tbuckley/cabot-search huggingface dataset:
Abstract 405: Inhibition of Class I Histone Deacetylases at Reperfusion Attenuates Ischemia-reperfusion Injury and Modifies Mitochondrial Acetylation
Authors: Daniel J Herr, Sverre E Aune, Donald R Menick
Journal: Circulation Research (2015)

Although rapid reperfusion of ischemic tissue is the treatment of choice for myocardial infarction, much of the resultant damage occurs as a consequence of reperfusion itself. Previously, we have shown that pretreatment with MS-275, a selective class I histone deacetylase (HDAC) inhibitor, preserves left-ventricular (LV) function and substantially reduces the area of infarcted tissue in isolated rat hearts subjected to ischemia-reperfusion (IR) injury. Here, we tested the hypothesis that MS-275 treatment at reperfusion reduces LV tissue damage and improves post-ischemic LV contractile function. To do this, hearts from male Sprague-Dawley rats were isolated and perfused ex vivo on a Langendorff perfusion apparatus. A saline-filled balloon was inserted into the left ventricle of the heart to monitor ventricular pressure development throughout the experiment. Hearts were subjected to 30 minutes of ischemia, followed by 60 minutes of reperfusion. MS-275 was administered during the entire reperfusion phase, and resultant functional data were compared to untreated hearts. There was no difference in any metric of pre-ischemic contractile function between groups. 10nM MS-275 administered at reperfusion significantly improved multiple measures of LV function, including dP/dtmax, -dP/dtmax, developed pressure and rate pressure product. We also observed a significant reduction in infarct area of treated hearts compared to control, as measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Unexpectedly, mass spectrometry analysis revealed significant changes in acetylation state of multiple mitochondrial enzymes. Administration of MS-275 during the reperfusion phase of IR is sufficient to partially rescue LV function from reperfusion-induced damage. This study emphasizes the importance of exploring class I HDAC inhibitors for protection against ischemia-reperfusion.
Development of an open-source, flexible framework for interinstitutional data sharing and collaboration.
Authors: Chaim Kirby, Peter F Ambros, David Billiter, Wendy B. London, Eneida Mendonca, Tom Monclair, Andrew DJ Pearson, Susan Lerner Cohn, Samuel Louis Volchenboum
Journal: Journal of Clinical Oncology (2012)

9583 Background: Clinical information, “-omic” datasets, and tissue samples are becoming more difficult to harmonize and manage for advanced data mining. We believe that clinical research data can be centralized and provide direct access to sample availability and associated data from a variety of information stores. Methods: We obtained a standardized set of anonymized patient data from the International Neuroblastoma Risk Group. The cohort consists of more than 11,000 children diagnosed worldwide between 1974 and 2002. The data consist of 34 metrics, such as age at diagnosis, stage of tumor, and other clinical and biological markers. We instantiated the dataset into a Postgres database, and using the Django web framework, created a data model for rapid development of tools and views and built a front-end interface for generating complex queries. To test the feasibility of accessing information on disparate and geographically distinct data samples, we have a formal agreement with the Children's Oncology Group Tumor Bank at The Research Institute at Nationwide Children's Hospital. Based on query results, we consume the Tumor Bank tissue inventory data through a web-facing application programming interface. The end-user is presented only with the number of patients who match their query search terms and for whom tissue samples are available. Results: We have completed our initial implementation and have agreements for collaboration with other international consortium groups. We have created a paradigm for statisticians to securely update and add data, and a verification system checks for internal validity and provides a report of the transaction. Our system can initiate queries and accept results in a variety of standards-compliant formats, and will be available in demonstration form by May 2012. Conclusions: Querying patient data while interrogating external sources allows researchers to observe which ancillary data and samples are available and to quickly download data or request any samples. While designed around a neuroblastoma dataset, our system can be applied to a variety of clinical scenarios and will be made available through an open-source license.
Chromosomal aneusomy in sputum predicts for lung cancer in nested case-control study
Authors: W. Franklin, A. P. Schulte, C. Zeng, H. J. Wolf, X. Yin, F. R. Hirsch, T. Byers, Y. E. Miller, A. E. Baron, M. Varella-Garcia
Journal: Journal of Clinical Oncology (2006)

