tbuckley/cabot-search huggingface dataset:
Safety of Imprime PGG, a novel innate immune cell modulator, in adults with stage IV non-small cell lung cancer: an integrated analysis of two randomized phase 2 studies.
Authors: Folker Schneller, Walburga Engel-Riedel, Michael Thomas, Jens Kollmeier, Parvis Sadjadian, Martin Wolf, Wolfgang Schuette, Corina Candiani Taitt, Richard Dale Huhn, Mable Ma, Paulette Mattson, Jamie R. Lowe, Ada H. Braun
Journal: Journal of Clinical Oncology (2015)

3071 Background: Imprime PGG (IPGG; beta-1,3/1,6 glucan), a yeast-derived pathogen-associated molecular pattern (PAMP), can prime innate immune effector cells to kill cancer cells opsonized by therapeutic antibodies. In two recent, identically designed phase 2 trials in patients (pts) with stage IV NSCLC, IPGG in combination with frontline carboplatin/paclitaxel (C/P) chemotherapy and bevacizumab (bev) or cetuximab (cet), respectively, was associated with numeric increases in objective tumor response rates and survival. This analysis evaluates the safety of IPGG across these studies. Methods: Patient-level data from two identically designed, randomized phase 2 trials of patients (pts) with stage IV NSCLC were combined for safety analyses. Results: A total of 177 pts were enrolled (118 IPGG, 59 Control [Ctrl]) and evaluable for safety. Overall (IPGG vs Ctrl), 99.2% (vs 100%) of pts experienced at least 1 treatment-emergent adverse event (AE) over the course of the study. Grade (Gr) III/IV AEs occurred in 85.6% vs 76.3% of pts, and serious AEs in 51.7% vs 42.4% of pts, respectively. Most common Gr III/IV AEs (occurring in at least 10% of pts in either arm) included neutropenia (35.6%, 37.3%), leukopenia (10.2%, 16.9%) and thrombocytopenia (11%, 11.9%). Gr III/IV AEs occurring at a ≥ 2% higher frequency in the IPGG arm included nausea (4.2%, 1.7%), abdominal pain (3.4%, 0%), fatigue (4.2%, 1.7%), hypersensitivity (2.5% vs 0%), polyneuropathy (5.9%, 3.4%) and pleural effusion (2.5%, 0%). Fatal AEs were experienced by 11% vs 3.4% of pts; no event occurred in > 1 pt in either arm, except general physical health deterioration (2.5%, 0%); all fatal AEs were deemed unrelated or unlikely related to IPGG. In the IPGG arm, 72% of pts experienced AEs reported as related to IPGG; of these, 10.2% were considered unlikely related and 61.9% were considered possibly or probably related to IPGG. AEs of specific interest (e.g. infusion-related reactions; immune-mediated AEs) as well as subset analyses by histology will be presented. Conclusions: IPGG was generally well tolerated in pts with stage IV NSCLC receiving C/P chemotherapy and cet or bev therapy frontline. Clinical trial information: NCT00874107 and NCT00874848.
Docetaxel in older patients for metastatic prostate cancer.
Authors: Frances May Mark, Adam Pollard, Alastair H Thomson
Journal: Journal of Clinical Oncology (2019)

