tbuckley/cabot-search huggingface dataset:
Gastric cancer staging in the era of neoadjuvant therapy and its prognostic implications.
Authors: Gina Kim, Patricia Friedmann, Peter Muscarella, John Christopher McAuliffe, Haejin In
Journal: Journal of Clinical Oncology (2019)

22 Background: Increasingly patients are undergoing neoadjuvant therapy for gastric cancer. The relationship between stage-based prognostic information available prior to treatment (cStage), after surgery (ypStage), and difference between cStage and ypStage (delta) remains unclear. We aim to describe the relationship between cStage and ypStage as relates to survival for gastric cancer patients. Methods: Data from the National Cancer Data Base (NCDB) from 2004-2015 was used for the analysis. Patients with gastric adenocarcinoma who received neoadjuvant therapy then underwent surgery were included. Kaplan Meier curves were used to model survival. Harrell’s C-statistics obtained from Cox Regression models were reported. Results: 9,959 patients met our inclusion criteria. Increases in cStage, ypStage and delta (ypStage-cStage) were associated with worse survival. Median overall survivals for cStages 1-4 were: 53.8, 39.5, 29.2, 20.9 months (logrank test, p&lt;0.0001). Median survivals for ypStage 0-4 were: 95.4, 89.7, 36.9, 23.4, 16.0 months (logrank test, p&lt;0.0001). Survival was further stratified by delta. A representative table comparing cStage 2 and ypStage 2 is shown below. A cox regression model with cStage as predictor of survival yielded a Harrell’s C-statistic of 0.555; when delta was added to the model, the C-statistic increased to 0.638. Separately, a Cox-regression model with ypStage as predictor yielded a C-statistic of 0.632; when delta was added to this model, the C-statistic increased negligibly to 0.638. Conclusions: Prognostic accuracy using cStage prior to treatment improved when tumor responsiveness was considered while this was not the case for ypStage. Pre-surgical prognostic information should be provided with a caveat that treatment response will influence survival. Post-surgery, the clinical stage is less relevant and ypStage can be used alone in providing prognostic information. [Table: see text]
Abstract 022: Cost-Effectiveness of Financial Incentives and Disincentives for Improving Diet and Health Through the Supplemental Nutrition Assistance Program
Authors: Junxiu Liu, Dariush Mozaffarian, Stephen Sy, Yue Huang, Yujin Lee, Parke Wilde, Shafika Abrahams-Gessel, Thiago de Souza Veiga Jardim, Tom Gaziano, Renata Micha
Journal: Circulation (2018)

Introduction: The 2018 Farm Bill represents a major opportunity to reduce disparities in diet and health. The largest component is the Supplemental Nutrition Assistance Program (SNAP), feeding 1 in 6 Americans. Potential options include subsidizing fruits &amp; vegetables (F&amp;V), restricting sugar-sweetened beverages (SSBs), or implementing a broader food incentive/disincentive framework that preserves choice. Their comparative health impacts and cost-effectiveness are not established. Methods: Using a validated microsimulation model (CVD PREDICT), we estimated changes in CVD events, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of 3 policy scenarios in SNAP adults: 1) 30% subsidy on F&amp;V; 2) 30% F&amp;V subsidy + SSB restriction; and 3) 30% subsidy on F&amp;V, whole grains, nuts/seeds, seafood, plant-based oils, and 30% disincentive on SSBs, junk food, and processed meats. Model inputs included national data from NHANES (2009-2014), policy effects from SNAP pilots and food pricing meta-analyses, diet-disease effects from meta-analyses, and policy, food subsidy, and healthcare costs. Results: From a societal perspective, all 3 scenarios were cost-savings at 5, 10, 20 y and lifetime ( Table ). At 5 y, a F&amp;V subsidy would prevent 32,218 CVD events, gain 18,072 QALYs, and save $1.04B ($6.05B lifetime). Corresponding values for a F&amp;V subsidy + SSB restriction were 63,898, 45,772, and $4.47B ($38.83B); and for a broader incentive/disincentive framework that preserved choice, 65,078, 26,663, and $3.98B ($29.90B). Government affordability varied by program duration and by whether subsidy costs for SNAP adults or all SNAP participants were included. Scenario 3 was generally most cost-effective or -saving, followed by scenario 2 and then scenario 1; all were cost-effective over a lifetime from a government affordability perspective. Conclusions: Financial incentives/disincentives through SNAP could generate substantial health benefits and be cost-effective or cost savings.
