Pub Date : 2023-12-01DOI: 10.1093/noajnl/vdad141.004
Taketo Ezaki, Toshihide Tanaka, R. Tamura, Yohei Yamamoto, Jun Takei, Yukina Morimoto, Ryotaro Imai, Y. Kuranari, Y. Akasaki, Yuichi Murayama, Keisuke Miyake, Hikaru Sasaki
Abstract The elucidation of the mechanism of action and resistance is imperative to overcome resistance to Bev and develop a more effective therapy. This study aims to investigate the status and change of alternative angiogenic factors regarding Bev usage using human specimens. The present study used 54 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naive Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory/autopsied Bev group). Importantly, naive Bev-refractory Bev of 22 specimens in 11 cases (including 4 autopsy specimens and 7 salvage surgery specimens) were obtained as paired specimens from the same patient. The expression of alternative angiogenic factors including basic fibroblast growth factor (bFGF), placental growth factor (PlGF), Angiopoietin1 (Ang-1), Angiopoietin2(Ang-2) and EphrinA2 were investigated via immunohistochemistry. PlGF expression was higher in the effective group than in the Naive group (p=0.048), and Ang-2 (0.047) and EphA2 (p=0.028) were higher in the relapse group than in the Naive group. Interestingly, in paired specimens, PlGF expression was higher in the refractory group than in the Naive group (p=0.036). This suggests that angiogenic factors other than VEGF are involved in recurrence. We provide the first clinicopathological evidence of the status of alternative angiogenic pathway after the Bev usage. These in situ observations will help to optimize therapy.
{"title":"10005-ANGI-1 REGULATION OF ALTERNATIVE ANGIOGENIC FACTORS IN BEVACIZUMAB THERAPY FOR GLIOBLASTOMA","authors":"Taketo Ezaki, Toshihide Tanaka, R. Tamura, Yohei Yamamoto, Jun Takei, Yukina Morimoto, Ryotaro Imai, Y. Kuranari, Y. Akasaki, Yuichi Murayama, Keisuke Miyake, Hikaru Sasaki","doi":"10.1093/noajnl/vdad141.004","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.004","url":null,"abstract":"Abstract The elucidation of the mechanism of action and resistance is imperative to overcome resistance to Bev and develop a more effective therapy. This study aims to investigate the status and change of alternative angiogenic factors regarding Bev usage using human specimens. The present study used 54 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naive Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory/autopsied Bev group). Importantly, naive Bev-refractory Bev of 22 specimens in 11 cases (including 4 autopsy specimens and 7 salvage surgery specimens) were obtained as paired specimens from the same patient. The expression of alternative angiogenic factors including basic fibroblast growth factor (bFGF), placental growth factor (PlGF), Angiopoietin1 (Ang-1), Angiopoietin2(Ang-2) and EphrinA2 were investigated via immunohistochemistry. PlGF expression was higher in the effective group than in the Naive group (p=0.048), and Ang-2 (0.047) and EphA2 (p=0.028) were higher in the relapse group than in the Naive group. Interestingly, in paired specimens, PlGF expression was higher in the refractory group than in the Naive group (p=0.036). This suggests that angiogenic factors other than VEGF are involved in recurrence. We provide the first clinicopathological evidence of the status of alternative angiogenic pathway after the Bev usage. These in situ observations will help to optimize therapy.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 32","pages":"v1 - v2"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138612659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1093/noajnl/vdad141.056
Y. Momii, Nobuhiro Hata, Minoru Fujiki
Abstract 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.
