tbuckley/cabot-search huggingface dataset:
Immune checkpoint inhibition-related colitis: Correlation between ulcers and need for infliximab.
Authors: Marnix Heimen Geukes Foppen, Elisa A. Rozeman, Sandra van Wilpe, Cindy Postma, Petur Snaebjornsson, Johannes V. Van Thienen, Monique Esther van Leerdam, Michel M van den Heuvel, Christian U. Blank, Jolanda van Dieren, John B. A. G. Haanen
Journal: Journal of Clinical Oncology (2017)

e21062 Background: Immune checkpoint inhibition has improved survival of patients with several types of advanced cancer. With these new treatments previously unseen adverse events (AE) have become relevant. Considering the fact that most of these immune related AEs can be reversed when identified early and treated adequately, the need for updated algorithms is crucial. Colitis is one of the most severe AEs upon anti-CTLA-4 (e.g. ipilimumab) monotherapy or combination therapies. Severe colitis with deep ulcerations is associated with life-threatening complications such as perforation. Therefore, early recognition and treatment is warranted. Anti-TNF therapy (infliximab) can resolve colitis fast. We sought to identify endoscopic features that indicate the need for early treatment with infliximab. Methods: We retrospectively analyzed all patients who developed diarrhea upon checkpoint inhibition. Only patients undergoing endoscopy were included. All patients were treated at the NKI between August 2010 and March 2016 for either metastatic melanoma or non-small cell lung cancer. Results: A total of 89 patients underwent an endoscopy due to immune related diarrhea (irDiarrhea). Patients were treated with either monotherapy anti-CTLA-4, anti-PD-(L)1, a combination of both, or the combination of anti-CTLA-4 and radiofrequency ablation. Median age was 58 years (range 30-88) and 54% of patients were female. A colonoscopy was performed in 64 (72%) patients and a sigmoidoscopy in 25 (28%) patients. Ulcers were seen during 29 endoscopies (32%). In 18 endoscopies (20%) there were ≤ 10 ulcers and in 11 endoscopies (12%) &gt; 10. Of all patients that had ulcers at endoscopy 23 (79%) required additional infliximab treatment for corticosteroid refractory colitis, while only 25 (42%) of patients without ulcers required additional infliximab ( p= 0.001). Conclusions: Patients with ulcerative irColitis require twice as often infliximab in addition to corticosteroids. Early treatment with infliximab may be indicated in ulcerative irColitis. Treatment based on endoscopic features makes colonoscopy an important diagnostic tool in irDiarrhea. Prospective analysis of endoscopy-driven management of irColitis is warranted.
Abstract 16198: Cystatin C-based Estimated Glomerular Filtration Rate (eGFR) is a Superior Predictor for Cardioembolic Stroke to Creatinine-based eGFR in Patients With Atrial Fibrillation
Authors: Naoto Hashimoto, Satoshi Nishiyama, Tetsu Watanabe, Masahiro Wanezaki, Gensai Yamaura, Harutoshi Tamura, Takanori Arimoto, Hiroki Takahashi, Tetsuro Shishido, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2016)

Introduction: Chronic kidney disease (CKD) is an important risk factor for cardioembolic stroke in patients with atrial fibrillation (AF). The estimated glomerular filtration rate (eGFR) is a popularized index for assessing kidney function and calculated using serum creatinine or cystatin C. Compared with creatinine-based eGFR (eGFRcr), cystatin C-based eGFR (eGFRcys) is less affected by age, gender and muscle mass. We investigated whether eGFRcys is associated with development of cardioembolic stroke in patients with AF. Methods: We performed transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) and measured eGFRcys and eGFRcr in 480 patients with paroxysmal AF or chronic AF (337 males, 64 ± 12 years). We excluded the patients who did not undergo TEE and those who had severe valvular heart disease and severe renal dysfunction. Results: There were 128 patients with new-onset cardioembolic stroke. eGFRcys showed better correlation with left atrial volume index and left atrial appe...
Abstract 18790: Upregulation of MicroRNA29 Family Protects From Cardiac Hypertrophy and Fibrosis Modulating DNA Methyltransferases in the Novel Animal Aging Model Nothobranchius Furzeri
Authors: Francesco Spallotta, Johanna Heid, Sandra Atlante, Roberto Ripa, Chiara Cencioni, Mario Baumgart, Giuseppina Milano, Alessandro Scopece, Carsten Kuenne, Stefen Guenther, Giacomo Rossi, Thomas Braun, Giulio Pompilio, Andreas M Zeiher, Alessandro Cellerino, Carlo Gaetano
Journal: Circulation (2016)

