tbuckley/cabot-search huggingface dataset:
Prediction of chemotherapy related toxicities in older Asian adults with cancer.
Authors: Angela Pang, Francis Ho, Samuel Guan Wei Ow, Yean Shin Ng, Woon Chai Yong, Chee Seng Tan, Bee Choo Tai
Journal: Journal of Clinical Oncology (2018)

e22021 Background: Whilst there is evidence supporting the benefit of chemotherapy (CTx) in elderly pts, their incidence of CTx related toxicity is also higher. The CARG chemotoxicity calculator (CTC) validated in the western population addresses this issue, though it has not been validated in the Asian cancer population of which 60% are 65 years and above. The primary objective of our study is to identify predictors of G3-5 CTx toxicities and to evaluate the potential utility of the CTC in older Asian CA pts. Methods: Our pilot study was conducted in the National University Cancer Institute, Singapore. For all medical oncology pts aged > / = 70 years, a comprehensive geriatric assessment (CGA) would be performed prior to the initiation of their CTx. Baseline cancer characteristics and investigations, including the 11 variables in the CTC were collected. They were then followed up for CTx related toxicities up to 3 months upon completion of treatment. Results: Amongst the 95 pts (mean age: 75; range: 70 – 89), their CA diagnoses include colorectal (CRC) (30; 31.6%), lung (19 ; 20%), breast (10 ;10.5%), non-CRC gastrointestinal (10; 10.5%) , genitourinary (6 ; 6.3% ), gynae (5; 5.3% ), head and neck (4;4.2%) and others (11, 11.6%) ; 35 (37%) of whom received CTx with curative intent, and 60 (63%) with palliative intent. The incidence of G3-5 CTx related toxicities was 67% (64). The most common toxicities were neutropenia 27% (26) and anaemia 15% (14) and there was 1 mortality from CTx related pneumonitis. In the univariate analysis, the factors associated with the incidence of CTx related toxicities were: i) Limited ability to walk a block, ii) Interference with social activity, iii) Use of an assistive ambulatory device, iv) Mini Cog Test Score < 4 and v) GI/GU CA. In multivariate analysis, GI/GU CA and a mini Cog test score < 4 were associated with CTx related toxicities Conclusions: Interestingly, there is a reduced risk of CTx related toxicities amongst patients with GI/GU CA, while mini Cog < 4 showed positive association. In our follow up study, we hope to further validate these factors and the utility of the CTC in our elderly CA population. Multivariate analysis: Characteristics OR (95% CI) p-value GI/GU CA 0.17 (0.06 – 0.48) 0.001 Mini COG ( < 4) 6.17 (1.60 – 23.82) 0.008
A single-institution study of renal outcomes in patients receiving checkpoint inhibitors.
Authors: Sarah Mushtaq, Daniel Alan Kerr, Abu-Sayeef Mirza, Bijal D. Shah, Claude Bassil
Journal: Journal of Clinical Oncology (2018)

e15079 Background: Checkpoint inhibitors (CPI) are becoming more widely used for various malignancies. The reported incidence of renal toxicities has varied , with a lower incidence reported in clinical trials but significantly higher in follow-up retrospective cohorts. Here, we present a single-institution retrospective study monitoring renal function in patients receiving CPI treatment. Methods: An IRB-approved retrospective analysis was performed using patients seen at Moffitt Cancer Center between 1/1/2015 and 1/1/2016 who were receiving CPI therapy (ipilimumab, nivolumab, pembrolizumab or any combination). Selected patients had up to 12 months follow-up including analysis of renal function. If available, serum electrolytes and urine studies were also collected. Primary endpoint was acute kidney injury (AKI), defined as increase in serum creatinine by > 0.3 mg/dL or ≥ 50% from baseline. Results: 206 patients were selected with most common diagnoses of melanoma (81%) or NSCLC (12%). Most patients (79%) also had stage 4 disease. There were 19 patients who had AKI, with a median age of 73 vs 68 in the non-AKI group (p = 0.057). There was no difference in HTN, DM, CKD stage, baseline creatinine, or baseline blood pressure between groups. There was no correlation between AKI and specific CPI therapy or combined CPI therapy. In the AKI group, there was a higher incidence of concomitant antihistamines (42% vs 15%, p = 0.003) and diuretics (37% vs 17%, p = 0.03). In the AKI group, 10 discontinued all CPI therapy due to disease status (progression or surveillance). 4 patients had AKI associated with autoimmune toxicity (2 colitis, 1 pancreatitis, 1 autoimmune nephritis) that resolved with steroids and stopping/changing CPI. 6 patients continued therapy without interruption, 4 had resolution of AKI. 5 patients had increasing SBP ( > 20 mmHg) at the time of AKI. Conclusions: In our cohort, CPI therapy was well-tolerated from the standpoint of renal function. Of the 19 (9%) patients who experienced AKI, only 4 patients (1.9%) had AKI associated with autoimmune-related toxicity. Our data suggest the concomitant use of other potentially nephrotoxic drugs (e.g., antihistamines, diuretics) may be associated with increased risk of AKI.
Pregnancy Outcomes in Women With Transposition of the Great Arteries After an Arterial Switch Operation
Authors: Victoria M. Stoll, Nigel E. Drury, Sara Thorne, Tara Selman, Paul Clift, Hsu Chong, Peter J. Thompson, R. Katie Morris, Lucy E. Hudsmith
Journal: JAMA Cardiology (2018)

