tbuckley/cabot-search huggingface dataset:
ETMR-04. EMBRYONAL TUMOR WITH MULTILAYERED ROSETTES: THE MD ANDERSON CANCER CENTER EXPERIENCE
Authors: Sumit Gupta, Dristhi Ragoonanan, Nelda Itzep, David Sandberg, Greg Fuller, Leena Ketonen, Heather Meador, Wafik Zaky, Soumen Khatua
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Embryonal Tumor with Multilayered Rosettes (ETMR) are rare tumors that are molecularly diagnosed by C19MC amplification. Rarity of this tumor has precluded profiling uniform therapeutic strategy. METHODS Retrospective review after institutional approval, identified 10 pediatric case of ETMR, treated at MD Anderson Cancer Center during the period of 2005 to 2019. RESULTS Median age of at diagnosis was 4.6 years. Tumor sites include frontal or parietal lobes (3), spine (3) and posterior fossa involving the brainstem (4). All patients received a combination of chemotherapy and radiation. 4 patients had metastasis at the presentation. 9 patients received focal radiation but only 6 of them received Craniospinal irradiation (CSI). Average dose of radiation was 50 Gy. Surgical resection was performed in all cases except the brainstem tumors. 7 children had recurrence including all the patients with metastasis at diagnosis (median time: 9.4 months), 1 passed away secondary to hemorrhage in brainstem and data was not available for 2 patients. 5/6 patients who received CSI had recurrence. CONCLUSIONS To-date no well-defined treatment regimens exists for these neoplasms, resulting in poor overall survival. Preclinical drug screen have shown the efficacy of topotecan, actinomycin D, and volasertib as potential new therapeutic candidates, though this has not translated successfully into the clinical arena. Given the limited success with current conventional therapeutic methods, molecular interrogation in addition to histopathological diagnosis are essential upfront, as it could provide clues to targeted therapy. Defining molecularly-based treatment with less toxicities and increased survival are warranted.
Residual normal B-cell profiles in monoclonal B-cell lymphocytosis versus chronic lymphocytic leukemia
Authors: Ignacio Criado, Elena Blanco, Arancha Rodríguez-Caballero, Miguel Alcoceba, Teresa Contreras, María Laura Gutiérrez, Alfonso Romero, Paulino Fernández-Navarro, Marcos González, Fernando Solano, Carlos Gómez, Martín Pérez-Andrés, Jacques J. M. van Dongen, Julia Almeida, Alberto Orfao
Journal: Leukemia (2018)

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, which is characterized by the accumulation of mature CD5 + /CD20 lo /CD23 + clonal B-cells in peripheral blood (PB), bone marrow (BM), and other lymphoid tissues [1].Currently, it is well-established that CLL is systematically preceded by a pre-leukemic stage, known as monoclonal B-cell lymphocytosis (MBL) [2]; MBL includes both low-count (MBL lo ) and high-count MBL (MBL hi ), depending on the number of PB clonal Bcells (<0.5 × 10 9 /L and ≥0.5 × 10 9 /L, respectively) detected
Strategic Response to an Outbreak of Circulating Vaccine-Derived Poliovirus Type 2 — Syria, 2017–2018
Authors: Chukwuma Mbaeyi, Zubair Mufti Wadood, Thomas Moran, Fazal Ather, Tasha Stehling-Ariza, Joanna Nikulin, Mohammad Al Safadi, Jane Iber, Laurel Zomahoun, Nidal Abourshaid, Hong Pang, Nikki Collins, Humayun Asghar, Obaid ul Islam Butt, Cara C. Burns, Derek Ehrhardt, Magdi Sharaf
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Since the 1988 inception of the Global Polio Eradication Initiative (GPEI), progress toward interruption of wild poliovirus (WPV) transmission has occurred mostly through extensive use of oral poliovirus vaccine (OPV) in mass vaccination campaigns and through routine immunization services (1,2). However, because OPV contains live, attenuated virus, it carries the rare risk for reversion to neurovirulence. In areas with very low OPV coverage, prolonged transmission of vaccine-associated viruses can lead to the emergence of vaccine-derived polioviruses (VDPVs), which can cause outbreaks of paralytic poliomyelitis. Although WPV type 2 has not been detected since 1999, and was declared eradicated in 2015,* most VDPV outbreaks have been attributable to VDPV serotype 2 (VDPV2) (3,4). After the synchronized global switch from trivalent OPV (tOPV) (containing vaccine virus types 1, 2, and 3) to bivalent OPV (bOPV) (types 1 and 3) in April 2016 (5), GPEI regards any VDPV2 emergence as a public health emergency (6,7). During May-June 2017, VDPV2 was isolated from stool specimens from two children with acute flaccid paralysis (AFP) in Deir-ez-Zor governorate, Syria. The first isolate differed from Sabin vaccine virus by 22 nucleotides in the VP1 coding region (903 nucleotides). Genetic sequence analysis linked the two cases, confirming an outbreak of circulating VDPV2 (cVDPV2). Poliovirus surveillance activities were intensified, and three rounds of vaccination campaigns, aimed at children aged <5 years, were conducted using monovalent OPV type 2 (mOPV2). During the outbreak, 74 cVDPV2 cases were identified; the most recent occurred in September 2017. Evidence indicates that enhanced surveillance measures coupled with vaccination activities using mOPV2 have interrupted cVDPV2 transmission in Syria.
Maternal Type 1 Diabetes and Risk of Autism in Offspring
Authors: Anny H. Xiang, Xinhui Wang, Mayra P. Martinez, Kathleen Page, Thomas A. Buchanan, R. Klara Feldman
Journal: JAMA (2018)

