tbuckley/cabot-search huggingface dataset:
Abstract P364: Validity of Self-Reported Cardiovascular Disease Risk From Survey Questions
Authors: Sue Duval, Jeremy Van’t Hof, Lyn M Steffen, Russell V Luepker
Journal: Circulation (2019)

Introduction: Simple questionnaires with dichotomous responses evaluating atherosclerotic risk factors are frequently used to assess cardiovascular disease (CVD) risk in research and clinical settings. Such methods are easier and less costly than direct measurements, but the validity of self-reported risk compared to calculated CVD risk is not well studied. Hypothesis: Self-reported history of hypertension, hyperlipidemia, diabetes and smoking will predict measured CVD risk. Methods: Using the ACC/AHA Pooled Cohort Risk Equations (PCE), we calculated 10 year CVD risk from a randomly selected population sample of 9,856 individuals aged 40-79 without a history of CVD in the Minnesota Heart Survey (MHS). Using log-linear regression models, we estimated sex-specific PCE risk from the individual’s self-reported history of 4 dichotomous risk factors; hypertension, hypercholesterolemia, diabetes, and smoking. Age was included in all models. Model performance was assessed internally using leave-one-out cross-validation. Results: The median PCE 10 year CVD risk in women was 2.1% (IQR: 0.8%-5.6%), and in men was 6.3% (3.1%–13.0%). Using the newly developed equations, which included only the 4 self-reported risk factors and age, the estimated median risk was 2.2% (0.9%-5.8%) in women, and 6.9% (3.2%–13.1%) in men. The measured and estimated PCE risk using a threshold of 7.5% to categorize low and high risk gave an accuracy of 95% for women and 87% for men. The multivariable model-estimated PCE corresponded closely with the actual PCE (Figure). Conclusions: Self-reported history of atherosclerotic risk factors may be useful to estimate CVD risk in individuals, avoiding actual measurements.
Identification of HPV16 genetic subtypes and sublineages in patients with HPV-positive head and neck cancer (HNC).
Authors: Gisela N Sulkowski, Moin Ahmad, Dzung Thach, Joeffrey J Chahine, Bhaskar Kallakury, John E. Niederhuber, Ramaswamy K Iyer, John F. Deeken
Journal: Journal of Clinical Oncology (2015)

e17097 Background: The cause for the rising incidence of HPV+ HNC remains unexplained. Research in cervical cancer has identified genetic variants of HPV16 that define subtypes -- European (E) vs Non-European (Non-E) -- and sublineages (E(p), E(As), Af-1, Af-2, NA1, AA1, and AA2) (Smith 2011). These differ in frequency and possibly oncogenic potential, including a 2-fold higher persistent infection risk and a 2- to 4-fold higher risk of causing cervical carcinogenesis from the Non-E compared to E subtypes. No similar work has been reported in HPV16+ HNC. Methods: DNA was isolated from tumor blocks from 10 patients with HPV16+ HNC. The E2/E4 overlap region of HPV16 was amplified with pairs of overlapping primers. PCR product was sequenced using Sanger sequencing. Patient’s viral sequence was aligned with the HPV16 genome using Sequencher software. Subtype/sublineage was assigned based on conserved, lineage-specific SNPs. Results: A total of 10 tumors were analyzed. Patient demographics were as follows: all male, primary sites were oropharyx (8) and unknown primary (2), stage at diagnosis were III (1), IVA (6) and IVB(3). All 10 patients were found to have HPV16 with SNPs that placed the virus in an identifiable subtype/sublineage. Seven patient samples were categorized as the European (E) subtype and three were the Non-European subtype. Conclusions: We found that genetically testing HNC tumors into HPV16+ subtypes/sublineages was feasible. In this small cohort we did not find a higher rate of Non-E HPV16 subtypes as would be expected from the cervical cancer literature. Instead HPV+ HNC may be due to the E and Non-E subtypes of the virus. Further investigation into the clinical utility of identifying subtypes and sublineages is warranted and ongoing.
Dysglycemia and the Density of the Coronary Vasa Vasorum
Authors: Hertzel C. Gerstein, Vidhya Nair, Ruchi Chaube, Heidi Stoute, Geoff Werstuck
Journal: Diabetes Care (2019)

