bluuebunny/crossref_metadata_2025 huggingface dataset:
10109- ANGI-4 INTRATUMORAL THROMBOSIS AS A HISTOLOGICAL BIOMARKER FOR PREDICTING EPIDERMAL GROWTH FACTOR RECEPTOR ALTERATION AND POOR PROGNOSIS IN PATIENTS WITH GLIOBLASTOMAS
Authors: Negoto Tetsuya , Furuta Takuya , Yoshitake Hidenobu , Moritsubo Mayuko , Hashimoto Aya , Takeshige Nobuyuki , Sakata Kiyohiko , Nakamura Hideo , Morioka Motohiro
Published: November 2024

PURPOSE

Intratumoral thrombosis is a specific finding in glioblastomas and considered the origin of palisading necrosis. Its distribution and contribution to the glioblastoma pathophysiology and systemic thrombosis are obscure, although deep vein thrombosis is a common complication in glioblastoma cases.

METHODS

Clinicopathological and genetic analyses were performed on 97 glioblastoma tissue specimens to elucidate the role of thrombotic events and associated molecular abnormalities.

RESULTS

Morphologically, intratumoral thrombosis was observed more frequently in vessels composed of single-layered CD34-positive endothelium and/or αSMA-positive pericytes in the tumor periphery, compared to microvascular proliferation with multi-channeled and pericyte-proliferating vessels in the tumor center. Intratumoral thrombosis was significantly correlated with the female sex, high preoperative D-dimer levels, and epidermal growth factor receptor (EGFR) amplification. The presence of one or more thrombi in 20 high-power fields was a predictive marker of EGFR amplification, with a sensitivity of 81.5% and specificity of 52.6%. RNA sequencing demonstrated that the group with many thrombi had higher EGFR gene expression levels than the group with few thrombi. The tumor cells invading along the vessels in the tumor periphery were positive for wild-type EGFR but negative for EGFRvIII, whereas the cells around the microvascular proliferation (MVP) in the tumor center were positive for both wild-type EGFR and EGFRvIII. Intratumoral thrombosis is an independent poor prognostic factor.

CONCLUSIONS

Aberrant but exquisitely regulated EGFR can induce thrombosis in non-MVP vessels in the tumor invasion area and then promote palisading necrosis, followed by hypoxia, abnormal angiogenesis, and further tumor cell invasion.
10180- ANGI-5 COMPREHENSIVE ANALYSIS OF MECHANISM OF INVASION AND DISSEMINATION FOR MALIGNANT BRAIN TUMOR USING XENOGRAFT MODELS
Authors: Kijima Noriyuki , Tachi Tetsuro , Achiha Takamune , Kuroda Hideki , Murakami Koki , Nakagawa Kanji , Wada Yuki , Kishima Haruhiko
Published: November 2024

BACKGROUND

Malignant brain tumors are frequently resistant to current treatments and have a poor prognosis. Many malignant brain tumors invade the surrounding brain tissue and/or show leptomeningeal metastasis when they recur. Thus, elucidating the mechanisms of invasion and leptomeningeal metastasis is important to improve the prognosis of malignant brain tumors. In this study, we comprehensively analyzed the mechanisms of invasion and leptomeningeal metastasis of malignant brain tumors using mouse xenograft models.

METHODS

Patient derived glioblastoma cells (GDC519) and breast cancer cell line, MDA-MB-231, were labeled with GFP and luciferase. GDC519 were transplanted into the right cerebral cortex of immunodeficient mice and when the mice got tumors, the right and left cerebrum were dissected separately. We sorted tumor cells by flow cytometry and extracted RNA from tumor cells in right and left cerebrum, respectively. We performed RNA sequencing and analyzed the transcriptome differences. On the other hand, MDA-MB-231 cells were injected into the right ventricle of immunodeficient mice. Tumor cells from cerebrospinal fluid, and spinal cords were sorted and analyzed the transcriptome differences by RNA sequencing.

RESULTS

In the model in which GDC519 was transplanted, we found significant differences in expressions of extracellular matrix related proteins, cell motility related proteins, and cell adhesion related proteins between tumor cells in right and left cerebrum. In addition, in the model in which MDA-MB-231 was transplanted into the right ventricle, we found significant differences in expressions of extracellular matrix related proteins and PI3K-Akt signaling pathway related proteins between tumor cells from cerebrospinal fluid and spinal cord.

CONCLUSION

These results suggest that it would be possible to identify molecules involved in the invasion and leptomeningeal metastasis of malignant brain tumors using a mouse xenograft model. Further studies are necessary to examine the functional role of these genes in invasion and leptomeningeal metastasis.
10096- CBMS-3 CURCUMIN ANALOGUE A SHOWS ANTI-TUMOR EFFECTS AT LOWER CONCENTRATIONS THAN CURCUMIN IN GLIOBLASTOMA CELLS
Authors: Ito Ryo , Hamabe Toshihide , Ono Masaya , Iwashimizu Sonoka , Inai Kyoko , Nakanishi Shunsuke , Sunagawa Yoichi , Katanasaka Yasufumi , Hawke Phillip , Arakawa Yoshiki , Miura Masatomo , Hasegawa Koji , Morimoto Tatsuya
Published: November 2024

PURPOSE

Curcumin (Cur), a natural compound, possesses antitumor activity against glioblastoma cells (GBM). However, the bioavailability of Cur is too low to exhibit beneficial effects in vivo. We hypothesized that Cur analogues with enhanced anti-tumor activity against GBM could increase bioavailability and effectiveness. This study investigated the anti-tumor activity of a Cur analog, Compound A (ComA), against GBM.

