tbuckley/cabot-search huggingface dataset:
Sunitinib treatment for longer than 2 years for renal cell carcinoma.
Authors: L. M. Pickering, A. Constantinidou, J. M. Larkin, S. A. Sohaib, P. Khatri, P. D. Nathan, A. Vinayan, T. Ferguson, S. St. Rose, M. E. Gore
Journal: Journal of Clinical Oncology (2010)

e15099 Background: Sunitinib has transformed the management of advanced renal cell carcinoma (RCC). Progression-free survival in the pivotal randomized study was 11 months but few data are reported regarding patients treated with sunitinib for longer periods. Methods: Patients with advanced RCC treated with sunitinib for over 2 years were identified from our institutional database and their characteristics and outcomes summarized. Results: Twenty eight patients were treated with sunitinib for over 2 years out of 109 treated in total between 2005 and September 2007. All 28 had undergone nephrectomy, median age was 56 (range 27-68) and 79% were male. Median number of lines of prior therapy was 1 (range 0-3), Motzer scores were 0 (n=6), 1 (n=7), 2 (n=7), 3 (n=6), 4 (n=1) and not known (n=1). Median ECOG PS was 1 (range 0-2). A median of 2 sites of metastatic disease were present at baseline (range 1-4). Sunitinib was started a median of 22 (range 1-83) months after diagnosis of advanced disease. Median duration of therapy as of September 2009 was 36 (range 24- 47+) months. All patients started sunitinib at 50mg daily on the 4/2 week schedule; toxicity was manageable although 75% (21/28) underwent dose modification. Reduction to 37.5mg on the 4/2 schedule occurred in 16 (57%) and to 25mg (4/2 or continuous) in 8 patients (29%). Eight patients underwent dose re-escalation after dose reduction. Best response was partial response (PR) in 13 (46%) and stable disease (SD) in 15 patients (54%). Median duration of therapy was 40 months (range 27-45+) in the PR group and 31 months (range 24-47+) in the SD group. Median overall survival was 45 (95% CI 39-51) months. Twenty two patients (79%) had progressed as of September 2009; 10 (45%) progressed initially in bone alone; all 10 were treated with surgery and/or radiotherapy and subsequently received sunitinib for a median of 19.5 (range 1-37) months. Conclusions: A quarter of patients treated with sunitinib for RCC received therapy for 2 years or longer. Toxicity was manageable with appropriate dose modification; subsequent dose re-escalation was feasible in a significant number of patients. There may be a group of patients in whom sunitinib therapy can be continued with clinical benefit after local therapy to progressive disease in bone. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer
Developing an inspired leader: How to maximize human talent to maximize operating results.
Authors: Aimee Greeter
Journal: Journal of Clinical Oncology (2019)

10522 Background: Healthcare is a personal industry–driven by people, for people. Developing the talent of individuals as leaders is critical to making the entire industry thrive. This session provides practical tools to develop highly competent leaders, who can then develop high-performing organizations. Methods: Using Noel Burch’s framework, this presentation shares effective methods of propelling leaders from uninspired to results-focused performers. With a focus on real-life examples, this interactive session gives instruction on how to maximize human talent as a means to driving enterprise-wide success. The topics to be covered include: (1) Conscious Competence Ladder: What Is It?; (2) Noel Burch’s work; (3) Key tenets of the Ladder; (4) Common misperceptions of the Ladder; (5) Conscious Competence Ladder and Healthcare: Why Does it Matter?; (6) Application of the Ladder to the healthcare industry; (7) Realities of Human Capital in healthcare; (8) “Exercising” Leadership: Is That Even Possible?; (9)Development of leadership as a skill; (10) Four-Step Process to Leadership Development in Healthcare: But How Do We Do That?; (11) Application of Leadership: But Won’t This Be Hard?; (11) Common pitfalls in leadership development; (12) Success Stories: Has Anyone Ever Even Done This in Healthcare?; (13) Conclusions, Q&amp;A: What Happens Next? Results: This session will enable participants to: (1)Describe the Conscious Competence Ladder model and its relevance to healthcare organizations; (2) Authenticate leadership as a skill that can be developed, and understand how to mature that skill within healthcare leaders using an efficient four-step process; and (3) Provide practical, effective methods to help people understand, process and use leadership skills to maximize the success of their peers, patients and community. Conclusions: In Q4 2017, for the first time ever, healthcare passed both manufacturing and retail as the United States’ largest employer. Simply put, there are now more health care laborers than any other industry. In sheer numbers alone, this is impressive. But, more impressive is the need to utilize and motivate this work force. Using effective and appropriate tools (such as those to be provided in this presentation), this massive healthcare work force can be empowered to drive significant benefits for an organization, its patients and its broader community.
Challenge of Rechallenge: When to Resume Immunotherapy Following an Immune-Related Adverse Event
Authors: Erica C. Nakajima, Evan J. Lipson, Julie R. Brahmer
Journal: Journal of Clinical Oncology (2019)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
Evolution of Excisional Surgery Practices for Melanoma in the United States
Authors: Michael P. Lee, Joseph F. Sobanko, Thuzar M. Shin, Nicole M. Howe, John S. Barbieri, Christopher J. Miller, Jeremy R. Etzkorn
Journal: JAMA Dermatology (2019)

