bluuebunny/crossref_metadata_2025_split huggingface dataset:
IM-03 CD206 expression in peripheral blood-derived induced-microglia-like cells as a surrogate biomarker for the specific immune microenvironment of glioma
Authors: Hata Nobuhiro , Tanaka Shunya , Ohgidani Masahiro , Inamine Shogo , Sagata Noriaki , Mukae Nobutaka , Hatae Ryusuke , Sangatsuda Yuhei , Kato Takahiro , Mizoguchi Masahiro 
Published: November 2020

Abstract
INTRODUCTION: As recent advancement of multimodal treatments including immune-check point inhibitors have not led to massive outcome improvement of glioma. Targeting the peculiar immune microenvironment of glioma is a promising approach to innovate a breakthrough treatment, however, there remains to be technical and ethical burdens for monitoring the bioactivities of immune cells in neural tissues. Herein, we examined the feasibility of non-invasive monitoring of glioma-associated microglia/macrophages (GAM) properties through utilization of our originally developed induced-microglia-like (iMG) cells technique. METHODS: We isolated primary microglia (pMG) from surgically-obtained brain tissues of 15 patients with neurosurgical diseases. We induced iMG cells from monocyte extracted from their corresponding peripheral blood by MACS treatment. Expression profiles of representative markers for an M1 and M2 microglia phenotype were analyzed in both pMG and iMG cells by qPCR. RESULTS: q-PCR revealed that a significant correlation of expression level of microglial markers between pMG and the corresponding iMG in each patient. Synchronous upregulations of CD206 were exclusively detected in patients with glioma. CONCLUSION: The present study suggested that iMG cells can be a less-invasive monitor tool for disease-related bioactivity of microglia, thereby seem to be utilized as an intermedium for investigation of relationship between microglia and neuronal diseases including glioma. CD206 upregulation detected by iMG technique can surrogate the specific microenvironment of glioma surrounding tissues and might be utilized as a future biomarker of glioma.
ACT-03 Clinical outcome and radiological findings of patients with recurrent glioblastomas treated by bevacizumab
Authors: Handa Hajime , Shibahara Ichiyo , Hide Takuichiro , Kumabe Toshihiro 
Published: November 2020

Abstract
Object: Seven years have passed since the approval of bevacizumab (BEV) in Japan. We retrospectively reviewed the clinical outcome and radiological findings of patients with recurrent glioblastomas (GB) treated by BEV. Method: We reviewed 116 patients, including 27 cases of newly diagnosed GB and 89 cases of recurrent GB, treated by BEV during the study period between 2013 June and 2019 September. Cumulatively, 116 patients received 1672 cycles of BEV. Among those, we focused on 74 patients with newly diagnosed GB treated by BEV at recurrence to examine clinical characteristics, outcome, and radiological findings of T2-circumscribed or double-positive proposed by Nowosieski et al. or Bahr et al., respectively. Result: The study cohort comprised median age of 66.8 years (range 10 to 81), median KPS of 60% (range, 20 to 100), median cycles of administration 11(1 to 59), median period of treatment 172 days (0 to 1413), median post-BEV survivals 266 days, and overall survival 693 days. Patients without progressive disease at 6 months post-BEV MRI (n = 23) presented favorable post-BEV survival of 713 days than those with progressive disease (n = 8) (p=0.0003). The radiological findings varied by patients, tumor lesions, and sequential imaging; thus, it was difficult to correlate with survival. Our data implied that the T2-circumscribed lesion was accompanied by no enhancement at T1 but hyperperfused at arterial spin labeling imaging, indicating that blood-brain barriers were intact and vascularization is activated. Conclusion: Although our cohort included patients with relatively high age, some had prolonged post-BEV survival. T2-circumscribed or double-positive was not useful to predict the survival; however, MRI at 6 months post-BEV can be an indicator for two years of post-BEV survival.
ACT-17 Protocol design of a matrix-type of novel clinical trial for lower-grade gliomas
Authors: Muragaki Yoshihiro , Nitta Masayuki , Saito Taiichi , Tsuzuki Shunsuke , Fukui Atsushi , Ikuta Soko , Maruyama Takashi , Komori Takashi , Kawamata Takakazu 
Published: November 2020

