tbuckley/cabot-search huggingface dataset:
MOR202 alone and in combination with pomalidomide or lenalidomide in relapsed or refractory multiple myeloma: Data from clinically relevant cohorts from a phase I/IIa study.
Authors: Marc S. Raab, Manik Chatterjee, Hartmut Goldschmidt, Hermine Agis, Igor W Blau, Hermann Einsele, Monika Martha Engelhardt, Barbara Ferstl, Martin Gramatzki, Christoph Röllig, Katja Weisel, Pia Kloepfer, Dominika Weinelt, Jan Endell, Rainer Boxhammer, Christian Peschel
Journal: Journal of Clinical Oncology (2016)

8012 Background: MOR202, a HuCAL-derived, human IgG1 CD38 monoclonal antibody induces ADCC and ADCP as effector functions; preclinical models show high activity of single-agent MOR202 and synergy in combination with immunomodulatory drugs (IMiDs), lenalidomide (LEN) or pomalidomide (POM). Unlike other CD38 antibodies, MOR202 does not induce complement-dependent cytotoxicity thought to be a major contributor to infusion-related reactions (IRRs). Methods: This is aninterim analysis of a multicenter, dose-escalation phase I/IIa study of MOR202 in relapsed or refractory multiple myeloma (MM). Preliminarysafety and efficacy data from 3 cohorts of patients (pts) treated with MOR202 alone or with an IMiD are presented: MOR202 4, 8 and 16 mg/kg weekly; MOR202 8 or 16 mg/kg weekly with either LEN or POM. Primary objectives were to evaluate the safety, maximum tolerated dose (MTD)/recommended phase II dose of MOR202. Results: As of November 23, 17 pts were treated. Pts receiving MOR202 alone or with POM were relapsed/refractory to prior bortezomib and LEN with a median of 4 and 3 prior regimens respectively. Pts given MOR202 + LEN had a median of 2 prior regimens, mainly bortezomib, cyclophosphamide and autologous stem cell transplant. The MTD has not been reached. MOR202 alone or with an IMiD was well tolerated with mainly hematological toxicity. No MOR202-related study discontinuations or deaths were recorded. A 2-hour MOR202 infusion was feasible in all pts. IRRs (grade 1) were seen in only 1/17 pts. Responses were reported in 6/15 evaluable pts: 2 very good partial responses (VGPR) and 4 partial responses (PR) with 5/6 still ongoing. The longest duration of response was > 10 months in a pt given MOR202 alone; all 9 pts receiving MOR202 alone derived clinical benefit (1 VGPR, 2 PR and 6 stable disease). Preservation of high CD38 levels on MM cells under MOR202 therapy was shown. Conclusions: In this analysis, MOR202 given as a 2-hour infusion showed excellent infusion tolerability and overall safety profile. Promising preliminary efficacy and long-lasting tumor control was seen for MOR202 +/- IMiDs. Clinical trial information: NCT01421186.
TCT-596 Worsened Renal Function after Transcatheter Aortic Valve Replacement Increases Long-term Mortality
Authors: Ricardo Cigarroa, Vaiibhav Patel, Deborah Furman, Nishtha Sodhi, Jonathan Passeri, Gus Vlahakes, Ignacio Inglessis, Igor Palacios, Anna Vatterott, Brian Lindman, Sammy Elmariah
Journal: Journal of the American College of Cardiology (2018)
The impact of the ASCO Choosing Wisely campaign for breast and prostate cancer on physician behavior.
Authors: Danielle Lee Rodin, Pragya Kakani, Meredith Rosenthal, Anna Sinaiko
Journal: Journal of Clinical Oncology (2018)