OBJECTIVE This study was conducted to determine the relationship between dysglycemia and the coronary artery vasa vasorum density. RESEARCH DESIGN AND METHODS The left anterior descending coronary artery was removed from 57 deceased individuals during autopsy, and the capillaries in the vessel wall were identified using fluorescent immunohistochemical staining. HbA1c was determined in postmortem whole blood for each individual. The density of the vasa vasorum in the intima-media and the adventitia was manually quantified and recorded by readers unaware of the individual’s other characteristics. RESULTS The individuals with diabetes had a lower density of the coronary vasa vasorum than those without diabetes. The higher the HbA1c, the lower the density of these vessels in the adventitia and entire vessel wall. CONCLUSIONS Dysglycemia-induced damage to the vasa vasorum may promote ischemic heart disease in people with diabetes.
Outcomes research for prognostic scores in hepatocellular cancer (HCC): Can we do any better?
Authors: Kerstin Schuette, Frederik Neubueser, Alexander Link, Christian Schulz, Joerg Arend, Tina Bretschneider, Peter Malfertheiner, Gerhard Treiber
Journal: Journal of Clinical Oncology (2015)

e15153 Background: The BCLC Staging classification is the preferred prognostic scoring system for HCC. Competing scoring systems like CLIP rely also on either subjective or difficult-to-determine parameters and most data have been derived from highly selected populations. Methods: To assess different parameters for survival outcome, we included pts. derived from 3 previous phase II trials and also pts. who could not be included into trials but who were prospectively followed up and treated individually. All pts. had RECIST measurements at baseline and after 8-12 weeks. We then compared the results with 2 newer scoring systems, relying either totally on laboratory parameters (BALAD-2 score) or on disease evaluation during follow-up (
Comparison of Cure Rates between Gemtuzumab Ozogamicin Plus Standard of Care Chemotherapy Vs Standard of Care Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia
Authors: Bogdan Muresan, Carla M. Mamolo, Joseph C Cappelleri, Ruth Mokgokong, Athina Palaka, Robert K. Hills, Nicholas Latimer, Bart Heeg
Journal: Blood (2018)
Dietary coconut oil ameliorates skin contact hypersensitivity through mead acid production in mice
Authors: Prabha Tiwari, Takahiro Nagatake, So‐ichiro Hirata, Kento Sawane, Azusa Saika, Yuki Shibata, Sakiko Morimoto, Tetsuya Honda, Jun Adachi, Yuichi Abe, Junko Isoyama, Takeshi Tomonaga, Hiroshi Kiyono, Kenji Kabashima, Jun Kunisawa
Journal: Allergy (2019)

Abstract Coconut oil is used as a dietary oil worldwide, and its healthy effects are recognized by the fact that coconut oil is easy to digest, helps in weight management, increases healthy cholesterol, and provides instant energy. Although topical application of coconut oil is known to reduce skin infection and inflammation, whether dietary coconut oil has any role in decreasing skin inflammation is unknown. In this study, we showed the impact of dietary coconut oil in allergic skin inflammation by using a mouse model of contact hypersensitivity (CHS). Mice maintained on coconut oil showed amelioration of skin inflammation and increased levels of cis‐5, 8, 11‐eicosatrienoic acid (mead acid) in serum. Intraperitoneal injection of mead acid inhibited CHS and reduced the number of neutrophils infiltrating to the skin. Detailed mechanistic studies unveiled that mead acid inhibited the directional migration of neutrophils by inhibiting the filamentous actin polymerization and leukotriene B 4 production required for secondary recruitment of neutrophils. Our findings provide valuable insights into the preventive roles of coconut oil and mead acid against skin inflammation, thereby offering attractive therapeutic possibilities.
Disparity by insurance status and race in receipt of aggressive and advanced treatments for high risk prostate cancer/PCa.
Authors: Brock R. Baker, Ramsankar Basak, Jahan J. Mohiuddin, Ronald C. Chen
Journal: Journal of Clinical Oncology (2015)

