tbuckley/cabot-search huggingface dataset:
Early-Life Selenium Status and Cognitive Function at 5 and 10 Years of Age in Bangladeshi Children
Authors: Helena Skröder, Maria Kippler, Fahmida Tofail, Marie Vahter
Journal: Environmental Health Perspectives (2017)

Background: In older adults, selenium status has been positively associated with cognitive function. We recently reported a positive association between maternal selenium status in pregnancy and children's cognitive function at 1.5 y. Objective: We followed up the children to assess if prenatal and childhood selenium status was associated with cognitive abilities at 5 and 10 y. Methods: This longitudinal cohort study was nested in Maternal and Infant Nutrition Interventions in Matlab (MINIMat), a population-based, randomized supplementation trial in pregnancy in rural Bangladesh. Selenium in maternal blood [erythrocyte fraction (Ery-Se) at baseline] and in child hair and urine was measured using inductively coupled plasma mass spectrometry. Children's cognition at 5 and 10 y was assessed using the Wechsler Preschool and Primary Scale of Intelligence™ and the Wechsler Intelligence Scale for Children®, respectively. In total, 1,408 children were included. Results: Multivariable-adjusted linear regression analyses showed that prenatal selenium status was positively associated with children's cognitive function at 5 and 10 y. An increase in maternal Ery-Se from the fifth to the 95th percentile [median: 0.44μg/g hemoglobin (Hb)] was associated with an increase in full developmental score of 3.5 [95% confidence interval (CI): 0.1, 7.0], corresponding to 0.16 standard deviation (SD) at 5 y, and 8.1 (95% CI: 3.8, 13), corresponding to 0.24 SD at 10 y. In addition, urine and hair selenium concentrations at 5 and 10 y of age were positively associated with cognitive function at 10 y, although associations were inverse for concentrations ≥98th percentile. Some associations were slightly stronger for girls than for boys. Conclusions: Measures of prenatal and childhood (below the 98th percentile) selenium status were associated with higher cognitive function scores at 5 and 10 y of age. https://doi.org/10.1289/EHP1691
ACTR-77. DURABLE RESPONSE TO BEVACIZUMAB IN ADULTS WITH RECURRENT PILOCYTIC ASTROCYTOMA
Authors: Andrea Wasilewski, Nimesh Mohile
Journal: Neuro-Oncology (2017)

Adult pilocytic astrocytomas (APA) are rare tumors with a more aggressive clinical course when compared to juvenile pilocytic astrocytoma (JPA). Recurrence rates for APA have been reported from 30–42%. APA are known to be highly vascular tumors and we hypothesized that they may be uniquely responsive to bevacizumab (BEV). We present a series of four consecutive adult patients with pathologically diagnosed WHO grade I pilocytic astrocytoma who had a robust and durable response to BEV at time of recurrence. Median age at diagnosis was 34 years (range: 23–66). Three tumors were located infratentorially and one in the thalamus. Three patients underwent a partial resection or near total resection and one patient underwent biopsy only. BRAF v600E mutation was absent in all patients. Ki-67 proliferation index was 5–9%. Initial treatment was radiation alone in 3 patients and concurrent radiation and temozolomide (TMZ) in one patient. All patients developed radiographic changes on MRI, including disease outside the radiation field, that were consistent with progressive disease based on RANO criteria. Median time to recurrence was 8.5 months (range: 4–10 months). All patients were treated with 6 cycles of BEV for recurrence and at the end of treatment, all patients had achieved a complete response. 1 patient also received adjuvant TMZ. Median follow-up time after BEV is 20.5 months (range: 7–34) and as of last follow up, no patient has recurred. Although, BEV has failed to demonstrate a survival benefit to date in all gliomas, this series suggests that BEV may have true anti-tumor activity in APA. Recurrence in APA in this series is consistent with previous reports and BEV may be an important agent to achieve durable disease control. Future multi-center studies to further assess efficacy are warranted.
NIMG-63. SPATIAL CHARACTERIZATION OF 11C-METHIONINE PET AND HIGH B-VALUE DW-MRI TUMOR SUBREGIONS IN PATIENTS UNDERGOING BIOLOGICALLY-BASED DOSE-INTENSIFIED CHEMORADIATION ON A PHASE II CLINICAL TRIAL
Authors: Michelle Kim, Morand Piert, Madhava Aryal, Hemant Parmar, Theodore Lawrence, Yue Cao
Journal: Neuro-Oncology (2017)

