bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4124: Clinical outcomes in women with metastatic HER2-Low breast cancer in the real world
Authors: Jiang Changchuan , Perimbeti Stuthi , Deng Lei , Shapiro Charles L. , Gandhi Shipra 
Published: June 2022

Abstract
Background: The development of novel anti-HER2 drugs opens new treatment options for patients with breast cancers, including women with lower expression of HER2. The aim of this study was to compare the clinical outcomes of HER2-low and HER2-zero metastatic breast cancer in the real world.
Methods: Female patients diagnosed with metastatic breast cancer and low HER2 expression or HER2-zero expression between 2010 and 2017, and who received systematic therapy, were identified from the National Cancer Database (NCDB). The National Cancer Data Base (NCDB) is a nationwide oncology outcomes database that collects information on approximately 70% of all new invasive cancer diagnoses in the United States.HER2-Low was defined as IHC1+ or 2+/ISH negative, whereas HER2-zero was defined as IHC0, based on the American Society of Clinical Oncology/College of American Pathologists guideline. The primary outcome was overall survival(OS). A multivariable Cox regression model was performed to estimate hazard ratios (HR), adjusting for age, race/ethnicity, education, comorbidities, grade, presence of visceral metastasis, and the type of cancer center where patients were treated. The analyses were stratified by hormone receptor status.
Results: A total of 22817 of 33417 (68%) were HER2-low and 10600 (32%) were HER2-zero. Hormone receptor-positivity was in 19988 (88%) with HER2-low tumors, whereas 8112 (77%) was in HER2-zero tumors. Women with HER2-low tumors had significantly longer overall survival (OS) than did with Her2-zero tumors in both hormone receptor-positive (median OS 39.0 months vs 37.1 months; adjusted HR: 0.93, 95%CI (0.90-0.96), p&lt;0.001) and hormone receptor-negative groups (median OS 15.8 months vs 14.1 months; adjusted HR: 0.92 95%CI (0.86-0.98), p=0.005).
Conclusion: In the metastatic setting, HER2-low tumors have a better survival than HER2-zero tumors, irrespective of hormone receptor status. Specific therapies, such as trastuzmab deruxtecan, have activity in women with HER-low breast cancers and additional therapeutics for HER-2 low should be sought.
Citation Format: Changchuan Jiang, Stuthi Perimbeti, Lei Deng, Charles L. Shapiro, Shipra Gandhi. Clinical outcomes in women with metastatic HER2-Low breast cancer in the real world [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4124.
Abstract 4247: Development of NK humanized mice models for the in vivo evaluation of NK cell engagers
Authors: Rettman Pauline , Bourges Dorothée , Meyer Laure-Marie , Rangara Ravi , Ponchet-Lac Anna , Moindrot Nicolas , Sidhu Sukhvinder , Nicolazzi Céline 
Published: June 2022

Abstract
Novel immunotherapeutic strategies targeting Natural Killer (NK) cells using monoclonal or multi-specific antibodies and immune modulator molecules are under development and there is a pressing need to have suitable mouse models for the evaluation of these therapeutics. To date, there are no validated in vivo mouse models that support the development of fully functional human NK cells. In recent years, the adoptive transfer of human peripheral mononuclear blood cells or CD34+ stem cells into highly immunodeficient mouse strains mostly allowed the evaluation of T cell-based therapies. However, these humanized mouse models have limitations and do not show an optimal development of innate immune cells such as NK, dendritic or myeloid cells. This is mostly due to the poor interspecies cross-reactivity of key factors necessary for cell development and maturation, like cytokines and growth factors.Here, we report the development and characterization of robust in vivo models that allow the engraftment and maintenance of fully functional human NK (huNK) cells, using several strains of immunodeficient transgenic mice for human cytokines (IL-15). The optimal parameters (source of immune cells, pre-conditioning regimen, route of administration) were identified. These models were characterized and validated by flow cytometry, and in vivo efficacy studies using an anti-CD20 Ab.In summary, we developed several murine models that exhibit significant numbers of functional huNK cells maintained over time in vivo. Different sources of human immune cell (CD34+ HSC, huNK cells) were used to implant immunodeficient huIL15 transgenic mice. HuNK cells were monitored by flow cytometry in all tested models. We showed huNK engraftment in both irradiated and non-irradiated models and confirmed the maintenance of expression of important functional NK markers on these cells. Efficacy studies performed in disseminated models showed promising results as efficacy of an anti-CD20 Ab, rituximab, was improved in presence of huNK cells, thus confirming the engagement of huNK cells in vivo in these models. Overall, we have developed several models that can sustain fully functional huNK cells over a period of several weeks that can be proficiently recruited in vivo by various NK-based therapeutics.