187 Background: Docetaxel use has led to a significant prolongation in overall survival in metastatic prostate cancer (MPC). There is however limited information on treatment tolerance and outcomes in patients 80 years old and over in routine clinical practice. With the ever aging population it is becoming more important to assess outcomes in this age group. Methods: Patients diagnosed with MPC and treated with docetaxel from 2006 to 2016 were identified and their records retrospectively reviewed via electronic clinical and prescribing systems in a single centre in the UK. Data was assessed for prostate specific antigen (PSA) response, number of cycles and dosing of docetaxel and castrate resistant overall survival (OS). Results: 209 consecutive patients with MPC receiving docetaxel were reviewed. Three patient groups were identified; younger than 75 years old (n = 150, 37 early (as part of initial therapy) docetaxel), 75-79 years (n = 40, 2 early docetaxel) and 80 years or over (n = 19, no early docetaxel). When comparing mean OS excluding early docetaxel treatment, respective mean survival times for each of the three age groups, younger to older were 1001, 1045 and 1294 days, with between class difference being insignificant. The PSA response rates to docetaxel excluding first line use were compared between the age groups and did not show a significant difference at 39% in the youngest group, 38% in the intermediate age group and 42% for the oldest patients. There was a trend that the older the patient, the more likely docetaxel was the final systemic treatment given at 42% (80 years or over), 32% (75-79 years) and 23% (younger than 75 years). The 80 years or over group received fewer docetaxel cycles (3.8, p = 0.006) and less dose per course (226mg/m2, p = 0.004) than the group less than 75 years (5.8 cycles, 409mg/m2) and 75-79 years (5.1 cycles, 341mg/m2). Conclusions: In this group of patients, in routine clinical practice, the 80 years and over age group received fewer cycles of docetaxel in MPC and less dose per course, but nevertheless achieved similar PSA response rates and castrate resistant OS. Given these results, docetaxel should be considered as a treatment option in suitable patients of 80 years and over.
Tumor locations significantly affect disease free survival and overall survival.
Authors: Hakan Buyukhatipoglu, Taner Babacan, Neyran Kertmen, Ozturk Ates, Gokmen Aktas, Mehmet Ali Nahit Sendur, Sercan Aksoy, Yavuz Yasin Ozisik, Kadri Altundag
Journal: Journal of Clinical Oncology (2015)

e12590 Background: The association of tumor quadrants and survival times has been investigated in limited previous retrospective trials. There are growing retrospective evidence that tumors located in medial quadrants have worse prognosis. This study provides the only, prospective and large evidence of the association of tumor locations and prognosis. Methods: This study is a long-term prospective observational single-center study. Between the years of 2003 and 2014 a total of 2120 breast cancer patients were included. All patients underwent surgery and axillary dissection or sentinel axillary sampling. Patients who were treated with neo-adjuvant chemotherapy were not enrolled in this study. Patients’ tumor locations were identified by mammography, breast ultrasonography or breast MRI, and physical examination. Adjuvant treatment options were depended upon physicians’ choice. The results of survival analyses were adjusted for other prognostic factors. Results: Of the tumor locations 57.4% located in ULQ, 13.4% in LLQ, 11.8% in UIQ, and 6.5% in LIQ. In terms of disease free survival (DFS) tumor locations significantly and independently affected DFS (p = 0.015). When compared to lower inner quadrant (LIQ) to other quadrants (ULQ, LLQ, and UIQ), tumors located in LIQ significantly affected DFS (p = 0.001), Hazard Ratio = 0.51 (95%CI: 0.34-0.77). Other than LIQ the remaining quadrants had no impact on DFS. In terms overall survival (OS) tumor locations significantly influenced OS (p = 0.05) when analyzed together. When compared to lower inner quadrant to other quadrants, tumors located in LIQ significantly affected OS (p = 0.022), HR = 0.56 (95%CI:0.34-0.91). The other quadrants had no impact on OS when analyzed together. However, UIQ had a trend towards significancy when compared to ULQ and Lower Lateral Quadrant (LLQ) (p = 0.109) (HR:0.69) Conclusions: Our data demonstrated that tumors located in Lower Inner Quadrants significantly impaired DFS and OS. This effect clearly independent of other prognostic factors such as grade, T stage, N stage, treatment options, age, LVI, ER and PR status. Internal mammary chain sampling might be necessary in medially located tumors, especially for located in Lower Inner Quadrant.
Cognitive Impairment, Hypoalbuminemia, High CRP Level and Past History of Gastro-Intestinal Ulcer: 4 Markers of Frailty Which Identify Older Patients with Malignant Hemopathies Who Shouldn't Benefit from Chemotherapy
Authors: Stephanie Dubruille, Cindy Kenis, Vincent Thibaud, Yves Libert, Michel Delforge, Lissandra Dal Lago, Myriam Roos, Cindy Borghgraef, Pepersack Thierry, Hans Wildiers, Dominique Bron
Journal: Blood (2018)
Bayesian Detection of Convergent Rate Changes of Conserved Noncoding Elements on Phylogenetic Trees
Authors: Zhirui Hu, Timothy B Sackton, Scott V Edwards, Jun S Liu
Journal: Molecular Biology and Evolution (2019)

