tbuckley/cabot-search huggingface dataset:
CTNI-46. A PHASE II TRIAL OF TUMOR TREATING FIELDS (TTFIELDS) CONCOMITANT WITH RADIOSURGERY FOR THE TREATMENT OF RECURRENT, BEVACIZUMAB-NAÏVE GLIOBLASTOMA
Authors: Maciej Harat, Maciej Blok, Magda Adamczak-Sobczak, Pawel Szymanski, Iza Miechowicz, Bogdan Malkowski
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Almost all GBM patients experience recurrent disease, and median survival after recurrence is 6 months. A phase III trial conducted to test safety and efficacy of TTFields alone versus chemotherapy (including bevacizumab) in recurrent GBM showed improved PFS at six months and one-year survival was 20% in both treatment arms. Stereotactic radiosurgery (SRS), another treatment option recommended at recurrence, has limitations due to the invasive nature of glioblastoma. TTFields may decrease the tumor aggressiveness outside the target area potentially by multiple pathways, including immunogenic cell death and DNA repair inhibition sensitizing to radiation. We hypothesize that combined SRS and TTFields will be complementary, improving outcomes with minimal toxicity. METHODS In this open-label, phase II trial 40 participants with recurrence will be treated with SRS and TTFields, starting in 2020. Recurrence will be defined on FET-PET or MRI using RANO criteria. At least 6 months between the end of the first course of radiotherapy and SRS is mandatory with recurrent tumor visible on FET-PET and/or MRI, with the maximum diameter &amp;lt; 5 cm by either technique. SRS must be delivered within 7 days of TTFields start. A 5-day SRS regimen is allowed. TTFields should be interrupted only during SRS. The sample size of the study was calculated for the comparison of survival against a historical control. With 40 patients followed until death, there is at least an 80% ability to detect a 19% difference in one-year survival rate and 17% difference in ORR (p=0.05) compared to the EF-11 clinical trial. The one-year survival and ORR rate were seen in 20% and 14% of TTFields patients in the historical control. Overall survival will be stratified by volume, PET-based treatment, SVZ invasion, MGMT methylation status, time to first progression, and TTFields compliance. Estimated study primary completion date is July 2023.
GCT-59. EPIDEMIOLOGY OF PEDIATRIC INTRA-CRANIAL GERM CELL TUMORS: COMPARING THE INCIDENCE OF INTRA-CRANIAL GERM CELL TUMORS IN THE NATIVE JAPANESE POPULATION AND IMMIGRANT JAPANESE POPULATIONS ABROAD
Authors: Ashley Plant, Tomonari Suzuki, Rosdaili Diaz Coronado, Sidnei Epelman, Luis Sakamoto, Sylvia Cheng, Takaaki Yanagisawa, Bernard Rosner, Susan Chi, Mark Kieran
Journal: Neuro-Oncology (2020)

Abstract Pediatric intra-cranial germ cell tumors (iGCTs) occur at an incidence of 0.6–1.2 cases/million/year in Western countries. The incidence is reported up to 5 times higher in the Japan. It is unknown whether this increased incidence is due to tumor biology or environment. The incidence of iGCTs in children ages 0–19 years was evaluated from 12/1/96-12/1/2016 in stable Japanese immigrant populations living abroad compared to current native Japanese registry data. Medulloblastoma incidence was used as a control to account for assumptions in the data. A review of the Brain Tumor Registry of Japan from 1984–2004 revealed an incidence of 2.5 cases/million/year and a lower incidence of medulloblastoma at 1.1 cases/million/year. Sites outside of Japan included Vancouver, Canada, Lima, Peru, and San Paolo, Brazil and together included a population of 853,174 Japanese persons. Within this population, 0 cases of iGCT were identified over a 20-years. The ratio of medulloblastoma to iGCT cases in Japan was identified as 1:2 while the ratio was 2:1, 6.5:1, and 5:1, respectively, in the other three locations. The data suggests increased incidence in the native Japan may not translate to higher incidence in immigrant Japanese populations abroad and a clear genetic component was not found in this preliminary data set. A more precise and comprehensive study is needed to determine the cause of this difference in incidence. This study also emphasizes the importance of national and state registries and is a call to collaborate on state and country level epidemiology studies.
NURS-01. INTRACEREBROVENTRICULAR DRUG ADMINISTRATION FOR TREATMENT OF PEDIATRIC BRAIN TUMORS
Authors: Caroline Fitzgerald, Kathryn Matson
Journal: Neuro-Oncology (2020)

