Pub Date : 2023-12-01DOI: 10.1093/noajnl/vdad141.088
Y. Miyakita, M. Ohno, Masamichi Takahashi, Shunsuke Yanagisawa, Y. Narita
Abstract PCNSL remains a poor prognosis, with many patients relapsing despite induction high-dose MTX-based chemotherapy and subsequent maintenance therapy. Most recurrences occur in the brain parenchyma, but in rare cases, systemic relapse may occur. We report the clinical and pathological features of the patients with systemic relapse of PCNSL. We examined 165 PCNSLs treated at our hospital since 2005. 102 of the 165 had recurrence, and 11 of these were diagnosed as systemic relapse. The 11 patients at the time of initial diagnosis had 8 males and 3 females, age 49-81 years (median 67), and KPS 50-90 (median 70). The 11 patients at the time of recurrence had age 62-66 years (median 71), KPS 50-100 (median 60), and the sites of recurrence were abdominal lymph nodes in 3 patients, gastrointestinal tract in 3, pleural effusion in 3, and others in 2. The time to systemic relapse ranged from 11.3 to 156.1 months (median 36.4), survival after recurrence ranged from 0.1 to 89 months (median 16.1), and overall survival ranged from 16.5 to 192 months (median 66.5). Tissue sampling at relapse was performed in 9 patients, 8 of whom had DLBCL. Recurrence of PCNSL is often in the brain, and although recurrence outside the CNS occurs in less than 10%, careful follow-up is necessary. Although it has been reported that recurrence in the testes and breast is common, in our case, recurrence in lymph nodes and pleural effusions was common, and genetic histological evaluation, including discussion of the difference from the primary CNS, is considered necessary. Although the prognosis and KPS of PCNSL are poor, there are cases in which a good condition can be maintained with reliable diagnosis and treatment. Detailed clinical information, including genetic analysis at the time of initial onset and at the time of recurrence, is needed.
{"title":"10223-ML-12 SYSTEMIC RELAPSE OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA","authors":"Y. Miyakita, M. Ohno, Masamichi Takahashi, Shunsuke Yanagisawa, Y. Narita","doi":"10.1093/noajnl/vdad141.088","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.088","url":null,"abstract":"Abstract PCNSL remains a poor prognosis, with many patients relapsing despite induction high-dose MTX-based chemotherapy and subsequent maintenance therapy. Most recurrences occur in the brain parenchyma, but in rare cases, systemic relapse may occur. We report the clinical and pathological features of the patients with systemic relapse of PCNSL. We examined 165 PCNSLs treated at our hospital since 2005. 102 of the 165 had recurrence, and 11 of these were diagnosed as systemic relapse. The 11 patients at the time of initial diagnosis had 8 males and 3 females, age 49-81 years (median 67), and KPS 50-90 (median 70). The 11 patients at the time of recurrence had age 62-66 years (median 71), KPS 50-100 (median 60), and the sites of recurrence were abdominal lymph nodes in 3 patients, gastrointestinal tract in 3, pleural effusion in 3, and others in 2. The time to systemic relapse ranged from 11.3 to 156.1 months (median 36.4), survival after recurrence ranged from 0.1 to 89 months (median 16.1), and overall survival ranged from 16.5 to 192 months (median 66.5). Tissue sampling at relapse was performed in 9 patients, 8 of whom had DLBCL. Recurrence of PCNSL is often in the brain, and although recurrence outside the CNS occurs in less than 10%, careful follow-up is necessary. Although it has been reported that recurrence in the testes and breast is common, in our case, recurrence in lymph nodes and pleural effusions was common, and genetic histological evaluation, including discussion of the difference from the primary CNS, is considered necessary. Although the prognosis and KPS of PCNSL are poor, there are cases in which a good condition can be maintained with reliable diagnosis and treatment. Detailed clinical information, including genetic analysis at the time of initial onset and at the time of recurrence, is needed.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 13","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":"138612977","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/vdad141.091
Kibe Yuji, F. Ohka, K. Motomura, J. Yamaguchi, Tomohide Nishikawa, Sachi Maeda, H. Shimizu, Yuhei Takido, R. Saito
Abstract BACKGROUND Diffuse hemispheric gliomas, H3 G34-mutant (DHG-G34m) are newly recognized pediatric-type diffuse high-grade gliomas. We describe detail imaging features of seven cases of DHG-G34m and consider about progression pattern of DHG-G34m. RESULTS H3 G34R/V was detected by sanger sequencing in all tumors. Mean age of onset was 16.5 years (range: 10-26). Tumors were located on frontal (n=2), parietal (n=2), temporal lobe (n=1) and insular cortex (n=1), respectively. In one case, gliomatosis cerebri-like multiple lesions involving the cortex and basal ganglia occurred. Magnetic resonance imaging showed T2/FLAIR high lesions with poor contrast enhancement in all cases. All tumors harbored restriction of diffusion. Strong accumulation of methionine was observed in six cases. Tumors of these cases harbored T2/FLAIR high lesions in the deep white matter which showed methionine accumulation. All patients underwent surgery (total resection in one case, partial resection in five cases, and biopsy in one case) followed by radiation chemotherapy. The mean progression free survival was 9.9 months (range: 1.6-33.1 months). All recurrent tumors harbored diffuse infiltration along the white matter adjacent to surgical cavity, which was temporarily reduced by bevacizumab, but eventually invaded into cerebral peduncle via pyramidal tract and into contralateral brain via corpus callosum or anterior commissure in six cases. Extensive infiltration of tumor cells into the contralateral brain and brain stem was confirmed in the autopsy brain of one case. The mean overall survival was 21.6 months (range: 8.9-48.3 months). CONCLUSION DHG-G34m showed deep white matter infiltration from the time of initial onset, which made gross total resection difficult. Residual lesions extensively infiltrated along the white matter and eventually invaded the brainstem and contralateral brain, leading to death.