7201 Background: Lung cancer usually is disseminated at diagnosis and prognosis is poor for most patients. Heavy smokers are known to be at high risk factor for lung cancer and are target population for lung cancer prevention. Sputum has long been considered a potential source of material for biomarker based early detection but no tests have been validated. Methods: Chromosome aneusomy was sought in sputum of 114 cases and 110 controls from the Colorado Sputum Screening Cohort Study, which includes heavy smokers with airflow obstruction matched on age, gender, and date of sample collection. Subject characteristics were as follows: mean age 67 (± 8 years), 75% males, 36% current smokers, mean pack-year 71.2 (± 33.5). The FISH probe LAVysion (Vysis/Abbott) was used, including the DNA targets EGFR, MYCC, 5p15 and CEP6. Results: The multi-target set showed the highest sensitivity (0.78) and specificity (0.95) rates in specimens collected within 12 months of lung cancer diagnosis. The individual probes EGFR, MYCC, 5p15 and CEP6 showed, respectively, decreasing sensitivity rates (0.78, 0.67, 0.62, and 0.29) and increasing specificity rates (0.84, 0.91. 0.86, and 0.95). Combinations of two specific probes (AND) or of any of two probes (OR) have not favorably impacted these coefficients. Proportion of abnormal sputum specimens was higher in squamous cell carcinoma than in adenocarcinoma or small cell carcinoma, both considering the set of specimens collected 12 months prior to disease diagnosis (92%, 75%, 60%) and all specimens (80%, 58%, 44%). Conclusions: Chromosomal aneusomy in sputum was demonstrated in a nested case-control cohort to be a promising marker for prediction of lung cancer risk in heavy smokers with airflow obstruction. Evaluation of four DNA targets was more effective than any single marker or combination of markers, and the test had high sensitivity in patients with squamous cell carcinoma. [Table: see text]
Phase I/II Study of Lenalidomide and High Dose Melphalan As Preparative Regimen in Autologous Transplant in Myeloma: Report of Phase II Efficacy and Safety Data
Authors: Attaya Suvannasankha, Sherif Farag, Rebecca Silbermann, Mary Cangany, Anita Rush-Taylor, Robin O'Bryant, Lisa Wood, Jean Pearson, Sarah Singleton, Andrea Bradley, Sandra Althouse, Susan Perkins, Deb Estes, Rafat Abonour
Journal: Blood (2015)
An EPIC electronic decision support tool to identify percentage of patients with stage IV thoracic or gastrointestinal malignancy who would benefit from concurrent palliative care but do not currently receive it.
Authors: Kerin B. Adelson, Amelia Anne Trant, Kim Framski, Mark Swidler, Nitu Kashyap
Journal: Journal of Clinical Oncology (2017)

133 Background: In 2016 ASCO updated its guideline for early integration of palliative care (PC) into standard oncologic care for all “inpatients and outpatients with advanced cancer.” PC has been shown to improve quality of life, align care at the end of life with patient preferences, and reduce health-care utilization. In preparation for the expansion of our palliative care service into ambulatory disease-based practices at Smilow Cancer Hospital at Yale-New Haven, we sought to create a decision support tool (DST) in the EPIC Electronic Health Record (EHR) that would identify patients for PC referral. Methods: This DST identifies patients with a GI or thoracic malignancy who have had an ICD-10 diagnosis of metastatic or stage IV disease, have not had a palliative care visit in the last 6 months, and are not enrolled in hospice. If the patient meets criteria, the DST will remind providers that “this patient meets ASCO and IOM criteria for concurrent palliative care with oncologic care ” and offers a one-click option to place the referral. To understand the volume of patients this DST would refer, we ran it silently in the EHR background from 7/15/16 through 9/1/16. We tracked how many patients were seen in the clinics, how many were eligible, and how many were referred to PC. Results: See table. Conclusions: Our silent BPA indicated that only 5% of patients eligible for a palliative care consult received it at baseline; this matches national data, which suggests that most patients who would benefit from PC do not receive it. This DST has the potential to dramatically improve PC referral rates and increase adherence with ASCO and IOM guidelines. We plan to move the DST into the live clinical EHR in 2017 after the integrated PC clinics are open. We anticipate that once our BPA is activated, we will see a dramatic increase in the number of eligible patients referred to palliative care. [Table: see text]
Magnetic resonance guided focused ultrasound surgery for palliation of painful bone metastasis: Results of a multicenter phase III trial.
Authors: Mark Hurwitz, Joshua E. Meyer, Dimitri Iozeffi, Pejman Ghanouni, David Gianfelice, Fiona M. Fennessy, Abraham Kuten, Suzanne LeBlang, Anne C. Roberts, Junsung Choi, Alessandro Napoli, Vladimir Turkevich, Clare M. Tempany, Yael Inbar, Raphael M. Pfeffer, James Mitchell Larner, Sergy Kanaev
Journal: Journal of Clinical Oncology (2013)

