tbuckley/cabot-search huggingface dataset:
Cancer screening patterns in caregivers accompanying patients to radiation oncology.
Authors: Jolinta Yin-Chu Lin, Tejan Diwanji, James Snider, Nancy Knight, William Regine
Journal: Journal of Clinical Oncology (2015)

e12567 Background: To explore cancer screening habits of caregivers, defined in this IRB-approved study as individuals accompanying patients to radiation oncology consultations. Our objectives were to: (1) determine the incidence of cancer screening in such caregivers; and (2) identify patterns and deficiencies in screening. Methods: In 2014 we distributed a 21-item survey on cancer screening history and concerns to caregivers ≥ 18 y old at radiation oncology consultations. Items included age, race, relationship to patients, screening status, smoking history, screening concerns, access to primary care physicians (PCPs), and insurance. Reported screening experience was compared with American Cancer Society/American Urological Association guidelines for breast, cervical, colon, and prostate cancer. Pearson χ2tests were used in statistical analyses. Results: 209 participants (median age, 55 y; 146 women [70%], 63 men [30%]) completed surveys. 25 caregivers (25%) ≥ 50 y reported not undergoing colonoscopies at least every 10 y. Age was a significant factor, with 30% of 50–60 y-old respondents in this group but only 6% of those 61–75 y (P = 0.0004). 25 women (17%) did not have pap smears at recommended intervals; 21 (17%) ≥ 40 y did not have annual mammograms. 7 men (24%) aged 55–69 y did not undergo annual PSA screens. 92% of participants had PCPs; only 58% reported being informed about recommended screening intervals. Participants ≤ 49 y were less likely to report PCP discussion of cancer screening than participants ≥ 50 y (41% and 66%, respectively; P = 0.0055). 98 respondents (47%) had ≥ 1 concern(s) about screening (68% of those ≤ 49 y, 37% > 50 y; P = 0.0001). Pap smear guideline noncompliance differed in women at urban and community sites (19% and 4%, respectively; P= 0.0184), with similar trends noted in colonoscopies and mammograms. Conclusions: This survey of caregivers identified cancer screening deficiencies and concerns that might be addressed by targeted interventions. With ~60% of cancer patients receiving radiation, advice and counsel in the radiation oncology setting could positively impact cancer screening behaviors in a relatively unexplored population of accompanying caregivers.
Very Low-Dose Decitabine Is Effective in Treating Intermediate or High Risk Myelodysplastic Syndrome
Authors: Hongmin Li, Liru Wang, Yue Wu, Li Su, Hong Zhao, Yongqing Zhang, Zhao Wang, Dayong Huang, Zhongxia Huang, Xiaoxiong Wu, Xiaohong Li, Fang Ye, Fan Yu, Hui Liu, Jingwen Wang, Jia Cong, Wanjun Sun, Huiren Chen, Jingbo Wang, Bing Han
Journal: Blood (2016)
Abstract P5-16-26: National trends in neoadjuvant therapy for breast cancer
Authors: F Schnabel, S Schwartz, T Hochman, J Chun, J Goldberg
Journal: Cancer Research (2017)

