tbuckley/cabot-search huggingface dataset:
THU-150-Factors associated with treatment failure with SOF+RBV in patients with genotype 2 chronic hepatitis C and consideration of retreatment with GLE+PIB in patients not responding to SOF+RBV
Authors: Atsunori Kusakabe, Masayuki Kurosaki, Jun Itakura, Kouji Joko, Takehiro Akahane, Haruhiko Kobashi, Tetsuro Sohda, Keiji Tsuji, Hiroyuki Matusawa, Hiroyuki Kimura, Ryoichi Narita, Koichiro Furuta, Namiki Izumi
Journal: Journal of Hepatology (2019)
Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence
Authors: Raoul Charles Coombes, Karen Page, Raheleh Salari, Robert K. Hastings, Anne Armstrong, Samreen Ahmed, Simak Ali, Susan Cleator, Laura Kenny, Justin Stebbing, Mark Rutherford, Himanshu Sethi, Anna Boydell, Ryan Swenerton, Daniel Fernandez-Garcia, Kelly L.T. Gleason, Katie Goddard, David S. Guttery, Zoe J. Assaf, Hsin-Ta Wu, Prashanthi Natarajan, David A. Moore, Lindsay Primrose, Scott Dashner, Antony S. Tin, Mustafa Balcioglu, Ramya Srinivasan, Svetlana V. Shchegrova, Alexander Olson, Dina Hafez, Paul Billings, Alexey Aleshin, Farah Rehman, Bradley J. Toghill, Allison Hills, Maggie C. Louie, Cheng-Ho Jimmy Lin, Bernhard G. Zimmermann, Jaqueline A. Shaw
Journal: Clinical Cancer Research (2019)

Up to 30% of patients with breast cancer relapse after primary treatment. There are no sensitive and reliable tests to monitor these patients and detect distant metastases before overt recurrence. Here, we demonstrate the use of personalized circulating tumor DNA (ctDNA) profiling for detection of recurrence in breast cancer.
Prognostic Restaging at the Time of 2nd-Line Therapy in Patients with AL Amyloidosis
Authors: Yi L. Hwa, Morie A. Gertz, Shaji K. Kumar, Martha Q. Lacy, Francis K. Buadi, David Dingli, Prashant Kapoor, Steven Zeldenrust, Nelson Leung, Suzanne R. Hayman, Wilson I Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Ronald S. Go, Eli Muchtar, Miriam Hobbs, Amie Fonder, Stephen J. Russell, Robert A. Kyle, S. Vincent Rajkumar, Angela Dispenzieri
Journal: Blood (2018)
THU-332-Healthcare resource utilisation, demographics, and comorbidities by diagnosis codes and histological stage in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in a large integrated healthcare delivery system in the U.S
Authors: Lisa Nyberg, Heather Patton, Kevin Chiang, Su-Jau Yang, Susan Caparosa, Julie Stern, Anders Nyberg
Journal: Journal of Hepatology (2019)
Can a BALF profile distinguish hot vs cold lung tumors?
Authors: J. Domagala-Kulawik, D. Dziedzic, M. Polubiec-Kownacka, T. Kryczka, I. Kwiecien
Journal: Annals of Oncology (2019)

Background: Immunotherapy brings evident benefits to lung cancer patients. However, the answer to this treatment is highly individualized and seems to be better in 'hot' tumors than in 'cold' ones. The vast majority of lung cancers are in their advanced stages at recognition, therefore the access to large fragments of tumor tissue and tumor environment is limited. The results of our previous studies showed the usefulness of bronchoalveolar lavage fluid (BALF) examination in the evaluation of immune status in a lung tumor site. The aim of this study was to assess if BALF may reflect the signs of 'hot' vs. 'cold' tumors. Methods: 36 lung cancer patients were investigated. The number of lymphocytes and the proportion of following lymphocyte subtypes were analysed by flow cytometry: T, B, T helper, T cytotoxic, NK cells, CD25+Th cells, T regulatory cells, CTLA4+Tregs. The concentration of IFNγ, TNFα, VEGF, TGFβ, IL-2, IL-10 was measured by Bio-Plex Pro Human Cytokine Assay. We defined 'hot' tumors by the presence of cell proportion or cytokine concentration above the median value and 'cold' tumors where these markers were lower than the median value. Results: There were 36% of BALF samples with more than 2 parameters below the median values, which may reflect 'cold' tumors. The indications of immune response (more than 7, e.g. 50%) were elevated in 53% samples. The majority of 'hot' tumors were in the type of adenocarcinoma or NOS, but without any relation to the EGFR mutations nor ALK alterations. No relation between the intensity of immune response in the BALF and the clinical stage of cancer was observed. Conclusions: BALF examination may help in distinguishing 'hot' and 'cold' lung cancer and may be useful in the characterization of local immune status before treatment. By extrapolating the results of this study we could recommend BALF as a source of useful biomarkers before immunotherapy. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: J. Domagala-Kulawik: Travel grants, consultations: BMS, MSD. All other authors have declared no conflicts of interest.
In early prostate cancer, radical prostatectomy reduced mortality more than watchful waiting at 23 years
Authors: Philipp Dahm, Timothy Wilt
Journal: Annals of Internal Medicine (2019)

