tbuckley/cabot-search huggingface dataset:
Prevalence and sociodemographic predictors of depression in patients with head and neck cancer - results from a national study.
Authors: Nosayaba Osazuwa-Peters, Eric Adjei Boakye, Kahee A. Mohammed, Christian J Geneus, Betelihem B Tobo, Jessica Fatla, Thomas E. Burroughs, Carl Freter, Mark V Varvares
Journal: Journal of Clinical Oncology (2016)

6064 Background: There is an increased risk of depression after a diagnosis of head and neck cancer (HNC) due to associated morbidity and quality of life issues. However, no nationally representative study has quantified prevalence and predictors of depression across head and neck subsites. We describe age-adjusted prevalence, and sociodemographic predictors of depression among patients with HNC cancer using a national dataset. Methods: We performed a cross-sectional analysis of 76,331 cases of HNC (international classification of disease, 9th edition), using the Nationwide Inpatient Sample 2008 – 2013 data. Weighted, multivariate logistic regression analysis was used to examine association between patients' sociodemographic and tumor anatomical site with and diagnosis of a major depressive disorder. Results: Overall prevalence of major depressive disorder in HNC was 9.2% with the highest prevalence being among patients with larynx cancer (31.3%). In the multivariate analysis, there were lower odds of depression among patients with cancer of salivary glands (odds ratio [OR] = 0.75, 95% = 0.67 – 0.85), gum (OR = 0.80, 95% = 0.67 – 0.95), and nasopharynx (OR = 0.82, 95% = 0.73 – 0.93), compared to larynx cancer. Sociodemographic predictors of depression included female gender (OR = 1.80, 95% = 1.70 – 1.90), and having Medicaid (OR = 1.09, 95% = 1.01 – 1.24) vs. private payer. Additionally, there were lower odds of depression among Blacks compared to Whites (OR = 0.57, 95% = 0.52 – 0.63), among patients in the west (OR = 0.85, 95% = 0.77 – 0.92) and south (OR = 0.82, 95% = 0.76 – 0.88, while those in the Midwest had higher odds of depression (OR = 1.12, 95% = 1.03 – 1.21). Finally, having advanced comorbidities (OR = 1.21 per one unit increase in Elixhauser comorbidity index, 95% = 1.19 – 1.23) was associated with higher odds of depression in these patients. Conclusions: Depression rates in HNC vary depending on anatomic subsite, and almost 1 out of 3 patients with cancer of the larynx may be depressed. With such a burden, it may be necessary for more psychological interventions to be integrated into clinical guidelines for the treatment HNC, particularly in high depression risk subsites such as the larynx.
Clinical symptoms and physical signs for non-small cell lung cancer patients in China: A nation-wide multicenter 10-year retrospective study.
