bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-44. MULTIPLE BIOMARKER ALGORITHM BASED ON CXCL13, IL-10, IL-2 RECEPTOR, AND β2-MICROGLOBULIN IN CEREBROSPINAL FLUID TO DIAGNOSE CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Sasayama Takashi , Tanaka Kazuhiro , Maeyama Masahiro , Nakamizo Satoshi , Tanaka Hirotomo , Nishihara Masamitsu , Hirose Takanori , Fujita Yuichi , Kohmura Eiji 
Published: November 2019

Abstract

BACKGROUND
Brain biopsy is the gold standard for the diagnosis of primary central nervous system lymphoma (PCNSL). However, the biopsy procedure has a risk of complications, such as hemorrhage and seizure. We have reported that cerebrospinal fluid (CSF) interleukin-10 (IL-10), soluble IL-2 receptor (sIL-2R), and β2-microglobulin (β2-MG) are the useful diagnostic biomarkers for PCNSL. Recently, the C-X-C motif chemokine ligand 13 (CXCL13) has been reported to be another useful biomarker for the PCNSL. The aim of this study was to validate the diagnostic performance of the CSF CXCL13 and diagnostic algorithm based on the combination of these biomarkers.

METHODS
We retrospectively examined the CSF CXCL13 concentration, as well as IL-10, sIL-2R, and β2-MG, in a case-control study (n=230). We used logistic regression analyses to create diagnostic algorithms based on these CSF biomarkers. To examine the utility of the multivariate diagnostic algorithm, we conducted the prospective study and evaluated the accuracy of this algorithm.

RESULTS
In case-control study, we have demonstrated that CSF CXCL13 levels were significantly higher in the patients with PCNSL (area under the curve (AUC)=0.981). A total of 84 patients were enrolled in the prospective study. The multivariate diagnostic algorithm using CSF levels of CXCL13, IL-10, sIL-2R, and β2-MG demonstrated excellent diagnostic performance: positive predictive value was 89% and negative predictive value was 100%. Four markers’ combination (CXCL13 + IL-10 + β2-MG + sIL-2R) had the highest AUC (AUC=0.998). The misdiagnosis cases of the algorithm were only 3 cases; CNS Sjögren’s syndrome, histiocytic sarcoma, and glioblastoma. In addition, CSF CXCL13 levels were prognostic biomarkers in PCNSL patients.

CONCLUSIONS
Our study suggests that the algorithm based on 4 CSF biomarkers had excellent diagnostic performance in CNS lymphoma. However, this algorithm should be further validated in prospective cohort studies with larger numbers of patients.
PATH-67. RECOMBINANT INTERLEUKIN-7 ENHANCES THE ANTI-TUMOR IMMUNITY OF A DENDRITIC CELL VACCINE IN A MURINE MALIGNANT GLIOMA
Authors: Hooy Oh Sol , Ahn Stephen , Sung Park Jae , Kil Hong Yong , Jeon Sin-Soo 
Published: November 2019

Abstract

BACKGROUND
Dendritic cell (DC)-based vaccines have been suggested as one of the promising immunotherapies for treating various cancers, including glioblastoma. We already developed a novel vaccination protocol with peptide-loaded DCs followed by a mixture of synthetic peptides, polyinosine- polycytidylic acid (poly-IC) and anti-CD40 antibodies (Trivax) in a melanoma mouse model. However, in a glioma mouse model, therapeutic efficacy is not as much as enough maybe due to relatively low antigenicity and blood brain barrier.

MATERIAL AND METHODS
IL-7, which is one of the most important cytokines to expand and develop T cells with anti-tumor immunity, was co-administrated intravenously with Trivax in an orthotopic murine malignant glioma.

