Pub Date : 2020-01-01DOI: 10.4103/glioma.glioma_5_20
Dongman Ye, Tao Yu, Ji Shi, H. Piao
Background and Aim: Gliomas are the most common type of brain tumor in the world. Surgical resection is one of the most effective therapeutic methods in terms of patient prognosis. However, it is difficult for neurosurgeons and health-care providers to select which imaging technology to best support the procedure. These technologies included intraoperative magnetic resonance imaging (iMRI), intraoperative ultrasound (iUS), fluorescence guidance with 5-aminolevulinic acid (5-ALA), and intraoperative neuronavigation. Hence, in this study, we compared the gross total resection (GTR), postoperative complications within or outside of the central nervous system, and postoperative clinical improvement by multiple meta-analyses, which allows the integration of data through direct and indirect comparisons.Materials and Methods: The PubMed, Cochrane Library, Web of Science, Embase, China Knowledge Resource Integrated Database, and WanFang databases were searched for publications before April 2018. Randomized controlled trials, two-arm and three-arm prospective studies, and retrospective studies in patients who underwent surgical treatment for glioma were included. The most important outcome measures were the rates of GTR, postoperative complications, and clinical improvement. Results: In terms of GTR, iMRI (odds ratio [OR] = 5.70, 95% confidence interval [CI]: 3.40–9.60), iUS (OR = 2.70, 95% CI: 1.10–6.90), 5-ALA (OR = 2.40, 95% CI: 0.64–8.90), and neuronavigation (OR = 1.90, 95% CI: 1.20–3.10) were found to be more effective than conventional surgery. In addition, iUS (OR = 0.15, 95% CI: 0.04–0.52), iMRI (OR = 0.24, 95% CI: 0.14–0.43), and neuronavigation (OR = 0.34, 95% CI: 0.18–0.56) were more found to result in fewer complications than conventional surgery. Furthermore, patients' clinical improvement was better with iMRI (OR = 8.10, 95% CI: 3.00–25.00), iUS (OR = 4.90, 95% CI: 0.76–33.00), and neuronavigation (OR = 2.60, 95% CI: 1.00–7.20) than with conventional surgery. Conclusions: The developed ranking probability table indicated that iMRI was superior in terms of the GTR and clinical improvement, while iUS was the least likely to result in postoperative complications. Hence, it was concluded that iMRI or iUS is the most advantageous imaging modality.
背景与目的：胶质瘤是世界上最常见的脑肿瘤类型。就患者预后而言，手术切除是最有效的治疗方法之一。然而，神经外科医生和医疗保健提供者很难选择最支持该手术的成像技术。这些技术包括术中磁共振成像（iMRI）、术中超声（iUS）、5-氨基乙酰丙酸（5-ALA）荧光引导和术中神经导航。因此，在这项研究中，我们通过多项荟萃分析比较了总切除率（GTR）、中枢神经系统内外的术后并发症以及术后临床改善，从而可以通过直接和间接比较整合数据。材料与方法：检索PubMed、Cochrane Library、Web of Science、Embase、中国知识资源综合数据库和万方数据库2018年4月前的出版物。随机对照试验、两组和三组前瞻性研究以及对接受神经胶质瘤手术治疗的患者的回顾性研究包括在内。最重要的结果指标是GTR的发生率、术后并发症和临床改善。结果：在GTR方面，发现iMRI（比值比[OR]=5.70，95%置信区间[CI]:3.40-9.60）、iUS（比值比=2.70，95%CI:1.10-6.90）、5-ALA（比值比2.40，95%CI:0.64-8.90）和神经导航（比值比1.90，95%CI=1.20-3.10）比传统手术更有效。此外，与传统手术相比，iUS（OR=0.15，95%CI:0.04-0.52）、iMRI（OR=0.24，95%CI:0.14-0.43）和神经导航（OR=0.34，95%CI:0.18-0.56）更容易导致更少的并发症。此外，与传统手术相比，iMRI（OR=8.10，95%CI:3.00-25.00）、iUS（OR=4.90，95%CI:0.76-33.00）和神经导航（OR=2.60，95%CI:1.00-7.20）患者的临床改善更好。结论：制定的分级概率表表明，iMRI在GTR和临床改善方面具有优势，而iUS最不可能导致术后并发症。因此，得出结论，iMRI或iUS是最有利的成像方式。
{"title":"Comparison of intraoperative magnetic resonance imaging, ultrasound, 5-aminolevulinic acid, and neuronavigation for guidance in glioma resection: A network meta-analysis","authors":"Dongman Ye, Tao Yu, Ji Shi, H. Piao","doi":"10.4103/glioma.glioma_5_20","DOIUrl":"https://doi.org/10.4103/glioma.glioma_5_20","url":null,"abstract":"Background and Aim: Gliomas are the most common type of brain tumor in the world. Surgical resection is one of the most effective therapeutic methods in terms of patient prognosis. However, it is difficult for neurosurgeons and health-care providers to select which imaging technology to best support the procedure. These technologies included intraoperative magnetic resonance imaging (iMRI), intraoperative