bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACT-4 EXPLORATORY PET EVALUATION OF BORON NEUTRON CAPTURE THERAPY FOR MALIGNANT GLIOMA REFRACTORY TO BEVACIZUMAB
Authors: Furuse Motomasa , Nihei Keiji , Kawabata Shinji , Ryo Hiramatsu , Nonoguchi Naosuke , Soeda Fumihiko , Ito Yuri , Takeno Satoshi , Aihara Teruhito , Takami Toshihiro , Miyatake Shin-Ichi , Ono Koji , Wanibuchi Masahiko 
Published: December 2022

Abstract

Background
We previously reported a phase II trial of accelerator-based boron neutron capture therapy (BNCT) for patients with malignant glioma, which showed a long median overall survival of 18.9 months. However, median progression-free survival was 0.9 months. In this trial, bevacizumab was permitted to use after progressive disease. The reason of discrepance between a short progression-free survival and a long overall survival was speculated that progression disease included pseudoprogression. But, efficacy of add-on bevacizumab on overall survival was not ignored.

Methods
The present study was approved by the Osaka Medical and Pharmaceutical University certificated review board and registered for Japan Registry of Clinical Trial (jRCTs051220019). Twenty-one patients who had malignant glioma refractory to bevacizumab treatment were planned to enroll in the study. The primary endpoint was a response rate of boronophenylalanine positron emission tomography. The secondary endpoints were a response rate of magnetic resonance image and safety.

Conclusion
Patients have been enrolled from June 2022. The efficacy of BNCT for malignant glioma could be elucidated by PET evaluation of tumor viability after BNCT.
ACT-20 PHASE 1/2, PROSPECTIVE, INTERNATIONAL MULTI-CENTER STUDY TO ESTABLISH THE SAFETY AND FEASIBILITY OF BLOOD-BRAIN-BARRIER DISRUPTION COMBINED WITH CARBOPLATIN FOR RECURRENT GLIOBLASTOMA; FIRST CLINICAL EXPERIENCE IN JAPAN
Authors: Kijima Noriyuki , Kanemoto Manabu , Oshino Satoru , Tani Naoki , Hosomi Koichi , Okita Yoshiko , Hirayama Ryuichi , Tachi Tetsuro , Kuroda Hideki , Utsuki Rena , Kagawa Naoki , Kishima Haruhiko 
Published: December 2022

Abstract
The prognosis for glioblastoma is still very poor despite intensive treatment by surgery, radiation, and chemotherapy. One of the reasons for poor prognosis of glioblastoma is blood-brain-barrier (BBB), which limits the delivery of chemotherapeutic agents to the brain. Focused ultrasound (FUS) therapy is approved for essential tremor and Parkinson disease in Japan and preclinical studies suggest low-intensity focused ultrasound (LIFU) administered with microbubbles (MB) can disrupt BBB and can improve the delivery of chemotherapeutic agents. Thus, currently, focused ultrasound therapy has gained attention in neuro-oncology and a number of clinical trials using FUS for the treatment of glioblastoma are underway. Our institutions (Osaka University Hospital and Saito Yukoukai Hospital) are the first in Japan to join the international multicenter study to examine the safety and feasibility of BBB disruption by FUS and MB combined with intravenous carboplatin for the treatment of recurrent glioblastoma. We are planning to enroll one recurrent glioblastoma patient for this study soon. BBB disruption strategies using FUS and MB for the treatment of neuro-oncological disease has potentials to improve the outcome of patients and many clinical trials will be performed in future.
RT-3 TREATMENT RESULTS OF AVAGAMMA THERAPY FOR RECURRENT GLIOBLASTOMA COMBINED WITH GAMMA KNIFE AND BEVACIZUMAB
Authors: Sato Kenichi , Asanome Taku , Ishida Yuuki , Sugio Hironori , Takanashi Masami , Nakamura Hirohiko 
Published: December 2022

Abstract

Purpose
We report the treatment results of AVAgamma therapy combining gamma knife (GK) and bevacizumab (Bev) for recurrent glioblastoma.

Subjects
From August 2013 to July 2022, 56 patients with recurrent glioblastoma treated with AVAgamma therapy as salvage therapy at the time of relapse after initial treatment. When the irradiation volume of GK was 15 ml or less, a single irradiation with a marginal dose of 20 to 26 Gy was performed. More than that received a single marginal dose of 12-15 Gy in two fractions or 8 Gy in three fractions. The mean therapeutic marginal dose was 23.9 Gy. Bev was administered 10 mg / kg or 15 mg / kg 1 to 10 times after GK.

Methods
Median progression-free survival (mPFS) and median survival (mOS) from AVAgamma treatment, and mOS and 5-year survival rate from initial treatment were compared with historical controls (GK group: 30 patients) who received only GK at the time of recurrence.

Results
The mPFS from AVAgamma therapy was 6 months, PFS-6m was 39%, OS-6m was 76%, and mOS was 10 months. The mOS from initial treatment was 25 months, which was prolonged compared to 21 months in the GK group (p=0.05). The 5-year survival rate for recurrent glioblastoma was 5% in the GK group and 22% in the AVAgamma group (p=0.04). The 5-year survival rate for glioblastoma with KPS is 70% or more at recurrence was 0% in the GK group and 33% in the AVAgamma group (p=0.017).

Discussion
Combined use of Bev with GK was considered to provide local control of recurrent lesions and prolong life prognosis in patients with good KPS at the time of recurrence.

Conclusion
AVAgamma therapy is thought to prolong the survival of recurrent glioblastoma and play an important role as salvage treatment.
RT-4 WORLD'S FIRST HEMISPHERE-SHAPE BRAIN-DEDICATED PET FOR SMALL LESION DETECTION
Authors: Takahashi Miwako , Akamatsu Go , Yamaki Tomohiro , Onodera Shinji , Yamaya Taiga 
Published: December 2022

Abstract
Positron emission tomography (PET) is useful to detect malignant tumors by imaging glucose or amino acid metabolism. Whole-body PET with the detector arrangement in a large diameter is currently used for brain imaging, however, the detector arrangement in small diameter is better for brain imaging. Stereotactic radiosurgery (SRS) treats brain tumor with maintaining cognitive function. Therefore, it needs more dedicated PET to identify small lesions and their localization. Then, we developed the world's first brain-dedicated PET with detectors arranged in a hemisphere of 28 cm diameter, attaining 2.2 mm in spatial resolution. This development was performed with ATOX CO., LTD and the brain-dedicated PET has been commercialized as VrainTM. Ten normal volunteers (22 - 45 age male) underwent 18FDG-PET using a whole-body PET (Discovery MI, GE) and the brain-PET for 10-min each, which were started 30-min and 45-min after FDG injection, respectively. A phantom with 10-22 diameter hot spheres and background (radioactivity ratio, 4:1) was also acquired by both PET systems, then estimated the radioactivity ratio in case of 2-mm diameter hot sphere. As a results, the inferior colliculus, substantia nigra, red nucleus, and brain stem raphe nucleus were identified with the brain-PET. The inferior colliculus was identified with the whole-body PET, but other nuclei were not. Based on phantom study, it was estimated that radioactivity in a 2-mm diameter sphere was measured with 1.4 - 2.9 times higher contrast than whole-body PET. The substantia nigra and the red nucleus has 5.0-6.0mm in short diameter on MRI T2WI axial image. The raphe nucleus extends laterally to 2.5mm on postmortem brain specimens. We concluded that our brain-dedicated PET can identify approximately 2.5mm diameter tumor clearly and will be particularly useful in SRS.
RT-7 DIFFERENTIATION AND TREATMENT OF RECURRENCE AND RADIATION NECROSIS IN THE TREATMENT OF MALIGNANT GLIOMAS
Authors: Tsuzuki Shunsuke , Nitta Masayuki , Saito Taiichi , Maruyama Takashi , Koriyama Shunichi , Kuwano Atsushi , Tamura Manabu , Ikuta Soko , Kawamata Takakazu , Muragaki Yoshihiro 
Published: December 2022

Abstract

Background
In the course of treatment of malignant gliomas, the appearance of contrast-enhanced lesions and surrounding T2/FLAIR high-signal after treatment is often experienced. There is no modality that can reliably diagnose whether the lesion is a recurrence or a response to treatment, including radiation necrosis. Furthermore, the choice of treatment modality is often difficult, such as reexcision, stereotactic irradiation, Avastin. Very few reports have examined the relationship between the irradiation field and histology.

Methods
Thirty-seven lesions in 30 patients who underwent repeat resection of malignant gliomas at our institution from October 2019 to December 2021 were analyzed retrospectively. Based on postoperative pathology, the patients were classified into two groups: recurrence group and radiation necrosis group.In each group, age, gender, histology at initial surgery, IDH status, radiation and chemotherapy, TNR of Methionine-PET, and the number of days after the end of treatment until the appearance of contrast lesions were considered.

Results
The recurrence group consisted of 20 patients with 26 lesions, mean age 48 years, male/female = 13/7, pathology was GBM 13, DA 1, AA 3, AO 2, AE 1, TNR 3.33 (1.41-6.32), and time to contrast appearance 547 (14-2427) days. PDT in combination with initial surgery was seen in 9 patients.The necrosis group consisted of 10 patients with 11 lesions, mean age 47 years, male/female = 4/6, pathology GBM 5, AA 2, AO 1, PXA 2. TNR 2.51 (1.20-3.75), 318 (24-678) days to contrast appearance, 2 patients had PDT.

Conclusions
Radiation necrosis tended to have lower TNR and shorter time to lesion appearance than recurrence, but no significant difference was observed. Improvement of diagnostic accuracy with modalities is desirable, and unnecessary irradiation is highly likely to contribute to ADL deterioration such as leukoencephalopathy and higher functional impairment.
RT-8 POST-IRRADIATION COURSE OF GLIOMAS OF THALAMUS AND BRAINSTEM
Authors: Yuri Shimizu , Narita Yoshitaka , Ichimura Koichi , Miyakita Yasuji , Ohno Makoto , Takahashi Masamichi , Yanagisawa Syunsuke , Shima Satoshi , Kojima Kanako , Kashihara Tairo , Takahashi Kana , Inaba Koji , Itami Jyun , Igaki Hiroshi 
Published: December 2022

Abstract

Objective
We retrospectively reviewed the post-irradiation course of cases treated with radiotherapy for the gliomas involving thalamus or brainstem.

Methods
Thirty-seven gliomas involving thalamus or brainstem treated with radiotherapy from 2007 to 2021 in our hospital were included. Median age was 47 (19-79) years, and KPS at the start of irradiation was 80% or less in 26 cases. Tumor localization was thalamus only/brainstem only/both thalamus and brainstem for 20/9/8 cases. Two cases did not undergo biopsy, and the others underwent surgery before irradiation. Two cases underwent partial excision of the lesion near the thalamus, 6 cases underwent partial excision from other than the thalamus-brainstem, and 27 cases underwent biopsy only. The pathological diagnosis based on the WHO classification at the time of surgery was glioblastoma (GBM) in 8 cases, high-grade glioma other than glioblastoma (HGG) in 23 cases (including 9 cases of diffuse midline glioma K27M), and low-grade glioma (LGG) in 6 cases.

Results
Median observation period was 16(2-66) months. Median PFS/median OS/5-year OS rate were 13 months/25 months/20% in all 37 cases. Median PFS was 66/18/7 months for LGG/ HGG/ GBM, and 5-year OS was 75/16/15%. Symptomatic cerebral edema associated with tumor growth was observed in one GBM 9 months after irradiation. In HGG, 7/23 cases underwent the VP shunting before irradiation, and one case who underwent ventriculostomy before irradiation had a VP shunting created for worsening hydrocephalus 3 months after irradiation. In one case of GBM, a VP shunt was created immediately after surgery.

Conclusions
Compared to the past reports of gliomas, it was suggested that the localization in thalamic brainstem was a factor for a worse prognosis in HGG.
MPC-1 IMMUNOHISTOLOGICAL COMPREHENSIVE ANALYSIS OF ANGIOGENIC FACTORS OTHER THAN VEGF IN GLIOBLASTOMAS IN RELATION TO THE USE OF BEVACIZUMAB
Authors: Ezaki Taketo , Tamura Ryota , Tanaka Toshihide , Miyake Keisuke , Kuranari Yuki , Yamamoto Yohei , Takei Jun , Akasaki Yasuharu , Toda Masahiro , Murayama Yuichi , Tamiya Takashi , Sasaki Hikaru 
Published: December 2022

Abstract
To date, few clinical observations have been reported for changes of alternative angiogenic factors (other than vascular endothelial growth factor [VEGF]) in human gliomas under bevacizumab (Bev). The elucidation of the mechanism of action and resistance is imperative to overcome resistance to Bev and develop a more effective therapy. This study aims to investigate the status and change of alternative angiogenic factors regarding Bev usage.The present study used 56 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naive Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory/autopsied Bev group). The expression of alternative angiogenic factors including basic fibroblast growth factor (bFGF), placental growth factor (PlGF), Angiopoietin1 (Ang-1), Angiopoietin2(Ang-2) and EphrinA2 were investigated via immunohistochemistry. In large tumor vasculature (diameter &gt;15μm), the expression of PlGF was significantly higher in the effective Bev group than naive Bev group. The expression of Ang-2 was persistently suppressed in the refractory/autopsied Bev group. In microtumor vasculature (diameter &lt;15μm), the expression of Ang-2 was higher in the effective group than naive Bev group. The status of PlGF was similar among these three groups.We provide the first clinicopathological evidence of the status of alternative angiogenic pathway after the Bev usage. These in situ observations will help to optimize therapy.
MPC-20 CLINICAL AND MOLECULAR FEATURES OF GLIOBLASTOMAS ARISING IN THE SETTING OF LI FRAUMENI SYNDROME
Authors: Kibe Yuji , Ohka Fumiharu , Aoki Kosuke , Motomura Kazuya , Yamaguchi Junya , Maeda Sachi , Nishikawa Tomohide , Shimizu Hiroki , Saito Ryuta 
Published: December 2022

Abstract

Introduction
Li Fraumeni Syndrome (LFS) is a rare autosomal dominant tumor predisposition syndrome caused by germline alterations of the TP53. Brain tumors are included in LFS core cancers. Choroid plexus carcinomas and medulloblastomas tend to present in pediatric LFS patients, while gliomas tend to present in adult LFS patients. There are few previous reports about gliomas arising in the setting of LFS. Here, we report clinical and molecular features of three cases of glioblastoma arising in the setting of LFS.

Results
Mean age at diagnosis was 40 years (range: 32-45). Two patients were male. Two patients had medical history of multiple tumors and family history of brain tumors. Magnetic resonance imaging of each patients revealed a left cerebellar peduncle lesion, a right parietal lobe lesion and two lesions in the pons and right parietal lobe, respectively. Pathological diagnoses of all cases were glioblastomas, IDH-wildtype. All patients underwent chemoradiotherapy after surgery. Mean progression free survival was 10.4 months (range: 5.1-17.0). All patients were admitted to palliative care mean 17.3 months (range: 14.4-21.4) after diagnosis. All patients had heterozygous germline mutations of TP53. Genetic analysis of tumor tissues revealed TP53 mutation and PDGFRA amplification in all patients. In all cases, mutation spots of TP53 in tumor-derived DNA were consistent with those of germ line mutations. In all cases, copy number alteration of TP53 gene in tumor-derived DNA were not detected. EGFR amplification, the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10-) and mutations of IDH, H3F3A, BRAF genes and TERT gene promoter were not detected in all tumor-derived DNA.

Conclusion
We experienced three cases of glioblastoma, IDH-wildtype arising in the setting of LFS. Clinical courses of all cases were poor. Notably, all tumor tissues harbored TP53 mutation and PDGFRA amplification, while no tumor tissues harbored TERTp mutation, EGFR amplification and 7+/10-.
ML-12 HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL TRANSPLANTATION (HDC-ASCT) FOR THE PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL)
Authors: Miyakita Yasuji , Inamoto Yoshihiro , Ohno Makoto , Takahashi Masamichi , Yanagisawa Shunsuke , Kawaguchi Yuki , Mukai Takayuki , Masaki Yasufumi , Fukuda Takahiro , Narita Yoshitaka 
Published: December 2022

Abstract
High-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) for the patient with primary central nervous system lymphoma (PCNSL) has been used as treatment at relapse or as consolidation therapy. We report on the efficacy, safety, and future issues of HDC-ASCT. Twelve patients with PCNSL (10 males and 2 females) underwent HDC-ASCT, ranging in age from 45 to 66 years (median 58 years) and KPS from 70 to 100 (median 90) at the time of HDC-ASCT. HDC-ASCT was performed at the time of consolidation therapy (without radiation) in 7 patients, at first recurrence in 4 (including 1 without radiation), and at second recurrence in 1. Department of Neurosurgery and Neuro-Oncology (NSNO) was in charge from diagnosis to just before transplantation, Department of Hematopoietic Stem Cell Transplantation (HSCT) was in charge of HDC-ASCT, and Department of NSNO was in charge after discharge again. The conditioning regimen consisted of busulfan 3.2mg/kg/day for 4 days and thiotepa 5mg/kg/day for the 2 following days, followed by ASCT. The observation period after HDC-ASCT ranged from 2.8 to 43 months (median 16.1 months), and the hospitalization period for HDC-ASCT ranged from 26 to 38 days (median 33 days), with no serious complications. All patients have returned to society and there have been no deaths to date, but two patients (after 4.7 months and 10.9 months) had relapses, of which two were treated with tirabrutinib, and one was subsequently treated palliatively. HDC-ASCT in PCNSL is an important option to improve outcomes. Since the main focus of this treatment is Department of HSCT, it is important to have sufficient cooperation and communication among the departments from the time of tumor diagnosis until after the patient is discharged from transplantation, and it is essential to be fully aware of each role.
MET-5 OUTCOME OF MULTIDISCIPLINARY TREATMENT FOR BRAIN METASTASES IN PATIENTS WITH MELANOMA IN THE ERA OF MODERN SYSTEMIC THERAPY
Authors: Mitsuya Koichi , Deguchi Shoichi , Ito Shohei , Nakasu Yoko , Hayashi Nakamasa 
Published: December 2022

Abstract

Objective
Recently modern systemic therapy and stereotactic irradiation have been developed. We reviewed the therapeutic outcome of brain metastases (BM) in patients with melanoma.

Methods
Data of patients with melanoma BM were retrospectively analyzed. Patients underwent multidisciplinary treatment, whole brain radiotherapy, stereotactic irradiation, immune check point inhibitor (ICI) and/or BRAF inhibitor, therapeutic indication was discussed at cancer board. If they had 3cm over diameter, surgical resection for BM was performed, when systemic life expectancy longer than three months after control of their BM and controlled extra-CNS metastases. Radiotherapy of BM was selected with number, size and location. Overall survival was analysis with Kaplan-Meier survival curves.

Results
Eighty-four patients were treated melanoma BM between November 2004 and December 2021 at our institution. Median age was 61 years, and 54% male. Sixty-seven patients were treated BM, but 17 were selected best supportive care from progressive systemic disease. After radiotherapy, 18 patients were administrated ICI, and BRAF inhibitor 10, both ICI and BRAF inhibitor 5, cytotoxic chemotherapy 13. Median overall survival (mOS) of treatment group was 132 days (95%CI: 90-230) from the diagnosis of brain metastases, and 35 days for BSC. MOS in patients both local (radiotherapy and/or surgery for BM) and systemic therapy was longer than that of local alone (209, 64 days, p&lt;0.0001). MOS of surgery group (n=10) was superior longer than the others (420, 92 days, p&lt;0.0001). For treatment period, patients diagnosed BM after 2014 longer than that before 2013 (175, 117 days, p&lt;0.0001), when ICI was started to use for melanoma in Japan.

Conclusion
Stereotactic irradiation and/or surgery supported with modern systemic therapy may be effective strategy in patients with melanoma BM. Further clinical investigations with larger cohort are needed to clarify appropriate assessments for patients with melanoma BM.
MET-9 LEPTOMENINGEAL CARCINOMATOSIS ~ ITS' ASSOCIATION WITH MOLECULAR AND PATHOLOGICAL SUBTYPES~
Authors: Iuchi Toshihiko , Hosono Junji , Setoguchi Taiki , Hasegawa Yuzo , Sakaida Tsukasa 
Published: December 2022

Abstract

Background
Leptomeningeal carcinomatosis (LMC) is the most difficult condition to treat brain metastases (BM), and the presence or absence of malignant cells in the cerebrospinal fluid (CSF) is important in determining treatment strategies. Here, we defined Type I LMC (CSF cytology positive) as LMC, and compared the risk of LMC in lung cancer (LC) by subtypes.

Patients and Methods
In principle, at our hospital, we confirm CSF cytology when any of the following is observed: enhanced lesion in contact with the cerebrospinal fluid cavity, cranial nerve symptoms, or concurrent hydrocephalus. Of the 833 cases of BM from LC diagnosed since 2005, 794 cases, excluding 39 cases for which molecular diagnosis was not performed, were enrolled.

Results
There existed EGFRm: 321 cases, ALK: 19 cases, without driver mutation (w/oDM): 313 cases, small cell lung cancer (SCLC): 141 cases. 1326 CSF cytological examinations were performed in 533 patients, and 162 were diagnosed as LMC. The frequency of LMC at diagnosis of BM was EGFRm: 8.7%, ALK: 5.3%, w/oDM: 3.2%, and SCLC: 0.0% (P&lt;0.0001). The time to LMC from diagnosis of LC was significantly shorter in EGFRm than ALK (H.R.:4.89, P=0.027), w/oDM (H.R.:2.96, P&lt;0.0001), and SCLC (H.R.:7.23, P&lt;0.0001). The use of TKIs after diagnosis of LC in EGFRm patients did not prevent LMC (HR: 0.932, P=0.493). The time to LMC from diagnosis of BM was also shorter in EGFRm in compared with ALK (H.R.: 4.89, P=0.027), w/oDM (H.R.: 3.94, P=0.057), and SCLC (H.R.: 8.94, P&lt;0.0001). L858R had a higher risk of LMC than Ex19deletion (HR: 1.59, P=0.037). Neither TKI use (HR: 0.989, P=0.971) nor radiotherapy (HR: 0.846, P=0.567) prevented LMC.

Conclusion
EGFRm has a higher risk of developing LMC than other subtypes, and it is thought to be a factor in the high risk of central nervous system death in this subtype.