tbuckley/cabot-search huggingface dataset:
Topical sildenafil in the treatment of hand-foot syndrome and hand-foot skin reaction: A retrospective study.
Authors: Christy Arrowood, Christel N. Rushing, Donna Niedzwiecki, Leigh Howard, Wanda Honeycutt, Herbert Hurwitz, Adela Cardones
Journal: Journal of Clinical Oncology (2018)

e22095 Background: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are painful, debilitating, and often dose-limiting complications of anticancer agents. These cutaneous reactions are encountered with chemotherapy and VEGF multikinase inhibitors (MKIs). There is no standard effective treatment for HFS/HFSR. Methods: We conducted a retrospective study to describe the efficacy of sildenafil 2% cream (S2C) in treatment of established HFS/HFSR. Patients treated with S2C for HFS/HFSR from Apr 2013 to Oct 2015 were identified in pharmacy records. Chart review was performed to collect clinical data such as patient characteristics, agent associated with HFS/HFSR, treatment response and duration. Primary outcome was clinical improvement of HFS/HFSR. Clinical improvement was graded as: none (no), mild (mild), moderate (mod), and marked (mark), defined as 0, < 1, 1, > 1 grade improvement, respectively in NCI CTCAE. Maximum overall improvement in pain or skin was summarized descriptively. Results: Fifty-three patients received S2C for HFS/HFSR. Two of 53 patients received S2C on 2 separate HFS/HFSR occasions with different regimens. We therefore had a total of 55 records over a 33 month period. There were 23 (42%) records of HFS/HFSR due to VEGF MKI, 19 (35%) from cape plus bevacizumab (bev)/ziv-aflibercept (ziv), and 13 (33%) from cape alone or plus other agent. Patients received S2C twice a day after onset of HFS/HFSR. Overall, 78% (43/55) had at least mild improvement of HFS/HFSR after S2C (25% mark, 15% mod, 38% mild, 16% no, 6% not evaluable). Of those receiving VEGF MKI, 57% (13/23) had mark/mod improvement (35% mark, 22% mod, 22% mild, 9% no, 13% not evaluable). Of those receiving cape plus bev/ziv, 26% (5/19) had mark/mod improvement (21% mark, 5% mod, 53% mild, 21% no). Of those receiving cape alone or plus other agent, 31% (4/13) had mark/mod improvement (15.5% mark, 15.5% mod, 46% mild, 23% no). No toxicity from S2C was reported. Conclusions: Sildenafil cream is a promising HFS/HFSR treatment. This study recorded a 78% rate of clinically meaningful improvement to established HFS/HFSR after S2C. Further studies are warranted to investigate the efficacy of topical sildenafil in treatment of HFS/HFSR.
First experience with osimertinib in patients with T790M mutation previously treated with EGFR – TKIs in Croatia.
Authors: Marko Jakopovic, Lela Bitar, Branka Cucevic, Sanja Plestina, Ivica Mazuranic, Sven Seiwerth, Ana Hecimovic, Andrea Vukic Dugac, Mateja Jankovic, Gzim Redzepi, Miroslav Samarzija
Journal: Journal of Clinical Oncology (2017)