Authors: Yixiang Zhu, Puyuan Xing, Le Wang, Zhouguang Hui, Shangmei Liu, Jiansong Ren, Debin Wang, Yunchao Huang, Xianzhen Liao, Xiaojing Xing, Lingbin Du, Li Yang, Yuqin Liu, Yongzhen Zhang, Kai Zhang, Youlin Qiao, He Jie, Min Dai, Jufang Shi, Li Junling
Journal: Journal of Clinical Oncology (2018)

e13586 Background: Lung cancer is the most common cancer worldwide, unfortunately, outcomes are poor, due to late diagnosis. Most lung cancers are diagnosed after the onset of symptoms. Previous study suggested it is possible a sustained increase in resections may improve long-term survival with raising public awareness of cancer symptoms and encouraging people with the symptoms to visit hospital. However, whether lung cancer symptoms were independently associated with diagnosis is unknown, especially in Chinese populations. Methods: We conducted a 10-year (2005-2014) nationwide multicenter retrospective clinical epidemiology study of lung cancer patients diagnosed in China. This study focused on the non-small cell lung cancer (NSCLC). We calculated odds ratios (OR) for variables independently associated with symptoms and physical signs, using multivariable conditional logistic regressions. Results: A total of 7184 lung cancer patients were surveyed, in which 6398 NSCLC patients with available information of symptoms and physical signs were included. The most common initial symptoms and signs was chronic cough (4156, 65%), followed by sputum with blood (2110, 33%), chest pain (1146, 17.9%), short breath (1090, 17%), neck and supraclavicular lymphadenopathy (629, 9.8%), weight loss (529, 8.3%), metastasis pain (378, 5.9%), fatigue (307, 4.8%), fever (272, 4.3%), and dyspnea (270, 4.2%). Patients having chronic cough and sputum with blood were more likely to be squamous carcinoma and stage III. While metastasis pain and neck and supraclavicular lymphadenopathy were more likely to occur in non-squamous carcinoma. Additionally, patients with stage IV had higher percentage of chest pain, short breath, dyspnea, weight loss and fatigue. In multivariable analyses, as compared with adenocarcinoma, squamous carcinoma had higher odds of symptoms (OR = 2.885, 95% confidence interval (CI) 2.477-3.359, p < 0.001), but not of signs (OR = 0.844, 95% CI 0.721-0.989, p = 0.036). The odds of both symptoms and physical signs were higher in later stage than earlier stage (p < 0.001). Conclusions: The symptoms and physical signs were associated with pathologic and clinical stage of NSCLC.
Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma.
Authors: Eudocia Quant Lee, Alona Muzikansky, David A. Reardon, Jorg Dietrich, Lakshmi Nayak, Dan G. Duda, Ugonma Nnenna Chukwueke, Rameen Beroukhim, Lisa M. Doherty, Caroline Kane, Debra C. LaFrankie, Brittney Fontana, Jennifer Stefanik, Sandra Ruland, Victoria Caruso, Jennifer Bruno, Sarah C. Gaffey, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2018)

2032 Background: Responses to bevacizumab in recurrent glioblastoma (GBM) are not durable. Plasma levels of basic fibroblast growth factor (bFGF) increase at the time of tumor progression. By concomitantly targeting vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and FGF receptor (FGFR) pathways, the multikinase inhibitor ponatinib may potentially help overcome some of the putative mechanisms of resistance and demonstrate antitumor effects. Methods: We performed a phase II trial of ponatinib in patients with bevacizumab-refractory GBM. Adult patients with KPS ≥ 60, measurable disease, normal organ and marrow function received ponatinib at 45 mg daily. No limit on the number of prior therapies but only one prior bevacizumab-containing regimen was allowed. Primary endpoint was 3-month progression free survival (PFS3). Based on a Simon optimal two-stage design, the trial was powered to discriminate between a 15% and 35% PFS3 rate, with an alpha error 0.10 and beta error 0.2. Plasma biomarkers of angiogenesis and inflammation were evaluated before and after treatment. Results: The study closed after the first stage. Fifteen patients enrolled, median age 62 [28-75], median KPS 80 [70-90], median number of prior relapses 2 [2-4]. PFS3 rate was 0, median OS was 98 days [95% CI 56, 257] and median PFS was 28 days [95% CI 27, 30]. No responses were seen, and 2 patients had SD (13%). Grade 3 adverse events possibly related to ponatinib included fatigue (n = 3), hypertension (2), lipase elevation (2), ALT elevation (1), AST elevation (1), GGT elevation (1), and lymphopenia (1). There were no grade 4 or 5 events attributable to treatment. Ponatinib treatment significantly increased plasma soluble (s)VEGFR1, sVEGFR2, sTIE2, VEGF, IFNγ, TNF-a, IL-6, IL-8, and IL-10 rapidly (at day 1) and persistently (until the end of treatment). Conclusions: Ponatinib was tolerated but associated with minimal activity in bevacizumab-refractory GBM patients. Circulating biomarker data indicate potent anti-VEGFR activity, and suggested that resistance to ponatinib may be related to inflammation. Clinical trial information: NCT02478164.
