tbuckley/cabot-search huggingface dataset:
Phase II study evaluating ipilimumab as a single agent in the first-line treatment of adult patients (Pts) with metastatic uveal melanoma (MUM): The GEM-1 trial.
Authors: Jose Maria Piulats Rodriguez, Maria Ochoa de Olza, Manuel Codes, Jose A. Lopez-Martin, Alfonso Berrocal, Margarita García, Alfonso Gurpide, Blanca Homet, Salvador Martin-Algarra
Journal: Journal of Clinical Oncology (2014)

9033 Background: Uveal melanoma is the most common primary intraocular malignant tumor in adults. Overall survival (OS) at 5 years is 62% due to high incidence of liver metastasis that are fatal within 4 -9 months from diagnosis. No standard treatment exists for MUM. Ipilimumab has demonstrated to improve both overall and long-term survival in patients with advanced cutaneous melanoma (Hodi FS, et al., NEJM 2010; Robert C, et al., NEJM 2011). However, MUM patients were excluded in these trials. Methods: GEM-1 (EudraCT 2010-024415-14) is an open label, single arm phase 2 trial that evaluates first line ipilimumab in adult pts with MUM.The study was conducted in 5 centers in Spain, belonging to the Spanish Melanoma Group (GEM). Eligible pts had progressive metastatic disease, ECOG-PS 0 or 1, and no prior systemic treatment for MUM. Treatment consisted of ipilimumab 10 mg/kg iv q3 weeks (wk) for 4 doses (induction) followed by q12 wk (maintenance) until progression, intolerance or withdrawal. Primary end point was OS and secondary PFS, OR and safety using immune response criteria. Results: 32 pts were enrolled from July 2011 to May 2013. One patient was ineligible due to absence of metastatic disease at baseline. An interim analysis showed preliminary data from the 31 patients. 18 pts were men, mean age (SD) 60 (10). 64.5% (20) and 35.5% (11) of pts were ECOG-PS 0 and 1 respectively and progressive liver metastasis at baseline were present in 25 pts (80.7%) being frequently multiple and affecting both lobes. Ten pts experienced G3 (abdominal pain, hypophysitis (3), emesis, diarrhoea, asthenia, proctalgia, bone pain and urinary tract infection) and 5 pts had G4 toxicities (hepatotoxicity (2), multi-organ failure, altered state of consciousness, and vascular compression). With a median follow-up of 5.5 (CI 95%: 3.4-11.1) months 13 pts were evaluable for response: 1 PR (7.7%) and 6 pts SD (46.2%). Mature OS and PFS data are expected by April 2014. Conclusions: This is the first ipilimumab clinical trial showing preliminary activity in MUM pts. Safety profile is similar to prior reports in cutaneous melanoma. Response rate seems promising while mature OS and PFS results are pending. Clinical trial information: 2010-024415-14.
Chemotherapy first, followed by chemoradiation (CRT) and then surgery, in the management of locally advanced rectal cancer (LARC).
