Patterns of bevacizumab use in patients with glioblastoma: an online survey among experts in neuro-oncology

Abstract Background Bevacizumab (BEV) received accelerated FDA approval in 2009 for the treatment of recurrent glioblastoma (rGBM). Unfortunately, prospective randomized controlled phase 3 studies (AVAglio and Radiation Therapy Oncology Group 0825 in newly diagnosed, European Organisation for Research and Treatment of Cancer 26101 in rGBM) failed to show an overall survival benefit with BEV added to standard therapy. In light of these data, we aimed to capture current utilization patterns and perceived value of BEV in the treatment of GBM among experts in the field. Methods An online questionnaire comprising 14 multiple choice questions was sent out in spring 2017 to 207 oncologists/neuro-oncologists treating patients with GBM at all National Cancer Institute–designated cancer centers in the United States. Results Sixty-two of 207 (30%) invitees responded (by training, 70% neuro-oncologists, 20% medical oncologists, 10% pediatric oncologists/neuro-oncologists). Participants reported use of BEV most frequently in rGBM for control of edema (85% of respondents) and/or when no other treatment options were available (68%). BEV is rarely used in newly diagnosed GBM (&amp;lt;5% of cases by 78% respondents and in 5% to 10% cases by 15% respondents). Sixty-six percent of participants indicated that they thought BEV improved symptoms, 30% that it improved symptoms and survival, 3% that it had no benefit in GBM patients. Conclusion In this cross-sectional online survey we found that among neuro-oncology experts in the United States in 2017, BEV is predominantly utilized in select patients with rGBM, and is only rarely used in a small subgroup of patients with newly diagnosed GBM for control of edema. The low response rate may have introduced a nonresponse bias. </jats:sec

The Design and Use of a Minimally-Invasive, Expandable Retractor for Deep-Seated Brain Lesions

Access to deep-seated brain lesions (e.g., tumors, aneurysms, hematomas, and other malformations) is challenging due to the potential for retraction-induced injury. Traditionally, neurosurgeons use dissection and blade retractors to push apart tissue to visualize and operate on target lesions. These blades apply focal pressure onto the brain, resulting in ischemia, edema, and parenchymal trauma, leading to complications in up to 29% of cases. Tubular retractors were introduced to distribute forces radially and have led to improved safety and clinical outcomes. However, reports indicate that tubular retractors still led to complications in up to 9.1% of cases. Other concerns include significant pressure in the direction of insertion and the displacement of anatomic landmarks leading to inaccurate stereotaxis. We present a novel, minimally-invasive brain retractor that utilizes an expandable soft balloon to further reduce retraction-induced injury and increase stereotactic accuracy with a minimal port of entry. The device consists of a balloon catheter system, a clear sheath, and integration with neuronavigation stylets. This approach can reduce the rate of iatrogenic injury and improve clinical outcomes for brain lesion operations. Furthermore, we illustrate the efficacy of this device in use compared to those of conventional tubular and blade retractors in a pig cadaver

Widely metastatic IDH1-mutant glioblastoma with oligodendroglial features and atypical molecular findings: a case report and review of current challenges in molecular diagnostics

Abstract Background Gliomas with 1p/19q-codeletion as well as mutation of isocitrate dehydrogenase (IDH) 1 are typically characterized as oligodendrogliomas with comparatively good response to treatment with radiation and chemotherapy. Case presentation We present the case of a 28-year-old man with an IDH1 and TP53 mutant high grade glioma with abnormalities in chromosomes 1 and 19 suggestive of anaplastic oligodendroglioma that rapidly progressed to widespread metastatic disease. Biopsy of a liver lesion confirmed metastasis of the patient’s known brain primary and chemotherapy with temozolomide was initiated. The patient’s rapidly growing tumor burden with fulminant liver failure and tumor lysis led to multisystem failure of which the patient died. Further molecular testing illustrated features more consistent with glioblastoma: multiple large chromosomal aberrations including loss of whole chromosome 1 and 2q; gain/amplification of MYCN, MET, and CDK4; loss of CDKN2A/B; and an ATRX mutation. Conclusion This case illustrates the importance of higher level molecular diagnostic testing for patients with particularly aggressive disease progression that is not concordant with standard prognoses. Additional data on cases with atypical alterations of 1p and 19q are needed to better understand the distinct biology of these cancers so that appropriate therapies can be developed

NIMG-55. A QUANTITATIVE ANALYSIS OF BRAIN VOLUME DYNAMICS IN PCNSL PATIENTS TREATED WITH HIGH-DOSE METHOTREXATE-BASED THERAPY

Abstract BACKGROUND Primary CNS lymphoma (PCNSL) is a rare, infiltrative disease. High-dose methotrexate (HD-MTX) is the backbone of induction regimens for PCNSL. While MTX-associated white matter changes are well-described, treatment-related brain volume loss is much less understood, especially in radiotherapy-naïve cohorts. Here, we aimed to longitudinally quantify the rates of brain volume loss in PCNSL patients treated with HD-MTX. SUBJECTS/METHODS We included 12 radiotherapy-naïve patients (age mean±SD 61±15y, range 37-84y, 9F) with histopathologically confirmed PCNSL who received HD-MTX induction (mean±SD 12±4 cycles, range 8-18) +/-rituximab. MRIs were collected from within 1 month of HD-MTX initiation until the end of follow-up (mean±SD: 3.7±2.9y). Longitudinal whole-brain segmentation was performed on FLAIR images using the Sequence Adaptive Multimodal Segmentation tool of FreeSurfer. Brain volumes were normalized to the initial scan, white matter lesion volumes were normalized to cerebral volume (nWML). RESULTS The average rate of cerebral volume change was -2.1±1.9%/year. Half of patients showed marked cerebral volume loss in the first year (-5.6±1.4% vs. -2.0±1.4%; n=10; p=0.003) with the most prominent change occurring within 6-months of treatment initiation (-4.2±1.7% vs. -0.5±1.6; n=12; p=0.004). Cerebral volume loss reached a plateau after the 1-year mark in both groups (0.3±0.8%/year vs. 1.4±3.3%/year; n=8; p=0.4). Patients younger than 61 years exhibited markedly higher rates of cerebral volume loss (-6.2±1.1%/year vs. 2.4±1.5%/year p=0.003), which was corroborated by strong inverse correlation between age and cerebral volume loss (Pearson’s r=-0.82, p=0.004). Neither the cerebellar volume, nor the nWML load correlated with age. CONCLUSION In the present cohort, brain volume loss was approximately four-fold higher than what is described in the healthy aging. Younger patients treated with HD-MTX exhibited more severe cerebral volume loss, which may be due to higher initial brain volume reserve. Detailed analyses of a larger sample are underway. </jats:sec

Additional file 1: of Widely metastatic IDH1-mutant glioblastoma with oligodendroglial features and atypical molecular findings: a case report and review of current challenges in molecular diagnostics

Figure S1. Routine hematoxylin and eosin stains (H&E) show separate and adjacent areas of lower grade (WHO grades II to III) infiltrating glioma (A, 200X; B, 200X). These areas were positive for IDH1 (R132H) mutant protein by ancillary immunohistochemical staining (C). Figure S2. Hematoxylin and eosin stains with neoplastic tissue largely composed of patternless sheets of cells (A, 100X; B, 40X; C, 200X) with rounded cytoplasmic contours, variable amounts of eosinophilic cytoplasm with minimal to no stellate cellular processes (D, 400X; E, 400X; F, 200X), large nuclei, and variably prominent nucleoli (D). Necrosis was predominantly zonal and frequently associated with sclerosed or thrombosed blood vessels (B, 40X). Rare foci suspicious for vascular invasion were also noted (E, 400X). Rare fragments showed adjacent areas of lower grade, infiltrating glioma (A). Figure S3. Single nucleotide polymorphism (SNP) array data using Illumina HumanCytoSNP-850K (v1.1) BeadChip platform (approximately 850,000 SNPs) and iScan microarray system and illustrated with KaryoStudio v2.0 software; red data show smoothed signal intensity values (LRR) (Log base 2 ratio of observed and expected intensities; LogR 0, copy number two) and blue data points represent the B-allele frequency (BAF) of each individual SNP (B-allele frequency of 0 equals no B-allele; 1 equals only B-alleles present). Loss of chromosomal segments is supported by the downward shift of the red vertical line (decrease in LRR, left shift) and loss of heterozygosity (LOH) in BAF (loss of heterozygous BAF track around 0.5 with variable redistribution of BAF in in region of LOH associated with the ratio of tumor to normal DNA in the sample), while gains/amplifications of genomic regions show upward shifts of the red vertical line (increase in LRR, right shift) and LOH in BAF. Other chromosomal variations, including gain of 7p and loss of 2q, 10p, 11p, 21q, and whole chromosomes 12 and 14 were noted. Table S1. Next generation sequencing panel covering the full coding regions of 644 cancer associated genes showed the presence of a number of additional genetic alterations. (DOCX 3476 kb

Metadata record for: HIT-COVID, a global database tracking public health interventions to COVID-19

This dataset contains key characteristics about the data described in the Data Descriptor HIT-COVID, a global database tracking public health interventions to COVID-19. Contents: 1. human readable metadata summary table in CSV format 2. machine readable metadata file in JSON forma

HIT-COVID, a global database tracking public health interventions to COVID-19

AbstractThe COVID-19 pandemic has sparked unprecedented public health and social measures (PHSM) by national and local governments, including border restrictions, school closures, mandatory facemask use and stay at home orders. Quantifying the effectiveness of these interventions in reducing disease transmission is key to rational policy making in response to the current and future pandemics. In order to estimate the effectiveness of these interventions, detailed descriptions of their timelines, scale and scope are needed. The Health Intervention Tracking for COVID-19 (HIT-COVID) is a curated and standardized global database that catalogues the implementation and relaxation of COVID-19 related PHSM. With a team of over 200 volunteer contributors, we assembled policy timelines for a range of key PHSM aimed at reducing COVID-19 risk for the national and first administrative levels (e.g. provinces and states) globally, including details such as the degree of implementation and targeted populations. We continue to maintain and adapt this database to the changing COVID-19 landscape so it can serve as a resource for researchers and policymakers alike.</jats:p