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BackgroundThe safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton’s tyrosine kinase inhibitor, were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL).MethodsPatients with relapsed/refractory PCNSL, Karnofsky performance status ≥70, and normal end-organ function received tirabrutinib 320 and 480 mg once daily (q.d.) in phase I to evaluate dose-limiting toxicity (DLT) within 28 days using a 3 + 3 dose escalation design and with 480 mg q.d. under fasted conditions in phase II.ResultsForty-four patients were enrolled; 20, 7, and 17 received tirabrutinib at 320, 480, and 480 mg under fasted conditions, respectively. No DLTs were observed, and the maximum tolerated dose was not reached at 480 mg. Common grade ≥3 adverse events (AEs) were neutropenia (9.1%), lymphopenia, leukopenia, and erythema multiforme (6.8% each). One patient with 480 mg q.d. had grade 5 AEs (pneumocystis jirovecii pneumonia and interstitial lung disease). Independent review committee assessed overall response rate (ORR) at 64%: 60% with 5 complete responses (CR)/unconfirmed complete responses (CRu) at 320 mg, 100% with 4 CR/CRu at 480 mg, and 53% with 6 CR/CRu at 480 mg under fasted conditions. Median progression-free survival was 2.9 months: 2.1, 11.1, and 5.8 months at 320, 480, and 480 mg under fasted conditions, respectively. Median overall survival was not reached. ORR was similar among patients harboring CARD11, MYD88, and CD79B mutations, and corresponding wild types.ConclusionThese data indicate favorable efficacy of tirabrutinib in patients with relapsed/refractory PCNSL.Trial registrationJapicCTI-173646.

BACKGROUND In BIOMARK trial, patients with newly diagnosed glioblastoma were treated with standard chemoradiotherapy combined with first-line bevacizumab; a subset of patients continued bevacizumab beyond progression (BBP). Neurocognitive function (NCF), symptom burden, and health-related quality of life (HRQoL) were examined as secondary endpoints. PATIENTS AND METHODS In the primary protocol, newly diagnosed glioblastoma patients aged 20-75 received standard 6-week radiotherapy combined with temozolomide and bevacizumab followed by 4-week cycles of temozolomide plus bevacizumab, and then 2-3-week cycles of bevacizumab monotherapy. Upon recurrence, patients were subjected to the secondary protocol with 2-3-week cycles of bevacizumab monotherapy with or without other chemotherapeutic agents. NCF tests (Hopkins verbal learning test-revised, trail making test, and controlled oral word association), EORTC QLQ-C30/BN20, and MDASI-BT were completed by the patients. Time to deterioration (TTD) was defined as the time from randomization until a pre-specified change from baseline without further improvement or death. The Kaplan-Meier method and the log-rank test were used to assess TTD for each subscale of the above tests. RESULTS Overall, 94 patients were enrolled in the study. Analyses were based on the full analysis set cohort (N=90), excluding non-glioblastoma diagnosis by central review. The median overall survival (OS) and progression-free survival (PFS) were 25.0 and 14.9 months, respectively. Baseline HRQoL and symptom burden subscales (emotional functioning, symptom severity score, affective factor, and focal factor) were significantly associated with PFS. The median TTD was 8.7, 7.5, 8.1 months for global health status/QoL, symptom severity score, interference score, respectively. Among patients who experienced recurrence, disease progression was apparently preceded by deterioration in terms of symptom burden. CONCLUSIONS Detailed analysis of HRQoL and symptom burden may aid care of glioblastoma patients throughout the disease trajectory.

