tbuckley/cabot-search huggingface dataset:
Variability in treatment choice among patients with breast, colorectal and lung cancer.
Authors: John Barron, Ralph A. Quimbo, Fang Tian, Jennifer Malin, Gayathri Sridhar, Anna Wallace, Nandini Selvam, Vincent J Willey
Journal: Journal of Clinical Oncology (2016)

6539 Background: The proliferation of novel treatment options has placed an increased emphasis on our need to better understand the variability in treatment choice and treatment patterns in oncology. The objective of this study was to characterize the variability in cancer treatment patterns for breast, colorectal and lung cancer. Methods: Pre-authorization requests for chemotherapy and/or targeted cancer treatments were utilized to identify breast, colorectal and lung cancer patients between 6/1/2014 and 4/30/2015 within the integrated clinical oncology and administrative claims data of the HealthCore Integrated Research Environment (HIRE) - Oncology. The earliest pre-authorization date was assigned as the index date. Demographics were evaluated by cancer type. Clinical characteristics and treatment patterns were assessed by cancer type and line of treatment. Results: 3,116 breast, 1,241 colorectal and 1,200 lung cancer patients were identified with mean ages of 52.6± 9.9, 55.5±9.3 and 60.3±8.1 years, respectively. Stage IV was most prevalent among colorectal (67%) and lung (74%) cancer patients and stage II among breast cancer patients (36%). Across breast (82%), colorectal (72%) and lung (74%) cancers, 1st line therapy represented the majority of pre-authorization requests. Among breast cancer patients, the most common 1st, 2nd and +3rd line therapies were docetaxel/cyclophosphamide (17%), fulvestrant (20%) and eribulin (18%), respectively. Among colorectal cancer patients, the most prevalent 1st, 2nd, and +3rd line therapies were fluorouracil/leucovorin/oxaliplatin (35%), fluorouracil/leucovorin/irinotecan/bevacizumab (29%), and irinotecan/cetuximab (20%), respectively. In lung cancer, the most common 1st, 2nd and +3rdline therapies were pemetrexed/carboplatin (19%), docetaxel (20%) and gemcitabine (20%). Conclusions: There was extensive variation in treatment patterns among breast, colorectal and lung cancer patients, particularly within 1st line therapy which represented the majority within each cancer type. This study provides initial insight on the relative generalizability of treatments requested by physicians participating within Anthem’s CCQP.
ECHO-305/KEYNOTE-654: A phase 3, randomized, double-blind study of first-line epacadostat plus pembrolizumab vs pembrolizumab plus placebo for metastatic non–small cell lung cancer (mNSCLC) with high PD-L1 levels.
Authors: Mark M. Awad, Mihaela Munteanu, Yufan Zhao, Lu Xu, Ayman Samkari, Luis G. Paz-Ares
Journal: Journal of Clinical Oncology (2018)

TPS9109 Background: The indoleamine 2,3-dioxygenase 1 (IDO1) intracellular enzyme and PD-1 receptor both suppress T-cell–mediated antitumor immunity, are coexpressed in multiple tumor types, and are correlated with poor prognosis. Epacadostat (E) is a potent and highly selective oral inhibitor of IDO1. Pembrolizumab (P; PD-1 inhibitor) is the standard of care for treatment-naive mNSCLC with high PD-L1 expression (tumor proportion score [TPS] ≥50%) and no EGFR or ALK genomic aberrations. Because encouraging activity and minimal additive toxicity were previously observed with E + P in mNSCLC in the phase 1/2 ECHO-202/KEYNOTE-037 study, this phase 3 global trial (NCT03322540) was initiated to compare E + P vs P + E-matched placebo as first-line treatment for patients with PD-L1 high mNSCLC. Methods: Eligible patients: aged ≥18 years, stage IV NSCLC (no EGFR-sensitizing mutation or ROS1/ALK translocations), TPS ≥50%, ECOG PS ≤1, no prior systemic therapy for mNSCLC, and no prior IDO1 inhibitors or immune checkpoint therapies. Approximately 588 patients will be randomized 1:1 to E 100 mg oral BID + P 200 mg IV Q3W or P + E-matched placebo, and stratified by tumor histology (squamous vs nonsquamous), ECOG PS (0 vs 1), and geographical location (East Asia vs non–East Asia). Patients receive treatment until disease progression, intolerable toxicity, investigator/patient decision to withdraw, or until they have received up to 35 cycles of E + P or P + placebo (~2 years). Eligible patients may continue study treatment beyond initial radiographic progression. Patients may discontinue treatment after confirmed complete response. Primary endpoints include PFS and OS. Secondary endpoints include ORR, duration of response, safety, and tolerability. Exploratory endpoints include patient-reported outcomes, E pharmacokinetics, pharmacodynamics, and potential relationship between baseline biomarkers and clinical activity (PFS, OS, ORR). Tumor response will be assessed by a blinded central review, per RECIST v1.1 criteria. Adverse events will be monitored throughout the study and graded per CTCAE v4.0. Clinical trial information: NCT03322540.