Abstract
Introduction: Differentiation between glioma grade 2 and 3 was performed based on histological findings. The current grade is an important prognostic factor due to its widespread use, economic efficiency, and data accumulation, but analog elements remain and the genetic marker is unknown. The concept of Lower-grade glioma including G2/3 is spreading. On the other hand, WHO grade is the criteria of clinical trials, and evidence is established for G2 with low risk and high risk, G3 alone or with G4. In Japan, JCOG 1303 and 1016 have been implemented for high-risk G2 and G3, respectively and will be finished next year. Therefore, we examined the feasibility and design of novel clinical trial for patients with grade 2/3 glioma. Method: With reference to clinical trials of high evidence level and public database registration, we researched trials, arms, and designs for each of 3 genotypes, oligodendroglioma (OD), astrocytoma IDH mutant and IDH wild (A-IDHm, A-IDHw). Results: The standard arm common to all genotypes is follow-up (EORTC22845) for G2 low-risk, and chemoradiotherapy (CRT) for G3. Standard arm for G2 high risk, depending on a genotype, is follow-up (EORTC22845), radiation alone (A-IDHm and IDHw, A-IDHw: RTOG9802 subanalysis), or PCV chemoradiotherapy (OD and A-IDHm: 9802). Furthermore, the standard arm and the test arm were replaced by the matrix-like method on each genotype. Results in the G2/3-targeted trial, there was no standard arm all in the three genotypes. In addition, there were a design of master protocols for many genotype and a design that has arms of randomization and observation. Conclusion: Applying the master protocol, the possibility of novel G2/3 target trial in which the arms existing in MATRIX form was suggested. With the improvement of the genetic analysis infrastructure, prospective observational research and a well-designed intervention research plan for each genotype are required.
PEDT-02 Clinical usage of NCC Oncopanel/FoundationOne CDx for pediatric/AYA patients with recurrent malignant brain tumors
Authors: Shibahara Ichiyo , Kumabe Toshihiro , Hide Takuichiro , Sasao Ryota , Sasaki Hikaru , Sasaki Jiichiro 
Published: November 2020

Abstract
Backgrounds: Analyses of somatic mutations in malignant brain tumors have been used to make effective treatment strategies. NCC Oncopanel and FoundationOne CDx are custom targeted next-generation sequencing (NGS) panels. The cost for this analysis is 560,000 yen covered by National Health Insurance in Japan since June 2019. These methods can be applied for the solid cancers with no established therapies and relapsed after the standard therapies. Following these inclusion criteria, most malignant brain tumors, especially recurrent malignant brain tumors in pediatric/AYA generations, can be included. Object: To report the results of our initial experiences. Methods: In the last one year, we utilized these NGS panels for five patients with recurrent malignant brain tumors in this generations: 2 epithelioid glioblastomas; 1 anaplastic meningioma; 1 diffuse astrocytoma (gliomatosis cerebri); 1 atypical choroid plexus papilloma. Results: Final recommended treatments are as follows: BRAF/MEK inhibitors, bevacizumab, or anti-PD-1 antibody for one epithelioid glioblastoma; MEK inhibitor for another epithelioid glioblastoma previously treated by BRAF inhibitor and bevacizumab; ERK1/2 inhibitors for anaplastic meningioma. The diffuse astrocytoma had IDHR132H mutation. There was no clinical trial using IDH inhibitor for recurrent diffuse astrocytoma; thus, the final recommendation for this case was rechallenge of temozolomide. To date, only one NGS for a choroid plexus papilloma has been reported (Arch Pathol Lab Med, 2017). Our case had multiple actionable gene alterations, including TERT mutation and amplification of various genes. Unfortunately, there was no druggable gene alteration among them. Conclusions: Insurance-covered cancer gene panel tests could represent effective treatment options for some malignant brain tumors in pediatric/AYA generations. If the relapse is local and can be treated by repeat resections, we think the surgery is the first-line choice. But, in another situation, information from NGS panels should be obtained positively. Efforts to increase the utility of off-label use of drugs are encouraged.
STMO-03 Surgical resection for precentral gyrus glioma
Authors: Kijima Noriyuki , Kinoshita Manabu , Hirayama Ryuichi , Kagawa Naoki , Kishima Haruhiko 
Published: November 2020