Source Citation Bill-Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in prostate cancer—29-year follow-up. N Engl J Med. 2018;379:2319-29. 30575473
Pemetrexed-based chemotherapy in advanced nonsquamous non-small cell lung cancer (NSCLC).
Authors: Abdulrahman Ali Alshehri, Saud Abdullrhman Alsubait, M.Ahsan Alamgir, Chandler Park, Sijin Wen, Jin Luo, Patrick Ma, Manish Monga
Journal: Journal of Clinical Oncology (2015)

e22245 Background: Pemetrexed in combination with platinum chemotherapy is an indicated regimen for treatment of adv non-squamous NSCLC. The purpose of this study is to evaluate the efficacy of pem-based chemotherapy in patients (pts) with adv non-squamous NSCLC treated at West Virginia University Mary Babb Randolph Cancer Center (MBRCC). Methods: We retrospectively analyzed the clinical data and outcome of pts with adv stage (IIIB/IV) non-squamous NSCLC who received pem-based chemotherapy at our institution from 2009 to 2014. Results were compared with the published data in the literature. Results: A total of 74 patients were included in the study with a median follow-up of 26 months. The median overall survival (OS) for all pts was 16.6 months (95% CI: 11.6 - 43.4); the median progression free survival (PFS) for all pts was 9.6 months (95% CI: 8.43 - 12.98). Among all, there were 65 pts who received pem-based regimen as first-line therapy and 9 pts who received it as subsequent treatment after prior progression. In the data analysis of comparison between pts who survived > 2 years (n = 17) and < 8 months (n = 15), there were no significant differences between the two groups in terms of sex, age, ECOG performance status, TNM stage at diagnosis and smoking history. Among pts who survived < 8 months, there were 67% with brain metastasis, in comparison to 29% with brain metastasis at diagnosis in those with survival > 2 years (p = 0.043). Presence of liver metastasis at diagnosis was reported in 47% of pts who survived < 8 months compared to only 6% in those with survival > 2 years (p = 0.015). Conclusions: Survival outcome for pts with non-squamous NSCLC who have been treated at MBRCC with pem-based chemotherapy was comparable to that of published data in two phase III trials (first line and maintenance setting). Clinically, sites of metastasis (liver and brain) have the most pronounced impact on the survival of our pts. Pathological specimens for all the pts were identified retrospectively and collected for further translational studies. We are currently conducting a molecular analysis for candidate predictive biomarkers of pem chemotherapy response, to examine the relationships among candidate biomarkers and survival (OS, PFS) outcome data of the pts.
The impact of long-term survival on treatment cost per month with ipilimumab (IPI).
Authors: Pinar Bilir, Ahmad A. Tarhini, Humin Li, Victor Barzey, Bjorn Bolinder, Sumati Rao, Julie Munakata
Journal: Journal of Clinical Oncology (2015)

