bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-52. UNCERTAINTY QUANTIFICATION IN RADIOMICS
Authors: Wang Lujia , Yoon Hyunsoo , Hawkins-Daarud Andrea , Singleton Kyle , Clark-Swanson Kamala , Smith Kris , Nakaji Peter , Eschbacher Jenny , Baxter Leslie , Gonzalez Ashlyn , Nespodzany Ashley , Bendok Bernard , Patra Devi , De Leon Gustavo , Zimmerman Richard , Porter Alyx , Krishna Chandan , Salomao Marcela , Hoxworth Joseph , Zhou Yuxiang , Mrugala Maciej , Tran Nhan , Wu Teresa , Swanson Kristin , Li Jing , Hu Leland 
Published: November 2019

Abstract

INTRODUCTION
The quantification of intratumoral heterogeneity – through radiomics-based approaches - can help resolve the regionally distinct genetic drug targets that may co-exist within a single Glioblastoma (GBM) tumor. While this offers potential diagnostic value under the paradigm of individualized oncology, clinical decision-making must also consider the degree of uncertainty associated with each model. In this study, we evaluate the performance of a novel machine-learning (ML) algorithm, called Gaussian Process (GP) modeling, that can quantify the impact of multiple sources of uncertainty in ML model development and prediction accuracy, including variabilities in the copy number measurement, radiomics features, training sample characteristics, and training sample size.

METHOD
We collected 95 image-localized biopsies from 25 primary GBM patients. We coregistered stereotactic locations with preoperative multi-parametric MRI features (conventional MRI, DSC perfusion, Diffusion Tensor Imaging) to generate spatially matched pairs of MRI and copy number variants (CNV) for for each biopsy. We developed a Gaussian Process (GP) model to predict CNV for Epidermal Growth Factor Receptor (EGFR) based on MRI radiomic features in each patient. We used leave-one-patient-out cross validation to quantify prediction accuracy and model uncertainty. Spatial prediction and uncertainty (p-value) maps were overlaid to help visualize regional genetic variation of EGFR and uncertainty of the radiomic predictions. RESULT: The initial GP radiomics model for EGFR amplification (CNV > 3.5) produced a sensitivity of 0.8 and specificity of 0.8. Samples/regions associated with high uncertainty (p-value >0.05) correlated with either 1) extrapolation of radiomic features from the training set-defined feature space or 2) insufficient training samples in the feature space.

CONCLUSION
We present a ML-based model that quantifies spatial genetic heterogeneity in GBM, while also estimating model uncertainties that result from multi-source data variabilities. This approach lays the groundwork for prospective clinical integration of modeling-based diagnostic approaches in the paradigm of individualized medicine.
NIMG-53. 3D BRAIN TUMOR MODELING FACILITATES NEURO-ONCOLOGY CLINIC VISIT AND IMPROVES PATIENT HEALTH LITERACY AND VISIT SATISFACTION
Authors: Landau Zoe , Flora Sarah , Tosha Gatson Na 
Published: November 2019

