tbuckley/cabot-search huggingface dataset:
Effect of amplification of xenobiotic detoxification pathways genes on survival in lung adenocarcinoma versus squamous cell carcinoma bases on the Cancer Genome Atlas provisional database.
Authors: Mohamed Shanshal, Lukman Aderoju Tijani, Fred L. Hardwicke, Hassan Kaleem, Nicholas C. D'Cunha, Henry Palangdao Igid, Muhammad Saad Khan, Catherine Jones, Sanjay Awasthi, Saba Radhi
Journal: Journal of Clinical Oncology (2017)

e14093 Background: Ral interacting protein (RLIP76) is a stress-responsive anti-apoptotic efflux transporter of the mercapturic acid pathway (MPy). The MPy enzymes are an essential component of the broader xenobiotic detoxification pathways (XDP) that are regulated by p53 (TP53) in response to xenobiotic/oxidative stress. Homozygous Rlip knockout (Rlip-/-) mice are resistant to benzopyrene induced adenocarcinoma and have constitutive activation of p53. The cancer-resistant phenotype of Rlip-/- mice is the diametric opposite of p53 homozygous knockout mice (p53-/-) mice, which die before the age of 24 weeks of spontaneous malignancy. Methods: Our preliminary studies show that creating Rlip deficiency through pharmacological or genetic methods caused all p53-/- mice to remain cancer-free at an unprecedented age of 32 weeks. This degree of cancer prevention has never been observed with any previous pharmacological or genetic intervention in p53-/- mice. Transcriptomic and epigenomic profiling of the cancer-free p53-/- mice revealed that the direction of change in expression of a network of Rlip-linked XDP enzymes and signaling proteins was identical to that in the cancer-resistant Rlip-/- mice. Results: We hypothesized that the activity of this Rlip-linked subset of the XDP enzymes/signaling proteins (designated XMN1) is a determinant of carcinogenic susceptibility caused by p53 loss. To examine this possibility, we queried the TCGA (The Cancer Genome Atlas) database to determine whether components of XMN1 were differentially expressed in human malignancy, and whether this was associated with overall survival. We focused on non-small cell lung cancer because of the high incidence of p53 mutations in these cancers. To our surprise, we found amplification or upregulation of XMN1 components conferred a reduced survival in lung adenocarcinoma but prolonged survival in squamous cell carcinoma. Conclusions: The mechanisms underlying this remarkable diametrically opposite effect on prognosis of are unknown and suggest opposed functions of XMN1 in Squamous verses Adenocarcinoma.
Circulating tumor DNA (ctDNA) as a marker of minimal residual disease (MRD) in localized non-small cell lung carcinoma (NSCLC).
Authors: Nicholas I. Simon, Andrew A. Davis, Nisha Anjali Mohindra, Victoria Meucci Villaflor, Young Kwang Chae
Journal: Journal of Clinical Oncology (2018)

8550 Background: ctDNA has been used to identify driver genomic alterations during treatment of metastatic NSCLC. Recent studies have also demonstrated ctDNA being used as a way to monitor response to therapy. Here we performed an analysis on a cohort of NSCLC patients (pts) with localized disease who underwent ctDNA testing after definitive treatments to determine whether ctDNA can be used as a marker of MRD. Methods: Between 2015-2018, 51 pts with localized NSCLC received ctDNA testing. ctDNA testing was done using the next generation sequencing (NGS) panel of 73 genes via digital sequencing technology (Guardant360). Statistical analysis was performed to determine which factors were associated with ctDNA levels and recurrence free survival (RFS). Results: Of the 51 pts analyzed, 23 pts had ctDNA testing performed after definitive treatment. Median duration of follow up was 10 months (range: 1 to 23). 30% (n = 7) had Stage I disease, 30% (n = 7) had Stage II disease, and 40% (n = 9) had stage III disease. 74% (n = 17) were adenocarcinoma while 26% (n = 6) were squamous cell carcinoma. 52% (n = 12) had no recurrence during our observation time, while 48% (n = 11) experienced progression. For definitive treatments, 35% (n = 8) underwent surgery alone, 43% (n = 10) underwent surgery with adjuvant chemotherapy, 4% (n = 1) underwent radiation alone, and 17% (n = 4) underwent chemoradiation therapy prior to their ctDNA levels [variant allele frequency (VAF)] being drawn. Of these, 13% (n = 3) tested negative for any ctDNA, while 87% (n = 20) were positive. None of the pts with undetectable levels of ctDNA experienced recurrence of cancer. Nine among 20 pts with detectable ctDNA had recurrence. Kaplan-Meir survival analysis revealed a trend toward significant association between the presence of detectable ctDNA and RFS (p = 0.055). Among pts with detectable ctDNA, there were no differences in RFS between pts with high vs. low ctDNA levels (cut off at 1% VAF). Presence of ctDNA was not associated with sex, smoking history, histology, stage, nor modality of definitive treatment. Conclusions: Our analysis demonstrates that ctDNA could potentially be used as a marker of MRD following definitive treatment for localized NSCLC.
Abstract 10964: Hyperfibrinolysis in Patients With out of Hospital Cardiac Arrest May Contribute to Poor Outcome
Authors: Hiroyuki Koami, Yuichiro Sakamoto, Satoshi Inoue
Journal: Circulation (2015)

Introduction: Hyperfibrinolysis (HF) in out-of-hospital cardiac arrest (OHCA) is often encountered in the emergency department (ED). However, only a few studies on the coagulopathy in post cardiac arrest syndrome (PCAS) were reported and it still remains a matter of debate. In recent years, thromboelastometry (ROTEM ® ), known as point-of-care testing, quickly provides a more complete picture of coagulation and fibrinolytic status. Hypothesis: We hypothesized that HF diagnosed by ROTEM in OHCA might be associated with poor outcome. Methods: 48 OHCA patients transported to the Saga University Hospital with ROTEM performed in the ED from January 2013 to December 2014 were enrolled in this study. A 15% or more of maximum lysis (ML) in EXTEM test and a 20 % or more improvement of ML in APTEM test compared with that in EXTEM were defined as HF. All patients were divided into two groups based on the presence of HF. Clinical characteristics, initial cardiac rhythms at the scene and ED, time from onset to blood sampling, complete blood test, standard coagulation test, blood gas analysis, ROTEM findings (EXTEM/ INTEM/ FIBTEM/ APTEM) and clinical outcome were evaluated. Results: HF was observed 72% of all OHCA patients, which wasn’t significantly related to epinephrine injection before blood sampling (p=0.510). Univariate analysis revealed that HF contributed to lower CRP values (p=0.050) and accelerated fibrinolytic parameters of ROTEM (EXTEM/INTEM/FIBTEM; p&lt;0.01). Any other parameters including initial cardiac rhythms and time from onset to blood sampling were not significantly different in the two groups. As for clinical outcome, the ratio of return of spontaneous circulation (ROSC) reached 10% (before the ED), 40% (after the ED), 18.8% (6hours after admission), 12.5% (24hours after admission), respectively. There was no statistical difference between HF and clinical outcome in this period. However, it should be noted that only 2 patients (4.2%) without HF survived for more than 28 days. HF had a tendency to poor 28-day mortality (p=0.069). In addition, Kaplan-Meier and log-rank analysis showed HF was a predictive factor for poor outcome of PCAS (p=0.099). Conclusions: HF in OHCA is associated with poor clinical outcome.
Overexpression of HMGA2 as a prognostic indicator in breast cancer.
Authors: Xiaochen Wang
Journal: Journal of Clinical Oncology (2016)

10091 Background: As a non-histone chromosomal protein, high mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes, and is upregulated in a variety of tumors. However, no detailed studies have examined the association between HMGA2 protein level and the prognosis of breast cancer (BC) patients. Here, we aimed to explore whether the levels of HMGA2 could predict prognosis for BC patients. Methods: We collected 273 BC specimens from the Second Affiliated Hospital of Zhejiang University (ZJU) as a training set. 310 specimens from the National Engineering Center for Biochip at Shanghai (SBC) were served as a validatory set to examine the expression of HMGA2 by immunohistochemical stainings. The Kaplan–Meier analysis and COX proportional hazard model were employed to analyze the survival rate. Results: We found that HMGA2 expression was significantly positive correlated with advanced tumor grade (p< 0.05) and poor survival of BC patients. The adjusted HRs for overall survival were 4.24, (95% CI: 1.17-15.37) and 2.06, (95% CI: 1.21-3.49) in training and validation sets, respectively. Subgroup analysis indicated that high level of HMGA2 was significantly correlated to poor prognosis, especially in the subgroups of advanced clinical stage (HR: 2.06, 95% CI: 1.14-3.72), low pathological grade (HR: 7.28, 95% CI: 1.57-33.83) and non-triple negative breast cancer cases (HR: 2.19, 95% CI: 1.22-3.91). Gene set enrichment analysis (GSEA) demonstrated a significant positive correlation between HMGA2 level and the gene expression signature of metaplastic and mesenchymal phenotype (p< 0.05). Conclusions: Expression of HMGA2 may indicate more advanced malignancy of breast cancer. Thus we believe HMGA2 could serve as a biomarker of poor prognosis and a novel target in treating BC tumors.
PD-1 blockade to treat mucosal and uveal melanoma: The University of Pittsburghh experience.
Authors: Ling Tian, Fei Ding, Cindy Sander, Amy Rose, Chelsea Pruckner, Melissa Wilson, Ahmad A. Tarhini, Diwakar Davar, John M. Kirkwood
Journal: Journal of Clinical Oncology (2016)

e21042 Background: Uveal and mucosal melanomas are rare subtypes with a mean age-adjusted incidence of 5.6 and 2.3 cases per million person-years. Metastatic uveal and mucosal patients (pts) tend to have lower response rates to therapy in general, and have been systematically excluded from most clinical trials of CTLA-4 and PD-1/PD-L1 inhibitors. Here, we report our experience treating uveal and mucosal melanoma with Nivolumab (Nivo), and Pembrolizumab (Pembro). Methods: Clinical and radiological data were collected on 17 pts who received Nivo or Pembro at a single institution for advanced uveal (N = 9) or mucosal (N = 9) melanoma. Baseline characteristics at the time of therapy and outcome data including best/current response, progression-free (PFS) and overall survival (OS) were collected. Response was calculated using RECIST 1.1. The influence of baseline characteristics on treatment outcomes was assessed using Cox analysis. Results: All uveal pts were treated for hepatic metastases. Metastatic burden for metastic mucosal melanoma pts was varied; including 4 with pulmonary or distant subcutaneous/lymphatic metastases (M1a/b), 3 with liver (M1c) and 2 with CNS metastases. Of 8 evaluable uveal pts, no complete responses (CR) were observed although partial responses (PR) and disease stabilization (SD) was observed in 2 (25%) and 3 (37.5%) pts respectively. 6/8 pts (75%) eventually progressed in the liver; although 2 pts remain alive and on therapy at a median of 11 months. Of the 6 evaluable mucosal pts, 1 CR (16.7%) and 2 PR (33.3%) were observed. 4/6 pts (66.7%) progressed – 2 systemically, 1 in CNS and 1 in systemic/CNS. Conclusions: This single institution series represents the largest report of pts with advanced uveal and mucosal melanoma treated with PD-1 blockade. Toxicity was as expected and manageable. Durable PR/CR was observed in a subset of pts and argue for further investigation of PD-1 blockade in this population.
Sociomarkers and biomarkers: predictive modeling in identifying pediatric asthma patients at risk of hospital revisits
Authors: Eun Kyong Shin, Ruhi Mahajan, Oguz Akbilgic, Arash Shaban-Nejad
Journal: npj Digital Medicine (2018)

The importance of social components of health has been emphasized both in epidemiology and public health. This paper highlights the significant impact of social components on health outcomes in a novel way. Introducing the concept of sociomarkers, which are measurable indicators of social conditions in which a patient is embedded, we employed a machine learning approach that uses both biomarkers and sociomarkers to identify asthma patients at risk of a hospital revisit after an initial visit with an accuracy of 66%. The analysis has been performed over an integrated dataset consisting of individual-level patient information such as gender, race, insurance type, and age, along with ZIP code-level sociomarkers such as poverty level, blight prevalence, and housing quality. Using this uniquely integrated database, we then compare the traditional biomarker-based risk model and the sociomarker-based risk model. A biomarker-based predictive model yields an accuracy of 65% and the sociomarker-based model predicts with an accuracy of 61%. Without knowing specific symptom-related features, the sociomarker-based model can correctly predict two out of three patients at risk. We systematically show that sociomarkers play an important role in predicting health outcomes at the individual level in pediatric asthma cases. Additionally, by merging multiple data sources with detailed neighborhood-level data, we directly measure the importance of residential conditions for predicting individual health outcomes.
Abstract 17849: Human Fetal Growth Model of Hypoplastic Left Heart Syndrome: Reduced Ventricular Growth Due to Decreased Preload
Authors: Sukriti Dewan, Adarsh Krishnamurthy, Roy C Kerckhoffs, Heather Sun, Jeffrey H Omens, Vishal Nigam, Andrew D McCulloch
Journal: Circulation (2014)

Introduction: Hypoplastic Left Heart Syndrome (HLHS) is a congenital condition with an under-developed left ventricle (LV) that provides inadequate blood flow postnatally. Predicting LV size at bir...
TCT-12 Elevated FFR values at the acute moment in non-culprit vessels of STEMI patients due to decreased adenosine responsiveness: a comparison with the adenosine free iFR
Authors: Nina van der Hoeven, Gladys Janssens, Guus de Waard, Henk Everaars, Peter van de Ven, Robin Nijveldt, Christopher Cook, Clemens von Birgelen, Javier Escaned, Justin Davies, Maarten van Leeuwen, Niels van Royen
Journal: Journal of the American College of Cardiology (2018)
Abstract 12234: Effects of Reducing Exposure to Air Pollution With a Filter on Exercise: A Randomized, Prospective, Double-Blind, Controlled Study of Heart Failure
Authors: Jefferson L Vieira, Guilherme V Guimaraes, Paulo A de Andre, Paulo H Saldiva, Edimar A Bocchi
Journal: Circulation (2015)

Background: The benefits of respiratory filters on patients with heart failure (HF) exposed to air pollution during daily activities have not been established. Methods: We tested the short-term effects of a filter intervention (FILTER) in a double-blind,randomized and 3-way crossover study with 30 HF patients and 15 control volunteers exposed, in three separate sessions, to clean air, dilute diesel exhaust (DE) or filtered DE. Pre-specified endpoints included variation in exercise tolerance (six-minute walking test [6mwt meters]; systemic blood pressure [BP mmHg], heart rate [HR bpm] and respiratory rate [RR rpm] responses) and gas-exchange variables (oxygen uptake [VO2 ml/kg/min]; oxygen saturation [Sat.O2 %]; ventilation and carbon dioxide production ratio [VE/VCO2 slope]; oxygen uptake per heart beat [O2Pulse ml/beat]; pulmonary ventilation [VE l/min]; tidal volume [Vt ml]; functional estimate of dead space [VD/Vt]) during a submaximal test. Results: In HF patients, DE adversely affected VO2 (11.0±3.9 vs. 8.4±2.8 ml/Kg/min; p &lt; 0.001) (figure), 6mwt (243.3±13.0 vs. 220.8±13.7 m; p = 0.030), and O2Pulse (8.9±1.0 vs. 7.8±0.7 ml/beat; p &lt; 0.001). When compared to DE-protocol, the FILTER reduced the particulate concentration from 325±31 to 25±6 μg/m3 (p &lt; 0.001), and in HF patients it was associated with an increase in VO2 (10.4±3.8 ml/Kg/min; p &lt; 0.001) (figure) and O2Pulse (9.7±1.1 ml/beat; p &lt; 0.001). FILTER was also associated, in HF and control groups, with significantly higher pulmonary ventilation, tidal volumes, functional estimate of dead space and CO2 exchange. Other variables as VE/VCO2 slope, HR, BP and RR did not differ between exposure protocols. Conclusion: Air pollution adversely affects exercise tolerance in HF patients. FILTER can reduce the particulate concentration during DE-exposure, preventing pollution-effects on VO2 and O2Pulse. ClinicalTrials.gov Identifier: NCT01960920
Patients with advanced renal cell carcinoma: Immediate or delayed treatment? Study of a cohort of patients followed at Instituto Oncológico Henry Moore (IOHM).
Authors: Eduardo L. Morgenfeld, Ernesto Gil Deza, Gaston Martin Reinas, Claudia Lorena Acuna, Dario Niewiadomski, Edgardo G. J. Rivarola, Sandra L. Ares, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2017)

e16073 Background: Most of the treatment guidelines for advanced renal cancer (RCC) agree about what drugs must be used, but don’t indicate when the treatment should be started. This decision is left to the desire of the patient (pt) and/or the common sense of the doctor. The aim of this paper is to study which could be the best time of initiation of systemic treatment (Tx) in advanced RCC. Methods: Between 1/1/2001 and 11/30/2016, 828 patients diagnosed with RCC were followed at IOHM. We selected all pt with clear cell or papillary stage IV RCC who received systemic Tx; 80 pt met this inclusion criteria. We reviewed all the clinical records of this population and separated two groups according to the time of initiation of systemic treatment: Group A (Immediate = within three months of diagnosis) or Group B (Delayed = beyond three months of diagnosis). We compared the population’s characteristics and outcome of each group. Results: The results are shown in the table. Conclusions: 1) In this cohort of 80 patients with advanced clear cell or papillary RCC, 47 pt (59%) received systemic treatment immediately after diagnosis and 33 pt (41%) postponed it at least three months. 2) Both groups were similar in age, surgical treatment, metastatic sites and systemic treatments. 3) There was no difference in survival rates with immediate or delayed treatments. [Table: see text]
Adults with advanced cancer: Spiritual and existential struggles.
Authors: Saneta Maiko, Alexia M. Torke, Shelley A. Johns, Ann H. Cottingham
Journal: Journal of Clinical Oncology (2018)

e22004 Background: Adults with advanced cancer face emotional and spiritual distress through cancer trajectory. Spirituality and religion (SR) have been found to be central to many Americans. RS play a significant role in coping with the distress among cancer patients and influences communication, decision-making and utilization. The spiritual care experts in the health system have traditionally had a limited presence in the outpatient setting. As cancer care moves to this setting, understanding the SR needs of advanced cancer patients in the outpatient setting is essential. This study was designed to assess the SR needs of advanced cancer patients with an estimated 2 weeks post diagnosis and < 12 months estimated survival. Methods: We used a semi-structured interview guide, 21 interviews were conducted at the Indiana Simon Cancer Center outpatient clinic with patients 18 years old or above whom their primary oncologist identified as having a < 12 months estimated survival. Excluded were patients with previous psychological illness, unable to pass a cognitive distress test and inability to speak English. Results: Among 528 cancer outpatients screened (Table 1), 31(55%) were eligible for enrolment and 21 (67, 7%) participated in interviews. Five core needs emerged in this study: Relationships with family
Multi-center retrospective study evaluating outcomes of grade 3A follicular lymphoma (FL).
Authors: Kyle Greene, Tycel Jovelle Phillips, Alexey Valeryevich Danilov, Michael Thomas Byrne, Jonathon Brett Cohen, Manali K. Kamdar, Ashwin Peres-da-Silva, Michael Churnetski, Zenggang Pan, Nathalie C Danielson, Adam Kittai, Deborah Marie Stephens
Journal: Journal of Clinical Oncology (2018)

7551 Background: Pathologic grading of FL (1, 2, 3A, 3B; based on increasing number of centroblasts) is prognostic and predictive. FL 3B is treated similarly to aggressive lymphomas with rituximab and anthracycline based chemo (RA). For FL 1-2, bendamustine and rituximab (BR) treatments are non-inferior to RA and better tolerated. Unfortunately, FL 3A was largely excluded from prospective trials and treatment with BR is extrapolated. We aimed to study pretreatment characteristics and the effect of treatment for FL 3A. Methods: We compiled disease characteristics of 178 patients (pts) with grade 3A FL from 1992-2017 from 6 academic institutions with sufficient follow-up. Those who were observed (n=15) were excluded. Data evaluated include: FLIPI Score (age, # involved sites, hemoglobin, stage) and gender. The outcomes were compared by treatment groups of: RA, BR, Rituximab only (RO) and other treatments (TX). Kaplan-Meier survival estimates were used to assess overall survival (OS) and progression free survival (PFS). Cox regression analysis was applied to remaining patient information. Results: We identified 163 treated pts (RA n=108, BR n=23, RO n=12, TX n=20.) Mean age was 59.8 (range 18-88) with 56% >60. Median OS and PFS were not reached, with the exception of PFS of 1.95 years for RO (p=0.03.) RO also had higher risk baseline features. No differences were observed between BR vs RA. Interestingly, age>60 trended towards better outcomes, but did not reach statistical significance (p=0.17.) Median follow-up was 3.5 years (range 21 days-27 years). Comparing 3-year PFS and OS of BR to RA (table 1), showed HR ~1 with high p-value suggesting similar efficacy. Conclusions: Controversy regarding optimal management of FL 3A continues. Age > 60 was protective and definitive therapy should be offered to all age groups when appropriate. Although limited by low pt numbers, our data suggest non-inferiority of BR to RA in FL 3A pts. Future prospective studies must include FL 3A pts so optimal treatments can be established. Survival comparison with pts who received RA. HR p-value 95% CI 3-Year PFS BR 1.09 0.881 0.49-2.85 TX 1.7 0.34 0391-4.83 RO 3.25 0.036 1.21-4.83 3 year OS BR 1.17 0.71 0.38-3.80 TX 2.1 0.081 0.57-5.14 RO 2.95 0.017 1.08-9.84