ultrasound (iUS), fluorescence guidance with 5-aminolevulinic acid (5-ALA), and intraoperative neuronavigation. Hence, in this study, we compared the gross total resection (GTR), postoperative complications within or outside of the central nervous system, and postoperative clinical improvement by multiple meta-analyses, which allows the integration of data through direct and indirect comparisons.Materials and Methods: The PubMed, Cochrane Library, Web of Science, Embase, China Knowledge Resource Integrated Database, and WanFang databases were searched for publications before April 2018. Randomized controlled trials, two-arm and three-arm prospective studies, and retrospective studies in patients who underwent surgical treatment for glioma were included. The most important outcome measures were the rates of GTR, postoperative complications, and clinical improvement. Results: In terms of GTR, iMRI (odds ratio [OR] = 5.70, 95% confidence interval [CI]: 3.40–9.60), iUS (OR = 2.70, 95% CI: 1.10–6.90), 5-ALA (OR = 2.40, 95% CI: 0.64–8.90), and neuronavigation (OR = 1.90, 95% CI: 1.20–3.10) were found to be more effective than conventional surgery. In addition, iUS (OR = 0.15, 95% CI: 0.04–0.52), iMRI (OR = 0.24, 95% CI: 0.14–0.43), and neuronavigation (OR = 0.34, 95% CI: 0.18–0.56) were more found to result in fewer complications than conventional surgery. Furthermore, patients' clinical improvement was better with iMRI (OR = 8.10, 95% CI: 3.00–25.00), iUS (OR = 4.90, 95% CI: 0.76–33.00), and neuronavigation (OR = 2.60, 95% CI: 1.00–7.20) than with conventional surgery. Conclusions: The developed ranking probability table indicated that iMRI was superior in terms of the GTR and clinical improvement, while iUS was the least likely to result in postoperative complications. Hence, it was concluded that iMRI or iUS is the most advantageous imaging modality.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"3 - 12"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49118091","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 : 2020-01-01DOI: 10.4103/glioma.glioma_28_19
Reneta Georgieva, E. Lyutfi, G. Stoyanov, D. Dzhenkov
Background and Aim: Glioblastoma multiforme (GBM) is a World Health Organization (WHO) Grade IV malignant tumor with astrocytic differentiation. Despite medical advances over the past few decades, the life expectancy of patients with GBM has remained relatively unchanged 8–12 months. There are two proposed mechanisms for the development of GBM – a natural progression of lower WHO-grade astrocytoma and de novo development. Both theories, however, center on neural progenitor cells in the central nervous system. The aim of this study was to evaluate the significance of CD34 neural stem cell progenitors in GBM. Materials and Methods: Fourteen cases (eight males and seven females, age 16–74 years) of tumors with astrocytic differentiation were evaluated using the automated immunohistochemistry detection algorithm of Qupath v0.2.0-m4. Due to CD34 marking not only neural progenitors but also endothelial cells, the tumors were evaluated over an area of 76 mm[2], with blood vessels excluded from the analysis. In superficial tumors, again, an area of 76 mm[2] was evaluated in the subpial one. This study was approved by the Committee on Ethics for Scientific Research, Medical University – Varna “Prof. Dr. Paraskev Stoyanov” (protocol no. 20[1]) on April 26, 2012. Results: The tumors included 11 GBMs, 2 gliosarcomas, and 1 WHO Grade II astrocytoma. Only the GBMs were subjected to statistical analysis due to the small sample size. Both the hotspot (P = 0.076) and subpial (P = 0.243) values did not show a correlation with patients' survival, with borderline expression being defined as >3.6% (high) and <3.6% (low). Conclusion: Despite the specific patterns of growth and diffuse spread of CD34+ progenitors, their percentage does not correlate with patients' survival.
{"title":"CD34 neural progenitor cells in glioblastoma multiforme","authors":"Reneta Georgieva, E. Lyutfi, G. Stoyanov, D. Dzhenkov","doi":"10.4103/glioma.glioma_28_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_28_19","url":null,"abstract":"Background and Aim: Glioblastoma multiforme (GBM) is a World Health Organization (WHO) Grade IV malignant tumor with astrocytic differentiation. Despite medical advances over the past few decades, the life expectancy of patients with GBM has remained relatively unchanged 8–12 months. There are two proposed mechanisms for the development of GBM – a natural progression of lower WHO-grade astrocytoma and de novo development. Both theories, however, center on neural progenitor cells in the central nervous system. The aim of this study was to evaluate the significance of CD34 neural stem cell progenitors in GBM. Materials and Methods: Fourteen cases (eight males and seven females, age 16–74 years) of tumors with astrocytic differentiation were evaluated using the automated immunohistochemistry detection algorithm of Qupath v0.2.0-m4. Due to CD34 marking not only neural progenitors but also endothelial cells, the tumors were evaluated over an area of 76 mm[2], with blood vessels excluded from the analysis. In superficial tumors, again, an area of 76 mm[2] was evaluated in the subpial one. This study was approved by the Committee on Ethics for Scientific Research, Medical University – Varna “Prof. Dr. Paraskev Stoyanov” (protocol no. 20[1]) on April 26, 2012. Results: The tumors included 11 GBMs, 2 gliosarcomas, and 1 WHO Grade II astrocytoma. Only the GBMs were subjected to statistical analysis due to the small sample size. Both the hotspot (P = 0.076) and subpial (P = 0.243) values did not show a correlation with patients' survival, with borderline expression being defined as >3.6% (high) and <3.6% (low). Conclusion: Despite the specific patterns of growth and diffuse spread of CD34+ progenitors, their percentage does not correlate with patients' survival.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"13 - 15"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70735481","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}
Background and Aim: The immune response to glioma is significantly impaired because of isocitrate dehydrogenase (IDH) mutations. However, the immune reaction to glioma is poorly understood. Materials and Methods: We selected 38 patients with IDH-mutant oligodendroglioma and divided them into low-grade and high-grade groups. Forty healthy people were selected as a control group. Blood samples were collected from the control group and from glioma group patients on the day before surgery and at 3 and 7 days after surgery, and numbers of immune cells were determined. This study was approved by the Institutional Ethics Committee of the Faculty of Medicine at Renmin Hospital of Wuhan University, China (approval No. 2018K-C017) on June 4, 2018. Results: The percentages of CD3+, CD4+, CD4+/CD8+, and CD3− CD19+ B-lymphocytes, and of CD3− CD16+ CD56+ natural killer cells were significantly lower (P < 0.05), and the percentage of CD4+ CD25+ regulatory cells was significantly increased (P < 0.05) in the glioma group compared with the control group. IDH-mutant oligodendroglioma patients with a higher grade of malignancy had lower levels of immune cells preoperatively and postoperatively (P < 0.05), and the levels of immune cells increased following surgery (P < 0.05). Conclusions: IDH-mutant oligodendroglioma patients with high-grade malignancy have a lower number of immune cells in peripheral blood compared with patients with low-grade malignancy. This finding can be used as an effective indicator to evaluate the malignancy and prognosis of IDH-mutant oligodendroglioma and provides a new avenue for the immunotherapy of gliomas.