The use of chemotherapy in elderly patients with metastatic non-small cell lung cancer: A National Cancer Database analysis.
Authors: Lara Ann Kujtan, Varsha Muthukumar, Kevin F Kennedy, Ashiq Masood, Janakiraman Subramanian
Journal: Journal of Clinical Oncology (2018)

e21235 Background: The median age at diagnosis of lung cancer is 70 years, and prospective studies have shown clear survival benefit for chemotherapy in elderly patients. However there are limited data on the use of chemotherapy and outcomes in patients over 80 years. We used the National Cancer Database (NCDB) to evaluate treatment patterns and outcomes for elderly patients with advanced non-small cell lung cancer (NSCLC). Methods: The NCDB was used to identify elderly patients with metastatic NSCLC diagnosed between 2004 and 2014. Elderly patients were defined as age ≥80 years. One-way ANOVA was used to compare continuous variables and chi-squared testing or Fisher’s exact testing were used to compare categorical variables. Hazard ratios were obtained via multivariable logistic regression analyses (MV). Results: We identified 38,498 elderly patients diagnosed with advanced NSCLC. Less than one-third (29%) received chemotherapy, although those who did had better overall survival (7.4 months vs 1.9 months, p< 0.001). MV showed decreased mortality with chemotherapy; patients treated at academic facilities fared better, and patients with Charlson-Deyo comorbidity score > 1 fared worse (Table 1). Patients aged 80-84 years who received chemotherapy had a median survival of 7.6 months and 1-year survival of 32.5%, similar to patients aged 85 or above who had a median survival of 7.0 months and 1-year survival of 30.9%. We also found that the proportion of elderly patients diagnosed with metastatic NSCLC increased over time while the use of chemotherapy appeared to decline. Conclusions: Chemotherapy improved overall survival in elderly patients with advanced stage NSCLC. Choice of treating facility and multiple comorbidities had significant impact on outcomes. Despite an increase in the proportion of elderly patients diagnosed with advanced NSCLC less than one-third receive chemotherapy. Table 1. Variable Hazard Ratio p-value Chemotherapy 0.46 (0.44,0.47) < 0.001 Facility Comprehensive vs Community 0.95 (0.92,0.98) 0.002 Academic vs Community 0.85 (0.82,0.88) < 0.001 Integrated vs Community 0.95 (0.91,0.99) 0.026 Charlson-Deyo score 1 vs 0 1.16 (1.13,1.19) < 0.001 > 1 vs 0 1.31 (1.27,1.35) < 0.001
Impact of high-deductible insurance on breast cancer care among lower-income women.
Authors: James Frank Wharam, Fang Zhang, Christine Lu, Anita K. Wagner, Larissa Nekhlyudov, Craig Earle, Soumerai Stephen, Dennis Ross-Degnan
Journal: Journal of Clinical Oncology (2018)

6560 Background: High-deductible health plans (HDHP) are increasingly common but delay important breast cancer diagnostic tests and treatment. We hypothesized that such delays would be especially pronounced among lower-income HDHP members. Methods: We used 2004-2012 data from a large US health insurer and a pre-post controlled survival design. We included 152,155 lower-income HDHP group members age 25-64 without evidence of breast cancer. These women were continuously enrolled for 1 year in a low-deductible (≤$500) plan followed by up to 4 years in a HDHP (≥$1000) after an employer-mandated switch. The comparison group included 1,316,548 contemporaneous, coarsened exact-matched lower-income women whose employers offered only low-deductible plans. Measures were times to first diagnostic breast imaging, breast biopsy, incident early-stage breast cancer diagnosis, and breast cancer chemotherapy. Outcomes were analyzed using Cox survival models adjusted for baseline patient characteristics. We also analyzed measures among 120,755 high-income HDHP members and their 1,095,592 high-income matched controls. Results: After the index date, lower-income HDHP members experienced delays in receipt of breast cancer diagnostic imaging (adjusted hazard ratio, aHR: 0.93 [0.92,0.95]), biopsy (0.89 [0.86,0.93]), early-stage breast cancer diagnosis (0.89 [0.80,0.98]), and chemotherapy initiation (0.80 [0.71,0.90]) compared with controls. Corresponding hazard ratios among high-income HDHP members (0.96 [0.95,0.98], 0.93 [0.89,0.97], 0.77 [0.69,0.85], and 0.76 [0.68,0.86], respectively) were similar to those of lower-income HDHP members and confidence intervals overlapped. Findings were also similar when analyzing an even lower income HDHP subgroup. Conclusions: Both lower-income and high-income women who were switched to HDHPs experienced delays in diagnostic breast imaging, breast biopsy, early-stage breast cancer diagnosis, and chemotherapy initiation. Further research should determine if such delays cause adverse health outcomes. Oncologists, primary care physicians, and population health managers should consider HDHPs a risk factor for delayed breast cancer services.
