tbuckley/cabot-search huggingface dataset:
Cisplatin dose intensity (CDDP-D) in human papillomavirus-positive (HPV+) localized oropharyngeal carcinoma (OPC) treated with chemoradiotherapy (CRT).
Authors: Marc Oliva Bernal, Shao Hui Huang, Wei Xu, Jie Su, Aaron Richard Hansen, Andrew J. Hope, Raymond Woo-Jun Jang, Andrew Bayley, Eric Xueyu Chen, Meredith Elana Giuliani, Jolie Ringash, Scott Victor Bratman, John Cho, John Waldron, Ilan Weinreb, Douglas Brian Chepeha, John Kim, Brian O'Sullivan, Lillian L. Siu, Anna Spreafico
Journal: Journal of Clinical Oncology (2018)

6044 Background: CDDP-D ≤ 200 mg/m2 has been shown to have a detrimental impact on overall survival (OS) in HPV negative disease with a similar trend in T4/N3 HPV+ patients (pts). We evaluated the impact of CDDP-D on OS in a larger cohort of HPV+ OPC, staged using 8th Ed. AJCC/UICC TNM staging criteria (TNM8-S). Methods: We performed a retrospective single institution analysis of HPV+ OPC pts treated with CRT (IMRT) between 2005-2015. HPV status was tested by p16 staining, supplemented by HPV DNA (ISH or PCR) if equivocal. All cases were re-classified using TNM8-S. Kaplan-Meier 5-year OS (5yOS) was calculated and compared by log-rank test between CDDP-D ( < 200, = 200 or > 200 mg/m2) stratified by stage. Significant univariate variables including TNM8-S, smoking history and CDDP-D were tested in multivariable analysis (MVA) to identify OS predictors. Results: A total of 506 pts were evaluated: median age 57.4 (range 31.3-80.9); smoking ≤ vs > 10 pack-year (PY), 52% vs 48%; TNM8-S I/II/III N = 200/183/123. Median CDDP-D: 200mg/m2. Median follow-up: 4.9 (range 0.6-12.7) years. 5yOS differed by TNM8-S I, II and III: 93 vs 82 vs 78% (p < 0.001). In the MVA, PY had a detrimental impact on OS (HR = 1.16, 95%CI: 1.05-1.29 p = 0.003); CDDP-D did not impact OS overall (HR: 0.71, 95%CI: 0.41-1.21 p = 0.4), but in the TNM8-S III subgroup there was a trend toward decreased OS with CDDP-D < 200 mg/m2 (table). Conclusions: No linear CDDP-D effect on OS was seen for HPV+ OPC overall, although < 200 mg/m2 may be detrimental in TNM8-S III. TNM8-S separated OS well in this large cohort of uniformly treated pts. Suboptimal 5yOS (78%) in TNM8-S stage III HPV+ disease suggests the need for novel strategies in this setting. 5yOS and MVA by TNM8-S. Variable CDDP-D mg/m2 No of pts TNM8-S (No of pts) I (200) II (183) III (123) 5yOS % (95%CI) < 200 125 89% (79-100) 82% (71-95) 63% (44-89) = 200 224 93% (88-99) 80% (71-90) 90% (82-99) > 200 157 95% (90-100) 85% (75-96) 74% (61-89) p value 0.14 0.63 0.11 MVA:HR (95%CI) = 200 vs < 200> 200 vs < 200 0.58 (0.19-1.8,p = 0.35) 0.31 (0.08-1.28,p = 0.11) 1.18 (0.52-1.33 p = 0.69) 0.85 (0.31-2.3 p = 0.74) 0.38 (0.14-1.05, p = 0.06) 0.88 (0.37-2.11, p = 0.77)
TCT-778 Impact of ticagrelor and aspirin versus clopidogrel and aspirin in symptomatic patients with peripheral arterial disease: Thrombus burden assessed by optical coherence tomography
Authors: Mehmet Cilingiroglu, Massoud Leesar, Ismail Ates, Deniz Mutlu, Marc Feldman
Journal: Journal of the American College of Cardiology (2018)
Harnessing novel immune escape mechanisms for cancer therapeutics: OXAB1 target validation, proof of concept and preclinical development.
Authors: Livija Deban, Wei Cao, Yaoyao Fu, Angelo Kaplan, Rachel Dusek, Arnima Bisht, Sudha Swaminathan, San Lin Lou, Manal Amoury, Bukky Adelegan, Joanne Berry, Jim Ackroyd, Chuck Hanum, Robert Boyd, Christian Rohlff, Haining Huang
Journal: Journal of Clinical Oncology (2018)

