bluuebunny/crossref_metadata_2025 huggingface dataset:
10079-MPC-6 RADIOLOGICAL AND MOLECULAR ANALYSIS OF WHO GRADE 4 BUTTERFLY GLIOMAS WITH A TAILORED SURGICAL APPROACH
Authors: Shibahara Ichiyo , Shigeeda Ryota , Tanihata Yoko , Fujitani Kazuko , Handa Hajime , Hyakutake Yuri , Toyoda Mariko , Uemasu Kouhei , Shinoda Mitsuhiro , Inukai Madoka , Komai Hideto , Sato Sumito , Hide Takuichiro , Kumabe Toshihiro
Published: December 2023

OBJECT

Surgical resection for butterfly gliomas (bG) are still under debate, but recent findings have shown that surgery prolongs survival. However, clinical and molecular background of bG still remains unknown and surgical strategies based on such findings are scarce.

OBJECTS AND METHODS

We treated 39 bG patients between 2005 and 2023, including 32 cases of glioblastoma and 5 cases of astrocytoma, WHO grade 4, IDH-mutant. For the validation, we reviewed 968 MRI obtained from the public datasets (UPENN-GBM, n=611; TCGA-GBM, n=255; CPTAC-GBM, n=61; IvyGAP, n=41).

RESULTS

Molecular analyses revealed that 51.3% of TERT promoter mutations, 59.0% of EGFR amplification/gain, 38.5% of PTEN hemi/homozygous, and 51.3% of CDKN2A hemi/homozygous deletion. Sequential radiological imaging before typical bG diagnosis demonstrated that bG harbors two subtypes which are corpus callosum (CC)-type and hemispheric (H)-type. The multisampling of H-type showed that accumulating alterations in the CC lesions than hemisphere, indicating an invasive trajectory from the hemisphere to the CC region. Survival analysis presented that CC-type was significantly poorer overall survival (OS) than H-type (263 days and 691 days, respectively, P = 0.018). The validation cohort also supported the poor survival of CC-type.

CONCLUSION

Our detail analyses demonstrated the possibility of two subtypes in bG. Unilateral trans-cortical approach from the larger tumor size with CC removal is favored in the H-type. On the other hand, bilateral trans-sulcal and interhemispheric approaches preserving the intact cortex and cingulate gyrus is an alternative for CC-type.
10084-TB-2 IN VITRO CHARACTERIZATION OF COMBINATION THERAPY IN GENETICALLY-ENGINEERED MURINE DIFFUSE MIDLINE GLIOMA MODELS
Authors: Tomita Yusuke , Takata Nozomu , Becher Oren
Published: December 2023

BACKGROUND

Diffuse midline glioma (DMG) is an incurable pediatric brain cancer without a FDA-approved drug that prolongs survival. Recent molecular analyses have suggested the potential efficacy of CDK4/6 inhibitors and MEK inhibitors. We recently established a genetically engineered murine DMG model that could capitulate the characteristics of human DMG. Here, we evaluated the features of DMG cells and the efficacy of the CDK4/6 inhibitor ribociclib and the MEK inhibitor trametinib in vitro.

METHODS

We used the RCAS/Tv-a avian retroviral system to generate DMG in Nestin-expressing progenitors in the neonatal mouse brainstem. We dissociated the DMG tissue to single cells and conducted the spheroid culture. We incubated the DMG cells with a hindbrain organoid to evaluate invasiveness. We treated the DMG cells with CDK4/6 inhibitor ribociclib and MEK inhibitor trametinib to evaluate the synergistic effect.

RESULTS

Induction of PDGF-A overexpression, H3.3K27M mutation, and p53 deletion resulted in gliomas in murine brainstem. Median survival of the murine DMG model was 62.5 days. From the DMG tissue, we successfully established the DMG cell line with spheroid culture. By incubating with the organoid, DMG cells could invade into the organoid. There was a mild synergistic effect with ribociclib and trametinib both in the cytotoxicity assay and the TUNEL apoptosis assay.

CONCLUSIONS

We could establish the DMG cell line that maintained the proliferative capability and invasiveness.
10085-RT-2 TREATMENT RESULTS OF AVAGAMMA THERAPY FOR RECURRENT GLIOBLASTOMA COMBINED WITH GAMMA KNIFE AND BEVACIZUMAB
Authors: Sato Kenichi , Asanome Taku , Ishida Yuuki , Yoshihara Ryuunosuke , Sugio Hironori , Takanashi Masami , Nakamura Hirohiko
Published: December 2023

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 2023, 64 patients with recurrent glioblastoma treated with AVAgamma therapy as salvage therapy at the time of relapse after initial treatment. The average age is 64.2 years, with 38 men and 26 women. The tumor volume is 150 ml or less, and KPS is 40% or more as the indication of AVAgamma therapy. The mean therapeutic borderline dose was 24.2 Gy. Bevacizumab 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=0.07). The 5-year survival rate for recurrent glioblastoma was 5% in the GK group and 22% in the AVAgamma group (p=0.07). The 5-year survival rate for glioblastoma with KPS greater than 70% at recurrence was 0% in the GK group and 29% in the AVAgamma group (p=0.09).

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.
10089-CO-4 DEVELOPMENT OF A PHYSICIAN SUPPORT SYSTEM FOR ANALYSIS OF GENETIC MUTATIONS IN BRAIN TUMORS AND SELECTION OF CLINICAL TRIALS USING LARGE-SCALE LANGUAGE MODELS (LLMS) WITH RETRIEVER
Authors: Takahashi Satoshi , Hana Taijyun , Koyama Tkafumi , Takasawa Ken , Kouno nobuji , Ishidu Kenichi , Hamamoto Ryuji
Published: December 2023

In the management of brain tumors, comprehensive genomic profiling testing is used to identify genetic mutations and understand their clinical significance to facilitate optimal therapeutic strategies. However, the test can identify non-standard mutations for brain tumor classification, and accurately presenting their clinical relevance is challenging. Providing accurate clinical trials per patient requests based on these results can also be time-consuming, creating the need for a physician support system. Large Language Models (LLMs) such as GPT, which are used for general conversation, question answering, and text generation, have limitations when used in specialized domains such as medicine. The information derived only from training data results in the inability of the LLM to handle specialized knowledge queries and verify certain facts, increasing the risk of generating incorrect information. To overcome these challenges, we developed a system that integrates a retriever with LLM. The retriever acts as an external memory, allowing LLM to access information beyond the training data. Because the retriever uses human-verified information, it mitigates the potential for incorrect information generation by LLM.In this presentation, we will discuss the use of this system in actual brain tumor diagnosis and treatment, and evaluate its accuracy and reliability. We believe that this system can help diagnose and treat patients with various genetic mutations, not limited to brain tumors.
10094-MPC-8 MOLECULAR PATHOLOGICAL ANALYSIS OF RADIATION-INDUCED GLIOBLASTOMA AFTER PEDIATRIC CEREBELLAR MEDULLOBLASTOMA TREATMENT
Authors: Ohe Naoyuki , Okubo Takafumi , Shoda Kenji , Yamada Tetsuya , Suzui Natsuko , Nakayama Noriyuki , Miyazaki Tatsuhiko
Published: December 2023

INTRODUCTION

The number of long-term survivors of pediatric medulloblastoma has been increasing due to improved treatment options. However, secondary cancer can be an issue for long-term survivors. We report the molecular pathological evaluation of two cases of radiation-induced glioblastoma. Patients: Of the 27 patients with cerebellar medulloblastoma treated at our institution, two who were 3 years old and 11 years old at the time of medulloblastoma diagnosis and both were girls, developed cerebellar glioblastomas after the initial treatment at five years and 11 months and 22 years and eight months, respectively. These two cerebellar glioblastomas were clinically diagnosed as radiation-induced secondary cancer.

RESULTS

Both of the two cases we clinically diagnosed as radiation-induced glioblastoma had negative IDH-1, EGFR expression and positive p53 expression in immunohistochemistry.

DISCUSSION

It has been reported that EGFR expression is negative as a molecular feature of radiation-induced glioblastoma, and the two cases we experienced were consistent with radiation-induced secondary cancers. In general, primary glioblastoma is positive for EGFR expression in the supratentorial region and negative in the infratentorial region. Therefore, in the case of supratentorial glioblastoma, it is useful to evaluate EGFR expression to distinguish primary glioblastoma from secondary glioblastoma.
10103-GMC-7 RETROSPECTIVE ANALYSIS ABOUT BEVACIZUMAB THERAPY FOR 10 YEARS AFTER AUTHORIZATION FOR MALIGNANT GLIOMAS IN OUR DEPARTMENT
Authors: Hashiba Tetsuo , Ueda Saori , Iwamura Haruka , Ueno Katsuya , Yamamura Natsumi , Miyata Mayuko , Lee Ichi , Kamei Takamasa , Yoshimura Kunikazu , Tenjin Hiroshi , Nonaka Masahiro , Asai Akio
Published: December 2023

In the treatment of malignant gliomas, drug therapy options are limited, and the Stupp regimen is still the standard treatment, In 2013, bevacizumab (BEV) was approved and became an option. Although BEV is not considered to prolong survival, it is currently used in many cases. We conducted a retrospective review of the use of BEV in our department 10 years after its approval. Of the 83 cases treated at our department, 70 were treated from the initial treatment to death or transfer to BSC. 70 cases consisted of 39 males and 31 females with a mean age of 63 years. Pathology was obtained in 69, and the diagnosis was made according to the WHO classification at each treated time. In the 21 cases where BEV was initially used, biopsy was performed in 13 cases and partial excision in 3 cases, indicating that BEV tended to be used from the time of initial presentation if there was residual disease. Of the 38 cases used at recurrence, 29 were treated with BEV alone, 8 with surgery followed by BEV for residual disease, and 6 of the 70 cases were still being followed. Of the remaining 64 patients, 55 died and 9 were transferred to BSC. The average number of times was 9.6 times, and the reasons for termination were invalidity in 45 cases, side effects in 10 cases, BSC transfer in 6 cases, patient request in 2 cases, and unknown in 1 case. In the 55 patients who died, the average overall survival was 21.4 months, the average survival time from the start of BEV to death was 8.9 months, and the average survival time from the end of BEV to death was 3.3 months. Based on 10 years of experience, it is necessary to find more efficient ways to use BEV.
10109-COT-13 LONG-TERM FOLLOW-UP OF FLAIR HIGH LESION IN THE BRAIN
Authors: Fujita Shohei , ohno Makoto , takahashi Masamichi , Yanagisawa Shunsuke , osawa sho , tsuchiya Takahiro , narita yoshitaka
Published: December 2023

AIM

Incidental FLAIR (Fluid Attenuated Inversion Recovery) high-intensity lesion in the brain can be considered as IDH-mutant low-grade glioma (LGG). Differential diagnosis includes trauma, ischemic changes, demyelinating diseases, and other inflammatory diseases. The biopsy is sometimes high risk for a young patient or an asymptomatic patient with a lesion in the brain stem, motor or language area. Imaging intervals vary among hospitals and the method for regular follow-up for these cases has not been established.

METHODS

We have studied 26 patients with FLAIR high lesion from 2012 to 2022. In cases of suspected LGG, the biopsy was performed, when necessary, after consultation with the patient and family. Our neurosurgery team protocol was to perform PET-MRI at the first consultation, and if there was negative, we have scheduled MRI examination at the next visit in one month. Then, MRI was performed every 2-3 months for the first year and every 3-6 months thereafter. The clinical features of these FLAIR high lesion and their differentiations from LGG in our cases are examined.

