tbuckley/cabot-search huggingface dataset:
P01.074 Interest of QuID-7 for insular localization gliomas
Authors: C Belin, T Bieth, S Cuzzubbo, R Ursu, A F Carpentier
Journal: Neuro-Oncology (2018)

Although insular infiltration by gliomas is relatively common, the related symptomatology is poorly known and therefore often undiagnosed. To better diagnose insular signs with a new designed questionnaire: the QuID -7. The QuID 7 covers 7 semiological fields corresponding to 27 items related to insular symptomatology, based on the literature data. Over a 13 month period, patients with a histological diagnosis of cerebral glioblastoma were reviewed. Those with a bifocal lesion, aphasic disorders or altered general state, were excluded. Questionnaires were administered at the same time point during the patients’ follow-up, corresponding to the first monthly cure of temozolomide. 44 patients were included, 30 of them (68%) with insular involvement. None of the patients refused the questionnaire. Administration time was about 10 minutes. Insular patients reported overall more signs than the non-insular group (75% versus 25 %) and in each semiological field: somato-sensorial (75 % vs 25%), viscero-sensorial (64% vs 36%), auditory (83% vs 17%), gustatory (76% vs 24%), language (81% vs 19%), neuropsychiatric (72% vs 28%). The most pathognomonic sign of insula involvement was the presence of symptoms ipsilateral to the lesion side, particularly for the somatosensory (7%) and auditory (44%) fields. The QuID 7 was well accepted and easily understood by all patients. QuID 7 brings a new visibility to the insular symptomatology for physicians in their medical practice. Moreover, our results point out (i) the importance of sensorial manifestation, and (ii) that symptoms related to an insular lesion can be ipsilateral to the lesion side.
TCT-511 Two-year Clinical Results with the Angiolite® Drug-Eluting Stent: The ANCHOR Study.
Authors: Rishi Puri, Imanol Otaegui, Manel Sabate, Antonio Serra, Marti Puigfel Pont, Armando Perez de Prado, Luis Nombela-Franco, Jose de la Torre Hernandez, Maria Rosario Ortas-Nadal, Andres Iñiguez, Felipe Fernandez-Vazquez, Carlos Cuellas-Ramon, Nieves Gonzalo, Victor Jimenez Diaz, Luis Duocastella, Maria Molina, Marc Amoros, Isabel Perez, Emilie Pelletier-Beaumont, Stephen Nicholls, Bruno Garcia, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2018)
Abstract 17307: Biomarkers, Cardiovascular Outcomes and Effect of Ezetimibe After Acute Coronary Syndrome in the IMPROVE-IT Trial
Authors: Arman Qamar, Robert P Giugliano, Michael A Blazing, Jeong G Park, Sabina A Murphy, Christopher P Cannon, Eugene Braunwald, David A Morrow
Journal: Circulation (2017)

Introduction: Addition of ezetimibe to statin therapy reduces the risk of recurrent cardiovascular (CV) events in patients (pts) with prior acute coronary syndrome (ACS). We evaluated the relations...
Abstract B039: Multinucleation precedes the emergence of drug resistance in prostate cancer
Authors: Gonzalo Torga, Ke-Chih Lin, Robert H. Austin, Kenneth J. Pienta
Journal: Cancer Research (2018)

Abstract Metastatic prostate cancer remains a lethal disease. Taxane chemotherapy used to be restricted to the hormone-resistant metastatic setting in which most patients with castration-resistant prostate cancer (CRPC) develop therapeutic resistance to chemotherapy, achieving limited therapeutic benefit. Recently, two trials demonstrated adjuvant chemohormonal therapy to increase survival in men with high-risk metastatic hormone-sensitive prostate cancer. Although chemotherapy has been extensively used for decades, how it affects tumor heterogeneity at the molecular level is poorly understood. Experiments with drug gradients in our engineered microfluidic device have shown that docetaxel therapy leads to multinucleation with a stiff distribution pattern of heterogeneous cell populations across the concentration gradient. Furthermore, in these experiments, multinucleation always preceded the development of drug resistance. To confirm these findings, we conducted experiments in conventional cell culture using different chemotherapeutic agents in several prostate cancer cell lines and confirmed multinucleation was a common feature among them. Interestingly, multinucleation occurred to some extent, independently of the mechanism of action of the drug tested. Aneuploidy, an inherent consequence of multinucleation, has been described as a common characteristic of tumors and proposed to drive tumor progression by increasing the potential for cellular transformation. However, whether this is a cause or a consequence of cancer remains unclear. Aneuploidy can be caused by very diverse molecular mechanisms such as mitotic slippage, endo-replication, or cell fusion. In cancer biology, it has been associated with epithelial-mesenchymal transition as well as with gain of stem-like potential. Recent data in prostate cancer demonstrated the association of multinucleation with chemotherapy, androgen-deprivation therapy, and radiotherapy. Although the data supporting the association of multinucleation with drug resistance are extensive, the effects of these therapies on tumor heterogeneity remain unknown. A better understanding of the resistance mechanisms might reveal new targets for cancer therapy. In this work, we focus on the characterization of the subset of cells within the tumor population that leads to the multinucleated phenotype, particularly the subpopulation with the potential to reverse polyploidy and repopulate tumor heterogeneity after therapy. Citation Format: Gonzalo Torga, Ke-Chih Lin, Robert H. Austin, Kenneth J. Pienta. Multinucleation precedes the emergence of drug resistance in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B039.
Use of supportive care at end-of-life for patients younger than 65 with incurable cancer.
Authors: Aaron David Falchook, Fang Tian, Stacie Dusetzina, Ramsankar Basak, Laura Hanson, Nandini Selvam, Ronald C. Chen
Journal: Journal of Clinical Oncology (2016)

6514 Background: There is increasing recognition of the importance of supportive care for cancer patients at the end of life. This includes palliative care consultation, home health nursing, and hospice. However, the prevalence in use of supportive care services for younger patients has not been previously described. We also examined whether ASCO’s 2012 Choosing Wisely campaign to reduce overuse of aggressive end-of-life care resulted in increased supportive care services use. Methods: Claims data from the HealthCore Integrated Research Database were analyzed, which includes ~60 million individuals enrolled in Blue Cross and/or Blue Shield licensed plans across 14 states. Patients aged ≤65 who died between 2007-2014 and who had diagnoses for metastatic lung, colorectal, breast, pancreatic, and prostate cancers were included. Poisson multivariable regression models assessed associations between age group, geographic region, gender, and regional education and income measures with supportive care use. Results: 28,731 patients were included. Overall, 39-42% of patients across cancers received supportive care services within the last 90 days of life (Table), including 15-19% of patients enrolled in hospice. Supportive care use increased for patients with lung (by 4%), colorectal (2%), breast (2%), and prostate (22%) cancers comparing early 2012 before Choosing Wisely to 2014; but decreased (5%) in pancreatic cancer. In addition, 53-55% of patients were prescribed medications for pain, anxiety, nausea, anorexia, depression, or delirium. Multivariable models showed regional variations in use of supportive care. Conclusions: Use of supportive care services for younger patients at the end of life increased modestly for several common cancers after the 2012 ASCO Choosing Wisely recommendations. However, there remains substantial underuse of hospice, home health nursing, and palliative care consultation among these patients. Supportive care within the last 90 days of life. Lung N = 12,764 Colorectal N =5,207 Breast N = 5,855 Pancreas N =3,397 Prostate N = 1,508 Overall Supportive Care (%) 39 40 39 42 40 Hospice (%) 16 17 15 19 17 Home health nursing (%) 12 12 12 11 12 Palliative care consultation (%) 20 19 20 21 20
Identification of APE1 as a chemotherapeutic prognostic marker for non-small cell lung cancer patients.
Authors: Mengxia Li, Dong Wang, Shiheng Zhang, Le He, Nan Dai
Journal: Journal of Clinical Oncology (2016)

e23065 Background: Given the critical role of DNA repair proteins in preserving genomic integrity, their overall functional status can serve as a promising biomarker for disease risk and therapeutic responsiveness. Our prior work revealed that the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) is present in the serum of study participants. Methods: Here, we measured APE1 protein levels in biopsy tissue and sera of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. Results: We found that serum APE1 level is significantly elevated in 229 number of 412 number NSCLC patients and correlates with its level in tissues (p < 0.001). The elevated APE1 level in both tissue and serum are associated with worse progression-free survival (HR: 2.165, P < 0.001, HR: 1.421, P = 0.012). After treatment, a low APE1 serum level was associated with better overall survival (HR: 0.497, P = 0.010). Conclusions: Our studies indicate that APE1 is a biomarker for diagnosing NSCLC and predicting therapeutic efficacy and prognosis. This study has identified a novel biomarker in APE1, a core DNA repair enzyme of the base excision repair pathway, for diagnosing NSCLC and predicting chemotherapeutic efficacy and prognosis. The chemotherapy-naïve serum APE1 level, correlating with its tissue level, inversely associated with progression-free survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival.
Abstract 18525: Novel Usefulness of Synthesized 18-Lead Electrocardiography in the Diagnosis of ST-Elevation Myocardial Infarction: A Pilot Study
Authors: Tadashi Ashida, Ken Nagao, Shigemasa Tani, Tsukasa Yagi, Hiroshi Takahashi, Eizo Tachibana, Shingo Furuya, Naoya Matsumoto, Atsushi Hirayama
Journal: Circulation (2016)

Background: Recently, synthesized 18-lead electrocardiography has been developed, which includes recordings obtained from synthesized right chest leads (syn-V3R-V5R) and synthesized posterolateral ...
A novel phase I/IIa open-label study of IMM-101 in combination with selected standard of care regimens in patients with metastatic cancer or unresectable cancer at study entry.
Authors: David Cunningham, Jean-Yves Blay, Aurelien Marabelle, David Stanbury, Satvinder Mudan, Laura Rosa Brunet
Journal: Journal of Clinical Oncology (2017)

e14627 Background: The MODULATE (IMM-101-011, EUDRACT 2016-001459-28) trial recruits patients with metastatic or unresectable cancer considered for a new line of recognised SOC (1 st , 2 nd or 3 rd line and beyond). IMM-101 is a heat-killed whole cell Mycobacterium obuense (National Collection of Type Cultures [NCTC] 13365) for intradermal injection. Methods: The primary objective of the study is to provide safety data for IMM-101 in combination with several selected SOC regimens. The secondary objectives of the study are to provide safety and tolerability data for extended administration (beyond 28 weeks) of the immunomodulator IMM-101 in combination with a number of selected SOC regimens. A particular focus of the study is to evaluate safety data for the combination of IMM 101 with anti PD1 and with anti-CTLA 4. Pre-clinical data suggests that IMM-101 increases the response to PD1 in a syngeneic in vivo model of EMT6 breast cancer. Furthermore, in a syngeneic B16 melanoma tumour model the combination of IMM-101 with anti-PD1 antibodies increased T effector cells in the tumour and reduced the numbers of T-regulatory cells; significantly shifting the T-cell ratio towards anti-tumour efficacy. Results: The study aims through its translational programme to evaluate the best combination partner for IMM-101 due to the SOCs immunogenic cell death capabilities and supportive immunological activities. MODULATE will monitor selected markers of tumour burden and immunological status in patients taking IMM-101. Conclusions: The MODULATE study will initially recruit patients in the UK and France with US sites added in Q4 2017. Clinical trial information: NCT03009058. [Table: see text]
Prevalence of depression and anxiety in older patients with multiple myeloma in North Carolina: A population-based, claims-based assessment.
Authors: Anureet Copeland, Ashley Freeman, Christopher Baggett, Lei Zhou, Thomas C. Shea, Sascha Alexander Tuchman, William Allen Wood
Journal: Journal of Clinical Oncology (2017)

