bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMU-41. VERSATILE MRNA-NANOPARTICLE PLATFORM TO REPROGRAM THE BRAIN TUMOR MICROENVIRONMENT AND PREDICT TREATMENT OUTCOME
Authors: Grippin Adam , Mendez-Gomez Hector , Wummer Brandon , Weidert Frances , Wildes Tyler , Dyson Kyle , Dobson Jon , Mitchell Duane , Sayour Elias 
Published: November 2022

Abstract
RNA vaccines have shown great promise as activators of immune responses against viral pathogens but their efficacy in cancer is unclear. Here, we describe a versatile, personalized mRNA-nanoparticle (RNA-NP) platform that can be customized to produce powerful anti-tumor immune activation, reprogram the brain tumor microenvironment, and predict vaccine efficacy just two days after treatment. Lipid mixtures (i.e. DOTAP, Cholesterol) with or without iron oxide nanoparticle-cores were complexed with mRNA encoding tumor antigens. Intravenous administration of RNA-NPs induced robust activation of innate immune cells resulting in prolonged survival in murine models of subcutaneous and intracranial melanoma. Inclusion of cholesterol in the lipid backbone enabled delivery of nucleic acids across the blood brain barrier and into tumor-associated myeloid cells in intracranial GL261 and KR158b tumors. These cholesterol-bearing liposomes not only activated innate immune cells in the tumor microenvironment (i.e. increased expression of CD80 and MHCII), but also enabled further manipulation of this compartment. Use of RNA-NPs to deliver siRNA targeting PD-L1 resulted in significant reduction in PD-L1 expression among tumor associated myeloid cells, leading to 37% long term survivorship in combination with systemic checkpoint blockade in an otherwise fatal model of GL261. We have also shown that IONPs incorporated into the cores of these particles enable non-invasive tracking of dendritic cells by MRI, enabling creation of a theranostic approach to: 1) enhance immunologic effects; 2) facilitate translocation across the blood-brain barrier; and 3) enable non-invasive imaging to predict response to RNA-NPs.
INNV-16. SPINAL POST-TREATMENT SURVEILLANCE IN MEDULLOBLASTOMA – A SYSTEMATIC REVIEW OF THE LITERATURE AND CLINICAL TRIALS
Authors: Park Christopher , Packer Roger , Rood Brian , Kilburn Lindsay , Bornhorst Miriam , Rossi Christopher , Fonseca Adriana , Hwang Eugene 
Published: November 2022

Abstract

BACKGROUND
Monitoring for dissemination in medulloblastoma involves spinal MRIs (sMRIs) and lumbar punctures (LPs). The frequency and duration of these studies vary depending on risk of dissemination; general practice varies between and within institutions. Our goal is to review the current practice in post-treatment monitoring via examination of published data, clinical trial standards, and expert practice.

METHODS
We reviewed the available literature and accessible clinical trial protocols. Using PRISMA guidelines, we conducted searches of Ovid MEDLINE, Embase, and PubMed to identify studies which detailed relapse rates and patterns, and recommended practice for patients with medulloblastoma aged 3-21 years. Eligible studies from 1990 to present were included.

RESULTS
Thirteen multi-institutional clinical trials from North America and Europe were analyzed for frequency of post-therapy surveillance with LPs/sMRIs. Several studies (n=8) recommend LPs/sMRIs every 3-6 months in standard risk and every 3 months in high risk disease for two years when initially completing therapy, and then often diverge in frequency after 2 years. Some studies (n=5) did not include post-treatment recommendations. Cumulative data on relapse from available clinical trial reports and single institution studies (n=673 relapses) demonstrated local failure rate of 18.4%, distant failure of 49.1%, and combined distant and local failure of 32.5%. Spine-only relapses were reported to occur in approximately 13-20%, with one small study reporting spine-only relapse rate of 37.5%.