6592 Background: In April 2012, ASCO published its Choosing Wisely (CW) list of low-value services not supported by clinical evidence. The effectiveness of this campaign in changing physician behavior in oncology remains unknown. Methods: Retrospective analysis of breast and prostate cancer patients diagnosed from 2010-2013 and contained in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Quarterly rates of imaging tests (positron emission tomography, computed tomography, bone scans) for staging in low-risk prostate cancer (T1-2a, Gleason < 7, PSA < 10 ng/mL) and for staging and post-treatment surveillance in early-stage breast cancer (AJCC I and II, N0, no neoadjuvant chemotherapy) was determined. Change in the proportion of patients receiving low-value tests before and after publication of the CW recommendations was evaluated using interrupted time series analysis. Tests were attributed to the specialty of the referring provider associated with the claim. Results: The cohorts consisted of 14,596 prostate, 43,591 breast staging, and 32,548 breast surveillance patients. Use of staging tests for prostate cancer was declining pre-CW (-0.52% per quarter) and experienced a small, but significant increase in the rate of decline post-CW to -0.79% per quarter, P = 0.0013; average utilization was 26.5% of patients pre-CW and 20.7% post. Use of surveillance imaging for breast cancer was stable pre-CW at 25.2%; it decreased post-publication by -0.61 percentage points per quarter (P < 0.001) to 21.3% post. No significant change in use of breast cancer staging was observed (-0.05% per quarter, P = 0.37), with an average rate of 10%. Low-value test orders by specialty presented in Table 1. Conclusions: Following CW, there was a modest change in some physician behaviors toward recommendations. Further multidisciplinary efforts coupled with incentives may be needed to educate providers on judicious use of imaging. Distribution of low-value tests by specialty. Surgeons Radiation Oncologists Medical Oncologists Primary Care Providers Other/ Unknown Prostate staging 63.9% 4.3% 1.6% 16.9% 13.2% Breast staging 44.7% 0.6% 17.8% 24.6% 12.4% Breast surveillance 8.3% 5.0% 25.0% 40.6% 21.1%
Abstract 14344: Be Heart Smart: A Statewide Prevention Program Delivered by Land-Grant Extension Educators
Authors: Karen S Yehle, Stephanie G Woodcox
Journal: Circulation (2016)

Introduction: Cardiovascular disease continues to be the leading cause of death. One-third of adults in Indiana have high blood pressure, nearly 40% have high cholesterol, and 66% are overweight or obese. Education about heart health is needed to make lifestyle changes to reduce the risk for heart disease. Time constraints in clinical settings are a barrier to providing education. The Cooperative Extension System housed at land-grant universities are a viable option to deliver preventative education statewide. Purpose: The purpose of this study was to develop, implement, and evaluate the impact of a heart disease prevention program by 1) examining changes in heart health knowledge of risk factors before and after four 60 minute face-to-face lessons taught by an Extension Educator, and 2) examining participants’ intentions to make lifestyle behavior changes based upon information learned (monitoring controllable risk factors, incorporating the DASH diet, physical activity and practicing stress reduction). ...
Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non–Small Cell Lung Cancer
Authors: Cesare Gridelli, Javier de Castro Carpeno, Anne-Marie C. Dingemans, Frank Griesinger, Francesco Grossi, Corey Langer, Yuichiro Ohe, Konstantinos Syrigos, Nick Thatcher, Ashis Das-Gupta, Matt Truman, Margarita Donica, Vlatka Smoljanovic, Jaafar Bennouna
Journal: JAMA Oncology (2018)

Bevacizumab treatment beyond progression has been investigated in breast and metastatic colorectal cancers. Avastin in All Lines Lung (AvaALL) is the first randomized phase 3 study of bevacizumab across multiple lines of treatment beyond progression in non-small cell lung cancer (NSCLC).To assess the efficacy and safety of continuous bevacizumab treatment beyond first progression in NSCLC.AvaALL was a randomized, open-label, phase 3b trial, conducted from 2011 to 2015 in 123 centers worldwide. Patients with nonsquamous NSCLC previously treated with first-line bevacizumab plus platinum-doublet chemotherapy and at least 2 cycles of bevacizumab maintenance were randomized (1:1) at first progression to receive bevacizumab plus standard of care (SOC) or SOC alone.Patients received bevacizumab (7.5 or 15 mg/kg intravenously every 21 days) and/or investigator's choice of SOC. For subsequent lines, patients treated with bevacizumab received SOC with or without bevacizumab; the SOC arm received SOC only.The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival from first to second (PFS2) and third progression (PFS3), time to second (TTP2) and third progression (TTP3), and safety.Between June 2011 and January 2015, 485 patients (median age, 63.0 years [range, 26-84 years]; 293 [60.4%] male) were randomized. Median OS was not significantly longer with bevacizumab plus SOC vs SOC alone: 11.9 (90% CI, 10.2-13.7) vs 10.2 (90% CI, 8.6-11.9) months (hazard ratio [HR], 0.84; 90% CI, 0.71-1.00; P = .104). Median PFS2 was numerically longer with bevacizumab plus SOC vs SOC alone: 5.5 (90% CI, 4.2-5.7) vs 4.0 (90% CI, 3.4-4.3) months (HR, 0.83; 90% CI, 0.70-0.98; P = .06). Median PFS3 appeared longer with bevacizumab plus SOC vs SOC alone: 4.0 (90% CI, 2.9-4.5) vs 2.6 (90% CI, 2.3-2.9) months (HR, 0.63; 90% CI, 0.49-0.83), as did TTP2 and TTP3. Grade 3/4 adverse events were more frequent with bevacizumab plus SOC (186 [76.5%]) vs SOC alone (140 [60.3%]). No new safety signals were observed.The primary end point was not met; however, OS was underpowered according to initial statistical assumptions. Continued therapy beyond first progression led to improved PFS3 (but not PFS2), TTP2, and TTP3. Although a result with P = .06 for PFS2 would conventionally be considered significant at a specified 2-sided α of .10, in the absence of adjustments for multiplicity, this result could be a chance finding. No new safety signals were identified with bevacizumab treatment beyond progression.clinicaltrialsregister.eu Identifier: 2010-022645-14; ClinicalTrials.gov identifier: NCT01351415.
Immunotherapy for advanced non-small cell lung cancer (NSCLC): Experience at Louis Stokes Cleveland VA Medical Center (LSCVAMC).
Authors: Paige Sinclair, Charles John Nock, Chris Burant, Candice Wenzell
Journal: Journal of Clinical Oncology (2018)

