bluuebunny/crossref_metadata_2025 huggingface dataset:
INNV-04. PRIMARY TREATMENT OF SMALL-TO-MEDIUM(< 3CM) SPORADIC VESTIBULAR SCHWANNOMAS: SYSTEMATIC REVIEW & META-ANALYSIS (2010 TO 2020)
Authors: Savardekar Amey , Terrell Danielle , LeLe Saudamini , Kosty Jennifer , Wang Chiachien Jake , Guthikonda Bharat
Published: November 2022

INTRODUCTION

Over the past two decades, the treatment of small-to-medium (< 3cm) sporadic vestibular schwannomas (VS) has experienced a definite shift to stereotactic radiosurgery vis-a-vis microsurgery. We performed a systematic review and meta-analysis of VS patients primarily treated with stereotactic radiosurgery (SRS) or microsurgery (MS), with particular attention to hearing preservation outcomes (HPO), tumor control (TC), and facial nerve dysfunction (FND). Materials and

METHODS

A systematic review was conducted (Medline database) for the period, 2010 to 2020. Studies with mean/median follow-up of >/= 3 years were included. Studies had to report an acceptable standardized hearing metric. HPO, TC, and treatment complications (with special attention to FND) were compared between the MS and SRS groups.

RESULTS

Thirty-two studies met our inclusion criteria: 10 for microsurgery and 23 for radiosurgery (one comparative study included in both arms). HPO were comparable between MS group and SRS group (56% and 59%, p=0.1527). TC was significantly better in MS group (98%) versus SRS group (92%) [p < 0.0001]. FND was significantly higher in MS group (11%) versus SRS group (2%) [p < 0.0001].

CONCLUSION

The ability to diagnose small sporadic VS earlier, allows patients time to consider all possible treatment options which include observation, radiosurgery, or microsurgery. The data presented in this study will assist physicians in their ability to appropriately counsel patients on the benefits and risks of both treatment modalities with the most recent evidence on the factors that contribute greatly to patients’ quality of life: HPO, TC and FND.
INNV-07. TUMOR TREATING FIELDS (TTFIELDS; 200 KHZ) POST-MARKETING SAFETY DATA FROM PATIENTS WITH GLIOBLASTOMA TREATED BETWEEN 2011–2022
Authors: Mrugala Maciej , Shi Wenyin , Iwamoto Fabio , Lukas Rimas , Palmer Joshua , Suh John , Glas Martin
Published: November 2022

Tumor Treating Fields therapy (TTFields; 200 kHz) is a noninvasive, locoregional, antimitotic treatment approved for newly diagnosed glioblastoma (ndGBM), recurrent (r) GBM, malignant pleural mesothelioma, and is being investigated in additional solid tumors. Approval in GBM was based on results of the phase 3 EF-11 (TTFields monotherapy; rGBM) and EF-14 (TTFields therapy/maintenance temozolomide; ndGBM), which showed clinical benefit without an increase in adverse events (AEs). Here we review post-marketing surveillance (PMS) data from patients with brain tumors who received TTFields therapy over an 11-year period. Unsolicited PMS data from patients with brain tumors who received TTFields therapy between October 2011 and March 2022, were included. Overall 23,822 patients were included in this analysis. Most patients (72%) were from North America; 24% from Europe, Middle East and Africa, and 4% from Japan. Birth year was available for 23,784 patients; of these, the average age at treatment start was 57 years (range: 3–103). Diagnoses were ndGBM (67%), rGBM (27%), astrocytoma (WHO grade 3; 4%) and other (2%). Overall, 71% of patients reported ≥ 1 AE, with the most common being skin reaction (42%), electric (tingling) sensation (14%), heat (warmth) sensation (12%), and seizure (11%). Furthermore, 56% of patients reported AEs possibly related to TTFields therapy, with the most frequently reported being skin reaction (42%), electric sensation (14%) and heat sensation (12%), occurring underneath the arrays. Numbers and types of AEs were comparable between age and diagnosis groups. PMS data from > 23,000 patients with brain tumors show that TTFields therapy (200 kHz) is well-tolerated, consistent with the known safety profile; no new safety signals were identified. TTFields therapy is not associated with systemic toxicity; most common possibly-related AEs are localized dermatologic events that can be managed with appropriate prophylaxis and treatment strategies.
INNV-21. FEASIBILITY OF A VIRTUAL REALITY (VR) INTERVENTION TARGETING DISTRESS AND ANXIETY IN PRIMARY BRAIN TUMOR (PBT) PATIENTS AT THE TIME OF NEUROIMAGING: INTERIM ANALYSIS OF A PHASE 2 CLINICAL TRIAL
Authors: King Amanda , Roche Kayla , Leeper Heather , Vera Elizabeth , Mendoza Tito , Mentges Kelly , Acquaye Alvina , Adegbesan Kendra , Boris Lisa , Burton Eric , Chambers Claudia , Choi Anna , Christ Alexa , Evans Karen , Grajkowska Ewa , Levine Jason , Lindsley Matthew , Lollo Nicole , Komlodi-Pasztor Edina , Miller Hope , Panzer Marissa , Penas-Prado Marta , Pillai Valentina , Polskin Lily , Reyes Jennifer , Rogers James , Sahebjam Solmaz , Sass Dilorom (Delia) , Shuboni-Mulligan Dorela , Stockdill Macy , Theeler Brett , Wall Kathleen , Wollet Alex , Wu Jing , Gilbert Mark , Armstrong Terri
Published: November 2022

BACKGROUND

PBT patients experience high levels of distress and anxiety symptoms at the time of neuroimaging, yet few non-pharmacological interventions are available. This phase 2 clinical trial interim analysis explored feasibility of a VR relaxation intervention for a PBT population.

