tbuckley/cabot-search huggingface dataset:
Genomic aberrations in advanced solid malignancies using next generation sequencing: A single institution experience.
Authors: Daniel Olson, Sachin Gopalkrishn Pai, Aparna Kalyan, Ricardo Lima Barros Costa, Sunandana Chandra, Benedito A. Carneiro, Young Kwang Chae, Jason B. Kaplan, Maria Matsangou, Nike Beaubier, Mary Frances Mulcahy, Massimo Cristofanilli, Francis J. Giles
Journal: Journal of Clinical Oncology (2016)

e23206 Background: The paradigm in the treatment of cancer is changing such that, treatment based on molecular targets and associated pathways is at the forefront rather than chemotherapy. The identification of different molecular “drivers” utilizing NGS technology has led to better understanding of advanced malignancies. Recently, the prevalence of potentially targetable genomic abnormalities in primary and metastatic breast cancer utilizing NGS method found that 84% of the evaluated cancers harbored at least one genomic alteration linked to potential treatment options. Validation of this NGS testing in 2,221 clinical cases revealed clinically actionable targets in 76% of tumors, corresponding to three times the number of actionable targets detected by other current diagnostic tests. It is for these reasons that the genomic landscape needs to be better characterized Methods: Medical records of all patients referred to the phase 1 clinic at our institution who had NGS performed were reviewed retrospectively from January 2014 to December 2015. Results: 159 cases were identified; 65 males and 94 were females. Mean age was 54.51 Years (Range 25-83 years). Gastrointestinal cancers accounted for 47.2% cases while gynecological, lung and breast cancer accounted for 11%, 10% and 9% respectively. There was an average of 15.31 aberrations per cancer (range: 4- 66). An average of 4.73 aberrations per cancers were found to be clinically relevant, while the rest were variance of unknown significance. FGF, CDK, KRAS, PI3K and FGFR were the most common clinically relevant aberrations and they accounted for 6%, 5.2%, 4.9%, 3.9% and 1.5% of the clinically relevant aberrations respectively. Breast cancer and Colon cancer accounted for 31% and 21% of the PIK3 aberrations. Cholangiocarcinoma, breast cancer accounted for 90% (45% each) of FGFR aberrations. Conclusions: In this single institution study for phase 1 trials, we found a small but significant number of patients amenable to targeted therapy. Multi-gene NGS panel testing can identify targetable aberrations such as PIK3 and FGFR genetic aberrations, justifying their use in clinical care for screening patients for early phase clinical trials
A pilot study using kernelled support tensor machine for distant failure prediction in lung SBRT
Authors: Shulong Li, Ning Yang, Bin Li, Zhiguo Zhou, Hongxia Hao, Michael R. Folkert, Puneeth Iyengar, Kenneth Westover, Hak Choy, Robert Timmerman, Steve Jiang, Jing Wang
Journal: Medical Image Analysis (2018)
Impact of closed Facebook group participation on women hematology/oncology physicians.
Authors: Julia Lee Close, Suzanne Marie Cole, Rasha Naz Beg, Stephanie L. Graff, Laurie Beth Matt-Amaral, Merry Jennifer Markham
Journal: Journal of Clinical Oncology (2018)

11013 Background: Making meaningful connections is an important aspect of career satisfaction. The Hematology Oncology Women Physician Group (HOWPG) is a private Facebook (FB) group of 936 women who practice within the hematology and oncology (H/O) field. We hypothesized that HOWPG adds value to the education, emotional wellness, and practice of oncology for its membership. A survey was conducted within HOWPG to define the impact this group has on members. Methods: A voluntary, anonymous 12-question online survey was distributed to members of HOWPG by sharing the survey link in the FB group 4 times between 11/16/2017-1/03/2018. Participants were surveyed regarding demographic data, general FB use vs. exclusive use of HOWPG, and opinions regarding HOWPG value and impact. Survey was approved by University of Florida institutional review board. Results: Of the 936 members of the site, between , and 169 completed the survey. 9% were fellows, 65% in practice < 10 years, 26% > = 10 years. 62% were less than 40 years of age and 35% between the ages of 40-49. 85% practice adult H/O, and the remainder divided between pediatric H/O, radiation oncology, surgical specialty and palliative care. 90% use FB at least daily, with 82% accessing the HOWPG group at least daily, 16% using less than daily but at least twice per week. The most common uses for the site included education (65%-89%), advice on complex cases (65%), emotional support (65%), and networking (55%). On a scale of 1-10, learning from clinical cases (9.0) and emotional support (8.4) were rated the most beneficial aspects. The aspects of the group rated most important were: membership limited to women, physicians, in the H/O field, secret group. Conclusions: The HOWPG FB group has provided an opportunity for education, clinical and emotional support. Social media can be an effective venue to educate physicians, augment patient care via advice, foster networking, reduce burnout, and improve career satisfaction amongst women physicians in the field of hematology and oncology.
Microfluidic purification and characterization of intact circulating tumor cells from peripheral blood.
Authors: Roberto Campos-Gonzalez, Myra Koesdjojo, Zendra Lee, Christopher Dosier, Tanisha Saini, Khushroo Gandhi, Lee Aurich, Alison Skelley, Gregory Yang, Tony Ward
Journal: Journal of Clinical Oncology (2016)

e23048 Background: We have developed a microfluidic chip-to-chip approach to purify circulating tumor cells (CTC’s). Methods: We use a DLD (deterministic lateral displacement) microchip containing an array of microposts arranged in sub-arrays of different gap sizes. The “product” outlet of the DLD chip is connected with a second magnetic-separation chip. Air pressure is applied to maintain a constant flow of sample and buffer. Whole blood is mixed with biotinylated antibodies to CD45 and sav-MNP’s (strepavidin-magnetic particles), diluted in buffer and passed through the DLD chip where the blood interacts with the posts and cells are bumped based on a deterministic lateral displacement principle, thus separating blood components. The “product” fraction from the DLD chip containing white blood cells and other larger cells is directed to the magnetic chip and the “waste” fraction containing red blood cells, platelets, debris, etc, is discarded. The second chip has an array of magnets, capturing the sav-MNP/CD45+-tagged cells thereby allowing the gentle free flow of rare cells towards the final product fraction. Results: The chip-to-chip configuration is able to process up to 8ml of blood, removing > 99.8% of red blood cells and > 99% of white blood cells, with the remaining cell populations suitable for further analysis and characterization. Validation of the chip-to-chip approach usisnsg MDA-MB-231, SKBR-3, and H1650 cells confirms a linear recovery of > 80% and viability of ~90%. The minimum cell size captured by our approach is approximately 6µm ensuring the isolation of small-sized CTC’s. Multi-color flow cytometry and imaging analysis of the isolated cells from blood of breast cancer patients confirms the purification and identification of unique populations of HER2+/CD45-/EpCAM+ and CD146+/CD44+ cells characteristic of breast carcinomas-among other rare cell populations. Conclusions: Our chip-to-chip approach allows a gentle purification of intact and viable rare cells from cancer patients’ blood, suitable for functional analysis, drug sensitivity tests and genetic characterization. Thus, we have developed a hands-free liquid biopsy capable of isolating and purifying rare circulating tumor cells.
Abstract P071: Creating Claims-based Risk Scores for Incident Coronary Heart Disease
Authors: Matt Mefford, Lei Huang, Monika Safford, Paul Muntner, Emily Levitan
Journal: Circulation (2016)

Background: A claims-based coronary heart disease (CHD) risk score may be useful to control for confounding and identify high risk groups in research using administrative data. Objective: To derive and validate a claims-based risk score for incident CHD in 2004-2011 Medicare 5% national samples and validate in the REasons for Geographic and Racial Differences in Stroke (REGARDS)-Medicare link population. Methods: We included Medicare beneficiaries with no evidence of CHD who had fee-for-service health insurance. When examining prescriptions, Medicare part D coverage was required. CHD was defined as the first inpatient claim for acute myocardial infarction (AMI). Three groups of predictors were included in the risk models (group 1: traditional CHD risk factors, group 2: other diagnoses and demographic characteristics, group 3: medications). Using Cox proportional hazards models, c-statistics and 95% CI were calculated for model discrimination and CHD rates were calculated across deciles of predicted risk testing calibration. Results: Of 990,836 individuals in the derivation cohort, 28,086 (2.8%) developed AMI over 5 years. The average age was 67.5 years, 57.6% (570,722/990836) were female, and 83.6% (828,338/990,836) were white, 10.7% (106,020/990,836) black, and 5.7% (56,477/990,836) other ethnicities. Models with group 1 variables had a moderate discrimination ( Table ). Adding group 2 variables improved model discrimination. Comparing the Framingham CHD risk score to our model with group 1 + 2 variables yielded similar discrimination. Group 3 variables (prescriptions) improved discrimination to 0.727 (0.714 - 0.741). Prediction models overestimated risk in the top decile in the Medicare 5% sample and the REGARDS-Medicare link population. Conclusion: In patients with no history of CHD, models including demographics and diagnoses from claims data exhibited discrimination and calibration similar to the Framingham Risk Score. The inclusion of prescription information further improved discrimination.
Clinical trajectory modeling to predict hospitalization or death after palliative chemotherapy.
Authors: Kenneth L. Kehl, Haitham Elmarakeby, Eliezer Mendel Van Allen, Deborah Schrag
Journal: Journal of Clinical Oncology (2018)