Abstract
Explanation of brain tumor imaging (BTI) complexities to patients is a challenge in neuro-oncology. With limited tools, neuro-oncologist attempt to demonstrate tumor volumes and anatomy, estimate surgical risks, and treatment responses. Arming clinicians with alternative BTI might help alleviate the stress of initial patient consults and follow-up surveillance visits. These interactions are critical to the physician-patient relationship, patient compliance, and satisfaction. Currently, 2D-MRI review is standard, often leaving the patient with a less-than-complete understanding of their tumor. Historically, 3D-Brain-Tumor-Modeling (3DBTM) has been used for neurosurgical simulation and planning. Here, we evaluated the use 3DBTM alongside routine MRI impact on patient health literacy and satisfaction. Our institution introduced 3DBTM as a best practice approach. Images were presented as 3D video or tangible 3D color renditions, or 2D MRI. We collected patient pre-visit and post-visit surveys to assess patient’s understanding of tumor features, opportunity to review images, and patient level of satisfaction. Data from 277 pre-visit and 159 post-visit surveys was collected from the Geisinger Neuro-Oncology Clinic over a six-month period. Post-visit survey categories included reviews of: 3DBTM (n=54), 2D-MRI (n=51), and no imaging (n=55). Patients without CNS tumors were excluded (n=101). Pre-visit surveys showed 30% (n=82) of patients had little-to-no prior understanding of their tumor location and size, and 53% (n=147) of patients believed that a 3DBTM would improve their understanding. Post-visit analysis demonstrated that only 21% (n= 29) of patients reported not seeing any imaging during the visit. Nearly 85% (n=46) of patients who had reviewed a 3DBTM noted improved tumor understanding. Of the patients who solely viewed 2D-MRI, 68% (n=35) reported improved understanding of their tumor but would like more advanced imaging teaching. In total, 84% of patients noted overall satisfaction with the clinic visit. These results support the use of 3DBTM in patient education and facilitating clinical interviews.
NIMG-64. IMPACT OF TUMOR LOCATION ON IMAGE-DERIVED VOLUME, PROLIFERATION RATE AND GROWTH VELOCITY IN GLIOBLASTOMA PATIENTS
Authors: Lorence Julia , Swanson Kristin , Rickertsen Cassandra , Ranjbar Sara , Johnston Sandra , Singleton Kyle , Porter Alyx , Bendok Bernard , Mitchell Ross , Rubin Joshua , Hu Leland , White Haylye , Whitmire Paula , Mrugala Maciej 
Published: November 2019

Abstract

INTRODUCTION
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults with a median overall survival (OS) of 15months. Despite advancements in treatments, prognosis is dismal and the prognostic significance of tumor location is not entirely understood. METHODOLOGY: In our study, we investigated sex-specific volumetric, tumor growth kinetics, and outcome differences among GBMs in various brain locations. Primary GBM patients with pretreatment magnetic resonance imaging (MRI) data (N=289, 173 males, 116 females) were selected from our brain tumor repository. Tumor abnormality was segmented on T1-weighted post-gadolinium contrast agent (T1Gd) MRIs. We utilized the Harvard-Oxford brain atlases to determine the location of GBMs.

RESULTS
Overall, our study found smaller tumors in the left hemisphere. This may be expected as left-hemispheric GBM symptoms could present earlier, leading to earlier diagnosis and treatment. However, when the cohort was split by sex, we found this observation significant for females only in the parietal lobe (p < 0.0001). Further, female GBMs demonstrated smaller necrotic volume in the left hemisphere (p = 0.030). Sex-specific differences in incidence were noted in the temporal and occipital lobes (2M:1F). Comparing tumor growth kinetics in different brain locations and hemispheres, females had significantly lower tumor proliferation rates in the left hemisphere (p = 0.009) and lower tumor proliferation rates in the left frontal lobe (p = 0.031). Controlling for treatment, patients with frontal lobe tumors had significantly longer OS compared to those with GBMs in the temporal lobe (p = 0.046, 312 days). Differences in growth velocities were noted between frontal and parietal lobe with frontal GBMs having lower velocities in comparison to parietal lobe GBMs.

CONCLUSION
Together, our results demonstrate that tumor growth and proliferation rates may vary based on location and sex. Additional research is needed to further explore the clinical significance of tumor location.
NIMG-69. RAPID INTRAOPERATIVE DIAGNOSIS OF GLIOMA RECURRENCE USING STIMULATED RAMAN HISTOLOGY AND DEEP NEURAL NETWORKS
Authors: Hollon Todd , Urias Esteban , Adapa Arjun , Jairath Neil , Save Akshay , Canoll Peter D , Lee Honglak , Freudiger Christian , Orringer Daniel 
Published: November 2019

Abstract
Accurate intraoperative diagnosis of recurrence versus treatment effect (TE) is essential for determining the management of suspected recurrent gliomas. Cytologic and histoarchitectural changes related to chemoradiation overlap with common findings in recurrent tumors (e.g. atypia, abnormal vasculature, necrosis). Moreover, H&E tissue processing artifact complicates interpretation. Stimulated Raman histology (SRH) uses the intrinsic biochemical properties of fresh, unprocessed surgical specimens to provide rapid label-free digital histologic images. Here, we report an automated technique using deep convolutional neural networks (ConvNet) that differentiates recurrent glioma and TE in fresh surgical specimens imaged using SRH with equivalent accuracy and 10x faster (tissue-to-diagnosis, 2 minutes) than conventional methods. Our ConvNet, based on Google’s Inception-ResNet-v2 architecture, was first trained on 3.6 million SRH images from 441 patients with the most common brain tumor subtypes. To optimize the network for classifying glioma recurrence, we used cross-validation (CV) on 35 patients (24 recurrent, 9 TE) for model hyperparameter tuning and to identify an optimal probability threshold to classify recurrence. To perform rigorous model validation, we used a 50 patient external testing set to evaluate overall model accuracy. Over 5 iterations of CV, the mean held-out classification accuracy was 94.8% (range, 91.4 - 97.1%). Using ROC analysis, we found that a probability of recurrence greater than 25% was the optimal threshold to render a recurrence diagnosis for whole-slide SRH images. Using our external testing set, we achieved a classification accuracy of 96% (total 48/50; 30/30 recurrences, 18/20 TE). Moreover, our method effectively identifies regions of glioma recurrence in whole slide SRH at no additional computational cost. Our study demonstrates the feasibility of applying deep learning for intraoperative diagnosis of recurrent gliomas in SRH imaged tissues. In the future, ConvNets may ultimately be used to guide decision-making in the surgical care of recurrent gliomas, independent of conventional neuropathology resources.
NIMG-75. RADIOMIC FEATURES LOCALIZED TO STEREOTACTIC BIOPSY LOCATIONS CAN CAPTURE EGFR PRESENCE IN GLIOBLASTOMA
Authors: Ismail Marwa , Correa Ramon , Bera Kaustav , Saeed Bamashmos Anas , Statsevych Volodymyr , Prasanna Prateek , Beig Niha , Madabhushi Anant , Ahluwalia Manmeet , Tiwari Pallavi 
Published: November 2019

Abstract

PURPOSE
Epidermal growth factor receptor amplification (EGFRamp), occurs in >60% of Glioblastoma (GBM) patients, and can predict response to alkylating chemotherapy. However, due to high genetic instability in GBM, a significant caveat to sampling EGFRamp during biopsy, is that reliable identification of its presence is dependent on the site of the biopsy, and may vary throughout the tumor. Previous studies have employed radiomics (computerized feature extraction) from the entire tumor to characterize EGFRamp presence. Our work is based on the rationale that radiomics measurements from stereotactic biopsy locations on Gd-T1w MRI, may allow to build accurate training models for predicting EGFRamp compared to using radiomic features from the entire tumor.

METHODS
MRI scans from 78 GBM subjects (33 EGFRamp, 45 non-amp) were obtained, of which 54 subjects were used for training while 24 were used for testing. Stereotactic biopsy locations were mapped by co-registering CT-images with MRIs (confirmed by two radiologists). For each biopsy region (1-cm diameter sphere), gradient entropy features and gender information were used to train a discriminant analysis classifier, on a voxel-wise manner. Our training model also included per-voxel spatial probabilities that were obtained by building atlases to quantify frequency of occurrence of EGFRamp and non-amp cases. All of these features were then used within the test set to predict EGFR status.

RESULTS
The model achieved a training accuracy of 81.4%, correctly classifying 17/23-amp, 27/31 non-amp cases. Accuracy on test set was 79.2% (7/10 amp, 12/14 non-amp cases correctly classified). Extracting features from the entire tumor achieved a training accuracy of 74% (17/23-amp, 23/31 non-amp cases correctly classified), and a testing accuracy of 70.8% (6/10 amp, 11/14 non-amp cases correctly classified).