Maternal Type 1 Diabetes and Risk of Autism in OffspringMaternal preexisting type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) diagnosed by 26 weeks' gestation have been associated with increased risk of autism spectrum disorder (ASD) in offspring. 1However, little is known about ASD risk associated with maternal preexisting type 1 diabetes (T1D).We extend previous observations by examining the risk of ASD in offspring associated with maternal T1D, T2D, and GDM.Methods | This retrospective cohort study included singleton children born at 28 to 44 weeks' gestation in Kaiser Permanente Southern California (KPSC) hospitals from January 1, 1995, through December 31, 2012.Children were tracked through electronic health records from age 1 year until the first date of the following: clinical diagnosis of ASD, last date of continuous KPSC membership, death, or study end date (December 31, 2017).The KPSC institutional review board approved this study and provided waiver of participant consent.Methods to identify ASD, T2D, and GDM exposure were described previously. 1 GDM exposure was divided into diagnosis by or after 26 weeks' gestation based on a prior finding that risk of ASD was elevated for exposure to GDM by 26 weeks. 1 T1D was identified using the algorithm developed for electronic health records data 2 and confirmed by prescription of insulin during pregnancy.
NURS-03. DEVELOPMENT OF A NEURO-ONCOLOGY LONG TERM FOLLOW UP NURSE CLINICIAN AT A TERTIARY HEALTH CARE CENTER
Authors: Naomi Evans, Dana Anderson
Journal: Neuro-Oncology (2018)

Brain tumours are the second most common malignancy in childhood. With advances in treatment overall survival is around 70% increasing to 80-90% for low grade tumours. Many of these survivors have significant long term health risks and late effects from therapy; including neurocognitive deficits, endocrine dysfunction and hearing loss adding unique challenges in providing follow up and education to prepare the survivor for transition. At our center we currently follow approximately 90 brain tumour survivors in our long term follow up (LTFU) clinic, as more children survive their disease this number will only increase with time. Historically these patients have been seen in a multidisciplinary clinic with the Neuro-Oncology nurse clinician (NONC) as the point person for the families. The NONC was responsible for all on treatment patients, palliative care, patients off treatment for less than two years and long term survivors. It was well recognised that the LTFU patients were not being adequately cared for given the acuity and high needs of the other patients. With the development of the NOLTFNC brain tumour survivors now have a dedicated clinician who is responsible for providing support, coordinating care, educating survivors and families about late effects and transitioning patients. The NOLTFNC has been in place for 18 months and we plan to evaluate the impact of this role on survivors and their families by asking them to fill out a questionnaire. The goal being to improve services as we move forward in providing LTFU care and preparing survivors for transition.
Clinical contribution of tumor marker CYFRA 21-1 in evaluation of response in therapy of NSCLC patients
Authors: Pavićević, Radomir, Bubanović, Gordana, Ana Krajna, Jasna Miličić, Peter Bialk, Lukrecija Pavićević, Dinko Stančić-Rokotov
Journal: European Respiratory Journal (2001)