A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis
Authors: Pauline T. Lukey, Stephen A. Harrison, Shuying Yang, Yim Man, Beverley F. Holman, Alaleh Rashidnasab, Gabrielle Azzopardi, Michael Grayer, Juliet K. Simpson, Philippe Bareille, Lyn Paul, Hannah V. Woodcock, Richard Toshner, Peter Saunders, Philip L. Molyneaux, Kris Thielemans, Frederick J. Wilson, Paul F. Mercer, Rachel C. Chambers, Ashley M. Groves, William A. Fahy, Richard P. Marshall, Toby M. Maher
Journal: European Respiratory Journal (2019)

Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is a potent inhibitor of PI3K/mTOR. A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study of omipalisib in subjects with IPF was conducted ( NCT01725139 ) to test safety, tolerability, pharmacokinetics and pharmacodynamics. Omipalisib was dosed at 0.25 mg, 1 mg and 2 mg twice daily for 8 days in four cohorts of four subjects randomised 3:1 to receive omipalisib or placebo (two cohorts received 2 mg twice daily). 17 subjects with IPF were enrolled. The most common adverse event was diarrhoea, which was reported by four participants. Dose-related increases in insulin and glucose were observed. Pharmacokinetic analysis demonstrated that exposure in the blood predicts lung exposure. Exposure-dependent inhibition of phosphatidylinositol 3,4,5 trisphosphate and pAKT confirmed target engagement in blood and lungs. 18 F-2 - fluoro-2-deoxy- d -glucose(FDG)-positron emission tomography/computed tomography scans revealed an exposure-dependent reduction in 18 F-FDG uptake in fibrotic areas of the lung, as measured by target-to-background, ratio thus confirming pharmacodynamic activity. This experimental medicine study demonstrates acceptable tolerability of omipalisib in subjects with IPF at exposures for which target engagement was confirmed both systemically and in the lungs.
Hypofractionated radiation therapy for unresectable/locally recurrent intrahepatic cholangiocarcinoma.
Authors: Alicia Smart, Theodore S. Hong, Natasa Petkovska, Bridget N. Noe, Andrew X. Zhu, Cristina Ferrone, Kenneth Tanabe, Jill N. Allen, Lorraine C. Drapek, Motaz Qadan, Janet E. Murphy, Lipika Goyal, Jennifer Yon-Li Wo
Journal: Journal of Clinical Oncology (2019)

412 Background: Our objective was to evaluate outcomes for patients with unresectable/locally recurrent intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated proton or photon radiation therapy (HF-RT). Methods: We retrospectively identified 66 patients with ICC who were treated with HF-RT from 2008-18. 51 patients had intrahepatic disease only, and 15 patients had extrahepatic disease at time of RT but received RT for biliary control. Median age at RT was 76 years (range: 30-92), including 27 patients (41%) ≥ 80 years. Median RT dose was 58.05 Gy (range: 37.5-67.5), delivered in 15 daily fractions. 32 patients received proton RT, and 34 patients received photon RT. Rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated by the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the Cox proportional hazards method. For multivariate analyses, variables with p &lt; 0.5 on univariate analysis were evaluated by backwards selection. Results: Median follow-up times from diagnosis and RT start were 21 and 14 months, respectively. In total, 5 patients (7.6%) developed local failure. Only 1 patient developed isolated local failure. The 2-yr outcomes were 93% LC, 37% PFS, and 55% OS. Among the 51 patients treated with definitive intent, the 2-yr LC was 96%, PFS 35%, OS 60%. Receipt of protons was significantly associated with younger age (p = 0.02), but not gender, race, ECOG status, metastatic disease at presentation, mean liver dose, cumulative GTV, or number of lesions. There were no significant predictors of LC or PFS, including RT dose. On UVA for OS, younger age, female gender, prior chemotherapy, prior surgery, and proton RT were associated with improved OS (p &lt; 0.05). On MVA, female gender (HR: 0.33, p = 0.001), prior chemotherapy (HR: 0.38, p = 0.002), and proton vs. photon RT (HR: 0.50, p = 0.05) remained significantly associated with OS. Conclusions: HF-RT yields high rates of local control and is an effective modality to optimize biliary control for unresectable/locally recurrent IC. HF-RT should be considered for elderly patients who are considered medically inoperable. Proton RT and chemotherapy may further improve outcomes.
