tbuckley/cabot-search huggingface dataset:
How far do laypersons believe in the cure of cancer? Results of the EDIFICE6 survey.
Authors: Thibault De La Motte Rouge, Sebastien Couraud, Morgan Roupret, Chantal Touboul, Christine Lhomel, Jerome Viguier, Francois Eisinger, Laurent Greillier, Jean F. Morere
Journal: Journal of Clinical Oncology (2019)

11616 Background: Advances in therapy and early detection, by population-based screening in particular, have significantly increased the number of patients cured from cancer. However, cancer patients’ chances of being cured varies strongly from one cancer to another. We studied the understanding of the concept of cure in the lay population and the factors associated with believing that cancer can be cured. Methods: The French nationwide observational survey, EDIFICE 6, was conducted online (June 26-July 28, 2017) on a core sample of 12 046 individuals (age, 18-69y). Representativeness was ensured by quota sampling on age, sex, profession, and stratification by geographical area/type of urban district. This analysis focused on understanding of the meaning of cure in breast (BC), cervical (CC), colorectal (CRC), lung (LC) and bladder (BLC) cancer for individuals with no history of cancer. Results: The majority of respondents believed that cure exists (BC 95%; CC 91%; CRC 89%; BLC 87%, LC 71%). Some agreed with the definition that cure is the disappearance of the disease (BC 42%; CC 38%; CRC 35%; BLC 33%, LC 25%), while others preferred the definition that cure is several years without disease (BC, CC 53%; CRC, BLS 54%; LC 46%). More men than women (P &lt; 0.05) believed that cure exists for CRC, BLC and LC. Socially non-vulnerable individuals were more likely to believe in cure than their vulnerable counterparts (P &lt; 0.05), as were individuals aged 50-69y (P &lt; 0.05) versus those of 18-50y, and for all cancer types except LC. In multivariate analysis, the variable “clinical research enables progress” was correlated with believing that cure exists (BC, OR = 2.93; CC, OR = 1.86; CRC, OR = 2.22; LC, OR = 1.57, BLC, OR = 2.06), as was “progress is rapid” (BC, OR = 1.61; CC, OR = 1.66; CRC, OR = 1.7; LC, OR = 1.84; BLC OR = 1.68), and also social non-vulnerability. However, the variables “prevention”, respectively screening/treatments, “are important for cancer control” had a low impact on the belief in cure (OR~1). Conclusions: The lay population is relatively optimistic about the cure for cancer. Confidence in the existence of cure relies on medical progress. However, factors related to individual behavior, e.g., prevention and screening, did not affect the perception of cure.
Recent Developments and Therapeutic Strategies against Hepatocellular Carcinoma
Authors: Mark Yarchoan, Parul Agarwal, Augusto Villanueva, Shuyun Rao, Laura A. Dawson, Thomas Karasic, Josep M. Llovet, Richard S. Finn, John D. Groopman, Hashem B. El-Serag, Satdarshan P. Monga, Xin Wei Wang, Michael Karin, Robert E. Schwartz, Kenneth K. Tanabe, Lewis R. Roberts, Preethi H. Gunaratne, Allan Tsung, Kimberly A. Brown, Theodore S. Lawrence, Riad Salem, Amit G. Singal, Amy K. Kim, Atoosa Rabiee, Linda Resar, Jeffrey Meyer, Yujin Hoshida, Aiwu Ruth He, Kalpana Ghoshal, Patrick B. Ryan, Elizabeth M. Jaffee, Chandan Guha, Lopa Mishra, C. Norman Coleman, Mansoor M. Ahmed
Journal: Cancer Research (2019)

Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.