Advanced imaging modalities including 11C-methionine PET (MET-PET) and high b-value diffusion MRI (DW-MRI) identify hypermetabolic and hypercellular tumor subregions and are prognostic for progression in patients undergoing chemoradiation for newly diagnosed glioblastoma (GBM)(1,2). We sought to characterize the relationship between these imaging modalities and conventional MRI. The initial 11 patients enrolled on a prospective phase II study (NCT02805179) of dose-intensified chemoradiation based on advanced imaging in patients with newly diagnosed GBM who underwent post-operative, pre-radiotherapy MET-PET and multiparametric MRI including high b-value DW-MRI (b=3000 s/mm2) were included in this study. Standard treatment volumes including Gd-enhanced tumor and surgical cavity (TVGd) and T2/FLAIR tumor volume (TVFLAIR) were outlined and compared with tumor subregions with abnormal uptake on MET PET (TVMET) and high b-value DW-MRI (TVHCV) using DICE correlation coefficient, defined using previously published methods. Median age was 65 years (56-77), 5/11 (45%) patients underwent subtotal resection, 2/11 (18%) biopsy alone, and 3/10 (30%) patients were MGMT methylated. Mean TVMET was 9.8 cc (0-25.9 cc), and mean TVHCV was 7.6 cc (1.7-20.4 cc), with the union on average 2.5x smaller than TVGd and 8.5x smaller than TVFLAIR. The mean volume of overlap between TVMET and TVHCV was only 1.6 cc (0-8 cc) and percentage overlap was 12% (0-34%), with no spatial overlap in 3 patients. No cases of TVMET and TVHCV extended beyond TVFLAIR, whereas 4 cc (1.1-12.5 cc) of combined TVMET and TVHCV extended beyond TVGd. TVMET and TVHCV subregions identified with known prognostic advanced imaging modalities demonstrate minimal spatial overlap and significant extension beyond the standardly boosted volume. Analyses correlating these subregions with recurrence and their relationship with other advanced imaging parameters before and during treatment are ongoing. Int J Radiat Oncol Biol Phys. 92(4):811-819, 2015. Int J Radiat Oncol Biol Phys. 73(2):479-85, 2009.
NIMG-25. ADVANCED MRI ASSESSMENT DURING DENDRITIC CELL IMMUNOTHERAPY
Authors: Marica Eoli, Valeria Cuccarini, Domenico Aquino, Elena Anghileri, Serena Pellegatta, Gaetano Finocchiaro, Maria Grazia Bruzzone
Journal: Neuro-Oncology (2017)

