tbuckley/cabot-search huggingface dataset:
EPID-28. THE IMPACT OF RITUXIMAB COMBINATION CHEMOTHERAPY ON THE CLINICAL OUTCOMES OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL): AN UPDATED META-ANALYSIS
Authors: Philip Haddad, Dalia Hammoud, Kevin Gallagher
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND PCNSL is a rare diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system accounting for approximately 2–5% of all primary brain tumors. Although there is no standard combination of chemotherapy, high-dose methotrexate is considered the backbone of all PCNSL chemotherapy regimens. Rituximab, an anti-CD20 antibody, has been a standard component of DLBCL combinations since it improves progression-free (PFS) and overall survival (OS). However, the role of Rituximab in the treatment of PCNSL has been controversial with contradictory RESULTS: A small meta-analysis conducted in 2019 found no associated survival advantage for Rituximab when added to chemotherapy. However, this meta-analysis was small and included only 2 studies. The purpose of this updated meta-analysis is to evaluate in a more comprehensive way the impact of Rituximab combination chemotherapy on the clinical outcomes of patients with PCNSL incorporating all available comparative studies. METHODS A review of the medical literature was conducted using online databases. Inclusion criteria consisted of PCNSL diagnosis, English language, and studies reporting OS and PFS with hazard ratios (HR) or Kaplan-Meier curves that compared similar regimens with and without Rituximab. A meta-analysis using an inverse variance method with a random-effects model was conducted. RESULTS Four comparative studies with a total of 467 patients were included in this meta-analysis. Two of these studies were retrospective comparative studies and two were randomized phase II trials. When added to chemotherapy, Rituximab was found to significantly improve the OS and PFS (HROS 0.75, 95%CI: 0.59–0.96, p=0.02; HRPFS 0.67, 95%CI: 0.53–0.85, p=0.001) with a heterogeneity estimate, I2=0%. CONCLUSIONS This is the first meta-analysis to show that adding Rituximab to chemotherapy is associated with OS and PFS in patients with PCNSL. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the routine use of Rituximab combinations in PCNSL.
The twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis
Authors: Javier Muñoz-Garcia, Denis Cochonneau, Stéphane Télétchéa, Emilie Moranton, Didier Lanoe, Régis Brion, Frédéric Lézot, Marie-Françoise Heymann, Dominique Heymann
Journal: Theranostics (2020)

Macrophages are specialized cells that control tissue homeostasis. They include non-resident and tissue-resident macrophage populations which are characterized by the expression of particular cell surface markers and the secretion of molecules with a wide range of biological functions. The differentiation and polarization of macrophages relies on specific growth factors and their receptors. Macrophage-colony stimulating factor (CSF-1) and interleukine-34 (IL-34), also known as "twin" cytokines, are part of this regluatory landscape. CSF-1 and IL-34 share a common receptor, the macrophage-colony stimulating factor receptor (CSF-1R), which is activated in a similar way by both factors and turns on identical signaling pathways. However, there is some discrete differential activation leading to specific activities. In this review, we disscuss recent progress in understanding of the role of the twin cytokines in macrophage differentiation, from their interaction with CSF-1R and the activation of signaling pathways, to their implication in macrophage polarization of non-resident and tissue-resident macrophages. A special focus on IL-34, its involvement in pathophsyiological contexts, and its potential as a theranostic target for macrophage therapy will be proposed.
GCT-24. RELAPSE PATTERN AND QUALITY OF LIFE IN PATIENTS WITH LOCALIZED GERMINOMA ORIGINATING FROM BASAL GANGLIA REGION
Authors: Bo Li
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The optimal radiation field in localized basal ganglia (BG) germinoma was not well defined, mostly due to unknown relapse patterns. In our institute, both focal radiotherapy (FR) and craniospinal irradiation (CSI) plus boost were considered in this population until whole-brain radiotherapy (WBRT) plus boost became an option in 2008. Thus, a retrospective study was conducted to address the issue. Furthermore, the health-related quality of life (HRQOL) was also evaluated. METHODS Patients who were diagnosed as localized BG germinoma between 2000 and 2017 were studied. HRQOL was evaluated by PedsQL 4.0 (≤15 years) and SF-36 (&amp;gt;15 years) questionnaires based on the age at last follow-up. RESULTS Among 161 patients included, 35 patients received FR, 109 patients received WBRT plus boost, and 17 patients received CSI plus boost. After a median follow-up of 83 months (range, 13 to 214 months), 15 patients relapsed in FR group, 4 in WBRT group and 0 in CSI group. The 5-year DFS was 74.3%, 97.2%, and 100%, respectively (p&amp;lt;0.001). Among 15 patients who relapsed after FR, 14 had positive radiological findings, in which 6 (42.8%) had lesions documented at the periventricular area, and 7 (50.0%) in the frontal lobe. HRQOL data were available in 69 patients, which generally scored low. In 38 patients evaluated by SF-36, those receiving CSI had significantly lower mental component scores than those receiving WBRT (p=0.027) or FR (p=0.011). CONCLUSIONS Patients with localized BG germinoma present a unique relapse pattern. WBRT, which covers at-risk areas, showed both better disease control and HRQOL.
DIPG-17. BIOPSY-PROVEN DIFFUSE MIDLINE GLIOMA IN ADOLESCENTS AND YOUNG ADULTS
Authors: Shota Tanaka, Shunsaku Takayanagi, Yuki Shinya, Mariko Kawashima, Masahiro Shin, Hirofumi Nakatomi, Nobuhito Saito
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Diffuse midline glioma (DMG) mostly affects young children. The newly-introduced disease entity DMG, H3K27M-mutant uniformly portends poor prognosis, and therefore that in the pons is usually treated based upon radiological diagnosis without histological confirmation. DMG is rarer in adolescents and young adults (AYA), and remains poorly characterized. In this study, we sought to investigate the clinical, pathological, and molecular profiles of DMG in AYA generation. METHODS Patients of age between 16 and 39 undergoing biopsy at the University of Tokyo Hospital between 2003 and 2019 were included in the study. Clinical data and images were retrospectively reviewed. Genetic analyses were performed in cases with abundant tissues. RESULTS Ten patients included 8 brainstem and 2 thalamic DMG. The median age was 25 years (range, 19–38). Pathological diagnosis was DMG, H3K27M-mutant in 3 patients, glioblastoma, IDH-mutant in 1, anaplastic astrocytoma, IDH-wildtype in 4, diffuse astrocytoma, IDH-mutant in 1, and diffuse astrocytoma, IDH-wildtype in 1. Genetic analyses detected H3F3A-K27M mutation in 2, HIST1H3B-K27M mutation in 1, IDH1-R132H mutation in 1, and IDH1-R132S mutation in 1. With a median follow-up of 23 months (range, 2–61), only 3 patients died 29–61 months after diagnosis, and the remaining 7 patients survived for 2–59 months. Neither IDH1 mutation nor H3K27M mutation was associated with survival in this series. CONCLUSION Survival of AYA patients with DMG was seemingly variable with some long survivors. H3K27M mutation was present in a subset of patients. A further study is warranted to correlate molecular profile with clinical pictures including patient survival.
NIMG-18. THE CLINICAL SIGNIFICANCE OF 13N-NH3, 18F-DOPA, AND 18F-FDG PET/CT IN THE DIFFERENTIAL DIAGNOSIS BETWEEN GLIOMA RECURRENCE AND TREATMENT EFFECTS
Authors: Cong Li, Chang Yi, Yingshen Chen, Shaoyan Xi, Cheng-Cheng Guo, Xiangsong Zhang, Zhongping Chen
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Glioma often recurs and the imaging evaluation whether the tumor has returned after glioma treatment is still challenging. PET/CT is one of the most important techniques to assess the post-treatment of glioma. However, differentiating tumor recurrence (TuR) from treatment effects (TrE) remains difficult. In this study, we aim to retrospectively compare the diagnostic performance of three PET tracers 13N-NH3, 18F-DOPA, and 18F-FDG on PET/CT in differentiating between TuR and TrE in post-treatment glioma patients. METHODS Forty-three patients with MRI-suspected recurrent glioma were included. The maximum and mean standardized uptake value (SUVmax and SUVmean) of the lesion and the lesion-to-normal Gray-matter cortex uptake (L/G) ratio were recorded and the reference standard was verified by surgical histopathology or more than 6 months of follow-up with clinical/radiological. The diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. RESULTS 34 patients were confirmed as glioma TuR and 9 patients met the standard of TrE. The median time interval from primary diagnosis surgery to PET/CT was 14.83 months (range, 4.10-62.77 months). The SUVmax of 13N-NH3 and 18F-DOPA PET/CT at the lesions was significantly higher than normal brain tissue (13N-NH3 0.696±0.095 vs 0.486±0.071, 18F-DOPA 0.455±0.079 vs 0.194±0.031, both P&amp;lt; 0.001), while 18F-FDG was not (6.918±0.525 vs 6.356±0.510, P=0.290). TuR showed significantly higher L/G ratios than TrE both in 13N-NH3 and 18F-DOPA PET/CT (13N-NH3, 1.573±0.099 vs 1.025±0.128, P=0.008; 18F-DOPA, 2.729±0.131 vs 1.514±0.141, P&amp;lt; 0.001). The sensitivity, specificity and the area under the curve (AUC) by ROC analysis were 57.7, 100% and 0.803 for 13N-NH3, and 84.6, 100% and 0.938 for 18F-DOPA respectively. CONCLUSIONS PET/CT is a powerful tool to distinguish glioma TuR from TrE, and 18F-DOPA PET/CT has remarkably better differential diagnosis efficacy than 13N-NH3 and 18F-FDG.
Does Prostate-Specific Membrane Antigen Avidity of Vertebral Hemangioma Change?
Authors: Kevser Oksuzoglu, Ceren Ozge Engur, Salih Ozguven, Halil Turgut Turoglu, Tanju Yusuf Erdil
Journal: Clinical Nuclear Medicine (2020)

Abstract Vertebral hemangiomas are the most common benign tumors of the spine and mostly occur in the thoracic spine. Mostly they are detected incidentally during imaging studies for other reasons. We present the case of vertebral hemangioma that showed prostate-specific membrane antigen uptake in the second 68 Ga–prostate-specific membrane antigen PET/CT, whereas no uptake was observed in the initial study.
COVD-02. COVID-19 AND CHILDHOOD CANCER CARE - THEMATIC ANALYSIS OF PUBLISHED SCIENTIFIC AND CLINICAL LITERATURE
Authors: Chris Barton
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The SARS-CoV-2 pandemic has affected modern medicine and healthcare provision profoundly. National and regional experiences with COVID-19 have been hugely variable across the globe, reflecting ethnic, governmental, cultural, economic and healthcare differences. This thematic analysis was performed to identify scientific and clinical literature relating to the impact of COVID-19 on children with cancer and treatment. METHODS The NHS Evidence portal was used to conduct a healthcare database advanced literature search. Duplicates were removed. Remaining results were screened using clear inclusion and exclusion criteria. RESULTS 172 results were identified and data extracted. Literature was identified from all 5 continents, with lower and middle income countries well represented. Key themes identified included: 1: Impact on patients already diagnosed, including decreased treatment regimens, impact on outpatient clinics, COVID susceptibility and travel restrictions; 2: Delays in presentation and diagnosis, and national screening programs; 3: The impact of COVID on healthcare professionals; 4: Impact on current and future research; 5: Consequence of global economic crisis on childhood cancer care; 6: Impact on long-term survivorship, late effects and surveillance monitoring. CONCLUSION COVID-19 has had a profound effect on health care, and the literature reflects the extent to which communities involved in childhood cancer care have worked together to minimise the impact. It is inevitable that there have been consequences of the pandemic on the treatment of existing patients, and the diagnosis of new ones, but evidence suggest these effects in the short term are minimal. The greatest concerns are for immediate and short-term research conduct.
MODL-13. GENETICALLY ENGINEERED PIG MODEL OF RHABDOID TUMOR PREDISPOSITION SYNDROME-1
Authors: Brian Na, C Dustin Rubinstein, Jennifer J Meudt, Jaclyn A Biegel, Alexander R Judkins, Brent P Lehman, Jamie L Reichert, Jeremie Vitte, Dhanansayan Shanmuganayagam, Marco Giovannini
Journal: Neuro-Oncology (2020)

Abstract Atypical teratoid/rhabdoid tumor (AT/RT) is the most common malignant CNS tumor of children below 6 months of age. The majority of AT/RT demonstrate genomic alterations in the SMARCB1 gene. There are two major hurdles in the development of safe and effective treatments for AT/RT: first, the mouse models do not fully recapitulate the disease seen in patients and their predictivity of clinical efficacy is still unproven. Second, due to a small patient population, the ability to recruit enough patients for clinical trials is challenging. Genetic studies have demonstrated that germline deletion of SMARCB1 exons 4 and 5 predisposes to AT/RT at an early age. Comparison of human, swine, and mouse SMARCB1 genes show similarities in gene and protein structure, with 100% amino acid identity between swine and human SMARCB1 isoforms. Thus, we hypothesized that germline deletion of exons 4 and 5 will predispose heterozygote swine to AT/RT development. SMARCB1+/- founder pigs are obtained using a CRISPR/Cas9 mediated gene-editing of conventional crossbred swine embryos, followed by embryo transfer into female swine surrogates. They are evaluated for clinical criteria used to diagnose AT/RT and by MRI at 6, 12, and 24 months of age, followed by histopathology and molecular analysis of the tumors as they are detected. Generating a large animal model of AT/RT would represent a breakthrough in the field from a genomic, pathophysiologic, pre-clinical and therapeutic perspective.
Radiomics For Surgical Planning and Prognostication
Authors: Nathaniel Braman
Journal: JAMA Network Open (2020)

Yunfang Yu, MD; Yujie Tan, MD; Chuanmiao Xie, MD, PhD; Qiugen Hu, MD; Jie Ouyang, MD; Yongjian Chen, MD; Yang Gu, MD; Anlin Li, MD; Nian Lu, MD; Zifan He, MD; Yaping Yang, MD; Kai Chen, MD; Jiafan Ma, MD; Chenchen Li, MD; Mudi Ma, MD; Xiaohong Li, MD; Rong Zhang, MD; Haitao Zhong, MD; Qiyun Ou, MD; Yiwen Zhang, MD; Yufang He, MD; Gang Li, MD; Zhuo Wu, MD, PhD; Fengxi Su, MD, PhD; Erwei Song, MD, PhD; Herui Yao, MD, PhD
PATH-26. RNA SEQUENCING OF FORMALIN-FIXED PARAFFIN-EMBEDDED SPECIMENS IN DIAGNOSTIC ROUTINE IDENTIFIES CLINICALLY RELEVANT GENE FUSIONS
Authors: Damian Stichel, Daniel Schrimpf, Jochen Meyer, Annika Wefers, Philipp Sievers, Stefan M Pfister, Wolfgang Wick, David T W Jones, Andreas von Deimling, Felix Sahm
Journal: Neuro-Oncology (2020)

Abstract Pediatric brain tumor entities harbor a variety of gene fusions. Whilst other molecular parameters like somatic mutations and copy number alterations have become pivotal for brain tumor diagnostics, gene fusions are only less well covered by routinely applied methylation arrays or targeted next-generation sequencing of DNA. In a routine diagnostic setting we established and optimized a workflow for investigation of gene fusions in formalin-fixed paraffin-embedded (FFPE) tumor tissues by using RNA sequencing. Assessing different tools for calling fusions from raw data, we found relevant fusions in 66 out of 101 (65%) analyzed cases in a prospective cohort collected over 26 months. In 43 (43%) cases the fusions were of decisive diagnostic relevance and in 40 (40%) cases the fusion genes rendered a druggable target. Besides the relevance of pathognomonic fusions for diagnostics, especially the detection of druggable gene fusions yields direct benefit to the patients. This approach allows for an unbiased search for fusion events in the tested samples. Besides rare variants of established fusions which were not detected by prior targeted analyses, we identified previously unreported fusion events. Exemplified on KIAA1549:BRAF fusion, we in addition provide an overview of the detection accuracy of different methods, including breakpoint detection in DNA methylation array data and fusion gene detection in DNA panel sequencing data. Our data show that RNA sequencing has great diagnostic as well as therapeutic value by clinically detecting relevant alterations.
Sphingosine 1-phosphate Receptor Modulator Therapy for Multiple Sclerosis: Differential Downstream Receptor Signalling and Clinical Profile Effects
Authors: Jerold Chun, Gavin Giovannoni, Samuel F. Hunter
Journal: Drugs (2020)

Lysophospholipids are a class of bioactive lipid molecules that produce their effects through various G protein-coupled receptors (GPCRs). Sphingosine 1-phosphate (S1P) is perhaps the most studied lysophospholipid and has a role in a wide range of physiological and pathophysiological events, via signalling through five distinct GPCR subtypes, S1PR1 to S1PR5. Previous and continuing investigation of the S1P pathway has led to the approval of three S1PR modulators, fingolimod, siponimod and ozanimod, as medicines for patients with multiple sclerosis (MS), as well as the identification of new S1PR modulators currently in clinical development, including ponesimod and etrasimod. S1PR modulators have complex effects on S1PRs, in some cases acting both as traditional agonists as well as agonists that produce functional antagonism. S1PR subtype specificity influences their downstream effects, including aspects of their benefit:risk profile. Some S1PR modulators are prodrugs, which require metabolic modification such as phosphorylation via sphingosine kinases, resulting in different pharmacokinetics and bioavailability, contrasting with others that are direct modulators of the receptors. The complex interplay of these characteristics dictates the clinical profile of S1PR modulators. This review focuses on the S1P pathway, the characteristics and S1PR binding profiles of S1PR modulators, the mechanisms of action of S1PR modulators with regard to immune cell trafficking and neuroprotection in MS, together with a summary of the clinical effectiveness of the S1PR modulators that are approved or in late-stage development for patients with MS.
GCT-09. HEALTH AND SOCIAL ISSUES IN THE LONG-TERM GERM-CELL TUMOR SURVIVORS
Authors: Tomoo Matsutani, Kentaro Horiguchi, Shiro Ikegami, Seiichiro Hirono, Hisayuki Murai, Naokatsu Saeki, Yasuo Iwadate
Journal: Neuro-Oncology (2020)

Abstract Germ cell tumor (GCT) is a rare juvenile CNS tumor that is more frequent in eastern Asia. Most survivors require continuous medical care for hormone replacement, maintenance of shunting devices, and late radiation-induced effects. In the present study, we retrospectively analyzed medical records of long-term GCT survivors, and make the health and social issues clear. Ninety-two GCT patients were treated in our institute from 1982 to 2018, and 81 patients, of which medical records are available, are included. The median follow-up period is 12.2 years, and 47 patients (58.1%) are followed for more than ten years. The overall survival rate is gradually decreasing more than ten years follow-up, such as 10-, 15- and 25-years survival are 92.3, 87.7, and 73.3%, respectively. In the long-term follow-up, eight subsequent malignancy and seven cerebrovascular events are recorded. These events occurred 20 years or more after the treatments, and six CNS malignancies were observed in survivors irradiated with 50Gy or more. As social issues, forty-two of 50 adult survivors had been employed after the treatments, but only thirty-four (70.8%) are still working. Of note, only nine (18.8% of adults) survivors got married. All four married women require any hormone replacement, while only one of 4 men requires the replacement. Long-term follow-up of GCT survivors revealed subsequent malignancy and social problems. A recent attempt to decrease the dose of irradiation might overcome some issues. As a conclusion, GCT survivors require a supporting program for not only health but also social issues.
Crisis Triage—Attention to Values in Addition to Efficiency
Authors: Matthew K. Wynia
Journal: JAMA Network Open (2020)

Hannah Wunsch, MD, MSc; Andrea D. Hill, PhD; Nicholas Bosch, MD, MSc; Neill K. J. Adhikari, MDCM, MSc; Gordon Rubenfeld, MD, MS; Allan Walkey, MD, MSc; Bruno L. Ferreyro, MD; Bourke W. Tillmann, MD; Andre C. K. B. Amaral, MD; Damon C. Scales, MD, PhD; Eddy Fan, MD, PhD; Brian H. Cuthbertson, MB, ChB, MD; Robert A. Fowler, MDCM, MS
EPID-03. SINGLE INSTITUTIONAL CLINICAL AND GENETIC ANALYSIS OF METASTATIC PROSTATE CANCER WITH AND WITHOUT BRAIN METASTASES
Authors: Ellen Jaeger, Albert Jang, John Xie, Pedro Barata, Elisa Ledet, Christopher Trevino
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Brain metastases (BMs) from metastatic prostate cancer (mPCa) are rare so little is known about clinical, genetic, and anatomic risk factors (RFs) for developing BMs. This single-center review of mPCa patients evaluates RFs for BM development. METHODS We reviewed records of mPCa patients at Tulane from 1991 – 2020 to evaluate disease, treatment, cell free DNA, and germline mutations between men with mPCa without confirmed BMs (smPCa) and men with mPCa and confirmed BMs (mPCaBMs). RESULTS We reviewed 580 patients with mPCa, of whom 11 had BMs (1.9%). Median age of stage 4 disease was 60.9 and 67.6 for men with mPCaBMs and smPCa respectively. Most mPCaBMs patients had Gleason 8 disease (81.8%) and higher median initial PSA (32 ng/mL) compared to 52.5% and 22.5 ng/mL for patients with smPCa. The development of castrate resistant disease (p=0.30) and overall survival (p=0.53) did not differ between the two populations. There were no differences in frequency of pathogenic mutations for the 68.9% (mPCaBMs) and 72.7% (smPCa) of patients with available genetic testing. Among the 11 mPCaBMs patients, 81.8% had supratentorial and 45.5% had infratentorial involvement (36.4% both). Forty-five percent had adjacent bony metastasis. Median time from SMs to BMs was 65 months (5.28 – 163.63 months), and median survival after diagnosis of BMs was 6.23 (0.49 – 70.82) months after treatment with WBRT, SRS, or GK. CONCLUSIONS The higher incidence of BMs likely reflects Tulane’s aggressive mPCa population. Interestingly 45% of BMs occurred from direct bony extension. Although 45% had infratentorial disease reflecting posterior fossa predilection, 82% of patients with BMs had supratentorial metastases. Our data suggest that men with mPCaBMs have aggressive disease and younger age at diagnosis. Due to sample size, no clinical or genetic statistically significant RFs for BMs were identified.