METHODS AND RESULTS

To evaluate the anti-tumor activity of ComA against GBM, an MTT assay was performed. Human GBM cell lines U251 and T98G were pre-treated with Cur or ComA, and then cell viability was examined using a CCK-8 kit. The IC50 values for U251 were 10.9 μM (Cur) and 2.9 μM (ComA), and those for T98G were 16.6 μM (Cur) and 4.7 μM (ComA). To examine the effects of Cur and ComA on non-tumor cells, the same MTT assay was performed on primary cultured astrocytes from neonatal rats. Neither Cur nor ComA resulted in reduced cell viability in astrocytes at concentrations that had had an anti-tumor effect on GBM cells. Next, a cell cycle analysis was performed on U251 and T98G cells using flow cytometry with PI staining. ComA induced G2/M phase arrest at lower concentrations than Cur. Furthermore, the amount of cellular uptake of Cur and ComA in these cells was quantified. Cellular uptake of ComA was 3.8 times higher than Cur in U251 cells and 3.5 times higher in T98G cells. Finally, when mice were orally administrated with Cur or ComA, the maximum plasma concentration of ComA was about 30 times higher than that of Cur.

DISCUSSION

These results suggest that ComA has an anti-tumor effect due to cell cycle arrest against GBM that occurs at lower concentrations than Cur. Further in vivo studies are required to develop ComA-based novel therapeutic agents against GBM.
10292- CBMS-7 HISTOLOGICAL GRADING AND MOLECULAR GENETIC BACKGROUND OF MENINGIOMAS
Authors: Eguchi Seiichiro , Zaitsu Kei , Ohtani Yuto , Iguchi Akira , Kawamata Takakazu
Published: November 2024

OBJECTIVES

In recent years, due to advances in omics analysis, new findings regarding the malignancy, growth potential, and prognosis of meningiomas have been reported. A classification based on molecular biology and genetic findings has a higher correlation with prognosis. Here, we report a comparative study of the histological malignancy and molecular genetic background of meningiomas using multi-omics analysis.

MATERIALS & METHODS

This study focused on 42 meningioma specimens including 17 meningothelial (G1), 18 atypical (G2) and 7 anaplastic (G3) subtypes, that were removed at our hospital. Metabolome and transcriptome analyses were performed on frozen specimens, multivariate analysis including PCA and PLS-DA was performed on the data obtained from the former, and DEG analysis, GO/pathway and hierarchical cluster analysis were performed on the latter data.

RESULTS

As a result of metabolome analysis, four samples were identified in G2 that had significantly different metabolic profiles from the others. These were designated as the G2 subtype (G2m). Transcriptome analysis confirmed the expression of just under 54,000 genes, and DEG analysis of these revealed that G2m had a significantly different gene expression profile from other G2s. Furthermore, pathway analysis revealed that the MAPK signaling pathway was enhanced in G2m, which was similar to that in G3. However, hierarchical cluster analysis showed that G2m was not similar to any of the profiles of G1-3 in the metabolome hierarchy.

DISCUSSIONS / CONCLUSIONS

It has been shown that among atypical meningiomas, there are subtypes that are molecular genetic similar to anaplastic meningiomas. It is thought that some subtypes of atypical meningiomas exhibit behavior similar to G1, while others are closer to G3. Furthermore, the influence of heterogeneity cannot be ignored even within the same tumor. In the future, it will be necessary to proceed with studies using single-cell RNA analysis.
10296- CBMS-8 CURCUMIN, AN INHIBITOR OF P300-HAT ACTIVITY, SUPPRESSED GLIOBLASTOMA CELL PROLIFERATION IN A STRUCTURE-ACTIVITY RELATIONSHIP STUDY
Authors: Inai Kyoko , Hamabe-Horiike Toshihide , Ono Masaya , Iwashimizu Sonoka , Ito Ryo , Nakanishi Syunsuke , Kawase Yuto , Naruta Ryuya , Sunagawa Yoichi , Katanasaka Yasufumi , Hawke Philip , Arakawa Yoshiki , Hasegawa Koji , Morimoto Tatsuya
Published: November 2024

PURPOSE

Glioblastoma (GBM) is the most common malignant brain tumor. In the treatment of GBM, it is difficult to completely remove tumor tissue by surgery alone, and radiotherapy and chemotherapy are typically used to treat the remaining tissue. However, GBM has a very poor prognosis, with a 5-year survival rate of approximately 10%. In recent years, molecular targeted therapies are becoming more common for all types of cancer, and histone acetylase (HAT) activity has attracted attention as a potential therapeutic target. It has been reported that the HAT activity of the transcriptional co-activator p300 plays a key role in the progression of pancreatic cancer. However, it is not clear whether p300-HAT activity is also crucial for the growth of GBM cells.

METHODS AND RESULTS

We previously reported that while the natural compound curcumin (Cur) inhibits p300-HAT activity, the Cur derivative GO-Y041 does not. To assess the role of p300-HAT activity in GBM cell proliferation, we compared the effect of Cur and GO-Y041 on the cells with an MTT assay. The human GBM cell line U87MG was treated with the two compounds, and cell viability was examined using CCK-8 kit. The results showed that the viability of the cells was significantly decreased by 10 μM Cur compared to the untreated group, while no decrease in viability was observed with 10 μM GO-Y041.