Authors: Andrea Cercek, Karyn A. Goodman, Carla Hajj, Emily Weisberger, Neil Howard Segal, Diane Lauren Reidy, Zsofia Kinga Stadler, Abraham Jing-Ching Wu, Martin R. Weiser, Philip Paty, Jose G. Guillem, Garrett Michael Nash, Larissa K. F. Temple, Julio Garcia-Aguilar, Leonard Saltz
Journal: Journal of Clinical Oncology (2013)

3605 Background: Standard pre-op CRT and post-op chemo for LARC delays the start of optimal systemic therapy by 18-22 weeks. To more promptly address micrometastases that could lead to distant failure, and supported by evidence of excellent primary tumor response to FOLFOX, we began offering FOLFOX as initial treatment for patients (pts) with high-risk LARC. More recently, we have begun offering all planned FOLFOX prior to CRT and surgery. Methods: We obtained an IRB waiver to review records of all clinical stage II/III RC pts treated with initial FOLFOX followed by CRT and total mesorectal excision (TME) at our institution between 2007 and 2012. Of approximately 300 rectal pts treated with CMT, 61 received some or all of their planned FOLFOX as initial therapy. Results: The median age of these 61 pts was 52 years, 54% male. At diagnosis, 84% had T3N1-2 or T4N0-1 tumors and 16% had T3N0 tumors. Of these, 57 received induction FOLFOX (median 7 cycles) then received pre-op CRT, while 4 pts achieved an excellent response to chemotherapy alone, declined CRT, and went directly to TME. Twelve pts did not undergo surgery; 9 had a complete clinical response and elected to be managed non-operatively; 1 refused recommended surgery despite incomplete tumor regression, 1 had surgery deferred due to comorbidities, and 1 developed distant metastatic disease prior to planned surgery. Of the 61 patients, 19 (31%) had either a pathCR (14) or a complete clinical response (5) leading to non-operative management. Of the 49 pts who underwent TME, all had R0 resections and 23 (47%) had tumor response &gt;90%, including 13 (27%) with pathCR. Of the 28 patients who received all 8 cycles of initial FOLFOX, 8 achieved a pathCR (29%) and 3 achieved a complete clinical responses (11%), managed non-operatively. All patients completed therapy as planned. There were no SAEs requiring delay in treatment during either FOLFOX or CMT. Conclusions: FOLFOX before CRT results in substantial tumor regression, a high rate of delivery of all planned therapy, and a substantial rate of pathCRs. Chemo and CMT before planned TME provides a favorable opportunity for consideration of non-operative management.
2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease
Authors: Rick A. Nishimura, Catherine M. Otto, Robert O. Bonow, Blase A. Carabello, John P. Erwin, Lee A. Fleisher, Hani Jneid, Michael J. Mack, Christopher J. McLeod, Patrick T. O’Gara, Vera H. Rigolin, Thoralf M. Sundt, Annemarie Thompson
Journal: Journal of the American College of Cardiology (2017)
INITIAL EXPERIENCE OF 265 CASES OF TRANS ULNAR ACCESS ANGIOPLASTY: INTERIM ANALYSIS OF A SINGLE CENTRE OBSERVATIONAL STUDY FROM AJULAST (AJMER ULNAR ANGIOPLASTY STUDY) COHORT
Authors: Rajendra Kumar Gokhroo, Shashi Kant Pandey, Ramsagar Roy, Avinash Anantharaj, Kailash Garhwal
Journal: Journal of the American College of Cardiology (2017)
A CASE OF BRUGADA SYNDROME DIAGNOSED AFTER CONVERSION OF SEEMINGLY LONE ATRIAL FIBRILLATION
Authors: Nikolay Mironov, Evgeny Maykov, Nikolay Shlevkov, Vyacheslav Kiktev, Kirill Gruzdev, Vladislav Vlodzyanovsky, Sergey Bakalov, Sergey Golitsyn
Journal: Journal of the American College of Cardiology (2017)
Pharmacokinetic modeling and simulation (PK M&amp;S) supported dose escalation of PF-03446962, a monoclonal antibody (mAb) against activin receptor like kinase 1, in patients with solid tumors.
