bluuebunny/crossref_metadata_2025 huggingface dataset:
ET-12 ANTI-VEGF THERAPY WITH KETOGENIC DIET AGAINST GLIOBLASTOMA IN MOUSE MODEL
Authors: Sasayama Takashi , Maeyama Masahiro , Tanaka Kazuhiro , Fujita Yuichi , Hashiguchi Mitsuru , Irino Yasuhiro , Kohmura Eiji
Published: December 2019

NTRODUCTUION

Malignant glioma cells critically depend on glucose as the main energy source to survive and sustain their aggressive properties. The ketogenic diet (KD) has been proposed as a complementary therapy for treatment of malignant gliomas. VEGF inhibitor (bevacizumab) decreases blood supply to tumor and clinically used for glioblastoma treatment. Therefore, we examined anti-tumor effect of the combination of bevacizumab (Bev) and KD using mouse model.

METHODS

U87MG cells were implanted into the right brain of nude mice. One week after the implantation, mice were randomized into four treatment groups: control group, KD group, Bev group, and combination (K+B) group. KetoCal 4:1 was administered to the mice for KD. Bev (10mg/kg) was injected from tail vein twice a week. Metabolic and histological analysis of the tumor, and survival analysis of the mice were performed.

RESULTS

3-hydroxy-butyrate, one of the ketone bodies, was significantly increased in the tumor of KD group, however, the metabolic enzymes of ketone bodies were not found an increased expression in immunostaining experiments. Principal component analysis (PCA) analysis demonstrated distinct clustering or a clear separation of the four groups. In K+B group, several TCA cycle-related enzymes (succinate dehydrogenase (SDH), fumarate-hydratase (FH)) were decreased, suggesting a repression of TCA cycle. In addition, several amino acids (tyrosine, valine, alanine, glutamic acid) were decreased in K+B tumor, however, alpha-ketoglutarate was significantly increased, suggesting dynamic metabolic remodeling. Histologically, Ki-67 index was most decreased in the K+B tumor among four groups. In survival analysis, Bev group had significant longer survival than control group (p=0.0016), and the K+B group had most longer survival time among four groups.

CONCLUSIONS

Drastic metabolic remodeling in the tumor occurred in the combination of Bev and KD This combination may be potentially useful for glioblastoma therapy.
IM-03 IMMUNOLOGICAL SUBTYPES OF GLIOBLASTOMA BASED ON TUMOR INFILTRATING CELLS
Authors: Yoshihiro Kushihara , Tanaka Syota , Yamasawa Erika , Koike Tsukasa , Hana Taijun , Kitagawa Yousuke , Takayanagi Syunsaku , Kakimi Kazuhiro , Saito Nobuhito
Published: December 2019

To discover novel biological targets in glioblastoma, genomic and immunological analysis were performed using The Cancer Genome Atlas (TCGA) data set. The RNA-seq data of 156 primary glioblastoma cases were subjected to CIBERSORT to detect tumor infiltrating cell fractions. Principal component analysis was performed on this data to detect factors that strongly contribute to the first principal component, and hierarchical clustering was performed. Survival curves were compared for each of the derived clusters. Finally, Gene Set Enrichment Analysis (GSEA) using HALLMARK Gene Set was performed. In the principal component analysis, we detected seven factors (NK cells resting, T cell regulatory, NK cells activated, Macrophage type 0, T cell gamma delta, Macrophage type 2, Macrophage type 1) which strongly contribute to the first principal component. Based on these seven factors, hierarchical cluster analysis resulted in T cell regulatory (Treg), Macrophage type 0 (M0), Macrophage type 2 (M2) and Macrophage type 1 (M1) clusters. There was no significant difference between these groups in CD8 T cell. M2 and M1 clusters displayed better OS with a significant difference. TNFA signaling via NFκB in Treg group, IFNα response, IFNγ response and ALLOGRAFT response in M2 group, G2M CHECKPOINT, GLYCOLYSIS, WNTβ catenin signaling, MITOTIC SPINDLE and TGFβ signaling in M1 group were upregulated. In conclusion, tumor microenvironment of glioblastoma can be divided into 4 immunological subtypes, Treg, M0, M1, and M2. Because of the contribution of innate immunity for shaping the tumor microenvironment of glioblastoma, immunotherapies targeting these innate immune cells are anticipated.
ACT-01 THE SECOND GENERATION ANAPLASTIC LYMPHOMA KINASE (ALK) INHIBITOR CERITINIB EFFECTIVELY INDUCES CELL DEATH IN HUMAN GLIOBLASTOMA CELLS
Authors: Kawauchi Daisuke , Takahashi Masamichi , Yamamuro Shun , Kobayashi Tatsuya , Uchida Eita , Iwadate Yasuo , Ichimura Koichi , Tomiyama Arata
Published: December 2019

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase which expresses only in the developmental stage of the brain during embryogenesis of human. On the other hand, a variety of ALK gene alterations, such as oncogenic fusion, activating point mutation, or wild type gene amplification, have been recently discovered as the powerful oncogene in various tumors, and these ALK mutations have also been known as the potential therapeutic targets against tumors harboring these ALK mutations. For example, ALK inhibitors have been already approved and used for the clinical treatment of non-small cell lung cancers harboring oncogenic ALK fusion.

Previously, we reported classical ALK inhibitors triggered cell death in human glioblastoma (GBM) cells, which did not express ALK, via suppression of transcription factor STAT3 activation but not in normal tissue-derived cells.

