bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACT-07 Clinical Trials of 11C-Methionine PET for brain tumors
Authors: Yamaguchi Shigeru , Shiga Tohru , Hirata Kenji , Terasaka Shunsuke , Kobayashi Hiroyuki , Shimosegawa Eku , Kagawa Naoya , Hirayama Ryuichi , Kinoshita Manabu , Kijima Haruhiko , Fujii Masazumi , Ichikawa Masahiro , Oriuchi Noboru , Kuge Yuji , Tamaki Nagara 
Published: November 2020

Abstract
Background: Although 11C-Methionine (MET) PET has widely used, 11C-MET tracer has not been approved in Japan. We conducted multi-center prospective clinical trials using MET for drug approval in diagnosis of brain tumors[Methods] Two trials using 11C-MET PET were performed in Hokkaido University, Osaka University and Fukushima Medical University; 1) Diagnostic accuracy in differentiating tumor recurrence from radiation injury after radiotherapy in brain tumors, 2) The diagnostic efficacy in newly-diagnosed gliomas. 1) The patients with suspected brain tumor recurrence underwent MET and 18F-Fluorodeoxyglucose (FDG) PET. When the target lesion showed MET and/or FDG uptake, the patients underwent target resection for pathological confirmation. Positive prediction values of each tracer uptake were assessed as primary outcome measure, and the sensitivities and specificities of each PET exams were also assessed. 2) The patients with suspected gliomas underwent MET PET. Tissue samplings were performed from MET uptake lesions without contrast-enhancement on MRI in each patient, and evaluated the existence of tumor cells. Diagnostic additional values of MET PET on contrast-enhanced MRI was also investigated. Safety of MET PET was also assessed in each trial.[Result] 1) 57 cases were investigated. 38 cases underwent surgery and 32 cases (84%) were confirmed tumor recurrence histopathologically. MET and FDG uptake in 32 recurrence cases were 100% and 50%, respectively. Sensitivities and specificities of tumor recurrence were 84% and 89% in MET, and 100% and 56% in FDG. 2) 53 glioma cases were enrolled. Viable tumor cells were proven in 98% in MET uptake lesion without contrast-enhancement. In 42 out of 53 cases (78%), MET PET depicted tumor area beyond the contrast-enhancement area on MRI. No severe adverse events were observed in both trials. [Conclusions] MET PET were effective in diagnosis of brain tumors, and safety of MET was demonstrated.
PEDT-03 A clinical trial of dendritic cell-based immunotherapy for refractory brain tumors in children
Authors: Akasaki Yasuharu , Yamaoka Masayoshi , Takei Jun , Nonaka Yuichirou , Hirotsu Tatsuya , Akiyama Masaharu , Yanagisawa Takaaki , Ohashi Touya , Ida Hiroyuki , Murayama Yuichi 
Published: November 2020

Abstract
Background/Objectives: Relapse or refractory brain tumor in childhood continue to have a dismal prognosis in spite of developing multidisciplinary treatment. Cancer immunotherapy is newly expected as next promising treatment for highly aggressive pediatric cancer. This trial was designed to evaluate the safety and clinical responses to an immunotherapy with fusions of dendritic cells (DCs) and tumor cells in patients with malignant brain tumors. Design/Methods: Patients with histopathologically confirmed high-grade or recurrent brain tumor were eligible for our immunotherapy. Autologous cultured tumor cells obtained from surgical specimens were fused with autologous DCs using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region and repeated 3–10 times in each 28–84 days cycle. Toxicity, progression-free survival (PFS), and overall survival (OS) of this trial were evaluated. Results: Six patients were enrolled, three with high grade glioma and three with ependymoma. Median age at first course of immunotherapy was 10 years (range 8–25 years) and median time of follow-up from first course of immunotherapy was 13.5 months (range 3–33 months). All patients with immunotherapy were well tolerated and no adverse event without local erythema in injected site. Median progression free survival and overall survival were 18 months and 18.5 months, respectively. Conclusions: FC immunotherapy with autologous DCs and tumor cells for brain tumor in children and young adults were extremely well tolerated and encouraging. Further phase II study of FC immunotherapy is planned to improve prognosis and overcome treatment related neurological sequelae for highly malignant tumors.
STMO-08 Validation of the endoscopic 5-ALA fluorescence diagnosis for intraventricular tumors
Authors: Nonaka Masahiro , Takeda Junichi , Hashiba Tetsuo , Asai Akio 
Published: November 2020

