bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-44. NON-INVASIVE ADVANCED IMAGING METRICS PROVIDE POTENTIAL BIOMARKERS FOR GBM BIOLOGICAL HETEROGENEITY AND IMMUNE LANDSCAPE VARIANCE
Authors: Kersch Cymon , Muldoon Leslie , Fu Rochelle , Claunch Cheryl , Neuwelt Edward , Barajas Ramon 
Published: November 2019

Abstract

BACKGROUND
Treatment of glioblastoma multiforme (GBM) is complicated by extensive tumor heterogeneity. We hypothesize that transcriptomic analysis of brain tumor regions with different magnetic resonance imaging (MRI) characteristics will define specific biological processes, providing a non-invasive method for tumor characterization and stratification.

METHODS
Previously at the University of California San Francisco, treatment naïve GBM tissue from gadolinium contrast enhancing lesion (CEL) and non-enhancing lesion (NCEL) regions were stereotactically sampled; prior to resection, relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were determined. The tissue samples were characterized by immunohistochemistry and assessed for gene expression by microarray analysis. We correlated gene expression patterns in the CEL, NCEL, and non-tumor gliotic brain samples with multimodal physiological imaging metrics and immunohistochemical phenotypes. Gene expression networks were probed using Gene Set Enrichment Analysis. Key immunologic genes were examined individually.

RESULTS
Samples with differing MRI and histological phenotypes demonstrated transcriptomic variance reflecting distinct biological networks. We found significant differences in immune pathways, with immune gene signature prominent in CEL areas, moderate in NCEL and low in gliotic non-tumor brain. Within homogenously enhancing areas of CEL and NCEL there was underlying heterogeneity detectable by variable rCBV, ADC and histological phenotypes, which correlate with differing gene expression profiles indicative of biological and immunological tumor microenvironments. Increasing rCBV was correlated with an anti-inflammatory immune response in the CEL and a pro-inflammatory immune response in the NCEL. ADC was negatively correlated with cell cycle and immune networks in CEL, while NCEL ADC was positively correlated with immune processes. GBM samples with the mesenchymal molecular subtype had the greatest immune response.

CONCLUSIONS
Multimodal MRI features identify regionally diverse transcriptomic-based biological and immunological phenotypes in GBM. We propose that imaging genomics provides a technique for localizing biological processes and tumor immune microenvironments across space and time in GBM.
NIMG-45. 3D SINGLE-SCAN FOR MULTI-CONTRAST-WEIGHTED MRI FOR LESION DETECTION IN PATIENTS WITH GLIOMAS
Authors: Liu Jing , Jakary Angela , Lafontaine Marisa , Wang Yan , Xu Duan , Saloner David , Butowski Nicholas , Hess Christopher , Villanueva-Meyer Javier , Chang Susan , Lupo Janine 
Published: November 2019

Abstract

INTRODUCTION
Multi-contrast-weighted (MCW) MRI allows derivation of T1-weighted, T2-weighted, and T2-FLAIR images and their parametric maps. Under current practice, these high-resolution 3D MR images are acquired separately with a total scan time is approximately 30 minutes. The goal of this study was to develop a novel sequence and processing strategy for MCW MRI and lesion detection of gliomas with 1mm isotropic resolution in 6 minutes, which can significantly improve clinical imaging workflow. The proposed whole brain, single-scan method enables the generation of segmented tumor regions that correspond the hyperintense lesion on T2-weighted or T2-FLAIR images (T2L).

METHODS
Our strategy involves using a highly accelerated 3D MRI sequence to achieve whole brain, MCW images that can be jointly segmented with modified k-means clustering. Six patients with enhancing gliomas were scanned with this sequence before the injection of gadolinium, 4 of which also received a repeat scan post-gadolinium. Our automatic segmentation of the T2L and manual definition of the contrast-enhancing lesion (CEL) was compared against manually segmented lesions drawn from conventional anatomical imaging.

RESULTS
Whole-brain MCW MRI was achieved with 1mm isotropic resolution in 6 mins. Grey-matter, white-matter, CSF, and the T2L could be automatically segmented with our clustering method. The resulting automatically-segmented T2L volume was not significantly different between our new sequence and clinically defined regions (average Dice Coefficient=0.81(+/-0.05); p=0.95).

CONCLUSIONS
Our novel, 6-minute scan and processing strategy was able to generate MCW anatomical images and automatically segment grey-matter, white-matter, and T2L volumes that were similar to manual segmentation of conventional anatomical imaging. We are currently extending the automatic segmentation to the CEL. This approach has the potential to improve clinical workflow by allowing time for therapy-specific advanced imaging and providing a noninvasive tool for monitoring tumor evolution. Validation is currently being performed in a larger cohort.
NIMG-54. DIFFUSION MRI PHENOTYPES PREDICT OVERALL SURVIVAL BENEFIT FROM BEVACIZUMAB IN RECURRENT GLIOBLASTOMA WITH A LARGE TUMOR BURDEN: EVIDENCE FROM CLINICAL PRACTICE AND A MULTICENTER PHASE 3 TRIAL
Authors: Patel Kunal , Raymond Catalina , Yao Jingwen , Tsung Joseph , Goldman Jodi , Schlossman Jacob , Tran Caleb , Brenner Andrew , Butowski Nicholas , Wen Patrick , Pope Whitney , Ji Matthew , Lai Albert , Leia Nghiemphu P , Rachmilewitz Minei Tamar , Cohen Yael , Harats Dror , Cloughesy Timothy , Ellingson Benjamin 
Published: November 2019

Abstract
We have previously shown that diffusion MR characteristics are a predictive imaging biomarker for survival benefit in recurrent glioblastoma treated with anti-VEGF therapy; however, contemporary clinical use of bevacizumab is often limited to patients with very large tumors and/or after multiple recurrences. We hypothesize that diffusion MR characteristics can be used to predict long-term survival benefit in these patients, which may be beneficial for clinical decision-making. The current study identified 83 recurrent glioblastoma patients from our institution who were treated with bevacizumab over the past 5 years with high quality anatomic and diffusion MRI data. Of these 83 patients, 35 had large contrast enhancing tumors (>20cc or >3.4cm diameter, group average). Additionally, we identified 37 recurrent glioblastoma patients from the bevacizumab treated control arm of a recent multicenter phase III trial (NCT02511405) with high quality data and large enhancing tumors for validation. Pre-treatment tumor volume was quantified using T1 subtraction maps and apparent diffusion coefficient (ADC) histogram analysis was used to phenotype patients as having high (> 1.24 um2/ms) or low (< 1.24 um2/ms) ADCL, the mean value of the lower peak using a double Gaussian mixed model. Median overall survival in patients with large volume recurrent glioblastoma was ~5.7 months. High ADCL was associated with significantly longer overall survival (OS) compared with low ADCL in both single center (P=0.0271, HR=0.486, mOS=5.5 vs. 2.8mo) and multicenter phase III data (P=0.0457, HR=0.507, mOS=7.9 vs. 5.7mo). Accounting for absolute tumor volume and age, both cohorts showed that ADCL was an independent prognostic factor for OS (Cox, P< 0.01). In summary, pre-treatment diffusion MR imaging is an independent predictive biomarker for OS in recurrent glioblastoma with a large tumor burden.
NIMG-58. SEX DIFFERENCES IN CONTRAST-ENHANCING GLIOMAS AT PRESENTATION
Authors: Johnston Sandra , Khurana Aditya , Whitmire Paula , Sharma Akanksha , Hawkins-Daarud Andrea , Ranjbar Sara , Hu Leland , Rubin Joshua , Egan Kathleen , Canoll Peter D , Porter Alyx , Mrugala Maciej , Kumthekar Priya , Swanson Kristin 
Published: November 2019

Abstract
Sex differences in brain tumor related epilepsy (BTE) as an initial symptom of glioma are rarely investigated. Sex differences are being explored with increased interest more recently. Epidemiological studies have generally indicated overall incidence of epilepsy to be slightly higher in males than females, but a higher incidence of idiopathic generalized epilepsy has been seen in females in some studies. Clinicians regularly face the challenge of anti-epileptic drug prescription determination in patients with newly identified brain mass and would greatly benefit from knowing clinical characteristics in BTE. We analyzed clinical characteristics in patients with pathologically-determined glioma with known seizure status at clinical presentation using non-parametric and Fisher’s Exact tests with the entire cohort and male and female separately. From our clinical data repository, we identified 223 patients (females, n=86 (39%); males, n=137 (61%)) divided by those that presented with seizure (SP, n=96, 43%; F, n= 28; M, n= 68) and those that presented without seizure (nSP, n=127, 57%, F n=58, M n=69). In sex-specific analysis males had a significantly (x2=6.28, p=0.01) higher proportion of SP (49.6%) than females (32.6%). There was a dependence between seizure presentation status and tumor grade in males (x2=5.94, p=0.015). Tumor kinetics in the female cohort showed significantly (p< 0.0001) more diffuse tumors in SP compared to nSP. Right-sided tumors were predominantly nSP, while left-sided tumors were split more evenly between SP and nSP. The predominance of nSP among right-sided tumors seems to be driven by females (74%), male right-sided tumors were split more evenly between SP and nSP. Seizure status is dependent on tumor location for the combined cohort, however not for males (x2=5.23, p=0.16) or females (x2=4.34, p=0.23). Clearly there are sex differences and similarities in clinical characteristics at glioma presentation. Further characterization could lead to improved adherence of national standards for AED prescription.
NIMG-65. PREDICTING PROGNOSIS AND CANCER HOTSPOT MUTATIONS USING QUALITATIVE MR IMAGING ANALYSIS IN GLIOBLASTOMA
Authors: Verduin Maikel , Compter Inge , Primakov Sergey , van Kuijk Sander , te Dorsthorst Maarten , Revenich Elles , ter Laan Mark , Pegge Sjoert , Meijer Anton , Beckervordersandforth Jan , Jan Speel Ernst , Jochems Arthur , de Leng Wendy , Anten Monique , Broen Martijn , Ackermans Linda , Schijns Olaf , Vooijs Marc , Tjan-Heijnen Vivianne , Lambin Philippe , Eekers Danielle , Jacobi-Postma Linda , Hoeben Ann 
Published: November 2019

Abstract

INTRODUCTION
Tumor heterogeneity poses one of the major limitations in improving the treatment for glioblastoma (GBM), which calls for new clinically relevant predictive models. This study aims to investigate non-invasive diagnostic methods, including patient characteristics and qualitative imaging analysis as a prognostic classifier and predictor for druggable oncogenes.

METHODS
We performed a retrospective analysis on 143 GBM patients (discovery cohort). Diagnostic MRIs were re-analyzed for qualitative imaging features (VASARI features). DNA was extracted from formalin-fixed, paraffin-embedded GBM tissue of the discovery cohort for next-generation sequencing (Ion Torrent Cancer Hotspot panel v2Plus), TERT-promoter mutation and MGMT-methylation analysis. Multivariable regression analysis was used to determine the prognostic and predictive value of VASARI features.

RESULTS
Of the 143 patients, median age was 61.4 years (range 15.5–84.6) with a median overall survival of 12 months (range 0–142). We observed IDH1 R132H mutation in 8.5%, MGMT-promotor methylation in 26.1%, TERT-promotor mutation (C250T;C228T) in 69.5%, EGFR mutation in 20.3% and EGFR amplification in 37.5% of all patients. A set of eight VASARI features was identified to be associated with overall survival (p< 0.001), which is currently being validated in an external dataset (n= 184). Interestingly, VASARI features appeared to be associated with IDH1-mutation (four features, p=0.004), TERT-promotor mutation (five features, p-value < 0.001), EGFR mutation (five features, p-value < 0.001) and EGFR amplification (seven features, p-value < 0.001) but not with MGMT-methylation (two features, p-value=0.054). Additional cancer hotspots are currently being analyzed and internal validation is ongoing.

CONCLUSION AND FUTURE PERSPECTIVES
We propose an integrated prognostic classifier comprising MRI features, also associated with GBM-specific molecular alterations. Additionally, quantitative MRI radiomics features are being extracted from the discovery and validation set and incorporated in the prognostic classifier. Subsequently, radiomics and VASARI features will be correlated to intratumoral heterogeneity, assessed by tissue micro-array analysis of the discovery cohort.
NIMG-73. NEUROLOGICAL ASSESSMENT IN NEURO-ONCOLOGY (NANO) CORRELATES WITH INTEGRATED PREDICTIVE RADIOGRAPHIC BIOMARKERS OF PROGRESSED HIGH GRADE ASTROCYTIC TUMORS (IPROMPT): A PROPOSED SUPPLEMENT TO RANO
Authors: Tosha Gatson Na , Bross Shane , Lockard Laura , Leese Erika , Manikowski Jesse , Mahadevan Anand , Conger , Andrew , Mongelluzzo Gino 
Published: November 2019

Abstract
This year nearly 86,000 persons in the US will be diagnosed with a primary brain tumor. Glioblastoma (GBM) is the deadliest and most common of these tumors in adults with overall survival around 15mos. Disease progression is inevitable, and effective second-line therapies are few. Delays in identifying progressed GBM risks neurologic decline, continuation of ineffective therapies, and increased tumor-mutational-burden, potentially rendering treatment less-effective. Brain tumor imaging can be ambiguous and is an active topic in neuro-oncology as there are currently no validated approaches to assessment of tumor treatment response. We present a single institution database including 622 gross-totally-resected GBMs (2006–2018) to evaluate changes in T2/FLAIR signal intensity (T2FSI), diffusion restriction, and contrast enhancement both in and around the resection cavity (RC) to determine earliest indicators of tumor progression. Analysis of NANO score was completed to correlate with predicted tumor progression. This is an early data release of an ongoing two-phased retrospective/prospective study with findings that support a novel integration of radiographic sequences and NANO to supplement established RANO criteria in earlier detection of GBM progression. Of 622 confirmed GBMs, 158 fit the rigorous criteria – included here are 58 cases. We report 70% (n=41) of patients show RC T2FSI correlating with restricted diffusion and increasing NANO score (0.5–1.4) as early as 3.8mos prior to and at time of radiographic progression, respectively. Previous studies have reported similar T2FSI but without associated NANO, less rigid inclusion criteria, and limited MRI sequences. We also report imaging phenomena, not previously described, such as FLAIR migration and FLAIR coring timed closely with progression. The proposed technique uses routine MRI, therefore readily standardized in clinical practice. With further validation, this novel integration of imaging and neurologic assessment might serve to supplement existing response criteria in GBM and improve clinician confidence in earlier detection of progression.
NCMP-01. RISK FACTORS ASSOCIATED WITH LATE HYPERGLYCEMIA IN BRAIN TUMOR PATIENTS WITH POSTOPERATIVE ADMINISTRATION OF DEXAMETHASONE
Authors: Ho Yang Seung 
Published: November 2019

Abstract
Dexamethasone is the corticosteroid most commonly used for the management of vasogenic edema in patients with brain tumors. The occurrence of hyperglycemia following corticosteroid administration is well known to physicians and health care givers. The purpose of the study is to investigate late onset of hyperglycemia and associated factors in patients with brain tumors. The inclusion criteria are as follows; 1) brain tumor patients underwent craniotomy; 2) steroid administered for at least 3 days longer perioperatively or postoperatively; 3) serum glucose levels examined for at least 3 months postoperatively The exclusion criteria are as follows; 1) steroid administered for less than 3 days; 2) patients diagnosed with type 1 diabetes, renal failure, hepatic failure or autoimmune diseases; 3) other medical illness treated with corticosteroid. A total of 101 patients were enrolled for the analysis. Fasting blood glucose of diabetes patients and non-diabetes patients was 160±93 mg/dl and 114±43 mg/dl, respectively. There was no difference of type of brain tumors, body mass index, hypertension, smoking history, hyperlipidemia, GOT, GPT, ESR, CRP, and Cr between diabetes patients and non-diabetes patients. The peak of Fasting blood glucose was noted on day 1 postoperatively in non-diabetes patients. Two peak of Fasting glucose levels were found on day 1 and 6 postoperatively in diabetes patients. Late hyperglycemia was determined as in patients with fasting blood glucose of >125 mg/dl during 3~6 months postoperatively. Fifteen patients out of 86 non-diabetes patients developed late hyperglycemia. There were significant differences of duration and total dose of dexamethasone administration between late hyperglycemia patients and non-late hyperglycemia patients. Steroid-induced hyperglycemia can develop late postoperatively even in non-diabetic patients with brain tumor treated with dexamethasone. Fasting blood glucose during the first week postoperatively can predict late hyperglycemia. Duration and total dosage of dexamethasone administered are associated with late hyperglycemia.
NCMP-07. SECONDARY ADRENAL INSUFFICIENCY IN ADULT PATIENTS WITH GLIOMA: A CASE SERIES
Authors: Mantilla Emmanuel , Abramowitz Jessica , Dan Tu , Pan Edward 
Published: November 2019

Abstract

Glucocorticoids (GC) are a mainstay in the treatment of gliomas to reduce cerebral edema and improving symptoms related to swelling. Prolonged GC use can lead to adrenal insufficiency (AI) due to the suppression of the hypothalamic-pituitary-adrenal axis. AI is challenging to diagnose as the tumor itself or the chemotherapy are blamed for the symptoms. This study aims to evaluate the risk factors predisposing patients with gliomas to develop AI during their treatment course.

METHODS
This is a retrospective case review. Charts in the neuro-oncology clinic from July 2018 to March 2018 were reviewed. Inclusion criteria include > 18 y/o, diagnosis of glioma WHO Grade II to IV, and diagnosis of secondary AI. Demographic profile, tumor characteristics, radiation dose, exposure or proximity to HPA, current treatment, and dexamethasone dose and duration of treatment were tabulated and compared.

RESULTS
Nine of ten patients were started on high dose of dexamethasone (> 8mg daily), and only one was started on a lower dose (< 4mg daily). Majority of the patients (50%) were on dexamethasone for less than a year (4–8 months), and a significant portion (40%) of the patients remained on dexamethasone for > 2 years, with one patient on steroids for 64 months. The minimum dose of dexamethasone needed to prevent symptoms ranged from 0.5mg to 2mg daily. Most received 60Gy of radiation, two received 59.4 Gy, and one received 54 Gy. Six patients had radiation exposure to the HP axis, while four didn’t.

CONCLUSION
Secondary adrenal insufficiency results from prolonged glucocorticoid use in patients with glioma. Dose and duration of GC are risk factors to its development. Radiation to the HPA axis may be a contributing factor to the development of AI in patients with glioma, although it can also be seen in patients with radiation distant from the HPA.
NCMP-19. STROKE IN CANCER PATIENTS
Authors: Ching Marilou , Komlodi-Pasztor Edina 
Published: November 2019

Abstract
Patients with malignancy have an increased tendency for venous and arterial embolism, and for increased risk for bleeding. Clinical decisions regarding anticoagulation in this population has been challenging and complicated by the availability of various anticoagulants. Currently, there is no evidence-based guideline available for the prevention of arterial embolism and thrombosis, such as stroke, in cancer patients. The aim of the study is to assess the use of anticoagulant medications in cancer patients who suffer a stroke. ICD-9/-10 codes were used to identify patients with cancer who were admitted between September 1, 2017 and November 30, 2017 to the Buffalo General Hospital with the diagnosis of stroke. Chart review was used to verify the history of cancer and stroke and to collect additional information. The diagnosis of acute stroke and cancer were verified in 87 patients. Among them, 31 patients had active malignancy. Of the 31 patients, 9 were diagnosed with intracranial hemorrhage and 22 with ischemic strokes. Of the 9 patients with intracranial hemorrhage,3 were anticoagulated and 1 patient was off anticoagulation. Of the 22 patients with ischemic stroke, 4 patients were anticoagulated, although 1 patient was underdosed based on INR. Seven of the 22 patients were taken off of anticoagulation; 3 had side effects and 4 were awaiting a surgical procedure. Five of the 9 patients with intracranial hemorrhage and 10 of the 22 patients with ischemic stroke were made comfort care and passed away shortly after the diagnosis of stroke.
PDCT-02. UNIQUE CONCURRENT ASSOCIATION OF SOMATIC AND GERMLINE NF1 MUTATIONS WITH GERMLINE MISMATCH REPAIR MUTATIONS IN PEDIATRIC GLIOBLASTOMA MULTIFORME
Authors: Baig Muhammed , Fuller Greg , Gupta Sumit , Tran Grace , Mork Maureen , Slopis John , Kamiya Carlos , Khatua Soumen , Zaky Wafik , Sadighi Zsila 
Published: November 2019

Abstract

INTRODUCTION
We report the first known cases of pediatric glioblastoma (GBM) with prior clinical NF1 diagnoses, one with concurrent germline Lynch syndrome (LS) and NF1, and the other with somatic NF1 mutation and germline constitutional mismatch repair deficiency (CMMRD). Pediatric GBMs in NF1 are rare but increase with age. LS and CMMRD differ by inheritance: autosomal dominant with heterozygous germline mutation (LS), or biallelic mutation (CMMRD) of one of the 4 (possibly 5) MMRD genes (MLH1, MSH2, MSH6, PMS2, or MSH3) - both can develop GBM.

METHODS
Two pediatric GBM cases with prior NF1 clinical diagnoses (neurocutaneous stigmata) were reviewed. Next generation sequencing and immunohistochemical staining were used for somatic and germline NF1 and MMR gene mutation detection, and for MMR protein expression, respectively.

RESULTS
Sixteen-year-old male with prior NF1 clinical diagnosis had headaches for one year preceding diagnosis and resection of right frontal GBM with somatic mutations of POLE and PMS2, but not NF1. His father had confirmed LS with MSH2 mutation and no neurocutaneous stigmata. Patient’s germline testing revealed pathogenic MSH2 and NF1 mutations, confirming LS and NF1. Current treatment is chemoradiation. Nineteen-year-old male with former NF1 clinical diagnosis had 2 GBMs, first in left midbrain diagnosed and biopsied (after 3 months of right hemiparesis) with somatic PMS2 and NF1 mutations, and a second left frontal lobe tumor diagnosed and resected 11 months later, with 2 pathogenic germline mutations of PMS2, inherited one from each parent, confirming CMMRD without NF1. Treatment was focal radiation administered to both sites followed by adjuvant chemotherapy.

CONCLUSION
Children with NF1 stigmata and GBM may have either concurrent NF1 and LS, or CMMRD with NF1 somatic mutations. Confirmatory germline and somatic MMR gene and NF1 mutation testing in children with GBM and NF1 stigmata should be considered as the specific diagnosis affects management.