RESULTS

Biopsy was performed in 5 cases, but no tumor was found. The male-to-female ratio was 7:19, which was more common in female. The median age at onset was 44 years (15-47 years), showing a bimodal distribution with peaks in younger and older individuals. Among 26 cases, 14 cases had been unchanged for more than 5 years. The median maximum lesion diameter was 17 mm (8-47 mm). An annual average increase of LGG has been reported to be 3-5 mm in (Pallud, 2010). There were no cases diagnosed as glioma in cases where no expansion was seen after 5 years or more.

CONCLUSION

In this study, the possibility of glioma was considered to be low for cases in which no expansion on MRI was seen after 5 years or more.
10121-BT-8 CLINICOPATHOLOGICAL ANALYSIS OF CENTRAL NERVOUS SYSTEM GERM CELL TUMORS -387CASES IN THE JCCG COHORT AND THE IGCT CONSORTIUM COHORT
Authors: Yoshimoto Shoko , Takami Hirokazu , Kimura Yui , Hibiya Yuko , Nakano Yoshiko , Matsushita Yuuko , Yakayanagi Shunsaku , Tanaka Shota , Saito Nobuhito , Hirato Junko , Yoshioka Takako , Kato Miho , Takimoto Tetsuya , Nakazato Yoichi , Suzuki Tomonari , Mukasa Akitake , Kazuhiko Sugiyama , Kanamori Masayuki , Nakada Mitsutoshi , Maehara Taketoshi , Nishikawa Ryo , Ichimura Koichi
Published: December 2023

BACKGROUND

Central nervous system germ cell tumors (CNS GCTs) are rare primary tumors that tend to occur in East Asian boys. In Japan, the Japan Children's Cancer Group (JCCG) and the CNS GCT Genome Analysis Consortium (iGCT Consortium) have been accumulating clinical and pathological data on CNS-GCT cases.

METHODS

Statistical analyses were performed on 178 cases in the JCCG's Solid Tumor Observational Study (2016-2022) and 209 cases in the iGCT Consortium (2011-2021) for age, gender, site of origin, and pathological diagnosis.

RESULTS

There were 306 primary cases and 44 recurrent cases, 296 (77%) males and 90 (23%) females, with a median age of 13 years, 11 years for JCCG and 16 years for iGCT Consortium, with differences between these two cohorts. The most common pathological diagnosis was germinoma in 200 cases (52%). Non-germinomatous germ cell tumors (NGGCTs) in 167 cases (43%), of which 69 cases (18%) were mixed GCT with germinoma, 34 cases were immature teratoma, mature teratoma in 32 cases (8%), yolk sac tumor in 20 cases (5%), mixed GCT without germinoma in 5 cases (1%), choriocarcinoma in 5 cases (1%), embryonal carcinoma in 2 cases (0.5%). The median age of patients with germinoma was 15 years, while with other histological types was 12 years. The pineal gland was the most common site (208 cases, 56%) and 114 cases (31%) occurred in the neurohypophysis. 38 cases of them were bifocal. Tumor development in the basal ganglia occurred in 40 cases (11%), and multiple lesions were seen in 37 cases (10%). In the neurohypophysis, the male-to-female ratio was 1:1, while in the pineal region was 11:1. In the neurohypophysis, 67% had germinoma and 9% had teratoma, whereas, in the pineal regions, 50% had germinoma and 19% had teratoma.

CONCLUSIONS

CNS GCT is closely correlated with age, sex, site of origin, and histology.
10127-COT-15 REGIONAL MEDICAL DISPARITIES AND RESPONSES TO THE INCREASING COMPLEXITY OF GLIOBLASTOMA TREATMENT
Authors: Momii Yasutomo , Hata Nobuhiro , Fujiki Minoru
Published: December 2023

Glioblastoma remains a poor prognosis, but with the approval of bevacizumab (BEV) and the alternating tumor treating fields therapy (TTF), combined treatment can now be expected to expand patients' ADL and extend prognosis. However, the shortening of the intervals between patient visits and the unipolarization of treatment are worryingly increasing the unevenness of treatment opportunities, depending on the social circumstances of the patients. In rural areas in particular, it is possible that the disparity in medical care by place of residence is becoming more serious, as transportation conditions make it more difficult for patients to receive regular medical examinations. In this study, we analyzed differences in treatment and prognosis by patient's area of residence, and examined the effects of unipolarization of multidisciplinary medical care in rural areas. Based on the results, we examined what measures should be taken to correct regional disparities. Method: Of 129 consecutive glioblastoma patients initially treated at the hospital between 2010 and 2021, 75 patients who continued treatment after recurrence were included in the study, and were divided into two groups according to their place of residence: a group in the neighborhood of the hospital (59 patients) and a remote group (16 patients). The relationship between overall survival, duration of maintenance therapy visits, and BEV use was also examined. Result: Although no significant differences were found, there was an increase of about 3 months in both median survival and duration of maintenance therapy visits in the neighboring areas. Conclusion: Compared to patients living in the proximity of our facility, patients living in remote areas tended to have shorter maintenance therapy visits and poorer survival. We must strive to be close to such patients and provide them with the best possible quality and appropriate medical care.
10150-GGE-16 INTRAOPERATIVE INTEGRATED DIAGNOSTIC SYSTEM FOR MALIGNANT CENTRAL NERVOUS SYSTEM TUMORS
Authors: Hayashi Takahiro , Ooshima Akito , Honma Hirokuni , Sugino Kyoka , Uchiyama Kaho , Kato Miyui , Takayama Yutaro , Sonoda Masaki , Iwashita Hiromitsi , Yamanaka Shoji , Fujii Masashi , Yamamoto Tetsuya , Tateishi Kensuke
Published: December 2023

INTRODUCTION

As the most of adult malignant brain tumors are gliomas and primary central nervous system lymphomas (PCNSL)., differentiating between PCNSL and glioma during surgery is crucial for determining the treatment strategy. Also, the WHO CNS5 criteria indicates common genetic alterations according to tumor types. Thus, intraoperatively identifying these genomic abnormalities could aid diagnosis, which may contribute in more personalized therapeutic approaches. Here, we report an intraoperative integrated diagnostic system (i-ID system) that combines frozen section (FS) diagnosis with quantitative PCR (qPCR) based genotyping.

