tbuckley/cabot-search huggingface dataset:
Impact of prostate cancer treatments on exercise behaviors of men attending an exercise counselling service implemented as standard care.
Authors: Sarah Weller, Phil Pollock, Lindsay Hedden, Eugenia Wu, Maria Spillane, Monita Sundar, Larry Goldenberg, Kristin L. Campbell, Celestia S. Higano
Journal: Journal of Clinical Oncology (2018)

e22057 Background: Exercise is an effective management strategy to reduce treatment side effects experienced by prostate cancer survivors (PCS), however, most PCS are insufficiently active. Exercise counselling implemented into medical clinics has the potential to address this gap. Currently, little is known about the effectiveness of exercise counselling in PCS and the impact of prostate cancer treatments on exercise behaviors. Methods: We conducted a retrospective chart review on PCS who attended an exercise counselling service implemented as standard care within the Prostate Cancer Supportive Care (PCSC) program. The service is one-one-one with a certified exercise physiologist and is offered to PCS at any disease state after diagnosis. Follow-up appointments are encouraged at 3-, 6- and 12-months. Physical measures, exercise volume, treatment side effects and goal setting are recorded each visit, with the overall aim of increasing physical activity. The analysis compared baseline and final visit exercise levels and the effect of treatment type, from July 2015 to October 2017. Results: 128 PCS (mean age = 67.6 years, SD ±7.0) attended an average of 2.5 exercise counselling sessions over 182 days. From baseline to final visit, clinically meaningful and significant increases were seen in weekly moderate-to-vigorous physical activity (MVPA) minutes (+65, p < 0.01), total weekly activity (Leisure Score Index) (+11.8, p < 0.0001), weekly resistance training sessions (+0.67, p < 0.001) and the proportion of PCS meeting the current MVPA and resistance training guidelines (+20.2% and +22.7%, p < 0.01). The largest improvements in MVPA were seen in PCS on active surveillance (p = 0.01), in PCS aged 60 to 70 years (p = 0.02) and in PCS who had received surgery (p < 0.0001). Men treated with brachytherapy were less likely to meet aerobic exercise guidelines at their final appointment (p < 0.05). Conclusions: An exercise counselling service as standard care was effective at improving exercise behaviors in PCS, however the magnitude of change varied depending on the nature of treatment. Future work will focus on the treatment-specific needs of PCS when implementing exercise interventions.
Intensification of older adults’ outpatient blood pressure treatment at hospital discharge: national retrospective cohort study
Authors: Timothy S Anderson, Charlie M Wray, Bocheng Jing, Kathy Fung, Sarah Ngo, Edison Xu, Ying Shi, Michael A Steinman
Journal: BMJ (2018)

Abstract Objectives To assess how often older adults admitted to hospital for common non-cardiac conditions were discharged with intensified antihypertensive treatment, and to identify markers of appropriateness for these intensifications. Design Retrospective cohort study. Setting US Veterans Administration Health System. Participants Patients aged 65 years or over with hypertension admitted to hospital with non-cardiac conditions between 2011 and 2013. Main outcome measures Intensification of antihypertensive treatment, defined as receiving a new or higher dose antihypertensive agent at discharge compared with drugs used before admission. Hierarchical logistic regression analyses were used to control for characteristics of patients and hospitals. Results Among 14 915 older adults (median age 76, interquartile range 69-84), 9636 (65%) had well controlled outpatient blood pressure before hospital admission. Overall, 2074 (14%) patients were discharged with intensified antihypertensive treatment, more than half of whom (1082) had well controlled blood pressure before admission. After adjustment for potential confounders, elevated inpatient blood pressure was strongly associated with being discharged on intensified antihypertensive regimens. Among patients with previously well controlled outpatient blood pressure, 8% (95% confidence interval 7% to 9%) of patients without elevated inpatient blood pressure, 24% (21% to 26%) of patients with moderately elevated inpatient blood pressure, and 40% (34% to 46%) of patients with severely elevated inpatient blood pressure were discharged with intensified antihypertensive regimens. No differences were seen in rates of intensification among patients least likely to benefit from tight blood pressure control (limited life expectancy, dementia, or metastatic malignancy), nor in those most likely to benefit (history of myocardial infarction, cerebrovascular disease, or renal disease). Conclusions One in seven older adults admitted to hospital for common non-cardiac conditions were discharged with intensified antihypertensive treatment. More than half of intensifications occurred in patients with previously well controlled outpatient blood pressure. More attention is needed to reduce potentially harmful overtreatment of blood pressure as older adults transition from hospital to home.
Abstract 20390: Clinical Outcome of Vasospastic Angina Patients Presenting With Aborted Sudden Cardiac Arrest
Authors: Taek Kyu Park, Jeong Hoon Yang, Young Bin Song, Joo-Yong Hahn, Jin-Ho Choi, Sang Hoon Lee, Hyeon-Cheol Gwon, Seung-Hyuk Choi
Journal: Circulation (2017)

