tbuckley/cabot-search huggingface dataset:
Abstract 12750: Exercise Ventilatory Power in Heart Failure. Definition of Functional and Hemodynamic Patterns by Cardiopulmonary Exercise Testing and Stress Echocardiography
Authors: Valentina Labate, Greta Generati, Marta Pellegrino, Francesco Bandera, Marco Guazzi
Journal: Circulation (2015)

Exercise Ventilatory Power (EVP; peak systolic blood pressure/exercise ventilation to CO2 production slope) is a new powerful prognostic marker that combines ventilator abnormalities with systemic hemodynamic during exercise. The phenotype and clinical relevance of patients with a worse EVP is broadly undefined and we aimed at this definition across a population of heart failure reduced ejection fraction (HFrEF) of different severity. Methods: 77 HFrEF patients (mean age 65±11; male 70%; ischemic etiology 59%; NYHA class I, II, III and IV 23%, 33%, 31% and 13%, respectively; mean LVEF 34±9 %) underwent cardiopulmonary exercise test (CPET) evaluation (ramp protocol on performed on a tilt-table cycleergometer) combined with simultaneous echocardiographic assessment. Results: Patients were divided in 2 EVP classes (cutoff 3) focusing on peak exercise echocardiographic variables. Conclusions: A low EVP translates in a very unfavorable phenotype characterized by a lower peak VO2 and CO response at peak exercise. Remarkable impairment in right heart function and pulmonary hemodynamics were also peculiar of a low EVP. All the LV-pulmonary circulation- RV apparatus is abnormally involved in the exercise response of the EVP HFrEF phenotype.
Regulatory-T cells (Tregs) in tumor infiltrating lymphocytes (TILs) from patients with advanced gastric cancer (AGC) after chemotherapy containing ramucirumab.
Authors: Daisuke Kotani, Yosuke Togashi, Akihito Kawazoe, Toshihiko Doi, Hiroyoshi Nishikawa, Kohei Shitara
Journal: Journal of Clinical Oncology (2017)

e15570 Background: Vascular endothelial growth factor-A (VEGF-A) and VEGF recepter-2 (VEGFR-2) axis is known to induce Tregs in tumor bearing mice. Ramucirumab (RAM), a monoclonal antibody for VEGFR-2, was recently approved for patients with AGC. However, little is known about the influence of RAM on Tregs in TILs from AGC patients. Methods: Patients with AGC who had been planned to receive chemotherapy containing RAM were prospectively enrolled for this study from January 2016 to August 2016. Paired samples were obtained from primary tumor at pre- and post-RAM therapy to analyze immune profiles of TILs using flow cytometry assay. Results: A total of 17 patients were analyzed. Median age was 68 years old (range, 46-79). All patients received one or more previous chemotherapy. RAM containing regimens included RAM+paclitaxel (n = 13), RAM monotherapy (n = 3) and RAM+irinotecan (n = 2). FOXP3 high CD45RA - CD4 + T cells (effector Tregs: eTregs) in CD4 + T cells was significantly decreased after RAM therapy compared with that in baseline (mean, 19.5% vs.13.6%, P = 0.036). In contrast, no significant change of CD8 + T cells was observed (mean, 36.7% vs. 36.0%, P = 0.86). Expression of programmed cell death-1 (PD-1) on CD8 + T cells was tended to be decreased after RAM therapy. Conclusions: eTregs in TILs was suggested to be decreased after RAM-containing therapy which warrants further evaluation in a larger cohorts. This observation might be a rationale to use RAM as an immunomodulator in combination of immune checkpoint inhibitors for AGC.
Psychosocial predictors of decision making for contralateral prophylactic mastectomy.
Authors: Abenaa M. Brewster, Susan K. Peterson, Isabelle Bedrosian, Wenli Dong, Scott B. Cantor, Robert Joseph Volk, Herbert L. DuPont, Yu Shen, Patricia Parker
Journal: Journal of Clinical Oncology (2016)

