tbuckley/cabot-search huggingface dataset:
P03.03 Dynamics of brain metastasis cavities between resection and adjuvant stereotactic radiotherapy and impact of the delay on local control
Authors: A Mousli, B Bihin, T Gustin, G Koerts, M Mouchamps, J F Daisne
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Adjuvant stereotactic radiotherapy (SRT) to the surgical cavity of brain metastases (BM) improves the local control. An early post-operative irradiation is desirable to limit the risk of recurrence while delaying it might reduce the risk of radionecrosis by reducing the size of the target volume (TV) thanks to the cavity constriction. The purpose of our study was to examine cavity dynamics after resection to determine if delaying SRT influences cavity size as well as local progression (LP). MATERIAL AND METHODS We reviewed 70 BM resection cavities treated with adjuvant SRT. A preoperative, immediate postoperative and at the time of SRT, 3D T1-weigthed MRI, were available for all patients. The volumes were retrospectively calculated with the PACS software Telemis® version 4 and the iPlan RT image software. For all cavities, the TV was obtained by expanding the cavity by a median margin of 2mm to account for microscopic spread. The surgical track and edema areas were not included in the TV. The dynamic evolution of cavities and LP according to the delay of SRT were analyzed. RESULTS The median time from surgery to SRT was 27 days (3–99). The median preoperative and SRT cavity volumes were 7.2 cc (ranges: 0.5–29.5) and 8 cc (ranges: 0.8–31), respectively. After margin expansion, the TV was increased to a median of 14.8 cc. The volumetric cavity changes were an increase by 2 cc in 35 %, whereas only 22.5 % decreased by 2 cc and 42.5% cavities were stable (defined as a change ≤2 cc). We noted that 11% of volume change were attributable to the delay (r2 = 0.11). forty-seven patients were treated within a delay of 30 days and experienced early LP in 10.6 % against 20 % beyond 30 days (p= 0.6). CONCLUSION In the interval between surgery and SRT, BM cavities dynamics are inconstant and unpredictable in function of time. Furthermore, delaying SRT may compromise local control, though the difference was not statistically significant due to the small size of our population. A preoperative SRT strategy looks more promising by alleviating the problem of time and reducing the volume of irradiated brain.
P13.05 Chemical Biopsy as an Alternative Sampling Method in Neurooncology
Authors: J Bogusiewicz, P Z Goryńska, K Jaroch, K Goryński, D Paczkowski, J Furtak, M Harat, B Bojko
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Histopathology is a gold standard for diagnostics of brain tumors but it is time consuming, demands removal of the part of the tissue what makes it highly invasive. That is why it seems to be relevant to develop new diagnostic methods addressing the abovementioned drawbacks. Ideal tool should be easy to use, as low invasive as possible and of high clinical value. The aim of the study was to assess the usefulness of chemical biopsy based on solid phase microextraction as a sampling method for lipidomic analysis of brain tumors. MATERIAL AND METHODS The experiment was carried out on 38 brain tumors. Sampling was performed ex vivo, directly after removal of brain tumors. SPME fibers (coated with biocompatible extraction phase, length and diameter of the coating 7mm and 200um, respectively) were inserted into the sample without prior preparation of the tissue. Desorption of lipids was performed in isopropanol-methanol mixture. Analysis of extracts was carried out using liquid chromatography coupled to high resolution mass spectrometry. RESULTS Wide range of tentative lipid species was obtained in the studies. Two histologically different types of brain tumors: gliomas and meningiomas were subjected to the chemical biopsy. The results showed very good separation between the tumor types in unsupervised chemometric tests. The lipid species responsible for this separation were previously reported in the literature as cancer biomarkers. With regards to malignancy grading of gliomas the separation was notable but not as clear as between the tumor types, what is probably related to high heterogeneity of this cancerous tissue and subjectivity of histopathological analysis which were a referring point in methods comparison. Very good agreement was noted for changes in lipidome obtained by chemical biopsy and histological subtypes of gliomas. However, the most promising results showed impact of IDH1 R132H mutation on lipidome of gliomas. CONCLUSION Chemical biopsy seems to be useful method in lipidomics studies and for differentiation of brain tumors according their histological origin and malignancy. It also enables to find a relation between IDH1 mutation and lipidomic profile. ACKNOWLEDGMENTS The work was supported by the grant 2015/18/M/ST4/00059 funded by National Science Centre, Poland. The authors want to acknowledge Supelco/MilliporeSigma for the SPME probes, Thermo Fisher Scientific for the access to Q-Exactive Focus mass spectrometer, Anchem for the technical support and Shim-Pol for the access to LCMS-8060 mass spectrometer and technical support.
OS12.3 L3MBTL3 is a novel suppressor of medulloblastoma tumorigenesis
Authors: J Rual
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Medulloblastoma is the most common malignant brain tumor of childhood. Therapeutic approaches to medulloblastoma have led to significant improvements but are achieved at a high cost to quality of life. Alternative therapeutic approaches are needed and molecular stratification of patients with medulloblastoma has yet to be routinely implemented in the clinic. TheNotchpathway governs cell proliferation in many biological contexts, including SHHand Group#3medulloblastoma tumorigenesis. Using our proteomic platform, we discovered an interaction between RBPJ, a key co-factor of Notch for the modulation of Notch signals, and L3MBTL3, a methyllysine reader.L3MBTL3 is recruited by RBPJ on chromatin at the enhancers of Notch/RBPJ target genes to repress their expression.Deletions ofthe L3MBTL3locus are observed in patientswith WNTand Group#3medulloblastomaand expression of L3MBTL3 in the SHHmedulloblastoma-derived cell DAOY inhibits cell growth, suggesting a putative tumor suppressor role for L3MBTL3 in medulloblastoma. METHODS To further investigate the putative role of L3MBTL3 as a suppressor of medulloblastoma tumorigenesis, we used our novel L3mbtl3KO mouse in combination with a genetically engineered ND2:SmoA1mouse model of SHHmedulloblastoma in a survival analysis. RESULTS Our survival analysis validated in vivoour hypothesis that L3mbtl3is a tumor suppressor in this disease context. Indeed, our data show that [ND2:SmoA1; L3mbtl3+/-] mice have a significantly lower survival rate than ND2:SmoA1 mice (P= 0.0322; Log-rank test). Hence, the RBPJ-L3MBTL3 interaction is at the heart of a molecular mechanism governing the repression of Notch/RBPJ target genes and malfunction of this molecular mechanism contributes to L3MBTL3’s tumor suppressor role in medulloblastomathrough aberrant “de-repression” of Notch/RBPJ target genes. CONCLUSION L3MBTL3 is a novel suppressor of medulloblastoma tumorigenesis. Our discovery providesinsights into the role of the L3MBTL3 inmedulloblastomathat could be harnessed in the future for the therapeutic benefit of patientswith medulloblastoma.
OS8.3 Gamma knife radiosurgery for large meningiomas: 10 years of experience
Authors: K Abdel Karim, A El-Shehaby, W Reda, R Emad Eldin, A Nabeel, S Tawadros
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The use of gamma knife radiosurgery for the treatment of intracranial meningiomas has been established as an effective and safe treatment modality. Larger meningiomas are typically managed by surgery followed by radiosurgery. For situations where patients are not amenable to surgery fractionated stereotactic radiotherapy is the traditionally suggested treatment. Treatment of large meningiomas (usually defined as &gt;10 cc) by stereotactic radiosurgery has been investigated in some recent reports, either by single-session, volume-staged or hypofractionation technique. However, there are no long-term results. The purpose of this study is to assess the long-term efficacy and safety of gamma knife radiosurgery for large (15 cc or more) intracranial meningiomas. MATERIAL AND METHODS In this study we included 80 patients with large meningiomas (³ 15 cc) who were followed up for more than 5 years. Non-benign meningiomas were excluded. Also, meningiomatosis and NF2 patients were not included. There were 18 males (22.5%) and 62 females (77.5%). The mean age was 46 years (20–83 years). Twenty-six patients (32.5%) had previous surgery. Tumor were supratentorial in 14 (17.5%) patients and skull base in 66 (82.5%) patients. The mean tumor volume was 22.3 cc (15–57.3 cc). The mean prescription dose was 11 Gy (9–12 Gy). RESULTS The mean follow up period was 8.4 years (5–17 years). The tumor shrank in 43 patients (54%), was stable in 30 patients (37%) and progressed in 7 patients (8%). The tumor control rate was 91%. Adverse radiation effects were observed in 11 patients (14%) but only 5 (6.5%) were symptomatic. These were temporary in all cases. CONCLUSION Gamma knife radiosurgery provides an effective and safe treatment option for large meningiomas. Low margin dose appears to be sufficient for tumor control. Surgery remains the first option in these cases.