DISCUSSION
Patterns of recurrence in medulloblastoma have shifted over time as therapeutic approaches have evolved, including more spinal-only recurrences. Standardized guidance regarding surveillance could have significant impact on clinical detection and streamline management to minimize unnecessary examinations. Early detection of recurrent disease could optimize treatment options for providers and families, whether focusing on curative approaches or quality of life.
INNV-22. A CASE REPORT OF MULTIPLE LESIONS DISAPPEARING AFTER TMZ+TTFIELDS+ DARAFENIB AND TRAMETINIB IN A PATIENT WITH GBM
Authors: Cai Boning , Ma Xiaodong , Qu Baoling 
Published: November 2022

Abstract
A 44-year-old female patient developed the disease with left visual field defect in both eyes. Brain MRI on September 13, 2021, showed irregular masses in the right basal ganglia, thalamus, and hippocampus of temporal lobe, with the lesion extending to the right midbrain and right optic tract. On September 28, 2021, intraoperative total resection of lesions in right gyrus, hippocampus, thalamus and cingulate herniawas performed under nuclear magnetic navigation and electrophysiological detection. The pathological integration diagnosis result was glioblastoma, IDH wild type with TERT C228T mutation, chromosome 7 amplification and BRAF V600E mutation, WHO grade 4, MGMT non-methylation, postoperative visual acuity same as before. Based on the protocols and data of the clinical trials that have been conducted, and the safety of simultaneous use of TTFields during radiotherapy is controllable and patients can benefit, we started the follow-up treatment: standard TMZ (75mg/m2/d), combined with TTFields and retaining the transducer arrays placed on the shaved scalp. The dose of 60/54Gy, 30 times was selected. The application time of TTFields was relatively long throughout the radiotherapy period, and patient compliance was good, with treatment duration of about 20 hours per day. One month after conventional radiotherapy, reexamination indicated that local T1 enhanced hypersignal and PWI showed hyperperfusion. The methionine PET suggested that tumor activity might still exist. We found that the BRAF V600E mutation may provide therapeutic benefit, so this patient was treated with TMZ (standard 5/28 regimen) +TTFields+ Darafenib and Trametinib. Nearly two months after the follow-up treatment, a re-examination found a remarkable phenomenon, the multiple lesions disappeared. At present, the patient continues to be treated with TTFields for a relatively long time, and the skin side effects are only grade ONE. The combination of TTFields with targeted agents and chemotherapy brought clinical benefit to the patient with manageable adverse reactions.
INNV-29. MULTISPECTRAL ANALYSIS FOR INTRA-OPERATIVE CHARACTERIZATION OF BRAIN TUMOURS, MARGINS OF RESECTION, AND ELOQUENT AREAS ACTIVATION – PRELIMINARY RESULTS
Authors: Anichini Giulio , Zepeng Hu , Leiloglu Maria , Gayo Iani , Patel Neekhil , Syed Nelofer , Nandi Dipankar , O’Neill Kevin , Elson Dan 
Published: November 2022

Abstract

BACKGROUND
The identification of intrinsic brain tumours’ boundaries and their anatomical relationship with eloquent connectomes is one of the main challenges in neurosurgery. Several new intra-operative spectroscopic technologies have been recently investigated for this purpose. Multispectral imaging (MSI) analysis is based on analysis of reflected light, divided in specific wavelengths ranges across the electromagnetic spectrum. By doing so, it can identify wavelengths invisible to the naked eye, and make them visible by applying specific filters.

METHODS
We have used MSI to acquire intraoperative images during brain tumours surgeries. The MSI camera has been adapted to be connected to the intra-operative microscope and acquire a stack of images of different spectra to be analysed on a separate time. The focus of the images acquisition includes tumour structure, its margins, and eloquent connectomes during awake surgery or neurostimulation to analyse the possibility of different perfusion signal during activation. Image segmentation using K-mean clustering has been used to detect structural information and identify tumour’s area and tumour’s margins, while oxygen maps have been created using linear least squares regression to detect areas of metabolic activity.

RESULTS
Twenty-three patients have been enrolled in the current study at the time of this submission. We have analysed the intra-operative acquisition using intra-operative microscope picture, pre- and post-operative MRI scan, and neurophysiological findings as ground truth. Our preliminary results show that MSI is a potential additional technology to visually show tumour core, margins, and different degree of perfusions on the tissues analysed during tumour surgery. Although on a very limited subgroup of patients, MSI seems to be reliable in identify eloquent areas activation during awake surgery. These results are promising and warrant more data acquisition to be confirmed.
INNV-31. PROTECT: PROCARBAZINE, LOMUSTINE, AND VINCRISTINE VERSUS TEMOZOLAMIDE IN HIGH-RISK, LOW-GRADE GLIOMAS: A RETROSPECTIVE COHORT STUDY
Authors: Jia Jason , Alshamsan Bader , Andronic Cristina , Fazzari Francesco , Leigh Jennifer , Shah Hely , Ng Terry 
Published: November 2022

Abstract

INTRODUCTION
Low-grade gliomas (LGG), specifically WHO grade 2 diffuse astrocytoma and oligodendroglioma, are increasingly considered for adjuvant chemotherapy with high-risk features (age ≥ 40y or subtotal resection). This is based on prospective studies showing improvement in survival with adjuvant procarbazine, CCNU, vincristine (PCV) or temozolomide (TMZ) in this cohort. Use of PCV or TMZ is variable without published head-to-head comparison. PROTECT is a Canadian multicentre retrospective study aiming to compare overall survival (OS) in high-risk LGGs receiving PCV or TMZ. We are presenting results from The Ottawa Hospital Cancer Centre (TOHCC).