e20106 Background: A recent pooled analysis of overall survival (OS) data across multiple studies has shown that IPI confirms long-term survival benefit up to 10 years in patients (pts) with advanced melanoma (MEL). This analysis assesses drug costs per month of survival over different horizons to improve understanding of the impact of initial IPI investment. Methods: This analysis incorporates survival gains from pooled analysis of long-term survival data from 10 prospective and two retrospective IPI studies. Using a 119-month follow-up period, median OS and mean OS (area under the curve [AUC]) were calculated using the pooled analysis Kaplan-Meier curve for IPI (Schadendorf et al, J Clin Oncol, in press). Average doses per pt, used to calculate average treatment cost, were derived from available dosing data from a subset of trials in the pooled analysis, and included any retreatment/maintenance doses. Average IPI cost per month of survival was calculated from start of treatment until 3 years and 10 years after initiation. Additional analysis assessed the effect on results of including OS data for pts who survived only up to 3 years compared with those who lived beyond 3 years. Results: Median OS was 11.4 months with a 3-year survival rate of 22% (N = 1,861). Survival plateaued at ~3 years, with maximum follow up of 119 months (median 11 months). For the entire cohort, AUC (mean OS) over a 3-year horizon was 15.2 months, while AUC over the 10-year horizon was 30.5 months. Including any retreatment/maintenance, pts took 3.68 doses on average, for an average cost per month of survival of $3,903 per pt given entire cohort average survival over a 10-year horizon. This value was 50% lower than the average cost per month of survival when considered for only up to 3 years ($7,826). Stratifying by survival, cost per month of survival difference was approximately 10-fold for pts living less than 3 years versus those surviving longer than 3 years ($12,659 vs $1,231 for long-term survivors). Conclusions: While costs are often evaluated over time of treatment administration, IPI costs per month greatly diminish when considered in the context of extended survival; this is critical to inform future comparative analyses.
RNA Splicing of the BHC80 Gene Contributes to Neuroendocrine Prostate Cancer Progression
Authors: Yinan Li, Ning Xie, Ruiqi Chen, Ahn R. Lee, Jessica Lovnicki, Emma A. Morrison, Ladan Fazli, Qingfu Zhang, Catherine A. Musselman, Yuzhuo Wang, Jiaoti Huang, Martin E. Gleave, Colin Collins, Xuesen Dong
Journal: European Urology (2019)

Prostate adenocarcinoma (AdPC) progression to treatment-induced neuroendocrine prostate cancer (t-NEPC) is associated with poor patient survival. While AdPC and t-NEPC share similar genomes, they possess distinct transcriptomes, suggesting that RNA splicing and epigenetic mechanisms may regulate t-NEPC development.To characterize the role of alternative RNA splicing of the histone demethylase BHC80 during t-NEPC progression.The expression of BHC80 splice variants (BHC80-1 and BHC80-2) were compared between AdPC and t-NEPC patient tumors. Regulatory mechanisms of RNA splicing of the BHC80 gene were studied, and the signal pathways mediated by BHC80 splice variants were investigated in t-NEPC cell and xenograft models.Global transcriptome analyses identified that the BHC80-2 variant is highly expressed in t-NEPC. Compared with the known histone demethylation activities of the BHC80 gene, we discovered a novel nonepigenetic action of BHC80-2, whereby BHC80-2 is localized in the cytoplasm to trigger the MyD88-p38-TTP pathway, which results in increased RNA stability of multiple tumor-promoting cytokines. While BHC80-2 does not induce neuroendocrine differentiation of cancer cells, it stimulates cell proliferation and tumor progression independent of androgen receptor signaling. Blockade of BHC80-2-regulated MyD88 signaling suppresses growth of several t-NEPC cell spheroid and xenograft models.Gain of function of BHC80-2 through alternative RNA splicing activates immune responses of cancer cells to promote t-NEPC development.The main obstacle to develop effective therapies for patients with t-NEPC is the lack of understanding on how t-NEPC is developed. Our study not only identifies a previously unknown BHC80-2-MyD88 signaling pathway that plays an important role during t-NEPC development, but also provides a proof of principle that targeting this signal pathway may offer an avenue to treat t-NEPC.
THU-226-Concomitant diabetes mellitus increases risk of liver fibrosis in treatment-naive chronic hepatitis B with low viral loads: Results from a matched case-control study
Authors: Hei Chun Justin Ma, Lung-Yi Mak, Ka-Shing Cheung, Yan Yue James Fung, Ching Lung Lai, Man-Fung Yuen, Wai-Kay Seto
Journal: Journal of Hepatology (2019)
NEJM Knowledge+ Pain Management and Opioids — A New Adaptive Learning Module
Authors: Ole-Petter R. Hamnvik, Daniel P. Alford, Catherine T. Ryan, Ilana T. Hardesty, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2019)

The United States has seen a dramatic rise in opioid use and misuse during the past three decades. In 2017, more than 11 million persons reported misusing prescription opioid analgesics during the ...
A genome-wide association study implicates <i>NR2F2</i> in lymphangioleiomyomatosis pathogenesis
Authors: Wonji Kim, Krinio Giannikou, John R. Dreier, Sanghun Lee, Magdalena E. Tyburczy, Edwin K. Silverman, Elżbieta Radzikowska, Shulin Wu, Chin-Lee Wu, Elizabeth P. Henske, Gary Hunninghake, Havi Carel, Antonio Roman, Miquel Angel Pujana, Joel Moss, Sungho Won, David J. Kwiatkowski
Journal: European Respiratory Journal (2019)

Introduction Lymphangioleiomyomatosis (LAM) occurs either associated with tuberous sclerosis complex (TSC) or as sporadic disease (S-LAM). Risk factors for development of S-LAM are unknown. We hypothesised that DNA sequence variants outside of TSC2 / TSC1 might be associated with susceptibility for S-LAM and performed a genome-wide association study (GWAS). Methods Genotyped and imputed data on 5 426 936 single nucleotide polymorphisms (SNPs) in 426 S-LAM subjects were compared, using conditional logistic regression, with similar data from 852 females from COPDGene in a matched case–control design. For replication studies, genotypes for 196 non-Hispanic White female S-LAM subjects were compared with three different sets of controls. RNA sequencing and immunohistochemistry analyses were also performed. Results Two noncoding genotyped SNPs met genome-wide significance: rs4544201 and rs2006950 (p=4.2×10 −8 and 6.1×10 −9 , respectively), which are in the same 35 kb linkage disequilibrium block on chromosome 15q26.2. This association was replicated in an independent cohort. NR2F2 (nuclear receptor subfamily 2 group F member 2), a nuclear receptor and transcription factor, was the only nearby protein-coding gene. NR2F2 expression was higher by RNA sequencing in one abdominal LAM tumour and four kidney angiomyolipomas, a LAM-related tumour, compared with all cancers from The Cancer Genome Atlas. Immunohistochemistry showed strong nuclear expression in both LAM and angiomyolipoma tumours. Conclusions SNPs on chromosome 15q26.2 are associated with S-LAM, and chromatin and expression data suggest that this association may occur through effects on NR2F2 expression, which potentially plays an important role in S-LAM development.
Tailoring the Approach to Embolic Stroke of Undetermined Source
Authors: Hooman Kamel, Alexander E. Merkler, Costantino Iadecola, Ajay Gupta, Babak B. Navi
Journal: JAMA Neurology (2019)

One-third of ischemic strokes have no identifiable cause after standard evaluation. In 2014, researchers termed these embolic strokes of undetermined source (ESUS) and argued that this entity would respond to anticoagulation. Two recent randomized clinical trials have not upheld this hypothesis, leading to questions about the ESUS concept.This article proposes that ESUS remains a useful concept, the clinical effect of which can be enhanced by considering 2 subsets defined by their likelihood of responding to anticoagulation. Recent studies indicate that some ESUS cases result from subclinical atrial fibrillation, atrial cardiopathy, unrecognized myocardial infarction, patent foramen ovale, or cancer, while other cases result from nonstenosing large-artery atherosclerosis, aortic atherosclerosis, or nonatherosclerotic vasculopathies. Evidence suggests that anticoagulation will prove superior to antiplatelet therapy for cases in the first group of causative mechanisms but not those in the second group, suggesting the need for personalized therapy.Although the ESUS concept as currently constructed cannot guide treatment, efforts to better understand ESUS and develop therapies tailored to specific mechanisms are likely to help reduce the burden of stroke.
Olanzapine versus fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent chemoradiation treatment.
Authors: Rudolph M. Navari, Cindy K Nagy
Journal: Journal of Clinical Oncology (2015)

