tbuckley/cabot-search huggingface dataset:
Angiogenic factor and cytokine analysis among patients with renal cell carcinoma treated with adjuvant VEGFR TKIs.
Authors: Wenxin Xu, Maneka Puligandla, Naomi B. Haas, Keith Flaherty, Robert Uzzo, Janice P. Dutcher, Robert S. DiPaola, Rupal Satish Bhatt
Journal: Journal of Clinical Oncology (2019)

586 Background: VEGFR TKIs are important therapeutic agents in RCC, but their adjuvant use remains limited. Investigating the effects of these medications on circulating angiogenic factors and cytokines in the adjuvant setting can elucidate whether changes in cytokine levels result from drug-host or drug-tumor interactions, and may reveal biomarkers to guide patient selection for adjuvant treatment. Methods: In the ECOG-ACRIN 2805 (ASSURE) trial, patients with resected RCC were randomized to sunitinib, sorafenib, or placebo. Plasma was collected at start of treatment and 4 or 6 weeks after treatment initiation. All paired samples available by July 2010 were analyzed, corresponding to 413 patients. We analyzed VEGF, PlGF, sFlt1, KDR/sVEGFR-2, Ang2, bFGF, HGF, IFNg, IL8, CXCL9, CXCL10, and CXCL11. Mixed effects models were used to test for changes from baseline. Cox models were used to assess associations between disease-free survival (DFS) and angiogenic factor and cytokine levels. Results: VEGF and PlGF increased after 4 weeks on either treatment (p &lt; 0.0001 for both), and at 6 weeks VEGF and PIGF levels returned to baseline for patients on sunitinib (corresponding to the 2 week break in the sunitinib schedule) but not sorafenib. Levels of sFLT-1 decreased after 4 weeks on suntinib and after 6 weeks on sorafenib (p &lt; 0.0001). sVEGFR2 decreased after both 4 and 6 weeks of treatment on both sunitinib and sorafenib (p &lt; 0.0001). Patients on placebo had no significant changes in circulating angiogenic factor or cytokine levels. CXCL-10 levels increased after 4 weeks on both sunitinib and sorafenib but not on placebo, and remained elevated at 6 weeks on sunitinib. Higher baseline CXCL-10 was associated with worse DFS (HR 1.41 per log increase in CXCL-10, Holm adjusted p-value 0.003, 95% CI 1.18-1.70). This remained significant after adjustment for T-stage, Fuhrman grade, and ECOG PS. Conclusions: Among patients treated with VEGFR TKIs in the adjuvant setting for RCC, drug-host interactions mediate changes in cytokines and angiogenic factors. Elevated CXCL-10 prior to treatment was associated with higher recurrence risk. Studies to understand the functional consequences of these changes are underway.
Genomic biomarkers to predict outcome in Gleason Score 9-10 disease.
Authors: Amar Upadhyaya Kishan, Tahmineh Romero, David Elashoff, Tristan Grogan, Matthew Rettig, Robert Evan Reiter, Phuoc T. Tran, Paul L. Nguyen, Nicholas George Nickols, Elai Davicioni, Daniel Eidelberg Spratt, Felix Y Feng, Joanne B. Weidhaas
Journal: Journal of Clinical Oncology (2019)

44 Background: Gleason score (GS) 9-10 prostate cancer (PCa) has classically been considered the most aggressive form of clinically localized disease. However, outcomes remain heterogeneous. Whether specific biomarkers may help guide prognostication within GS 9-10 disease remains unknown. Methods: Microarray-derived gene expression data were obtained from six retrospective radical prostatectomy cohorts (n=1076) and two prospective cohorts with data from the Decipher GRID (n=7000). A total of 957 patients had GS 9-10 disease. Clinical outcomes data (i.e., distant metastasis [DM] and prostate cancer-specific mortality [PCSM]) were available for 1077 patients (201 with GS 9-10 disease). We filtered for genes with high expression levels and differential expression between GS 9-10 and GS ≤8 (via Wilcoxon test with adjustment for false discovery rate [FDR]), and then used using weighted gene co-expression network analysis [WGCNA] to identify distinct modules. Genes with both a low p-value and a high connectivity within each module were included as potential predictors in logistic regression models constructed using elastic net regularization. We also chose genes within the GS 9-10 cohort with q-value &lt;0.01 and &lt;0.3 after FDR correction for outcomes of DM and PCSM, respectively. We used the cross-validated AUC for quantifying the discrimination of each gene set. Results: We identified a set of 12 genes with an AUC of 0.81 for discriminating GS 9-10 vs. GS ≤8. A separate set of 7 genes had an AUC of 0.83 for predicting DM within GS 9-10 patients, compared with an AUC of 0.68 within GS ≤8 patients. A third set of 13 genes had an AUC of 0.93 for predicting PCSM within GS 9-10 patients, but an AUC of only 0.57 for predicting PCSM within GS ≤8. Conclusions: These data suggest that a genomic biomarker signature can strongly discriminate GS 9-10 from GS ≤8. Separate gene sets can also predict DM and PCSM within GS 9-10 patients with high fidelity, but are not as predictive of these outcomes within GS ≤8 patients. These data support the hypothesis that GS 9-10 disease is a biologically distinct yet heterogeneous entity, and biomarker discovery efforts to better guide upfront treatment intensification in this subset are feasible and warranted. (NCT02609269).
Abstract P291: Racial/Ethnic Differences in the Shopping Behaviors and Fruit and Vegetable Consumption of Low-Income Farmers Market Incentive Program Users in Illinois
Authors: Chelsea R Singleton, Nicollette Kessee, Corey Chatman, Connie Spreen
Journal: Circulation (2019)

Introduction: Studies have shown that low-income populations in the US often consume fewer servings of fruits and vegetables (FVs) per day compared to higher income populations. Farmers market incentive programs provide monetary incentives to Supplemental Nutrition Assistance Program (SNAP) participants to support their procurement of fresh FVs. Information on the racial/ethnic differences in FV consumption among SNAP participants who utilize farmers market incentive programs is scarce. This research aimed to address this need by examining racial/ethnic differences in the farmers market shopping behaviors and frequency of FV consumption among users of the Link Match program in Illinois. We hypothesized that Non-Hispanic Black program users will consume FVs less frequently than Non-Hispanic White users. Methods: A cross-sectional evaluation of 328 Link Match users (39.6% Non-Hispanic White; 45.4% Non-Hispanic Black; and 15.0% Other) was conducted during the 2016 and 2017 farmers market seasons in Illinois. Information on user demographics, farmers market shopping behaviors, and frequency of FV consumption in the prior month was collected. Chi-square and ANOVA tests were used to assess racial/ethnic differences in farmers market shopping behaviors. Multivariable-adjusted logistic regression models were used to examine the association between race/ethnicity and daily consumption of FVs among program users. Results: A significantly higher percentage of Non-Hispanic Black Link Match users reported being an infrequent farmers market user (i.e., shopping ≤ once a month) compared to Non-Hispanic White and Other users (p = 0.01). After adjusting for covariates (i.e., demographics, market location), Non-Hispanic Black users had lower odds of consuming fruit daily (OR: 0.44; 95% CI: 0.22-0.86) compared to Non-Hispanic White users. Other users had lower odds of consuming vegetables daily (OR: 0.30; 95% CI: 0.12-0.71) compared to Non-Hispanic White users. Conclusions: Significant racial/ethnic differences in shopping behaviors and FV consumption were observed among Link Match users in Illinois. Future research should examine the nutritional and health implications of these differences.
A phase Ib study of neoadjuvant immune biomarker modulation with cetuximab and motolimod in head and neck cancer (HNC).
Authors: Benjamin Alexander Kansy, Sandra Poveda Gibson, Raghvendra Mohan Srivastava, James Kyle Bryan, Robert Mark Hershberg, Robert L. Ferris
Journal: Journal of Clinical Oncology (2015)

TPS3092 Background: HNC is an immunosuppressive disease, with low absolute lymphocyte counts, impaired activity of effector cells such as natural killer cells (NK), and poor antigen-presenting function. The anti-EGFR monoclonal antibody cetuximab (CTX) prolongs survival in HNC, but only in a subset of patients. This limited efficacy may be due to immunosuppressive cells such as myeloid derived suppressor cells and suppressive macrophages. The clinical efficacy of CTX may be augmented by immune stimulation. Motolimod (formerly VTX-2337) is a novel Toll-like receptor 8 (TLR8) agonist which stimulates myeloid dendritic cells, monocytes, and NK cells. Preclinical data have demonstrated enhanced CTX and NK cell-mediated lysis of HNC cells and dendritic cross-priming of EGFR-specific CD8+ T cells. CTX and motolimod in HNC patients was tolerable and active in a phase Ib study, with enhanced mobilization and activation of NK cells. Our hypothesis is that the differential clinical response of HNC to treatment with CTX and motolimod reflects the role of cellular immune activation, immune escape mechanisms, and TLR8 stimulation enhancement of the immune response in the circulation and in the tumor microenvironment. Methods: This is a prospective phase Ib clinical trial (NCT02124850) of preoperative treatment with CTX and motolimod. The primary objective is to determine the extent to which the administration of neoadjuvant CTX plus motolimod modulates immune biomarkers in peripheral blood and HNC tumors. An exploratory objective of the study is to assess whether this modulation of biomarkers can predict anti-tumor response. Subjects must have HNC stage II–IVA and be surgical candidates. CTX and motolimod will be administered for a 3–4 week preoperative period. Immune biomarkers will be quantitatively assessed. The biomarker modulation and biopsies of skin/acneiform rash will be studied in correlation with clinical response by CT or MRI scan. Tumor apoptosis/proliferation will be assessed by biopsy pre- and post- treatment with CTX /motolimod. All patients will receive definitive surgical resection. Enrollment target is fifteen complete specimens (tumor, peripheral blood mononuclear cells and serum). Clinical trial information: NCT02124850.
Sarcopenia in bladder cancer patients is an unmodifiable outcomes predictor.
Authors: Gregory John Barton, Jeanette Wang, Andrew Chang, Wei Phin Tan, Joseph J Fantony, Paul E Wischmeyer, Rajan T. Gupta, Brant Allen Inman
Journal: Journal of Clinical Oncology (2019)

480 Background: Sarcopenia, a severe loss of skeletal muscle mass, predicts poor outcomes in bladder cancer (BC). But, why sarcopenia occurs in BC is unknown. Our objective was to assess if diet and physical activity were the primary factors causing sarcopenia, and thus assess if sarcopenia could be addressed by lifestyle interventions. Methods: 286 patients filled out the International Physical Activity Questionnaire Long Form (IPAQ-L) and the Diet History Questionnaire II (DHQ2), had a CT abdomen/pelvis within 6 months of questionnaire administration and met inclusion criteria. The DHQ2 was converted into Healthy Eating Index 2010 scores (HEI2010). Skeletal muscle area (SM, cm 2 ) area was measured at the L3 level using Slice-O-Matic software and divided by height (m 2 ) to arrive at skeletal muscle index (SMI). Sarcopenia was defined as SMI &lt; 52.4 in men and &lt; 38.5 in women. Three raters read the images and inter-rater reliability was measured by the intra-class correlation coefficient (ICC). Associations among patient demographics, tumor characteristics, physical activity, diet quality, and body composition were examined by stratified analyses and regression models with R 3.2.3. Results: Reliability was very high, ICC=0.97. Sarcopenia was present in 71% of males and 55% of females. Key predictors of decreasing SMI included increasing age (p &lt; 0.001), female gender (p &lt; 0.001), and white race (p &lt; 0.001). When adjusted for these unmodifiable patient factors, there was no association between SMI and variables such as Elixhauser comorbidity score, AJCC stage, tumor grade, and procedure type. With respect to modifiable lifestyle factors, there was no association between SMI and average weekly MET-min of physical activity level (p = 0.99) nor the daily consumption of calories (p = 0.69), protein (p = 0.28), fat (p = 0.19), or carbohydrate (p = 0.77). The HEI2010 diet score was not associated with SMI (p = 0.66). Conclusions: The three strongest predictors of decreasing muscle mass (i.e. sarcopenia) in BC patients are age, gender, and race. Modifiable risk factors, such as diet and physical activity levels, did not affect sarcopenia. Therefore, we would not expect that targeted lifestyle interventions would affect sarcopenia and improve BC outcomes.