A growing number of women are approaching childbearing age after arterial switch surgery for transposition of the great arteries. Prepregnancy counseling requires updated knowledge of the additional cardiovascular risks pregnancy poses for this cohort of women and the potential effect on their offspring; however, to our knowledge, this information is currently unknown.To determine the pregnancy outcomes of women with transposition of the great arteries after an arterial switch operation, as well as the outcomes of their offspring.This cohort study assessed women who had had arterial switch surgery from 1985 to the present and who were 16 years or older as of January 2018. All women with a previous arterial switch surgery for transposition of the great arteries with completed or ongoing pregnancy were included. Data were collected in a level 1 congenital cardiology center and joint obstetrics-cardiology clinic in Birmingham, United Kingdom.Patients were assessed before, during, and after pregnancy.Adverse maternal cardiac events (arrhythmia, heart failure, aortic dissection, or acute coronary syndrome) and aortic root dilatation, aortic regurgitation, and left ventricular function before and after pregnancy were the main outcomes. Mode of delivery and fetal outcomes were considered secondary outcomes.A total of 25 pregnancies were identified in 15 women; 8 women had had 1 pregnancy, while 7 were multiparous. There were no adverse maternal cardiac events. Before pregnancy, 8 women (53%) had no aortic regurgitation, 1 (7%) had a trivial degree of regurgitation, 4 (26%) had mild regurgitation, and 2 (14%) had moderate regurgitation. After pregnancies, 1 woman (7%) had minor progression of aortic regurgitation. Five women (36%) had mild neoaortic root dilatation prepregnancy, but none developed progressive dilatation in the first year post-partum. A total of 24 pregnancies were completed by the end of the study, with all infants born alive and well. Nineteen modes of delivery were known; there were 7 cesarean deliveries (37%), of which 2 (11%) were recommended for aortic dilatation and 5 (26%) for obstetric indications or maternal choice.Pregnancy is well tolerated after arterial switch operation; no adverse maternal cardiac events or early progression of neoaortic root dilatation or aortic regurgitation were observed in this study. These results provide evidence to allow reassurance of women with previous arterial switch surgery who are planning pregnancies.
Association between hospital volume and overall survival of patients with metastatic non-small cell lung cancer.
Authors: Gaurav Goyal, Adam C. Bartley, Ronald S. Go
Journal: Journal of Clinical Oncology (2017)