Abstract Purpose:Neoadjuvant therapy has been widely integrated in the treatment of locally advanced breast cancer. Over time, this strategy has been extended to include patients with earlier stage disease to allow for assessment of in vivo response to treatment. The aim of this study was to describe the national trends in neoadjuvant therapy for all invasive breast cancers with a particular focus on triple negative disease and HER2 status. Methods: The National Cancer Database (NCDB), an oncology outcomes database that collects data from more than 1500 Commission on Cancer (CoC) accredited cancer programs, was queried for all women diagnosed with invasive breast cancer from 2006-2013. Patients with unknown systemic therapy sequence were excluded. Women were classified by whether or not they received neoadjuvant systemic, chemo and/or endocrine, therapy. Results: We identified 1,221,976 cases that were eligible for this analysis. Of these, 29.7% were HER2 negative, 18.4% were classified as triple negative, and 8.9% received neoadjuvant systemic therapy. The percentage of patients receiving neoadjuvant therapy increased from 7.5% in 2006 to 9.8% in 2012 with a slight decrease to 9.5% in 2013. This increase in the use of neoadjuvant therapy over the time period was statistically significant (p&amp;lt;0.0001). There was a small increase in the percent of patients with HER2 positive status who received neoadjuvant therapy, from 5.7% in 2006 to 6.5% in 2013. During this time period, there was a 9% increase in the percent of triple negative patients who received neoadjuvant therapy (13.1% in 2016 to 22.1% in 2013). Number and percent of patients who received/did not receive neoadjuvant therapy by year2006 (N=136117)2007 (N=143033)2008 (N=148888)2009 (N=154713)2010 (N=154040)2011 (N=162333)2012 (N=163395)2013 (N=159457)No Neoadjuvant Therapy | 125908 (92.5)131559 (91.98)136593 (91.74)141364 (91.37)139459 (90.53)146500 (90.25)147401 (90.21)144306 (90.5)Neoadjuvant Therapy | 10209 (7.5)11474 (8.02)12295 (8.26)13349 (8.63)14581 (9.47)15833 (9.75)15994 (9.79)15151 (9.5) Conclusions: Over the time period from 2006-2013, there has been an apparent increase in the percentage of patients who received neoadjuvant therapy. This trend is accompanied by increases in the percentage of TNBC patients and in Her2 positive patients who received neoadjuvant therapy. Other factors and the joint effects of these factors on the observed increase in the use of neoadjuvant therapy are under evaluation to elucidate the basis for this observation in the NCDB data. Citation Format: Schnabel F, Schwartz S, Hochman T, Chun J, Goldberg J. National trends in neoadjuvant therapy for breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-26.
NLRP3 Inflammasome-Derived ASC Specks Are a Diagnostic Biomarker for Myelodysplastic Syndromes (MDS)
Authors: Ashley A Basiorka, Zhenjun Ma, Kathy L Mcgraw, David Sallman, Brittany A Irvine, Najla H Al Ali, Eric Padron, Javier Pinilla-Ibarz, Rami S. Komrokji, Lubomir Sokol, Sheng Wei, Alan F List
Journal: Blood (2016)
Abstract IA07: Patient-derived tumor xenografts for genotype-drug response correlations in colorectal cancer
Authors: Livio Trusolino
Journal: Clinical Cancer Research (2016)

Abstract Ten years after completion of the Human Genome Project, genetic alterations with causative roles in cancer have been identified. Inhibitors that target “druggable” mutant gene products have been developed. Finally, a number of these drugs have entered the clinic and are now used in patients. Some fundamental issues need to be addressed before the informative potential of genome- wide molecular surveys is translated into clinical benefit. First, given the heavy mutational load accrued during neoplastic progression, driver alterations are difficult to distinguish from passenger events. Second, next-generation approaches are likely to identify previously neglected small subsets of very rare variants, which requires population-scale studies for statistically solid genotype/response correlations. Third, not always does the presence of an oncogenic driver predict response. Therefore, treatment paradigm may not be decided on the sole basis of the mutational status of a single gene with potential cancer-causing function, but rather on the basis of the heterogeneous context in which that mutation is found (“precision medicine”). All these challenges also apply to metastatic colorectal cancer (mCRC). Less than 20% of mCRC patients respond to anti-EGFR antibodies “the gold standard targeted therapy”, which calls for the identification of novel predictive biomarkers and suggests that uncharacterized drivers other than EGFR can sustain the growth of different CRC subsets. The categorization of tumor subpopulations featuring specific driver lesions, the validation of such lesions as targets, and the need for discrimination between “actionable” opportunities and those with weak clinical transferability require reliable preclinical models. The scope of our research is to refine genetic, mechanistic and therapeutic annotation of mCRC subsets using predictive in vivo models – namely, large collections of molecularly annotated patient-derived tumorgrafts as a means to systematically increase the success rate of rationally based clinical trials that emanate from preclinical findings. Citation Format: Livio Trusolino. Patient-derived tumor xenografts for genotype-drug response correlations in colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA07.
Abstract ES5-2: ES5-2 Non-endocrine strategies: Beyond the estrogen receptor
Authors: P Brown
Journal: Cancer Research (2017)