{"title":"10236-NI-11 IMAGING FEATURES AND CONSIDERATION OF PROGRESSION PATTERN OF DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT","authors":"Kibe Yuji, F. Ohka, K. Motomura, J. Yamaguchi, Tomohide Nishikawa, Sachi Maeda, H. Shimizu, Yuhei Takido, R. Saito","doi":"10.1093/noajnl/vdad141.091","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.091","url":null,"abstract":"Abstract BACKGROUND Diffuse hemispheric gliomas, H3 G34-mutant (DHG-G34m) are newly recognized pediatric-type diffuse high-grade gliomas. We describe detail imaging features of seven cases of DHG-G34m and consider about progression pattern of DHG-G34m. RESULTS H3 G34R/V was detected by sanger sequencing in all tumors. Mean age of onset was 16.5 years (range: 10-26). Tumors were located on frontal (n=2), parietal (n=2), temporal lobe (n=1) and insular cortex (n=1), respectively. In one case, gliomatosis cerebri-like multiple lesions involving the cortex and basal ganglia occurred. Magnetic resonance imaging showed T2/FLAIR high lesions with poor contrast enhancement in all cases. All tumors harbored restriction of diffusion. Strong accumulation of methionine was observed in six cases. Tumors of these cases harbored T2/FLAIR high lesions in the deep white matter which showed methionine accumulation. All patients underwent surgery (total resection in one case, partial resection in five cases, and biopsy in one case) followed by radiation chemotherapy. The mean progression free survival was 9.9 months (range: 1.6-33.1 months). All recurrent tumors harbored diffuse infiltration along the white matter adjacent to surgical cavity, which was temporarily reduced by bevacizumab, but eventually invaded into cerebral peduncle via pyramidal tract and into contralateral brain via corpus callosum or anterior commissure in six cases. Extensive infiltration of tumor cells into the contralateral brain and brain stem was confirmed in the autopsy brain of one case. The mean overall survival was 21.6 months (range: 8.9-48.3 months). CONCLUSION DHG-G34m showed deep white matter infiltration from the time of initial onset, which made gross total resection difficult. Residual lesions extensively infiltrated along the white matter and eventually invaded the brainstem and contralateral brain, leading to death.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 1","pages":"v23 - v23"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138614680","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 BACKGROUND Epithelioid Glioblastoma (E-GBM) has been identified as a pathological subtype of Glioblastoma. It is a rare glioblastoma and is mainly known in case reports, and the details of its clinical features and genetic characteristics are not clear. Here, we retrospecivly studied the results of clinical course and genetic features of E-GBM. METHODS Four patients who underwent surgery at our institution and were diagnosed with E-GBM were included in this study. Histological diagnosis was obtained by surgical excision in all cases. We extracted DNA from the resected tissues and analyzed glioma-related genes using various methods such as high resolution melting (HRM), MGMT methylation-specific HRM, digital PCR, and Multiple ligation-dependent probe amplification (MLPA) analysis. Moreover, we assayed methylation EPIC BeadChip arrays for each sample. RESULTS E-GBM tended to develop at a slightly younger age than other general glioblastoma. All patients underwent surgical resection followed by radiation therapy and concurrent temozolomide therapy. However, none of the patients were able to transition to temozolomide maintenance therapy due to disease progression, and the overall survival period was 8 to 19 weeks, indicating an extremely poor prognosis. Genetic analysis revealed both TERT promoter mutations and BRAFV600E mutation in all cases. In addition, IDH mutation was not found, and MGMT promoter methylation was unmethylated in all cases. EGFR amplification, CDKN2A/2B homozygous deletion and 1p/19q co-deletion were not found in any cases. Methylation-based classification did not reach E-GBM in all samples. CONCLUSION The simultaneous mutations of TERT promoter with BRAFV600E could serve as diagnostic molecular markers for the diagnosis of E-GBM. Standard therapy for glioblastoma was not expected to be effective in treating this tumor. It was considered necessary to introduce new therapeutic strategies such as early administration of BRAF and MEK inhibitors.
{"title":"10111-MPC-11 CLINICAL AND MOLECULAR NEUROPATHOLOGICAL FEATURES OF EPITHELIOID GLIOBLASTOMA","authors":"Takeo Uzuka, Takuma Sumi, Hadzuki Matsuda, Hiroyoshi Akutsu","doi":"10.1093/noajnl/vdad141.049","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.049","url":null,"abstract":"Abstract BACKGROUND Epithelioid Glioblastoma (E-GBM) has been identified as a pathological subtype of Glioblastoma. It is a rare glioblastoma and is mainly known in case reports, and the details of its clinical features and genetic characteristics are not clear. Here, we retrospecivly studied the results of clinical course and genetic features of E-GBM. METHODS Four patients who underwent surgery at our institution and were diagnosed with E-GBM were included in this study. Histological diagnosis was obtained by surgical excision in all cases. We extracted DNA from the resected tissues and analyzed glioma-related genes using various methods such as high resolution melting (HRM), MGMT methylation-specific HRM, digital PCR, and Multiple ligation-dependent probe amplification (MLPA) analysis. Moreover, we assayed methylation EPIC BeadChip arrays for each sample. RESULTS E-GBM tended to develop at a slightly younger age than other general glioblastoma. All patients underwent surgical resection followed by radiation therapy and concurrent temozolomide therapy. However, none of the patients were able to transition to temozolomide maintenance therapy due to disease progression, and the overall survival period was 8 to 19 weeks, indicating an extremely poor prognosis. Genetic analysis revealed both TERT promoter mutations and BRAFV600E mutation in all cases. In addition, IDH mutation was not found, and MGMT promoter methylation was unmethylated in all cases. EGFR amplification, CDKN2A/2B homozygous deletion and 1p/19q co-deletion were not found in any cases. Methylation-based classification did not reach E-GBM in all samples. CONCLUSION The simultaneous mutations of TERT promoter with BRAFV600E could serve as diagnostic molecular markers for the diagnosis of E-GBM. Standard therapy for glioblastoma was not expected to be effective in treating this tumor. It was considered necessary to introduce new therapeutic strategies such as early administration of BRAF and MEK inhibitors.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 7","pages":"v12 - v13"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138619075","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/vdad141.008
Yuta Mitobe, Yukihiko Sonoda, C. Kitanaka
Abstract The development of MDM4 inhibitors as an approach to reactivating p53 in human cancer is attracting increasing attention; however, whether they affect the function of MDM2 and how they interact with MDM2 inhibitors remain unknown. We addressed this question in the present study using CEP-1347, an inhibitor of MDM4 protein expression. The effects of CEP-1347, the genetic and/or pharmacological inhibition of MDM2, and their combination on the p53 pathway in malignant brain tumor cell lines expressing wild-type p53 were investigated by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 alone or in combination with MDM2 inhibition were examined by dye exclusion and/or colony formation assays. The treatment of malignant brain tumor cell lines with CEP-1347 markedly increased MDM2 protein expression, while blocking CEP-1347-induced MDM2 overexpression by genetic knockdown augmented the effects of CEP-1347 on the p53 pathway and cell growth. Blocking the MDM2-p53 interaction using the small molecule MDM2 inhibitor RG7112, but not MDM2 knockdown, reduced MDM4 expression. Consequently, RG7112 effectively cooperated with CEP-1347 to reduce MDM4 expression, activate the p53 pathway, and inhibit cell growth. The present results suggest CEP-1347-induced MDM2 overexpression combined with the selective inhibition of MDM2's interaction with p53, while preserving its ability to inhibit MDM4 expression, as a novel and rational strategy to effectively reactivate p53 in wild-type p53 cancer cells.
{"title":"10014-CBMS-2 CONCURRENT TARGETING OF MDM4 AND MDM2 USING CEP-1347 AS AN EFFECTIVE THERAPEUTIC STRATEGY FOR P53 WILD-TYPE MALIGNANT BRAIN TUMORS","authors":"Yuta Mitobe, Yukihiko Sonoda, C. Kitanaka","doi":"10.1093/noajnl/vdad141.008","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.008","url":null,"abstract":"Abstract The development of MDM4 inhibitors as an approach to reactivating p53 in human cancer is attracting increasing attention; however, whether they affect the function of MDM2 and how they interact with MDM2 inhibitors remain unknown. We addressed this question in the present study using CEP-1347, an inhibitor of MDM4 protein expression. The effects of CEP-1347, the genetic and/or pharmacological inhibition of MDM2, and their combination on the p53 pathway in malignant brain tumor cell lines expressing wild-type p53 were investigated by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 alone or in combination with MDM2 inhibition were examined by dye exclusion and/or colony formation assays. The treatment of malignant brain tumor cell lines with CEP-1347 markedly increased MDM2 protein expression, while blocking CEP-1347-induced MDM2 overexpression by genetic knockdown augmented the effects of CEP-1347 on the p53 pathway and cell growth. Blocking the MDM2-p53 interaction using the small molecule MDM2 inhibitor RG7112, but not MDM2 knockdown, reduced MDM4 expression. Consequently, RG7112 effectively cooperated with CEP-1347 to reduce MDM4 expression, activate the p53 pathway, and inhibit cell growth. The present results suggest CEP-1347-induced MDM2 overexpression combined with the selective inhibition of MDM2's interaction with p53, while preserving its ability to inhibit MDM4 expression, as a novel and rational strategy to effectively reactivate p53 in wild-type p53 cancer cells.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"92 1","pages":"v2 - v3"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138621780","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/vdad141.026
Shunichiro Miki, Tomoyuki Koga, F. Furnari
Abstract Activation of the RAS/MAPK pathway has been introduced in most of the glioblastoma models reported to date. To examine the roles of this pathway in tumorigenesis from different cells of origin, we differentiated human induced pluripotent stem cells (hiPSCs) with CDKN2A/2B null, PTEN null, and TERT promoter mutation (TPM), which we have previously generated, into neural stem cells (NPCs) and astrocytes, and also prepared cell lines with lentiviral EGFRvIII overexpression in both. 4 cell lines were transplanted into the brains of immunodeficient mice, and differences in tumorigenesis were compared between NPCs and astrocyte states with and without MAPK/RAS pathway activity. In NPCs, overexpression of EGFRvIII significantly shortened the time required for tumorigenesis. In Astrocytes, however, tumor formation was observed only in cells with EGFRvIII overexpression. RNA sequencing revealed the primary spheres formed from the tumors with EGFRvIII overexpression clustered similarly regardless of whether they were derived from NPCs or astrocytes, suggesting that similar tumors were formed from both sources. To further clarify the effect on the RAS/MAPK pathway, we prepared CDKN2A/2B null, PTEN null, TPM, and NF1 null iPSCs. Tumor formation was also confirmed when the cell line was differentiated into astrocytes and transplanted into immunodeficient mice. Although the cell of origin of glioblastoma is still controversial, recent reports indicate that tumorigenesis itself starts from undifferentiated cells. Our results suggest that the RAS/MAPK pathway activation in glioblastoma enhances tumorigenesis, allows cells to differentiate during the process, and also enables cells to transform even after differentiation by acquiring the activation.
{"title":"10050-TB-1 ADDITIONAL RAS/MAPK PATHWAY ACTIVATION ALLOWS CELLS TO DIFFERENTIATE DURING TUMORIGENESIS.","authors":"Shunichiro Miki, Tomoyuki Koga, F. Furnari","doi":"10.1093/noajnl/vdad141.026","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.026","url":null,"abstract":"Abstract Activation of the RAS/MAPK pathway has been introduced in most of the glioblastoma models reported to date. To examine the roles of this pathway in tumorigenesis from different cells of origin, we differentiated human induced pluripotent stem cells (hiPSCs) with CDKN2A/2B null, PTEN null, and TERT promoter mutation (TPM), which we have previously generated, into neural stem cells (NPCs) and astrocytes, and also prepared cell lines with lentiviral EGFRvIII overexpression in both. 4 cell lines were transplanted into the brains of immunodeficient mice, and differences in tumorigenesis were compared between NPCs and astrocyte states with and without MAPK/RAS pathway activity. In NPCs, overexpression of EGFRvIII significantly shortened the time required for tumorigenesis. In Astrocytes, however, tumor formation was observed only in cells with EGFRvIII overexpression. RNA sequencing revealed the primary spheres formed from the tumors with EGFRvIII overexpression clustered similarly regardless of whether they were derived from NPCs or astrocytes, suggesting that similar tumors were formed from both sources. To further clarify the effect on the RAS/MAPK pathway, we prepared CDKN2A/2B null, PTEN null, TPM, and NF1 null iPSCs. Tumor formation was also confirmed when the cell line was differentiated into astrocytes and transplanted into immunodeficient mice. Although the cell of origin of glioblastoma is still controversial, recent reports indicate that tumorigenesis itself starts from undifferentiated cells. Our results suggest that the RAS/MAPK pathway activation in glioblastoma enhances tumorigenesis, allows cells to differentiate during the process, and also enables cells to transform even after differentiation by acquiring the activation.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"48 1","pages":"v7 - v7"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138622024","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/vdad141.073
Kengo Yamada, R. Matsuda, Ryosuke Maeoka, S. Yokoyama, M. Kotsugi, K. Tamura, S. Yamada, F. Nishimura, I. Nakagawa, Eishu Boku
Abstract To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed malignant glioma treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation. This single-center retrospective study included 45 patients with newly diagnosed malignant glioma who received BCNU wafer implantation after tumor resection between March 2013 and December 2021. The patients were categorized into two groups based on whether VO occurred during the malignant glioma resection. While 20 patients received VO, 25 did not receive VO. Recurrence patterns classified as local, diffuse, distant, or multifocal and time to recurrence were compared between patients with and without VO. Median survival time was comparable between patients with VO and patients without VO (32 months vs. 26 months, p = 0.95). Recurrence occurred in 28/46 patients (60.8%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (12 [60%] vs. 16 [64%], p = 1.0). No significant differences were seen between the two groups in time to recurrence (p = 0.657) or recurrence patterns (p = 0.13). Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.
{"title":"10181-STMO-9 EFFECT OF INTRAOPERATIVE VENTRICULAR OPENING ON RECURRENCE PATTERNS FOLLOWING BCNU WAFER IMPLANTATION FOR NEWLY DIAGNOSED MALIGNANT GLIOMA","authors":"Kengo Yamada, R. Matsuda, Ryosuke Maeoka, S. Yokoyama, M. Kotsugi, K. Tamura, S. Yamada, F. Nishimura, I. Nakagawa, Eishu Boku","doi":"10.1093/noajnl/vdad141.073","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.073","url":null,"abstract":"Abstract To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed malignant glioma treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation. This single-center retrospective study included 45 patients with newly diagnosed malignant glioma who received BCNU wafer implantation after tumor resection between March 2013 and December 2021. The patients were categorized into two groups based on whether VO occurred during the malignant glioma resection. While 20 patients received VO, 25 did not receive VO. Recurrence patterns classified as local, diffuse, distant, or multifocal and time to recurrence were compared between patients with and without VO. Median survival time was comparable between patients with VO and patients without VO (32 months vs. 26 months, p = 0.95). Recurrence occurred in 28/46 patients (60.8%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (12 [60%] vs. 16 [64%], p = 1.0). No significant differences were seen between the two groups in time to recurrence (p = 0.657) or recurrence patterns (p = 0.13). Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"4 18","pages":"v18 - v18"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138624577","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/vdad141.087
Yosuke Seiya, N. Sasaki, Makoto Kobayashi, Rei Hidaka, K. Saito, Takashi Hibiya, Yuki Yamagishi, Kensuke Ikeda, Keiichi Kobayashi, Takashi Komori, Hirofumi Nakatomi, Nobuyuki Takayama, Junji Shibahara, M. Nagane
Abstract Adult T cell leukemia (ATL) manifesting only in the central nervous system (CNS) at presentation is rare. We present a case of primary CNS ATL. 54 year old male presenting with multiple enhanced lesions in the cerebrum went under biopsy and was diagnosed as T-cell lymphoma. While systemic workup was negative, human T-cell leukemia virus type 1 (HTLV-1) antibody was found to be seropositive. Southern blotting using peripheral blood DNA revealed positivity for clonal proliferation of HTLV-1 infected cells. He was therefore clinically diagnosed as primary CNS ATL. He received chemotherapy using methotrexate, procarbazine and vincristine (MPV), and gained a complete response unconfirmed (CRu) after completion of four cycles. However, relapse occurred after the fifth cycle of MPV. Salvage treatment using etoposide, cisplatin, cytarabine and prednisone (ESHAP), whole brain radiation therapy, and lenalidomide, were delivered as second, third, and fourth line therapies, but were ineffective and disease continued to progress. He was therefore treated by best supportive care. Primary CNS ATL should be considered in the differential diagnosis of brain tumors. Southern blotting using peripheral blood might be useful for clinical diagnosis in such cases.
{"title":"10221-ML-11 A CASE OF PRIMARY CENTRAL NERVOUS SYSTEM ADULT T CELL LEUKEMIA","authors":"Yosuke Seiya, N. Sasaki, Makoto Kobayashi, Rei Hidaka, K. Saito, Takashi Hibiya, Yuki Yamagishi, Kensuke Ikeda, Keiichi Kobayashi, Takashi Komori, Hirofumi Nakatomi, Nobuyuki Takayama, Junji Shibahara, M. Nagane","doi":"10.1093/noajnl/vdad141.087","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.087","url":null,"abstract":"Abstract Adult T cell leukemia (ATL) manifesting only in the central nervous system (CNS) at presentation is rare. We present a case of primary CNS ATL. 54 year old male presenting with multiple enhanced lesions in the cerebrum went under biopsy and was diagnosed as T-cell lymphoma. While systemic workup was negative, human T-cell leukemia virus type 1 (HTLV-1) antibody was found to be seropositive. Southern blotting using peripheral blood DNA revealed positivity for clonal proliferation of HTLV-1 infected cells. He was therefore clinically diagnosed as primary CNS ATL. He received chemotherapy using methotrexate, procarbazine and vincristine (MPV), and gained a complete response unconfirmed (CRu) after completion of four cycles. However, relapse occurred after the fifth cycle of MPV. Salvage treatment using etoposide, cisplatin, cytarabine and prednisone (ESHAP), whole brain radiation therapy, and lenalidomide, were delivered as second, third, and fourth line therapies, but were ineffective and disease continued to progress. He was therefore treated by best supportive care. Primary CNS ATL should be considered in the differential diagnosis of brain tumors. Southern blotting using peripheral blood might be useful for clinical diagnosis in such cases.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 33","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":"138612133","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/vdad141.009
Takahiro Sanada, Manabu Kinoshita, Takahiro Sasaki, Shota Yamamoto, Seiya Fujikawa, Shusei Fukuyama, Nobuhide Hayashi, J. Fukai, Noriko Okita, Masahiro Nonaka, T. Uda, Hideyuki Arita, K. Mori, Kenichi Ishibashi, Koji Takano, Namiko Nishida, T. Shofuda, E. Yoshioka, D. Kanematsu, M. Tanino, Y. Kodama, Masayuki Mano, Y. Kanemura
Abstract PURPOSE The study aims to explore MRI phenotypes that predict the methylation status of the promoter region of MGMT (pMGMT) in glioblastoma. MATERIALS AND METHODS 202 histologically and molecularly confirmed glioblastoma patients (pMGMT methylated: 103, unmethylated: 99) at the Kansai Network for Molecular Diagnosis of Central Nervous Tumors (KNBTG) were used as a test cohort. 104 patients from the Cancer Imaging Archive (TCIA) / Cancer Genome Atlas (TCGA) dataset (pMGMT methylated: 103, unmethylated: 99) were used as a validation cohort. "Thickened structure" was defined when the solid component of the tumor had either a circumferential extension or occupied more than 50% of the entire volume of the tumor. "Methylated contrast phenotype" was defined by imaging findings with one of the following three features: indistinct enhancing circumferential border, heterogenous enhancement, and nodular enhancement. The inter-rater agreement between three independent blinded raters was first evaluated, and then the relationship between the image findings and pMGMT methylation status was investigated. RESULTS Fleiss's Kappa coefficient for "Thickened structure" was 0.68 for the KNBTG cohort and 0.56 for the TCIA cohort and for " Methylated contrast phenotype", 0.32 and 0.35, respectively. The odds ratio of "Methylated contrast phenotype" detecting pMGMT hypermethylation was 2.4 (p = 0.003) for the KNBTG cohort. The odds ratio of "Methylated contrast phenotype" associated with pMGMT methylation was 4.5 (p = 0.001) for those restricted to tumors presenting a "Thickened structure". The odds ratio for pMGMT methylation detected by "Methylated contrast phenotype" was 3.4 (p = 0.005) for the TCIA cohort. It was 7.1 (p = 0.009) when restricting to tumors presenting a "Thickened structure". CONCLUSION Glioblastoma showing both a "Thickened structure" structure and "Methylated contrast phenotype" is associated with pMGMT methylation, which may be a clinically useful imaging feature.
{"title":"10015-NI-1 PREDICTION OF MGMT PROMOTOR METHYLATION STATUS IN GLIOBLASTOMA BY CONTRAST-ENHANCED T1-WEIGHTED IMAGE","authors":"Takahiro Sanada, Manabu Kinoshita, Takahiro Sasaki, Shota Yamamoto, Seiya Fujikawa, Shusei Fukuyama, Nobuhide Hayashi, J. Fukai, Noriko Okita, Masahiro Nonaka, T. Uda, Hideyuki Arita, K. Mori, Kenichi Ishibashi, Koji Takano, Namiko Nishida, T. Shofuda, E. Yoshioka, D. Kanematsu, M. Tanino, Y. Kodama, Masayuki Mano, Y. Kanemura","doi":"10.1093/noajnl/vdad141.009","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.009","url":null,"abstract":"Abstract PURPOSE The study aims to explore MRI phenotypes that predict the methylation status of the promoter region of MGMT (pMGMT) in glioblastoma. MATERIALS AND METHODS 202 histologically and molecularly confirmed glioblastoma patients (pMGMT methylated: 103, unmethylated: 99) at the Kansai Network for Molecular Diagnosis of Central Nervous Tumors (KNBTG) were used as a test cohort. 104 patients from the Cancer Imaging Archive (TCIA) / Cancer Genome Atlas (TCGA) dataset (pMGMT methylated: 103, unmethylated: 99) were used as a validation cohort. \"Thickened structure\" was defined when the solid component of the tumor had either a circumferential extension or occupied more than 50% of the entire volume of the tumor. \"Methylated contrast phenotype\" was defined by imaging findings with one of the following three features: indistinct enhancing circumferential border, heterogenous enhancement, and nodular enhancement. The inter-rater agreement between three independent blinded raters was first evaluated, and then the relationship between the image findings and pMGMT methylation status was investigated. RESULTS Fleiss's Kappa coefficient for \"Thickened structure\" was 0.68 for the KNBTG cohort and 0.56 for the TCIA cohort and for \" Methylated contrast phenotype\", 0.32 and 0.35, respectively. The odds ratio of \"Methylated contrast phenotype\" detecting pMGMT hypermethylation was 2.4 (p = 0.003) for the KNBTG cohort. The odds ratio of \"Methylated contrast phenotype\" associated with pMGMT methylation was 4.5 (p = 0.001) for those restricted to tumors presenting a \"Thickened structure\". The odds ratio for pMGMT methylation detected by \"Methylated contrast phenotype\" was 3.4 (p = 0.005) for the TCIA cohort. It was 7.1 (p = 0.009) when restricting to tumors presenting a \"Thickened structure\". CONCLUSION Glioblastoma showing both a \"Thickened structure\" structure and \"Methylated contrast phenotype\" is associated with pMGMT methylation, which may be a clinically useful imaging feature.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 12","pages":"v3 - v3"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138615853","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/vdad141.015
J. Fukai, Nobuhide Hayashi, H. Nakatogawa, Hiroshi Kawaji, Y. Kodama, T. Shofuda, E. Yoshioka, D. Kanematsu, A. Katsuma, Miho Sumida, Noriyuki Kijima, Y. Okita, K. Mori, Y. Kanemura
Abstract OBJECT This study investigates clinical and molecular features, including the survival outcomes, of patients with histone H3-mutant gliomas and the differences among generations: children (-13 years), adolescence and young adult (AYA) (14-39 years), and older adult (40- years) patients. Particularly, we focused on the older adult cases. METHODS We collected pediatric and adult glioma cases harboring histone H3 mutations (K27M and G34R/G34V) enrolled in Kansai Network (118 cases) and retrospectively analyzed clinical characteristics and genetic status, including overall survival times (OS). Additionally, the differences between the older adult (40- years) and the younger generations (-39 years) were evaluated. RESULTS The older adult patients were not infrequently enrolled in the H3 K27-mutant glioma group (n = 47) (40-79 years old)), although H3 G34-mutant glioma cases belonged to around AYA generation (11-45 years old). Most popular location was brainstem in children (8/15, 53%) and thalamus in AYA (29/56, 52%), while cerebrum as well as brainstem and thalamus were common in the older adults (15/47, 32%; 15/47, 32%; 11/47, 24%). Histologically, diagnosis of non-GBM was not uncommon (63/105, 60%). There were no significant age-specific differences in genetic status (IDH1/2, TERT promoter, MGMT promoter, TP53, BRAF, FGFR1, EGFR). In general, tumor biopsy followed by radiation and chemotherapy was the main treatment regimen regardless of patient age (92/115, 80%). Particularly in the H3 K27-mutant gliomas, there was no statistically significant difference in OS among generations (median OS of children/AYA/older adult, 16.6/18.4/15.9 months). CONCLUSIONS We report clinicopathological features and survival outcomes of histone H3-mutated glioma patients in Kansai Network cohort. Histone H3 mutation could exist in the older adult cases with diffuse gliomas at cerebral location. There was a little difference in clinical and pathological features among generations. The prognosis of the older adults was as poor as those of children and AYA.
{"title":"10025-MPC-3 DIFFERENCE AMONG GENERATIONS IN PATIENTS WITH HISTONE H3-MUTATED GLIOMAS","authors":"J. Fukai, Nobuhide Hayashi, H. Nakatogawa, Hiroshi Kawaji, Y. Kodama, T. Shofuda, E. Yoshioka, D. Kanematsu, A. Katsuma, Miho Sumida, Noriyuki Kijima, Y. Okita, K. Mori, Y. Kanemura","doi":"10.1093/noajnl/vdad141.015","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.015","url":null,"abstract":"Abstract OBJECT This study investigates clinical and molecular features, including the survival outcomes, of patients with histone H3-mutant gliomas and the differences among generations: children (-13 years), adolescence and young adult (AYA) (14-39 years), and older adult (40- years) patients. Particularly, we focused on the older adult cases. METHODS We collected pediatric and adult glioma cases harboring histone H3 mutations (K27M and G34R/G34V) enrolled in Kansai Network (118 cases) and retrospectively analyzed clinical characteristics and genetic status, including overall survival times (OS). Additionally, the differences between the older adult (40- years) and the younger generations (-39 years) were evaluated. RESULTS The older adult patients were not infrequently enrolled in the H3 K27-mutant glioma group (n = 47) (40-79 years old)), although H3 G34-mutant glioma cases belonged to around AYA generation (11-45 years old). Most popular location was brainstem in children (8/15, 53%) and thalamus in AYA (29/56, 52%), while cerebrum as well as brainstem and thalamus were common in the older adults (15/47, 32%; 15/47, 32%; 11/47, 24%). Histologically, diagnosis of non-GBM was not uncommon (63/105, 60%). There were no