Abstract Intrathecal (IT) chemotherapy, given via lumbar puncture (LP) or an intracerebroventricular (ICV) device has become a safe and effective way to deliver chemotherapy into the cerebrospinal fluid (CSF) space. The blood brain barrier makes treating tumors with CSF dissemination difficult with systemic chemotherapy alone. IT chemotherapy is often necessary for tumors which disseminate into the CSF space including embryonal tumors and choroid plexus carcinomas. It is also used for relapsed or recurrent tumors. Giving IT chemotherapy via an ICV device instead of via an LP can be preferable as it requires no deep sedation and allows for more uniform drug distribution. Drugs given IT include methotrexate, cytarabine, hydrocortisone, etoposide, and topotecan. ICV devices can be placed in patients with adequate CSF flow and a flow study can be done if needed to confirm. Accessing the ICV device for administration of chemotherapy is typically done by a physician or nurse practitioner using sterile technique. Our institution has had success using music therapy and child life specialists for assistance with coping during the procedure as patients are awake. The procedure has few complications the most common being infection usually with skin flora. It can also cause nausea and headache. There are few long term risks.
Abstract P474: The Association Between Acculturation and Cardiovascular Disease Risk Factors: The African Immigrant Health Study
Authors: Ruth-alma N Turkson-ocran, Diana Baptiste, Oluwabunmi Ogungbe, Binu Koirala, Yvonne Commodore-mensah
Journal: Circulation (2020)

Introduction: African immigrants are a growing population with over 2.1 million residing in the United States (U.S). Like African Americans, their African descent counterparts, African immigrants have an increased risk of developing cardiovascular disease (CVD). Hypothesis: We hypothesized that greater length of residence in the U.S. will be associated with an increased number of CVD risk factors among African Immigrants. Methods: The African Immigrant Health Study was a cross-sectional study of African immigrants living in the Baltimore-Washington, D.C Metropolitan area. The main outcome of interest was high CVD risk, defined as the presence of ≥2 CVD risk factors including hypertension, diabetes, high cholesterol, and overweight/obesity. The secondary outcomes were the 4 CVD risk factors examined individually. The exposure was length of U.S. stay, used as a proxy for acculturation and defined as &lt; 10 years or ≥ 10 years in the U.S. Logistic regression was used to examine the odds of high CVD risk and the individual CVD risk factors, adjusting for relevant covariates. Results: We included N=317 African immigrants, with mean(±se) age 48(±12) years, 61% were female, 63% had a Bachelor’s degree or higher, 81% were employed, and 59% had lived in the US ≥10 years. Unadjusted, African immigrants with longer length of stay were more likely to have the four CVD risk factors examined. African Immigrants who had lived in the U.S. ≥ 10 years were 1.89 times (95%CI: 1.03-3.46) more likely to have ≥2 CVD risk factors than those who had lived in the U.S. &lt; 10 years after adjusting for age, income, employment status, insurance status, and routine place for healthcare. The unadjusted and adjusted results are presented in the Table. Conclusion: African immigrants who had lived in the US ≥10 years were more likely to have more CVD risk factors than those who had lived in the U.S. for &lt;10 years. CVD risk increases with length of stay in this population, underscoring the need for length of stay to be considered as a meaningful determinant of CVD risk.
Multimodality Therapy for Locoregional Nasopharyngeal Carcinoma—A Decision Tool for Treatment Optimization
Authors: Ari Joseph Rosenberg
Journal: JAMA Network Open (2020)

Lu-Lu Zhang, PhD; Fei Xu, PhD; Di Song, MD; Meng-Yao Huang, MD; Yong-Shi Huang, MD; Qi-Ling Deng, MD; Yi-Yang Li, MD; Jian-Yong Shao, PhD
THER-09. ONCOLYTIC ADENOVIRUS, DNX-2401, FOR NAIVE DIFFUSE INTRINSIC PONTINE GLIOMAS: A PHASE I CLINICAL TRIAL
Authors: Ignacio Iñigo-Marco, Marisol Gonzalez-Huarriz, Marc García-Moure, Ibon Tamayo, Sandra Hervas, Ruben Hernandez, Maria Buñales, Carlos DeAndrea, Maria Villalba, Chris Jones, Alan MacKay, Esther Hulleman, Jasper Van der Lugt, Guillermo Aldave, Blanca Lopez-Ibor, Ana Patiño-Garcia, Ricardo Diez-Valle, Juan Fueyo, Candelaria Gomez-Manzano, Jaime Gallego Perez de Larraya, Sonia Tejada, Marta M Alonso
Journal: Neuro-Oncology (2020)