6538 Background: Young and healthy men with high-risk PCa require aggressive treatment. We examined treatment received by these men using the National Cancer Data Base, which contains 70% of incident cancers across the US. We hypothesized a disparity by race and insurance on receipt of aggressive treatment and access to advanced surgical (robotic) and RT (proton or intensity-modulated RT) techniques. Methods: 12,778 men age < 65 with Charlson comorbidity score 0 diagnosed with NCCN high-risk PCa from 2010-12 were included. Logistic regression examined factors associated with treatment. Results: 97% received definitive treatment (either radical prostatectomy or radiation). However, there was a dramatic difference in use of RP by race (White 73%, Black 50%) and insurance (Private 71%, Medicaid 38%)(Table). On multivariate analysis (MVA) which adjusted for age, facility type and regional sociodemographics, race (Black vs White, OR .45, p < .001) and insurance (vs private, Medicaid OR .32, uninsured .39, p < .001 for both) remained associated with prostatectomy as primary treatment. Among surgical patients, 73% with private insurance received robotic surgery compared to 54% Medicaid patients (Table). In MVA, insurance was significantly associated with robotic surgery (vs private, Medicaid OR .48, uninsured .42, p < .001 for both). In MVA for RT patients, Medicaid vs private insurance was associated with less advanced technology (OR .73, p = .02). Black vs White race were not significantly different in receipt of advanced surgical or RT technologies. Conclusions: Young/healthy men with high-risk PCa who lack private insurance or were non-white were treated less aggressively. Medicaid and uninsured patients were also less likely to receive advanced surgical and RT technologies. These findings are difficult to explain medically and point to differences in treatment access. Percentage of patients receiving each treatment. Primary Treatment p Surgical Technique p RT Technique p Prostatectomy Not Robotic Not Advanced Not Race White 73 28 < .001 72 28 < .001 71 29 .002 Black 50 50 68 32 66 34 Hispanic 61 39 61 39 67 33 p p p Insurance Private 71 29 < .001 73 27 < .001 70 31 .01 Medicaid 38 62 54 46 61 39 Uninsured 44 56 51 49 68 33
A retrospective analysis of treatment patterns in metastatic castration-resistant prostate cancer patients treated with radium-223.
Authors: A. Oliver Sartor, Sreevalsa Appukkuttan, Ronald E. Aubert, Jeffrey Weiss, Joy Wang, Stacey Simmons, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2019)