In this study we presented dynamics of tumor marker CYFRA 21-1 level that is evaluated as a response to therapy (surgery or chemotherapy) in 500 NSCLC patients. Serum level of CYFRA 21-1 was measured with electrochemiluminescence method using fully automated system Elecsys 2010 (Roche Diagnostics). The level of CYFRA 21-1 in NSCLC patients was determined before and after the therapy. In 95% surgically treated patients we observed a significant decrease of CYFRA 21-1 level after the therapy to the average level of healthy population (p<0.001). In 5% patients the increase of CYFRA 21-1 level was observed after the surgery, which indicated the tumor biological activity. This allowed the clinicians to apply an additional therapy. From 141 patients who underwent surgery followed by chemotherapy in 35% CYFRA 21-1 level indicated the inefficiency of therapy, which was also proved clinically. This allowed the clinicians to replace applied chemotherapy.Introducing the protocol including the evaluation of CYFRA 21-1 level before and after therapy we proved the contribution of tumor marker CYFRA 21-1 to the selection and control of therapy and the assessment of therapy efficiency.
Variability of current global practice patterns in the management of metastatic colorectal cancer
Authors: T. Bekaii-Saab, K. Marcello, G. Fisher, S. Kopetz, J. Strickler, A. Venook, K. Obholz
Journal: Annals of Oncology (2018)

Introduction: Therapeutic options for mCRC have changed dramatically in recent years, greatly increasing the complexity of therapeutic decision-making. Treatment guidelines may limit flexibility to individualize patient care. The aim of this analysis was to assess "real world" global practice patterns for metastatic colorectal cancer (mCRC) compared with recommendations from US experts based on patient cases entered by clinicians into an online decision support tool designed to provide specific, patient-individualized expert recommendations. Methods: A panel of 5 experts provided treatment recommendations for 311 unique case scenarios across 1st- (1L), 2nd- (2L), and 3rd-line (3L) settings for mCRC. Individual scenarios were defined by key patient and disease characteristics including mutation status, microsatellite instability (MSI), sidedness of primary tumor, and previous therapy. To use the tool, clinicians entered their patient and disease factors and were surveyed about their intended treatment plan for that case. The expert treatment recommendations for that specific case were then provided to the clinician. Results: Analysis includes 755 cases entered by healthcare practitioners (HCPs) globally, comprising 30% Europe, 29% US, and 41% rest of the world (ROW). Practice pattern highlights: in the 1L setting, 100% of experts chose a VEGF inhibitor for patients with right-sided, RAS/BRAF wild type (WT) mCRC vs 56% of HCPs surveyed in the tool. In left-sided RAS/BRAF WT mCRC, 80% of experts selected an EGFR inhibitor in 1L and 100% in 2L (in patients who received prior VEGF inhibitor) vs 41% and 44% of HCPs, respectively. In patients with RAS-mutated (MT) tumors who had received prior irinotecan and oxaliplatin, as well as a VEGF inhibitor, 60% of experts selected regorafenib and 40% selected TAS-102 in this 3L setting vs 33% and 22% of HCPs, respectively. In patients with BRAF V600E -MT mCRC, 100% of experts selected a VEGF inhibitor (bevacizumab) as the biologic agent in 1L and 60% selected vemurafenib/cetuximab in 2L, whereas 64% of HCPs selected a VEGF inhibitor in 1L and only 7% planned to use vemurafenib/cetuximab in 2L. In patients with MSI-high tumors, 1 of 5 experts would use an immune checkpoint inhibitor in 1L vs 43% of HCPs. In both 2L and 3L, 100% of experts would use immune checkpoint inhibitors for MSI-high patients vs 62% of HCPs in 2L and 54% in 3L. Conclusion: Planned treatment by global HCPs for mCRC show a substantial variance from the US expert treatment recommendations for the same cases, particularly treatment based on the site of the primary tumor and BRAF V600E mutation status, and for patients with MSI-high tumors. A detailed analysis of expert treatment selections vs planned treatment of HCPs, including a comparison of trends by region (US vs Europe vs ROW) and the overall impact of the recommendations from US-based experts on global practice will be presented.
Sixty seconds on . . . the Mediterranean diet
Authors: Sue Mayor
Journal: BMJ (2018)

Well. Everything seemed so simple, with big studies showing that eating a Mediterranean diet—think Greek island lunch with olive oil, vegetables, fruit, nuts, and cereals but light on dairy and red or processed meats—reduced cardiovascular disease (CVD). Until this week, that is, when Spanish researchers retracted their landmark study (PREDIMED)1 because of “irregularities in randomisation procedures.”

