tbuckley/cabot-search huggingface dataset:
ATIM-02. DURABLE RESPONSES OBSERVED IN IDH1 WILDTYPE AND MUTANT RECURRENT HIGH GRADE GLIOMA (rHGG) WITH TOCA 511 & TOCA FC TREATMENT
Authors: Timothy Cloughesy, Joseph Landolfi, Michael Vogelbaum, Derek Ostertag, Bradley Elder, Bob Carter, Clark Chen, Steven Kalkanis, Albert Lai, Tom Mikkelsen, Phioanh Nghiemphu, David Piccioni, William Accomando, Oscar Diago, Daniel Hogan, Douglas Jolly, Katie Wood, Liqiang Yang, Harry Gruber, Asha Das, Tobias Walbert
Journal: Neuro-Oncology (2017)

Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that selectively infects dividing cancer cells, integrates into the genome and replicates due to immune defects in tumors. Toca 511 spreads through tumors and stably delivers the gene encoding an optimized yeast cytosine deaminase that converts the prodrug Toca FC (an investigational, extended-release formulation of 5-fluorocytosine) into 5-fluorouracil. 5-fluorouracil kills infected cancer cells and surrounding cancer cells, myeloid derived suppressor cells and tumor associated macrophages, thus enabling immune activity against the tumor. In this phase 1 trial (NCT01470794), ascending doses of Toca 511 were injected into the resection bed of patients with rHGG, followed by multiple courses of oral Toca FC. Additional cohorts included combination of the investigational therapy with bevacizumab or lomustine. Objective responses (ORs) are observed in patients with IDH1 wildtype and mutant tumors, including 3 complete responses (CRs) and 2 partial responses with the investigational therapy, and 1 CR with the investigational therapy and bevacizumab. The IDH1-mutant patients treated at 1st recurrence all had CRs and the fact that a CR in rHGG is rare suggests that the investigational treatment may be playing a role. ORs are observed 6–19 months after Toca 511 injection, consistent with an immunologic mechanism. Median time to initial response is 9.2 months; median duration of response (mDoR) is 25.2 months. Excluding combination cohorts, mDoR is 26.7 months. All responders are alive 21.2+ to 42.6+ months, suggesting a correlation of durable responses (ORs lasting > 24 weeks) with overall survival. In a 24-patient subgroup who received the recommended Ph2 Toca 511 dose, a durable response rate of 20.8% was observed. Across the Phase 1 program, the safety profile remains favorable. Updated clinical benefit, safety, immune activity, and molecular profiles will be reported.
P3.02-082 High Mobility Group Box 1 Antagonist Limits Metastatic Seeding in the Lungs via Reduction of Cell-Cel Adhesion
Authors: A. Karsch-Bluman, B. Amoyav, N. Friedman, H. Shoval, E. Ella, O. Wald, O. Benny
Journal: Journal of Thoracic Oncology (2017)
ATIM-04. A MULTI-INSTITUTIONAL PILOT STUDY OF PROPHYLACTIC CRANIAL TUMOR-TREATING FIELDS FOR PATIENTS WITH EXTENSIVE-STAGE SMALL CELL LUNG CANCER
Authors: Nitesh Rana, Jerry J Jaboin, Michael D Chan, Albert Attia
Journal: Neuro-Oncology (2017)