A pilot trial assessing apatinib combined with docetaxel (DTX) as second-line chemotherapy for EGFR negative advanced non-small-cell lung cancer (NSCLC).
Authors: Yong Song
Journal: Journal of Clinical Oncology (2018)

e21113 Background: Apatinib is a new tyrosine kinase inhibitor against vascular endothelial growth factor receptor 2 and improves outcomes in patients (pts) with metastatic gastric cancer as a third line of treatment. Recently, it has been reported effective as third- or later-line treatment in advanced NSCLC. This prospective study tried to assess the efficacy and safety of apatinib combined with DTX as second-line treatment of EGFR negative NSCLC. Methods: In this open-label single-arm study, pts recived oral apatinib (500mg, p.o. qd) with DTX(60mg/m2, i.v. d1 q3w) as second-line therapy. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the RECIST 1.1. Treatment was continued until disease progression, death, or intolerable toxicity. Results: Between September 2016 and December 2017, 25 pts were enrolled. In 25 pts, there were 19 pts available for efficiency evaluation and 24 pts available for safety evaluation. In the first evaluation of efficacy at one month, computed tomography scan evaluation revealed that partial response (PR) occurred in 7 of 19 pts and other 12 showed stable disease (SD). The objective response rate was 36.84% and disease control rate was as high as 100.00%. Most of the adverse reactions (AEs) were at grade 1 or 2. The grade 3 AEs were hypertension (n = 5, 20.83%), hand-foot syndrome (n = 2, 8.33%), diarrhea (n = 1, 4.17%), mouth ulceration (n = 3, 12.5%), thrombocytopenia (n = 1, 4.17%). No grade 4 AE or drug-related mortality occurred. Conclusions: Apatinib has a potential application prospect in second-line therapy combined with DTX for EGFR negative NSCLC pts. The research team will continue the study. Clinical trial information: ChiCTR-OPN-15007034.
TCT-707 A Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus Eluting Stent in the Treatment of Subjects with up to two de novo Coronary Artery Lesions – BIOFLOW IV: 3 Year Clinical Results
Authors: Ton Slagboom, Ralph Toelg, Bernhard Witzenbichler, Michael Haude, Monica Masotti, Rafael Jose Ruiz-Salmeron, Adam Witkowski, Ron Waksman, Shigeru Saito
Journal: Journal of the American College of Cardiology (2018)
Predictive plasma proteomic biomarkers of immunotherapy toxicity in patients (pts) with metastatic melanoma (MM).
