bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-53. RATIO OF T1-WEIGHTED TO T2-WEIGHTED SIGNAL INTENSITY AND IDH MUTATION IN GLIOMA
Authors: Kinoshita Manabu , Uchikoshi Masato , Takano Koji , Sakai Mio , Arita Hideyuki , Nakanishi Katsuyuki , Kanemura Yonehiro , Kishima Haruhiko 
Published: November 2021

Abstract

INTRODUCTION
Identifying IDH mutation status before treatment is essential for Lower-grade glioma (LrGG) treatment. We have previously revealed that IDH mutated LrGG consists of tumor tissues with significantly longer T1 and T2 relaxation time and is a useful radiological feature to identify IDH mutation status. The ratio of T1-weighted to T2-weighted signal intensity (rT1/T2) is a way to retrieve semi-quantitative relaxation time information of the tissue bypassing the need to perform relaxometry. This investigation aimed to elucidate the correlation between rT1/T2 and T1-, T2-relaxation time (-relax) in glioma tissue and to explore the possibility of rT1/T2 as a radiological surrogate marker to identify IDH mutation status in LrGG.

MATERIALS AND METHODS
We analyzed 8 LrGGs (IDHwt:4, IDHmt:2, IDHmt&1p19q-CODEL:2) in which relaxometry was performed. rT1/T2 maps were reconstructed as described in previous literature. Regions-of-interest were designed based on T2WI and FLAIR. The correlations between rT1/T2 and T1- and T2-relax were analyzed. Furthermore, We also investigated the correlation of IDH mutation status and rT1/T2.

RESULTS
106,488 voxels were analyzed. The correlation between rT1/T2 and T1- and T2-relax were rT1/T2=1.6e-0.0003T1-relax and rT1/T2=1.2e-0.002T2-relax (R=0.77 and 0.70). rT1/T2 of IDH-wildtype tumor was significantly higher than that of IDH-mutant tumor (1.0 vs. 0.75, p&lt; 0.0001). Voxel-wise analysis of rT1/T2 map was able to discriminate IDH-wildtype tumor from the mutant tumor with an AUC of 0.82.

CONCLUSIONS
rT1/T2, which can be calculated from MRI acquired during routine clinical practice, is a promising radiological surrogate marker to identify IDH mutation status in LrGG.
NIMG-76. DISCRETE LOWER-GRADE GLIOMA (DLGG) VERSUS INFILTRATIVE LOWER-GRADE GLIOMA (ILGG): CORRELATION OF RADIOLOGICAL CHARACTERISTICS WITH CLINICAL OUTCOMES
Authors: Ali Khan Ahsan , Hamza Bajwa Mohammad , Khan Noman , Khalid Muhammad Usman , Mubarak Fatima , Ather Enam Syed 
Published: November 2021

Abstract

INTRODUCTION
Lower grade gliomas encompass grade 2 and 3 tumors. However, this term is more generalized and does not include the spectrum of radiological and tumor morphological patterns seen. Here we have established two distinct patterns of radiographic appearance seen within lower grade gliomas: ILGG and DLGG. Imaging plays a vital role in diagnosis, surveillance, characterization, and monitoring of intracranial tumors. Of particular importance is the differentiation of tumor features to reliably predict malignancy, tumor grade, possible molecular or genetic features, disease progression and recurrence, potential for malignant transformation, and postoperative outcomes. Our study will look at these radiographic characteristics of diffuse and infiltrating lower grade gliomas and discuss their predictive value. Understanding the distinct nature of these varieties of LGG will help us in surgical decision-making, prognostication, biopsy target and precision medicine.

METHODS
Pre-operative and post-operative MRI images of Grade 2 and 3 tumors were identified and analyzed in order to extract radiographic data, and correlated with patient demographics, clinical outcomes, extent of surgical resection, and molecular genetic analysis.

RESULTS
Out of 35 patients evaluated, 22 (62.9%) were labeled ILGGs and 13 (37.1%) were deemed DLGGs according to the pre-defined criteria. T2 habitat was higher in ILGG (mean = 2162) than DLGG (mean = 1482) as well as size, in cm (6.02 vs. 4.92). ADC habitat, lesion ADC, and percentage of the lesion that showed contrast-enhancement were similar. T2-FLAIR mismatch was significantly higher in ILGG (p = 0.02). Post-operative KPS scores were significantly higher in the DLGG group (p = 0.03).

