tbuckley/cabot-search huggingface dataset:
Illness perceptions and quality of life in cancer: Does communication with the physician matter?
Authors: Marina Kretsch, Laurence Chone, Elisabeth Spitz
Journal: Journal of Clinical Oncology (2014)

e20576 Background: This study focuses on how patients perceived the very first disclosure by a physician of the risk of having cancer and the impact of this disclosure on their perception of the disease and quality of life. Perception of communication was measured in two situations: 1) the first time the physician informed the patient that he/she had a risk of cancer, 2) the last consultation the patient had with his/her referred specialist. Methods: The current analysis was conducted on a sample of 218 patients with cancer at all stages of the disease (curative, palliative and monitoring). Measurement tools included the Medical Communication Competence Scale (MCCS) as well as the Brief-Illness Perception Questionnaire (BIPQ), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life questionnaire for cancer patients (EORTEC QLQ C-30). Data were analyzed using hierarchical multiple regression analysis. Results: Results showed that the patients’ perception of the first disclosure of the risk of cancer accounted for a significant amount of the variance of their perception of the consequences, duration (time line) and treatment control of the disease, symptom frequency as well as their quality of life, anxiety and depression. The perception of the communication with the specialist accounted for a significant proportion of the variance of their perception of treatment control, their comprehension of the disease and their level of anxiety. Conclusions: Many studies have been performed on communication with specialists regarding diagnosis disclosure. However, few studies have focused on the conditions in which the patient learns for the first time from a health professional the risk that he/she may have cancer. Results of this study show that these first moments of disclosure, most often made by a general practitioner, a specialist or a resident in medicine, have an impact on the future perception of the disease by the patient.
Attempt to Prove the Existence of Abnormal B Lymphocyte As Myeloma-Initiating Cells from B Cell-Derived Induced Pluripotent Stem Cells
Authors: Aki Yanagi, Naohiro Tsuyama, Yukari Yanai, Yu Abe, Misaki Sugai, Akinobu Ota, Karnan Sivasundaram, Tomonari Shigemura, Megumi Sasatani, Kenji Kamiya, Ichiro Hanamura, Takayuki Ikezoe, Masafumi Onodera, Akira Sakai
Journal: Blood (2018)
The role of MEK inhibition in neuroblastoma tumor cells.
Authors: Peter E. Zage, Sarah Woodfield, Linna Zhang, Kathleen Scorsone
Journal: Journal of Clinical Oncology (2014)

10068 Background: Neuroblastoma is the most common extracranial solid tumor of childhood. High-risk cases of neuroblastoma have extremely poor long-term survival rates, and novel therapies are needed. The RAS/MAPK pathway has been shown to be involved in neuroblastoma tumorigenesis. We hypothesized that RAS/MAPK pathway inhibition via MEK inhibition with MEK162 would be effective against neuroblastoma tumor cells. Methods: We evaluated expression and activity of MEK and ERK in a panel of neuroblastoma tumor cells using Western blots and neuroblastoma tumor cell viability after treatment with MEK162 using MTT assays. Expression of NF1 protein was determined by Western blot. Analyses were performed for changes in RAS/MAPK pathway activity after MEK162 treatment. Results: Neuroblastoma tumor cell lines displayed differential responses to MEK162, with some cell lines being very sensitive and others being resistant. IC50 values for sensitive cell lines ranged from <10nM to 5mM, while resistant cells did not demonstrate any reduction in cell viability at doses exceeding 20mM. NF1 expression correlated with responses to MEK162. MEK162 treatment resulted in reduced ERK phosphorylation in sensitive neuroblastoma cells, while increased levels of MEK phosphorylation were seen in resistant cells. Conclusions: Treatment of neuroblastoma tumor cells with MEK162 inhibits RAS/MAPK pathway activity, resulting in cell death in sensitive cell lines. Resistant neuroblastoma tumor cell lines displayed increased MEK phosphorylation in response to MEK162, suggesting a possible feedback loop leading to treatment resistance. Inhibition of MEK represents a potential new therapeutic strategy for neuroblastoma, and further preclinical studies of MEK162 are warranted.
Frailty markers for prediction of mortality in first-line chemotherapy for colon cancer patients: Results of MOST/ASRO 101 study.
Authors: Frederique Retornaz, Olivier Guillem, Dany Gholam, Jean francois Codoul, Cecile Bratisevic, Francois Morvan, Yves Rinaldi, Nicolas Barriere, Sophie Nahon, Chantal Butaud, Olivier Guerin, Rabia Boulahssass, Frederique Rousseau
Journal: Journal of Clinical Oncology (2014)