Citation Format: Pauline Rettman, Dorothée Bourges, Laure-Marie Meyer, Ravi Rangara, Anna Ponchet-Lac, Nicolas Moindrot, Sukhvinder Sidhu, Céline Nicolazzi. Development of NK humanized mice models for the in vivo evaluation of NK cell engagers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4247.
Abstract 435: COVID-19 & cancer prevention in Texas: Reasons cited for HPV vaccination hesitancy and refusal during the pandemic
Authors: Chido-Amajuoyi Onyema , Pande Mala , Yu Robert , Shete Sanjay 
Published: June 2022

Abstract
Background: HPV vaccination is highly effective at preventing several squamous cell carcinomas. However, the uptake of this vaccine remains sub-optimal in the US, with further exacerbation of this poor uptake during the pandemic. This study aims to describe changes and barriers to HPV vaccination during the COVID-19 pandemic as observed by healthcare professionals (HCPs) in the state of Texas.
Methods: Data for this study were derived from a statewide cross-sectional survey of HCPs in the state of Texas (n=1283). Survey instruments were developed at MD Anderson Cancer Center, and reviewed by its IRB. Survey frequencies were used to estimate for the proportional distribution of changes as observed by HCPs regarding HPV vaccination i) uptake ii) hesitancy and iii) refusal during the COVID-19 pandemic. HCPs who observed increases in vaccination hesitancy or refusal, were then asked for the reasons cited by their patients. Survey frequencies were then used to determine the proportional distribution of the reasons cited for HPV vaccination hesitancy and refusal during the pandemic. All statistical analysis were conducted using R version 3.5.2.
Results: Overall, 730 HCPs responded to the study questions of interest. A predominant proportion of respondents were employed in group practice settings or university teaching/affiliated hospitals. About 20% of HCPs in Texas observed decreases in HPV vaccination uptake. Observed increments in HPV vaccination hesitancy and refusal were reported by 17.1% and 14.8% of HCPs, respectively. Among HCPs who observed increased hesitancy and refusal, difficulties in scheduling clinic visit during the pandemic and fear of contracting corona virus during the clinic visit were the most cited reasons.
Discussion: Findings of the index study suggest that the COVID-19 pandemic has had a negative impact on HPV vaccination in Texas. Results identify perceived barriers to HPV vaccination unique to the pandemic. With the pandemic still ongoing, amid the emergence of novel strains with heightened virulence, despite the presence of highly effective FDA-approved vaccines, findings of this study provides useful insight for public health interventions, as well as to guide physician-patient interactions around HPV vaccination.
Citation Format: Onyema Chido-Amajuoyi, Mala Pande, Robert Yu, Sanjay Shete. COVID-19 & cancer prevention in Texas: Reasons cited for HPV vaccination hesitancy and refusal during the pandemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 435.
Abstract 455: Automating integration of histomorphologic and immunohistochemistry data using computer vision tools
Authors: Lee Michael K. , Faust Kevin , Rabindranath Madhumitha , Diamandis Phedias 
Published: June 2022

Abstract
Background: Modern diagnostic pathology workflows involve the integration of histomorphologic, immunohistochemical (IHC), and molecular data to reach a final diagnosis. Recently, advances in deep learning have revolutionized pathology by providing the prospect for expert-level autonomous image analysis tools. Despite recent innovations in deep learning, integrating histomorphologic and molecular information found on respective H&E- and IHC-stained tissue sections still remains a challenge. Here, we aim to address this issue by incorporating computer vision tools, including deep learning and scale-invariant feature transform (SIFT), to align H&E-stained sections with accompanying IHC studies for automated subclassification of gliomas.
