tbuckley/cabot-search huggingface dataset:
Natural History of Untreated Hepatocellular Carcinoma in a US Cohort and the Role of Cancer Surveillance
Authors: Natalia Khalaf, Jun Ying, Sahil Mittal, Sarah Temple, Fasiha Kanwal, Jessica Davila, Hashem B. El-Serag
Journal: Clinical Gastroenterology and Hepatology (2016)

Determining the natural history and predictors of survival in patients with untreated hepatocellular carcinoma (HCC) in the United States is useful to test existing tumor classifications, identify subgroups of patients likely to benefit from treatment, and estimate lead time related to HCC surveillance.We identified a national cohort of 518 veterans diagnosed with HCC from 2004 through 2011, with follow-up ending in 2014, who received no palliative or curative treatment. We examined the association between postdiagnosis survival and patient factors, tumor characteristics, and prediagnosis surveillance.The mean age at HCC diagnosis was 65.7 years and most patients had hepatitis C (60.6%). Almost all patients (99%) died within the observation period; the median overall survival time was 3.6 months and survival times were 13.4, 9.5, 3.4, and 1.6 months for patients of Barcelona Clinic Liver Cancer stages 0/A, B, C, and D, respectively. In addition, model for end-stage liver disease and levels of α-fetoprotein were predictive of survival. Nearly 28% received prediagnosis HCC surveillance, which was associated with detection of disease at an earlier stage (Barcelona Clinic Liver Cancer 0/A/B; 26.4% vs 14.4%; P = .0006) and slightly longer survival than patients with no surveillance overall (5.2 months vs 3.4 months; P = .021); there was no difference in survival times of patients with 0/A stage who did versus did not receive surveillance (10.3 months vs 10.5 months).Patients with HCCs, including those detected through surveillance, survived for short time periods in the absence of treatment, irrespective of their initial stage at diagnosis. Model for end-stage liver disease scores and levels of α-fetoprotein were prognostic factors, independent of Barcelona Clinic Liver Cancer stage. The lead time related to detection by surveillance was modest (<2 months) and therefore unlikely to explain the survival benefit associated with surveillance in previous studies.
Comment on Muraki et al. Potato Consumption and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies. Diabetes Care 2016;39:376–384
Authors: Antonio C. Bossi
Journal: Diabetes Care (2016)

In their excellent article, Muraki et al. (1) reported that a greater consumption of potatoes, especially french fries, was associated with a higher type 2 diabetes (T2D) risk, independent of BMI and other risk factors. Similarly, in another very recent interesting article, Bao et al. (2) observed that higher levels of potato consumption before pregnancy were associated with greater risk of gestational diabetes mellitus and that substitution of potatoes with other kind of vegetables, legumes, or whole-grain foods might lower the risk. Whether (or not) potatoes should be included in the vegetable food …
Physician and patient factors influencing management recommendations in stage I testicular seminoma: A survey among radiation oncologists in the United States.
Authors: N. D. Arvold, P. J. Catalano, C. Sweeney, K. E. Hoffman, P. L. Nguyen, T. A. Balboni, S. D. Fossa, L. B. Travis, C. Beard
Journal: Journal of Clinical Oncology (2011)