RESULTS
Co-administration of the Trivax and recombinant IL-7 (Trivax7) increased the number of survivin specific T cells measured using ELISPOT assay and the population of central memory T cells, comparing with administration of Trivax. The tumor size of orthotopic mouse model in Trivax 7 group was smaller than those of Trivax only group. Finally, overall survival in Trivax 7 was longer than those of Trivax only. In addition, there was a prolonged survival of antigen-specific T cells in Trivax7 group than Trivax only group.

CONCLUSION
In summary, our novel combinational immunotherapy may overcome the limitations of current cell-based cancer vaccines and could be applicable for the treatment of glioblastoma patients.
NCOG-04. COGNITIVE FUNCTIONS BEFORE RADIOTHERAPY IN PEDIATRIC PATIENTS WITH BRAIN TUMORS
Authors: Li Juan , Cai Linbo , Lai Mingyao , Hu Qingjun 
Published: November 2019

Abstract

OBJECTIVE
To assess the cognitive functions before radiotherapy in pediatric patients with brain tumors and explore the related influence factors.

METHODS
Before radiotherapy for brain tumors, adaptive behavior scale (adaptive quotient) and Wechsler intelligence scale for children were used to evaluate the cognitive functions in pediatric patients. Herein the assessment items of verbal IQ, performance IQ, total score and the corresponding percentile. The cognitive functions of pediatric patients with different pathological diagnoses, lesion locations, with or without epilepsy, hydrocephalus or hypopituitarism were compared.

RESULTS
A total of 128 pediatric patients were enrolled in this study. The mean verbal IQ score was 83.7±20.8 (range, 36–128), and the corresponding percentile mean value was 27.699±30.3. The mean performance IQ score was 82.83±20.5 (range, 30–126), and the corresponding percentile mean value was 26.6±29.1. The total score of Wechsler intelligence scale was 0–128, with a mean value of 81.4±21.7, and the corresponding percentile was 0–97, with a mean value of 25.5±28.5. Moreover, the adaptive quotient for all enrolled patients was 32–164, with a mean value of 95.1±29.4. The results of multivariate analysis on the clinical factors related to cognitive functions revealed that the mean performance IQ, the corresponding percentile and the mean of the total score of Wechsler intelligence scale in patients with lesions involving basal ganglia region were 76±16, 15.1±19.6 and 75.29±15, respectively, which were lower than 84±20.7, 28±19.1 and 82.4±22 in those with lesion without involving basal ganglia region, with statistical differences (P= 0.031, 0.018, 0.046).

CONCLUSION
The cognitive functions before radiotherapy in pediatric patients with brain tumors are proved to be inferior to those in normal children. The performance IQ and total score of pediatric patients with brain tumors involving basal ganglia region were lower than those of the other patients for the lesions have affected the limb movement.
NCOG-09. TREATMENT DECISION MAKING IN THE SETTING OF ADVANCED CANCER
Authors: Triebel Kristen , Maulhauser Kyler , Fiveash John , Marrotta Dario , Gammon Meredith , Vance David , Nabors Louis 
Published: November 2019

Abstract

OBJECTIVE
To investigate medical decision-making capacity (MDC) in patients with advanced stage cancer.

METHODS
Participants were 113 newly diagnosed adults with brain metastases and 41 adults with metastatic cancer without brain metastases who were recruited from an academic medical center and 40 demographically-matched healthy controls recruited from the community. We evaluated MDC using the Capacity to Consent to Treatment Instrument (CCTI) Vignette B and its four clinically relevant consent standards (expressing a treatment choice, appreciation, reasoning, and understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, and severe impairment) on the consent standards were also assigned to each participant using cutoff scores derived statistically from the performance of the control group.

RESULTS
Both of the metastatic cancer groups (with and without brain metastasis) performed significantly below controls on consent standards of understanding and reasoning. The brain metastasis group performed below the non-metastatic cancer group on understanding. Capacity compromise was defined as performance ≤1.5 standard deviations (SD) below the control group mean. Using this definition, approximately 65% of the participants with brain metastases and 51% of participants with metastatic cancer without brain metastases were impaired on at least one MDC standard.