Methods: To test the workflow, we trained the publicly available VGG19 convolutional neural network (CNN) using patches of pathologist-annotated H&E-stained WSIs to recognize histological patterns of 16 common tissue and brain tumor classes, including diffuse glioma, meningioma, metastatic carcinoma, and schwannoma. To complement the histomorphologic analysis, we optimized several deep learning classifiers, including Mask R-CNN, to recognize various IHC markers, such as Ki-67, IDH1-R132H and ATRX, relevant for molecular subclassification of gliomas. For the integrated analysis, we employed SIFT to align lesional regions of H&E and IHC images.
Results: The histomorphologic classifier excelled at classification with accuracies of 100% for glioma, meningioma and metastatic carcinoma, and 93% for schwannoma (n = 125). The Mask R-CNN was tested on 147 images generated from 34 brain tumor Ki-67 WSIs and showed a high concordance with aggregate pathologists’ estimates (n = 3 assessors; y = 0.9712x -1.945, r = 0.9750). Using the deep learning classifiers and SIFT, we were able to identify tumor regions from the H&E images and align them to their corresponding IHC images. This resulted in significant improvement of ATRX and IDH1-R132H quantification compared to unaligned WSIs. Finally, SIFT and partially sampling the lesional regions decreased computational time significantly without compromising accuracy.
Conclusion: SIFT can work in concert with deep learning tools to help examine the histomorphologic and molecular patterns of various brain tumors and provide a framework for integrating deep learning tools to provide automated diagnoses.
Citation Format: Michael K. Lee, Kevin Faust, Madhumitha Rabindranath, Phedias Diamandis. Automating integration of histomorphologic and immunohistochemistry data using computer vision tools [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 455.
Abstract 498: TARE and PVE as pre-operative strategies in highly selected patients with primary and metastatic hepatic malignancies
Authors: Freitas Julia Pedo , Podila Pradeep , Powell Daniel K. , Angel Wes , Deneve Jeremiah L. , Dickson Paxton V. , Glazer Evan S. 
Published: June 2022

Abstract
Background: The treatment of malignancies confined to the liver (hepatocellular carcinoma [HCC], intrahepatic cholangiocarcinoma [ICC], metastatic neuroendocrine tumors [NET] and colorectal hepatic metastases [CRHM]) is challenging. Liver resection leading to post-operative liver failure is a devastating complication that can be mitigated by pre-resection embolization techniques to increase the future liver remnant, such as portal vein embolization (PVE) and transarterial radioembolization (TARE). The purpose of this study was to understand the natural history of this treatment algorithm in disparate patient populations.
Methods: This was a retrospective case-control study from 2008 to 2018. The population consisted of non-transplant eligible patients that had various malignancies without extra-hepatic disease who underwent TARE, PVE, or resection at our institution; they were propensity matched based on co-morbidities, etiology of liver disease, Child-Pugh Score, and ECOG performance status. Statistical analyses were performed with chi-square.
Results: We identified 196 patients with an average age of 57.8±12.6 years and 119 patients were male (60.7%). There were 137 Caucasian patients (CC, 70%) and 59 African American patients (AA, 30%). The tumor histologies were 61 HCC, 31 ICC, 65 CRHM, 12 NET, and 28 other. 148 of these patients underwent liver resection. HCC patients were more likely to undergo TARE (36.4%) compared to ICC (20%), CRHM (23.6%), or NET (9.1%, P= 0.043). While AA patients were more likely to undergo any embolization procedure compared to CC patients (47% vs 31%, P=0.03), they were less likely to undergo PVE (P=0.018). 126 patients (64%) did not undergo any pre-resection embolization procedures. Of patients requiring pre-resection embolization, CRHM patients were more likely to undergo PVE (80%) than other patients (P=0.029). TARE was a bridge to resection for 9 patients.