Authors: Meghan Mooradian, Xuesong Gu, Donald P. Lawrence, Justine Vanessa Cohen, Tatyana Sharova, Genevieve Marie Boland, Towia A. Libermann, Ryan J. Sullivan
Journal: Journal of Clinical Oncology (2018)

e21569 Background: Mechanisms underlying immune checkpoint inhibition (ICI) efficacy and toxicity have yet to be fully elucidated and, to date, there are no reliable biomarkers predictive of the development of immune-related adverse events (irAEs) or efficacy. Methods: Pts with MM who developed select irAEs (colitis, hepatitis and arthritis) while receiving ICI (anti-PD-1, anti-CTLA-4 or combination anti-PD-1/CTLA-4) were identified. Using SOMAscan (SomaLogic; Boulder, CO), a proteomics platform that enables measurement of 1,305 proteins, quantitative plasma protein profiles were generated from banked plasma samples to identify candidate protein biomarkers predictive of irAEs and of progression-free survival (PFS). Comparator samples from pts without toxicity served as matched controls. Baseline protein expression was assessed and in evaluable pts, change in protein expression pre- and post-treatment was performed. PFS data was captured. Results: 36 pts were tested; 28 with confirmed irAEs and 8 controls. Baseline expression of IL-17, CXCL10 and TGFb1 was associated with irAE development. Baseline IL-17 and CXCL10 expression was especially prominent in cases of ICI-induced arthritis, whereas TGFb1 was linked to both ICI-induced arthritis and colitis. Independent ELISA validation studies of the candidate biomarkers are underway and will be presented. The one-year PFS of the toxicity cohort was 54% and 65% in those treated with PD-1 inhibition +/- anti-CTLA-4, respectively. Elevated TGFb1, as well as LGALS3 and DLL4, were associated with poorer outcomes. Conclusions: This study demonstrates the feasibility of SOMAscan to identify potential biomarkers of toxicity and outcome. Previous literature has linked IL-17 and CXCL10 in autoimmunity, and TGFb1 with a more pleiotropic role in immune regulation and melanoma pathogenesis. Our findings illustrate their possible role in the development of irAEs and outcome. If confirmed to be mechanistically involved in irAEs, targeted inhibitors of these proteins may serve as effective methods to abrogate or even prevent ICI-induced toxicity without compromising efficacy.
Mutational processes shape the landscape of TP53 mutations in human cancer
Authors: Andrew O. Giacomelli, Xiaoping Yang, Robert E. Lintner, James M. McFarland, Marc Duby, Jaegil Kim, Thomas P. Howard, David Y. Takeda, Seav Huong Ly, Eejung Kim, Hugh S. Gannon, Brian Hurhula, Ted Sharpe, Amy Goodale, Briana Fritchman, Scott Steelman, Francisca Vazquez, Aviad Tsherniak, Andrew J. Aguirre, John G. Doench, Federica Piccioni, Charles W. M. Roberts, Matthew Meyerson, Gad Getz, Cory M. Johannessen, David E. Root, William C. Hahn
Journal: Nature Genetics (2018)
Predicting venous thromboembolism in hospitalized cancer patients: a risk assessment tool.
Authors: Rushad Patell, Lisa A. Rybicki, Paul Elson, Shiva Shrotriya, Keith McCrae, Alok A. Khorana
Journal: Journal of Clinical Oncology (2016)

6598 Background: Quality panels and regulators have focused on inpatient venous thromboembolism (VTE) as a priority preventable illness. VTE is very prevalent in cancer but risk varies, predictors are incompletely understood and prophylaxis is inconsistently administered. A previously validated risk tool [Khorana Score, KS] can identify VTE risk in cancer outpatients with 5 easily available variables (cancer site, hemoglobin, platelet and leucocyte counts and BMI). We evaluated the utility of KS in predicting risk of VTE in hospitalized cancer patients. Methods: We conducted a retrospective cohort study of consecutive adults admitted to general oncology at Cleveland Clinic from 2013-14 (n = 3531). Patients were excluded for VTE on admission (n = 304), incomplete KS data (n = 439) or other