9502 Background: The purpose of the study was to compare the effectiveness of olanzapine (OLN) and fosaprepitant (FOS) for the prevention of nausea and vomiting in patients receiving concurrent highly emetogenic chemotherapy (HEC) and radiation therapy for head and neck and esophageal cancer. Methods: A randomized, double-blind, phase III trial was performed in chemo and radiation therapy naïve patients receiving concurrent local radiation and cisplatin, > 70 mg/m2, based chemotherapy comparing OLN to FOS in combination with palonosetron (PAL) and dexamethasone (DEX). The OLN, PAL, DEX (OPD) regimen was 10 mg of oral OLN, 0.25 mg of intravenous PAL, and DEX 20 mg intravenous pre-chemotherapy, day 1, and 10 mg/day of oral OLN alone on days 2-4 post-chemotherapy. The FOS, PAL, DEX (FPD) regimen was 150 mg of intravenous FOS, 0.25 mg intravenous PAL, and 12 mg intravenous DEX, day 1, and 4 mg DEX twice a day, days 2 and 3. Distribution of patients to different groups were similar in gender, types of cancer, and radiotherapy regimens. Results: One hundred and nine patients consented to the protocol and were randomized. One hundred patients were evaluable. Complete response (CR) (no emesis, no rescue) was 88% for the acute period (24 hours post-chemotherapy), 76% for the delayed period (days 2-5 post-chemotherapy), and 76% for the overall period (0-120 hours) for 51 patients receiving the OPD regimen. CR was 84% for the acute period, 73% for the delayed period, and 73% for the overall period in 49 patients receiving the FPD regimen. Patients without nausea (0, scale 0-10, visual analogue scale) were: OPD: 86%, acute; 71%, delayed; and 71%, overall; FPD: 77%, acute; 41%, delayed; and 41%, overall. There were no grade 3 or 4 toxicities. CR and control of nausea in subsequent chemotherapy cycles were equal to or greater than cycle one for both regimens. Conclusions: For the overall period, OPD was comparable to FPD in the control of emesis; nausea was significantly (p < 0.01) improved with OPD compared to FPD.
THU-444-Alteration of miRNAs expression in patients with HCV-related cirrhosis who developed HCC after therapy with DAAs
Authors: Antonietta Romano, A. Brocca, Giulio Ceolotto, Valeria Calvino, Luisa Cavalletto, Zoe Mariño, Sofía Pérez-del-Pulgar, Sabela Lens, Loreto Boix, María Reig, Jordi Bruix, Ranka Vukotic, Valeria Guarneri, Pietro Andreone, Francesco Paolo Russo, Saverio Parisi, Paolo Angeli
Journal: Journal of Hepatology (2019)
The association between the working alliance and sharing concerns by advanced cancer patients.
Authors: Gil Bar-Sela, Sivan Yochpaz, Rachel Gruber, Doron Lulav- Grinwald, Inbal Mitnik, Dan Koren
Journal: Journal of Clinical Oncology (2015)

e20553 Background: Recent studies have shown that a strong therapeutic alliance between cancer patients and medical staff is associated with adherence to treatment and better health outcome. Cancer patients deal with various types of concerns, such as physical, psychological and social ones, which are not always shared with healthcare professionals. Little is known about the factors that influence this sharing. Objectives: To assess the correlation between the strength of the working alliance and the type of concerns that patients choose to share with their physician and nurse. Methods: Advanced cancer patients treated with chemotherapy completed the Working Alliance Inventory- Short Revised (WAI-SR) and a checklist of topics, in which they rated their degree of concern about them during the treatment period, and the degree of sharing them with their physician/nurse. Results: Fifty-two patients (34 women and 18 men) completed the study. The strength of the working alliance on all its sub-scales (goals, practical tasks, and emotional bond) was similar with respect to treating physicians and nurses. The four topics that concerned patients the most were family's coping with their illness (81%), fear of future suffering (71%), symptom control (67%) and the oncological treatment (65%). These topics were shared with the physician by 52%, 59%, 83% and 74% of the patients respectively, while approximately half of the patients shared these concerns with the nurse. Patients with a strong working alliance with the physician shared to a higher extant the personal and main concern regarding family's coping (66%). In addition, a Strong working alliance with the physician was correlated with sharing concerns regarding family's coping (r = 0.529, p< .01) and future suffering (r = 0.278, p< .05). A strong working alliance with the nurse was correlated with discussing symptoms control (r = 0.298, p< .05). Conclusions: These findings provide preliminary support for the effect of the working alliance on the type of concerns that advanced cancer patients choose to discuss with their physicians and nurses, as well as its role in encouraging patients to discuss personal issues with the physician.