tbuckley/cabot-search huggingface dataset:
Association of ideal cardiovascular health at age 50 with incidence of dementia: 25 year follow-up of Whitehall II cohort study
Authors: Séverine Sabia, Aurore Fayosse, Julien Dumurgier, Alexis Schnitzler, Jean-Philippe Empana, Klaus P Ebmeier, Aline Dugravot, Mika Kivimäki, Archana Singh-Manoux
Journal: BMJ (2019)

To examine the association between the Life Simple 7 cardiovascular health score at age 50 and incidence of dementia.Prospective cohort study.Civil service departments in London (Whitehall II study; study inception 1985-88).7899 participants with data on the cardiovascular health score at age 50.The cardiovascular health score included four behavioural (smoking, diet, physical activity, body mass index) and three biological (fasting glucose, blood cholesterol, blood pressure) metrics, coded on a three point scale (0, 1, 2). The cardiovascular health score was the sum of seven metrics (score range 0-14) and was categorised into poor (scores 0-6), intermediate (7-11), and optimal (12-14) cardiovascular health.Incident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017.347 incident cases of dementia were recorded over a median follow-up of 24.7 years. Compared with an incidence rate of dementia of 3.2 (95% confidence interval 2.5 to 4.0) per 1000 person years among the group with poor cardiovascular health, the absolute rate differences per 1000 person years were -1.5 (95% confidence interval -2.3 to -0.7) for the group with intermediate cardiovascular health and -1.9 (-2.8 to -1.1) for the group with optimal cardiovascular health. Higher cardiovascular health score was associated with a lower risk of dementia (hazard ratio 0.89 (0.85 to 0.95) per 1 point increment in the cardiovascular health score). Similar associations with dementia were observed for the behavioural and biological subscales (hazard ratios per 1 point increment in the subscores 0.87 (0.81 to 0.93) and 0.91 (0.83 to 1.00), respectively). The association between cardiovascular health at age 50 and dementia was also seen in people who remained free of cardiovascular disease over the follow-up (hazard ratio 0.89 (0.84 to 0.95) per 1 point increment in the cardiovascular health score).Adherence to the Life Simple 7 ideal cardiovascular health recommendations in midlife was associated with a lower risk of dementia later in life.
Departments involved during the first episode of acute heart failure and subsequent emergency department revisits and rehospitalisations: an outlook through the NOVICA cohort
Authors: Òscar Miró, Ana García Sarasola, Carolina Fuenzalida, Sofía Calderón, Javier Jacob, Alfons Aguirre, Da M. Wu, Miguel A. Rizzi, Pierre Malchair, Antonio Haro, Sergio Herrera, Víctor Gil, Francisco J. Martín‐Sánchez, Pere Llorens, Pablo Herrero Puente, Héctor Bueno, Alberto Domínguez Rodríguez, Christian E. Müller, Alexandre Mebazaa, Ovidiu Chioncel, Aitor Alquézar‐Arbé
Journal: European Journal of Heart Failure (2019)
Survival disparities of diffuse large B-cell lymphoma in a community-based cancer center.