National Comprehensive Cancer Network guidelines for melanoma have consistently recommended wide local excision as the standard of care since their inception. Although surgery with more comprehensive margin assessment (eg, Mohs surgery) has been advocated for certain subsets of melanoma, how often these techniques are used in clinical practice is uncertain.To examine trends in the use of comprehensive margin assessment surgery for melanoma by tracking claims data for Mohs surgery.This national cross-sectional analysis examined claims data from the Optum Clinformatics Data Mart, a nationally representative database. The study cohort consisted of 79 108 patients undergoing surgical excision for melanoma from January 1, 2001, through December 31, 2016. Data were analyzed from January 1, 2001, through December 31, 2016.The primary outcome was the likelihood of a melanoma being treated with Mohs surgery over time, evaluated by multivariable logistic regression and expressed as the odds of treatment per additional calendar year.Among 79 108 patients with melanoma (median age, 63 years [interquartile range {IQR}, 51-73]; 47 407 men [59.9%]), 75 047 were treated with conventional excision (median age, 62 years [IQR, 50-73 years]; 44 786 men [59.7%]) and 4061 with Mohs surgery (median age, 67 years [IQR, 56-76 years]; 2621 men [64.5%]). Mohs surgery was used in 5.1% of all surgical cases, with the rate of Mohs surgery increasing 304% from 2.6% in 2001 to 7.9% in 2016. Odds of receiving Mohs surgery for melanoma increased significantly in more recent calendar years (odds ratio [OR], 1.02 per calendar year; 95% CI, 1.01-1.03; P < .001). Immunohistochemistry (IHC) use was only coded with Mohs surgery in 1087 cases (26.8%), and the odds of receiving Mohs surgery with IHC increased in more recent calendar years (OR, 1.13 per calendar year; 95% CI, 1.10-1.15; P < .001). Use of Mohs surgery and Mohs surgery with IHC for melanoma differed widely across geographic census divisions with greater than 3-fold variation between the regions with highest and lowest use in every period (eg, for 2013 through 2016, the East South Central region used Mohs surgery in 8.8% of melanoma excisions compared with 2.6 in the New England region).Despite stable guidelines for melanoma surgery, the results of this study suggest that surgical practices for melanoma are evolving. Wide variations in surgical practice patterns for melanoma are present in the United States. This study's findings suggest that the effect of variations in surgical techniques on outcomes requires scrutiny and further study.
Aautoimmune Hemolytic Anemia: Pattern of Clinical Presentation and Management Outcome — a Nine Year Observation from a Tertiary Care Hospital in Saudi Arabia
Authors: Mahsen AlSaleh, Tarek Owaidah, Abdullah AlJefri, Saba Parween, Roula Barmada, Silgy Jose, Bouchra Safi, Viqaruddin Mohammed, Joumana AlEita
Journal: Blood (2017)
Anlotinib and irinotecan for advanced Ewing sarcoma after failure of standard therapy: A multicenter, two-cohort, single-arm, open label, phase Ib/II trial (NCT03416517).
Authors: Jie Xu, Lu Xie, Wei Guo, Xiaodong Tang, Rongli Yang, Taiqiang Yan, Kuisheng Liu, Jin Gu
Journal: Journal of Clinical Oncology (2019)