Abstract
Primary motor cortex glioma is usually considered unresectable because of its high risk for motor deficit. However, recent reports suggest that surgical resection for primary motor cortex brain tumor is feasible for selected patients. In this study, we analyzed the neurological outcomes for 27 patients who underwent surgical resections for precentral gyrus glioma. Glioma grades for 27 patients were Grade II in 6 cases, Grade III in 7 cases, and Grade IV in 13 cases. 11 patients were recurrent glioma cases and glioma grade for those patients were Grade II in 4 cases, Grade III in 3 cases, and Grade IV in 4 cases. Extent of resection for 27 patients was biopsy in 2 cases, partial resection in 16 cases, and more than 90% of resections in 9 cases. 6 patients underwent awake surgery and glioma grade for those patients were Grade II in 3 cases, Grade III in 2 cases, and Grade IV in 1 case. Median extent of resection for patients who underwent awake surgery was 90%. Transient neurological worsening was observed in 5 patients, however, no patient exhibited permanent neurological deficit. Surgical resections for primary motor cortex glioma were feasible in selected patients without severe neurological complication. Careful intraoperative awake mapping is desirable to achieve maximum resections.
10031-RT-02 Results of reactor-based BNCT for 44 cases of recurrent and refractory high-grade meningiomas and road to accelerator based BNCT
Authors: Miyatake Shin-Ichi , Kawabata Shinji , Wanibuchi Masahiko , Takai Satoshi , Takeuchi Koji , Ono Koji , Ko Naonori , Sakurai Yoshinori , Tanaka Hiroki , Suzuki Minoru 
Published: November 2020

Abstract
Introduction: High-grade meningioma (HGM) is difficult clinical entity to treat. Especially recurrent HGM after some radiotherapy has very miserable prognosis. For example median overall survival (mOS) of recurrent HGM after radiotherapy is reported as 2 years. We applied tumor-selective particle radiation BNCT using nuclear reactor for 44 recurrent HGMs. Methods: From 2005 to 2019, we treated 44 recurrent and refractory HGMs by reactor-based BNCT. The patients’ WHO grades are grade 2:20 cases, grade 3:24 cases. Prior to BNCT, totally 114 times operations and 72 times SRS and 14 times external beam radiotherapy were applied for them. OS, tumor shrinkage, causes of treatment failure were analyzed. Results: Median follow-up was 26.0 months. MOS after BNCT was 29.6 (95% CI:16.1–40.4) months. Grade 2 and 3 showed mOS as 44.4 (27.4-) and 21.55 (10.6–30.6) months, respectively and there is statistically significance (p=0.0009). All treated tumor showed rapid shrinkage on MRI. Treatment failure patterns are local recurrence, out of field recurrence, systemic metastasis, CSF dissemination, as 35.5%, 20.6%, 17.6%, 8.8 %, respectively. These results showed good local tumor control and prolonged survival for recurrent HGM cases. Conclusions: Our cases were heavily treated with repetitive surgeries and repetitive radiotherapy. In addition the rate of grade 3 patients was extremely high. In a word our cases seemed to have poor prognosis. In spite of these poor condition, reactor-based BNCT exerted good local control and prolonged survival for recurrent and refractory HGMs. Depending on the clinical results, PMDA gave us the permission to apply investigator-lead clinical trial for recurrent and refractory HGMs using accelerator-based BNCT with financial support from AMED (one of the agency of Japanese government). In our talk, let us open some results from this trial.
MPC-02 Prognostic effects of molecular factors in elderly patients with IDH-wildtype Glioblastomas
Authors: Fukai Junya , Hayashi Nobuhide , Arita Hideyuki , Umehara Toru , Yoshioka Ema , Shofuda Tomoko , Kanematsu Daisuke , Kodama Yoshinori , Kinoshita Manabu , Okita Yoshiko , Nonaka Masahiro , Uda Takehiro , Sakamoto Daisuke , Sasaki Takahiro , Uematsu Yuji , Nakao Naoyuki , Mori Kanji , Kanemura Yonehiro 
Published: November 2020