Conservation of DNA sequence over evolutionary time is a strong indicator of function, and gain or loss of sequence conservation can be used to infer changes in function across a phylogeny. Changes in evolutionary rates on particular lineages in a phylogeny can indicate shared functional shifts, and thus can be used to detect genomic correlates of phenotypic convergence. However, existing methods do not allow easy detection of patterns of rate variation, which causes challenges for detecting convergent rate shifts or other complex evolutionary scenarios. Here we introduce PhyloAcc, a new Bayesian method to model substitution rate changes in conserved elements across a phylogeny. The method assumes several categories of substitution rate for each branch on the phylogenetic tree, estimates substitution rates per category, and detects changes of substitution rate as the posterior probability of a category switch. Simulations show that PhyloAcc can detect genomic regions with rate shifts in multiple target species better than previous methods and has a higher accuracy of reconstructing complex patterns of substitution rate changes than prevalent Bayesian relaxed clock models. We demonstrate the utility of PhyloAcc in two classic examples of convergent phenotypes: loss of flight in birds and the transition to marine life in mammals. In each case, our approach reveals numerous examples of conserved nonexonic elements with accelerations specific to the phenotypically convergent lineages. Our method is widely applicable to any set of conserved elements where multiple rate changes are expected on a phylogeny.
Low vs high hemoglobin trigger for transfusion in vascular surgery: a randomized clinical feasibility trial
Authors: Anders Møller, Henning B. Nielsen, Jørn Wetterslev, Ole B. Pedersen, Dorthe Hellemann, Per Winkel, Klaus V. Marcussen, Benedicte G. U. Ramsing, Anette Mortensen, Janus C. Jakobsen, Saeid Shahidi
Journal: Blood (2019)
The Proteogenomic Landscape of Curable Prostate Cancer
Authors: Ankit Sinha, Vincent Huang, Julie Livingstone, Jenny Wang, Natalie S. Fox, Natalie Kurganovs, Vladimir Ignatchenko, Katharina Fritsch, Nilgun Donmez, Lawrence E. Heisler, Yu-Jia Shiah, Cindy Q. Yao, Javier A. Alfaro, Stas Volik, Anna Lapuk, Michael Fraser, Ken Kron, Alex Murison, Mathieu Lupien, Cenk Sahinalp, Colin C. Collins, Bernard Tetu, Mehdi Masoomian, David M. Berman, Theodorus van der Kwast, Robert G. Bristow, Thomas Kislinger, Paul C. Boutros
Journal: Cancer Cell (2019)
Abstract P210: Long-Term Outcomes After ST-Elevation Myocardial Infraction After Reducing Fibrinolytic Use in a Rural Cohort
Authors: Catherine P Benziger, Richard Mullvain, Patrick Moran, Rakin Solaiman, Ron Regal, Paul Hitz, Ross Blood, Krysta Kaas, Wilson Ginete
Journal: Circulation (2019)

