timely manner (OR=1.40, 95% CI=1.004- 1.95). There were no significant associations of diabetes with the utilization, adherence and persistence of endocrine therapy, timely initiation of chemotherapy, and completion of radiation therapy. Conclusions. Comorbid diabetes was associated with lower likelihoods of the utilization of radiation and chemotherapy and completion of chemotherapy in Medicaid-insured women with breast cancer. Efforts are needed to improve adherence to recommended adjuvant therapy in Medicaid- insured diabetic women with breast cancer. Funding support: National Cancer Institute (R01CA215418) and American Cancer Society-Denim Days Research Scholar Grant (RSG-18-116-01-CPHPS).

Citation Format: Yun Wang, Min Lian, Ying Liu. Diabetes and the quality of adjuvant therapy in Medicaid-insured women with breast cancer [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-215.
Abstract PO-233: HPV+ and HPV- HNSCC show similar nrf2 nuclear and cytoplasmic staining patterns
Authors: Anibire Oladipupo O. , Jose Oyinloye , Williams Kenyada , Ballard Billy R. , Izban Michael G. , Marshall Dana
Published: December 2020

This study set out to observe and better understand the differences, if any, in staining patterns for the oxidative stress response transcription factor Nrf2 in HNSCC patients who were HPV+ non- tobacco and alcohol users vs. HPV- tobacco and alcohol users. Increased Nrf2 activity is associated with resistance to therapy and poor outcomes. Tissues samples were obtained from the head and neck cancer repository of Nashville General Hospital at Meharry and Meharry Medical College. Nashville General Hospital at Meharry is a safety net hospital that serves the under- and uninsured citizens of Davidson County TN. FFPE sections were stained with anti- human Nrf2 antibody (Abcam 31163) and scored using a semi-quantitative evaluation gradient scale from 0-3 with 0 indicating no stain and 3 indicating strong positive Nrf2 staining. This study made use of 5 HPV+ and 2 HPV- patients. The results show that all HNSCC in the HPV+ and HPV- samples revealed positive staining for Nrf2 that ranged from weak to intense. We observed that the poorly differentiated HNSCC had a strong positive nuclear stain for Nrf2 when compared to lower tumor grades. Irrespective of whether the patient was in the HPV+ nonsmoker-nondrinker or HPV- smoker-drinker group, histological data indicates there was a positive correlation between increased Nrf2 staining and worsening tumor grade. These preliminary data suggest that potential use of Nrf2 as a prognostic biomarker for HNSCC will need to be evaluated differently for HPV+ and HPV- tumors, as HPV+ tumors are generally more responsive to therapy. Developing therapy that specifically targets Nrf2 could potentially play an immense role in managing HNSCC. Some of the limitations encountered in this study includes limited sample size.

Citation Format: Oladipupo O. Anibire, Oyinloye Jose, Kenyada Williams, Billy R. Ballard, Michael G. Izban, Dana Marshall. HPV+ and HPV- HNSCC show similar nrf2 nuclear and cytoplasmic staining patterns [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-233.
Abstract PO-242: Viral hepatitis among foreign-born communities in the Washington- Baltimore metropolitan area: 5-year prevalence data and implications for linkage to care follow-up
Authors: Le Daisy , Coriolan Annie , Pan Jane , Berg Carla Jean , Hong Y. Alicia , Nguyen Angeline , Le Hai Chi , Abroms Lorien Cindy , Juon Hee-Soon , Yang Y. Tony
Published: December 2020

Background: Viral hepatitis is a major public health problem around the world and in the United States, with significant morbidity and mortality. This research aimed to provide updated prevalence estimates and linkage-to-care rates for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among foreign-born immigrants in the Washington-Baltimore metropolitan area. Methods: This retrospective cohort study analyzed screening data obtained from over 275 community-based outreach events held from 2015 to 2019. Through strategic collaborations and culturally-appropriate programs, the Hepatitis B Initiative of Washington DC was able to provide no-cost HBV and HCV testing, vaccination, and treatment linkage-to-care services to 9,489 and 9,427 individuals, respectively. We examined the prevalence of positive HBV (HBsAg+) and HCV (HCVAb+) infections and linkage-to-care with associated sociodemographic characteristics. Results: Overall, prevalence amongst foreign-born clients screened over the 5-year period was 4.3% for HBV and 1.1% for HCV. The highest HBV prevalence was among participants born in Malaysia (8.5%), Cambodia (7.7%), and Vietnam (6.9%), whereas HCV prevalence was highest among participants born in Mongolia (5.0%), Cameroon (3.2%), and Burma (1.5%). Among the 378 HBV- and 102 HCV-infected individuals who were referred to care, linkage- to-care rates were 87.0% (2016-2019) and 47.1% (2017-2019) respectively. Among those linked to care, an overwhelming proportion reported not having health insurance (74.8%) and/or a usual source of care (75.3%); the majority were also female (52.8%), over 30 years of age (96.6%), and born in Asia (78.0%). Conclusions: Foreign-born individuals from Asia and Africa had the highest prevalence of viral hepatitis. These results underscore the need to disaggregate screening data by country of birth to inform prevention and linkage-to-care programs and their impact. Additionally, optimal HBV and HCV screening and linkage-to-care can be achieved among harder-to-reach at-risk populations through partnerships with community organizations, health centers, and public health departments.