CONCLUSION
Radiomic features, trained using features from only the stereotactic biopsy locations, may be more reliable in training models to predict EGFR mutation in GBM.
NIMG-77. RESPONSE ASSESSMENT USING MULTIPARAMETRIC MRI DURING CHEMORADIATION PREDICTS OVERALL SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Kim Michelle , Aryal Madhava , Parmar Hemant , Li Pin , Schipper Matthew , Wahl Daniel , Lawrence Theodore , Cao Yue 
Published: November 2019

Abstract

INTRODUCTION
Identifying both aggressive hypercellular (HCV) and hyperperfused (hCBV) regions of glioblastoma (GBM) prior to radiation (RT) using multiparametric MRI (mpMRI) predicts PFS and recurrence better than either technique alone, and is under investigation in a phase II trial as a novel target for dose-intensified RT. We hypothesized that early response in combined HCV/hCBV could be assessed using mpMRI and predict OS better than baseline assessment.

METHODS
Forty-three patients with newly diagnosed GBM underwent prospective high b-value (b=3000 s/mm2) DW-MRI and DCE-MRI pre-RT and 3 weeks into RT. Twenty patients were treated on a dose-escalation trial specifically targeting HCV/hCBV identified by mpMRI. An automated threshold method was used to generate HCV (mean contralateral normal brain+2SD) and hCBV (contralateral normal frontal grey matter+1SD). Survival was calculated using Kaplan-Meier method and compared using log-rank test. Age, gender, performance status, RT dose, extent of surgery, MGMT methylation, and imaging characteristic were tested in Cox proportional hazards models for survival.

RESULTS
Most patients had gross total (47%) or subtotal resection (37%), and 25% were MGMT methylated. Significant volumetric reduction during RT was observed in the Gd-enhanced volume (4.4 cc reduction, 95%CI 1.1–7.7, 17%), as well as HCV (1.8 cc reduction, 95%CI 0.2–3.4, 19%) and hCBV (1.1 cc reduction, 95%CI -0.4–2.6, 10%). No difference was observed between MGMT subgroups, but patients treated on protocol specifically targeting the mpMRI volume had significant reduction in combined HCV/hCBV (-4.4 cc, 95%CI -6.6,-2.3) vs non-protocol patients (-0.3 cc, 95%CI -2.6,2.0, p=0.006). A reduction in combined HCV/hCBV was associated with superior OS (AHR 0.60, 95%CI 0.40–0.89, p=0.01), while baseline imaging (all p< 0.90) and change in Gd-enhanced volume (p=0.61) were not.

CONCLUSIONS
Significant early response in HCV/hCBV during treatment is observed when targeted with dose-intensified RT, and is associated with improved OS with potential for adaptive strategies in future trials.
NCMP-02. MYASTHENIA GRAVIS INDUCED BY AVELUMAB
Authors: Yuen Carlen , Fleming Gini , Soliven Betty , Myers Michael , Rezania Kourosh 
Published: November 2019

Abstract
Monoclonal antibodies targeting PD- 1 (nivolumab and pembrolizumab) and PD-L1 (avelumab, atezolizumab, and durvalumab) are FDA approved for the treatment of metastatic cancers. Immune-related adverse events (irAEs) are autoimmune diseases which occur following treatment with PD-1 and PD-L1 inhibitors. Neurological irAEs following PD-L1 blockade are rarely reported, and mainly consist of Myasthenia Gravis (MG) and myositis. MG induced by avelumab has not been previously reported. We present a 74-year-old female with stage IV ovarian adenocarcinoma who entered a clinical trial involving avelumab and entinostat after disease progression following extensive resection, chemotherapy with doxorubicin, then docetaxol and cisplatin. She developed progressive generalized weakness and fatigue two months after entering the trial, leading to respiratory weakness and hypoventilation, and resulting in intubation and mechanical ventilation. Exam showed head-drop, diplopia, and proximal > distal upper and lower limb weakness. Antibodies to acetylcholine receptors, muscle specific tyrosine kinase, and voltage-gated calcium channels (P/Q and N type) were negative, and serum creatine kinase was normal. Repetitive nerve stimulation showed significant decrement in the left spinal accessory nerve motor response with recording at trapezius. She was diagnosed with seronegative MG and was treated with IVIG, 2 grams/kg divided over 4 days, prednisone 60 mg daily, and pyridostigmine, which resulted in successful extubation, followed by gradual resolution of MG symptoms over a period of 3 months. At approximately 2 year follow-up, she remains on maintenance IVIG at 0.5 grams/kg every 3 weeks, as she develops proximal lower limb and neck extension weakness at the end of each IVIG cycle. We conclude that MG is a potentially life threatening but treatable irAE associated with avelumab. Our case also adds to the accumulating literature of the role of PD-1 signaling in the pathogenesis of autoimmune diseases of the muscles and neuromuscular junctions.
NCMP-04. OPSOCLONUS-MYOCLONUS SYNDROME ASSOCIATED WITH CONTACTIN-ASSOCIATED PROTEIN-LIKE 2 AUTOANTIBODY IN THE SETTING OF NON-SMALL CELL LUNG CARCINOMA
Authors: Rosenow Christian , Dawit Sara , Henry Katharine , Farrugia Luca , Sharma Akanksha , Grill Marie 
Published: November 2019

Abstract

INTRODUCTION
Opsoclonus–myoclonus syndrome (OMS) is a rare neurological disorder characterized by spontaneous multidirectional saccadic eye movements, myoclonus, and ataxia. It is suspected to be an autoimmune mediated process precipitated by a paraneoplastic or infectious trigger. Among the pediatric population, OMS is often associated with neuroblastoma and anti-Hu antibody. Paraneoplastic syndromes in adults manifesting as OMS are most commonly described in breast, gynecological and small cell lung cancer with associated anti-neuronal antibodies (ANNA-2; anti-Ri). We describe the first case of OMS associated with lung adenocarcinoma and Contactin-associated protein-like 2 (Caspr2) antibody. CASE REPORT: A 46-year-old-woman with history of limited small cell lung cancer (SCLC) status-post chemotherapy with cisplatin and etoposide and prophylactic whole brain radiation, presented with new onset gait instability, nausea, vomiting, vertigo, and opsoclonus. Two months prior to her presentation, a chest computed topography (CT) revealed no evidence of recurrent disease. Brain MRI revealed T2 hyperintensities in the white matter and central pons presumably related to chronic small vessel ischemic changes, unchanged from prior imaging. CSF studies revealed normal cell count, glucose, and protein. Gram stain, culture and meningoencephalitis panel were negative. Her paraneoplastic panel revealed a positive Caspr2 antibody. A repeat CT chest for cancer surveillance revealed a new lung mass. Immunotherapy treatment included plasmapheresis, corticosteroids, and intravenous immunoglobulin therapy. She underwent a biopsy of the new pulmonary lesion and the pathology was consistent with non-small cell lung carcinoma. Her symptoms slowly improved after treatment. Unfortunately, her disease progressed on repeat PET scan despite surgical resection of the lung mass. She ultimately elected for hospice.

CONCLUSION
We report a novel antibody, Caspr2, occurring in association with paraneoplastic OMS. While SCLC is the most common neoplasm associated with OMS among adults, non-small cell lung carcinoma should be considered. Prompt immunotherapy and neoplasm treatment may result in improvement.
NCMP-05. THE INCIDENCE AND IMPACT OF POST-OPERATIVE STROKE IN SURGERY FOR LGG
Authors: Berger Asaf , Tzarfati Garry , Costa Mathias , Serafimova Marga , Korn Akiva , Alfassi Tali , Aviram Daniel , Kashinian Alon , Ram Zvi , Grossman Rachel 
Published: November 2019

Abstract

BACKGROUND
Postoperative neurological deficits may outweigh the benefit conferred by maximal resection of gliomas. We evaluated the incidence of ischemic events in patients undergoing surgery for low-grade gliomas (LGG) and the long-term neurological and cognitive sequelae.

METHODS
Between 2013–2017, 168 patients underwent surgical resection or biopsy for LGG at our center. A full dataset, including pre- and postoperative magnetic resonance imaging (MRI) and long-term clinical evaluation findings, was available for 82 patients (study group). Ischemic complications, overall and progression-free survival, and functional and neurocognitive outcomes were evaluated.

RESULTS
The immediate postoperative MRI revealed an acute ischemic stroke adjacent to the tumor resection cavity in 19 patients (23%), 13 of whom developed new neurological deficits due to the ischemic event. Infarcts were more common in patients with recurrent tumors, especially those involving the Sylvian fissure (p< 0.05). Surgery for insular gliomas had the strongest association with postoperative infarcts. Survival of patients w/wo a postoperative infarct was the same. The median Karnofsky-Performance Status was lower for the infarct group vs. the non-infarct group at 3 months post-surgery (p=0.016), with a gradual significant improvement for the former over one year (p=0.04). Immediately after surgery, 27% of the patients without infarcts and 58% of those with infarcts experienced a new motor deficit (p=0.037), decreasing to 16% (p=0.028) and 37% (p=0.001), respectively, at one year. Neurocognitive analysis findings before and 3 months after surgery were unchanged, but patients with an infarct had a significant decrease in naming (p=0.04). Confusion during awake craniotomy was a strong predictor of an ischemic stroke.

CONCLUSIONS
Intraoperative strokes are more prevalent among patients who undergo recurrent surgeries, especially in the insula. Although they do not affect survival, these strokes negatively impact the patients’ activity and performance status, especially during the first 3 postoperative months, with gradual functional improvement over one year.
NCMP-09. NEUROLYMPHOMATOSIS, A RARE INDEX MANIFESTATION OF CD5/CD10 NEGATIVE MATURE B CELL LYMPHOMA PRESENTING AS SUBACUTE SENSORIMOTOR LAMBOSACRAL POLYRADICULONEUROPATHY
Authors: Hrachova Maya , Xiao-Tang Kong , Zhao Xiaohui 
Published: November 2019

Abstract

INTRODUCTION
Neurolymphomatosis (NL) is a rare entity characterized by direct invasion of neoplastic cells into endoneurium of cranial or peripheral nerves, nerve roots or plexuses. It is most commonly seen with non-Hodgkin’s lymphoma with occurrence rate of 0.2%. Here we report a case of subacute length-dependent sensorimotor lumbosacral polyradiculoneuropathy secondary to NL as the first manifestation of CD5−/CD10− mature B-cell lymphoma. CASE REPORT: A 54-year old man with diabetes mellitus type 2, hypertension and psoriasis presented with subacute onset of progressive lower extremity weakness with pertinent examination findings of bilateral mildly asymmetrical distal greater than proximal lower extremities weakness, length depended hypoesthesia, fasciculations and decreased reflexes. EMG/NCS study showed active and chronic denervation changes concerning for multilevel lumbosacral polyradiculopathy. Routine blood investigations produced normal findings. CSF examination showed nucleated cells at 125 cells/HPF with lymphocyte predominance, protein at 538 mg/dL, and glucose 18 mg/dL. Flow cytometry identified mature CD5-/CD10- B cell lymphocytes. MRI spine identified marked enhancement, thickening, nodularity of cauda equine nerve roots and focus of myelopathy at the left posterior conus. Based on the clinical and radiographic findings a diagnosis of neurolymphomatosis was made and her underwent workup for systemic lymphoma.

DISCUSSION
Our case demonstrates the importance of comprehensive evaluation of sensorimotor polyradiculoneuropathy as rare entities such as neurolymphomatosis could mimic common etiologies.