reasons (n = 6). Data collected included demographics, BMI, cancer type, length of stay (LOS), use of anticoagulants and baseline laboratory values (+48 hours). Univariate risk factors were identified with logistic regression analysis. Multivariable risk factors were identified with stepwise logistic regression, confirmed with bootstrap analysis. Results are summarized as odds ratio (OR) and 95% confidence interval (CI). Results: The study population comprised 2,782 patients of whom 108 (4%) developed VTE during hospitalization. Median age was 62 (range, 19-98) years and 56% male. Median LOS was 5 (range, 0-152) days. In univariate analysis, male sex (OR 1.68, 95% CI 1.11-2.53), low hemoglobin (1.49, 1.01-2.19), elevated leukocytes (1.91, 1.28-2.84), BMI ≥ 35 kg/m2(1.69, 1.04-2.76), KS ≥ 3 ( 2.23, 1.16-4.28), anticoagulant use (0.55, 0.38-0.81) and increased LOS (1.39, 1.32-1.48) were associated with VTE. In multivariable analysis, only KS ≥ 3 (2.54 1.29-5.03), male sex (1.89, 1.23-2.9) and increased LOS (1.4, 1.32-1.49,) were predictive of VTE. Recursive partitioning analysis suggested optimal cut point to predict VTE was KS ≥ 2 (1.73, 1.16-2.59). Conclusions: This is the first report to validate KS as a risk tool to predict VTE in hospitalized cancer patients and suggests that a cut-off score of ≥ 2 is optimal. Using this tool to identify high-risk patients could lead to more consistent and successful application of thromboprophylaxis.
Role of type 2A phosphatase regulatory subunit B56α in regulating cardiac responses to β-adrenergic stimulation in vivo
Authors: Sarah-Lena Puhl, Kate L Weeks, Alican Güran, Antonella Ranieri, Peter Boknik, Uwe Kirchhefer, Frank U Müller, Metin Avkiran
Journal: Cardiovascular Research (2018)

Abstract Aims B56α is a protein phosphatase 2A (PP2A) regulatory subunit that is highly expressed in the heart. We previously reported that cardiomyocyte B56α localizes to myofilaments under resting conditions and translocates to the cytosol in response to acute β-adrenergic receptor (β-AR) stimulation. Given the importance of reversible protein phosphorylation in modulating cardiac function during sympathetic stimulation, we hypothesized that loss of B56α in mice with targeted disruption of the gene encoding B56α (Ppp2r5a) would impact on cardiac responses to β-AR stimulation in vivo. Methods and results Cardiac phenotype of mice heterozygous (HET) or homozygous (HOM) for the disrupted Ppp2r5a allele and wild type (WT) littermates was characterized under basal conditions and following acute β-AR stimulation with dobutamine (DOB; 0.75 mg/kg i.p.) or sustained β-AR stimulation by 2-week infusion of isoproterenol (ISO; 30 mg/kg/day s.c.). Left ventricular (LV) wall thicknesses, chamber dimensions and function were assessed by echocardiography, and heart tissue collected for gravimetric, histological, and biochemical analyses. Western blot analysis revealed partial and complete loss of B56α protein in hearts from HET and HOM mice, respectively, and no changes in the expression of other PP2A regulatory, catalytic or scaffolding subunits. PP2A catalytic activity was reduced in hearts of both HET and HOM mice. There were no differences in the basal cardiac phenotype between genotypes. Acute DOB stimulation induced the expected inotropic response in WT and HET mice, which was attenuated in HOM mice. In contrast, DOB-induced increases in heart rate were unaffected by B56α deficiency. In WT mice, ISO infusion increased LV wall thicknesses, cardiomyocyte area and ventricular mass, without LV dilation, systolic dysfunction, collagen deposition or foetal gene expression. The hypertrophic response to ISO was blunted in mice deficient for B56α. Conclusion These findings identify B56α as a potential regulator of cardiac structure and function during β-AR stimulation.
Factors associated with follow-up physician visits among women with early stage breast cancer.