CONCLUSION
T2-FLAIR mismatch can be a significant classifier for lower-grade gliomas. Our study shows there are differences in tumor morphology of diffuse and infiltrative lower-grade gliomas which can be correlated to outcomes after surgery.
*Indicates corresponding author.
NCMP-01. NOVEL BIOMARKERS FOR RADIATION-INDUCED NEUROTOXICITY
Authors: Makranz Chen , Lubotzky Asel , Zemmour Hai , Shemer Ruth , Glaser Benjamin , Cohen Jonathan , Maoz Myriam , Sapir Eli , Weizman Noam , Feldman John , Lossos Alexander , Dor Yuval , Zick Aviad 
Published: November 2021

Abstract

BACKGROUND
Brain radiotherapy is the main therapeutic modality for brain metastases (BM), but carries short and long term toxicities, termed radiation-induced neurotoxicity (RIN), and classified to acute, early-delayed and late-delayed RIN according to its time onset. Although diagnosis of RIN is crucial for patient management, there is an unmet need for sensitive biomarkers for RIN. Here we report on a novel non-invasive biomarker for detection and monitoring RIN. As radiotherapy is known to induce brain cells apoptosis as well as BBB disruption, we hypothesized that circulating cell free DNA fragments derived from dying brain cells will be elevated in the blood of patients with RIN. Using comparative methylome analysis we identified 13 genomic loci showing brain-specific DNA methylation patterns, including markers for neurons, oligodendrocytes, and astrocytes. We searched for these brain-derived cfDNA (bncfDNA) in plasma samples of patients following brain irradiation.

METHODS
We followed 24 patients treated by brain radiotherapy for BM by clinical and radiological examinations before, during and after treatment. In addition, we serially collected blood samples for DNA analysis, and correlated bncfDNA levels with clinical and radiological assessment.

RESULTS
Patient`s median age was 60 years. Most common primary tumor sites were breast (25%), lung (20.8%) and melanoma (12.5%). RIN was detected in 10 patients (62%). BncfDNA levels increased up to 292.4 fold in acute RIN, up to 138533.1 in early-delayed RIN, and up to 58.4 fold in late-delayed RIN. Resolution of RIN correlated with decrease in bncfDNA. Changes in bncfDNA levels were independent of tumor response and suggested to reflect both symptomatic and asymptomatic RIN.

CONCLUSION
Increase in bncfDNA levels characterizes RIN independent of tumor response. Thus, BncfDNA may serve as a novel biomarker for brain cells death incurred by radiotherapy. Further studies are required to explore the clinical utility of bncfDNA as a RIN biomarker.
NCMP-02. NEUROTOXICITY RELATED TO CAR T-CELL THERAPY IN PATIENTS WITH SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Yuen Carlen , Wesley Sarah , Van Besien Koen , Hsu Jing-Mei , Reshef Ran , Iwamoto Fabio , Haggiagi Aya , Magge Rajiv 
Published: November 2021

Abstract

INTRODUCTION
Patients with secondary CNS lymphoma (SCNSL) were excluded from the pivotal trials that led to the approval of chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory (R/R) B-cell lymphomas due to concern for neurotoxicity (NT). Limited evidence exists for axicabtagene ciloleucel (axi-cel, Yescarta®) in SCNSL patients.

METHODS
In this retrospective study, 15 R/R lymphomas patients with SCNSL (14 DLBCL, 1 chronic lymphocytic leukemia) were treated with commercial axi-cel between March 2019 and April 2021 for systemic disease and assessed for NT using the Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and CTCAE toxicity grading systems.

RESULTS
Seven of 15 patients (47%) developed NT, all of whom had cytokine release syndrome (CRS). Four (27%) developed severe NT (Grade III-IV). In the 8 patients (53%) with active SCNSL, 6 (75%) did not develop NT and 2 (25%) developed severe NT. In the 4 severe NT patients, all had multifocal CNS disease and 3/4 (75%) had leptomeningeal disease. Two thirds of patients previously treated with RT developed severe NT (1 whole brain RT, 1 skull base). The third patient had RT to the eye. Four of 8 (50%) patients with prior intrathecal chemotherapy developed severe NT. Five patients relapsed (3 in the CNS), none of whom had NT. At 11.7 month median follow-up, 8 patients remain alive, 5 are deceased (1 from NT, 3 from progression, 1 from infection), 2 lost to follow-up. The patient who died from NT had prior temporal arteritis. Three additional patients with autoimmune disease did not develop severe NT.