e15148 Background: Evasion of the host’s immune system by tumor cells is a well-established mechanism of tumor establishment and progression. Using proteomic analysis of membrane-associated proteins from whole tumors, tumor infiltrating lymphocytes (TIL), and activated/exhausted T cell models, we have identified a receptor–ligand axis involved in an active immune escape mechanism; and we have generated an antibody targeting this axis with potential therapeutic benefit. Methods: We have developed OXAB1, an agonistic humanized mAb targeting OX001R that shows enhanced activity in in vitro and ex vivo studies. We have conducted in vitro assessment of T cell cytokine production and cytotoxicity; ex vivo assessment of TIL activation in 3D explant system; in vivo assessment of anti-tumor efficacy of OXAB1 in a humanized animal model of lung cancer. Results: The receptor (OX001R) is expressed on activated T cells and NK cells. The ligand (OX001L) is expressed on various cancer cells. OX001L downregulation reportedly correlates with poor survival and increased risk of metastasis in multiple cancers. Analysis of NSCLC samples demonstrated that OX001L downregulation (p=0.0001) and PD-L1 upregulation significantly correlate with the degree of tumor T cell infiltration. In vitro studies showed that tumor cells downregulate OX001L and upregulate PD-L1 upon T cell engagement. OX001L downregulation requires direct cell-cell contact, thus involving a distinct mechanism when compared with soluble factor mediated PD-L1 upregulation. We found that anti-OX001R agonist antibodies promote T cell activation resulting in enhanced IL-2 and IFNγ production. Anti-OX001R agonist antibodies efficiently activate patient TIL in ex vivo 3D tumor explants. Agonistic anti-OX001R antibody demonstrated significant anti-tumor activity, with tumor growth inhibition comparable and additive to that seen with pembrolizumab. Conclusions: Our results extend the research into cancer immune escape-associated therapeutics by identifying and validating the OX001R/OX001L immune escape axis, and support the clinical translation of an anti-OX001R agonistic antibody in cancer therapy.
Maintenance therapy with trastuzumab +/- fluoropyrimidine in non-progressive HER-2 positive advanced gastroesophageal cancer patients after first-line chemotherapy.
Authors: Anthony Lopez, Hsiang-Chun Chen, Kazuto Harada, Mariela A. Blum Murphy, Jane Elizabeth Rogers, Irene Thomas, Fatemeh Ghazanfari Amlashi, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2018)

e16071 Background: The maintenance of anti-HER2 is often used in breast cancer patients despite the lack of strong evidence. In patients with HER-positive advanced gastroesophageal adenocarcinoma (AGA), trastuzumab in combination with chemotherapy based on 5-FU and platinum salts is considered as the standard-of-care. Our objective was to evaluate the efficacy of trastuzumab +/- fluoropyrimidine as maintenance therapy in non-progressive patients. Methods: We retrospectively analyzed patients with AGA who started 1st-line chemotherapy at the MDACC between August 2008 and December 2016. Primary endpoints were time to failure (TTF), defined as the time interval between start of maintenance therapy and first progression date or death date, overall survival (OS) and progression-free survival (PFS). Secondary endpoint was the evolution of left ventricular ejection function (LVEF) on maintenance therapy. Results: Of the 46 patients analyzed, 83% were male, 100% had a performance status of 0 or 1. Primary location of the tumor was mainly the gastroesophageal junction (87%), with synchronous metastases in 90% of the cases. After first-line chemotherapy, complete response, partial response and stable disease rates were respectively 12%, 76% and 12%. The median time of receiving trastuzumab alone (17%) or combined with fluoropyrimidine (83%) was 14.7 months (range, 0.2-98.0). The median TTF was 1.1 years (95% CI, 0.4-2.1). Only number of metastasis was significantly associated with TTF in univariate analysis (hazard ratio [HR], 1.54; p = 0.04). The median follow-up time among survivors was 2.1 years (range, 0.6 to 9.2). The median OS was 4.1 years (95% CI, 2.3 years – not estimable), with a 3-year survival rate of 60% (95% CI, 41%-74%). Only age was associated with OS (HR, 2.93; p = 0.05). The median PFS was 1.4 years (95% CI, 0.8-2.0). The median LVEF pre- and post-treatment were both 57.5%. Conclusions: After disease control with first-line trastuzumab-based biochemotherapy, maintenance therapy with trastuzumab +/- fluoromyrimidine seems effective and safe. Prospective randomized controlled study is warranted for confirming this strategy.
Virtual reality in GI endoscopy: intuitive zoom for improving diagnostics and training
Authors: Alexander Hann, Benjamin M Walter, Niklas Mehlhase, Alexander Meining
Journal: Gut (2018)