Abstract The objective of this trial is to determine the safety, tolerability, and toxicity of DNX-2401 in newly diagnosed DIPG patients (NCT03178032) followed by radiotherapy. Secondary endpoints are overall survival at 12 months, percentage of responses and induced immune response against tumor. Tumor biopsy was performed through the cerebellar peduncle, followed by intratumoral injection of DNX-2401 (N=12). Three patients were treated with 1x1010vp and given the lack of toxicity we escalated to 5x1010vp. The procedure was well tolerated and reduced tumor volume was demonstrated in all patients after combined treatment (virus + radiotherapy). We performed molecular studies (RNAseq and the Oncomine Childhood Research Panel from Thermo Fisher). The immune cell composition of the biopsies pre-virus injection was assessed using multiplexed quantitative immunofluorescence. T cells were hardly detectable in these tumors while macrophages were abundant. Using a multiplexed TCR-sequencing mRNA-based assay to analyze 18 available paired pre- and post-treatment samples from the trial, we detected increased clonal T cell diversity following treatment with the virus. We also measured pre and post treatment neutralizing antibodies and their relationship with survival. Finally, we performed functional studies using 2 cell lines isolated from patients included in this trial to assess the response to the virus (infectivity, viability, T-cell recognition). In summary, the virus has shown safety and efficacy in some patients. The information obtained in this clinical study would aid understanding the response of DIPG patients to viral therapies and, therefore, to better tailor this strategy to improve the survival of these patients.
Molecular Characterisation of TP53 Aberrations in 1,777 Myeloma Trial Patients
Authors: Vallari Shah, Amy L Sherborne, Sidra Ellis, David C. Johnson, Farzana Begum, Jack Kendall, Brian A Walker, John R Jones, Charlotte Pawlyn, Suvi Savola, Matthew W Jenner, Mark T Drayson, Roger G. Owen, David Cairns, Walter M Gregory, Richard S Houlston, Faith E Davies, Gordon Cook, Gareth J. Morgan, Graham Jackson, Martin F Kaiser
Journal: Blood (2017)
PATH-04. AN ENHANCED AI-DRIVEN PLATFORM FOR PRECISION MOLECULAR BRAIN TUMOR DIANOSTICS
Authors: Martin Sill, Felix Sahm, Daniel Schrimpf, David Capper, Stefan M Pfister, Andreas von Deimling, David T W Jones
Journal: Neuro-Oncology (2020)

Abstract Tumors of the CNS represent one of the most complex groups of human cancer, with a vast number of different entities occurring across a spectrum of ages and anatomic locations. This heterogeneity makes accurate diagnosis challenging, with the current gold standard relying on multiple subjective elements. We recently proposed a classification algorithm based on tumor DNA methylation profiling as an objective way to assign samples to over 80 distinct molecular classes. Here we present a substantial update to our machine learning-based algorithm, with more than 170 molecular classes now being represented amongst the 5,915 samples in our reference cohort. These new classes include further subclassification of known groups such as medulloblastoma and ependymoma, as well as multiple new molecular entities described here for the first time. A further improvement is the introduction of a more rationally layered output, making use of ‘families’ of closely-related molecular classes to improve the compatibility with the current WHO classification of CNS tumors. This approach is designed to increase the clinical relevance of the primary output, while also retaining the full information content from the random forest-driven classification. Benchmarking our new algorithm by cross-validation and on an independent validation cohort indicates a retention of the excellent accuracy of diagnosis (error-rate &amp;lt; 4%), with a significant improvement in the proportion of confidently classifiable tumors compared with our previous tool. We believe that this approach, freely accessible through an online web portal, has the potential to enhance diagnostic precision and thereby support clinical care for brain tumor patients.
Factors Associated with Positive SARS-CoV-2 Test Results in Outpatient Health Facilities and Emergency Departments Among Children and Adolescents Aged &lt;18 Years — Mississippi, September–November 2020
Authors: Charlotte V. Hobbs, Lora M. Martin, Sara S. Kim, Brian M. Kirmse, Lisa Haynie, Sarah McGraw, Paul Byers, Kathryn G. Taylor, Manish M. Patel, Brendan Flannery, Carmen S. Arriola, Eric P. Griggs, Ashley K. Simon, Meagan E. Stephenson
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