Abstract Powel Brown, Parijatham Thomas, Abhijit Mazumdar, Diane Weber, Robin Coyne, Lana Vornik, Terry Bevers, and Abenaa Brewster Department of Clinical Cancer Prevention; University of Texas MD Anderson Cancer Center; Houston, TX. Breast cancer prevention has been demonstrated to be possible using anti-estrogen drugs. However, these drugs only prevent the development of estrogen receptor-positive breast cancers, and are often not acceptable to women. Therefore, there has been a major effort to develop more acceptable breast cancer preventive strategies. In this presentation I will review the current approaches to breast cancer prevention, with a focus on risk-based preventive interventions, including behavioral measures to reduce breast cancer risk in average risk individuals, and drug-based interventions in high risk individuals. While anti-estrogen hormonal therapies are still the most effective preventive therapy other than prophylactic breast surgery, other strategies are being tested that offer great promise. Interventions that have been shown to be effective in preclinical studies include novel molecularly targeted drugs (such as PARP inhibitors, mTOR inhibitors, and RXR-selective retinoids), re-purposed drugs (such as metformin and statin drugs), and vaccines. In addition, novel schedules and formulations are being tested to avoid the toxicity of traditionally used drugs such as tamoxifen and aromatase inhibitors. High-risk individuals who may particularly benefit from preventive therapy include women with premalignant lesions (atypical hyperplasia and lobular carcinoma-in-situ lesions), ductal carcinoma-in-situ breast cancers, or a genetic predisposition to breast cancer. With continued advances in molecularly targeted drug development and improved personalized risk assessment, effective, safe, and acceptable breast cancer preventive strategies will soon be available. Citation Format: Brown P. ES5-2 Non-endocrine strategies: Beyond the estrogen receptor [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES5-2.
Smoking and estrogen plus progestin (E+P) and lung cancer incidence and mortality.
Authors: Rowan T. Chlebowski, Heather A. Wakelee, Thomas E Rohan, Jingmin Liu, Michael S. Simon, Hilary Tindle, Catherine R Messina, Jean Wactawski-Wende, Karen Johnson, Ann G. Schwartz, Margery Gass
Journal: Journal of Clinical Oncology (2013)

1524 Background: In the Women’s Health Initiative (WHI) randomized, placebo-controlled clinical trial, E+P increased deaths from lung cancer (those cancer-attributed) and after lung cancer (regardless of cause) (Lancet 2009:374:1243). To examine smoking status influence on this process, a cohort combining WHI clinical trial (CT) and observational study (OS) participants, the latter meeting criteria as in the CT, was identified to examine E+P associations with lung cancer incidence and outcome. Methods: 31,966 postmenopausal women (12,299 CT, 19,668 OS) with no prior hysterectomy and no prior hormone therapy use were classified at baseline as not hormone users or E+P users and as current or never smokers. Lung cancers were verified by medical record review. Multi-variant adjusted Cox proportional hazards regression, including pack-year use, calculated hazard ratios (HRs, 95% confidence intervals [CI]) for groups defined by smoking status and E+P use for lung cancer incidence, deaths from lung cancer and deaths after lung cancer. Results: After 12 years mean follow-up, 664 lung cancers were diagnosed with 444 deaths from lung cancer and 513 deaths after lung cancer. Analyzed from cohort entry; see Table. In nonusers of E+P, lung cancer incidence, deaths from lung cancer, and deaths after lung cancer were significantly and substantially greater in current smokers vs never smokers (p&lt; .0001 for all comparisons). In current smokers, lung cancer incidence, deaths from lung cancer and deaths after lung cancer were significantly and substantially greater in E+P users vs non-users (p=.0021, .0005 and .0002, respectively). Conclusions: E+P use in current smokers nearly doubles their already high risk of death from and after lung cancer. Based on this risk, current smokers should not use E+P. [Table: see text]
Prognostic Role of Transfusion Requirement and Validation of the IPSS Prognostic System in Myelodisplastic Syndromes.
Authors: Flavia Salvi, Daniela Gioia, Daniela Cilloni, Ernesta Audisio, Margherita Bonferroni, Gianni Cametti, Antonella Darbesio, Stefano D’Ardia, Chiara Dellacasa, Dario Ferrero, Roberto Freilone, Simona Gatto, Silvia Franceschetti, Carlo Marinone, Filippo Marmont, Enzo Scassa, Anna Tonso, Mario Boccadoro, Gianluca Gaidano, Andrea Gallamini, Eugenio Gallo, Mario Girotto, Giuseppe Saglio, Alessandro Levis
Journal: Blood (2006)
Poor emergency department performance is down to sicker patients, report finds
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The declining performance of emergency departments in England is largely the result of sicker patients with more complex health conditions and not due to poor access to GPs, a report from the King’s Fund has found.1

Its latest quarterly monitoring report found that 80% of NHS finance directors who responded to a survey identified higher numbers of patients with severe illnesses and complex health needs as a key reason for the pressures that have led to the worst emergency department waiting times since the four hour target was introduced 13 years ago.

Around 70% of respondents said that delays in discharging patients were a key reason for declining performance. This compared with 27% who identified poor access to GPs as a key factor and 20% …
Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients
Authors: Harry Dolstra, Mieke W.H. Roeven, Jan Spanholtz, Basav N. Hangalapura, Marleen Tordoir, Frans Maas, Marij Leenders, Fenna Bohme, Nina Kok, Carel Trilsbeek, Jos Paardekooper, Anniek B. van der Waart, Peter E. Westerweel, Tjeerd J.F. Snijders, Jan Cornelissen, Gerard Bos, Hans F.M. Pruijt, Aniek O. de Graaf, Bert A. van der Reijden, Joop H. Jansen, Arnold van der Meer, Gerwin Huls, Jeannette Cany, Frank Preijers, Nicole M.A. Blijlevens, Nicolaas M. Schaap
Journal: Clinical Cancer Research (2017)

Purpose: Older acute myeloid leukemia (AML) patients have a poor prognosis; therefore, novel therapies are needed. Allogeneic natural killer (NK) cells have been adoptively transferred with promising clinical results. Here, we report the first-in-human study exploiting a unique scalable NK-cell product generated ex vivo from CD34+ hematopoietic stem and progenitor cells (HSPC) from partially HLA-matched umbilical cord blood units.Experimental Design: Ten older AML patients in morphologic complete remission received an escalating HSPC-NK cell dose (between 3 and 30 × 106/kg body weight) after lymphodepleting chemotherapy without cytokine boosting.Results: HSPC-NK cell products contained a median of 75% highly activated NK cells, with <1 × 104 T cells/kg and <3 × 105 B cells/kg body weight. HSPC-NK cells were well tolerated, and neither graft-versus-host disease nor toxicity was observed. Despite no cytokine boosting being given, transient HSPC-NK cell persistence was clearly found in peripheral blood up to 21% until day 8, which was accompanied by augmented IL15 plasma levels. Moreover, donor chimerism up to 3.5% was found in bone marrow. Interestingly, in vivo HSPC-NK cell maturation was observed, indicated by the rapid acquisition of CD16 and KIR expression, while expression of most activating receptors was sustained. Notably, 2 of 4 patients with minimal residual disease (MRD) in bone marrow before infusion became MRD negative (<0.1%), which lasted for 6 months.Conclusions: These findings indicate that HSPC-NK cell adoptive transfer is a promising, potential "off-the-shelf" translational immunotherapy approach in AML. Clin Cancer Res; 23(15); 4107-18. ©2017 AACR.
Abstract 12728: Impact of Cardiac Function and Hemodynamics on Mortality in Patients After the Fontan Operation
Authors: Hideo Ohuchi, Yosuke Hayama, Jun Negishi, Kanae Noritake, Aya Miyazaki, Isao Shiraishi
Journal: Circulation (2016)