Evaluating changes induced by immunotherapies on conventional brain MRI can be difficult because those treatments may produce an inflammatory response. To explore the contribution of quantitative MRI biomarkers, we examined advanced MRI findings in first diagnosis glioblastoma (GBM) patients treated with dendritic cell (DC) immunotherapy added to standard treatment. A retrospective analysis was performed on longitudinal MRIs obtained by 22 patients enrolled in the EUDRACT N° 2008-005035-15 trial. The following parameters were collected: tumor volume (TV), mean normalized tumoral CBV (rCBV), Mean normalized tumoral ADC (rADC), semi-automatic ADC mean (ADCmean), ADC mode (ADCmode), ADC kurtosis (ADCkurt), ADC skewness (ADCskew). Ten patients were defined, based on PFS >12 months, to have received benefit from the treatment (responder patients). After the first four vaccinations rADC significantly decreased in responders only (1.34 ± 0.17 vs 1.23 ±0.23 p=0.028). A decrease in rADC mean value ≥ 0.13 and a change in ADCskew ≥ -0.14 were significant predictors of longer PFS (17.2 vs 10.2 p=0.04; 15.4 vs 9.3 m p=0.02) and OS (33 vs 19.9 p=0.003; 29 vs 12.4 p=0.002). During the follow-up 18 patients experienced progression and 7 pseudoprogression according to RANO criteria. A significant increase of rCBV (4.25 to 5.38, p=0.04), and a significant decrease in rADCmean (1.17 vs 1.01) (p=0.004) were only observed in patients with true tumor progression. A ΔrCBV value ≥ 2.07 was able to distinguish the two conditions with a sensitivity of 100% and specificity of 60% (p=0.004). An early decrease in rADC and limited reduction of ADCskew are related to longer survival in GBM patients treated with DC immunotherapy, added to standard care, suggesting the relevance of hypercellularity in the first phase of the treatment. Modification of rCBV can be useful in distinguishing progression and pseudoprogression
Histopathologic response and growth patterns of colorectal cancer liver metastases (CRCLM) in patients treated with triplets plus bevacizumab (bev) or anti-EGFRs
Authors: F. Marmorino, C. Cremolini, F. Pietrantonio, A. Pellegrinelli, G. Zucchelli, F. Loupakis, S. Lonardi, G. Aprile, F. Morano, M. Prisciandaro, G. Masi, A. Mennitto, F. Bergamo, G.G. Cardellino, M. Fassan, M. Casagrande, M. Milione, G. Fontanini, F. de Braud, A. Falcone
Journal: Annals of Oncology (2017)
EXTH-40. TUMOR IRON STATUS SENSITIZES GLIOBLASTOMA CELLS TO THE CYTOTOXICITY OF AN INHIBITOR OF THE IRON-DEPENDENT M2 SUBUNIT OF RIBONUCLEOTIDE REDUCTASE
Authors: Hisham S Alhajala, Devashish Joshi, Mona M Al-Gizawiy, Bo Hedlund, Howard L Elford, Kathleen M Schmainda, Christopher R Chitambar
Journal: Neuro-Oncology (2017)

Glioblastoma cells have an increased requirement for iron relative to normal brain cells. This increased demand for iron is to support ribonucleotide reductase (RRM2) activity, mitochondrial function, and signaling through the mTOR and WNT pathways which are altered in brain tumors. Given that GBM cells are rapidly proliferating, whereas normal brain cells are not, we examined the expression of RRM2 in GBM and the effect of a RR inhibitor on the proliferation of U87 and D54 GBM cells in vitro. Human GBM D54 and U87 cell lines were incubated for 96 hours with the iron chelator deferoxamine (DFO) and the RRM2 inhibitor Didox in combination at a molar ratio of 1:10. Cell proliferation was measured by MTT assay. Data were analyzed using SigmaPlot and drug synergy was determined using CalcuSyn computer programs. RRM2 expression was identified by immunohistochemical staining (IHC) of patient-derived tissue. Western blot assay was used to measure RRM2 expression in GBM cells. Dose-dependent effects of drugs were seen in both cell lines. In D54 cells, DFO and Didox had IC50s of 8 μM and 83 μM, respectively. In U87 cells, the IC50 for DFO and Didox was10 μM and 132 μM, respectively. Combined treatment at a ratio of 1:10 showed synergistic inhibition of cell proliferation. The Combination Index was <1 by pharmacologic criteria. Overexpression of the M2 subunit of RR in tumor tissue, but not in non-dividing normal brain cells, was confirmed by IHC staining and Western blotting. The combination of an iron chelator and RR inhibitor Didox synergistically inhibits the growth of GBM cells in vitro. The potential of Didox and other RR inhibitors in the treatment of GBM will be further investigated in an in vitro model of the blood brain barrier and an animal brain tumor model.
P1.03-008 Analysis of Data on Interstitial Lung Disease Onset and Its Risk Following Treatment of ALK-positive NSCLC with Xalkori
Authors: A. Gemma, M. Kusumoto, Y. Kurihara, N. Masuda, S. Banno, Y. Endo, H. Houzawa, N. Ueno, E. Ohki, A. Yoshimura
Journal: Journal of Thoracic Oncology (2017)
“Teve a gripe na semana passada?” Um enquérito telefónico para avaliar a prevalência da gripe na população sueca
Authors: L Payne, S Kühlmann-Berenzon, K Ekdahl, J Giesecke, L Högberg, P Penttinen
Journal: Eurosurveillance (2005)