In this study, we investigated the anti-tumor effect of newly-developed ALK inhibitors in GBM cells. As a result, a second generation ALK inhibitor ceritinib induced cell death in various human GBM cell lines with lower concentration compared to other ALK inhibitors. Besides, ceritinib also suppressed STAT family activity in these GBM cell lines. From these results, we consider ceritinib might be a novel therapeutic agent against GBMs, and further investigation about the specific anti-tumor mechanism of ceritinib in GBM cells is currently on-going.
ACT-09 RETROSPECTIVE INVESTIGATION ABOUT STATUS AND RESULT OF ADMINISTRATION OF BEVACIZUMAB FOR MALIGNANT GLIOMAS IN THE REAL WORLD
Authors: Hashiba Tetsuo , Ueno Katsuya , Naito Nobuaki , Miyata Mayuko , Yamamura Natsumi , Lee Ichi , Iwata Ryoichi , Takeda Junnichi , Yoshimura Kunikazu , Nonaka Masahiro , Asai Akio
Published: December 2019

6 years have passed after approval of Bevacizumab for malignant gliomas in Japan, we analyzed the application and the results in our institution. Subjects were 56 patients who were histologically diagnosed as malignant gliomas. Bevacizumab was used in 41 patients among them. In 14 patients, Bevacizumab was introduced after initial therapy. The resection rates were below partial resection in 11 of the 14 patients. In 12 patients, administrations were finished and the average use was 7.6 times. The reason was PD in 6, and side effect in 4. Eight patients died, the average OS of those who died was 9.9 months, the average PFS after Bevacizumab was 5.4 months, and the average time from discontinuation to death was 2.1 months. In 27 patients used at the time of recurrence, the initial excision rate tended to be higher than in the former cases. In 22 patients the administrations were finished and the average use was 11.1 times. The reason was PD in 17, and side effect in 4. Twenty patients have died, the average OS of those who died was 22.3 months, the average PFS after Bevacizumab was 7.1 months, and the average time from discontinuation to death was 2.6 months. In 12 of 15 unused patients subtotal or total resections were achieved. From results, when it is difficult to control by surgery or TMZ, Bevacizumab is used in most patients, and considering the nature of tumor, it can be said that all patients will be considered for use sometime. However, PFS after introduction is not good and the prognosis after discontinuation is poor. It is necessary to conduct initial treatment that can delay introduction, to provide care that does not lead to discontinuation due to side effects, and to examine what treatment is possible at the time of exacerbation.
STMO-01 APPLICATION OF THE AMINOLEVULINIC ACID HYDROCHLORIDE FOR INTRAOPERATIVE DETECTION OF MALIGNANT BRAIN TUMORS
Authors: Kobayashi Keiichi , Saito Kuniaki , Shimada Daisuke , Matsumoto Yoshie , Shimizu Saki , Iijima Shouhei , Noguchi Akio , Shibahara Jyunji , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

BACKGROUND

A maximal safe resection has been shown as an independent prognosis factor for high grade glioma (HGG). Intraoperative photo dynamics diagnosis (PDD) facilitates an increased rate of tumor resection, thereby taking an important role in accomplishment of “ maximal safe resection “ along with neuro-navigation and monitoring of motor nerve function. Since the approval of aminolevulinic acid (5-ALA) for PDD in 2013 in Japan, we have been utilizing the PDD when HGG is suspected by preoperative assessments. Here we retrospectively analyze clinical findings in PDD-mediated tumor resection.

METHODS

From February 2014 to March 2019, 285 consecutive patients (132 females) with suspected HGG underwent total of 302 PDD-mediated resection. Median age was 61 yo (13–90). A single oral dose of 5-ALA 20 mg/kg was given within three hours before microsurgery. Positivity of excited fluorescence was assessed qualitatively under surgical microscope.

RESULTS

Among 195 gliomas, the fluorescence positivity rates were 89.6% (120/134) for glioblastoma, 40.5% (15/37) for grade III, and 13.6% (3/22) for grade II. The positive rates for other histologies were 30.2% (13/43) for malignant lymphoma, 32.1% (9/28) for metastatic brain tumor, 0% (0/7) for meningioma (include atypical), and 4.5% (1/22) for other types. In gliomas the high positivity correlated with histological grades, while all fluorescence-positive grade II gliomas were recurrent tumors. Serious adverse events were not observed.

CONCLUSIONS

The qualitative PDD showed a clinical utility to aid accurate resection in glioblastoma, whereas its positivity was inconsistent in lower grade gliomas as well as other malignant brain tumors. This unreliability might attribute, at least in part, to fluorescent intensity heterogeneity in situ, a reduced excitation by an inappropriate radiation angle of the light source, and the qualitative fluorescence detection. Impacts of introducing quantitative detection system as well as molecular and histopathological features on better discrimination will be discussed.
STMO-05 SURGICAL AND FUNCTIONAL OUTCOME OF AWAKE SURGERY FOR INSULAR GLIOMA
Authors: Hirono Seiichiro , Matsutani Tomoo , Iwadate Yasuo
Published: December 2019

BACKGROUND

Insular glioma is still challenging entity for neurosurgeons because of its deep location and the surrounding vascular structures and eloquent white matter fibers. Objective. To clarify the surgical and neurofunctional outcome of awake surgery for patients with insular glioma (IG).

METHODS

We conducted a retrospective review of 42 consecutive patients with insular glioma (IG) and non-insular glioma (non-IG) who underwent awake craniotomy. In addition to surgical outcome including operative complication, the detailed objective neurocognitive evaluation were also analyzed.

RESULTS

Ten IG and 32 non-IG patients were included in this study. Preoperative tumor volume in IG group was smaller than non-IG group (15.3cc, 21.9cc, p=0.14). More patients (8 in 12) in IG patients had tumor in the right hemisphere than non-IG group (12 out of 32, p=0.06). All the resection were performed according to the functional boundary decided by the cortical and subcortical mapping. Preoperatively, IG patients showed better cognitive function in the TMT-B and categorical fluency test (p=0.035, p=0.026, respectively).Postoperatively, the median residual volume and the resection rate in IG and non-IG group were 2.2cc vs 0cc (p=0.10) and 85.5% vs 100% (p=0.025) respectively, suggesting better resection in non-IG group. In terms of complications, 2 patients (20%) in IG group showed infarction in acute postoperative MR images and mild hemiparesis which recovered completely at 3-month evaluation after operation. In contrast, 16 out of 32 non-IG patients (50%) demonstrated new impaired neurocognitive function, which still persisted at final follow-up in 9 out of 16. Most of their postoperative MR images showed no ischemic lesion, suggesting white matter disconnection as main cause of new deficits. More non-IG patients demonstrated the prolonged time in TMT-A than IG patients at 3-month evaluation.

CONCLUSION

Subcortical white matter disconnection, not ischemic change, are the main reason of postoperative neurocognitive dysfunction in non-IG patients.
MPC-03 IMMUNOHISTOCHEMICAL ANALYSIS OF TUMOR ASSOCIATED MACROPHAGE INDUCED AFTER BIODEGRADABLE CARMUSTINE WAFER IMPLANTATION IN HUMAN GLIOBLASTOMA
Authors: Shibahara Ichiyo , Hagiwara Hiroyuki , Miyasaka Kazuhiro , Sato Sumito , Inukai Madoka , Yasui Yoshie , Hide Takuichiro , Kumabe Toshihiro
Published: December 2019

The carmustine (BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. Biomaterials to treat cancers hold therapeutic potential; however, how they behave inside the tumor microenvironment requires further study. We previously investigated the tumor microenvironment after BCNU wafer implantation, and found that CD68-positive macrophage was significantly introduced around the wafer (Shibahara et al. J Neurooncol 2018). Recent studies demonstrated the importance of tumor-associated macrophage (TAM). However, we could not clarify whether the increased macrophage around the wafer was pro-tumor or anti-tumor phenotype. In the present study, we immunohistochemically examined expressions of CD68, IBA1, CD163, TMEM119, BIN1, CD31, and VEGF to investigate TAM after the wafer implantation. Quantitative evaluation revealed that CD68-positive cells were significantly increased (P = 0.0009), whereas TMEM119-positive cells were significantly decreased (P = 0.0081) after wafer implantation compared to tissue from cases without wafer implantation. CD163, a known marker of poor prognosis in glioblastoma, did not differ with and without wafer implantation. Among factor analyzed, BCNU wafer did not induce protumor TAM, but reduced microglial marker, TMEM119. In addition to the aspect of chemotherapy, BCNU wafer may have potential to modify the tumor microenvironment such as TAM.
MPC-04 MOLECULAR FEATURES AND CLINICAL OUTCOMES OF ELDERLY GLIOBLASTOMA PATIENTS: ANALYSES OF KANSAI NETWORK AND TCGA COHORTS
Authors: Fukai Junya , Arita Hideyuki , Umehara Toru , Yoshioka Ema , Shofuda Tomoko , Kodama Yoshinori , Kinoshita Manabu , Okita Yoshiko , Nonaka Masahiro , Uda Takehiro , Sakamoto Daisuke , Mori Kanji , Kanemura Yonehiro
Published: December 2019

INTRODUCTION

Aging is a negative prognostic factor in glioblastoma (GB) and the genetic background in clinical outcome of elderly GB could exist. This study investigates the difference of elderly patients from younger ones regarding molecular characteristics as well as clinical outcomes in IDH-wildtype GB.

METHODS

We collected adult cases diagnosed with IDH-wildtype GB and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network) (212 cases) and The Cancer Genome Atlas (TCGA) project (359 cases). Clinical and pathological characteristics were analyzed retrospectively and compared between elderly cases (≥70 years) and younger ones (≤50 years). Molecular analysis included copy number alterations (CNAs) of eight genes (EGFR, PDGFRA, PTEN, CDKN2A, CDK4, MDM2, TP53, NFKBIA).

RESULTS

Included in the study were 92 (≥70 years)/33 (≤50 years) cases of Kansai Network and 88 (≥70 years)/69 (≤50 years) cases of TCGA. Median overall survival was 12.8 (≥70 years)/ 21.0 (≤50 years) months in Kansai Network cohort and 8.8 (≥70 years)/ 21.09 (≤50 years) months in TCGA cohort. MGMT promoter was methylated in 50 (54.3%) (≥70 years)/14 (42.4%) (≤50 years) tumors in Kansai Network and 34 (48.6%) (≥70 years)/16 (36.4%) (≤50 years) tumors in TCGA. TERT promoter was mutated in 51 (55.4%) (≥70 years)/13 (39.4%) (≤50 years) tumors in Kansai Network and unknown in TCGA. Significant difference of CNA profiles between ≥70 years and ≤50 years was as follows: PTEN del, 43 (46.7%)/8 (24.2%); CDK4 amp, 17 (18.5%)/1 (3.0%) in Kansai Network and CDKN2A del, 69 (78.4%)/ 42 (60.9%) in TCGA.

CONCLUSION

Elderly patients have several potential factors for poor prognosis and different molecular profiles might explain the survival differences among generations.
MPC-05 TUMOR RELATED EPILEPSY AND IDH MUTATIONS IN GLIOMAS
Authors: Wakabayashi Hikaru , Inaji Motoki , Fujii Shoko , Aoyama Jiro , Hashimoto Satoka , Tamura Kaoru , Maehara Taketoshi
Published: December 2019

OBJECTIVE

Tumor related epilepsy (TRE) is an important complication in the treatment of brain tumors. In recent studies, it is assumed that isocitrate dehydrogenase (IDH) mutations are concerned with TRE in gliomas. Here, we examined the association between IDH mutations and TRE in our cases.

METHODS

115 patients who had a supratentorial glioma and were treated in our hospital from February 2009 to November 2018 were retrospectively assessed for IDH mutations and TRE.

RESULTS

38 patients were the IDH mutant group (16 females, mean age 43.7±12.9 years, mean follow-up time 44.0 months). 77 patients were the IDH wild group (35 females, mean age 61.6±16.6 year, mean follow-up time 18.1 months). Compared to the IDH wild group, the IDH mutant group was significantly younger and mean follow-up time was longer. There was no difference in the postoperative radiation and chemotherapy in both groups. The incidence of seizures as presenting symptom was 20 patients (52.6%) in the IDH mutant group and 16 patients (20.8%) in the IDH wild group, and was significantly higher in the IDH mutant group (p<0.01). 27 patients (71.1%) in the IDH mutant group had TRE at least once during follow-up time and 39 patients (50.0%) in the IDH wild group (p=0.06). In addition, the median OS for the group with seizure onset (36 patients) was 69.2 months and the group with the other onset forms (79 patients) was 22.4 months. The seizure onset group had a significantly better prognosis (p<0.05).

CONCLUSION

Gliomas with IDH mutations have a higher incidence of TRE. Although IDH mutations are considered to be a risk factor for TRE, which is consistent with previous studies, but it is suggested that differences in survival may have an effect on the incidence of TRE.
MPC-07 MECHANISMS OF BETTER PROGNOSIS IN IDH-MUTATED ASTROCYTOMA WITH 19Q-LOSS
Authors: Otani Ryohei , Uzuka Takeo , Higuchi Fumi , Matsuda Hadzki , Kim Phyo , Ueki Keisuke
Published: December 2019

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas (Otani et al. Cancer Sci 2018). The purpose of the present study was to reveal how 19q-loss contributed to better prognosis and the morphology in the subgroup. We compared expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis.

136 up-regulated genes and 203 down regulated genes were extracted in 19q-loss astrocytomas compared with 19q-intact astrocytomas. Significantly changed genes distributed throughout all chromosomes, but more down-regulated genes were on 19q and 4p, and more up-regulated genes were on 4q.

Genes associated with apoptosis, cell adhesion, and antigen presentation were up-regulated, and genes associated with Ras signaling pathway were down-regulated. These changes could result in better prognosis. By contrast, there was few expression changed gene associated with oligodendroglioma-like morphology although up-regulation of genes associated with axon guidance and down-regulation of genes associated with cell shape might result in the morphology or neuronal differentiation. Expression pattern of 19q-loss astrocytomas indicated no tendency of oligodendroglial differentiation.

Better prognosis of 19q-loss astrocytomas was derived from expression changes associated with tumor proliferation and tumor immunity.
NI-02 THE ASSOCIATION BETWEEN 11C-METHIONINE UPTAKE, IDH GENE MUTATION, AND MGMT PROMOTER METHYLATION IN PATIENTS WITH GRADE II AND III GLIOMAS
Authors: Okita Yoshiko , Shofuda Tomoko , Kanematsu Daisuek , Yoshioka Ema , Kodama Yoshinori , Mano Masayuki , Kinoshita Manabu , Nonaka Masahiro , Fujinaka Toshiyuki , Kanemura Yonehiro
Published: December 2019

AIM

We evaluated the association between 11C-methionine positron emission tomography (11C-methionine PET) findings, isocitrate dehydrogenase (IDH) gene mutation, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with grade II and III gliomas.

MATERIALS AND METHODS

Data were collected from 40 patients with grade II and III gliomas who underwent both magnetic resonance imaging (MRI) and 11C-methionine positron emission tomography (PET) as part of their pre-surgical examination. We examined IDH mutation through DNA sequencing, and MGMT promoter methylation through quantitative methylation-specific polymerase chain reaction (PCR).

RESULTS

A threshold of MGMT promoter methylation of 1.0% was significantly associated with tumor/normal tissue (T/N) ratio. The T/N ratio in samples with MGMT promoter methylation ≥1.0% was higher than that in samples with MGMT promoter methylation <1.0%, and the difference was statistically significant (p = 0.011). Reliable prediction of MGMT promoter methylation (<1.0% vs ≥1.0%) was possible using the T/N ratio under the receiver operator characteristic (ROC) curve with a sensitivity and specificity of 75% each (cut-off value = 1.6) (p = 0.0226, AUC = 0.76172). Conversely, the T/N ratio had no association with IDH mutation (p = 0.6). The ROC curve revealed no reliable prediction of IDH mutation using the T/N ratio (p = 0.606, AUC = 0.60577).

CONCLUSION

11C-methionine PET parameters can predict MGMT promoter methylation but not IDH mutation status. 11C-methionine uptake may have limited potential to reflect DNA methylation processes in grade II and III gliomas.
NI-04 WHICH RADIOLOGICAL IMAGING IS BEST TO DISCRIMINATE RADIATION NECROSIS FROM TUMOR PROGRESSION? - SUBANALYSIS OF SYSTEMATIC REVIEW FOR RADIOLOGICAL DIAGNOSIS OF RADIATION NECROSIS
Authors: Furuse Motomasa , Nonoguchi Naosuke , Yamada Kei , Shiga Tohru , Combes Jean-Damien , Ikeda Naokado , Kawabata Shinji , Wanibuchi Masahiko , Kuroiwa Toshihiko , Miyatake Shin-Ichi
Published: December 2019

BACKGROUND

It is challenging to discriminate radiation necrosis from tumor progression, especially in malignant glioma. Therefore many radiological imaging studies have been reported. In this study, we performed a systematic review of radiological diagnosis for radiation necrosis and analyzed the best radiological imaging for malignant glioma.

METHODS

We divided diagnostic approaches into two categories as follows-CT and MRI (conventional radiological imaging studies), and SPECT and PET (nuclear medicine studies). Our librarians conducted a comprehensive systematic search on Pub Med, Cochrane Library, and the Japan Medical Abstract Society up to March 2015. The searching keywords included radiation necrosis, recurrence, imaging modalities such as MRI, diagnosis, and differential. In a meta-analysis, diagnostic odds ratio (DOR) was calculated. A subanalysis was performed, dividing into tumor types, gliomas and metastatic brain tumors.

RESULTS

Of 188 and 239 records extracted from the database, 20 and 26 studies were included in the meta-analysis after exclusion of case reports and studies with incompatible content and insufficient information. Gd-enhanced MRI exhibited the lowest sensitivity (63%) and DOR (2.2). On the other hand, combined multiple imaging studies including MRS and perfusion image displayed the highest sensitivity (96%) and DOR (5.9). In the subanalysis for glioma, Gd-enhanced MRI and 18F-FDG-PET revealed low DORs (1.7 and 2.3). Conversely, 18F-FET-PET and combined multiple imaging studies showed high DORs (6.8 and 5.9).

CONCLUSIONS

Gd-enhanced MRI had low diagnostic ability for differentiation of radiation necrosis. In glioma patients, 18F-FDG-PET was not useful to discriminate radiation necrosis from tumor progression. Combined multiparametric imaging including lesional metabolism and blood flow could enhance diagnostic accuracy and be useful to differentiate radiation necrosis from tumor progression even in glioma patients.
NI-09 CLINICAL SIGNIFICANCE OF T2-FLAIR MISMATCH SIGN IN LOWER GRADE GLIOMAS
Authors: Deguchi Shoichi , Mitsuya Koichi , Kakuda Yuko , Oishi Takuma , Hayashi Nakamasa
Published: December 2019

Lower grade glioma is classified based on genetic information of mutation of IDH1/2 gene and co-deletion of chromosome 1p19q. Knowledge of these genetic information preoperatively is useful for making surgical planning, treatment strategy and prognostication. Recently, T2-FLAIR mismatch sign has been reported to be specific for astrocytoma with IDH mutation (mut) / non-1p19q co-deletion (co-del). This study aims to verify it in our patients. We retrospectively analyzed 152 patients aged over 15 years who were pathologically diagnosed with WHO grade 2 or 3 gliomas from April 2003 to December 2018. We excluded 88 patients without genetic information or without T2-weighted and FLAIR images. T2-FLAIR mismatch sign was defined as in the original description, namely, with homogeneously hyperintense signal on T2-weighted image and a peripheral hyperintense signal with central hypointensity signal on FLAIR image. Among 22 patients with IDH mut / non-1p19q codel, 10 were positive for T2-FLAIR mismatch sign. On the other hand, only one patient was positive for T2-FLAIR mismatch sign respectively in 19 with IDH mut / 1p19q codel and 23 patients with IDH wild-type. Sensitivity, specificity, positive predictive value, and negative predictive value of T2-FLAIR mismatch for the patients with IDH mut / non-1p19q codel are 0.46 (95% confidence interval: 0.24–0.68), 0.95 (0.84–0.99), 0.83 (0.52–0.98). and 0.77 (0.63–0.88), respectively. In 22 patients with IDH mut / non-1p19q codel, we compared 10 patients with and 12 without T2-FLAIR mismatch sign. Median age was 35 and 39 years old. WHO grade 3 was 3 patients each. Tumor location was frontal lobe in 9 (90%) and 10 patients (83%). A statistically significant difference was not found in these factors. PFS and OS were not reached in both groups. The specificity of the T2-FLAIR mismatch sign for astrocytoma with IDH mut / non-1p19q codel was very high, which may be helpful as preoperative imaging marker.
NI-23 ULTRA-HIGH-RESOLUTION CT ANGIOGRAPHY FOR BRAIN TUMOR SURGERY
Authors: Saito Kuniaki , Kobayashi Keiichi , Iijima Shohei , Matsumoto Yoshie , Shimada Daisuke , Koyanagi Masamichi , Gomyo Miho , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

BACKGROUND

Preoperative accurate evaluation of arteries and veins can help avoid ischemic complication of brain tumor surgery. The latest ultra-high-resolution CT (UHRCT) angiography (Aquilion PrecisionTM; Canon Medical Systems) has recently become available for clinical testing of the main arteries and critical perforating arteries by brain CTA, compared to conventional CT.

METHODS

UHRCT provides slice collimation of 0.25 mm x 160 and matrix size of 1024 x 1024 or 2048 x 2048. Major features of this CT scanner include an improved detector system (the minimal slice thickness, 0.25 mm; the maximal channel number, 1792) and a small x-ray focus (the smallest size, 0.4 x 0.5 mm) compared to a standard multi-detector CT (MDCT) scanner (the minimal slice thickness, 0.5 mm; the maximal channel number, 896; the smallest x-ray focus size, 0.8 x 0.9 mm).

RESULTS

Until July 2019, 168 patients with brain tumor underwent UHRCT angiography. As high resolution image could visualize cortical arteries and cortical veins clearly, it helped to decide approach route to the tumor and achieve accurate biopsy of even small lesion. Identification of tumor feeders and passing arteries allowed for efficient feeder coagulation and preservation of passing artery, avoiding the ischemic change of surrounding brain. Improved image reconstruction could visualize perforating arteries, which helped to preserve perforator by predicting the location during tumor removal.

CONCLUSION

UHRCT angiography can visualize even tiny arteries and veins around the tumor, and contributes to avoid the risk of ischemic complication.
NQPC-03 PROGNOSTIC SIGNIFICANCE OF QUALITY-OF-LIFE EVALUATION OVER TIME IN CLINICAL PRACTICE FOR PATIENTS WITH GLIOBLASTOMA
Authors: Yamagishi Yuki , Taku Mikiko , Hanayama Naomi , Saito Kuniaki , Kobayashi Keiichi , Yamada Shin , Okajima Yasutomo , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

BACKGROUNDS

Evaluation of quality of life (QOL) has been considered as an indispensable modality for assessment of treatment impact for patients with malignant brain tumor, especially glioblastoma. However, changes in patients’ QOL under clinical practice with current standard of care (SOC) have not been clearly and routinely explored, so that solid baseline QOL data under SOC are not available for reliable comparison with those with novel treatments. Here we retrospectively examined changes in QOL during SOC in glioblastoma patients.

PATIENTS AND METHODS

Patients with histologically confirmed glioblastoma treated in our institute from April 2016 to April 2019, who underwent QOL evaluations using EORTC QLQ-C-30/BN-20 were eligible. Outcomes were assessed with clinical factors including therapeutic regimens.

RESULTS

Forty-two patients, median age 64 yo (25–87), male/female 26/16, were identified having longitudinal QOL data along with medical records. Median initial KPS and mini-mental state examination (MMSE) score were 70 (20–90) and 27, respectively, suggesting this cohort containing those in good performance status. In four patients whose QOL queries were answered by a family, median MMSE was 16, indicating the impaired NCF affect self-report ability. Long term survivors without progression remained at an adequate functional scale level, while those who recurred declined in functional scale after progression, often accompanied with an increase in symptom scales associated with tumor location. The domains of declined functional scales varied among patients, and there was no clear tendency associated with patients’ backgrounds such as age and gender. The functional scale level improved in most cases when the recurrent disease was successfully treated, but it gradually declined in a stepwise fashion by repeated recurrences.

CONCLUSIONS

Changes in QOL in patients with glioblastoma were found to associate with disease status. The small number of patients who could be evaluated for QOL over time prevented extracting significant factors affecting QOL outcomes.
NQPC-06 FUNCTIONAL OUTCOMES OF INITIAL TREATMENTS FOR PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA ASSESSED BY ADL AND NEUROCOGNITIVE FUNCTION
Authors: Taku Mikiko , Kobayashi Keiichi , Yamagishi Yuki , Saito Kuniaki , Shimada Daisuke , Matsumoto Yoshie , Kikuchi Hana , Yamada Shin , Shiokawa Yoshiaki , Nagane Motoo , Okajima Yasutomo
Published: December 2019

BACKGROUNDS

Primary central nervous system lymphoma (PCNSL) frequently causes severe damage of activities of daily living (ADL) and neurocognitive function (NCF) due to extensive brain infiltration, necessitating their appropriate assessment and measures even in clinical practice. Since few studies have focused on the changes in the level of ADL and NCF in the course of PCNSL treatment, we retrospectively analyzed the effect of initial treatment of PCNSL in view of ADL and NCF.

METHODS

Among 55 patients (13 male/9 female) with newly-diagnosed PCNSL treated in our institution from January 2014 to June 2019, 22 were evaluated with both ADL and NCF. Remission induction therapies consisted of high-dose methotrexate alone (two patients), R-MPV (rituximab, methotrexate, procarbazine, and vincristine)(17 patients), and R-MPV+radiaotherapy (three patients), according to the patients’ conditions. Rehabilitation staffs intervened from the beginning, providing specific exercises and periodically evaluating scores of Karnofsky Performance Status (KPS) and Mini Mental State Examination (MMSE).

RESULTS

Mean age was 68.4 yo (range 34 to 85). After induction therapies, there were 11 complete responses (CRs), eight partial responses (PRs), and three progressive diseases (PDs). Both KPS and MMSE scores improved after induction therapy, from median 70 (40–90) to 80 (50–90), and from 24 (0–30) to 27(0–30), respectively. Among three patients who underwent RT, MMSE declined in two (one CR/one PR).

CONCLUSIONS

Case-adjusted induction therapies resulted in significant radiographical responses, and the longitudinal evaluation of ADL and NCF by rehabilitation staffs could validate their maintenance or improvement over time through effective treatments and early rehabilitation intervention. However, three was difficulty in assessing patients with higher brain dysfunction such as aphasia and social adjustment disorder. Further study is needed to include more patients and to explore more appropriate evaluation batteries and timings during and after completion of induction therapy for PCNSL.
NQPC-13 THE EFFICACY OF RAVEN’S COLORED PROGRESSIVE MATRICES FOR PATIENTS WITH BRAIN TUMOR
Authors: Yahiro Sachiko , Matsuoka Aiko , Miyakita Yasuji , Ohno Makoto , Takahashi Masamichi , Narita Yoshitaka
Published: December 2019

BACKGROUND

Mini-Mental State Examination (MMSE) and Raven’s Colored Progressive Matrices (RCPM) are cognitive function tests used to assess speech and visual cognitive functions in patients with brain tumor and aphasia, respectively. We investigated the distribution and correlation between MMSE and RCPM scores in patients with brain tumor, who underwent tumor resection, to identify the test characteristics.

METHOD

Among the 122 patients who underwent tumor resection in our hospital from April 2018 to March 2019, and potentially required rehabilitation, 43 patients (i.e., 19 men and 24 women) who underwent pre- and post-operative MMSE and RCPM were further investigated. Median age during surgery was 54 years (20–86 years). Relationship between the pre- and post-operative MMSE and RCPM scores were evaluated using the Spearman’s rank correlation coefficient. Additionally, we investigated the characteristics of patients who scored low on either of the tests.

RESULTS

Median pre- and post-operative MMSE scores were 29 points (14–30) and 29 points (21–30), respectively. Median pre- and post-operative RCPM scores were 33 points (25–36) and 35 points (18–36), respectively. The pre- and post-operative correlation coefficient between MMSE and RCPM scores were 0.376 and 0.699, respectively. Among the 12 patients with lower pre-operative scores on MMSE, as compared to RCPM, 8 patients had impaired attention and 4 patients had aphasia. One patient who scored lower on RCPM test, as compared to MMSE, had reduced analogical reasoning ability. Postoperatively, no patient scored low on MMSE as compared to RCPM, and one patient who scored lower on RCPM than MMSE had left hemi-spatial neglect.