10048 Background: Patients (pts) with multiple myeloma (MM) experience physical symptoms and complications from disease or treatment that include bone pain, fatigue, anorexia, and insomnia. However, the prevalence of psychiatric comorbidities and their impact on short and long-term outcomes has been understudied. The aim of this analysis was to identify the prevalence of anxiety and depression in older pts with MM in the state of North Carolina. We also sought to evaluate if comorbid depression and anxiety impacted short and long-term outcomes in these patients. Methods: Using the University of North Carolina Integrated Cancer Information and Surveillance System (ICISS), we retrospectively identified a statewide cohort of 536 pts (ages 65-80) diagnosed with MM from 2006-2012 who had continuous enrollment in Medicare or Medicaid. Patients were identified through insurance claims by ICD-9 diagnosis codes for anxiety or depression or antidepressant medications filed at any time from 6 months prior to MM diagnosis to 12 months after MM diagnosis. Results: The mean age of pts in the cohort was 72 years. Pts were 68% non-Hispanic white, 42% rural, and 51% male. Of the 536 pts, 200 (37%) had a diagnosis of anxiety or depression and/or were being treated with an antidepressant. 54% of those with psychiatric comorbidity had a relevant diagnosis or medication in the 6 months prior to MM diagnosis. Of those with psychiatric comorbidities, 70% were diagnosed with fatigue and 57% were diagnosed with pain. In multivariate analysis, there was no association of psychiatric comorbidity with mortality (HR, 1.03; 95% CI, 0.83-1.28), but psychiatric comorbidity was associated with an increased likelihood of hospitalization or ER visit (RR, 1.17; 95% CI, 1.05-1.30) and increased opiate use within 1 year after diagnosis (RR, 1.66; 95% CI, 1.27-2.16). Conclusions: The presence of psychiatric comorbidity identifies a subset of older MM pts at risk for high symptom burden and increased health care utilization. The association of psychiatric comorbidity with increased opiate use in cancer pts may also have public health implications.
cGMP-dependent protein kinase I (cGKI) modulates human hepatic stellate cell activation
Authors: Andras Franko, Marketa Kovarova, Susanne Feil, Robert Feil, Robert Wagner, Martin Heni, Alfred Königsrainer, Marc Ruoß, Andreas K. Nüssler, Cora Weigert, Hans-Ulrich Häring, Stefan Z. Lutz, Andreas Peter
Journal: Metabolism (2018)

BackgroundThe activation of hepatic stellate cells (HSCs) plays a crucial role in liver fibrosis, however the role of HSCs is less understood in hepatic insulin resistance. Since in the liver cGMP-dependent protein kinase I (cGKI) was detected in HSC but not in hepatocytes, and cGKI-deficient mice that express cGKI selectively in smooth muscle but not in other cell types (cGKI-SM mice) displayed hepatic insulin resistance, we hypothesized that cGKI modulates HSC activation and insulin sensitivity.Materials and MethodsTo study stellate cell activation in cGKI-SM mice, retinol storage and gene expression were studied. Moreover, in the human stellate cell line LX2, the consequences of cGKI-silencing on gene expression were investigated. Finally, cGKI expression was examined in human liver biopsies covering a wide range of liver fat content.ResultsRetinyl-ester concentrations in the liver of cGKI-SM mice were lower compared to wild-type animals, which was associated with disturbed expression of genes involved in retinol metabolism and inflammation. cGKI-silenced LX2 cells showed an mRNA expression profile of stellate cell activation, altered matrix degradation and activated chemokine expression. On the other hand, activation of LX2 cells suppressed cGKI expression. In accordance with this finding, in human liver biopsies, we observed a negative correlation between cGKI mRNA and liver fat content.ConclusionsThese results suggest that the lack of cGKI possibly leads to stellate cell activation, which stimulates chemokine expression and activates inflammatory processes, which could disturb hepatic insulin sensitivity.
Analysis of feasibility of geriatric assessment tools in elderly cancer patients and effects on anti-cancer treatment planning.
Authors: Ulug Mutlu Gunaydin, Asli Tufan Cincin, Senay Gunaydin, Faysal Dane, Nalan Babacan, Mehmet Akif Ozturk, Perran Fulden Yumuk
Journal: Journal of Clinical Oncology (2018)