9553 Background: The concept of frailty may help in to detect vulnerability in patients with digestive cancer in surgery setting. We investigated whether frailty markers predict grade 3-4 toxicity or 6 months death in older colon cancer patients receiving a first line chemotherapy. Methods: This prospective multicenter study included patients aged ≥75 years, with colon cancer, receiving first line of chemotherapy for adjuvant or metastatic situation. Five frailty markers were examined (nutrition, physical activity, energy, mobility, strength). Logistic regression was used to examine the association between frailty markers and grade 3-4 toxicity at 3 and 6 months, and cox regression to examine deaths at 6 months. Results: 99 participated, and 98 were eligible for analysis. Median age was 79 years. At baseline, 26 patients (26.5%) had 3 or more frailty markers. Twenty six (26.5%) had grade 3-4 toxicity after 3 months, and 18 (18.4%) after 6 months. Twelve patients died during the 6 months follow-up. In multivariate analysis, at 3 months and 6 months, none of the studied frailty marker predicted grade 3-4 toxicity. At six months, significant predictive factors for death were the frailty marker “energy” (Hazard Ratio [HR]; 13.92 (95% CI [3.22-60.15] p=0.0004) and presence of 3 or more frailty markers at baseline (HR, 4.50 (95% CI [1.30-15.64] p=0.02). Conclusions: Frailty markers are predictive of death at 6 months but are not predictive of severe toxicity. These results suggest that frailty markers, in particular “energy” should be taken into account when treating an elderly cancer population. Further researcher investigating the usefulness of frailty markers is needed.
Synergistic Anti-Leukemic Activity with Combination of FLT3 Inhibitor Quizartinib and MDM2 Inhibitor Milademetan in FLT3-ITD Mutant/p53 Wild-Type Acute Myeloid Leukemia Models
Authors: Michael Andreeff, Weiguo Zhang, Prasanna Kumar, Oleg Zernovak, Naval G. Daver, Takeshi Isoyama, Kouichi Iwanaga, Noriko Togashi, Takahiko Seki
Journal: Blood (2018)
Metabolomic profiling of gastrointestinal stromal tumor (GIST) in human tissue samples and xenografts.
Authors: Danny Yakoub, Vered Marks, Zhiqiang Wang, Elizabeth Paulus, Tony Capobianco, Jonathan C. Trent, Jamie Walls, Alan S Livingstone
Journal: Journal of Clinical Oncology (2014)

10516 Background: There is a growing need for novel agents to treat resistant GIST. The goal of this study was to characterize and identify potential therapeutic targets in the metabolic profile of GIST. Methods: Tumor, adjacent control tissue samples from 7 patients (five exposed to imatinib) and two tumor samples from xenografts in nude mice models (non-exposed) were extracted for analysis. 1H-NMR spectra, using a 500MHz spectrometer equipped with a cryoprobe head, were acquired and processed. Energy state, glucose (cytosolic glycolysis versus mitochondrial Krebs cycle), protein and lipid metabolism (indicators of proliferation and invasiveness) metabolomic profiles were assessed globally in correlation with clinical and histopathologic findings. Results: Findings suggest shift from cytosolic glycolysis (glucose decrease and increased lactate with minimal changes in pyruvate) towards the mitochondrial Krebs cycle (elevated glutamine and glutamate synthesis) in all tumor samples. Aspartate, myoinositol, and cell membrane phospholipids such as phosphocholine/glycerophosphocholine were greater in untreated GIST xenografts compared to treated tumors. Alanine, taurine, proline, ADP and phosphocholine were significantly higher in tumor tissue extracts compared to control (imatinib treated) (p<0.05). Tumor stage, mitotic index or mutation type did not correlate with metabolomic profile. Differences were accentuated among untreated patients. Partial Least Squares-Discriminant Analysis (PLS-DA) model successfully separated tumor tissues from controls (R2Y=0.56, Q2Y=0.22). Conclusions: Metabolomic profiling of patient and xenograft GIST samples exposed to KIT inhibitors suggest that cytosolic glycolysis and phospholipid biology may be important not only in the GIST phenotype but may be ameliorated with KIT inhibition by imatinib. Further understanding of GIST metabolomics may lead to the identification of new therapeutic targets.
A retrospective analysis of the effect of continuing bevacizumab beyond disease progression in patients with non-small cell lung cancer.
Authors: Takashi Yokoi, Takayasu Kurata, Yoshitaro Torii, Yuichi Katashiba, Maiko Niki, Yusuke Sawai, Yuta Yamanaka, Naoko Murakami Satsutani, Shosaku Nomura
Journal: Journal of Clinical Oncology (2014)