CONCLUSION
In this limited cohort, presence of SCNSL did not increase NT incidence compared to historical outcomes of CAR T-cell therapy patients without SCNSL. This cohort will be compared to CAR T-cell therapy patients without SCNSL. Prospective studies of CAR T-cell therapy in SCNSL patients will be informative.
NCMP-11. SPINAL CORD INFARCT AFTER CAR-T TREATMENT
Authors: Shah rusha , Venur Vyshak , McGranahan Tresa 
Published: November 2021

Abstract
Cortical and subcortical neurotoxicity from CAR-T therapy is a well described complication in literature, with over 40% of patients experiencing at least one neurologic side effect. However, spinal cord toxicity from CAR-T therapy is less well described. To our knowledge, this is the first reported case of a spinal cord infarct following CAR-T therapy. A 44 year old male with primary refractory DLBCL without CNS involvement, which was refractory to R-CHOP, R-ICE, and hyperCVAD part B underwent CD-19 CAR-T treatment. The day after infusion he developed grade 1 cytokine release syndrome (CRS) with fever and up trending inflammatory markers. Infectious work up was negative and he was treated with tocilizumab and dexamethasone. His fever resolved and markers down trended. On day 5 post CAR-T, he became encephalopathic, developed severe back pain, and was unable to move his bilateral lower extremities. He was treated with 2nd and 3rd doses of tocilizumab, dexamethasone and was started on anakinra. Patient’s mental status cleared by day 7 and he was found to have a dermatome sensory level at T10 with flaccid bilateral lower extremity paralysis. MRI Brain was unremarkable, but a spinal MRI showed longitudinally extensive cord edema and diffusion restriction at T10. Due to an initial question of transverse myelitis, he was treated with a 3-day course of IV methylprednisolone, with no improvement in symptoms. CSF studies were unable to be obtained due to his thrombocytopenia. Repeat MRI obtained 10 days after initial imaging showed resolution of cord edema, but continued areas of FLAIR hyperintensity at T10 through the conus. Despite aggressive rehabilitation services, four months later, patient remained paralyzed in his lower extremities with an indwelling foley catheter. He remains in a complete remission.
NCMP-21. IMMUNE-RELATED ACUTE MOTOR AXONAL NEUROPATHY: A SMALL CASE SERIES AND REVIEW OF THE LITERATURE
Authors: Pina Yolanda , Tran Nam , Verma Neha , Vogelbaum Michael , Forsyth Peter , Mokhtari Sepideh , Peguero Edwin 
Published: November 2021

Abstract

BACKGROUND
Immunotherapy revolutionized cancer treatment in the past decade, with a significant increased survival in patients with solid tumors. However, immune checkpoint inhibitors (ICIs) have been associated with a growing number of neurotoxicities, some of which can be fatal if not recognized and treated promptly. Some of these neurotoxicities include very uncommon syndromes like Acute Motor Axonal Neuropathy (AMAN). Herein we present four oncological cases of patients who underwent immunotherapy and developed AMAN.

METHODS
Four patients were diagnosed with immune-related AMAN between 2017 and 2000 at H. Lee Moffitt Cancer Center. Patients were treated with standard of care.

RESULTS
We describe four oncological patients who developed a motor axonal neuropathy (i.e., AMAN) confirmed on nerve conduction studies following 2 cycles of immunotherapy, including a 28 year old woman with melanoma brain metastasis and a 50 year old woman with renal cell carcinoma both treated with ipilimumab and nivolumab, a 32 year old man with Hodgkin lymphoma who was treated with nivolumab and brentuximab, and a 77 year old woman with renal urothelial cancer who was treated with pembrolizumab and cabozantinib. All four patients were promptly recognized as having immune-related neurotoxicity (irNs), were promptly treated (i.e., high dose steroids +/- IVIG +/- other immunomodulators), and significantly improved and have remained stable.

