bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-28. VALIDATION OF MODIFIED RESPONSE ASSESSMENT IN NEURO ONCOLOGY (mRANO) DETERMINED PFS AS A STRONG PREDICTOR OF OVERALL SURVIVAL IN RECURRENT GLIOBLASTOMA TREATED WITH A TARGETED IMMUNOTOXIN
Authors: Ellingson Benjamin , Chandhasin Chandtip , Coello Melissa , Merchant Nina , Merchant Fahar 
Published: December 2020

Abstract

INTRODUCTION
The current study compared the modified response assessment in neuro-oncology (mRANO)(1), iRANO (2), and standard RANO criteria (3) as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM).

METHODS
A total of 47 patients with rGBM were enrolled in a phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and an independent radiologic faculty (IRF), then standard RANO, iRANO, and mRANO criteria were applied. Differences of PFS and the association between PFS and OS were evaluated.

RESULTS
41 of 47 patients were evaluable for response. Both local site and IRF-determined PFS was significantly shorter using standard RANO compared to iRANO (log-rank, P&lt; 0.0001; HR=0.3) and mRANO (P&lt; 0.0001; HR=0.3). No difference in PFS was observed between iRANO and mRANO (Local, P=0.67; IRF, P=0.59). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (Local, P=0.47; IRF, P=0.34). Using the iRANO, a weak association driven by a few outliers was observed between confirmed PFS and OS via local site measurements (P=0.017), but not central IRF measurements (P=0.18). Importantly, 24 of 41 patients (59%) were censored using iRANO and not included because they did not have confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2=0.66, P&lt; 0.0001) and IRF-determined reads (R2=0.57, P=0.0007).

CONCLUSION
No correlation between PFS and OS was observed for standard RANO or iRANO, but a strong correlation was identified between both locally-determined and centrally-determined PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.
NIMG-39. UTILITY OF PHYSIOLOGIC MR METRICS IN DISTINGUISHING TRUE-PROGRESSION FROM PSEUDOPROGRESSION IN GLIOBLASTOMAS STRATIFIED BY MGMT PROMOTER METHYLATION
Authors: Chawla Sanjeev , Wang Sumei , Nazem Amir , Burke Morgan , MacLean Nasrallah , Bagley Stephen , Brem Steven , Mohan Suyash 
Published: December 2020

Abstract

BACKGROUND
Methylation of O6-methyl-guanine-methyl transferase MGMT gene promoter is associated with favorable prognosis in glioblastoma (GBM) patients treated with surgery and chemoradiation therapy (CRT).

OBJECTIVE
To investigate potential of diffusion and perfusion MR imaging in distinguishing TP from PsP in GBM patients stratified by MGMT status.

METHODS
A cohort of 92 patients demonstrating new/increasing enhancing lesions within six months of completion of CRT underwent 3T MR imaging. Median values of mean diffusivity (MD), fractional anisotropy (FA), anisotropy coefﬁcients [linear(CL), planar (CP), and spherical (CS)] and maximum relative cerebral blood volume (rCBVmax) were computed from enhancing lesions. Patients were classified as TP (n=65) and PsP (n=27) based on histopathology or follow-up MRI scans. Mann-Whitney, independent-sample T-tests and receiver operating characteristic (ROC) curve analyses were performed to distinguish TP from PsP. Of 92 patients, MGMT status was available from 60 patients [MGMT-methylated (n=23) and MGMT-unmethylated (n=37)]. Statistical analyses were also performed in distinguishing TP (n=15) and PsP (n=8) from MGMT-methylated and MGMT-unmethylated subgroups (TP=28; PsP=9). A p-value of 0.05 was considered significant.

RESULTS
Significantly higher rCBVmax and FA and a trend towards higher CP were observed in TP compared to PsP. Among these parameters, rCBVmax had the best sensitivity=62%, specificity=68% and accuracy=67% in distinguishing TP from PsP. ROC analysis revealed sensitivity=54%, specificity=78% and accuracy=68% after combination of these parameters. In MGMT methylated patients, only rCBVmax was significantly higher in TP than in PsP with sensitivity=79%, specificity=67% and accuracy=74% at a threshold rCBVmax value of 2.23. In MGMT unmethylated group, a trend towards higher rCBVmax was observed in TP than in PsP with sensitivity=67%, specificity=77%, accuracy=69%, threshold value=2.89.

CONCLUSION
Physiologic imaging parameters demonstrate variable diagnostic values for detecting PsP in GBM patients stratified by MGMT status. The best parameter in distinguishing TP from PsP was rCBVmax in patients demonstrating MGMT promoter methylation.
NIMG-40. RADIOGENOMIC SIGNATURES OF DRIVER GENES IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS BASED ON PRE-OPERATIVE MULTI-PARAMETRIC MRI
Authors: Fathi Kazerooni Anahita , Toorens Erik , Bakas Spyridon , Akbari Hamed , Sako Chiharu , Mamourian Elizabeth , Ha Sung Min , Thakur Nina , Rosado Jennifer-Marie , Bagley Stephen , Ganguly Tapan , MacLean Nasrallah , Davatzikos Christos 
Published: December 2020

Abstract

PURPOSE
Non-invasive and quantitative biomarkers of somatic mutations derived from multi-parametric MRI (MP-MRI) could potentially help in predicting the response of patients to therapy, leading to development of targeted and personalized treatments. In this study, we developed radiogenomic signatures of multiple driver genes using artificial intelligence (AI) methods.

METHODS
In this study, 2740 radiomic features, including shape and volumetric measures computed for different tumorous regions, and characteristics derived from histograms and gray-level co-occurrence matrix (GLCM), were extracted from pre-operative MP-MRI (T1, T1Gd, T2, T2-FLAIR, DTI, and DSC-MRI) scans of 161 patients with newly diagnosed glioblastoma. The tumor samples, collected surgically from these patients, were sequenced using an in-house targeted next generation sequencing (NGS) panel of genes. We constructed quantitative imaging signatures of somatic mutations in several genes from 161 IDH-wildtype glioblastoma patients, including ATRX, FGFR2, EGFR, MET, NF1, PDGFRA, PIK3CA, PTEN, RB1, TP53, using cross-validated SVM classifiers.

RESULTS
The cross-validated classification performance for each signature was assessed by area under the receiver operating characteristic (ROC) curve (AUC), indicating the following results: PTEN (n = 69, AUC = 0.64), EGFR (n = 52, AUC = 0.72), TP53 (n = 51, AUC = 0.67), NF1 (n = 33, AUC = 0.74), ATRX (n = 22; AUC = 0.74), FGFR2 (n = 6, AUC = 0.82), MET (n = 26, AUC = 0.77), PDGFRA (n = 14, AUC = 0.82), PIK3CA (n = 14, AUC = 0.78), RB1 (n = 14, AUC = 0.81).

CONCLUSION
Using multi-parametric MRI, we developed quantitative non-invasive in vivo signatures with the potential for pre-operative assessment of a glioblastoma’s molecular characteristics. These non-invasive radiogenomic biomarkers may be useful for understanding the molecular composition of a glioblastoma prior to surgical resection, thus enabling earlier selection of patients for targeted therapy trials and possible neoadjuvant treatment.
NIMG-46. RADIOGENOMIC FEATURES PREDICT CLINICALLY RELEVANT GENOME-WIDE ALTERATION SIGNATURES IN GLIOBLASTOMA
Authors: Nuechterlein Nicholas , Li Beibin , Fink James , Haynor David , Holland Eric , Shapiro Linda , Cimino Patrick 
Published: December 2020

Abstract

BACKGROUND
Previously, we have shown that combined whole-exome sequencing (WES) and genome-wide somatic copy number alteration (SCNA) information can separate IDH1/2-wildtype glioblastoma into two prognostic molecular subtypes (Group 1 and Group 2) and that these subtypes cannot be distinguished by epigenetic or clinical features. However, the potential for radiographic features to discriminate between these molecular subtypes has not been established.

METHODS
Radiogenomic features (n=35,400) were extracted from 46 multiparametric, pre-operative magnetic resonance imaging (MRI) of IDH1/2-wildtype glioblastoma patients from The Cancer Imaging Archive, all of whom have corresponding WES and SCNA data in The Cancer Genome Atlas. We developed a novel feature selection method that leverages the structure of extracted radiogenomic MRI features to mitigate the dimensionality challenge posed by the disparity between the number of features and patients in our cohort. Seven traditional machine learning classifiers were trained to distinguish Group 1 versus Group 2 using our feature selection method. Our feature selection was compared to lasso feature selection, recursive feature elimination, and variance thresholding.

RESULTS
We are able to classify Group 1 versus Group 2 glioblastomas with a cross-validated area under the curve (AUC) score of 0.82 using ridge logistic regression and our proposed feature selection method, which reduces the size of our feature set from 35,400 to 288. An interrogation of the selected features suggests that features describing contours in the T2 abnormality region on the FLAIR MRI modality may best distinguish these two groups from one another.

CONCLUSIONS
We successfully trained a machine learning model that allows for relevant targeted feature extraction from standard MRI to accurately predict molecularly-defined risk-stratifying IDH1/2-wildtype glioblastoma patient groups. This algorithm may be applied to future prospective studies to assess the utility of MRI as a surrogate for costly prognostic genomic studies.
NIMG-50. INITIAL EXPERIENCE: DETECTION OF ABERRANT HYPERPOLARIZED [1-13C]PYRUVATE METABOLISM IN PATIENTS WITH GBM PRIOR TO RESECTION
Authors: Autry Adam , Gordon Jeremy , LaFontaine Marisa , Chen Hsin-Yu , Villanueva-Meyer Javier , Chang Susan , Clarke Jennifer , Xu Duan , Lupo Janine , Larson Peder , Vigneron Daniel , Li Yan 
Published: December 2020

Abstract

INTRODUCTION
Detecting radiological response or resistance to treatment in patients with GBM is difficult with conventional MRI. In response to this challenge, hyperpolarized carbon-13 (HP-13C) MRI techniques were developed to probe real-time [1-13C]pyruvate metabolism.

METHODS
Dynamic HP-13C MRI was acquired pre-operatively from 6 patientswith recurrent GBM following intravenous injection of HP [1-13C]pyruvate. Five were confirmed with tumor progression and one had treatment effects without progression. Frequency-selective echo-planar imaging (8 slices, 3s temporal resolution, 3.38 cm3 spatial resolution, 60s acquisition) captured [1-13C]pyruvate metabolism to [1-13C]lactate and [1-13C]bicarbonate in the brain. Proton imaging included 3-D FLAIR, T1-weighted post-Gd IRSPGR, and spectroscopy. Carbon-13 voxels with non-enhancing lesion (NEL) or contrast-enhancing lesion (CEL) were identified for subsequent analysis. Temporally-summed HP-13C metabolite data within the CEL and NEL were evaluated using the pyruvate-to-lactate ratio; a modified ratio that takes into account vascular contributions of pyruvate; and parameter percentile ranks over the entire brain. Proton spectroscopy data were processed to obtain choline-to-NAA index (CNI) maps, which provide z-scores of relative tissue abnormality.

RESULTS
All of the anatomic lesions displayed abnormal CNI with maximum values of 3.22-6.35. The 5 patients with CEL lesions demonstrated 87th– 98thpercentile levels of pyruvate in the brain; and 95th-100thpercentile levels of lactate in 4 progressed patients and 60thpercentile in the patient presenting with treatment effects. For the patient with an exclusively non-enhancing lesion, percentile levels of pyruvate and lactate were 66thand 88thin the brain, respectively. The mean+/-SD percentile of the lactate-to-pyruvate and modified ratios were 75+/-22, 86+/-23 and 60+/-3, 71+/-12 in the progressed and non-progressed patients, respectively.

CONCLUSION
These data importantly demonstrate aberrant [1-13C]pyruvate metabolism in patients with GBM in both contrast-enhancing and non-enhancing lesions. Ongoing studies will further characterize the utility of HP imaging markers.
NIMG-61. UNUSUAL PRESENTATION OF NEUROSARCOIDOSIS: A CASE SERIES
Authors: Kleinschmidt-Demasters B K , Ormond David , Winograd Evan 
Published: December 2020

Abstract

INTRODUCTION
Neurosarcoidosis is a rare diagnosis, and even with known systemic disease or history, often remains a diagnosis of exclusion. Typical imaging findings of neurosarcoidosis include white matter lesions coupled with meningeal enhancement, or “sugarcoating” near the skull base. Occasionally, imaging can be quite unusual and mimic other entities. Other diagnoses to rule out include neoplastic, autoimmune, or infectious pachymeningitis, neoplastic lesions, neurosyphilis or tuberculosis.

METHODS
Our neuropathology database was queried for neurosarcoidosis from January 2008 until December 2019. These cases were then reviewed for cases with unusual presentations for further review and discussion.

RESULTS
Here we present 16 cases of neurosarcoidosis with histories and/or imaging that did not conform to the typical appearance of neurosarcoidosis. Along with a rare radiographic presentation, these cases also lacked CSF, laboratory, or systemic findings to suggest a diagnosis of neurosarcoidosis. 15 of these cases presented intracranially while 1 case presented within the spinal cord.

CONCLUSIONS
Neurosarcoidosis presentations can vary greatly. A better understanding of some unique patient presentations can help improve noninvasive diagnosis, although biopsy often remains necessary for confirmation.
NIMG-68. MATHEMATICAL MODELING OF THERMAL DAMAGE ESTIMATE VOLUMES IN MAGNETIC RESONANCE-GUIDED LASER INTERSTITIAL THERMAL THERAPY
Authors: Liang Allison , Munier Sean , Danish Shabbar 
Published: December 2020

Abstract

BACKGROUND
Magnetic resonance-guided laser interstitial thermal therapy is a minimally invasive procedure that produces real-time thermal damage estimates of ablation (TDE). Orthogonal TDE-MRI slices provides an opportunity to mathematically estimate ablation volume.

OBJECTIVE
To mathematically model TDE volumes and validate with post-24 hours MRI ablation volumes.

METHODS
Ablations were performed with the Visualase Laser Ablation System (Medtronic). Using ellipsoidal parameters determined for dual-TDEs from orthogonal MRI planes, TDE volumes were calculated by two definite integral methods (A and B) implemented in Matlab (MathWorks). Post 24-hours MRI ablative volumes were measured in OsiriX (Pixmeo) by two-blinded raters and compared to TDE volumes via paired t-tests and Pearson’s correlations.

RESULTS
Twenty-two ablations for 20 patients with various intracranial pathologies were included. Average TDE volumes calculated with Method A was 3.44 ± 1.96 cm3 and with Method B was 4.83 ± 1.53 cm3. Method A TDE volumes were significantly different than post-24 hours volumes (P &lt; 0.001). Method B TDE volumes were not significantly different than post-24 hours volumes (P = 0.39) and strongly correlated with each other (r = 0.85, R2 = 0.72, P &lt; 0.0001). A total of 8/22 (36%) method A versus 17/22 (77%) method B TDE volumes were within 25% of the post 24-hours ablative volume.

CONCLUSION
We present the first iteration of a viable mathematical method that integrates dual-plane TDEs to calculate volumes resembling 24 hours post-operative volumes. Future iterations of our algorithm will need to determine additional calculated variables that improve the performance of volumetric calculations.
PATH-02. CHARACTERIZATION OF FUNCTIONAL NETWORK EFFECTS IN THE CEREBRAL CORTEX DURING BRAIN TUMORIGENESIS IN THE MOUSE
Authors: Cramer Samuel , Popa Laurentiu , Haley Samuel , Dhawan Sanjay , Carter Russell , Ning Jianfang , Aronson Justin , Kodandaramaiah Suhasa , Ebner Timothy , Chen Clark 
Published: December 2020

Abstract

INTRODUCTION
Neuro-cognitive decline is near universal in glioblastoma patients and negatively impacts the quality of life for afflicted patients. Yet, there is little information on longitudinal effects of brain tumor growth on cerebral cortical function and network connectivity.

OBJECTIVE
To address this knowledge gap, we examined in vivo Ca2+ flux imaging in a transgenic murine glioblastoma model.

METHODS
Mesoscopic Ca2+ imaging was performed after implant of GL261 glioblastoma cells into a transgenic mice strain (Thy1-GCaMP6f) that expresses the fast calcium indicator GCaMP6f in Layer II/III and Layer V pyramidal neurons. Independent component analysis (ICA), correlation matrix and graph theory approaches were used to assess changes in network connectivity.

RESULTS
ICA defined canonical cerebral network consisting of nodal convergence and connectivity between nodes. The overall network structure remained unaltered after tumor implant. A decrease in the strength of connectivity was observed immediately following tumor implant. This temporary suppression was followed by progressive, global increase in the strength of nodal connectivity (p &lt; 0.0001). By two weeks post-tumor implant, 50% of the nodes exhibited increased connectivity compared to baseline. Progressive activation of select nodes was also observed in the weeks following tumor implant (p &lt; 0.01). In aggregate, these results suggest that activation of select network nodes as well as enhanced connectivity as means to compensate for the deleterious effects of glioblastoma growth.

CONCLUSIONS
Our results indicate that focal brain tumor growth induces a reorganization of both local and remote cortical activity. The finding bear pertinence to the pathogenesis of neuro-cognitive decline and tumor associated epilepsy.
PATH-06. ASSESSMENT OF CIRCULATING TUMOR DNA IN CEREBROSPINAL FLUID BY WHOLE EXOME SEQUENCING TO DETECT GENOMIC ALTERATIONS OF GLIOBLASTOMA
Authors: Duan Hao , He Zhenqiang , Chen Zhenghe , Mou Yonggao 
Published: December 2020

Abstract
Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF comparing with the corresponding tumor tissue samples (3.56±0.75 vs. 2.22±0.32, P=0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.12% ± 6.03% vs. 73.83% ± 5.95%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3F3A which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.
PATH-19. MOLECULAR, HISTOLOGIC AND CLINICAL CHARACTERISTICS OF OLIGODENDROGLIOMAS: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY
Authors: Dono Antonio , Alfaro-Munoz Kristin , Yan Yuanqing , Lopez-Garcia Carlos , Soomro Zaid , Williford Garret , Takayasu Takeshi , Robell Lindsay , Majd Nazanin , de Groot John , Esquenazi Yoshua , Kamiya-Matsuoka Carlos , Ballester Leomar Y 
Published: December 2020

Abstract
In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.