As of December 14, 2020, children and adolescents aged <18 years have accounted for 10.2% of coronavirus disease 2019 (COVID-19) cases reported in the United States.* Mitigation strategies to prevent infection with SARS-CoV-2, the virus that causes COVID-19, among persons of all ages, are important for pandemic control. Characterization of risk factors for SARS-CoV-2 infection among children and adolescents can inform efforts by parents, school and program administrators, and public health officials to reduce SARS-CoV-2 transmission. To assess school, community, and close contact exposures associated with pediatric COVID-19, a case-control study was conducted to compare exposures reported by parents or guardians of children and adolescents aged <18 years with SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing (case-patients) with exposures reported among those who received negative SARS-CoV-2 RT-PCR test results (control participants). Among 397 children and adolescents investigated, in-person school or child care attendance ≤14 days before the SARS-CoV-2 test was reported for 62% of case-patients and 68% of control participants and was not associated with a positive SARS-CoV-2 test result (adjusted odds ratio [aOR] = 0.8, 95% confidence interval [CI] = 0.5-1.3). Among 236 children aged ≥2 years who attended child care or school during the 2 weeks before SARS-CoV-2 testing, parents of 64% of case-patients and 76% of control participants reported that their child and all staff members wore masks inside the facility (aOR = 0.4, 95% CI = 0.2-0.8). In the 2 weeks preceding SARS-CoV-2 testing, case-patients were more likely to have had close contact with a person with known COVID-19 (aOR = 3.2, 95% CI = 2.0-5.0), have attended gatherings† with persons outside their household, including social functions (aOR = 2.4, 95% CI = 1.1-5.5) or activities with other children (aOR = 3.3, 95% CI = 1.3-8.4), or have had visitors in the home (aOR = 1.9, 95% CI = 1.2-2.9) than were control participants. Close contacts with persons with COVID-19 and gatherings contribute to SARS-CoV-2 infections in children and adolescents. Consistent use of masks, social distancing, isolation of infected persons, and quarantine of those who are exposed to the virus continue to be important to prevent COVID-19 spread.
RARE-20. MALIGNANT PERIPHERAL NERVE SHEATH TUMOR OF A CRANIAL NERVE IN AN INFANT WITH NEUROCUTANEOUS MELANOSIS
Authors: Lacey Carter, Naina Gross, Rene McNall-Knapp, ,and Jo Elle Peterson
Journal: Neuro-Oncology (2020)

Abstract At one month of age, a female presented with a giant congenital nevus along lower back and thighs and hydrocephalus. A ventriculoperitoneal shunt was placed. An MRI was done at six months, initially reported as normal. At eleven months of age, five months after original MRI, patient presented with dysconjugate gaze and lethargy. MRI showed new 3.8 x 3.7 x 3.4 cm right cerebellopontine angle mass extending into Meckel’s cave and foramen ovale along with leptomeningeal disease extending from the mass along the entire length of the spinal cord. Retrospective review of prior MRI revealed subtle leptomeningeal enhancement concerning for neurocutaneous melanosis (NCM). Given the leptomeningeal disease, family elected for open biopsy and debulking of lesion instead of aggressive resection. Histologically, the mass showed hypercellular spindle cell neoplasm with mitotic activity and necrosis mixed with remnants of normal cranial nerve. GFAP was negative, excluding a glioma. HMB-45, MITF, panmelanoma, and Melan-A were negative, excluding melanoma. A negative myogenin stain ruled out ectomesenchymoma. S-100 protein and SOX-10 positivity with variable loss of staining for trimethylation of histone H3 K27 were indicative of malignant peripheral nerve sheath tumor (MPNST). Given the course of the mass, trigeminal nerve MPNST was presumed. Given the poor prognosis of intracranial MPNST and NCM, family elected to forgo treatment and was discharged with hospice. She died 25 days after surgery. Cranial nerve MPNST is rare. MPNST in patients with NCM has not previously been reported to our knowledge.
Better Regenerative Output After Cellular Input: Healing Hearts by Combining Basic Fibroblast Factor and Cell-Based Therapy⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Stefanie Dimmeler, Marc Tjwa
Journal: Journal of the American College of Cardiology (2008)
GCT-37. PREVALENCE OF AUTISM SPECTRUM DISORDER AND OTHER NEURODEVELOPMENTAL DISORDERS IN PEDIATRIC PATIENTS WITH INTRACRANIAL GERM CELL TUMORS
Authors: Kevin X Liu, Roshan V Sethi, Margaret B Pulsifer, Alissa M D’Gama, Beverly Lavally, Nancy J Tarbell, Torunn I Yock, Shannon M MacDonald
Journal: Neuro-Oncology (2020)