{"title":"10127-COT-15 REGIONAL MEDICAL DISPARITIES AND RESPONSES TO THE INCREASING COMPLEXITY OF GLIOBLASTOMA TREATMENT","authors":"Y. Momii, Nobuhiro Hata, Minoru Fujiki","doi":"10.1093/noajnl/vdad141.056","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.056","url":null,"abstract":"Abstract 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.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 26","pages":"v14 - v14"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138613610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract INTRODUCTION NTRK fusion gene-positive CNS tumours are rare and there are only two reports in Japan of the use of entrectinib, both in children; This is third case and the first adult case was experienced; the patient was treated by taking entrectinib. The diagnosis and treatment course are reported here and the problems with current oncopanel testings are discussed. CASE Female in her 60s. She came to the hospital on her own with a chief complaint of unstable walk. A mass with a maximum diameter of 8 cm was found in the right temporal occipital lobe. She underwent craniotomy followed by radiotherapy, and in-house panel testing (PleSSision Rapid Neo) detected two BCR-NTRK2 fusion genes. Subsequently, no NTRK gene abnormalities were detected in the foundation-one. Sanger sequencing was performed by ourselves, which could still detect gene mutations, and the patient was submitted to the NCC Onco-Panel at his own expense, where NTRK fusion gene abnormalities could be detected, and after review by the in-house ethics committee, he was started on entrectinib. The tumor showed a shrinking effect and has been stable for eight months. RESULT In the in-house panel test, NTRK2 covered Intron8,9,10,11,12 and two BCR-NTRK2 fusion genes were detected, (Exon1-Exon13) and (Exon1-Exon12). Foundation one covered Intron12 and no genetic variants were detected this time. Subsequently, the NCC OncoPanel test covered Intron 9, 10, 12, 13 and 14 and was able to detect fusion gene mutations. Different results were obtained for NTRK2 fusion gene mutations in each panel test, with different detection coverage. The differences in NTRK fusion gene mutations between tests indicate that it is important to reconfirm which panel test to choose. CONCLUSION Third case in Japan and first adult case of NTRK fusion gene mutation-positive brain tumor; may need to be addressed in NTRK fusion gene detection, recognizing differences in cancer multi-gene panel testing.
{"title":"10114-GMC-10 EXPERIENCE WITH DIFFERENTIAL NTRK2 FUSION GENE DETECTION IN CANCER MULTI-GENE PANEL TESTING","authors":"Jun Muto, Eishi Sugihara, Kentaro Tsukamoto, Eiji Yamada, Tamotsu Sudo, Hideyuki Saya, Yuichi Hirose","doi":"10.1093/noajnl/vdad141.050","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.050","url":null,"abstract":"Abstract INTRODUCTION NTRK fusion gene-positive CNS tumours are rare and there are only two reports in Japan of the use of entrectinib, both in children; This is third case and the first adult case was experienced; the patient was treated by taking entrectinib. The diagnosis and treatment course are reported here and the problems with current oncopanel testings are discussed. CASE Female in her 60s. She came to the hospital on her own with a chief complaint of unstable walk. A mass with a maximum diameter of 8 cm was found in the right temporal occipital lobe. She underwent craniotomy followed by radiotherapy, and in-house panel testing (PleSSision Rapid Neo) detected two BCR-NTRK2 fusion genes. Subsequently, no NTRK gene abnormalities were detected in the foundation-one. Sanger sequencing was performed by ourselves, which could still detect gene mutations, and the patient was submitted to the NCC Onco-Panel at his own expense, where NTRK fusion gene abnormalities could be detected, and after review by the in-house ethics committee, he was started on entrectinib. The tumor showed a shrinking effect and has been stable for eight months. RESULT In the in-house panel test, NTRK2 covered Intron8,9,10,11,12 and two BCR-NTRK2 fusion genes were detected, (Exon1-Exon13) and (Exon1-Exon12). Foundation one covered Intron12 and no genetic variants were detected this time. Subsequently, the NCC OncoPanel test covered Intron 9, 10, 12, 13 and 14 and was able to detect fusion gene mutations. Different results were obtained for NTRK2 fusion gene mutations in each panel test, with different detection coverage. The differences in NTRK fusion gene mutations between tests indicate that it is important to reconfirm which panel test to choose. CONCLUSION Third case in Japan and first adult case of NTRK fusion gene mutation-positive brain tumor; may need to be addressed in NTRK fusion gene detection, recognizing differences in cancer multi-gene panel testing.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 59","pages":"v13 - v13"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138613970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1093/noajnl/vdad141.001
R. Y. Osamura
Abstract It has been well known that the terminology has been changed from pituitary adenoma(4th WHO) which means benign epithelial tumors to pituitary neuroendocrine tumor(5th WHO 2022). It is apparent that the anterior pituitary cells and derived tumors contain intracytoplasmic neurosecretory granules and belong to neuroendocrine cells, and naturally neuroendocrine tumors. The pancreatic and gastrointestinal neuroendocrine neoplasms(NEN) are composed of well differentiated neuroendocrine tumors(NET) and poorly differentiated neuroendocrine carcinoma(NEC). NETs are potentially malignant(metastatic) tumors and are further graded to G1,G2,G3 by proliferative activities(mitoses or Ki-67 indices) showing correlation with prognosis . PitNET which means pituitary NET is now classified by transcription factors(PIT1,TPIT,SF1) and some tumors show clinical symptoms,(hormone production) invasive growth and rarely metastasize indicating potential malignant behavior. From this broad biological spectrum of PitNET, ICD-O coding /3(primary malignancy) has been proposed(5th WHO CNS, Pediatrics and Endocrine volumes). It has been known that some histological patterns (Sparsely granulated somatotroph PitNET, Crooke cell PitNET and others) are related more aggressive growth of PitNETs, but metastatic behavior is very hard to predict histologically. So in WHO 4th edition, the term pituitary carcinoma was used only after confirming metastasis or remote spread. The metastatic tumors are now called metastatic PitNETs. Five tiered grading by proliferation and invasion has been also proposed(Trouillas). Now we need more updated genomic studies such as single cell RNA sequencing to clarify biologic behavior of the individual PitNET cells to further clarify the their nature. . In my talk, several points of interests regarding PitNETs will be discussed by demonstrating histology and biology of representative cases.
{"title":"ED-1 PITUITARY TUMORS IN 5TH WHO CLASSIFICATION 2022: WHAT DO YOU MEAN BY PITNET?","authors":"R. Y. Osamura","doi":"10.1093/noajnl/vdad141.001","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.001","url":null,"abstract":"Abstract It has been well known that the terminology has been changed from pituitary adenoma(4th WHO) which means benign epithelial tumors to pituitary neuroendocrine tumor(5th WHO 2022). It is apparent that the anterior pituitary cells and derived tumors contain intracytoplasmic neurosecretory granules and belong to neuroendocrine cells, and naturally neuroendocrine tumors. The pancreatic and gastrointestinal neuroendocrine neoplasms(NEN) are composed of well differentiated neuroendocrine tumors(NET) and poorly differentiated neuroendocrine carcinoma(NEC). NETs are potentially malignant(metastatic) tumors and are further graded to G1,G2,G3 by proliferative activities(mitoses or Ki-67 indices) showing correlation with prognosis . PitNET which means pituitary NET is now classified by transcription factors(PIT1,TPIT,SF1) and some tumors show clinical symptoms,(hormone production) invasive growth and rarely metastasize indicating potential malignant behavior. From this broad biological spectrum of PitNET, ICD-O coding /3(primary malignancy) has been proposed(5th WHO CNS, Pediatrics and Endocrine volumes). It has been known that some histological patterns (Sparsely granulated somatotroph PitNET, Crooke cell PitNET and others) are related more aggressive growth of PitNETs, but metastatic behavior is very hard to predict histologically. So in WHO 4th edition, the term pituitary carcinoma was used only after confirming metastasis or remote spread. The metastatic tumors are now called metastatic PitNETs. Five tiered grading by proliferation and invasion has been also proposed(Trouillas). Now we need more updated genomic studies such as single cell RNA sequencing to clarify biologic behavior of the individual PitNET cells to further clarify the their nature. . In my talk, several points of interests regarding PitNETs will be discussed by demonstrating histology and biology of representative cases.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 38","pages":"v1 - v1"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138619200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1093/noajnl/vdad141.028
Ryuichi Hirayama, Shuhei Yamada, Takamitsu Iwata, Yuki Kawamoto, Kanji Nakagawa, Kouki Murakami, R. Utsugi, T. Tachi, Hideki Kuroda, Noriyuki Kijima, Y. Okita, Naoki Kagawa, H. Kishima
Abstract BACKGROUND The natural history of meningiomas is still unclear, and no guidelines have been established based on objective indices regarding the necessity and timing of therapeutic intervention. Objective: We attempted to provide statistics on the characteristics of tumor volume change, stratify tumor growth by risk factors, and generate a predictive tumor volume curve based on the statistics, with the aim of describing the natural history of meningiomas. METHODS 313 cases were included in the study, with the origin of meningioma being the circumflex and parasagittal sinus areas and the cerebral sickle region, and with multiple MRI scans performed at intervals of at least 3 months. Relative growth rate (RGR) and annual volume change (AVC) were calculated by tumor volume, and the patients were classified into three groups according to the combination of gender, age, and MRI T2WI signal intensity, and compared. RESULTS The median RGR and AVC of the entire cohort were 6.1% and 0.20 cm3/year, respectively, and there were significant differences between groups in gender (p=0.018) and MRI T2WI (p < 0.001) for RGR and tumor location (p=0.025) and initial tumor volume (p < 0.001)for AVC. The median RGR and AVC in the classification were 17.5% and 1.05 cm3/year for the very high growth group, 8.2% and 0.33 cm3/year for the high growth group, and 3.4% and 0.04 cm3/year for the low growth group, showing significant differences between the groups (p < 0.001). The predicted tumor volume curve showed an average 2.24-fold or 5.24 cm3 increase in volume over 5 years in the very high-growth group, while little tumor volume change was observed in the low-growth group. CONCLUSION The combination of growth risk factors allowed stratification of tumor growth and provided a predictive tumor volume curve for each county. The results may assist in the treatment of supratentorial meningiomas.