A vigilância sentinela subestima de muito vezes o verdadeiro peso da gripe numa populacao porque esse sistema esta baseado nas consultas em centros medicos. Foi levado a cabo um imquerito telefonico na populacao sueca para avaliar o peso da gripe a nivel nacional, durante uma semana da estacao gripal 2004-5. Numeros de telefone de linhas fixas foram selecionadas de modo aleatorio. Os lares correspondentes foram contactados e os seus habitantes responderam a um questionario sobre a gripe entre o 14 e o 20 de fevereiro (semana 7 de 2005). Tambem foram feitas preguntas sobre o seu estatuto vacinal de gripe, sobre os sintomas e o impacto da doenca na sua vida diaria. A prevalencia auto-definida durante a semana 7 foi assim estimada a 7,7%. Applicando como definicao de caso de sindrome gripal “tosse-febre-dores musculares”, a prevalencia baixou a 3,6%. Este enquerito deu uma melhor medida do peso da doenca na populacao que a taxa habitual estimada unicamente pelo sistema de vigilância sentinela.
Meningitis por el virus Toscana en Portugal, 2002-2005
Authors: L Santos, J Simões, R Costa, S Martins, H Lecour
Journal: Eurosurveillance (2007)

La infeccion por el virus Toscana es de naturaleza endemica en Italia, pero tambien esta documentada en otros paises de la cuenca mediterranea. Nuestro objetivo era investigar episodios de meningitis causada por el virus Toscana (VTOS) en ninos y adultos jovenes de una zona metropolitana del norte de Portugal.
P1.06-020 Unequal Access to Health Care System Have a Higher Impact in Upgrading Staging for 8th TNM Ed
Authors: M.T. Ruiz Tsukazan, A. Vigo, L. Lago, G. Lenz, V. Duval Da Silva, J. Figueiredo Pinto, J. Rios, M.H. Sostruznik
Journal: Journal of Thoracic Oncology (2017)
NTOX-04. INVESTIGATION OF N-ACETYLCYSTEINE FOR THE PREVENTION OF CISPLATIN CHEMOTHERAPY-RELATED COGNITIVE IMPAIRMENTS
Authors: Naomi Lomeli, Kaijun Di, Jennifer Czerniawski, John F Guzowski, Daniela A Bota
Journal: Neuro-Oncology (2017)