Randomized phase II trial of sorafenib, capecitabine and oxaliplatin (SECOX) versus single agent sorafenib in patients with advanced hepatocellular carcinoma.
Authors: Thomas Cheung Yau, Vikki Tang, Roland Ching-Yu Leung, Gin Wai Kwok, Ann-Shing Lee, Ada Law, Joanne Chiu, Bryan Li, Tan To Cheung
Journal: Journal of Clinical Oncology (2019)

365 Background: We aimed to compare the efficacy and tolerability of SECOX regimen with sorafenib alone as first-line treatment of advanced hepatocellular cancer (HCC) in a multicenter, open-label and randomized setting. Methods: Patients not suitable for surgery or various loco-regional therapies and no prior systemic therapy for advanced HCC were recruited in 3 centres. Eligible patients were randomly assigned to receive either SECOX (sorafenib 400 mg BD continuously, oxaliplatin 85 mg/m 2 on D1, and capecitabine 1700 mg/m 2 on D1-7 q2w) or sorafenib alone continuously in 1:1 ratio. Primary endpoint was time-to-progression (TTP). Secondary endpoints were tolerability, overall tumor response rate, overall survival (OS) and progression-free survival (PFS). Results: Forty-six patients were randomized and treated, of whom 22 were in the SECOX arm. Median age was 64 years and majority of the patients were male (72%). 40 patients (87%) were hepatitis B carrier, and 42 patients (91%) had Child-Pugh A liver function. Thirty patients (65%) had received prior non-systemic treatment for HCC. Median duration of follow-up was 7.8 months (mos) (range 0.3-25.8). At the time of analysis,one patient in the SECOX arm is still receiving treatment. Median TTP was 3.2 mos (95% CI 1.7-5.8) for SECOX vs 2.8 mos (95% CI 1.8-4.0) for sorafenib. The hazard ratio (HR) for TTP was 0.91 (95% CI 0.5-1.7; p=0.77; predetermined futility boundary HR ≥ 0.86). Median OS was 7.1 mos (95% CI 3.0-15.3) for SECOX vs 12.5 mos (95% CI 7.2-15.4) for sorafenib (p=0.29). Median PFS was 3.1 mos (95% CI 1.6-5.8) for SECOX vs 2.7 mos (95% CI 1.8-4.0) for sorafenib. 2 patients (9%) and no patients achieved partial response in the SECOX and sorafenib arms, respectively. The clinical benefit rate (CR+PR+SD) was 36% for the SECOX arm and 21% for the sorafenib arm (p=0.50). Incidence of treatment-related adverse events (trAEs) was common in both SECOX and sorafenib arms (64% and 71% respectively, p=0.75). The most common grade 3-4 trAE was ALP increase (14%) for SECOX and hand-foot skin reaction (25%) for sorafenib. Conclusions: The addition of capecitabine and oxaliplatin to sorafenib did not result in significant improvement in TTP. Clinical trial information: NCT02716766.