Abstract
BACKGROUND: Geriatric neuro-oncology is an important research field, because the elderly patients is growing at a very rapid rate. This study investigates molecular features and their prognostic effects in the elderly glioblastomas (GBM). METHODS: We collected adult cases diagnosed with IDH-wildtype GBM and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors (212 cases). Clinical and molecular features were analyzed retrospectively and independent prognostic factors were identified statistically. Focusing on the elderly (&gt;=70 years) cases, the association between molecular factors and overall survivals (OS) was examined. RESULTS: Included in the study were 92 elderly cases (43.4%) and median OS was 12.8 months. MGMT promoter was methylated in 50 (54.3%). Triple CNA (EGFR amplification/gain & PTEN deletion & CDKN2A deletion) was detected in 23 (25.0%). NFKBIA was deleted in 23 (25.0%). In the elderly cases, adjuvant radiation and temozolomide (RT+TMZ) was performed in 39 (42.4%) (mOS = 17.1 months). Statistical analyses of the elderly plus non-elderly cases treated with RT+TMZ (148 cases), MGMT promoter, triple CNA and NFKBIA were identified as independent molecular prognostic factors. In the elderly group, however, there was no significant difference in OS according to MGMT status (methylated = 18.7 vs. unmethylated = 17.1, p = 0.3885) or triple CNA status (triple = 13.6 vs. non-triple = 19.6, p = 0.1734). On the other hand, statistical difference was observed according to NFKBIA status (del = 12.1 vs. non-del = 18.7, p = 0.0157*) even in the elderly cases. CONCLUSION: Prognostic effects of molecular factors might be attenuated in the elderly patients. Further investigation in a larger population is necessary.
MPC-11 Comprehensive gene expression analysis of IDH-mutated astrocytomas with 19q-loss
Authors: Otani Ryohei , Mukasa Akitake , Uzuka Takeo , Higuchi Fumi , Matsuda Hadzki , Tanaka Shota , Kim Phyo , Ueki Keisuke 
Published: November 2020

Abstract
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. To further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior, we compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas,136 up-regulated genes and 203 down-regulated genes were extracted. Down-regulated genes in the 19q-loss astrocytomas were heavily clustered to 19q and 4p, and up-regulated genes to 4q. It was noted that fibroblast growth factor 1 associated with stem cell maintenance was down-regulated in 19q-loss astrocytomas and genes associated with glioma progression were differentially expressed, these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, 19q-loss astrocytomas did not shift to oligodendrogliomas with 1p/19q codeletion but were a subgroup in astrocytomas. These results indicated that 19q-loss in astrocytomas is more likely to be an acquired event rather than early event in oncogenesis like 1p/19q codeletion in oligodendrogliomas, and the biological and morphological features of 19q-loss astrocytomas were possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.
NI-01 Usefulness of preoperative evaluation of glioma elasticity by the magnetic resonance elastography
Authors: Koizumi Shinichiro , Kurozumi Kazuhiko 
Published: November 2020

Abstract
Introduction: The elasticity of intracranial tumors is difficult to assess non-invasively because the lesion is surrounded by the skull. Therefore, intracranial tumors have not been verified before surgery in terms of elastic modulus. Magnetic resonance elastography (MRE) is an epoch-making method capable of non-invasively imaging the elasticity of internal organs. We have examined the elasticity of meningiomas and pituitary adenomas and reported their usefulness. This time, we measured the glioma elasticity and verified usefulness of MRE.
Method: Twenty-four gliomas (mean age 51.8±15.7 years, male: female = 17: 7) who underwent tumor resection after MRE imaging from July 2017 to May 2020 were targeted. The average elasticity was measured as an evaluation of tumor elastic modulus by MRE. Gliomas were divided into a low-grade glioma group (LGG: Grade 1, 2) and a high-grade glioma group (HGG: Grade 3, 4). Then, a comparative statistical study was conducted.
Results: The average values of the average elasticity of LGG group (9 cases) and HGG group (15 cases) were 1.8±0.8 kPa and 2.5±0.8 kPa, respectively. The average elasticity was significantly higher in the HGG group (p=0.023). In the ROC analysis, the cutoff value was 2.1 kPa (sensitivity 70%, specificity 70%). Therefore, it was suggested that the tumor is likely to be HGG when the average elasticity is 2.1 kPa or more.
Discussion: The glioma elasticity by preoperative MRE was significantly higher in the HGG group. Based on actual surgical experience, the tumor seems to be hard in the HGG group, and it was judged to be consistent with this our MRE research. The preoperative evaluation of glioma elasticity by MRE was considered useful, and it might help in planning a surgical strategy considering malignant grade.
NI-09 Amide Proton Transfer (APT) image is useful for diagnostic imaging of glioma
Authors: Shirota Masami , Nitta Masayuki , Saitou Taiichi , Tuduki Syunsuke , Fukui Atsushi , Ikuta Souko , Yoshida Ayako , Abe Kayoko , Muragaki Yoshihiro , Kawamata Takakazu 
Published: November 2020