Conclusions: AA patients underwent more embolization procedures compared to CC patients. It is not clear whether this was because that population required more interventions to optimize FLR or had limited access to care.
Citation Format: Julia Pedo Freitas, Pradeep Podila, Daniel K. Powell, Wes Angel, Jeremiah L. Deneve, Paxton V. Dickson, Evan S. Glazer. TARE and PVE as pre-operative strategies in highly selected patients with primary and metastatic hepatic malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 498.
Abstract 500: Neuropsychological symptoms in patients with head and neck cancer undergoing radiation therapy: A network analysis
Authors: Lin Yufen , Bruner Deborah W. , Paul Sudeshna , Miller Andrew H. , Saba Nabil F. , Higgins Kristin A. , Shin Dong M. , Zhang Wenhui , Miaskowski Christine , Xiao Canhua 
Published: June 2022

Abstract
Objectives: Patients with head and neck cancer experience neuropsychological symptoms (NPS) (i.e., depression, fatigue, sleep disturbance, pain, and cognitive dysfunction) during radiation therapy (RT) that decrease their functional status and quality of life. The purposes of this study were to examine and visualize the relationships among NPS within networks over time and evaluate demographic and clinical characteristics associated with symptom networks.
Methods: A total of 192 patients (mean age 59.5±10.1 years, 75% male, 81% White) completed symptom questionnaires four times, namely, before RT (T1), 1 month (T2), 3 months (T3), and 1 year (T4) after RT. Network analysis was used to explore relationships among the five common NPS. Centrality indices, including strength, closeness, and betweenness, were used to describe the degrees of symptom interconnection. The network comparison test was used to assess the differences between two symptom networks.
Results: Depression (reported by 13%-24% of patients) was associated with the other four symptoms, and fatigue (reported by 54%-77% of patients) was associated with the other three symptoms across four times. Based on centrality indices, depression (rstrength=1.1-1.4, rcloseness=0.07-0.08, rbetweeness=4-12) was the most central symptom in all four symptom networks, followed by fatigue (rstrength=0.8-1.0, rcloseness=0.05-0.06, rbetweeness=0-2). Higher levels of stress and no alcohol use were associated with stronger symptom networks in network global strength (low stress: 1.49 vs. moderate to high stress: 1.92; p=0.02; no alcohol use: 2.38 vs. alcohol use: 1.75; p=0.01), but not in network structure or edge strength prior to RT. No significant differences were found in other time points.
Conclusions: Network analysis provided a novel approach to gain insights into the relationships of co-occurring NPS and identify central symptoms and associated characteristics. Clinicians can use this information to develop personalized symptom management interventions that target central symptoms and interactions within a network.
Citation Format: Yufen Lin, Deborah W. Bruner, Sudeshna Paul, Andrew H. Miller, Nabil F. Saba, Kristin A. Higgins, Dong M. Shin, Wenhui Zhang, Christine Miaskowski, Canhua Xiao. Neuropsychological symptoms in patients with head and neck cancer undergoing radiation therapy: A network analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 500.
Abstract 5013: Integrated analysis of intragastric microbiome and human gene expression uncovers genetic, microbial, and immunological associations in gastritis and gastric cancer
Authors: Park Chan Hyuk , Hong Changjin , Lee A-reum , Sung Jaeyun , Hwang Tae Hyun 
Published: June 2022

Abstract
Background: Gastric carcinogenesis has been found to be associated with intragastric microbiome, gastric mucosal gene expression, and immune cells comprising the tumor microenvironment separately in independent studies. However, to date, there has been no multi-omic investigations analyzing these biological traits simultaneously. Thus, there is a paucity in our understanding of the intricate relationship between intragastric microbes and the host in gastric disease. To address this gap, we aimed to comprehensively investigate the microbiome, host gene expression, and immune cells in the stomach across a range of different states along the gastric carcinogenesis pathway.