Citation Format: Daisy Le, Annie Coriolan, Jane Pan, Carla Jean Berg, Y. Alicia Hong, Angeline Nguyen, Hai Chi Le, Lorien Cindy Abroms, Hee-Soon Juon, Y. Tony Yang. Viral hepatitis among foreign-born communities in the Washington- Baltimore metropolitan area: 5-year prevalence data and implications for linkage to care follow-up [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-242.
Abstract PO-257: Disparities in unawareness of hepatitis C virus among U.S. adults: An analysis of the 2019 Health Information National Trends Survey
Authors: Islam Jessica Y. , Spees Lisa , Camacho-Rivera Marlene , Vidot Denise C. , Yarosh Rina , Wheldon Christopher W.
Published: December 2020

Purpose Infection with Hepatitis C virus (HCV) is often asymptomatic and chronic infection may lead to liver cancer. In light of the 2020 USPSTF update to HCV screening guidelines to include all adults between 18-79 years old, our objective was to investigate demographic disparities in HCV unawareness with a specific interest in age and race/ethnicity. We estimated (1) HCV unawareness by demographic groups, (2) determinants of HCV unawareness, and (3) sources of health information among those with high HCV unawareness. Methods We used weighted nationally- representative data from the 2019 Health Information National Trends Survey(N=5438) to estimate frequencies of socio-demographic characteristics by HCV unawareness and determinants of HCV unawareness through multivariable logistic regression. We further estimated risk differences (RD) with 95% confidence intervals(CIs) of HCV unawareness by age and race/ethnicity compared to older non- Hispanic(NH)-Whites. Results Overall, 17.3% of adults were unaware of HCV.

Younger adults <55 years (20.7%) were more likely to be unaware of HCV compared to older adults ≥55 years (11.6%, χ2 p<0.001). Multivariable analyses showed that younger age, low English fluency, and Hispanic or NH-Asian ethnicity were associated with HCV unawareness. When compared to NH-Whites ≥55 years, the largest differences in HCV unawareness was observed among NH-Asians (RD:25.6%,95%CI:8.2-43.1) and Hispanics (RD:17.1,95%CI:6.3-27.9) adults <55 years.

Younger adults unaware of HCV reported primarily obtaining their health information from the internet (75.5%). Conclusions Younger adults, Hispanics, and NH-Asians are more likely to be unaware of HCV. Public health messaging should be targeted to these demographic groups to improve HCV screening coverage. Social media campaigns may increase reach as most young adults unaware of HCV obtain their health information on the internet.

Citation Format: Jessica Y. Islam, Lisa Spees, Marlene Camacho-Rivera, Denise C. Vidot, Rina Yarosh, Christopher W. Wheldon. Disparities in unawareness of hepatitis C virus among U.S. adults: An analysis of the 2019 Health Information National Trends Survey [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-257.
Abstract PR02: Improving monitoring and treatment adherence among underserved Asian Americans with chronic hepatitis B through a patient navigator-led intervention
Authors: Ma Grace X. , Zhu Lin , Zhai Shumenghui , Tan Yin , Ma Xiaoli , Ogunwobi Olorunseun O. , Naidoo Michelle , Ting Tsunyou , Wang Min Qi
Published: December 2020

Background: Asian Americans have the highest incidence and mortality rates of hepatocellular carcinoma among all U.S. racial/ethnic groups. Inadequate hepatitis B (HBV) monitoring and treatment contribute to poorer outcomes and increased healthcare costs. We conducted a Patient Navigator-led Intervention (PNMI) through a randomized controlled trial to improve monitoring and treatment adherence among Asian Americans with chronic HBV infection. Methods: From 2015 to 2017, we enrolled 532 eligible Asian American adults living with chronic HBV (CHB) in greater Philadelphia area, New Jersey, and New York City. They were non-compliant with HBV follow up care, and randomly assigned to either intervention or control group. Generalized linear mixed-effects models (GLMM) were used to estimate the odds ratio (OR) for the rates of doctor’s visit for CHB and having ALT test. Results: Our findings indicated that intervention group had higher rate of doctors’ visits than that of control group at both 6-month (77.22% v. 45.75%) and 12 months assessments (90.73% v. 60.61%). More intervention group participants received ALT test than control group did at 6-month (52.90% v. 25.10% at 6 months) and 12-month (75.40% v. 46.75%). Results of the GLMM showed that those in the intervention group were more likely than those in the control group to have doctor’s visit and ALT test at 6- and 12-month follow-ups. Conclusions: The findings from this culturally and linguistically appropriate PNMI intervention demonstrated strong effects on adherence to hepatitis B virus (HBV) follow-up care among non-adherent Asian American patients living with chronic HBV infection. These findings suggest opportunities for implementation the evidence-based best practice that could lead to reducing disparities in chronic liver disease and liver cancer among high-risk, underserved populations.

