tbuckley/cabot-search huggingface dataset:
Development of a patient‐reported outcomes symptom measure for patients with nontransfusion‐dependent thalassemia (NTDT‐PRO<sup>©</sup>)
Authors: Ali Taher, Vip Viprakasit, Maria Domenica Cappellini, Pranee Sutcharitchan, Richard Ward, Dalia Mahmoud, Abderrahmane Laadem, Anzalee Khan, Chad Gwaltney, Gale Harding, Kenneth Attie, Xiaosha Zhang, Jun Zou, Joseph Pariseau, X. Henry Hu, Antonis Kattamis
Journal: American Journal of Hematology (2018)

Abstract β‐Thalassemia, a hereditary blood disorder caused by reduced or absent synthesis of the β‐globin chain of hemoglobin, is characterized by ineffective erythropoiesis, and can manifest as nontransfusion‐dependent thalassemia (NTDT) or transfusion‐dependent thalassemia (TDT). Many patients with NTDT develop a wide range of serious complications that affect survival and quality of life (QoL). Patient‐reported outcomes (PRO), including health‐related QoL (HRQoL), are important tools for determining patient health impairment and selecting appropriate treatment. However, there are currently no disease‐specific PRO tools available to assess symptoms related to chronic anemia experienced by patients with NTDT. This study aimed to develop a new, US Food and Drug Administration (FDA)‐compliant PRO of chronic anemia symptoms, the NTDT‐PRO © tool, for use in patients with NTDT. Participants had a median age of 36 years (range, 18‐47) and 60% were female. The initial development of the NTDT‐PRO tool involved concept‐elicitation interviews with 25 patients from 3 centers (in Lebanon, Greece, and Canada); subsequent interview discussions and clinical input resulted in the generation of 9 items for inclusion in the draft NTDT‐PRO. Following a round of cognitive interviews involving 21 patients from 2 centers (in Lebanon and Greece), 4 items (Pain, Headaches, Ability to Concentrate, and Paleness) were removed from the draft NTDT‐PRO. The final NTDT‐PRO comprises 6 items that measure Tiredness, Weakness, and Shortness of Breath, with or without Physical Activity. The NTDT‐PRO is a new disease‐specific HRQoL tool for patients with NTDT, developed using a thorough methodology based on FDA 2009 PRO development guidelines.
Abstract 10948: Patient-reported Quality of Life is a Predictor of Outcomes After Left Ventricular Assist Device Compared to Medical Therapy - Results From the ROADMAP Study
Authors: Josef Stehlik, Donald C Haas, Jerry D Estep, Craig H Selzman, Joseph G Rogers, Carmelo A Milano, Douglas A Horstmanshof, James W Long, Brian Bruckner, Nader Moazami, Keyur B Shah, Vigneshwar Kasirajan, Rohinton Morris, Jerome M Thomas, David W Drucker, David E Lanfear, Robert J Brewer, Juan M Aranda, Charles T Klodell, Joyce Chuang, David J Farrar, Randall C Starling
Journal: Circulation (2015)

Introduction: The ROADMAP study examined outcomes in subjects with non-inotrope dependent advanced heart failure (n-HF) selected for either left ventricular assist device (LVAD) or optimal medical management (OMM). At 12 months, more LVAD subjects achieved the composite endpoint of survival and ≥75m improvement in 6-minute walk distance (6MWD), while all-cause mortality was similar in the 2 groups. This suggests the focus in decision-making should be on health related quality of life (HRQoL). Aim: The aim of this study was to identify predictors of favorable outcome in n-HF patients treated with LVAD or OMM. Methods: We analyzed ROADMAP study data from 200 n-HF pts receiving LVAD or OMM. HRQoL was assessed with the EQ-5D visual analog scale (VAS) that ranged from 0 (worst) to 100 (best) health status. Results: At baseline, both LVAD and OMM group had markedly impaired exertional capacity and HRQoL (Table 1). We found that baseline VAS was a powerful predictor of the utility of LVAD therapy. Subjects with VAS&lt;60 at baseline were more likely to achieve a positive outcome at 12 months (defined as survival with ≥75m 6MWD increase or survival with HRQoL VAS≥60) with LVAD compared to OMM (Table 1) thus favoring LVAD for these patients. No significant difference between treatments was seen for those with VAS≥60 at baseline (Table 1), supporting continued OMM. Similar results were seen when the examined outcome was survival as treated on original therapy (Figure 1). Conclusions: Patients with poor baseline QoL benefit the most from LVAD therapy compared to continued OMM. HRQoL assessed by EQ5D VAS provides valuable information that can aid in identification of suitable candidates for LVAD therapy.
Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts
Authors: Elizabeth R Volkmann, Donald P Tashkin, Myung Sim, Ning Li, Ellen Goldmuntz, Lynette Keyes-Elstein, Ashley Pinckney, Daniel E Furst, Philip J Clements, Dinesh Khanna, Virginia Steen, Dean E Schraufnagel, Shiva Arami, Vivien Hsu, Michael D Roth, Robert M Elashoff, Keith M Sullivan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objective</h3> To assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II. <h3>Methods</h3> SLS I randomised 158 patients with SSc-ILD to 1 year of oral cyclophosphamide (CYC) vs placebo. SLS II randomised 142 patients to 1 year of oral CYC followed by 1 year of placebo vs 2 years of mycophenolate mofetil. Counting process Cox proportional hazard modelling identified variables associated with long-term mortality in SLS I and II. Internal validation was performed using joint modelling. <h3>Results</h3> After a median follow-up of 8 years, 42% of SLS I patients died, and when known the cause of death was most often attributable to SSc. There was no significant difference in the time to death between treatment arms in SLS I or II. Higher baseline skin score, older age, and a decline in the forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLCO) over 2 years were independently associated with an increased risk of mortality in SLS I. The Cox model identified the same mortality predictor variables using the SLS II data. <h3>Conclusion</h3> In addition to identifying traditional mortality risk factors in SSc (skin score, age), this study demonstrated that a decline in FVC and DLCO over 2 years was a better predictor of mortality than baseline FVC and DLCO. These findings suggest that short-term changes in surrogate measures of SSc-ILD progression may have important effects on long-term outcomes.
CBMT-01. PARAOXONASE-2 IS HIGHLY EXPRESSED IN GBM AND PROMOTES GBM CELL SURVIVAL
Authors: Hae-Ri Song, Hannah Cho, Edlira Hoxha
Journal: Neuro-Oncology (2018)

Paraoxonase-2 (PON2), a member of paraoxonase family, is an anti-oxidant enzyme that is implicated in cell survival. Recent evidence demonstrated that PON2 promotes apoptosis resistance in the selective tumor cells. Here, we report genetic regulation and role of PON2 in glioma. We showed that PON2 is highly expressed in glioblastomas (GBM) compared to non-tumor brains and that high PON2 expression is associated with poor survival in patients with GBM. Functional studies showed that knockdown of PON2 inhibits cell growth, induces apoptosis, and increases pro-apoptotic factor CHOP. Using transcriptome and transcription factor motif analysis, we showed that Nuclear Factor I-A (NFIA), a glioma-promoting transcription factor, positively regulates PON2 transcription and protein level and that PON2 and NFIA expression is highly correlated in GBM. Moreover, NFIA directly regulated PON2 transcription through binding to the PON2 promoter. Consistent with this finding, PON2 knockdown-induced growth inhibition is reversed by ectopic expression of NFIA. Furthermore, Nfia-deficient brain shows decrease in expression of PON2, providing genetic evidence that supports NFIA-PON2 regulatory relationship. Collectively, these data suggest that the pro-survival effect of PON2 is at least partly mediated by NFIA in GBM, advancing our understanding of the emerging role of PON2 in glioma.
Preventive sublingual immunotherapy with House Dust Mite extract modulates epitope diversity in pre‐school children
Authors: Marta Ponce, Fabian Schroeder, Christina Bannert, Klara Schmidthaler, Christian Skjødt Hansen, Katrine Lindholm Bøgh, Regina Soldo, Stephen Kwok‐Wing Tsui, Andreas Weinhäusel, Zsolt Szépfalusi, Thomas Eiwegger
Journal: Allergy (2018)

Abstract Background The preventive effect of allergen immunotherapy ( AIT ) on allergy and asthma development is currently assessed using primary and secondary AIT approaches. Knowledge of the immunological effects of these interventions is limited and the impact on epitope diversity remains to be defined. Methods We used high‐density peptide arrays that included all known Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) allergens and the whole proteome of Der f to study changes in House Dust Mite ( HDM ) linear peptide recognition during a 2‐year preventive double‐blind placebo‐controlled sublingual HDM AIT pilot study in 2‐5‐year‐old children with sensitization to HDM but without symptoms. Results Preventive AIT ‐treated patients showed significantly higher IgG epitope diversity to HDM allergens compared to placebo‐treated individuals at 24 months of treatment ( P &lt; 0.05), while no increase in IgE diversity was seen. At 24 months of treatment, IgG4 diversity for HDM allergens was significantly higher in the pAIT ‐treated patients compared to placebo group ( P &lt; 0.05). Potentially beneficial changes in epitope recognition throughout the treatment are also seen in peptides derived from Der f proteome. Conclusion These data suggest a beneficial immunomodulation of preventive sublingual immunotherapy at a molecular level by favoring a broader blocking repertoire and inhibiting epitope spreading.
Interventions for infantile haemangiomas of the skin: abridged Cochrane systematic review and<scp>GRADE</scp>assessments
Authors: M. Novoa, E. Baselga, S. Beltran, L. Giraldo, A. Shahbaz, H. Pardo‐Hernandez, I. Arevalo‐Rodriguez
Journal: British Journal of Dermatology (2018)

Background Infantile haemangiomas (IH) are soft swellings of the skin that occur in 3–10% of infants. When haemangiomas occur in high-risk areas or when complications develop, active intervention is necessary. Objective To update a Cochrane Review assessing the interventions for the management of IH in children. Methods We searched for randomized controlled trials in CENTRAL, MEDLINE, Embase, LILACS, AMED, PsycINFO, CINAHL and six trials registers up to February 2017. We included 28 trials (1728 participants) assessing 12 interventions. Results We downgraded evidence from high to moderate/low for issues related to risk of bias and imprecision. Oral propranolol (3 mg kg−1 daily) probably improves clinician-assessed clearance vs placebo [risk ratio (RR) 16·61, 95% confidence interval (CI) 4·22–65·34; moderate quality of evidence (QoE)]; we found no evidence of a difference in terms of serious adverse events (RR 1·05, 95% CI 0·33–3·39; low QoE). We found the chance of reduction of redness may be improved with topical timolol maleate (0·5% gel applied twice daily) when compared with placebo (RR 8·11, 95% CI 1·09–60·09; low QoE). We found no instances of bradycardia or hypotension for this comparison. Conclusions Our key results indicate that oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harm.
SURG-07. BETWEEN-HOSPITAL VARIATION IN MORTALITY AND SURVIVAL AFTER GLIOBLASTOMA SURGERY
Authors: Philip De Witt Hamer, Vincent Ho, Koos Zwinderman, Linda Ackermans, Hilko Ardon, Sytske Boomstra, Wim Bouwknegt, Wimar van den Brink, Clemens Dirven, Niels van der Gaag, Olivier van der Veer, Bas Idema, Fred Kloet, Jan Koopmans, Mark ter Laan, Marco Verstegen, Michiel Wagemakers, Pierre Robe
Journal: Neuro-Oncology (2018)

PURPOSE: To measure between-hospital variation in risk-standardized survival outcome after glioblastoma surgery and to explore the association between survival and hospital characteristics in conjunction with patient-related risk factors. Data of 2,409 adults with first-time glioblastoma surgery at 14 hospitals were obtained from a comprehensive, prospective population-based Quality Registry for Neurological Surgery in the Netherlands between 2011 and 2014. We compared the observed survival with patient-specific risk-standardized expected early (30-day) mortality and expected late (2-year) survival, based on patient age, performance status, and year of treatment. Summarized outcomes per hospital were analyzed in funnel plots. Hospital characteristics were analyzed in logistic regression and Cox proportional hazards models. Overall 30-day mortality was 5.2% and overall 2-year survival was 13.5%. Median overall survival varied between 4.8 and 14.9 months among hospitals, and biopsy percentages ranged between 16% and 73%. One hospital had lower than expected early mortality, and four hospitals had lower than expected late survival. Higher hospital volume was related with lower early mortality (P=0.031). A 10% increase in volume was associated with 3.9% relative decrease in early mortality, but not with overall survival. Patient-related risk factors (lower age; better performance; more recent years of treatment) were significantly associated with longer overall survival. Of the hospital characteristics, longer overall survival was associated with lower biopsy percentage (HR: 2.09, 1.34–3.26, P=0.001), and not with academic setting (HR: 0.951, 0.858–1.05), nor with hospital volume (HR: 0.954, 0.866–1.05). Hospitals vary more in late survival than early mortality after glioblastoma surgery. Widely varying biopsy percentages indicate treatment variation. Patient-related factors have a stronger association with overall survival than hospital-related factors.
Abstract 16682: Computational analysis of Right Ventricular Curvature From 3D echocardiography: Implications on Pulmonary Hypertension Severity
Authors: Maria Chiara Palumbo, Francesco Bandera, Eleonora Alfonzetti, Enrico G Caiani, Marco Guazzi
Journal: Circulation (2017)

Introduction: Clinical significance of progressive right ventricular (RV) deformation in the evolution of left and right ventricular dysfunction is quite underinvestigated. Hypothesis: To investiga...
RBTT-07. NUTMEG: A RANDOMISED PHASE II STUDY OF NIVOLUMAB AND TEMOZOLOMIDE (TMZ) VS TMZ ALONE IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM): TRIAL IN PROGRESS
Authors: Mustafa Khasraw, Kerrie McDonald, Sonia Yip, Roel Verhaak, Amy Heimberger, Merryn Hall, Lauren Fisher, Elizabeth Barnes, Mark Rosenthal, Craig Gedye, Elizabeth Hovey, Benjamin Ellingson, John Simes, Annette Tognela, Eng-Siew Koh, Hui Gan, Michael Back, Zarnie Lwin
Journal: Neuro-Oncology (2018)

An increase of mutations as we age is well documented in GBM and in cancer in general. Elderly patients with GBM may have higher mutational burden and may be more likely to respond to immunotherapies. NUTMEG is a randomised Phase II study comparing post radiation NivolUmab and TMZ versus TMZ alone in Elderly patients with newly diagnosed GBM. 102 patients will be randomized in a 2:1 allocation to receive short course RT (40Gy/15 daily fractions) and TMZ 75mg/m2) followed by 6 cycles of adjuvant TMZ (150-200mg/m2 days (D) 1–5 q28 days) with Nivolumab (240 mg D1, 15 q28 days for cycles (C) (1–4; 480 mg D1 Q 28 days for C5-6) versus 6 cycles of adjuvant TMZ (150-200mg/m2 D1-5 q28) alone. The study is stratified for ECOG performance status, age (< 70 vs 70), MGMT methylation and extent of resection. An independent safety monitoring committee is overseeing the trial and will review safety data for the first 10 patients treated on the experimental arm (TMZ + Nivolumab). The primary endpoint is Overall Survival (OS). Secondary endpoints include: 6 month Progression Free Survival, adverse events (AEs) and immune AEs, Quality of life, neurological function (NANO Scale), and correlation of modified RANO and iRANO in the experimental arm. Translational research endpoints include correlation of clinical endpoints with mutational burden, comprehensive immune characteristics and novel MRI sequences including pH-weighted MRIs. The expected proportion of patients alive at 24 months is predicted to be 15.7%. A hazard ratio of more than 0.69 in favour of the Nivolumab + TMZ arm will be considered sufficient to warrant further investigation including converting this study into a phase III trial. PROGRESS: At 3 June 2018, 6/18 study sites are open in Australia with 5 patients randomized. ACTRN12617000267358.
Inhibition of inflammation by PEITC, CUR, SFN alone and in combination in RAW cells
Authors: Ka Lung Cheung
Journal: Cancer Research (2008)

5477   Accumulating evidence from epidemiological and clinical studies indicates that chronic inflammatory disorders harbor an increased risk of cancer development. ROS/RNS can cause oxidative damage to DNA, proteins, and lipids. NF-κB is activated by a wide variety of stimuli such as oxidative stress, TNF, IL-1, LPS and UV light. The binding of NF-κB to specific sequence in the promoter region of genes triggers the transcriptional activation of NF-κB-regulated genes which are involved in tumor cell proliferation, angiogenesis and metastasis. Therefore, tumorigenesis resulting from inflammation could possibly be prevented by inhibiting the activation of NF-κB and its inflammation markers like TNF, IL-1, NO, PGE2. It is widely accepted that isothiocyanates such as SFN and PEITC are strong phase-II detoxifying/antioxidant enzymes inducer. On the other hand, CUR has been shown to be strongly linked to the anti-inflammatory effect. Therefore it would be interesting to see if combination of these compounds can inhibit inflammation or carcinogenesis, achieving lower toxicity and higher efficacy. In this study, we report that combination of PEITC/SFN or Curcumin/SFN has a more significant effect than the compounds alone in down-regulating inflammation in RAW cells. The synergistic effects in the inhibition of TNF, IL-1, NO and PGE2 are the most significant. Enzymes like iNOS and COX2 are also synergistically reduced. In summary, this study suggests that combination of Curcumin/SFN or PEITC/SFN maybe more effective in preventing inflammation-induced carcinogenesis. (Supported in part by NIH R01-CA073674).
Reply to V. Turan et al
Authors: Matteo Lambertini, Ann H. Partridge, Lucia Del Mastro
Journal: Journal of Clinical Oncology (2018)

We appreciate the interest of Turan et al 1 in our systematic review and individual patient-level data metaanalysis of randomized controlled trials (RCTs) that explored the role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal patients with breast cancer. 2
TMIC-28. GLIOBLASTOMA EXPLOITS CELL SURFACE GLYCOSYLATION-MEDIATED IMMUNE REGULATORY CIRCUITS FOR IMMUNE ESCAPE
Authors: Sophie Dusoswa, Jan Verhoeff, Erik Abels, Xandra Breakefield, David Noske, Tom Würdinger, Marike Broekman, Yvette Van Kooyk, Juan Garcia-Vallejo
Journal: Neuro-Oncology (2018)

Glioblastoma is the most aggressive brain malignancy, for which conventional therapy has failed to achieve major improvements in survival since 2005. Glioblastoma-associated immune infiltrates are dominated by tumour-associated macrophages (TAM), which could be the key mediators of immune suppression. Recently we proposed the tumour “glyco-code” as a novel target for immunotherapy, and source for biomarkers. Malignant transformation is associated with aberrant expression of cell surface glycans, which play crucial roles in processes such as migration, angiogenesis and immune modulation. Here we investigated the glioblastoma glycocalyx as a tumour-intrinsic immune suppressive mechanism via tumour infiltrating macrophages. We detected increased expression of tumour-associated truncated O-linked glycans in patient-derived glioblastoma- versus control tissues by immunofluorescence and ELISA based assays. In concert, the macrophage galactose lectin (MGL) receptor, which interacts with truncated O-linked glycans, was overexpressed on glioblastoma infiltrating TAM, also detected by immunofluorescence, and confirmed on RNA level in TCGA data. Unsupervised, high-dimensional mass cytometry (CyTOF) analysis of a murine immunocompetent orthotopic glioblastoma model overexpressing truncated O-linked glycans revealed increased tumor infiltration by CCR2+, PD-L1+ macrophages. At a systemic level, we discovered increased frequencies of CCR2+ peripheral dendritic cells (pDC), and a decrease in CCR2+ monocyte frequencies in the bone marrow of these mice. Moreover, we observed a drastic increase in correlations between glioblastoma infiltrating CCR2+ macrophages and several myeloid cell subsets in the bone marrow using network analysis of frequency correlation statistics. Our results suggest that glioblastomas overexpress truncated O-linked glycans and exploit cell surface glycosylation- mediated immune regulatory circuits for systemic immune modulation and recruitment of suppressive TAM.
NIMG-31. BREAST CANCER SUBTYPE AS A DETERMINANT OF THE INTRACRANIAL METASTASES LOCATION
Authors: Heba Fouad, Paolo Nucifora, Kseniya Masterova, Edward Melian
Journal: Neuro-Oncology (2018)

The frequency of brain metastases (BM) in patients with metastatic breast cancer is up to 10–24% during the course of their disease. Studies have shown that the metastatic behavior is correlated to the sub-type of the breast cancer. Breast cancer sub-types are determined by the gene expression of the cancer cells. The five groups are luminal A [estrogen receptor (ER /PR+ HER2-)]; luminal B (ER /PR+ HER2+); HER2 over-expressing; normal breast-like; and Triple negative (TN) carcinomas basal-like. Patients with TN and HER2+ tumors are at higher risk of BM. We hypothesize that the genetic sub-type that influence how the breast cancer metastasizes can also have implications in where the metastasis occurs. An IRB approved retrospective review of the medical records of 50 patients referred from the radiation oncology with breast cancer BM in our institution spanning April 2006 to April 2018. Patients were divided into groups according to the age, location of the intracranial metastases, breast cancer sub-type, primary tumor stage, Ki-67 proliferation marker, previous chemotherapy. The breast cancer sub-types were recorded from the pathology reports. The location of the intracranial metastases was done by reviewing the first MRI brain study with positive metastases; the findings on the post contrast fat suppressed axial T1 weighted images and the study date were recorded. Sixteen patients were ER/PR+ HER2-, thirteen were ER/PR+ HER2+, eighteen were TN and 3 HER2 over-expressing. The cerebellum metastases were observed in twenty-eight patients. Eleven of the twenty-eight were of ER/PR+ HER2+, ten were TN, five were ER/PR+ HER2- and 2 were HER2 over-expressing. By using the Chi-square statistical analysis there was a significant association between the ER/PR+ HER2+ sub-type and the presence of cerebellar metastasis (p<0.05). We conclude that breast cancer BM expressing ER/PR+ HER2+ have preferential cerebellar involvement.