METHODS

PBT patients seen at NIH were recruited to participate in this single arm trial conducted via telehealth. English-speaking, adult patients with upcoming neuroimaging who can self-report symptoms and have reported distress on previous MD Anderson Symptom Inventory-Brain Tumor assessments were eligible. Exclusion criteria include recent surgery or seizures, anxiety disorders, nausea, or visual deficits. The primary intervention consisted of a brief VR session done within 2 weeks prior to neuroimaging with patient-reported outcomes (PROs) collected before and immediately post-intervention, as well as 1 week and 4 weeks later, with self-directed VR use over 1 month. A qualitative phone interview was also completed to assess patient satisfaction.

RESULTS

Fifty-five patients were screened and approached with 40 (73%) responding to initial reach-out and 20 ultimately enrolling (9 declines, 11 screen fails). Decline reasons included: no distress/anxiety (30%), treatment-related toxicities (11%), and unknown (59%). Seven (64%) failed screening due to exclusionary anxiety disorders (36% GAD, 18% PTSD, 9% claustrophobia). Of those enrolled, 65% were ≤ 50 years, 50% were male, 90% were White/non-Hispanic, 85% had good KPS ( > 80), 65% had high-grade tumors, and most were on active treatment. All enrolled patients completed the VR intervention and participation period, PROs questionnaires, weekly check-ins, and qualitative interview. Most patients (90%) reported frequent VR use with 7 mild adverse effects reported (headache, dizziness, nausea, neck pain).

CONCLUSION

These findings suggest that this intervention is feasible for this population with high enrollment and study completion, though incidence of anxiety disorders was higher than anticipated and a comprehensive evaluation of this cohort is planned.
INNV-26. EMERGENCE OF VIRTUAL TUMOR BOARD [VTB] IN NEURO-ONCOLOGY: OPPORTUNITIES AND CHALLENGES
Authors: Ekhator Chukwuyem , Kesari Santosh , Tadipatri Ramya , Fonkem Ekokobe , Grewal Jai
Published: November 2022

INTRODUCTION

Virtual tumor board [VTB] platforms are an important aspect of cancer management. They enable easier access to a multidisciplinary team of experts. In order to deliver high-quality cancer care, it is necessary to coordinate numerous therapies and providers, and maintain open lines of communication among all professionals involved. Design/

METHODS

We performed a systematic search of all VTBs incorporating a platform designed for this specific role. We reviewed the records of Genomet, Medical University of South Carolina[MUSC] and Xcures virtual tumor boards. Summary data examined include year of launch, demographics, characteristics of cases, average response time, advantages, and how they handle protected health information.

RESULTS

30% of VTBs examined launched in 2017. All had a HIPAA compliant online environment. Xcures records reveals median age of female patients was 57yrs and the median age of male patients was 55 years. The data showed that 44% with a confirmed treatment preferred VTB integrated option. 76% of patients in Xcures registry consist of primary CNS tumors. There are at least 556 patients in the tumor registry which included 46% Glioblastoma cases [96% primary, 4% secondary]. MUSC VTB shows 112 thoracic tumor cases and 9 neuro-Oncology cases. Genomet VTB data shows age range from 6 months to 84 years [mean age 44.5 years] with 69.6% males and 30.4% females, 43.5% glioblastoma, 8.7% adenocarcinoma, 8.7% infratentorial tumor. Average response time observed in all cases was ≤ 24 hours.

CONCLUSION

VTBs allow for quicker expert analysis of cases. More studies are needed to gain additional insight into user engagement metrics.
PATH-02. ANALYSIS OF MICRORNA EXPRESSION IN BRAIN METASTASES USING NEXT-GENERATION SEQUENCING
Authors: Jancalek Radim , Vecera Marek , Siegl Frantisek , Sana Jiri , Trachtova Karolina , Hendrych Michal , Vybihal Vaclav , Smrcka Martin , Hermanova Marketa , Kazda Tomas , Slaby Ondrej
Published: November 2022

BACKGROUND

Brain metastases (BMs) are intracranial tumors that frequently occur in adult cancer patients. Because the prognosis of patients with BM individually varies, it would be useful to improve prognostic scoring tools by including new high-performance biomarkers. MicroRNAs (miRNAs) appear to be promising in this regard as they are highly stable and, thus, suitable for both next-generation sequencing (RNA-Seq) and retrospective analyses in formalin-fixed and paraffin-embedded (FFPE) tissues.Material and

METHODS

Total RNA enriched for miRNAs was isolated from 71 freshly frozen histopathologically confirmed BMs with origin in 5 tumor types (ca lung - 37%, melanoma - 23%, ca breast - 18%, RCC - 15%, CRC - 7%) using mirVana miRNA Isolation Kit (Thermo Fisher Scientific). Sequencing libraries were prepared from RNA using the QIAseq miRNA Library Kit (Qiagen) and sequenced using the NextSeq 500 platform (Illumina). The miRNA molecules were subsequently transcribed from total RNA samples isolated from a retrospective set of 119 FFPE tissues using the TaqMan Advanced miRNA cDNA Synthesis Kit, and the expression of selected miRNAs was validated in a pilot experiment by qPCR using TaqMan Fast Advanced Master Mix and appropriate TaqMan MicroRNA Assays (all from Thermo Fisher Scientific).

RESULTS

The differential analysis identified 373 miRNAs with significantly different expression among the 5 BMs groups (p< 0.001). A molecular classifier based on the expression of 32 miRNAs was able to classify all samples correctly. Out of these, seven, including miR-122-5p, miR-141-3p, miR-146a-5p, miR-194-5p, miR-200c-3p, miR-211-3p, and miR-215-5p, were chosen for subsequent validation and their significantly different expression in 5 BMs groups was validated.

CONCLUSIONS

Presented results confirm the importance of studying dysregulated miRNA expression in BM and the diagnostic potential of validated miRNAs. The study was prepared with the grant support of the Ministry of Health of the Czech Republic - grant No. NV18-03-00398.
PATH-10. A CASE OF ADULT THALAMIC DIFFUSE MIDLINE GLIOMA, H3 K27-ALTERED WITH AN IMPRESSIVE RESPONSE TO RADIOTHERAPY AND CONCOMITANT PLUS ADJUVANT TEMOZOLOMIDE
Authors: Rousseau Julien , Labidi Moujahed , Bahary Jean-Paul , Bélanger Karl , Berthelet France , Lapointe Sarah
Published: November 2022

Diffuse midline glioma (DMG), H3 K27-altered is a newly defined diagnosis in the 2021 WHO Classification of Tumors of the Central Nervous System. H3 K27 alterations are associated with a uniformly poor prognosis in children with DMG, but they have been linked to improved survival in adults. Clinical experience in adults with DMG, H3 K27M-altered remains limited. Consequently, there exists a knowledge gap regarding the optimal management and responsiveness to chemoradiation therapy, which translates into the current absence of standard treatment. Here we present the case of an 18-year-old female patient treated for a thalamic DMG, H3 K27-altered at a Canadian tertiary center. The patient first presented with headache, dysarthria, and signs of increased intracranial pressure. Her initial brain magnetic resonance imaging demonstrated a right thalamo-mesencephalic lesion with central nodular enhancement and secondary hydrocephalus. She underwent an endoscopic third ventriculostomy followed by a subtotal resection, and pathology confirmed the presence of a DMG, H3 K27-altered, WHO grade 4. She was treated with combined radiotherapy and concomitant plus adjuvant (12 cycles) temozolomide. The Stupp regimen induced a spectacular response with a reduction in tumor dimensions on T2/FLAIR (20 x 18 mm versus 60 x 51 mm), > 50% decrease in size of the enhancing component, complete resolution of mass effect, and return to functional independence (KPS = 100%). Unfortunately, her disease progressed 16 months after diagnosis and she passed away 8 months later, despite having received 3 cycles of ONC201 through a clinical trial. Her progression-free survival (16 months) was superior to that reported in the literature, which could be related to her young age, subtotal resection status, and thalamic location. Although the addition of chemotherapy to adjuvant radiotherapy has not been shown to improve survival in children with DMG, the Stupp regimen may provide a survival benefit in adults.
PATH-18. SHOULD LEPTOMENINGEAL DISSEMINATION (LMD) AT DIAGNOSIS WITH AN H3K27M MUTATION BE ENOUGH TO BE CONSIDERED A DIFFUSE MIDLINE GLIOMA (DMG) H3K27M ALTERED?
Authors: La Janet , McGranahan Tresa
Published: November 2022

Currently diffuse midline glioma (DMG) H3K27M-altered is defined as a diffuse, infiltrating midline glioma with an altered H3K27M pathway. A number of brain tumors have been reported with alterations in H3K27M that do not meet DMG diagnostic criteria and the clinical significance of H3K27M alteration in these tumors is unknown. Patients with extensive leptomeningeal disease often do not undergo large tumor resections and as a result there is limited tissue available for histologic evaluation. We present two patients who presented with leptomeningeal disease (LMD) and given extent of disease were only able to undergo subtotal resection. In both of these cases, the pathology specimens were found to have H3K27M alterations by immunohistochemistry but did not meet the diagnostic criteria for DMG due to the lack of histologic evidence of infiltration. Both patients were young women (age 23 and 28) who presented with new headaches, nausea, and vomiting and were found to have extensive LMD. Both were treated initially with proton craniospinal radiation and concurrent temozolomide. Within 1 year of initial diagnosis, both had radiographic and clinical progression of both parenchymal and LMD. Despite aggressive treatment, both patients clinically declined and transitioned to hospice within 2 years of diagnosis. Our understanding of the H3K27M altered pathway at this time is limited, and the significance of this mutation is unknown in tumors where an infiltrating component is not captured histologically. While LMD is rare at initial presentation of DMG, it is seen commonly at disease progression. We propose that the presence of H3K27M alteration with known leptomeningeal disease at diagnosis should be considered grade 4 histology and DMG for the purposes of prognostication and clinical trial consideration. Given ability to detect this mutation in CSF sampling, this may spare patients from surgical intervention and expedite time to treatment.
PATH-25. LEPTOMENINGEAL, DURAL, AND EXTRACRANIAL METASTASIS OCCUR IN DIVERSE TYPES OF ADULT HIGH-GRADE GLIOMA
Authors: Travers Sarah , Kleinschmidt-DeMasters B K , Ryan Ormond D
Published: November 2022

BACKGROUND

Leptomeningeal and extracranial metastases in adult high-grade gliomas are being increasingly recognized as critical issues. Our group has a longstanding interest in this issue, having published multiple examples in 2015 (PMID: 26308254) and 1996 (8617464). We now update our experience, illustrating that dissemination can occur in diverse types of high-grade gliomas, even those with purportedly more favorable prognoses.

METHODS

Search of records, 2018-present, to identify patients with leptomeningeal, dural, and/or extracranial spread clinically recognized prior to patient demise.

RESULTS

Leptomeningeal dissemination was identified in 6 patients: one astrocytoma (frontal lobe, IDH1 R132H+, metastatic to 3-levels spinal cord), a second astrocytoma (frontal lobe, IDH1 R132H+, metastatic to spinal cord with intracranial dissemination), one glioblastoma, small cell type (PIK3CA, CDH1, TP53 mutations, temporal lobe metastatic to cervical cord), one high-grade glioma with piloid features (HGAP, metastatic at presentation; BRAF-mutant, classified by DNA methylation (NIH)) and one high-grade glioma with no match to DNA methylation class (metastatic at presentation, NIH). There were three additional patients: one patient with glioblastoma with FGFR: TACC3 fusion with short-interval dural and cervical lymph node metastases (in Press), one patient with glioblastoma with EGFR amplification and dural invasion and one patient with glioblastoma with massive dural spread and bony invasion at presentation.