Background: ST-elevation myocardial infarction (STEMI) guidelines recommend lytic therapy if unable to receive primary percutaneous coronary intervention (PPCI) within 120 min. from first medical contact (FMC). Sparse data exists from rural areas; we aimed to evaluate outcomes in rural population after implementing STEMI protocol. Methods: Retrospective chart review of NCDR ACTION and internal STEMI registries presenting to 2 PCI-capable hospitals (Essentia Health in Duluth, MN and Fargo, ND) between 5/2009-12/2017. Only patients with rural rural-urban commuting area (RUCA) codes were included. Analysis included using standard STEMI metrics with Cox regression and Kaplan-Meier survival curves for survival analysis, and logistic regression for 30-day and 1-year mortality and 30-day readmission. Results were adjusted for age and sex. Results: There were 1229 STEMI activations with 1033 true STEMI events (28.3% female, mean age 63.6 years). Among true STEMIs, 73.3% presented to a non-PCI capable hospital and were transferred to PCI-capable hospital. Only 9.9% were field activated and transported directly to PCI-capable hospital. FMC to device time was &lt;120 min. 33.2% of the time with a median FMC to device time of 135 min. (IQR 111-174 min.). Positive ECG to device time was &lt;120 min. 53.9% of the time with a median ECG to device time of 116 min. (IQR 99-144 min). Lytic use decreased over time from 30.2% in 2009-10 to 6.8% in 2016-17. Survival was not different comparing PPCI vs. lytic therapy (hazard ratio 1.21; 95% CI: 0.83, 1.75, p=0.32). For PPCI, 30-day and 1-year mortality were 8.6% (CI:6.8%-10.4%) and 12.8% (CI:10.6%-15.0%), respectively, while for lytics, 30-day and 1-year mortality were 7.2% (CI:4.6%-9.8%) and 10.8% (CI:7.1%-14.3%), respectively. The 30-day readmission for PPCI was not significantly different compared to lytics (7.6%, CI:6.7%-8.7% for PPCI vs. 12.0% CI:9.8%-14.6% for lytic, p=0.056). Conclusion: PPCI in rural areas was associated with similar outcomes compared to lytic therapy for STEMI patients.
WHO calls for more action to protect children from online junk food advertising
Authors: Sophie Arie
Journal: BMJ (2019)

Governments need to do more to understand how much children are being influenced by online advertising for junk food and to protect them from it, the World Health Organisation has said.

Despite existing policies, “exposure of children and young people to the online marketing of unhealthy food products tobacco and alcohol is common,” said Joao Breda, head of the WHO European Office for the Prevention and Control of Non-communicable Diseases.

We have “regulatory frameworks that do not fully protect children and young people and they may need improvements,” he said at the launch of a new report.1

WHO, which has been monitoring digital advertising of …
Capecitabine as a treatment for hereditary palmoplanter keratodermas.
Authors: Ahmad Jajeh
Journal: Journal of Clinical Oncology (2015)

