bluuebunny/crossref_metadata_2025_split huggingface dataset:
TB-08 PATIENT DERIVED XENOGRAFT’S BIOBANK FROM KANSAI MOLECULAR DIAGNOSIS NETWORK FOR CENTRAL NERVOUS SYSTEM TUMORS
Authors: Kijima Noriyuki , Kanematsu Daisuke , Shofuda Tomoko , Nonaka Masahiro , Iwata Ryoichi , Fukai Junya , Inoue Akihiro , Sasayama Takashi , Tsuyuguchi Naohiro , Kawashima Toshiyuki , Higuchi Yuichiro , Suemizu Hiroshi , Mori Kanji , Kishima Haruhiko , Kanemura Yonehiro 
Published: December 2019

Abstract
Patient-derived xenografts (PDXs) are essential tools for translational research for brain tumors. However, it is sometimes difficult for each institution to establish PDXs because it needs experiences and techniques and it also takes a lot of works to establish them. Thus we aim to establish patient derived xenograft’s biobank among institutions of Kansai Molecular Diagnosis Network for Central Nervous System (CNS) Tumors, Osaka, Japan. We have already began sharing two anaplastic astrocytoma PDXs, twelve glioblastoma IDH wild type PDXs, two medulloblastoma Shh subgroup PDXs, one atypical teratoid/rhabdoid tumor (AT/RT) PDX, and three metastatic brain tumor PDXs. Furthermore these PDXs can also be cultured in vitro, except 2 medulloblastoma SHH subgroup PDXs, 1 AT/RT PDX. However, we have not yet established any PDXs from low grade glioma, ependymoma, primary central nervous system lymphoma (PCNSL), diffuse intrinsic pontine glioma (DIPG).
We began sharing these PDXs among the institutions of Kansai Molecular Diagnosis Network for CNS Tumors, Osaka, Japan. However, further improvement is necessary to succeed in establishing PDX from low grade glioma, PCSNL, DIPG, etc. and get enough number of PDXs so we can share PDXs from almost all of the brain tumors.
BOT-03 INVESTIGATION OF NOVEL SPRAY TYPE FLUORESCENT PROBE FOR GLIOBLASTOMA DETECTION
Authors: Kitagawa Yosuke , Tanaka Shota , Kuriki Yugo , Yamamoto Kyoko , Hana Taijun , Koike Tsukasa , Kushihara Yoshinori , Yamazawa Erika , Takayanagi Shunsaku , Kamiya Mako , Urano Yasuteru , Saito Nobuhito 
Published: December 2019

Abstract

PURPOSE
5-ALA is commonly used as an intraoperative tool in malignant glioma surgery, which has been proven effective for radical tumor resection and extended progression-free survival. However, there are some limitations in its use, such as false positivity, false negativity, and inability of re-administration. We aim to develop a novel fluorescent labeling system which can be repeatedly administered by spray during surgery, using hydroxymethyl rhodamine green (HMRG) as fluorescent scaffold originally designed at our university for cancer detection.

METHODS
Primary probe screening was performed using the homogenized glioblastoma (GBM) samples with the fluorescent probe library comprised of more than 320 kinds of HMRG fluorescent scaffold combined with various types of dipeptides. Second probe screening was performed using fresh GBM specimens and the selected probes in primary screening. To identify the responsible enzymes, diced electrophoresis gel (DEG) assay was performed. This method utilizes the combination of two dimensional electrophoresis (isoelectric point and molecular weight) and a multiwell-plate-based fluorometric assay to find protein spots with the specified activities.

RESULTS
The prominent probes were selected based upon the above two-step screenings. We identified two enzymes by proteome analysis and experiments using inhibitors, which was further confirmed with real-time PCR and western blotting.

DISCUSSION
This screening methodology is innovative in that it is based on selecting probes from the probe library that respond to clinical samples rather than creating probes from the responsible enzymes. Practical fluorescent probes can be established even for low-grade gliomas, which would be a breakthrough for rapid intraoperative diagnosis in glioma surgery.