6581 Background: For women with unilateral breast cancer, a surgical option is the removal of the cancer-free breast (contralateral prophylactic mastectomy, CPM). CPM among women with unilateral breast cancer is increasing despite the lack of evidence that it improves overall survival. There are limited data regarding factors associated with the decision to have CPM which limits the development of interventions to support informed decision-making. Methods: We recruited 343 women with newly diagnosed non-hereditary breast cancer prior to their first surgical consultation between 2012 and 2015. Women completed questionnaires assessing knowledge and level of interest in different surgical procedures including CPM, individuals with whom they discussed CPM and psychosocial factors. Results: The mean age of the participants was 56 years (range 25-82) and 48 women (14%) had CPM. Women were 57% white, 17% African American, 16% Hispanic, 10% other races. In univariate analyses, discussion of CPM with the medical oncologist (p = 0.03) and a strong interest in having mastectomy for the primary breast cancer (p < 0.001) were associated with CPM but discussion with the primary care provider (p = 0.63), spouses (p = 0.62) or breast cancer survivors (p = 0.45) was not associated with CPM. Women who had more breast cancer worry (p < 0.001), more intrusive thoughts about recurrence (p = 0.05), and more distress about body image (p = 0.003) were more likely to have CPM. In multivariable analysis, age (OR [odds ratio] 0.95, 95% CI [confidence interval] 0.91-0.99, p = 0.036 for every year increase in age), strong versus low interest in having mastectomy for the primary breast cancer (OR 12.16, 95% CI 1.53 -96.4, p = 0.02) and breast cancer worry (OR 1.17, 95% CI 1.10-1.36, p = 0.03 for every unit increase) remained significantly associated with CPM. Conclusions: Because of the important role that medical oncologists play in the decision making process of CPM, education regarding CPM should be focused on these providers in addition to surgeons. Addressing cancer worry among breast cancer patients is an area for intervention with decision support tools and counseling to ensure only patients most likely to derive clinical or psychosocial benefits will receive CPM.
Subtyping of triple-negative breast cancer (TNBC): A cohort study.
Authors: Christoph Thomssen, Caroline Hartung, Martin Porsch, Kathrin Stückrath, Jörg Buchmann, Eva J. Kantelhardt, Martina Vetter
Journal: Journal of Clinical Oncology (2018)

e12563 Background: Triple negative breast cancer is characterized by the lack of protein expression of ER, PR and HER2, and is associated with unfavorable prognosis. According to suggestions by the Vanderbilt group, TNBC tumors can be subdivided into six presumably clinically meaningful subtypes (Lehmann 2011, Masuda 2013). We assessed these molecular subtypes in a consecutive cohort of patients with early TNBC. Methods: Non-metastasized, primarily operated breast cancer patients (n = 1,074 from 6 German breast centers) were included in the PiA cohort (Prognostic assessment in routine Application, NCT 01592825) with a median F/U of 56 months (0-78). Tumor characteristics of 99 TNBC were based on local pathology. RNA was obtained from 84 formalin fixed paraffin embedded TNBC tumor tissues and analyzed using the GeneChip U133 Plus 2.0 and GeneChip U219 PrimeView (n = 22) array (Affymetrix, Santa Clara, CA). Using the online Vanderbilt predictor tool, the molecular subtypes were determined (http://cbc.mc.vanderbilt.edu/tnbc). Results: The following TNBC subtypes were found (U133 Plus 2.0): basal-like1 (BL1; n = 17, 20%), basal-like2 (BL2; n = 10, 12%), immunomodulatory (IM; n = 19, 23%), mesenchymal (M; n = 11, 13%), mesenchymal/stem-like (MSL; n = 5, 6%), luminal androgen receptor (LAR; n = 10, 12%), unclassified (UNS; n = 8, 9%); 4 were excluded as ER positive. The two chips showed concordance of the results in 16 of 22 parallel runs (73%). At 5 yrs., 79% of all TNBC pts. (n = 99) were free of invasive disease (95% CI, 74.3-83.7). We observed 15 recurrences in 80 TNBC-pts. (6 local recurrences, 9 distant metastases) and 14 breast cancer related deaths. The Kaplan-Maier-estimates did not show any relevant difference in event-free survival probability of the Vanderbilt subtypes. Conclusions: In our cohort of TNBC pts., subtyping according to Lehmann’s suggestion was possible. We found a fair correlation between the two arrays that were used in this study. Similar to Lehmann we could not demonstrate a relevant impact of the subtypes on event-free survival.
Randomized trial of a symptom monitoring intervention for hospitalized patients with cancer.
Authors: Charn-Xin Fuh, Margaret Ruddy, Brandon Temel, Sara D'arpino, Barbara J. Cashavelly, Ephraim P. Hochberg, Vicki Jackson, Joseph Greer, David P. Ryan, Areej El-Jawahri, Jennifer S. Temel, Ryan David Nipp
Journal: Journal of Clinical Oncology (2018)