CONCLUSION
Over half of participants with metastatic cancer regardless of whether they have brain disease have reduced capacity to make treatment decisions. The finding of impaired MDC in patients without brain metastases is surprising and suggests this group likely exhibits cognitive deficits that impact their ability to understand and reason about different treatment options. This finding suggests that clinicians need to carefully consider the patient’s ability to engage in treatment decision making when they are discussing treatment options for metastatic cancer. These results also indicate a need for the development and investigation of interventions to support MDC in this patient population.
NCOG-11. NEUROPSYCHOLOGICAL OUTCOMES FOLLOWING AWAKE CRANIOTOMY FOR LOW GRADE GLIOMA
Authors: O’Hara Daniel , Miller Amy , Goodden John , Graham Christopher , Kitchingman Hayley , Mathew Ryan , Richards Oliver , Chumas Paul 
Published: November 2019

Abstract

BACKGROUND
Awake craniotomy is an established treatment for tumours in eloquent brain regions. It aims to achieve maximal resection without significant neurological and functional morbidity. There is an emerging evidence base about the neuropsychological outcomes following awake craniotomy for low grade gliomas (LGGs) with inconsistent findings potentially reflective of methodological confounders such as the inclusion of mixed tumour types and the use of varied neurocognitive measures and timescales for repeat testing. We describe detailed neuropsychological outcomes for a cohort of patients following awake craniotomy for LGGs.

METHOD
Data were collected from patients undergoing first-time awake resection of presumed LGGs at Leeds Teaching Hospitals, UK between 2010 and 2018. Patients were included if they consented to and completed the full battery of pre- and postoperative neuropsychological testing. Neuropsychometric testing involved assessment of general intellectual functioning, language, memory, executive functioning, perception, processing speed and mood. Data were analysed using paired-samples t-test or Wilcoxon signed-rank test with Bonferroni correction for multiple statistical comparisons.

RESULTS
Twenty-two patients undergoing awake craniotomy for presumed supratentorial LGG (13 left hemisphere, 9 right hemisphere; mean age 35 years) met the above inclusion criteria. Tumour location was heterogenous (11 insular, 9 frontal, 1 temporal, 1 parietal). Histopathology confirmed WHO Grade II diffuse astrocytoma (n=11), WHO Grade II oligodendroglioma (n=10) and WHO Grade III anaplastic oligodendroglioma (n=1). No statistical differences in neurocognitive test scores were found pre- and post-neurosurgery (mean follow-up was 61 weeks). Other outcomes including extent of resection and reliable change statistics for neurocognitive tests and measures of mood were also analysed.

CONCLUSION
No significant change in neurocognitive functioning was found in patients following recovery from awake craniotomy for LGG. Our findings suggest that awake craniotomy is a safe treatment for LGG and that neuropsychological input is an important part of the treatment pathway for patients with LGG.
NIMG-01. T2WI-FLAIR MISMATCH SIGN IN LOWER GRADE GLIOMA AND DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR
Authors: Onishi Shumpei , Yamasaki Fumiyuki , Takano Motoki , Yonezawa Ushio , Taguchi Akira , Sugiyama Kazuhiko , Kurisu Kaoru 
Published: November 2019

Abstract

BACKGROUND
T2-FLAIR mismatch sign was reported as a specific imaging marker for diffuse astrocytoma with IDH-mutant and 1p/19q non-codeletion. However, most of the previous studies for T2-FLAIR mismatch were confirmed only among lower grade glioma (LGG). The purpose of this study is to explore the T2-FLAIR mismatch sing in supratentorial non-enhancing tumor including LGG and dysembryoplastic neuroepithelial tumor (DNET) and to unveil the exception rules of the sign.