e20518 Background: EGFR T790M mutation is responsible for around 60% cases of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in patients who have lung cancer with an activating EGFR mutation. Methods: We administered osimertinib 80 mg once daily in 8 patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with first and second-line EGFR tyrosine kinase inhibitors. Results: We treated 8 patients with osimertinib with stage IV lung adenocarcinoma. Four patients were males and four were females, median age 62 (raging from 54 to 82). Four patients were never smoker, and four were ex-smokers. All patients had initially deletion 19 in EGFR gene and then developed T790M mutation. In all patients T790M was proven from tumor tissue. Majority of patients were ECOG 1. All patients were previously treated with first or second line EGFR TKIs (erlotinib, gefitinib or afatinib) and had radiologically documented disease progression. Three patients were treated with osimertinib in third line setting, 2 in fourth, one in fifth, one in sixth and one even in tenth line setting. Median time to response was 4 weeks (raging from 3 to 7). All 8 patients had partial response (PR) with still no recorded disease progression. Duration of response is from 7 to 46 weeks and still ongoing. No significant side effects were observed. Conclusions: Osimertinib is highly active in patients with lung adenocarcinoma which harbor EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. There were no serious side effects of treatment.
TCT-345 Optical coherence tomography appraisal of residual thrombus burden in patients with ST-segment elevation myocardial infarction undergoing bivalirudin versus unfractionated heparin infusion. The MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) OCT study
Authors: Hector Garcia-Garcia, Andrea Picchi, Gennaro Sardella, Marianna Adamo, Enrico Frigoli, Ugo Limbruno, Roberto Diletti, Giacomo Boccuzzi, Marco Zimarino, Marco Contarini, None Filippo Russo, Paolo Calabro', Giuseppe Andò, Stefano Garducci, Cataldo Palmieri, Carlo Briguori, Kayode Kuku, Martina Rothenbuehler, Alexios Karagiannis, Marco Valgimigli
Journal: Journal of the American College of Cardiology (2018)
Abstract 18153: Screening for Atrial Fibrillation is Feasible in US Managed Care Outpatient Facilities
Authors: William Keen, Julie Martin, Cesar Lopez, Miguel Pena-Ruiz, Kenneth Antons, Sonni Longson, Michael Fechter, Jason Brown, Michael Lalich, Ben Freedman
Journal: Circulation (2017)

Introduction: It is estimated that approximately one third of ischemic strokes are caused by atrial fibrillation (AF), and in almost one third of these, there was no prior diagnosis of AF. Screenin...
Whole transcriptome analysis to reveal differentially expressed genes between paired osteosarcoma and normal bone samples.
Authors: Xuan Dung Ho, Phuong Phung, Van Quang LE, Van Hieu Nguyen, Ene Reimann, Ele Prans, Gea Kõks, Katre Maasalu, Aare Märtson, nghi Thanh Nhan Le, Le Huy Trinh, hoang Gia Nguyen, Sulev Kõks
Journal: Journal of Clinical Oncology (2016)

e22508 Background: In present study we performed whole transcriptome analysis of bone samples of 18 osteosarcoma patients confirmed with histology and we compared the result of tumoral to non-tumoral samples from the same patient. We sequenced total RNA from 36 samples (18 tumoral bone samples and 18 non-tumoral bone samples) matching in pairs for each osteosarcoma patient. Methods: We extracted RNA from 18 tumor normal paired osteosarcoma fresh bone samples. RNAseq data were analyzed with DESeq2 and Reactome packages of R. Results: We found 6775 genes expressed differentially between the normal bone and osteosarcoma tissues. The differential expression had FDR corrected statistical significance below 0.1. 4092 genes were up-regulated and 2683 were down-regulated. Among those genes, BTNL9, MMP14, ABCA10, ACACB, COL11A1 and PKM2 were expressed differentially with the highest significance between tumor and normal bone. Functional annotation with the Reactome identified significant changes in the pathways related to the extracellular matrix degradation and collagen biosynthesis. Activation of PKM2 indicates the Warburg effect in tumor tissues. Conclusions: We identified differential expression of 6775 genes between the normal and osteosarcoma tissues with very high confidence. The up-regulation of COL family genes (COL11A1, COL2A1, COL10A1, COL3A1, COL6A1) with interaction with some others indicates the changes in the regulation of the synthesis and degradation of collagen and extracellular matrix that seems to be an important mechanism of osteosarcoma.
Ultra-low doses of TX-004HR to improve symptoms of vulvar and vaginal atrophy (VVA) while maintaining serum levels of estradiol within the normal postmenopausal range.
Authors: Shari Beth Goldfarb, Jeanne Carter, Brian Bernick, Sebastian Mirkin
Journal: Journal of Clinical Oncology (2018)