OS2.2 Chemotherapy for spinal gliomas in adults
Authors: D Gramatzki, J Felsberg, O Bähr, B Hentschel, M Westphal, G Schackert, J C Tonn, U Herrlinger, M Löffler, T Pietsch, J Steinbach, G Reifenberger, P Roth, M Weller
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Chemotherapy is a treatment option in patients diagnosed with anaplastic gliomas or glioblastomas of the spinal cord, or with recurrent lower graded WHO spinal gliomas that are no longer amenable to local treatment. The low incidence of spinal cord gliomas, particularly in adults, limits the ability to perform clinical trials. The role of chemotherapy in these tumors has remained unclear. MATERIAL AND METHODS We performed a retrospective study of 22 patients diagnosed with spinal gliomas who were treated with chemotherapy at any time during the disease course. Benefit from chemotherapy was estimated by applying Response assessment in neuro-oncology criteria. Data on radiotherapy, as well as the number of neurosurgical interventions were taken into consideration. RESULTS Most patients were diagnosed with astrocytoma WHO grade I-IV (N=14), the remaining patients were diagnosed with ependymoma (N=8). Median follow-up from start of chemotherapy was 92 months (95% CI, 72.6–111.4). The O6-methylguanyl-DNA-methyltransferase(MGMT)promoter methylation status was available in tumors of 12 patients: 9 tumors (75%) had an unmethylated MGMTpromoter. More than 50% of the patients had more than one neurosurgical intervention. After prior surgery 10 patients in the first-line setting had chemotherapy combined with radiotherapy, while 3 patients received chemotherapy only. The remaining 9 patients had initially received radiation therapy and chemotherapy was given at time of recurrence. In patients diagnosed with astrocytoma mainly temozolomide (TMZ) was applied (N=10), while one patient received CCNU and three patients had combination chemotherapy. Patients diagnosed with ependymoma had hydroxyurea (N=1), CCNU (N=1), TMZ (N=3) or combination chemotherapy (N=3). In the group of patients who had chemotherapy combined with radiation, response rates were as follows: anaplastic astrocytoma 3 stable diseases (SD), glioblastoma 1 complete response (CR) and 1 SD, and anaplastic ependymoma 1 SD. After chemotherapy in the group of patients previously irradiated, the following response rates were observed: 1 SD in pilocytic astrocytoma, 1 SD in diffuse astrocytoma, 3 SD in myxopapillary ependymoma, and 2 SD and 1 partial response (PR) in anaplastic ependymoma. All other patients experienced progressive disease. There was no indication for a favorable prognostic role ofMGMTpromoter methylation. CONCLUSION Spinal cord gliomas represent a heterogeneous group of tumors. Survival outcomes in response to chemotherapy in adult spinal glioma patients vary substantially, but individual patients appear to derive benefit from chemotherapy.
Serum biomarkers for detection of cardiomyopathy in survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.