Chemotherapy-related cognitive impairment (CRCI) is a major clinical problem, which diminishes the quality of life of cancer survivors. We focus on the neurocognitive impairments provoked by cisplatin, a chemotherapy agent widely used as treatment for various malignancies including ovarian, testicular, head and neck cancers, and pediatric brain tumors. More than 30% of advanced ovarian cancer patients develop CRCI during and after cisplatin-based chemotherapy. We examined mitochondrial dysfunction as a mechanism underlying cisplatin CRCI, and the ability of the antioxidant N-acetylcysteine to mitigate these toxicities in a rat model, and in-vitro in cultured rat hippocampal neurons and neural stem/progenitor cells (NSC). We examined the effects of cisplatin on neuronal morphology, apoptosis, and cognition in rats. We assessed the effects of cisplatin on mitochondrial respiratory function, reactive-oxygen species (ROS) production, caspase-9 activation, and glutathione levels in-vitro. Cisplatin reduced neuronal dendritic branching and spine density and induced apoptotic cell death in the rat hippocampus. Chronic cisplatin treatment impaired cognitive function; this impairment was mitigated by N-acetylcysteine administration. In-vitro, cisplatin damaged mitochondrial DNA, impaired respiratory activity, elevated ROS levels, and depleted glutathione. N-acetylcysteine mitigated cisplatin-induced neural ROS levels and glutathione depletion, apoptotic cell death, and neuronal post-synaptic density-95 puncta loss, while not interfering with cisplatin’s anti-cancer effect in two ovarian cancer cell lines when administered 10 h following cisplatin. The cognitive deficits caused by cisplatin in rats result from the loss of excitatory synapses and dendritic spines that anchor them, as well as from injury to mature and developing neurons. This neuronal toxicity derives from mitochondrial damage. Importantly, treatment with N-acetylcysteine mitigates cisplatin-induced neurotoxicity and cognitive deficits. We are planning a Phase I study to examine if NAC administration to ovarian cancer patients receiving cisplatin is safe, and if it ameliorates the cognitive deficits previously described in this patient population.
RTHP-30. EFFICACY AND SAFETY OF INTENSITY-MODULATED RADIOTHERAPY (IMRT) FOR WHOLE VENTRICLES IN PATIENTS WITH INTRACRANIAL GERMINOMA
Authors: Etsuko Hattori, Yoshiki Arakawa, Susumu Miyamoto
Journal: Neuro-Oncology (2017)

As for the radiotherapy of intracranial germinoma, irradiation area and dose have been able to decrease based on its histological type. The localized germinoma achieves as good outcome as whole-brain and whole-spine radiation when treated by whole-ventricle irradiation with chemotherapy. The aim of this study is to evaluate the outcome of intracranial germinomas treated with whole-ventricle irradiation using Intensity-Modulated Radiation Therapy (IMRT) at Kyoto University Hospital from 2002 to 2016. 29 patients were diagnosed as intracranial germinoma and treated with radiotherapy and/or chemotherapy at our institution. 17 patients were done whole-ventricle irradiation with IMRT; 7-fields, total 24-30Gy. Patients with high-hCG or remaining tumor performed additional focal irradiation. The treatment plan was compared IMRT with 3DCRT. The median follow-up period is 79 months. All patients have not experienced any adverse events but one patient with turner syndrome had tumor relapse in her optic nerve 44 months after the treatment. As compared to 3DCRT, IMRT achieved irradiated volume reduction of normal brain tissue and improvement of PTV coverage. IMRT improves target dose delivery and spares organs at risk, and it is presumed to reduce late adverse effects without impairing local control rate. Because 81% of intracranial germinomas appear at the time of childhood and adolescence, it is important to use effective and safety irradiation technique, but it is necessary to make a plan delivering adequate dose for high risk area such as basal ganglia.
OA 17.07 Long-Term Survival in Atezolizumab-Treated Patients with 2L+ NSCLC from Ph III Randomized OAK Study
Authors: M. Satouchi, L. Fehrenbacher, M. Cobo Dols, J. Han, J. Von Pawel, R. Bordoni, T. Hida, K. Park, D. Moro-Sibilot, P. Conkling, C. Matheny, W. Yu, P. He, M. Kowanetz, M. Gandhi, M. Ballinger, A. Sandler, D.R. Gandara
Journal: Journal of Thoracic Oncology (2017)
ACTR-38. SAFETY AND EFFECTIVENESS OF BEVACIZUMAB IN JAPANESE PATIENTS WITH MALIGNANT GLIOMA: POST-MARKETING SURVEILLANCE RESULTS
Authors: Ryo Nishikawa, Motoo Nagane, Ayaka Shimizu, Takashi Tamura, Masako Ura
Journal: Neuro-Oncology (2017)