Brain metastases are common in patients diagnosed with small cell lung cancer (SCLC). Prophylactic cranial irradiation (PCI) has been shown to potentially improve survival in patients with extensive-stage small cell lung cancer (ES-SCLC) but has detrimental effects on quality-of-life (QoL). Tumor treating fields (TTFields) are a regional non-invasive, antimitotic treatment with minimal toxicity, approved for recurrent and newly diagnosed glioblastoma. Prophylactic cranial TTFields may allow for sufficient intracranial control and prevent the formation of brain metastases with minimal late cognitive effects potentially improving survival and QoL for patients with ES-SCLC. To test the feasibility of prophylactic cranial TTFields therapy in preventing brain metastases in ES-SCLC patients with partial or complete response of extracranial disease after at least 4 cycles of first-line chemotherapy. Secondary endpoints include overall survival, development of brain metastases, neurocognitive function, and QOL outcomes. This is a prospective, single-arm, open-label multicenter pilot study. All patients will undergo TTFields treatment using the NovoTTF-200A System set to an output frequency of 200 kHz. The feasibility of TTFields prophylaxis will be measured as the percentage of patients continuing TTFields therapy until intracranial tumor progression, discontinuation due to disease limiting toxicity, or continuation of therapy for at least 6 months. TTFields will be discontinued in patients who develop intracranial failure while on therapy. All patients who develop intracranial failure may undergo whole brain radiotherapy or best supportive care at the discretion of the treating physician. All study follow-up procedures are to continue according to protocol until death, or until another criteria for removal is met. Because the primary endpoint is feasibility, the proposed sample size is not driven by statistical hypotheses. A sample size of 25 was set to accumulate more extensive patient data for planning the next clinical phase of this potential prophylactic treatment.
NIMG-83. AMINO ACID PET AND PERFUSION MRI IN CONTRAST-ENHANCING AND NON-ENHANCING REGIONS OF GLIOBLASTOMAS
Authors: Edit Bosnyak, Flora John, Natasha L Robinette, Alit Yousif, Geoffrey R Barger, Sandeep Mittal, Csaba Juhasz
Journal: Neuro-Oncology (2017)

Perfusion-weighted MRI (PWI) and amino acid PET are increasingly used for glioma imaging before and after initial treatment. While some studies found a good correlation between these two imaging modalities, others demonstrated discrepancies in various glioma groups and found only a limited spatial overlap of regions with the highest amino acid uptake and highest perfusion. In this study, we compared amino acid uptake measured by PET and relative cerebral blood volume (CBV) from PWI in contrast-enhancing and non-enhancing portions of glioblastomas. Contrast-enhanced T1, T2/FLAIR images, CBV maps from PWI, and alpha[C-11]-methyl-L-tryptophan (AMT)-PET images were co-registered in 23 patients (mean age: 56 years) with newly-diagnosed (n=10) or recurrent (n=13) glioblastoma. Tumoral amino acid uptake and CBV, expressed as tumor/contralateral normal brain (cortex for AMT, white matter for CBV, respectively) [T/N] ratios, were measured and compared in contrast-enhancing and non-enhancing (but T2/FLAIR-positive) regions. High AMT uptake on PET was measured in 23 contrast-enhancing regions of 21 patients (mean T/N ratio: 2.43). Similarly, high AMT uptake was also found in 18 adjacent non-enhancing regions of 16 patients (mean T/N: 2.35), indicating tumor-infiltrated brain. On the other hand, 27 contrast-enhancing regions (in 21 patients) showed significantly lower AMT uptake (mean T/N: 1.45; p<0.001). Relative CBV values showed very similar values in high-AMT and low-AMT contrast-enhancing tumor portions (mean T/N white matter ratios: 5.7 in both regions) and were slightly lower in non-enhancing PET+ brain regions (T/N: 4.9). Corresponding AMT and CBV T/N ratios showed no significant correlations. AMT/CBV comparative findings were similar in pre- and post-treatment glioblastoma subgroups. Amino acid PET and perfusion MRI provide substantially different diagnostic information in newly-diagnosed and recurrent glioblastomas. High amino acid uptake on PET can detect metabolically active tumor portions in contrast-enhancing and non-enhancing regions regardless of perfusion status.
P2.02-013 Investigation of Genomic and TCR Repertoire Evolution of AAH, AIS, MIA to Invasive Lung Adenocarcinoma by Multiregion Exome and TCR Sequencing
Authors: X. Hu, J. Fujimoto, L. Ying, A. Reuben, R. Chen, C. Chow, J. Rodriguez-Canales, W. Sun, J. Hu, E.R. Parra, B. Carmen, C. Wu, X. Mao, X. Song, J. Li, C. Gumbs, S.G. Swisher, J. Zhang, J. Heymach, W.K. Hong, I. Wistuba, A. Futreal, D. Su, J. Zhang
Journal: Journal of Thoracic Oncology (2017)
STEM-24. CORE CLOCK GENES REGULATE CANCER STEM CELLS IN BRAIN TUMOR
Authors: Zhen Dong, Guoxin Zhang, Qiulian Wu, Jeremy Rich
Journal: Neuro-Oncology (2017)