CONCLUSION

Although these new 9 individual cases provide no insights into the epidemiology of GBM leptomeningeal, dural and extracranial metastases, our single-institution series, using updated molecular classifications not always available in retrospective studies, shows that dissemination can occur in any, and all, types of adult high-grade gliomas. We put this cohort in perspective with our experience with dissemination in other low and high-grade tumor types: anaplastic myxopapillary ependymomas (30417460), H3 K27M-altered high-grade gliomas (29393845), pineal parenchymal tumors of intermediate differentiation (34418607), myxoid glioneuronal tumor, PDGFRA-mutant (34297434) and spinal cord gangliogliomas (25015869).
PATH-43. HISTOLOGY OF RADIATION-INDUCED PSEUDOPROGRESSION WITH MULTIPLE FOCI IN TREATED GLIOBLASTOMA
Authors: Banerjee Somdeb , Tran Di , Trevino Christopher
Published: November 2022

Radiation induced pseudoprogression (PsP) of brain tumors is defined radiologically as new or enlarging areas of non-tumor magnetic resonance imaging (MRI) contrast enhancement developing within the initial 3-6 months after completing radiation. Distinguishing PsP from genuine tumor progression is of the utmost importance in deciding the clinical course of a patient. Although it is typically diagnosed radiologically, obtaining tissue histopathology can clarify diagnostic uncertainty. However, there is no consensus on defining PsP pathologically. We present the case of a 38-year-old man with a glioblastoma, IDH-wild type, CNS WHO Grade 4 (MGMT promoter methylated) with steroid-refractory PsP, and correlate both radiologic and pathologic features. After initial treatment with a gross total resection and radiation with concurrent temozolomide, he developed a new contrast-enhancing, mass-neutral enhancing lesion consistent with PsP, which did not resolve despite 4 cycles of temozolomide and prolonged steroid treatment. The enhancing lesion was resected, and the pathological examination demonstrated areas of non-pseudopallisading necrosis, numerous macrophages, astrocytosis, hyalinization of blood vessels, and low mitotic activity in the brain parenchyma with residual infiltrative glioma. These features were consistent with radiation-treatment effect and supported a diagnosis of PsP. Over time, varying definitions for PsP include a percentage threshold of treatment effect or necrosis per sample. However, the authors recognize potential sampling bias. Therefore, we recommend including treatment-related effects coupled with the absence of tumor proliferation in the results. These features include fibrinoid necrosis, hyalinization of blood vessels, and eosinophilic coagulation necrosis. From a therapeutic standpoint, it is important to comment on the presence or absence of residual glioma cell proliferation. This case highlights a unique paring of focal histopathology with correlative sections on MRI for pseudoprogression which has not been previously presented.
PATH-44. VARIANT ALLELIC FREQUENCY OF DRIVER MUTATIONS PREDICTS SUCCESS OF GENOMIC METHYLATION CLASSIFICATION IN CNS TUMORS
Authors: Jamshidi Pouya , Galbraith Kristyn , Mccord Matthew , Santana-Santos Lucas , Jennings Lawrence , Snuderl Matija , Horbinski Craig
Published: November 2022

Whole genome CpG DNA methylation profiling is an extremely valuable tool in the workup of central nervous system (CNS) tumors. Reliability of such profiling depends on sufficient tumor cellularity. Many neoplastic entities have well-known driver mutations that occur in virtually 100% of tumor cells, and next-generation sequencing (NGS) assays can detect those mutations and report their relative amounts in the form of Variant Allelic Frequency (VAF). Since NGS and methylation profiling are often done on the same tumor block, we sought to determine whether driver mutation VAF affects the accuracy of methylation profiling, and whether VAF can help establish more rigorous cutoffs for quality assurance. Using NGS and Infinium Epic850K methylation arrays, we evaluated 153 CNS neoplasms representing a range of entities, including TERT promoter-mutant glioblastoma, IDH-mutant astrocytoma, IDH-mutant oligodendroglioma, SHH-driven medulloblastoma, and CTNNB1-driven adamantinomatous craniopharyngioma. VAFs of each driver mutation ranged between 1-60%. One hundred eleven of 153 cases (73%) had a methylation classification score ≥ 0.9, the most widely accepted cutoff for a successful result. A fit-of-mixture analysis via CutoffFinder (PMID: 23251644) suggested that the optimal VAF cutoff=31%, generating an AUC of 0.87. Ninety-six of 107 (89%) cases with a VAF of 31% or higher had a methylation classification score ≥ 0.9, whereas only 15/46 (33%) below 31% were classifiable with methylation profiling (P< 0.0001 by Fisher’s exact test). An independent validation cohort from NYU (N=50) showed nearly identical results, with 37/50 (74%) of cases having a methylation classification score ≥ 0.9, an optimal cutoff=0.32 with an AUC=0.84, and % classification above and below the 0.32 cutoff being 30/34 (88%) and 7/16 (44%), respectively (P=0.002) These data indicate that VAF of driver mutations can serve as a useful predictor of classification success via methylation profiling, and should be taken into account when interpreting methylation profiling results.
NIMG-05. DYNAMIC SUSCEPTIBILITY CONTRAST MRI IN THE EVALUATION OF BRAIN METASTASES: CURRENT PRACTICE REVIEW AND RATIONALE FOR STUDY OF BASELINE PERFUSION IMAGING PRIOR TO STEREOTACTIC RADIOSURGERY (STARBEAM-X)
Authors: Dobeson Caroline , Birkbeck Matthew , Bhatnagar Priya , Hall Julie , Pearson Rachel , West Serena , English Philip , Butteriss David , Lewis Joanne
Published: November 2022