Authors: Erjian Wang, Hossein Borghaei, Laura Williams Goff, Cristina Noberasco, Roger B. Cohen, Corrado Gallo Stampino, James Andrew Williams, Filippo De Braud, Jordan Berlin
Journal: Journal of Clinical Oncology (2012)

2595 Background: PF-03446962 is a first in class mAb. The PK of mAbs is complex, as their clearance (CL) can be linear or non-linear, besides extremely slow. Caution must be exercised when designing mAbs’ dose escalation schemes. Along with safety and activity evaluation, we used PK M&amp;S in real time to ensure that subsequent recommended doses did not expose too many patients to subtherapeutic levels while preserving safety. Methods: The model incorporated both Michaelis-Menten approximation and linear components. A prespecified target exposure was defined by preclinically projected therapeutic and toxic concentrations. The PK M&amp;S results were used to make dose escalation decisions. Results: Eight dose levels (0.5, 1, 2, 3, 4.5, 6.75, 10, and 15 mg/kg) were studied in 44 patients. CL of PF-03446962 exhibited nonlinear characteristics at low doses and linear at high doses. CL was saturated at dose levels of 3 mg/kg and above. Mean half-life was 2.6 days for the first dose level and 12-15 days after CL saturation. The dose ratio of 15 to 0.5 mg/kg was 30, while its corresponding Cmax and AUC ratios were 46 and 97, respectively. However, the PK M&amp;S accurately predicted exposure following each dose. 95% of the observed drug concentrations across all dose levels were within the predicted values. Concentrations at the 4.5 mg/kg dose exceeded the predicted efficacious level over the dosing period. None of 44 patients in the study were exposed to the toxic level derived from a study in monkeys. PK data also implied a biologically active dose at 2 mg/kg dose and above, confirmed by observing target toxicities (ie, telangiectasia) and clinical tumor responses. One patient with PR was at the 2 mg/kg dose and 2 patients with PR were at the 10 mg/kg. The PK M&amp;S well predicted the drug exposure following multiple doses in patients, indicating that patients did not develop antidrug immunogenicity. Conclusions: The PK M&amp;S based approach ensured that the majority of patients were treated at or near the therapeutic dose. It can be readily implemented in the conduct of dose escalation trials of antitumor mAbs, while minimizing risk to patients and maximizing efficiency.
Complementary and alternative medicine (CAM) and supportive care at leading cancer centers: A systematic analysis of websites
Authors: J. A. Brauer, A. El Sehamy, J. M. Metz, J. J. Mao
Journal: Journal of Clinical Oncology (2009)

e17528 Background: With increasing frequency, cancer patients and their family members are turning to the Internet to educate themselves about their disease and treatment options, including CAM and supportive care. However, very little is known about how national leading cancer centers represent these therapies via their websites. Methods: Simulating the patients’ perspective, we performed a systematic analysis of the websites of 41 National Cancer Institute (NCI) designated comprehensive cancer centers. Two researchers independently evaluated websites, recorded CAM information, and rated quality of the websites using a 4-item Likert scale (overall, information, presentation, and navigation) with Cronbach's alpha = 0.97. Rating was adequately correlated between the two raters (correlation coefficient 0.8). Results: Of 41 centers, 12 (29%) did not have functional websites with regards to information related to CAM. The most common CAM approaches mentioned were: acupuncture (59%), meditation/nutrition/spiritual support/yoga (56% for each), massage therapy (54%), and music therapy (51%). Twenty-three (56%) presented information on support groups, 19 (46%) on patient seminars, 18 (44%) on survivorship effort, and 17 (41%) on symptom management clinics. Twenty-nine (71%) of these websites had a telephone number available, 22 (54%) mentioned at least one ongoing research opportunity, and 19 (46%) provided links to the National Center for Complementary and Alternative Medicine website. Median rating of the quality of websites was 50 out of 100, with only 7 (17%) of centers receiving a composite score 80 (excellent) or better. Conclusions: While a growing number of leading cancer centers provide information about CAM and supportive oncology information for patients via their websites, the quality and ease of navigation of these sites remain highly variable. Effective development and redesign of many of the websites is needed to better inform and empower patients and families seeking CAM and supportive care information. No significant financial relationships to disclose.
Feasibility of highly intensive chemotherapy for AIDS-related Burkitt lymphoma.
Authors: Yuki Kojima, Suzuko Moritani, Hiroyuki Nakamura, Hideyuki Yamamoto, Yasuhiko Miyata, Hiroatsu Iida, Haruhiko Ohashi, Hirokazu Nagai
Journal: Journal of Clinical Oncology (2013)

e19521 Background: Burkitt lymphoma (BL) progresses very rapidly, but highly intensive chemotherapy (e.g. CODOX-M/IVAC, hyper-CVAD/MA) has been shown to be a promising strategy. In this time, AIDS-related lymphoma is treated with similarly to non-AIDS lymphoma, nevertheless it is not clear whether the highly intensive regimens are feasible and beneficial for AIDS-related Burkitt (AIDS-BL) or not. The purpose of the current study is to compare the toxicity of AIDS-BL to non-AIDS-BL retrospectively. Methods: We collected the data of all patients (pts) with BL between 2004 and 2011 at our institution. Chart review was performed for all identified pts. The effects of treatment and the clinical variables on overall survival (OS) were assessed. Results: We identified 25 Burkitt lymphomas, and a total of 108 cycles of highly intensive chemotherapy were administered. Nine of these 25 were AIDS-BL (median age, 51; range, 36 to 68) and 16 were non-AIDS-BL (median age, 60; range, 27 to 75). As chemotherapeutic regimens, 15 (60%) were treated with CODOX-M/IVAC, 8 (32%) with hyper-CVAD/MA, and 2 (8%) with EPOCH. Of 12 pts (48%) treated with rituximab-contain regimens. Completion rate of planned chemotherapy was 64%. The median follow-up was 34.3 months. Three-year OS was 73.6%. There were no significant differences in OS between chemotherapeutic regimens (p=0.94) and between AIDS-BL and non-AIDS-BL (p=0.39). The overall incidence of grade 3/4 febrile neutropenia was 64.8% (70 of 108 cycles), 60.5% for HIV-infected and 67.7% for HIV-negative case, respectively. Grade 4 thrombocytopenia was frequently observed in AIDS-BL (72.1% vs. 40.0%), and incidence of grade 3/4 anemia was not different (79.1% vs. 70.8%). Conclusions: This study showed that clinical outcomes, including toxicities, of AIDS-BL were similar to non-AIDS-BL when BL treated with highly intensive chemotherapy.
DISTURBED EXPRESSION OF IMMUNOREGULATORY LONG NONCODING RNAS IN CIRCULATING IMMUNE CELLS FROM PATIENTS WITH EARLY MYOCARDIAL INFARCTION
Authors: Wolfgang Poller, Martina Gast, Shinichi Nakagawa, Jan Haas, Andrea Stroux, Christian Mueller, Daniela Börnigen, Dirk Westermann, Carsten Skurk, Ursula Rauch-Kröhnert, Kannanganattu Prasanth, Stefan Blankenberg, Benjamin Meder, Ulf Landmesser, Tanja Zeller
Journal: Journal of the American College of Cardiology (2017)
Duration of systemic therapy for ovarian cancer: A systematic review and meta-analysis.
Authors: Adnan Nagrial, Anne Long, Venessa T. Chin, Jonathan Robert Carter, Philip James Beale
Journal: Journal of Clinical Oncology (2014)

5549 Background: The optimal duration of systemic treatment to maximise survival and quality of life (QOL) in ovarian cancer following surgery or in the recurrent setting is unclear. In addition maintenance therapy is not universally recommended in published guidelines. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) comparing longer versus shorter durations of systemic treatment as well as maintenance regimens. Methods: We searched MEDLINE, EMBASE, and CENTRAL to December 2013 for RCTs comparing (1) duration - a defined number of cycles of treatment versus a higher number of cycles of the same treatment and (2) maintenance - initial treatment versus the same initial therapy followed by additional cycles of a different treatment. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), adverse events (AE) and QOL. Hazard ratios (HR), confidence intervals (CI) and p-values (p) were estimated with a fixed-effects or random-effects model based on the heterogeneity of included studies using Revman 5.2.3. Results: We included 22 eligible trials (6 assessing duration, 16 assessing maintenance treatment) including 7,609 patients. Longer duration of chemotherapy prolonged PFS significantly (HR 0.77, 95% CI 0.66 to 0.90, p = 0.001) but not OS (HR 0.95, 95% CI 0.81 to 1.12, p = 0.54). Maintenance therapy did not prolong PFS (HR 0.91, 95% CI 0.81 to 1.02, p= 0.11) or OS (HR 0.94, 95% CI 0.87 to 1.02, p = 0.15). However, subgroup analysis showed that the effect of maintenance therapy on PFS was greater in the recurrent cancer setting (HR 0.57 vs. 0.96, p value for interaction = 0.02). Effects of maintenance therapy on PFS were similar with the use of chemotherapy or targeted therapy (HR 0.96 vs. 0.84, p = 0.31). The AEs were more frequent with both longer durations of therapy and during maintenance therapy. QOL was assessed in only 5 trials with inconsistent results. Conclusions: A longer duration of therapy in ovarian cancer significantly increased PFS but not OS at the cost of increased AEs. Maintenance therapy improved PFS in the recurrent cancer setting. Future studies of extended and maintenance therapy should focus on QOL as well as survival.
