tbuckley/cabot-search huggingface dataset:
RADT-01. THE EFFICACY AND SAFETY OF TWO-STAGED STEREOTACTIC RADIOSURGERY FOR LARGE POSTERIOR FOSSA METASTASES: POST-TREATMENT VOLUMETRIC CHANGES IN TUMOR SIZE, PERI-TUMORAL EDEMA, AND FOURTH VENTRICLE
Authors: Yusuke Hori, Baha’eddin Muhsen, Krishna Joshi, Wei Wei, Hamid Borghei-Razavi, Samuel Chao, Alireza Mohammadi, Gene Barnett, John Suh, Lilyana Angelov
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Two-staged stereotactic radiosurgery (2-SSRS) delivers a high radiation dose to large (≥2 cm) brain metastases to achieve improved tumor control. However, treating large posterior fossa metastases (LPFM) with SRS is challenging because of the potential risk of increased peritumoral edema (PTE) and compression to brain stem and/or obstructive hydrocephalus of the fourth ventricle (4V). METHODS 21 patients (22 LPFM) treated with 2-SSRS were retrospectively reviewed. Volumetric analysis for tumor, PTE, and 4V volume was assessed for objective response. We defined local failure (LF) as ≧ 71.5% of volumetric increase, equivalent to ≧ 20% increase in maximum diameter (RECIST criteria). Kaplan-Meier estimated overall survival (OS), time-to-local failure, and linear mixed model estimated and compared measurements between time points. RESULTS The median age was 61 years (range: 39–79 years), and nine patients (42.9%) were female. The most common primary cancer was NSCLC (47.6%), followed by breast (14.3%) and renal (14.3). Median OS was 13 months (95% CI: 6–24 months) with median follow-up 18 months (range 7–42 months). The median tumor, PTE and 4V volumes at diagnosis were 7.43 cm3, 18.9 cm3, and 0.95 cm3 respectively. At the first follow-up (median 51 days after the second session), mean tumor (–59%, p&amp;lt; 0.0001) and PTE (–47%, p=0.0008) volumes decreased, while mean 4V volume (+35%, p=0.001) increased. Significant volumetric changes were maintained at second (median 179 days after the second session) follow-up for tumor (–43%, p=0.01) and 4V (+44%, p=0.002), but not for PTE (+8%, p=0.87). Tumor LC rate was 83% (95% CI: 64–100%) at 1 year, and no patient developed the post-treatment hydrocephalus requiring CSF diversion or required surgical resection for tumor progression. CONCLUSIONS This is the first report documenting detailed time courses and excellent safety/ efficacy of 2-SSRS for LPFM. Additional studies with longer follow-ups are needed.
68P Evaluation of flat dosing for nivolumab (NIVO) + ipilimumab (IPI) in first-line (1L) unresectable malignant pleural mesothelioma (MPM): CheckMate 743 (CM 743)
Authors: A.S. Tsao, P. Baas, A. Nowak, G. Zalcman, N. Fujimoto, S. Peters, C. Baudelet, P. Aanur, M. Osawa, A. Tendolkar, None Y.Feng, J. Sheng
Journal: Annals of Oncology (2020)
Abstract P142: Meta-analyses Of Genome-wide Association Studies Accounting For Gene-psychosocial Factor Interactions Identify Novel Loci For Blood Pressure Traits
Authors: Myriam Fornage, Daokun Sun, Melissa A Richard, Solomon K Musani, Yun Ju Sung, Thomas W Winkler, Nora Franceschini
Journal: Circulation (2020)

Background: Genome-wide association studies (GWAS) have identified hundreds of genetic loci for blood pressure (BP) traits and advanced our understanding of BP regulation and hypertension etiology. Psychological and social factors are known to influence BP and risk of cardiovascular diseases. Accounting for psychosocial factors may help identify BP loci and extend our knowledge of its genetic architecture. Methods: To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptomatology, trait anxiety, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. Results: In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p &lt;5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response ( PLCL2 ), synaptic function and neurotransmission ( LIN7A, PFIA2 ), as well as genes previously implicated in neuropsychiatric or stress-related disorders ( FSTL5, CHODL ). Conclusion: These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.
Suppressing Sart1 to modulate macrophage polarization by siRNA-loaded liposomes: a promising therapeutic strategy for pulmonary fibrosis
Authors: Ting Pan, Qing Zhou, Kang Miao, Lei Zhang, Guorao Wu, Jun Yu, Yongjian Xu, Weining Xiong, Yong Li, Yi Wang
Journal: Theranostics (2020)

Idiopathic pulmonary fibrosis (IPF) is a chronic and diffuse form of interstitial lung disease of unknown etiology with a fatal outcome. Although various strategies for IPF have been developed over the last few decades, no significant positive impact on the prognosis of IPF has been observed. According to the current paradigm, macrophages have been recognized to play a significant role in IPF pathogenesis. Here, we report a potential nanomedicine-based gene therapy for IPF based on regulate macrophage polarization. Method: C57BL/6 mice were obtained and used to establish a bleomycin (BLM)-induced pulmonary fibrosis animal model, and Sart1 siRNA-loaded liposomes were designed for in vivo experiment. The experimental animals were administered BLM intratracheally on day 0 and treated with Sart1 siRNA on days 14 and 17. In the in vitro experiment, we further examined the function of Sart1 in macrophages. Results: Our data indicated that the liposomes could passively target the fibrotic area in the lung and efficiently accumulate in macrophages. The suppression of Sart1 by siRNA-loaded liposomes significantly protected mice against BLM-induced lung injury and fibrosis, which was attributed to attenuated M2 macrophage infiltration in the lung. Conclusion: Our study provides a valuable reference for modulating macrophage polarization and a promising strategy for the treatment of pulmonary fibrosis in clinical settings.
NCMP-03. INTRATHECAL TRASTUZUMAB TREATMENT OF HER-2 POSITIVE LEPTOMENINGEAL BREAST CANCER: THE UNIVERSITY OF MICHIGAN EXPERIENCE
Authors: Kelsey Peters, Lindsay Robell, Aki Morikawa, Yoshie Umemura, Yilun Sun, Denise Leung, Aaron Mammoser, Anoop Gill, Larry Junck
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Breast cancer is the most common solid tumor to metastasize to the leptomeninges, affecting up to 5% of breast cancer patients. Overall survival for patients with leptomeningeal metastases (LM) is poor, with median survival of 4–6 months following diagnosis. There is limited data available on the efficacy of intrathecal (IT) trastuzumab in the treatment of Her-2 positive LM. METHODS A total of 30 patients with Her-2 positive breast cancer with LM treated at the University of Michigan from 2008–2020 were identified retrospectively. Of these, 13 patients were treated with IT trastuzumab beginning in June 2010 and followed through April 2020. Initial dose was 50–80 mg twice weekly for a minimum of 4 weeks, followed by slow taper. The 17 patients with Her-2 positive breast cancer with LM who did not receive IT trastuzumab served as control. RESULTS The median age of patients in the treatment group was 42 and 52 in the control group. Whole brain radiation therapy was received by 92% of patients in the treatment group and 76% in the control group. The median overall survival from diagnosis of LM to death was 20 months (interquartile range [IQR] 13–60 months) in the treatment group and 6 months (IQR 2–17 months) in the control group. Survival at 3 years and 5 years was 40% and 13%, respectively for the treatment group and 8% and 0% (no data available at 60 months), for the control group. Hazard ratio for death with IT trastuzumab 0.38 (95% CI 0.16–0.91, p=0.024). IT trastuzumab was overall well-tolerated (one patient developed meningitis, while another had shunt malfunction necessitating removal of the reservoir). CONCLUSIONS Patients with HER2+ LM who received IT trastuzumab demonstrated significantly improved OS compared to control with minimal toxicity.