Methods: Gastric biopsy samples were obtained from healthy individuals or patients with gastritis or gastric cancer (biopsy cohort, n=30). Surgical samples (of cancer and adjacent severe gastritis tissues) were obtained from gastric cancer patients (surgery cohort, n=40). Using 16S rRNA gene sequencing, RNA-seq, and cell-type enrichment analysis of each participant’s biospecimens, we identified associations between the microbiome and host transcriptome or inferred immune cell types.
Results: Microbiome composition and gene expression patterns showed significant differences between disease states (healthy, gastritis, or cancer). Expression of ‘Cell cycle’ pathway genes was enriched in gastric cancer in both biopsy and surgery cohorts. In the biopsy cohort, Helicobacteraceae, which was abundant in gastritis, was highly correlated with FAM3D, which was previously found to be involved in gastrointestinal inflammation. In the surgery cohort, Lachnospiraceae, which was abundant in gastric cancer, was highly correlated with UBD, which is known to regulate mitosis and reduce cell cycle time. Cell-type enrichment analysis revealed lower B cell infiltration in gastric cancer than in gastritis (both cohorts). Tissue-infiltrating B cells were associated with Helicobacteraceae.
Conclusions: Associations between the intragastric microbiome, human gene expression, and tissue-infiltrating immune cells are unique to gastric disease state. The findings herein may aid the discovery of novel biomarkers or therapeutic targets of gastric cancer.
Citation Format: Chan Hyuk Park, Changjin Hong, A-reum Lee, Jaeyun Sung, Tae Hyun Hwang. Integrated analysis of intragastric microbiome and human gene expression uncovers genetic, microbial, and immunological associations in gastritis and gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5013.
Abstract 5027: PTMcosmos: A web portal of post-translational modifications and proteogenomic resources in cancer
Authors: Wang Liang-Bo , Govindan Akshay , Cao Song , Ding Li 
Published: June 2022

Abstract
PTMcosmos is a comprehensive database with an interactive web portal designed to catalog and visualize post-translational modifications (PTMs) in humans. It contains 469,183 experimentally-validated PTM sites and their supporting evidence from UniProt Knowledge Base, PhosphoSitePlus, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). PTMcosmos summarizes the entire spectrum of CPTAC proteomics data on human cancer patients, including protein and PTM peptide abundance data from 10 different cancer types. Additionally, PTMcosmos contains cancer somatic mutations from The Cancer Genome Atlas (TCGA), thus allowing for the collective integration and analysis of different data types. In PTMcosmos, we have built an ensemble of interactive visualization tools that allow researchers to investigate altered PTM functions due to genetic alterations in close proximity. The database is live at https://ptmcosmos.wustl.edu. We used PTMcosmos to investigate PTM regulation across cancer types. First, we examined the differential abundance of the PTM sites of cancer driver genes, focusing primarily on phosphorylation of the tumor suppressor retinoblastoma protein (encoded by RB1) and acetylation of the histone acetyltransferase E1A Binding Protein P300 (EP300) across cancer types. We analyzed the association between these PTM events and downstream targets, as well as with tumor subtypes, significantly mutated gene (SMG) mutation status, and clinical features. Second, we investigated the association of the protein abundance of cancer driver genes with ubiquitylsites in lung squamous cell carcinoma (LSCC) to nominate potentially novel modes of regulation of these proteins’ activities. We further analyzed the tumor subtype specificity and tumor-normal abundance changes of these ubiquitylsites and their corresponding substrate proteins, identifying several EGFR ubiquitylsites which may regulate EGFR abundance in LSCC. Finally, we identified the linear and spatial clustering of mutations and PTM sites, identifying multiple mutation-PTM clusters in cancer related genes, including TP53, PIK3CA, CTNNB1, EGFR, and IDH1. We envision that PTMcosmos will serve both the CPTAC consortium and the wider research community to better understand the role of PTMs in cancer.
Citation Format: Liang-Bo Wang, Akshay Govindan, Song Cao, Li Ding. PTMcosmos: A web portal of post-translational modifications and proteogenomic resources in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5027.