6509 Background: Hospitalization or death within 30 days of palliative-intent chemotherapy for metastatic cancer represent undesirable outcomes. An automated framework for predicting the risk of hospitalization or death within 30 days of chemotherapy could inform clinical decision-making, research, and quality improvement efforts. Methods: We piloted a machine learning framework for time-dependent clinical trajectory modeling using administrative data and applied it to prediction of hospitalization or death within 30 days of palliative cytotoxic chemotherapy. Patients with stage IV non-small cell lung cancer (NSCLC) diagnosed 2008-2013 were identified in SEER-Medicare. Inpatient, outpatient, durable medical equipment, prescription, home health, and hospice claims were extracted. The sequence of claims for the 60 days, or “clinical trajectory,” prior to each date of chemotherapy was embedded into a feature space based on context similarity, and the sequence was fed into a stacked ensemble model to predict hospitalization or death within 30 days of each chemotherapy date. These administration dates were divided into 80% training and 20% validation sets. Discrimination was measured with the c-statistic (AUC). No manual feature engineering was performed. Results: 43,250 dates of chemotherapy administration were identified for 6,067 patients with stage IV NSCLC. 8,057 chemotherapy dates (19%) were followed by hospitalization (N = 7,629) and/or death (N = 1,688) within 30 days. In the validation set, our framework predicted the composite of hospitalization or death with an AUC of 0.83. Among 42,823 chemotherapy dates that were not followed by death without hospitalization within 30 days, our framework predicted hospitalization with an AUC of 0.84. Conclusions: Clinical trajectory modeling predicts hospitalization or death within 30 days of palliative-intent cytotoxic chemotherapy for stage IV NSCLC with good discrimination. These results could inform clinical decision-making and targeted cancer care delivery interventions.
A comparison of short-term outcomes of neck dissection for head and neck cancers using Thunderbeat™, LigaSure™ or treatment without an energy-based device: A case controlled study
Authors: Kensuke Suzuki, Minaki Shimizu, Tomofumi Sakagami, Masao Yagi, Takuo Fujisawa, Shunsuke Sawada, Akira Kanda, Yoshiki Kobayashi, Hiroshi Iwai
Journal: International Journal of Surgery (2018)
Abstract 14820: Sirt7 Deficiency in Blood Vessel Components Impairs Vascular Function by Inhibiting Cell Cycle- and Inflammatory-Related Protein Expression
Authors: Yuichi Kimura, Yasuhiro Izumiya, Satoshi Araki, Satoru Yamamura, Yoshiro Onoue, Shinsuke Hanatani, Hisao Ogawa
Journal: Circulation (2015)

Introduction: Aging is a well-established cardiovascular risk factor and associated with vascular dysfunction. Sirt7, one of the members of mammalian sirtuin family, is thought to be involved in age-related diseases. However, little is known about the relative contribution of Sirt7 in vascular dysfunction. Hypothesis: Sirt7 maintains vascular cell functions and its deficiency plays a critical role in vascular diseases. Methods: Sirt7 loss- and gain-of-function experiments were performed with human aortic smooth muscle cells (HAoSMCs) and human umbilical vein endothelial cells (HUVECs). In vivo, blood flow recovery was evaluated by hindlimb ischemia model in homozygous Sirt7 deficient (Sirt7-/-) and wild-type (WT) mice. Irradiated WT mice were intravenously received bone marrow (BM) cells from WT or Sirt7 -/- mouse to achieve BM transfer. Results: An RNAi-medicated Sirt7 knockdown resulted in a significant inhibition of HAoSMCs proliferation following serum or Platelet-derived growth factor BB (PDGF-BB) stimulation as determined by cell count, BrdU cell proliferation assay and MTS proliferation assay. Knockdown of endogenous Sirt7 also reduced cell migration as revealed by Boyden chamber migration assay. The Cyclin D1 and Cyclin dependent kinase 2 (CDK2) protein levels were significantly decreased in Sirt7 siRNA-treated HAoSMCs in response to serum or PDGF-BB stimulation. In endothelial cells, knockdown of Sirt7 attenuated tube formation, proliferation and migration. These changes were accompanied by reduced ERK activation and VCAM-1 mRNA and protein expression in Sirt7 siRNA-treated HUVECs. Conversely, overexpression of Sirt7 by adenovirus enhanced tube formation and cell proliferation. In vivo, blood flow recovery in response to hindlimb ischemia was significantly attenuated in Sirt7-/- mice compared with WT mice. There was no difference in blood flow recovery between WT mice transplanted with WT or Sirt7-/- BM cells suggesting that Sirt7 deficiency in vascular cells have a predominant effect on attenuated blood flow recovery in response to hindlimb ischemia. Conclusions: Sirt7 in blood vessel components have an important role in maintenance of vascular function. Sirt7 could be a promising therapeutic target for vascular diseases.
A pilot randomized sham-controlled trial of MC5-A scrambler therapy in the treatment of chronic chemotherapy-induced peripheral neuropathy (CIPN).
Authors: Thomas J. Smith, A. Rab Razzak, Amanda L. Blackford, Jennifer Ensminger, Catherine Saiki, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2018)