10005 Background: Hospitalized patients with cancer experience a high symptom burden, which is associated with poor health outcomes and increased healthcare utilization. We conducted a pilot randomized trial to assess the feasibility and preliminary efficacy of a symptom monitoring intervention to improve symptom management in hospitalized patients with advanced cancer. Methods: We randomly assigned patients with advanced cancer and unplanned hospitalizations who were admitted to the oncology service to a symptom monitoring intervention or usual care. Patients in both arms daily self-reported their symptoms (Edmonton Symptom Assessment System and Patient Health Questionnaire-4) via tablet computers. Patients assigned to the intervention had their symptom reports presented graphically with alerts for moderate/severe symptoms during daily team rounds. We defined the intervention as feasible if participants completed > 75% of their daily symptom assessments. We also observed daily team rounds to determine how often clinicians discussed and developed a plan to address patients’ symptoms. We used regression models to assess intervention effects on patients’ symptoms throughout their hospital stay and readmission risk. Results: From 10/26/16-6/30/17, we randomized 150 patients (81.1% enrollment rate; median age = 64.0 [22.7-92.8]; 40.7% female). The most common cancers were gastrointestinal (36.7%) and lung (22.0%). Patients completed 89.4% of their daily symptom assessments. Clinicians discussed 60.4% of the symptom reports and developed a plan during rounds to address patients’ symptoms 20.8% of the time. Compared with usual care, patients assigned to the intervention had a greater proportion of days with lower psychological distress (B = 0.12, P = .008). Intervention patients experienced improvements in their average symptom scores for drowsiness (B = -0.54, P = .033) and dyspnea (B = -0.43, P = 0.009). Intervention patients had lower risk of readmissions (hazard ratio = 0.68, P = .221), although this difference was not significant. Conclusions: This symptom monitoring intervention is feasible and demonstrates encouraging preliminary efficacy for improving patients’ symptoms and risk for readmissions. Clinical trial information: NCT02891993.
Genomic instability (GI) score post-neoadjuvant chemotherapy (NACT) to predict overall survival (OS) in high grade ovarian cancer (HGSOC).
Authors: Aurelie Auguste, Elena Cojocaru, Soizick Mesnage, Audrey Le Formal, Romy chen-Min-Tao, Sebastien Gouy, Philippe Morice, Enrica Bentivegna, Julien Adam, Catherine Lhomme, Patricia Pautier, Catherine Genestie, Alexandra Leary
Journal: Journal of Clinical Oncology (2016)

5573 Background: Many HGOC are genomically unstable which likely explains their chemosensitivity. How GI changes with NACT, or relates to tumor immune infiltration and prognosis is poorly described. Aim: Evaluate GI score (GIS) in pre and post-NACT tumors and its correlation with stromal tumor infiltrating lymphocytes (sTILs) and OS. Methods: 60 OC tumor samples (29 pre, 27 post and 4 relapses) with high cellularity (70-90%) and available matched frozen and FFPE samples were subjected to aCGH and an evaluation of percent sTILs, respectively. Samples included 51 HGSOC and 9 low grade serous OC (LGOC). GI score was calculated as the number of altered segments ( > 15Mbp and < chromosome arm) and the cut-off for high GIS defined as > median GIS in untreated HGOC samples. In addition tumors were classified as homologous recombination deficient (HRD) if a somatic or germline HR mutation was identified. Overall survival was estimated by Kaplan-Meier. Results: At baseline, the median GIS was 27 (range = 1-51) in HGSOC and much lower in LGOC (median = 3). In the one HGSOC patient with samples from 2 anatomically distant sites, GIS was stable (10 and 10). A high GIS was also significantly correlated with high sTILs post-NACT (R2= 0.25, p = 0.018). Among HGSOC, GIS was significantly lower post-NACT (median = 9.5, p = 0.037) but higher at relapse (median = 38). HRD tumors showed markedly reduced GIS in post- vs. pre-NACT samples (median = 1 vs 33, p = 0.0357). Patients with a high pre-NACT GIS only showed a trend towards improved outcome (OS = 41.2mo vs. 35.1mo, p = 0.4). However a low GIS post-NACT significantly predicted improved OS (41.5mo vs 19.3mo, HR = 0.15, p = 0.030). Conclusions: GI decreased significantly in HGSOC post-NACT suggesting that chemotherapy may select genomically stable subclones. The GIS after NACT more significantly predicted OS than the GIS in untreated HGSOC suggesting that an evaluation of GI in HGSOC at interval debulking after NACT may provide useful prognostic information. Comprehensive studies to characterize the genomically stable tumor post-NACT may identify novel maintenance targeted therapies to eradicate residual clones and improve outcomes for patients with HGSOC.
Access to cancer drugs in Europe years 2005-2014.
Authors: Nils Erik Wilking, Peter Lindgren, Ulla Wilking, Bengt Jönsson
Journal: Journal of Clinical Oncology (2016)

e18015 Background: Cancer drugs are fundamental parts of cancer care. The costs of new cancer drugs have increased dramatically over the last 10-20 years. This study investigates the introduction and access to cancer drugs in Europe 2005-14. Methods: Sales data from IMS health was standardized to population, incidence and/or mortality of specific cancers for comparisons between countries. Price and currency differences were adjusted using sales in weight or DDD (defined daily dose). Results: Cancer drugs sales in Europe were € 7.4 billion in 2005 and € 19.5 billion in 2014. Eight countries (Austria, Belgium, France, Germany, Italy, Netherlands, Spain, UK) accounted for more than 80% of sales in both 2005 and 2014. France spent most on cancer drugs in 2005 but was passed by Germany in 2014, having 25% of cancer drug sales in the EU-28. Of the top 5 drugs in 2005, 2 were not in the top 10 in 2014 (docetaxel and oxaliplatin) and one (paclitaxel) was at the bottom of the list. Trastuzumab has almost doubled its share as No1, and several new agents are listed, e.g. bevacizumab and lenalidomide. Interestingly, among the top 5 drugs in 2014, 3 have recently lost exclusivity or will in the near future (trastuzumab, rituximab and imatinib). Cancer drugs’ share of direct costs for cancer care has doubled since 2005 and was 21% in 2014. The newest drugs make up only 8% of total sales, varying between 4% and 11% per year in different countries, with the higher share in richer countries. Countries in Eastern and Southern Europe with low GDP per capita have sales at about 1/3 of that in countries in Western Europe, both in 2005 and in 2014. Conclusions: Access to cancer drugs, especially new innovative drugs, varies in Europe and is mainly depending on the countries’ economic status, and this has not changed over time. There are also significant variations in access between countries of similar economic power, indicating opportunities for improvement through policies aimed at evidence based and cost-effective cancer care.
Whole-body MRI (WB MRI) including diffusion weighted (DW) imaging for the surveillance of melanoma patients at high risk for recurrence following surgery or systemic therapy.
Authors: Yanina Jansen, Inneke Willekens, Carola Brussaard, Bart Neyns
Journal: Journal of Clinical Oncology (2017)

e21072 Background: Patients (pts) with locally advanced melanoma have a high risk of recurrence following complete surgical resection of macrometastases. Recent therapeutic progress has led to a growing number of stage IV pts achieving a durable complete remission (CR). For both populations no standards are established for surveillance with medical imaging. This prospective study explored the usefulness of surveillance by WB MRI for the early detection of melanoma recurrences. Methods: Pts with advanced melanoma (AJCC stages IIIb/-c or -IV) who were disease free following resection of macrometastases (cohort 1) and pts in CR following immunotherapy (cohort 2) were included. All pts underwent WB MRI, includingT1, Short Tau Inversion Recovery and DW imaging, Q4 mths the first 3 years of follow-up and Q6 mths in the following 2 years. Results: From Oct 2014 to Jan 2017, 43 pts were included (26 pts in cohort 1; 17 in cohort 2). 4 Pts were excluded (pacemaker [1pt], claustrophobia [1 pt], clinical recurrence before the first MRI [2 pt]). Mean follow-up was 103 wks (range 14–127). In total, 182 WB MRIs were performed (median number per pt: 4.5 [range 3-7]). A total of 16 pts were diagnosed with suspected lesions on WB MRI. Of these, 8 pts were diagnosed with melanoma recurrences (7 pts in cohort 1 and 1 pt in cohort 2). A total of 8 suspected lesions (8 Pts) identified on MRI (4 lymph node, 1 muscle, 1 bone, and 2 liver lesion) were considered to be of non-neoplastic origin based on additional diagnostic imaging and follow-up. No invasive procedures resulting in a false negative result were triggered by MRI. In 2 pts from cohort 2 a solitary subcutaneous metastasis was first detected by clinical examination (1 could be identified on MRI retrospectively, 1 was found in between MRIs). WB MRI was safe without any clinically meaningful ( &gt; gr1) adverse event. Conclusions: Exploration of WB MRI for the surveillance of melanoma patients following resection of melanoma macrometastases or CR on systemic therapy indicates that it is a safe and sensitive imaging technique sparing patients cumulative exposure to x-rays and contrast media. Clinical trial information: NCT02907827.
P19 Analysis of the Status of Lymphocyte Infiltration in Patients Diagnosed with Non–Small Cell Lung Cancer
Authors: E. Richardet, L. Acosta, M. Paradelo, M. Pairola, C. Ditada, G. Ferreira, M. Molina, L. Dicalbo, M. Richardet
Journal: Journal of Thoracic Oncology (2018)
MABp1 to improve clinical outcomes of patients with symptomatic refractory metastatic colorectal cancer patients: Per-protocol population analysis of phase III study (PT026).
Authors: Lucjan Wyrwicz, Mark P. Saunders, Thierry Andre, Tomasz Sarosiek, Radim Nemecek, Wojciech Rogowski, Krzysztof Leśniewski-Kmak, George A. Fisher, Michael Stecher, Prasant Mohanty, John Simard, Tamas Hickish
Journal: Journal of Clinical Oncology (2017)