Abstract
Intraoperative 5-ALA fluorescence diagnosis (PDD) has been shown to improve tumor resection rates in surgery for malignant glioma. Recently, the usefulness of PDD has been reported in tumors other than malignant glioma. However, the fluorescence of intraventricular tumors is not easy to observe under the microscope, because excitation light could not reach enough to the deepest part of the brain. Therefore, we performed endoscopic 5-ALA fluorescence diagnosis of intraventricular tumors and evaluated its usefulness. Ten cases of intraventricular tumors were included in the study. There were 3 germ cell tumors, 2 metastatic brain tumors, 2 pilocytic astrocytomas, 1 malignant lymphoma, 1 subependymoma, and 1 medulloblastoma (recurrent). The tumors were located in the third ventricle in four cases, the lateral ventricle in three cases, the lateral ventricle and the third ventricle in two cases, and the aqueduct in one case. Tumor removal was performed in 6 cases and tumor biopsy in 4 cases. Intraoperative fluorescence could be observed in eight cases: three germ cell tumors, two metastatic brain tumors, two pilocytic astrocytomas, and one malignant lymphoma. Subependymoma and medulloblastoma did not show fluorescence. Among the cases with confirmed fluorescence, the fluorescent sites were targeted for biopsies for germ cell tumors and malignant lymphomas. For metastatic brain tumors and pilocytic astrocytomas, the extent of removal was determined at the time of removal, and the presence of residual tumor was confirmed by fluorescence after removal. Endoscopic 5-ALA fluorescence diagnosis for intraventricular tumors was useful in determining the target of biopsy or the extent of excision and in assessing residual tumors.
STMO-09 Recovery from speech deficit after injury to frontal aslant tract in glioma surgery
Authors: Saito Kuniaki , Kobayashi Keiichi , Shimada Daisuke , Iijima Shohei , Sasaki Nobuyoshi , Sasaki Yuta , Shiokawa Yoshiaki , Nagane Motoo 
Published: November 2020

Abstract
BACKGROUND: The frontal aslant tract (FAT) is a white matter fiber connecting the superior frontal gyrus to the lateral inferior frontal gyrus. Damage to FAT in dominant hemisphere can lead to speech deficits which, in most cases, resolve within weeks to months. However, little is known about mechanisms of recovery and factors for predicting permanent language deficits. METHODS: Eighteen patients with glioma (age ranged 24 to 78, 10 glioblastomas and 8 lower grade gliomas) located in the medial frontal lobe in the dominant hemisphere involving the supplementary motor area (SMA) and FAT were included. FAT was visualized using diffusion tensor imaging tractography in pre- and postoperative MRI. Postoperative language deficit, resected area of FAT and surrounding brain regions including the cingulate gyrus and corpus callosum (CC) were retrospectively reviewed. RESULTS: In 17 of 18 cases, postoperative language deficits were observed. Speech deficits resolved within a month in 12 cases, while recovery was incomplete in five cases. In two patients without complete recovery, CC located beneath SMA was removed because of tumor infiltration. Other two patients had substantial injury of middle third portion of FAT. The last case had preceding infarction in the contralateral frontal white matter including FAT. In cases with complete language recovery, transcallosal fibers connecting the contralateral SMA to the ipsilateral inferior frontal gyrus were detected by postoperative DTI-tractography. These fibers were damaged anywhere along its length in patients without complete language recovery, indicating that they may play an important role in recovery after FAT injury. CONCLUSION: Injury to CC or middle third portion of FAT can cause permanent language disorder. Transcallosal fibers from contralateral SMA seems to be involved in the recovery from language deficit after injury to FAT. In glioma surgery involving dominant SMA or FAT, these fibers should be preserved to avoid permanent speech deficit.
STMO-11 Supratotal resection of Glioblastoma with Methionine PET
Authors: Ko Ozaki , Hirono Seiichiro , Matsutani Tomoo , Iwadate Yasuo 
Published: November 2020

Abstract
Objective: To assess the resection of both of contrast-enhanced (CE) and methionine-uptake (MU) and the oncological outcome in newly diagnosed glioblastoma. Methods: This retrospective study included a glioblastoma cohort from Chiba University who met the two criteria, i) total resection of CE tumor, ii) preoperative evaluation with methionine positron emission tomography (Met-PET). Data regarding the pattern of recurrence and overall survival were collected. Results: Among 247 cases with glioblastoma, total resection of CE was achieved in 112. Preoperative Met-PET was performed in 30 out of 112. The median age at operation, a period of follow-up, and the preoperative tumor volume in 30 patients were 56 year-old, 17.9 months, and 18.8 cc respectively. The promoter region of the O6-methylguanine-DNA methyltransferase was methylated in 37%. Radiological comparison revealed that Met uptake was detected beyond the CE area in 13 out of 30, and the Met uptake was also resected with awake mapping technique in 7 patients (supratotal resection group; STR). The median progression-free survival (PFS) in STR was 23 months, and all the patterns of recurrence were distant recurrence. In contrast, the PFS in total resection group (TRG) was 9 months (p=0.09, Wilcoxon). Furthermore, 14 out of 17 recurrence were local in TRG subgroup. While the median OS in TRG was 18 months, it has not reached in STR (p=0.04, Wilcoxon). Conclusions: The resection of both of CE and MU was associated with better PFS and OS. This finding must be validated in a larger cohort with a multicenter study.
MPC-04 Utility of comprehensive cancer genome analysis for brain tumors
Authors: Miwa Kazuhiro , Takei Hiroaki , Ito Takeshi , Yokoyama Kazutoshi , Yano Hirohito , Shinoda Jun , Ishihara Satoshi , Nakayama Noriyuki , Iwama Toru , Kato Yasutka 
Published: November 2020

Abstract
Objective: Our hospital has been designated as a cancer genome medical cooperation hospital, and it is our responsibility to play a central role in cancer medicine. We were one of the first local hospitals to clinically apply cancer genome analysis, and in January 2019, we started PleSsision-Rapid testing as a clinical study without patient burden. This study examines data from patients with brain tumors, subjects it to cancer genome analysis, and reports on its utility and efficacy.
Method: Genome analysis was performed by PleSsision-Rapid examination for patients with brain tumors who underwent surgery between January 2019 and July 2020. Tissue DNA extracted from pathological specimens was used to perform next-generation sequencing (NGS) analysis. In the PleSsision-Rapid test, 160 genes are comprehensively analyzed, examined by genomics, and evaluated for the presence or absence of actionable and druggable mutations, and the mutation rate is determined.
Results: There were 15 cases total. Histopathological diagnoses included glioblastoma (n=5), diffuse astrocytoma (n=1), metastatic brain tumor (n=4), meningioma (n=2), central nervous system primary malignant lymphoma (n=1), germinoma (n=1), and Langerhans cell histiocytosis (n=1). Of these 15 brain tumor cases, actionable mutations were detected in 80.0% of cases and druggable mutations were detected in 66.6%. The average mutation rate was 8.59±5.32 (range, 1.3 to 22.8) per patient.
Conclusion: Although future improvements will be needed for cancer genome analysis in brain tumors, this strategy may be useful for the selection of molecularly targeted drugs with high antitumor efficacy. We will continue to accumulate and study such cases in the future.
MPC-06 Cutting-edge of Cancer Genomic Medicine for brain tumors
Authors: Mizoguchi Masahiro , Hata Nobuhiro , Kuga Daisuke , Hatae Ryusuke , Sangatsuda Yuhei , Fujioka Yutaka , Takigawa Kosuke , Funakoshi Yusuke , Koga Yuhki 
Published: November 2020