How Businessmen May Reform Health Care Cost
Authors: Surafel Tsega
Journal: Annals of Internal Medicine (2019)

Letters19 March 2019How Businessmen May Reform Health Care CostSurafel Tsega, MDSurafel Tsega, MDThe Mount Sinai Hospital, New York, New York (S.T.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0638 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read McMahon and Chopra's commentary (1) with interest. In 2015, a disrupter emerged with no experience in medicine or science, only an idea that, if true, was revolutionary: A simple pinprick could change the way patients underwent blood testing. That idea, unfortunately, proved not to be true (let alone revolutionary) and instead was the impetus for an investigation of fraud (2). We should be mindful of this story of Theranos as we speculate on the announcement in 2018 of another attempt to disrupt the health care industry with the goal of padding profit.The failures of ...References1. McMahon LF, Chopra V. Starving the hungry tapeworm: how businessmen may reform health care cost. Ann Intern Med. 2018;169:120-1. [PMID: 29809240]. doi:10.7326/M18-0432 LinkGoogle Scholar2. Carreyrou J. Hot startup Theranos has struggled with its blood-test technology. The Wall Street Journal. 16 October 2015. Accessed at www.wsj.com/articles/theranos-has-struggled-with-blood-tests-1444881901 on 11 June 2018. Google Scholar3. Papanicolas I, Woskie LR, Jha AK. Health care spending in the United States and other high-income countries. JAMA. 2018;319:1024-1039. [PMID: 29536101] doi:10.1001/jama.2018.1150 CrossrefMedlineGoogle Scholar4. Keefe PR. The family that built an empire of pain. The New Yorker. 30 October 2017. Accessed at www.newyorker.com/magazine/2017/10/30/the-family-that-built-an-empire-of-pain on 11 June 2018. Google Scholar5. Kliff S. An ER visit, a $12,000 bill—and a health insurer that wouldn't pay. Vox. 29 January 2018. Accessed at www.vox.com/policy-and-politics/2018/1/29/16906558/anthem-emergency-room-coverage-denials-inappropriate on 11 June 2018. Google Scholar Author, Article, and Disclosure InformationAffiliations: The Mount Sinai Hospital, New York, New York (S.T.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0638. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoStarving the Hungry Tapeworm: How Businessmen May Reform Health Care Cost Laurence F. McMahon Jr. and Vineet Chopra Metrics 19 March 2019Volume 170, Issue 6Page: 428-429KeywordsConflicts of interestDisclosureHealth careHealth care qualityHealth care sectorHematologic testsOpioidsPatients ePublished: 19 March 2019 Issue Published: 19 March 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Higher Monocyte Chemoattractant Protein-1 Levels in Myelofibrosis Are Sustained By the rs1024611 Single Nucleotide Polymorphism and Correlate with Disease Subtype and Severity
Authors: Elena Masselli, Giulia Pozzi, Cecilia Carubbi, Luca Pagliaro, Elena Follini, Benedetta Cambò, Monica Crugnola, Giuliana Gobbi, Prisco Mirandola, Franco Aversa, Marco Vitale
Journal: Blood (2018)
A retrospective analysis of the role of proton pump inhibitors on colorectal cancer disease survival.