{"title":"10053-MNG-1 STRATIFICATION OF TUMOR VOLUME GROWTH RATE USING RISK FACTORS IN SUPRATENTORIAL MENINGIOMAS","authors":"Ryuichi Hirayama, Shuhei Yamada, Takamitsu Iwata, Yuki Kawamoto, Kanji Nakagawa, Kouki Murakami, R. Utsugi, T. Tachi, Hideki Kuroda, Noriyuki Kijima, Y. Okita, Naoki Kagawa, H. Kishima","doi":"10.1093/noajnl/vdad141.028","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.028","url":null,"abstract":"Abstract BACKGROUND The natural history of meningiomas is still unclear, and no guidelines have been established based on objective indices regarding the necessity and timing of therapeutic intervention. Objective: We attempted to provide statistics on the characteristics of tumor volume change, stratify tumor growth by risk factors, and generate a predictive tumor volume curve based on the statistics, with the aim of describing the natural history of meningiomas. METHODS 313 cases were included in the study, with the origin of meningioma being the circumflex and parasagittal sinus areas and the cerebral sickle region, and with multiple MRI scans performed at intervals of at least 3 months. Relative growth rate (RGR) and annual volume change (AVC) were calculated by tumor volume, and the patients were classified into three groups according to the combination of gender, age, and MRI T2WI signal intensity, and compared. RESULTS The median RGR and AVC of the entire cohort were 6.1% and 0.20 cm3/year, respectively, and there were significant differences between groups in gender (p=0.018) and MRI T2WI (p < 0.001) for RGR and tumor location (p=0.025) and initial tumor volume (p < 0.001)for AVC. The median RGR and AVC in the classification were 17.5% and 1.05 cm3/year for the very high growth group, 8.2% and 0.33 cm3/year for the high growth group, and 3.4% and 0.04 cm3/year for the low growth group, showing significant differences between the groups (p < 0.001). The predicted tumor volume curve showed an average 2.24-fold or 5.24 cm3 increase in volume over 5 years in the very high-growth group, while little tumor volume change was observed in the low-growth group. CONCLUSION The combination of growth risk factors allowed stratification of tumor growth and provided a predictive tumor volume curve for each county. The results may assist in the treatment of supratentorial meningiomas.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 9","pages":"v7 - v8"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138619923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1093/noajnl/vdad141.090
Yoshiki Fujikawa, Shinji Kawabata, Ryozo Kayama, Kohei Tsujino, Hideki Kashiwagi, Yusuke Fukuo, R. Hiramatsu, T. Takata, Hiroki Tanaka, Minoru Suzuki, N. Hu, S. Miyatake, Toshihiro Takami, M. Wanibuchi
Abstract BACKGROUND Boron Neutron Capture Therapy (BNCT) is a particle beam therapy that can target at the cellular level. This study evaluated the effectiveness of BNCT on spinal cord gliomas using animal models. METHODS F98 rat glioma or 9L rat gliosarcoma cell lines were implanted in rats' spinal cords to create a model. BPA, a boron compound, was administered and the biodistribution compared. Neutron irradiation was performed post-BPA injection, and the effectiveness was evaluated by survival period and hindlimb muscle strength using the Basso-Bresnahan-Beattie (BBB) score. RESULTS Significant boron accumulation was observed in tumors. In irradiation experiments, the BNCT group showed suppressed BBB score decrease and a significantly extended survival period compared to other groups. No cases of death or lower limb function decline were observed in the sham-BNCT group. CONCLUSION BNCT for spinal cord gliomas was shown to be safe and effective. The spinal cord is an organ at risk in irradiation for spinal cord and spine tumors. As it has a history of being a safety evaluation organ when applying BNCT to the central nervous system, BNCT may be applicable to cases such as recurrence after radiation therapy.