9500 Background: Pain due to bone metastases is a common cause of cancer-related morbidity. Magnetic resonance guided focused ultrasound surgery (MRgFUS) is a non-invasive approach to thermal tissue ablation. This multi-center phase III trial assessed efficacy of MRgFUS compared with sham treatment to alleviate pain due to bone metastases. Methods: Subjects with a painful bone metastasis amenable to MRgFUS treatment for whom radiation therapy was ineffective or contraindicated were randomized 3:1 to MRgFUS or sham treatment in a single blind design. Un-blinding of sham subjects who did not experience significant pain relief within 2 weeks was permitted with crossover allowed to salvage MRgFUS treatment. Pain response and impact on quality of life (QOL) were assessed using the numerical rating scale (NRS) and Brief Pain Inventory-Quality of Life (BPI-QOL). Safety was also assessed. Results: 142 randomized subjects were included in an intent-to-treat analysis. 67% (95%CI: 57.5-76.0%) of 107 subjects in the MRgFUS arm experienced clinically significant pain relief, equating with an anchor descriptor of “much improved” or better at 3 months compared to 20% of 35 sham arm subjects (p&lt;0.0001). Median baseline and 3 month NRS scores were 7.0 and 2.0 for the MRgFUS arm vs. 7.0 and 6.0 for the sham arm. A clinically significant improvement at 3 months in BPI-QOL score for MRgFUS but not sham treatment was noted [average change: 2.4 vs. 0.2 respectively, (p&lt;0.0001)]. MRgFUS treatment was well tolerated. Conclusions: MRgFUS, as demonstrated by this phase III trial, results in excellent rates of pain relief and improvement in QOL for patients with oncologic related bone pain who are not candidates for radiation therapy. Given these excellent results coupled with a favorable side effect profile, MRgFUS should be considered a primary choice for this patient population. Clinical trial information: NCT00656305.
Adjuvant chemotherapy for patients with T2N0M0 non-small cell lung cancer.
Authors: Daniel Morgensztern, Saiama Naheed Waqar, Aalok Patel, Siddhartha Devarakonda, Sadaf Huma Waqar, Feng Gao, Cliff Grant Robinson, Jeffrey D. Bradley, Maria Quintos Baggstrom, Ramaswamy Govindan, Varun Puri
Journal: Journal of Clinical Oncology (2015)

7520 Background: Adjuvant chemotherapy (CT) improves overall survival (OS) in patients with completely resected stage II and III non-small cell lung cancer (NSCLC). However, its role in patients with stage IB disease remains unclear. We therefore evaluated the role of adjuvant CT in patients with completely resected T2N0M0 NSCLC. Methods: Patients with pathologic stage T2N0M0 NSCLC who underwent complete (R0) resection from 2003 to 2010 were identified from the National Cancer Database (NCDB). Patients were grouped based on tumor size: 3-3.9 cm, 4-4.9 cm, 5-5.9 cm and 6-7 cm. Survival curves according to the CT status were estimated by the Kaplan-Meier product-limit method and compared by log-rank test. Cox proportional hazard model was used to evaluate whether adjuvant CT was an independent predictor for survival for each tumor size groups. Results: Among the 29,908 patients meeting inclusion criteria, there were 5,209 (17.4%) and 24,699 (82.6%) patients in the CT and observation groups respectively. Patients treated with CT were younger (median age 65 vs 71 years, p < 0.001), had smaller median tumor sizes (3.7 vs 4.1 cm, p < 0.001), and a lower incidence of sub-lobar resection (5.6% vs 8.2%, p < 0.001). Adjuvant CT improved median OS compared to observation for all tumor size groups in both univariate (UVA) and multivariate (MVA) analyses (Table). Conclusions: Adjuvant CT was associated with improved OS in all tumor size groups for patients with completely resected T2N0M0 NSCLC. Despite the biases inherent in a database study, the benefit from adjuvant CT in patients with tumors < 4 cm suggests a possible role in this patient population and the need for revisiting its current status as an exclusion criteria for adjuvant trials. Adjuvant chemotherapy versus observation. Median OS (months) 5 year OS UVA-HR(95% CI) MVA-HR(95% CI) All patients 95.6 vs 67.0 67.9 vs 54.6% 0.64 (0.61-0.68) 0.70 (0.66-0.74) 3-3.9cm NR vs 71.3 70.5 vs 57.9% 0.66 (0.61-0.73) 0.75 (0.68-0.85) 4-4.9cm 90.7 vs 64.7 66.5 vs 52.7% 0.61 (0.55-0.68) 0.70 (0.63-0.77) 5-5.9cm 87.9 vs 58.8 65.9 vs 49.3% 0.60 (0.53-0.69) 0.68 (0.60-0.78) 6-7cm 86.9 vs 54.6 65.3 vs 46.8% 0.55 (0.47-0.64) 0.62 (0.53-0.72)
Monitoring inbaskets with feedback to providers enhances the timeliness of patient care.
Authors: Kerin B. Adelson, Amelia Anne Trant, Michael Strait, Rory Kaplan, Vanna Dest, Adam Roshka, Catherine A. Lyons, Kevin A. Vest, Tessa Steffen, Rogerio Lilenbaum
Journal: Journal of Clinical Oncology (2017)