METHODS
Patients age ≥ 18y with LGG that received PCV or TMZ within 6 months of primary brain tumor resection at TOHCC from 2005 to 2019 were included. The primary outcome is OS. Secondary outcomes include 1)time to progression (TTP), 2)rate of completion of 6 cycles of PCV or TMZ, and 3)rate of hospitalization or death due to chemotherapy-related complications.

RESULTS
Of 250 cases, 20 patients (11 diffuse astrocytoma, 9 oligodendroglioma) were eligible. IDH status was mutated in 11, wild-type in 1, and unknown in 5 cases. 1p/19q co-deletion was present in 6, non-co-deleted in 1, and unknown in 13 cases. Six patients received PCV, and 14 received TMZ. Hematologic toxicity (CTCAE Grade 1-2) occurred in 3 PCV patients and 0 of 11 of assessable TMZ patients; no severe toxicity was observed. Median follow-up was 64.5 (IQR 42.5–88) months. The median OS and TTP for PCV and TMZ groups were not reached. The 5-year OS and TTP were 75% vs. 100 % (p=0.08) and 83.3% vs 81.3% (p=0.7) respectively.

CONCLUSIONS
There are insufficient cases and follow-up time to determine OS and TTP amongst patients treated with PCV or TMZ. Hematologic toxicity appears to be more common with PCV. Patient screening and data collection is ongoing at 8 other cancer centres.
PATH-33. “GENETIC AND EPIGENETIC PROFILING IDENTIFIES TWO DISTINCT CLASSES OF SPINAL MENINGIOMAS”
Authors: Ricklefs Franz , Fita Krystian , Mohme Malte , Westphal Manfred , Lamszus Katrin , Mawrin Christian , Schüller Ulrich , Eicker Sven 
Published: November 2022

Abstract

BACKGROUND
Spinal meningiomas account for 1.2-12 % of all meningiomas and 25-45 % of all spinal tumours. 20 % of intracranial, but only 4.6 % of spinal meningiomas recur requiring additional treatment. Whereas the classification of intracranial meningiomas has evolved considerably in recent years and uses genetic and epigenetic parameters, the classification of spinal meningiomas is based solely on histopathological findings. By embedding epi-/genetic features, the prognosis of intracranial meningiomas could be significantly improved, which is still lacking for spinal meningiomas. In our work, we integrated genetic and epigenetic parameters into the classification of spinal meningiomas.

METHODS
We performed epi-/genetic profiling of 50 spinal meningiomas. 497 intracranial meningiomas served as a reference cohort. Copy number variations (CNV) were inferred from the methylation data. Principal component (PCA) and t-SNE analysis were conducted. Clinical and histopathological parameters (location, size, recurrence, WHO°, pathological subtype) were correlated with methylation signatures using the DKFZ brain tumour classifier.

RESULTS
The methylation signature of spinal meningiomas matched to that of intracranial meningiomas (50/50), although meningioma subgroup assignment was achieved in only 13/50 cases. PCA and t-SNE analysis showed that most spinal meningiomas separate from cranial meningiomas and form two distinct clusters. Cluster 1 matched the methylation class ben-2, while cases in cluster 2 were heterogenous and had a low MSC score. Cases of cluster 1 were located in the upper spine, are more common in males and had an AKT1E17K mutation. NF2 mutations were found mainly in the second cluster, in line with a chr.22 q loss. Interestingly 4 tumors did not associate with the two spinal meningioma clusters and had a particular higher recurrence rate.

