Abstract The main treatment for metastatic brain tumors is radiation therapy or surgical removal. Since the pembrolizumab, an anti-PD1 monoclonal antibody, was revealed to be effective for brain metastases of lung cancer, it has been used as a therapeutic option. However, the predictive factors of its efficacy have been unclear. If the efficacy of pembrolizumab can be predicted prior to the treatment of metastatic brain tumors, it will have a significant impact on subsequent treatment strategies. In this study, we performed a retrospective analysis of patients with metastatic brain tumors from lung cancer treated with pembrolizumab to investigate predictive factors of pembrolizumab efficacy. From January 2018 to July 2023, 73 patients were treated with pembrolizumab for brain metastases of lung cancer at our institution. Among them, 16 patients who had received pembrolizumab for at least 1 year were included. Median age was 68 years (45-86), 10 were male (63%), and median period of pembrolizumab treatment was 105 months (49-319). Patients with brain metastasis which was well controlled for at least 2 years after starting pembrolizumab were defined as effective, and those who required new treatment were defined as invalid. There were 11 effective cases and 5 invalid cases. We compared clinical characteristics, genetic characteristics of the primary tumor, and imaging characteristics of metastatic brain tumors between the effective and ineffective cases, and identified predictive factors for efficacy of pembrolizumab.
{"title":"10195-MET-11 THE PREDICTIVE FACTORS OF EFFICACY OF PEMBROLIZUMAB IN BRAIN METASTASES OF LUNG CANER","authors":"Shinji Kawamura, Ryohei Otani, Ryoji Yamada, Sakura Shimizu","doi":"10.1093/noajnl/vdad141.076","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.076","url":null,"abstract":"Abstract The main treatment for metastatic brain tumors is radiation therapy or surgical removal. Since the pembrolizumab, an anti-PD1 monoclonal antibody, was revealed to be effective for brain metastases of lung cancer, it has been used as a therapeutic option. However, the predictive factors of its efficacy have been unclear. If the efficacy of pembrolizumab can be predicted prior to the treatment of metastatic brain tumors, it will have a significant impact on subsequent treatment strategies. In this study, we performed a retrospective analysis of patients with metastatic brain tumors from lung cancer treated with pembrolizumab to investigate predictive factors of pembrolizumab efficacy. From January 2018 to July 2023, 73 patients were treated with pembrolizumab for brain metastases of lung cancer at our institution. Among them, 16 patients who had received pembrolizumab for at least 1 year were included. Median age was 68 years (45-86), 10 were male (63%), and median period of pembrolizumab treatment was 105 months (49-319). Patients with brain metastasis which was well controlled for at least 2 years after starting pembrolizumab were defined as effective, and those who required new treatment were defined as invalid. There were 11 effective cases and 5 invalid cases. We compared clinical characteristics, genetic characteristics of the primary tumor, and imaging characteristics of metastatic brain tumors between the effective and ineffective cases, and identified predictive factors for efficacy of pembrolizumab.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 70","pages":"v19 - v19"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138612373","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/vdad141.069
Tachi Tetsuro, Noriyuki Kijima, Hideki Kuroda, Syunya Ikeda, Koki Murakami, Kanji Nakagawa, R. Utsugi, Yuki Kawamoto, Ryuichi Hirayama, Y. Okita, Naoki Kagawa, Naoki Hosen, H. Kishima
Abstract There is an urgent need to find new treatments for brain tumors with poor prognoses, such as glioblastoma (GBM). Recently, CAR-T cell therapy, which uses genetically engineered T cells to express chimeric antigen receptors (CAR) has been actively investigated. However, although CAR-T cell therapy has shown efficacy in preclinical GBM models, CAR-T cells have a number of limitations. When adapted for clinical use, it may exhibit undesirable side effects such as graft-versus-host disease or cytokine-releasing syndrome. Furthermore, generating an autologous product for each patient needs time and effort and is restrictive for widespread clinical use. In contrast, cord blood-derived natural killer (NK) cells show a robust safety profile in vivo and are an attractive therapeutic option for cancer treatment. In this study, we focused on developing CAR-NK therapy against GBM and used B7H3 which has recently been studied as a tumor antigen. First, we generated CAR-T cells expressing CAR against B7H3 and confirmed their antitumor effect in vitro and in vivo. Next, we generated CAR-NK cells with similar scFV from code blood. We generated eight donors of CAR-transfected NK cells and investigated the gene transfer and cell growth rate. We tested three donors of CAR-transfected NK cells and found that one of them had robust cytolytic activity against GBM cells in vitro. Overall, this study suggests that cord blood-derived CAR-NK cells targeting B7H3 may be a promising therapy for GBM.
{"title":"10172-IM-6 DEVELOPMENT OF CAR-NK CELL THERAPY TARGETING B7H3 AGAINST GLIOBLASTOMA","authors":"Tachi Tetsuro, Noriyuki Kijima, Hideki Kuroda, Syunya Ikeda, Koki Murakami, Kanji Nakagawa, R. Utsugi, Yuki Kawamoto, Ryuichi Hirayama, Y. Okita, Naoki Kagawa, Naoki Hosen, H. Kishima","doi":"10.1093/noajnl/vdad141.069","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.069","url":null,"abstract":"Abstract There is an urgent need to find new treatments for brain tumors with poor prognoses, such as glioblastoma (GBM). Recently, CAR-T cell therapy, which uses genetically engineered T cells to express chimeric antigen receptors (CAR) has been actively investigated. However, although CAR-T cell therapy has shown efficacy in preclinical GBM models, CAR-T cells have a number of limitations. When adapted for clinical use, it may exhibit undesirable side effects such as graft-versus-host disease or cytokine-releasing syndrome. Furthermore, generating an autologous product for each patient needs time and effort and is restrictive for widespread clinical use. In contrast, cord blood-derived natural killer (NK) cells show a robust safety profile in vivo and are an attractive therapeutic option for cancer treatment. In this study, we focused on developing CAR-NK therapy against GBM and used B7H3 which has recently been studied as a tumor antigen. First, we generated CAR-T cells expressing CAR against B7H3 and confirmed their antitumor effect in vitro and in vivo. Next, we generated CAR-NK cells with similar scFV from code blood. We generated eight donors of CAR-transfected NK cells and investigated the gene transfer and cell growth rate. We tested three donors of CAR-transfected NK cells and found that one of them had robust cytolytic activity against GBM cells in vitro. Overall, this study suggests that cord blood-derived CAR-NK cells targeting B7H3 may be a promising therapy for GBM.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 4","pages":"v17 - v17"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138612810","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/vdad141.032
Kyoko Inai, Toshihide Hamabe-Horiike, Masaya Ono, Sonoka Iwashimizu, Ryo Ito, Yoichi Sunagawa, Y. Katanasaka, Yoshiki Arakawa, Koji Hasegawa, T. Morimoto
Abstract PURPOSE Glioblastoma (GBM) has a high risk of recurrence and a poor prognosis due to the difficulty of surgical resection and resistance to the standard treatment, temozolomide. Therefore, the development of noble therapeutic agents against GBM is required. This study investigated the anti-tumor activity of the curcumin (Cur) analog Compound B (ComB) against GBM. METHODS AND RESULTS To evaluate anti-tumor activity against GBM, we performed an MTT assay. The human glioblastoma cell lines U87-MG and U251 were pre-treated with Cur or ComB, and then cell viability was examined using a cell counting kit, and IC50 values were calculated. The IC50 value for U87-MG of Cur was 9.78 μM, and that of ComB was1.28 μM. The IC50 value for U251 of Cur was 9.50 μM, and that of ComB was 0.64 μM. To examine the effects of ComB on normal cells, the same MTT assay was performed on primary cultured astrocytes prepared from neonatal rats. ComB did not reduce cell viability in astrocytes at concentrations that had an anti-tumor effect on GBM cells. Next, a cell cycle analysis was performed with Propidium Iodide (PI) staining and an apoptosis assay with Annexin V/PI staining using flow cytometry. ComB induced cell cycle G2/M arrest and apoptosis at lower concentrations than Cur. qPCR showed that mRNA expression levels of CDK1 and CyclinB1, which play an essential role in the progression from the G2 phase to the M phase, decreased by ComB at lower concentrations than Cur. DISCUSSION These results suggest that ComB, at lower concentrations than Cur, has an anti-tumor effect without affecting normal cells by inducing cell cycle arrest and apoptosis against GBM. Further detailed analysis and in vivo studies are expected to lead to the development of novel therapeutic agents for GBM.
{"title":"10073-CBMS-6 CURCUMIN ANALOG B EXHIBIT ANTI-TUMOR ACTIVITY AGAINST GLIOBLASTOMAAT LOWER CONCENTRATIONS THAN CURCUMIN","authors":"Kyoko Inai, Toshihide Hamabe-Horiike, Masaya Ono, Sonoka Iwashimizu, Ryo Ito, Yoichi Sunagawa, Y. Katanasaka, Yoshiki Arakawa, Koji Hasegawa, T. Morimoto","doi":"10.1093/noajnl/vdad141.032","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.032","url":null,"abstract":"Abstract PURPOSE Glioblastoma (GBM) has a high risk of recurrence and a poor prognosis due to the difficulty of surgical resection and resistance to the standard treatment, temozolomide. Therefore, the development of noble therapeutic agents against GBM is required. This study investigated the anti-tumor activity of the curcumin (Cur) analog Compound B (ComB) against GBM. METHODS AND RESULTS To evaluate anti-tumor activity against GBM, we performed an MTT assay. The human glioblastoma cell lines U87-MG and U251 were pre-treated with Cur or ComB, and then cell viability was examined using a cell counting kit, and IC50 values were calculated. The IC50 value for U87-MG of Cur was 9.78 μM, and that of ComB was1.28 μM. The IC50 value for U251 of Cur was 9.50 μM, and that of ComB was 0.64 μM. To examine the effects of ComB on normal cells, the same MTT assay was performed on primary cultured astrocytes prepared from neonatal rats. ComB did not reduce cell viability in astrocytes at concentrations that had an anti-tumor effect on GBM cells. Next, a cell cycle analysis was performed with Propidium Iodide (PI) staining and an apoptosis assay with Annexin V/PI staining using flow cytometry. ComB induced cell cycle G2/M arrest and apoptosis at lower concentrations than Cur. qPCR showed that mRNA expression levels of CDK1 and CyclinB1, which play an essential role in the progression from the G2 phase to the M phase, decreased by ComB at lower concentrations than Cur. DISCUSSION These results suggest that ComB, at lower concentrations than Cur, has an anti-tumor effect without affecting normal cells by inducing cell cycle arrest and apoptosis against GBM. Further detailed analysis and in vivo studies are expected to lead to the development of novel therapeutic agents for GBM.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 45","pages":"v8 - v9"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138614543","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/vdad141.052
Yuhei Takido, F. Ohka, K. Motomura, J. Yamaguchi, Sachi Maeda, Tomohide Nishikawa, Y. Kibe, H. Shimizu, R. Saito
Abstract OBJECTIVE Tumor-Treating Fields therapy has been the standard therapy for newly diagnosed glioblastoma since 2018 in Japan. The patients are recommended to use the system for 18 or more hours per day. In practice, some patients could not use it long-term and dropped out from this therapy. We examined factors related to interruption of NovoTTF use. METHODS We reviewed the clinical course of NovoTTF-100A system (NovoTTF) in cases at our hospital from April 2018 to May 2023. We compared the group that continued to use NovoTTF or used it until the disease progressed (Group A) with the group that discontinued it for their own reasons (Group B). RESULTS There were 22 patients, 14 in group A and 8 in group B. The mean preoperative tumor volume was 25.3 cm3 in group A and 38.7 cm3 in group B (p=0.27). The mean number of days of NovoTTF use was 437 in Group A and 27 in Group B (p<0.05). The mean usage rate was 70% in group A and 22% in group B (p<0.05). Tumors were located in 6 frontal lobes, 3 temporal lobes, 3 parietal lobes, 1 basal ganglia, and 1 thalamus in group A, while 1 frontal lobe, 6 temporal lobes, and 1 parietal lobe in group B. Among six temporal lobe cases in group B, five revealed temporal lesions in the dominant hemisphere, causing moderate or severe aphasia before surgery. CONCLUSION The group that continued NovoTTF maintained its usage rate as well as the number of days of use, while the group of cases that discontinued for their own reasons had a low use rate. Five of the eight discontinued cases had temporal lobe lesions in the dominant hemisphere and had aphasia symptoms. Difficulties in understanding the need for NovoTTF may have contributed to the discontinuation.
{"title":"10119-ACT-9 LONG-TERM USAGE OF TUMOR-TREATING FIELDS THERAPY FOR TREATMENT OF MALIGNANT GLIOMA","authors":"Yuhei Takido, F. Ohka, K. Motomura, J. Yamaguchi, Sachi Maeda, Tomohide Nishikawa, Y. Kibe, H. Shimizu, R. Saito","doi":"10.1093/noajnl/vdad141.052","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.052","url":null,"abstract":"Abstract OBJECTIVE Tumor-Treating Fields therapy has been the standard therapy for newly diagnosed glioblastoma since 2018 in Japan. The patients are recommended to use the system for 18 or more hours per day. In practice, some patients could not use it long-term and dropped out from this therapy. We examined factors related to interruption of NovoTTF use. METHODS We reviewed the clinical course of NovoTTF-100A system (NovoTTF) in cases at our hospital from April 2018 to May 2023. We compared the group that continued to use NovoTTF or used it until the disease progressed (Group A) with the group that discontinued it for their own reasons (Group B). RESULTS There were 22 patients, 14 in group A and 8 in group B. The mean preoperative tumor volume was 25.3 cm3 in group A and 38.7 cm3 in group B (p=0.27). The mean number of days of NovoTTF use was 437 in Group A and 27 in Group B (p<0.05). The mean usage rate was 70% in group A and 22% in group B (p<0.05). Tumors were located in 6 frontal lobes, 3 temporal lobes, 3 parietal lobes, 1 basal ganglia, and 1 thalamus in group A, while 1 frontal lobe, 6 temporal lobes, and 1 parietal lobe in group B. Among six temporal lobe cases in group B, five revealed temporal lesions in the dominant hemisphere, causing moderate or severe aphasia before surgery. CONCLUSION The group that continued NovoTTF maintained its usage rate as well as the number of days of use, while the group of cases that discontinued for their own reasons had a low use rate. Five of the eight discontinued cases had temporal lobe lesions in the dominant hemisphere and had aphasia symptoms. Difficulties in understanding the need for NovoTTF may have contributed to the discontinuation.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 9","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":"138616689","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/vdad141.078
T. Matsutani, S. Hirono, Masayoshi Kobayashi, Yoshinori Higuchi
Abstract In 2020, Tirabrutinib (TIR) was approved in Japan as a novel treatment for primary CNS lymphoma (PCNSL). However, the position of TIR in relation to the existing therapy, methotrexate (MTX)-based therapy, is still unclear. We are currently using TIR for patients who have insensitivity to MTX, have short-term recurrence after MTX, or have difficulty receiving MTX, with the principle of readministering MTX-based therapy to patients with recurrent disease. The subjects were ten patients treated with TIR at our institute, 6 with multiple relapses, 3 with inability to MTX, and 1 with difficulty in MTX treatment, and the mean number of relapses was 3.8 when Tirabrutinib was used. The mean number of treatments was 104 days, and 7 patients discontinued treatment due to tumor progression, while 3 patients discontinued due to severe skin problems. The median progression-free survival was 99 days, and only one patient was controlled for more than one year. 4 patients received the best supportive care for recurrence after TIR, and one patient received radiotherapy. The four patients in the MTX-based retreatment group had two progressions and two no progressions at the time of the abstract, with a progression-free survival of 133 days, and two patients had CTCAE grade 4 hematologic toxicities that had not occurred with previous therapy. One patient treated surgically died of postoperative pneumocystis pneumonia. Tirabrutinib showed a high early response rate, but the duration of tumor control tended to be shorter than with MTX-based retreatment. This may be due to its use in our institution after multiple relapses and its aggressive administration in MTX-naive patients. It is also important to note that chemotherapy after TIR use is associated with increased hematologic toxicity.