Co-mutations of DNA damage response system as predictive biomarker for immune checkpoint blockades.
Authors: Zhijie Wang, Jing Zhao, Guoqiang Wang, Fan Zhang, Yuzi Zhang, Hua Dong, Xiaochen Zhao, Jianchun Duan, Hua Bai, Yanhua Tian, Rui Wan, Lei Xiong, Shangli Cai, Tony Mok, Jie Wang
Journal: Journal of Clinical Oncology (2018)

3024 Abstract Background: Selecting appropriate biomarkers for immune checkpoint blockades (ICBs) remains a clinical challenge. Quantitative biomarkers, for instance, PD-L1 expression or tumor mutation burden, are limited by their vague cut-off value, intra-tumor heterogeneity distribution and dynamic alterations. Qualitative biomarkers, including dMMR/MSI-H, are potent predictors, but merely a minority of patients harbor this abnormality. Therefore, a more prevalent biomarker would be highly desirable. In humans, DNA damage response (DDR) system is indispensable in maintaining genomic integrity. We hypothesize genetic mutations of DDR pathways may increase genomic instability and manifest as up-regulated neoantigen load and TMB, contributing to higher susceptibility to immune checkpoint blockades (ICBs). Methods: Whole-exome sequencing data from 8552 solid tumors, across 29 cancer types from The Cancer Genome Atlas were included for analysis. The expression signatures of immune genes were compared across distinct DDR subgroups. Statistics concerning the correlation between DDR pathway mutations and treatment outcomes were evaluated in four cohorts treated with ICBs. Results: Co-mutations of HRR-MMR or HRR-BER pathways (defined as co-mut +) were correlated with higher neoantigen load and TMB. Co-mut + exhibited anabatic levels of immune gene expression signatures, including genes related to T-effector, IFNγ pathway, T cell receptors and tumor micro-environment. In these four validation cohorts, the progression-free survival (PFS) was longer in co-mut + patients with non-small cell lung cancer (NSCLC) than co-mut – (median, not reached vs. 4.1 months, P = 0.02) and the overall survival was longer in co-mut + melanoma patients than co-mut – (median, 32.4 vs. 10.8 months, P = 0.04). Subgroup analysis of NSCLC cohort demonstrated that co-mut + is predictive to longer PFS in patients with PD-L1 expression < 50% (median, 8.3 vs. 2.7 months, P = 0.03) or low TMB (median, not reached vs. 3.8 months, P = 0.04). Conclusions: Co-mutations of HRR-MMR or HRR-BER are a potential prognostic biomarker for ICBs immunotherapy, and warrant future prospective investigations.