9044 Background: Prior studies have shown superior surgical outcomes of stage I-III non-small cell lung cancer (NSCLC) in centers with higher patient volumes. However, there is a lack of such information in stage IV NSCLC. In this study, we aim to determine the association between the number of patients with stage IV NSCLC treated annually at a treatment facility (volume) and all-cause mortality (outcome). Methods: Using the National Cancer Database, we identified patients diagnosed with stage IV NSCLC between 2004 and 2013. We classified the facilities by quartiles (Q; mean patients with NSCLC treated per year): Q1: &lt; 13.8; Q2: 13.8 to 23.6, Q3: 23.6 to 30.3, and Q4: &gt; 30.3. We used sandwich variance estimators to account for clustering of patients within facilities and Cox regression to determine the volume-outcome relationship, adjusting for demographic (sex, age, race), socioeconomic (insurance type), receipt of chemotherapy, and comorbid (Charlson-Deyo score) factors and year of diagnosis. Results: There were 281,654 patients with stage IV NSCLC treated at 1,275 facilities. The median age at diagnosis was 66 years, and 55.7% were men. The median annual facility volume was 23.6 patients per year (range, 1.0 to 301.4). The distribution of patients according to facility volume was: Q1: 6.6%, Q2: 14.9%, Q3: 25.4%, and Q4: 53.1%. The unadjusted median overall survival by facility volume was: Q1: 4.4 months, Q2: 4.5 months, Q3: 4.7 months, and Q4: 5.3 months ( P&lt; .001). Multivariable analysis showed that facility volume was independently associated with all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a small but significantly higher risk of death (Q3 hazard ratio [HR], 1.05 [95% CI, 1.03 to 1.07]; Q2 HR, 1.06 [95% CI, 1.03 to 1.09]; Q1 HR, 1.09 [95% CI, 1.06 to 1.13]). Conclusions: Patients who were treated for stage IV NSCLC at lower-volume facilities had a significantly higher risk of all-cause mortality compared with those who were treated at lower-volume facilities. [Table: see text]
Exercise does not ‘wear down my knee’: systematic reviews and meta-analyses
Authors: Alessio Bricca
Journal: British Journal of Sports Medicine (2018)

I investigated the impact of exercise on knee joint articular cartilage. This aim was investigated in three different systematic reviews (SRs) of randomised controlled trials (RCTs) in healthy animals and in humans at risk of or with knee osteoarthritis (OA).

Exercise is the first-line treatment for knee OA.1 Yet, many people still believe that exercise may ‘ wear down my knee ’ creating a barrier to exercise.

Articular cartilage is the hallmark of OA and the structure I studied in my PhD. It is a connective tissue that covers bone ends in the joints and provides lubrication of the meeting surfaces, allowing the transmission of loads with a low frictional coefficient. Aggrecan, collagen and molecular biomarkers are the molecules responsible for maintaining cartilage integrity, function and metabolism, and …
Clinical trial of biopsies in oncology: Patient-reported impact (BIOPSY).
Authors: Michelle K. Wilson, Stephanie Lheureux, Sunu Cyriac, Neesha C. Dhani, Marcus O. Butler, David Gutierrez, Victoria Mandilaras, Josee-Lyne Ethier, Ilaria Colombo, Yeh Chen Lee, Yada Kanjanapan, Luisa Bonilla, Wendy Hunt, Valerie Bowering, Amit M. Oza
Journal: Journal of Clinical Oncology (2017)

e17034 Background: Modest prospective data reports the impact of biopsies on patients (pts) with respect to adverse events (A/E) and anxiety. With increasing use of biopsies in clinical practice and trials, BIOPSY was designed to prospectively assess this. Methods: Pts undergoing a biopsy for diagnosis and/or research at Princess Margaret Cancer Centre were eligible. Surveys at 1 wk prior to biopsy and 1 wk and 1 mth post-biopsy assessed anxiety, A/E and pt experience. Anxiety was measured with a modified hospital anxiety and depression scale (HADS) score. Results: From 3/2015 to 1/2017, 51, 47 and 39 pts completed 1, 2 and 3 surveys respectively. Median age was 61 years. 40 biopsies were for research (78%) and 11 for diagnosis (22%). 46 pts were involved in a clinical trial (90%). 47 pts had a gynecological cancer (92%). 45 pts felt well-informed of the possible risks of the biopsy (88%). 23 pts noted the biopsy would not impact them directly (45%). 48 pts supported the use of tissue for future unrelated research (94%). Feelings of anxiety about the biopsy improved with time (table 1). 28 pts had pain 1 wk post-biopsy (60%) which was a moderate or major problem in 9 pts (19%). 2 pts reported reduced dignity with the biopsy (4%). 12 pts at 1 wk (26%) felt another biopsy would be a moderate-major issue. At 1 mth 3 of these pts reported a biopsy was now a mild problem. No significant A/E occurred. At baseline only 2 pts felt a biopsy would deter them from entering a clinical trial (4%). 42 pts at 1 wk (89%) and 30 pts at 1 mth (77%) felt they would consent to another biopsy for research. On univariate analysis pts with at least moderate pain post-biopsy at 1 wk or 1 mth (p=0.03) or an elevated HADS score at 1 mth (p=0.02) appeared less likely to agree to a further research biopsy but numbers were small. Conclusions: Anxiety and pain are potentially modifiable A/E that impact whether a pt will agree to a further biopsy. Overall, most pts tolerated their biopsy well, supported its use for future unspecified research and were open to further biopsies. [Table: see text]
Monitoring response of PDL-1 directed immunotherapy in patients with advanced NSCLC using serum CEA levels.
Authors: Rajasree Roy, Wallace Chan, Dilip Patel, Sandy Nissel-Horowitz, Angela Caramalis, Melanie Diaz, Adrienne Thomas, Lawrence H Durban, Bhoomi Mehrotra
Journal: Journal of Clinical Oncology (2017)