BACKGROUND Boron neutron capture therapy (BNCT) is tumor-selective particle radiation and theoretically efficacious especially for tumors with infiltrative nature, such as glioblastoma (GBM). The aim of this study is to assess safety and efficacy of accelerator-based BNCT (AB-BNCT) using cyclotron-based neutron generator, BNCT30, and 10B-boronophenylalanine (borofalan(10B)) agent, SPM-011, in patients with recurrent malignant gliomas, chiefly GBM. METHODS The multi-institutional open-label, phase II clinical trial for recurrent 27 cases of malignant gliomas (MG) (24 cases were GBM) was conducted with above AB-BNCT system, using 500mg/kg of SPM-011 (study code, JG002). The patients were enrolled from February 2016 to June 2018. The inclusion criteria are bevacizumab-naïve MG, recurrent after standard treatment composed of XRT and chemotherapy with TMZ. Neutron-irradiation time were determined not to exceed to 8.5 Gy-Eq for scalp dose. Primary endpoint was 1-year survival rate and secondary ones were median overall survival (mOS), median progression free survival (mPFS). The results were compared to previous Japanese domestic bevacizumab trial for recurrent GBM (JO22506) which had the similar inclusion criteria with JG002. RESULTS 1-year survival rate and mOS of recurrent GBM cases in JG002 was 79.2% (95% CI:57.0–90.8) and 18.7 months (95% CI:12.9–23.4) respectively, while those of JO22506 was 34.5% (90% CI:20.0–49.0) and 10.5 months (95% CI:8.2–12.4), respectively. Median PFS of JG002 and JO22506 were 0.9 and 3.3 months, respectively. Most important adverse event in JG002 was brain edema. Brain edema in 21 out of 27 cases was treated with bevacizumab after progress disease. CONCLUSIONS AB-BNCT demonstrated acceptable safety and prolonged survival for recurrent MG chiefly GBM. AB-BNCT might produce brain edema somewhat after the treatment, which might be the unavoidable adverse event of re-irradiation for recurrent MG, however that seemed to be controlled well with bevacizumab.

BACKGROUND Clinical benefit of continuing bevacizumab beyond progression is unknown in glioblastomas. A biomarker analysis of the AVAglio trial suggested that proneural subtype of IDH-wildtype glioblastoma patients may receive an OS benefit from a first-line bevacizumab. This study explored biomarkers that may predict survival of glioblastoma patients treated with concurrent irradiation, temozolomide (TMZ) and bevacizumab (BEV) followed by BEV beyond progression (BBP). METHODS In the primary protocol, newly diagnosed GBM patients aged 20–75 received concurrent TMZ (75 mg/m2, D1-42), irradiation (2 Gy x 5 QW x6) and BEV (10 mg/kg Q2W x 3) followed by ≤12 4-week cycles of TMZ (150–200 mg/m2, D1-5) plus BEV (10 mg/kg, D1 and 15) and then 2 or 3-week cycles of BEV monotherapy (15 or 10 mg/kg). Upon PD/recurrence during the primary protocol, the patients were subjected to the secondary protocol with 2-3-week cycles of BEV monotherapy with or without other chemotherapeutic agents (BBP). The primary endpoint was 2-year survival rate in patients receiving BBP. Fresh-frozen tumor specimen were subjected to genome-wide methylation, copy number, expression and mutation analysis. A subset of the control cohort of the AVAglio study was used as BEV-negative control. RESULTS A total of 94 GBM patients were enrolled at 39 centers between June 2015 and January 2017. Efficacy analyses were based on the full analysis set (FAS) cohort (N=90), excluding non-GBM diagnosis by central review. The median time to PD/recurrence was 453 days in the FAS and 348 days in patients receiving BBP (N=27). The 2-year survival rate (90% CI) was 52.4% (43.3–60.8%) and 28.8% (15.4–43.7%), respectively. The 2-year survival rate in GBM patients receiving BBP was lower than expected (50%). That of proneural and mesenchymal IDH-wt GBM in the biomarker cohort (n=83) were 52.9% (31.7–70.3%) and 56.6% (41.6–69.1%), respectively. A full biomarker analysis will be presented.

To improve clinical outcomes, a less invasive screening test for detection of diffuse glioma is needed. The purpose of this study is to establish models using serum microRNAs (miRNAs) to distinguish between diffuse glioma patients from non-cancer controls (Glioma Index) and between glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and metastatic brain tumors (Meta) (3-Tumor Index). A total of 580 patients, including 266 with brain or spinal tumors and 314 non-cancer controls, were analyzed. Non-cancer control samples were collected from the National Cancer Center Biobank and members of the general population undergoing routine health examinations. Expression of serum 2565 miRNAs was assessed in each sample, and the expression profiles were compared between diffuse glioma patients and non-cancer controls, and between GBM, PCNSL, and Meta. Diagnostic models were established using a training set, and diagnostic performance was confirmed in validation and exploratory sets and area under the receiver operating curve (AUC), sensitivity, specificity, and accuracy were used to evaluate their diagnostic performances. The Glioma Index was constructed using three miRNAs. The AUC was 99%, with sensitivity of 95% and specificity of 97% in the validation set. The Glioma Index classified 93% of PCNSL, 89% of Meta, 91% of benign brain tumors, and 0% of spinal tumors as positive in the exploratory set. The 3-Tumor Index was constructed using 48 miRNAs and had an accuracy of 0.80 in the validation set, positively detecting 94.1% of GBM, 80% of Meta, and 50% of PCNSL. In conclusion, we developed novel serum miRNA discriminant models to detect diffuse glioma from non-cancer control and to discriminate tumor histology. These models could serve as less invasive screening tools or complementary diagnostic tools, thereby decreasing neurosurgical risks.

