bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

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 (>=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

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

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

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<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 <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

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 < 1.6 immediately discontinued TMZ, and patients with T/N > 1.6 were either to continued or discontinued TMZ. Progression-free survival (PFS) was compared between patients with T/N > 1.6 and T/N < 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 > 1.6 underwent tumor recurrence. PFS was significantly longer in patients with T/N < 1.6 than T/N > 1.6 in DA and AA (p < 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.
NQPC-08 Short-time intensive rehabilitation for patients with newly diagnosed glioblastoma
Authors: Matsutani Masao , Ideguchi Makoto , Maeda Takeshi , Okamura Daijiro , Muraya Shoichi , Katoh Momoka
Published: November 2020

PURPOSE: Many reports presented that patients with GBM had stable HRQoL during their remission time. However, there are few reports on the situation of ADL that is the basis of QOL. This prospective study was designed to evaluate the effectiveness of intensive rehabilitation for physically disabled patients with GBM after the initial treatment. PATIENTS and METHOD: Sixteen patients with newly-diagnosed glioblastoma presenting with severe physical disabilities were registered after the completion of postsurgical radiation therapy combined with TMZ. All patients were evaluated by means of a core set of clinical scales of Functional Independence Measure (FIM), Sitting Balance score, Standing Balance score, and Mini-mental State Examination (MMSE). Patients were evaluated before the beginning and at the end of rehabilitation treatment. The daily rehabilitation program consisted of individual 180-min. sessions of treatment, seven days a week, for four to six consecutive weeks. Speech therapy was included when aphasia was diagnosed. RESULTS: Fifteen of 16 patients presented with improved physical functioning score, and seven of 16 patients returned to their independent life at home, CONCLUSION: A short-time intensive rehabilitation (4 to 6seeks) is effective for GBM patients during TMZ withdrawal period after the postoperative radiation therapy. This effective program requires close teamwork with the medical cooperation teams in the medical and rehabilitation hospitals: explanation to patients of the significance of the short-term rehabilitation, which is different from stroke rehabilitation, adjustment of hospitalization date considering radiotherapy and chemotherapy schedule, and adjustment of MRI imaging or bevacizumab administration schedule during rehabilitation.
ML-02 Chemotherapy for patients with relapsed or refractory primary CNS lymphoma
Authors: Nagane Motoo , Sasaki Nobuyoshi , Kobayashi Keiichi , Saito Kuniaki , Shimada Daisuke , Matsumoto Yoshie , Iijima Shohei , Yamagishi Yuki , Shimizu Saki , Sasaki Yuta , Shiokawa Yoshiaki
Published: November 2020

BACKGROUNDS: Standard of care for patients with primary CNS lymphoma (PCNSL) has been high-dose methotrexate (HD-MTX)-based multiagent immunochemotherapy, particularly with R-MPV-A with or without whole-brain radiotherapy (WBRT), however, the optimal treatment for relapsed/refractory (r/r)PCNSL has not been established yet. Approval of a second-generation BTK inhibitor, tirabrutinib, for r/rPCNSL in Japan in March 2020, prompted us to evaluate retrospectively efficacy of R-MPV-A for r/rPCNSL to compare their activities. PATIENTS: Histologically proven PCNSL patients treated at relapse in our institution from April 2000 to November 2019 were analyzed. Outcomes were compared between those treated with RMPVA or other regimens. RESULTS: Among 148 PCNSL patients identified, 73 had at least one relapse, of whom 47 received salvage chemotherapy including 23 treated with RMPVA, 14 with HD-MTX monotherapy, and 11 with DeVIC (DEX, etoposide, ifosfamide, CDBCA). Median age/KPS were 69 yo (20–87)/ 80 (40–100), 27 patients had received prior WBRT. RMPVA was given at the first relapse in 11 patients, median number of RMPV cycles was 8 (1–4 cycles: 10; 8 cycles 13). CR/CRu were achieved in 19 (83%), response rate was 87%, while there were two PDs (9%). After median follow-up of 21.9 months, the median PFS after salvage RMPVA was 13.0 m (95%CI: 9.1–16.9), 1-year overall survival (OS) was 82%, median OS was 70.0 m (95%CI: 12.9–127.1), which were longer than those in 24 patients with salvage treatment other than RMPVA (mPFS 4.4 m, P=0.054; mOS 13.6 m, P=0.009). Median PFS and OS for HD-MTX monotherapy were 5.1m and 36.6 m, while those for DeVIC were 4.4 m and 9.1 m, respectively. Treatment was generally well-tolerated but there was one treatment-related death. CONCLUSIONS: Salvage RMPVA at relapses was active and associated with longer survival compared with other regimens, necessitating further development of salvage regimens incorporating tirabrutinib in the future studies.
ML-09 The REAL-WORLD of Elderly PCNSL Therapy in Tohoku and Niigata Area According to Retrospective Analysis: A Collaborative Investigation of the Tohoku Brain Tumor Study Group
Authors: Asano Kenichiro , Yamashita Yoji , Ono Takahiro , Natsumeda Manabu , Beppu Takaaki , Matsuda Kenichiro , Ichikawa Masahiro , Kanamori Masayuki , Matsuzaka Masashi , Kurose Akira , Saito Kiyoshi , Sonoda Yukihiko , Ogasawara Kuniaki , Fujii Yukihiko , Shimizu Kuniaki , Ohkuma Hiroki , Kitanaka Chifumi , Kayama Takamasa , Tominaga Teiji
Published: November 2020

Introduction: Recently, the number of cases of primary central nervous system lymphoma in elderly patients(EL-PCNSL) has been increasing. However, the treatment may be insufficient because of poor performance status and pre- and posttreatment complications. Therefore, we analyzed the risk factors for EL-PCNSL in the Tohoku and Niigata areas of Japan and clarified the REAL-WORLD of EL-PCNSL therapy. Materials & Methods: We investigated surgical and nonsurgical cases of patients aged 71 years or older from eight facilities during the last 8 years. We analyzed patient information, radiotherapy/chemotherapy or not, PFS, OS, RRs, second-line therapy, pre- and posttreatment complications, outcomes, and risk factors for poor prognosis. The log-rank test was used for univariate analysis, and Cox regression analysis was used for a multivariate analysis of risk factors. Results: Of the 142 cases registered, five differed from PCNSL pathologically, three receiving BSC were excluded, 31 were treated without biopsy, three were treated based on CSF-findings, and 100 were treated with biopsy. Total 134 cases were followed. The median age was 76 years, pretreatment KPS was 50%, and 118 cases(88%) had 217 pretreatment complications. The treatment contents consisted of various combinations depending on the attending physician. The retrospective overall PFS was 16 months and OS was 24 months. In the early treatment phase, out of 16 cases with dropout, four tumor and four complication deaths occurred. There were 77 deaths(58%), 39 internal tumor deaths(51%), and 33 complication deaths(43%). Poor prognostic risk factors were <60% posttreatment KPS, complications involving pretreatment cardiovascular and central nervous system disease, posttreatment pneumonia or severe infection, and absence of radiation or chemotherapy. Conclusions: Pretreatment KPS did not affect poor outcomes, but posttreatment KPS <60% and pre- and posttreatment complications did. Radiotherapy and chemotherapy are reportedly effective, but additional research to clarify the details of these modalities is needed.
ML-13 The primary treatment outcomes and future problems of PCNSL elderly patients in our institute
Authors: Kambe Atsushi , Amisaki Hidefumi , Kuwamoto Yuhei , Shimizu Tsuyoshi , Nakajima Sadao , Torihashi Koichi , Uno Tetsuji , Sakamoto Makoto , Kurosaki Masamichi
Published: November 2020

Background and purpose: Since the introduction of HD-MTX, cognitive symptoms after irradiation have become a problem mainly in elderly patients. In this study, we evaluated the treatment outcomes of over 70 years old PCNSL patients after HD-MTX introduction. Subjects and methods: From April 2009 to December 2019, there were 46 cases of PCNSL patients who had been treated in our institute. The HD-MTX treatment group had 42 cases and the R-MPV-A treatment group had 4 cases. In the HD-MTX treatment group, 30–40 Gy of whole brain irradiation was performed (n=32), but cases of SRS or no irradiation (n=10) were included due to poor PS. The R-MPV-A treatment group was performed with whole brain 23.4 Gy + local 21.6 Gy or no irradiation. The remission rate and outcome (mOS) were examined. Results: The background of all 46 patients was 28 males and 18 females, with an average age of 75.8 years (70–87 years). The pathological diagnosis was DLBCL in all cases. The remission rate after chemotherapy in the HD-MTX treatment group was 52.4% (22/42). The post-irradiation remission rate was 78.6% in cases of whole-brain irradiation (n=14) among non-remission cases (n=20). The mOS of the whole-brain irradiation cases was 58.5 months (n=18) in the remission cases (n=22), but was 38.7 months (n=14) in the non-remission cases (n=20). The mOS of patients with SRS or no irradiation (n=10) was 12.4 months. The R-MPV-A treatment group (n=4) had a remission rate of 100% after chemotherapy. Of the 26 cases whose cause of death could be identified in the HD-MTX treatment group, 58% (15/26) had tumor-related death and 30% (8/26) had pneumonia or suffocation. Conclusion: R-MPV-A has a high remission rate even in elderly patients, and if the irradiation dose can be reduced or avoided with R-MPV-A, ADL maintenance will be expected in elderly patients.
ML-20 Outcome of high-dose methotrexate-based chemotherapy with or without Rituximab for primary central nervous system lymphoma
Authors: Takezaki Tatsuya , Ota Kazutaka , Kuroda Junichiro , Shinojima Naoki , Takeshima Yuki , Matsuura Jin , Yamamoto Takahiro , Makino Keishi , Mukasa Akitake
Published: November 2020

High-dose methotrexate based chemotherapy(HD-MTX) improved outcome of primary central nervous system lymphoma(PCNSL), but the prognosis is still poor. Recent studies showing that Rituximab is very effective for systemic lymphoma, the role of Rituximab for PCNSL is unclear. 34 patients diagnosed PCNSL received HD-MTX chemotherapy adding rituximab. Response rates were 74%(20/27) for newly diagnosed PCNSL patients, 85.7%(6/7) for recurrent PCNSL patients. Major side effects were infusion reaction and respiratory infections disease. We have to compare the outcome of HD-MTX chemotherapy retrospectively.
ML-21 Tirabrutinib monotherapy for relapsed/refractory primary central nervous system lymphoma
Authors: Kobayashi Keiichi , Sasaki Nobuyoshi , Saito Kuniaki , Yamagishi Yuki , Matsumoto Yoshie , Sasaki Yuta , Shimizu Saki , Shiokawa Yoshiaki , Nagane Motoo
Published: November 2020

Backgrounds & purpose: Prognosis of patients with primary central nervous system lymphoma (PCNSL) remains poor despite multiagent immunochemotherapy, and standard of care for relapsed or refractory (r/r) PCNSL has not been established. Recent progresses on molecular genetics and biology of PCNSL have led to development of novel molecular targeted therapies, especially targeting Bruton’s tyrosine kinase (BTK), located in the B-cell receptor and Toll-like receptor signaling pathways. Tirabrutinb, a second generation BTK inhibitor, was approved for r/rPCNSL in March 2020 in Japan. Methods: Patients with r/rPCNSL treated with tirabrutinib since December 2017 were eligible for this retrospective study. Tirabrutinib was given orally at doses 320–480 mg/day daily until progression or unacceptable toxicity. Results: A total of 7 patients were enrolled (6 relapses, 1 refractory), 4 males, median age was 73 (range, 54–80 years), and median KPS was 70 (70–90). Three patients had received prior whole brain radiotherapy. Median number of prior therapies was 1 (1–2). Best overall response rate was 57.1%; 42.9% with a complete response (CR/CRu), 14.3% with a partial response (PR), while there were 3 PDs (42.9%). Four patients experienced PD and estimated median progression-free survival (mPFS) was 29.6 months. All patients were alive at the data cutoff with median follow up of 21.4 months (2–30.4). Common adverse events (AEs) include grade 4 neutropenia (n=1), grade 3 lymphopenia (n=3), and hepatic dysfunction (n=1). Toxic rash was observed in four patients (grade 3 in one, grade 2 in three) leading to discontinuation of tirabrutinib in two patients, while others continued on TIR with dose reduction and steroid use. The median time to rash presentation was 28 days (12–28). Conclusions: Tirabrutinib was well tolerated with frequent minor to moderate skin rash emerging within one month and active for r/rPCNSL. Long-term efficacy and safety profile need to be determined with a larger cohort.
ML-23 The outcome of malignant lymphoma of the central nervous system in a single institution
Authors: Kuwahara Kiyonori , Ohba Shigeo , Matsumura Kazuyasu , Higashiguchi Saeko , Kojima Daijiro , Muto Jun , Nakae Shunsuke , Nishiyama Yuya , Yamada Seiji , Adachi Kazuhide , Abe Masato , Hasegawa Mitsuhiro , Hirose Yuichi
Published: November 2020

Background: Although high dose-methotrexate therapy has been performed for primary central nervous system malignant lymphoma (PCNSL), R-MPV (rituximab, methotrexate (MTX), procarbazine and vincristine) therapy is currently the first line therapy for (PCNSL) in our hospital. This study examines the results of R-MPV therapy comparing with past treatment. Method/Subjects: Thirty-seven patients treated at our hospital from 2009 to 2020 were included. Overall survival time, progression free survival time, and toxicities were evaluated. Results: The average age of patients was 65.7 years. Patients included 21 males and 16 females. Thirty-six patients were diagnosed DLBCL by resected brain tumor tissues, and one was diagnosed DLBCL by vitreous biopsy. As initial treatment, rituximab±HD-MTX therapy (R±MTX group) was performed in 20 cases, HD-MTX therapy plus radiation (R±MTX+RT group) was performed in 12 cases, and RMPV therapy was performed in 5 cases (R-MPV group). Median OS of all cases was 69 months and median PFS was 38 months. Median OS was 69 months in R±MTX group and could not be calculated in R±MTX+RT, and R-MPV groups. Median PFS was 16 months and 56 months in R±MTX group and R±MTX+RT, respectively, and could not be calculated in the R-MPV group. Although the R-MPV group had a short follow-up period, the results were considered to be comparable to those of the R±MTX+RT group. On the other hand, grade 3/4 adverse events occurred in 50%, 25%, and 100%, respectively. Conclusion: R-MPV therapy may delay the timing of radiation and reduce the amount of radiation. On the other hand, the frequency of adverse events is high, and more strict management of treatment is required.
BT-09 Anhidrosis in neurohypophyseal germinoma treated with CBDCA and VP-16
Authors: Adachi Koji , Ansai Shinichi , Yamaguchi Fumio , Igarashi Yumi , Morita Akio
Published: November 2020

Introduction: Acquired generalized anhidrosis (AGA) is the disease with non-congenital, non-segmented diffuse sweating dysfunction and is associated with neurological signs and dysautonomia except for anhidrosis. Here we have experienced 2 cases of AGA in the patient with neurohypophyseal germinoma after carboplatin (CBDCA) plus etoposide (VP-16) (CARE) therapy. Relationship of AGA to neurohypophyseal germinomas and their treatment is discussed. Cases: We experienced two young (26 y/o and 27 y/o) female neurohypophyseal germinoma cases of anhidrosis. They received CARE as chemotherapy and whole ventricular irradiation. They showed heat retention 2 to 3 years after initial treatment without recurred germinoma. Because acetylcholine sweating test was negative and skin biopsy revealed normal sweat gland structure, the diagnosis of acquired idiopathic generalized anhidrosis (AIGA), idiopathic pure sudomotor failure subtype, was initially made. After steroid pulse therapy, sweat function recovered partially and completely. Discussion: AIGA and germinoma are both rare diseases. So, the present 2 cases have similar clinical settings, that anhidrosis may not be idiopathic but secondary. Affected responsible site of anhidrosis in the present cases is thought to be acetylcholine receptor in the sweat cells. The present cases did not have any known disease with anhidrosis and did not receive any medication which cause anhidrosis written in the statement of the virtues of a medicine. Commonly used drugs in both cases are infusion solutions, CARE and related drugs, hormone stimulating test agents. Recently anhidrosis is reported in a case of cancer of unknown primary tumor site after using CBDCA and PTX. Both of the present cases are used CBDCA, which may cause anhidrosis. Conclusion: CBDCA may attributed to the occurrence of AGA based on hypothalamic vulnerability.
COT-01 Experience of introducing alternating electric field therapy for an elderly glioblastoma patient living alone
Authors: Hayashi Nobuhide , Koyama Yoshiki , Tsuji Eisaku , Okada Hideo , Kuwata Toshikazu
Published: November 2020

Introduction: In December 2017, alternating electric field therapy (EFT) for glioblastoma was covered by insurance in Japan, but because of treatment complexity, the number of cases of introduction remains small, and the threshold for introduction is even higher for elderly patients living alone. Case presentation: The patient was an 84-year-old man, who are living alone, and an open biopsy was performed for a contrast-enhanced neoplastic lesion in the left frontal lobe. The clinical diagnosis was glioblastoma and Ki-67 was 60%. Following initial treatment, the tumor recurred within 1 month prior to the initiation of alternating EFT. Nonetheless, steroid was administered, he could not walk without aid and was forced get admitted on the day after the introduction, and rehabilitation treatment was instituted. Motor aphasia was slowly disappeared, and he could walk stably without help after 2 weeks and was discharged on day 28. Magnetic resonance imaging prior to discharge indicated that the tumor had shrunk and cerebral edema had ameliorated. Following discharge, the treatment could be continued with the help of a home-visiting nurse, and no adverse events were noted. Discussion: In the current case, treatment with temozolomide (TMZ) could not be conducted because of neutropenia, but alternating EFT may have been effective because of the high mitotic activity of the tumor. In Japan, from December 2017 to April 2020, alternating EFT was initiated in 440 patients, 5 (1.1%) of whom were patients living alone, including the current case. The other four were all men in their 50s and not elderly. Conclusion: In the case of elderly patients living alone, medical practitioners may be able to control the tumor by preparing the environment for alternating EFT for patients and keeping the patient willing to undergo treatment.
COT-02 The opening of tumor treating fields with online support system
Authors: Sadahiro Hirokazu , Sugimoto Kazutaka , Nomura Sadahiro
Published: November 2020

Background: EF-14 trial showed the efficacy of tumor treating fields (TTF), and TTF was approved as a standard therapy for glioblastoma. In TTF opening, Device Support Specialist (DSS) should explain how to use it for the patient and family. However no DSS does always stay in our Yamaguchi prefecture, and DSS has to come to our hospital across other prefectures. On the other hand, COVID-19 infection is still spreading and it is sometimes tough to move from a big city to countryside. Here, we would present the first experience of TTF opening with online DSS support. A case report: A 68 years old man had right hemiparesis. MRI showed multiple lesions in the left hemisphere, and biopsy showed glioblastoma. After 1 month from chemo and radiotherapy, TTF was introduced. DSS from Tokyo explained how to use TTF via PC camera with TV monitor. A skilled neurosurgeon and special nurse also helped them in front of him. His head and the attached array were well checked from DSS with PC camera moving around him. Everything was smooth and he started TTF. Conclusion: Online medicine should be absolutely spreading. In countryside, it is hard that DSS comes to our hospital from a big city. TTF opening could be favorable via online system with skilled medical stuffs.
COT-08 Analysis of prognosis of biopsy/partial resection cases of malignant glioma
Authors: Yamamoto Yohei , Teshigawara Akihiko , Takei Jun , Tanaka Toshihide , Akasaki Yasuharu , Murayama Yuichi
Published: November 2020

Introduction: Malignant glioma is the most common and aggressive primary brain tumor and requires multimodality treatment. Regarding surgical treatment, it is desirable to achieve maximum resection while considering function preservation. There is consensus that the survival prognosis is prolonged in gross or subtotal resection. However, there are cases in which biopsy or partial resection is performed due to the spread of lesions at the time of onset, underlying diseases, and social background. The purpose of this study was to retrospectively analyze the cases of malignant glioma at our university and to find out the factors related to the prognosis of cases in which removal was insufficient.

Target: 55 cases of malignant glioma treated at our university since 2013 who underwent biopsy or partial resection.

Method: Overall/progression-free survival period is the end point, and parameters are age, bevacizumab use, pathological diagnosis, photodynamic diagnosis use at operation, immunotherapy, ventricular invasion, contralateral invasion, sex, preoperative Performance Status (PS), postoperative PS, left or right, navigation use, steroid use, anticonvulsant drug type, radiation, IDH mutation, 1p19q co-deletion, MGMT methylation, TERT mutation, p53 mutation, biopsy or partial resection. After narrowing down the evaluation items by univariate analysis(Logrank test), multivariate analysis(Cox proportional hazard model)was performed.

Result: The univariate analysis was significant in 5 items including bevacizumab use, radiation therapy, levetiracetam use, postoperative PS70 or higher, and partial resection instead of biopsy. Multivariate analysis detected two statistically significant differences, bevacizumab use and post-operative PS70 and above. There was no difference in the timing of bevacizumab use.

Consideration: In poorly resection cases, the weight of postoperative treatment is high, so continuity of treatment and selection of postoperative treatment are important, and maintenance of ADL and use of bevacizumab are significant among them.
COT-11 Administration of Bevacizumab for patients who failed to complete Stupp regimen after glioblastoma surgery
Authors: Kon Takashi , Imaizumi Yoichi , Kobayashi Yusuke , Sato Yosuke , Shimizu Katsuyoshi , Mizutani Tohru
Published: November 2020

Stupp regimen is widely used as the standard treatment after glioblastoma surgery, but in some cases treatment must be discontinued for various reasons. We experienced Bevacizumab in two patients who were unable to continue treatment in the Stupp regimen, and report our experience with literature review. First patient is a man in his 60s. Resection of glioblastoma of the left cerebral hemisphere was performed, and postoperatively right hemiparesis and aphasia remained. Irradiation and administration of Temozolomide were performed, but Temozolomide was unable to continue because of side effects. After systemic management, Bevacizumab was administered, and reduction of residual tumor and peripheral edema were observed, and the patient began to speak. After 12 cycles of administration, the tumor regrew, and he died. Second patient is a woman in her 80s. Craniotomy was performed for hemorrhagic infarction of the left cerebral hemisphere, postoperatively, aphasia, right hemiparesis remained, bedridden, and was unable to eat. Four months after initial surgery, a tumor was found in left parietal lobe and was resected. The pathological diagnosis was glioblastoma. For the treatment of recurrence, the patient was unable to be transferred for radiochemotherapy, so the patient was treated with Temozolomide and Bevacizumab. The patient’s condition became better, eat by herself, and could play in rehabilitation facility on the wheelchair. After 12 cycles of bevacizumab, the tumor subsequently enlarged, and died. Although the effect is limited, there are some cases in which Bevacizumab administration could maintain patient’s condition by controlling tumor growth for a certain period of time. From the experience of these patients, it seems that even in patients with postoperative poor Karnofsky Performance Status (KPS)and elderly people, Bevacizumab administration would be an option before transitioning to end-of-life care.