METHODS
Forty-four patients of non-enhancing LGG and DNET were included in this study. LGG（diffuse astrocytoma with IDH mutant (IDHmut-Noncodel), oligodendroglioma with IDH-mutant and 1p19q codeletion (IDHmut-Codel), diffuse astrocytoma with IDH wildtype (IDHwt)）and DNET were diagnosed based on WHO 2016 classification. The tumors were evaluated MRI by 2 independent reviewers to assess presence or absence of T2-FLAIR mismatch sign. CT was also performed to evaluate the localized thinning of the skull bone. Inter-reviewer agreement with Cohen’s kappa (κ) was calculated. RESULT: Ten out of 18 cases (55.6%) of IDHmut-Noncodel presented T2-FLAIR mismatch sign. None of the other LGG (IDHmut-Codel and IDHwt) presented T2-FLAIR mismatch. Eight out of 11 cases (72.7%) of DNET also present the T2-FLAIR mismatch. The overlying part of the skull bone thinning was observed in 5 cases of DNET, but none of LGG presented the localized skull bone thinning. The inter-rater agreement for the T2-FLAIR mismatch and the localized thinning of the skull bone were excellent (κ= 1.00).

CONCLUSION
The T2-FLAIR mismatch sign was specific marker for IDHmut-Noncodel among LGG. However, DNET also presented the T2-FLAIR mismatch sign. The localized skull bone thinning could be useful for differentiating between IDHmut-Noncodel and DNET
NIMG-03. PROSPECTIVE PHASE II RANDOMIZED TRIAL COMPARING PROTON THERAPY VS. PHOTON IMRT FOR GBM: SECONDARY ANALYSIS COMPARISON OF PROGRESSION FREE SURVIVAL BETWEEN RANO VS. CLINICAL AND RADIOLOGICAL ASSESSMENT
Authors: Al Feghali Karine , Randall James , Wefel Jeffrey , Guha-Thakurta Nandita , Grosshans David , Dibaj Seyedeh , McAvoy Sarah , Li Jing , McGovern Susan , McAleer Mary , Ghia Amol , Paulino Arnold , Sulman Erik , Penas-Prado Marta , Wang Jihong , DeGroot John , Heimberger Amy , Armstrong Terri , Gilbert Mark , Mahajan Anita , Brown Paul , Chung Caroline 
Published: November 2019

Abstract

PURPOSE
To compare tumor progression based on clinical radiological assessment and on Response Assessment in Neuro-Oncology (RANO) criteria between GBM patients treated with proton radiotherapy (PT) vs. photon intensity modulated radiotherapy (IMRT).

METHODS
Eligible patients were enrolled on the described prospective phase II trial and had MR imaging at baseline and follow-up beyond 12 weeks from treatment completion. ‘Clinical’ progression was based on a radiology report of progression in combination with changes in treatment due to suspected disease progression. A single blinded observer applied RANO criteria to determine the RANO-based tumor progression.

RESULTS
Of 90 enrolled patients, 66 were evaluable, with median follow-up of 19.8 (Range: 3.2–65.1) months; median of 22.6 months for PT (n=25) vs. 18.9 months for IMRT (n=41). Median time to progression (TTP) was 7.9 months based on clinical progression criteria (8.1 months IMRT, 6.3 months PT) and 7.2 months (7.3 months IMRT, 5.7 months PT) by RANO criteria (p=ns for all). Median ‘clinical’ progression-free survival (PFS) was 8.7 (Range: 6.4–11.1) months; 8.9 months IMRT vs. 8.7 months PT (p=0.065). Median RANO PFS was 8.3 (range, 5.8–11.6) months: 8.3 months IMRT vs. 6.9 months PT (p=0.226). There were 14 discrepant cases: 3 had progression based on ‘clinical’ but not RANO criteria, and 11 had progression based on RANO but not ‘clinical’ criteria.

CONCLUSION
Based on this secondary analysis of a randomized trial of PT vs. IMRT for GBM, there was no difference in tumor progression relative to treatment technique used. There was no statistical difference in PFS noted between clinical and RANO-based assessments, but RANO criteria identified progression more often than clinical assessment, and TTP was shortened with the use of RANO criteria alone. Further development of tumor assessment tools that improve consistency and accuracy of determining tumor progression are needed to guide therapeutic trials in GBM.
NIMG-08. 2-HYDROXYGLUTARATE MAGNETIC RESONANCE SPECTROSCOPY IN BRAINSTEM TUMOR PATIENTS IN VIVO
Authors: Choi Changho , Tiwari Vivek , Levy Michael , Maher Elizabeth , Pan Edward , Patel Toral , Mickey Bruce 
Published: November 2019

Abstract
Evaluation of 2-hydroxyglutarate (2HG) by magnetic resonance spectroscopy (MRS) has significant application in assessing the isocitrate dehydrogenase (IDH) mutational status in brain tumor patients noninvasively. This clinical role of 2HG MRS may be demonstrated most clearly in patients with brainstem lesions, where surgical biopsy presents high risk of permanent neurological injury. We conducted 2HG MRS in 20 subjects with a radiographically identified brainstem tumor (13 male and 7 female, age 20 - 73, median age 38). Proton MRS data was acquired from the T2-FLAIR volume using a 2HG-tailored MRS protocol (PRESS TE 97 ms). The millimolar concentration of 2HG was estimated with reference to water. Excluding data with unacceptable quality, data from 16 patients were included in subsequent analysis. The 16 patients were clearly divided into two groups in terms of 2HG level. The tumors in 5 patients showed a clearly discernible 2HG signal (2.25 ppm) while those in 11 patients did not. The 2HG estimation ranged from 2.1 to 6.3 mM in the 5 patients (IDH mutation) and from 0 to 0.7 mM in the 11 patients (most likely IDH wildtype). The mean concentration of 2HG differed significantly between the groups (p=3.3×10−6). One tumor was confirmed to be IDH mutated from autopsy. A representative case for 2HG MRS utility was a patient in whom 2HG was estimated to be 5.3 mM in the first MRS scan and the clinical decision was made to follow with 2HG MRS without surgery and chemoradiation therapy. The patients had 22 follow-up MRS scans for 5.4 years (scan intervals ~3 months), during which the tumor was stable clinically and radiographically. The present study demonstrates the clinical utility of 2HG MRS in brainstem tumors. 2HG MRS provides reliable estimation of 2HG and can be utilized for evaluating the IDH mutation status in brainstem lesion noninvasively.
NIMG-09. NONINVASIVE PERFUSION IMAGING BIOMARKER OF MALIGNANT GENOTYPE IN ISOCITRATE DEHYDROGENASE MUTANT GLIOMAS
Authors: Mureb Monica , Jain Rajan , Poisson Laila , Aguiar Littig Ingrid , Nunes Neto Lucidio , Wu Chih-Chin , Ng Victor , Patel Sohil , Patel Seema , Serrano Jonathan , Kurz Sylvia , Cahill Daniel , Bendszus Martin , von Deimling Andreas , Placantonakis Dimitris , Golfinos John , Kickingereder Philipp , Snuderl Matija , Chi Andrew 
Published: November 2019

Abstract

OBJECTIVE
A small subset of IDHmut astrocytomas behave aggressively, similarly to IDHwt glioblastoma. Genomic correlates of poor prognosis IDHmut astrocytomas include global relative DNA hypomethylation, MYCN amplification copy number variation (CNV) abundance, and CDKN2A/B homozygous deletion. We sought to identify a non-invasive imaging correlate of poor prognosis IDHmut astrocytomas.

METHODS
30 IDHmut astrocytomas (NYU=18, TCGA=12) were included. Relative cerebral blood volume was obtained from 4 regions of interest within the highest perfusion areas. Genomic CNV analysis and CDKN2A/B copy number status was obtained using Illumina Infinium 450k or Illumina EPIC methylation array data. Associations between rCBV, survival, and genomic alterations were evaluated. An additional 22 IDHmut astrocytomas were obtained from another institution for validation.