CONCLUSION

The pre-operative cognitive functions of patients with impaired attention and aphasia can be evaluated with RCPM using visual tasks without interference caused by these impairments. Minute pre- and post-interventional cognitive changes can be assessed with both MMSE and RCPM together.
10070: MET-02 NON-SMALL-CELL LUNG CANCER WITH SYNCHRONOUS BRAIN METASTASIS IN THE ERA OF MOLECULAR TARGETED DRUGS: TREATMENT OUTCOME AND RISK FACTORS
Authors: Uzuka Takeo , Higuchi Fumi , Kim Phyo , Ueki Keisuke
Published: December 2019

Brain metastasis is associated with worse prognosis in patients with non-small cell lung cancer (NSCLC). However, recent advances in molecular targeted therapy are rapidly changing the treatment strategy for NSCLC. Here, we conducted a retrospective study to clarify the prognosis and risk factors in NSCLC patients with synchronous brain metastasis. Seventy-four patients who were treated at our institute between Jan 2013 and Apr 2019 were included. The association between overall survival (OS) and clinicopathological features, such as neurological symptoms at diagnosis, histology, EGFR and ALK mutation status, number of intracranial metastases, extracranial systemic metastasis, Karnofsky performance status (KPS) at diagnosis, and initial therapy, were examined. OS was calculated from the day of diagnosis with brain metastasis or NSCLC. Of the 51 men and 23 women enrolled (median 70.0 years of age, range 40–84), 26 patients (35.1%) exhibited neurological symptoms at diagnosis. EGFR and ALK mutations were present in 24 (32.4%) patients. The median OS for all patients was 23.0 months. Factors significantly associated with worse OS in univariate analysis were symptomatic lesions and the absence of a driver mutation. Driver mutation status was only an independent prognosis factor in multivariate analysis. On lung-mol GPA score, the patients greater than or equal to 2.5 were significantly better prognosis compared with less than 2.5 (median OS: 40.0 VS 10.0 months, respectively). Our cohort of 74 NSCLC patients with synchronous brain metastasis had a median OS of 23.0 months. This much longer OS may reflect recent advances in treatment, particularly the availability of molecular targeted drugs. Lung-mol GPA score was considered as a useful tool to estimate the prognosis; thus, the information of KPS score, extracranial metastasis, brain metastases numbers, and driver mutation status are essential to build a treatment strategy for synchronous brain metastasis from NSCLC.
MET-04 EVALUATION OF PERITUMORAL BRAIN PARENCHYMA USING CONTRAST-ENHANCED FIESTA IMAGING FOR DIFFERENTIATING METASTATIC BRAIN TUMORS AND GLIOBLASTOMAS
Authors: Yamamoto Junkoh , Kakeda Shingo , Korogi Yukunori , Saito Takeshi , Nakano Yoshiteru
Published: December 2019

Introduction: Metastatic brain tumors and glioblastomas commonly revealed heterogenous enhancement lesions with peritumoral brain edema on magnetic resonance imaging (MRI). In particular, distinguishing solitary metastatic brain tumors from glioblastomas is difficult on conventional MRI. Fast imaging employing steady-state acquisition (FIESTA) can emphasize the water content signal with a high spatial resolution. In this study, we evaluate a role of contrast-enhanced FIESTA(CE-FIESTA) by focusing on the peritumoral brain parenchyma between metastatic brain tumors and glioblastomas. Materials and Methods: We included patients who underwent initial surgery and were histologically diagnosed with metastatic brain tumor (43 cases) or glioblastoma (14 cases) between November 2008 and May 2016. We evaluated CE-FIESTA findings of peritumoral brain parenchyma. Next, we performed an observer performance study with neuroradiologists based on the findings of peritumoral brain parenchyma using conventional MRI and CE-FIESTA. Results: CE-FIESTA revealed hyperintense rim in peritumoral brain parenchyma. We classified hyperintense rim in three groups, as follow: type A, no hyperintense rim; type B, partial hyperintense rim; and type C, extended hyperintense rim. Regarding the diagnosis of metastatic brain tumors, the observer performance demonstrated high sensitivity (95.3%), specificity (85.7%) and accuracy (93.0%) of type C on CE-FIESTA, and thus, CE-FIESTA could distinguish metastatic brain tumors from glioblastomas with high accuracy. Conclusions: CE-FIESTA may provide useful information for distinguish metastatic brain tumors from glioblastomas, focusing on the differences in the peritumoral brain parenchyma.
BT-07 PATIENT DERIVED XENOGRAFT MODELS OF EPITHELIOID GLIOBLASTOMA AND THERAPEUTIC VULNERABILITY IN MOLECULAR TARGET THERAPY
Authors: Sasame Jo , Tateishi Kensuke , Ikegaya Naoki , Miyake Shigeta , Miyake Yohei , Nakamura Taishi , Udaka Naoko , Yamanaka Shoji , Yamamoto Tetsuya
Published: December 2019

Epithelioid glioblastoma (E-GBM) predominantly arises at younger age and promotes dismal prognosis. Because of its rare etiology, pathological and genetical characterization of E-GBM remains elusive. Herein, we report unique patient-derived E-GBM xenograft (PDX) models from 3 E-GBM patients (2 BRAFV600E mutant and 1 BRAFV600E wild-type). Two BRAF mutant E-GBM cells (YMG62 and YMG89) were originated from adolescent and young adult patients and harbored TERT promoter mutation and CDKN2A homozygous deletion, while 1 BRAFV600E E-GBM cell (YMG64) was from elderly patient and had TERT wild-type. YMG62 and YMG89 could be propagated at multiple passage in vitro, while YMG64 could not be maintained. PDX models were established from YMG62, YMG89, and YMG64. All PDX tumors were preferentially disseminated and negative expression of GFAP, which were recapitulated to the patient characteristics. BRAF and MEK inhibitor mildly suppressed cell viability in vitro. Collectively, E-GBM PDX models recapitulate patient characteristics, which may be helpful to elucidate tumor biology and establish novel therapeutic target in E-GBM.
CS-01 GIANT CELL TUMOR IN THE SKULL BASE BONE TREATED WITH ANTI-RANKL INHIBITOR
Authors: Kajiwara Yoshinori , Takechi Akihiko , Watanabe Yosuke , Miyoshi Hiroyuki , Shiraishi Takeshi
Published: December 2019