Citation Format: Grace X. Ma, Lin Zhu, Shumenghui Zhai, Yin Tan, Xiaoli Ma, Olorunseun O. Ogunwobi, Michelle Naidoo, Tsunyou Ting, Min Qi Wang. Improving monitoring and treatment adherence among underserved Asian Americans with chronic hepatitis B through a patient navigator-led intervention [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 PR02.
Abstract PR12: Dynamic clustering of cancer genomics datasets beyond pre-defined human categories
Authors: Mohsen Hussein , Blenman Kim , Pusztai Lajos
Published: December 2020

Background: The history of the race concept sheds the light on the lack of scientific basis of racial categories. Early attempts of using race in scientific practice (ca. 17th century) took place during times of colonial expansions and the transatlantic slave trade. The lenses through which scientists approached race categories changed over the next centuries, but legacies of using race categories in genetic studies are still embedded in some of today’s practices. Consequently, this engenders the need for novel approaches that transcend categories of or related to race in genomics to avoid unintended consequences and improve the study of disease. Methods: We introduce an approach that dynamically generates trait-specific cohorts based on genomic clustering at a subset of loci known to contribute to the disease under study. Reflecting the broad diversity of traits, the number of clusters and cluster memberships vary depending on the trait and its implicated genomic regions. Our method hence directs the lens of studying human biodiversity with respect to disease to the trait level rather than “population level.” Results: We test our approach on cancer and control whole genome sequencing datasets to partition each based on predisposition to 8 cancer types. Focusing on COSMIC genes known to have a germline contribution to cancer, we demonstrate that resulting clusterings vary across cancer types and transcend race, ethnicity—and ancestry categories, supporting our call to generate dynamic categorization sets at the trait level. Conclusion: Our suggested method highlights the importance of historical perspectives to co-shape today’s scientific practice. Experimental results resonate with previous joint calls from scholars in genetics and the humanities and social sciences to focus on the study racial and ethnic disparities in health as a result of rampant societal and environmental disparities—rather than genomic differences partly based on historical attempts to impose fixity on fluid social constructs.

Citation Format: Hussein Mohsen, Kim Blenman, Lajos Pusztai. Dynamic clustering of cancer genomics datasets beyond pre-defined human categories [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 PR12.
Abstract PO-049: SARS-CoV-2 multiepitope vaccine constructs designed to drive long-term immunity in the majority of the population
Authors: Yarmarkovich Mark , Warrington John M. , Farrel Alvin , Maris John M.
Published: December 2020

The current SARS-CoV-2 pandemic has precipitated an urgent need for a safe and effective vaccine to be developed and deployed in a highly accelerated timeframe as compared to standard vaccine development processes. Upfront selection of epitopes most likely to induce a safe and effective immune response can accelerate these efforts. Optimally designed vaccines maximize immunogenicity towards regions of proteins that contribute most to protective immunity, while minimizing the antigenic load contributed by unnecessary protein domains that may result in autoimmunity, reactogenicity, or enhanced infectivity. Adopting tools developed for population-scale characterization of HLA presentation of tumor antigens and cross-reactivity of TCRs with tumor self-antigens, we have generated an immunogenicity map of SARS-CoV-2 to inform vaccine design based on analyses across five parameters: 1) stimulation of CD4 and CD8 T cells; 2) immunogenicity across the majority of human HLA alleles; 3) targeting both evolutionarily conserved regions, as well as newly divergent regions of the virus that increase infectivity; 4) targeting linear and conformational B-cell epitopes; and 5) targeting viral regions with the highest degree of dissimilarity to the self-immunopeptidome such as to maximize safety and immunogenicity. Using these analyses, we have generated 11 SARS-CoV-2 vaccine constructs optimized for long-term immunity across the majority of the population. These constructs contain combinations of epitopes selected from our analysis such as to drive affinity-enhanced memory response in combination with current spike protein vaccine strategies, for use as T-cell vaccines, and a stand-alone vaccine designed to drive memory B- and T-cell responses in the majority of the population. Epitopes were optimized using our immunogenicity algorithm to minimize immunogenicity across the junctions between epitopes and cloned into pVAX vectors, using signal peptides targeting the lysosome, ER, and cytoplasmic secretion, such as to promote presentation to CD4, CD8, and B cells, respectively. Finally, we describe methods for identifying immunodominant epitopes arising from vaccination using barcoded, multiplexed tetramers. Vaccine constructs are currently undergoing testing in transgenic mice expressing human HLA-A2. We expect that these constructs will help drive long-term immunity across the population, targeting conserved regions across multiple coronaviruses.