Abstract PURPOSE/OBJECTIVE(s) Intracranial germ cell tumors (IGCTs) are rare tumors of the central nervous system with peak incidence around puberty. Due to the developmental origins of IGCTs, we investigated the prevalence of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), in our retrospective institutional cohort of patients diagnosed with IGCTs. MATERIALS/METHODS A retrospective review of medical records was conducted for 105 patients who were diagnosed with IGCTs and treated at Massachusetts General Hospital between 1998 and 2016. All patients with ASD had thorough neuropsychological assessment at the time of radiotherapy that confirmed their diagnoses. RESULTS Median age at diagnosis was 12.8 years (range: 4.3–21.6) and median follow-up time was 4.7 years (range: 0.4–15.8). Seventeen patients with IGCTs were diagnosed with NDDs prior to cancer diagnoses, including five patients with ASD, and three patients with chromosomal abnormalities, including one patient with Down syndrome. Interestingly, four of five patients with ASD developed pure germinomas, giving an ASD prevalence rate of 6.5% and 2.3% in the pure germinoma and NGGCT cohorts, respectively. All other patients had no known diagnoses of NDDs. CONCLUSIONS Our study found 17 patients with IGCTs were diagnosed with NDDs prior to their cancer diagnoses. An ASD prevalence of 6.5% in the pure germinoma cohort is more than three-fold greater than the national prevalence, suggesting there may be an association between ASD and pure germinomas. Future prospective studies with larger cohorts are still needed to examine associations between NDDs and ASD and IGCTs.
RADT-33. RADIOSURGERY VERSUS COMBINATION RADIOSURGERY-BEVACIZUMAB FOR THE TREATMENT OF RECURRENT HIGH-GRADE GLIOMA: A SYSTEMATIC REVIEW
Authors: Daniel Kulinich, John Sheppard, Thien Nguyen, Aditya Kondajji, Ansley Unterberger, Adam Enomoto, Kunal Patel, Quinton Gopen, Isaac Yang
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND High-grade gliomas (HGG) comprise the most common primary adult brain cancers and universally recur. Combination re-radiation therapy (reRT) and bevacizumab (BVZ) therapy for recurrent HGG is common, but its reported efficacy is mixed. OBJECTIVE To assess clinical outcomes after reRT±BVZ in recurrent HGG patients receiving stereotactic radiosurgery (SRS), hypo-fractionated (HFSRT), or fully fractionated RT (FSRT). METHODS We performed a systematic review of PubMed, Web of Science, Scopus, Embase, and Cochrane databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified studies reporting outcomes for patients with recurrent HGG treated via reRT±BVZ. Cohorts were stratified by BVZ treatment status and reRT modality (SRS, HFSRT, and FSRT). Outcome variables were overall survival (OS), and progression-free survival (PFS). RESULTS 34 of 1,742 identified articles survived inclusion criteria (2%) and reported data on 954 patients receiving reRT alone and 445 patients receiving reRT+BVZ. All patients initially underwent standard-of-care therapy for their primary HGG. In a multivariate analysis that adjusted for median patient age, WHO Grade, RT dosing, reRT fractionation regimen, time between primary and reRT, and reRT target volume, BVZ therapy was associated with significantly improved OS (2.51 [0.11, 4.92] months, P=.041) but no significant improvement in PFS (1.40 [-0.36, 3.18] months, P=.099). Patients receiving BVZ also had significantly lower rates of RN (2.2% vs 9.5%, P &amp;lt; .001). CONCLUSIONS Combination reRT+BVZ may improve OS and reduce rates of RN in recurrent HGG, but further controlled studies are needed to confirm these effects.