11012 Background: Both protracted irinotecan and anti-angiogenesis therapy have shown promising results in Ewing sarcoma. We did this phase Ib/II trial to first define the proper dose of irinotecan in combination with anlotinib in Ewing sarcoma and then evaluate efficacy. Methods: Patients diagnosed with recurrent or refractory Ewing sarcoma were enrolled and sub-classified into cohort A (≥16y) or cohort B ( &lt; 16y). In the dose-defining phase Ib portion, anlotinib was given at a fixed dose of 12mg D 1-14 every 21 days, while the de-escalated 3+3 design was used to detect the recommended dose of irinotecan in each cohort from an initial level of 20mg/m 2 /d dx5x2. Recommended phase 2 dose (RP2D) was defined as the highest dose at which no more than 30% patients experience a DLT in the first two courses. In the next dose-expanding phase II portion, the primary endpoint was objective response rate at 12 weeks (ORR 12w ). A conventional two-stage study design model was used. Results: 41 patients were enrolled with 29 in cohort A and 12 in cohort B. For cohort A, first 5 patients were treated at initial level in phase Ib portion, two of whom subsequently experienced delayed diarrhea as dose-limiting toxicity (DLT). Additional six patients were then treated at a lower dose of 15mg/m 2 . Since no more DLT was recorded, it was used as RP2D. 23/24 patients in cohort A phase II were available for response evaluation at 12 weeks, with one complete response (CR), 14 partial response (PR) (including one CMR who has a negative PET/CT scan but still abnormal lesions in MR scan), 2 stable disease (SD) and 6 progressive disease (PD). ORR 12w was 62.5%. For cohort B, no DLT was noticed in the first six patients treated at the initial level which was used as RP2D later. Finally, 12 patients were included in cohort B. ORR 12w was 83.3% with two CR, 8 PR (including one CMR) and two PD. Although effective, cohort B were closed because of slow enrollment. Most common grade 3/4 adverse events were diarrhea, abdominal pain and neutropenia. The genotype of UGT1A1*1 and UGT1A1*28 were not associated with the risk of diarrhea. Conclusions: The combination of irinotecan and anlotinib demonstrated an acceptable toxicity profile with promising evidence of clinical efficacy in advanced Ewing sarcoma. Clinical trial information: NCT03416517.
Trends in the Prevalence of Exposure to e-Cigarette Aerosol in Public Places Among US Middle and High School Students, 2015 to 2018
Authors: Andy S. L. Tan, Cabral A. Bigman, Susan Mello, Ashley Sanders-Jackson
Journal: JAMA Network Open (2019)

This survey study examines trends in and factors associated with exposure to secondhand smoke from combusted tobacco and secondhand aerosol from electronic cigarettes (e-cigarettes) among US youth from 2015 to 2018.
Apatinib plus camrelizumab (SHR-1210) for unresectable high-grade osteosarcoma (APFAO) progressing after chemotherapy: A prospective, open label, phase II trial.
Authors: Lu Xie, Wei Guo, Jie Xu, Xin Sun, Kuisheng Liu, Bingxin Zheng, Ting Ren, Yi Huang, Xiaodong Tang, Taiqiang Yan, Rongli Yang, Kunkun Sun, Danhua Shen, Yuan Li
Journal: Journal of Clinical Oncology (2019)

11013 Background: Results of previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. Given the recent success of immunotherapies, combinations of antiangiogenics with immune checkpoint blockers have become an attractive strategy. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy. Methods: We did this open-label phase 2 trial in Peking University People’s Hospital. We enrolled patients (≥14 years) with advanced osteosarcoma progressing after chemotherapy. Patients received 500 mg apatinib orally taken once daily plus 200 mg camrelizumab intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treatment. This trial is registered with ClinicalTrials.gov. (NCT03359018). Results: We enrolled 41 patients between January 1, and September 4, 2018. 20 (48.8%, 95%CI 32.8%-64.8%) of 41 patients were progression free at 6 months. Until final follow-up, the objective response rate was 21.95% (9/41). And the 6-m PFS rate and 4-m PFS rate were 54.32% (95% CI 37.62%-68.33%) and 70.00% (95% CI 53.24%–81.73%) respectively. Median PFS was 6.50 (95% CI 4.23–7.50) months while the median OS has not reached yet. And there were no statistical differences in the response rates or PFS between different PD-L1 expression groups ( P=0.153 and 0.231). Whereas target lesions with only pulmonary metastasis had obviously longer PFS than those lesions located at other places ( P &lt;0.001). We also summarized all those lesions’ progression patterns as follows: slow pulmonary lesions’ progression(N=7), stable disease with lung but new lesions outside lung(N=4) and bone lesions’ progression(N=13), of which we found that there was obvious difference in PFS ( P=0.009) between different progression groups.Toxic effects led to dose reductions, or short interruptions, or both in 20 (48.78%) of 41 patients. There were no treatment-related deaths. Conclusions: The combination of apatinib and camrelizumab obviously prolonged PFS than single apatinib in the treatment for patients with advanced osteosarcoma progressing after chemotherapy. Those with pulmonary metastatic lesions obviously had longer PFS. Whether patients benefit from overall survival needs further observation. Clinical trial information: NCT03359018.
Effect of pretreatment distress on daily fatigue after chemotherapy for breast cancer
Authors: S. C. Higgins, G. H. Montgomery, D. H. Bovbjerg
Journal: Journal of Clinical Oncology (2007)