Introduction and Hypothesis: The short-lived (6 months) turquoise killifish Nothobranchius furzeri (NF) is a novel and convenient model organism for aging studies in which the impact of microRNAs (...
Preventive effect of traditional Japanese medicine, syakuyakukanzoto on neurotoxicity of FOLFOX plus bevacizumab for metastatic colorectal cancer: A phase II study.
Authors: Hiroaki Takagi, Shinya Kajiura, Ayumu Hosokawa, Naoki Horikawa, Itsurou Terada, Taishi Hata, Yuka Kobayashi, Yuji Tsukioka, Kazuhisa Yabushita, Takashi Matsuo, Hiroki Yoshita, Takayuki Ando, Toshiro Sugiyama
Journal: Journal of Clinical Oncology (2018)

e15526 Background: A combination of 5-fluorouracil/folinic acid and oxaliplatin plus bevacizumab (FOLFOX+BV) is a standard regimen for chemotherapy of metastatic colorectal cancer (mCRC). The aim of this study is to evaluate the preventive effect of traditional Japanese medicine, Syakuyakukanzoto on oxaliplatin-induced neurotoxicity associated with FOLFOX+BV administration. Methods: The primary endpoint of this phase II study was to evaluate neurotoxicity administration at the dose of 500mg/m2 oxaliplatin. From April 2009 to September 2013, a total of 41 non-pretreated patients with mCRC. Syakuyakukanzoto (7.5g/day) had been administered since initial FOLFOX+BV administration. Neurotoxicity was evaluated according to Neurotoxicity Criteria of Debiopharm (DEB-NTC). Results: Patient characteristics (n = 41) were: median age = 66 years (range 36-78 years); male/female = 22/19; primary tumor in the colon/rectum = 22/19; ECOG PS 0/1 = 35/6; numbers of metastatic sites 0/1/2/3 = 0/16/24/1. A total of 725 cycles of therapy have been administered. Median number of cycles was 14 (range 1-95). Median number of oxaliplatin cycles was 10 (range 1-22). Median cumulative dose of oxaliplatin was 800 mg/m2 (range 85-1410mg/m2). At a dose of 500mg/m2 oxaliplatin, grade 1-2 DEB-NTC neurotoxicity occurred 29.4% (10/34) patients, but there was no grade 3 DEB-NTC neurotoxicity. Median time to treatment failure of oxaliplatin was 6.0 months. The most common grade 3/4 CTCAE were neutropenia (34.1%), hypertension (29.3%) and fatigue (9.8%). The response rate of the 38 patients with measurable lesions was 55.2% (21/38). Median progression free survival was 14.9 months and median overall survival was 33.9 months. Conclusions: The primary endpoint of neurotoxicity was met. The administration of traditional Japanese medicine, Syakuyakukanzoto may reduce oxaliplatin-induced neurotoxicity without negatively affecting tumor response or survival in patients with colorectal cancer who are administered FOLFOX+BV therapy.
Sequencing in metastatic castrate-resistant prostate cancer with enzalutamide in a post-chemotherapy setting.
Authors: Bruce A. Feinberg, Bhavik Pandya, Janna Radtchenko, David Garofalo, Scott Flanders, Bruce Brown, Arie Barlev, Menaka Bhor
Journal: Journal of Clinical Oncology (2016)