{"title":"10203-ML-6 TIRABRUTINIB FOR PRIMARY CNS LYMPHOMA: A SINGLE INSTITUTE RETROSPECTIVE ANALYSIS","authors":"T. Matsutani, S. Hirono, Masayoshi Kobayashi, Yoshinori Higuchi","doi":"10.1093/noajnl/vdad141.078","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.078","url":null,"abstract":"Abstract In 2020, Tirabrutinib (TIR) was approved in Japan as a novel treatment for primary CNS lymphoma (PCNSL). However, the position of TIR in relation to the existing therapy, methotrexate (MTX)-based therapy, is still unclear. We are currently using TIR for patients who have insensitivity to MTX, have short-term recurrence after MTX, or have difficulty receiving MTX, with the principle of readministering MTX-based therapy to patients with recurrent disease. The subjects were ten patients treated with TIR at our institute, 6 with multiple relapses, 3 with inability to MTX, and 1 with difficulty in MTX treatment, and the mean number of relapses was 3.8 when Tirabrutinib was used. The mean number of treatments was 104 days, and 7 patients discontinued treatment due to tumor progression, while 3 patients discontinued due to severe skin problems. The median progression-free survival was 99 days, and only one patient was controlled for more than one year. 4 patients received the best supportive care for recurrence after TIR, and one patient received radiotherapy. The four patients in the MTX-based retreatment group had two progressions and two no progressions at the time of the abstract, with a progression-free survival of 133 days, and two patients had CTCAE grade 4 hematologic toxicities that had not occurred with previous therapy. One patient treated surgically died of postoperative pneumocystis pneumonia. Tirabrutinib showed a high early response rate, but the duration of tumor control tended to be shorter than with MTX-based retreatment. This may be due to its use in our institution after multiple relapses and its aggressive administration in MTX-naive patients. It is also important to note that chemotherapy after TIR use is associated with increased hematologic toxicity.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 0","pages":"v19 - v20"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138617932","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 OBJECT Surgical resection for butterfly gliomas (bG) are still under debate, but recent findings have shown that surgery prolongs survival. However, clinical and molecular background of bG still remains unknown and surgical strategies based on such findings are scarce. OBJECTS AND METHODS We treated 39 bG patients between 2005 and 2023, including 32 cases of glioblastoma and 5 cases of astrocytoma, WHO grade 4, IDH-mutant. For the validation, we reviewed 968 MRI obtained from the public datasets (UPENN-GBM, n=611; TCGA-GBM, n=255; CPTAC-GBM, n=61; IvyGAP, n=41). RESULTS Molecular analyses revealed that 51.3% of TERT promoter mutations, 59.0% of EGFR amplification/gain, 38.5% of PTEN hemi/homozygous, and 51.3% of CDKN2A hemi/homozygous deletion. Sequential radiological imaging before typical bG diagnosis demonstrated that bG harbors two subtypes which are corpus callosum (CC)-type and hemispheric (H)-type. The multisampling of H-type showed that accumulating alterations in the CC lesions than hemisphere, indicating an invasive trajectory from the hemisphere to the CC region. Survival analysis presented that CC-type was significantly poorer overall survival (OS) than H-type (263 days and 691 days, respectively, P = 0.018). The validation cohort also supported the poor survival of CC-type. CONCLUSION Our detail analyses demonstrated the possibility of two subtypes in bG. Unilateral trans-cortical approach from the larger tumor size with CC removal is favored in the H-type. On the other hand, bilateral trans-sulcal and interhemispheric approaches preserving the intact cortex and cingulate gyrus is an alternative for CC-type.
摘要目的手术切除蝴蝶胶质瘤(bG)仍存在争议，但最近的研究结果表明手术延长了生存期。然而，bG的临床和分子背景仍然未知，基于这些发现的手术策略很少。目的与方法我们在2005 - 2023年间治疗了39例bG患者，其中32例为胶质母细胞瘤，5例为星形细胞瘤，WHO分级4级，idh突变。为了验证，我们回顾了从公共数据集获得的968个MRI (UPENN-GBM, n=611;TCGA-GBM n = 255;CPTAC-GBM n = 61;IvyGAP, n = 41)。结果分子分析显示，51.3%的TERT启动子突变，59.0%的EGFR扩增/增益，38.5%的PTEN半/纯合，51.3%的CDKN2A半/纯合缺失。典型bG诊断前的序列放射成像显示bG有两种亚型，胼胝体(CC)型和半球(H)型。h型的多次采样显示CC病变的累积改变比半球多，表明从半球到CC区域的浸润轨迹。生存分析显示，cc型总生存期(OS)明显低于h型(263天和691天，P = 0.018)。验证队列也支持cc型的低生存率。结论我们的详细分析表明bG可能存在两种亚型。单侧经皮质入路切除较大肿瘤的CC对h型更有利。另一方面，双侧经脑沟和半球间入路保留完整的皮层和扣带回是cc型的另一种选择。
{"title":"10079-MPC-6 RADIOLOGICAL AND MOLECULAR ANALYSIS OF WHO GRADE 4 BUTTERFLY GLIOMAS WITH A TAILORED SURGICAL APPROACH","authors":"Ichiyo Shibahara, Ryota Shigeeda, Yoko Tanihata, Kazuko Fujitani, Hajime Handa, Yuri Hyakutake, Mariko Toyoda, Kouhei Uemasu, Mitsuhiro Shinoda, M. Inukai, Hideto Komai, Sumito Sato, T. Hide, Toshihiro Kumabe","doi":"10.1093/noajnl/vdad141.036","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.036","url":null,"abstract":"Abstract OBJECT Surgical resection for butterfly gliomas (bG) are still under debate, but recent findings have shown that surgery prolongs survival. However, clinical and molecular background of bG still remains unknown and surgical strategies based on such findings are scarce. OBJECTS AND METHODS We treated 39 bG patients between 2005 and 2023, including 32 cases of glioblastoma and 5 cases of astrocytoma, WHO grade 4, IDH-mutant. For the validation, we reviewed 968 MRI obtained from the public datasets (UPENN-GBM, n=611; TCGA-GBM, n=255; CPTAC-GBM, n=61; IvyGAP, n=41). RESULTS Molecular analyses revealed that 51.3% of TERT promoter mutations, 59.0% of EGFR amplification/gain, 38.5% of PTEN hemi/homozygous, and 51.3% of CDKN2A hemi/homozygous deletion. Sequential radiological imaging before typical bG diagnosis demonstrated that bG harbors two subtypes which are corpus callosum (CC)-type and hemispheric (H)-type. The multisampling of H-type showed that accumulating alterations in the CC lesions than hemisphere, indicating an invasive trajectory from the hemisphere to the CC region. Survival analysis presented that CC-type was significantly poorer overall survival (OS) than H-type (263 days and 691 days, respectively, P = 0.018). The validation cohort also supported the poor survival of CC-type. CONCLUSION Our detail analyses demonstrated the possibility of two subtypes in bG. Unilateral trans-cortical approach from the larger tumor size with CC removal is favored in the H-type. On the other hand, bilateral trans-sulcal and interhemispheric approaches preserving the intact cortex and cingulate gyrus is an alternative for CC-type.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"168 4","pages":"v9 - v9"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138621403","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/vdad141.013
Yohei Yamamoto, Toshihide Tanaka, Jun Takei, A. Teshigawara, Shohei Nawate, Kyoichi Tomoto, Takuya Ishi, Y. Hasegawa, Y. Akasaki, Yuichi Murayama
Abstract INTRODUCTION In recent years, the positioning of surgical treatment for metastatic brain tumors has changed. To extract conditions suitable for surgical treatment, the background factors for each primary lesion were verified by retrospective analysis of our case. SUBJECTS AND METHODS From 2014 to 2022, 425 patients with metastatic brain tumors diagnosed and treated at our university were included. There were 219 lung cancers, 46 breast cancers, 64 gastrointestinal cancers, 26 renal cell carcinomas, and 70 others. First, the tumor volume and edema volume were measured, and the ROC curve was drawn for the presence or absence of symptoms to determine the cutoff value. After that, statistical analysis was performed on the following items for each primary lesion. The items were tumor volume (T), edema volume (E), tumor edema ratio (E/T), age, KPS, hemorrhage, cyst formation, meningitis, metastasis to other organs, posterior fossa, simultaneous detection, and single tumor. RESULTS The symptomatic cutoff was 1514mm3 for tumor volume (sensitivity 0.86 specificity 0.74) and 15616 mm3 for edema volume (sensitivity 0.85 specificity 0.85). The tumor edema ratio was significantly higher in renal cell carcinoma. Factors with significant differences were older age and multiple lesions in lung cancer, younger age and posterior fossa in breast cancer, lower KPS in gastrointestinal cancer, and solitary cases and bleeding in renal cell carcinoma. DISCUSSION/CONCLUSION In this analysis, many cases of brain metastasis from renal cell carcinoma are solitary, and because they exhibit extensive edema that seems to be affected by VEGF, they tend to develop symptoms while they are small, and they are characterized by hemorrhage easily during the course. These findings suggest that patients with brain metastases from renal cell carcinoma should be given priority for surgical treatment.
{"title":"10022-MET-2 CLINICAL FEATURES OF RENAL CELL CARCINOMA BRAIN METASTASES COMPARED WITH OTHER CARCINOMAS","authors":"Yohei Yamamoto, Toshihide Tanaka, Jun Takei, A. Teshigawara, Shohei Nawate, Kyoichi Tomoto, Takuya Ishi, Y. Hasegawa, Y. Akasaki, Yuichi Murayama","doi":"10.1093/noajnl/vdad141.013","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.013","url":null,"abstract":"Abstract INTRODUCTION In recent years, the positioning of surgical treatment for metastatic brain tumors has changed. To extract conditions suitable for surgical treatment, the background factors for each primary lesion were verified by retrospective analysis of our case. SUBJECTS AND METHODS From 2014 to 2022, 425 patients with metastatic brain tumors diagnosed and treated at our university were included. There were 219 lung cancers, 46 breast cancers, 64 gastrointestinal cancers, 26 renal cell carcinomas, and 70 others. First, the tumor volume and edema volume were measured, and the ROC curve was drawn for the presence or absence of symptoms to determine the cutoff value. After that, statistical analysis was performed on the following items for each primary lesion. The items were tumor volume (T), edema volume (E), tumor edema ratio (E/T), age, KPS, hemorrhage, cyst formation, meningitis, metastasis to other organs, posterior fossa, simultaneous detection, and single tumor. RESULTS The symptomatic cutoff was 1514mm3 for tumor volume (sensitivity 0.86 specificity 0.74) and 15616 mm3 for edema volume (sensitivity 0.85 specificity 0.85). The tumor edema ratio was significantly higher in renal cell carcinoma. Factors with significant differences were older age and multiple lesions in lung cancer, younger age and posterior fossa in breast cancer, lower KPS in gastrointestinal cancer, and solitary cases and bleeding in renal cell carcinoma. DISCUSSION/CONCLUSION In this analysis, many cases of brain metastasis from renal cell carcinoma are solitary, and because they exhibit extensive edema that seems to be affected by VEGF, they tend to develop symptoms while they are small, and they are characterized by hemorrhage easily during the course. These findings suggest that patients with brain metastases from renal cell carcinoma should be given priority for surgical treatment.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"32 S113","pages":"v4 - v4"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138623042","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/vdad141.043
N. Ohe, Takafumi Okubo, Kenji Shoda, Tetsuya Yamada, N. Suzui, N. Nakayama, Tatsuhiko Miyazaki
Abstract INTRODUCTION The number of long-term survivors of pediatric medulloblastoma has been increasing due to improved treatment options. However, secondary cancer can be an issue for long-term survivors. We report the molecular pathological evaluation of two cases of radiation-induced glioblastoma. Patients: Of the 27 patients with cerebellar medulloblastoma treated at our institution, two who were 3 years old and 11 years old at the time of medulloblastoma diagnosis and both were girls, developed cerebellar glioblastomas after the initial treatment at five years and 11 months and 22 years and eight months, respectively. These two cerebellar glioblastomas were clinically diagnosed as radiation-induced secondary cancer. RESULTS Both of the two cases we clinically diagnosed as radiation-induced glioblastoma had negative IDH-1, EGFR expression and positive p53 expression in immunohistochemistry. DISCUSSION It has been reported that EGFR expression is negative as a molecular feature of radiation-induced glioblastoma, and the two cases we experienced were consistent with radiation-induced secondary cancers. In general, primary glioblastoma is positive for EGFR expression in the supratentorial region and negative in the infratentorial region. Therefore, in the case of supratentorial glioblastoma, it is useful to evaluate EGFR expression to distinguish primary glioblastoma from secondary glioblastoma.