e21148 Background: Utilization of immunotherapy in the veteran population with lung cancer is not well described. The purpose of this study was to evaluate the use of nivolumab (nivo) versus chemotherapy (chemo) in veterans with previously treated advanced NSCLC at LSCVAMC. Methods: This retrospective chart review included veteran subjects with stage IIIB or IV NSCLC who received at least one dose of nivo or chemo at LSCVAMC following disease recurrence after at least one prior platinum-containing chemo regimen from January 1, 2010 to August 31, 2017. Subjects who received immunotherapy as 1st line (1L) or received more than 4 lines of chemo were excluded. Subjects who received nivo were matched 1:1 to patients who received chemo based on the line of therapy nivo was used (index therapy). The primary endpoint was overall survival (OS) percentage at 1 year following start of index therapy. Secondary endpoints included overall response rate, incidence of adverse events, and rate of discontinuation of treatment due to adverse events. Results: There were 98 subjects (49 nivo, 49 chemo) included. Histology was squamous in 49%, adenocarcinoma in 45%, and other in 6%. The index therapy was 2L in 61 subjects, 3L in 33 subjects, and 4L for 4 subjects. In nivo and chemo groups, ECOG = 1 in 42 and 15 subjects and ECOG = 2 in 8 and 12 subjects, respectively, and not documented in 12 subjects in chemo group. OS at 1 year was 32% in the nivo group and 16% in the chemo group. Treatment discontinuation due to adverse events occurred in 12% in the nivo group and 41% in the chemo group. Conclusions: The percentage of subjects alive at 1 year was higher in the nivo group compared to chemo group. OS rates found in this study were lower than previously published studies. This may be related to the high number of subjects with squamous histology, ECOG 2, and evaluation of subjects receiving index therapy as 3L or 4L.
A phase I study to evaluate the pharmacokinetics of a new oncology nce, apatinib mesylate tablets, with and without food following single and multiple doses in healthy subjects.
Authors: Luana Pesco Koplowitz, Barry Koplowitz, Cheol Hee Park, Arlo N. McGinn
Journal: Journal of Clinical Oncology (2017)