Stereotactic radiosurgery (SRS) is an established focal treatment for brain metastases with high local control rates. An important side-effect of SRS is the development of radionecrosis. On conventional MR imaging, radionecrosis and tumour progression often have similar appearances, but have contrasting management approaches. Perfusion MR imaging is often used in the post-treatment setting in order to help distinguish between the two, but image interpretation can be fraught with challenges.Perfusion MR plays an established role in the baseline and post-treatment evaluation of primary brain tumours and a number of studies have concentrated on the value of perfusion imaging in brain metastases. Of the parameters generated, relative cerebral blood volume is the most widely used variable in terms of its clinical value in differentiating between radionecrosis and tumour progression.Although it has been suggested that the rCBV tends to be elevated in active metastatic disease following treatment with radiosurgery, but not with treatment-related changes, the literature available on interpretation of the ratios provided in the context of defining tumour progression is not consistent.We provide an overview of the role perfusion MRI plays in the assessment of brain metastases and introduces the rationale for the STARBEAM-X study (Study of assessment of radionecrosis in brain metastases using MR perfusion extra imaging), which will prospectively evaluate baseline perfusion imaging in brain metastases. We present here the results of the first three patients recruited to the feasibility phase of this study. We hope this study will allow insight into the vascular appearance of metastases from different primary sites, and aid in the interpretation of post-treatment perfusion imaging.
NIMG-08. AN INTEGRATED INFORMATICS MODEL COMBINING CLINICAL FACTORS, RADIOMICS AND A NOVEL CONNECTOMICS FRAMEWORK TO DISTINGUISH PATHOLOGICALLY-PROVEN RADIONECROSIS FROM PROGRESSION IN TREATED BRAIN METASTASES
Authors: Lee Emerson , Cao Linda , Vishwa Parekh , Chen Scott , Redmond Kristin , Peng Luke , Michael Jacobs , Kleinberg Lawrence
Published: November 2022

PURPOSE/OBJECTIVE(S)

To distinguish radionecrosis (RN) from true progression (TP) in brain metastases treated with stereotactic radiosurgery (SRS), we apply machine learning to create a multi-domain model that incorporates clinical factors, multiparametric radiomics(mpRads), and tumor connectomics, a novel MRI-based complex graph theory framework that describes the intricate network of relationships within the tumor and surrounding tissue.

MATERIALS/METHODS

Metastases treated with SRS that had pathologic confirmation of RN vs. TP after imaging progression were included from a single institution. Regions of interest were manually segmented using the single largest diameter of the T1 post-contrast(T1C) lesion plus the corresponding area of T2 FLAIR hyperintensity. We developed an Integrated Radiomics Informatics System (IRIS) based on an isomap support vector machine (IsoSVM) model to classify TP from RN using leave-one-out cross-validation (LOOCV). Class imbalance was resolved using differential misclassification weighting during model training using IRIS. Area under the receiver operating characteristic (AUC-ROC) and AUC-PR (precision recall) analysis were performed.

RESULTS

We analyzed 135 lesions in 110 patients. There were 43 cases (31.9%) of RN and 92 cases (68.1%) of TP. The top-performing connectomics features were degree centrality (increased with RN) and average path length (decreased with RN), suggesting greater “connectivity” and increased similarity in intralesional features between the T1C and FLAIR signal regions in RN cases. The top-performing radiomics feature was multidimensional entropy (increased in TP), demonstrating greater heterogeneity in TP cases. Finally, the top-performing clinical features were prior RT before SRS, histology, and treated lesion size. The LOOCV IsoSVM model successfully classified TP from RN with an AUC-ROC of 0.84 (95% CI: 0.77-0.90) and AUC-PR of 0.90 (95% CI: 0.82-0.95). The F1 score was 0.89.

CONCLUSION

Our novel machine-learning framework was able to efficiently combine features from multiple domains (i.e., radiomics, connectomics, and clinical factors) to distinguish pathologically-proven TP from RN with excellent discrimination.
NIMG-24. LONGITUDINAL MR SPECTROSCOPY TO DETECT PROGRESSION IN PATIENTS WITH LOWER-GRADE GLIOMA IN THE SURVEILLANCE PHASE
Authors: Avalos Lauro , Luks Tracy , Gleason Tyler , Damasceno Pablo , Li Yan , Lupo Janine , Phillips Joanna J , Bush Nancy Ann Oberheim , Taylor Jennie , Chang Susan M , Villanueva-Meyer Javier
Published: November 2022

BACKGROUND

Monitoring lower-grade gliomas (LrGGs) for disease progression is made difficult by the limits of anatomical MRI to distinguish treatment-related tissue changes from tumor progression. MR spectroscopic imaging (MRSI) offers additional metabolic information that can help address these challenges. The goal of this study was to compare longitudinal changes in multiparametric MRI, including diffusion-weighted imaging, perfusion imaging, and 3D MRSI, for LrGG patients who progressed at the final time point and those who remained clinically stable.

METHODS

Forty-one patients with LrGG who were clinically stable were longitudinally assessed for progression. Changes in anatomical, diffusion, perfusion, and MRSI data were acquired and compared between patients who remained clinically stable and those who progressed.

RESULTS

Thirty-one patients remained stable, and 10 patients progressed. Over the study period, progressed patients had a significantly greater increase in normalized choline, choline-to-N-acetylaspartic acid index (CNI), normalized creatine, and creatine-to-N-acetylaspartic acid index (CRNI), than stable patients. CRNI was significantly associated with progression status and WHO type. Progressed astrocytoma patients had greater increases in CRNI than stable astrocytoma patients.