{"title":"10235-TB-9 TRANSLATIONAL RESEARCH OF BORON NEUTRON CAPTURE THERAPY FOR SPINAL CORD AND SPINE TUMOR IN ANIMAL MODELS","authors":"Yoshiki Fujikawa, Shinji Kawabata, Ryozo Kayama, Kohei Tsujino, Hideki Kashiwagi, Yusuke Fukuo, R. Hiramatsu, T. Takata, Hiroki Tanaka, Minoru Suzuki, N. Hu, S. Miyatake, Toshihiro Takami, M. Wanibuchi","doi":"10.1093/noajnl/vdad141.090","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.090","url":null,"abstract":"Abstract BACKGROUND Boron Neutron Capture Therapy (BNCT) is a particle beam therapy that can target at the cellular level. This study evaluated the effectiveness of BNCT on spinal cord gliomas using animal models. METHODS F98 rat glioma or 9L rat gliosarcoma cell lines were implanted in rats' spinal cords to create a model. BPA, a boron compound, was administered and the biodistribution compared. Neutron irradiation was performed post-BPA injection, and the effectiveness was evaluated by survival period and hindlimb muscle strength using the Basso-Bresnahan-Beattie (BBB) score. RESULTS Significant boron accumulation was observed in tumors. In irradiation experiments, the BNCT group showed suppressed BBB score decrease and a significantly extended survival period compared to other groups. No cases of death or lower limb function decline were observed in the sham-BNCT group. CONCLUSION BNCT for spinal cord gliomas was shown to be safe and effective. The spinal cord is an organ at risk in irradiation for spinal cord and spine tumors. As it has a history of being a safety evaluation organ when applying BNCT to the central nervous system, BNCT may be applicable to cases such as recurrence after radiation therapy.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 1","pages":"v22 - v23"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138620791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract 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.
{"title":"10150-GGE-16 INTRAOPERATIVE INTEGRATED DIAGNOSTIC SYSTEM FOR MALIGNANT CENTRAL NERVOUS SYSTEM TUMORS","authors":"Takahiro Hayashi, Akito Ooshima, Hirokuni Honma, Kyoka Sugino, Kaho Uchiyama, Miyui Kato, Yutaro Takayama, Masaki Sonoda, Hiromitsi Iwashita, Shoji Yamanaka, Masashi Fujii, Tetsuya Yamamoto, K. Tateishi","doi":"10.1093/noajnl/vdad141.059","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.059","url":null,"abstract":"Abstract 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.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"15 7‐8","pages":"v15 - v15"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138625061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1093/noajnl/vdad141.005
Akira Gomi, Hirofumi Oguma, Kensuke Kawai
Abstract INTRODUCTION In the new WHO Brain Tumor Classification of 2021, pediatric-type gliomas are classified separately from adult-type tumors. Additionally, with the advancement of cancer genomics, treatment options have expanded. Here we consider surgery for pediatric low-grade gliomas. METHODS We retrospectively analyzed 41 cases of low-grade gliomas or glioneuronal tumors in patients under 18 years of age who underwent surgery at our institute from 2002 to March 2023. We discussed surgical strategies based on molecular classification. RESULTS Among the cases, there were 34 gliomas and 7 glioneuronal tumors. According to the new WHO classification, they corresponded to 1) Adult-type diffuse gliomas, 2) Pediatric-type diffuse low-grade gliomas, 3) Circumscribed astrocytic tumors, or 4) Glioneuronal and neuronal tumors. Cases without molecular diagnosis were also considered in light of the new WHO classification. DISCUSSION Among molecularly diagnosed astrocytomas involving the cerebral hemisphere, brain stem, spinal cord, there were no cases of 1), and 2) 3) were the main cases. It is important in surgical selection to note that these cases generally have a more favorable prognosis compared to the adult type and have usefulness in diagnosing MAPK pathway abnormalities leading to the selection of molecularly targeted drugs. 3) includes pilocytic astrocytoma, subependymal giant cell astrocytoma, and pleomorphic xanthoastrocytoma. Among these, in the treatment of pilocytic astrocytomas located in the optic pathway and hypothalamus, biopsy becomes necessary for molecular diagnosis and the selection of appropriate therapeutic agents. Conversely, for unilateral optic nerve gliomas, options other than resection may be considered. 4) is primarily associated with epilepsy-related tumors. Surgical resection holds the promise of controlling epilepsy in these cases. However, various genetic abnormalities have been identified, which could prove useful in diagnosis and treatment. CONCLUSION Based on the new WHO classification, a reevaluation of treatment strategies for pediatric brain tumors is necessary.
{"title":"10006-PEDT-1 PEDIATRIC LOWER GRADE GLIOMA SURGERY IN THE ERA OF GENOMIC MEDICINE","authors":"Akira Gomi, Hirofumi Oguma, Kensuke Kawai","doi":"10.1093/noajnl/vdad141.005","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.005","url":null,"abstract":"Abstract INTRODUCTION In the new WHO Brain Tumor Classification of 2021, pediatric-type gliomas are classified separately from adult-type tumors. Additionally, with the advancement of cancer genomics, treatment options have expanded. Here we consider surgery for pediatric low-grade gliomas. METHODS We retrospectively analyzed 41 cases of low-grade gliomas or glioneuronal tumors in patients under 18 years of age who underwent surgery at our institute from 2002 to March 2023. We discussed surgical strategies based on molecular classification. RESULTS Among the cases, there were 34 gliomas and 7 glioneuronal tumors. According to the new WHO classification, they corresponded to 1) Adult-type diffuse gliomas, 2) Pediatric-type diffuse low-grade gliomas, 3) Circumscribed astrocytic tumors, or 4) Glioneuronal and neuronal tumors. Cases without molecular diagnosis were also considered in light of the new WHO classification. DISCUSSION Among molecularly diagnosed astrocytomas involving the cerebral hemisphere, brain stem, spinal cord, there were no cases of 1), and 2) 3) were the main cases. It is important in surgical selection to note that these cases generally have a more favorable prognosis compared to the adult type and have usefulness in diagnosing MAPK pathway abnormalities leading to the selection of molecularly targeted drugs. 3) includes pilocytic astrocytoma, subependymal giant cell astrocytoma, and pleomorphic xanthoastrocytoma. Among these, in the treatment of pilocytic astrocytomas located in the optic pathway and hypothalamus, biopsy becomes necessary for molecular diagnosis and the selection of appropriate therapeutic agents. Conversely, for unilateral optic nerve gliomas, options other than resection may be considered. 4) is primarily associated with epilepsy-related tumors. Surgical resection holds the promise of controlling epilepsy in these cases. However, various genetic abnormalities have been identified, which could prove useful in diagnosis and treatment. CONCLUSION Based on the new WHO classification, a reevaluation of treatment strategies for pediatric brain tumors is necessary.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"23 s2","pages":"v2 - v2"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138627339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1093/noajnl/vdad141.089
J. Yamaguchi, F. Ohka, K. Motomura, Y. Kibe, H. Shimizu, Tomohide Nishikawa, Sachi Maeda, Yuhei Takido, R. Saito
Abstract The WHO Classification the 5th edition describes that identification of alterations in IDH gene, histone H3 gene, CDKN2A gene, and other genes are quite important for the diagnosis and grading of diffuse gliomas. It is important to efficiently analyze important genetic abnormalities and utilize them in actual clinical practice. In our institute, we have recently performed genetic analysis which is important for the diagnosis of glioma in all patients. Here, we report the results of these analyses. From March 2019 to June 2023, we performed Sanger sequencing for analyses of IDH1/2, H3F3A, TERT promoter, BRAF, and FGFR1 mutation in 235 patients with suspected glioma who underwent biopsy or resection at our hospital and affiliated institutions. In 145 cases, we performed MLPA analyses for detection of 1p/19q codeletion, CDKN2A homozygous deletion (HD), EGFR amplification, and Chromosome 7p gain/10q loss. Sanger sequencing identified 81 TERT promoter mutations, 70 IDH mutations (including 3 IDH2 mutations), 8 BRAF V600E mutations, 4 H3 K27M mutations, 3 H3 G34R/V mutations, and 1 FGFR1 mutation The alterations most frequently identified in MLPA were CDKN2A HD in 26 cases and 1p/19q codeletion in 19 cases. Of the 214 cases in which the pathology diagnosis was neoplastic disease, 85 (39.8%) had no abnormalities in the above genetic analysis. In 32 of these cases, the pathological diagnosis was glioblastoma, IDH-wildtype, while in many other cases, the pathological diagnosis was low-grade glioma. Genetic analysis focusing on important genes for diagnosis according to WHO classification the 5th edition was useful for diagnosis in many cases, but careful consideration is needed for diagnosis in cases without these genetic alterations.