Citation Format: Mark Yarmarkovich, John M. Warrington, Alvin Farrel, John M. Maris. SARS-CoV-2 multiepitope vaccine constructs designed to drive long-term immunity in the majority of the population [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-049.
Abstract PO-060: COVID-CANCER HUIL STUDY: Registry of oncologic patients diagnosed with Covid-19 in Infanta Leonor University Hospital in Madrid, Spain
Authors: Rogado Jacobo , Obispo Berta , Serrano-Montero Gloria , Merino Almudena Martin , Lopez-Alfonso Ana , Pangua Cristina , Pérez-Pérez Mar , Fontán-Vela Mario , Lara Miguel Ángel
Published: December 2020

Background: Covid-19 has been shown to present more complications in immunosuppressed patients. We determine whether differences exist in Covid-19-related mortality between cancer patients and general population in our hospital, and we also describe associated risk factors.

Methods: We reviewed 2,216 medical records of all patients admitted to hospitalization in Infanta Leonor University Hospital in Madrid, Spain, with Covid-19 diagnosis between 5 March and 13 May, 2020. Study data were collected and managed using REDCap electronic data capture tools. We described Covid-19 cumulative incidence in cancer patients, treatment outcome, mortality, and associated risk factors.

Results: We detected 85/2,216 cancer patients between all Covid-19 diagnoses. Mortality rate: 40/85 cancer patients vs. 260/2,131 in general ward (p<0.001). Median age: 76 years old (34-94), 50/85 male patients. Most frequent histologies were lung cancer (22/85), colorectal cancer (19/85), prostate cancer (15/85), and breast cancer (10/85). Most frequent staging was metastatic disease (32/85). Only 2/85 patients were admitted to ICU. Mortality was associated with older median age (79.5 vs. 73, p=0.03), high d dimer levels (1630 vs. 830, p=0.03), high LDH levels (315.5 vs. 224, p=0.003), bilateral pneumonia (24/42 vs. 5/22 with unilateral pneumonia, p=0.02), ARDS (12/13 vs. 28/72 without ARDS, p<0.0001), and metastatic disease (20/32 metastatic vs. 20/53 non-metastatic patients, p=0.02). Differences were maintained in multivariate analyses regarding ARDS (OR 23.7, p=0.007) and metastatic disease (OR 2.5, p=0.05).

Conclusions: Covid-19 had a significant mortality in cancer patients. High D dimer and LDH levels and ARDS development in elderly metastatic patients carry an elevated risk of death in cancer patients diagnosed with Covid-19. However, only 2/85 patients were admitted to ICU and these data were decisive. It is a priority to create measures to avoid Covid-19 transmission in oncologic patients.

Citation Format: Jacobo Rogado, Berta Obispo, Gloria Serrano-Montero, Almudena Martin Merino, Ana Lopez-Alfonso, Cristina Pangua, Mar Pérez-Pérez, Mario Fontán-Vela, Miguel Ángel Lara. COVID-CANCER HUIL STUDY: Registry of oncologic patients diagnosed with Covid-19 in Infanta Leonor University Hospital in Madrid, Spain [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-060.
Abstract PO-069: SRMS correlated with immune infiltration and lung cancer: Allusion for COVID-19
Authors: Swarna Beesetti , Wang Yong-Dong , Potts Malia B.
Published: December 2020

Background: The non-receptor tyrosine kinase, SRMS (Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites) is a member of the BRK family kinases (BFKs) that represents an evolutionarily conserved relative of the Src family kinases (SFKs) and is shown to restrain autophagy in mammalian cells. Gene enrichment analyses using the Ingenuity Pathway analyses (IPA) of SRMS interacting partners predicted viral infection as a significantly increased cellular processes. However, the correlation between SRMS and prognosis in LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma) or its impact on COVID-19 is understudied.

Methods: We analyzed the expression levels of SRMS, and the correlation between SRMS and immune infiltration level in LUAD and LUSC was investigated using TIMER database. Open Target platform was used to analyze the association of SRMS with disease. In addition, we used GSE30589 databases to elucidate the changes of SRMS expression in vitro after SARS-CoV infection in Vero E6 and MA-104 cells.

Results: SRMS was elevated in LUAD and LUSC compared to normal tissues. The expression of SRMS was negatively correlated with the level of immune infiltration of CD8+T cells in LUAD and LUSC. We found that the expression of SRMS increased in vitro after SARS-CoV infection in Vero E6 and MA-104 cells.