e20509 Background: Immunotherapy (IT) response measurements in advanced NSCLC management are evolving. We describe here our retrospective single institutional experience in measuring serum CEA levels as an early response determinant and correlation with radiographic assesment. Methods: Retrospective chart review was performed after obtaining IRB approval. Demographic information, stage, histology, prior treatment, IT agent used, radiographic response assesment and serum CEA levels were recorded. Patients were evaluable if they had elevated baseline serum CEA levels (normal range non smokers: 0-3 ng/ml, smokers 0-5 ng/ml), had recieved at least two cycles of IT and had radiographic response assessment performed. Results: Six eligible patients were identified. Median age 60 yrs; M:F1:5, SCC n=1, Adeno: n=5; Smoking history positive n=4; Stage IV n=6, EGFR mut+ n=2; IT agent used: nivolumab: n=5; atezolizumab: n=1. IT as 1st line of Rx n=1; 2nd line n=3, 3rd line: n=2. On first radiographic assesment: three patients had progressive disease (PD), Two patients had PR, one patient (#1) had an intial PR and subsequently PD with subsequent rise in CEA level to 16.1 corelating with PD on radiographs. Conclusions: Serum CEA levels appear to correlate well with response assesment in patients with advanced NSCLC while being treated with immunotherapy. This small study is hypothesis generating and is currently being evaluated in a larger series. [Table: see text]
Clinical and molecular features predicting long-term response (LTR) to anti-PD-(L)1 based therapy in patients with NSCLC.
Authors: Hira Rizvi, Andrew J. Plodkowski, Megan Tenet, Darragh Halpenny, Niamh Long, Jennifer L. Sauter, Francisco Sanchez-Vega, Walid K Chatila, Nikolaus Schultz, Marc Ladanyi, Kathryn Cecilia Arbour, Jamie E. Chaft, Matthew David Hellmann
Journal: Journal of Clinical Oncology (2018)