Background: High central venous pressure (CVP) with low cardiac output (CO) characterizes Fontan hemodynamics. However, the association of these characteristics with prognosis remains controversial, especially in adult patients. Purpose: To elucidate associations of Fontan hemodynamics with the mortality. Method and Results: We evaluated cardiac function and hemodynamics in 431 consecutive Fontan survivors (≥ 6 months), including 170 adults, that included CVP (mmHg), cardiac index (CI; L/min/m 2 ), systemic ventricular end-diastolic volume index (EDVI; ml/m 2 ) and ejection fraction (EF; %), and arterial oxygen saturation (SpO 2 ; %). The latest variables were compared with the 5-year all-cause mortality. During follow-up, 22 child and 15 adult patients died. In child and adult patients, higher CVP (hazard ratio [HR]:1.36 and 1.29, respectively, p &lt; 0.01-0.0001), larger EDVI (HR: 1.01 and 1.03, respectively, p &lt; 0.01 for both) and lower SpO 2 (HR: 0.93 and 0.90, p &lt; 0.001 for both) predicted the mortality. Lower EF predicted the mortality only in child patients (HR: 0.42, p &lt; 0.0001). There was an opposite impact of CI on mortality (p &lt; 0.001), i.e., lower CI in child patients (HR: 0.40, 95% confidence interval: 0.20-0.79, p &lt; 0.01), whereas higher CI in adult patients (HR: 2.21, 95% confidence interval: 1.13-4.07, p &lt; 0.05) predicted the mortality and the cutoff value was 2.46 and 2.90, respectively. Conclusions: High-CO-associated CVP with preserved EF predicted mortality in adult Fontan patients. The failing pathophysiology in some long-term Fontan survivors may differ from that in child patients although both of them have high CVP in common.
The Novel BCR-ABL1 V304D Mutation Induces Pan-Tyrosine Kinase Inhibitor Resistance by a Unique Kinase Lateral Escape Mechanism and Is Associated with Very Poor Prognosis In Patients (PTS) with Chronic Myeloid Leukemia (CML).
Authors: Sabrina Pricl, Don L Gibbons, Paola Posocco, Erik Laurini, Maurizio Fermeglia, Hagop M. Kantarjian, Moshe Talpaz, Jorge Cortes, Matthew Young, Hanshi Sun, Luke F. Peterson, Nicholas Donato, Alfonso Quintás-Cardama
Journal: Blood (2010)
Impact of T-Cell Chimerism on Clinical Outcome in 117 Patients Who Underwent Allogeneic Stem Cell Transplantation with a Busulfan-Containing Reduced-Intensity Conditioning Regimen.
Authors: Bungo Saito, Takahiro Fukuda, Hiroki Yokoyama, Saiko Kurosawa, Toshihiro Takahashi, Shigeo Fuji, Noriko Takahashi, Kinuko Tajima, Sung-Won Kim, Shin-ichiro Mori, Ryuji Tanosaki, Yoichi Takaue, Yuji Heike
Journal: Blood (2007)
Children with atopic dermatitis and frequent emollient use have increased urinary levels of low‐molecular‐weight phthalate metabolites and parabens
Authors: L. E. K. Overgaard, K. M. Main, H. Frederiksen, S. Stender, P. B. Szecsi, H. C. Williams, J. P. Thyssen
Journal: Allergy (2017)

Parabens may be added to cosmetic and personal care products for preservation purposes. Low-molecular weight (LMW) phthalate diesters function as plasticizers, fixatives or solvents in such products, but may also be found in small quantities as contaminants from plastic containers.To evaluate the association between emollient use, atopic dermatitis and FLG mutations, respectively, with urinary concentrations of phthalate metabolites and parabens in Danish children.Eight hundred and forty-five Danish children 4-9 years of age were studied. Urinary concentrations of phthalate metabolites and parabens were determined, and children were genotyped for common FLG loss-of-function mutations. Information about atopic dermatitis and use of emollients was obtained from questionnaires completed by parents.The prevalence of atopic dermatitis was 16.1%. Phthalate metabolite and paraben levels were generally higher in children with frequent use of emollients compared to uncommon users, reaching statistical significance for some LMW phthalates and parabens. While there was no association with common FLG mutations, children with atopic dermatitis had significantly higher urinary levels of one LMW phthalate and two parabens, respectively, when compared to children without atopic dermatitis.Emollient use and atopic dermatitis were associated with modestly increased internal LMW phthalate and paraben exposure in 4-9 year old children. It is unknown whether the difference is explained by increased use of the specific emollients that are used to treat pruritic and inflamed skin, and/or whether the impaired skin barrier allows chemicals to penetrate more easily. Moreover, the putative toxicological burden is unknown.