{"title":"10094-MPC-8 MOLECULAR PATHOLOGICAL ANALYSIS OF RADIATION-INDUCED GLIOBLASTOMA AFTER PEDIATRIC CEREBELLAR MEDULLOBLASTOMA TREATMENT","authors":"N. Ohe, Takafumi Okubo, Kenji Shoda, Tetsuya Yamada, N. Suzui, N. Nakayama, Tatsuhiko Miyazaki","doi":"10.1093/noajnl/vdad141.043","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.043","url":null,"abstract":"Abstract INTRODUCTION The number of long-term survivors of pediatric medulloblastoma has been increasing due to improved treatment options. However, secondary cancer can be an issue for long-term survivors. We report the molecular pathological evaluation of two cases of radiation-induced glioblastoma. Patients: Of the 27 patients with cerebellar medulloblastoma treated at our institution, two who were 3 years old and 11 years old at the time of medulloblastoma diagnosis and both were girls, developed cerebellar glioblastomas after the initial treatment at five years and 11 months and 22 years and eight months, respectively. These two cerebellar glioblastomas were clinically diagnosed as radiation-induced secondary cancer. RESULTS Both of the two cases we clinically diagnosed as radiation-induced glioblastoma had negative IDH-1, EGFR expression and positive p53 expression in immunohistochemistry. DISCUSSION It has been reported that EGFR expression is negative as a molecular feature of radiation-induced glioblastoma, and the two cases we experienced were consistent with radiation-induced secondary cancers. In general, primary glioblastoma is positive for EGFR expression in the supratentorial region and negative in the infratentorial region. Therefore, in the case of supratentorial glioblastoma, it is useful to evaluate EGFR expression to distinguish primary glioblastoma from secondary glioblastoma.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"8 5","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":"138624733","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/vdad141.074
H. Nakatogawa, Hiroshi Kawaji, Nobuhide Hayashi, J. Fukai, Noriyuki Kijima, T. Shofuda, E. Yoshioka, D. Kanematsu, A. Katsuma, Miho Sumida, C. Inenaga, K. Mori, Y. Kanemura
Abstract INTRODUCTION Diffuse midline glioma (DMG), H3K27-altered, is a CNS WHO grade 4 glioma that usually located mainly in the brainstem, thalamus and spinal cord. However, DMG located in non-midline lesions are now described as pediatric-type high grade glioma, H3K27-altered, NEC (NDMG). On the other hand, diffuse hemispheric glioma, H3G34-mutant (DHG) located in the cerebral hemispheres, and is classified under the WHO 2021 classification. It is unknown that the differences in clinical characteristics of these hemispheric tumors with H3F3A mutations. In the present study, we report a comparative study of the clinical characteristics of two groups of NDMG and DHG. METHODS Among 4128 brain tumor samples collected in the Kansai Network for Molecular Diagnosis of Central Nervous System Tumors, 16 NDMG and 9 DHG cases were examined for comparison of clinical characteristics. RESULTS There were no differences in gender, tumor location, or pathology between NDMG and DHG. The median age was 47.3 years in NDMG and 26.2 years in DHG, and NDMG was significantly older than DHG (p=0.003). There was no significant difference in MGMT promoter methylation between NDMG and DHG (p=0.087). The Kaplan-Meier survival curve showed no significant difference, with a median survival of 495 days for NDMG and 587 days for DHG (p=0.765). There was no significant different survival rate between WHO grade 3 (n=15) and grade 4 (n=9) for pathological diagnosis. DISCUSSION AND CONCLUSION We compared the clinical characteristics of NDMG and DHG. There are some reports that NDMG and DHG gliomas located in non-midline lesion. Removing much tumor volume may improve the prognosis of non-midline glioma. We discuss the gliomas with H3F3A mutations located in a hemispheric lesions by literature review.
{"title":"10184-BT-14 CLINICAL FEATURE OF HEMISPHERIC GLIOMA WITH H3F3A, PEDIATRIC-TYPE HIGH GRADE GLIOMA, H3 K27-ALTERED, NEC AND DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT, CNS WHO GRADE 4","authors":"H. Nakatogawa, Hiroshi Kawaji, Nobuhide Hayashi, J. Fukai, Noriyuki Kijima, T. Shofuda, E. Yoshioka, D. Kanematsu, A. Katsuma, Miho Sumida, C. Inenaga, K. Mori, Y. Kanemura","doi":"10.1093/noajnl/vdad141.074","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.074","url":null,"abstract":"Abstract INTRODUCTION Diffuse midline glioma (DMG), H3K27-altered, is a CNS WHO grade 4 glioma that usually located mainly in the brainstem, thalamus and spinal cord. However, DMG located in non-midline lesions are now described as pediatric-type high grade glioma, H3K27-altered, NEC (NDMG). On the other hand, diffuse hemispheric glioma, H3G34-mutant (DHG) located in the cerebral hemispheres, and is classified under the WHO 2021 classification. It is unknown that the differences in clinical characteristics of these hemispheric tumors with H3F3A mutations. In the present study, we report a comparative study of the clinical characteristics of two groups of NDMG and DHG. METHODS Among 4128 brain tumor samples collected in the Kansai Network for Molecular Diagnosis of Central Nervous System Tumors, 16 NDMG and 9 DHG cases were examined for comparison of clinical characteristics. RESULTS There were no differences in gender, tumor location, or pathology between NDMG and DHG. The median age was 47.3 years in NDMG and 26.2 years in DHG, and NDMG was significantly older than DHG (p=0.003). There was no significant difference in MGMT promoter methylation between NDMG and DHG (p=0.087). The Kaplan-Meier survival curve showed no significant difference, with a median survival of 495 days for NDMG and 587 days for DHG (p=0.765). There was no significant different survival rate between WHO grade 3 (n=15) and grade 4 (n=9) for pathological diagnosis. DISCUSSION AND CONCLUSION We compared the clinical characteristics of NDMG and DHG. There are some reports that NDMG and DHG gliomas located in non-midline lesion. Removing much tumor volume may improve the prognosis of non-midline glioma. We discuss the gliomas with H3F3A mutations located in a hemispheric lesions by literature review.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"120 11","pages":"v18 - v19"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138609466","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/vdad141.053
Shoko Yoshimoto, H. Takami, Yui Kimura, Y. Hibiya, Y. Nakano, Yuuko Matsushita, Shunsaku Yakayanagi, S. Tanaka, Nobuhito Saito, J. Hirato, T. Yoshioka, Miho Kato, Tetsuya Takimoto, Yoichi Nakazato, Tomonari Suzuki, A. Mukasa, Sugiyama Kazuhiko, Masayuki Kanamori, Mitsutoshi Nakada, Taketoshi Maehara, R. Nishikawa, Koichi Ichimura
Abstract BACKGROUND Central nervous system germ cell tumors (CNS GCTs) are rare primary tumors that tend to occur in East Asian boys. In Japan, the Japan Children's Cancer Group (JCCG) and the CNS GCT Genome Analysis Consortium (iGCT Consortium) have been accumulating clinical and pathological data on CNS-GCT cases. METHODS Statistical analyses were performed on 178 cases in the JCCG's Solid Tumor Observational Study (2016-2022) and 209 cases in the iGCT Consortium (2011-2021) for age, gender, site of origin, and pathological diagnosis. RESULTS There were 306 primary cases and 44 recurrent cases, 296 (77%) males and 90 (23%) females, with a median age of 13 years, 11 years for JCCG and 16 years for iGCT Consortium, with differences between these two cohorts. The most common pathological diagnosis was germinoma in 200 cases (52%). Non-germinomatous germ cell tumors (NGGCTs) in 167 cases (43%), of which 69 cases (18%) were mixed GCT with germinoma, 34 cases were immature teratoma, mature teratoma in 32 cases (8%), yolk sac tumor in 20 cases (5%), mixed GCT without germinoma in 5 cases (1%), choriocarcinoma in 5 cases (1%), embryonal carcinoma in 2 cases (0.5%). The median age of patients with germinoma was 15 years, while with other histological types was 12 years. The pineal gland was the most common site (208 cases, 56%) and 114 cases (31%) occurred in the neurohypophysis. 38 cases of them were bifocal. Tumor development in the basal ganglia occurred in 40 cases (11%), and multiple lesions were seen in 37 cases (10%). In the neurohypophysis, the male-to-female ratio was 1:1, while in the pineal region was 11:1. In the neurohypophysis, 67% had germinoma and 9% had teratoma, whereas, in the pineal regions, 50% had germinoma and 19% had teratoma. CONCLUSIONS CNS GCT is closely correlated with age, sex, site of origin, and histology.
{"title":"10121-BT-8 CLINICOPATHOLOGICAL ANALYSIS OF CENTRAL NERVOUS SYSTEM GERM CELL TUMORS -387CASES IN THE JCCG COHORT AND THE IGCT CONSORTIUM COHORT","authors":"Shoko Yoshimoto, H. Takami, Yui Kimura, Y. Hibiya, Y. Nakano, Yuuko Matsushita, Shunsaku Yakayanagi, S. Tanaka, Nobuhito Saito, J. Hirato, T. Yoshioka, Miho Kato, Tetsuya Takimoto, Yoichi Nakazato, Tomonari Suzuki, A. Mukasa, Sugiyama Kazuhiko, Masayuki Kanamori, Mitsutoshi Nakada, Taketoshi Maehara, R. Nishikawa, Koichi Ichimura","doi":"10.1093/noajnl/vdad141.053","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.053","url":null,"abstract":"Abstract BACKGROUND Central nervous system germ cell tumors (CNS GCTs) are rare primary tumors that tend to occur in East Asian boys. In Japan, the Japan Children's Cancer Group (JCCG) and the CNS GCT Genome Analysis Consortium (iGCT Consortium) have been accumulating clinical and pathological data on CNS-GCT cases. METHODS Statistical analyses were performed on 178 cases in the JCCG's Solid Tumor Observational Study (2016-2022) and 209 cases in the iGCT Consortium (2011-2021) for age, gender, site of origin, and pathological diagnosis. RESULTS There were 306 primary cases and 44 recurrent cases, 296 (77%) males and 90 (23%) females, with a median age of 13 years, 11 years for JCCG and 16 years for iGCT Consortium, with differences between these two cohorts. The most common pathological diagnosis was germinoma in 200 cases (52%). Non-germinomatous germ cell tumors (NGGCTs) in 167 cases (43%), of which 69 cases (18%) were mixed GCT with germinoma, 34 cases were immature teratoma, mature teratoma in 32 cases (8%), yolk sac tumor in 20 cases (5%), mixed GCT without germinoma in 5 cases (1%), choriocarcinoma in 5 cases (1%), embryonal carcinoma in 2 cases (0.5%). The median age of patients with germinoma was 15 years, while with other histological types was 12 years. The pineal gland was the most common site (208 cases, 56%) and 114 cases (31%) occurred in the neurohypophysis. 38 cases of them were bifocal. Tumor development in the basal ganglia occurred in 40 cases (11%), and multiple lesions were seen in 37 cases (10%). In the neurohypophysis, the male-to-female ratio was 1:1, while in the pineal region was 11:1. In the neurohypophysis, 67% had germinoma and 9% had teratoma, whereas, in the pineal regions, 50% had germinoma and 19% had teratoma. CONCLUSIONS CNS GCT is closely correlated with age, sex, site of origin, and histology.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 2","pages":"v13 - v14"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138610016","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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