CONCLUSIONS

LrGG patients in surveillance with tumors that progressed had significantly increasing choline and creatine metabolite signals on MRSI, with a trend of increasing T2 FLAIR volumes, compared to LrGG patients who remained stable. These data show that MRSI can be used in conjunction with anatomical imaging studies to gain a clearer picture of LrGG progression, especially in the setting of clinical ambiguity.
NIMG-32. POSTPROGRESSION SURVIVAL AND MRI FEATURES AT PROGRESSION IN MGMT-METHYLATED GLIOBLASTOMA FOLLOWING TEMOZOLOMIDE (TMZ) OR CCNU/TMZ THERAPY - AN ANALYSIS OF THE CETEG/NOA-09-TRIAL
Authors: Zeyen Thomas , Paech Daniel , Weller Johannes , Schäfer Niklas , Tzaridis Theophilos , Duffy Cathrina , Nitsch Louisa , Schneider Matthias , Steinbach Joachim , Hau Peter , Schlegel Uwe , Seidel Clemens , Krex Dietmar , Grauer Oliver , Goldbrunner Roland , Zeiner Pia , Tabatabai Ghazaleh , Galldiks Norbert , Stummer Walter , Hattingen Elke , Glas Martin , Radbruch Alexander , Herrlinger Ulrich , Schaub Christina
Published: November 2022

INTRODUCTION

In the randomized CeTeG/NOA-09 trial, combined CCNU/TMZ was superior to TMZ therapy regarding overall survival (OS) in newly diagnosed patients with MGMT-methylated glioblastoma. Using modified RANO criteria, however, progression-free survival (PFS) and pseudoprogression rates were similar in both arms. Exploring the hypothesis of undetected pseudoprogressions being accountable for this discrepancy, we analyzed patterns of postprogression survival (PPS) and MRI features at RANO-defined progression.

METHODS

86 CeTeG/NOA-09 patients with progression (modified RANO criteria) and MRI evaluable for standardized T1 and FLAIR volumetry at baseline and progression were included. Patients were further subdivided to short PPS (< 24 months) or long PPS (> 24 months) and a PPS/PFS ratio was calculated.

RESULTS

In the CCNU/TMZ arm, long PPS patients (n=10) tended to a shorter PFS (median 7.3 months) than short PPS patients in the same arm (n=33, 14 months, p=0.089, logrank test) and long PPS patients in the TMZ arm (n=9, 12.7 months, p=0.21). The mean PPS/PFS ratio in the long PPS group was markedly higher in the CCNU/TMZ arm (5.8) compared to the TMZ arm (3.3, p=0.043, Mann-Whitney test). Patients with long PPS of the CCNU/TMZ arm showed a nonsignificant tendency to a stronger volumetric increase in T1 enhancement (mean delta 6184,86 vs. 697.5 mm³) and FLAIR–T1-enhancement (mean delta 42671 vs 16860 mm³) at progression as compared to long PPS patients of the TMZ arm.

CONCLUSION

Combining a substantially increased PPS/PFS ratio (long OS despite particularly short PFS according to RANO) with indications for increased contrast enhancement and FLAIR volume at progression, the patients with long PPS in the CCNU/TMZ arm appear to differ from those in the TMZ arm. These observations support the hypothesis that this group (~25% of CCNU/TMZ-treated patients) contained patients with pseudoprogression undetected by modified RANO criteria.
NIMG-34. QUANTIFICATION OF GLYCOLYTIC FLUX REDUCTION IN RECURRENT GLIOBLASTOMA AFTER EGFR INHIBITION USING MOLECULAR MR-PET
Authors: Ellingson Benjamin , Nathanson David , Yao Jingwen , Hagiwara Akifumi , Raymond Catalina , Salamon Noriko , Pope Whitney , Lai Albert , Nghiemphu Phioanh L , Cloughesy Timothy
Published: November 2022

In recently published work, we demonstrated that acute inhibition of the EGFR – the most frequently altered oncogene in GBM – can rapidly reduce glycolysis in a subset of GBM. To quantify this effect, we propose a new combination metabolic MR-PET imaging biomarker that combines 18F-FDG PET, DSC perfusion MRI, diffusion MRI, and pH- and oxygen-sensitive amine CEST-SAGE-EPI. Specifically, this “glycolytic index” or GI, can be defined as elevated glucose uptake (18F-FDG standard uptake value), elevated tumor acidity (MTRasym@3ppm), and lower oxygen utilization (relative cerebral metabolic rate of oxygen, rCMRO2, defined as R2’ x rCBF/rCBV from oxygen-sensitive SAGE-EPI and DSC perfusion), normalized to cell density (using ADC from diffusion MRI). In the current study, we explored the use of Tagrisso® (Osimertinib or AZD9291), which has very high brain to plasma ratios (> 1) and has proven effective in CNS metastasis of EGFR mutant lung cancer, as a potential treatment for EGFR amplified recurrent GBM. We have conducted a clinical trial (NCT03732352) to determine whether we observe similar metabolic imaging changes in EGFR mutated or amplified recurrent glioblastoma patients after treatment with osimertinib. Consistent with prior in vitro and in vivo results, treated patients exhibited a reduced glycolytic flux as indicated by reduction in 18F-FDG PET uptake (-3% change in SUV), tumor acidity (-19% change in MTRasym@3ppm) on pH-weighted CEST MRI, and glycolytic index (GI) (-25% change) in EGFR amplified recurrent GBM within 24 hours of treatment. Preliminary data suggests early change in GI correlates with and predicts both PFS (Pearson correlation, R2=0.3463, P=0.0441; Log-rank, P=0.0467) and OS (R2=0.6368, P=0.0019; Log-rank, P=0.0192). These preliminary data establish the scientific premise that a “glycolytic index” created using 18F-FDG PET, DSC perfusion, diffusion MRI, and pH- and oxygen-weighted amine CEST-SAGE-EPI may be an important tool for quantifying and visualizing glycolytic flux in GBM.
NIMG-50. ASSOCIATION BETWEEN SALINITY, ACIDITY, DIFFUSIVITY, AND HYPOXIA IN HUMAN GLIOMAS USING MULTI-NUCLEAR MRI
Authors: Cho Nicholas S , Thakuria Shruti , Sanvito Francesco , Hagiwara Akifumi , Wang Chencai , Nagaraj Raksha , Lu Jianwen , Oshima Sonoko , Raymond Catalina , Cloughesy Timothy , Liau Linda M , Everson Richard G , Nghiemphu Phioanh L , Lai Albert , Ellingson Benjamin
Published: November 2022

INTRODUCTION

Sodium MRI has been recently explored in brain tumors to potentially reveal complementary information with proton MRI about the tumor microenvironment. However, there remains limited investigation combining sodium and quantitative proton MRI techniques. This pilot study explored the associations of sodium MRI with diffusion-, pH-, and hypoxia-weighted MRI biomarkers in gliomas.

METHODS

Eleven patients with gliomas (n=8 IDH-wild-type; n=3 IDH-mutant) who obtained sodium, anatomical, diffusion-, pH-, and hypoxia-weighted MRI were studied. All images were obtained on a 3T Siemens Prisma with a dedicated multi-nuclear head coil. Regions-of-interest were segmented on the contrast-enhancing (CE) (n=10), FLAIR (n=11), and necrotic regions (n=9). Sodium values were normalized to the mean values of the eyes. Median sodium, apparent diffusion coefficient (ADC), ADC(L) from bimodal histogram analyses, MTRasym (acidity), and R2’ (hypoxia) values were obtained.

RESULTS

There was increased sodium in necrosis compared to FLAIR regions (mean difference=0.24; P/i>< 0.05) and compared to CE regions (mean difference=0.17; P/i>=0.07). There were significant positive correlations between sodium and ADC in CE (R=0.94; P/i>< 0.0001) and FLAIR regions (ρ=0.77; P/i>< 0.01), but not in necrosis (R=0.44; P/i>=0.24). There was also a significant positive correlation with ADC(L) in CE regions (R=0.90; P< 0.001) but not in FLAIR regions (ρ=0.50; P/i>=0.12). Furthermore, there was a significant positive correlation between sodium and MTRasym in necrosis (R=0.74; P/i>< 0.05) and a positive trend in CE regions (R=0.55; P=0.10). There was also a negative trend between sodium and R2’ in FLAIR regions (ρ=-0.58; P/i>=0.11).

CONCLUSIONS

Because ADC and ADC(L) are inversely related to cell density, increased sodium in gliomas may reflect increased extracellular space stemming from lower cell density, as sodium concentration is higher extracellularly. Positive associations between sodium and acidity as well as negative associations between sodium and hypoxia may reflect alterations in coupled sodium-pH and sodium-hypoxia homeostasis in gliomas.
NIMG-74. RADIOIMMUNOMIC SIGNATURES IN PEDIATRIC LOW-GRADE GLIOMA BASED ON MULTIPARAMETRIC MRI SCANS
Authors: Kazerooni Anahita Fathi , Kraya Adam A , Kim Meen Chul , Khalili Nastaran , Arif Sherjeel , Jin Run , Rathi Komal , Familiar Ariana , Madhogarhia Rachel , Haldar Debanjan , Bagheri Sina , Anderson Hannah , Shaikh Ibraheem Salman , Haldar Shuvanjan , Ware Jeffrey B , Vossough Arastoo , Storm Philip B , Resnick Adam C , Davatzikos Christos , Nabavizadeh Ali
Published: November 2022

Understanding the immune microenvironment in pediatric low-grade glioma (pLGG) patients may help in identification of the patients who benefit from anti-tumor immunotherapies. However, surgical resection is not feasible for many pLGG tumors in certain anatomical locations. Therefore, developing non-invasive tools that characterize the tumor microenvironment prior to therapeutic interventions could contribute to stratification and enrollment of the patients into relevant clinical trials. In this work, we derived radiomic signatures of immune profiles (radioimmunomics) based on machine learning (ML) analysis of readily available conventional MRI scans. Transcriptomic data for a cohort of 197 subjects was retrospectively collected from Open Pediatric Brain Tumor Atlas (OpenPBTA). The patients were categorized into three groups (Group1-3) based on their immunological profiles using consensus clustering algorithm. This analysis revealed greater immune cell infiltration in non-BRAF mutated pLGGs. Group1 showed more enrichment in M1 macrophages, and microenvironment and immune scores compared to Group2 and Group3. Elevated tumor inflammation score (TIS), as a predictor of clinical response to anti-PD-1 blockade, was observed in Group1 compared to Group2 (p= 1.4e-7) and Group3 (p= 0.0054). Radiomic features, including volumetric, morphologic, histogram, and texture descriptors, were extracted from the segmented tumor regions on multiparametric MRI (mpMRI) scans of 71 (of 197) patients. Multivariate ML models were trained to predict the three immunological groups based on radiomic features using cross-validated random forest classifier along with recursive feature elimination, which yielded AUC of 0.72 for this multi-class classification problem. Our findings indicate the presence of distinct immunological groups in pLGG tumors, with possibly more favorable response to immunotherapies in Group1 tumors. Furthermore, we developed radioimmunomic signatures based on pre-operative conventional mpMRI that can potentially stratify the patients based on their immune tumor microenvironment. Based on these initial promising results, we are exploring additional features to increase the accuracy of radioimmunomics model.
NIMG-82. RADIOGENOMIC SIGNATURES OF KEY DRIVER GENES IN GBM REVEAL MOLECULAR HETEROGENEITY OF THE TUMOR MICROENVIRONMENT LINKED TO SPATIAL DISTRIBUTION: IMPACT ON THE TRAJECTORY OF GLIOMA EVOLUTION
Authors: Kazerooni Anahita Fathi , Akbari Hamed , Toorens Erik , Grigoriadis Dimitris , Hu Xiaoju , Sako Chiharu , Mamourian Elizabeth , Bagley Stephen , Binder Zev A , Lustig Robert , Brem Steven , O'Rourke Donald , Ganguly Tapan , De Subhajyoti , Hatzigeorgiou Artemis , Bakas Spyridon , Nasrallah MacLean , Davatzikos Christos
Published: November 2022

Somatic genomic alterations acquired during GBM growth enhance adaptation of tumor cells to their microenvironment and give rise to molecular heterogeneity. Radiogenomics could facilitate exploration of the underlying pathobiology of tumor growth in specific microenvironments and thereby, promote precision medicine for the patients. We derived radiogenomic signatures of key driver genes and evaluated molecular compositions of tumor groups with predisposition to specific brain regions. Pre-operative multiparametric conventional MRI scans of 357 IDH-wildtype GBM patients with available targeted NGS data were jointly segmented and registered into a common template. We constructed spatial distribution atlases for tumors harboring mutations in driver genes and identified four distinct groups of tumor locations with predilection to the left frontal cingulate region (Group1), right temporal (Group2), right parietal (Group3), and occipital pole (Group4). Evaluation of the differences in molecular features of the tumor groups included: (1) exploring similarities of genomic profiles across all four groups by evaluating cosine similarity metric (CSM) between mutational signatures; (2) quantification of molecular heterogeneity based on Mutant Allele Tumor Heterogeneity (MATH) scores; and (3) inference of the evolutionary trajectories. Groups 1 and 4 were the most different, and Groups 2 and 3 were the most similar tumors, molecularly. The mutational signatures between Groups 1 and 4 revealed a CSM of 0.35. Group1 showed significantly lower MATH score (less heterogeneity) compared to Group4 (p< 0.05). Evaluation of evolutionary patterns suggested NF1 mutation as an early event in Group1, without subsequent gain of function or mutation in EGFR. In contrast, in Group4, EGFR mutations were early events triggering PTEN mutations later in the evolutionary trajectory. Radiogenomic signatures revealed distinct molecular underpinnings for the tumors with predilection towards specific brain regions that may suggest existence of different tumor microenvironments in different brain regions that cause intra- and inter-patient heterogeneity in the molecular tumor composition.
NIMG-94. A RARE CASE OF INFRATENTORIAL CEREBELLAR VERMIS MULTINODULAR AND VACUOLATING NEURONAL TUMOR
Authors: Lomax Jerica , Kuoy Edward , Kong Xiao-Tang
Published: November 2022

INTRODUCTION

Multinodular and vacuolating neuronal tumor (MVNT) is a rare entity that was first recognized by the World Health Organization Classification of Tumors of the Central Nervous System in 2016. The majority of MVNT cases reported were supratentorial in location and only a small subset of cases included infratentorial involvement. In the supratentorial, MVNT is often a nidus for seizure and surgical resection is for seizure control. Infratentorial MVNT lesions are typically not or only mildly symptomatic; thus, surgical intervention may not be warranted. Here we describe the clinical course of a patient who was found to have a cerebellar vermis lesion that consistent with infratentorial MVNT.

CASE REPORT

A 41-year-old man sought care due to new onset headache. A brain magnetic resonance imaging (MRI) exam revealed a coalescence of bubble-like cystic lesions in the cerebellar vermis that were T1 hypointense, T2/Flair hyperintense without contrast enhancement. Initially, the lesions were attributed to neurocysticercosis but work-up was not supporting the diagnosis. MRA of head and neck found no cerebral stenosis or vascular malformation. The unique MRI features support infratentorial MVNT diagnosis. Disease course, work-up and MRI features are not consistent with low grade glioma, subacute ischemia infarct, demyelinating disease or chronic fungal or parasite infection. Brain MRI surveillance has completed every 6 months; no interval change to the cerebellar vermis lesions has been seen over past two years. Clinically, the patient has been doing well and his headache has resolved.

DISCUSSION

MRI features of MVNT are predominantly mixed solid and cystic, bubble-like, T2/Flair-hyperintense, T1 hypointense lesions in the deep cortical region and superficial white matter without contrast enhancement. This case demonstrates that although no specific criteria to diagnose MVNT, neurologists and neuro-oncologists should be aware of the distinguishing radiographic features, which can help patients avoid unnecessary testing and potentially harmful interventions.
NIMG-97. A FULLY AUTOMATED MRI-BASED DEEP-LEARNING ALGORITHM FOR CLASSIFYING GERMINOMAS AND NONGERMINOMATOUS GERM CELL TUMORS
Authors: Li Yanong , Qiu Xiaoguang
Published: November 2022

Intra-cranial germ cell tumors (iGCTs) are classified into two pathological subtypes Germinomas (GEs) and nongerminomatous germ cell tumors (NGGCTs). Accurate preoperative determination of iGCT subtypes is essential to guide clinical decision making and prognosis assessment. This study aims to develop a deep-learning algorithm to automatically segment iGCTs and classify subtypes using preoperative T2-weighted (T2W) images. Brain MR imaging and corresponding pathologic information were retrospectively obtained from 594 subjects including 269 GEs and 325 NGGCTs from Beijing Tiantan Hospital between January 1, 2008, and October 31, 2020, and subdivided into training (n=416) and test (n=178) sets for iGCTs segmentation, and classification using 3D nnU-Net based on T2W images. An internal validation cohort (including 56 GEs and 17 NGGCTs) and two external validation cohorts (Center 1 including 13 GEs and 12 NGGCTs；Center 2 including 17 GEs and 12 NGGCTs) were prospectively designed as an independent sets for testing the iGCT-net. Dice scores were computed to assess tumor segmentation. Accuracy and area under the curve (AUC) were calculated to assess the GEs and NGGCTs classification. Additionally, sensitivity analysis of different tumor location (suprasellar, pineal and basal ganglia regions) was performed to access the classification accuracy. The iGCT-net for tumor segmentation achieved a mean dice score of 0.80 in all cohorts. For tumor classification, the iGCT-net achieved the mean accuracy of 90.96% of all cohorts, which was superior to that using demographics and morphologic features (mean = 67.50%, p< 0.01). For different tumor location (suprasellar region, pineal region, and basal ganglia region), the iGCT-net showed an mean accuracy of 87.94%, 89.38% and 65.74% in test set, internal validation set and external validation cohorts. A fully automatic deep learning algorithm to segment iGCT and discriminate GEs and NGGCTs with high accuracy based on only T2W images from a large dataset is successfully developed.