e19132 Background: Randomized studies showed that the addition of bevacizumab to standard chemotherapy regimens significantly improved outcome in previously untreated patients with advanced non-squamous non-small cell lung cancer (NSCLC). However, there is no evidence to support the benefit of continued usage of bevacizumab beyond disease progression in patients with non-squamous NSCLC treated with the bevacizumab-based chemotherapy in first-line therapy. We retrospectively analyzed the efficacy and safety of docetaxel plus bevecizumab beyond progression (BBP) patients with non-squamous NSCLC whose disease has progressed after first-line treatment with bevacizumab. Methods: We retrospectively reviewed advanced non-squamous NSCLC patients who were treated with docetaxel plus BBP as second-line after disease progression in first-line treatment with bevacizumab plus a platinum-based doublet between November 2009 and March 2013. Results: Twenty two patients received the combination chemotherapy of docetaxel plus BBP as second-line. Sixteen were male, and median age was 63 (40-75). Twenty one patients received CBDCA plus pemetrexed in the first-line, and one patient received CDDP plus gemcitabine. Objective responses were observed in 7 (31.8%) patients (7 PR) and stable disease in 12 (54.6%). Total clinical benefit (CR+PR+SD) was observed in 19 (86.4%). The median number of cycle was 5.5, progression free survival (PFS) was 4.5 months and overall survival (OS) was 17.2 months. Severe adverse events were observed in 17 (77.3%) patients. Seventeen patients experienced neutropenia (include one febrile neutropenia) and three had general fatigue. Conclusions: Although retrospective analysis, these results suggest that docetaxel plus BBP in second line setting shows sufficient clinical benefit compared with historical control with favorable toxicity profile.
A Phase II Trial of Nivolumab Combined with Ibrutinib for Patients with Richter Transformation
Authors: Nitin Jain, Alessandra Ferrajoli, Sreyashi Basu, Philip A. Thompson, Jan A. Burger, Tapan M. Kadia, Zeev E. Estrov, Naveen Pemmaraju, Wanda Lopez, Beenu Thakral, Joseph David Khoury, Carlos E. Bueso-Ramos, Jorge Blando, Susan M. O'Brien, Hagop M. Kantarjian, James P Allison, Michael J Keating, Padmanee Sharma, William G. Wierda
Journal: Blood (2018)
The use of endobronchial ultrasound to place fiducial markers for targeted radiation therapy.
Authors: Christopher Parks, Patricia L. Thompson, Rabih Bechara
Journal: Journal of Clinical Oncology (2014)

e18529 Background: Radiation therapy is a common treatment modality for patients with thoracic involvement with there tumors. As advanced radiation systems have become available the use of fiducial markers to increase safety and accuracy has increased. Historically these markers were placed transthoracicly which is not ideal due to a high incidence of pneumothorax. Recently placement via navigational bronchoscopy has become available which has decreased the pneumothorax rate, but is not ideal for central lesions. Methods: 10 consecutive patients in whom placement of fiducial markers was requested by radiation oncology for central lesions were selected. Using a linear ebus bronchoscope (Olympus) with a standard 21 gauge needle the central lesions were identified. Then under real time ultrasound guidance a total of 33 fiducial markers were placed. The location of the markers was immediately confirmed via ultrasound and later by computed tomography. Monitoring for adverse events including bleeding, pneumothorax, and malposition of the markers was undertaken. Results: 33 fiducial markers were placed successfully via endobronchial ultrasound. There were no adverse events noted during this study. Conclusions: Endobronchial ultrasound is a safe and effective way to place fiducial markers.
Abstract 17400: Evaluation of Estimated and Directly Measured Remnant Lipoprotein Cholesterol: The Very Large Database of Lipids
Authors: Kamil F Faridi, Renato Quispe, Aditya D Hendrani, Parag H Joshi, Eliot A Brinton, Daniel E Cruz, Maciej Banach, Peter T Toth, Krishnaji Kulkarni, Seth S Martin, Steven R Jones
Journal: Circulation (2016)

Introduction: Remnant lipoproteins (RLP) are triglyceride-rich cholesterol-containing particles and an emerging risk factor for development of cardiovascular disease, but there is no standard metho...
Association of loss of BAP1 expression in cell renal cell carcinomas with PDL1 expression.
Authors: Richard Wayne Joseph, Payal Kapur, Daniel Serie, John C. Cheville, Jeanette Eckel-Passow, Mansi Parasramka, Thai Huu Ho, Eugene D. Kwon, Robert Houston Thompson, James Brugarolas, Alexander S. Parker
Journal: Journal of Clinical Oncology (2014)

4530 Background: A subset (10-20%) of clear cell renal cell carcinoma (ccRCC) tumors evades the immune system through expression of programmed death ligand 1 (PDL1), and these tumors are associated with a more aggressive clinical course. Related to this, loss of PBRM1 or BAP1 expression in ccRCC is also associated with poor outcomes. Herein, we evaluate whether loss of PBRM1 or BAP1 expression is associated with PDL1 expression in ccRCC tumors. Methods: From the Mayo Clinic Renal Tumor Registry we identified 1,010 patients undergoing nephrectomy for localized ccRCC from 1990-2004 who had immunohistochemistry (IHC) for PDL1, BAP1, and PBRM1 as part of previous investigations. A pathologist (PK) classified PBRM1 and BAP1 as either positive or negative and excluded those with heterogeneous or weak staining. A separate pathologist (JCC) defined PDL1+ tumors as those with ≥5% on IHC. We examined the association of PDL1 expression with PBRM1 and BAP1 separately and in combination using two-sided p-values from Fisher exact tests. Results: Among the 1,010 patients, 126 (12%) were excluded for unclear PBRM1/BAP1 expression leaving a total of 884 (88%) for evaluation. The distribution of each marker is as follows: 87 (10%) BAP1 negative, 458 (52%) PBRM1 negative, and 81 (9%) PDL1 positive (see Table). BAP1-negative tumors were more likely to be PDL1 positive than BAP1-positive tumors (17% vs 8%, p=0.0102)); however, the absolute difference was small (9%). In contrast, PDL1 expression did not differ by PBRM1 status (10% vs 9%, p=0.56). In a combined analysis grouping tumors by both PBRM1 and BAP1 expression, there remained a significant association with PDL1 positivity (p=0.015). Conclusions: In this study, BAP1 negative tumors were more likely to be positive for PDL1; however, the majority of BAP1 negative tumors are PDL1 negative. PBRM1 expression was not associated with PDL1 positivity. PDL1- n=803 (91%) PDL1+ n=81 (9%) P value Univariate PBRM1 0.56 + 384 (90.1%) 42 (9.9%) - 419 (91.5%) 39 (8.5%) BAP1 0.0102 + 731 (91.7%) 66 (8.3%) - 72 (82.8%) 15 (17.2%) Combined 0.015 PBRM1/BAP1 +/+ 327 (92.1%) 28 (7.9%) -/+ 404 (91.4%) 38 (8.6%) +/- 57 (80.3%) 14 (19.7%) -/- 15 (93.8%) 1 (6.3%)
Urban and rural differences in outcomes of head and neck cancer (HNC).
Authors: Tian Yang Darren Liu, Jason D. Kim, Ali Moghaddamjou, Khodadad R. Javaheri, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2014)

6570 Background: Management of HNC is becoming more specialized where effective treatments frequently require multidisciplinary and multimodality care. Concerns exist that access to such complex care may be suboptimal for marginalized subsets of the population. Our aim was to examine for potential urban and rural disparities in HNC outcomes within a population-based single payer healthcare system. Methods: All patients diagnosed with HNC from 2001 to 2010 and referred to any 1 of 5 regional comprehensive cancer centers in British Columbia, Canada were reviewed. Based on census data, patients were classified into 4 categories: 1) rural 2) small urban 3) moderate urban and 4) large urban areas. Kaplan Meier methods and Cox regression were used to correlate site of residence with overall survival (OS), controlling for prognostic factors that included socio-demographics and other tumor and treatment-related characteristics. Results: A total of 3,036 patients were included: median age was 64 years, 74% were men, and 32% were ECOG 0/1. The majority resided in large urban areas (55%) followed by rural (22%), moderate urban (13%), and small urban (10%). There were no clinically significant differences in baseline characteristics across the 4 groups. In multivariate-adjusted models, advanced age >/= 65 years (HR 1.58, 95%CI 1.21-2.06, p<0.001), ECOG 2+ (HR 4.20, 95%CI 2.41-4.93, p<0.001), and lack of multimodality treatment (HR 2.88, 95%CI 1.72-4.81, p<0.001) correlated with inferior OS, but site of residence did not (Table). In subgroup analyses that stratified by type of treatment (radiation, chemotherapy, and/or surgery) and anatomic location of HNC (oral cavity, oropharynx, larynx, hypopharynx, nasopharynx), OS remained similar irrespective of urban or rural residence. Conclusions: Urban-rural differences in outcomes were not observed. The centralization of HNC management in this large population-based cohort represents an appropriate model of care for cancers in which multimodality treatments are increasingly complex and where disparities in access may be prevalent. Residence HR for death 95%CI P-value Rural 1.0 -- -- Small urban 1.27 0.77-2.10 0.35 Moderate urban 0.84 0.52-1.37 0.49 Large urban 1.19 0.80-1.56 0.51
The Tuberculosis Network European Trials group (TBnet) ERS Clinical Research Collaboration: addressing drug-resistant tuberculosis through European cooperation
Authors: Frank van Leth, Folke Brinkmann, Daniela M. Cirillo, Keertan Dheda, Raquel Duarte, Lorenzo Guglielmetti, Liga Kuksa, Christoph Lange, Carole Mitnick, Alena Skrahina, Khalequ Zaman, Graham Bothamley
Journal: European Respiratory Journal (2019)

While the incidence of tuberculosis (TB) has fallen steadily within the European Union, the region has by far the highest estimated incidence of multidrug-resistant (MDR)-TB among TB patients [1, 2], which hampers the goal of the World Health Organization (WHO) of TB elimination in the region [3]. MDR-TB has the potential to be the most important infectious threat to European health over the coming decades, unless effective treatment can be found and relapses prevented. The Tuberculosis Network European Trials group (TBnet) continues the successful ERS Clinical Research Collaboration on drug-resistant tuberculosis <http://ow.ly/gGH330mHrDa>
Integration of palliative care into standard oncology practice in the Czech Republic.
Authors: Marek Sochor, Ondrej Slama, Martin Loucka
Journal: Journal of Clinical Oncology (2014)

e20546 Background: Patients with advanced cancer experience symptoms that worsen quality of life (QoL). Palliative care (PC) is traditionally applied after antineoplastic therapy. A concept of early integration of palliative care (EPC) into standard oncology practice, has been shown to provide benefits for QoL, symptoms, and survival. However, successful integration of PC into oncological practice is related to specific features of health care systems. The aim of our project is to monitor the access to PC in cancer centers in the Czech Republic and to test the feasibility of integration of EPC under circumstances of a Czech health care system. Methods: The presented study is a national survey conducted in 13 cancer centers in the Czech Republic. These are the centers of excellence of Czech oncological care. The survey was online platform focused on the provision and access to services of supportive and palliative care. Firstly we asked on integration of specialists in PC, pain, nutrition, rehabilitation, social, psychological and spiritual care and established PC teams in these centers. The second part were questions on use of these services in patients undergoing anticancer therapy. In the last part were questions on typical direction of patients after anticancer therapy has ceased. Results: In Czech cancer centers are integrated PC specialists in 4 of them. Other supportive care specialists are integrated more frequently: pain 7, nutrition 9, rehabilitation 7, psychology 9, social and spiritual care 8. The proportion of patients who used palliative/supportive care services during curative treatment is: pain 24,5%, nutrition 23,5%, psychology 14,5%, social 42%, and spiritual care 16,5%. After termination of anticancer therapy is 47% patients followed and treat in cancer centers. From the rest is 13,5% directed to PC outpatient clinics, to GP 16,5%, to inpatient hospice care 12,5%, and to home hospice care 10,5%. Conclusions: Access to palliative care in Czech cancer centers is very low. Education and dissemination of goals of PC can improve this situation. For this purpose we will start a prospective randomized controlled trial of early integration of palliative care into standard oncology practice in newly diagnosed metastatic cancers.