Abstract
Introduction: APT image(APT),which images the concentration of amide groups that increases in tumors, is expected to be applied clinically in diagnostic imaging of glioma. Purpose: APT was compared with MET-PET based on the pathological diagnosis results, and it was retrospectively verified that APT was useful for diagnostic imaging of glioma. Methods: A total of 46cases with glioma (WHO 2016 Grade: GII/III/IV) and Pseudoprogression were included. APT measured the APT measurement value by placing the region of interest in the tumor part. MET-PET was administered with 370MBq and the accumulation ratio(TNR) between the tumor part and the normal part was measured. Results: The APT measurement value in all cases was 2.22±1.01 and the TNR was 2.58±1.50,and a correlation was observed between the APT measurement value and the TNR(r=0.6, p&lt;0.001).When the accuracy of discrimination between GII/III/IV (32cases) and Pseudoprogression(14cases) by APT measurement was verified, the sensitivity was 91% and the specificity was 100% at the threshold of 1.81. In the verification of malignancy diagnosis, the measured APT value of GII (6cases) was 2.18±0.43,the measured APT value of GIII (11cases) was 2.67±0.69,and the measured APT value of GIV (15cases) was 2.99±0.61.The measured value showed a significant difference. The measured APT value in the oligodendroglioma group (GII/III:10cases) was 2.37±0.66,the TNR was 3.52±1.41,and the measured APT value in the astrocytoma group (GII/III: 7cases)Was 2.67±0.45 and TNR was 2.41±0.87.In the oligodendroglioma group, the measured APT value was lower and the TNR was higher than in the astrocytoma group. Conclusion: It was suggested that APT may have the same diagnostic ability as MET-PET in diagnosing malignant tumors and distinguishing between recurrence and Pseudoprogression. Patients with an actual APT of 1.81 or higher should consider treatment strategies, and follow-up may be an option for patients with an APT of &lt;1.81.APT,which is not affected by the blood-brain barrier, has little variation in measured values and is considered to be useful for diagnostic imaging of glioma.
NI-19 Use of 11C-methionine PET for decision of discontinuation of adjuvant chemotherapy with temozolomide
Authors: Beppu Takaaki , Sato Yuichi , Sasaki Toshiaki , Terasaki Kazunori , Ogasawara Kuniaki 
Published: November 2020

Abstract
Background: The aim was to clarify whether positron emission tomography with 11C-methyl-L-methionine (met-PET) is useful to decide on discontinuation of TMZ-adjuvant therapy in patients with residual diffuse astrocytic tumor. Methods: Subjects were 44 patients with residual tumor comprising 17 with IDH1-mutant diffuse astrocytoma (DA), 13 with IDH1-mutant anaplastic astrocytoma (AA), and 14 with IDH1-wild glioblastoma (GB). All patients received TMZ-adjuvant chemotherapy (median, 12 courses), and whether to discontinue or continue TMZ-adjuvant chemotherapy was decided on the basis of the tumor-to-normal ratio in standardized uptake value from met-PET (T/N); patients with T/N &lt; 1.6 immediately discontinued TMZ, and patients with T/N &gt; 1.6 were either to continued or discontinued TMZ. Progression-free survival (PFS) was compared between patients with T/N &gt; 1.6 and T/N &lt; 1.6 in each tumor type. Median observation period was 434 days after met-PET scanning. Results: The number of patient who underwent recurrence was 10 in DA, 7 in AA, and 11 in GB. All patients showing T/N &gt; 1.6 underwent tumor recurrence. PFS was significantly longer in patients with T/N &lt; 1.6 than T/N &gt; 1.6 in DA and AA (p &lt; 0.01 in both types), but was no significant difference between 2 groups in GB (p = 0.06). Sixteen of 17 patients (94%) in DA and AA showed recurrence from residual tumor, whereas 4 of 11 patients (36%) in GB showed recurrent tumor at remote regions which were different from residual tumor. Conclusions: The present study suggested that met-PET is beneficial to decide to discontinue adjuvant chemotherapy with TMZ in patients with residual tumors of DA and AA, but not useful for patients with GB. Reasons for unsuccessful results in GB might have been small sample size, failure of establishing the cut off value in T/N, recurrences at remote regions where not be assessed by met-PET.