9022 Background: The transcendent feature of response to anti-PD-(L)1 therapy is durable, long-term responses, which can last up to years. Much effort in biomarkers has focused exclusively on initial response, but not all responses remain durable. The features predicting which patients will derive long-term response (LTR) may be even more important to identifying with precision those patients who most profoundly benefit from PD-1 blockade. Methods: Patients with advanced NSCLC who were treated with anti-PD-(L)1 based therapy from April 2011 through November 2016 were identified. LTR was defined as patients with progression-free survival lasting longer than 18 months. Efficacy was assessed by RECIST v1.1. Tumor mutation burden (TMB) was determined using MSK-IMPACT and PD-L1 expression by IHC. Fisher’s exact test was used to compare proportions between two groups and Mann-Whitney U to compare continuous variables. Results: Of 766 patients with NSCLC treated with anti-PD-(L)1 based therapy, 62 (8%) had LTR. Among those with LTR, 77% had complete/partial response as best response and 68% remain progression-free (median follow up 2.5 years). The median TMB was 12.24 mutations/Mb (n = 32), which represents the 82th percentile of all NSCLC cases profiled by MSK-IMPACT (n = 3000, median 5.66 mutations/Mb). No patient with LTR harbored an EGFR mutation. Of 36 patients with PD-L1 testing, 75% had PD-L1 expression ≥ 1% and 44% had PD-L1 expression ≥ 50%. When compared to patients without LTR, those with LTR were more likely to be smokers (81% vs 92%, p = 0.026), PD-L1 expression > 0% (44% vs 75%, p < 0.001) and ≥ 50% (35% vs 44%, p = 0.01), and TMB > median (54% vs 78%, p = 0.009). When compared to those with transient response ( < 18 months), those with LTR had significantly higher TMB (p = 0.002), but not PD-L1 expression (p = 0.44). Conclusions: Smoking status, PD-L1 expression, and TMB correlate with long-term response in NSCLC patients treated with anti-PD-(L)1 based therapy. TMB, but not PD-L1 expression, is distinctly increased in those with LTR compared to those with transient response. The features predicting initial response compared to durable response may be distinct.
Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan
Authors: Yuanzhi He, Wei Zhang, Tao Guo, Guoqing Zhang, Wei Qin, Liu Zhang, Caifen Wang, Weifeng Zhu, Ming Yang, Xiaoxiao Hu, Vikramjeet Singh, Li Wu, Ruxandra Gref, Jiwen Zhang
Journal: Acta Pharmaceutica Sinica B (2018)

Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile γ-cyclodextrin (γ-CD) metal-organic framework (CD-MOF) large molecular cages in which azilsartan (AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague–Dawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering (SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the γ-CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six γ-CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs.
Abstract 16100: Favorable Effects of Omega-3 Polyunsaturated Fatty Acids on Novel Inflammatory Biomarkers and Left Ventricle Function in Patients With Heart Failure
Authors: Dimitris Karlis, Evangelos Oikonomou, Theodoros Zografos, Gerasimos Siasos, Christina Chrysohoou, Stella Brili, Georgios Lazaros, Sotirios Tsalamandris, Georgia Vogiatzi, Angelos Papanikolaou, Alexis Antonopoulos, Georgios Georgiopoulos, Dimitris Tousoulis
Journal: Circulation (2016)

Introduction: Omega-3 polyunsaturated fatty acids (PUFAs) exert anti-inflammatory properties and have been tested in patients with systolic heart failure (HF). Soluble suppression of tumorigenicity...
Synoptic pathology data extraction for SNOMED CT coding using dataZOEK.
Authors: Triparna Ghosh-Choudhury, Jan van Soelen, Walter Scott Campbell
Journal: Journal of Clinical Oncology (2018)

e18601 Background: Data contained in the pathology report is essential for the diagnosis of cancer and an invaluable source of information for cancer research. However, most surgical pathology reports exist in textual form, thus rendering the data difficult to access. Extraction of these pathology data from text to structured, encoded data elements would expose such data for easy access and reuse to enhance patient care and new discoveries. A method to automate the identification and extraction of pathology synoptic data to encode these data using SNOMED CT is discussed and presented. Methods: 25 de-identified breast cancer biopsy and resection pathology reports in PDF form were submitted to salesSEER and trained in the dataZOEK™ application. dataZOEK is a data mining technology that provides access to unstructured text, PDFs, and images. Twelve (12) synoptic data elements representing tumor site, histology type, histologic grade, ER, and PR status assessments were selected for extraction. These terms were extracted and associated with the SNOMED CT concepts developed by UNMC investigators in collaboration with SNOMED International and the College of American Pathologists. Results: Within the 25 patient cases, there were a total of 444 data elements. dataZOEK correctly identified 414 of the 444 resulting in 93% accuracy. Out of 12 SNOMED CT codes, 11 codes were identified, converted, and stored with at least 89% accuracy. Histological type was identified with a 76% accuracy, which presents an opportunity to improve extraction through standardization of physician terminology. It took a total of 6.5 minutes to complete the process of transforming, identifying, and converting specified data elements to SNOMED CT, an otherwise time consuming and costly manual process. Conclusions: dataZOEK can be utilized to accurately and efficiently populate synoptic pathology SNOMED codes into a database. The adoption of dataZOEK technology in medical centers contributing to SNOMED globally will automate access to valuable patient information. This information can then be used to improve patient care, support research initiatives, and to predict future demographic service needs.