CONCLUSION
Genetic and epigenetic profiling of spinal meningiomas identifies two distinct classes of spinal meningiomas, which may allow an improved prognosis that could lead to a better guidance for adjuvant therapy.
PATH-34. SOLITARY FIBROUS TUMOR: NATURAL HISTORY AND PROGNOSIS IN ACCORDANCE WITH THE WHO 2021 CLASSIFICATION OF CNS TUMORS
Authors: Eschbacher Kathryn , Jenkins Sarah , Fritchie Karen , Moskalev Evgeny , Caron Alissa , Link Michael , Brown Paul , Guajardo Andrew , Brat Daniel , Wu Ashely , Santagata Sandro , Louis David , Brastianos Priscilla , Kaplan Alexander , Alexander Brian , Rossi Sabrina , Ferrarese Fabio , Raleigh David , Nguyen Minh , Gross John , Vega Jose Velazquez , Rodriguez Fausto , Perry Arie , Alverez Maria Martinez-Lage , Haller Florian , Giannini Caterina 
Published: November 2022

Abstract
Meningeal solitary fibrous tumor (SFT) is a rare tumor with high propensity to recur and metastasize, even late in the course of disease. The WHO 2021 classification of CNS tumors divides SFT in 3 grades, based on mitotic index and necrosis. We re-examined our cohort of 126 patients (57 F, 69 M; mean age 53.0 years) with SFT, confirmed by STAT6 nuclear positivity and/or NAB2::STAT6 fusion, with extended follow-up (median 7.6 years; range 4 days-26.6 years). Tumors included 76 grade 1, 36 grade 2 and 14 grade 3 according to 2021 WHO criteria, evaluated at primary resection (n=90), recurrence (n=35), or metastasis (n=1). Fifty-six patients had one or more post-surgical events, the earliest event being local recurrence (n=41) or metastasis (n=15). Forty patients died (29 of disease; 9 of other causes; 2 unknown). Overall survival (OS), and progression-free survival (PFS, recurrence and/or metastasis) from time of primary resection (n=90) were not significantly associated with grade; however, risk of metastasis differed significantly (5-year estimates: 4.1%, 15.3%, and 37.8% for grades 1, 2, and 3 SFT, respectively; p=0.005). NAB2::STAT6 fusion status was known in 101 cases (51 = ex5-7-ex16-17, 26 = ex4_ex2-3; 12 = ex2-3_exANY/other and 12 =no fusion). Disease specific 5-year survival in primary tumors with molecular data (n = 75) was 80.0% in patients whose tumors harbored ex5-7_ex16-17 compared to 93.3% in all others combined (p=0.014). Targeted TERT promoter mutation testing was performed in 98 patients, revealing patients with tumors lacking TERT promoter mutation (n = 88) were younger at time of surgery than those harboring a mutation (n=10; p = 0.022), and none with a mutation harboring concurrent ex5-7_ex16-17 fusion (p = 0.0009). In summary, WHO 2021 grade is associated with risk of metastasis. Patients whose tumors harbor ex5-7_ex16-17 fusion have a higher risk of dying from the disease.
PATH-40. A GIANT CELL LESION RESEMBLING REPARATIVE GIANT CELL GRANULOMA WITH FN1-TEK FUSION, IN THE SPECTRUM OF CALCIFIED CHONDROID MESENCHYMAL NEOPLASM?
Authors: Kong Xiao-Tang , Movassaghi Mehrnaz , Perez-Rosendahl Mari , Choi Yoon , Yong William 
Published: November 2022

Abstract

A newly described entity called “calcified chondroid mesenchymal neoplasms” includes chondroid neoplasms with variable amounts of calcification and FN1 fusions [Liu et al, Mod Pathol 2021]. We report a case of a left temporal bone giant cell granuloma-like lesion that also shows an FN1-TEK fusion. Close monitoring with MRI images after surgery has showed no recurrence. Case report: a 33-year-old male developed left jaw pain and he was diagnosed with a temporomandibular joint disorder. He felt left ear fullness and 2 years later experienced severe pain and swelling in the left temporal region. Imaging showed an expansile osseous lesion with multi-cystic components involving the left sphenoid bone as well as all portions of the temporal bone including the mastoid, middle ear cavity, and glenoid fossa. Pathology showed a hemorrhagic giant cell lesion that was negative for H3G34W mutation and USP6 rearrangement, suggesting a reparative giant cell granuloma. A subsequent NGS with the Tempus 648 gene panel did not identify somatic or germline mutations, but an additional Tempus RNA fusion test found a FN1-TEK fusion suggesting the possibility of neoplasia. Close monitoring with brain MRI over past 9 months has shown no signs of recurrence.