{"title":"10233-GMC-17 CLINICAL SIGNIFICANCE OF GENETIC ANALYSIS FOR GLIOMA CASES IN OUR INSTITUTE","authors":"J. Yamaguchi, F. Ohka, K. Motomura, Y. Kibe, H. Shimizu, Tomohide Nishikawa, Sachi Maeda, Yuhei Takido, R. Saito","doi":"10.1093/noajnl/vdad141.089","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.089","url":null,"abstract":"Abstract The WHO Classification the 5th edition describes that identification of alterations in IDH gene, histone H3 gene, CDKN2A gene, and other genes are quite important for the diagnosis and grading of diffuse gliomas. It is important to efficiently analyze important genetic abnormalities and utilize them in actual clinical practice. In our institute, we have recently performed genetic analysis which is important for the diagnosis of glioma in all patients. Here, we report the results of these analyses. From March 2019 to June 2023, we performed Sanger sequencing for analyses of IDH1/2, H3F3A, TERT promoter, BRAF, and FGFR1 mutation in 235 patients with suspected glioma who underwent biopsy or resection at our hospital and affiliated institutions. In 145 cases, we performed MLPA analyses for detection of 1p/19q codeletion, CDKN2A homozygous deletion (HD), EGFR amplification, and Chromosome 7p gain/10q loss. Sanger sequencing identified 81 TERT promoter mutations, 70 IDH mutations (including 3 IDH2 mutations), 8 BRAF V600E mutations, 4 H3 K27M mutations, 3 H3 G34R/V mutations, and 1 FGFR1 mutation The alterations most frequently identified in MLPA were CDKN2A HD in 26 cases and 1p/19q codeletion in 19 cases. Of the 214 cases in which the pathology diagnosis was neoplastic disease, 85 (39.8%) had no abnormalities in the above genetic analysis. In 32 of these cases, the pathological diagnosis was glioblastoma, IDH-wildtype, while in many other cases, the pathological diagnosis was low-grade glioma. Genetic analysis focusing on important genes for diagnosis according to WHO classification the 5th edition was useful for diagnosis in many cases, but careful consideration is needed for diagnosis in cases without these genetic alterations.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 12","pages":"v22 - v22"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138610093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1093/noajnl/vdad141.042
M. Natsumeda, Kazuhiro Ando, J. Watanabe, Haruhiko Takahashi, Y. Tsukamoto, M. Okada, Y. Fujii, Makoto Oishi
Abstract BACKGROUND We have previously reported elevated expression of podoplanin and high incidence of post-operative venous thromboembolism (VTE) in IDH-wildtype gliomas (Watanabe et al., World Neurosurgery, 2019). Podoplanin binds to C-type lectin-like receptor-2 (CLEC-2) on the surface of platelets and induces platelet aggregation, potentially leading to the development of VTE. In the present report, we monitor serum podoplanin and CLEC-2 after surgery in malignant glioma patients to directly determine if this is the cause of post-operative VTE. METHODS Fourty-four malignant glioma patients undergoing surgery at the Department of Neurosurgery, Niigata University Hospital between April, 2018 and August, 2020 were assessed. Platelet counts as well as serum D-dimer, podoplanin, soluble CLEC-2, and C2PAC index (soluble CLEC-2 divided by platelet count) were measured within 10 days after surgery. Serum podoplanin and soluble CLEC-2 were assessed by enzyme-linked immunosorbent assay (ELISA). Values for IDH-wildtype glioma patients and IDH-mutant glioma patients were compared to patients undergoing microvascular decompression (MVD) and healthy volunteers (HV). RESULTS Post-operative VTE was observed in 8 out of 35 (23%) IDH-wildtype glioma patients, compared to 1 out of 9 (11%) IDH-mutant glioma patients. Serum soluble CLEC-2 levels (p = 0.0004) and C2PAC index (p = 0.0002) were significantly elevated in IDH-wildtype glioma patients compared to IDH-mutant glioma, MVD and HV groups. A C2PAC index threshold of 3.7 provide an 87.5% sensitivity and 51.9% specificity to predict post-operative VTE in IDH-wildtype gliomas. We serially monitored podoplanin and soluble CLEC-2 in select patients, and found that podoplanin is transiently elevated, followed by soluble CLEC-2 after surgery. CONCLUSION Platelet aggregation due to the activation of podoplanin-CLEC2 axis leads to post-operative VTE in IDH-wildtype malignant glioma patients. The C2PAC index is a potential biomarker for the early detection of VTE after surgery in these patients.