{"title":"Levels of peripheral immune blood cells are related to the grade of isocitrate dehydrogenase-mutant oligodendroglioma","authors":"Jing Cheng, Yanqin Fan, Gang Deng, Baohui Liu, Junmin Wang, Qianxue Chen","doi":"10.4103/glioma.glioma_20_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_20_19","url":null,"abstract":"Background and Aim: The immune response to glioma is significantly impaired because of isocitrate dehydrogenase (IDH) mutations. However, the immune reaction to glioma is poorly understood. Materials and Methods: We selected 38 patients with IDH-mutant oligodendroglioma and divided them into low-grade and high-grade groups. Forty healthy people were selected as a control group. Blood samples were collected from the control group and from glioma group patients on the day before surgery and at 3 and 7 days after surgery, and numbers of immune cells were determined. This study was approved by the Institutional Ethics Committee of the Faculty of Medicine at Renmin Hospital of Wuhan University, China (approval No. 2018K-C017) on June 4, 2018. Results: The percentages of CD3+, CD4+, CD4+/CD8+, and CD3− CD19+ B-lymphocytes, and of CD3− CD16+ CD56+ natural killer cells were significantly lower (P < 0.05), and the percentage of CD4+ CD25+ regulatory cells was significantly increased (P < 0.05) in the glioma group compared with the control group. IDH-mutant oligodendroglioma patients with a higher grade of malignancy had lower levels of immune cells preoperatively and postoperatively (P < 0.05), and the levels of immune cells increased following surgery (P < 0.05). Conclusions: IDH-mutant oligodendroglioma patients with high-grade malignancy have a lower number of immune cells in peripheral blood compared with patients with low-grade malignancy. This finding can be used as an effective indicator to evaluate the malignancy and prognosis of IDH-mutant oligodendroglioma and provides a new avenue for the immunotherapy of gliomas.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"174 - 181"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45437830","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 : 2019-10-01DOI: 10.4103/glioma.glioma_26_19
Chengming Xu, Yao-dong Zhao, Congyan Wu, Lei Li
Glioma is the most common primary tumor of the central nervous system. In addition to traditional anticancer drugs, some common nonchemotherapeutic drugs have been considered by some scholars, such as nonsteroidal anti-inflammatory drugs, metformin, and statins. These drugs are often used for the treatment of noncancerous diseases. However, it was found that those drugs could be considered for the clinical treatment of glioma, especially in combination with chemotherapy drugs, which may improve the treatment effect. This process is called “repurposing.” Here, we aim to review these drugs and the literature. These “old drugs” have been used clinically for many years, and their safety and feasibility are high. Such combinations are expected to become a new strategy in chemotherapy for glioma in the clinic.
{"title":"Repurposing drugs for the treatment of glioma","authors":"Chengming Xu, Yao-dong Zhao, Congyan Wu, Lei Li","doi":"10.4103/glioma.glioma_26_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_26_19","url":null,"abstract":"Glioma is the most common primary tumor of the central nervous system. In addition to traditional anticancer drugs, some common nonchemotherapeutic drugs have been considered by some scholars, such as nonsteroidal anti-inflammatory drugs, metformin, and statins. These drugs are often used for the treatment of noncancerous diseases. However, it was found that those drugs could be considered for the clinical treatment of glioma, especially in combination with chemotherapy drugs, which may improve the treatment effect. This process is called “repurposing.” Here, we aim to review these drugs and the literature. These “old drugs” have been used clinically for many years, and their safety and feasibility are high. Such combinations are expected to become a new strategy in chemotherapy for glioma in the clinic.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"159 - 164"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46937812","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 : 2019-10-01DOI: 10.4103/glioma.glioma_21_19
J. Rissardo, A. Caprara
Dear Editor, We read the article entitled, “Patterns of computed tomographic findings in patients from Maiduguri, Nigeria, diagnosed with a brain tumor” in the esteemed “Glioma” with great interest. Ali et al.[1] published a retrospective study in which neuroimaging of brain tumors was evaluated with patient’s age, sex, and clinical information. In this context, their study results are important for their region that may lead to early diagnosis, prompt management, and avoiding severe complications.
{"title":"Cranial computed tomography scan in brain tumors","authors":"J. Rissardo, A. Caprara","doi":"10.4103/glioma.glioma_21_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_21_19","url":null,"abstract":"Dear Editor, We read the article entitled, “Patterns of computed tomographic findings in patients from Maiduguri, Nigeria, diagnosed with a brain tumor” in the esteemed “Glioma” with great interest. Ali et al.[1] published a retrospective study in which neuroimaging of brain tumors was evaluated with patient’s age, sex, and clinical information. In this context, their study results are important for their region that may lead to early diagnosis, prompt management, and avoiding severe complications.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"185 - 185"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48303410","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 : 2019-10-01DOI: 10.4103/glioma.glioma_24_19
G. Stoyanov
The 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) was one of the first to introduce genetic subtyping in the histological groups of these tumors.[1] However, since its introduction and based on the lack of histological criteria in the article summary of the classification, which is often cited as the classification itself, nonpathologists have become extremely ignorant of the difficulties in identifying these rare and diverse tumor entries.[2]
{"title":"The 2016 revision of the World Health Organization classification of tumors of the central nervous system: Evidence-based and morphologically flawed","authors":"G. Stoyanov","doi":"10.4103/glioma.glioma_24_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_24_19","url":null,"abstract":"The 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) was one of the first to introduce genetic subtyping in the histological groups of these tumors.[1] However, since its introduction and based on the lack of histological criteria in the article summary of the classification, which is often cited as the classification itself, nonpathologists have become extremely ignorant of the difficulties in identifying these rare and diverse tumor entries.[2]","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"165 - 166"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44496270","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 : 2019-10-01DOI: 10.4103/glioma.glioma_27_19
Zhongping Chen
Glioma is one of the most common primary malignant tumors in the central nervous system and glioblastoma (GBM) is the deadly disease. Excessive angiogenesis and adequate blood supply result in rapid proliferation and invasion in GBM. Therefore, targeting angiogenesis may be an effective way to inhibit glioma progression. Currently, there are two categories in targeting angiogenesis in GBM: vascular endothelial growth factor monoclonal antibody and vascular endothelial growth factor receptor tyrosine kinase inhibitors. Unfortunately, none of these ways yield efficient overall survival improvement in GBM, implying that it is difficult to really block the tumor angiogenesis by blocking a single pathway. Expectantly, there are some clinical trials showing that a combination of antiangiogenesis and immunotherapy may exert synergism on suppressing glioma growth and improving patients' prognosis.
{"title":"Anti-angiogenic therapy for glioma: Puzzle and hope","authors":"Zhongping Chen","doi":"10.4103/glioma.glioma_27_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_27_19","url":null,"abstract":"Glioma is one of the most common primary malignant tumors in the central nervous system and glioblastoma (GBM) is the deadly disease. Excessive angiogenesis and adequate blood supply result in rapid proliferation and invasion in GBM. Therefore, targeting angiogenesis may be an effective way to inhibit glioma progression. Currently, there are two categories in targeting angiogenesis in GBM: vascular endothelial growth factor monoclonal antibody and vascular endothelial growth factor receptor tyrosine kinase inhibitors. Unfortunately, none of these ways yield efficient overall survival improvement in GBM, implying that it is difficult to really block the tumor angiogenesis by blocking a single pathway. Expectantly, there are some clinical trials showing that a combination of antiangiogenesis and immunotherapy may exert synergism on suppressing glioma growth and improving patients' prognosis.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"182 - 184"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43432231","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 : 2019-10-01DOI: 10.4103/glioma.glioma_25_19
Chengcheng Guo, Qunying Yang, Jia-wei Li, Shao‐xiong Wu, M. Deng, Xiao-jing Du, K. Sai, Xiaobing Jiang, Zheng-he Chen, Ji Zhang, Fu-Hua Lin, Jian Wang, Yinsheng Chen, Chao Ke, Xiangheng Zhang, Xue Ju, Y. Mou, J. Bacha, A. Steinø, S. Kanekal, C. Kwan, G. Johnson, R. Schwartz, J. Langlands, Dennis Brown, Zhongyan Chen
Background and Aim: Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) gene, which confers a limited response to standard-of-care treatment with temozolomide (TMZ), resulting in a lower survival. Dianhydrogalactitol (VAL-083) is a novel bi-functional DNA-targeting agent that induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated repair of the O6 guanine alkylator TMZ. A Phase 2 study has been initiated for VAL-083 in newly diagnosed MGMT unmethylated GBM. Subjects and Methods: The study has two parts: part 1 is a dose–escalation and induction format to enroll up to ten patients in which they received VAL-083 at 20, 30, or 40 mg/m2 per day for 3 days every 21 days concurrently with standard radiation treatment and VAL-083 for up to eight additional cycles. Part 2 comprises an expansion phase to enroll up to twenty additional patients. This study was performed with approval by the Institutional Review Board of Sun Yat-sen University Cancer Center (B2016-058-01) on January 13, 2017, and registered with the ClinicalTrials.gov (NCT03050736) on February 13, 2017. Results: After completion of dose escalation, VAL-083, 30 mg/m2 per day, in combination with radiation therapy, was generally safe and well tolerated. At the cutoff date, 23 patients had been enrolled, 14 of whom had been treated in the expansion phase. Consistent with prior studies, myelosuppression was the most common adverse event. Pharmacokinetic assessment indicated that the levels of VAL-083 were as high in the cerebrospinal fluid as in plasma, 2 h postinfusion. Of the 22 patients who had reached their four precycle magnetic resonance imaging assessments, 12 were assessed with disease progression, with a median progression-free survival of 9.9 (95% confidence interval 7.3–12.0) months for all the patients studied. Conclusion: These preliminary data support VAL-083 as a potentially valuable treatment option for newly diagnosed GBM.
{"title":"Phase 2 clinical trial of VAL-083 as first-line treatment in newly-diagnosed MGMT-unmethylated glioblastoma multiforme (GBM): Halfway report","authors":"Chengcheng Guo, Qunying Yang, Jia-wei Li, Shao‐xiong Wu, M. Deng, Xiao-jing Du, K. Sai, Xiaobing Jiang, Zheng-he Chen, Ji Zhang, Fu-Hua Lin, Jian Wang, Yinsheng Chen, Chao Ke, Xiangheng Zhang, Xue Ju, Y. Mou, J. Bacha, A. Steinø, S. Kanekal, C. Kwan, G. Johnson, R. Schwartz, J. Langlands, Dennis Brown, Zhongyan Chen","doi":"10.4103/glioma.glioma_25_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_25_19","url":null,"abstract":"Background and Aim: Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) gene, which confers a limited response to standard-of-care treatment with temozolomide (TMZ), resulting in a lower survival. Dianhydrogalactitol (VAL-083) is a novel bi-functional DNA-targeting agent that induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated repair of the O6 guanine alkylator TMZ. A Phase 2 study has been initiated for VAL-083 in newly diagnosed MGMT unmethylated GBM. Subjects and Methods: The study has two parts: part 1 is a dose–escalation and induction format to enroll up to ten patients in which they received VAL-083 at 20, 30, or 40 mg/m2 per day for 3 days every 21 days concurrently with standard radiation treatment and VAL-083 for up to eight additional cycles. Part 2 comprises an expansion phase to enroll up to twenty additional patients. This study was performed with approval by the Institutional Review Board of Sun Yat-sen University Cancer Center (B2016-058-01) on January 13, 2017, and registered with the ClinicalTrials.gov (NCT03050736) on February 13, 2017. Results: After completion of dose escalation, VAL-083, 30 mg/m2 per day, in combination with radiation therapy, was generally safe and well tolerated. At the cutoff date, 23 patients had been enrolled, 14 of whom had been treated in the expansion phase. Consistent with prior studies, myelosuppression was the most common adverse event. Pharmacokinetic assessment indicated that the levels of VAL-083 were as high in the cerebrospinal fluid as in plasma, 2 h postinfusion. Of the 22 patients who had reached their four precycle magnetic resonance imaging assessments, 12 were assessed with disease progression, with a median progression-free survival of 9.9 (95% confidence interval 7.3–12.0) months for all the patients studied. Conclusion: These preliminary data support VAL-083 as a potentially valuable treatment option for newly diagnosed GBM.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"167 - 173"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45384028","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 : 2019-05-01DOI: 10.4103/glioma.glioma_16_19
M. Harat, S. Dzierzęcki, K. Dyttus-Cebulok, M. Ząbek, R. Makarewicz
Background and Aim: The benefit of stereotactic radiosurgery (SRS) in recurrent glioblastoma multiforme (GBM) remains unclear, partly due to disease heterogeneity. Subventricular zone (SVZ) invasion is a prognostic factor for primary GBM, but whether SVZ involvement is also prognostic in recurrent GBM treated with SRS is unknown. Here, we aimed to determine prognostic factors after first GBM recurrence. Materials and Methods: Thirty-nine consecutive patients with a first recurrence of glioblastoma treated at the Gamma Knife Center, Warsaw, Poland and the Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland, between 2012 and 2016 were retrospectively reviewed. Magnetic resonance images were reviewed according to SVZ invasion by primary tumors and at the time of recurrence. Outcomes were evaluated using univariable and multivariable analyses. The study protocol was approved by the Ludwik Rydygier Collegium Medicum of Nicolas Copernicus University Institutional Review Board (approved No. KB 494/2018) on June 19, 2018. Results: SRS was the only prognostic factor for overall survival after recurrence in multivariable analysis. The median overall survival after the first recurrence was 18 months in the SRS group versus 6.5 months in the non-SRS group (P = 0.02). Survival after the first recurrence treated with SRS was shorter when recurrences were localized to the SVZ. Conclusion: SRS appears to be an effective salvage modality for small recurrent GBMs. Although SVZ-positive tumors have a worse prognosis, these tumors may benefit from SRS.
{"title":"Impact of stereotactic radiosurgery on first recurrence of glioblastoma","authors":"M. Harat, S. Dzierzęcki, K. Dyttus-Cebulok, M. Ząbek, R. Makarewicz","doi":"10.4103/glioma.glioma_16_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_16_19","url":null,"abstract":"Background and Aim: The benefit of stereotactic radiosurgery (SRS) in recurrent glioblastoma multiforme (GBM) remains unclear, partly due to disease heterogeneity. Subventricular zone (SVZ) invasion is a prognostic factor for primary GBM, but whether SVZ involvement is also prognostic in recurrent GBM treated with SRS is unknown. Here, we aimed to determine prognostic factors after first GBM recurrence. Materials and Methods: Thirty-nine consecutive patients with a first recurrence of glioblastoma treated at the Gamma Knife Center, Warsaw, Poland and the Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland, between 2012 and 2016 were retrospectively reviewed. Magnetic resonance images were reviewed according to SVZ invasion by primary tumors and at the time of recurrence. Outcomes were evaluated using univariable and multivariable analyses. The study protocol was approved by the Ludwik Rydygier Collegium Medicum of Nicolas Copernicus University Institutional Review Board (approved No. KB 494/2018) on June 19, 2018. Results: SRS was the only prognostic factor for overall survival after recurrence in multivariable analysis. The median overall survival after the first recurrence was 18 months in the SRS group versus 6.5 months in the non-SRS group (P = 0.02). Survival after the first recurrence treated with SRS was shorter when recurrences were localized to the SVZ. Conclusion: SRS appears to be an effective salvage modality for small recurrent GBMs. Although SVZ-positive tumors have a worse prognosis, these tumors may benefit from SRS.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"145 - 152"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44960813","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 : 2019-05-01DOI: 10.4103/glioma.glioma_50_18
H. Padilla-Zambrano, E. García-Ballestas, A. Agrawal, Maximiliano Paez-Nova, A. Pacheco-Hernandez, L. Moscote-Salazar
Historically, brainstem gliomas have been one of the most difficult types of neoplasms to treat. They comprise 10%–20% of pediatric tumors of the central nervous system. The average age of diagnosis is 7–9 years, without a predilection for gender. The advent of magnetic resonance imaging and radiotherapy has significantly aided in the diagnosis and treatment of brainstem gliomas.
{"title":"Pediatric diffuse intrinsic pontine gliomas","authors":"H. Padilla-Zambrano, E. García-Ballestas, A. Agrawal, Maximiliano Paez-Nova, A. Pacheco-Hernandez, L. Moscote-Salazar","doi":"10.4103/glioma.glioma_50_18","DOIUrl":"https://doi.org/10.4103/glioma.glioma_50_18","url":null,"abstract":"Historically, brainstem gliomas have been one of the most difficult types of neoplasms to treat. They comprise 10%–20% of pediatric tumors of the central nervous system. The average age of diagnosis is 7–9 years, without a predilection for gender. The advent of magnetic resonance imaging and radiotherapy has significantly aided in the diagnosis and treatment of brainstem gliomas.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"127 - 132"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44617185","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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