bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-54. RADIOMIC FEATURES FROM LESION HABITAT PREDICT RESPONSE TO COMBINATION OF NIVOLUMAB AND BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA: A FEASIBILITY STUDY
Authors: Verma Ruchika , Rauf Yasmeen , Yadav Ipsa , Statsevych Volodymyr , Chen Jonathan , Evanoff Wendi , Ahluwalia Manmeet , Tiwari Pallavi 
Published: November 2021

Abstract

PURPOSE
The use of immunotherapy in glioblastoma management is under active investigation. Glioblastomas are “cold” tumors, meaning that they have inactivated or fewer tumor infiltrative lymphocytes in addition to substantial tumor necrosis, attributing to their poor response to immunotherapy. A significant challenge is the apriori identification of Glioblastoma patients who will respond favorably to immunotherapy. In this work, we evaluated the ability of computerized MRI-based quantitative features (radiomics) extracted from the lesion habitat (including enhancing lesion, necrosis, and peritumoral hyperintensities) to predict response and progression-free survival (PFS) in recurrent GBM patients treated with combination of Nivolumab and Bevacizumab.

METHODS
Immunotherapy response assessment in neuro-oncology (iRANO) criteria along with PFS were used to analyze n=50 patients enrolled in a randomized clinical trial where patients received Nivolumab with either standard or low dose Bevacizumab. These patients were assessed to see if they had complete response, partial response, stable disease (i.e. responders, n=31), or disease progression (i.e. non-responders, n=19). Lesion habitat constituting necrotic core, enhancing tumor, and edema were delineated by expert radiologist on Gd-T1w, T2w and FLAIR MRI scans. COLIAGE radiomic features from each of the delineated regions were selected using minimum redundancy maximum relevance (mRMR) via cross-validation, to segregate non-responder patients from responders. A multivariable cox proportional hazard model was used to predict survival (PFS).

RESULTS
CoLlAGe correlation, sum average, and sum variance features (capture local heterogeneity) from the lesion habitat, were found to segregate non-responder patients from responders with an accuracy of 86%, followed by 80% using features from peritumoral hyperintensities and 78% from enhancing tumor. In our survival analysis, C-index of 0.688 was obtained using features from the entire lesion habitat, followed by peritumoral hyperintensities (0.675) and enhancing tumor (0.656).

CONCLUSION
Radiomic features from the lesion habitat may predict response to combination of Nivolumab and Bevacizumab in recurrent Glioblastomas.
NIMG-60. PREDICTING OVERALL SURVIVAL IN GLIOBLASTOMA USING HISTOPATHOLOGY VIA AN END-TO-END DEEP LEARNING PIPELINE: A LARGE MULTI-COHORT STUDY
Authors: Verma Ruchika , Cohen Mark , Toro Paula , Mokhtari Mojgan , Tiwari Pallavi 
Published: November 2021

Abstract

PURPOSE
Glioblastoma is an aggressive and universally fatal tumor. Morphological information as captured from cellular regions on surgically resected histopathology slides has the ability to reveal the inherent heterogeneity in Glioblastoma and thus has prognostic implications. In this work, we hypothesized that capturing morphological attributes from high cellularity regions on Hematoxylin and Eosin (H&E)-stained digitized tissue slides using an end-to-end deep-learning pipeline will enable risk-stratification of GBM tumors based on overall survival.

METHODS
A large multi-cohort study consisting of N=514 H&E-stained digitized tissue slides along with overall-survival data (OS) was obtained from the Ivy Glioblastoma atlas project (Ivy-GAP (N=41)), TCGA (N=379), and CPTAC (N=94). Our deep-learning pipeline consisted of two stages. First stage involved segmenting cellular tumor (CT) from necrotic-regions and background using Resnet-18 model, while the second stage involved predicting OS, using only the segmented CT regions identified in the first stage. For the segmentation stage, we leveraged the Ivy-GAP cohort, where CT annotations confirmed by expert neuropathologists were available, to serve as the training set. Using this training model, the CT regions on the remaining cohort (TCGA, CPTAC) (i.e. test set) were identified. For the survival-prediction stage, the last layer of ResNet18 model was replaced with a cox layer (ResNet-Cox), and further fine-tuned using OS and censor information. Independent validation of ResNet-Cox was performed on two hold-out sites from TCGA and one from CPTAC.

RESULTS
Our segmentation model achieved an accuracy of 0.89 in reliably identifying CT regions on the validation data. The segmented CT regions on the test cohort were further confirmed by two experts. Our ResNet-Cox model achieved a concordance-index of 0.73 on MD Anderson Cancer Center (N=60), 0.71 on Henry Ford Hospital (N=96), and 0.68 on CPTAC data (N=41).

CONCLUSION
Deep-learning features captured from cellular tumor of H&E-stained histopathology images may predict survival in Glioblastoma.
NIMG-62. 68(GA)DOTATATE PET-BASED RADIATION CONTOURING CREATES SMALLER AND MORE PRECISE RADIATION VOLUMES FOR MENINGIOMA PATIENTS
Authors: Perlow Haley , Yang Michael , Siedow Michael , Gokun Yevgeniya , McElroy Joseph , Matsui Jennifer , Beyer Sasha , Arnett Andrea , Boulter Daniel , Fritz Joel , Miller Eric , Blakaj Dukagjin , Zoller Wesley , Cadieux Catherine , Eiler Daniel , Addington Mark , DiConstanzo Dominic , Grecula John , Raval Raju , Chakravarti Arnab , Palmer Joshua 
Published: November 2021

Abstract

PURPOSE
Radiation treatment planning for meningiomas conventionally involves MRI contrast enhanced images to define residual tumor. However, the gross tumor volume may be difficult to delineate for patients with a meningioma in the skull base, sagittal sinus, or post resection. Advanced PET imaging using 68(GA)DOTATATE PET, which has been shown to be more sensitive and specific than MRI imaging, can be used for target volume delineation in these circumstances. We hypothesize that 68(GA)DOTATATE PET scan-based treatment planning will lead to smaller radiation volumes and will detect additional areas of disease compared to standard MRI alone.

METHODS
Our data evaluated retrospective, deidentified, and blinded gross tumor volume (GTV) contour delineation with 7 CNS specialists (3 neuroradiologists, 4 CNS radiation oncologists) for 26 patients diagnosed with a meningioma who received both a 68(GA)DOTATATE PET and an MRI for radiation treatment planning. Both the MRI and the PET were non-sequentially contoured by each physician for each patient.

RESULTS
The mean MRI volume for each physician ranged from 24.14-35.52 ccs. The mean PET volume for each physician ranged from 10.59-20.54 ccs. The PET volumes were significantly smaller for 6 out of the 7 physicians. In addition, 7/26 (27%) patients had new non-adjacent areas contoured on PET by at least 6 of the 7 physicians that were not contoured by these physicians on the corresponding MRI. These new areas would not have been in the traditional MRI based volumes.

CONCLUSION
Our study supports that 68(GA)DOTATATE PET imaging can help radiation oncologist create smaller and more precise radiation treatment volumes. Utilization of 68(GA)DOTATATE PET may find undetected areas of disease which in turn can improve local control and progression free survival. 68(GA)DOTATATE PET guided treatment planning should be studied prospectively.
NIMG-64. TYPE OF BONY INVOLVEMENT PREDICTS GENOMIC SUBGROUP IN SPHENOID WING MENINGIOMAS
Authors: Jin Lan , Youngblood Mark , Gupte Trisha , Vetsa Shaurey , Nadar Arushii , Barak Tanyeri , Yalcin Kanat , Aguilera Stephanie , Mishra-Gorur Ketu , Blondin Nicholas , Omay S Bulent , Pointdujour-Lim Renelle , Judson Benjamin , Alperovich Michael , Aboian Mariam , McGuone Declan , Gunel Murat , Erson-Omay Zeynep , Fulbright Robert , Moliterno Jennifer 
Published: November 2021

Abstract

OBJECTIVE
As sphenoid wing meningiomas (SWMs) are associated with varying degrees of bony involvement, we sought to understand potential relationships between genomic subgroup and this feature.

METHODS
Patients treated at Yale-New Haven Hospital for SWM were reviewed. Genomic subgroup was determined via whole exome sequencing, while the extent of bony involvement was radiographically classified as frank tumor invasion (TI), hyperostosis only (HOOs), or both (TI+HO). Among additional clinical variables collected, a subset of tumors was identified as spheno-orbital meningiomas (SOMs). Predictive logistic regression models were developed for genomic subgroups based on pre-operative clinical features.

RESULTS
Among 64 SWMs, 53% had HOO, 9% had TI, and 14% had TI+HO; nine SOMs were identified. Tumors with invasion (i.e., TI or TI+HO) were more likely to be WHO grade II (p: 0.028). Additionally, tumors with invasion were nearly 30 times more likely to harbor NF2 mutations (OR: 27.6; p: 0.004), while hyperostosis only (without frank tumor invasion) were over 4 times more likely to have a TRAF7 mutation (OR: 4.5; p: 0.023). SOMs were a significant predictor of underlying TRAF7 mutation (OR: 10.21; p: 0.004).

CONCLUSIONS
SWMs with invasion into bone tend to be higher grade and are more likely to be NF2 mutated, while SOMs and those with hyperostosis are associated with TRAF7 variants. Pre-operative prediction of molecular subtypes based on radiographic bony characteristics may have significant biological and clinical implications based on known recurrence patterns associated with genomic drivers.
NIMG-65. RESTING-STATE FUNCTIONAL MRI DEMONSTRATES DAMAGE TO FUNCTIONAL CONNECTIVITY IN MENINGIOMA PATIENTS WITH PERIFOCAL EDEMA
Authors: Stoecklein Veit , Wunderlich Stephan , Papzov Boris , Liu Hesheng , Schmutzer Michael , Thon Niklas , Schichor Christian , Tonn Jörg-Christian , Stoecklein Sophia 
Published: November 2021

Abstract

BACKGROUND
Meningiomas are common intracranial tumors which usually carry a benign prognosis. Some meningiomas cause perifocal edema which might indicate that this subset could interfere with normal brain function. Resting-state functional MRI (rsfMRI) can be used to assess whole brain functional connectivity (fc) which can be used as a marker for disease severity in patients with intracranial tumors, as was recently shown by our group in a cohort of glioma patients. In this study, we investigated whether the presence of perifocal edema in preoperative patients with meningioma leads to fc.

METHODS
Patients with suspected meningioma were prospectively included and functional resting state MRI scans were obtained. The resulting data was processed according to our recently published method and abnormality of fc was quantified for each individual patient. Abnormality of fc was then correlated with tumor and edema volume as well as WHO grade.

RESULTS
26 patients (23 WHO grade I, 3 WHO grade II) were included. 13 patients had perifocal edema. There was a highly significant correlation between edema volume and higher abnormality of fc both in the lesional and the contra-lesional hemisphere (r=0.51, p=0.008 and r=0.61, p=0.001). Patients with no perifocal edema showed only very low abnormality of fc. Tumor volume was not correlated with abnormal fc in both the lesional and the contralesional hemispheres (r=0.23, p=0.27 and r=0.28, p=0.17). There was also no significant correlation between WHO grade and abnormality of fc.

CONCLUSION
RsfMRI showed significant abnormal fc in meningioma patients with perifocal edema in contrast to patients without edema, independent of tumor volume. This demonstrates that the presence of edema but not the tumor volume is relevant for disturbances of fc.
NIMG-66. USING 68GA-DOTATATE PET FOR POSTOPERATIVE GAMMA KNIFE RADIOSURGERY PLANNING IN PATIENTS WITH MENINGIOMA
Authors: Park David , Ma Daniel , Goenka Anuj , Schulder Michael 
Published: November 2021

Abstract

BACKGROUND
Patients with meningiomas are typically treated with maximal safe surgical resection. After subtotal resection or at the time of tumor recurrence, stereotactic radiosurgery (SRS) is often used as the treatment of choice. While magnetic resonance imaging (MRI) is typically used for SRS target delineation, differentiating tumor growth from postoperative change can be challenging. 68Ga-DOTATATE, a positron emission tomography (PET) radiotracer targeting the somatostatin receptor type 2 (SSTR2), has been shown to be a reliable biomarker of meningiomas.

METHODS
We present a consecutive case series of 13 patients with pathology-proven meningioma who received a 68Ga-DOTATATE PET prior to SRS between April 2019 and April 2021. Treatment planning was done at first using MRI only. The DOTATATE-PET images were then used to assess the accurate identification of tumor.

RESULTS
Ten of the patients had WHO grade 2 meningioma and three patients had WHO grade 1 tumor. Nine patients had recurrent meningiomas and four patients had newly diagnosed disease. Overall, the 68Ga-DOTATATE PET scan revealed additional tumor beyond what was seen on MRI in 5/13 patients. The SRS plan was changed to intensity-modulated radiation therapy (IMRT) for three patients and to octreotide injection in one patient. In one patient, after 68Ga-DOTATATE PET identified previously unrecognized recurrent meningioma in the resection cavity, SRS was performed. In three others, questionable tumor recurrence was seen on MRI, and then confirmed on 68Ga-DOTATATE-PET, but patient observation only was continued due to the small lesion size.

CONCLUSION
Incorporation of 68Ga-DOTATATE PET data changed SRS treatment in 5/13 our patients with meningioma after prior surgery. We have made this a routine part of our treatment planning and we recommend this method to optimize the use of SRS or RT in these patients. Further data collection is ongoing.
NCMP-04. BRAIN-UMAP: THE GENETIC INTERSECTION BETWEEN NEUROSCIENCE, NEUROLOGY, PSYCHIATRY, AND ONCOLOGY
Authors: Arora Sonali , Nuechterlein Nicholas , Pattwell Siobhan , Holland Eric 
Published: November 2021

Abstract
Whole transcriptome sequencing (RNA-seq) is an important tool for understanding genetic mechanisms underlying human diseases and gaining a better insight into complex human diseases. Several ground-breaking projects have uniformly processed RNASeq data from publicly available studies to enable cross-comparison. One noteworthy study is the recount2 pipeline, which in 2017, has reprocessed ~70,0000 samples from Short Read Archive(SRA), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx). This vast dataset also includes gene expression data for GTEx-defined brain regions, neurological and psychiatric disorders (such as Parkinson's, Alzheimer’s, Huntington’s) and gliomas (such as TCGA, Chinese Glioma Genome Atlas (CGGA)). We apply uniform manifold approximation and projection (UMAP), a non-linear dimension reduction tool, to bulk gene expression data from brain-related diseases to build a BRAIN-UMAP, which allows for visualization of gene expression profiles across datasets. This UMAP shows that while gliomas form a distinct cluster, the neurological and psychiatric diseases are similar to GTEX-defined normal brain regions which exhibit tissue-specific profiles and patterns. Incorporating gliomas from various publicly available datasets also allows for the ability to observe unique clustering of particular subtypes, which can increase our genetic understanding of the disease. We also present a resource where researchers interested in mechanisms, can easily compare, and contrast the expression of a given gene and/or pathway of interest across various diseases, gliomas, and normal brain regions. Our current study, focusing on brain related diseases, offers insight into what may be possible for the broader neuroscientific community if we continually reprocess newly available brain related RNASeq samples using recount2. Additionally, if we build similar uniformly processing pipelines for other kinds of next-generation sequencing data, we would be able to use multi-omic sequencing data to find novel associations between biological entities and increase our mechanistic knowledge of the disease.
NCMP-08. CHALLENGING DIAGNOSIS AND MANAGEMENT OF PCNSL IN AN IMMUNOSUPPRESSED PATIENT ON MYCOPHENOLATE MOFETIL FOR MYASTHENIA GRAVIS
Authors: Bricoune Ornella , Mokhtari Sepideh , Etame Arnold , Robinson Timothy , Pina yolanda , Macaulay Robert 
Published: November 2021

Abstract

INTRODUCTION
Primary CNS lymphoma (PCNSL) typically presents with non-focal neurologic symptoms including disorientation, poor balance and memory and singel or multifocal periventricular MRI lesions. Deviations in characteristic findings can delay diagnosis and require additional diagnostic tests.

OBSERVATION
A 68-year-old man with a recent zoster infection and acetylcholine receptor antibody positive myasthenia gravis (MG) on Mycophenolate Mofetil for 22 years presented at another institution with left eye vision changes, and focal neurological deficits. A brain MRI showed an enhancing lesion within his left medulla extending to the cerebellum. Cerebrospinal fluid (CSF) analysis was positive for EBV and negative for malignancy. He was diagnosed with VZV vasculopathy and discharged home on IV Acyclovir for 14 days and a 5-day course of oral prednisone 60 mg. Three months later, a repeat brain MRI showed multiple new enhancing lesions bilaterally along the periventricular white matter with involvement of the corpus callosum with several lesions in peripheral locations of the cerebrum, cerebellum, and brainstem. He presented to local ER with intermittent encephalopathy, acute left eye vision blurriness and was started on steroids. He was transferred to our institution and had CSF analysis which was positive for EBV and negative for malignancy. Due to rapid progression of his symptoms, he underwent gross total resection of the left frontal lesion which showed EBV-induced diffuse large B-cell lymphoma (DLBCL). His Mycophenolate Mofetil was discontinued and he had a dramatic improvement in his left eye vision and cognitive deficits within 24 hours after one dose of Rituximab IV 500 mg/m2.

DISCUSSION
In the setting of periventricular lesions and EBV positivity on CSF, EBV-induced DLBCL should be highly considered.

CONCLUSION
Misdiagnosis or delay in diagnosis of PCNSL due to the presence of atypical features in disease presentation and radiographic findings could lead to progression of PCNSL.
NCMP-10. DYSGRAPHIA AS THE EARLIEST PRESENTING SYMPTOM OF SEVERE CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY NEUROTOXICITY: A SINGLE CENTER EXPERIENCE
Authors: Yuen Carlen , Rezania Kourosh , Kelly Thomas , Bishop Michael 
Published: November 2021

Abstract

INTRODUCTION
Chimeric antigen receptor (CAR) T-cell therapy, including axicabtagene ciloleucel (axi-cel; Yescarta®) and tisagenlecleucel (tisa-cel; Kymriah®), are FDA approved for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Neurotoxicity (NT) associated with CAR T-cell therapy (immune effector cell-associated neurotoxicity syndrome [ICANS]) can be fatal. Timely data, in the form of an abbreviated bedside mini-mental status exam, is thought to lead to earlier identification of NT. However, existing literature validating this method is limited.

MATERIALS AND METHODS
In this retrospective study, patients with R/R DLBCL treated with commercial axi-cel or tisa-cel in our center from December 2017 to September 2018 were assessed for NT with the CTCAE v4 criteria and the CAR-T-cell-therapy-associated TOXicity (CARTOX-10) scoring system.

RESULTS
Twenty-six patients with R/R DLBCL were treated with CAR T-cell therapy (25 axi-cel/[Yescarta®] and 1 tisagenlecleucel [Kymriah®]). Twenty-three (88%) developed NT with 8 (31%) experiencing severe NT (Grade III-IV). Tremor and dysgraphia occurred in all patients with severe NT. Lower average CARTOX-10 score (p=&lt; 0.01), dysgraphia (p&lt; 0.01), inattention (p=.018), and disorientation (p=.01) were significantly associated in patients with severe NT. A trend towards significance was observed between tremor and severe NT (p=.08). All patients with severe NT had both dysgraphia and tremor 8/8 (100%) and 2/8 (25%) had concurrent dysnomia. Death occurred in 12/26 (46%) of patients due to disease progression (n=11) and cardiac failure due to myositis (n=1).

CONCLUSION
In our limited cohort, dysgraphia, inattention, and disorientation are heralding symptoms of severe NT in adult R/R DLBCL patients treated with commercial CAR T-cell therapy. Dysgraphia was the earliest presenting symptom in patients with severe CAR T-cell neurotoxicity and was likely a manifestation of motor dysfunction rather than a component of dysphasia. Further studies with a larger cohort are needed to validate our findings.
NCOG-01. RADIATION THERAPY MANAGEMENT FOR METASTATIC DISEASE TO THE BRAIN IN NSCLC PATIENTS – SURVIVAL OUTCOMES OF THE BRITISH COLUMBIA POPULATION 1996-2016
Authors: Stubbs Terry , DeVries Kimberly , Proulx Ryan , Ho Clement , Cheung Arthur , Nichol Alan , Krauze Andra 
Published: November 2021

Abstract

BACKGROUND
Radiation therapy (RT) for brain metastases in patients with non-small cell lung cancer (NSCLC) has undergone considerable evolution but remains controversial.

METHODS
Records for 2212 patients with NSCLC who received RT to the brain at one of six locations between 1996-2016 were retrospectively analyzed. Data were obtained from the institutional cancer registry following ethics approval. Overall survival (OS) was calculated from diagnosis of lung cancer to death, and Kaplan-Meier curves were compared by Log-rank and Cox regression.

RESULTS
Median OS was 11.8 months (95%CI 11-12.6 months). Median age was 65, and 1254 patients (57%) were female. ECOG performance status at diagnosis was 0 (12%), 1 (31%), 2 (17%), 3 (14%), 4 (2%), and unknown (24%). Younger age (HR=0.99, 95%CI 0.98-0.99), female sex (HR=0.80, 95%CI 0.74-0.88), and better ECOG performance status (p&lt; 0.0001) were associated with superior OS. There was better OS in 932 patients (42%) that received chemotherapy (HR=0.63, 95%CI 0.58-0.69) and 603 (27%) that underwent surgery (HR=0.55, 95%CI 0.50-0.61). 2004 patients (91%) received 1 RT course, while 208 (9%) received multiple courses in various combinations of whole brain RT (WBRT) and stereotactic radiosurgery (SRS). SRS (HR=0.70, 95%CI 0.57-0.86) and multiple RT courses (HR=0.55, 95%CI 0.46-0.65) were associated with better OS. Median time from primary diagnosis to brain RT was 2.5 months, and from end of first brain RT to death was 3.5 months. A longer diagnosis to brain RT interval was associated with better OS (HR=0.95, 95%CI 0.95-96).

CONCLUSIONS
NSCLC patients with brain metastases continue to face poor prognosis, particularly when lung cancer diagnosis to first brain RT interval is short. Our analysis revealed younger age, female sex, and better ECOG performance status as predictors of superior survival. SRS and multiple RT courses also revealed superior survival, likely the result of patient selection and hence interpreted with caution.