Circadian rhythms are self-sustainable endogenous 24 hours oscillations, present in every living system and cell, driving daily cycles of biological process, including cell division and metabolism. Circadian rhythm disruption by shift work or core clock genes dysfunction is associated with high risk of tumor development, indicating a putative tumor-suppressive role of circadian rhythm. Using a subpopulation of stem-like cells, coming from human glioblastoma displaying cellular hierarchies, we characterized the role of core clock genes in these stem-like cells. We found that circadian rhythm transcriptional factors Clock and Bmal1 in glioblastoma stem-like cells (GSC) is required for the growth of GSC in vitro and in vivo. Disruption of canonical circadian pathway components produce anti-brain tumor effects, including decreased proliferation, impaired self-renew, increased cell apoptosis and depletion of GSC. Loss of Bmal1 and Clock led to mitochondrial respiration dysregulation and impaired the tricarboxylic acid cycle by regulating genes and enzymes expression in this process. Our finding established a novel role for the core circadian rhythm genes in glioblastoma stem-like cells.
2017 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary
Authors: Theresa M. Olasveengen, Allan R. de Caen, Mary E. Mancini, Ian K. Maconochie, Richard Aickin, Dianne L. Atkins, Robert A. Berg, Robert M. Bingham, Steven C. Brooks, Maaret Castrén, Sung Phil Chung, Julie Considine, Thomaz Bittencourt Couto, Raffo Escalante, Raúl J. Gazmuri, Anne-Marie Guerguerian, Tetsuo Hatanaka, Rudolph W. Koster, Peter J. Kudenchuk, Eddy Lang, Swee Han Lim, Bo Løfgren, Peter A. Meaney, William H. Montgomery, Peter T. Morley, Laurie J. Morrison, Kevin J. Nation, Kee-Chong Ng, Vinay M. Nadkarni, Chika Nishiyama, Gabrielle Nuthall, Gene Yong-Kwang Ong, Gavin D. Perkins, Amelia G. Reis, Giuseppe Ristagno, Tetsuya Sakamoto, Michael R. Sayre, Stephen M. Schexnayder, Alfredo F. Sierra, Eunice M. Singletary, Naoki Shimizu, Michael A. Smyth, David Stanton, Janice A. Tijssen, Andrew Travers, Christian Vaillancourt, Patrick Van de Voorde, Mary Fran Hazinski, Jerry P. Nolan
Journal: Circulation (2017)

The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 pediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have prioritized and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question.
P2.03-052 Local Ablative Therapy for Oligoprogressive, EGFR-Mutant, Non-Small Cell Lung Cancer (NSCLC) After Treatment with Osimertinib
Authors: C. Kim, N. Roper, C. Hoang, M. Connolly, C. Cultraro, E. Szabo, M. Waris, E. Padiernos, A. Kesarwala, S. Gao, S. Steinberg, D. Wong, J. Khan, A. Rajan, U. Guha
Journal: Journal of Thoracic Oncology (2017)
Oxytocin-receptor-expressing neurons in the parabrachial nucleus regulate fluid intake
Authors: Philip J. Ryan, Silvano I. Ross, Carlos A. Campos, Victor A. Derkach, Richard D. Palmiter
Journal: Nature Neuroscience (2017)

Brain regions that regulate fluid satiation are not well characterized, yet are essential for understanding fluid homeostasis. We found that oxytocin-receptor-expressing neurons in the parabrachial nucleus of mice (OxtrPBN neurons) are key regulators of fluid satiation. Chemogenetic activation of OxtrPBN neurons robustly suppressed noncaloric fluid intake, but did not decrease food intake after fasting or salt intake following salt depletion; inactivation increased saline intake after dehydration and hypertonic saline injection. Under physiological conditions, OxtrPBN neurons were activated by fluid satiation and hypertonic saline injection. OxtrPBN neurons were directly innervated by oxytocin neurons in the paraventricular hypothalamus (OxtPVH neurons), which mildly attenuated fluid intake. Activation of neurons in the nucleus of the solitary tract substantially suppressed fluid intake and activated OxtrPBN neurons. Our results suggest that OxtrPBN neurons act as a key node in the fluid satiation neurocircuitry, which acts to decrease water and/or saline intake to prevent or attenuate hypervolemia and hypernatremia.
PDTM-19. TOCA 511 &amp; TOCA FC: PRE-CLINICAL PROOF OF CONCEPT IN MEDULLOBLASTOMA
Authors: Angela M Richardson, Sara A Collins, Akihito Inagaki, Valerie L Armstrong, Martine Roussel, Douglas Jolly, David J Robbins, Nagi Ayad, Noriyuki Kasahara
Journal: Neuro-Oncology (2017)

Toca 511, a clinical-stage retroviral replicating vector (RRV) encoding an optimized yeast cytosine deaminase (CD) prodrug activator gene, in combination with Toca FC (extended-release 5-fluorocytosine (5-FC)), is designed to produce 5-FU which kills cancer cells and immune-suppressive myeloid cells in the tumor microenvironment, leading to anti-cancer immune activation and long-term survival. This combination treatment is currently under evaluation in an international Phase 2/3 trial in patients with recurrent high-grade glioma. In the present study, we investigated the feasibility of further applying Toca 511 & Toca FC in medulloblastoma, the most common malignant tumor of the pediatric nervous system. Aggressive chemotherapy regimens increase survival in children with this disease; however, systemic toxicity limits efficacy. Here we have initiated the first preclinical studies to evaluate RRV-mediated prodrug activator gene therapy in medulloblastoma. Human medulloblastoma cell lines (HDMB03, DAOY) or patient-derived primary medulloblastoma cells were transduced with RRVs encoding either Emerald green fluorescent reporter (RRV-EMD) or the CD enzyme (RRV-CD). RRV replication in vitro, examined by flow cytometry for EMD fluorescence, showed spread to >90% of cells in culture by day 10 post-inoculation. In contrast to non-transduced or RRV-EMD-transduced controls, RRV-CD-transduced medulloblastoma cells exhibited significant dose-dependent reduction of viability upon exposure to 5-FC, as measured by MTS assay. In vivo, stereotactic intracerebellar implantation of non-transduced HDMB03 cells into nude mice resulted in cell dose-dependent median survival time and eventual 100% lethality at all cell doses tested. In this orthotopic medulloblastoma model, mice with RRV-CD-transduced intracerebellar HDMB03 tumors demonstrated increased survival upon 5-FC treatment, as compared to mice treated with PBS or implanted with non-transduced cells. These results support further investigation of RRV-CD-mediated prodrug activator gene therapy for this pediatric malignancy.
Exercise ameliorates neurocognitive impairments in a translational model of pediatric radiotherapy
Authors: Iman Sahnoune, Taeko Inoue, Shelli R Kesler, Shaefali P Rodgers, Omaima M Sabek, Steen E Pedersen, Janice A Zawaski, Katharine H Nelson, M Douglas Ris, J Leigh Leasure, M Waleed Gaber
Journal: Neuro-Oncology (2017)

While cranial radiation therapy (CRT) is an effective treatment, healthy areas surrounding irradiation sites are negatively affected. Frontal lobe functions involving attention, processing speed, and inhibition control are impaired. These deficits appear months to years after CRT and impair quality of life. Exercise has been shown to rejuvenate the brain and aid in recovery post-injury through its effects on neurogenesis and cognition. We developed a juvenile rodent CRT model that reproduces neurocognitive deficits. Next, we utilized the model to test whether exercise ameliorates these deficits. Fischer rats (31 days old) were irradiated with a fractionated dose of 4 Gy × 5 days, trained and tested at 6, 9, and 12 months post-CRT using 5-choice serial reaction time task. After testing, fixed rat brains were imaged using diffusion tensor imaging and immunohistochemistry. CRT caused early and lasting impairments in task acquisition, accuracy, and latency to correct response, as well as causing stunting of growth and changes in brain volume and diffusion. Exercising after irradiation improved acquisition, behavioral control, and processing speed, mitigated the stunting of brain size, and increased brain fiber numbers compared with sedentary CRT values. Further, exercise partially restored global connectome organization, including assortativity and characteristic path length, and while it did not improve the specific regional connections that were lowered by CRT, it appeared to remodel these connections by increasing connectivity between alternate regional pairs. Our data strongly suggest that exercise may be useful in combination with interventions aimed at improving cognitive outcome following pediatric CRT.
Sarampión: una situación por debajo del nivel óptimo en Francia
Authors: R Branchet, P Chauvin, A Flahault
Journal: Eurosurveillance (2000)

La red centinela francesa (Sentinelles) creada en 1984 esta formada por medicos generales de todo el pais (1) que participan voluntariamente. Los miembros de la red garantizan la vigilancia epidemiologica semanal de 10 indicadores de salud (sindrome gripal, sarampion, varicela, parotiditis, hepatitis virica, diarrea aguda, serologias de VIH, uretritis masculina, suicidio y hospitalizaciones). Las descripciones de casos se recogen por medio de la telematica, via Internet (http://www.b3e.jussieu.fr/sentiweb) o Minitel, segun la preferencia del medico general participante en Sentinelles.
IMMU-42. ONO-AE3-208 PROMOTES ANTI-TUMOR IMMUNE ACTIVITY AND SURVIVAL IN GLIOMA MODELS
Authors: Gary Kohanbash, Tohru Kotani, Pavlina Chuntova, Karsen Shoger, Naznin Jahan, Shruti Shrivastav, Diego Carrera, Kira Downey, Brandyn Castro, Kazuhiko Takeda, Hideho Okada
Journal: Neuro-Oncology (2017)

Myeloid Derived Suppressor Cells (MDSCs) are present in most solid tumors, including glioblastoma (GBM), where they can block the activation of tumor-reactive T-cells and support tumor growth. Our lab and others have demonstrated the important roles of cyclooxygenase (COX)-2 as well as its enzymatic product, prostaglandin E2 (PGE2), in MDSC development, accumulation, and function. PGE2 mediates cellular responses through its receptors, EP1-EP4, of which EP4 is known to play an important role in anti-tumor immune responses. We therefore evaluated the impact of ONO-AE3-208, an EP4 antagonist, on MDSC function, tumor growth, and T-cell activation in gliomas. Our in vitro studies demonstrated that while PGE2 and ONO-AE3-208 treatment did not alter the growth of SB28 mouse glioma cells, ONO-AE3-208 reversed the MDSC phenotype of bone marrow cells induced by PGE2 or SB28 glioma cell line-derived conditioned media. Similarly, ONO-AE3-208 restored interferon-γ production by CD8 T-cells following PGE2 treatment. In vivo, ONO-AE3-208 treatment significantly prolonged survival of mice bearing established intracranial C57BL/6-syngeneic SB28 gliomas in wild-type but not RAG1-/- immunodeficient mice. Immunostaining and flow cytometry revealed that ONO-AE3-208-treated gliomas were infiltrated by fewer MDSCs compared with control mice. RT-PCR analysis of glioma-infiltrating MDSCs demonstrated that ONO-AE3-208 treatment suppressed Arg1 and Cox2 expression levels in both Ly6G+ and Ly6C+ MDSC populations as well as Tgfb1 and Il4ra levels in Ly6G+ MDSCs. Consistently, glioma-infiltrating lymphocytes in ONO-AE3-208 treated tumor-bearing mice revealed enhanced Ifng expression compared with control mice, suggestive of enhanced T-cell activity. Finally, combination therapy using anti-PD1 monoclonal antibody with ONO-AE3-208 in the anti-PD1-sensitive GL261 glioma model resulted in further prolonged survival compared with anti-PD1 therapy alone. Our data demonstrate that ONO-AE3-208 may be useful in the treatment of glioma patients to suppress MDSCs and promote anti-tumor immunity.
Estimation of 12-weeks life expectancy in patients (pts) with metastatic gastric cancer (mGC) candidated for second-line treatment: the “Gastric Life” nomogram
Authors: F. Morano, F. Pietrantonio, F. Barretta, V. Fanotto, M. Niger, F. Nichetti, F. Bergamo, N. Silvestris, L. Fornaro, R. Bordonaro, M. Baretti, D. Santini, G. Tomasello, L. Antonuzzo, S. Noventa, A. Avallone, S. Di Donato, E. Maiello, F. De Vita, G. Aprile
Journal: Annals of Oncology (2017)
CMET-30. LEPTOMENINGEAL METASTASES: OUTCOMES WITH AGGRESSIVE MULTIMODALITY TREATMENT
Authors: Rachel Smith, Christina Boman, Srivani Thatikonda, Timothy Dziuk, Hari Tumu, Beth Hellerstedt, Debra Patt, Carl Nuesch, Rachel Pearson, Karen Cohen, Craig Kemper, Courtney Sheinbein, Stanley Kim, Jerry Fain, Carlos Rubin de Celis, Jason Melear, Morris D Groves
Journal: Neuro-Oncology (2017)

Leptomeningeal metastases (LM) affect 5–8% of cancer patients; median survivals historically have ranged from 12–16 weeks. Earlier intervention, multimodal treatment, intrathecal chemotherapy, and targeting relevant molecular drivers may improve outcomes. Under an IRB-approved protocol, we retrospectively reviewed our experience with consecutively diagnosed LM patients seen at the Austin Brain Tumor Center. Relevant data was extracted from the medical records and images. Ninety-two consecutive patients with LM were identified. Median age was 56 (range: 27–82), 61 were female (66%). Median KPS at presentation was 90 (30–100). Histologies were: breast, n=37 (40%); lung, n=18 (20%); primary CNS tumors, n=16 (17%); hematologic malignancies, n=12 (13%); other solid tumors, n=9 (10%). Cerebrospinal fluid (CSF) was + in 37 (40%), MRI was + in 86 (93%). Eighty-three (90%) patients were treated, nine (10%) received palliation only. Seventy (76%) patients received XRT, 14 of these (20%) craniospinal XRT; Fifty-one (55%) patients received intrathecal (IT) chemotherapy, IT topotecan in 35 (67%). Median survivals (ranges) in weeks: All patients: 48 (1–853+, 25 censored); treated patients: 53 (2 - 853+, 25 censored); untreated patients: 5 (1–46); breast: 60 (6 - 267+, 10 censored), 1- and 2-year survivals: 59% and 16%, respectively; HER2+ breast (n=16): 73 (6 - 163+, 7 censored); EGFR+ NSCLC (n=14): 29 (2 - 203+, 2 censored); primary CNS tumors: 36 (2–853+, 5 censored); hematologic cancers: 72 (1–376, 6 censored); other solid tumors: 33 weeks (3–376, 2 censored). All CSF + patients: 41 (2–267+, 9 censored). Diagnosis by imaging only patients: 51 (1 - 853+, 16 censored). This report shows improvement in LM survivals over literature controls. Notable is the median survival in breast cancer LM of > 1 year. These improvements in survival may be due to earlier intervention, use of targeted drugs, use of craniospinal XRT, and/or chronic IT chemotherapy use.
P2.13-019 Attrition Rate in Community-Based Lung Cancer Screening: One and Done
Authors: A. Carlson, C. Wilshire, J. Fathi, J. Rayburn, C. Gilbert, S. Blanshan, B. Louie, R. Aye, A. Farivar, E. Vallieres, J. Gorden
Journal: Journal of Thoracic Oncology (2017)