180 Background: Radium-223 (RA-223) is the first FDA approved targeted alpha therapy that significantly improves overall survival (OS) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) with symptomatic bone metastases. There is limited real world data describing RA-223 current use. Methods: A retrospective patient chart review was done of men who received at least 1 cycle of Ra-223 for mCRPC in 10 centers throughout the US (4 academic, 6 private practices). All pts had a minimum follow-up of 4 months, or placed in hospice or death. Descriptive analyses for clinical characteristics and treatment outcomes were performed. Results: Among the 200 pts (mean age-73.6 years, mean Charlson comorbidity index-6.9) RA-223 was initiated on average 1.6 years from mCRPC diagnosis (first line use (1L)=38.5%, 2L=31.5% and ≥3L=30%). 78% completed 5-6 cycles of RA-223 with mean therapy duration of 4.2 months. Among all pts, 43% received RA-223 as monotherapy (no overlap with other mCRPC therapies) while 57% had combination therapy with either abiraterone or enzalutamide. Median OS following RA-223 initiation was 21.2 months (95% CI 19.6- 29.2). Table provides the RA-223 utilization by type of clinical practice. Conclusions: Utilization of RA-223 in this real world data set was distinct from clinical trial data. Most patients received RA-223 in combination with abiraterone or enzalutamide, therapies that were unavailable when the pilot trial was conducted. Median survival was 21.2 months. Real world use of RA-223 has evolved as newer agents have become FDA approved in bone-metastatic CRPC. Academic and community patterns of practice were more similar than distinct. [Table: see text]
Protmune, a Next-Generation Graft for GvHD Prophylaxis in Allogeneic Hematopoietic Cell Transplantation: 1-Year Safety and Efficacy Phase 1 Data
Authors: Richard T. Maziarz, John Edwards, James Essell, Cesar Freytes, Chatchada Karanes, Ayman Saad, Dimitrios Tzachanis, Monica Diaz, Amanda Medcalf, Chris Storgard, Abhinav Deol
Journal: Blood (2018)
Evaluation of rapid whole-body magnetic resonance as screening strategy for early cancer detection in 57 Brazilian Li-Fraumeni syndrome patients.
Authors: Daniele Paixao, Marcos Duarte Guimaraes, Amanda Franca Nobrega, David Malkin, Rubens Chojniak, Maria Isabel Waddington Achatz
Journal: Journal of Clinical Oncology (2015)

1534 Background: Li-Fraumeni Syndrome (LFS) is a rare autosomal dominant syndrome associated with germline mutations in TP53 gene. Carriers have a high risk for developing multiple early onset cancers, most commonly breast cancer, sarcomas, brain and adrenocortical carcinomas. Screening strategies for early diagnosis in carriers constitute a major challenge due to the diverse spectrum and ages of onset of tumors. Rapid whole body MRI (RWB–MRI) has been proposed as a screening strategy. In Brazil, there is a high prevalence of a founder mutation (p.R337H TP53) present in 0.3% of the South/Southeastern Brazilian population. Due to genetic modifiers, tumors occur at a later age in p.R337H carriers. Methods: The aim of this study is to evaluate the efficacy of RWB–MRI as a screening strategy in p.R337H TP53 carriers and in classical LFS mutation carriers. A total of 84 RWB–MRI were performed in 57 TP53 germline mutation carriers (49 p.R337H TP53), including 27 patients who performed a second exam 12 months after the first RWB–MRI. Results: Two malignant lesions were detected by RWB–MRI: (1) in a 19–year old p.R337H female carrier RWB-MRI demonstrated bilateral renal cortical alterations, confirmed with abdominal MRI which showed an enhancing solid lesion in the right kidney. The lesion was surgically removed and pathological findings confirmed a papillary renal cell carcinoma; (2) in a 30 year old p.R337H female carrier, RWB–MRI detected a solid right breast nodule. Breast MRI detected two solid lesions. Biopsy of each lesion confirmed diagnoses of a ductal carcinoma in situ and benign phyllodes tumor, respectively. Incidental findings were detected in 26/57 patients and further imaging modalities were performed in 9/26 cases which ruled out malignancies and no unnecessary biopsies were performed. No malignant lesions were detected in 8 classical LFS patients. Conclusions: Preliminary results from this study demonstrate the feasibility and effectiveness of RWB–MRI in detecting malignant lesions among 49 p.R337H TP53 mutation carriers.
Pegylated liposomal doxorubicin-induced palmar plantar erythrodyesthesia: Identification of risks factors.
Authors: Zahra Ajgal, Nicolas Chapuis, George Emile, Anatole Cessot, jean-Marie Tigaud, Pascaline Boudou-Rouquette, Bruno Borghese, Michaela Fontenay, Francois Goldwasser, Jérôme Alexandre
Journal: Journal of Clinical Oncology (2015)

e13569 Background: Pegylated liposomal doxorubicin (PLD) is widely used in relapsing ovarian carcinoma (ROC). Its original formulation is metabolized by the monocyte-macrophage system. One of its main toxicities is the Palmo plantar erythrodyesthesia (PPE) syndrome. PPE can severely impair patients (pts) quality of lifeleading to treatment discontinuation. To date, no predictive factors of PPE have been identified. Methods: Data of pts treated with PLD between 2005 and 2014 were retrospectively collected. A case-control study was performed, comparing main baseline clinical and biological characteristics of patients experiencing PPE and those who did not, after at least three cycles of PLD. A pilot analysis of blood monocytes subpopulations quantification by flow cytometry (classical, intermediate and non - classical) according to CD14 and CD16 expression was performed in selected patients. Results: Among 88 patients treated with PLD, 28 experienced PPE of any grade (31%, 95%CI: 21-41).The first occurrence of PPE was after cycle 1, cycle 2 or cycles 3 to 6 in 11, 32 and 57% of cases, respectively. Baseline characteristics of pts with PPE were compared to 27 control pts who received at least 3 cycles. In both groups, most patients were female (54/56) and had ROC (33/56). The only clinical parameter associated with the occurrence of PPE was age older than 70: the proportion of pts older than 70 years was 61% and 15% in pts with and without PPE, respectively (p = 0,04 by Khi2 test). Monocytes count and inflammatory parameters were not associated with PPE. However, preliminary analysis of monocytes subpopulation in 9 additional pts revealed a large inter-patient variability. Conclusions: In contrast to most acute toxicities, PPE occurred more frequently after several cycles, suggesting a PLD body accumulation through repeated cycles. PPE was more frequent in pts older than 70 yrs. Monocytes subpopulations may have different role on PLD metabolism and warrant further studies.
Neuronal autoantibodies associated with cognitive impairment in melanoma patients
Authors: F. Bartels, T. Strönisch, K. Farmer, K. Rentzsch, F. Kiecker, C. Finke
Journal: Annals of Oncology (2019)

Cancer-related cognitive impairment is an important complication in cancer patients, yet the underlying mechanisms remain unknown. Over the last decade, the field of paraneoplastic neurological syndromes has been dramatically changed by the discovery of new neuronal autoantibodies, some of them associated with cognitive impairment. We aimed to assess the prevalence of neuronal autoantibodies in melanoma patients and their association with neurological and cognitive dysfunction.
Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial
Authors: O. Trédan, Q. Wang, D. Pissaloux, P. Cassier, A. de la Fouchardière, J. Fayette, F. Desseigne, I. Ray-Coquard, C. de la Fouchardière, D. Frappaz, P.-E. Heudel, A. Bonneville-Levard, A. Fléchon, M. Sarabi, P. Guibert, T. Bachelot, M. Pérol, B. You, N. Bonnin, O. Collard, C. Leyronnas, V. Attignon, C. Baudet, E. Sohier, J.-P. Villemin, A. Viari, S. Boyault, S. Lantuejoul, S. Paindavoine, I. Treillleux, C. Rodriguez, V. Agrapart, V. Corset, G. Garin, S. Chabaud, D. Pérol, J.-Y. Blay
Journal: Annals of Oncology (2019)
Efficacy and Safety of Venetoclax (Ven) + Rituximab (R) or Ven + Bendamustine (B) + R Randomized Versus B + R in Patients (pts) with Relapsed/Refractory (R/R) Follicular Lymphoma (FL): Final Analysis of Phase II CONTRALTO Study
Authors: Pier Luigi Zinzani, Ian W. Flinn, Sam Yuen, Max S. Topp, Chiara Rusconi, Isabelle Fleury, Christopher K Arthur, Barbara Pro, Giuseppe Gritti, Michael Crump, Katell Le Du, Divya Samineni, Arijit Sinha, Elizabeth A Punnoose, Edith Szafer-Glusman, Nathalie Danesi, Adam Petrich, Martin Kornacker, Kathryn Humphrey, Mehrdad Mobasher, Wolfgang Hiddemann
Journal: Blood (2018)
CB-839, a glutaminase inhibitor, in combination with cabozantinib in patients with clear cell and papillary metastatic renal cell cancer (mRCC): Results of a phase I study.
Authors: Funda Meric-Bernstam, Richard J. Lee, Bradley Curtis Carthon, Othon Iliopoulos, James Walter Mier, Manish R. Patel, Nizar M. Tannir, Taofeek Kunle Owonikoko, Naomi B. Haas, Martin Henner Voss, James J. Harding, Ramaprasad Srinivasan, Geoffrey Shapiro, Melinda L. Telli, Pamela N. Munster, Richard D. Carvajal, Yonchu Jenkins, Sam H. Whiting, Johanna C. Bendell, Todd Michael Bauer
Journal: Journal of Clinical Oncology (2019)