Conclusion: SRMS expression increased significantly in LUAD and LUSC, and this elevated SRMS was negatively correlated with immune infiltration at tumors. SARS-CoV infection increased the SRMS expression. This suggests that patients with LUAD and LUSC may be more susceptible to SARS-CoV-2 due to increased SRMS levels that inhibit autophagy and alter tumor microenvironment correlated with reduced immune infiltration, which in turn may worsen the prognoses of LUAD and LUSC patients after SARS-CoV-2 infection.

Citation Format: Beesetti Swarna, Yong-Dong Wang, Malia B. Potts. SRMS correlated with immune infiltration and lung cancer: Allusion for COVID-19 [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-069.
Abstract PO-077: Use of aromatase inhibitors and risk of cardiovascular disease: A population-based study
Authors: McVicker Lauren , Cardwell Christopher , McMenamin Úna
Published: December 2020

Background: Adjuvant endocrine therapy, including aromatase inhibitors (AI) or tamoxifen, is recommended for women diagnosed with estrogen receptor- and/or progesterone receptor-positive breast cancer as it significantly reduces the risk of recurrence and breast cancer-specific mortality. AIs are the preferred treatment for postmenopausal women; however, concerns have been raised with respect to their cardiovascular safety. Some meta-analyses of randomized controlled trials report an increase in cardiovascular disease (CVD) risk with use of AIs compared to tamoxifen; however, “real-world” observational studies have yielded inconsistent findings.

Objectives: We aimed to conduct a population-based study in Scotland to investigate whether breast cancer patients treated with AIs are at an increased risk of cardiovascular disease compared to patients treated with tamoxifen.

Methods: Women newly diagnosed with breast cancer, from 2009 to 2017, were identified from the Scottish Cancer Registry. AI and tamoxifen use were identified from the nationwide Scottish Prescribing Information System. The primary outcome was CVD, based on incidence or death from CVD obtained from hospital admission and death records, respectively. Cox regression models calculated hazard ratios (HRs) and 95% intervals (CIs) comparing AI use to tamoxifen use and risk of CVD, using an as treated exposure definition. Analyses were adjusted for a range of potential confounders and subgroup analysis investigated risk by CVD subtypes including myocardial infarction, heart failure, ischemic stroke, venous thromboembolism, and angina.

Results: The cohort contained 28,712 breast cancer patients, followed for 110,999 person years, during which there were 776 cardiovascular events. Compared to tamoxifen use, AI use was associated with an increased risk of any CVD event (adjusted HR 1.14, 95% CI: 1.02, 1.27), which was particularly marked for ischemic stroke (adjusted HR 1.27, 95% CI: 0.99, 1.63). There were no clear associations for other CVD subtypes.

Conclusions: Our preliminary results suggest an increased risk of CVD, and specifically ischemic stroke, in AI users compared to tamoxifen. Additional analyses will be conducted to further investigate these associations, including dose-response.

Citation Format: Lauren McVicker, Christopher Cardwell, Úna McMenamin. Use of aromatase inhibitors and risk of cardiovascular disease: A population-based study [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-077.
Abstract PO-089: The impact of Covid-19 on public generosity toward cancer-related crowdfunding efforts
Authors: Fischer Katrina A. , Miller Robert E. , Anand Sidharth , Glaspy John
Published: December 2020

Background: Many patients with cancer rely on public crowdfunding platforms to generate financial support toward costs associated with their medical care. It is unclear how financial uncertainties resulting from the Covid-19 pandemic may impact patient need and public support toward routine cancer-focused campaigns.

Methods: Using custom code for web scraping, we identified all campaigns that were generated on the crowdfunding platform GoFundMe.com in the “Medical, Illness and Healing” category between 8/17/2019 and 5/8/2020. This date represents six months of fundraising prior to the first official shelter-in-place order on 3/17/2020. We then abstracted campaigns that included the word “cancer,” originated in the United States, and had raised at least one dollar. Of these cancer-related campaigns, we collected the dollar amount raised in the first 30 days of campaign generation and the total raised to date. Campaigns generated between 2/17/2020 and 3/16/2020 were not included in pre/post-Covid calculations because these campaigns would potentially include contributions made after 3/17/2020 within their first 30-day values.

Results: 19,669 cancer campaigns were identified during the study period (16,823 between 8/17/19 and 2/17/20 and 2,846 between 3/17/20 and 5/8/20), raising on average 83% of total funds within the first 30 days of campaign generation. In the six months prior to the first shelter-in-place order (8/17/19-2/17/20), there were on average 91 new cancer campaigns generated daily. Within the first 30 days, these campaigns averaged $4,472 (median $1,815). After 3/17/20, an average of 54 campaigns were generated daily, representing a 40% decline in daily campaign generation. Within the first 30 days, these campaigns averaged $6,130 (median $2,950), representing a 36% and 60% increase from baseline respectively.

Conclusion: Public generosity has increased toward cancer fundraising campaigns since the Covid-19 pandemic, but fewer patients are creating new campaigns. Patients can be reassured that they will likely continue to benefit from public support and should not feel limited in asking for help during this period of economic uncertainty. As philanthropy sometimes increases during disaster periods, it is unclear if continued support will persist as longer-term economic changes take effect.