CONCLUSION
HMRG-based aminopeptidase fluorescent probes may be effective for GBM detection.
ACT-02 BORON NEUTRONS CAPTURE THERAPY FOR RECURRENT HIGH-GRADE MENINGIOMAS, FROM REACTOR TO ACCELERATOR
Authors: Miyatake Shin-Ichi , Kawabata Shinji , Wanibuchi Masahiko , Suzuki Minoru , Sakurai Yoshinori , Tanaka Hiroki , Aihara Teruhito , Akita Kazuhiko , Ko Naonori , Ono Koji 
Published: December 2019

Abstract

INTRODUCTION
Recurrent high-grade meningiomas (rHGM) are difficult to control. We have applied tumor-selective particle radiation, reactor-based boron neutron capture therapy (BNCT) with excellent tumor control.

METHODS
Forty-six recurrent and treatment-refractory high grade meningiomas were treated with reactor-based BNCT by Osaka Medical College (OMC) and Kyoto University Research Reactor team collaboratively until February 2019. Tumor shrinkage, overall survival (OS), progression free survival (PFS), Lesion/Normal (L/N) ratio in boronophenylalanine positron emission tomography (BPA-PET) and causes of treatment failures are analyzed.

RESULTS
Subjects had been almost always treated heavily, high-risk patients for prognosis. They were received surgery 3 times and some radiotherapy 2 times averagely, prior to BNCT. All cases responded well and markedly shrunk by BNCT. The mean L/N ratio in BPA-PET was 4.0 which is higher than glioblastomas. Two-year PFS was 49.0% (95% CI: 28.84–66.49). Unfortunately follow-up was insufficient and 2 year OS was very similar to 2 year PFS. Treatment failures were observed as recurrence out of fields of neutron irradiation, systemic metastasis and in field local recurrence almost equally.

SUMMARY AND PROSPECTS
Median PFS and OS of rHGM are 5 months and 2 years respectively in literatures. We achieved relatively favorable results by reactor-based BNCT. On the other hand, we performed accelerator-based BNCT clinical trial for recurrent glioblastomas steadily first in the world. Based on these backgrounds, we applied investigator-lead, clinical trial of accelerator-based BNCT for rHGM as RCT design. Government (PMDA and AMED) has approved our proposal. We start this trial with the primary endpoint as PFS, from August 2019. Treatment arm is BNCT and control one is best-supportive care. If the subjects in control arm show progress disease in follow-up, they can be treated by BNCT as rescue treatments. We will introduce details of this trial in our presentation.
ACT-05 PREDICTIVE FACTORS RELATING TO OUTCOME AFTER RESECTION OF LOW-GRADE GLIOMAS WITHOUT CHEMOTHERAPY OR RADIOTHERAPY
Authors: Ikuta Soko , Maruyama Takashi , Saito Taiichi , Nitta Masayuki , Tsuzuki Syunsuke , Fukui Atsushi , Kawamata Takakazu , Muragaki Yoshihiro 
Published: December 2019

Abstract

BACKGROUND
There are several treatment options, including observation, after surgical removal of low-grade gliomas (LGG). If postoperative chemotherapy and/or radiotherapy are not provided, resection-alone approach will probably be alternative to a natural course of LGG under observation. The objective of this study was evaluation of prognostic factors associated with overall survival (OS) of patients with LGG treated with surgery alone.

METHODS
A consecutive series of 236 adult patients who underwent surgery for LGG without adjuvant therapy was analyzed retrospectively. In 193 cases (82%) histopathology of the tumor was re-classified based on evaluation of IDH1 mutational status and 1p/19q co-deletion according to criteria of WHO classification 2016. Cox proportional hazards model was used for statistical analysis.

RESULTS
Median extent of resection (EOR) was 95% (range, 1–100%) and in 210 cases (89%) EOR was &gt;=90%. During postoperative follow-up tumor progression was noted in 106 patients, and 30 patients died of disease. Overall, 10-year OS rate was 82.0%. There was statistically significant difference (P &lt;0.001) in OS among molecularly re-classified tumors, with 10-year OS rates of 90%, 79%, and 75% in cases of OD, DA IDH1-mutant, and DA IDH1-wild, respectively. In patients with EOR &gt;=90% 10-year OS rate was 75%. Multivariate analysis revealed that only EOR &gt;=90% (RR, 0.23; 95% CI, 0.09–0.66; P&lt;0.007) and presence of 1p/19q co-deletion (RR, 0.41; 95% CI, 0.16–0.97; P = 0.042) are independently associated with OS. In patients with EOR &gt;=90% such factors as type of disease manifestation, time interval between onset of symptoms and surgery, and molecular subtype of the tumor did not show significant associations with OS.

CONCLUSION
Survival outcome in patients with LGG who underwent surgical resection alone may be predicted by EOR and presence of 1p/19q co-deletion. In cases with EOR &gt;=90% molecular subtype of the neoplasm does not impact OS.
ACT-14 A FIRST-IN-HUMAN STUDY OF MUTANT IDH1 INHIBITOR DS-1001B IN PATIENTS WITH RECURRENT GLIOMAS
Authors: Arakawa Yoshiki , Mineharu Yohei , Wakabayashi Toshihiko , Natsume Atsushi , Miyakita Yasuji , Narita Yoshitaka , Yamasaki Fumiyuki , Sugiyama Kazuhiko , Hata Nobuhiro , Muragaki Yoshihiro , Nishikawa Ryo , Shinojima Naoki , Kumabe Toshihiro , Saito Ryuta , Ito Kazumi , Tachibana Masaya , Kakurai Yasuyuki , Yamaguchi Tomoyuki , Nishijima Soichiro , Tsubouchi Hiroshi 
Published: December 2019

Abstract

BACKGROUND
WHO grade II/III gliomas frequently harbor isocitrate dehydrogenase 1 (IDH1) mutations, resulting in intratumoral accumulation of oncometabolite D-2-hydroxyglutarate (D-2-HG) and subsequent clonal expansion. DS-1001b is an oral selective inhibitor of mutant IDH1 R132X that was designed to penetrate the blood-brain barrier.

METHODS
In this first-in-human, multicenter, phase I study (NCT03030066), eligible patients (pts) with recurrent/progressive IDH1 mutant glioma received DS-1001b twice daily (bid), continuous. A modified continual reassessment method was used for dose escalation. RANO and RANO-LGG criteria were used to assess tumor response. Pts who planned to undergo salvage surgery after developing progressive disease (PD) and who provided informed consent received DS-1001b treatment until surgery. Tumor samples were also obtained from those pts to measure the free form of DS-1001b and D-2-HG levels.

RESULTS
Between Jan 2017 and May 2019, DS-1001b (125–1400 mg bid) had administered for 47 pts, and 15 pts were continuing treatment. Maximum tolerated dose (MTD) was not reached. Most AEs were Gr 1–2. Gr 3 AEs were observed in 40% of pts. No Gr 4 or 5 AEs or serious drug-related AEs were reported. One dose limiting toxicity was Gr 3 white blood cell count decreased (1000 mg bid). Of 35 evaluable pts with contrast enhancing gliomas, one, five and 11 achieved complete response, partial response and stable disease (SD), respectively. Of evaluable 12 pts with contrast non-enhancing gliomas, four achieved minor response and eight achieved SD. Peak plasma concentration (Cmax) and area under the curve (AUC) increased dose-dependently.

CONCLUSIONS
DS-1001b was well tolerated up to 1400 mg bid with favorable brain distribution, and MTD was not reached. Recurrent/progressive IDH1 mutant glioma pts responded to treatment. Investigation is ongoing to determine the recommended Phase II dose. The latest data will be updated. Funding source: This study was funded by Daiichi Sankyo Co., Ltd.
ACT-26 ABT-414 (DEPATUX-M) IN NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA: WHERE DO WE STAND?
Authors: Preusser Matthias 
Published: December 2019

Abstract
Epithelial growth factor receptor (EGFR) amplifications are found in approximately half of glioblastoma cases and targeting of the EGFR axis is an attractive treatment paradigm in this tumor type. However, several anti-EGFR drugs have failed to achieve significant and meaningful improvements in clincial trials. ABT-414 (Depatux-M) is an antibody-drug conjugate (ADC) that combines a cytotoxic agent with an antibody targeting EGFR, thus aiming at specific tummor cell killing through intracellular toxin delivery. The activity of ABT-414 has been evaluated in two large clinical trials enrolling glioblastoma patients. Intellance-2 enrolled 260 patients with first recurrence of EGFR-amplified glioblasoma into a chemotherapy control arm (temozolomide or lomustine) or one of two experimental arms (ABT-414 monotherapy or ABT-414 combined with temozolomide). Depatux-M in combination with temozolomide showed a trend towards improved survival times compared to temozolomide/lomustine alone, with patients relapsing more than 4 months after the last adjuvant temozolomide cycle deriving the greatest benefit. Intellance-1 was a randomized, placebo-controlled Phase 3 study and was designed to evaluate the efficacy and safety of Depatux-M versus placebo when administered with concurrent radiation and temozolomide and with adjuvant temozolomide in subjects with newly diagnosed EGFR-amplified glioblastoma. The primary endpoint was overall survival. Recently, it was announced that a preplaned interim analysis based on data from 639 patients showed the lack of a survival benefit for patients exposed to Depatux-M. In summary, the currently available data do not support routine use of Depatux-M in glioblastoma patients and further studies are needed to understand resistance mechanisms limiting therapeutic efficacy of EGFR-targeting in glioblastoma.
MPC-01 PROGNOSTIC ROLE OF TERT PROMOTER IMPROVES THE STRATIFICATION OF IDH-MUTATED LOWER GRADE GLIOMA
Authors: Arita Hideyuki , Ohno Makoto , Nakamura Taishi , Tanaka Shota , Miyake Yohei , Saito Kuniaki , Tamura Kaoru , Okita Yoshiko , Fukai Junya , Uda Takehiro , Hata Nobuhiro , Amura Sabit , Kurozumi Kazuhiko , Eriel Sandika , Yamaguchi Shigeru , Kanamori Masayuki 
Published: December 2019

Abstract
TERT promoter mutation is associated with favorable prognosis and 1p/19q codeletion in IDH-mutated gliomas. The current diagnostic system, however, did not incorporate this change as a diagnostic marker in this entity. We investigated the value of prognostication incorporating TERT using the Japanese original cohort of 560 IDH-mutated adult gliomas. We collected the information of molecular status of IDH, TERT and 1p/19q and patient clinical data including Karnofsky performance status (KPS). TERT mutation and 1p/19q codeletion were found in 303 and 285 cases, respectively. For the purpose of this study, the patient cohort was divided into four groups by a combination of 1p/19q and TERT status, and the characteristics of 1p/19q intact-TERT mutated group (Astro-TERT group) (n=24) were dissected in light of the differences comparing with 1p/19q intact-TERT wild (Astro-group, n=251) or 1p/19q codeleted-TERT mutated (Oligo-group, n=279) cases. Astro-TERT group with any grade showed intermediate overall survival between the Oligo-group and Astro-group although the survival differences were not statistically significant (median OS: not reached (NR) versus NR, and 106 months, respectively. p&gt;0.05). In grade II-III gliomas, the survival curve of the Astro-TERT group overlapped with that of the Oligo-group while the Astro-TERT group showed short survival as well as the Astro-group. We further conducted subgroup analysis by adjusting KPS in grade II-III tumors. In the subgroup with favorable KPS (90–100) and gradeII-III (n=438), The OS of Astro-TERT group (median NR) was significantly longer survival than that of Astro-group (median NR p=0.032), and was comparable with that of the Oligo-group (median NR, p&gt;0.05). Thus, TERT promoter status provides the additional information for prognostication at least in grade II-III gliomas in the current diagnostic system.
MPC-08 CLINICOPATHOLOGICAL ANALYSIS OF 12P GAIN IN INTRACRANIAL GERM CELL TUMORS
Authors: Satomi Kaishi , Takami Hirokazu , Fukushima Shintaro , Nakazato Yoichi , Tanaka Shota , Saito Nobuhito , Kanamori Masayuki , Kumabe Toshihiro , Kobayashi Keiichi , Nagane Motoo , Iuchi Toshihiko , Yoshimoto Koji , Tamura Kaoru , Maehara Taketoshi , Sakai Keiichi , Sugiyama Kazuhiko , Yokogami Kiyotaka , Takeshima Hideo , Nonaka Masahiro , Asai Akio , Nishikawa Ryo , Matsutani Masao , Ichimura Koichi 
Published: December 2019

Abstract

BACKGROUND
Gain of short arm of chromosome 12 (12p) is commonly observed in testicular germ cell tumors (tGCTs). 12p gain is also frequently seen in intracranial GCTs (iGCTs). However, little is known about the clinical significance of 12p gain in iGCTs.

MATERIALS AND METHODS
We have collected over 200 fresh frozen tissue samples of iGCTs through the Intracranial Germ Cell Tumor Genome Analysis Consortium in Japan. Firstly, we analyzed DNA methylation status in 83 iGCTs, 3 seminomas and 6 normal control samples using Infinium Human Methylation 450K BeadChip array (Illumina, CA). Idat files were processed using R (Version 3.5.3) and minfi package (1.30.0) to generate copy number variations. Compared with average genome-wide copy number level, 12p gain was determined. Then, 58 iGCTs with clinicopathological information were analyzed for progression-free survival (PFS) and overall survival (OS). Those tumors that consist of only either germinoma and/or mature teratoma components were classified as Favorable Histology (FH) and all the others that contains malignant histological components were classified as Unfavorable Histology (UFH).

RESULT
12p gain was observed in 100% (3/3) of seminoma, 13.6% (3/22) of germinoma, 16.7% (1/6) of mature teratoma, 25% (1/4) of immature teratoma, 55% (11/20) of mixed germ cell tumor, 100% (4/4) of yolk sac tumor, 100% (1/1) of embryonal carcinoma, and 100% (1/1) of choriocarcinoma. In total, 44.6% (37/83) of iGCT showed 12p gain. Regarding histological classification, the 12p gain rate in UFH (72%, 18/25) was significantly higher than that in FH (12.1%, 4/33, P&lt;0.01). Both PFS and OS were significantly worse in iGCTs with 12p gain (PFS: P=0.027, OS: P=0.0012).

DISCUSSION
12p gain can be a molecular marker to predict prognosis and histological malignancy in iGCTs.
MPC-15 FEASIBILITY OF GLIOMA SPECIFIC ONCOPANEL IN THE DIAGNOSIS OF GLIOMA
Authors: Yoshimoto Koji , Higa Nayuta , Akahane Toshiaki , Yonezawa Hajime , Uchida Hiroyuki , Tanimoto Akihide 
Published: December 2019

Abstract

AIM
Molecular classification of glioma is a mandatory in the diagnosis of glioma according to the WHO 2016 classification of tumors of the central nervous system. However, WHO does not indicate the molecular methodology to be integrated, and the versatility and cost-effectiveness of molecular diagnosis is a concern. In this study, we evaluate the feasibility of a glioma specific tailored NGS panel where driver gene mutation and 1p/19q codeletion can be analyzed in a single platform.

MATERIALS AND METHODS
We developed a glioma specific tailored NGS panel consisting of 48 key driver genes including IDH1/2, TP53, PTEN, EGFR, PDGFR, NF1, RB1, CDKN2A, and the TERT promoter. DNA was extracted from FFPE tumor tissues histologically identified by a pathologist, and from patient derived blood to serve as a control. In this system, gene mutations and copy number alterations can be precisely characterized, thus 1p/19q co-deletion can also be evaluated. We have analyzed 106 glioma patients (Grade II: 19 cases, Grade III: 23 cases, Grade IV: 64 cases) using this system.

RESULTS
From these 106 cases, IDH1 and TERT promoter mutations were detected in 33 cases (28%) and 55 cases (52%), respectively. 1p/19q co-deletion was detected in 19 cases (18%), with IDH1 mutations in all cases. In 57 Grade IV cases, TP53, PTEN, RB1, NF1, PDGFRA mutations were detected in 25 cases (43%), 24 cases (41%), 10 cases (17%), 8 cases (14%) and 6 cases (10%). Although EGFR mutation frequency was low (3%), amplification was detected in 14 cases (24%). As for deletion, PTEN and CDKN2A loci were deleted in 36 cases (62%) and 30 cases (52%), respectively. To note, MET alterations were detected in 2 cases. The cases in which histopathological diagnosis is difficult to make have a tendency to show atypical genetic alterations.

CONCLUSION
Diagnosis of glioma patients with this glioma-specific tailored NGS panel is feasible.
MPC-18 CATEGORIZATION OF LOWER GRADE GLIOMA USING ONCOPANEL
Authors: Uchida Hiroyuki , Akahane Toshiaki , Higa Nayuta , Kirishima Mari , Hiraki Tsubasa , Yonezawa Hajime , Tanimoto Akihide , Yoshimoto Koji 
Published: December 2019

Abstract

PURPOSE
We are developing a 48-gene OncoPanel (Kagoshima Brain Tumor 48 OncoPanel) specializing in glioma diagnosis. Clinical application of genetic diagnosis derived from genetic alterations detected by OncoPanel, including IDH mutation, 1p/19q-codeletion, and other gene mutations in lower-grade glioma was verified.

