tbuckley/cabot-search huggingface dataset:
QOL-32. THE PROMOTE STUDY: HEALTH-RELATED QUALITY OF LIFE COMMUNICATION NEEDS OF CHILDREN, ADOLESCENTS, AND THEIR FAMILIES ATTENDING OUTPATIENT CONSULTATIONS AFTER TREATMENT FOR A BRAIN TUMOUR
Authors: Shelly Stubley, Anita Freeman, Christina Liossi, Anne-Sophie Darlington, Martha Grootenhuis, Darren Hargrave, Christopher Morris, David Walker, Colin Kennedy, Kim Bull
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Childhood brain tumours and their treatment can reduce health-related quality of life (HRQoL) and cause anxiety and depression, withdrawal, and social isolation. Improved communication within outpatient consultations may allow early identification and treatment of these issues. We explored family communication needs in survivors of childhood brain tumours receiving six-monthly follow-up outpatient review within the English NHS. METHODS Semi-structured interviews were conducted with 18 families whose child aged 8–17 years had finished treatment for a brain tumour within the preceding five years. Thematic analysis used the Framework Method. RESULTS Adjusting to change and finding a “new normal” was the overarching theme to emerge. HRQoL issues included fatigue, coping with physical changes, challenges at school, isolation, and adjusting to changes in abilities. Survivors described a need for greater knowledge about and more support with changes in cognitive functioning. Parents spoke about the impact on the wider family and their changed role in supporting the child’s HRQoL. Communication barriers included short-term memory loss, shyness, and the need to suppress or regulate emotions evoked by these issues. Communication needs included more information regarding recovery and rehabilitation and/or help managing anxiety or emotional health. CONCLUSION The above communication needs and barriers should be addressed. Having a digital record to document and monitor this information systematically could improve service planning and provide patients and their families with the resources to reach their full potential and experience a better HRQoL.
Clonal Evolution in CLL
Authors: Simon Bouzy, Marine Armand, Clementine Gabillaud, Elise Chapiro, Nadia Bougacha, Fotini Kostopoulou, Frederic Davi, Magali Le Garff-Tavernier, Karim Maloum, Veronique Leblond, Veronique Morel, Damien Roos-Weil, Anne Lavaud, Jean Gabarre, Choquet Sylvain, Santos Susin, Olivier Bernard, Florence Nguyen-Khac
Journal: Blood (2017)
EPEN-26. NON-CANONICAL NF-κB SIGNALING DRIVES MESENCHYMAL EPENDYMAL CELL SUBPOPULATION IN PFA EPENDYMOMA
Authors: Andrea Griesinger, Faith Harris, Andrew Donson, Austin Gillen, Kent Riemondy, Sujatha Venkataraman, Vladimir Amani, Michael Handler, Todd Hankinson, Nicholas Foreman
Journal: Neuro-Oncology (2020)

Abstract NF-κB signaling is a hallmark of PFA1 ependymoma. Loss of LDOC1, through epigenetic silencing, leads to constitutively active NF-κB signaling and chronic IL-6 secretion. In this study, we investigate the loss of LDOC1 within the PFA tumor clusters. Using our PFA scRNAseq database, in which there are 5 clusters within the tumor cell compartment: mesenchymal (MEC), ciliated (CEC), transportive (TEC), and undifferentiated (UEC). LDOC1 expression was significantly reduced and had an inverse correlation with genes defining the unfavorable MEC subpopulation, predominate in PFA1. This is consistent with our findings that MEC was defined by an NF-κB2 signaling profile. In contrast, LDOC1 expression was higher and positively correlated with genes defining the favorable CEC subpopulation, mostly seen in PFA2. RELA expression, which we studied as a target of LDOC1, was not localized to MEC and was wide-spread throughout the PFA compartment. RELB, part of non-conical NF-κB signaling, was expressed only the MEC subpopulation correlating with IL-6 gene expression found only in this subpopulation. In MAF-811, a PFA cell line with more CEC-like gene phenotype, RELB co-immunoprecipates with the active form of NF-κB2 in both the nucleus and cytoplasm. IL-6 gene expression is almost completely lost when NF-κB2 is knock-down using shRNA. Additionally, loss of LDOC1 leads to over 3 fold increase in NF-κB2 expression. Combined with our previous work, this would suggest that NF-κB2 drives IL-6 expression by binding with RELB in MEC subpopulation and targeting loss of LDOC1 may shift the MEC subpopulation toward the more favorable CEC subpopulation.