e22028 Background: Cancer is predominantly a disease of elderly. Geriatric assessment (GA) of elderly cancer patients is recommended, while GA is time-consuming and hard to perform in an outpatient oncology clinic. We investigated effects of GA on anti-cancer treatment decisions and if these tools can be used in our daily clinical practice. Methods: Fourtyone patients 65 years or older with solid organ malignancies were included in this study. G8 screening tool, fTRST screening tool, FRAIL questionnaire, basic and instrumental activities of daily living scales, depression screening questionnaire and timed up and go test were implemented and durations of each test were recorded. Test results and related medical records of patients were presented to 3 medical oncologists after blinding first treatment decision, to explore if these data changed their treatment plans. They were also asked to score the tests which influenced them during their treatment planning. Multivariate logistic regression and correlation analysis were performed. Results: Medical oncologists, who were aware of the GA results, recommended changing treatment plans in 43.9% of patients. In 12 patients, all medical oncologists prefer to alter treatment plans and at least two medical oncologists recommended modification in treatment plan in 4 patients. Results of fTRST screening tool and FRAIL questionnaire significantly influenced this (p = 0.035 and p = 0.002 respectively). Each test lasted for approximately one minute. Albumin levels of patients whose treatment plans were changed were significantly lower than the others (p < 0.019). Conclusions: Our findings showed that the geriatric screening tools may affect the anti-cancer treatment plans of elderly patients. There is an increasing need for a brief, standardised screening tool to assess elderly patients with cancer. When comprehensive geriatric assessment is not possible, treatment plans may be modified by fTRST screening tool, FRAIL questionnaire and serum albumin level.
Rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with breast cancer.
Authors: Lee Steven Schwartzberg, Rudolph M. Navari, Sujata Arora, Daniel Powers, Karin Jordan, Bernardo Leon Rapoport
Journal: Journal of Clinical Oncology (2016)

10121 Background: Addition of the neurokinin-1 receptor antagonist (RA) rolapitant to standard antiemetic therapy improved CINV control in a phase 3 trial of patients administered anthracycline/cyclophosphamide (AC)–based chemotherapy or non–AC-based moderately emetogenic chemotherapy. Methods: Patients were randomized 1:1 to double-blind treatment with 180 mg oral rolapitant or placebo plus an oral 5-hydroxytryptamine type 3 (5-HT3 ) RA and dexamethasone prior to chemotherapy. In a post hoc analysis, we assessed the efficacy and safety of rolapitant in patients with breast cancer who received AC-based chemotherapy (n=680) and those who received AC- or non–AC-based chemotherapy (n=845). Endpoints included complete response (CR; no emesis and no use of rescue medication), no emesis, no nausea (maximum visual analogue scale [VAS] <5 mm), and complete protection (CP; no emesis, no use of rescue medication, and no significant nausea [maximum VAS <25 mm]) in the overall (0–120 h), acute (≤24 h), and delayed (>24–120 h) phases. Results: CR rates in both the overall and delayed phases were higher with rolapitant versus control in the AC and combined subgroups (P<.05; Table). Rolapitant also improved no emesis rates in the AC and combined subgroups in both the overall (P<.001) and delayed (P<.01) phases. The frequency of treatment-emergent adverse events overall was 69.2% for rolapitant versus 69.7% for control; the overall safety profile was comparable. Conclusions: Rolapitant added to standard 5-HT3 RA/dexamethasone therapy improved CINV control in patients with breast cancer receiving AC-based chemotherapy and the overall population of patients with breast cancer receiving AC-/non–AC-based chemotherapy. Clinical trial information: NCT01500226.Endpoint, % AC-Based AC-/Non–AC-Based Rolapitant (n=333) Control (n=347) P* Rolapitant (n=417) Control (n=428) P* Overall phase CR 62 54 .024 63 55 .023 No emesis 72 59 <.001 74 63 <.001 No nausea 34 35 .676 35 37 .520 CP 54 50 .275 55 51 .195 Acute phase CR 76 77 .835 78 78 .963 No emesis 83 80 .359 84 82 .351 No nausea 54 59 .187 57 62 .116 CP 68 71 .307 70 73 .396 Delayed phase CR 67 59 .034 67 60 .039 No emesis 76 66 .007 77 69 .005 No nausea 37 39 .597 39 40 .641 CP 57 54 .453 58 55 .324 *Unstratified Cochran-Mantel-Haenszel test.