MATERIAL & METHODS

Rapid histopathological diagnosis by FS was performed for all cases. For cases requiring differentiation from PCNSL, rapid immunohistochemical staining (R-IHC) for CD20 and GFAP was performed. qPCR genotyping was used for the rapid evaluation of IDH1R132H, IDH2R172K, TERTC228T, C250T, BRAFV600E, H3F3AK27M, MYD88L265P, and CDKN2A copy number alteration. The diagnostic accuracy for adult diffuse glioma and PCNSL using i-ID system was examined.

RESULTS

i-ID system was required 100 min to obtain complete information. After retrospectively analyzing of 151 cases for setting diagnostic algorithm, 101 cases were prospectively assessed for diagnostic potential. The matched ratios for IDH1/2, TERT, BRAF, H3F3A, and CDKN2A evaluations using qPCR were 100%, 98.8%, 100%, 100%, and 93.9%, respectively. In cases of glioblastoma, astrocytoma, and oligodendroglioma, the sensitivity of FS was low, with values of 0.18, 0.17, and 0.00, respectively. On the other hand by combining genotyping, the sensitivity improved up to 0.94, 1.00, and 0.88, respectively. The sensitivity for PCNSL improved from 0.47 (genotyping alone) to 0.95 with combination of R-IHC. Overall, i-ID based intraoperative diagnosis was matched to the permanent diagnosis in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) PCNSL patients, respectively.

CONCLUSIONS

The i-ID system provides rapid and reliable integrated diagnosis of adult malignant CNS tumors.
10154-PEDT-6 RETROSPECTIVE STUDY OF 12 PEDIATRIC EPENDYMOMAS TREATED AT OUR HOSPITAL
Authors: Shiba Yoshiki , Yamaguchi Junya , Takido Yuhei , Shimizu Daiki , Kibe Yuji , Maeda Sachi , Nishikawa Tomohide , Ohka Fumiharu , Motomura Kazuya , Saito Ryuta
Published: December 2023

Ependymoma is an important disease in pediatric brain tumors, but reports with a large number of cases are scarce. In this study, we investigated the clinical course of 12 cases of ependymoma in children treated at our hospital.The median age was 2.5 years (0-15 years), and 10 had posterior fossa and 2 had supratentorial onset. Surgery was performed in all cases, and total resection was achieved in 9 cases (75%). Five cases were diagnosed as ependymoma, Grade II, and seven cases were diagnosed as anaplastic ependymoma, Grade III, according to the WHO revised 4th edition. Adjuvant therapy was administered in 8 patients, 6 with radiotherapy and 2 with combination chemotherapy and radiotherapy. Recurrence was seen in 6 cases, 4 of which were local recurrences and 2 of which were dissemination. The 2-year and 5-year progression-free survival rates were both 60%, and the 2-year and 5-year survival rates were 100% and 66.6%. Progression-free survival/overall survival analysis was performed, and the above results were considered to be equivalent to the published data of 27 cases (Peralia et al. Cell 2022). Progression-free survival tended to be favorable in patients with complete resection (HR = 0.18, 95% CI: 0.025-1.28) and patients with supratentorial disease (HR = 0.18, 95% CI: 0.030-1.11). No difference was seen by WHO grade (HR = 1.022, 95% CI: 0.20-5.24). Our cohort also yielded the same results regarding prognostic factors as previously reported, and WHO grade did not correlate with prognosis. The WHO 5th edition classification adopts molecular diagnosis and further subclassifies ependymoma. Since molecular diagnostics require advanced analytical techniques, there is a problem that it is difficult to put them into practical use, but surrogate markers that can be applied clinically have also been reported. This time, we will reclassify pediatric ependymoma using surrogate markers and compare it with the old classification.
10157-BOT-1 DISCRIMINATION OF EPENDYMOMA AND MEDULLOBLASTOMA BY RAMAN SPECTROSCOPY
Authors: Kawamoto Yuki , Okita Yoshiko , Tenma Kenta , Nakagawa Kanji , Utsugi Reina , Murakami Koki , Kuroda Hideki , Tachi Tetsuro , Hirayama Ryuichi , Kijima Noriyuki , Kagawa Naoki , Fujita Katsumasa , Kishima Haruhiko
Published: December 2023

Introduction

Ependymoma and medulloblastoma are difficult to diagnose by imaging and histology. Since the treatment strategies differ between the two, an accurate and prompt diagnosis is required. Raman spectroscopy can measure tissue-specific molecular vibrations. It shows extract biomolecular information characteristic of tumor tissue. We observed the tissues of ependymoma and medulloblastoma by Raman spectroscopy, and attempted to establish a new differentiation method.

Methods

The subjects were 13 patients with ependymoma and 5 patients with medulloblastoma who underwent resection from July 2017 to June 2023 at our institution. Their formalin-fixed paraffin-embedded (FFPE) section were observed by Raman spectroscopy. Raman spectra were collected using a line-illumination Raman microscopy developed at the department of Applied Physics, Osaka University. 532 nm excitation light was focused on the sample by an objective lens (Nikon 25x, NA1.1, CFI75). Excitation intensity and measurement time were 3 (mW/um2 ) and 5 seconds, respectively.