Abstract MP24: Comparison of on-site versus Remote Support for a Mobile-Device Pilot Study: A Collaboration Between the Framingham Heart Study and Health eHeart Study (FHS-HeH)
Authors: Nicole L Spartano, Fangui Sun, Kathryn L Lunetta, Ludovic Trinquart, Maureen Valentino, Emily S Manders, Mark J Pletcher, Gregory M Marcus, David D McManus, Emelia J Benjamin, Caroline S Fox, Jeffrey E Olgin*, Joanne M Murabito*
Journal: Circulation (2018)

Background: New “e-Cohort” study designs provide resource-effective methods for collecting participant data. It is unclear if implementing an e-cohort without direct, in-person participant contact can achieve successful participation rates. The FHS-HeH randomized pilot study compared two distinct implementation strategies for co-enrolling participants from the Framingham Heart Study (FHS) into the Health eHeart Study, a digital cohort with infrastructure for collecting mHealth data. Methods: FHS participants who had an email address and smartphone were randomized to one of two approaches: remote vs. on-site support. In the remote arm, participants received an email containing an enrollment URL, and, upon enrollment, were sent four Bluetooth sensor devices. Participants in the on-site arm were invited to visit FHS and were provided in-person support for enrollment and connecting the devices. Results: Compared to participants that declined, individuals that accepted an invitation to participate in our pilot study (n=101 remote , n=101 on-site ) were more often women, highly educated, and younger (Figure 1). All on-site participants completed the consent, compared to 93% of the remote arm. Of participants who consented to participate, connection and initial use of devices was also higher in the on-site arm (100% connected the activity monitor, 94% the blood pressure cuff and scale, and 84% the electrocardiogram) compared to the remote arm (74%, 75%, 80%, and 42%). Roughly 75-78% of those that initially connected in both arms were still using the devices by the 3 rd month and 58-60% were still participating by the 6 th month. Conclusions: Our pilot study demonstrated that deployment of mobile devices among middle-aged and older adults in the context of an on-site clinic visit was associated with higher initial rates of device use as compared to offering only remote support. Once connected, drop-off rates were similar in both groups.
Genomic alterations in appendiceal carcinoma using circulating DNA.
Authors: Walid Labib Shaib, Ali Roberts, Mehmet Akce, Christina Wu, Olatunji B. Alese, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2019)

658 Background: Appendiceal cancers (AC) comprise around 0.5% of all gastrointestinal neoplasia. The genomic landscape of AC has not been well studied. The yield of circulating tumor DNA (ctDNA) from the plasma of patients with AC has not been reported. The aim of this study is to confirm the feasibility of NGS using ctDNA and characterize common alternations in the genomic profile of AC. Methods: The molecular alterations in 372 plasma samples from 303 patients with AC using clinical-grade NGS of ctDNA (Guardant 360) across multiple institutions, was evaluated. The test detects single nucleotide variants in 54 -73 genes, copy number amplifications, fusions, and indels in selected genes. Results: A total of 303 AC patients were evaluated; 169 female (56%). Median age was 56.8 (range: 25-83). ctDNA NGS testing was done on 372 plasma samples; 48 patients had testing performed twice, 9 three times, and 1 was tested four times. Genomic alterations were defined in 207 (55.6%) samples with a total of 288 alterations identified after excluding variants of uncertain significance (VUSs) and synonymous mutations. TP53 associated genes were most commonly altered (n = 96, 33.3%), followed by KRAS (n = 41, 14.2%), APC (n = 19, 6.6%), EGFR (n = 15, 5.2%), BRAF (n = 13, 4.5%), NF1 (n = 13, 4.5%), MYC (n = 9, 3.1%), GNAS (n = 8, 2.7%), PI3CA (n = 7, 2.4%), MET (n = 6, 2.08%), ATM in 6 (1.6%). Other genomic alterations of low frequency, but clinically relevant: AR (n = 4, 1.39%), TERT (n = 4, 1.39%), ERBB2 (n = 4, 1.39%), SMAD4 (n = 3, 1.04%), CDK4 (n = 2, 0.69%), NRAS (n = 2, 0.69%), FGFR1 (n = 2, 0.69%), FGFR2 (n = 2, 0.69%), PTEN (n = 2, 0.69%), RB1 (n = 2, 0.69%), and CDK6, CDKN2A, BRCA1, BRCA2, JAK2, IDH2, MAPK, NTRK1, CDH1, ARID1A, and PDGFRA were all reported once. Conclusions: Evaluation of ctDNA was feasible among individuals with AC. The frequency of genomic alterations in ctDNA testing is similar to those previously reported in tissue NGS. Liquid biopsies are non-invasive methods that can provide personalized options for targeted therapies in patients with AC.