RESULTS
CNV stable (CNV-S, n=14) astrocytomas demonstrated significantly lower mean rCBV than and CNV unstable (CNV-U, n=16) (P=0.0.0155) ones. IDHmut astrocytomas with CDKN2A/B homozygous deletion (n=7) had higher rCBV (3.9 ± 2.3, mean ± SD) compared to those without this alteration (n=22; 1.8 ± 1.9, mean ± SD; P=0.0489). In the validation set, there was no significant evidence in rCBV between CNV-S and CNV-U tumors (P=0.3976). These results were sensitive to a single outlier in the CNV-S group. Excluding this case with rCBV=7.15, the CNV-S tumors demonstrated significantly lower mean rCBV (P=0.0279). IDHmut astrocytomas with CDKN2A/B homozygous deletion (n=9) tended to have higher rCBV (4.2 ± 1.8, mean ± SD) compared to those without this alteration (n=16; 2.5 ± 1.5, mean ± SD; P=0.0757, t-test). This led to significant discrimination (P=0.0328, Wilcoxon).

CONCLUSION
Our study is the first to identify a non-invasive imaging biomarker for prognostic genomic alterations in IDHmut astrocytomas. Greater CNV abundance and/or CDKN2A/B homozygous deletion have higher rCBV and worse prognosis. Our methods can be applied to standard clinical practice and may enhance informed treatment decisions in the preoperative and immediate postoperative settings.
NIMG-14. THE RELATION BETWEEN T2-FLAIR MISMATCH SIGN AND ADC VALUES REFLECTING PATHOLOGICAL MICROSTRUCTURE IN LOWER-GRADE GLIOMAS
Authors: Fujita Yuichi , Sasayama Takashi , Nagashima Hiroaki , Tanaka Kazuhiro , Hashigutchi Mitsuru , Kohmura Eiji 
Published: November 2019

Abstract

BACKGROUND
Although the recent studies have identified “T2-FLAIR mismatch sign” specific to IDH-mutant and 1p/19q-intact gliomas, it is unclear what the mismatch sign represents. We aimed to investigate the mechanisms and validate the clinical utility.

METHODS
We identified 79 lower-grade gliomas treated at Kobe University Hospital, and classified into three groups: (i) LGGIDH(m),1p19q(-) (n = 18): IDH-mutant and 1p/19q-intact, (ii) LGGIDH(m),1p19q(+) (n=26): IDH-mutant and 1p/19q co-deleted, (iii) LGGIDH(w) (n=35): IDH wild-type. We retrospectively analyzed the relation with apparent diffusion coefficient (ADC) values, metabolites in magnetic resonance spectroscopy and pathological features, and examined the influence of the presence of the mismatch sign on progression-free survival (PFS) and overall survival in LGGIDH(m),1p19q(-).

RESULTS
Compared to the rim presenting hyperintense on T2WI and FLAIR, the core presenting hyperintense on T2WI and reversely hypointense on FLAIR had significantly higher ADC values (p = 0.002). The core/rim ratios of ADC values were significantly higher in the cases with the mismatch sign (p = 0.001), not depending on IDH status, 1p/19q status and WHO grade. There was no significant difference in metabolites changing between the presence and absence of the mismatch sign. The cases with the mismatch sign in LGGIDH(m),1p19q(-) had abundant microcysts as a pathological feature, and longer PFS than those without the mismatch sign (5-yr PFS: 100% vs 37.5%). Multivariate analysis found the mismatch sign to be the only significant predictor for preferable PFS in LGGIDH(m),1p19q(-) (p = 0.044).

CONCLUSION
Our study provided the new evidence that the T2-FLAIR mismatch sign had the significantly different ADC values between the core and the rim, suggesting that the mismatch sign reflected the difference of the tumor cellularity and the microenvironment.