我们之前报道过idh野生型胶质瘤中podoplanin表达升高和术后静脉血栓栓塞(VTE)发生率高(Watanabe et al.， World Neurosurgery, 2019)。Podoplanin与血小板表面的c型凝集素样受体2 (C-type lectin-like receptor-2, CLEC-2)结合，诱导血小板聚集，可能导致静脉血栓栓塞的发生。在本报告中，我们在恶性胶质瘤患者手术后监测血清podoplanin和CLEC-2，以直接确定这是否是术后静脉血栓栓塞的原因。方法对2018年4月至2020年8月在新泻大学医院神经外科接受手术的44例恶性胶质瘤患者进行评估。术后10天内测定血小板计数及血清d -二聚体、足平面蛋白、可溶性CLEC-2、C2PAC指数(可溶性CLEC-2除以血小板计数)。采用酶联免疫吸附试验(ELISA)检测血清podoplanin和可溶性CLEC-2。将idh野生型胶质瘤患者和idh突变型胶质瘤患者与微血管减压(MVD)患者和健康志愿者(HV)的价值进行比较。结果:35例idh野生型胶质瘤患者中有8例(23%)出现术后静脉血栓栓塞，而9例idh突变型胶质瘤患者中有1例(11%)出现术后静脉血栓栓塞。与idh突变型胶质瘤、MVD和HV组相比，idh野生型胶质瘤患者血清可溶性CLEC-2水平(p = 0.0004)和C2PAC指数(p = 0.0002)显著升高。C2PAC指数阈值为3.7，预测idh野生型胶质瘤术后静脉血栓栓塞的敏感性为87.5%，特异性为51.9%。我们在选定的患者中连续监测podoplanin和可溶性CLEC-2，发现podoplanin在手术后短暂升高，随后是可溶性CLEC-2。结论idh野生型恶性胶质瘤患者术后VTE的发生与podoplanin-CLEC2轴活化引起的血小板聚集有关。C2PAC指数是这些患者术后早期发现静脉血栓栓塞的潜在生物标志物。
{"title":"10091-COT-12 ELUCIDATING THE PATHOPHYSIOLOGY OF POST-OPERATIVE VENOUS THROMBOEMBOLISM IN IDH-WILDTYPE MALIGNANT GLIOMAS","authors":"M. Natsumeda, Kazuhiro Ando, J. Watanabe, Haruhiko Takahashi, Y. Tsukamoto, M. Okada, Y. Fujii, Makoto Oishi","doi":"10.1093/noajnl/vdad141.042","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.042","url":null,"abstract":"Abstract BACKGROUND We have previously reported elevated expression of podoplanin and high incidence of post-operative venous thromboembolism (VTE) in IDH-wildtype gliomas (Watanabe et al., World Neurosurgery, 2019). Podoplanin binds to C-type lectin-like receptor-2 (CLEC-2) on the surface of platelets and induces platelet aggregation, potentially leading to the development of VTE. In the present report, we monitor serum podoplanin and CLEC-2 after surgery in malignant glioma patients to directly determine if this is the cause of post-operative VTE. METHODS Fourty-four malignant glioma patients undergoing surgery at the Department of Neurosurgery, Niigata University Hospital between April, 2018 and August, 2020 were assessed. Platelet counts as well as serum D-dimer, podoplanin, soluble CLEC-2, and C2PAC index (soluble CLEC-2 divided by platelet count) were measured within 10 days after surgery. Serum podoplanin and soluble CLEC-2 were assessed by enzyme-linked immunosorbent assay (ELISA). Values for IDH-wildtype glioma patients and IDH-mutant glioma patients were compared to patients undergoing microvascular decompression (MVD) and healthy volunteers (HV). RESULTS Post-operative VTE was observed in 8 out of 35 (23%) IDH-wildtype glioma patients, compared to 1 out of 9 (11%) IDH-mutant glioma patients. Serum soluble CLEC-2 levels (p = 0.0004) and C2PAC index (p = 0.0002) were significantly elevated in IDH-wildtype glioma patients compared to IDH-mutant glioma, MVD and HV groups. A C2PAC index threshold of 3.7 provide an 87.5% sensitivity and 51.9% specificity to predict post-operative VTE in IDH-wildtype gliomas. We serially monitored podoplanin and soluble CLEC-2 in select patients, and found that podoplanin is transiently elevated, followed by soluble CLEC-2 after surgery. CONCLUSION Platelet aggregation due to the activation of podoplanin-CLEC2 axis leads to post-operative VTE in IDH-wildtype malignant glioma patients. The C2PAC index is a potential biomarker for the early detection of VTE after surgery in these patients.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 1084","pages":"v11 - v11"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138610658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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