DISCUSSION

These results suggest that p300-HAT activity may play an important role in the proliferation of GBM cells. However, as Cur also acts on proteins other than p300, it is still not completely clear whether p300-HAT activity is essential for GBM growth. To provide insights into the role of p300-HAT activity in GBM cell growth, we will generate cells in which p300-HAT activity alone can be abolished using genetic engineering techniques to pursue the development of novel GBM therapies.
10159- SPDR-4 A RUNX1 SWITCH-OFF APPROACH INHIBITS THE PIF1-P21 AXIS, ONE OF THE MECHANISMS OF GLIOBLASTOMA MALIGNANCY MAINTENANCE
Authors: Yamamoto Etsuko , Masuda Tatsuya , Matsui Yasuzumi , Mineharu Youhei , Makino Yasuhide , Takada Shigeki , Sano Noritaka , Tannji Masahiro , Kamikubo Yasuhiko , Sugiyama Hiroshi , Arakawa Yoshiki
Published: November 2024

BACKGROUND

Glioblastoma is a high-grade brain tumor and Long-term survival is difficult even with multidisciplinary treatment, necessitating the development of novel therapeutic approaches. Although the transcription factor RUNX1 has been implicated in the maintenance of glioblastoma malignancy, its role is still unclear. We have previously demonstrated that administration of a new drug that inhibits transcription of the RUNX family, chlorambucil-conjugated PI polyamide (Chb-M’, co-developed by Kamikubo and Sugiyama), or RUNX1 knockdown, results in cell growth inhibition in glioblastoma cell lines and that the RUNX1-BIRC5-p21 axis is implicated.

METHODS AND RESULTS

Since RUNX1 is a transcription factor associated with multiple gene transcription, we performed microarray experiments using Chb-M’. Since PIF1 association was suggested, chromatin immunoprecipitation and reporter assay were performed, and these showed that RUNX1 directly regulates PIF1. The RUNX1-PIF1-p21 pathway was also found to be involved in the mechanism of glioblastoma malignancy maintenance, as RUNX1 knockdown decreased PIF1 and PIF1 knockdown suppressed cell proliferation and increased p21. Chb-M’ administration in mice glioblastoma model clearly reduced tumor size and prolonged survival compared to controls. In addition, FITC-binding Chb-M’ was administered to mice, and FITC selectively accumulated in tumors, indicating that Chb-M’ was shown to have tumor-specific effects.

DISCUSSION AND CONCLUSION

Chb-M’ has been shown to exert its antitumor effect via the PIF1/p21 axis, and Chb-M’ acts in vivo in a tumor-specific manner, making it a potential new therapeutic agent for glioblastoma. Furthermore, Chb-N’, which has higher cellular affinity than Chb-M’, has been developed and is currently under preclinical investigation.
10082- ET-9 ANTITUMOR AROMA THERAPY WITH FRANKINCENSE ESSENTIAL OIL FOR GLIOBLASTOMA
Authors: Saito Norihiko , Hirai Nozomi , Koyahara Yuki , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Ito Keisuke , Iwabuchi Satoshi
Published: November 2024

INTRODUCTION

Aromatic essential oils have antibacterial, antifungal, antiviral, anti-inflammatory, and antitumor effects. We previously investigated the antitumor effects of aromatic essential oils administered by inhalation as a novel treatment for glioblastoma. The aromatic monoterpene α-pinene, a component of many essential oils, is known to inhibit tumor growth. This study analyzed the antitumor effects of frankincense essential oil, mainly composed of α-pinene, and explored its potential for antitumor aroma therapy in glioblastoma.

METHODS AND RESULTS

Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used. Tumor cells cultured in the presence of frankincense essential oil for 72 hours showed growth inhibition, suggesting that the evaporated components acted on nearby tumor cells. α-Pinene and limonene, the main components of frankincense, also showed similar effects alone. Inhalation studies in mice demonstrated that 30 minutes of α-pinene inhalation had the same brain transfer effect as 90 minutes. Intraperitoneal administration of α-pinene showed minimal brain transfer. For limonene, brain transfer increased with 90 minutes of inhalation compared to 30 minutes. Inhalation resulted in higher brain transfer than intraperitoneal administration. Additionally, α-pinene’s antitumor effects suggested induction of apoptosis and cell cycle arrest.

DISCUSSION

α-Pinene, comprising about 40% of frankincense essential oil, was found to inhibit tumor cell growth in malignant gliomas. This study suggests that α-pinene exerts antitumor effects when administered by inhalation.

CONCLUSION

α-Pinene in frankincense essential oil has antitumor effects and may be a novel “aroma” therapy for treating glioblastoma.
10199- ET-16 NEAR-INFRARED PHOTOIMMUNOTHERAPY FOR THE TREATMENT OF MALIGNANT BRAIN TUMORS
Authors: Natsumeda Manabu , On Jotaro , Shibuma Satoshi , Watanabe Jun , Tsukamoto Yoshihiro , Okada Masayasu , Ogura Ryosuke , Oishi Makoto
Published: November 2024

BACKGROUND

Near-infrared photoimmunotherapy (NIR-PIT) is a novel intraoperative local therapy. It involves a photosensitizer a near-infrared dye (IR700) conjugated to monoclonal antibodies targeting surface antigens of cancer cells. After binding the monoclonal antibody-IR700 conjugate, irradiation with near-infrared light causes highly selective and potent cell death.

METHODS AND RESULTS

The antibodies used for NIR-PIT are as follows: podoplanin for malignant gliomas, SSTR2 for malignant meningiomas, and SSTR5 for GHoma. Expression of surface antigens in cell lines was confirmed by western blot and flow cytometry. We developed lasers for in vitro and in vivo assays. Time-lapse video recordings showed cell rupture and cell viability assays showed irradiation dose-dependent cytotoxicity after treatment with antibody-IR700 conjugate and near-infrared irradiation. In vivo and ex vivo studies were also performed, showing cell death. High selectivity and potency of NIR-PIT were observed, but proper penetration of light and kinetics of antibody were issues that remain to be solved. Preliminary studies confirmed that NIR-PIT is an exciting potential treatment for malignant brain tumors.
10176- IM-7 B7-H3-TARGETED CAR-T AND CAR-NK CELLS AGAINST HUMAN GLIOBLASTOMA
Authors: Tachi Tetsuro , Kijima Noriyuki , Kuroda Hideki , Murakami Koki , Hosen Naoki , Kishima Haruhiko
Published: November 2024

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor, necessitating novel therapies. Chimeric antigen receptor (CAR) T-cell therapy has recently shown efficacy against GBM. However, this approach is costly and time-consuming due to its personalized nature. Alternatively, CAR-transduced natural killer (NK) cells offer a potential “off-the-shelf” immunotherapy option, as they do not cause graft-versus-host disease. This study aimed to assess the anti-GBM efficacy of CAR T and NK cells targeting B7-H3, a protein highly expressed in GBM. To achieve this, CAR T cells targeting B7-H3 were developed using known anti-B7-H3 scFv sequences. Additionally, cord blood-derived NK cells were transduced with the B7-H3 CAR. Both types of CAR-modified cells were tested for their anti-GBM activity in vitro. Moreover, their anti-tumor effects were evaluated in an in vivo xenograft model using patient-derived GBM cells. The results demonstrated that both B7-H3 CAR T cells and CAR NK cells exhibited significant cytotoxicity against patient-derived GBM cells in vitro. Furthermore, intracranial injection of these CAR-modified cells into the xenograft model significantly reduced tumor growth. In conclusion, B7-H3 targeted CAR T cells and cord blood-derived CAR NK cells both show potential in eliminating GBM cells, suggesting promising avenues for future GBM treatment strategies.
10185- BOT-2 ANTITUMOR AROMA THERAPY WITH LEMONGRASS ESSENTIAL OIL FOR GLIOBLASTOMA
Authors: Hirai Nozomi , Saito Norihiko , Koyahara Yuki , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Ito Keisuke , Iwabuchi Satoshi
Published: November 2024

BACKGROUND

In glioblastoma, the only chemotherapy with a clear prognostic effect is temozolomide. Research and development of novel therapies to overcome glioblastoma resistance to treatment is ongoing. We have been studying antitumor aromatherapy using aromatic compounds in aromatic essential oils as a new treatment for glioblastoma. In this study, we focus on citral, the main component of lemongrass essential oil, and report that lemongrass essential oil shows anti-tumor effects in glioma cells and mouse brain tumor models.

METHODS

We used human glioma cells (U251, T98G) and mouse brain tumor cells (RSV-M). We examined the proliferation ability of lemongrass in glioma cells by transpiration and direct administration. The antitumor aroma effect of lemongrass essential oil inhalation in a mouse glioma brain tumor model was evaluated by survival time analysis using the Kaplan-Meier method.

RESULTS

After 72 hours of incubation of tumor cells in the presence of lemongrass essential oil, U251, T98G, and RSV-M all showed anti-proliferative effects, suggesting that the transpired lemongrass essential oil components acted on tumor cells in the vicinity. Direct administration of lemongrass essential oil also inhibited cell proliferation in all glioma cells in a dose- and time-dependent manner. Then, we examined the antitumor effect of lemongrass essential oil in a mouse brain tumor model using RSV-M. The results showed that the survival period was significantly prolonged in the lemongrass essential oil-inhaled group (n=6) compared to the control group (n=6) (p=0.0102), and the cumulative survival rate was not less than 50% at the end of the study.

CONCLUSION

Citral is the main component of lemongrass essential oil, containing about 80%. Citral may have an antitumor effect on glioblastoma, as evidenced by its transpiration effect. In addition, its antitumor effect was also observed in animal experiments, suggesting that it could be a new treatment for glioblastoma.
10154- ACT-8 CURRENT STATUS AND PROBLEMS OF GLIOBLASTOMA TREATMENT USING THE NOVOTTF-100A SYSTEM
Authors: Ogawa Takahiro , Takahashi Yoshinobu , Taniyama Ichita , Yamanaka Takumi , Hashimoto Naoya
Published: November 2024

PURPOSE

The AC electric field tumor therapy system (NovoTTF-100A system: NovoTTF) in combination with temozolomide chemotherapy is now covered by insurance as maintenance therapy for glioblastoma. While the system is expected to prolong survival, it is recommended to be used for at least 18 hours per day (75% of the time), making it difficult for some patients to continue using the system. We investigated the effect of NovoTTF usage rate on the efficacy of treatment based on our own experience.

METHOD

Thirteen patients with first-episode glioblastoma treated with NovoTTF between January 1, 2020 and June 30, 2024 were included in this study. 6 patients in the high daily use rate group (>75%) and 7 patients in the low daily use rate group (<75%) were compared.

RESULTS

The median age of patients in the high-use group was 63 (50-78) years, and 74 (50-79) years in the low-use group. 2-year survival rates were 33.3% and 0%, respectively, with some patients in the high-use group surviving longer than 2 years. Skin lesions occurred in 33.3% of the high-use group and 71.4% of the low-use group, with a higher incidence of skin lesions in the low-use group. The mean daily use rate was 86.0% (78.8-97.0) in the high use group and 38.3% (26.0-69.0) in the low use group, and the mean days of use were 342.5 (5-1086) and 88.7 (20-240), respectively. The median KPS was 90 (50-100) in the high use group and 90 (60-100) in the low use group.

CONCLUSION

The high NovoTTF use rate group tended to be younger and had a lower frequency of skin lesions, and there were cases of long-term survival. It is important to increase the use of NovoTTF for elderly patients and skin disorders.
10207- IMT-4 REAL-WORLD DATA AND IMMUNOHISTOLOGICAL STUDY OF AUTOLOGOUS FORMALIN-FIXED TUMOR VACCINE FOR NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Koriyama Shunichi , Nitta Masayuki , Tsuzuki Shunsuke , Kobayashi Tatsuya , Lyu Wendong , Komori Takashi , Masui Kenta , Kawamata Takakazu , Muragaki Yoshihiro
Published: November 2024

BACKGROUND

Glioblastoma (GBM) is a highly malignant tumor with a poor prognosis despite advances in treatment. At our institution, an autologous formalin-fixed tumor vaccine (AFTV) has been used as postoperative adjuvant therapy in addition to standard temozolomide and chemoradiotherapy. We present real-world data and analyze the correlation between AFTV, molecular markers, and clinical outcomes in newly diagnosed GBM patients.

METHODS

This study included 402 newly diagnosed GBM patients treated at our institution between 2005 and 2021. Patients were divided into AFTV (n = 158) and non-AFTV (n = 244) groups. The AFTV group demonstrated a significantly prolonged median progression-free survival (PFS) of 15.0 months compared to 7.8 months in the non-AFTV group (p<0.01) and a median overall survival (OS) of 31.3 months versus 19.4 months (p<0.01). In the subset of 60 patients who underwent gross total resection (GTR), the PFS was 18.4 months, and the OS reached 42.4 months, showing additional benefits. Among 115 elderly GBM patients, typically considered to have a poor prognosis, the AFTV group showed improved outcomes with a PFS of 14.2 months and OS of 27.3 months (p<0.01). In 131 patients who experienced early recurrent within 6 months, AFTV treatment resulted in an OS of 15.1 months compared to 9.4 months in the non-AFTV group (p<0.01). While no significant difference was observed in IDH-mutation, PDL-1 expression analysis in 53 patients revealed that those without PDL-1 expression had a better response to AFTV, with a median OS of 35.3 months compared to 28.4 months in PDL-1 positive patients.

CONCLUSION

AFTV significantly extends survival in GBM patients, particularly in those with GTR, elderly patients, and early recurrent cases. PDL-1 expression may influence AFTV efficacy, indicating the importance of this marker in ongoing and future clinical trials. Multidisciplinary treatment, including AFTV, offers promising potential for improving patient outcomes.
10046- STMO-4 AWAKE SURGERY WITH INTRAOPERATIVE MRI FOR INSULAR GLIOMA
Authors: Takada Shigeki , Makino Yasuhide , Yamamoto Etsuko , Sano Noritaka , Sawada Masahiro , Tanji Masahiro , Mineharu Yohei , Kikuchi Takayuki , Arakawa Yoshiki
Published: November 2024

BACKGROUND

Surgical resection of insular glioma remains challenging due to the complex functional involvement and the intricate vascularization of the insular lobe. We perform awake surgery with intraoperative MRI for insular glioma. We report the outcome of the surgical treatment for insular gliomas at our hospital.

METHODS

We retrospectively reviewed the records of 27 consecutive patients with insular gliomas who underwent surgical treatment between 2014 and 2024. The extent of resection (EOR), ischemic complication and Karnofsky Performance Status (KPS) at postoperative discharge were analyzed in the awake surgery (AS) group compared to the non-awake surgery (NAS) group.

RESULTS

In 12 cases, basal ganglion was involved (basal ganglionic involvement). Berger-Sanai zone III&IV was the most common site within the insula (10 cases), followed by I, II, III&IV (6 cases). Surgical resection was performed in 24 cases (biopsy in 3 cases). Elective awake surgery: 18 cases (of which 5 were abandoned due to poor arousal); intraoperative MRI: 24 cases. Additional resection after intraoperative MRI review was performed in 10 cases. The followings were studied in 24 cases where surgical resection was performed. In characteristics, basal ganglionic involvement was significantly different (3 patients in AS group and 7 patients in NAS group, p=0.04). The mean EOR was 81.4% in AS group vs. 53.4% in NAS group (p=0.008). Ischemic complication rate on postoperative MRI was 15.4% (2 cases) in AS group and 9.1% (1 case) in NAS group; all of them had no permanent neurological symptoms. The deterioration of KPS at discharge was not found in both groups.

DISCUSSION

The EOR of insular glioma in awake surgery with intraoperative MRI in this study was comparable to previous reports. It was indicated that awake surgery with intraoperative MRI contributes greatly to maximum safe resection for insular glioma.
10222- STMO-16 THE FENCE-POST METHOD WITH BONY SURFACE MATCHING REGISTRATION.
Authors: Sadahiro Hirokazu , Sugimoto Kazutaka , Ishihara Hideyuki
Published: November 2024

Neuronavigation has become an indispensable system for brain tumor surgery, and the fence-post method is useful for removal of intramedullary tumors. However, accurate registration is difficult in the lateral or prone position, and the fence-post method is hesitated. Skull registration is considered to be highly accurate, and we have found a method to perform skull registration with a limited amount of exposed skull. We have found a method to perform skull registration with a limited number of exposed skulls, and we report the results of the fence-post method using this method. from May 2023 to August 2024, patients who underwent the fence-post method in the lateral or supine position were included in the study. The navigation system was a StealthStation S8 (Medtronic), and skull registration was performed from CT. If impossible, a skull section was made in the navigation system according to the surgical site, and registration was performed using the skull localized in the surgical field. We encluded 11 cases, five with glioma and six with metastatic brain tumors. Two cases required a craniotomy larger than 10 cm for temporal lobectomy, and in these cases, skull registration was possible without any special modification. In the other 9 cases, the craniotomy was less than 10 cm, and normal skull registration was not possible, but the skull was limited to the operative field, and the fence-post technique was performed. Three cases of glioma were subtotal, and the others were total resections without complications. If the skull is localized to the operative field and sectioned within the navigation system, skull-based registration will be possible, improving the accuracy of the fence-post method and contributing to the safety of the surgery.
10271- STMO-23 TUMOR RECURRENCE PATTERNS AFTER SURGICAL RESECTION OF INTRACRANIAL LOW-GRADE GLIOMAS
Authors: Muragaki Yoshihiro , Fukuya Yasukazu , Ikuta Soko , Maruyama Takashi , Tsuzuki Shunsuke , Saito Taiichi , Kawamata Takakazu
Published: November 2024

INTRODUCTION

Tumor recurrence patterns after resection of intracranial low-grade gliomas (LGG) generally remain obscured. The objective of the present retrospective study was their multifaceted analysis, evaluation of associated factors, and assessment of impact on prognosis.