Authors: Vinicius Machado Jorge, Andrew Chua Tiu, Peter Moussa, Sorab Gupta, Djeneba Audrey Djibo, Claudia M. Dourado
Journal: Journal of Clinical Oncology (2019)

7541 Background: Non-Hodgkin’s Lymphoma (NHL) is a heterogeneous group of hematologic malignancy from immature or mature lymphocytes or natural killer cells. It is the 9 th leading cause of death for both sexes. Diffuse Large B Cell Lymphoma (DLBCL), a subset of NHL, comprises 30 – 40% of all NHL. The etiology for the racial disparities in survival among patients with DLBCL is still unknown. The Revised International Prognostic Index (R-IPI), a tool which predicts the outcome of DLBCL patients, has not yet been fully validated in African Americans (AA). Methods: We conducted a single cohort study of patients diagnosed with DLBCL from January 1, 2007 to December 31, 2017 from our tumor registry in a single community-based cancer center. We abstracted demographic, clinical, histopathologic, treatment, and R-IPI variables. Our primary endpoint was overall survival (OS). Our secondary endpoints were factors that determine mortality through Cox multivariate analysis. Results: Among 381 patients with NHL, 181 (47.5%) patients had biopsy-proven DLBCL. Median age was 65 years old, 47% were males, 41% were AA, 44% were Caucasians, 46% were stage IV by Ann-Arbor staging. African-Americans (AA) had a median OS of 15.7 months (95% CI, 10.31 to 23.90) compared to non-AA 93.6 months (95% CI, 61.48 to 142.57). Even after adjusting for race, R-IPI was correlated with mortality on all patients. Lactate dehydrogenase levels were significantly higher in AA (P&lt;0.001) but there was no difference in the interval from diagnosis to initiation of treatment in all groups. The presence of B symptoms HR 1.80 (95% CI, 1.17 to 2.77), African-American race HR 2.19 (95% CI, 1.38 to 3.52), positive HIV HR 2.16 (95% CI, 1.15 to 4.05), chronic liver disease HR 1.87 (95% CI, 1.09 to 3.23), and malnutrition HR 2.46 (95% CI, 1.30 to 4.65) were all independently associated with increased mortality. Histopathologic features such as the cell of origin, BCL6, and BCL2 rearrangements were not independently associated with increased mortality. Conclusions: There is an overwhelming disparity in survival among AA with DLBCL. The R-IPI is a reliable tool for predicting mortality in AA with DLBCL.
Efficacy of low-dose ketoconazole in the treatment of castration-resistant prostate cancer (CRPC): A single-institution experience.
Authors: Cinzia Ortega, Fiorella Ruatta, Veronica Prati, Valentina Ballatore, Antonio Capaldi, Elisabetta Garibaldi, Pietro Gabriele, Giovanni Muto, Massimo Aglietta
Journal: Journal of Clinical Oncology (2012)

e15133 Background: The management of rising PSA in CRPC remains controversial. Secondary hormonal manipulations are commonly used before starting chemotherapy. Ketoconazole, an antimycotic that affects the synthesis of androgens and other steroids, has shown direct cytotoxic effects in prostate cancer. This retrospective study describes our experience with low doses of ketoconazole and prednisone treatment for CRPC. Methods: From 4/2007 to 12/2011, 65 patients with progressive CRPC who were previously treated with maximal androgen blockade received 200 mg ketoconazole orally bid with orally replacement prednisone (5 mg bid) and maintained LHRH-agonists. Performance status of all patients was ECOG0. Overall, 34/65 (52.3%) patients had only bone metastases, 12/65 (18.5%) had nodal metastases, 17/65 (26.2%) both and only 2/65 (3.1%) had bone plus lung mets. All patients had low tumor burden and PSADT &gt;6 months. Thirty-six out of 53 patients with bone mets received concomitant zoledronic acid. PSA response was defined as a &gt;50% fall in PSA from baseline and PSA nadir was calculated. Progression was defined by objective disease progression or PSA increase of &gt;50% above nadir or &gt;25% above baseline. Patients were monitored clinically and with serial PSA measurements every 1-month. Results: Median age was 74.05 (range: 52.8-84.4) years; median baseline PSA was 29.95 (range: 1.18-1348.8) ng/ml; median duration of the treatment was 5.87 (range: 0.57-52.4) months. All pts were evaluable for PSA response. At a median F.U.of 15.4 mos. 19/65 patients (29.2%) showed a decrease in PSA &gt;50%, with a median TTP of 17.23 mos for responders. Overall TTP was 5.86 mos and it was not affected by metastatic sites (p= 0.71).Toxicity was mild and no patients discontinued therapy because of side-effects. Five out of 65 patients had G2 (CTC.AE 4) nausea and moderate elevated transaminases. No acute hepatitis or adrenal insufficiency was observed. Conclusions: Our data confirm that low-dose ketoconazole is an effective and well-tolerated treatment in patients with CRPC and should be considered in the subset of patients with low-volume disease and a rising PSA level despite maximal androgen blockade.