10074 Background: More than 60% of postmenopausal breast cancer (BC) patients have symptoms of dyspareunia and vaginal dryness that often result from endocrine therapy, and are challenging to treat. Local vaginal estrogens are proven safe and effective for VVA treatment, but a major concern of BC patients is the potential risk of systemic absorption and adverse breast effects; and it is contraindicated by the FDA to be used in this population. TX-004HR, an investigational, vaginal, softgel capsule of soluble 17β-estradiol (E2), is being developed to treat menopausal VVA. Serum E2 levels following TX-004HR treatment, which significantly reduced moderate-to-severe dyspareunia and vaginal dryness, were determined and compared with that of the normal postmenopausal range. Methods: A 12-wk, randomized, placebo-controlled, phase 3, safety/efficacy study (REJOICE) was conducted in menopausal women with VVA. TX-004HR (4 or 10 µg) was administered daily for 14 d, then twice weekly for 10 wks. Serum E2 levels using validated GC/MS/MS and pharmacokinetics (PK) were determined in 17-19 subjects/group on days 1 and 14 of daily dosing and day 84 of twice-weekly maintenance dosing. Results: The day 1, 0-h, mean±SD, serum E2 level was 4.05±2.69 pg/mL (95th percentile 8.49 pg/mL). The mean 24-h average levels on day 1 for the placebo, 4 µg, and 10 µg groups were 4.86±3.22, 3.92±1.46, and 5.76±3.13 pg/mL, respectively. Day 14 mean serum levels were lower than those on day 1; 4.34±2.77, 3.63±1.78, and 4.59±2.27 pg/mL, respectively. No accumulation of E2 was observed on day 14. On day 84 (maintenance phase), serum E2 levels were 4.36, 4.25, and 4.79 pg/mL, respectively. Primary efficacy and safety endpoints had been met for both doses. Changes in E2 levels from baseline to day 14 and day 84 were similar. Conclusions: TX-004HR (4 or 10 µg) improved VVA symptomatology, while maintaining serum E2 levels within the normal postmenopausal range. Although not yet studied in BC patients, further study in this population, especially in those taking aromatase inhibitors, is warranted. Clinical trial information: NCT02253173.
Prognostic factors in osteosarcoma: A single institution study.
Authors: Haotong Wang, Alex Jacobson, Ruoyu Miao, Saveli Goldberg, David C. Harmon, Edwin Choy, Gregory Michael Cote, Francis J Hornicek, Kevin Raskin, Gunnlaugur Nielsen, Thomas F. DeLaney, Yen-Lin Chen
Journal: Journal of Clinical Oncology (2016)

e22503 Background: We reviewed the long term clinical characteristics and outcomes of patients treated for osteosarcoma in our institution. Methods: We reviewed 328 osteosarcoma patients treated from 1996 to 2013. Patients with limited follow up were excluded, resulting in 295 cases for analysis. Clinical and pathologic variables were recorded. Prediction methods using Kaplan-Meier analysis and Cox proportional hazards regression ware used to analyze survival outcomes and risk variables. Results: Of the 295 patients 139 (47%) patients are female and 156(53%) patients are male. The median age is 28 (range 3 -384). 58 (20%) presented with metastatic disease. 36 (12%) presented with Stage 1 disease and 137 (46%) and 62 (21%) with Stage 2 and 3, respectively. The median follow up time is 52 months. 254 (85%) patients were treated with surgery and 41 (14%) patients did not have surgery. 226 (77%) patients had chemotherapy; of those, 35 (12%) patients had pre-operative chemotherapy, 35 (12%) had post-operative chemotherapy and 69 (23%) had both pre- and post-operative chemotherapy. 90 (31%) patients had radiation therapy (RT) and 205 (69%) did not have RT. 5-year, 10-year and 15-year DSS is 77.9% (95% confidence interval, CI, 72.3% to 83.5%), 73.1% (95% CI, 66.7% to 79.6%), and 65.4% (95% CI, 55.9% to 74.9%), respectively. We identified age at diagnosis (p = 0.001), radiation associated osteosarcoma (p = 0.016), primary tumor site (p = 0.022), histology subtype (p = 0.002), pathology grade (p = 0.001), and AJCC stage (p < 0.001) as significant pre-treatment factors for DSS. Multi-variant analysis shows age (p < 0.001, HR = 1.038 per year), telangiectatic and chondroblastic osteosarcoma as histology subtypes (p < 0.001, HR = 3.013), and AJCC Stage more than 1 (p < 0.001, HR = 2.314 per additional stage ) as worse characteristics for prognosis. Conclusions: We identified significant prognostic factors for osteosarcoma patients. This could be helpful for predicting survival rate and making clinical decisions.
Identifying systemic cancer therapy treatment and dosing in structured electronic data.
Authors: Nikki M Carroll, Jeff Holzman, Debra P. Ritzwoller
Journal: Journal of Clinical Oncology (2018)

e18599 Background: Researchers need efficient and validated processes to accurately summarize treatment and total dose history data for patients treated for cancer. We developed and validated an algorithm that was agnostic to the source of data, but could characterize entire courses of systemic therapy treatment in patients diagnosed with breast, colorectal, or lung cancer. The algorithm identifies all courses of systemic therapy, the specific drug regimens within each course, the number of cycles within each course of therapy, and the total dose of each drug regimen. Methods: The algorithm was built and validated on six different cohorts of patients with incident breast, colorectal, or lung cancer. The ability of the algorithm to accurately identify courses of therapy, specific regimens, cycles and dosing was compared to chart review and the tumor registry. Performance was measured by sensitivity, specificity, percent correct match, and false positive rate. Results: Overall algorithm performance was high and we achieved a false positive rate of 0%. Our algorithm better captured therapies that included oral systemic therapies relative to the EHR-based systemic/infusion therapy tables alone. Conclusions: We constructed a highly sensitive and accurate algorithm that matched entire courses of treatment in patients diagnosed with breast, colorectal, or lung cancers. This algorithm gives us the ability to study the impact systemic dose intensity has on patient outcomes including treatment related toxicities, recurrence, and overall survival. Tumor Registry Gold Standard Chart Review Gold Standard Breast Cancer Sensitivity 100 100 False Positive Rate 0 0 Accuracy 100 100 First Course Regimen Match, % 90 90 Number of Infused Cycles Match, % - 90.9 Number of Oral Cycles Match, % - 33.3 Total Drug Dose Match, % - 100 Colorectal Cancer Sensitivity 100 100 False Positive Rate 0 0 Accuracy 100 100 First Course Regimen Match, % 90 88 Number of Infused Cycles Match, % - 87.8 Number of Oral Cycles Match, % - 50.2 Total Drug Dose Match, % - 100 Lung Cancer Sensitivity 97.4 100 False Positive Rate 0 0 Accuracy 98.1 100 First Course Regimen Match, % 93.6 94 Number of Infused Cycles Match, % - 88.5 Number of Oral Cycles Match, % - 29.6 Total Drug Dose Match, % - 100
O1 SINGLE CELL CHARACTERISATION OF ABDOMIAL AORTIC ANEURYSMS BY MASS CYTOMETRY (CYTOF) REVEALS A CHRONIC INFLAMMATORY CELL INFILTRATE PREDOMINATED BY T AND B CELLS
Authors: Ismail Cassimjee, Regent Lee, David Ahern, Patricia Green, Inhye Park, Ashok Handa, Claudia Monaco
Journal: Cardiovascular Research (2018)
Community based lung cancer screening program: Evaluation of the initial lung cancer screening CT scan.
Authors: Tripurari Mishra, Ari Hakimian, Michael Vercillo, Axel Joob
Journal: Journal of Clinical Oncology (2018)