3530 Background: Refractory metastatic colorectal cancer (mCRC) patients derive minimal benefit from further exposure to toxic agents. MABp1 is an anti-interleukin 1 alpha antibody that is shown to prolong survival (NCT01767857) and improves outcomes when assessed with a primary endpoint based on a constellation of objective and patient self-reported measures (NCT02138422) (Hickish T. et al Lancet Oncology 2017). In the latter study, clinically advanced patients were enrolled (symptomatic, ECOG 1,2), and 18% of patients progressed prior to reaching the endpoint assessments. Here we present the outcomes in per-protocol population (PP), those patients completing week 8 assessments. Methods: 309 patients randomized 2:1 to receive MABp1 versus placebo. Patients were ECOG 1-2, with mCRC refractory to chemotherapy, any degree of weight loss, and cancer-associated symptoms. The composite primary endpoint assessed the rate of patients achieving stabilization or improvement in lean body mass (LBM) and two of three symptom measures (pain, fatigue, appetite loss) from screening to the week 8 assessment. The study was designed for placebo cross-over, thus OS analysis for MABp1 vs placebo was not possible. Results: 57 patients (38 MABp1 [18%] and 19 placebo [19%]) discontinued study prior to the week 8 assessment due to disease progression, including 17 (8%) and 11 (11%) deaths in MABp1 and placebo respectively. 62% of placebo patients received MABp1 after 8 weeks. 252 patients, 40% in MABp1 (68/169) vs 23% in placebo (19/83) met the primary endpoint (p = 0.003). 139 patients were available for PP survival analysis (90 MABp1 vs 49 Placebo). Median OS of those achieving the primary endpoint was 11.7 months vs 5.7 months for those that did not (HR 0.39; p &lt; 0.0001). Radiographic stable disease was improved (42% vs 12%; p &lt; 0.001) and incidence of SAEs (6% vs 15%; p = 0.11) reduced in those achieving the primary endpoint. Conclusions: Achieving the primary endpoint was associated with improvement in outcomes, RECIST stabilization, SAEs and survival. Further study should confirm the effect of MABp1 on survival in this population. Clinical trial information: NCT02138422.
Abstract 15288: Partial Band Mitral Annuloplasty Could Preserve Mitral-Aortic Valve Dynamic Coupling: Comparison Between Pre- and Post-Operative Mitral and Aortic Annular Motion
Authors: Noriyuki Wakana, Tetsuhiro Yamano, Hiroyuki Watanabe, Michiyo Yamano, Naohiko Nakanishi, Takehiro Ogata, Kan Zen, Takeshi Nakamura, Hiroyuki Yamada, Kiyoshi Doi, Hitoshi Yaku, Satoaki Matoba
Journal: Circulation (2016)

Introduction: Mitral valve (MV) repair with an annuloplasty ring might unfavorably affect synchronous behavior of mitral-aortic coupling (MAC); however, differences of various types of ring have ne...
Self-dependent effects of various doses of magnetite nanoparticles on tumors with different histological structures in experiments in vivo.
Authors: Galina Vitalyevna Zhukova, Oleg Ivanovich Kit, Alla Ivanovna Shikhlyarova, Tatiana Albertovna Barteneva, Marina Igorevna Bragina, Elena Alekseevna Shirnina, Tatiana Anatolevna Kurkina
Journal: Journal of Clinical Oncology (2016)

e23199 Background: The influence of iron oxide nanoparticles (NPs) as monofactors on malignant tumors is poorly studied. Self-dependent antitumor effect of magnentite NPs in experiments in vivo has been shown (Garkavi L.Kh. et al., 2010). The purpose of the study was to analyze the effect of magnentite NPs in two different doses on development of tumors with various histological structures. Methods: The study included male outbred rats with sarcoma 45 (S-45, n = 45) and Pliss lymphosarcoma (PLS, n = 50) and female С57Black/6 mice with B16 melanoma (n = 50). Magnetite NPs (10±2 nm) as magnetic fluid were injected peritumorally along the borders of tumors transplanted subcutaneously. The distance of injection loci to the tumor borders was 0.7-1 cm in mice and 1.5 cm in rats. NPs were used in two single doses that differed by more than 10 times - 17.7 and 1.25 mg/kg. Animals received a total of 6 injections every 2-3 days. 3 weeks after the firs injection animals were decapitated. Tissues of tumor and peritumoral zone were studied by light and electron microscopy. Results: Effect characteristics differed depending on the tumor type. Rats with S-45 showed inhibition of tumor growth (by 35-73 %, p < 0.05) and PR and CR (up to 70% of the cases). Male rats with PLS showed tumor regression only, including tumors over 20 cm3, PR or CR (up to 50% of the cases). B16 melanoma growth was inhibited (up to 78% in 30-40% of the cases) and/or life span of the mice increased by 1.5 times. Magnetite NPs in rats were more effective in the lower dose (by 1.3-2 times in comparison with the higher dose). Microscopic examination of tissues of tumor and peritumoral zone with an effective exposure detected the signs of activation of cell-cell interactions with monocyte participation. Conclusions: The degree of self-dependent antitumor effects of magnentite NPs depends on histological structure of tumor and the dose applied. We suppose that tumor-associated macrophages change their polarization under the influence of magnetite nanoparticles. The study was supported by RScF research project 14-35-00051