The association of physical activity before and after lymphoma diagnosis with survival outcomes
Authors: Priyanka A. Pophali, Andrew Ip, Melissa C. Larson, Allison C. Rosenthal, Matthew J. Maurer, Christopher R. Flowers, Brian K. Link, Umar Farooq, Andrew L. Feldman, Cristine Allmer, Susan L. Slager, Thomas E. Witzig, Thomas M. Habermann, Jonathon B. Cohen, James R. Cerhan, Carrie A. Thompson
Journal: American Journal of Hematology (2018)

Abstract The impact of physical activity (PA) on lymphoma survival is not known. The association of PA and change in PA with overall (OS), lymphoma‐specific (LSS) and event‐free (EFS) survival was evaluated in a prospective cohort of newly diagnosed lymphoma patients (2002‐2012). We calculated Leisure Score Indexes (mLSI) from the self‐reported usual adult PA (baseline) and at 3‐years post‐diagnosis (FU3), grouping patients by active vs insufficiently active by the American Cancer Society PA guidelines. Associations of PA with survival were assessed using hazard ratios (HRs) and 95% confidence intervals (CI) from Cox models stratified by lymphoma subtype, adjusted for age, sex, baseline BMI, and comorbidity score with change scores further adjusted for baseline PA. Three thousand sixty participants were evaluable at baseline and 1371 at FU3. Active patients had superior survival from baseline [HR (CI): OS 0.82 (0.72‐0.94); LSS 0.74 (0.61‐0.90); EFS 0.92 (0.82‐1.02)] and FU3 [HR (CI): OS 0.64 (0.46‐0.88); LSS 0.32 (0.18‐0.59); EFS 0.82 (0.61‐1.10)] compared to insufficiently active. An increase in mLSI from baseline to FU3 (vs stable mLSI) was associated with superior OS (HR = 0.70, CI 0.49‐1.00) and LSS (HR = 0.49, CI 0.26‐0.94).The continuous change in mLSI at FU3 was significantly associated with OS, LSS and EFS; maintained across subgroups and appeared linear. Higher PA among lymphoma patients at diagnosis and 3 years is significantly associated with OS, LSS, and EFS. Increasing PA after diagnosis is significantly associated with improved OS and LSS supporting an important role for PA in lymphoma survivorship and the need for intervention trials.
Epicardial Left Atrial Appendage Exclusion Reduces Blood Pressure in Patients With Atrial Fibrillation and Hypertension
Authors: Mohit K. Turagam, Venkat Vuddanda, Niels Verberkmoes, Toshiya Ohtsuka, Ferdi Akca, Donita Atkins, Sudharani Bommana, Maximilian Y. Emmert, Rakesh Gopinathannair, Gansevoort Dunnington, Abdi Rasekh, Jie Cheng, Sacha Salzberg, Andrea Natale, James Cox, Dhanunjaya R. Lakkireddy
Journal: Journal of the American College of Cardiology (2018)
DNA methylation footprints during soybean domestication and improvement
Authors: Yanting Shen, Jixiang Zhang, Yucheng Liu, Shulin Liu, Zhi Liu, Zongbiao Duan, Zheng Wang, Baoge Zhu, Ya-Long Guo, Zhixi Tian
Journal: Genome biology (2018)

In addition to genetic variation, epigenetic variation plays an important role in determining various biological processes. The importance of natural genetic variation to crop domestication and improvement has been widely investigated. However, the contribution of epigenetic variation in crop domestication at population level has rarely been explored. To understand the impact of epigenetics on crop domestication, we investigate the variation of DNA methylation during soybean domestication and improvement by whole-genome bisulfite sequencing of 45 soybean accessions, including wild soybeans, landraces, and cultivars. Through methylomic analysis, we identify 5412 differentially methylated regions (DMRs). These DMRs exhibit characters distinct from those of genetically selected regions. In particular, they have significantly higher genetic diversity. Association analyses suggest only 22.54% of DMRs can be explained by local genetic variations. Intriguingly, genes in the DMRs that are not associated with any genetic variation are enriched in carbohydrate metabolism pathways. This study provides a valuable map of DNA methylation across diverse accessions and dissects the relationship between DNA methylation variation and genetic variation during soybean domestication, thus expanding our understanding of soybean domestication and improvement.