Introduction: Cardiac arrest is a lethal complication in patients with vasospastic angina (VSA). Although VSA patients responding to vasodilator therapy have a good prognosis, the long-term clinica...
Effect of friend leukemia virus integration 1 on tumorigenesis of small cell lung cancer cells and activation of the miR-17-92 pathway.
Authors: Jiuwei Cui, Lingyu Li, Wei Song, Jifan Hu, Wei Li, Xu Yan
Journal: Journal of Clinical Oncology (2017)

e20015 Background: Small cell lung cancer (SCLC) is regarded as the most devastative type of human lung malignancies, mostly due to their rapid and disseminated growth pattern. However, the molecular factors that drive rapid progression of SCLC remain unclear. Friend leukemia virus integration 1( FLI1),an Ets transcription factor family member, was identified as a proto-oncogene in some tumors via regulation of different target genes. In this study, we explored the potential role of FLI1 in SCLC. Methods: FLI1 protein expression was evaluated by immunohistochemistry in 67 primary SCLC, 20 non-small cell lung cancer (NSCLC) and 20 normal lung specimens. Correlation between FLI1 expression and clinical characteristics was evaluated with the logistic regression. Cell proliferation, cell cycle, apoptosis, colony formation assays in vitro and tumorigenesis assay in vivo were used to explore the function of FLI1 in SCLC cells. Use the miR-17-92 promoter/luciferase reporter assay to identify the regulation of FLI1 on miR-17-92 cluster promoter. Results: Immunohistochemical staining data showed that FLI1 was significantly upregulated in SCLC tissues compared to that in NSCLC and normal lung tissues ( p&lt; 0.01). The expression score of FLI1 oncoprotein was associated with the extensive stage of SCLC and the overexpressed Ki67. Knockdown of FLI1 promoted apoptosis and induced repression of cell proliferation, tumor colony formation and in vivo tumorigenicity in highly aggressive SCLC cell lines. Importantly, we discovered that FLI1 promoted tumorigenesis by activating the miR-17-92 cluster family transcritption. Conclusions: This study uncovers that FLI1 is an important driving factor that promotes tumor growth in SCLC through the miR-17-92 pathway, and may serve as an attractive target for therapeutic intervention of SCLC.
RM-1929 photo-immunotherapy in patients with recurrent head and neck cancer: Results of a multicenter phase 2a open-label clinical trial.
Authors: Ann M. Gillenwater, David Cognetti, Jennifer Maria Johnson, Joseph Curry, Samith Thomas Kochuparambil, Darren McDonald, Mary J. Fidler, Kerstin Stenson, Nilesh Vasan, Mohammad Razaq, John Campana, Frank Mott
Journal: Journal of Clinical Oncology (2018)

6039 Background: Patients with recurrent HNSCC (rHNSCC) have limited therapeutic options and poor prognosis. We report promising results of a Phase 2a trial of photoimmunotherapy (PIT) for the treatment of rHNSCC using a novel targeted light activated drug RM-1929; a conjugate of the EGFR-directed monoclonal antibody cetuximab with the phthalocyanine dye, IRDye 700DX. Methods: A multi-institutional, open label Phase 2a study of rHNSCC patients who could not be satisfactorily treated with surgery, radiation, or platinum chemotherapy was conducted to evaluate the safety and efficacy of RM-1929. For each treatment, non-thermal red light was applied to the tumors 24 hours after intravenous infusion of RM1929. Light was applied by surface illumination for superficial disease or interstitial illumination via intratumoral placement of fiber optic diffusers for deep tumors. Therapeutic response was calculated using CT RECIST 1.1 determined by an independent blinded radiologist. Results: Thirty rHNSCC patients were enrolled in this Phase 2a trial. Safety data are currently evaluable from 30 subjects, outcome data from 28 subjects. There were no dose-limiting toxicities or skin photosensitivity reactions observed. SAEs reported to be possibly related to study treatment, included treatment site pain, tumor hemorrhage, and swelling. Objective response rate was 28% (8/28), complete response was 14% (4/28). Median progression free survival for 28 evaluable patients was 173 days (5.7 months). Median overall survival for the entire 30 patient cohort was 278 days (9.1 months). Conclusions: Photoimmunotherapy with RM1929 in patients with rHNSCC is safe and well tolerated. CT RECIST 1.1 PFS, ORR and CR response rates are improved over those of standard therapies in this heavily pre-treated population. Future clinical trials are planned to evaluate the therapeutic potential of RM1929 alone or in combination with other treatment modalities. Clinical trial information: NCT02422979.
Association of mucosal Fusobacterium with clinical stage and immune gene signatures of rectal adenocarcinoma.
Authors: Michael Sangmin Lee, Cheryl Ann Carlson, Benjamin F. Calvo, Bert H. O'Neil, Nicole Amber McCoy, Dante S. Bortone, Benjamin Garrett Vincent, Temitope O Keku
Journal: Journal of Clinical Oncology (2018)

12112 Background: Alterations in gut microbial composition are associated with development and progression of colorectal cancer (CRC), and may contribute to interpatient biologic and clinical heterogeneity. Fusobacterium is enriched in CRC and is associated with a proinflammatory microenvironment. We hypothesized that Fusobacterium was associated with distinct clinicopathologic characteristics and inflammatory gene signatures among patients with locally advanced rectal cancer. Methods: Patients with T3-4 or N+ rectal adenocarcinoma planned to receive neoadjuvant chemoradiation were prospectively consented to undergo pretreatment endoscopic tumor biopsy. The V1-V2 region of the 16S bacterial ribosomal RNA gene was sequenced to identify tumor mucosal microbiota taxonomy. Tumor mRNA sequencing (RNASeq) was also completed and gene set enrichment analysis (GSEA) with curated immunologic signatures in MSigDB was performed. Multivariate analyses were conducted using PRIMER VII and SPSS v24 software. P-values were determined using Mann-Whitney tests, and Benjamini-Hochberg procedure was used and only results with false discovery rate < 0.25 are presented. Results: Of 43 total samples, 37 had adequate bacterial 16S rRNA gene sequencing, and 31 also had adequate RNA quality for RNASeq analysis. Among the 37 patients, mean age at diagnosis was 54 (range 30-77) and pre-treatment clinical stage was II (30%) vs. III-IV (70%). Higher clinical stage (stage III-IV vs II) was associated with enrichment of Fusobacterium (16.2% vs 5.6%, p = 0.019) and Parvimonas (4.6% vs 1.4%, p = 0.033) genera. In the 9 subjects with > 20% relative abundance of Fusobacterium, 179/4872 Immunologic gene sets, were enriched with p-value < 0.01 and FDR < 0.20. Significant gene sets included increased myeloid cell signatures, like monocytes/macrophages and neutrophils, and decreased effective cytotoxic T cell signatures. Conclusions: Fusobacterium was more abundant in the mucosal microbiome of rectal cancer with higher clinical stage and was associated with different immune gene signatures. Further investigation into the impact of Fusobacterium on immune cell infiltration and function in colorectal cancers is warranted.
Estimation of left ventricular ejection fraction with low-dose gated tomographic radionuclide angiography using cadmium-zinc-telluride gamma camera in patients receiving cardio-toxic chemotherapy: A dramatic radiation reduction.
Authors: Matthieu Bailly, Gilles Metrard, Helene Besse, Sofiane Mouzoune, Gilles LE Rouzic, Sabine Gauvain
Journal: Journal of Clinical Oncology (2016)

e14030 Background: Tomographic radionuclide angiography (TRA) is a simple non-invasive procedure which can monitor left ventricular ejection fraction (LVEF) with automatic processing software, resulting in excellent reproducibility. New gamma cameras using cadmium-zinc-telluride (CZT) detectors enables reduction of the patient radiation dose. We compared LVEF and left ventricular (LV) volumes between low dose and standard-dose TRA using a CZT camera. Methods: Between September and December 2015, patients receiving potentially cardiotoxic chemotherapy and undergoing TRA were consecutively included. CZT acquisition was performed in « List-Mode » after injection of 550MBq 99mTc-labelled human serum albumin and lasted 7 minutes (recommended activity: 550-1110MBq, Society of Nuclear Medicine Guidelines). Each acquisition was analyzed full dose and equivalent half dose by the same physician, using the same software (Quantitative Blood Pool SPECT, Cedars Sinai) to generate LVEF and LV volumes. Results: 80 patients were analyzed (40% male, mean age 60 years and BMI 28 kg/m2). There was no significant difference in LVEF and LV systolic and diastolic volumes between full dose and equivalent half dose acquisition (p< 0.005). The contrast-to-noise ratio wasn't visually decreased. Effective dose were 3.3 millisieverts (mSv) and 1.65mSv respectively for full-dose and equivalent half-dose acquisitions using our parameters. Conclusions: LVEF and LV volumes can accurately be determined using fast low-dose CZT acquisition (7 minutes, < 2mSv, below natural radiation) in patients receiving cardio-toxic chemotherapy. This dose reduction up to 50% from the lowest recommended administered activity allows repeated scans in those patients, with reduced dosimetry. Further dose reductions may be achievable.
Economic burden of empiric drug utilization in metastatic renal cell carcinoma emphasizes the need for early biomarkers of response.
Authors: Viola Chen, Cynthia Gong, Chiyuan A Zhang, Sandy Srinivas, Howard E Lee, Alice C. Fan
Journal: Journal of Clinical Oncology (2017)

e16072 Background: While targeted therapies have significantly changed clinical practice for metastatic renal cell carcinoma (RCC), the economic burden of these drugs is increasing without concomitant advances in strategies for choosing among such agents. We present a model of cost savings using a hypothetical biomarker panel of early response to guide selection of targeted and immune therapies in metastatic RCC patients. Methods: Using the Stanford RCC Outcomes database, we identified patients diagnosed with metastatic RCC who received any of the following: sunitinib, pazopanib, axitinib, sorafenib, cabozantinib, nivolumab, lenvatinib &amp; everolimus, temsirolimus from 2003 through 2016 at Stanford Cancer Center. Primary outcomes included short-term and long-term costs of treatment according to standard-of-care imaging criteria. Drug costs were inferred from the 2017 Veterans Affairs Federal Supply Schedule pricing in USD. A hypothetical biomarker cost was set at $4,620—the current market price of an actively employed diagnostic test in breast cancer, OncotypeDX. These parameters were combined in a Markov model to simulate patient treatment courses and to assess the impact of an early response biomarker on drug expenditures. Results: 370 patients received a range of one to six lines of successive therapy. 170 (45.9%) were long-term patients with cumulative drugs costs totaling $31 million, or on average $185,362 per patient, and $104,521 per individual line of therapy received. 200 (54%) were short-term patients who received less than 3 months of targeted therapy. The costs of such potentially ineffective treatment totaled $4.1 million, or $15,455 per patient per individual line of therapy received. Application of an early biomarker panel at the outset would result in a potential cost savings of up to $6,215 per patient. Conclusions: Bothmetastatic RCC patients and payers suffer high costs from ineffective therapy. Our findings suggest an economic benefit for developing biomarker panels to predict early therapeutic response. Such biomarkers can result in immediate cost savings, and possibly improved quality-of-life for those liberated from unnecessary drug toxicity.
Tumor growth and regression rate constants from the CLARINET study as surrogate endpoints for progression free survival: A novel assessment approach in cancer therapy.
Authors: Clarisse Dromain, Arturo Loaiza-Bonilla, Thomas Beveridge, Beloo Mirakhur, Julia Wilkerson, Antonio Tito Fojo
Journal: Journal of Clinical Oncology (2018)

e24329 Background: Tumor size following cancer-related therapy is the result of regression of the treatment-sensitive fraction and growth of the treatment-resistant fraction, occurring simultaneously at constant rates. Exponential rate constants for tumor regression/decay (d) and growth (g) can be calculated using a novel equation, f = e(g · t) + e(-d · t) -1. Previous studies have established that g is associated with overall survival, increases after treatment cessation, and can be used to assess treatment effectiveness in small patient cohorts by benchmarking to reference data sets from large trials. Using this approach, we have analyzed data from the CLARINET Study that evaluated lanreotide autogel/depot (LAN) 120 mg/4 weeks for the treatment of neuroendocrine tumors (NETs). Methods: Available computed tomography (CT) imaging data from 97 LAN & 101 placebo (PBO) patients from CLARINET were analyzed to estimate exponential rate constants for g and d. Results: 92% of the LAN and 94% of PBO data could be fit to one of the equations to derive g and d values, with p values for the fits of < 0.001 in most data sets. g in LAN treated patients was significant slower vs PBO (4.6e-4 day-1 vs 6.2e-4 day-1; p = 0.00315). No significant difference was observed in d (LAN: 8.3e -4 day-1 vs PBO: 7.9e -4 day-1; p = 0.33746). g did not increase over prolonged periods on LAN administration (up to 700 days). Simulated sample size analysis with g as the endpoint in LAN vs PBO showed a sample size of 48 sufficient to detect a difference in median g with 80% power. Conclusions: The growth rate constant, g, has the potential to elucidate differences in treatment efficacy in NETs, as is many solid tumors. Consistent with its principal mechanism of action as a growth retardant drug, LAN works primarily by slowing tumor growth rather than accelerating tumor regression in treatment of NETs. The growth retarding effect seen with LAN in this study was sustained over a time. Clinical trial information: NCT00353496.
Secondary acute myeloid leukemia (sAML) in patients with myeloproliferative disorder (MPD).
Authors: Sravanthi Paluri, Smith Giri, Rajesh Shrestha, Vijaya Raj Bhatt
Journal: Journal of Clinical Oncology (2016)

e18513 Background: We utilized Surveillance, Epidemiology, and End Results (SEER) 13 database to determine the risk of sAML in MPD diagnosed in 2000-12 Methods: Multiple primary standardized incidence ratio (SIR) session was used to calculate SIR and absolute excess risk (AER).We estimated the cumulative incidence of sAML with death as a competing event. Gray's test was used to study differences in cumulative incidence among different groups. Fine and Gray regression model was used for multivariate analysis. Results: 9335 patients had polycythemia vera (PV) (43.8%), primary myelofibrosis (PMF) (11.8%) or essential thrombocythemia (ET) (44.4%). The median age was 65 yrs (0-100 yrs); 49% were males and 78% whites. During a median follow up of 48 months (0-239 mths), 83 patients developed sAML with a SIR of 15.23 (95% CI, 12.13-18.87, p<0.01) and AER of 18.79 per 10000 population. The median age at diagnosis of sAML was 72 yrs (46-95 yrs); 69% were male and 80% whites. The cumulative incidence of sAML was 0.74% (95% CI 0.56-0.97) at 5 years and 1.62% (95% CI 1.24-2.09) at 10 yrs. The 10 yr cumulative incidence was higher in PMF (2.96%; 95% CI 1.90-4.39) versus ET (1.68%; 95% CI 1.03-2.62) and PV (1.24%; 95% CI 0.81-1.83)(p<0.001). The 10 yr cumulative incidence was higher for patients >60 years versus ≤60 years (1.25% vs 1.86%, p= 0.04) and male versus female (2.17% vs 1.09%, p<0.001). In multivariate regression analysis, PMF, male and diagnosis after 2006 were associated with an increased risk (Table 1). Conclusions: Men with PMF diagnosed in recent years are at the highest risk of sAML.This population-based study provides a risk of sAML in different subsets of patients with MPD, which may be utilized for patient education and serves as a platform for future studies Multivariate regression of cumulative incidence of sAML. Variable Hazard Ratio 95% CI P value Age ≤ 60 years 1.00 > 60 years 1.57 0.95-2.58 0.07 Race White 1.00 Black 1.24 0.59-2.62 0.57 Others 1.17 0.58-2.34 0.66 Gender Male 1.00 Female 0.44 0.27-0.71 < 0.01 MPD subtype Polycythemia Vera 1.00 Primary Myelofibrosis 2.49 1.45-4.27 < 0.01 Essential Thrombocythemia 1.08 0.64-1.83 0.76 Year of diagnosis 2000-2006 1.00 2007-2012 2.05 1.38-3.04 < 0.01
ZoptEC: Phase III randomized controlled study comparing zoptarelin with doxorubicin as second line therapy for locally advanced, recurrent, or metastatic endometrial cancer (NCT01767155).
Authors: David S. Miller, Giovanni Scambia, Igor Bondarenko, Anneke M. Westermann, Ana Oaknin, Amit M. Oza, Alla Sergeevua Lisyanskaya, Ignace Vergote, Robert Michael Wenham, Sarah Madhu Temkin, Hani Gabra
Journal: Journal of Clinical Oncology (2018)

5503 Background: Zoptarelin (AEZS-108, AN-152, ZEN-008) is a luteinizing hormone-releasing hormone (LHRH)-cytotoxic hybrid molecule composed of doxorubicin chemically linked to the carrier molecule D-Lys6-LHRH. The primary objective of this study was to compare the overall survival (OS) of patients treated with zoptarelin vs doxorubicin. The secondary objectives included comparing efficacy based on progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and safety. Methods: In an international multi-center trial, patients with advanced, recurrent, or metastatic endometrial cancers who had failed prior platinum and taxane therapy were centrally randomized 1:1 to zoptarelin (267mg/m2) or doxorubicin (60 mg/m2), I.V. every 21 days for up to nine cycles. Results: Zoptarelin was given to 256 patients and doxorubicin to 255 for a median of 5 vs 4 cycles respectively. The median OS for patients treated with zoptarelin was 10.9 months compared to 10.8 months for patients treated with doxorubicin (HR = 1.06; C.I. 0.87, 1.30). PFS was 4.7 months for both (HR = 0.89, C.I. 0.71, 1.11). ORR was 12% vs 14% and CBR was 54% vs 52% (p = NS). The most common grade > 2 adverse events were Neutropenia 47% vs 45%, Leukopenia 21% vs 18%, and Anemia 20% vs 15%. Febrile neutropenia was seen in 9% vs 4%. Absolute decline of LVEF from baseline of > 15% or absolute value < 45% was found in 7% vs 13%. Conclusions: Zoptarelin did not improve OS, PFS, ORR, CBR, or adverse events compared to doxorubicin as second line therapy for advanced endometrial cancers. Clinical trial information: NCT01767155.