e14049 Background: Apatinib Mesylate (YN968D1) is a selective inhibitor of VEGFR-2 being developed for the treatment of advanced gastric cancer. Objectives: 1. Evaluate single- and multiple-dose PKs 2. Evaluate food effect on bioavailability 3. Evaluate dose-proportionality 4. Determine CYP3A4 and 2C19 metabolic effects on the PKs Methods: Single ascending-dose (SAD), open-label, crossover of 2 oral doses of apatinib mesylate tablets (100 mg and 250 mg, [81 mg and 201 mg apatinib]) in healthy male and female volunteers with a minimum 3-day washout between dosing, plus a multiple ascending-dose (MAD), open-label, crossover study of the same doses. Both doses were administered with and without food in a crossover for the SAD and MAD parts. PK blood samples were collected for each dosing period. Subjects were genotyped for CYP3A4 and CYP2C19. WinNonlin 6.4 used for analysis. Results: 24 male and female subjects completed the SAD study section. They were extensive or intermediate metabolizers of CYP2C19, and 23/24 were normal metabolizers of CYP3A4. 22 male and female subjects completed the MAD study section. Most were extensive, intermediate or ultra-rapid metabolizers of CYP2C19; 21/22 subjects were normal metabolizers of CYP3A4. Conclusions: For the 100 mg dose in the SAD and MAD parts of the study, there was no significant food effect. For the 250 mg dose in SAD and MAD parts, food appeared to increase bioavailability by 20–30% in the SAD part, and 30–40% in the MAD part. Noncompartmental PK analysis of the SAD and MAD showed medium t max value delayed at 2 doses when apatinib was administered with food. Compartmental PK analysis showed food delayed initiation in absorption and reduced first order absorption rate constant. Dose proportionality was confirmed only for the AUC 0-∞ value from the SAD-fasted cohort but inconclusive for C max and AUC parameters under other dosing regimens. Visual inspection of the effect of CYP2C19 genotype on the clearance of apatinib did not show correlation. Inspection of CYP3A4 genotype on the calculated clearance values was tenuous given the intermediate metabolizers (N = 1), compared to extensive metabolizers.
HEALTH-RELATED QUALITY OF LIFE IN OBESITY HYPOVENTILATION SYNDROME (OHS) PRIOR TO INITIATION OF HOME MECHANICAL VENTILATION (HMV)
Authors: P. Murphy, K. Brignall, A. Williams, C. Davidson, M. Hind, A. Simonds, J. Moxham, M. Polkey, N. Hart
Journal: Thorax (2009)
What is the outcome of receiving subsequent therapy among patients (pts) with advanced/metastatic (Adv/Met) gastric or gastroesophageal junction cancer (GC/GEJC)? Experience from electronic health records (EHR).
Authors: Dung T. Le, Yelena Yuriy Janjigian, Patrick Alexander Ott, Beata Korytowsky, Hannah Le, Trong Kim Le, Ying Zhang, Gregory Maglinte, Dhiren Patel, Tong Shangguan, Ian Chau
Journal: Journal of Clinical Oncology (2018)

e16023 Background: The 5-year survival rate for adv/met GC/GEJC is about 5%. First- and second-line (1L, 2L) therapies have modest clinical efficacy and limited options for later lines. This study explored real-world treatment patterns and outcomes for adv/met GC/GEJC across lines of therapy (LOT). Methods: Adult pts with adv/met GC/GEJC in the Flatiron Health EHR database from 01Jan2011-30Nov2017 were selected. The index date was the date of adv/met diagnosis. Median overall survival (OS) for each LOT, estimated by Kaplan-Meier method, was calculated from the initiation of first observed treatment for each line to death. Duration of therapy (DOT) was time from start date to the end date of each LOT. Results: Of 2,952 pts with adv/met GC/GEJC adenocarcinoma, 770 pts (26%) received no treatment; 2,182 pts (74%) received 1L; of which, 936 pts (43%) had 2L, 396 pts (18%) had 3L, and 154 pts (7%) had 4L+. Median age was 68 years, 56% were white, 52% had stage IV as initial diagnosis, primary site for 56% was GC, 35.5% had ECOG performance status of ≥2, and 20% had HER2+ tumors. Among HER2+ pts, 298 pts (81%) received treatment; and 60 pts (20%) received treatments other than trastuzumab. In 1L, the 3 most frequently used regimens were FOLFOX/CAPEOX (23.6%), carboplatin+paclitaxel (CAR+PAC) (15.7%), and EOX (4.9%). In 2L, regimens were PAC+ramucirumab (RAM) (15.9%), FOLFOX/CAPEOX (14.2%), and FOLFIRI (5.8%). There were no consistent treatments in 3L and later LOTs consisted of sporadic use of PAC+RAM, RAM monotherapy, and irinotecan. Median survival was ~10.6 months in pts from 1L start, 7.5 months in 2L, 6.2 months in 3L, and 2.8 months in 4L+, with median DOT of 2 months across all LOTs. The recent use of immunotherapy accounts for 3.3% (n = 73) across all LOTs. Conclusions: Treatment patterns in US community-based practices showed that over 25% of adv/met GC/GEJC pts remained untreated and the majority of 1L pts never received subsequent therapy. Furthermore, pts progressed quickly on each line, leading to poor outcomes. These data signal the need for more effective treatment options, especially in later lines of therapy.
Abstract 14565: Prediction of Sudden Cardiac Death in Patients With Chronic Heart Failure by the Combination of the Cardiac MIBG Global Washout Rate and Regional Washout Rate Dispersion
Authors: Hironori Yamamoto, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Kentaro Ozu, Takumi Kondo, Kaoruko Sengoku, Tsutomu Kawai, Satoshi Takahashi, Masashi Ishimi, Hideyuki Hakui, Masatake Fukunami
Journal: Circulation (2013)