BACKGROUND Biological features of pediatric glioma differ significantly from those of adult glioma, and limited data are available on those of AYA patients. Here, we focused on AYA patients with glioma, especially those harboring BRAF V600E mutation, and investigated their clinical and genetic features. METHOD: We retrospectively analyzed AYA patients with brain tumors harboring BRAF V600E, who were treated in two hospitals in Japan. RESULTS Clinical information was available for 14 patients. The median age at diagnosis was 25 years (range: 15–38). Five patients were diagnosed with glioblastoma (GBM), including one epithelioid type. These patients were over 25. Although one patient with GBM died of the disease 6.9 years after initial diagnosis, the remaining patients were alive. Two patients were alive without recurrence at 38 and 51 months after the treatment. The patient with epithelioid glioblastoma experienced early recurrence. The remaining nine patients (64%) were diagnosed with low-grade glioma, including ganglioglioma, pilocytic astrocytoma, diffuse astrocytoma, oligodendroglioma, pleomorphic xanthoastrocytoma, and polymorphous low-grade neuroepithelial tumor of the young. No patients died of the disease, and four patients are alive without recurrence after initial operation without adjuvant treatment. Two patients are (epithelioid glioblastoma and ganglioglioma) currently undergoing treatment with a BRAF inhibitor for recurrent tumors. DISCUSSION Although the number of this study is limited, our study suggested that the prognosis of AYA patients with BRAF-V600E positive GBM may not be as dismal as that of children or adults.

The national cancer registries began in January 2016 and the actual number of cancer patients in 2016 including primary brain tumors in Japan was released as a preliminary report in January 2019. According to the report, 667 incidence of pediatric brain tumors were reported in aged 0–14 years (boy: 382; girl: 285), of them 537 patients underwent surgery, chemotherapy, or radiation therapy (diagnosis: 516, undiagnosed: 21), and 130 patients were followed up without any treatments. The breakdown of tumor types was 279 Neuroepithelial tumors, 73 Embryonal tumors (61 Medulloblastomas), and 63 Germ Cell Tumors (GCTs). The crude rate per 100,000 population in 2016 was 4.23 for all pediatric brain tumors, 1.77 for Neuroepithelial tumor, 0.39 for Medulloblastoma, and 0.40 for GCTs. In comparison, the United States CBTRUS2019 (2012–2016) reported that the age-adjusted incidence rates per 100,000 population in the United States was 5.74 for all pediatric brain tumors, 4.15 for Neuroepithelial tumors, 0.48 for Medulloblastoma, and 0.22 for GCTs. The age-adjusted incidence in Japan based on the US population in 2000 was 4.21 for all pediatric brain tumors, Neuroepithelial tumor 1.77, Medulloblastoma 0.39, and GCTs 0.39, suggesting that the incidence of Neuroepithelial tumor and Medulloblastoma is lower whereas that of GCTs is approximately twice comparing to the US. By taking advantage of the national cancer registry data, which was publicly opened to researchers in 2019, we report the incidence of primary brain tumors and its comparison worldwide based on the re-classification criteria of primary brain tumors including benign tumor.