Authors: Farah Quyyumi, Melissa Kate Accordino, Donna Buono, Alfred Neugut, Grace Hillyer, Jason Dennis Wright, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2018)

6531 Background: In patients with early stage breast cancer (BC), follow-up guidelines vary widely among national organizations. ASCO recommends clinical examination every 3-6 months for 3 years, every 6-12 months for the next 2 years, and then annually. We sought to evaluate patterns and predictors of provider follow-up care within the first five years following diagnosis. Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset, we evaluated patients diagnosed with stage I-II BC who underwent lumpectomy from 2002-2007 with follow-up to 2012. Patients who died in the 5 years following diagnosis were excluded. We defined discontinuation of follow-up care as > 12 months without a visit claim from either a surgeon, medical oncologist (MO) or radiation oncologist (RO). We performed a multivariate logistic regression analysis to determine factors associated with discontinuation. Patients were censored if a new cancer was diagnosed. Results: A total of 30,053 BC patients were included in the analysis. In addition to the surgeon, 85.8% saw a MO, 71.9% saw a RO, and 65.8% saw all 3 providers in the first year. The mean number of total visit claims for years 2-5 were 4.2, 3.1, 2.5 and 2.1, respectively. During the 5 years, 6,302 (21.0%) patients discontinued follow-up visits. Discontinuation increased with increasing age. Women with a higher stage cancer were less likely to discontinue follow-up (OR 0.78, 95% CI 0.73-0.83). Patients with a low grade tumor were more likely to discontinue follow-up compared to those with a high grade cancer (OR 1.09, 95% CI 1.02-1.18). For every year of diagnosis, patients were 3% less likely to discontinue seeing all three physicians. Hormone status, race, SES and marital status were not associated with discontinuation of follow-up visits. Conclusions: Clinical practice guidelines for surveillance of BC after diagnosis are based on expert opinion and have an unclear effect on outcomes. Coordination of follow-up care between oncology specialists may reduce discontinuation rates and increase clinical efficiency. More research is needed to determine the optimal follow-up for maintaining adherence to therapy, reducing over-testing and decreasing cost.
Implementation of a disease specific survivorship program for men with prostate cancer and their partners.
Authors: Celestia S. Higano, Phil Pollock, Richard J Wassersug, Christine Zarowski, Marcy Dayan, Sarah Weller, Cheri Van Patten, Stacy Elliott, Monita Sundar, Sarah Mahovlich, Erik Wibowo, Martin Gleave, Peter Black, Alan So, Larry Goldenberg
Journal: Journal of Clinical Oncology (2016)

e21569 Background: Treatment for localized prostate cancer (PC) can adversely impact the quality of life for the patient (pt) and his partner. Addition of androgen deprivation therapy (ADT) when indicated can result in further symptoms. We hypothesized that PC pts and partners would benefit from a clinical, educational, research-based approach that would focus on their specific needs. Methods: A multi-disciplinary survivorship program, the Prostate Cancer Supportive Care (PCSC) Program, was established in the Vancouver Prostate Centre with funding from government agencies and philanthropic sources in January 2013. The program was originally organized around 5 thematic modules: information about PC and primary treatment options (TX); sexual health and intimacy (SH); lifestyle changes in diet and exercise (DE); managing the side effects of ADT; incontinence and pelvic floor physiotherapy (PT). In late 2015, a psycho-oncology (PO) module was initiated to address emotional needs of patients and their partners. Group educational sessions for each module are held 1-2 times monthly and individual clinic appointments with SH, PT, PO and DE clinicians are also available. Urologists, radiation oncologists, primary care physicians, nurses and pharmacists refer pts to PCSC. Results: Of 917 pts who enrolled (167 in 2013; 369 in 2014; 281 in 2015), 741 (81%) chose to participate in at least one module (TX, 28%; SH, 65%; DE, 20%; ADT, 15%; PT, 37%). Median age at enrollment was 66 yrs (range 42 to 92); 51.6% enrolled within 12 months of diagnosis. Feedback from couples, participating clinicians, and allied health personnel has been overwhelmingly positive. In addition, the PCSC population is proving to be a rich source of pts for research projects and training opportunities for young MDs. Conclusions: The results demonstrate that implementation of a PC specific survivorship program is feasible, well received and has other unanticipated benefits. SH and PT are the most commonly utilized services. Newly obtained funding will extend PC supportive care services to additional sites in BC. Since SH and PT expertise are not widely available across BC, training programs that focus in these areas for PC are in development.