Incidence of and risk factors (RFs) for development of non-alcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) for pancreatic cancer: A single institutional review.
Authors: Amy McGhee-Jez, Amisha Ahuja, Ritu Nahar, Samik Shah, Rebecca Loh, Sarah Houtmann, Rashesh Shah, Inna Chervoneva, Harish Lavu, Steven J. Cohen, Dina Halegoua-De Marzio, Atrayee Basu Mallick
Journal: Journal of Clinical Oncology (2019)

398 Background: PD may increase the risk of development of NAFLD, a precursor for non-alcoholic steatohepatitis and cirrhosis. Studies have not clearly identified consistent RFs for NAFLD, but patients with post-PD NAFLD do not appear to have the traditional RFs for NAFLD such as metabolic syndrome. The primary objective of this study was to identify the incidence of and RFs for post-PD NAFLD. Methods: Retrospective chart review was done on 425 patients who underwent PD for a cancer diagnosis at our institution from 2007 to 2017 and had at least 6 months of postoperative follow up. Cox proportional hazards model was used to examine multiple potential pre-operative RFs for NAFLD including body mass index (BMI), estimated surgical blood loss, LFTs, hemoglobin, albumin, age, sex, comorbidities, and tobacco use as predictors of time to develop post-PD NAFLD. Patients without post-PD NAFLD were considered censored at the time of last follow-up. The proportional hazard assumptions were validated. Post-PD NAFLD was identified by review of radiology reports. Results: Sixty (14.1%) of the 425 patients had post-PD NAFLD. The male to female ratio was 236:189 and median follow up time was 1 year. Median age was 65 years with median time to NAFLD development of 7 months. Multivariate Cox Proportional Hazard model identified higher BMI and female sex as RFs for the development of post-PD NAFLD. Each 1-point increase in BMI implied an 8.43% increase in the hazard of fatty liver (HR = 1.083, 95% CI: 1.032-1.136; p=0.001). Females had 89.7% higher hazard of fatty liver compared to males (HR = 1.897, 95% CI: 1.084 - 3.319; p=0.025). There was no statistically significant association between post-PD NAFLD and other pre-operative characteristics studied. Conclusions: Female sex and higher BMI may be RFs for the development of NAFLD post-PD. No other pre-operative RFs were identified. In conclusion, patients with higher BMI and female gender may need closer monitoring for earlier detection and management of NAFLD. [Table: see text]
Blinatumomab in Combination with Immune Checkpoint Inhibitors of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Preliminary Results of a Phase I Study
Authors: Jonathan Webster, Marlise R. Luskin, Gabrielle T. Prince, Amy E. DeZern, Daniel J. DeAngelo, Mark J. Levis, Amanda Blackford, Elad Sharon, Howard Streicher, Leo Luznik, Ivana Gojo
Journal: Blood (2018)
Diabetes Distress, Intentional Hyperglycemia at Work, and Glycemic Control Among Workers With Type 1 Diabetes
Authors: Ulla M. Hansen, Timothy Skinner, Kasper Olesen, Ingrid Willaing
Journal: Diabetes Care (2019)

The aim was to explore relationships between work-related factors, work-related diabetes distress (WRDD), diabetes distress (measured by Problem Areas in Diabetes [PAID]-5 scale), intentional hyperglycemia at work (IHW), and glycemic control.A cross-sectional survey was conducted with 1,030 working adults with type 1 diabetes and linked with electronic health record data from a specialist diabetes clinic in Denmark. With use of structural equation modeling, two alternative models were compared, based on fit indices, statistical significance, and theoretical meaningfulness.A combined model provided the best fit to the data. WRDD was more strongly affected by work ability, opportunity to self-manage at work, being treated differently, and job demands. PAID-5 was more strongly affected by identity concern and blame and judgment. Both PAID-5 and WRDD were associated with more frequent IHW, which was associated in turn with worse glycemic control.Work-related factors are associated with WRDD and PAID-5. Distress increases the frequency of IHW, which is, in turn, associated with worse glycemic control. Future studies should investigate ways to balance diabetes management and work life without compromising diabetes care.
Langerhans cells increase their expression of integrin αvβ8 through migration and are needed for Tregs induction by epicutaneous immunotherapy (EPIT)
Authors: Vincent Dioszeghy, Lucie Mondoulet, Léo Laoubi, Veronique Dhelft, Camille Plaquet, Adeline Bouzereau, Christophe M. Dupont, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2019)
A prospective evaluation of vitamin B1 (thiamine) level in myeloproliferative neoplasms: clinical correlations and impact of JAK2 inhibitor therapy
Authors: Naseema Gangat, Amy Phelps, Terra L. Lasho, Christy M. Finke, Rangit Vallapureddy, Curtis A. Hanson, Rhett P. Ketterling, Mrinal M. Patnaik, Animesh Pardanani, Ayalew Tefferi
Journal: Blood Cancer Journal (2019)

Vitamin B1 (Thiamine) deficiency might result in Wernicke's encephalopathy (WE); the latter was reported in clinical studies with the JAK2 inhibitor fedratinib resulting in disruption of clinical development, despite efficacy in patients with myelofibrosis (MF) 1 .Existing data regarding risk of WE and thiamine deficiency in patients with myeloproliferative neoplasms (MPN) is conflicting with one study suggesting an increased risk (MPN vs. non-MPN: 1.09 vs. 0.39/1000 person-year, HR = 2.19) 2 while none were noted to be thiamine deficient in another study involving 92 MPN patients 3 .Therefore, the objectives of the current study were, (i) to provide an accurate estimation of the incidence of thiamine deficiency in patients with MPN, (ii) assess clinical correlations of thiamine level and (iii) determine the impact of JAK2 inhibitor therapy on thiamine level in MPN.After Institutional review board approval, patients referred to our center with a suspected diagnosis of MPN were prospectively enrolled.All clinical and laboratory variables including treatment details were collected at the time of referral.Liquid chromatography-tandem mass spectrometry analysis of thiamine diphosphate in whole blood was performed at the time of referral.Reference range for thiamine level in whole blood was 70-180 nmol/ L. The JMP® Pro 13.0.0software from SAS Institute, Cary, NC, USA, was used for all statistical analysis.
CD19 Redirected CAR NK Cells Are Equally Effective but Less Toxic Than CAR T Cells
Authors: Concetta Quintarelli, Simona Sivori, Simona Caruso, Simona Carlomagno, Iolanda Boffa, Domenico Orlando, Marika Guercio, Biancamaria Cembrola, Angela Pitisci, Stefano Di Cecca, Giuseppina Li Pira, Luciana Vinti, Biagio De Angelis, Lorenzo Moretta, Franco Locatelli
Journal: Blood (2018)