DISCUSSION
A recent small series describes a novel entity called calcified chondroid mesenchymal neoplasm that has FN-1 fusions including a FN1-TEK fusion in one case. The case in that series with FIN1-TEK fusion also showed prominent giant cells. It is unclear whether giant cell granuloma-like lesions with FN1-TEK fusion belong in the calcified chondroid mesenchymal neoplasm spectrum or are a separate non-neoplasm entity that shares the same alteration. More studies are warranted.
PATH-47. THE CHALLENGE AND THERAPEUTIC RELEVANCE OF A NON-MATCHING CLASSIFIER OUTPUT USING GENOME-WIDE DNA METHYLATION FOR CLINICAL ROUTINE
Authors: Drexler Richard , Eckhardt Alicia , Bode Helena , Fita Krystian , Lamszus Katrin , Westphal Manfred , Dührsen Lasse , Schüller Ulrich , Mohme Malte 
Published: November 2022

Abstract
DNA methylation-based classification of central nervous system tumours has been increasing in importance for routine clinical workups and offers novel opportunities in discriminating subtypes which could lead to a more customized therapy. However, there are still unclassifiable entities for which defining an effective therapeutic regimen is challenging. The aim of our study was to gain further insight in these challenging cases. We included 81 patients with a calibrated score below 0.9 in the classifier output, who underwent surgery for a tumour of the central nervous system (CNS). 47 patients had a different output using the classifier version v11b4 when compared to their histological diagnosis. Of these, 41 patients (87.2 %) did not have any diagnosis from the methylation classifier (“no matching methylation class”). Surgical and clinicopathological features as well as DNA input had no impact on the calibrated score. Cases with non-classifiable tumors had a significantly longer time until a decision for adjuvant therapy and these cases were presented more often in neurooncological tumor boards (p&lt; 0.01). Further analyses in 23 glioblastoma patients revealed comparable results for the overall survival, but a significantly shorter progression-free survival in cases with a discrepancy between the histological and classifier diagnosis. Application of the latest classifier version v12.5 enabled classification in 67.9% of cases, resulting in re-classification with a high calibrated score (&gt; 0.9) in 25.7% of the tumors. Taken together, our study presents unclassifiable cases and the possible clinical impact when waiting for the accurate diagnosis in these challenging cases. Even though DNA methylation profiling significantly contributes to advanced CNS tumour diagnostics, clinicians should be aware of a prolonged interval to treatment initiation, especially for highly malignant brain tumours. Therefore, we would recommend to schedule adjuvant treatment as early as possible if surgical and histological results are suspicious for this disease.
NIMG-13. DEEP LEARNING-BASED AUTOMATIC DETECTION AND SEGMENTATION OF BRAIN METASTASES FOR STEREOTACTIC ABLATIVE RADIOTHERAPY USING BLACK-BLOOD MAGNETIC RESONANCE IMAGING
Authors: Kim Tae Hyung , Yoo Sang Kyun , Kim Hojin , Kim Jin Sung , Yoon Hong In 
Published: November 2022

Abstract

PURPOSE/OBJECTIVES
Stereotactic ablative radiotherapy (SABR) is becoming popular in the treatment of Brain metastases (BM). However, detection and manual delineation of BM are labor-intense processes, and normal blood vessels are occasionally mistaken for metastatic lesions. In this study, we investigated the efficacy and accuracy of a deep learning (DL) model for the detection and segmentation of BM using black-blood (BB) magnetic resonance imaging (MRI).

MATERIALS/METHODS
The BB MRI data of 48 patients with 806 BMs were collected to train and validate the DL model. Since MRI data have an inconsistent intensity scale across the patients, we applied piecewise linear histogram matching algorithm, also called the Nyul normalization. To deal with bias corruption in the patient, N4 bias field correction was applied. The modified U-Net was implemented to automatically detect and segment BMs. The detection performance was measured with sensitivity and average false positives and the segmentation performance was measured with the dice score (DSC).

RESULTS
Twelve patients with 132 BMs were randomly selected as the test-set for evaluating our trained model. In the test-set, 19.2% BMs had a volume of &lt; 0.02 cc, max volume of 16.642 cc, min volume of 0.009 cc, median volume of 0.071 cc, and mean volume of 1.158 cc. The sensitivity was 96.87% and average false positives were 0.2. We consider &lt; 0.02 cc volume as the small volume. 100% sensitivity for BMs with volumes ≥ 0.02 cc, and 84.6% sensitivity for BMs with volumes &lt; 0.02 cc volume. The DSC was 86.27 (range, 77-91.2).

CONCLUSIONS
Our model can detect and segment BMs on BB MRI data with good detection and segmentation performance. Further study is on a way to generate a synthetic BB image from the T1-Gd image by applying this model.