Authors: Stephanie Dixon, Carrie R. Howell, Lu Lu, Kirsten K. Ness, Juan Plana, Vijaya Joshi, Russell V Luepker, Jean-Bernard Durand, Bonnie Ky, Daniel John Lenihan, Daniel M. Green, Robyn Partin, MS, Aimee Santucci, Rebecca M. Howell, Deokumar Srivastava, Melissa M. Hudson, Leslie L. Robison, Gregory T. Armstrong
Journal: Journal of Clinical Oncology (2019)

e21526 Background: Childhood cancer survivors are at increased risk for cardiovascular morbidity and mortality. Little is known about the utility of cardiac biomarkers (NT-proBNP, cardiac troponin-T [TnT]) for long-term surveillance. Methods: Cross-sectional analyses of 1213 survivors ≥18 years of age and ≥10 years from cancer diagnosis (786 exposed to cardiotoxic therapy [174 radiation therapy (RT) alone, 366 anthracycline alone, 246 both] and 427 unexposed). TnT &gt; 0.01 ng/ml and NT-proBNP levels &gt; 97.5 th percentile age- and sex-specific cutoffs were considered abnormal. Three-dimensional left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diastolic function and cardiomyopathy (CM) according to the CTCAE v4.03 were evaluated. Generalized linear models estimated risk ratios (RR) and 95% confidence intervals (CI). Results: Among survivors (median 8.7 [range 0.0-23.6] years at diagnosis; 35.5 [range 19.1-62.2] years at evaluation), NT-proBNP and TnT were abnormal in 22.5% and 0.4%, respectively. A dose-dependent increased risk for abnormal NT-proBNP was seen with exposure to chest RT (referent no RT, 1- &lt; 20 Gy RR 1.62 [CI 1.07-2.46], 20- &lt; 30 Gy RR 1.68 [1.23-2.30], ≥30 Gy RR 3.66 [2.89-4.64]; p for trend &lt; 0.0001) and anthracycline (referent no anthracycline, 1-200mg/m 2 RR 1.39 [1.01-1.91], 201-350mg/m 2 RR 2.28 [1.74-2.99], &gt; 350mg/m 2 RR 2.99 [2.27-3.95]; p for trend &lt; 0.0001). Survivors with CM at the time of evaluation had abnormal NT-proBNP (grade 2 CM RR 1.46, CI 1.08-1.99; grade 3-4 CM 2.66, 2.02-2.39). However, among exposed survivors previously undiagnosed with clinical CM, NT-proBNP had poor sensitivity and moderate specificity in identifying those with new onset of abnormal LVEF ( &lt; 53%), GLS or diastolic dysfunction: sensitivity (29%, 30%, 33%), specificity (75%, 77%, 76%). Also, 132 (20.2%) had abnormal NT-proBNP with normal LVEF (≥53%). Conclusions: Abnormal NT-proBNP levels were prevalent and associated with prior cardiotoxic therapy and established CM but were not sensitive for detection of new onset CM. Longitudinal follow-up is needed to determine whether abnormal NT-proBNP in the large number of survivors without CM is predictive of future CM.
P11.07 LAPTM5 functions as a tumor suppressor via CD40 - NFêB pathway inhibition and represents a potential biomarker for temozolomide sensitivity in CD40 proficient glioblastoma
Authors: A Berberich, F Bartels, Z Tang, S Pusch, N Hucke, T Kessler, Z Dong, B Wiestler, F Winkler, M Platten, W Wick, A Abdollahi, D Lemke
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioma therapy is challenged by the invasive nature of glioma resulting in tumor recurrence and treatment resistance. Lysosomal protein transmembrane 5 (LAPTM5) was identified to inhibit invasion by screening for invasion-associated genes in glioma. The aim of this study was to decipher the function of LAPTM5 in glioblastoma and its interaction with the CD40 receptor which was shown to be highly expressed in up to 40% of glioblastoma. METHODS LAPTM5 expression was correlated with clinical outcome of glioma patients. Knockdown of LAPTM5 was performed in different glioma cell lines to analyze the impact on clonogenicity, invasiveness, sensitivity to temozolomide chemotherapy and tumorigenicity in-vitro and in-vivo in a subcutaneous xenograft mouse model. Expression array was used to elucidate the underlying pathways. CD40 knockdown and overexpression was induced to prove the crosstalk of LAPTM5 and CD40. RESULTS LAPTM5 expression correlated with better overall survival in high grade glioma patients and acted as a tumor suppressor in CD40 positive glioblastoma cells. LAPTM5 inhibited CD40-mediated NFκB activation resulting in anti-invasive, anti-clonogenic and temozolomide sensitizing effects in-vitro and in-vivo. Vice-versa, knockdown of LAPTM5 enhanced tumorigenicity by activation of the NFκB pathway which was overcome by NFκB inhibition. Importantly, CD40 expression was required for LAPTM5-mediated tumor suppressive activity. CONCLUSION LAPTM5 conveyed tumor suppressive and temozolomide sensitizing effects in CD40-positive glioblastoma by inhibition of CD40-mediated NFκB activation and thereby might provide a reasonable biomarker for sensitivity to temozolomide in CD40-positive glioblastoma.
ERS and ATS diagnostic guidelines for primary ciliary dyskinesia: similarities and differences in approach to diagnosis
Authors: Amelia Shoemark, Sharon Dell, Adam Shapiro, Jane S. Lucas
Journal: European Respiratory Journal (2019)

<b>ERS and ATS guidelines for PCD diagnosis present different recommendations. Authors from both guidelines clarify similarities, differences and steps required to develop an internationally agreed pathway. TEM or genotyping confirm a diagnosis of PCD.</b>http://bit.ly/2SR7GWm
Liver Transplantation in Unauthorized Immigrants in the United States
Authors: Brian P. Lee, Norah A. Terrault
Journal: Hepatology (2019)

Background and Aims Eleven million unauthorized immigrants reside in the United States and may account for 3% of deceased organ donors. Recently introduced federal and state legislation propose to address access to organ transplantation among unauthorized immigrants. The national landscape of liver transplantation (LT) for unauthorized immigrants is unknown. Approach and Results We included all US LT recipients between March 2012 and December 2018 who were linked to Pew Center of Research data to estimate the population of unauthorized immigrants in each US state and by country of origin, based on US Census data. We categorized patients as unauthorized immigrants versus US citizens/residents. The main outcome measures were (1) the proportion of LTs performed for unauthorized immigrants compared with the proportion of unauthorized immigrants among total population in each US state and (2) graft failure and death post‐LT. Of 43,192 LT recipients, 43,026 (99.6%) were US citizens/residents and 166 (0.4%) were unauthorized immigrants. Among unauthorized immigrants, most LTs were performed in California (47%) and New York (18%). The absolute difference in proportion of LTs performed for unauthorized immigrants compared with the proportion of unauthorized immigrants among the total population differed among states, ranging from +20% in California to −12% in Texas. The most common countries of birth among LT recipients who were unauthorized immigrants were Mexico (52%), Guatemala (7%), China (6%), El Salvador (5%), and India (5%). In competing risk analysis, unauthorized immigration status (vs. US citizens/residents) was associated with a similar risk of graft failure (subdistribution hazard ratio [sHR] 0.74; 95% confidence interval [CI], 0.40‐1.34; P = 0.38) and death (sHR 0.68; 95% CI, 0.36‐1.29; P = 0.23). Conclusions LT for unauthorized immigrants is rare, and disparities in access to LT by state are present. Patient and graft survival among unauthorized immigrants is comparable with citizens/residents.
Lymphoplasmacytic Lymphoma Not Associated with an IgM Monoclonal Paraprotein Has Distinctive Clinical and Biological Features and a Similar Outcome As Compared with Waldenstrom's Macroglobulinemia: Multicentric Study of the Rete Ematologica Lombarda
Authors: Marzia Varettoni, Emanuela Boveri, Silvia Zibellini, Virginia Valeria Ferretti, Alessandra Tedeschi, Elisa Doni, Michele Merli, Lucia Farina, Maria Goldaniga, Luca Arcaini, Irene Defrancesco, Anna Maria Frustaci, Laura Bandiera, Giuseppe Isimbaldi, Silvia Uccella, Antonello Domenico Cabras, Umberto Gianelli, Luca Baldini, Marco Paulli, Mario Cazzola
Journal: Blood (2017)
Electrodeposited PEDOT:Nafion Composite for Neural Recording and Stimulation
Authors: Stefano Carli, Michele Bianchi, Elena Zucchini, Michele Di Lauro, Mirko Prato, Mauro Murgia, Luciano Fadiga, Fabio Biscarini
Journal: Advanced Healthcare Materials (2019)

Microelectrode arrays are used for recording and stimulation in neurosciences both in vitro and in vivo. The electrodeposition of conductive polymers, such as poly(3,4-ethylene dioxythiophene) (PEDOT), is widely adopted to improve both the in vivo recording and the charge injection limit of metallic microelectrodes. The workhorse of conductive polymers in the neurosciences is PEDOT:PSS, where PSS represents polystyrene-sulfonate. In this paper, the counterion is the fluorinated polymer Nafion, so the composite PEDOT:Nafion is deposited onto a flexible neural microelectrode array. PEDOT:Nafion coated electrodes exhibit comparable in vivo recording capability to the reference PEDOT:PSS, providing a large signal-to-noise ratio in a murine animal model. Importantly, PEDOT:Nafion exhibits a minimized polarization during electrical stimulation, thereby resulting in an improved charge injection limit equal to 4.4 mC cm-2 , almost 80% larger than the 2.5 mC cm-2 that is observed for PEDOT:PSS.
Introduction to the Outlines of the Principles of Differential Diagnosis, with Clinical Memoranda.
Journal: JAMA (1899)

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