DIPG-04. THERAPEUTIC STRATEGY FOR DIFFUSE MIDLINE GLIOMAS. A SINGLE CENTER EXPERIENCE
Authors: Takumi Yamanaka, Yoshinobu Takahashi, Tamaki Morisako, Toshiki Nagai, Seisuke Tanigawa, Daisuke Umebayashi, Hayato Takeuchi, Kazunori Tatsuzawa, Mitsuru Miyachi, Shigeki Yagyu, Tomoko Iehara, Hajime Hosoi, Naoya Hashimoto
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Diffuse midline gliomas have unfavorable prognoses due to the difficulty of surgery and chemo-radiation resistances. The purpose of this study is to overview our surgical experiences and prognoses of this challenging neoplasm. MATERIALS AND METHODS Five patients of diffuse midline gliomas who were treated between 2016 and 2019 were enrolled. Tumor locations, surgical procedures, molecular diagnoses, and prognoses were retrospectively reviewed. RESULTS There were 3 male and 2 female patients, and the median age was 15 years ranged from 7 to 21 years. Tumors were located at the basal ganglia in 1 patient, thalamus in 1, brain stem in 2, and cervical spine in 1. Mutations of H3 K27M genes were detected in 4 surgically treated patients, except for 1 patient, who were radiologically diagnosed as diffuse intrinsic pontine glioma (DIPG). Focal irradiation of ranged 35 to 54Gy were administered in all cases along with temozolomide in 2 cases and bevacizumab in 2 cases. The median survival time was 13 months ranged from 4 to 18 months. DISCUSSION Supratentorial tumors were maximumly resected, whereas just biopsies were performed in cases of exophytic brain stem and spinal tumors. Diagnosis of DIPG was made without using surgical specimens. Therapeutic strategies should be discussed with a concern to the patients’ qualities of life for this tumor entity with dismal prognosis.
LINC-21. SURVEY ON THE RESOURCES AVAILABLE FOR PEDIATRIC NEURO-ONCOLOGY IN CHILE, SOUTH AMERICA
Authors: Mohammad H Abu-Arja, Nicolás Rojas del Río, Andres Morales La Madrid, Alvaro Lassaletta, Rosita Moreno, Miguel Valero, Veronica Perez, Felipe Espinoza, Eduardo Fernandez, José Díaz, José Santander, Juan Tordecilla, Veronica Oyarce, Katherine Kopp, Ute Bartels, Ibrahim Qaddoumi, Jonathan L Finlay, Adrián Cáceres, Ximena Espinoza, Diana S Osorio
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND We report the human and material resources available in Chilean institutions providing pediatric neuro-oncology services. METHODS A cross-sectional survey was distributed to 17 hospitals providing pediatric neuro-oncology services (Programa Infantil Nacional de Drogas Antineoplásicas (PINDA) centers=11, Private=6). RESULTS Response rate was 71% (PINDA=8; Private=4). Pediatric neuro-oncology services were mainly provided within general hospitals (67%). Registries for pediatric central nervous system (CNS) tumors and chemotherapy-related toxicities were available in 100% and 67% of centers, respectively. Children with CNS tumors were treated by pediatric oncologists in 92% of institutions; none were formally trained in neuro-oncology. The most utilized treatment protocols were the national PINDA protocols followed by the Children’s Oncology Group protocols. All World Health Organization essential medicines for childhood cancer were available in more than 80% of participating institutions except for gemcitabine, oxaliplatin, paclitaxel, and procarbazine. The median number of pediatric neurosurgeons per institution was two (range,0–8). General neuro-radiologists were available in 83% of institutions. Pathology specimens were sent to pediatric neuropathologists (33%), neuropathologists (25%), adult pathologists (25%), and pediatric pathologists (16.7%). In-house pediatric radiation oncologists were available in 25% of centers. Intensity-modulated radiotherapy, conformal radiotherapy and cobalt radiotherapy were utilized by 67%, 58% and 42% of hospitals, respectively. Only one center performed autologous hematopoietic cell transplant for pediatric CNS tumors. CONCLUSIONS These results provide a glimpse into the pediatric neuro-oncology services available in Chile. A wide range of up-to-date treatment modalities is available for children with CNS tumors in Chile. Establishing formal pediatric neuro-oncology training may be beneficial.