BIOM-50. GENETIC PREDISPOSITION TO LONGER TELOMERE LENGTH AND RISK OF CHILDHOOD, ADOLESCENT AND ADULT-ONSET EPENDYMOMA
Authors: Chenan Zhang, Quinn Ostrom, Eleanor Semmes, Vijay Ramaswamy, Helen Hansen, Libby Morimoto, Adam de Smith, Melike Pekmezci, Zalman Vaksman, Hakon Hakonarson, Sharon Diskin, Catherine Metayer, Michael Taylor, Joe Wiemels, Melissa Bondy, Kyle Walsh
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Ependymoma is the third most common brain tumor in children, with well-described molecular characterization but poorly understood underlying germline risk factors. Telomerase reactivation in somatic cells has been linked to ependymoma progression, recurrence, and survival, and has been implicated as an important prognostic marker and potential therapeutic target. METHODS To investigate whether inherited predisposition to longer telomere length influences ependymoma risk, we utilized case-control data from three studies: 1) a population-based pediatric and adolescent ependymoma case-control sample from California (153 cases, 696 controls), 2) a hospital-based pediatric posterior fossa type A ependymoma (EPN-PF-A) case-control study from Toronto’s Hospital for Sick Children and the Children’s Hospital of Philadelphia (83 cases, 332 controls), and 3) a multicenter adult-onset ependymoma case-control dataset nested within the Glioma International Case-Control Consortium (GICC) (103 cases, 3287 controls). We investigated the individual effect of telomere-length associated SNPs on ependymoma risk, as well as the combined effect of these SNPs through polygenic score and Mendelian randomization analyses. RESULTS We observed an association between genetic predisposition to longer LTL and increased risk of adolescent-onset (P= 3.97x10-3) and adult-onset (P =0.042) ependymoma, but not ependymoma diagnosed in children &amp;lt; 12 years old (P=0.21), or among the pediatric EPN-PF-A sample (P=0.59). Comparing ependymoma patients ages 12–19 to those under 12 years of age demonstrated that age significantly modified the association between longer telomere length and ependymoma risk (P=0.021). CONCLUSIONS These findings complement emerging literature suggesting that dysregulated telomere maintenance is important for ependymoma pathogenesis and that longer telomere length is a risk factor for various neoplasms of the peripheral and central nervous system.
Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota
Authors: Xin-Yu Lu, Bing Han, Xin Deng, Si-Ying Deng, Yan-Yan Zhang, Pei-Xin Shen, Teng Hui, Rui-Heng Chen, Xing Li, Yuan Zhang
Journal: Gut Microbes (2020)

Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.
99P The association between antibiotic use and survival in renal cell carcinoma patients treated with nivolumab: A multi-center study
Authors: D.C. Guven, R. Acar, E. Yekeduz, I. Bilgetekin, N. Kose Baytemur, C. Erol, F. Ceylan, M.A. Sendur, U. Demirci, Y. Urun, N. Karadurmus, M. Erman, S. Kilickap
Journal: Annals of Oncology (2020)
E74-Like Factor 3 Is a Key Regulator of Epithelial Integrity and Immune Response Genes in Biliary Tract Cancer
Authors: Masami Suzuki, Mihoko Saito-Adachi, Yasuhito Arai, Yuko Fujiwara, Erina Takai, Shinsuke Shibata, Masahide Seki, Hirofumi Rokutan, Daichi Maeda, Masafumi Horie, Yutaka Suzuki, Tatsuhiro Shibata, Tohru Kiyono, Shinichi Yachida
Journal: Cancer Research (2020)

The transcription factor E74-like factor 3 (ELF3) is inactivated in a range of cancers, including biliary tract cancer (BTC). Here, we investigated the tumor-suppressive role of ELF3 in bile duct cells by identifying several previously unknown direct target genes of ELF3 that appear to be implicated in biliary duct carcinogenesis. ELF3 directly repressed ZEB2, a key regulator of epithelial-mesenchymal transition, and upregulated the expression of CGN, an integral element in lumen formation. Loss of ELF3 led to decreased cell-cell junctions and enhanced cell motility. ALOX5 and CXCL16 were also identified as additional direct targets of ELF3; their corresponding proteins 5-lipoxygenase and CXCL16 play a role in the immune response. Conditioned medium from cells overexpressing ELF3 significantly enhanced the migration of natural killer cells and CD8+ T cells toward the conditioned medium. Gene expression profiling for BTC expressing high levels of ELF3 revealed significant enrichment of the ELF3-related genes. In a BTC xenograft model, activation of ELF3 increased expression of ELF3-related genes, enhanced the tubular structure of the tumors, and led to a loss of vimentin. Overall, our results indicate that ELF3 is a key regulator of both epithelial integrity and immune responses in BTC. SIGNIFICANCE: Thease finding shows that ELF3 regulates epithelial integrity and host immune responses and functions as a tumor suppressor in biliary tract cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/2/489/F1.large.jpg.