Phase I study of the EGFR tyrosine kinase inhibitor erlotinib in combination with docetaxel and radiation in locally advanced squamous cell cancer of the head and neck (SCCHN)
Authors: P. Savvides, S. S. Agarwala, J. Greskovich, A. Argiris, J. Bokar, M. Cooney, C. Hoppel, D. W. Stepnick, P. Lavertu, S. Remick
Journal: Journal of Clinical Oncology (2006)

5545 Background: EGFR is highly expressed in SCCHN, representing a promising therapeutic target. Erlotinib (E) is an EGFR tyrosine kinase inhibitor that may potentiate the efficacy of concurrent radiation (RT) and docetaxel (D). We sought to establish the MTD, toxicities and preliminary efficacy of the combination of RT, D and E in patients (pts) with SCCHN. Methods: Patients with previously untreated stage III-IVB SCCHN were enrolled in a phase I dose-escalating study with standard once-daily RT (70.2 Gy, 1.8 Gy/day), weekly D for the duration of RT and daily E for two weeks prior, during and up to two years following RT. 4 dose levels (DL) were evaluated [D (mg/m 2 )/E (mg): 15/50, 15/100, 20/100, 20/150]. A 3+3 escalation design was followed. Pharmacokinetic studies (PK) were performed. Results: A total of 23 patients were enrolled (6 pts at each DL 1–3, 5 pts at DL4). Primary site: oral cavity (n = 1), pharynx (n = 15) and larynx (n = 7). 20 patients (87%) had stage IV disease. Three dose-limiting toxicities were observed, 1 at each DL (1–3), including a death within 30 days from last treatment (DL1), grade 3 mucositis resulting in holding RT (&gt;5 days) (DL2) and grade 4 mucositis (DL3). No DLT to date on DL4 with 3/5 pts evaluable. In patients enrolled at DL 1–3 (n = 18), post concurrent chemoRT, best response was CR (n = 15), not evaluable (n = 2), death on study (n = 1). 3/3 pts who underwent planned neck dissection had a pathologic CR. 9 patients are currently receiving adjuvant E and 1 has completed the 2-year course. 3 patients have relapsed. Interpatient variability of E peak plasma concentrations measured after the first dose was observed at all dose levels: 458 ± 173 ng/mL (DL1), 686 ± 364 (DL2), 1017 ± 241 (DL3), 833 ± 222 (DL4) (mean ± s.d., n = 6, 6, 6, 2 at DL1–4 respectively). Adjuvant erlotinib plasma concentration data will be presented separately. No significant PK interaction of erlotinib with docetaxel was noted. Conclusions: The combination of daily erlotinib with weekly docetaxel and RT for pts with stage III-IVB SCCHN is feasible and active. A phase II trial is planned. Supported in part by NIH grants nos. CA62502 and M01 RR-000080. No significant financial relationships to disclose.
Use of Eculizumab in a Patient with Refractory Autoimmune Hemolytic Anemia with Heterozygous NFκB1 Mutation
Authors: Katharine Halligan, Lana Vasiljevic, Phillip Roehrs, Andrew Mcginnitie, Sung-Yun Pai, Rachael F. Grace, Maria Olivares Boucher, Lauren Weintraub
Journal: Blood (2017)
Increased cytoplasmic localization of KLF5 in prostate cancer
Authors: H. T. Tsai, M. Datta, H. Frierson, X. Dong, Y. Qiu, S. Sun, J. Dong
Journal: Journal of Clinical Oncology (2006)

14652 Background: KLF undergoes genomic deletion, transcriptional downregulation, and excessive protein degradation in prostate cancer cells, but its protein expression has not been examined in prostate cancer specimens. Methods: We performed immunohistochemical staining on a tissue microarray composed of 37 benign prostate tissues, 58 primary prostate cancers, and 9 metastatic tumors. Cultured cells without KLF5 expression and those expressing KLF5 through gene transfection were used as controls. Each sample was scored for presence of staining, nuclear or cytoplasmic localization of staining, and intensity of staining (0, no staining; 1, below counterstain; 2, equal to counterstain; 3, strong staining obscuring counterstain). KLF5 expression was correlated with pathologic characteristics of tumors by performing Chi-square analysis and two tailed t tests. Results: KLF5 staining was noted in all 104 specimens, either as nuclear staining, cytoplasmic staining, or both. While no significant differences were seen in the intensity of the nuclear staining between benign and tumor groups, a significant increase in cytoplasmic staining was seen in tumor specimens (2.24 vs. 1.71, p = 0.0002). In addition, samples with high cytoplasmic and low nuclear KLF5 were more likely to be tumor samples (p = 0.0413). No significant differences were seen between samples with Gleason grades, or between primary tumors and metastases. Conclusions: Increased cytoplasmic localization of KLF5 may impair KLF5’s transcription factor function in the development and/or progression of prostate cancer. No significant financial relationships to disclose.
Myeloid Malignancy Variant Curation Expert Panel: An ASH-Sponsored Clingen Expert Panel to Optimize and Validate Acmg/AMP Variant Interpretation Guidelines for Genes Associated with Inherited Myeloid Neoplasms
Authors: Lucy Godley, Xi Luo, Justyne Ross, Sarah Jackson, Anupriya Agarwal, Panagiotis Baliakas, Alison A. Bertuch, Anna L. Brown, Michael C. Chicka, Courtney D. DiNardo, Mark D. Fleming, Sioban Keel, Chimene Kesserwan, Zejuan Li, Minjie Luo, Luca Malcovati, Shannon K. McWeeney, Kim E. Nichols, Christopher C. Porter, Anna Raimbault, Lesley Rawlings, Mark Routbort, Gabriella Ryan, Jean Soulier, Nancy E. Speck, Tom Vulliamy, Michael Francis Walsh, Ying Wang, Liying Zhang, Sharon Plon, David Wu
Journal: Blood (2018)
Mutational status of KRAS and BRAF of an Argentinian population of colorectal tumors.
Authors: Paula Lopez Ruitti, Ruben Salanova, Julieta Nafissi, Guillermo Rabossi, Guillermo Bramuglia, Yanina Powazniak
Journal: Journal of Clinical Oncology (2012)

e14109 Background: Activating mutation of the KRAS oncogene is an established predictive biomarker for resistance to anti–epidermal growth factor receptor (anti-EGFR) therapies in advanced colorectal cancer (CRC). BRAF, another component of the EGFR-MAPK signal transduction pathway, is also subject to a common activating mutation in CRC. The aim of this report is to present the mutational status of KRAS, BRAF of an Argentinian population of CR tumors. Methods: Tumor blocks were obtained from 85 consenting patients of various public and private hospitals. We analyzed the presence of KRAS point mutations in codons 12 and 13, and the BRAF-V600E from formalin paraffin fixed sections with Polymerase Chain Reaction (PCR) amplification-sequencing. Results: From a total of 85 patients, 46% F and 54% M, with a median age of 64 years (range, 28-85), 72% (61) where found to be wild type, while the other 28% (24) showed the KRAS mutation in the following amino acids: G12V 30% (7), G12D 17% (4), G12C 17% (4), G12S 9% (2), G12A 4% (1), G13D 25% (6). We analyzed in 45 patients the mutational status of BRAF-V600E, 29 patients presented BRAF and KRAS wild type, 12 had a KRAS mutation while the BRAF was wild type, and 4 patients reveled a mutation of BRAF in the presence of a KRAS wild type. Conclusions: The type of mutation observed in this study corresponds to the findings of previous studies, where the most common KRAS mutation detected was G12V in codon 12 followed by G13D in codon 13. A preliminary report based in 146 patients from Argentine (Perazzo F, et al. 2009) revealed marked differences in KRAS mutation rates compared to our findings, showing the following percentage of mutations: G12V 62% vs. 30% , G12D 26% vs. 17% and G13R 1.7% vs. 0%, G13D 0% vs. 25%, respectively. BRAF mutational status was according to international and national reports.
300% increase rate in juvenile cancer cases unrelated to AIDS: Is it real?
Authors: F. G. Gercovich, E. Gil Deza, G. Martin Reina, C. Garcia Gerardi, M. Abal, D. Santillan, F. Tognelli, J. Calarame, E. Rivarola, E. Morgenfeld
Journal: Journal of Clinical Oncology (2009)

e17535 Background: Juvenile Cancer (JC) involves patients between 18 and 29 years old (adult pt less than 30 yo) and can be or not associated to AIDS. The non-AIDS JC pt challenge the clinical oncologist in many ways: there are few preventive measures, avoiding delayed toxicities is mandatory (fertility, cognitive impairment) and there is a lack of evidence-based treatments for uncommon tumors. The aim of this paper is to evaluate the incidence and clinical outcome of JC non AIDS related at the IOHM. Methods: A JC search in the patient database of the IOHM was made. The inclusion criteria was: new cancer pt diagnosed between 18 and 29 yo. The following variables were analyzed: age, gender, date, absolute and relative annual incidence and diagnosis. The tumors were classified as expected (germinal, hematological, sarcoma, melanoma, CNS, thyroid, cervix, trophoblastic disease) or unexpected (breast, colon, ovarian, gastric, pancreatic, head and neck). The Mean Annual New Case (MANC) incidence for pt older than 30 yo (non-JC) and JC in two different four year periods (“A”: 2001–2004, “B”: 2005–2008) were calculated in order to analyze the relative risk between both populations for these periods. Results: A total of 12.828 new pt were managed at the IOHM between January 2001 and January 2008, with 336 of them (2.6%) being JC. Mean age (range) = 23.3 years (18–29). Gender: male = 180 (53%) and female = 156 (47%). Diagnosis: Expected tumors 269 pt (80%) (testicular tumors = 89 pt; lymphoma = 75 pt; sarcoma = 35 pt; melanoma = 17 pt; others = 53), Unexpected tumors 67 pt (20%) (gastrointestinal = 23 pt; breast cancer = 17 pt; ovarian = 13 pt; head and neck = 7 pt; others = 7 pt). MANC for Non JC in A=1458.25 pt/y; MANC for Non JC in B = 1748.75 pt/y (RR Non JC B/A = 1.2). MANC JC in A = 18.5 pt/y; MANC JC in B = 52.75 pt/y (RR JC B/A = 2.85). Conclusions: 1) In our database, 336 cases of JC out of 12.828 new cancer patients between were found 2001 and 2008; 2) Expected tumors represent 80% of the cases; 3) An unexplained trend of new cases of JC is seen in this 8-year period. The comparison of the first 4 years and the second 4 years shows a relative risk increase of 300% of cases in this population. If other investigators confirm this data, a severe public health problem may be unrecognized. No significant financial relationships to disclose.
Clinical prognostic factors associated with outcome in renal cell cancer (RCC) patients with prior tyrosine kinase inhibitors or immunotherapy treated with everolimus.
Authors: Robert J. Amato, Amber Lea Flaherty, Yufeng Zhang, Mika Stepankiw
Journal: Journal of Clinical Oncology (2013)

e15544 Background: Everolimus was approved for treating RCC patients who failed sunitinib or sorafenib by the Food and Drug Administration in 2009. We sought to develop a predictive clinical model predicting benefit for patients treated with everolimus as 2 nd - or 3 rd -line therapy for metastatic RCC. Methods: The study included 66 patients with RCC who failed immunotherapy or tyrosine kinase inhibitors to identify risk factors for progression-free survival (PFS) and overall survival (OS). Forty-one patients were updated with outcomes from the original phase II study (Amato 2009 Cancer) and an additional 25 patients were added from the expansion study. Kaplan-Meier method was used to calculate PFS and OS. Univariate and multivariate analyses were constructed using COX Proportional Hazard model and step-wise procedure. The model was validated by measuring the overall concordance index using the rms R package. Results: For the entire population, median PFS was 5.9 months (range, 0.4-34.5), and median OS was 16.1 months (range, 1.3-39.5). The univariate analysis revealed 5 factors associated with PFS and 9 factors associated with OS. From the multivariate analysis, 3 variables were kept in the final PFS model (LDH&gt;203, no lung metastases, lymphocytes &lt;25). Patients were assigned to 1 of 2 risk groups: ≤1 factor (favorable risk, median PFS 9.7 months) or ≥2 factors (poor risk, median PFS 2.8 months). Four variables were kept in the final OS model (lymphocytes &lt;25, LDH &gt;203, presence of bone metastasis, platelets ≥300). Patients were assigned to 1 of 3 groups: ≤1 factor (favorable risk, median OS 29.6 months), 2 factors (intermediate risk, median OS 14.3 months), or ≥3 factors (poor risk, median OS 7.2 months). Conclusions: A prognostic model was developed composed of 3 readily available clinical parameters for PFS and 4 clinical parameters for OS to help stratify patients into favorable, intermediate, and poor prognosis groups for the treatment of everolimus in clear cell RCC patients. These risk groups can be used by physicians to identify patients most likely to respond to everolimus. Results of the analysis will be presented.
Risk of more advanced cancer at surgery in African American men eligible for active surveillance.
Authors: Amirali H Salmasi, Misop Han, Isaac Yi Kim
Journal: Journal of Clinical Oncology (2012)

e15214 Background: African-American (AA) men have a higher risk for developing prostate cancer (PCa) and dying of PCa compared to Caucasian men. Active surveillance (AS) is an acceptable management for males with low volume and low grade PCa. In Caucasian men who were eligible for AS, the risk of non-organ-confined disease [NOC] at radical prostatectomy (RP) ranges between 7.8 and 10.9% (Kang et al 2011, Mufarrij et al 2010). It is unclear whether AA men with favorable risk PCa can undergo AS safely. We evaluated changes in staging and grading of PCa in a cohort of AA males that met the criteria for AS but underwent RP. Methods: Between 1997 and 2011, 1536 AA men underwent RP at either Johns Hopkins Medical Institutions or Cancer Institute of New Jersey. Pathological characteristics of patients who fulfilled the inclusion criteria under the National Cancer Institute (NCI) AS criteria were examined. NOC (ECE/SV+/LN+) and upgrading (Gleason &lt;7 in biopsy to Gleason &gt;6 in RP) was evaluated. We tried to identify preoperative predictors of more advanced cancer (NOC and/or upgrading). Results: We identified 212 men who underwent RP, eligible for AS based on NCI criteria. Among 212 men, 92 (37.7%) men showed NOC and/or upgrading, defined SV involvement in 5 (2.4%), ECE in 53 (25%), and increased Gleason (&lt;7 to &gt;6) in 69 (32%) men. Pre-operative PSA level (OR 1.2, p &lt; 0.05) and age (OR 1.06, p &lt; 0.01) were significantly associated with more advanced cancer. No significant association was found between BMI, tissue percentage, or positive cores with more advanced cancer. Conclusions: AS in AA with prostate cancer carries higher risk of NOC compared to non-AA population. More stringent AS entrance criteria may be necessary for AA men.