Giant cell tumor of bone is a rare and osteolytic neoplasm that that usually affecting the epiphyses in long bones of the extremities. They seldom occur in the skull, preferentially affecting the sphenoid and temporal bones. Most pathologically benign, and total removal by surgery was regarded as the first treatment, however, it was very difficult in skull lesion. In 2014 the molecular targeting drug anti-RANKL inhibitor was approved in Japan. We report a case in which an anti-RANKL inhibitor was administered to a skull base bone giant cell tumor that was difficult to remove completely. A 56-year-old man with a sudden right neck pain followed by dysphoria and dysphagia was referred to our hospital. Computed tomography showed 4.4 x 2.0 cm osteolytic lesion involving the right occipital bone and occipital condyle. Magnetic resonance imaging demonstrated an extensive soft-tissue mass occupying. Surgical biopsy was performed and the pathological diagnosis was giant cell tumor. Patient received the anti-RANKL inhibitor (Denosumab®). After 4 weeks, ossification was observed, and neurological symptoms were improved after 12 weeks. Patient has been on good course for 5 years without recurrence and is still following-up.
CS-11 PITUITARY EPENDYMOMA: A CASE REPORT
Authors: Fukami Tadateru , Yoshimura Yayoi , Fujikawa Ryoko , Nozaki Kazuhiko
Published: December 2019

INTRODUCTION

Neoplasms of the sellar region generally includes pituitary adenoma, craniopharyngioma, meningioma. We report a case of pituitary ependymoma.

CASE

A 39 years-old man. He experienced the sense of discomfort of the inside upper part field of vision of the left eye for a few months since May, 201X. Ophthalmological examination showed right homonymous hemianopia of right upper 1/4. He was introduced to the department of neurosurgery of nearby hospital. MRI showed intrasellar tumor and the lesion was partially removed because of solidness by endoscopic transsphenoidal surgery on July, 201X. Postoperative pathological diagnosis was pituitary adenoma. The residual tumor was followed up, but the compression to the left optic nerve was not resolved. So he was introduced to our hospital in January, 201X+1 and endoscopic transsphenoidal surgery was performed on May, 201X+1.

OPERATION

Supposing the change to extended transsphenoidal surgery, we prepared rescue flap. Enlarging the window of sellar floor and removing the tuberculum sellae, the tumor was totally removed. The boundary between the tumor and the normal pituitary gland was obscure. We inserted fat piece to the intrasellar space, and reconstructed the sellar floor with the absorbable plate following fixation with a polyglycolic acid sheet, fibrin glue, and sinus balloon.

PATHOLOGY

Fusiform cells having an oval or a short spindle shape nucleus multiplied in strand and palisading pattern through capillary vessels were the main findings, and ependymal rosettes were confirmed. Immunohistchemical study showed chromograninA(focally+), synaptophysin (-), EMA (+, dot and ring pattern), CAM5.2(+), bcl-2(+), TTF-1(-), S100(focally+), GFAP(-). Final diagnosis was pituitary ependymoma. Mild diabetes insipidus was occurred postoperatively but it was controlled medically. Now he is followed up in outpatient department.

DISCUSSION

Pituitary ependymoma was reported only eight cases in the past literatures. Though it is extremely rare, pituitary ependymoma should be included as a differential diagnosis of the sellar tumors.
COT-13 THE USEFULNESS OF THE CEREBRAL ANGIOGRAPHY FOR RESECTION OF THE MALIGNANT GLIOMA
Authors: Matsumoto Yoshie , Saito Kuniaki , Shimada Daisuke , Amano Tatsuo , Sasamori Hiroki , Horikawa Hiroshi , Kobayashi Keiichi , Noguchi Akio , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

OBJECTIVE

Maximal safe resection is a standard of care (SOC) for treatment of malignant glioma in light of quality of life (QOL) maintenance and better outcomes. This strategy is especially important when vital perforating arteries such as lateral striate arteries (LSA) and anterior choroidal arteries,are involved in tumor and its periphery,as their damage causes serious deterioration in the activities of daily life. Here we report a utility of preoperative cerebral angiography in glioma surgery.

METHODS

Six cases of perforator-involving malignant gliomas, consisting of five glioblastomas and one anaplastic ganglioma, operated from December 2018 to July 2019 were evaluated with preoperative imaging using sophisticated cerebral angiographic techniques and fusion imaging with MRI.

RESULTS

In all six cases, perforating arteries passed through or around the tumors. The cerebral angiography revealed the origin of LSA in all patients; one at M1,two at M1-M1 junction, and three at the superior trunk of M2. Anterior choroidal arteries and Heubner’s recurrent arteries were also identified preoperatively. By knowing the precise locations of these perforators,intraoperative resection of vascular-rich malignant gliomas could be performed with precaution of avoiding their unnecessary injury. No symptomatic complications occurred after angiography. Postoperative MRI disclosed a potential embolic infarction in the perforator territory in one patient,which resolved in a few days.

CONCLUSIONS

Visualization of perforators by angiography was helpful in detailed evaluation of surgical strategy and facilitated safe resection also leading to shortening of operating time. Compared to another modalities,angiography provided the best special resolution for visualization of vital perforating arteries involved in malignant gliomas.