e13522 Background: Hereditary Palmoplanter (Epidermolytic) Keratodermas is an Autosomal Dominant trait that is characterized by immense yellow waxy thickening of skin surrounded by erythematous border( halo) and fissure/cracks associated with extensive scaling of the palms and soles. Different therapeutic agents been used without much success such as topical steroids, Alitretinoin and keraltolytic agents. This abstract will describe our result with Capecitabine; Fluoropyrimidine( Prodrug of 5-flurouracil/ 5FU) an oral agent chemotherapy in the treatment of Palmoplanter Keratodermas. Capcetabine has shown non-inferiority result when compared to 5FU in the treatment of colorectal cancer. Methods: Capecitabine 1000 mg/ m2 orally twice daily for fourteen days every 28 days ( Cycle) for two cycles given to 35 years old male with severe form of Plamoplanter Keratodermas that has failed different modalities of therapy. This followed by reduced dose of Capecitabine 500 mg/m2 twice daily for 14 days in the next 3 cycles. Complete Blood Count CBC with differential and Comprehensive Metabolic Profile were monitored every two weeks. Results: Patient had 70% response interm of resolution of thick skin , fissures and halo erythema in the first cycle. He was able not to use any topical lubricating or steroidal ointment from the first cycle. Conclusions: Capecitabine is an excellent form of therapy for Hereditary Palmerplanter Keratoderma. More experience with more number of patients needed to identify the appropriate dose and number of cycles needed for therapy. Prior anecdotal experience with intravenous continuous infusion of 5FU in this hereditary skin disorder prompted us to use Capecitabine since it is more convenient form of therapy.
Metabolic Tumor Volume and Soluble Cytokines Levels in Newly Diagnosed Hodgkin Lymphoma: What It Brings into the Staging Precision?
Authors: VIT K Prochazka, Lenka Henzlova, Marie Lukasova, Veronika Hanackova, Eva Kriegova, Zuzana Mikulkova, Gabriela Gabcova, Jiri Minarik, Alice Sýkorová, Eva Krcalova, Jiri Dolezal, Pavel Koranda, Tomas Papajik
Journal: Blood (2018)
PAzopanib as first line in MEtastatic RCC patients: A “real-world” ITalian experience (PAMERIT study)—Preliminary results.
Authors: Alessandra Mosca, Ugo De Giorgi, Giuseppe Procopio, Umberto Basso, Giacomo Carteni, Sebastiano Buti, Emanuele Naglieri, Luca Galli, Orazio Caffo, Giuseppe Fornarini, Francesco Boccardo, Gaetano Facchini, Franco Morelli, Paolo Andrea Zucali, Claudia Caserta, Giuseppe Di Lucca, Zuzana Sirotova, Alessandra Gennari, Paolo Bruzzi, Camillo Porta
Journal: Journal of Clinical Oncology (2019)

611 Background: Pazopanib (Pazo) became a standard of care in metastatic renal cell cancer (mRCC) patients (pts) based on 2 prospective trials, but “real life” data are slight. Methods: We retrospectively analyzed clinical outcomes in a large series of mRCC pts routinely treated with 1st line Pazo, among 39 Italian Centers. Descriptive statistics has been performed using Chi-Square and Pearson rank correlation test. Progression-free survival (PFS), overall survival (OS) and safety data are still under investigation. Results: 474 mRCC pts have been collected and divided in 4 age categories: 1) ≤50 yrs old (9.4%); 2) 51-64 yrs old (32.6%); 3) 65-74 yrs old (33.0%); 4) ≥75 yrs old (25.0%). According to Heng score, 25.6%, 48.4% and 10.4% pts had good, intermediate and poor prognosis, respectively, without correlations with age (p = 0.128). Clear cell was the most represented histology (87.3%), independently from age (p = 0.556). 84.6% pts underwent nephrectomy, mainly younger pts (p = 0.000). Pazo initial daily dose was 800 mg in 76.5% pts, 600 mg in 10.8% pts and 400 mg in 12.7% pts, with a significant dose reduction in elderly pts: Pazo 800 was administered in 86.7% of ≤50 yrs old pts and in 54.2% of ≥75 yrs old pts (p = 0.000). Complete (CR)/partial response (PR), stable and progressive disease have been recorded in 37%, 39.5% and 23.5% pts, respectively. Radiological response directly correlated either with age (CR/PR in 55.6% of ≤50 yrs old pts vs 28.8% of ≥75 yrs old pts; p = 0.009) and with Heng score (CR/PR in 47.1% of good prognosis pts vs 24.5% of poor prognosis pts; p = 0.002). Conclusions: “Real world” data showed that younger (≤50 yrs old) mRCC pts more frequently underwent nephrectomy, received Pazo 800 mg daily and obtained CR/PR, with respect to elderly pts (≥75 yrs old). CR/PR to Pazo is associated with good prognosis. PFS and OS will be provided.
Abstract P283: Serum Metabolites and Cardiac Death in Patients on Hemodialysis
Authors: Jiun-Ruey Hu, Morgan E Grams, Josef Coresh, Seungyoung Hwang, Csaba Kovesdy, Eliseo Guallar, Eugene P Rhee, Tariq Shafi
Journal: Circulation (2019)

Introduction: Cardiovascular death is the leading cause of mortality in patients on hemodialysis. Traditional risk factors such as diabetes and hypertension do not fully account for this excess risk. Toxic metabolites that accumulate in renal failure may be responsible for accelerated cardiovascular disease, but these metabolites remain undefined. Hypothesis: The goal of this pilot study was to determine if an untargeted metabolomic approach could identify metabolites associated with cardiac death in dialysis patients. Methods: In this matched case-control study nested in the HEMO study, cases experienced cardiac death vs. were alive, respectively, at 12 months after enrollment. Cases and controls were matched on sex, race, diabetes, cardiac disease, age, and albumin. Cardiac death included death from ischemic heart disease, heart failure, and arrhythmias. Serum samples frozen at the 4 month visit were profiled by mass spectrometry. Conditional logistic regression assessed each metabolite’s association with cardiac death. Results: A total of 47 cases and 47 controls were studied. 777 metabolites available for analysis after data preprocessing. At the p&lt;0.005 threshold, several metabolites were positively associated with cardiac death, and several metabolites were negatively associated with cardiac death. However, no metabolite had significant associations using false discovery rate thresholds. Conclusions: Our study is an example of the use of metabolomics as a strategy for identification of metabolites that may explain the high risk of cardiac death in patients undergoing hemodialysis. Figure 1: Odds ratio for 1-year risk of cardiac death per doubling of metabolite level for each metabolite in the HEMO Study
Systematic review and REMARK scoring of renal cell carcinoma (RCC) prognostic circulating biomarker manuscripts.
Authors: Marco Adelmo James Iafolla, Sarah Louise Picardo, Kyaw Lwin Aung, Aaron Richard Hansen
Journal: Journal of Clinical Oncology (2019)

569 Background: No validated biomarkers exist to help guide prognosis of RCC patients. This study seeks to determine the current state of published prognostic RCC biomarker manuscripts and evaluate their quality using the REMARK criteria. Methods: The phrase “(renal cell carcinoma OR renal cancer OR kidney cancer OR kidney carcinoma) AND circulating AND (biomarkers OR cell free DNA OR tumor DNA OR methylated cell free DNA OR methylated tumor DNA)” was searched in Embase, Medline and PubMed during March 2018. One author (MI) selected all relevant manuscripts from the search results, and two authors (MI and SP) independently scored all relevant manuscripts using the REMARK guidelines (maximum 20 points comprised of 20 items subdivided into 48 criteria). Results: The search identified 525 publications: 73 were valid, 436 were rejected, and 26 were uncertain of their relevance. Amongst the valid publications, 33 were manuscripts of primary research (remainder: 26 review papers, 14 abstracts): manuscripts evaluating ≥ 2 biomarkers (n = 8) and novel biomarkers not published elsewhere (n = 7) comprised the majority. The median REMARK score was 10.6 (range 6.4-14.2). All manuscripts stated their marker, study objectives and method of case selection. The lowest scoring criteria were lack of: description of time between storage of blood/serum and marker assay (n = 2); flow or study profile diagram (n = 2); blinding of the person making the marker assessment to clinical outcomes (n = 3); and pre-specified hypotheses (n = 3). In total, only 8 studies reported a hazard or odds ratio. Using Pearson’s correlation, there was no association with either year of publication (median 2014; range 2004-2018; r 2 = 0.14; p = 0.44) or impact factor (median 5.168; range 1.2-26.303; r 2 = 0.24; p = 0.17) with REMARK score. Conclusions: Despite several published manuscripts on RCC prognostic biomarkers, most poorly adhere to the REMARK guidelines; this may be the cause for the paucity of a validated RCC biomarker to help supplement or supplant current clinical prognostic criteria. Better designed studies and appropriate reporting of methods, results and interpretation are required to address this urgent unmet need.