e16524 Background: Enzalutamide (ENZA) is an oral androgen receptor inhibitor that targets multiple steps within the androgen signaling pathway. It was first approved in August 2012 for the treatment of patients with metastatic castrate-resistant prostate cancer (mCRPC) who have previously received docetaxel (DOC), representing advancement in the treatment of mCRPC. This study was conducted to better understand sequences of use with ENZA in a post-chemotherapy setting. Methods: Patients who initiated ENZA following chemotherapy for mCRPC were retrospectively identified from September 2012−May 2014 in a community oncology electronic medical records database. Patients on clinical trials, with treatment for secondary malignancies, age < 18, and pre-chemotherapy ENZA use were excluded. The entire available treatment history, including key variables, was extracted and evaluated. Results: Of the 352 patients who met inclusion criteria, 223 (63%) received ≥ 2 therapies prior to ENZA. Median age was 68.8 years at diagnosis; 72.8 at ENZA start. Median Charlson Comorbidity Index was 6. 130 unique post-chemotherapy ENZA sequences were identified. The top three sequences accounted for 34% of the total patients and included DOC/ENZA, DOC/abiraterone (ABI)/ENZA, and ABI/DOC/ENZA; 127 other sequences were identified in the remaining 230 patients, including: radium 223, mitoxantrone, paclitaxel, sipuleucel-t (SIP), cabazitaxel (CBZ) and combination therapies. Conclusions: This analysis highlights significant unmet need and remarkable variation in treatment with ENZA for patients with mCRPC post chemo. Such variation of therapy use underscores the complexity of mCRPC treatment and the need for multiple treatment options. Further understanding of patterns of care and outcomes may support optimal sequencing for patients with mCRPC. Education of current guidelines and clinical pathways could ensure optimal efficacy and safety. Top 10 sequences Patients % DOC/ENZA 60 17 DOC/ABI/ENZA 43 12 ABI/DOC/ENZA 19 5 SIP/DOC/ENZA 12 3 DOC/ABI/CBZ/ ENZA 9 3 DOC/ENZA/CBZ 8 2 DOC/ABI/ENZA/ CBZ 8 2 CBZ/ENZA 7 2 DOC/ENZA/ABI 7 2 DOC/CBZ/ENZA 6 2 Other sequences 173 49
Phase III randomized trial of surgery followed by conventional radiotherapy (5 fr/Wk) (Arm A) vs concurrent chemoradiotherapy (Arm B) vs accelerated radiotherapy (6fr/Wk) (Arm C) in locally advanced, stage III and IV, resectable, squamous cell carcinoma of oral cavity- oral cavity adjuvant therapy (OCAT): Final results (NCT00193843).
Authors: Sarbani Ghosh Laskar, Devendra Chaukar, Mandar Deshpande, Abhishek Chatterjee, Rohini W Hawaldar, Santam Chakraborty, Shilpi Sharma, Jai Prakash Agarwal, Tejpal Gupta, Ashwini Narsingrao Budrukkar, Vedang Murthy, P. S. Pai, Pankaj Chaturvedi, Gouri Pantvaidya, Anuja Deshmukh, Deepa Nair, Sudhir Vasudevan Nair, Kumar Prabhash, Amit Joshi, Anil D'Cruz
Journal: Journal of Clinical Oncology (2016)

6004 Background: To evaluate the impact of post-operative adjuvant concurrent chemotherapy or accelerated radiotherapy (6 instead of 5 fractions / week), on local-regional control (LRC) and overall survival (OS) in locally advanced, resectable, squamous cell carcinoma of oral cavity. Methods: To demonstrate a 10% improvement in LRC with a type I error of 5% and power of 80% this 3-arm, phase III randomized trial was designed to include 900 patients, stratified by T and N stage. Radiotherapy (RT) in Arms A and B was 56-60Gy/ 28-30#/ 6weeks (5fractions/ week). The total RT dose was same in Arm C but delivered over 5weeks (6 fractions/ week). Concurrent chemotherapy (CT) was Inj Cisplatin, 30mg/m2, weekly. Results: From June 2005 to March 2013, 299, 300 and 301 patients were allocated to Arms A, B and C, respectively. Age, gender, sub site, stage of disease and adverse prognostic factors were equally distributed. 90% had T3-T4 tumors, while 48% had N2-3 disease. Only 12 (0.4%) had positive margins, 54.7% had extracapsular invasion (ECE) and 329 (36.5%) had multiple nodal involvement. Median RT dose was 60Gy. Patients received a median of 6 cycles of CT with a median cumulative cisplatin dose of 250 mg. Ninety four percent patients completed planned RT. At a median follow-up of 58 months (range: 0 – 128), there were 105, 92, and 112 locoregional recurrences in arms A, B and C, respectively. The 5 year LRC for arms A and B was 59.9% and 65.1% (arm B vs arm A: p = 0.203, HR: 0.83, 95% CI: 0.63 – 1.10) and 58.2% for arm C (arm C vs arm A: p = 1.02, HR: 1.02, 95%CI: 0.78 – 1.30). Advanced T & N stage, tongue involvement, and ECE had poorer outcomes but with no significant difference in LRC or OS between the three arms even with these high risk features. Acute grade 3 or more (CTCAE Vr 3.0) skin and mucosal toxicity were comparable between arms. Conclusions: Intensification of adjuvant radiotherapy with concurrent chemotherapy or accelerated radiotherapy did not result in improved disease outcomes in resectable oral cavity cancers. Clinical trial information: NCT00193843.
Guideline adherence and clinical outcome in vulnerable and healthy breast cancer patients: Results of a prospective cross-sectional study in Germany.
Authors: Elna Kuehnle, Wulf Siggelkow, Iris Schrader, Kristina Luebbe, Stefanie Noeding, Alexander Moser, Jutta John, Thomas Noesselt, Momme Arfsten, Peter Hillemanns, Thilo Dörk, Tjoung-Won Park-Simon
Journal: Journal of Clinical Oncology (2017)

e18132 Background: In 2003 the German Cancer Society and the German Society for Breast Disease introduced a number of Quality Indicators (QIs) to improve standards of breast cancer care. Although QIs should be based on clinical evidence, evidence for important subpopulations (i.e. vulnerable patients) is often limited. In this prospective cross-sectional study we assessed conformity and non-conformity of guidelines and their impact on clinical outcome in a real-world setting. Methods: This prospective analysis included patients with primary breast cancer. Patients with stage IV and recurrent breast cancer were excluded. Data was collected from 2012-2016 in six certified breast care centers using a personal questionnaire and data from the patients' medical records. Guideline adherence to a set of 11 QIs was explored. Overall survival (OS) and disease free survival (DFS) were correlated with fulfillment of QIs and tumor characteristics. Results: Survival analysis was conducted in 2390 patients with a median follow-up of 16 months. 88 (4%) patients had a recurrent disease. 31 (1.3%) patients died of breast cancer. Tumor stage, grading, Her2- and hormone receptor status and Ki-67 correlated with DFS and OS. 1725/1907 patients (90.5%) received a guideline adherent treatment. The most prevalent reasons for non-conformity were old age (24.7%) and/or comorbidity (20.9%). Breast cancer specific DFS and OS were not significantly different between patients treated adherent or not adherent to the guidelines. In contrast, survival analysis of death other than breast cancer showed a significantly worse OS (p = 0.006) for patients not treated according to guideline recommendation. Conclusions: Conformity of clinical guidelines was observed in the majority of patients including healthy and vulnerable patients. These patients tended to have a longer breast cancer specific survival. Patients who were not considered suitable for guideline-adherent therapy died more often from other medical reasons rather than from breast cancer. In our study 10% of the patients had a limited life expectancy due to old age and co-morbidities with no assumed benefit from guideline adherence.
Heart Centers for Women
Authors: Gina P. Lundberg, Laxmi S. Mehta, Rupa M. Sanghani, Hena N. Patel, Niti R. Aggarwal, Neelum T. Aggarwal, Lynne T. Braun, Sandra J. Lewis, Jennifer H. Mieres, Malissa J. Wood, Robert A. Harrington, Annabelle S. Volgman
Journal: Circulation (2018)

Heart Centers for Women (HCW) developed as a response to the need for improved outcomes for women with cardiovascular disease (CVD). From 1984 until 2012, more women died of CVD every single year in comparison with men. Initially, there was limited awareness and sex-specific research regarding mortality or outcomes in women. HCW played an active role in addressing these disparities, provided focused care for women, and contributed to improvements in these gaps. In 2014 and 2015, death from CVD in women had declined below the level of death from CVD in comparison with men. Even though awareness of CVD in women has increased among the public and healthcare providers and both sex- and gender-specific research is currently required in all research trials, not all women have benefitted equally in mortality reduction. New strategies for HCW need to be developed to address these disparities and expand the current HCW model. The HCW care team needs to direct academic curricula on sex- and gender-specific research and care; expand to include other healthcare professionals and other subspecialties; provide new care models; address diversity; and include more male providers.
Caregiver burden in head and neck cancer and the perceived educational needs.
Authors: Mark J. Stavas, Stewart M. Bond, Nancy L. Wells, Karen L. Schumacher, Mary S. Dietrich, Barbara A. Murphy
Journal: Journal of Clinical Oncology (2016)