225 Background: Post-orchiectomy adjuvant radiotherapy (RT) for stage I seminoma is associated with long-term toxicity, and management strategies with a lower treatment burden achieve the same excellent cure rate. Because studies suggest that radiation oncologists in the United States (U.S.) continue to recommend RT for these patients, we sought to identify factors associated with management recommendations. Methods: We conducted a one-time internet-based survey among 578 randomly selected U.S. radiation oncologists specialized in genitourinary oncology. Results: Response rate was 45% (n = 261). Forty-nine percent of respondents worked in university-affiliated practices. Sixty-two percent of respondents always/usually recommended adjuvant RT for stage I seminoma patients, whereas 21% always/usually recommended surveillance and 3% always/usually recommended chemotherapy. One-third (33%) expressed concerns that patients who relapsed during surveillance could not be salvaged, and 97% recommended against surveillance if they felt a patient was unreliable for regular follow-up. Although 88% of physicians were aware of a risk of second malignant neoplasms (SMN) after adjuvant RT, 85% underestimated the magnitude of this risk. Only 20% of physicians were aware of a possible association between sub-diaphragmatic RT and an increased risk of cardiovascular disease. Compared to physicians not typically recommending RT, physicians who always/usually recommended RT were more likely to believe that patients may not be salvaged at relapse during surveillance (p = 0.008) and were less aware of the association between RT and SMN (p = 0.04). Conclusions: Respondents who always/usually recommend post-orchiectomy RT for stage I seminoma patients are more likely to underestimate late RT morbidity and to believe surveillance is associated with increased mortality. Given the equivalent efficacy and reduced morbidity of surveillance compared to RT, our findings underscore the need for ongoing physician education to increase appropriate clinical implementation of surveillance strategies. No significant financial relationships to disclose.
Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients With Hereditary Hemorrhagic Telangiectasia
Authors: Kevin J. Whitehead, Nathan B. Sautter, Justin P. McWilliams, Murali M. Chakinala, Christian A. Merlo, Maribeth H. Johnson, Melissa James, Eric M. Everett, Marianne S. Clancy, Marie E. Faughnan, S. Paul Oh, Scott E. Olitsky, Reed E. Pyeritz, James R. Gossage
Journal: JAMA (2016)

<h3>Importance</h3> Epistaxis is a major factor negatively affecting quality of life in patients with hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu disease). Optimal treatment for HHT-related epistaxis is uncertain. <h3>Objective</h3> To determine whether topical therapy with any of 3 drugs with differing mechanisms of action is effective in reducing HHT-related epistaxis. <h3>Design, Setting, and Participants</h3> The North American Study of Epistaxis in HHT was a double-blind, placebo-controlled randomized clinical trial performed at 6 HHT centers of excellence. From August 2011 through March 2014, there were 121 adult patients who met the clinical criteria for HHT and had experienced HHT-related epistaxis with an Epistaxis Severity Score of at least 3.0. Follow-up was completed in September 2014. <h3>Interventions</h3> Patients received twice-daily nose sprays for 12 weeks with either bevacizumab 1% (4 mg/d), estriol 0.1% (0.4 mg/d), tranexamic acid 10% (40 mg/d), or placebo (0.9% saline). <h3>Main Outcomes and Measures</h3> The primary outcome was median weekly epistaxis frequency during weeks 5 through 12. Secondary outcomes included median duration of epistaxis during weeks 5 through 12, Epistaxis Severity Score, level of hemoglobin, level of ferritin, need for transfusion, emergency department visits, and treatment failure. <h3>Results</h3> Among the 121 patients who were randomized (mean age, 52.8 years [SD, 12.9 years]; 44% women with a median of 7.0 weekly episodes of epistaxis [interquartile range {IQR}, 3.0-14.0]), 106 patients completed the study duration for the primary outcome measure (43 were women [41%]). Drug therapy did not significantly reduce epistaxis frequency (<i>P</i> = .97). After 12 weeks of treatment, the median weekly number of bleeding episodes was 7.0 (IQR, 4.5-10.5) for patients in the bevacizumab group, 8.0 (IQR, 4.0-12.0) for the estriol group, 7.5 (IQR, 3.0-11.0) for the tranexamic acid group, and 8.0 (IQR, 3.0-14.0) for the placebo group. No drug treatment was significantly different from placebo for epistaxis duration. All groups had a significant improvement in Epistaxis Severity Score at weeks 12 and 24. There were no significant differences between groups for hemoglobin level, ferritin level, treatment failure, need for transfusion, or emergency department visits. <h3>Conclusions and Relevance</h3> Among patients with HHT, there were no significant between-group differences in the use of topical intranasal treatment with bevacizumab vs estriol vs tranexamic acid vs placebo and epistaxis frequency. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01408030
Single-dose activity of PSMA ADC against prostate cancer xenograft and explant tumors.
Authors: D. Ma, T. Parsons, W. C. Olson
Journal: Journal of Clinical Oncology (2010)

e13534 Background: Prostate-specific membrane antigen (PSMA) is an attractive target for antibody-targeted therapy of prostate cancer due to its abundant and selective expression on the surface of prostate cancer cells. We have generated a novel antibody-drug conjugate (ADC) by linking a fully human PSMA monoclonal antibody to monomethylauristatin-E (MMAE), a potent tubulin inhibitor. Here, we describe the use of PSMA ADC to treat SCID mice bearing LNCaP xenografts or LuCaP explants derived from surgical resections of prostate cancer patients. Methods: PSMA expression in LNCaP and LuCaP tumor cells was evaluated by flow cytometry. Activity of PSMA ADC, assessed by decrease in tumor volume, was evaluated in LNCaP xenograft and LuCaP explant models. SCID mice were implanted subcutaneously with cultured LNCaP tumor cells or disaggregated human LuCaP 70 or LuCaP 77 prostate tumor tissue obtained from tumor-bearing mice. When average tumor size reached ∼300mm3, animals were randomized into groups of 9–10 mice and each animal was treated with a single intravenous dose of vehicle control, a control ADC of irrelevant specificity, or PSMA ADC. Treatment effects were assessed by measuring tumor volume and overall survival for up to 41 days post-treatment. Results: Surface expression of PSMA was assessed by flow cytometry, with a rank order of expression as follows: LNCaP > LuCaP 70, LuCaP 77, LuCaP 105 > LuCaP 96.1 > LuCaP 35V, LuCaP 141. Single-dose PSMA ADC demonstrated significant activity against LNCaP xenografts at a dose of 5 mg/kg (p<0.0001 relative to either vehicle or control ADC) and against LuCaP 77 explants at a dose of 10 mg/kg (p=0.0003 relative to either vehicle or control ADC). A trend toward delayed tumor growth was observed in the LuCaP 70 tumor model. Conclusions: Single-dose PSMA ADC showed activity against LNCaP xenografts and LuCaP explants derived from surgical resections of prostate cancer patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PSMA Development Company, LLC
Next-Generation Sequencing: Role in Gynecologic Cancers
Authors: Tarra Evans, Ursula Matulonis
Journal: Journal of the National Comprehensive Cancer Network (2016)

Next-generation sequencing (NGS) has risen to the forefront of tumor analysis and has enabled unprecedented advances in the molecular profiling of solid tumors. Through massively parallel sequencing, previously unrecognized genomic alterations have been unveiled in many malignancies, including gynecologic cancers, thus expanding the potential repertoire for the use of targeted therapies. NGS has expanded the understanding of the genomic foundation of gynecologic malignancies and has allowed identification of germline and somatic mutations associated with cancer development, enabled tumor reclassification, and helped determine mechanisms of treatment resistance. NGS has also facilitated rationale therapeutic strategies based on actionable molecular aberrations. However, issues remain regarding cost and clinical utility. This review covers NGS analysis of and its impact thus far on gynecologic cancers, specifically ovarian, endometrial, cervical, and vulvar cancers.
Forging a Community Health Partnership: Hillsborough County, Florida-Reply
Authors: Edward L. Baker
Journal: JAMA (1995)

<h3>In Reply.</h3> —The partnership described by Dr Penzell and colleagues clearly illustrates one of our central points: as managed care (particularly when capitation is a central feature) becomes an increasingly prominent form of medical care financing, private clinicians can succeed ultimately only if governmental public health agencies are strong partners. A central driving force for the new partnership is derived from a shared vision of "healthy people in healthy communities." In this regard, we must emphasize a key point about which Penzell et al are silent. The improvement of community health status will occur only partly as a result of improved access to clinical care by a larger percentage of the population. Even more critical are the maintenance and enhancement of those essential public health services designed to protect and promote the health of the community as a whole (eg, communitywide health status assessment systems, tuberculosis case management), which are
Cost and resource utilization associated with glioblastoma among commercially insured adults in the United States (US).
Authors: Shan Jiang, Kala Hill, Dipen Patel, Adrian Reg Waldeck, Marc Botteman, Andrew David Norden
Journal: Journal of Clinical Oncology (2016)

2011 Background: Few studies have evaluated the economic burden of GBM—the most common type of high-grade brain tumors in adults. We assessed healthcare costs and resource utilization in newly-diagnosed GBM patients in a commercially-insured US population. Methods: The analysis included subjects identified in the IMS Pharmetrics Lifelink Plus claims database from 01/2009 to 03/2014 who were aged ≥18 years; had ≥1 malignant brain cancer diagnosis (ICD9-CM, 191.xx) (with first diagnosis date = “index” date); were treated with temozolomide (TMZ); had brain surgery ≤90 days prior to TMZ initiation; and were continuously enrolled for ≥12 months pre-index and ≥1 month post-index. Per-patient per-month (PPPM) costs (i.e., average allowed charges for all claims) and cumulative costs from 3 months pre- to up to 6, 12, or 60 months post-index were calculated. Results: 2,981 patients were included (median age: 56 years; 60% male). During the post-index period, the per-patient median (interquartile range, IQR) number of inpatient, emergency department (ED), and outpatient visits were 2 (1-5), 2 (1-3), and 22 (12-31), respectively; the median (IQR) length of stay was 5 (3-10) days. Table 1 presents cumulative per-patient costs by key categories and maximum follow-up time. Excluding TMZ, the 3 most costly medication classes prescribed (on PPPM-basis) were anticoagulants ($515), antidiabetic agents ($84), and anticonvulsants ($72). Conclusions: The economic burden of newly-diagnosed GBM is substantial, with costs exceeding $200,000 within a year post-diagnosis. Key cost drivers include inpatient care, chemotherapy, and radiation costs. Cumulative per-patient costs in US$ (% total) by maximum length of follow-up. Cost category 3-months pre-index to 6 months post-index 3-months pre-index to 12 months post-index 3-months pre-index to 60 months post-index Total costs $165,848 (100%) $212,331 (100%) $311,804 (100%) Inpatient $75,604 (46%) $87,326 (41%) $114,563 (37%) Chemotherapy $24,545 (15%) $43,761 (21%) $78,425 (25%) Radiation $32,463 (20%) $33,364 (16%) $37,775 (12%) ED $1,846 (1%) $2,383 (1%) $3,352 (1%) Others $31,390 (19%) $45,497 (21%) $77,689 (25%)
CSF1R Expression of Hodgkin Reed Sternberg Cells Is Associated with the Number of Macrophages in the Tumor Microenvironment and Is Correlated with Treatment Outcome
Authors: Christian Steidl, Arjan Diepstra, Tang Lee, Pedro Farinha, Adele Telenius, Merrill Boyle, Sohrab P Shah, Lorena Barclay, Anke Van Den Berg, Kerry J. Savage, Joseph M. Connors, Randy D. Gascoyne
Journal: Blood (2011)
Abstract MP064: Dietary Contributors to Glycemic load in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: James M Shikany, Abraham J Letter, P. K Newby, Jamy D Ard, Suzanne E Judd
Journal: Circulation (2012)

Glycemic load (GL) is a measure that incorporates both the quality (i.e., glycemic index) and quantity of dietary carbohydrate and is a measure of the overall glycemic impact of the diet. In observational studies, high-GL diets have been associated with a greater prevalence of multiple coronary heart disease risk factors, including type 2 diabetes, overweight/obesity, dyslipidemia, inflammation, and abnormal blood clotting. To begin to develop interventions to reduce dietary GL, it is necessary to identify the major contributors to GL at the population level. We studied contributors to GL in 21,636 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study (7074 white men, 2472 black men, 7287 white women, and 4803 black women) whose mean (SD) age was 64.9 (9.3) years at baseline (2003-2007). Mean daily GL, as well as individual carbohydrate food and food group contributors to GL, were determined for each participant using intake data from the Block 1998 semi-quantitative food frequency questionnaire administered at baseline. Mean (SD) daily GL was 107.1 (44.1), 115.0 (53.8), 89.9 (40.6), and 100.0 (49.6) g/d in white men, black men, white women, and black women, respectively. Sugar-sweetened beverages was the main carbohydrate food group contributing to GL in both black men and women and were important contributors to GL in white men and women (Figure). Regular soft drinks in particular were the leading individual carbohydrate contributor to GL in black men (4.0 median % of daily GL). The main carbohydrate food group contributing to GL in both white men and women was breads. Dark breads were the leading individual carbohydrate contributors to GL in white men, white women, and black women (2.7, 3.2, and 2.4 median % of daily GL, respectively). Sugar-sweetened beverages were a major contributor to dietary GL in this sample of US adults, especially in blacks. Decreasing the consumption of these beverages should be considered in future interventions to reduce dietary GL.
Correlation of PITX2 gene expression and invasive potential of breast cancer cells.
Authors: R. Aft, S. Pillai, N. Dasgupta, T. Fleming, M. Watson
Journal: Journal of Clinical Oncology (2010)

10646 Background: We have found that expression of PITX2, a gene normally involved in development, in the bone marrow (BM) of women with newly diagnosed breast cancer correlates with the early development of distant metastatic disease. PITX2 is not expressed in the BM of healthy volunteers, suggesting that the source of PITX2 expression is disseminated tumor cells. This study was conducted to understand PITX2 expression as it relates to the metastatic breast cancer phenotype. Methods: PITX2 has three different transcript variants. The expression of each transcript variant was quantified by qRT-PCR. PITX2 expression in the MDAMB231 cell line was stably silenced using shRNA lentiviral constructs against all isoforms of PITX2 (Sigma, St. Louis) and selecting with puromycin. Cells with total knockdown of the gene were used for matrigel invasion assays. Briefly, 3 × 104 cells were suspended in growth factor free media and added to each well of an invasion chamber. Complete growth medium was added to the lower chamber as chemoattractant. The number of invasive cells was counted at 24h and 48h after seeding. Control cells included empty vector, a non-targeting sequence, and shRNA against the unrelated gene, Beta2-Microglobulin. Percentage invasion was calculated as the number of cells passing through the Matrigel to the total number of cells present before harvest. All experiments were repeated three times. Chi-square was used for analysis. Results: PITX2 isoform A was expressed in the invasive cell lines MDA MB 231 and C1A1 while isoform C was expressed in non-invasive cell lines MCF7 and MCF10A. In the matrigel invasion assay, knockdown of PITX2 in MDA MB231 reduced invasiveness 3-fold compared to the controls at 24 and 48 hours (p < 0.0001). Conclusions: The level of PITX2 expression in several human breast cancer cell lines is correlated with their invasive potential. Down-regulating PITX2 transcript expression abrogates the invasive phenotype. These functional results corroborate our previous clinical findings that PITX2 expression is associated with disseminated tumor cells and the rapid development of disease. PITX2 in disseminated tumor cells may serve as a new therapeutic target in preventing the development of metastatic disease. No significant financial relationships to disclose.
Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: Results from the PRECISION V randomized trial.
Authors: T. J. Vogl, J. Lammer, R. Lencioni, K. Malagari, A. Watkinson, F. Pilleul, A. Denys, C. Lee
Journal: Journal of Clinical Oncology (2010)

e14660 Background: To evaluate the toxicity focussing on hepatic, gastrointestinal and cardiac parameters following PRECISION TACE with DC Bead versus conventional transarterial chemoembolization (cTACE) in the treatment of intermediate-stage hepatocellular carcinoma (HCC). Methods: This prospective, randomized, multicenter study was conducted under best practice trial management and authorized by local institutional review boards. Informed consent was obtained. 212 patients (185 men/27 women; mean: 67 years) were randomized to be treated with DC Beads or cTACE. The majority of both groups presented in a more advanced stage. Safety was measured by rate of adverse events (South West Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed by means of left ventricular ejection fraction (LVEF) in MRI or echocardiography. Results of the two groups were compared using the chi-square test and Student's t-test. Mean maximum alanine transaminase increase in the DC Bead group was 50% in the cTACE group (p<0.001) and 59% for aspartate transaminase (p<0.001). For bilirubin, mean increase was 5.30±15.13 vs. 13.53±73.89μmol/L. Concerning gastrointestinal disorders 120 adverse events (AEs) occurred in 57/93 (61.3%) patients in the DC Bead group vs. 114 in 49/108 (45.4%) in cTACE. Concerning hepatobiliary disorders serious AEs occurred in 8/93 (8.6%) vs. 11/108 (10.2%) patients. LVEF showed an increase in the DC Bead group by +2.7±10.1 percentage points and a small decrease by -1.5±7.6 in the cTACE group, p=0.018. PRECISION TACE is safe, even in more advanced HCC patients. Serious liver and cardiac toxicity were significantly lower in the DC Bead group. No significant financial relationships to disclose.
Joint research projects will focus on social impact of Zika in Brazil
Authors: Cláudia Collucci
Journal: BMJ (2016)

Researchers from the United Kingdom and Brazil are being invited to pitch projects that look at the social effects of the Zika virus in Brazil, in a partnership launched by the British Council and the Oswaldo Cruz Foundation (Fiocruz), whose aim is to promote health and social development through science and technology.

The programme will …