P04.03 Radiotherapy for subependymal giant cell astrocytoma: time to challenge a historical ban? Case report and review of the literature
Authors: R Kamel, D Van den Berge
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Subependymal giant cell astrocytoma (SEGA) is a low-grade glioma that occurs in patients with tuberous sclerosis complex (TSC). SEGA typically grows within the ventricles causing hydrocephalus and sudden death. Surgical resection is the traditionally preferred treatment and expert opinion advises strongly against the use of radiotherapy, insomuch that it is not even mentioned as a treatment option in reviews or guidelines. Nevertheless, surgical resection of big volume or bilaterally growing SEGA can be very challenging. Recently, success has been reported with the use of mTOR inhibitor, everolimus, in reducing tumor volume. However, regrowth was observed after drug cessation requiring long-term if not life-long drug administration and thus raising concerns regarding side effects and high treatment costs. Here, we report about a case with inoperable bilateral SEGA that was successfully treated with fractionated stereotactic radiotherapy alone (30x2Gy) with a follow up period of 8 years before being treated with everolimus for renal involvement of TSC. Currently, the patient has been followed up for 13 years. MATERIAL AND METHODS All of the patient’s pre and post treatment MRI’s were used for detailed volumetric assessment of the response of the SEGA on each side separately. Systematic review of the literature was conducted via PubMed and Up-to-date using the search terms: ‘treatment of SEGA’, ‘radiotherapy in SEGA’, ‘SRS in SEGA’, ‘treatment of tuberous sclerosis complex’, ‘radiotherapy treatment in low grade astrocytoma’, etc. The article references were queried for the terms ‘radiotherapy’, ‘induced tumors’ and ‘malignant tumors’. Secondary references were added to the database and reprocessed similarly. Reviews about radiation-induced tumors were also added to the database. Attention was given to reports containing data about irradiated SEGA and about high-grade brain tumors in TSC patients. The database was locked on 1-02-2018 containing 1298 article references and 780 full-text articles. RESULTS In our case, the successive volumetric assessments on MRI’s demonstrated 80% volume reduction after radiotherapy alone, further enhanced to 90% after everolimus administration. Literature review shows no valid evidence for contra-indicating fractionated stereotactic radiotherapy in SEGA and shows that surgery is still associated with high re-operation and post-operative complications rates. CONCLUSION A slow progressive response of SEGA on both sides to radiotherapy was observed similar to the response seen in other benign intracranial tumors. We believe that stereotactic radiotherapy alone or sequentially combined with everolimus deserves to be studied as an alternative to resection in difficult cases that do not require immediate volume reduction.
OS7.5 Healthcare utilization, medication use, and productivity loss in glioma patients with depressive symptoms and their family caregivers
Authors: F W Boele, F Jansen, D Meads, I M Verdonck-de Leeuw, J J Heimans, J C Reijneveld, S C Short, M Klein
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Gliomas are associated with great societal burden through both direct (health and social care) and indirect (e.g., productivity loss) costs, but socioeconomic reports are scarce. We describe costs in a sample of glioma patients at high risk for depression and their family caregivers, and explore relationships between costs and treatable symptoms (depression; fatigue; cognitive complaints). MATERIAL AND METHODS Data from a nationwide randomised trial comparing internet-based therapy for depressive symptoms with waitlist controls were used. Healthcare utilization, medication use, and productivity loss based on the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness (TIC-P) were described and costs in the past 4 weeks were calculated. Caregivers reported on their own costs and wellbeing We used generalized linear regression models to predict costs using multiple observations per participant and robust standard errors. We included depressive symptoms (CES-D), fatigue (CIS), cognitive complaints (MOS), tumour grade (low-/high-grade), and disease status (stable/progression/active treatment). RESULTS Data from 91 glioma patients and 46 caregivers were used with multiple assessments from baseline through 12 months follow-up. Baseline data showed that over a 4 week period, 64.8% of patients (M=€394.99, sd=856.83) and 41.3% of caregivers (M=€131.11, sd=392.89) had used healthcare services. Medication was used by 90.1% of patients (M=€100.83, sd=191.07) and 43.5% of caregivers (M=€13.19, sd=21.03). Productivity loss resulted in M=€1231.19, sd=2185.35 for patients and M=€310.92, sd=841.36 for caregivers. In total, mean direct and indirect costs were €1632.22 (sd=2314.25) for patients and €447.85 (sd=1002.94) for caregivers. In patients, more depressive symptoms and cognitive complaints were associated with increased healthcare use costs; higher tumour grade and active disease were linked with higher medication costs (all p&lt;.05). Active treatment was related to higher overall costs (p&lt;.05). In caregivers, increased caregiver fatigue was associated with higher productivity loss and overall costs; more caregiver cognitive complaints were associated with higher total costs; higher tumour grade was associated with higher healthcare use and total costs; and patient active treatment was linked with higher healthcare use costs (all p&lt;.05). CONCLUSION Direct and indirect costs are substantial in glioma patients and caregivers. This indicates that the true cost of brain tumours is a burden shared between patients, caregivers, the healthcare system, and society more widely. Tentative links between costs and symptoms of depression, fatigue, and cognitive complaints indicate that adequate support may lead to cost reductions. Multivariable regression models are currently being prepared.
Ameliorating Effects of Very High Hemoglobin F Levels and Glucose-6-Phosphate Dehydrogenase Deficiency in Sickle Cell Patients Along with Associated Clinical Manifestations: A Report from Al Ahsa, Easter Province, Saudi Arabia
Authors: Nawaf Alanazi, AbudalloHull Rula, Giuseppe Saglio, Zafar Iqbal
Journal: Blood (2017)
P12.10 Treatment of pharmacoresistent epilepsy by combining stereotactic destruction and authologous mesenchymal stem cells
Authors: E Slobina, T Dokukina, F Khlebokazov, N Misyuk, M Makhrov, P Korolevich, I Shamruk, S Marchuk
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Existing anti-epileptic drugs (AED) have limited efficiency in many patients, necessitating the search for alternative approaches such as stereotactic radiosurgery (SRS) and followed by stem cell therapy to improve results of previous treatment. MATERIAL AND METHODS From 2016 to 2017, a prospective study included 6 patients with a combined pathology, a median of 56 years of age, in the past TBI - 3 patients, a solitary metastatic focus in the brain (GM) - 2 patients. The indications for stereotactic intervention were both the presence of a metastatic lesion of the GM, and the bitemporal epilepsy with generalized convulsive, complex and simple partial attacks, regardless of the presence of an organic focus on CT or MRI GM. SRS was undertaken in patients undergoing a course of anticonvulsant drug therapy in combination with other types of symptomatic therapy in the absence of therapeutic effect. The frequency of generalized convulsive seizures ranged from 2–3 to 7–10 per month, complex partial from daily to 2–3 per month. SRS was performed on a stereotactic irradiation system with conical “BrainLab” collimators mounted on a linear CLINAC accelerator and allowing the session of SRS arc arches. Total dose was 12–30 Gy in isocenter, 1 fraction. After 2–3 monthes from SRS the patients received AED supplemented with single intravenous administration of undifferentiated autologous MSC (target dose of 1 × 106 cells/kg), followed by a single intrathecal injection of neurally induced autologous MSC (target dose of 0.1 × 106 cells/kg). RESULTS duration of epilepsy at the time of surgery ranged from 3 to 42 years. Cessation of attacks after 2–3 months after SRS with followed MSC therapy in 2 out of 6 patients was achieved remission (no seizures for one year and more), and 3 patients became responders to AEDs additionally, reduction of the pathological EEG pattern (disappearance of beta focusing, reduction of theta2-index to 23.6). Persistent clinical onco- and neurological remission 18 months. Reduction of the dose of enkorata-chrono - 3 patients, complete abolition of anticonvulsant therapy - 2 patients. MSC injections were well tolerated and did not cause any severe adverse effects. CONCLUSION MSC possess unique immunomodulatory properties and are a safe and promising candidate for cell therapy in AED resistant epilepsy patients in the frame of combined treatment.
Predictive value of an electronic frailty index (FI) in U.S. Veterans with newly diagnosed non-small cell lung cancer (NSCLC).
Authors: Ayesha Rizwan Sheikh, David Cheng, Nathanael Fillmore, Nhan Do, Mary T. Brophy, David P. Tuck
Journal: Journal of Clinical Oncology (2019)

11545 Background: Frailty is a well-established predictor of survival, but assessing it in a real-world healthcare setting is often time-consuming and impractical. We sought to determine if a quantitative measure of frailty, computed automatically from electronic health records using the cumulative deficit model, also predicts overall survival in patients with NSCLC. Methods: We conducted a retrospective cohort study of Veterans identified to have NSCLC in the VA Precision Oncology Data Repository. Frailty was assessed using a previously validated FI, the Frailty Index for Veterans Affairs (VA-FI), consisting of 31 deficits. We categorized non-frail patients into non-frail (0-0.1) and pre-frail (0.1-0.2) groups, and frail patients into mild (0.2-0.3), moderate (0.3-0.4) and severe ( &gt; 0.4) groups. Associations of frailty and survival were assessed using Kaplan-Meier estimates and Cox models. The added value of frailty status for predictive performance was quantified using the continuous net-reclassification index (NRI). Results: The cohort included 359 patients with NSCLC. The mean age was 66 years, and 96.1% were male, including 76.3% Caucasian and 16.2% African-American. The majority had an advanced stage cancer (15.9% and 44.3% with stages III and IV respectively) with minority falling into the early stage category (15.3% and 6.1% with stages I and II respectively). A substantial proportion of patients were identified to be frail (30%). The frailty categories differentiated survival profiles of patients with 2-year survival ranging from 0.41 for non-frail patients to 0.08 for the severely frail patients (log-rank p &lt; 0.001). Frail patients exhibited significantly shorter survival than non-frail group even after adjusting for age, gender, and stage in a multivariate Cox model (hazard ratio 1.7, p &lt; 0.001). Inclusion of frailty status in the Cox model significantly improved 2-year risk estimates of survival (NRI 0.35; 95% CI 0.27–0.47). Conclusions: Frailty as determined by VA-FI is a significant predictor of survival independent of stage and demographic factors among NSCLC patients in this VA cohort. VA-FI is an automated and a practically feasible tool to better estimate life expectancy and help individualize patient care.
Association Between Soft Drink Consumption and Mortality in 10 European Countries
Authors: Amy Mullee, Dora Romaguera, Jonathan Pearson-Stuttard, Vivian Viallon, Magdalena Stepien, Heinz Freisling, Guy Fagherazzi, Francesca Romana Mancini, Marie-Christine Boutron-Ruault, Tilman Kühn, Rudolf Kaaks, Heiner Boeing, Krasimira Aleksandrova, Anne Tjønneland, Jytte Halkjær, Kim Overvad, Elisabete Weiderpass, Guri Skeie, Christine L. Parr, J. Ramón Quirós, Antonio Agudo, Maria-Jose Sánchez, Pilar Amiano, Lluís Cirera, Eva Ardanaz, Kay-Tee Khaw, Tammy Y. N. Tong, Julie A. Schmidt, Antonia Trichopoulou, Georgia Martimianaki, Anna Karakatsani, Domenico Palli, Claudia Agnoli, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, Bas Bueno-de-Mesquita, W. M. Monique Verschuren, Jolanda M. A. Boer, Roel Vermeulen, Stina Ramne, Emily Sonestedt, Bethany van Guelpen, Pernilla Lif Holgersson, Konstantinos K. Tsilidis, Alicia K. Heath, David Muller, Elio Riboli, Marc J. Gunter, Neil Murphy
Journal: JAMA Internal Medicine (2019)

Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date.
Agonist Selectivity and Ion Permeation in the α3β4 Ganglionic Nicotinic Receptor
Authors: Anant Gharpure, Jinfeng Teng, Yuxuan Zhuang, Colleen M. Noviello, Richard M. Walsh, Rico Cabuco, Rebecca J. Howard, Nurulain T. Zaveri, Erik Lindahl, Ryan E. Hibbs
Journal: Neuron (2019)
Use of laser capture microdissection to derive poor prognosis gene expression signatures of epithelial abdominal malignant mesothelioma
Authors: A. C. Borczuk, J. Chen, F. Parikh, C. A. Powell, R. N. Taub
Journal: Journal of Clinical Oncology (2009)

e22098 Background: Prior work in abdominal malignant mesothelioma (AMM) has established a poor prognosis profile of biphasic AMM when compared to more favorable prognosis epithelial AMM. It is evident, however, that epithelial AMM shows heterogeneity in biologic behavior and prognosis. Given improvements in therapy and survival in AMM, stratification of patients with epithelial AMM into favorable and poor prognosis subgroups is desirable and gene expression profiles may provide poor prognosis signatures to further guide therapy. Methods: Favorable and poor prognosis subgroups were defined as 1000 days of survival time (based on median survival of 90 patients with AMM at Columbia Presbyterian as of Sept 2007). Fourteen frozen epithelial AMM (7 favorable prognosis, 7 poor prognosis) with high quality RNA were laser capture microdissected using a PALM Zeiss microscope and analyzed using Affymetrix U133 Plus 2 microarrays. Unsupervised hierarchical clustering and supervised subgroup analysis were performed using BRB tools version 3.2. Results: Unsupervised hierarchical clustering revealed 2 main clades that contained 6 of 7 poor prognosis and 6 of 7 favorable prognosis tumors, respectively. Supervised class comparison revealed a 39-gene signature that distinguished the 2 classes (permutation values of p &lt; .001). High expression of Nde1, UHRF1, and EZH2 by qPCR on a set of 32 AMM (using an upper quartile cutoff) was associated with poor survival (Log rank statistic p&lt;.01, p&lt;.003 and p&lt;.03 respectively). Immunohistochemistry performed on tissue microarrays of 122 AMM for p16 loss and increased EZH2, Col3A1 and UHRF1 immunoreactivity was associated with poor survival (Log rank statistic p&lt;.0001, p&lt;.009, p&lt;.0001 and p&lt;.012, respectively). Conclusions: Using a training set of laser captured favorable and poor prognosis epithelial AMM, a 39-gene signature was obtained that is associated with prognosis. Validation of several of the candidate genes by qPCR expression and immunohistochemistry was performed, confirming favorable and poor prognosis strata among the epithelial AMM. Identification of poor prognosis epithelial AMM at the time of initial biopsy/tumor cytoreduction could lead to more aggressive primary therapeutic intervention. No significant financial relationships to disclose.
TP53 Pathway Alterations Drive Radioresistance in Diffuse Intrinsic Pontine Gliomas (DIPG)
Authors: Coralie Werbrouck, Cláudia C.S. Evangelista, María-Jesús Lobón-Iglesias, Emilie Barret, Gwénaël Le Teuff, Jane Merlevede, Romain Brusini, Thomas Kergrohen, Michele Mondini, Stéphanie Bolle, Pascale Varlet, Kevin Beccaria, Nathalie Boddaert, Stéphanie Puget, Jacques Grill, Marie-Anne Debily, David Castel
Journal: Clinical Cancer Research (2019)

Diffuse intrinsic pontine gliomas (DIPG) are the most severe pediatric brain tumors. Although accepted as the standard therapeutic, radiotherapy is only efficient transiently and not even in every patient. The goal of the study was to identify the underlying molecular determinants of response to radiotherapy in DIPG.We assessed in vitro response to ionizing radiations in 13 different DIPG cellular models derived from treatment-naïve stereotactic biopsies reflecting the genotype variability encountered in patients at diagnosis and correlated it to their principal molecular alterations. Clinical and radiologic response to radiotherapy of a large cohort of 73 DIPG was analyzed according to their genotype. Using a kinome-wide synthetic lethality RNAi screen, we further identified target genes that can sensitize DIPG cells to ionizing radiations.We uncover TP53 mutation as the main driver of increased radioresistance and validated this finding in four isogenic pairs of TP53WT DIPG cells with or without TP53 knockdown. In an integrated clinical, radiological, and molecular study, we show that TP53MUT DIPG patients respond less to irradiation, relapse earlier after radiotherapy, and have a worse prognosis than their TP53WT counterparts. Finally, a kinome-wide synthetic lethality RNAi screen identifies CHK1 as a potential target, whose inhibition increases response to radiation specifically in TP53MUT cells.Here, we demonstrate that TP53 mutations are driving DIPG radioresistance both in patients and corresponding cellular models. We suggest alternative treatment strategies to mitigate radioresistance with CHK1 inhibitors. These findings will allow to consequently refine radiotherapy schedules in DIPG.