Not so fast. The Spanish research group reanalysed their data and published an updated report at the same time as retracting …
Treatment and testing patterns among patients with HER2+ advanced/metastatic gastric, esophageal or gastroesophageal junction (GEJ) adenocarcinoma in the United States
Authors: Y. Janjigian, L. Hess, Y. Zhu, Y. Fang, A. Liepa, C. Kuder, S. Chin
Journal: Annals of Oncology (2018)

Introduction: It is estimated that 9-23% of patients diagnosed with advanced or metastatic gastric, esophageal or GEJ adenocarcinoma have tumors that overexpress HER2 in the United States. Current treatment guidelines recommend HER2 testing as part of the initial workup of patients diagnosed with unresectable disease. For patients with tumors that overexpress HER2, trastuzumab-based therapy is recommended in the first-line (1L) setting. Despite evidence for HER2 testing and 1L treatment guidelines for patients whose tumors overexpress HER2, data are lacking with regard to the implementation of testing practices and recommended treatment patterns in real-world practice settings. The aim of this study was to fill this gap in knowledge. Methods: This retrospective observational study analyzed data from the Flatiron Gastric/Esophageal electronic medical records database of US community and academic clinics, which at the time of analysis included longitudinal data from >5600 patients diagnosed with advanced or metastatic gastric, esophageal or GEJ cancers from 2011 to 2017. Eligible patients for this study were 18+ years of age at diagnosis who initiated anti-cancer systemic therapy on or after 01 Jan 2013. Patients with squamous tumors were excluded. Descriptive statistics were used to define the patient characteristics, HER2 testing patterns (only reported by community practices in the dataset), and treatment regimens and sequences across lines of therapy. Results: community practice settings. Of community practices, 24.7% of patients in this study were not tested for HER2 at any time during the study period; 21.1% of patients with gastric, 28.9% with esophageal, and 24.1% with GEJ adenocarcinoma were not tested for HER2. Of the 2035 patients who had a HER2 test during the study period, 1587 (78.0%) had testing completed from baseline through start of 1L therapy. Of those tested, 504 patients (24.8%) had a HER2+ result during the study period and 732 (36.0%) had multiple HER2 tests. Among the 504 patients with HER2+ tumors, 293 (58.1%) received trastuzumab; 207 (41.1%) received it in the 1L setting and 88 (17.5%) received it across multiple lines of therapy (1L plus 2L and/or 3L). Conclusion: Despite clinical guidelines and recommendations for HER2 testing and treatment among patients with gastric, esophageal or GEJ adenocarcinomas, only about 3/4 of patients are tested before 1L and less than half of patients with HER2+ tumors received trastuzumab in the 1L setting as recommended. Despite the lack of evidence for continuation of HER2 targeted therapy across lines of therapy, this practice was observed in this study. There is a need for educational efforts to improve testing rates and for the appropriate care of the patient whose tumor overexpresses HER2.
TBIO-19. MASS SPECTROMETRY OF COMMON CEREBELLAR TUMOURS IDENTIFIES DIFFERENCES IN METABOLISM
Authors: Christopher Bennett, Sarah Kohe, Simrandip Gill, Nigel Davies, Lisa Storer, Timothy Ritzmann, Warwick Dunn, Daniel Tennant, Richard Grundy, Andrew Peet
Journal: Neuro-Oncology (2018)

Metabolic profiling by Magnetic Resonance Spectroscopy has shown the three most common paediatric cerebellar tumours are metabolically distinct; however, these techniques are limited by their sensitivity. Mass spectrometry is more sensitive and able to detect many more metabolites. In this study, metabolic phenotyping was performed to investigate the water-soluble metabolome and the lipidome of the three most common paediatric cerebellar tumours with the aim of informing a detailed metabolic pathway analysis. A discovery based experiment was performed on 60 surgically resected snap frozen pilocytic astrocytomas, ependymomas and medulloblastomas using UPLC-MS assays to detect water soluble and lipid metabolites. Principal component analysis demonstrates separation of the tumours based on the relative concentration of thousands of detected metabolites. The relative concentrations of glucose and glycolytic intermediates varied between the tumour types, as did metabolites involved in purine and pyrimidine metabolism. Key metabolites within the taurine metabolism pathway were found to be higher in medulloblastoma. Alterations were observed in lipid metabolism, with a wide range of relative concentration differences in di- and triacylglycerides, sphingolipids, ceramides, cardiolipins and glycerophospholipids. This study has shown that these tumours are metabolically distinct and offer the opportunities for stratified diagnosis and treatment. Some of the observed changes in relative concentration between the tumours reflect findings from spectroscopic studies, particularly with regards to taurine which is known to be higher in medulloblastoma. The ability of mass spectrometry to identify and measure lipid species and low concentration metabolites from tissue could allow targetable metabolic differences to be characterised and exploited.
GERM-06. REDUCED RADIOTHERAPY DOSE AND VOLUME FOLLOWING CHEMOTHERAPY FOR INTRACRANIAL GERMINOMA WITH B-HCG LEVEL < 200 MIU/ML: PRELIMINARY RESULTS OF SMC G-13 TRIAL
Authors: Ji Won Lee, Do Hoon Lim, Ki Woong Sung, Hyung Jin Shin
Journal: Neuro-Oncology (2018)

We performed a prospective single arm trial (NCT02782754) to investigate whether pre-RT chemotherapy could reduce the necessary dose and volume of RT while preventing relapse/progression of intracranial germinoma with b-HCG level < 200 mIU/mL. A total of 32 patients who were diagnosed with intracranial germinoma with b-HCG level < 200 mIU/mL were enrolled in this study. Four cycles of chemotherapy were given prior to RT. A 18 Gy of craniospinal RT for M+ tumors, whole brain RT for basal ganglia tumor, otherwise whole ventricle RT followed by 12.6 Gy of local RT to the primary site was administered following pre-RT chemotherapy. The site of primary tumor was suprasellar in 10, pineal in 10, bifocal in 11, and basal ganglia in 1. Ten patients had leptomeningeal seedings. Toxicity during chemotherapy was mild except bone marrow suppression. Pre-RT tumor status was CR in 26 patients, PR in 4, MR in 1, and not evaluated yet in 1. All patients remain event free during a median follow-up of 3.1 years (rage, 0.2-5.1) from diagnosis. Late effects from chemo-radiotherapy evaluated in 14 patients at 3 years from off-therapy were not significant except neuroendocrine dysfunction in 10 patients who already had neuroendocrine dysfunction at diagnosis and avascular necrosis of hip in one patient. Pre-RT chemotherapy can reduce the necessary dose and volume of RT. A longer follow-up is needed to assess whether our strategy will ultimately reduce overall late adverse effects without jeopardizing survival.
LDHA in Neuroblastoma Is Associated with Poor Outcome and Its Depletion Decreases Neuroblastoma Growth Independent of Aerobic Glycolysis
Authors: Carmen Dorneburg, Matthias Fischer, Thomas F.E. Barth, Wolfgang Mueller-Klieser, Barbara Hero, Judith Gecht, Daniel R. Carter, Katleen de Preter, Benjamin Mayer, Lisa Christner, Frank Speleman, Glenn M. Marshall, Klaus-Michael Debatin, Christian Beltinger
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To investigate whether lactate dehydrogenase A (LDHA), an important component of the LDH tetramer crucial for aerobic glycolysis, is associated with patient outcome and constitutes a therapeutic target in neuroblastoma (NB). Experimental Design: Expression of LDHA mRNA and protein was determined in 709 and 110 NB patient samples, respectively, and correlated with survival and risk factors. LDHA and LDHB were depleted in human NB cell lines by CRISPR/Cas9 and shRNA, respectively, and aerobic glycolysis, clonogenicity, and tumorigenicity were determined. Expression of LDHA in relation to MYCN was measured in NB cell lines and in the TH-MYCN NB mouse model. Results: Expression of LDHA, both on the mRNA and the protein level, was significantly and independently associated with decreased patient survival. Predominant cytoplasmic localization of LDHA protein was associated with poor outcome. Amplification and expression of MYCN did not correlate with expression of LDHA in NB cell lines or TH-MYCN mice, respectively. Knockout of LDHA inhibited clonogenicity, tumorigenicity, and tumor growth without abolishing LDH activity or significantly decreasing aerobic glycolysis. Concomitant depletion of LDHA and the isoform LDHB ablated clonogenicity while not abrogating LDH activity or decreasing aerobic glycolysis. The isoform LDHC was not expressed. Conclusions: High expression of LDHA is independently associated with outcome of NB, and NB cells can be inhibited by depletion of LDHA or LDHB. This inhibition appears to be unrelated to LDH activity and aerobic glycolysis. Thus, investigations of inhibitory mechanisms beyond attenuation of aerobic glycolysis are warranted, both in NB and normal cells. Clin Cancer Res; 24(22); 5772–83. ©2018 AACR.