bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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 &gt; 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

Abstract

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 ( &gt; 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

Abstract

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

Abstract

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&lt; 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

Abstract
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), &gt; 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

Abstract
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

Abstract

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

Abstract
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

Abstract
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&lt; 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

Abstract
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.