CONCLUSION
This is the first case series of patients with AMAN following two cycles of immunotherapy, who were successfully treated. It is crucial to develop a better understanding of irNs, including those rare conditions that are difficult to diagnose and treat, as the utilization of these immunomodulating therapies continues to expand to include other solid malignancies. Neurologists should be involved early on in any case of suspected irN to assist in the management of these complicated patients and a swift work up should be initiated for timely diagnosis and treatment.
NCOG-05. RISK FACTORS FOR PROLONGED LENGTH OF STAY AND POSTOPERATIVE COMPLICATIONS IN PATIENTS WITH INTRAMEDULLARY SPINAL CORD TUMORS
Authors: Kouam Romaric Waguia , Wang Timothy 
Published: November 2021

Abstract

INTRODUCTION
Primary spine tumors are rare neoplasms that affect about 0.62 per 100,000 individuals in the US. Intramedullary spinal cord tumors (IMSCTs) are the rarest of all primary tumors involving the spine and can cause pain, imbalance, urinary dysfunction and neurological deficits. These types of tumors oftentimes necessitate surgical treatment, yet there is a lack of data on length of stay and complication rates following treatment. Given that treatment candidacy, quality of life, and outcomes are tied so closely to these metrics, it is important to illustrate the risk factors for prolonged length of stay and their association with post-op complications with the ultimate goal of improving patient selection and preoperative optimization.

METHODS
The National Surgical Quality Improvement Program (NSQIP) database was queried for all patients undergoing surgery for treatment of intramedullary spinal cord tumors between 2005 and 2017. Univariate and multivariate analysis were performed to assess patient risk factor influencing prolonged length of stay and post-op complications.

RESULTS
A total of 638 patients were included in the analysis. Pre-operative American Society of Anesthesiology (ASA) physical status classification of 3 and above ( OR 1.89; p=0.0005), dependent functional status ( OR 2.76; p=0.0035) and transfer from facilities other than home ( OR 8.12; p&lt; 0.0001) were independent predictors of prolonged length of stay ( &gt;5 days). The most commonly reported complications were pneumonia (5.7%), urinary tract infection (9.4%), septic shock (3.8%), superficial incisional infection (5.7%), organ or space infection (5.7%), pulmonary embolism (11.3%), DVT requiring therapy (15.1%) and wound dehiscence (5.7%).

CONCLUSION
Our study demonstrated the significant influence of clinical variables on prolonged hospitalization of IMSCT patients. This should be factored into clinical and surgical decision making and when counseling patients of their expected outcomes.
NCOG-13. TUMOR-RELATED MOLECULAR DETERMINANTS OF NEUROCOGNITIVE DEFICITS IN PATIENTS WITH DIFFUSE GLIOMA
Authors: van Kessel Emma , Berendsen Sharon , Baumfalk Anniek , Venugopal Hema , Krijnen Eva , Spliet Wim , van Hecke Wim , Giuliani Fabrizio , Seute Tatjana , van Zandvoort Martine , Snijders Tom , Robe Pierre 
Published: November 2021

Abstract

BACKGROUND
Cognitive impairment is a common and debilitating symptom in patients with diffuse glioma and is the result of multiple factors. We hypothesized that molecular tumor characteristics influence neurocognitive functioning (NCF), and we aimed to identify tumor-related markers of NCF in diffuse glioma patients.

METHODS
We examined the relation between cognitive performance (executive function, memory and psychomotor speed) and intratumoral expression level of molecular markers, in treatment-naive patients with diffuse glioma. We performed a single-center study in a prospectively collected cohort, through a two-step design: (1) differential expression and gene set enrichment analysis (GSEA) to identify candidate oncogenetic markers for cognitive impairment in a hypothesis-free manner. Nineteen molecular markers of interest were derived from this set of genes as well as from prior knowledge; (2) correlation of cognitive performance (executive function, memory and psychomotor speed) to intratumoral expression level of these nineteen molecular markers, measured with immunohistochemistry.

RESULTS
After correcting for tumor volume and location, we found significant associations, between expression level of CD3 and IDH on the one hand with psychomotor speed on the other; between IDH, ATRX, BDNF, CSNK2B, EAAT1, GAT-3, SRF and memory performance; and between IDH, P-STAT5b, CSNK2B and executive functioning. P-STAT5b, CD163, CD3 and SEMA3 were independently associated after further correction for histopathological grade.

CONCLUSION
Several molecular characteristics of gliomas are independent determinants of patients’ cognitive functioning. This suggests that besides tumor volume, location and histological grade, variations in glioma biology influence cognitive performance through mechanisms that include perturbation of neuronal communication. These results pave the way towards targeted cognition improving therapies in neuro-oncology.
NCOG-14. REAL-WORLD RETROSPECTIVE ANALYSIS OF TUMOR TREATING FIELDS IN THE TREATMENT OF HIGH-GRADE GLIOMA BASED ON CHINESE POPULATION
Authors: Chen Lingchao , Chen Junrui , Song Kun , Nie Jingtao , Zhuang Dongxiao , Wang Yang , Yao Yu , Wu Jinsong , Qin Zhiyong 
Published: November 2021

Abstract

OBJECTIVES
Tumor Treating Fields (TTFields) has been approved for the treatment of newly diagnosed and relapsed glioblastoma（GBM）in China in 2020. Only few TTFields data in Asia patients were reported. This retrospective analysis is aimed at investigating the efficacy, safety and the potential relationship with biomarkers of TTFields treatment in the real-world clinical practice of the Chinese glioma population.