HepaVac-101 first-in-man therapeutic cancer vaccine phase I/II clinical trial for hepatocellular carcinoma patients.
Authors: Luigi Buonaguro, Andrea Mayer-Mokler, Roberto Accolla, Yuk Ting Ma, Regina Heidenreich, Antonio Avallone, Ester Simeone, Alfred Koenigsrainer, Markus Loeffler, Cecile Gouttefangeas, Christian Flohr, Joerg Ludwig, Hans-Georg Rammensee, Mercedes Iñarrairaegui, Sven Francque, Tanguy Chaumette, Toni Weinschenk, Carsten Reinhardt, Senta Ulrike Gnad-Vogt, Harpreet Singh
Journal: Journal of Clinical Oncology (2018)

TPS3135 Background: HCC is the third leading cause of death from cancer globally with an extremely variable 5-year survival rate. The HepaVac-101 phase I/II, first-in-man, therapeutic cancer vaccine single-arm clinical trial is performed as part of the HepaVac project, funded by the European Commission's 7th Framework Program under the Grant Agreement Nr. 602893 (www.hepavac.eu). The HepaVac-101 trial identification numbers are NCT03203005 (Clinical trials.gov) and 2015-003389-10 (EudraCT). and Methods: The therapeutic cancer vaccine IMA970A is a multi-peptide-based HCC vaccine composed of 16 newly discovered and overexpressed tumor-associated peptides (TUMAPs) directly identified from resected HCC tissues. Of these TUMAPs, 7 are restricted to HLA-A*02, 5 to HLA-A*24 and 4 to HLA class II. CV8102 is a novel RNA based immunostimulatory agent inducing a balanced Th1/Th2 immune response. A total of 40 patients with very early, early and intermediate stage of HCC are enrolled to be treated with a single pre-vaccination infusion of low-dose cyclophosphamide, followed by 9 intradermal vaccinations consisting of IMA970A plus CV8102. The study drugs are applied without concomitant anti-tumor therapy, in order to reduce risk of tumor recurrence/progression in patients having received all indicated standard treatments and without evidence of active disease. The primary endpoints of the HepaVac-101 clinical trial are safety, tolerability, and immunogenicity. Secondary/exploratory endpoints are additional immunological parameters in circulation, infiltrating T-lymphocytes in tumor tissue, biomarkers in blood and tissue, DFS/PFS and OS. Once safety of this vaccination approach has been established in the first 10 patients the addition of a checkpoint inhibitor will be considered. Suitable patients enrolled at Tuebingen are invited to participate in a trial extension investigating an actively personalized vaccine (APVAC). The HepaVac-101 trial is conducted in 6 centers located in 5 European countries. Five centers are actively recruiting patients. As of the time of abstract submission, 4 HCC patients have been screened for HLA haplotype and 1 is eligible for vaccination. Clinical trial information: NCT03203005.
TCT-494 Influence of High Device Positioning on Outcomes after Transcatheter Aortic Valve Replacement with Contemporary Self-Expanding Valves
Authors: Zhen-Gang Zhao, Hasan Jilaihawi, Cezar Staniloae, Eleonora Vapheas, Run Du, Moyang Wang, Muhamed Saric, Peter Neuburger, Michael Querijero, Alan Vainrib, Kazuhiro Hisamoto, Nicholas Amoroso, Tara Collins, Emily Clark, Illya Pushkar, Tonya Robin, Danielle Sin, Binita Shah, Zachary Taylor, Hanah Lee, Samantha Vidal, Daniel Bamira, Ricardo Benenstein, Mathew Williams
Journal: Journal of the American College of Cardiology (2018)