Results

We observed a Raman peak at 1240 cm-1 (Amide II3) that was significantly different in both ependymoma and medulloblastoma, and a similar tendency was observed for each specimen. It can suggest differences in amino acids, proteins, and lipids within tumor tissue.

Discussion and conclusion

We investigated whether it is possible to make a differential diagnosis between ependymoma and medulloblastoma using Raman spectroscopy. It was suggested that we can detect the molecular difference between the two using FFPE sections. Raman spectroscopy is a label-free measurement technique that does not require staining of biological samples, allowing simple and rapid evaluation. In the future, we plan to verify the validity of the differential method using specimens collected during surgery and frozen specimens.
10162-STMO-8 A SINGLE CENTER RETROSPECTIVE ANALYSIS OF AWAKE CRANIOTOMY FOR BRAIN METASTASIS.
Authors: Yanagisawa Shunsuke , Ono Makoto , Takahashi Masamichi , Osawa Sho , Tuchiya Takahiro , Fujita Syohei , Miyakita Yasuji , Narita Yoshitaka
Published: December 2023

BACKGROUND/AIM

Awake surgery is often used for resecting glioma, but it is controversial whether it should be performed for brain metastasis, because brain tumor is rather demarcated than glioma. However, a small number of hospitals can perform awake craniotomy by limitation of hospital capacity. Here we show a single center retrospective analysis of awake craniotomy for brain metastasis to examine the safety and efficacy of awake craniotomy.

MATERIAL/METHOD

We analyzed consecutive 50 cases from January 2016 to May 2023 in our hospital. Rehabilitation staff evaluated their neurological status within a week before and after surgery.

RESULT

Patients characteristics were as follow. Median age was 62 (16-81). Left side tumor were 43 (86.0%). Frontal lobe was 36 (72.0%),temporal lobe 8 (16.0%), parietal lobe 5 (10.0%), occipital lobe 1 (2.0%). Primary cancer was lung 26 (52.0%), gastrointestinal lesion 7 (14.0%), breast 6 (12.0%), soft tissues 4 (8.0%), uterus 1 and malignant melanoma 1, respectively. Radiation necrosis after stereotactic radiosurgery for brain metastases was 5 (10.0%). Preoperative KPS 100-90 was 25 (50.0%), KPS 80 was 10 (20.0%) and less than or equal to KPS 70 was 15 (30.0%). Gross total removal was 43, partial removal was 7. MMSE of before and after surgery was mean 27.1 and median 29. Median OS was 18.8 months (95%CI: 11.2-526).

DISCUSSION/CONCLUSION

We selected most awake craniotomy for a tumor on left frontal lobe and each evaluationg scales showed no deterioration. Awake craniotomy for brain metastasis is probed to be performed without deteriorating patient's neurological function.
10168-BOT-2 ANTITUMOR AROMA THERAPY WITH LEMONGRASS ESSENTIAL OIL FOR GLIOBLASTOMA
Authors: Saito Norihiko , Hirai Nozomi , Koyahara Yuki , Sato Sho , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Sakurai Takatoshi , Iwabuchi Satoshi
Published: December 2023

Aromatic essential oils have been used in cancer treatment to enhance immunity, induce sedation, and reduce the side effects of chemotherapy. Recently, essential oils have been reported to have anti-tumor effects. We have been investigating anti-tumor aroma of essential oils as a novel treatment for glioblastoma and have found that hiba essential oil has a proliferation inhibitory effect. In this study, we investigated the antitumor effect of lemongrass essential oil for glioblastoma and its antitumor aromatherapy. Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used. Lemongrass essential oil was added to each tumor cell line, and growth inhibition was observed in all cell lines. In addition, lemon grass essential oil showed growth inhibition effect when the tumor cells were separated from the oil, as was the case with direct administration, suggesting that the lemongrass essential oil components that evaporated acted on tumor cells in the surrounding area. The antitumor component of lemongrass essential oil was isolated and identified as citral, an antitumor factor, by gas chromatography. Analysis of the effects of citral showed that it strongly inhibited MARK4 activity and growth in three cell lines. The mechanism revealed that citral decreased the phosphorylation of Tau protein. MARK4 is highly expressed in glioblastoma and has been reported to be involved in cell proliferation. This study suggests a potential mechanism for citral to inhibit tumor cell proliferation via MARK4 in malignant gliomas. Citral is a volatile monoterpene and may exert its antitumor effect by evaporation diffusion. Lemongrass essential oil contains citral, which shows antitumor effects, and is expected to be applied to a new glioblastoma therapy using "aroma".
10170-GMC-14 CRANIOPHARYNGIOMA REFRACTORY TO SURGERY AND RADIOSURGERY SUCCESSFULLY TREATED WITH ENCORAFENIB AND BINIMETINIB: A CASE REPORT
Authors: Tanaka Shota , Takayanagi Shunsaku , Kage Hidenori , Oda Katsutoshi , Yamada Shozo , Takami Hirokazu , Saito Nobuhito
Published: December 2023

Craniopharyngioma is prone to recurrence despite aggressive surgery; repeated surgery and radiotherapy are associated with risks of pituitary insufficiency, visual inacuity and anopsia, and neurocognitive dysfunction, adversely affecting patients' activity of daily life and quality of life. In a recent clinical trial in the US, molecular targeted therapy with vemurafenib and cobimetinib has achieved excellent objective response rate in BRAF-mutant cranopharyngioma. We report a case of BRAF-mutant papillary craniopharyngioma refractory to multiple surgeries and radiosurgery that was successfully treated with encorafenib and binimetinib. Molecular targeted therapy with BRAF inhibitor and MEK inhibitor can be a treatment option for BRAF-mutant craniopharyngioma, even after multiple recurrences with surgeries and radiotherapy.
10172-IM-6 DEVELOPMENT OF CAR-NK CELL THERAPY TARGETING B7H3 AGAINST GLIOBLASTOMA
Authors: Tetsuro Tachi , Kijima Noriyuki , Kuroda Hideki , Ikeda Syunya , Murakami Koki , Nakagawa Kanji , Utsugi Reina , Kawamoto Yuki , Hirayama Ryuichi , Okita Yoshiko , Kagawa Naoki , Hosen Naoki , Kishima Haruhiko
Published: December 2023

There is an urgent need to find new treatments for brain tumors with poor prognoses, such as glioblastoma (GBM). Recently, CAR-T cell therapy, which uses genetically engineered T cells to express chimeric antigen receptors (CAR) has been actively investigated. However, although CAR-T cell therapy has shown efficacy in preclinical GBM models, CAR-T cells have a number of limitations. When adapted for clinical use, it may exhibit undesirable side effects such as graft-versus-host disease or cytokine-releasing syndrome. Furthermore, generating an autologous product for each patient needs time and effort and is restrictive for widespread clinical use. In contrast, cord blood-derived natural killer (NK) cells show a robust safety profile in vivo and are an attractive therapeutic option for cancer treatment. In this study, we focused on developing CAR-NK therapy against GBM and used B7H3 which has recently been studied as a tumor antigen. First, we generated CAR-T cells expressing CAR against B7H3 and confirmed their antitumor effect in vitro and in vivo. Next, we generated CAR-NK cells with similar scFV from code blood. We generated eight donors of CAR-transfected NK cells and investigated the gene transfer and cell growth rate. We tested three donors of CAR-transfected NK cells and found that one of them had robust cytolytic activity against GBM cells in vitro. Overall, this study suggests that cord blood-derived CAR-NK cells targeting B7H3 may be a promising therapy for GBM.
10177-ML-5 HIGH-DOSE CHEMOTHERAPY FOLLOWED BY AUTOLOGOUS STEM CELL TRANSPLANT FOR RECURRENT CNS LYMPHOMA
Authors: Mishima Kazuhiko , Tkahashi Naoki , Suzuki Tomonari , Mizuno Reina , Shirahata Mitsuaki
Published: December 2023

BACKGROUND

The prognosis of relapsed central nervous system lymphoma (CNSL) is poor, and effective standard treatment has not been established. The BTK inhibitor or HD-MTX-based chemotherapy is re-administered if the patient responds to HD-MTX-based therapy at initial treatment, but durable remission is difficult to achieve. Thiotepa (TT) was approved in Japan as a pre-treatment for autologous hematopoietic stem cell transplantation in malignant lymphoma, and autologous stem cell transplantation (ASCT)-assisted high-dose chemotherapy (HDC) can be performed. TBC (TT, busulfan, and cyclophosphamide) and BCNU+TT are used in Europe and the US, but treatment-related mortality (TRM) has been reported in about 10% of patients. The regimen approved in Japan is BuTT (busulfan and TT) and there is little information on its efficacy and safety in relapsed CNSL. In this study, we examined the efficacy and safety of HDC-ASCT at Saitama Medical University. Subjects: Nine patients with recurrent CNSL (primary CNSL: 6 cases, secondary CNSL: 3 cases) since May 2021, age ≤ 65 years, KPS ≥ 70, are included in this study.

METHODS

After response to induction (R)MPV regimen, peripheral blood stem cells were harvested after administration of G-CSF and plerixafol, pretreated with BuTT regimen (Bu: 3.2 mg/kg, day-8 to -5, TT: 5 mg/kg, day-4, -3), and transplanted on Day 0.

RESULTS

Adverse events of Grade 3 or higher were febrile neutropenia in 5 cases, neutropenia in 9 cases, thrombocytopenia in 9 cases, pharyngitis in 5 cases, oral candida in 1 case, pleuritis in 1case, abdominal pain in 1 case, nausea in 1 case, and sepsis 1 case, but all recovered, and no TRM was observed. Six patients with primary CNSL and two with secondary CNSL are currently alive without recurrence, and one with non-CR secondary CNSL died of progression in two months.

CONCLUSION

HDC-ASCT is an effective salvage treatment for relapsed CNSL.
10184-BT-14 CLINICAL FEATURE OF HEMISPHERIC GLIOMA WITH H3F3A, PEDIATRIC-TYPE HIGH GRADE GLIOMA, H3 K27-ALTERED, NEC AND DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT, CNS WHO GRADE 4
Authors: Nakatogawa Hirokazu , Kawaji Hiroshi , Hayashi Nobuhide , Fukai Junya , Kijima Noriyuki , Shofuda Tomoko , Yoshioka Ema , Kanematsu Daisuke , Katsuma Asako , Sumida Miho , Inenaga Chikanori , Mori Kanji , Kanemura Yonehiro
Published: December 2023

INTRODUCTION

Diffuse midline glioma (DMG), H3K27-altered, is a CNS WHO grade 4 glioma that usually located mainly in the brainstem, thalamus and spinal cord. However, DMG located in non-midline lesions are now described as pediatric-type high grade glioma, H3K27-altered, NEC (NDMG). On the other hand, diffuse hemispheric glioma, H3G34-mutant (DHG) located in the cerebral hemispheres, and is classified under the WHO 2021 classification. It is unknown that the differences in clinical characteristics of these hemispheric tumors with H3F3A mutations. In the present study, we report a comparative study of the clinical characteristics of two groups of NDMG and DHG.

METHODS

Among 4128 brain tumor samples collected in the Kansai Network for Molecular Diagnosis of Central Nervous System Tumors, 16 NDMG and 9 DHG cases were examined for comparison of clinical characteristics.

RESULTS

There were no differences in gender, tumor location, or pathology between NDMG and DHG. The median age was 47.3 years in NDMG and 26.2 years in DHG, and NDMG was significantly older than DHG (p=0.003). There was no significant difference in MGMT promoter methylation between NDMG and DHG (p=0.087). The Kaplan-Meier survival curve showed no significant difference, with a median survival of 495 days for NDMG and 587 days for DHG (p=0.765). There was no significant different survival rate between WHO grade 3 (n=15) and grade 4 (n=9) for pathological diagnosis.

DISCUSSION AND CONCLUSION

We compared the clinical characteristics of NDMG and DHG. There are some reports that NDMG and DHG gliomas located in non-midline lesion. Removing much tumor volume may improve the prognosis of non-midline glioma. We discuss the gliomas with H3F3A mutations located in a hemispheric lesions by literature review.
10204-NQPC-7 EFFECTIVENESS AND PROBLEM OF CONVALESCENT REHABILITATION FOR INDEPENDENT LIVING IN THEIR HOUSE OF PATIENTS WITH BRAIN TUMOR
Authors: Ideguchi Makoto , Matsutani Masao , Sakamoto Hirohiko , Kitamura Takayuki , Sato Akira , Ito Shoichi , Teshima Sawane , Ueyama Mai , Takao Yuki , Omata Akiko
Published: December 2023

OBJECTIVE

The goal of brain tumor (BT) treatment is to achieve independent living (IL) in the house that KPS (Karnofsky Performance Status) is 70. However, 30% of KPS after postoperative concomitant chemoradiotherapy is between 30 to 60. Therefore, it is necessary to achieve IL in these patients. We report effectiveness for improvement of KPS, achievement of IL, and influence for health-related quality of life (HR-QoL) of convalescent rehabilitation.

METHODS

138 patients with BT (average of age: 63, male/female: 76/62) who admitted in our hospital in purpose of rehabilitation, whose KPS were from 40 to 60 were enrolled from 2017. The rate of improvement (RoI) that KPS upgrade by one degree and the rate of IL (RoIL) were evaluated, and the factors to influence them were analyzed. Additionally, HR-QoL using QLQ-C30 and BN-20 on admission and discharge was evaluated.

RESULTS

While rehabilitation for KPS 50 achieved 70% of RoI and 60% of RoIL, that with KPS40 or less resulted in 40% of RoI and 18% of RoIL. Primary GBM 47cases with KPS60 achieved 83% of RoI and RoIL, and with KPS40 also achieved 27% of RoI and 17% of RoIL. Multivariate analysis revealed that MMSE≥24 contributed to RoI, and MMSE≥24 and KPS≥50 to the RoIL with statistically significance. HR-QoL survey revealed that financial and future uncertainty in patients with BT were higher than that in stroke, QoL scales tended to deteriorate during the hospital, and this tendency was particularly strong in patients with malignancy.

CONCLUSIONS

Our data revealed that rehabilitation in in patients with BT for KPS 60 or less was significantly effective to achieve IL. On the other hand, it is the issue to improve ADL in patients with KPS40 or less by effective rehabilitation and to approach the improvement of mental health.
10214-COT-24 A RARE CLINICAL CASE OF LUMBAR METASTASIS FROM GLIOSARCOMA
Authors: Kakuta Kiyohide , Asano Kenichiro , Mizukami Ai , Nomura Yu , Ueno Kota , Watanabe Ryota , Yanagiya Keita , Kinoshita Shohei , Sasaki Takao , Fujiwara Nozomi , Katagai Takeshi , Morita Takahiro , Kurose Akira , Saito Atsushi
Published: December 2023

Gliosarcoma (GS) is a variant of glioblastoma (GBM) and has been shown to be prone to extracranial metastasis. We report a rare case of lumbar metastasis of Gliosarcoma (GS) based on histopathological findings.37-year-old male.He underwent emergency surgery for a left frontal subcortical hemorrhage. Pathological diagnosis confirmed GS. Postoperatively, the patient underwent conventional radiation chemotherapy. Later, in conjunction with cranioplasty, the remaining lesion was additionally excised and maintenance therapy was administered for 9 months. Subsequently, a follow-up MRI revealed an intracranial disseminated lesion, although the primary site was not affected. At the same time, he had difficulty moving due to back pain, and MRI revealed extracranial metastases in the second lumbar vertebra and retroperitoneum. Lumbar biopsy confirmed the diagnosis of metastasis. Pathological findings at the initial surgery showed that the tumor consisted of GS and gemistocyte-like components, and immunostaining and genetic findings showed IDH wild type GBM. Additional tissue samples showed predominantly gemistocyte-like components and no GS component, and the genetic profile was similar.Lumbar biopsies showed predominantly GS and no gemistocyte-like components. MGMT methylation changed from methylation-negative to positive and then negative by immunostaining and MS-PCR. In a previous report, Feldheim et al. performed a meta-analysis of MGMT methylation changes in relapsing GBM and reported increased methylation after relapse. In addition, Jimenez et al. quantitatively analyzed MGMT methylation in recurrent GBM by pyrosequencing and found an increased rate of methylation in about half of the cases. These reports indicate that MGMT methylation is altered following therapeutic intervention. In the present case, it was hypothesized that an intracranial lesion that was initially unmethylated was methylated by the intervention, but an unmethylated, treatment-resistant GS component metastasized to the extracranial space. The clinical course of this case was a rare example of evidence of a change in MGMT methylation due to therapeutic intervention.
10215-ML-7 CLINICAL OUTCOME OF TIRABRUTINIB IN PCNSL REFRACTORY TO R-MPV THERAPY
Authors: Ohka Fumiharu , Yamaguchi Junya , Motomura Kazuya , Kibe Yuji , Nishikawa Tomohide , Maeda Sachi , Shimizu Hiroki , Takido Yuhei , Saito Ryuta
Published: December 2023

In recent years, R-MPV therapy has been widely used for treatment of primary central nervous system lymphoma (PCNSL). Although a high response rate and favorable prognosis have been reported with R-MPV therapy using multiple drugs, the treatment strategy for cases refractory to induction therapy has not been established. High-dose radiotherapy is currently recommended for refractory cases, however, the efficacy and frequency of adverse events such as leukoencephalopathy are not yet clear. Tirabrutinib has been available for recurrent or refractory PCNSL cases since 2020. However, there have been few reports on the results of tilabrutinib in these refractory cases. We have been using tirabrutinib for these refractory cases since its introduction. Here, we compared the results of tirabrutinib with those before the introduction of tirabrutinib. We investigated 30 cases with PCNSL treated with R-MPV at our hospital since 2013. 5 (16.7%) of the 30 cases revealed refractory to R-MPV. Two cases were promptly treated with irradiation (total 40-45 Gy) and both remitted, but one (a 70's male) had extensive white matter changes. One case (40's female) also had white matter changes but maintained CR for 4 years and 8 months. All three patients treated with tirabrutinib achieved CR or PR immediately, and two patients (a 60's woman and a 70's man) received whole brain irradiation of 23.4 Gy at 26 and 28 days after tirabrutinib introduction and remained in remission for 2 years 3 months and 2 years 4 months respectively with no significant white matter changes. The results suggest that tirabrutinib may be useful for cases refractory to R-MPV therapy. Because the long-term results of tirabrutinib are not yet clear, careful consideration should be given to the necessity of radiotherapy for cases who have achieved remission with tirabrutinib.
10220-NI-9 PREDICTION OF AN EFFECT OF ELIMINATING HIGH INTENSITY AREAS ON FLAIR IMAGING AFTER ONE-SHOT BEVACIZUMAB FOR GLIOBLASTOMA
Authors: Beppu Takaaki , Sato Yuichi , Fujiwara Shunrou , Ogasawara Kuniaki
Published: December 2023

PURPOSE

Bevacizumab (BEV) demonstrates an affect of alleviating high intensity areas (HIA) on FLAIR imaging in glioblastoma, although it shows differences between patients. We investigated prediction factors of alleviating HIA after one-shot BEV.

METHODS

Twenty patients with glioblastoma enrolled in this study. MRI including arterial spin labeling (ASL) were performed before and after administrating BEV (one-shot at 10 mg/kg). From eliminating volume of HIA on FLAIR between before and after BEV, we assessed the eliminating rates (1-pre-volume/post-volume%). All patients were divided into two groups, either less or more than the mean of the eliminating rate. We compared results of plausible factors before BEV, including HIA volume, enhancing volume on T1WI with contrast media, tumor locations, presence of central necrosis, and CBF T/N on ASL, between two groups.

RESULTS

The mean of the eliminating rate of HIA volume on FLAIR between before and after BEV was 40.7%. Between two groups less than and more than eliminating rate of 40.7%. only CBF T/N at a large region of interest surrounding entire tumor showed a significant difference, which patients with larger eliminating rate showed smaller CBF T/N.

CONCLUSION

The results in this study suggested a possibility that CBF T/N on ASL is a predction factor of alleviating HIA after one-shot BEV. CBF T/N on ASL has been reported to correlates to the amount of expression of VEGF. In patients with smaller CBF T/N, the VEGF-neutralizing effect from one-shot BEV is likely to be relatively high.
10236-NI-11 IMAGING FEATURES AND CONSIDERATION OF PROGRESSION PATTERN OF DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT
Authors: Yuji Kibe , Ohka Fumiharu , Motomura Kazuya , Yamaguchi Junya , Nishikawa Tomohide , Maeda Sachi , Shimizu Hiroki , Takido Yuhei , Saito Ryuta
Published: December 2023

BACKGROUND

Diffuse hemispheric gliomas, H3 G34-mutant (DHG-G34m) are newly recognized pediatric-type diffuse high-grade gliomas. We describe detail imaging features of seven cases of DHG-G34m and consider about progression pattern of DHG-G34m.

RESULTS

H3 G34R/V was detected by sanger sequencing in all tumors. Mean age of onset was 16.5 years (range: 10-26). Tumors were located on frontal (n=2), parietal (n=2), temporal lobe (n=1) and insular cortex (n=1), respectively. In one case, gliomatosis cerebri-like multiple lesions involving the cortex and basal ganglia occurred. Magnetic resonance imaging showed T2/FLAIR high lesions with poor contrast enhancement in all cases. All tumors harbored restriction of diffusion. Strong accumulation of methionine was observed in six cases. Tumors of these cases harbored T2/FLAIR high lesions in the deep white matter which showed methionine accumulation. All patients underwent surgery (total resection in one case, partial resection in five cases, and biopsy in one case) followed by radiation chemotherapy. The mean progression free survival was 9.9 months (range: 1.6-33.1 months). All recurrent tumors harbored diffuse infiltration along the white matter adjacent to surgical cavity, which was temporarily reduced by bevacizumab, but eventually invaded into cerebral peduncle via pyramidal tract and into contralateral brain via corpus callosum or anterior commissure in six cases. Extensive infiltration of tumor cells into the contralateral brain and brain stem was confirmed in the autopsy brain of one case. The mean overall survival was 21.6 months (range: 8.9-48.3 months).

CONCLUSION

DHG-G34m showed deep white matter infiltration from the time of initial onset, which made gross total resection difficult. Residual lesions extensively infiltrated along the white matter and eventually invaded the brainstem and contralateral brain, leading to death.