METHODS

Study group comprised 81 consecutive adult patients (46 men and 35 women; median age, 37 years) with recurrent diffuse astrocytomas (DA; 51 cases) and oligodendrogliomas (OD; 30 cases). The median length of follow-up after primary surgery was 6.7 years.

RESULTS

Early (within 2 years after primary surgery) and non-early (>2 years after primary surgery) recurrence was noted in 23 (28%) and 58 (72%) cases, respectively. Fast (< 6 months) and slow (>6 months) radiological progression of relapse was noted in 31 (38%) and 48 (59%) cases, respectively. Tumor recurrence was local and non-local in 71 (88%) and 10 (12%) cases, respectively. Recurrence patterns have differed in OD, IDH1-mutant DA, and IDH wild-type DA. Early onset, fast radiological progression, and non-local site of relapse had statistically significant negative impact on overall survival of patients and were often associated with malignant transformation of the tumor (38 cases). However, in subgroup with extent of resection > 90% (56 cases) no differences in recurrence characteristics were found between 3 molecularly defined groups of LGG.

CONCLUSIONS

Recurrence patterns after resection of LGG show significant variability, differ in distinct molecularly defined types of tumors, and demonstrate definitive impact on prognosis. Aggressive resection at the time of primary surgery may result in more favorable characteristics of recurrence at the time of its development.
10039- RT-1 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: November 2024

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 2024, 68 patients with recurrent glioblastoma treated with AVAgamma therapy as salvage therapy at the time of relapse after initial treatment. When the GK irradiated volume was 15 ml or less, a borderline dose of 20-26 Gy was administered in a single fraction, and when it was greater than that, a borderline dose of 24-30 Gy was administered in 2-5 fractions. The mean therapeutic marginal dose was 24 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-6month was 40%, OS-6month was 77%, and mOS was 11 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=0.05). The 5-year survival rate for glioblastoma with KPS>70% at recurrence was 0% in the GK group and 27% in the AVAgamma group (p=0.14).

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.
10260- MPC-25 INTEGRATED DIAGNOSIS OF GLIOMA IN KYOTO UNIVERSITY HOSPITAL
Authors: Takeucih Yasuhide , Mineharu Yohei , Arakawa Yoshiki
Published: November 2024

In 2021, WHO classification of tumours of the central nervous system (CNS) was published, which drastically changed the diagnostic approach of the tumors in the CNS. Although the latest classification has gradually become more widespread, it is still not easy to search for genetic mutations at many institutions in Japan, including Kyoto University Hospital (KUHP), and this remains an obstacle to the use of the above classification. At the 40th Brain Tumor Society Meeting held in 2022, we introduced our efforts in the diagnosis of glioma, including: (1) holding preoperative/postoperative clinical, imaging, and pathology conferences, (2) consultation to Kansai Molecular Diagnosis Network for CNS Tumors, (3) submission of specimens for cancer gene panel testing for insurance purposes, and (4) external consultation, DKFZ classification by methylation array analysis, and comprehensive analysis using next-generation sequencers. In our hospital during the 3 years from 2021 to 2023, approximately 140 cases of glioma including recurrence were diagnosed. The results of IDH1 R132H and H3K27M immunostaining and genetic abnormalities were consistent in all cases. On the other hand, some gliomas that were IDH1 R132H negative by immunostaining were reclassified as glioblastoma (n=13) or IDH2 mutant astrocytoma (n=1) based on molecular pathological findings, meaning that the diagnosis obtained from the initial pathological diagnosis may not be the correct one based on the molecular pathological findings. One case could not be classified even after performing (2)-(4) above, and one was found to have novel genetic abnormalities. As many medical institutions face difficulties in brain tumor classification based on the latest WHO classification, we would like to share our approach in this presentation and contribute to the improvement of brain tumor pathology diagnosis in Japan.
10068- NI-4 PREDICTIVE FACTOR OF TUMOR-SHRINKING EFFECTS FROM BEVACIZUMAB IN NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMAS
Authors: Beppu Takaaki , Sato Yuichi , Uchida Shun , Fujiwara Shunrou , Ogasawara Kuniaki , Akamatsu Yosuke
Published: November 2024

PURPOSE

Even after short-term administration of bevacizumab (Bev) demonstrates dramatically rapid volume reduction of glioblastoma. However, an extent of effect varies among patients. This study aimed to search prediction factors for tumor reduction in contrast-enhanced area (CEA) and peritumoral high intensity on FLAIR after Bev.

METHODS

Thirty patients with untreated primary glioblastoma and 34 patients with recurrent glioblastoma enrolled in this study. The former and latter received one-shot and two-shot Bev, respectively. MRI including arterial spin labeling (ASL) were performed before and after administrating Bev. We calculated tumor reduction rate (1-pre-volume/post-volume %) of CEA and HIA from MRI before and after Bev in each patient. Based on reduction rates, all patients were divided into three groups, Group A, patients with reduction rate more than mean value in both CEA and HIA; Group B, patients with reduction rate more than mean value in either CEA or HIA; Group C, patients with reduction rate more than mean value in neither CEA nor HIA. We compared findings of plausible factors, including volumes of CEA and HIA, tumor locations, presence of central necrosis, and CBFT/N on ASL, between three groups.

RESULTS

The reduction rates of CEA and HIA were 29.2% and 42.2% in untreated primary glioblastoma, and 46.5% and 36.3% in recurrent glioblastoma, respectively. The number of patients assigned into Groups A, B, and C were 9, 12, 9 in primary glioblastoma, and 8, 16, 8 in recurrent glioblastoma, respectively. Among factors, only CBFT/N showed a significant difference between 3 groups in both primary and recurrent glioblastomas in univariate analysis. Multi-variate analysis also showed CBFT/N could be a prediction factor in primary glioblastoma.

CONCLUSION

The present study suggested that CBFT/N becomes a prediction factor for reductions of tumor volumes after short-term administration of Bev in glioblastoma.
10219- NI-18 FUNCTIONAL RESECTION BOUNDARY INDICATED BY THE T2-FLAIR MISMATCH SIGN IN IDH-MUTANT GLIOMAS
Authors: Kinoshita Masashi , Nakajima Riho , Tanaka Shingo , Tamai Sho
Published: November 2024

INTRODUCTION

In IDH-mutant gliomas, the T2-FLAIR mismatch sign is a characteristic imaging marker suggestive of astrocytoma. Recently, it has been reported that IDH-mutant astrocytoma showing this feature have a good prognosis; however, the reason for this is still unclear. In this study, we investigated factors associated with gross-total resection of IDH-mutant gliomas in which awake surgery was performed, and validated the characteristics obtained from T2-FLAIR mismatch sign with results of functional mapping.

METHODS

From 2014 to 2023, 60 patients who underwent awake surgery and were diagnosed with IDH-mutant gliomas (WHO grade 2-3; 22 astrocytoma and 38 oligodendroglioma) were included in this study. T2-FLAIR mismatch sign, gross-total resection (GTR), and the following background factors that might have effects on the extent of resection in previous reports were extracted; primary or recurrent tumor, existence of positive functional mapping on the resection boundary of white matter, laterality and localization of the lesion, histopathological diagnosis, and WHO grading. First, statistical analysis of the relationship between GTR, T2-FLAIR mismatch sign, and background factors was performed using stepwise regression analysis. Second, neuroimaging analysis was performed to determine the spatial relationship between lesions and white matter mapping in cases with T2-FLAIR mismatch sign.

RESULTS

Twenty-six cases had no residual lesion after surgery, nine of which had T2-FLAIR mismatch sign and were diagnosed with astrocytoma. Analysis of GTR and background factors showed that T2-FLAIR mismatch sign (p=0.0043), no positive white matter mapping (p=0.0059), and WHO grade 2 (p=0.0182) were statistically significant factors that contributed to GTR. Furthermore, in 7 of the 9 cases with T2-FLAIR mismatch sign, GTR on postoperative neuroimaging was obtained with positive mappings on the normal white matter as the resection boundary.

CONCLUSION

IDH-mutant gliomas with T2-FLAIR mismatch sign may achieve GTR by awake surgery due to the absence of functional regions within the tumor.
10064- ML-2 CLINICAL CHARACTERISTICS OF NON-COMPLETE RESPONDERS TO MTX-BASED INDUCTION THERAPY IN PATIENTS WITH PRIMARY CNS LYMPHOMA
Authors: Nagane Motoo , Sasaki Nobuyoshi , Saito Kuniaki , Kobayashi Keiichi , Kugasawa Kazuha
Published: November 2024

BACKGROUND

The standard care for primary CNS lymphoma (PCNSL) is high-dose methotrexate (HD-MTX)-based induction therapy including R-MPV followed by consolidation therapy with a high CR/CRu rate. However, non-CR (refractory) patients may face poor prognosis, yet factors predicting response to R-MPV remain unclear. We conducted a retrospective analysis of newly diagnosed PCNSL cases treated with R-MPV at our facility.

METHODS

A total of 107 patients treated with R-MPV between November 2011 and December 2023 were identified. Clinical background factors, molecular pathological findings, the number of R-MPV cycles, dose reductions or drug discontinuations, response rates, PFS, and OS were analyzed.

RESULTS

The median age and KPS were 70 years (range 34-90) and 70 (30-90), respectively. Ocular lesions were present in 11 cases (11%), MYD88 mutations were found in 55 (66%), and 26 (38%) were of the GCB subtype. The median number of R-MPV cycles was 7 (1-8), with dose reduction or drug discontinuation in 75 cases (70%). After R-MPV, CR/CRu were achieved in 84 cases (79%), PR in 15 (14%), SD in 2 (2%), and 6 cases had PD (6%), with a non-CR rate of 21.5%. The median PFS was 87.8 months, with median OS not reached and a 5-year OS rate of 79.5%. The median PFS for CR cases was not reached, while for non-CR cases it was 22.5 months (P<0.001). For cases with or without methotrexate or procarbazine dose reduction/discontinuation, PFS was 42.2 months vs. not reached, respectively. The only factor significantly correlated with CR was the number of cycles (P<0.001), with a particularly significant correlation for 4 or more cycles (P<0.001).

CONCLUSIONS

Fewer number of R-MPV cycles (<4) was significantly associated with non-CR. As non-effective cases might result in early discontinuation, further analysis considering possible confounding factors is necessary.
10242- ML-11 A CASE OF PRIMARY CAVERNOUS SINUS MALIGNANT LYMPHOMA DIAGNOSED BY CRANIAL BIOPSY
Authors: Tamura Takeaki , Nakayama Noriyuki , Ohmura Kazufumi , Yamada Tetsuya , Izumo Tsuyoshi
Published: November 2024

BACKGROUND AND AIMS

Following neuroimaging studies, stereotactic irradiation is frequently utilized to treat cavernous sinus tumors. However, differentiating these tumors presents a significant challenge due to the overlapping imaging characteristics of various benign and malignant conditions, including cavernous hemangiomas, pituitary adenomas, schwannomas, meningiomas, sarcoidosis, and metastatic brain tumors.

PATIENT PRESENTATION

We report a rare case of diffuse large B-cell lymphoma (DLBCL) diagnosed via cranial biopsy of a cavernous sinus tumor. A 57-year-old man presented with a one-month history of diplopia and right-sided facial discomfort. Physical examination revealed right abducens nerve palsy and hypoesthesia in the distribution of the second branch of the right trigeminal nerve. Gadolinium-enhanced magnetic resonance imaging (MRI) demonstrated a homogeneously enhancing mass extending from the right cavernous sinus to the ipsilateral optic nerve canal, Meckel’s space, and foramen ovale. Whole-body computed tomography (CT) revealed no abnormalities. A cranial tumor biopsy was performed via an extradural temporopolar approach, resulting in a histopathological diagnosis of DLBCL.

TREATMENT AND RESULTS

Postoperatively, the patient underwent treatment with R-MPV (rituximab, methotrexate, vincristine, and procarbazine), pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone), and methotrexate infusion. Two months post-treatment, MRI revealed a reduction in the mass lesion, accompanied by improvements in both diplopia and trigeminal neuralgia.

INTERPRETATION

Primary malignant lymphoma of the cavernous sinus is characterized by a poor prognosis, with overall survival typically limited to a few months. Patients commonly present with facial pain and ocular motility disturbances. The lack of distinctive imaging findings complicates preoperative diagnosis. Although rare, primary malignant lymphomas should be included in the differential diagnosis of cavernous sinus tumors. Accurate histopathological diagnosis of these tumors is crucial for determining appropriate treatment regimens.
10291- ML-17 EXPRESSION OF ICAM-1,INTEGRINΒ1 IN INTRAVASCULAR LARGE B-CELL LYMPHOMA WITH CNS
Authors: Yoshitake Hidenobu , Negoto Tetsuya , Hashimoto Aya , Moritsubo Mayuko , Furuta Takuya , Sakata Kiyohiko , Nakamura Hideo , Morioka Motohiro
Published: November 2024

BACKGROUND

Intravascular lymphoma (IVLBCL) is generally characterized by growth within the microvasculature of extralymphatic organs and lack of invasion into the vessel wall or extravascular space. We experienced a case of concomitant intracranial DLBCL without IVL findings during the course of treatment for IVLBCL. Such cases are rare but have been reported in the past, and the origin of the tumor and the mechanism of metastasis are unknown. We investigated pathologically the deletion of cell adhesion molecules (ICAM-1, integrinβ1), which is considered to be a characteristic feature of IVLBCL, in this case.

METHODS

Among the cases treated at our hospital, 2 cases developed central nervous system intravascular lymphoma (CNS-IVL) after developing IVLBCL, 1 case developed CNS-IVL and subsequently relapsed cutaneous IVL, and 20 other PCNSL cases that followed the usual course of the disease were examined for ICAM-1 and integrinβ1 The histological characteristics of the 20 PCNSL cases were examined by immunostaining for ICAM-1 and integrinβ1.

RESULTS

In normal PCNSL, ICAM-1 and integrinβ1 were strongly expressed around blood vessels and tumor cells, and were absent in areas diffusely infiltrated into the brain parenchyma. In contrast, ICAM-1 and integrinβ1 in tumor cells were generally absent in patients with concomitant IVLBCL.

DISCUSSION

Deletion of cell adhesion molecules in IVLBCL is considered to be a factor that prevents invasion of vascular endothelium and loss of migration to lymph nodes. Interestingly, even in PCNSLs without evidence of IVL, there are areas of weak expression of cell adhesion molecules, suggesting that phenotype may be altered during the invasion process. The amount of specimens obtained from random skin biopsies is often extremely small. Therefore, histological findings will continue to be important.
10268- MET-24 A CASE OF BRAIN METASTASIS OF UTERINE CANCER REFRACTORY TO TREATMENT DUE TO RAPID CLINICAL PROGRESSION.
Authors: Ueno Takahiro , Ro Buntou , Tsuzuki Shunsuke , Koriyama Shunichi , Kawamata Takakazu , Muragaki Yoshihiro
Published: November 2024

The patient was a 57-year-old woman. She underwent laparotomy 14 months before her ER visit because of enlarged pelvic lymph nodes during follow-up for uterine adenomyosis. The pathological diagnosis was adenocarcinoma of adenomyosis origin, with metastasis to pelvic lymph nodes and a diagnosis of FIGO classification stage 3C1. She had been treated with six courses of TC (Paclitaxel+Carboplatin) postoperatively and was judged CR 2 months before the visit. She had visited the ER due to nausea and dizziness, and a head scan revealed a cerebellar tumor. She was admitted to the hospital on the same day for close examination and treatment. After admission, an MRI revealed a single, uniformly contrasted lesion, which was suspected of metastatic brain tumor from uterine cancer. On the 10th day of admission, we performed tumor resection and ventricular drainage. On the 15th day, nausea and dizziness improved, and the patient could eat full meals. On the 18th day, back pain and gastric discomfort due to postoperative defecation disorder appeared. FDG-PET performed on the 22nd day revealed systemic metastases, including thoracic spine and retroperitoneum. On the 33rd day, the patient developed impaired consciousness, and spinal fluid analysis showed positive atypical cells and hydrocephalus on a CT scan. After the surgery, her consciousness disorder improved, but she complicated thoracoabdominal effusion, urinary retention, and hydronephrosis, and died of multiple organ failure on the 47th day of hospitalization. Brain metastases from uterine cancer are rare, and there is little information on their clinical features, management, and prognosis. At the time of diagnosis, the patient was in an advanced state of organ failure due to metastatic lesions. When we detect brain metastasis in patients with uterine cancer, we should note that a high rate of metastasis to other organs would exist. Then, early systemic examination and therapeutic intervention are necessary.