132 Background: The adoption of Electronic Health Records (EHRs) has changed the workflow for providers. The “inBasket” feature supplants telephone and email communications, replaces paper results review and has become the way to track incomplete encounters. Failure to promptly complete medical records leads to unread notes and impairs multidisciplinary communication. Also, unclosed encounters lead to potential penalties and uncollected fees. One benefit of the inBasket, is that it can be monitored. Methods: We created a report that tracked EPIC inBasket activities by provider including numbers of open charts, unchecked results, phone calls, incomplete dictations and orders needing cosign. The report shows the number and length of time each activity has been delinquent. In December 2015 we began emailing automated reports to all providers with their monthly results. In January 2016 we began an enforcement process for providers with &gt;50 open charts: 30 days to complete charts or practice would be closed to new patients; if &gt;50 remained after 30 days providers had 60 days before complete suspension from practice. We modeled the financial impact of chart closure by creating a weighted average by payor of fees collected per visit. For charts that would have been delinquent beyond payor filing deadlines this represents actual increased revenue. For charts that would have eventually been closed before the filing deadline this represents earlier revenue capture. Results: See table. Conclusions: Inbasket monitoring with structured feedback to providers led to improvement in the number of open charts, the focus of corrective action. We did not see consistent improvements in the other inbasket metrics. Future work will involve a similar approach to all inBasket metrics. Closing charts also has a significant financial impact; we estimate that $483,049 in fees that could have been lost due to exceeding payor deadlines became collectable. [Table: see text]
What patients want to know about disease and treatment
Authors: Z. Nikolic-Tomasevic, S. Jelic, S. Jezdic
Journal: Journal of Clinical Oncology (2004)

8240 Background: Treatment of metastatic carcinomas is accompanied with disturbing facts about disease and treatment, therefore many doctors as well as patients, prefers “not-to-tell if not-asked” and vice versa attitude. Also, communication with patients is complicated because little is known about what patients actually wants to know about disease and treatment. To improve communication with patients, we have conducted a survey with primary aim to determine how well our patients are informed and which information they find to be most useful. Also, age related differences are analyzed. Methods: The self-designed questioner (18 questions) is distributed among 200 hospitalized patients at the medical oncology department. Patients were stratified according to gender, age and education. Results: There were 99 females, 101 males; 31% of patients are elderly (>60 yrs, median 67). Age related differences were most prominent. Elderly patients are most interested about treatment duration (79%), less for side effects (40%), and the rate of treatment failure (30%).Younger patients are almost equally interested for all treatment aspects. 52% elderly patients, think that information about rate of expected response is not useful at all, as compared to 28% of younger; 93% elderly would prefer verbal information rather that written inform consent (only 7%); 72% of younger patients prefers verbal information, 21% would like to get all informing options (verbal, written, internet); 15% of elderly don't know any relevant information about diseases (as compared to 1% of younger patients); 59% of the elderly were not informed about the side effects of the treatment (25 % of younger). None of the elderly patients claimed to be disinterested to get more information about disease and treatment (7,5% of younger). Conclusions: Majority of patients are most interested about treatment duration, side effects of treatment, and rate of therapy failure. Elderly patients were clearly less informed about all aspects of the planed treatment. However, it seems that elderly patients are at least equally interested about disease and treatment and prefer rather verbal communication with the doctors, than written information. No significant financial relationships to disclose.
Paclitaxel (T) plus ifosfamide (I) followed by high-dose carboplatin (C) and etoposide (E) with autologous stem cell support for patients (pts) with previously treated germ cell tumors (GCT): TI-CE results and prognostic factor analysis in 107 pts
Authors: D. R. Feldman, J. Sheinfeld, D. F. Bajorin, P. Fischer, S. Turkula, N. Ishill, S. Patil, M. Bains, G. J. Bosl, R. J. Motzer
Journal: Journal of Clinical Oncology (2009)