Updated efficacy and safety of KEYNOTE-052: A single-arm phase 2 study investigating first-line pembrolizumab (pembro) in cisplatin-ineligible advanced urothelial cancer (UC).
Authors: Jacqueline Vuky, Arjun Vasant Balar, Daniel E. Castellano, Peter H. O'Donnell, Petros Grivas, Joaquim Bellmunt, Thomas Powles, Dean F. Bajorin, Noah M. Hahn, Ronald De Wit, Mary Savage, Lei Pang, Tara L. Frenkl, Stephen Michael Keefe, Elizabeth R. Plimack
Journal: Journal of Clinical Oncology (2018)

4524 Background: Based on initial results from the phase 2 KEYNOTE-052 study (NCT02335424), pembro was approved for the treatment of cisplatin-ineligible patients with advanced UC. The results of the long-term follow-up analysis of KEYNOTE-052 are presented. Methods: Eligible patients were cisplatin ineligible (ECOG PS 2, CrCl ≥30 to <60 mL/min, grade ≥2 neuropathy/hearing loss, NYHA Class 3 heart failure), had advanced UC, and had received no prior chemotherapy for metastatic disease. Patients received pembro 200 mg IV Q3W for up to 24 months. Imaging was performed at wk 9, then Q6W for 12 months, and Q12W thereafter. The primary end point was confirmed ORR (RECIST v1.1, independent central review). Results: Efficacy and safety were assessed in 370 patients. Median age was 74 years; 10.8% of patients were ≥85 years old; 42.2% were ECOG PS 2; and 85.1% had visceral disease. As of the Nov 30, 2017, data cutoff, median (range) follow-up was 11.5 (0.1-31.3) mo. Confirmed ORR was 28.9% (95% CI, 24.3-33.8); 30 (8.1%) and 77 (20.8%) patients had complete response and partial response, respectively. Median duration of response was not reached (NR) (95% CI, 21.4 mo to NR); 82% and 68% of patients had a response of ≥6 and ≥12 mo, respectively. Median OS was 11.5 (95% CI, 10.0-13.3) mo; 6-and 12-mo OS rates were 67.2% and 47.5%, respectively. In patients with a PD-L1 expression combined positive score of ≥10 (n=110), ORR was 47.3% (95% CI, 37.7-57.0) and median OS was 18.5 mo (95% CI, 12.2 mo to NR). Median OS was NR (12.4 mo to NR) in patients with lymph node–only disease (n=51) and was 13.1 (95% CI, 11.0-16.8) mo in patients with ECOG PS 0/1 (n=214) and 9.7 (95% CI, 5.7-11.6) mo in patients with ECOG PS 2 (n=156). Treatment-related adverse events (AEs) occurred in 67.6% of patients; most common (≥15%) were fatigue (18.1%) and pruritus (17.8%). Grade ≥3 treatment-related AEs occurred in 20.3% of patients. Immune-mediated AEs occurred in 24.6% of patients. Conclusions: Pembro continues to be well tolerated and elicits clinically meaningful, durable antitumor activity in a broad spectrum of cisplatin-ineligible patients with advanced UC. Clinical trial information: NCT02335424.
TCT-416 Balloon vs Self-Expandable valve for the treatment of bicuspid Aortic valve sTenosis: insights from the BEAT international collaborative registry
Authors: Antonio Mangieri, Didier Tchetche, Won-Keun Kim, Jan-malte Sinning, Uri Landes, Ole De Backer, Ran Kornowski, Gherardo Busi, Enrico Poletti, Jeffrey Popma, Georg Nickenig, Chiara de Biase, Lars Søndergaard, Antonio Colombo
Journal: Journal of the American College of Cardiology (2018)