549 Background: Glutaminase (GLS) is a key enzyme that controls glutamine utilization, a metabolic pathway upregulated in RCC and important for tumor proliferation and survival. CB-839 is a first-in-clinic, small molecule, reversible, oral GLS inhibitor that synergizes with cabozantinib (Cabo), a VEGFR2/MET/AXL inhibitor, in preclinical RCC models to inhibit metabolic pathways and enhance anti-tumor activity. Cabo monotherapy is associated with a 17% overall response rate (ORR) for clear cell (cc) mRCC (Choueiri et al. Lancet Oncol. 2016). Here we present findings from a Phase 1 study cohort evaluating the safety, efficacy, and recommended Phase 2 dose (RP2D) of CB-839 + Cabo in patients (pts) with mRCC as 2L+ therapy. Methods: Eligible pts had mRCC with cc or papillary histology, ECOG 0-1, RECIST measurable disease, and, for cc pts, treatment with ≥1 prior anti-VEGF therapy. Escalating doses of CB-839 (600-800 mg PO BID) plus Cabo (60 mg PO QD) were evaluated using a 3+3 design. Tumor response was assessed per RECIST 1.1 every 8 wks. Results: The CB-Cabo cohort enrolled 13 pts with a median 3 (range, 0-7) prior lines of therapy. No maximum tolerated dose was reached; 800 mg was selected as the CB-839 RP2D. The most common treatment-related AEs (occurring in &gt;25% of pts) were diarrhea (62%), decreased appetite (46%), ALT increased (39%), fatigue (39%), AST increased (31%), nausea (31%), and rash (31%); Gr ≥3 treatment-related AEs included diarrhea, hypertension, platelet count decreased, and hallucination (n=1 each). Among 12 evaluable pts, ORR was 42% and disease control rate (DCR = complete response + partial response [PR] + stable disease [SD]) was 100%: 42% (5/12) PR, 58% (7/12) SD. Among 10 evaluable cc mRCC pts, 50% (5/10) had PRs, 50% (5/10) SDs. As of Sept 24, 2018, 5 pts received &gt;12 months treatment; 4 remain on study. Conclusions: CB-839 plus Cabo showed encouraging clinical activity and tolerability in heavily pretreated mRCC pts, with response rates for cc mRCC (50% ORR, 100% DCR) comparing favorably to historical Cabo monotherapy. A randomized Phase 2 study of CB-839 + Cabo vs. Cabo + placebo in cc mRCC is ongoing. (CANTATA; NCT0342821) Clinical trial information: NCT02071862.
The Transcription Factor TAp63 Exerts Pro-Survival Effects in Chronic Lymphocytic Leukemia Acting through the BCL2 Pathway
Authors: Stamatia Laidou, Stavroula Ntoufa, Sofia Papanikolaou, Konstantia Kotta, Maria Koutroumani, Theodoros Moysiadis, Achilles Anagnostopoulos, Anastasia Kouvatsi, Niki Stavroyianni, Anastasia Hadzidimitriou, Antonios M. Makris, Nikos Papakonstantinou, Kostas Stamatopoulos
Journal: Blood (2018)