METHODS
High-grade glioma patients who were under TTFields treatment from May 2019 to May 2021 in Shanghai Huashan Hospital were analyzed, including baseline data, efficacy data and incidence of adverse events.

RESULTS
Eighty-two patients (median age 51.0 [26.0 - 47.0] years) with high-grade glioma were enrolled, including 60 newly diagnosed GBM, 16 recurrent GBM, and 6 WHO grade III gliomas. The median time was 9.9 (4.6-15.7) months for follow-ups, median time for TTFields treatment was 4.3(1.1-20.35) months. The median compliance rate was 90% (40%-97%). For newly diagnosed GBM (n=60) and recurrent GBM (n=16), the 6-month PFS rate were 78.4% (95%CI: 63.9-87.6) and 46.7% (95%CI: 21.2- 67.8) respectively. The 10-month OS rate were 86.3% (95%CI: 69.6- 94.2) and 60.0% (95%CI: 12.6- 88.2) respectively. The 6-month PFS rate in the IDHw/TERTm population was 69.9% (95%CI: 45.9-84.9) and 78.3% (95%CI: 46.5-92.5) in the IDHw/TERTw patients with newly diagnosed GBM. 59(72%) patients had skin-related adverse reactions, and majority are grade 1-2 (grade 1-2, 69.5%; grade 3, 2.5%).

CONCLUSIONS
This is the 1st retrospective analysis done using TTFields in the treatment of high-grade gliomas in the Chinese population with the largest sample size. From our short follow up, TTFields appears good efficacy among GBM patients. The incidence of skin adverse reactions is higher comparable to published data, but mainly consisted of grade1-2. Long-term efficacy data need to be further followed-up.
NCOG-17. FACTORS INFLUENCING POOR INDEPENDENCE LEVEL FOLLOWING RESECTION OF THE RIGHT TEMPORO-PARIETAL GLIOBLASTOMAS
Authors: Nakada Mitsutoshi , Nakajima Riho , Okita Hirokazu , Kinoshita Masashi 
Published: November 2021

Abstract
In glioma surgeries, cognitive outcomes for the dominant hemisphere have gained much attention compared to the non-dominant hemisphere. For non-dominant hemispheric glioblastomas, we previously observed decreased independence level following glioblastoma resection of the posterior temporal to the parietal lobes. Here, we investigated the reason for the poor Karnofsky Performance Status (KPS) in such glioblastomas. A total of 41 patients with resection of the right cerebral hemispheric primary glioblastoma were enrolled for the study. Several kinds of neuropsychological functions and KPS of the brain regions were evaluated at pre- and postoperative 3 months by performing the Spearman’s correlation analysis and voxel-based lesion symptom mapping (VLSM). Additionally, the correlation between the resected volume of each gyrus or white matter tract and neuropsychological function score was analyzed. KPS at chronic phase (73.6) declined significantly compared with preoperation (81.0, p = 0.020). Functional factors influencing the KPS were general cognitive function, visuospatial cognition, emotion recognition, executive function, and apathy. The VLSM analysis revealed that the resection of the ventral parietal lobe and supramarginal gyrus (VPL-SMG) resulted in significantly poor KPS. Among the functional factors affecting KPS, VPL-SMG resection contributed to significantly lower scores in visuospatial cognition, emotion recognition, and apathy than those without resection (p = 0.0045, 0.047, and 0.0002, respectively). Further, we investigated whether the damage of the VPL-SMG could result in KPS related functional deficit. We found visuospatial cognition related to the posterior occipital lobe, SMG, arcuate fasciculus (AF), and dorsal superior longitudinal fasciculus, emotion recognition to the middle to inferior occipital gyrus and AF, and apathy to the inferior parietal lobe and middle temporal gyrus. We concluded that deficits of visuospatial cognition, emotion recognition, and apathy due to the damage of the cortical and white matter areas, including the VPL-SMG, were responsible for KPS of the non-dominant hemispheric glioblastomas.