NIMG-26. DIAGNOSIS OF PSEUDOPROGRESSION FOLLOWING RADIOTHERAPY PLUS LOMUSTINE-TEMOZOLOMIDE CHEMOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS USING FET PET
Authors: Jan-Michael Werner, Garry Ceccon, Johannes Weller, Christina Schaub, Caroline Tscherpel, Philipp Lohmann, Elena Bauer, Niklas Schäfer, Gabriele Stoffels, Christoph Kabbasch, Christian Baues, Simone Marnitz, Gereon R Fink, Karl-Josef Langen, Ulrich Herrlinger, Norbert Galldiks
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The CeTeG/NOA-09 trial demonstrated a significant survival benefit of radiotherapy plus lomustine-temozolomide chemotherapy in glioblastoma patients with methylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter compared to standard temozolomide chemoradiation (1). However, data on pseudoprogression following treatment according to the CeTeG/NOA-09 trial is lacking. Due to the limited specificity of conventional MRI we evaluated the value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the differentiation of pseudoprogression from actual tumor progression. METHODS Twenty-one patients with newly diagnosed IDH-wildtype glioblastoma and methylated MGMT promoter with conventional MRI findings suspicious for tumor progression according to RANO criteria (2) after radiotherapy completion were investigated using FET PET. The maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) were calculated. Pseudoprogression was diagnosed neuropathologically or clinicoradiologically (i.e, if (i) a stable clinical course, (ii) stable or improved MRI findings, and (iii) no treatment change occurred within the next six months). Diagnostic performance of FET PET parameters was evaluated using receiver-operating-characteristic (ROC) analyses and Fisher’s exact test. Imaging results were also related to progression-free survival (PFS). RESULTS Pseudoprogression was identified in 9 of 21 patients (43%). In the majority of patients (n=8; 89%), pseudoprogression was diagnosed clinicoradiologically. The median time between radiotherapy completion and pseudoprogression was nine weeks (range, 5-25 weeks). ROC analysis yielded an optimal cutoff value of 1.95 for TBRmean to differentiate between pseudoprogression and tumor progression (sensitivity, 89%; specificity, 75%; accuracy, 81%; area under the curve, 0.72±0.13; P = 0.008). CONCLUSIONS In a considerable number of patients, pseudoprogression may occur following radiotherapy plus off-study lomustine-temozolomide chemotherapy according to the CeTeG/NOA-09 trial. FET PET appears of value for the differentiation of pseudoprogression from tumor progression in this group of patients. Literature: 1. Herrlinger et al., 2019 Lancet; 2. Wen et al., 2010 J Clin Oncol
CTIM-32. PHASE II AND BIOMARKER STUDY OF PEMBROLIZUMAB OR PEMBROLIZUMAB PLUS BEVACIZUMAB FOR RECURRENT GLIOBLASTOMA PATIENTS
Authors: David Reardon, Annette Molinaro, Katherine Peters, Jennifer Clarke, Justin Jordan, John de Groot, Phioanh Nghiemphu, Thomas Kaley, Howard Colman, Christine McCluskey, Timothy Smith, David Cote, Mariano Severgnini, Jennifer Yearley, Qing Zhao, Wendy Blumenschein, Gabriel Duda, Alona Muzikansky, Rakesh Jain, Patrick Wen, Lakshmi Nayak
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Vascular endothelial growth factor (VEGF) is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase 2 study of pembrolizumab, a programmed death-1 (PD-1) blocking antibody alone or with the anti-VEGF antibody bevacizumab in recurrent glioblastoma with detailed analyses of biomarkers and patient neurologic function. METHODS Eighty bevacizumab-naive, recurrent glioblastoma patients were randomized to receive pembrolizumab with bevacizumab (cohort A, n=50) or pembrolizumab monotherapy (cohort B, n=30). The primary endpoint was six-month progression-free survival (PFS-6). Exploratory endpoints included evaluation of tumor PD-L1 expression, TIL density, immune activation gene expression signature and plasma cytokines with outcome. Changes in neurologic function were prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale. RESULTS Pembrolizumab alone or with bevacizumab was well tolerated but of limited benefit. For cohort A, PFS-6 was 26.0% (95% CI: 16.3, 41.5), median OS was 8.8 months (95% CI: 7.7, 14.2), ORR was 20% and median duration of response was 48 weeks. For cohort B, PFS-6 was 6.7% (95% CI: 1.7, 25.4), median OS was 10.3 months (95% CI: 8.5, 12.5) and ORR was 0%. Factors associated with worsened OS included baseline dexamethasone use and increased post-therapy plasma VEGF (cohort A) and wild-type IDH1, unmethylated MGMT and increased baseline PlGF and sVEGFR1 levels (cohort B), but tumor immune markers were not informative. The NANO scale effectively predicted neurologic function. CONCLUSIONS Although well tolerated, pembrolizumab was ineffective both as monotherapy and with bevacizumab for recurrent glioblastoma. Nonetheless, radiographic responses to combinatorial therapy were durable. Baseline dexamethasone use and plasma cytokines but not tumor immunologic biomarkers were associated with outcome. Neurologic function evaluated by the NANO scale contributed to outcome assessment.