DOUBLE RIGHT CORONARY ARTERY ENGENDERING INADEQUATE BLOOD SUPPLY TO THE INFERIOR LEFT VENTRICULAR WALL
Authors: Mehran Abolbashari, Subrata Kar, Sucheta Gosavi, Waseem Shami, Sarmad Said, Yuefeng Chen, Ahmed Ibrahim, Mohamed Teleb, Harsh Agrawal
Journal: Journal of the American College of Cardiology (2017)
Trends toward declining aggressive care at end of life among older cancer patients in the Deep South.
Authors: Elizabeth Ann Kvale, Gabrielle Betty Rocque, Kerri S. Bevis, Aras Acemgil, Richard A. Taylor, Wendy Demark-Wahnefried, Kelly Kenzik, Yufeng Li, Karen Meneses, Michelle Martin, Mona Fouad, Nedra Lisovicz, Edward E. Partridge, Maria Pisu
Journal: Journal of Clinical Oncology (2015)

e20558 Background: Healthcare utilization and costs escalate dramatically in the final months of life. However, it is not clear on a population level how these expenses distribute between therapies that are focused on life extension and those that are more palliative in orientation. Methods: Claims data were obtained forMedicare beneficiaries ≥ 65 years old diagnosed with cancer within the UAB Health System Cancer Community Network (UAB CCN) from 2008-2014. For 10 quarters between January 2012 and June 2014, we determined the proportion of deceased beneficiaries who had aggressive care including ER visits, hospitalizations, ICU admissions, or chemotherapy in the last 2 weeks of life, and hospice utilization (admission or less than 3 days of hospice) in the quarter when death occurred. A lay navigation program with an emphasis on palliative care was implemented in the UAB CCN in the second quarter of 2013. Patients in the Program and those who were not were included in this analysis. Descriptive analyses and linear regression were used to test for trends over time. Results: Among 5,861 decedents included in the analyses, over the 10 quarters events in the last 2 weeks of life ranged from 18.5% to 15.8% for ICU admissions (14.6% decrease, p = 0.11), from 39.2% to 32.0% for ER visits (18.4% decrease, p = 0.03), and from 4.7% to 3.5% for chemotherapy (25.5% decrease, p = 0.11). Over the 10 quarters, hospice enrollment ranged from 70.7% to 77.4% (9.48% increase; p = 0.06), and the proportion of patients on hospice for less than 3 days changed from 7.8% to 7.5% (3.85% decrease, p = 0.30). Conclusions: Despitenational trends demonstrating increasingly aggressive care at end of life, in the UAB CCN there was a consistent trend toward decreased aggressive care and increased hospice care. Future efforts are needed to increase access to palliative care to reduce aggressive care and increase hospice care. The project described was supported by Grant Number 1C1CMS331023 from the Department of Health and Human Services, Centers for Medicare & Medicaid Services. The contents of this abstract are solely the responsibility of the authors and do not necessarily represent the official views of the U.S. Department of Health and Human Services or any of its agencies.