significant age-specific differences in genetic status (IDH1/2, TERT promoter, MGMT promoter, TP53, BRAF, FGFR1, EGFR). In general, tumor biopsy followed by radiation and chemotherapy was the main treatment regimen regardless of patient age (92/115, 80%). Particularly in the H3 K27-mutant gliomas, there was no statistically significant difference in OS among generations (median OS of children/AYA/older adult, 16.6/18.4/15.9 months). CONCLUSIONS We report clinicopathological features and survival outcomes of histone H3-mutated glioma patients in Kansai Network cohort. Histone H3 mutation could exist in the older adult cases with diffuse gliomas at cerebral location. There was a little difference in clinical and pathological features among generations. The prognosis of the older adults was as poor as those of children and AYA.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 9","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":"138617018","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 BACKGROUND AND OBJECTIVE In our recent Glioblastoma multiforme (GBM) cases, postoperative epilepsy mostly occurred later than twenty-eight days after surgery. CD44, a stem cell marker, is known to relate with tumor cell invasiveness, however, little are known with epilepsy nor glutamate (Glu). We investigated the relationship between CD44 and the pathophysiology of this post operative late-phase epilepsy. MATERIALS AND METHODS A total of 10 GBM cases received surgery and postoperative treatment at our institute were divided into two groups; 4 cases of epilepsy onset, group E, and 6 cases without, group NE. In each group, the tumor was separated into core and periphery, from which Glu was measured (Amino Acid Analyzer L8900; Hitachi High-Tech Corporation) with expression of xCT, EAAT2 and CD44 examined (Western blot). The same objects were also examined on our three glioma stem-like cell (GSC) lines. In addition, we figured Factor X (F-X) as a key related factor, and evaluated the same objects on the GSCs under conditioned F-X (under submission). RESULTS Group E showed higher Glu than group NE both in the core and periphery. CD44 expression was significantly higher in group E in the periphery, and xCT was higher in group E both in the core and periphery. EAAT2 was lower in group E both in the core and periphery. Among the GSCs, GSC-2 had the highest CD44 expression while having the lowest xCT and extracellular Glu, and the highest EAAT2. In addition, CD44 knockdown in GSC-2 resulted in significant increase of xCT expression and extracellular Glu. Furthermore, changing the concentration of F-X low to high led to decreased expression of CD44 and increased xCT. CONCLUSION The postoperative epileptogenicity could be gained by the increase of Glu which results from the alterations of CD44, xCT and EAAT2. F-X could enhance the ability of Glu discharge.
{"title":"10027-CBMS-3 POSTOPERATIVE EPILEPTOGENICITY IN GLIOBLASTOMA ARE ACHIEVED AS THE RESULT OF INTERACTIVE FLUCTUATIONS OF GLUTAMATE AND STEM CELL MARKER","authors":"Kosuke Kusakabe, Akihiro Inoue, Takanori Ohnishi, Yawara Nakamura, Yoshihiro Ohtsuka, Masahiro Nishikawa, Hajime Yano, Junya Tanaka, Hideaki Watanabe, Takeharu Kunieda","doi":"10.1093/noajnl/vdad141.016","DOIUrl":"https://doi.org/10.1093/noajnl/vdad141.016","url":null,"abstract":"Abstract BACKGROUND AND OBJECTIVE In our recent Glioblastoma multiforme (GBM) cases, postoperative epilepsy mostly occurred later than twenty-eight days after surgery. CD44, a stem cell marker, is known to relate with tumor cell invasiveness, however, little are known with epilepsy nor glutamate (Glu). We investigated the relationship between CD44 and the pathophysiology of this post operative late-phase epilepsy. MATERIALS AND METHODS A total of 10 GBM cases received surgery and postoperative treatment at our institute were divided into two groups; 4 cases of epilepsy onset, group E, and 6 cases without, group NE. In each group, the tumor was separated into core and periphery, from which Glu was measured (Amino Acid Analyzer L8900; Hitachi High-Tech Corporation) with expression of xCT, EAAT2 and CD44 examined (Western blot). The same objects were also examined on our three glioma stem-like cell (GSC) lines. In addition, we figured Factor X (F-X) as a key related factor, and evaluated the same objects on the GSCs under conditioned F-X (under submission). RESULTS Group E showed higher Glu than group NE both in the core and periphery. CD44 expression was significantly higher in group E in the periphery, and xCT was higher in group E both in the core and periphery. EAAT2 was lower in group E both in the core and periphery. Among the GSCs, GSC-2 had the highest CD44 expression while having the lowest xCT and extracellular Glu, and the highest EAAT2. In addition, CD44 knockdown in GSC-2 resulted in significant increase of xCT expression and extracellular Glu. Furthermore, changing the concentration of F-X low to high led to decreased expression of CD44 and increased xCT. CONCLUSION The postoperative epileptogenicity could be gained by the increase of Glu which results from the alterations of CD44, xCT and EAAT2. F-X could enhance the ability of Glu discharge.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 32","pages":"v4 - v5"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138617547","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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