METHODS
The 48 genes consist of 24 genes related to glioma and 24 genes on chromosomes 1 and 19. DNA was extracted from tumor FFPE samples and blood samples, and then single nucleotide variants and copy number variants were detected using next-generation sequencer.

RESULTS
Among the 99 diffuse glioma cases that had undergone OncoPanel analysis by July 2019, 40 cases diagnosed histologically as WHO grade 2 or 3 diffuse glioma were included. The integrated diagnosis by conventional gene analysis were Diffuse astrocytoma 10 cases, anaplastic astrocytoma 11 cases, oligodendroglioma 10 cases, anaplastic oligodendroglioma 9 cases. IDH1 mutation was detected in 30 cases, of which in 19 cases 1p/19q-codeletion was detected, all with TERT mutation. Among 11 cases with 1p/19q-non-codeletion, ATRX mutation was detected in 10 cases and was almost mutually exclusive with TERT mutation. In 10 cases without IDH mutation, EGFR amplification or mutation was detected in 6 cases, of which 4 cases were accompanied by TERT mutation.

DISCUSSION
KBT48 can detect TERT and ATRX mutations in a mutually exclusive manner and can improve the classification accuracy of oligodendroglioma and astrocytoma. Groups with gene profiles similar to glioblastoma with EGFR amplification/mutation and TERT mutation can also be classified.

CONCLUSIONS
In the diagnostic classification of lower-grade glioma, KBT48 can well classify into oligodendroglioma group, astrocytoma group and glioblastoma-like group, and is considered to be applicable in clinical practice.
NI-01 CONTRAST-ENHANCED MRI AND POSITRON EMISSION TOMOGRAPHY FOR DISTINGUISHING THE GRADE OF GLIOMA
Authors: Takei Hiroaki , Ohwashi Etsuko , Ikegame Yuka , Asano Yoshitaka , Shinoda Jun , Miwa Kazuhiro , Ito Takeshi , Yokoyama Kazutoshi , Nakayama Noriyuki , Yano Hirohito , Ikuta Sohko , Maruyama Takashi , Muragaki Yoshihiro , Iwama Toru 
Published: December 2019

Abstract

OBJECTIVE
Grading of glioma according to the WHO classification plays an important role in the treatment of patients with glioma. It is widely recognized that malignant gliomas exhibit contrast enhancement on MRI, whereas low-grade gliomas do not exhibit contrast enhancement. However, we sometimes encounter malignant gliomas without contrast enhancement on MRI. In this study, we evaluated the diagnostic accuracy of contrast-enhanced MRI and PET for distinguishing the WHO grade of glioma.

METHODS
A total of 105 patients with newly diagnosed cerebral glioma were included in the study. All patients underwent 11C-Methionine (MET), 11C-Choline (CHO), 18F-Fluorodeoxyglucose (FDG) PET and MRI. The specificity and sensitivity of MRI contrast enhancement and mean T/N ratios of these three tracers for each WHO grade were analyzed.

RESULTS
Contrast enhancement was observed in 35 patients (33%) of the total. Contrast enhancement was observed in 1/30 (3%) in grade 2, 8/43 (19%) in grade 3, and 26/30 (87%) in grade 4. The sensitivity and specificity of MRI for differentiating grade 2 from grade 3 was 11.1% and 54.7%, respectively. In contrast, the cutoff value, sensitivity, and specificity of each tracer for differentiating grade 2 from grade 3 were: 1.70, 66.7%, and 58.1% for MET; 2.15, 76.7%, and 51.2% for CHO; and 0.64, 80.0%, and 32.6% for FDG, respectively. DISCUSSION: A correlation between contrast enhancement of MRI and WHO grade was observed to some extent; however, only 19% grade 3 gliomas showed contrast enhancement. The sensitivity and specificity of PET for differentiating between grade 2 and 3 was relatively higher than that of MRI; however, it was not suitable for clinical use.

CONCLUSION
Contrast-enhanced MRI may not be reliable for determining the WHO grade for glioma, in particular differentiating between grade 2 and 3. Comprehensive evaluation with MRI and PET can provide more accurate diagnosis.