NCOG-52. TUMOR TREATING FIELDS IN MENINGIOMA
Authors: Christian Mawrin
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND High-grade meningioma are aggressive intracranial tumors and currently only limited treatment options exist. Therefore, there is a need for further studies in search of new therapies. Tumor Treating TTFields (TTFields) therapy serves as an effective treatment against glioblastoma (GBM). Phase 3 clinical trials investigate the use of TTFields in other intracranial tumors, i.e. brain metastases of the non-small cell lung cancer. We here provide an overview of the currently available data regarding the use of TTFields in meningioma. MATERIALS AND METHODS We performed a literature search using the term “Tumor treating fields” “NovoTTF”, “TTFields” and “Optune” in combination with “Meningioma”. A brief overview of TTFields in meningioma is provided here. RESULTS In vitro studies using patient-derived anaplastic grade III meningioma cell lines showed that TTFields treatment at a frequency of 200 kHz causes a significant reduction of cell proliferation and clonogenicity as well as altering cell morphology. In a case report of a 44-year-old woman suffering from a right anterior temporal tumor as well as a distant right parietal extra-axial convexity meningioma TTFields and Temozolomide treatment was initiated. Brain MRI scans 8, 16 and 20 weeks later showed a reduction in the meningioma tumor size of 42%, 58% &amp; 60%, respectively. Currently, two ongoing trials test the efficacy and safety of the use of TTFields in meningioma patients: a phase II single arm trial (n=27), investigating the combination of TTFields and Bevacizumab in recurrent or progressive meningioma (NCT02847559); and a pilot trial, investigating the effects of TTFields as monotherapy on recurrent atypical and anaplastic meningioma (NCT01892397). CONCLUSIONS First data indicate that TTFields might be an option in future high-grade meningioma treatment. Clinical trials need to show safety and efficacy for the TTFields treatment in meningioma patients.
EXTH-28. MOLECULAR CHARACTERIZATION OF HUMAN GLIOMAS AND IDENTIFICATION OF NEOPLASMS RESPONSIBLE FOR NEW BIOPHARMACEUTICALS OBTAINED FROM ANIMAL VENOM: A TRANSLATIONAL APPROACH
Authors: Natalia Barreto dos Santos, Monize Valeria da Silva, Jaqueline de Lima Munhoz, Thomaz A A da Rocha-e-Silva, Rafael Sutti, Liana Verinaud, João Luiz Vitorino Araujo, Catarina Raposo
Journal: Neuro-Oncology (2020)

Abstract Gliomas correspond to approximately 80% of primary malignant brain tumors in adults. Associate histopathological classification to the identification of the molecular profile of these tumors is a great strategy to predict the tumor’s behavior and its responsiveness to the treatments. Studies have shown the potential of using biopharmaceuticals against cancer. Our research group has recently found two main subfractions isolated from Phoneutria nigriventer spider venom (PnV) (called SF1 and SF11) that can act decreasing the number of migrating cells during transwell assay. Therefore, the present study aimed to characterize, as regards molecular identity, the responsiveness of glioma samples collected from patients to the molecules purified from the PnV, in order to improve diagnostic and prognostic predictions, as well as contribute to the development of new drugs. After consent of the patients, samples of the tumors clinically diagnosed as glioma were collected during the surgical procedure to cultivation, that were performed until 10 passages to establish a lineage before use. To analyze its responsiveness to PnV in a migration assay, cultured human glioblastoma (1-JA63) cells were treated with PnV-isolated (HPLC) subfractions (SF1 and SF11 at 1 µg/ml) for 12 and 48 h (control stayed in IMDM) in a transwell system. SFs (mainly SF1) treatment induced a significant reduction in the number of migrating cells after 48 hours of exposure, in comparison to the control (untreated). Ongoing trials continue the establishment of another tumor samples of gliomas and migration tests with PnV subfractions will be carried out, to compare their effects in relation to other degrees of the disease also correlating the tumor response to the drug with the molecular profile. The results will contribute to the development of a potential individualized therapy also adding information about the correlation between the molecular identity of the tumor and its prognosis.
MODL-14. SMALL MOLECULE TARGETING OF ONCOGENIC FGF2-FGFR SIGNALING IN BRAIN TUMORS
Authors: Karthiga Santhana Kumar, Cyrill Brunner, Matthias Schuster, Oliver Zerbe, Michael Grotzer, Gisbert Schneider, Martin Baumgartner
Journal: Neuro-Oncology (2020)

Abstract FGF2, the ligand of FGF receptors (FGFRs), is expressed in the developing and adult brain. FGF2-FGFR1 signaling causes the induction and maintenance of cancer stem cells through ERK-dependent up-regulation of ZEB1 and Olig2 in glioblastoma. In SHH medulloblastoma, Olig2 triggers tumor initiation from GCPs, maintains quiescent stem-like cells during the disease and contributes to tumor outgrowth at recurrence. We found that FGF2-FGFR signaling causes increased growth and tissue invasion through the FGFR adaptor protein FRS2 in SHH and group-3 medulloblastoma 1. Thus, targeting of FGFR-FRS2 signaling could abrogate brain tumor growth and spread by repressing tumor-promoting functions that are induced by microenvironmental FGF2. Using virtual screening combined with functional validation, we identified protein-protein interaction inhibitors (F2i) that bind FRS2 and abrogate FGFR signaling to the MAP-ERK pathway. Consistent with the requirement of FRS2 for pro-invasive signaling downstream of FGFR1 in medulloblastoma, F2i also efficiently block FGF2-induced migration and invasion in medulloblastoma-derived cells. Selected F2i display excellent binding kinetics with a similar Kd as the natural ligand domain of FGFR and cause steric alterations in the targeted protein domain. On-target activity was confirmed by thermal proteome profiling. Neither in silico screening nor empirical testing revealed significant off-target activity of the compounds. No toxicity of F2i was observed in cell-based models with confirmed functional activity on invasion and MAPK activation. Thus, we identified novel, low molecular weight pharmacological protein-protein interaction inhibitors with an excellent potential to specifically block FGFR functions relevant for brain tumor progression. 1. Santhana Kumar et al., CellReports23, 3798–3812.e8 (2018).
RADT-32. NATIONAL TRENDS IN RADIATION DOSE FOR LOW GRADE GLIOMAS
Authors: Rodney Wegner, Zachary Horne, Stephen Abel, Linda Xu, Alexander Yu, Tulika Ranjan, Stephen Karlovits
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Adjuvant radiation is used in patients with low grade gliomas (LGG) with high risk characteristics. Randomized trials have examined dosing schemes ranging from as low as 45 Gy to higher than 60 Gy, with no difference in outcome. We used the National Cancer Database (NCDB) to see which doses were used in this patient population, and if any difference were seen in outcome. METHODS We queried the NCDB for patients with WHO Grade 2 brain tumors treated with surgery and adjuvant radiotherapy. We divided the cohort into dose groups: 45-50 Gy, 50.4-54 Gy, and &amp;gt;54 Gy. Multivariable logistic regression was used to identify predictors of low and high dose radiation. Propensity matching was used to account for indication bias. RESULTS We identified 1,437 patients meeting the above criteria. Median age was 45 years. Forty-eight percent had astrocytoma subtype and 70% had subtotal resection. The majority of patients (69%) were treated to between 50.4-54 Gy. Half of all patients were treated with radiation alone. 1p19q status was recorded in 32% of patients, and 13% overall were co-deleted. Predictors of high dose radiation were increased income, astrocytoma subtype, chemotherapy receipt, and treatment in 2014. Patients treated to a dose of &amp;gt;54 Gy had a median survival of 73.5 months and was not reached in those treated to a lower dose (p=0.0041). Subset analysis of patients with astrocytoma subtype showed median survivals of 79.0 and 51.2 months for low and high dose, respectively (p=0.13). When limited to oligodendrogliomas corresponding 5 year survival rates were 86% and 65%, in favor of lower doses (p=0.0004). CONCLUSIONS This analysis shows that 50.4-54 Gy is the most widely used radiation regimen for ow grade gliomas. There appeared to be no benefit to higher doses, although factors not recorded are likely confounding the RESULTS: