bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-13. INTRAOPERATIVE EVALUATION OF IDH MUTATION STATUS AND TUMOR INVASION IN GLIOMA
Authors: Brown Hannah , Garcia Diogo , Chen Rong , Jentoft Mark , Middlebrooks Erik , Chaichana Kaisorn , Quinones-Hinojosa Alfredo , Cooks R Graham 
Published: November 2021

Abstract

BACKGROUND
Intraoperative detection of residual tumor and isocitrate dehydrogenase (IDH) mutations can assist in maximizing surgical resection beyond contrast enhancing margins and guide intraoperative surgical decision making for glioma patients. We aimed to evaluate the use of desorption electrospray ionization-mass spectrometry (DESI-MS) for intraoperative assessment of IDH mutations and estimation of tumor cell percentage (TCP).

METHODS
This is a prospective study using intraoperative DESI-MS analysis of freshly obtained tissue samples to evaluate IDH mutations via 2-hydroxyglutarate (2-HG) intensity and TCP via measurement of N-acetylaspartic acid (NAA) intensity and characteristic lipid profiles. These IDH mutation and TCP estimates were subsequently validated by a senior neuropathologist.

RESULTS
A total of 247 biopsies from a 49-patient study were previously collected and analyzed at Indiana University. Assessment of TCP in 203 margin and core biopsies based on NAA intensity yielded sensitivity, specificity, and accuracy values of 91, 76, and 83%, whereas TCP assessment based on characteristic lipid profiles yielded 76, 85, and 81%, respectively. Assessment of IDH mutation status of 71 core biopsies yielded sensitivity, specificity, and accuracy values of 89, 100, and 94%. Further validation of the methodology is being performed in an ongoing collaboration with Mayo Clinic-Jacksonville, where we have collected 178 biopsies from 24 patients. Preliminary results of IDH mutation assessments indicate 100% sensitivity, specificity, and accuracy.

DISCUSSION/CONCLUSION
We present a novel system to allow intraoperative evaluation of IDH status and to guide surgical resection by TCP measurement from tissue biopsies. Prospectively, we propose to modify our DESI-MS system by placing a surgical material (e.g. cottonoid) along the surgical margin and transferring material from the blot to a microscope slide prior to DESI-MS analysis. This will allow the retention of the spatial distribution of diagnostic molecules while analyzing a wall of the surgical cavity without the need for biopsy.
PATH-27. MGMT PROMOTER STATUS IN IDH1/2 MUTANT ANAPLASTIC ASTROCYTOMA PATIENTS ASSESSED BY DNA METHYLATION PROFILING AND QMS-PCR: A REPORT FROM THE EORTC BRAIN TUMOR GROUP
Authors: Tesileanu Mircea , French Pim , Sanson Marc , Brandes Alba Ariela , Wick Wolfgang , Clement Paul , Kros Johan , Gorlia Thierry , Golfinopoulos Vassilis , van den Bent Martin 
Published: November 2021

Abstract

BACKGROUND
Temozolomide efficacy in high-grade glioma is related to MGMTp methylation. We compared the prognostic and predictive effect of MGMTp between DNA methylation profiling (MGMT-STP27 model) and qMS-PCR in IDH1/2mt anaplastic astrocytoma patients.

METHODS
The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4Gy radiotherapy, radiotherapy with concurrent temozolomide, radiotherapy with 12 cycles of adjuvant temozolomide, or radiotherapy with concurrent and adjuvant temozolomide. MGMTp methylation status was assessed with the MGMT-STP27 model using 850k EPIC data, and qMS-PCR. IDH1/2 mutation status was determined with next-generation sequencing. OS was measured from randomization date.

RESULTS
We identified 444 IDH1/2mt anaplastic astrocytoma patients. MGMTp was methylated in 365/440 patients (83.0%) with MGMT-STP27 data, and 168/361 patients (46.5%) with qMS-PCR data. The agreement between both modalities is 59.9% (Cohen’s Kappa score 0.229). At database lock, 289 patients with MGMT-STP27 data were alive and 236 patients with qMS-PCR data. The median OS of MGMTp methylated glioma patients was 9.1 yrs [95%CI 7.5-not reached] for the MGMT-STP27 model, and not reached [95%CI 9.1-not reached] for qMS-PCR. For MGMTp unmethylated glioma patients, the median OS was 6.9 yrs [95%CI 6.2-not reached] for the MGMT-STP27 model, and 6.8 yrs [95%CI 6.2-9.7] for qMS-PCR. The HR for OS based on MGMTp methylation was 0.88 [95%CI 0.58-1.31] for the MGMT-STP27 model, and 0.72 [95%CI 0.50-1.03]) for qMS-PCR. The HR for OS after radiotherapy with any temozolomide vs radiotherapy alone for the MGMT-STP27 model was 0.53 [95%CI 0.37-0.78] for MGMTp methylated, and 0.54 [95%CI 0.25-1.18] for MGMTp unmethylated glioma patients; and for MS-PCR was 0.34 [95%CI 0.19-0.61] for MGMTp methylated, and 0.53 [95%CI 0.33-0.85] for MGMTp unmethylated glioma patients.

CONCLUSION
MGMTp methylation, regardless of assay, was neither prognostic nor predictive for outcome to temozolomide in IDH1/2mt anaplastic astrocytoma patients.
PATH-41. POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG WITH FGFR3-TACC3 FUSION MIMICKING HIGH-GRADE GLIOMA: CASE REPORT AND SERIES OF HIGH-GRADE CORRELATES
Authors: Golub Danielle , Pan Peter C , Liechty Benjamin , Slocum Cheyanne , Bale Tejus , Pisapia David J , Juthani Rupa 
Published: November 2021

Abstract

BACKGROUND
Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently-described entity that can occasionally histologically and molecularly mimic high-grade glioma. The histologic and molecular features that predict aggressive behavior in FGFR3-TACC3 altered tumors are unclear.

CASES
We present a rare case of an indolent neuroepithelial neoplasm in a 59-year-old female with imaging initially suggestive of high-grade glioma and analyze common molecular features between this case and a series of high-grade gliomas. After total resection, pathology of the case patient revealed predominantly low-grade cytomorphology, abundant microcalcifications, unusual neovascularization, and a low proliferation index. The lesion was diffusely CD34 immunoreactive and harbored both an FGFR3-TACC3 fusion and a TERT promoter mutation. Based on the overall histologic and molecular profile, a diagnosis of PLNTY was favored. The patient was thereafter observed without adjuvant therapy with no evidence of progression at 15-month follow-up. In contrast, a series of eight adult patients with glioblastomas harboring FGFR3-TACC3 fusions and correspondingly aggressive clinical courses are also presented. Common molecular findings included IDH-wildtype status, absence of 1p19q codeletion, and CDKN2A loss. TERT promoter mutations and lack of MGMT promoter methylation were also frequently observed. These patients demonstrated a median 15-month overall survival and a 6-month progression-free survival.

CONCLUSIONS
PLNTY is a rare low-grade entity that can display characteristics of high-grade glioma, particularly in adults. The potential for a unique entity mimicking PLNTY which may act as a precursor lesion for a more malignant phenotype should be considered in cases with FGFR3-TACC3 fusions and other high-grade features.
NIMG-07. BEYOND RANDOM AND NUMERIC LESIONS: DIFFERENT IMAGING PATTERNS OF CENTRAL NERVOUS SYSTEM METASTASIS BASED ON PRIMARY TUMOR LOCATION AND MOLECULAR PROFILE
Authors: Magalhães Júlia , Moreno Raquel , Takahashi Jorge , Lucato Leandro , Silva Carlos 
Published: November 2021

Abstract
The purpose of this exhibit is to discuss different imaging patterns of central nervous system (CNS) metastasis based on their primary cancer site and to review the recent literature of the particularities of CNS metastasis distribution in the era of molecular advancement in oncology. Selected cases extracted from our institutions database will be presented. The cases will be didactically organized to illustrate the most common imaging characteristics and distribution of brain metastasis based on their organ of origin, such as lung, breast, renal, skin, testicle and gastrointestinal tract. (SCHROEDER T. et al., J Neurooncol. 2020). We will also discuss the correlation between tumor imaging findings and genetic profile. We intend to review well-known CNS metastasis imaging patterns, as preferential involvement of the posterior fossa and anatomic watershed areas in cases of lung cancer (TAKANO, K. et al. Neuro-Oncology, 2016) and the rarity of parenchyma metastasis from prostate cancer (HATZOGLOU V. et al, J Neuroimaging. 2014). We will also demonstrate newly described imaging findings in correlation with primary tumors genetic mutations, such as higher incidence of leptomeningeal involvement in triple negative breast cancer and increase in the number of brain lesions in cases of EGFR positive lung cancer. Familiarity with the most prevalent imaging characteristics of central nervous system metastasis helps oncologists and radiologists not to miss out a CNS progression in case of a known tumor, and also helps to direct systemic investigation of a primary tumor when brain metastasis is the initial presentation. The correlation between molecular profile and the most common sites of CNS involvement can help on treatment planning, including brain radiation (Yanagihara TK,et al., Tomography. 2017), and also bring to discussion the mechanisms of tumor dissemination, which can be targets for future treatments.
NIMG-08. A MULTI-CENTER RADIOMICS-BASED MODEL TO DIFFERENTIATE BETWEEN NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PLEXIFORM NEUROFIBROMAS AND MALIGNANT PERIPHERAL NERVE SHEATH TUMORS
Authors: Ly Ina , Liu Tianyu , Cai Wenli , Kwon Daniel , Michaels Olivia , Bredella Miriam , Jordan Justin , Dombi Eva , Widemann Brigitte , Hirbe Angela , Borcherding Dana , Srihari Divya , Melecio-Vázquez Mairim , Chi Ping , Boswell Demetrius , de Blank Peter , Pollard Kai , Pratilas Christine , Salamon Johannes , Mautner Viktor , Mulder Zachary , Steensma Matthew , Lee Shernine , Korf Bruce , Blakeley Jaishri , Plotkin Scott 
Published: November 2021

Abstract

BACKGROUND
Several MRI features are proposed to distinguish between plexiform neurofibromas (PNF) and malignant peripheral nerve sheath tumors (MPNST) in neurofibromatosis type 1 (NF1), including tumor size, margins, and degree of heterogeneity. However, most of these features are descriptive in nature, subject to intra-/interrater variability, and based on small single-institution studies. The goal of this study was to identify radiomic features that can differentiate between NF1-associated PNF and MPNST.

METHODS
31 MPNSTs and 24 PNFs from five centers were segmented on short TI inversion recovery sequences using a semi-automated segmentation software (3DQI). Standard pre-processing was performed, including N4 bias field correction, intensity normalization (using a mean of 120 SI and standard deviation of 80 SI), and resampling to 1 mm3 voxel resolution. 1688 radiomic features were extracted from the tumor region of interest using PyRadiomics, an open-source Python radiomics package. To classify tumors as PNF or MPNST, we implemented the Boruta algorithm and correlation removal for selection of important features. A Random Forest model was built using the top ten selected features. Five-fold cross-validation was performed and repeated 100 times. Model performance was evaluated using the area under the ROC curve (AUC), sensitivity, specificity, accuracy, and confidence intervals.

RESULTS
The top ten features included in the model were five intensity features, two shape features, and three texture features. The model demonstrated an AUC of 0.891 (95% CI 0.882-0.899), sensitivity of 0.744, specificity of 0.847, and accuracy of 0.802 (95% CI 0.792-0.813).

CONCLUSIONS
Our machine learning model demonstrated high performance in classifying tumors as either PNF or MPNST in NF1 individuals. Inclusion of additional tumors for model training and testing on an independent dataset are underway. Ultimately, our model may enable improved differentiation between PNF and MPNST compared to descriptive MRI features, permit early patient risk stratification, and improve patient outcomes.
NIMG-18. [18F]FLUCICLOVINE PET TO DISTINGUISH PSEUDOPROGRESSION FROM TUMOR PROGRESSION IN POST-TREATMENT GLIOBLASTOMA
Authors: Nabavizadeh S Ali , Doot Robert K , Young Anthony J , Bagley Stephen J , Ware Jeffrey B , Schubert Erin , Jr Fraser Henderson , Pantel Austin , Chen H Isaac , Lee John Y K , Desai Arati , O’Rourke Donald M , Nasrallah MacLean , Brem Steven 
Published: November 2021

Abstract
Differentiation of true tumor progression (TP) from pseudoprogression (PsP) is a major unmet need in patients with glioblastoma. [18F]Fluciclovine is a synthetic amino acid PET radiotracer that is FDA-approved in biochemical recurrence in prostate cancer. The study aim was to assess the value of [18F]Fluciclovine PET in differentiation of histologically confirmed (“true”) TP and PsP in post-treatment of glioblastoma. METHODS: 23 patients with glioblastoma with new contrast-enhancing lesions or lesions showing increased enhancement ( &gt; 25% increase) on standard MRI after completion of radiation underwent 60-minutes dynamic [18F]Fluciclovine PET imaging. Patients subsequently underwent resection of enhancing lesion and tumor percentage vs. treatment-related changes were quantified on histopathology. Patients were considered "true” TP if tumor represented ≥ 50% of the resected specimen, mixed TP-PsP if &lt; 50% and &gt; 10%, and PsP if tumor represented ≤ 10%. Summed 30- to 40-minute post-injection PET images were used to measure SUVpeak and SUVmax (g/mL units). RESULTS: 15 patients with “true” TP, 3 with mixed TP-PsP, and 5 with PsP were included. There was a positive correlation between SUVpeak by PET and tumor percentage by histology (Rho= 0.56, p= 0.006). Patients who demonstrated “true” TP had significantly higher SUVpeak compared to patients with histological PsP (4.8±1.6 vs 2.9± 1.0, p= 0.02, AUC= 0.91, n=20). SUVpeak cut-off of 3.3 provided 93% sensitivity, 80% specificity, and 90% accuracy for differentiation of “true” TP from PsP. Patients with “true” TP/mixed TP-PsP also had significantly higher SUVpeak than patients with PsP (4.6±1.5 vs 2.9± 1.0, p= 0.03, AUC= 0.88, n=23). SUVmax and partial volume-corrected SUVpeak and SUVmax exhibited similar performance. CONCLUSION: Our results indicated that [18F]Fluciclovine PET imaging can accurately differentiate “true” TP from PsP. Further studies are required to confirm these promising early results and determine optimal criteria for interpreting [18F]Fluciclovine PET to distinguish PsP from TP.
NIMG-20. DIFFERENTIATION OF TREATMENT-RELATED CHANGES FROM TUMOR PROGRESSION FOLLOWING BRACHYTHERAPY IN PATIENTS WITH WHO II AND III GLIOMAS USING FET PET
Authors: Bauer Elena , Werner Jan , Brunn Anna , Deckert Martina , Ruess Daniel , Ruge Maximilian , Celik Eren , Fink Gereon , Langen Karl-Josef , Galldiks Norbert 
Published: November 2021

Abstract

BACKGROUND
Following brachytherapy, the differentiation of radiation-induced changes (e.g., radiation necrosis) from actual tumor progression using MRI is challenging. To overcome this diagnostic uncertainty, we evaluated the diagnostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in glioma patients treated with brachytherapy.

MATERIAL AND METHODS
From 2006-2019, we retrospectively identified WHO grade II or III glioma patients (i) treated with brachytherapy using Iodine-125 seeds, (ii) equivocal or progressive MRI findings inside the radiation field, and (iii) additional FET PET imaging for diagnostic evaluation. Static FET PET parameters such as maximum and mean tumor-to-brain ratios (TBR) and dynamic FET PET parameters (i.e., time-to-peak, slope) were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses and Fisher’s exact test. Diagnoses were confirmed histologically or clinicoradiologically.

RESULTS
Following brachytherapy, suspect MRI findings occurred after a median time of 33 months (range, 5-111 months). In 10 of 21 patients (WHO grade II, n=5; WHO grade III, n=16), treatment-related changes were diagnosed. The best diagnostic performance for identification of treatment-related changes was obtained using maximum TBRs (threshold &lt; 3.20;accuracy, 86%; sensitivity, 100%; specificity, 73%; P=0.007). Mean TBRs reached an accuracy of 76% (threshold &lt; 2.05; sensitivity, 89%; specificity, 64%; P=0.010). Dynamic PET parameters did not reach statistically significant results.

CONCLUSION
Our data suggest that static FET PET parameters add valuable diagnostic information to diagnose radiation-induced changes in glioma patients treated with brachytherapy.
NIMG-27. REGORAFENIB RESPONSE ASSESSMENT USING FET PET IN PATIENTS WITH PROGRESSIVE GLIOMA
Authors: Werner Jan-Michael , Bauer Elena , Lohmann Philipp , Tscherpel Caroline , Brunn Anna , Deckert Martina , Kabbasch Christoph , Stoffels Gabriele , Fink Gereon , Langen Karl-Josef , Galldiks Norbert 
Published: November 2021

Abstract

BACKGROUND
The REGOMA phase 2 trial showed an encouraging overall survival benefit of the multikinase inhibitor regorafenib in glioblastoma patients at first progression. We used O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the early assessment of response to regorafenib in patients with progressive glioma in an advanced disease stage.

METHODS
Thirty patients with progressive glioma were treated according to the REGOMA trial and prospectively followed. FET PET and MRI were performed at baseline and after the second cycle of regorafenib. Static PET parameters such as maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) and metabolic tumor volumes (MTV) were calculated. Threshold values of FET PET parameters to predict a response were established by ROC analyses using an overall survival of ≥ 6 months as reference. The predictive value of FET PET parameters and their changes concerning overall survival was subsequently evaluated using the Kaplan-Meier test. MRI changes were evaluated according to the RANO criteria.

RESULTS
Up to now, 18 of 30 patients (glioblastoma, 83%; age range, 24-71 years) were eligible for data evaluation. The median number of tumor relapses before regorafenib was 2 (range, 1-4). During regorafenib (median cycles, 4; range, 2-9 cycles), CTCAE grade 3 or 4 side effects occurred in 56% and 11%, respectively. The median overall survival was 6 months (range, 3-18 months). After two cycles of regorafenib, a TBRmean reduction of 13% predicted a significantly longer overall survival (12 vs. 6 months; P=0.034). In contrast, MRI changes evaluated according to RANO criteria (i.e., Stable Disease or Partial Response vs. Progressive Disease) were not predictive (11 vs. 8 months; P=0.644).

CONCLUSION
Data suggest that amino acid PET using the tracer FET may be clinically valuable for identifying responders to regorafenib early after treatment initiation.
NIMG-56. USING RADIOMIC FEATURES FROM DAILY MAGNETIC RESONANCE IMAGING TO PREDICT RESPONSE TO RADIATION THERAPY IN GLIOBLASTOMA PATIENTS: A PILOT STUDY
Authors: Cullison Kaylie , Simpson Garrett , Maziero Danilo , Jones Kolton , Stoyanova Radka , Diwanji Tejan , Azzam Gregory , De la Fuente Macarena , Ford John , Mellon Eric 
Published: November 2021

Abstract
A dilemma in treating glioblastoma is that MRI after chemotherapy and radiation therapy (chemoRT) shows areas of presumed tumor growth in up to 50% of patients. These areas can represent true progression (TP), tumor growth with tumors non-responsive to treatment, or pseudoprogression (PP), edema and tumor necrosis with favorable treatment response. On imaging, TP and PP are usually not discernable. Patients in this study undergo six weeks of chemoRT on a combination MRI/RT device, receiving daily MRIs. The goal of this study is to explore the correlation of radiomics features with progression. The tumor lesion and surrounding areas of growth/edema were manually outlined as regions of interest (ROIs) for each daily T2-weighted MRI scan. The ROIs were used to calculate texture features: statistical features based on the gray-level co-occurrence matrix (GLCM), the gray-level zone size matrix (GLZSM), the gray-level run length matrix (GLRLM), and the neighborhood gray-tone difference matrix (NGTDM). Each of these matrix classes describe the probability of spatial relationships of gray levels occurring within the ROI. Daily texture features were averaged per week of treatment for each patient. Patient response was retrospectively defined as no progression (NP), TP, or PP. A Kruskal-Wallis test was performed to identify texture features that correlated most strongly with patient response. Forty texture features were calculated for 12 patients (19 treated, 7 excluded due to no T2 lesion or progression status unknown, 6 NP, 3 TP, 3 PP). There was a trend of more texture features correlating significantly with response in weeks 4-6 of treatment, compared to weeks 1-3. A particular texture feature, GLSZM Small Zone Low Gray-Level Emphasis, showed increasing difference between PP and TP over time, with significant difference during week 6 of treatment (p=0.0495). Future directions include correlating early outcomes with greater numbers of patients and daily multiparametric MRI.
NIMG-61. CLINICAL UTILITY OF SOMATOSTATIN RECEPTOR PET IMAGING BIOMARKERS FOR CHARACTERIZATION OF MENINGIOMA AMONG INCIDENTAL CNS LESIONS
Authors: Ensign Shannon Fortin , Argarwal Muskan , Badawy Mohamed , Halfdanarson Thorvardur , Johnson Derek , Sonbol Mohamad (Bassam) , Kendi Ayse 
Published: November 2021

Abstract

BACKGROUND
Somatostatin receptor (SSTR) PET/CT is utilized with increasing frequency in the clinical treatment of neuroendocrine tumors. Incidental CNS lesions are commonly noted and presumed to be meningiomas, however 68Gallium (Ga-68)-DOTATATE radionuclide use lacks specificity for meningioma identification. Currently there is no established SSTR-based imaging criteria for classification of incidental CNS lesions.

METHODS
We retrospectively analyzed patients across clinical and radiological databases at Mayo Clinic who had undergone both Ga-68-DOTATATE PET/CT and brain MR imaging who had an incidental CNS lesion identified with clinical or radiographic prediction of meningioma. Known meningioma diagnoses prior to imaging were excluded. Imaging indication, semi-quantitative measures, and corresponding clinical history were analyzed to identify metrics impacting both the predictive and descriptive utility of SSTR-based imaging as compared to corresponding MRI prediction in incidental CNS lesions.

RESULTS
Among 59 patients with a CNS lesion identified on both imaging modalities, most scans were performed for a history of neuroendocrine tumor (71%). Cases with concordant lesion type prediction of meningioma between imaging modalities (N = 25) displayed a higher median SUV max and Krenning score on Ga-68-DOTATATE PET compared to cases with concordant prediction of other lesions (N=10) or discordant prediction of meningioma (N=24). Ga-68-DOTATATE was more likely to discordantly predict meningioma as compared to the corresponding patient MRI in cases with lower SUV max values. The addition of Qclear technology was significantly associated with diagnostic clarification in cases of imaging discordant tumor type prediction. Prior cranial radiation or use of a somatostatin mimetic did not affect quantitative radiographic measures in lesion characterization, and MRI-based tumor size was similar across groups.

CONCLUSION
The continued development of SSTR-based imaging biomarker signatures across incidental CNS lesion subtypes will further define the role of this imaging modality in the clinical diagnosis and management of presumed meningiomas.