5027 Background: Pts with incomplete response (IR) to first-line chemotherapy or relapsed primary mediastinal non-seminomatous GCT (NSGCT) have &lt;10% 3-year (yr) survival with conventional-dose salvage regimens (Cancer. 67:1305). The doses, schedule, and safety of TI-CE in this population were previously reported (J Clin Oncol. 25: 85). Efficacy and prognostic factor analysis are now presented. Methods: Phase I/II trial of TI-CE conducted in GCT pts with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, IR to first-line therapy, or relapse/IR to ifosfamide/cisplatin-based conventional-dose salvage). Univariate and multivariate analyses of prognostic factors were performed. Einhorn (N Eng J Med. 357:340) and Beyer (J Clin Oncol. 14: 263) prognostic models were also assessed. Results: Of 107 pts, primary site was testis in 72, mediastinum (all NSGCT) in 21, and other in 14. 81 had 1 prior line of therapy and 26 had ≥2. 79 were platinum-refractory and 7 had late relapses. A complete response was achieved in 54 (50%) and partial response with negative markers in 8 (8%). 5-yr disease-free survival (DFS) was 47% and overall survival 52% with a median follow-up of 61 months (m). No relapses occurred after 2 yrs. 5/21 (24%) primary mediastinal NSGCT and 2/7 late relapses are continuously disease-free. On multivariate analysis, primary mediastinal site (p = 0.0002), ≥2 lines of prior therapy (p = 0.0005), baseline HCG &gt;1000 (p = 0.01), and lung metastases (p = 0.02) significantly predicted adverse DFS. By Beyer model, 79% were intermediate and 21% poor risk (0 good risk). DFS was better for intermediate than poor risk pts (p &lt; 0.002), with 2-year rates of 54% and 23%, respectively. By Einhorn model, 15% pts were good, 38% intermediate, and 47% poor risk; good/intermediate risk pts had superior DFS compared to poor risk pts (p &lt; 0.05) with DFS at 2 yrs of 69% vs. 44%. Conclusions: TI-CE is effective salvage therapy for GCT pts with poor prognostic features. Mediastinal primary site and ≥2 lines of prior therapy were most predictive of adverse DFS. Beyer &amp; Einhorn models can assist in predicting outcome. No significant financial relationships to disclose.
SNP-Arrays Provide New Insights Into the Pathogenesis of Richter Syndrome (RS)
Authors: Andrea Rinaldi, Ekaterina Chigrinova, Ivo Kwee, Davide Rossi, Paola MV Rancoita, Jonathan C. Strefford, David Graham Oscier, Kostas Stamatopoulos, Theodora Papadaki, Francoise Berger, Ken H. Young, Fiona Murray, Richard Rosenquist, Timothy C. Greiner, Wing C. Chan, Luca Arcaini, Marco Lucioni, Roberto Marasca, Giorgio Inghirami, Marco Ladetto, Francesco Forconi, Sergio Cogliatti, Hana Votavova, Steven H. Swerdlow, Stephan Stilgenbauer, Miguel Piris, Andras Matolcsy, Dominic Spagnolo, Eugene Nikitin, Alberto Zamò, Valter Gattei, Laura Pasqualucci, Emanuele Zucca, Gianluca Gaidano, Francesco Bertoni
Journal: Blood (2011)
Prevalence of adenomas and hyperplastic polyps in carriers of HNPCC (LYNCH Syndrome)
Authors: A. Liljegren, G. Barker, J. Mathers, A. Lindblom, B. Nilsson, S. Rotstein, J. Burn, T. Bishop
Journal: Journal of Clinical Oncology (2004)

1007 Background: The aim of this study was to estimate the prevalence of adenomas and hyperplastic polpys in a large cohort of individuals with HNPCC. These prevalences have been estimated previously in smaller studies and the results found to be variable. Methods: 392 individuals enrolled in the CAPP2 study - a chemoprevention trial - classified as HNPCC and with a detected mutation in one of the mismatch repair genes (hMSH2, hMLH1 or hMSH6) were studied. Information about the number, size, and location of adenomas and hyperplastic polyps found at the recruits' first life time colonoscopy was analysed in a cross-sectional study. Results: The prevalence of adenomas and hyperplastic polyps in the whole study population was 18% and 10 % respectively. Increased age was a predictor for detecting an adenoma at first colonoscopy going from 7.3% in the under 35 years of age to 33.3% in the oldest age group >55 years of age. There was no differences in prevalence between males and females for adenomas, but males were about 50% more likely to have a hyperplastic polyp (non significant). A significant positive correlation was found between the adenomas and hyperplastic polyps in the study population. The adenomas were evenly distributed in the colon but the hyperplastic polyps were primarily located in the distal colon. Conclusion: The positive correlation between adenomas and hyperplastic polyps shows that hyperplastic polyps may serve as a marker for synchronous adenomas. No significant financial relationships to disclose.