Background: Cardiac MIBG imaging, which has been mainly evaluated on the planar images, provides prognostic information in patients with chronic heart failure (CHF). The identification of CHF pts a...
Cancer survivorship in hematologic malignancies: Lifestyle changes after diagnosis.
Authors: Pannaga G. Malalur, Manas Agastya, Sandhya Wahi-Gururaj, Chad L Cross, Delva Deauna-Limayo, Edwin Kingsley
Journal: Journal of Clinical Oncology (2018)

e22089 Background: Studies show that patients make lifestyle changes soon after certain solid tumor diagnoses, suggesting that this may be a teachable moment to motivate and promote healthy behaviors. This study aims to determine if the diagnosis of hematologic malignancies has a similar impact. Methods: We surveyed a sample of 113 patients at a community oncology center and requested them to complete anonymous questionnaires addressing lifestyle choices on smoking, alcohol consumption, recreational drug use, diet, and exercise habits before and after diagnosis of a hematologic malignancy. We also inquired about support systems utilized such as psychiatry services. Data distributional assumptions were examined using the Shapiro-Wilk test and by visual examination of measures of skewness and kurtosis. Paired-samples t-test were used for analyses of continuous data; categorical responses were analyzed using the McNemar-Bowker test. Results: Patients exhibited significant reduction in smoking, (Χ2 = 31.0, p < 0.001) with 82.4% of one pack per day smokers quitting after diagnosis, and nearly all smokers at least reducing the amount smoked. There was also a significant decrease in the total number of smoking years for patients (mean reduction = 4.1 years, p = 0.023). Alcohol use overall did not differ significantly (Χ2 = 10.6, p < 0.102). However, 10.3% of patients reported complete alcohol abstinence after diagnosis. Changes in diet and exercise were not statistically significant overall. 16.5% of patients reported seeing a psychiatrist before diagnosis; of these patients, 47.1% stopped thereafter (not statistically significant). Having external support systems correlated with improved diet as well as decrease in total smoking years. Conclusions: This study demonstrates that patients exhibited positive lifestyle changes after being diagnosed with a hematologic malignancy. Clinicians should take advantage of this ‘teachable moment’ at the time of diagnosis to educate patients about beneficial health behavior changes. As advances in cancer therapeutics have led to an increase in cancer survivors, this education is crucial in reducing the risk of developing chronic comorbidities as well as secondary malignancies.
Factors associated with delayed diagnosis and treatment in patients with cancer.
Authors: Ilker Nihat Okten, Bilge Aktas Sezen, Ulug Mutlu Gunaydin, Sinan Koca, Turkan Ozturk, Hasan Tahsin Ozder, Mahmut Gumus
Journal: Journal of Clinical Oncology (2018)

e22141 Background: Different studies have shown that diagnosis and treatment delays in malignant diseases has an adverse effect on quick progression of the disease. Particularly, in cases where screening programs are not sufficient, success of cancer treatment is expected to be low. We investigated the reasons of delay in diagnosis and the duration until the start of first treatment in the patients who applied to our center, to define if there is a lack of management on proper time and to guide improving early diagnosis and treatment. Methods: Ninty patients who were referred to our center with different cancer diagnoses were interviewed face-to-face. We asked the starting time of complaints regarding their cancer, the duration of appliance to the hospital and the reason of delay until first management if there is. We also investigated the period of time from diagnosis to treatment. Results: Sixty-two percent of our patients were female and median age was 61 (25-92). The median time between the first complaints and histopathological diagnosis was 51.5 days (1-700).The median duration of histopathological examination was 12 (1-41) days and the median time between pathological diagnosis to treatment was 26 (1-118) days. 17% of the patients were diagnosed with routine screening programs. The disease was diagnosed at an earlier stage in patients who were screened properly than who were not, despite no statistical significance (p: 0.127). Screening rates were higher in women compared to men (p: 0.041). In our patients, the diagnostic delay was due to ignorance (52.2%), loss of time in reaching early diagnosis and treatment methods (43.5%), fear of having any kind of disease (2.2%), and alternative and complementary medicine use (2.2%). The delay was longer in patients with subjective complaints (pain, weakness) than the ones with objective complaints (mass, bleeding) (0.017). Conclusions: Ignorance of complaints was the major reason in diagnostic delay. Screening rates were also found to be lower than expected. Raising awareness in both areas and improving access to medical facilities may contribute to early detection of cancer and effective treatment.