NIMG-08. PREDICTION OF LOWER-GRADE GLIOMA MOLECULAR SUBTYPES USING DEEP LEARNING
Authors: Yoshihiro Muragaki, Yutaka Matsui, Takashi Maruyama, Masayuki Nitta, Taiichi Saito, Shunsuke Tsuzuki, Manabu Tamura, Yasukazu Fukuya, Hidetsugu Asano, Kaori Kusuda, Takakazu Kawamata, Ken Masamune
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION It is useful to know the molecular subtype of lower-grade gliomas (LGG) when deciding on a treatment strategy. This study aims to diagnose this preoperatively. METHODS A deep learning model was developed to predict the 3-group molecular subtype using multimodal data including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The performance was evaluated using leave-one-out cross validation with a dataset containing information from 217 LGG patients. RESULTS The model performed best when the dataset contained MRI, PET, and CT data. The model could predict the molecular subtype with an accuracy of 96.6% for the training dataset and 68.7% for the test dataset. The model achieved test accuracies of 58.5%, 60.4%, and 59.4% when the dataset contained only MRI, MRI and PET, and MRI and CT data, respectively. The conventional method used to predict mutations in the isocitrate dehydrogenase (IDH) gene and the codeletion of chromosome arms 1p and 19q (1p/19q) sequentially had an overall accuracy of 65.9%. This is 2.8 percent point lower than the proposed method, which predicts the 3-group molecular subtype directly. CONCLUSIONS AND FUTURE PERSPECTIVE A deep learning model was developed to diagnose the molecular subtype preoperatively based on multi-modality data in order to predict the 3-group classification directly. Cross-validation showed that the proposed model had an overall accuracy of 68.7% for the test dataset. This is the first model to double the expected value for a 3-group classification problem, when predicting the LGG molecular subtype. We plan to apply the techniques of heat map and/or segmentation for an increase in prediction accuracy.
Mucocutaneous Manifestations of Multisystem Inflammatory Syndrome in Children During the COVID-19 Pandemic
Authors: Trevor K. Young, Katharina S. Shaw, Jinal K. Shah, Asif Noor, Risa A. Alperin, Adam J. Ratner, Seth J. Orlow, Rebecca A. Betensky, Gail F. Shust, Philip J. Kahn, Vikash S. Oza
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> To date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms. <h3>Objective</h3> To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020. <h3>Design, Setting, and Participants</h3> A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C. <h3>Main Outcomes and Measures</h3> Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C. The characterization of mucocutaneous features was verified by 2 board-certified pediatric dermatologists. <h3>Results</h3> Twenty-five children (11 girls [44%]; median age, 3 years [range, 0.7-17 years]) were identified who met definitional criteria for MIS-C; an additional 10 children (5 girls [50%]; median age, 1.7 years [range, 0.2-15 years]) were included as probable MIS-C cases (patients met all criteria with the exception of laboratory test evidence of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection or known exposure). The results of polymerase chain reaction tests for SARS-CoV-2 were positive for 10 patients (29%), and the results of SARS-CoV-2 immunoglobulin G tests were positive for 19 patients (54%). Of the 35 patients, 29 (83%) exhibited mucocutaneous changes, with conjunctival injection (n = 21), palmoplantar erythema (n = 18), lip hyperemia (n = 17), periorbital erythema and edema (n = 7), strawberry tongue (n = 8), and malar erythema (n = 6) being the most common findings. Recognition of mucocutaneous findings occurred a mean of 2.7 days (range, 1-7 days) after the onset of fever. The duration of mucocutaneous findings varied from hours to days (median duration, 5 days [range, 0-11 days]). Neither the presence nor absence of mucocutaneous findings was significantly associated with overall disease severity. <h3>Conclusions and Relevance</h3> In this case series of hospitalized children with suspected MIS-C during the COVID-19 pandemic, a wide spectrum of mucocutaneous findings was identified. Despite their protean and transient nature, these mucocutaneous features serve as important clues in the recognition of MIS-C.