Authors: Ravi Ramjeesingh, Cassandra Graham, Christine Orr, Corey Sean Bricks, Wilma M Hopman, Nazik Hammad
Journal: Journal of Clinical Oncology (2015)

e14517 Background: Proton pump inhibitors (PPI) are one of the most commonly used medications. A limited number of studies have identified a weak-to-moderate association between PPI use and colorectal cancer (CRC) risk but none to date have identified an effect of PPI on CRC survival. Methods: To identify a potential association between PPI and colorectal cancer survival, we performed a retrospective chart review of CRC patients treated at the Cancer Center of Southeastern Ontario diagnosed from January 2005 to December 2011. 1304 colorectal cancer patient charts were identified through Ontario Cancer Registry Data based on confirmed ICD-10 diagnosis codes and patient, tumor and treatment variables were extracted into the database. Results: Preliminary analysis indicated that 117 (9.0%) patients were using PPIs at the time of oncology consult. Those on PPI were more often on ASA (38.5% vs 19.3%, p < 0.0001) and statins (38.5% vs 23.3%, p = 0.0005) and were found have a statistically significantly higher rate of cardiac disease (78.6% vs 57.4%, p < 0.0001). There was no identifiable difference in the tumor characteristics between the 2 groups, including tumor location, differentiation, lymph node status and stage. Univariate analysis identified a non-statistically significant difference in survival with those on PPI having a decrease in 1, 2 and 5 yr OS (Table). Multivariate Cox regression analysis, when taking into account patient demographics (sex, age, comorbidities, BMI, smoking and alcohol history) and tumor characteristics (including stage, differentiation and nodal status) identified a statistically significant effect of PPI on risk of dying in our patient population (HR = 1.350, C.I 1.006-1.813, p = 0.046). Conclusions: Taken together, our work suggests a potential adverse effect of PPI on overall survival of colorectal cancer patients. PPIs # of Deaths N (%) 1 yr OS % (p-value) 2 yr OS % (p-value) 5 yr OS % (p-value) No 451/1187 (38.0) 86.7 (ref) 76.8 (ref) 62.9 (ref) Yes 55/117 (47.0) 82.1 (0.161) 70.1 (0.111) 55.2 (0.1651)
Abstract MP70: Impact of Systematic Approaches to Tobacco Treatment: The Ottawa Model for Smoking Cessation
Authors: Mustafa Coja, Kerri-Anne Mullen, Robert Reid, Andrew Pipe
Journal: Circulation (2019)

Introduction: Tobacco use is the largest preventable cause of death. It is a major risk factor for each of the leading chronic diseases, including cancer, heart disease, stroke, and respiratory illness. Smoking cessation is the single most powerful preventive intervention available. The Ottawa Model for Smoking Cessation (OMSC) is a systematic, comprehensive approach to clinical tobacco dependence treatment. It is designed to assist health professionals to transform clinical practice through knowledge translation, implementation support, and quality evaluation. Hypothesis: We assessed the hypothesis that with the addition of a systematic approach to addressing tobacco use, an increase in provider-level support would be realized. Methods: Using a detailed Workplan, OMSC Outreach Facilitators work with sites to adapt their clinical practices and to implement an evidence-based smoking cessation program. This process is comprised of six phases of step-by-step instructions for planning, implementing, evaluating and sustaining an evidence-based clinical cessation system. Metrics are collected on smoking status, brief yet strategic advice to stop smoking, rates of delivery of evidence-based cessation support, and patient quit rates. Data from Electronic Medical Records and from the OMSC patient database are used to measure program outcomes. Results: Over 440 organizations have implemented the OMSC resulting in thousands of healthcare providers across Canada being trained on the latest clinical approaches to smoking cessation. Collectively, the OMSC network has intervened with more than 400,000 patients, providing them with evidence-based interventions. An analysis of almost 4,000 patients within the OMSC primary care network has shown significant increases of rates of Ask, Advise and Act among providers after implementing the program. For patients referred to the OMSC follow-up program, smoking status was assessed for the primary care and hospital programs, respectively. In 2017-18, 60 day outcomes for primary care patients indicated that 22%-57% (125 of 561; 125 of 218) were smoke-free at this time point. For hospitalized patients who reached the 180 day time point, the range was found to be 18%-48% (1156 of 6473; 1156 of 2399). The lower range represents all patients, assuming those not reached have returned to smoking, while the upper range represents only those patients who were reached by the OMSC follow-up program. Conclusions: With the application of a systematic, evidence-based program, there was an increase in the rates of delivery of smoking cessation best practices by healthcare providers. As a result, more patients made further assisted quit attempts resulting in long-lasting quit rates. The OMSC program has shown to be effective in changing provider behaviour with respect to smoking cessation, and in turn, has helped to increase quit rates among patients who smoke.