Among the many areas which may benefit from virtual reality (VR), GI endoscopy could be an important one. We developed a system to magnify the endoscopic image on forward movement of the endoscopists head to zoom into areas of interest during real-time endoscopy, called intuitive zoom. We could show that VR could be conveniently incorporated into daily endoscopic work when it comes to closely examining operator-defined regions of interest. Additionally, applied light intensity-derived three-dimensional (3D)reconstruction of the intestinal mucosa was used to better assess lesions such as polyps using the Paris classification. These new techniques might improve routine endoscopic diagnosis and therapy and open a new world of endoscopic training.

### Study background

Flexible endoscopy is performed using a two-dimensional (2D) image of the working area. Although this is regarded as a standard since 1970,1 new technologies allowing for stereoscopic vision thus improving visual spacial perception emerge. VR is used to generate realistic images that replicate a real environment by using head mounted displays (HMDs). Since 2016, after the introduction of the HMDs Oculus Rift (Oculus VR, California, USA) and HTC VIVE (HTC, New Taipei City, Republic of China), the technology became available at consumer prices. Until now, VR is often used for training purposes like surgical training.2 3 VR is also used for endoscopic training although most simulators just project a virtual endoscopic image on a flat screen without full immersion of the examiner.4–6 To explore the potential of VR in real-time flexible endoscopy, we developed a setup for performing endoscopic interventions aided by special features that can be easily implemented in VR.

### Methods

Endoscopic examinations were performed using an Olympus GIF-HQ190 and CF-HQ190I (Hamburg, Germany). VR was implemented using the headset HTC VIVE accompanied by the VIVE Tracker. Interaction of the user with the devices was programmed using the cross-platform …
TCT-626 Comparative Effectiveness of Different Types of Contemporary Drug-Eluting Stents in Patients with De Novo Long Coronary Artery Lesions
Authors: Do-yoon Kang, Cheol Hyun Lee, Mineok Chang, Kyusup Lee, Osung Kwon, Pil Hyung Lee, Jung-Min Ahn, Seung-Whan Lee, Young-Hak Kim, Seong-Wook Park, Duk-Woo Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
<i>FLI1</i> circular RNA as biomarkers for tracking disease progression and as potential therapeutic targets in small cell lung cancer.
Authors: Jiuwei Cui, Lingyu Li, Jifan Hu
Journal: Journal of Clinical Oncology (2018)

e20573 Background: Small cell lung cancer (SCLC) is ranked as the most devastative type of human lung malignancies. We have found Friend leukemia virus integration 1 (FLI1) circular RNA (cFLI1) is aberrantly expressed in SCLC tissues and closely correlates with the malignant phenotype of SCLC. Here, we explored the clinical significance of cFLI1s in SCLC patients. Methods: Initially, Using RNA fluorescence in situ hybridization (FISH) and quantitative PCR, we evaluated the expression levels of cFLI1 in 56 primary SCLC tissues and 50 non-small cell lung cancer (NSCLC) tissues. Subsequently, We confirmed its clinical relevance in longitudinal analyses of serum exosome cFLI1s (exo-cFLI1s) levels across time of SCLC patients (n = 165). Results: We found that cFLI1 (derived from exon 4-2-3 of FLI1) was aberrantly upregulated in SCLC tissues compared with NSCLC tissues(p < 0.0001), and positive associated with lymph node metastasis(p < 0.01). Serum exo-cFLI1 was significantly upregulated in SCLC tissues compared with healthy individuals (p = 0.0221), and exo-cFLI1 level in patients with extensive stage SCLC was significantly higher than that in limited stage SCLC patients(p = 0.0014). SCLC patients with lower level of exo-cFLI1 experienced longer disease remissions than those with higher exo-cFLI1 level (p = 0.038). Through tracking at several time-points during the course of treatment, we found that serum level of exo-cFLI1 was significantly reduced compared with their baseline levels when the disease of SCLC patients were partial remission (PR) or complete remission (CR) after 6 courses of first-line chemotherapy(p = 0.018). Conclusions: cFLI1 level is closely correlated with clinical response of SCLC patients who were receiving ongoing chemotherapy, and cFLI1 may be a promising biomarker for tracking disease progression and serve as potential therapeutic targets of SCLC.
Cardiac assessment within 5 years of lymphoma treatment can detect patients with high risk of cardiotoxicity and undiagnosed coronary artery disease.
Authors: Neelam Mistry, Manali K. Kamdar, Lavanya Kondapalli, Debashis Ghosh, Derek Smith
Journal: Journal of Clinical Oncology (2018)

e19562 Background: Cardiotoxicity afflicts 10-20% of cancer survivors thus compromising long term survival. Based on ASCO guidelines cancer patients (pts) are considered at increased risk of developing cardiotoxicity (CT) if they receive high dose (HD) anthracyclines (A) or HD radiation therapy (RT) or low dose (LD) A + LD RT, or LD A with ≥ 2 cardiovascular (CV) risk factors (RF) or age ≥ 60 years (y) at diagnosis, or compromised cardiac function before or during treatment. The incidence and timing of these RF are not well-studied in lymphoma pts. In 2015 a collaboration between cardio-oncology (CO) and lymphoma specialists at the University of Colorado led to the development of a novel clinic for lymphoma pts who received A or RT. We report our initial findings from the CO-lymphoma clinic. Methods: Retrospective study of lymphoma pts seen in CO clinic from 2015-2017 within 5y of lymphoma therapy. Chart review included demographics, A and RT dosing, imaging, CV RF and treatment details. Results: 46 pts were included, median time from treatment initiation to first CO visit was 9 months, median age was 45y, 52% male. Pts received CHOP (30.4%), ABVD (36.9%), and EPOCH (28.3%). Based on ASCO guidelines we found 31/46 (67%) pts were at increased risk of CT from treatment alone (52% HD A, 8.6% HD A + HD RT, 2.2% HD RT, 4.3% LD A + LD RT). 12/46 (26.1%) had LD A and ≥ 2 CV RF, 5/46 (10.9%) received LD A at ≥ 60Y and 1/46 (2.2%) had an MI. 13/46 pts (28.3%) had coronary calcifications on treatment-related scans but only 1 pt had a clinical diagnosis of coronary artery disease. Interventions at the CO clinic included RF modification, pt education, screening labs and imaging. 30 pts had pre- and post-treatment echocardiograms (TTE). Ejection fraction was not significantly different between pre and post-treatment TTE (p = 0.23, 95% CI -0.04-0.01). 13/46 (28%) pts were found to have arrhythmias after therapy, most commonly sinus arrhythmia. Conclusions: CO intervention within 5y of lymphoma treatment led to recognition of increased risk of cardiotoxicity and prompt management of modifiable CV RF and coronary artery disease. There was no significant change in systolic function within 5y of lymphoma treatment.
A Lesion on the Scalp
Authors: Zaid Abdel-Rahman, Kedar Inamdar, Haythem Ali
Journal: JAMA Oncology (2018)

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A feasibility study to examine the role of a mindfulness-based wellness curriculum for early clinical trainees.
Authors: Monica Sheila Chatwal, Marc McDowell, Christine Vinci, Richard R. Reich, Angela Reagan, Jhanelle Elaine Gray
Journal: Journal of Clinical Oncology (2018)

TPS11020 Background: Physician wellness has become a topic of great interest within the medical field as rates of burnout, depression, and career dissatisfaction have increased. This topic is of particular interest in oncology, with 45%-80% of practicing oncologists worldwide reporting symptoms of burnout (Hlubocky et al. ASCO 2017). Despite the growing interest, there are few programs to address these issues in early clinical trainees, specifically hematology oncology fellows. Mindfulness is a strategy that can be used to recognize and cope with stress and burnout and foster resiliency. Several studies evaluate its use in chronic illness, but also physician burnout. The goal is not to focus on relaxation, but rather on self-awareness, thus extending into a form of "reflective practice" (Epstein, JAMA 1999). This may translate into more effective clinical experiences and stress management skills. Methods: This is a single-center, non-randomized pilot project to assess the feasibility and impact of a mindfulness-based wellness curriculum. All hematology oncology fellows at our institution are eligible for enrollment. A total of six monthly 30 minute sessions will be conducted within the framework of the existing didactic conferences. Each session is led by a social worker trained in mindfulness techniques. Participants will complete questionnaires pre- and post-intervention. Primary aim is feasibility determined through recruitment, participation, completion and compliance rates. This will also provide data for sample size estimation for a full-scale RCT. Secondary aim is acceptability, assessed using post-intervention questions addressing usefulness of the program. Exploratory aim is to collect and examine data on self-reported stress and self-awareness – Mindful Attention Awareness Scale (MAAS) (Carlson, 2005) and Perceived Stress Scale (PSS) (Cohen, 1983). Enrollment began in December 2017 and 27 of 28 eligible participants have enrolled and completed pre-session questionnaires. One session has been conducted to date. To our knowledge, this is the first study assessing this type of intervention in this population.
Neutropenic fever outcomes per institutions’ teaching status.
Authors: Zachary Michael Trisel, Stuthi Perimbeti, Daniel Kyung, David Lane Topolsky, Pamela A. Crilley, Kristine Marie Ward, Michael Styler
Journal: Journal of Clinical Oncology (2018)