NCMP-23. PEMBROLIZUMAB-ASSOCIATED CD8+ VASCULITIC MONONEURITIS MULTIPLEX IN A PATIENT WITH MESOTHELIOMA: FIRST CASE REPORT
Authors: Michaela Baldauf, Kapauer Monika, Jörger Markus, Flatz Lukas, Regulo Rodriguez, Stephan Frank, Ansgar Felbecker, Hundsberger Thomas
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Immunotherapy, especially with immune checkpoint inhibitors (ICPI), has increasingly become an attractive treatment modality for various types of cancers. However, many patients develop ICPI-associated autoimmune adverse events such as pneumonitis, colitis or rarely neurological syndromes. Large and medium vessel vasculitis haS only occasionally been reported. Here we report the first case of ICPI-associated mononeuritis multiplex in a patient with malignant mesothelioma, caused by a histological proven small vessel vasculitis. CASE REPORT A 61-year old female developed subacute progressive painful and asymmetric sensorimotor deficits on distal extremities. Electrophysiologically, signs of a severe axonal neuropathy of both legs and the right arm were found, and swellings of the corresponding nerves were seen upon nerve ultrasound exam. The clinical and electrophysiological findings were reminiscent of mononeuritis multiplex. Laboratory work up including CSF examination was normal. More than two years prior to developing peripheral nerve deficits, the patient had been diagnosed with malignant pleural mesothelioma and treated with the anti-PD1 monoclonal antibody pembrolizumab on progression after chemotherapy. Biopsy of the right sural nerve revealed a small vessel vasculitis with a lymphocyte predominance of CD8+ T cells over CD4+ T as well as B lymphocytes. Despite discontinuation of pembrolizumab and immunosuppressive treatment (high dose methylprednisone, cyclophosphamide) complemented by opioid therapy, painful allodynia persisted. CONCLUSION ICPI-associated autoimmune disorders also include small vessel vasculitis with rare phenotypes such as mononeuritis multiplex. Further studies are required to improve our understanding of the link between ICPIs, and the pathogenic process leading to vasculitis, as well as to optimize treatment options for those rare diseases.
18F-FDG and 68Ga-DOTATOC PET/CT Findings in a Case of Abdominal Leiomyosarcoma
Authors: Margherita Lorusso, Giuseppe Angelico, Michela Quirino, Valentina Scolozzi, Maria Lucia Calcagni
Journal: Clinical Nuclear Medicine (2020)

Abstract We report the case of a 58-year-old man with mesenteric nodule at CT performed for abdominal pain. In the suspicion of neoplastic disease, he underwent 18 F-FDG PET/CT that did not show abnormal uptake. The nodule was monitored alternating CT and MRI. Two years after the first detection, MRI revealed an increase in size, and 18 F-FDG PET/CT was repeated for metabolic evaluation, showing increased metabolic activity. In suspicion of neuroendocrine tumor, for anatomical site, slow growth, and clinical symptoms, 68 Ga-DOTATOC PET/CT was performed showing focal uptake, indicating high expression of somatostatin receptors. The final pathology report was consistent with high-grade leiomyosarcoma.