tbuckley/cabot-search huggingface dataset:
EXTH-15. RADIATION-INDUCED LATE MALIGNANT MENINGIOMA TRANSFORMATION: CDK 4/6 INHIBITOR THERAPY
Authors: Arabinda Das, Faith Middleton, Daniel G McDonald, William Alexander Vandergrift, Kenneth N Vanek, Pierre Giglio, Sunil J Patel, Libby Kosnik Infinger, Abhay K Varma, Scott M Lindhorst, David Cachia
Journal: Neuro-Oncology (2017)

Meningiomas are the most common primary brain tumor reported in the United States each year and account for approximately 30% of primary neoplasms. Though in most cases the etiology of meningiomas is unclear, prior exposure to radiation is responsible for a subset of meningiomas. Some have speculated that there may be a relationship between pretreatment characteristics and radiotherapy parameters in the development of radiation-induced meningiomas (RIM). Compared with their sporadic counterparts, currently, the clinical treatment involves is similar with radiation used as a first line therapy. Novel therapeutic agents being investigated in the treatment of these tumors, rely on the direct or cell cycle-mediated induction of DNA damage to promote cellular apoptosis. Our pre-clinical data showed that disruption of p16INK4a-Cdk4-Rb (retinoblastoma) pathways plays a significant role in the development of RIM in Rb+ low-gradelow-grade meningioma cells. These observations highlight the critical role of the p16INK4a-Cdk4-Rb pathway in RIM and suggest that targeting this pathway might be a promising strategy to improve the therapeutic efficacy among RIM patients. Pretreatment characteristics and radiotherapy parameters which may influence the time interval for development of radiation-induced Rb+ meningiomas (RIM) were identified. Our results also demonstrated that CDK 4/6 Inhibitor, significantly suppresses radiation induced malignant transformation and prolonged survival in a cell-free, slice culture model and xenograft model of meningioma. Success of the proposed therapeutic strategies in both in vitro and in vivo models may form the basis for future research.
P2.08-007 Five-Year Results of Concurrent Chemotherapy and Isotoxic Radiotherapy Dose-Escalation with IMRT in Stage III NSCLC (NCT01166204)
Authors: D. De Ruysscher, B. Reymen, G. Bootsma, A. Dingemans, W. Geraedts, C. Pitz, W. Van Elmpt, M. Oellers, A. Van Baardwijk, R. Wanders, J. Van Loon
Journal: Journal of Thoracic Oncology (2017)
SURG-07. CIRCUMFERENTIAL RESECTION OF GLIOBLASTOMA: A NOVEL SURGICAL TECHNIQUE FOR MAXIMISING EXTENT OF RESECTION AND PROLONGING SURVIVAL
Authors: Michael Opoku-Darko, Magalie Cadieux, Wajid Sayeed, Jacob Easaw, John Kelly
Journal: Neuro-Oncology (2017)

Evidence suggests that cytoreduction is associated with improved survival in glioblastoma (GBM) and that maximal, or gross total resection of the tumor offers the best chance for prolonged survival. We developed a novel surgical technique for removal of GBM called Circumferential resection during which we identify the interface between the enhancing rim of GBM and surrounding brain structures enabling more complete resection. We evaluate the impact of this method on extent of resection and survival in glioblastoma. We retrospectively evaluated 127 consecutive patients with newly diagnosed GBM treated at our institution. Forty-seven (37%) had circumferential resection (CR) by the senior author and the other 80(63%) had debulking/piecemeal (“non-circumferential”) resection(NCR). All patients underwent adjuvant chemoradiotherapy as per the Stupp protocol. Tumor volumetric analysis was performed using Osirix software. Overall survival and survival as stratified by treatment and extent of resection (EOR) were evaluated using Kaplan-Meier survival analysis. Clinical characteristics between CR and NCR cohorts were similar. Mean age at diagnosis was 59 years and 81(63.9%) were male. Pre-operative tumor volume was 31.8 cm3 vs. 40.6 cm3 (p=0.05) for CR vs. NCR respectively. Patients who had CR had higher median EOR (100.0 vs. 90.4, p<0.0001). The median OS for the entire cohort was 13.2 months. Median OS for CR and NCR was 17.7 and 11.0 months respectively (p<0.0001). EOR significantly impacted survival. Among the CR cohort, median survival was 22.5 and 11.5 months for >98% and <98% EOR respectively while median survival for the NCR cohort was 14.4 and 9.6 months for >98% and <98% EOR respectively. Post-operative Karnofsky Performance Scale (median, interquartile range) was 80(70-90) and 70(70-90) for CR and NCR patients respectively (p=0.43). Circumferential resection helps maximise the extent of resection in glioblastoma surgery and significantly prolongs survival without compromise to functional status.
QLIF-38. TUMOR TREATING FIELDS FOR THE TREATMENT OF GLIOBLASTOMA MULTIFORME IN DAILY PRAXIS: EXPERIENCE FROM TWO HOSPITALS IN GERMANY
Authors: Stephanie May, Julia Goebel, Rüdiger Gerlach, Dietmar Krex
Journal: Neuro-Oncology (2017)