In Japan, when bevacizumab was approved for malignant glioma patients in 2013, there were limited data on Japanese patients. In the global P3 AVAglio study, the incidence of cerebral hemorrhage, including tumor-related bleeding, and infections was higher in patients who received bevacizumab. This surveillance study was conducted to assess the safety and effectiveness of bevacizumab in patients with newly diagnosed or recurrent malignant glioma. Patients who received bevacizumab for malignant glioma from September 2013 to March 2015 were centrally registered in this study, with 18 months follow-up. Safety, including incidence of cerebral hemorrhage and infection, and one-year survival were assessed. Of 268 patients from 74 institutions in Japan who were enrolled in this study, 258 were analyzed. Patients included in the analysis comprised 137 male and 121 female patients; 80 patients with newly diagnosed glioma and 178 with recurrent glioma; and 155 patients with glioblastoma and 103 with another type. The median age was 61.0 years (range, 3–92). Of 258 patients, 161 were treated with temozolomide. The KPS was ≥70 in 145 patients, 60–50 in 84 patients, and ≤40 in 29 patients. The median duration of administration was 138 days. The incidence of adverse drug reactions (ADRs) was 29.8%, and the incidence of Grade ≥3 ADRs was 15.1%. The incidences of ADRs of interest, cerebral hemorrhage and infection, were 5.4% and 3.8%, respectively. The one-year survival rate was 78.0% in patients with newly diagnosed glioblastoma (n=57), 72.0% in those with residual tumors (n=46), and 38.9% in those with recurrent glioblastoma (n=98). The results suggest no new safety concerns, and effectiveness was consistent with previously reported data. Therefore, bevacizumab is considered one of the treatment options for malignant glioma patients in clinical practice.
Biliary tract carcinoma and chronic viral hepatitis in Italy: the GICO (Gruppo Italiano COlangiocarcinoma) experience
Authors: R. Filippi, G. Frega, C. Vivaldi, A. Casadei Gardini, G. Aprile, N. Silvestris, M.A. Satolli, L. Faloppi, D. Santini, E.S. Lutrino, E. Vasile, M. Valgiusti, D. Basile, O. Brunetti, R. Spadi, M. Russano, M. Scartozzi, C. Cagnazzo, G. Brandi, F. Leone
Journal: Annals of Oncology (2017)
EXTH-64. RAPID IN SITU GEL-FORMING BY LIGHT-IRRADIATION FOR COMBINATION OF CHEMOTHERAPY AND RADIOTHERAPY IN BRAIN TUMOR
Authors: Chiungyin Huang, Pinyuan Chen, Kuochen Wei
Journal: Neuro-Oncology (2017)

About 40,000 people are diagnosed with primary brain tumors in the United States each year, an estimated 15,000 have glioblastoma multiforme (GBM), which is still associated with poor prognosis with 14.6 month of median survival after surgical resection combined with chemotherapy and radiation. Preventing tumor recurrence after surgical resection of a brain tumor is a significant clinical challenge because current methods deliver chemotherapeutic agents in a rapid manner and are not effective against the residual tumor cells, such as Gliadel®. To overcome this drawback, we develop a rapid gelled hydrogel which can tightly adhere on the tissues for controlled chemotherapy, radiotherapy, and enhanced laser interstitial thermal therapy (LITT) to improve the survival after surgical resection. The principle goals are to i) determine the prevailing factors that affect efficient encapsulation of chemotherapeutic drugs (i.e., Epirubicin or Temozolomide) and radio-sensitizer (i.e., Cisplatin) within hydrogels, ii) demonstrate efficiency of gelation, LITT enhancement, in vitro drug release, iii) evaluate the efficiency in human cancer cells and in vivo tumor model. Our preliminary results have successfully demonstrated the feasibility of this grant and our materials design. We believe this synergistic strategy presents a new approach to the development of a local drug delivery system for the prevention of brain tumor recurrence.
P2.02-020 Molecular Characteristics of Patients with PTEN Mutations in Chinese Non-Small Cell Lung Cancer
Authors: X. Zheng, C. Xu, W. Wang, W. Zhuang, Z. Song, Y. Zhu, R. Chen, Y. Guan, X. Yi, Y. Chen, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)