Citation Format: Katrina A. Fischer, Robert E. Miller, Sidharth Anand, John Glaspy. The impact of Covid-19 on public generosity toward cancer-related crowdfunding efforts [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-089.
Abstract S03-01: Pan-HLA prediction of SARS-CoV-2 epitopes
Authors: Campbell Katie M. , Steiner Gabriela , Wells Daniel K. , Ribas Antoni , Kalbasi Anusha
Published: December 2020

Introduction: Delineating antiviral T-cell responses to SARS-CoV-2 may shed light on the heterogeneity of clinical outcomes and inform vaccine or therapeutic approaches. Viral antigens can be predicted using computational tools that calculate the binding affinity between viral peptides and antigen presentation machinery. However, in order to account for the role of host genetics in the diversity of responses, this analysis must be performed with consideration of the global diversity of the human leukocyte antigen (HLA) proteins responsible for antigen presentation.

Methods: We deployed binding predictions across the SARS-CoV-2 peptidome for 9,360 Class I HLA alleles (2,987 HLA-A; 3,707 HLA-B; 2,666 HLA-C; 9-mers) using a consensus approach of 7 algorithms and 3,486 Class II HLA alleles (15-mers) using a consensus approach of 4 algorithms. All pMHC predictions were filtered to include only those with consensus binding less than 500 nM.

Results: There were 368,145 unique combinations of peptides and HLA alleles (pMHCs) with a predicted binding affinity of less than 500nM, including 1,103 unique 9-mer and 2,547 15-mer peptides and 1,022 MHC Class I and 8,075 MHC Class II HLA proteins. Of these pMHCs, 82% of 9-mers overlapped with 15-mers, suggesting cross-presentation to both CD4 and CD8 T cells in a subset of individuals. We evaluated this filtered dataset with respect to the population frequency of HLA haplotypes. While the predicted susceptibility of SARS-CoV-2 antigen presentation differed greatly across countries, there was a subset of 21 Class I antigens shared by common HLA types across 30 or more countries (out of 79 countries with reported population frequency data). Our database has been made publicly available, and we have developed a user interface to explore the results based upon viral proteins, HLA alleles, or country populations of interest.

Conclusions: With the ongoing SARS-CoV-2 pandemic, there are worldwide efforts to generate a successful vaccine and to evaluate clinical samples to understand the viral pathogenesis and diverse outcomes in patients. This application can serve as a guide to identify responses of putative SARS-CoV-2-specific T cells across patients with a broad range of HLA haplotypes internationally.

Citation Format: Katie M. Campbell, Gabriela Steiner, Daniel K. Wells, Antoni Ribas, Anusha Kalbasi. Pan-HLA prediction of SARS-CoV-2 epitopes [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S03-01.
Abstract S07-03: Scientia potentia est: How the Italian world of oncology changes in the COVID19 pandemic
Authors: Ballatore Zelmira , Bastianelli Lucia , Merloni Filippo , Ranallo Nicoletta , Cantini Luca , Mariotti Lorenzo , Catani Claudia , Burattini Michela , Lucarelli Alessandra , Berardi Rossana
Published: December 2020

Background: After COVID-19 was declared a pandemic by the World Health Organization, a response from the Italian Health System to react to an unprecedented condition became necessary and sudden. COVID- 19 pandemic required oncologists to redefine clinical organization and management of cancer patients. The aim of our study was to take a picture of the situation of Italian oncologies and to evaluate the difficulties in patients’ management.

Methods: Between 18th March and 9th April 2020 we conducted an online survey (Google Forms). It consisted of 45 questions ranging from individual perception of pandemic management by oncologic centers to physicians’ and nurses’ psychological distress and patient care. The survey was anonymous and broadcast to oncology health workers by mailing contacts, word of mouth, and social networks.

Results: A total of 383 oncology health workers participated in the survey. The majority was female (72%) and from central Italy (46%). Impressively, a total of 357 (93%) participants declared the Oncologic Department reorganized routine clinical activity, but only 41% were adequately trained about the required procedures. 20% of the survey attendees thought they had not received adequate and timely protective devices with respect to clinical needs, and according to 58% the supply of these devices was only partial. 34% of professionals declared that they did not have or know a defined common guideline to reschedule patients’ treatments. More than 80% of interviewees declared feeling worried about being at greater risk of contagion than the general population, and 92% feared to transmit virus to family members. Deferring treatments has caused fear/anxiety in 228 of the interviewed (60%). Symptoms of stressful situations emerged with a deterioration in sleep quality in 62% of professionals, worsening of mood (69%), and lower concentration ability (49%).

Conclusions: Our survey demonstrated the flexibility of oncologic teams. However, the emergency response quality has been heterogeneous, and several drawbacks emerged from this first analysis. Information, protection, testing, and training of health care professionals are keywords that should be kept in mind to encourage recovery after this tragedy and to be ready to face a similar emergency in the near future.

Citation Format: Zelmira Ballatore, Lucia Bastianelli, Filippo Merloni, Nicoletta Ranallo, Luca Cantini, Lorenzo Mariotti, Claudia Catani, Michela Burattini, Alessandra Lucarelli, Rossana Berardi. Scientia potentia est: How the Italian world of oncology changes in the COVID19 pandemic [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S07-03.
Abstract S12-02: Risk of morbidity and mortality in COVID-19 patients with cancer
Authors: Alpert Naomi , Marcellino Bridget , Rapp Joseph , Lieberman-Cribbin Wil , Taioli Emanuela
Published: December 2020

Introduction: Morbidity and mortality of cancer patients with COVID-19 have not been examined. The goal of this analysis was to compare the demographics and clinical characteristics of COVID-19 cancer patients to the rest of COVID-19 patients and assess whether cancer is associated with morbidity or mortality.

Methods: COVID-19-positive patients with an inpatient or emergency encounter at the Mount Sinai Health System between 03/01/20-05/27/20 were included in the analysis. Patients were compared across cancer status (noncancer, non-solid cancers, and solid cancers) on demographics and clinical characteristics. Multivariable logistic regressions were used to model the associations of cancer status with sepsis, acute venous thromboembolism, and mortality.

Results: There were 5,516 COVID-19 positive patients included, 96 (1.7%) with non-solid cancers and 325 (5.8%) with solid cancers. Those with solid cancers were significantly older (mean: 70.9 vs. 63.8 and 63.2 years) and more likely to be non-Hispanic Black (26.5% vs. 23.9% and 22.9%) than noncancer and non-solid cancers patients. Those with cancer had significantly more additional comorbid conditions (42.7% and 49.8% ≥2 comorbidities for non-solid and solid cancers, vs. 30.4% for noncancer). Platelets (mean [noncancer]: 223.8, mean [non-solid cancer]: 182.6, mean [solid cancer]: 218.3 × 103/μL), white blood cell count (mean [noncancer]: 8.4, mean [non-solid cancer]: 6.7, mean [solid cancer]: 8.0 × 103/μL), hemoglobin (mean [noncancer]: 13.1, mean [non-solid cancer]: 11.2, mean [solid cancer]: 12.0 g/dL), and red blood cell count (mean [non-cancer]: 4.5, mean [non-solid cancer]: 3.7, mean [solid cancer]: 4.1 × 106/μL) were significantly lower in cancer patients, and lowest in those with non-solid cancers. After adjustment and compared to noncancer patients, those with cancer had significantly higher risk of acute venous thromboembolism (ORadj: 1.77, 95% CI: 1.01-3.09) and sepsis (ORadj: 1.34, 95% CI: 1.09-1.64). There was no significant difference in mortality (ORadj: 1.02, 95% CI: 0.81-1.29). There was no significant difference in all outcomes for solid and non-solid cancer types.

Conclusion: COVID-19 patients with cancer, particularly solid tumors, are significantly older, with more comorbidities than those without cancer. There was no statistically significant difference in mortality for COVID-19 patients with cancer, but a significantly higher risk of thromboembolism and sepsis. Further research into the effect that cancer treatments may have in inflammatory and immune responses to COVID is warranted.

Citation Format: Naomi Alpert, Bridget Marcellino, Joseph Rapp, Wil Lieberman-Cribbin, Emanuela Taioli. Risk of morbidity and mortality in COVID-19 patients with cancer [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S12-02.
Abstract PO-19: Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis
Authors: Gong Chun , Krupka Joanna A. , Gao Jane , Grigoropoulos Nicholas F. , Cucco Francesco , Barrans Sharon , Igor De Los Mozos , Peixun Zhou , Sorca Forde , Jamie Matthews , Amos Burke , Kwan Sze Siu , Philip Beer , Cathy Burton , Peter Campbell , Vikki Rand , Suzanne Turner , Jernej Ule , Eve Roman , Reuben Tooze , Thomas Oellerich , Ming Du , Shamith Samarajiwa , Hodson Daniel J.
Published: December 2020

DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we show that loss-of-function DDX3X mutations are also commonly found in MYC-translocated diffuse large B-cell lymphoma. We reveal functional cooperation between mutant DDX3X and MYC in ex vivo cultured human germinal center B cells. By integrating results of iCLIP, ribosome profiling, and proteomics, we show WT DDX3X promotes the translation of mRNAs encoding components of the core translational machinery, thereby driving global protein synthesis. Loss-of-function DDX3X mutations act to buffer the effect of abrupt MYC expression and moderate MYC-driven global protein synthesis, thereby buffering MYC-induced proteotoxic stress during early lymphomagenesis. Established lymphoma cells subsequently restore full protein synthetic capacity by aberrant expression of DDX3Y, a Y-chromosome homologue that is normally expressed exclusively in testis. These findings show how sequential dysregulation of DDX3X and DDX3Y acts to titrate global protein synthesis to suit the stage-specific needs of developing lymphoma cells and identify DDX3Y as an attractive, male-specific therapeutic target absent from normal human B cells but required for the survival of male lymphomas.

Citation Format: Chun Gong, Joanna A. Krupka, Jane Gao, Nicholas F. Grigoropoulos, Francesco Cucco, Sharon Barrans, De Los Mozos Igor, Zhou Peixun, Forde Sorca, Matthews Jamie, Burke Amos, Sze Siu Kwan, Beer Philip, Burton Cathy, Campbell Peter, Rand Vikki, Turner Suzanne, Ule Jernej, Roman Eve, Tooze Reuben, Oellerich Thomas, Du Ming, Samarajiwa Shamith, Daniel J. Hodson. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-19.
Abstract PO-42: TBL1XR1 mutations drive extranodal lymphomagenesis by inducing a protumorigenic memory B-cell fate
Authors: Venturutti Leandro , Teater Matt , Zhai Andrew , Chadburn Amy , Babiker Leena , Kim Daleum , Staudt Louis , Green Michael , Farinha Pedro , Weng Andrew , Steidl Christian , Morin Ryan , Scott David , Privé Gil , Melnick Ari
Published: December 2020

The most aggressive B-cell lymphomas frequently manifest extranodal distribution and carry somatic mutations in the poorly characterized gene TBL1XR1. Here, we show that TBL1XR1 mutations skew the humoral immune response towards generating abnormal immature memory B-cells (MB), while impairing plasma cell differentiation. At the molecular level, TBL1XR1 mutants co-opt SMRT/HDAC3 repressor complexes towards binding the MB cell transcription factor (TF) BACH2, at the expense of the germinal center (GC) TF BCL6, leading to pre-memory transcriptional reprogramming and cell-fate bias. Upon antigen recall, TBL1XR1 mutant MB cells fail to differentiate into plasma cells and instead preferentially reenter new GC reactions, providing evidence for a cyclic re-entry lymphomagenesis mechanism. Ultimately, TBL1XR1 alterations lead to a striking extranodal immunoblastic lymphoma phenotype that mimics the human disease. Both human and murine lymphomas feature expanded MB-like cell populations, consistent with a MB-cell origin and delineating an unforeseen pathway for malignant transformation of the immune system.

Citation Format: Leandro Venturutti, Matt Teater, Andrew Zhai, Amy Chadburn, Leena Babiker, Daleum Kim, Louis Staudt, Michael Green, Pedro Farinha, Andrew Weng, Christian Steidl, Ryan Morin, David Scott, Gil Privé, Ari Melnick. TBL1XR1 mutations drive extranodal lymphomagenesis by inducing a protumorigenic memory B-cell fate [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-42.
Downregulation of miRNA-451a Promotes the Differentiation of CD4+ T Cells towards Th2 Cells by Upregulating ETS1 in Childhood Asthma
Authors: Wang Tianyue  , Zhou Qianlan , Shang Yunxiao
Published: December 2020

Children exposed to common aeroallergens may develop asthma that progresses into adulthood. Inflammation regulated by T helper 2 (Th2) cells, a specific subpopulation of CD4+ T lymphocytes, is involved in asthmatic injury. Herein, our microarray data indicated that microRNA-451a-5p (miRNA-451a) expression decreased by 4.6-fold and ETS proto-oncogene 1 (ETS1) increased by 2.2-fold in the peripheral blood lymphocytes isolated from asthmatic children (n = 4) as compared to control individuals (n = 4). The negative correlation between miRNA-451a and ETS1 was further validated in 40 CD4+ T cell samples (10 healthy vs. 30 asthmatic samples). In vitro, naïve CD4+ T cells isolated from control individuals were cultured under Th2 cell polarizing condition. miRNA-451a expression decreased while ETS1 increased in CD4+ T cells in the setting of Th2 cell polarization. Moreover, miRNA-451a knockdown enhanced Th2 cell polarization – cells positive for both GATA3 (GATA binding protein 3, a Th2-transcription factor) and CD4 increased, and the generation of Th2 cell cytokines, interleukin (IL)5 and IL13, increased. In contrast, miRNA-451a overexpression inhibited Th2 cell differentiation. Interestingly, dual-Luciferase assay proved ETS1 as a novel target of miRNA-451a. Moreover, enforced expression of ETS1 partially restored miRNA-451a-induced inhibition of IL5 and IL13, and increased the GATA3+CD4+ cell population. Collectively, our work demonstrates that downregulation of miRNA-451a upregulates ETS1 expression in CD4+ T cells, which may contribute to Th2 cell differentiation in pediatric asthma.