e18553 Background: Neutropenic fever (NF) can result in significant mortality if not managed properly and in swift fashion. There has been a recent shift from small oncology private practices commonly affiliated with non-teaching hospitals (NTH) to large teaching hospitals (TH) with an abundance of specialized faculty and financial resources. We sought to analyze admissions for NF comparing TH versus NHT institutions’ mortality in breast (BC), lung (LC), renal (RC), prostate (PC) and multiple myeloma (MM) from 2006-2014. Methods: We analyzed data from the Healthcare Cost and Utilization Project’s National Inpatient Sample between 2006-2014 using ICD 9 codes for a primary diagnosis of BC, LC, MM, RC and PC. NF was used as a secondary diagnosis. TH and NTH mortality was compared using hazard ratios (HR) which were controlled for confounding factors of age, race, sex, income, insurance status, & comorbidities. Results: There were 77,215 admissions (weighted [w] 383,225) to TH vs 42,860 to NTH (w: 208,430). NTH accounted for 35.21% admissions, 0.031% related to NF. TH accounted for 64.72% with 0.076% related to NF (p = 0.0033). HR of death related to NF during during hospitalization within 30 days were compared for TH vs NTH. Results are listed below. Conclusions: Most admissions for NF occurred at TH. This could be related to resource requirements, higher acuity patients or more intensive regimens used in TH. Hospital mortality of NF at NTH was increased for RC and MM. This may be due to delays in implementing appropriate antimicrobial therapy. However, there was no significant difference in outcomes for BC, LC and PC, possibly due to the routine use of growth factor support or shorter duration of neutropenia in the chemotherapy regimens used in these cancers. With the continual shift in health care delivery to consolidate, it remains important for small NTH to be able to manage oncologic emergencies such as a NF resulting in the same hospital mortality outcomes. TH vs NTH Hazard Ratio 95% Cl P value BC 1.033 0.83 - 1.285 0.7743 LC 1.031 0.955 - 1.113 0.4355 MM 3.662 3.253 - 4.121 < .0001 PC 1.52 0.61-2.16 0.65 RC 2.85 1.71-4.75 < .0001
Effect of micronutrient malnutrition on periodontal disease and periodontal therapy
Authors: Henrik Dommisch, Denica Kuzmanova, Daniel Jönsson, Melissa Grant, Iain Chapple
Journal: Periodontology 2000 (2018)

Abstract Periodontitis is a complex chronic inflammatory noncommunicable disease, initiated by the development of a dysbiotic microbial plaque biofilm below the gingival margin. Whilst the pathogenic biofilm is a “necessary cause” of periodontitis, it is insufficient on its own to cause the disease, and a destructive immune‐inflammatory response is a key to the translation of risk to destructive events. Other exposures or “component causes” include individual genetic predisposition, lifestyle (including smoking and nutrition), and environmental factors. Dietary nutrients are essential for life as they provide crucial energy sources in the form of macronutrients, as well as important cofactors in the form of micronutrients, which regulate the functionality of enzymes during the regulation of anabolic and catabolic processes in human cells. Moreover, micronutrients can regulate gene transcription factors, such as the proinflammatory nuclear factor kappa B and the anti‐inflammatory nuclear factor (erythroid‐derived 2)‐like 2. This review focuses on the role of vitamins (vitamin A, carotenoids, the vitamin B complex, vitamins C, D, and E, and coenzyme Q10) and minerals (calcium, magnesium, iron, zinc, potassium, copper, manganese, and selenium) in human physiology and the impact of their deficiencies upon periodontal health and disease.