e22206 Background: Chemotherapy induced peripheral neuropathy (CIPN) affects 30-40% of cancer patients, often for life, with no uniformly effective treatment. Scrambler Therapy (ST) appeared to benefit the majority of patients with CIPN with reductions in pain numbness and tingling, but in uncontrolled trials. We performed a randomized sham-controlled Phase II trial of ST in patients with CIPN. Methods: 31 patients were randomized and evaluable. The main endpoint was “average pain” at one month. Each received ten 45 minute sessions of ST on the dermatomes close to the painful areas, or sham treatment on the back, typically at L3-5 where spinal cord stimulation would be done. Outcomes included the Brief Pain Inventory-CIPN and the EORTC CIPN-20 scale. Patients were evaluated before treatment (day 0), day 10, and days 30, 60 and 90. Results: 31 patients (pts) completed the trial. There was no clinically or statistically significant difference between the sham and the “real” ST group at day 10, 30, 60 or 90. There were no important differences on the BPI or the EORTC CIPN-20. Individual responses were noted during the ST treatment on the real arm, but most dissipated by day 30. There was improvement on the sensory subscale of the CIPN-20 at 2 months in the “real” group. (p = 0.141) No side effects were observed. All “real” patients wanted to continue treatment if available. Conclusions: We observed no difference between sham and real ST treatment in CIPN. Potential reasons for failure to demonstrate a difference include following: ST does not work; the sham treatment had some effect; small sample size with heterogeneous patients; operator error in treatment by placing the distal electrode on areas of damaged nerves, usually on numb but not painful areas; or a combination of factors. Subsequent patients treated using electrode placement starting well above any area of altered sensation with monthly booster sessions has been successful. Further trials starting ST well above the CIPN-damaged areas are planned.
Abstract 15760: Left Atrial Dysfunction in Patients With Anderson - Fabrys Disease Using Magnetic Resonance Imaging Derived Left Atrial Phasic Function
Authors: Anna M Calleja, Qin Li, Ming-Yen Ng, Djeven P Deva, Andrew Crean, Christiane Gruner, Mark Iwanochko, Paaladinesh Thavendiranathan
Journal: Circulation (2015)

Background: Anderson-Fabrys disease (AFD) is an x-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase. This results in accumulation of globotriaosylceramide in various organs. The hallmark of cardiac involvement is left ventricular hypertrophy (LVH). However, autopsy studies have demonstrated involvement of the left atrium (LA) as well. There is currently limited data on left atrial volumes and function in patients with AFD. We sought to assess LA phasic volumes and function in patients with AFD using cardiac MRI (CMR) cine data. Method and Results: This was a retrospective study. Consecutive patients with clinically indicated CMR at our center were included. CMR acquired 2 and 4 chamber steady state free precession (SSFP) cine data were used to measure LA volume and phasic function with commercially available off-line software (eSieVVI, Siemens Medical System). We included 37 patients with AFD (18 males, mean age 48±13 yrs) and 22 age balanced healthy volunteers (8 males, mean age of 40±14 yrs). LA maximal and conduit volumes were not different between AFD and controls, but the LA minimal was larger (Table). Volume derived reservoir, conduit, and pump function were significantly reduced in AFD (Table). Strain measured reservoir and pump function were also significantly reduced in AFD. An inverse correlation was seen between LA reservoir strain and left ventricular (LV) mass (r=-0.53) and myocardial late gadolinium enhancement (LGE) measured using the 4 (r=-0.67) and 6 (r=-0.67) standard deviation thresholds. Conclusion: This is the first study to demonstrate abnormal LA function in patients with AFD using both volumetric and strain techniques. Patients with AFD had reduced LA reservoir and pump function with modest correlation with disease severity based on the burden of LV LGE and LV mass. Further studies are needed to assess the relationship between LA function and prognosis including the development of atrial arrhythmia.
Opportunities and Challenges for Dietary Arsenic Intervention
Authors: Keeve E. Nachman, Tracy Punshon, Laurie Rardin, Antonio J. Signes-Pastor, Carolyn J. Murray, Brian P. Jackson, Mary Lou Guerinot, Thomas A. Burke, Celia Y. Chen, Habibul Ahsan, Maria Argos, Kathryn L. Cottingham, Francesco Cubadda, Gary L. Ginsberg, Britton C. Goodale, Margaret Kurzius-Spencer, Andrew A. Meharg, Mark D. Miller, Anne E. Nigra, Claire B. Pendergrast, Andrea Raab, Ken Reimer, Kirk G. Scheckel, Tanja Schwerdtle, Vivien F. Taylor, Erik J. Tokar, Todd M. Warczak, Margaret R. Karagas
Journal: Environmental Health Perspectives (2018)

Summary: The diet is emerging as the dominant source of arsenic exposure for most of the U.S. population. Despite this, limited regulatory efforts have been aimed at mitigating exposure, and the role of diet in arsenic exposure and disease processes remains understudied. In this brief, we discuss the evidence linking dietary arsenic intake to human disease and discuss challenges associated with exposure characterization and efforts to quantify risks. In light of these challenges, and in recognition of the potential longer-term process of establishing regulation, we introduce a framework for shorter-term interventions that employs a field-to-plate food supply chain model to identify monitoring, intervention, and communication opportunities as part of a multisector, multiagency, science-informed, public health systems approach to mitigation of dietary arsenic exposure. Such an approach is dependent on coordination across commodity producers, the food industry, nongovernmental organizations, health professionals, researchers, and the regulatory community. https://doi.org/10.1289/EHP3997
Integrating tobacco treatment into cancer care: A first snapshot of RCT findings.
Authors: Elyse R. Park, Giselle Katiria Perez, Susan Regan, Alona Muzikanksy, Nancy Rigotti, Douglas E. Levy, Jennifer S. Temel, Mary E. Cooley, Ann H. Partridge, William F. Pirl, Kelly Irwin, Emily R. Friedman, Sarah Borderud, Kelly Hyland, Julia Rabin, Kim Sprunck, Diana Kwon, Jamie S. Ostroff
Journal: Journal of Clinical Oncology (2018)

6505 Background: Despite ASCO recommendations that tobacco use be assessed and managed, most cancer patients who smoke do not receive tobacco treatment. Evidence-based tobacco treatment has not yet been integrated into routine oncology care, and the optimal tobacco treatment strategy in this context is unknown. Methods: We conducted a two-arm, two-site RCT to compare sustained counseling plus medication (Intervention Group; IG) to standard tobacco counseling (comparison group; CG) to assist newly diagnosed cancer patients to quit smoking. Both treatment groups received 4 weekly telephone-delivered motivational counseling sessions. The IG additionally received 4 biweekly plus 3 monthly counseling sessions (total 11) and 12-weeks of free FDA-approved cessation medication (nicotine replacement therapy (NRT; patch/lozenge), varenicline, or bupropion). Eligibility criteria included a recent cancer diagnosis (breast, GI/GU, gyn, head & neck, lymphoma, lung, melanoma), cigarette use in the past 30 days, and English/Spanish speaking. The primary outcome was 6-month biochemically verified abstinence. Results: 303 (70% of confirmed eligibles) patients were enrolled and randomized to a treatment group. Participants were 56% female; 82% white non-Hispanic and 10% black; mean age = 58.3 (sd = 9.7); 40% had a non-smoking related tumor. 86% completed the 6-month surveys. 80% of IG patients used a smoking cessation medication, among which 83% selected NRT. Using intention-to-treat, 6-month quit rates were 33% in the IG group vs. 19% in the CG group (p < .02). Using intention-to-treat, 57% of IG patients were adherent to sustained counseling (≥7 sessions), which was associated with increased 6-month quit rates (p < .0001). Cost per patient was $1,273 (IG) vs. $838 (CG). Conclusions: Among newly-diagnosed cancer patients, a treatment program of sustained telephone-delivered counseling and free medication produced a higher 6-month quit rate vs. a briefer counseling program. The cost-per-quit compared favorably to other cessation interventions. Findings provide strong support for the benefit of sustained tobacco treatment and a model for effective implementation of tobacco treatment into oncology care settings nationwide. Clinical trial information: NCT01871506.