FGFR: Proof-of-concept study of AZD4547 in patients with FGFR1 or FGFR2 amplified tumours.
Authors: Elizabeth Catherine Smyth, Nicholas C. Turner, Sanjay Popat, Shethah Morgan, Kate Owen, Angela Gillbanks, Vikram Kumar Jain, David Cunningham
Journal: Journal of Clinical Oncology (2013)

TPS2626 Background: Genetic modifications of the FGFR family of transmembrane tyrosine kinase growth factor receptors are described in a range of cancers. Amplification of FGFR2 is detected in up to 10% of oesophagogastric cancers where it is associated with poor prognosis. FGFR1 amplification has also been demonstrated in 10% of breast cancers, is more common in luminal B ER positive tumors, and is also associated with inferior survival outcomes. Finally, FGFR1 amplification has been described in up to 22% of squamous cell lung cancers. AZD4547 is a potent and selective inhibitor of FGFR-1, 2 and 3 receptor tyrosine kinases. Preclinically, AZD4547 potently inhibits growth in FGFR amplified gastric and lung cancer cell lines and induces dose dependent tumor growth inhibition and regression in FGFR amplified tumour xenograft and patient derived explant models. Methods: This is an open label, phase II non-randomised multi-centre study to assess the efficacy of AZD4547 monotherapy and resulting molecular changes in serial biopsies in pts with previously treated FGFR1 amplified advanced breast cancer, FGFR2 amplified advanced oesophagogastric cancer, or FGFR1 amplified advanced squamous lung cancer. Eligibility include centrally verified FGFR amplified tumour (ratio &gt;2.2), PS=0-2, ability to comply with the collection of tumor biopsies (mandatory at baseline and on days 10-14), calcium and phosphate within normal limits, measurable disease (RECIST 1.1), and no history of significant eye disease. Pts may be prescreened for FGFR amplification on archival tissue while undergoing first line or adjuvant chemotherapy. Sixteen pts will be enrolled per cohort. All pts will receive AZD4547 80mg bd on a two week on, one week off schedule. The primary endpoint is correlation between change in pERK in pretreatment and day 10-14 biopsy and change in tumour diameter on week 8 CT. Secondary endpoints include ORR, DCR and PFS. Multiple exploratory translational endpoints are also planned. The study is currently open at the Royal Marsden Hospital and will open at 15 selected UK cancer centres. This study is sponsored by the Royal Marsden Hospital, funded by AstraZeneca and has been adopted to the UK National Cancer Research Network (NCRN) portfolio. Clinical trial information: 2011-003718-18.
FRAME GEOMETRY AND HEMODYNAMIC FINDINGS OF SAPIEN 3 TRANSCATHETER HEART VALVE IN PATIENTS WITH BICUSPID AORTIC VALVE DISEASE
Authors: Hiroyuki Kawamori, Sunghan Yoon, Tarun Chakravarty, Yoshio Maeno, Mohammad Kashif, Yigal Abramowitz, Geeteshwar Mangat, Sharjeel Israr, Masaki Miyasaka, Tanya Rami, Hasan Jilaihawi, Wen Cheng, Rahul Sharma, Raj Makkar
Journal: Journal of the American College of Cardiology (2017)
EFFECT OF COENZYME Q10 ON LEFT VENTRICULAR REMODELING AND MORTALITY IN PATIENTS WITH HEART FAILURE: A META-ANALYSIS
Authors: Angkawipa Trongtorsak, Kitravee Kongnatthasate, Paweena Susantitaphong, Veraprapas Kittipibul, Aekarach Ariyachaipanich
Journal: Journal of the American College of Cardiology (2017)
Rapid detection of yeast infections in patients with febrileneutropenia by PCR-RFLP
Authors: Filip Růžička, Veronika Holá, Miroslav Votava, Renata Tejkalová, Miloš Dendis, Radek Horváth, Karel Zitterbart, Jaroslav Štěrba, Iva Kocmanová
Journal: Clinical Microbiology and Infection (2005)