e21673 Background: Head and neck cancer (HNC) caregivers (CG) engage in time consuming, complex and potentially distressing tasks. While the psychosocial impact of HNC CG has been studied, few reports focus on specific CG tasks. We developed the HNC Caregiving Task Inventory (CTI) to characterize various aspects of CG task burden. We report results of an analysis of CG task burden, task difficulty/discomfort, and expressed need for education. Methods: Eligibility: designated primary CG for HNC patient at any point across the disease and treatment trajectory. Study design: cross sectional. Questionnaire: The CTI contains 11 domains and 58 task items: General Function (11); Medical Care (8); Nutrition (4); Feeding Tube (5); Tracheostomy Care (3); Oral Care (2); Speech and Voice (3); Skin Care (2); Rehabilitation (3); Psychosocial (6); and Symptom Management (11). Each item includes an endorsement (yes or no) with a rating of difficulty and discomfort (1-5 scale) for endorsed items. For each domain, CG specifies educational needs that capture whether CG received prior education and whether additional education was needed. Statistics: Mann-Whitney tests were used to determine statistical significance. Results: 106 CG completed the CTI. CG Characteristics: white (92%), female (82%), mean age 56. The median number of tasks performed was high, indicating high overall burden. Within each domain, the average difficulty and discomfort was low ( ≤ 2), however, most CG reported moderate to severe discomfort or distress ( ≥ 3) with a least one task. Medical care, symptom management and psychosocial tasks were the most difficult or discomforting. In 6 of 11 domains (Nutrition, Speech and Voice, Skin Care, Rehabilitation, Psychosocial, Symptom Management) there was a statistically significant association of CG reports of high difficulty or discomfort with the perceived need for more teaching. Conclusions: In order to be effective, educational interventions must be directed in a timely manner to individuals with specific needs and who are open to directed teaching. The results of this analysis support the development of interventional programs that target CG with high levels of task related difficulty and distress.
TCT-237 Long-Term (8-13 Year) Clinical Outcomes in Pre-Diabetics after Drug-Eluting Stenting: More Like Diabetics or Non-Diabetics?
Authors: Stephen Ellis, Russell Raymond, Ravi Nair, Conrad Simpfendorfer, Christopher Bajzer, E. Murat Tuzcu, A. Michael Lincoff, Samir Kapadia
Journal: Journal of the American College of Cardiology (2018)
Angiotensinogen gene silencing to predict bevacizumab response in recurrent glioblastoma patients.
Authors: Thomas Urup, Linn Gillberg, Signe Regner Michaelsen, Ib Jarle Christensen, Helle Broholm, Ulrik Niels Lassen, Kirsten Grønbæk, Hans Skovgaard Poulsen
Journal: Journal of Clinical Oncology (2018)

2027 Background: Bevacizumab in combination with chemotherapy has shown activity in recurrent glioblastoma patients. Patients who achieve response to bevacizumab have improved survival as well as quality of life. Recently, we found that low gene expression of angiotensinogen (AGT) was a predictive factor for bevacizumab response in recurrent glioblastoma patients. Because promoter methylation of AGT has been associated with AGT gene silencing, we investigated if AGT promoter methylation in tumor tissue predicts response to bevacizumab combination therapy in recurrent glioblastoma patients. Methods: The study includes 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both RANO response and biomarker evaluable. DNA methylation of 7 CpG sites in the CEBPA binding site (~200 bp from TSS) of the AGT promoter was measured using pyrosequencing. AGT gene expression in tumor tissue was measured by NanoString analysis. For each CpG site, methylation levels were associated with angiotensinogen gene expression using Spearman correlations and to treatment response using Mann-Whitney U test and logistic regression analysis. Results: Preliminary results on 58 of 82 patients analyzed: AGT gene expression was inversely associated with AGT promoter methylation on CpG site 1 (P = 0.049) and borderline significant on CpG site 2 (P = 0.074). Compared to non-responding patients, responders expressed significantly higher methylation levels of CpG site 1 (P = 0.015), 2 (P = 0.013) and 3 (P = 0.045). DNA methylation levels at CpG site 4-7 were not associated with AGT gene expression or response. By univariate analysis, increased methylation of the AGT promoter region were predictive for bevacizumab response on CpG site 1 (2-fold increase: OR = 1.81; 95%CI: 1.02-3.23; P = 0.043) and on CpG site 2 (2-fold increase: OR = 2.08; 95%CI: 1.04-4.17; P = 0.040). Conclusions: Increased methylation of the AGT promoter regions is associated with AGT gene silencing and is predictive for bevacizumab response in recurrent glioblastoma patients. Updated results will be presented.