In March 2020, Tirabrutinib (TIR), a second-generation oral Bruton’s tyrosine kinase inhibitor, was approved for the indication of relapsed or refractory PCNSL (r/rPCNSL) based on the results of a phase I/II study in Japan. In this study, 44 Japanese patients with r/rPCNSL were treated with TIR QD at 320 mg, 480 mg, or 480 mg in the fasted condition (480 mg fasted QD). The primary endpoint was overall response rate (ORR) assessed by an independent review committee according to International PCNSL Collaborative Group criteria. We previously reported the results of this study with data cutoff in June 2019 (Narita et al. Neuro Oncol. 2020). In the report, 17 of 44 patients were treated with TIR at 480 mg fasted QD which is an approved dose, and had ORR of 52.9%, median progression-free survival of 5.8 months, and median overall survival of not reached (median follow-up: 3.8 months). In 44 patients, ORR was similar among patients harboring either of the oncogenic mutants CARD11, MYD88, CD79B, or wild type. Throughout the whole patients, most common adverse events (AEs) at any grade were rash (31.8%), neutropenia (22.7%), leukopenia (18.2%), and lymphopenia (15.9%), and grade ≥3 AEs were neutropenia (9.1%), lymphopenia, leukopenia, and erythema multiforme (6.8% each). One patient with 480 mg QD had grade 5 AEs (pneumocystis jirovecii pneumonia and interstitial lung disease). We will present one-year follow-up data of this study at the meeting. As of data cutoff (February 2020), 11 of 44 patients continued to receive TIR, including 6 patients with 480 mg fasted QD. Updated data for overall survival, duration of response, and time to onset of AEs will also be presented. TIR is a promising new treatment for r/rPCNSL.

BACKGROUND: We conducted a phase III trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality. METHODS: We randomly assigned 88 recurrent glioblastoma patients to receive PPV (n = 58) or the placebo (n = 30) at a 2-to-1 ratio. Four of 12 warehouse peptides selected based on preexisting peptide-specific immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks. RESULTS: Our trial met neither the primary (overall survival [OS]) nor secondary endpoints. Unfavorable factors for OS of 58 PPV patients compared with 30 placebo patients were SART2-93 peptide selection (n = 13 vs 8, hazard ratio [HR]: 15.9), ≥70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the median OS for PPV patients without SART2-93 selection plus one of these 3 favorable factors (

Mutations in isocitrate dehydrogenase 1 or 2 genes (IDH1/2) frequently occur in lower-grade gliomas and secondary glioblastomas. Mutant IDH1/2 proteins gain a new ability to produce the oncometabolite 2-hydroxyglutarate (2HG). Recently, IDH1/2 mutations were suggested to be related with seizure onset through the structural similarity of 2HG to the excitatory neurotransmitter glutamate. Therefore, we sought to investigate the relationship between seizure onset and IDH1/2 status, tissue 2HG concentration and distribution. We assessed 149 patients with WHO grade II-IV glioma, whose IDH1/2 status were identified and measured serum and tissue 2HG concentrations in 123 and 104 patients by using liquid chromatography-tandem mass spectrometry method. The matrix assisted laser desorption and ionization mass spectrometry imaging (MALDI-MSI) was use to analyze tissue 2HG distribution for 12 tissue samples. Seizure onset was observed in 34 among 56 (60.7%) patients with IDH mutant tumor, whereas in 18 among 93 (19.4%) patients with IDH wild-type tumor (p

Despite of recent intense investigations, no effective molecular targeting therapy has been successfully developed in patients with glioblastomas (GBMs). Approximately 60–80% of GBM harbor mutations in the promoter region of telomerase reverse transcriptase (TERT), which leads to its upregulation. It has been reported recently that TERT has an RNA-dependent RNA polymerase (RdRP) activity and TERT-RdRP activity controls cell cycle and maintains stem cell phenotype, suggesting that TERT can be directly targeted to suppress tumor cell proliferation. We have previously identified eribulin mesylate, which is an FDA-approved drug used to treat breast cancer and liposarcoma, as a specific inhibitor of RdRP activity of TERT and investigated the antitumor efficacy of eribulin using multiple human GBM cell lines in preclinical mouse brain tumor models. All GBM cell lines tested in vitro that harbored TERT promoter mutations were highly sensitive to eribulin with IC50 below 1nM. Intraperitoneal administration of eribulin (0.5 mg/kg), which was equivalent to the dose used in human (1.4 mg/m2), significantly prolonged the survival of multiple mouse brain tumor models established with U87MG or LN229 (p

PURPOSEGenetic alterations found in WHO grade 2 and 3 gliomas include IDH1/2 and TERT promoter mutations and 1p19q co-deletion, which alterations are known to have great impact on the prognosis of the patient. In this research, the authors attempted to test the hypothesis that genetic alterations could contribute to the locations and heterogeneity of the tumor by analyzing 191 WHO grade 2 and 3 gliomas via MR radionomics.METHODS191 WHO grade 2 and 3 gliomas were retrospectively collected and the genomic DNA of the tumor was sequenced for IDH1/2 and TERT promoter mutations. Treatment naive MR images were also collected. T2 weighted, T1 weighted, FLAIR and Gd-enhanced T1 weighted images were collected for analysis. Voxel-based lesion mapping (VLM), and redionomics analysis was performed for all images and were further challenged to construct a model that predicts genetic alterations within the tumor. 126 patients were allocated as training set and 65 for validation set. Patient cohort was divided into the following 3 groups; IDH mt/TERTp wt, IDH mt/TERTp mt and IDH wt. A multi-regression model was constructed using the training set to predict the 3 genetic subgroups and the validation set was used for model validation.RESULTSVLM revealed that IDH mt/TERTp wt gliomas dominated temporal lobe involvement while IDH mt/TERTp mt occupied the frontal lobe. IDH wt tumors, on the other hand, located at much posterior lobes and centered at the deep white matter. 15 radionomic features were identified for model construction to predict 3 genetic subgroups of WHO grade 2 and 3 gliomas. When these 15 texture elements were used to construct a prediction model of the 3 genetic subgroups, AUCs calculated from the training set ranged from 0.7 to 0.75. Accuracy for prediction was 63% for the training set and 60% for the validation set.

ISN-Harrlem consensus guidelines proposed incorporation of molecular information into the diagnostic criteria of brain tumors. The current recommendation for diffuse glioma is to identify IDH mutations and subclassify them into either astrocytoma or oligodendroglioma using the 1p19q or ATRX status. However, a major challenge in this scheme is to stratify IDH-wt tumors. We analyzed a series of 759 adult diffuse gliomas consisted of 171 WHO grade II, 218 grade III and 370 grade IV tumors for the IDH1/2, 1p19q and TERT promoter status. The combined IDH/TERT classification divided the series into four groups with distinct histopathological profiles and outcome. The IDH/TERT co-mutated tumors (Group A, n = 154) mainly consisted of oligodendroglial tumors (78%) and mostly harbored 1p19q co-deletion (93%). The second group was composed of IDH-mutant/TERT-wt (Group B, n = 131) and enriched with astrocytomas (69%). The double-negative (IDH wt and TERT wt) group (Group C, n = 239) showed a mixed histology, GBM being the most common (62%), however all the other histologies were also present. Tumors with IDH-wt/TERT-mut (Group D, n = 235) were mostly GBM (80%) or AA(15%). Overall survival (OS) significantly differed across the four groups (A, Not reached; B, 79 months; C, 21 months; D, 16 months). WHO grade did not associate with OS in Group A, B and D, suggesting the homogenous nature of these groups respectively. On the contrary, lower grade tumors showed significantly longer survival than grade IV tumors (33 months vs. 17 months, p < 0.001) in Group C, suggesting that IDH-wt gliomas are biologically heterogeneous group. We showed that TERT promoter mutation is a useful diagnostic marker which can stratify both IDH-mutant and IDH-wt gliomas into prognostically distinct subgroups.

BACKGROUND: Although it is recognized that methylation status of MGMT promoter is predictive for the response to temozolomide in newly diagnosed glioblastoma (GBM), at least in elderly patients, there is no study examining the ability of quantitative MGMT methylation status to predict volumetric changes of residual tumor in magnetic resonance images (MRIs) after surgery, radiation and temozolomide therapy. In this study, we performed retrospective volumetric analysis of the residual tumor in glioblastoma patients and investigated the relationship of MGMT status assessed by pyrosequencing. METHOD: Among 160 newly diagnosed GBM patients treated in our institute since 2006, volumetric analysis of the residual tumor was performed retrospectively in patients who were with residual unresected tumors after surgery, treated with standard radiation and temozolomide therapy. Patients who were without residual tumors or treated with bevacizumab were excluded. The MGMT methylation status was quantitatively assessed by averaging methylation at the 16 CpG sites measured by pyrosequencing. Enhanced tumor volume in MRI was measured at four time points of pre-operation, beginning of the treatments, three and six months after the initial treatment. RESULT: Forty four patients were enrolled (M:F = 25:19, median age: 61 y.o., median KPS: 70). The quantitative MGMT methylation data and tumor volume ratio, normalized to pre-treatment volume, were significantly correlated at 3 and 6 months after the initial treatment (p = 0.0002 and 0.0004, respectively). For the response rate, patients with lower MGMT methylation than 10% showed more progressive disease (defined as more than 50% gain in tumor volume) compared to patients with higher MGMT methylation than 10% at 3 and 6 months after initial treatment (3 months: 67.9% vs 18.8%, 6 months: 70.8% vs 15.4%, respectively). CONCLUSION: Quantitative MGMT methylation status analyzed by pyrosequencing may be useful to predict disease progression in glioblastomas treated with partial tumor removal followed by radiation and temozolomide therapy.

BACKGROUND: The Brain Tumor Registry of Japan (BTRJ) was founded to investigate the statistical characteristics of brain tumors in Japan from 1975. The 13th edition of the BTRJ is published in 2014 (Neurologia medico-chirurgica Vol. 54 (2014) Supplement). METHODS: Data on primary or metastatic brain tumor cases that were newly diagnosed from 2001 to 2004 were collected from 2009 until the end of 2012. Approximately 330 neurosurgeons, medical doctors, and staff from 109 institutions collected 16,338 data from clinical records. These institutions included most universities, colleges, and hospitals with Japan Neurosurgical Society-authorized boards. These data were collected via the Internet Data and Information Center for Medical Research. Data, including the birthplace, age, tumor sites, diagnostic method, therapy (surgery, radiation, or chemotherapy), and the outcome of these treatments, according to the World Health Organization (WHO) 2007 brain tumor classification were collected. Survival data were analyzed using the Kaplan-Meier method. RESULTS: 5-year overall survival (OS) and 5-year progression free survival (PFS) of major brain tumors are as follows; grade II diffuse astrocytoma: 75%, 57%, grade II oligodendroglial tumor: 90%, 74.6%, grade III anaplastic astrocytoma: 41.1%, 28.7%, grade III anaplastic oligodendroglial tumor: 68.2%, 54%, glioblastoma: 10.1%, 9.2%, primary CNS lymphoma: 64.4%, 34.7%, null cell pituitary adenoma: 98.3%, 85.1%, neurinoma: 98.8%, 89.5%, grade I meningioma: 97.9%, 90.5%, grade II meningioma: 91.2%, 60.6%, grade III meningioma: 86.6%, 53.4%, chordoma: 89.1%,48.1%. CONCLUSIONS: Trends and problems in the treatment and outcomes of brain tumors of Japan in 2001-2004 will be presented and discussed.

BACKGROUND: (blind field). METHODS: Data on primary or metastatic brain tumor cases that were newly diagnosed from 2001 to 2004 were collected from 2009 until the end of 2012. Approximately 330 neurosurgeons, medical doctors, and staff from 109 institutions collected 16,338 data from clinical records. These institutions included most universities, colleges, and hospitals with Japan Neurosurgical Society-authorized boards. These data were collected via the Internet Data and Information Center for Medical Research. Data, including the birthplace, age, tumor sites, diagnostic method, therapy (surgery, radiation, or chemotherapy), and the outcome of these treatments, according to the World Health Organization (WHO) 2007 brain tumor classification were collected. Survival data were analyzed using the Kaplan-Meier method. RESULTS: Overall survival (OS, months), progression free survival (PFS, months), 5-year OS, 5-year PFS of each grade of gliomas are as follows; pilocytic astrocytoma; NR (not reached), NR, 92.1%, 73.8%, diffuse astrocytoma: NR, 84.1, 75%, 57%, grade II oligodendroglial tumor: NR, NR, 90%, 74.6%, anaplastic astrocytoma: 38, 19, 41.1%, 28.7%, grade III anaplastic oligodendroglial tumor: NR, 71, 68.2%, 54%, glioblastoma: 15, 8.1, 10.1%, 9.2%. CONCLUSIONS: The 5-year OS of grade II and III gliomas improved compared to that in 1997-2000 but that of glioblastoma did not. Based on the data of BTRJ 2001-2004, trends and problems in treatment and outcomes of gliomas will be presented and discussed. SECONDARY CATEGORY: n/a.