A recent clinical trial combining tumor treating fields (TTFields) with adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme (GBM) demonstrated a significant increase in progression-free (PFS) and overall survival (OS). The aim of our surveillance study was to examine the implementation of this new therapy approach in clinical practice and to analyze the acceptance and compliance. Patients with a diagnosed GBM of two independent centers in Germany were treated with TTFields (Optune®). TTFields are applied via four transducer arrays and are generated by a portable device. Study data indicate the therapy compliance supposed to be above 75 %. We created a questionnaire that covers handling of the device, side effects, overall satisfaction and if they would recommend the therapy. Additionally, we analyzed the relationship of PFS and therapy compliance. During an observation period of 15 months, 21 patients received TTFields. More patients will follow. Twelve patients treated with TTFields took part in the survey. All patients were very satisfied with technical support and supply. Most patients reported easy handling in everyday life (58 %), the remaining patients perceived some limitations. Side effects were limited to skin irritation (50 %), sleep disturbance and back pain (25 % of the patients). Around 63 % had a recommended compliance. Within the observation period 29 % died, 10 % showed progressive and 71 % showed stable disease. Although several patients described limitations in everyday life, 83 % would decide on TTFields treatment again. The survey of patients with ongoing TTFields treatment in two independent centers revealed a good therapy acceptance and compliance. The PFS tends to approach the published data. Although patients reported of handling difficulties and side effects, most patients could integrate the therapy in their everyday life and would decide on the treatment again.
SURG-34. FLUORESCENCE-GUIDED SURGERY WITH 5-AMINOLEVULINIC ACID FOR RESECTION OF PEDIATRIC BRAIN TUMORS
Authors: Takafumi Wataya
Journal: Neuro-Oncology (2017)

Whereas in the adult population 5-Aminolevulinic acid (5-ALA) fluorescence guidance has been widely accepted for improving the extent of resection of malignant glioma, the application in children remains unknown. We present here our application of 5-ALA in brain tumor surgery of 11 pediatric patients, and usefulness and limitation is discussed. MATERIAL- This is a retrospective analysis of 11 patients (age 1-18 years) with suspected brain tumor regardless of tumor location or status of contrast-enhancement on MRI. After individual informed consent was obtained in each case from the parents, 5-ALA was administered with 20 mg/kg, 3 hours before induction of anesthesia. The operations were performed under standard white light using a microscope, and the neurosurgeon repeatedly applied external violet-blue illumination system (Esperaluz, CCS inc. Kyoto) to visualize red fluorescence in the operative field. Patients’ profile, MRI findings, and final pathology were analyzed. In 8 different tumor pathologies (Pilocytic astrocytoma, glioblastoma multiform (GBM), oligodendroglioma, astroblastoma, medulloblastoma, ependymoma, primitive neuroectodermal tumor (PNET), choroid plexus carcinoma, sarcoma), 4 (GBM, oligodendroglioma, astroblastoma and ependymoma) showed strong red-fluorescence by excitation with Esperaluz. One of 2 ependymoma case didn’t show fluorescence. Positive fluorescent has not been not observed in the patients ages younger than 4-year-old. No adverse side effect was observed. 5-ALA can be safely administered to the pediatric patients, and surgeons felt it useful on resection surgery. A part of gliomas with WHO grading greater than 2, but not all showed positive fluorescence. Non-glioma like medulloblastoma, PNET, or sarcoma showed negative fluorescence even with high grading. Young patients had difficulty to take 5-ALA due to its taste. However, it was successfully taken without tasting by sipping through straws. Fluorescence-guided surgery with 5-ALA was considered safe and useful procedure for resection of pediatric brain tumors.
NCOG-07. MEMORY FUNCTIONING IN LOW-GRADE GLIOMA PATIENTS TREATED WITH EITHER RADIOTHERAPY (RT) OR TEMOZOLOMIDE (TMZ) CHEMOTHERAPY. A CORRELATIVE ANALYSIS OF EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT (EORTC) STUDY 22033-26033
Authors: Martin Klein, Josephine Drijver, Martin van den Bent, Khê Hoang-Xuan, Martin J B Taphoorn, Jaap C Reijneveld, Mohamed Ben Hassel, Danielle Eekers, Tzahala Tzuk, A Lucas, Vassilis Golfinopoulos, Thierry Gorlia, Roger Stupp, Brigitta G Baumert
Journal: Neuro-Oncology (2017)

In EORTC study 22033−26033 primary treatment with radiotherapy was compared to temozolomide chemotherapy alone in patients with high-risk low-grade glioma. There was no difference in progression-free survival between treatment modalities [Baumert et al. Lancet Oncol. 2016;17:1521-1532]. Considering the potential long-term deleterious impact of radiotherapy on memory functioning, this study also focused on the question whether temozolomide chemotherapy would be associated with a more favorable neurotoxic profile regarding memory functioning. Memory functioning using the Rey Auditory Verbal Learning Test (Free Recall and Delayed Recall) was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Total score over 5 trials of 15 items for free recall and total score on delayed recall were used as memory outcome measures. Using a mixed linear model memory functioning was compared between treatment arms and over time. In dedicated centers, a total of 98 patients (radiotherapy 52 patients, temozolomide 46 patients) were assessed at baseline. At 12 months compliance had dropped to 66%, thus analyses were restricted to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in the memory functioning, gender, age, or educational level. When compared to healthy matched controls, patients in both treatment arms at baseline had significantly lower free recall (p <.001) but not delayed recall. Over the relatively short time course of 1 year there was no change in memory functioning in either treatment arm. In patients with high-risk low-grade glioma there is no indication that radiotherapy has a more deleterious effect on memory function when compared to temozolomide chemotherapy from baseline up to 12 months follow-up. Further data maturation is needed not only for overall survival analyses but also for the full appreciation of long-term effects of radiotherapy in these patients.
PDTM-43. CHARACTERISATION OF CELL MIGRATION IN LOW AND HIGH GRADE PAEDIATRIC GLIOMAS FOR ASSESSMENT OF THE FIBROBLAST GROWTH FACTOR RECEPTOR 1 (FGFR1) AS A THERAPEUTIC TARGET
Authors: Naomi Egbivwie, Julia Cockle, Matthew Humphries, Azzam Ismail, Filomena Esteves, Claire Taylor, Ruth Morton, Tracy Warr, Susan C Short, Anke Brüning-Richardson
Journal: Neuro-Oncology (2017)

Our previous research in anti-migratory intervention in paediatric gliomas has highlighted the need for novel treatments to target tumour invasion based on individual tumour biology. Recurrent fibroblast growth factor receptor 1 (FGFR1) mutations in paediatric gliomas have been recently reported. Here we characterised cell migration in rare paediatric low-grade gliomas (pLGG) and high-grade gliomas (pHGG) and investigated FGFR1 as a suitable target for chemotherapeutic intervention. Five patient derived pLGG cell lines (IN1520, IN1591, IN2017, IN2566, IN2866) and two established pHGG cell lines (SF188 and KNS42) were examined for their migratory ability in 2D and 3D migration models as well as for their responses to treatment with three different FGFR1 inhibitors. FGFR1 levels (both inactive and active) were assessed by immunofluorescence. We also carried out mutational analysis of exons containing codons 546 and 655,656 & 658. We established distinct migratory abilities in all cell lines. In 2D, random migration velocity values ranged from 0.06 to 0.12 mM/min (pLGG cell lines) and 0.1 and 0.2 mM/min (KNS42 and SF188). In 3D invasion assays the migration indices (MI) ranged from 0.28 to 0.54 (pLGG) and were 0.07 and 0.53 for KNS42 and SF188. All pLGG cell lines had higher levels of FGFR1 and activated FGFR1 compared to the pHGG cell lines. Three pLGG cell lines migrated faster after FGFR1 stimulation with FGF2. Significant anti-migratory effects were observed in pHGG with two inhibitors, however, inhibition elicited pro- or anti-migratory responses among the different pLGG cell lines. No mutations in the investigated exons were detected. We describe for the first time the migratory ability of patient-derived pLGG cell lines and their response to FGFR1 inhibition. Differential responses in these cell lines highlights the importance of personalised treatment and a possible role of FGFR1 in paediatric glioma cell migration.
P1.15-007 Randomized Phase III Trial of Enoxaparin in Addition to Standard Treatment in Small Cell Lung Cancer: The RASTEN Trial
Authors: E. Gezelius, L. Ek, B. Bergman, P. Bendahl, H. Anderson, U. Falkmer, S. Verma, J. Sundberg, M. Wallberg, M. Belting
Journal: Journal of Thoracic Oncology (2017)
Small luminal-like breast cancer: determinants of adjuvant chemotherapy use
Authors: A. Bettini, L. Gerratana, G. Pelizzari, M. Bonotto, D. Basile, M.G. Vitale, C. Bozza, M. Bartoletti, V. Fanotto, C. Lisanti, M. Cinausero, M. Mansutti, A.M. Minisini, G. Fasola, F. Puglisi
Journal: Annals of Oncology (2017)
Investigation d’un cluster de tuberculose dans une agence pour l’emploi, Manchester, Royaume-Uni
Authors: A Kirkpatrick, C Bell, M Petrovic, M Woodhead, A Barrett, E Duffell, A Verma, F Reynolds
Journal: Eurosurveillance (2006)

Pendant l’ete 2005, quatre cas de tuberculose active provenant du meme lieu de travail a Manchester, au Royaume-Uni, ont fait l’objet d’une investigation. Le cas index avait ete diagnostique en decembre de l’annee precedente. A cette epoque, un depistage des contacts professionnels les plus proches avait confirme que tous etaient exempts de la maladie. De plus, aucun ne necessitait une chimioprophylaxie pour une infection tuberculeuse latente (ITBL), selon les criteres recommandes au niveau national,. 
En juin 2005, deux contacts professionnels ont developpe une TB extrapulmonaire primaire progressive (pleurale). Suite a une evaluation detaillee des risques, le programme de depistage a ete elargi pour inclure 137 personnels employes par l’agence pour l’emploi ou avaient ete identifies les quatre premiers cas. Ce depistage etait base sur le test Mantoux de sensibilite a la tuberculine, le test CXR et le dosage des interferons gamma. Parmi les 137 personnes depistees, la maladie active a ete identifiee chez une personne supplementaire et une chimioprophylaxie a ete proposee a six autres personnes affectees par une ITBL. Les isolats du cas index et des deux premiers cas secondaires etaient indiscernables par la methode MIRU-VNTR (mycobacterial interspersed repetitive unit-variable number tandem repeat) avec un typage de 15 loci. Aucun prelevement du quatrieme cas de tuberculose active n’etait disponible pour les tests. 
La gestion de cet incident a beneficie des progres du genotypage et des tests diagnostics de l’ITBL. Cependant, une recherche plus approfondie au niveau des consequences epidemiologiques dues au genotypage reste a faire. De meme, il reste a etudier la signification d’un test interferon gamma positif pour evaluer le risque de developper une tuberculose active.
Interdisciplinary Perspectives on Sun Safety
Authors: Alan C. Geller, Nina G. Jablonski, Sherry L. Pagoto, Jennifer L. Hay, Joel Hillhouse, David B. Buller, W. Larry Kenney, June K. Robinson, Richard B. Weller, Megan A. Moreno, Barbara A. Gilchrest, Craig Sinclair, Jamie Arndt, Jennifer M. Taber, Kasey L. Morris, Laura A. Dwyer, Frank M. Perna, William M. P. Klein, Jerry Suls
Journal: JAMA Dermatology (2017)

Overexposure to the sun is associated with an increased risk of melanoma and nonmelanoma skin cancer, but indications of improvements in sun protection behavior are poor. Attempts to identify emerging themes in skin cancer control have largely been driven by groups of experts from a single field. In December 2016, 19 experts from various disciplines convened for Interdisciplinary Perspectives on Skin Cancer, a 2-day meeting hosted by the National Academy of Sciences. The group discussed knowledge gaps, perspectives on sun exposure, implications for skin cancer risk and other health outcomes, and new directions. Five themes emerged from the discussion: (1) The definition of risk must be expanded, and categories for skin physiology must be refined to incorporate population diversities. (2) Risky sun exposure often co-occurs with other health-related behaviors. (3) Messages must be nuanced to target at-risk populations. (4) Persons at risk for tanning disorder must be recognized and treated. (5) Sun safety interventions must be scalable. Efficient use of technologies will be required to sharpen messages to specific populations and to integrate them within multilevel interventions. Further interdisciplinary research should address these emerging themes to build effective and sustainable approaches to large-scale behavior change.
NCOG-15. LONG-TERM IMPACT OF RADIATION DOSE AND VOLUME ON INTELLECTUAL FUNCTIONING (IQ) FOR CHILDREN DIAGNOSED WITH MEDULLOBLASTOMA: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP (COG)
Authors: Leanne Embry, Anthony Gioia, Yimei Li, Yunayuan Han, Patricia Cullen, Anna Janss, Jeff Michalski, Catherine Billups, Robert Noll, Kristina Hardy
Journal: Neuro-Oncology (2017)

To examine longitudinal neuropsychological functioning in children receiving treatment for medulloblastoma on COG clinical trial ACNS0331. Children aged 3 and older diagnosed with medulloblastoma participated in neuropsychological testing as part of the original study design or in conjunction with COG protocol ALTE07C1. Children under 8 were randomized to receive craniospinal irradiation (CSI) of either 18 Gy (reduced dose) or 23.4 Gy (standard dose); all children aged 8+ received 23.4 Gy. All children received either a 54 Gy boost to the entire posterior fossa (standard boost) or tumor bed (reduced volume boost), plus standard chemotherapy. Intellectual functioning (IQ) of children was evaluated an average of 0.67 (+0.21) and 2.99 (+0.59) years post-diagnosis. Of 464 eligible and evaluable patients enrolled on ACNS0331, 337 (72.6%) completed intellectual testing at one or both timepoints (mean age at diagnosis=9.1 [SD=4.06], range 3-19 years; 65.3% male; 83.1% white). Mean estimated IQ was in the average range at both timepoints (mean IQ T1=95.7 + 15.14; mean IQ T2=94.4 + 14.21), and declined an average of 2.2 (+ 9.98) points over time. Among children aged 3-7 at diagnosis, those randomized to standard dose CSI exhibited greater IQ declines over time than those in the lower-dose group (-7.2 vs. -0.4, respectively; p= .04). Among all ages, younger children (p <.01) and those who received a standard boost volume (p=.01) exhibited lower IQ at T2. Results of this prospective, randomized clinical trial suggest that children receiving a boost to the whole posterior fossa experience steeper declines in intellectual functioning over time. In addition, reducing whole-brain dose for younger children was also associated with less decline. Results suggest that strategies to limit the CSI dose and/or boost volume in children treated for medulloblastoma may improve neuropsychological outcomes. These approaches need to be weighed against the possible impact on disease control.
TMOD-38. EXTENT OF GLIOBLASTOMA INVASION PREDICTS OVERALL SURVIVAL FOLLOWING UPFRONT RADIOTHERAPY CONCURRENT WITH TEMOZOLOMIDE
Authors: Susan Christine Massey, Haylye White, Corbin Rayfield, Cassandra R Rickertsen, Kamala Clark-Swanson, Scott Whitmire, Sandra K Johnston, Alyx Porter, Maciej Mrugala, Bernard Bendok, Kristin R Swanson
Journal: Neuro-Oncology (2017)

Temozolomide concurrent with radiation (Stupp protocol) has been one of the most important advances in the treatment of Glioblastoma (GBM), significantly increasing survival times (Stupp 2005, 2009). We examined whether GBM response to Stupp could be associated with patterns of tumor cell invasion using our previously developed patient–specific mathematical models. Drawing from our clinical research database, we identified a cohort of 47 newly diagnosed GBM patients receiving Stupp protocol with MRI followup spanning pre-surgery through first progression. These MRIs allowed us to quantify the distribution of tumor cells throughout the brain with our previously established invasion metric D/ρ (Wang 2009). High D/ρ tumors are more invasive, having a greater proportion of tumor cells beyond the imageable regions of the tumor. We examined whether this index changed following treatment with Stupp protocol. Using linear regression, Cox proportional hazard, and survival analyses (Kaplan-Meier) we examined whether this index in either setting, and/or the change in this index was correlated with patient outcomes. Initial (pre-treatment) D/ρ values were positively correlated with overall survival (p=0.016). Further, patients for which D/ρ decreased between diagnosis and recurrence had favorable outcomes (p=0.0496). Patients who had more diffuse tumors (high D/ρ) initially were more likely to become less diffuse (low D/ρ) at recurrence whereas patients who have low D/ρ initially become more diffuse (p=0.004). This change suggests a shift in tumor phenotype from a more–diffuse pattern of growth to less–diffuse, which may reflect the exposure of those diffusely invaded tumor cells to widely distributed radiation dose and the blood-brain barrier permeable TMZ. Taken together, these data suggest that tumors with increased diffuse invasion are more likely to respond to Stupp and experience improved overall survival.