9090 Background: Fatigue is one of the most frequently reported and aversive side effects of cancer chemotherapy. Prospective research has found that cancer patients’ levels of emotional distress prior to treatment are predictive of other side effects (e.g., nausea), but studies of such effects on fatigue are lacking. The present study prospectively tested the hypothesis that patients’ levels of emotional distress in the clinic prior to their first treatment infusion would predict the severity of their post-infusion fatigue. Methods: Sixty Stage I (32.6%) and II (67.4%) breast cancer patients (mean age=44.5 yrs), receiving standard outpatient chemotherapy (e.g., CMF), participated. The independent variable, emotional distress, was assessed (0–100) with a visual analog scale (VAS). The dependent variable, post treatment fatigue (PTF) was assessed (0–100) over each of the subsequent 6 days using end-of-day diaries, which also included assessment of distress (0–100). To explore temporal specificity, pretreatment distress was assessed for “last night”, “this morning” and “right now.” Results: Consistent with previous reports, PTF levels peaked at day 2 and began to decline after day 3, although they remained elevated across the period (p&lt;.026). Repeated measures analysis indicated a significant main effect of pretreatment distress “right now” on PTF (p&lt;.009); prior distress levels were less predictive. Additional regression analyses, controlling for pretreatment fatigue and daily distress, revealed a strongly selective effect of pretreatment distress on post peak PTF on days 5 (p&lt;.002) and 6 (p&lt;.026). Conclusions: This study is the first to demonstrate time-specific effects of pretreatment distress on PTF. Possible mechanisms of these effects now warrant investigation, as do possible benefits of brief interventions to reduce distress immediately prior to treatment. No significant financial relationships to disclose.
Permanent Percutaneous Carotid Artery Filter to Prevent Stroke in Atrial Fibrillation Patients
Authors: Vivek Y. Reddy, Petr Neuzil, Tom de Potter, Jan van der Heyden, Selma C. Tromp, Benno Rensing, Eva Jiresova, Libor Dujka, Veronika Lekesova
Journal: Journal of the American College of Cardiology (2019)

Patients with high stroke risk and atrial fibrillation who are unsuitable to oral anticoagulants (OACs) require other stroke prevention strategies. A novel permanent coil filter directly placed into both common carotid arteries (CCAs) was designed to capture emboli >1.4 mm in diameter.The multicenter, nonrandomized, first-in-human clinical CAPTURE (Carotid Artery Implant for Trapping Upstream Emboli for Preventing Stroke in Atrial Fibrillation Patients) trial sought to determine the feasibility and safety of bilateral CCA filter placement.Eligible patients had atrial fibrillation, CHA2DS2-VASc (Congestive heart failure, Hypertension, Age 75 years, Diabetes, Stroke/transient ischemic attack, Vascular disease, Age 65 to 74 years, Sex category) ≥2, OAC unsuitability, CCA size 4.8 to 9.8 mm, and no carotid stenosis >30%. Under ultrasound guidance, after direct transcutaneous carotid puncture with a 24-gauge needle, a motorized unit expels the filter to unfurl in the artery. Patients received aspirin/clopidogrel for 3 months, and aspirin thereafter. Primary endpoints were: 1) procedural success-bilateral, properly positioned CCA filters; and 2) 30-day incidence of major adverse events-death, stroke, major bleeding, filter migration, CCA thrombus, or stenosis. Carotid ultrasounds were conducted post-procedure, pre-discharge, at 1 week, and at 1, 3, 6, and 12 months.At 3 centers, 25 patients were enrolled: age 71 ± 9 years, CHA2DS2-VASc = 4.4 ± 1.0, prior embolism in 48%. Procedure success was 92% (23 of 25 patients); 1 patient had unilateral deployment. There were no device/procedure-related major adverse events; minor puncture site hematomas/edema occurred in 5 of 25 (20%). After 6-month mean follow-up, asymptomatic thrombi were detected in 4 patients (1 bilateral, 4 unilateral), adjudicated as captured (n = 3), unclassified (n = 2), or in situ (n = 0). In all patients, the thrombi dissolved with subcutaneous heparin. In 1 patient, 2 device/procedure-unrelated minor strokes occurred.Permanent carotid filter placement for stroke prophylaxis is technically feasible and safe. (Carotid Artery Implant for Trapping Upstream Emboli for Preventing Stroke in Atrial Fibrillation Patients [CAPTURE]; NCT03571789).
The European Group for Blood and Marrow Transplantation Risk Score Predicts Outcome of Elderly Patients with Allogeneic Stem Cell Transplantation for Acute Leukemia and Myelodysplastic Syndrome
Authors: Sheng-Hsuan Chien, Yao-Chung Liu, Chia-Jen Liu, Jin-Hwang Liu, Jyh-Pyng Gau, Tzeon-Jye Chiou
Journal: Blood (2017)
Nose and Throat Work for the General Practitioner.
Journal: JAMA (1904)

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Prediction of mortality benefit based on periodic repolarisation dynamics in patients undergoing prophylactic implantation of a defibrillator: a prospective, controlled, multicentre cohort study
Authors: Axel Bauer, Mathias Klemm, Konstantinos D Rizas, Wolfgang Hamm, Lukas von Stülpnagel, Michael Dommasch, Alexander Steger, Andrezej Lubinski, Panagiota Flevari, Markus Harden, Tim Friede, Stefan Kääb, Bela Merkely, Christian Sticherling, Rik Willems, Heikki Huikuri, Marek Malik, Georg Schmidt, Markus Zabel, Béla Merkely, Peter Perge, Zoltan Sallo, Gabor Szeplaki, Markus Zabel, Lars Lüthje, Simon Schlögl, Helge Haarmann, Leonard Bergau, Joachim Seegers, Gerd Hasenfuß, Pascal Munoz-Exposito, Tobias Tichelbäcker, Aleksandra Kirova, Tim Friede, Markus Harden, Marek Malik, Katerina Hnatkova, Marc Vos, Stefan N. Willich, Thomas Reinhold, Rik Willems, Bert Vandenberk, Magdalena Klinika, Krapinske Toplice, Panayota Flevari, Andreas Katsimardos, Dimitrios Katsaras, Robert Hatala, Martin Svetlosak, Andrzej Lubinski, Tomasz Kuczejko, Jim Hansen, Christian Sticherling, David Conen, Sestre Milosrdnice, Nikola Pavlović, Šime Manola, Ozren Vinter, Ivica Benko, Anton Tuinenburg, Axel Bauer, Christine Meyer-Zürn, Christian Eick, Jesper Hastrup, Josep Brugada, Elena Arbelo, Gabriela Kaliska, Jozef Martinek, Michael Dommasch, Alexander Steger, Stefan Kääb, Moritz F. Sinner, Konstantinos D. Rizas, Wolfgang Hamm, Nikolay Vdovin, Mathias Klemm, Lukas von Stülpnagel, Iwona Cygankiewicz, Pawel Ptaszynski, Krzysztof Kaczmarek, Izabela Poddebska, Svetoslav Iovev, Tomáš Novotný, Milan Kozak, Heikki Huikuri, Tuomas Kenttä, Ari Pelli, Jaroslaw D. Kasprzak, Dariusz Qavoq, Sandro Brusich, Ervin Avdovic, Marina Klasan, Jan Galuszka, Milos Taborsky, Vasil Velchev, Rüdiger Dissmann, Przemysław Guzik, Dieter Bimmel, Christiane Lieberz, Stefan Stefanow, Norman Rüb, Christian Wolpert, Lars S. Maier, Steffen Behrens, Zrinka Jurisic, Frieder Braunschweig, Florian Blaschke, Burkert Pieske, Zoran Bakotic, Ante Anic, Robert H.G. Schwinger, Pyotr Platonov
Journal: The Lancet (2019)
Accuracy of whole-genome sequencing to determine recent tuberculosis transmission: an 11-year population-based study in Hamburg, Germany
Authors: Roland Diel, Thomas A. Kohl, Florian P. Maurer, Matthias Merker, Karen Meywald Walter, Jörg Hannemann, Albert Nienhaus, Philip Supply, Stefan Niemann
Journal: European Respiratory Journal (2019)

<b>WGS typing with a five-SNP c:d:ut-off delineates recent transmission chains with highest accuracy and also provides high-resolution resistance patterns, thus enabling direct clinical benefits</b>http://bit.ly/2Pk37Wo