1562 Background: Low-dose chest CT for lung cancer screening has shown to have a significant impact on the early diagnosis of lung cancer. In the initial trials, approximately a 20% decrease in lung cancer mortality was found. Patients enrolled in a community-based lung cancer screening program initiated in March 2013 at Lutheran General Hospital and Illinois Masonic Hospital were evaluated for initial outcomes. Methods: All patients who completed an initial consultation in oncology clinic from March 2013-June 2017 were included in the analysis. Eligibility criteria for the program included patients within the age range of 55-77, with a > 30 pack year history, and that were current smokers or quit tobacco less than 15 years ago. Individuals between 50-55 years old were also included if they had > 20 pack year smoking history and at least one additional risk factor. All patients with significant abnormalities were discussed at a multidisciplinary conference prior to embarking on any invasive procedures. Also, they underwent a low-dose chest CT for lung cancer screening and were subsequently seen in consultation by a thoracic surgeon. All patient data was entered into a REDCap database and subsequently evaluated. Results: 392 patients were enrolled during the study timeframe. Majority of the patients were caucasian (88%) and male (60%). They were referred by their primary physician (95%). The average age of the sample was 64 years (±6.6). 211 (53.8%) patients were found to have pulmonary nodules. A total of 506 pulmonary nodules were found with an average size of 4.9 (± 4.3) mm. Of the 392 patients who underwent lung cancer screening, a total of 11 lung cancers were found (2.8%). Of the 11 patients, 6 (55%) patients were Stage I, 1 (9%) patient was Stage II, 2 (18%) patients were Stage III, and 1 (9%) patient was Stage IV. There was also 1 (9%) patient with limited stage small cell carcinoma. Conclusions: Of the 11 cancer patients identified, 64% presented with early stage lung cancer on initial lung cancer screening. In fact, 55% of the patients presented with Stage I lung cancer. These data suggest that lung cancer screening is a viable tool in discovering early stage lung cancer with the potential to improve lung cancer survival.
OS1.3 Clinical significance of plasma EVs in Glioblastoma patients
Authors: M Del Bene, D Osti, G Rappa, M Santos, V Matafora, C Richichi, S Faletti, G Beznoussenko, A Mironov, A Bachi, L Fornasari, D Bongetta, P Gaetani, F DiMeco, A Lorico, G Pelicci
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is the most common primary brain tumor. Despite aggressive treatment (surgery, chemo- and radiotherapy), the prognosis is dismal (median overall survival: 14m). Actually, early diagnosis and treatment monitoring represent major unmet needs. Extracellular vesicles (EVs) are potentially optimal biomarkers owing to high stability and their presence in blood and cerebrospinal fluid. These features, combined to their genetic and proteomic composition that mirrors the intratumoral environment, highlight EV applicability as blood-based biomarkers for disease diagnosis and therapeutic monitoring. We collected plasma samples from healthy controls (n=33), GBMs (n=43) and different central nervous system malignancies (n=25). EVs were isolated and subjected to an integrated analysis relying on transmission electron microscopy, Nanoparticle Tracking Analysis, and mass spectrometry in order to assess morphology, size, concentration and protein composition. An orthotopic mouse model of human GBM was employed to confirm human plasma EV quantifications. Possible associations between plasma EV concentration and clinical features were analyzed. All statistical tests were two-sided. We observed a significant EVs enrichment in GBM patients plasma if compared to healthy control and patients harboring other CNS malignancies. GBM surgical removal was accompanied by a relevant drop in the concentration of circulating EVs followed by a re-increase at the relapse; this indicates the tumor mass as the major donor of circulating EVs in GBM patients. This phenomenon was confirmed by mouse model. The analyses of EV protein cargo revealed a specific signature, which included members of the complement/coagulation cascade and regulators of iron metabolism. Our work demonstrates the potential applicability of circulating EVs as reliable cancer biomarker for GBM patients. Furthermore we observed that EV concentration and protein cargo might provide information about response to therapies and tumor progression.
APC Targeting: mRNA Delivery System for Targeting Antigen‐Presenting Cells In Vivo (Adv. Healthcare Mater. 17/2018)
Authors: Cristina Fornaguera, Marta Guerra‐Rebollo, Miguel Ángel Lázaro, Cristina Castells‐Sala, Oscar Meca‐Cortés, Victor Ramos‐Pérez, Anna Cascante, Núria Rubio, Jerónimo Blanco, Salvador Borrós
Journal: Advanced Healthcare Materials (2018)

The study in article 1800335 by Salvador Borrós and co-workers, takes advantage of the known versatile properties of the oligopeptide end-modified poly (β-amino esters) (OM-PBAEs) to complex mRNA and form nanoparticles. It is demonstrated that the selection of the appropriate end-oligopeptide modifications enables the specific targeting and major transfection of antigen-presenting cells (APC) in vivo, after intravenous administered.
10-Year Outcomes of Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Artery Disease
Authors: Duk-Woo Park, Jung-Min Ahn, Sung-Cheol Yun, Yong-Hoon Yoon, Do-Yoon Kang, Pil Hyung Lee, Seung-Whan Lee, Seong-Wook Park, Ki Bae Seung, Hyeon-Cheol Gwon, Myung-Ho Jeong, Yangsoo Jang, Hyo-Soo Kim, In-Whan Seong, Hun Sik Park, Taehoon Ahn, In-Ho Chae, Seung-Jea Tahk, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial
Authors: Eric Jonasch, Ian E McCutcheon, Dan S Gombos, Kamran Ahrar, Nancy D Perrier, Diane Liu, Christine C Robichaux, Mercedes F Villarreal, Justin A Weldon, Ashley H Woodson, Patrick G Pilie, Gregory N Fuller, Steven G Waguespack, Surena F Matin
Journal: The Lancet Oncology (2018)
Hematopoietic cell transplant comorbidity index (HCT-CI) to assess AML induction risk.
Authors: Martin W. Schoen, Kahee A. Mohammed, Carl Freter, Jack M Lionberger
Journal: Journal of Clinical Oncology (2017)

e18519 Background: Induction therapy for acute myeloid leukemia (AML) is intense and methods for risk appraisal of therapy are controversial. Formal comorbidity assessment may allow for improved prognostication in addition to age. The HCT-CI(+/-Age) was developed to inform risk of patients undergoing stem cell transplant, and has found use in predicting early outcomes in AML induction. We applied HCT-CI retrospectively to our experience to analyze the predictive power regarding patient survival during induction. Methods: 140 cases induced with idarubicin and cytarabine (IA) or IA plus cladribine (IAC) between Jan 2008 and Sept 2015. HCT-CI (+/- Age) was derived from information available prior to chemotherapy and NCCN Leukemia Risk were calculated. Death prior to discharge from the initial induction hospitalization was the primary outcome for logistic regression. Results: 107 patients received IAC and 33 IA with mean age of 57 and 66 years respectively (p&lt;0.01). Regimen did not predict death (p=0.27). Median age was 61 (range 20-86) with mean scores of 2.0±0.2 (HCT-CI) and 2.9±0.2 (HCT-CI+Age). In univariate analysis HCT-CI (+/-Age) predicted death during induction. In multivariate analyses, when HCT-CI (+/-Age) was adjusted for (NCCN risk and regimen) or (age and regimen) predictive power was maintained (Table). Conclusions: These data suggest that HCT-CI predicts death during induction of AML and age did not augment prediction, up to age 70. We conclude that HCT-CI(+/-Age) may be a more useful tool than age alone or clinical instinct to help patients and providers make difficult decisions about therapy. [Table: see text]
The Violence of Uncertainty — Undermining Immigrant and Refugee Health
Authors: Breanne L. Grace, Rajeev Bais, Benjamin J. Roth
Journal: New England Journal of Medicine (2018)

Interview with Dr. Breanne Grace on immigrant and refugee health and the effects of systematic personal, social, and institutional instability. (09:02)Download Immigrants and refugees in the United States have long faced structural violence due to unequal health care access. Now they're being subjected to "the violence of uncertainty," enacted through systematic instability that exacerbates inequality and generates fear.