Abstract
Kyushu University Hospital was designated a Cancer Genome Core Hospital in April 2018, and the multi-gene panel test has been introduced since August 2019. The expert panel has been held for 21 cases of the central nervous system (11 adult glioma, 5 pediatric brain tumors, 5 extramedullary tumors). Actionable gene abnormalities were newly detected in two cases. First case is epithelioid glioblastoma with BRAF V600E mutation, and second is embryonal tumor with VCL-ALK fusion. For the first case, BRAF/MEK inhibitor can be used by the prospective trial of patient-proposed healthcare services with multiple targeted agent based on the result of gene profiling by multigene panel test (NCCH1901). For the second case, we are planning to introduce ALK inhibitor by indicator-initiated clinical trial while continuing ICE therapy. The current approved agents for tumor-agnostic treatment are immune checkpoint inhibitors for mismatch repair deficient (dMMR) cases and TRK inhibitors for NTRK fusion gene-positive cases. We selected microsatellite instability (MSI) test and immunostaining of MMR gene for the indication of immune checkpoint inhibitor for recurrent glioma and Lynch syndrome that require dMMR evaluation, but FoundationOne CDx (F1CDx) allows simultaneous evaluation of MSI and MMR gene abnormalities. Regarding the indication of TRK inhibitors, F1CDx assay is selected as a companion diagnosis for ALK, NTRK1/2/3 fusion gene analysis for pediatric cases. At present, the actionable gene abnormalities are detected by multi-gene panel tests in about 10% of brain tumors. Development of tumor-agnostic treatment will expand the molecular target therapy for brain tumor in the future. Based on the experience of different schemes for molecular targeted therapy, it became clear that it is necessary to establish a cancer genome medical system for prompt introduction of precision medicine for highly malignant brain tumors.
MPC-08 Molecular risk stratification using genome-wide DNA methylation data of standard-risk medulloblastomas treated with 18-Gy craniospinal irradiation
Authors: Irikura Tomoya , Fukuoka Kohei , Mori Makiko , Oshima Koichi , Arakawa Yuki , Tanami Yutaka , Ichimura Koichi , Nakazawa Atsuko , Kurihara Jun , Koh Katsuyoshi 
Published: November 2020

Abstract
A novel risk stratification of medulloblastoma has been proposed based on retrospective data from patients undergoing standard treatment. However, it remains unclear whether the classification is applicable to patients receiving reduced-dose craniospinal irradiation (CSI). We performed molecular diagnosis and copy number analysis using methylation array on patients with standard-risk medulloblastoma treated with 18 Gy CSI at our institution. Nine tumor samples were available for analysis from seven patients who had a median age of 7.4 years at disease onset and a median observation period of 73 months. Three patients had recurrence, and another patient developed radiation-induced glioblastoma. From the three recurrent cases, one was molecularly diagnosed as SHH subtype with MYCN amplification; another case was a Group 4 tumor without favorable prognostic chromosomal aberrations, and the remaining patient experienced a very late relapse despite low-risk stratification. Of the recurrence-free cases, one was classified as WNT subtype, and another was a Group 4 tumor with chromosome 7 gain, and loss of chromosomes 8 and 11, both of which were associated with good prognosis. Methylation analysis also unveiled the fact that the recurrent tumor diagnosed as relapsing medulloblastoma by conventional diagnostic tools was in fact a radiation-induced glioblastoma. Our data suggested that the new risk stratification may be useful for cases treated with CSI reduced to 18 Gy. However, due to the presence of the late-relapsed case stratified to low risk, further investigations with a larger cohort should be required to confirm the data.
ML-04 The influence of surgical intervention for high-dose Methotrexate chemotherapy in the patients with primary central nervous system lymphoma
Authors: Okamoto Michinari , Yamaguchi Shigeru , Ishi Yukitomo , Motegi Hiroaki , Kobayashi Hiroyuki , Terasaka Shunsuke , Houkin Kiyohiro 
Published: November 2020

Abstract
Object: Surgical resection is not the standard of treatment for primary central nervous system lymphoma (PCNSL). Some recent studies suggest that resection might be beneficial. The aim of this study was to examine the effect of surgical treatment in terms of the time from surgery to chemotherapy.
Methods: We retrospectively analyzed all patients with PCNSL treated at Hokkaido University Hospital between 2001 and 2018 to assess the effect of selection for resection on the response of Methotrexate chemotherapy. We identified the days from surgery to chemotherapy, complications, the response of Methotrexate (CR/CRu rate) and prognostic factors including progression free survival (PFS) and overall survival (OS).
Results: A total 105 patients were identified. 84 patients underwent biopsy and 21 patients underwent surgical resection. Their median age were 63 [31–78] and 68 [44–77], respectively. Their Karnofsky Performance Status (KPS) were 70 [30–100] and 70 [40–100]. There were any significant difference. Patients undergoing biopsy and those undergoing resection had comparable rates of complications for all complication type. Overall, 4 biopsy patients and 5 resection patients experienced at least one complication. They were composed of 2 asymptomatic bleeding, 1 wound abscess, 1 hydrocephalus in biopsy patients, 1 epidural abscess, 1 epilepsy, 1 chronic subdural hematoma, 2 temporary hemiparesis. Although the days from surgery to chemotherapy were significantly shorter in patients underwent biopsy than in those underwent resection (P=0.0015), PFS was significantly longer in patients underwent resection than in those underwent biopsy (P=0.0403), whereas there was no difference in OS.
Discussion: Resection could delay the postoperative treatment. In this study, there was a significant delay of postoperative treatment in resection patients, however, CR/CRu rate after MTX was significantly better in those underwent resection than biopsy. We can see that resection for PCNSL might not necessarily worsen the prognosis.
ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid
Authors: Yamagishi Yuki , Sasaki Nobuyoshi , Matsushita Yuko , Shimizu Saki , Saito Kuniaki , Kobayashi Keiichi , Shiokawa Yoshiaki , Nagane Motoo , Ichimura Koichi 
Published: November 2020

Abstract
Backgrounds & Purpose: Central nervous system lymphoma (CNSL) is the second most common primary malignant brain tumor. Brain biopsy is indispensable to confirm the diagnosis of CNSL, but has a potential risk of inducing hemorrhagic complications in the brain. Therefore, liquid biopsy using the cerebrospinal fluid (CSF) has attracted an attention as a less invasive diagnostic method. In this study, we established a digital PCR-based method to detect MYD88 mutations in CSF and evaluated its efficacy. Methods: Matched CSF and biopsy samples from CNSL patients collected before the start of chemotherapy were used. Cellular DNA and cell free DNA (cfDNA) of CSF were separately extracted from the pellet and the supernatant fraction of CSF, respectively. Presence of the MYD88 L265P mutation was examined in each fraction by the digital PCR. The mutational status obtained by liquid biopsy was compared with that of the matched biopsy specimen examined by pyrosequencing. Result: A total of 36 paired samples were used. When the cutoff value of Target/Total ratio was 0.25%, sensitivity, specificity, and area under the curve (AUC) of the digital PCR detection using cellular DNA were 92.9%, 100%, and 0.95, respectively, while they were 100%, 100%, and 1.00 using cfDNA. Conclusion: We showed that the digital PCR method was highly sensitive and specific in detecting MYD88 mutations in the CSF. We propose that CSF liquid biopsy may serve a clinically applicable surrogate to make a diagnosis of CNSL.
ML-07 High expression of PD-L1 on tumor-associated macrophage is a predictive factor for favorable prognosis in PCNSL
Authors: Furuse Motomasa , Kuwabara Hiroko , Ikeda Naokado , Hattori Yasuhiko , Ichikawa Tomotsugu , Kagawa Naoki , Kikuta Kenichiro , Tamai Sho , Nakada Mitsutoshi , Wakabayashi Toshihiko , Kuroiwa Toshihiko , Wanibuchi Masahiko , Miyatake Shin-Ichi 
Published: November 2020

Abstract
PD-L1 and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we investigated the expressions of PD-L1 and PD-L2 in surgical specimens from needle biopsies and craniotomies to compare tumor tissue with surrounding tumor tissue (peritumoral tissue) and analyzed the correlation between expression of PD-L1/PD-L2 and survival in patients with PCNSL. We retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis. The tumor cells did not express very much PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95%CI: 0–94.6) than intratumoral macrophages (27.5%; 95%CI: 0–81.1, p=0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p=0.0429), with very low coefficient correlation (ρ=0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p=0.0008; better MSKCC score, p=0.0103; peritumoral macrophages: low proportion of LDH elevation, p=0.0064) and longer OS (for intratumoral macrophages: high PD-L1=60 months, 95%CI=30–132.6; low PD-L1=24 months, 95%CI=11–48; p=0.032; for peritumoral macrophages: high PD-L1=60 months, 95%CI=30.7-NR; low PD-L1=14 months, 95%CI=3–26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR=0.30, 95%CI=0.12–0.77, p=0.0129). Macrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL.