Patrick Y Wen, Matthias Preusser, Nathalie L Albert
Theranostics is a new treatment modality integrating molecular imaging with targeted radionuclide therapy. Theranostic agents have received regulatory approval for some systemic cancers and have therapeutic potential in neuro-oncology. As clinical trials are developed to evaluate the efficacy of theranostic agents in brain tumors, specific considerations will have to be considered, taking into account lessons learned from previous studies examining other treatment modalities in neuro-oncology. These include the need for molecular imaging or surgical window-of-opportunity studies to confirm adequate passage across the blood-brain barrier, optimizing eligibility criteria and selection of the most appropriate response criteria and endpoints to address issues such as pseudoprogression. This review will discuss some of the issues that should be considered when designing clinical trials for theranostic agents.
{"title":"Design and conduct of theranostic trials in neuro-oncology: Challenges and opportunities.","authors":"Patrick Y Wen, Matthias Preusser, Nathalie L Albert","doi":"10.1093/neuonc/noae162","DOIUrl":"https://doi.org/10.1093/neuonc/noae162","url":null,"abstract":"<p><p>Theranostics is a new treatment modality integrating molecular imaging with targeted radionuclide therapy. Theranostic agents have received regulatory approval for some systemic cancers and have therapeutic potential in neuro-oncology. As clinical trials are developed to evaluate the efficacy of theranostic agents in brain tumors, specific considerations will have to be considered, taking into account lessons learned from previous studies examining other treatment modalities in neuro-oncology. These include the need for molecular imaging or surgical window-of-opportunity studies to confirm adequate passage across the blood-brain barrier, optimizing eligibility criteria and selection of the most appropriate response criteria and endpoints to address issues such as pseudoprogression. This review will discuss some of the issues that should be considered when designing clinical trials for theranostic agents.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taishi Nakase, Geno A Guerra, Quinn T Ostrom, Tian Ge, Beatrice S Melin, Margaret Wrensch, John K Wiencke, Robert B Jenkins, Jeanette E Eckel-Passow, Melissa L Bondy, Stephen S Francis, Linda Kachuri
Background: Polygenic risk scores (PRS) aggregate the contribution of many risk variants to provide a personalized genetic susceptibility profile. Since sample sizes of glioma genome-wide association studies (GWAS) remain modest, there is a need to efficiently capture genetic risk using available data.
Methods: We applied a method based on continuous shrinkage priors (PRS-CS) to model the joint effects of over 1 million common variants on disease risk and compared this to an approach (PRS-CT) that only selects a limited set of independent variants that reach genome-wide significance (P < 5 × 10-8). PRS models were trained using GWAS stratified by histological (10 346 cases and 14 687 controls) and molecular subtype (2632 cases and 2445 controls), and validated in 2 independent cohorts.
Results: PRS-CS was generally more predictive than PRS-CT with a median increase in explained variance (R2) of 24% (interquartile range = 11-30%) across glioma subtypes. Improvements were pronounced for glioblastoma (GBM), with PRS-CS yielding larger odds ratios (OR) per standard deviation (SD) (OR = 1.93, P = 2.0 × 10-54 vs. OR = 1.83, P = 9.4 × 10-50) and higher explained variance (R2 = 2.82% vs. R2 = 2.56%). Individuals in the 80th percentile of the PRS-CS distribution had a significantly higher risk of GBM (0.107%) at age 60 compared to those with average PRS (0.046%, P = 2.4 × 10-12). Lifetime absolute risk reached 1.18% for glioma and 0.76% for IDH wildtype tumors for individuals in the 95th PRS percentile. PRS-CS augmented the classification of IDH mutation status in cases when added to demographic factors (AUC = 0.839 vs. AUC = 0.895, PΔAUC = 6.8 × 10-9).
Conclusions: Genome-wide PRS has the potential to enhance the detection of high-risk individuals and help distinguish between prognostic glioma subtypes.
背景:多基因风险评分(PRS多基因风险评分(PRS)综合了许多风险变异的贡献,提供了个性化的遗传易感性特征。由于胶质瘤全基因组关联研究(GWAS)的样本量仍然不大,因此需要利用现有数据有效捕捉遗传风险:方法:我们采用了一种基于连续收缩先验(PRS-CS)的方法来模拟 100 多万个常见变异对疾病风险的联合影响,并将其与只选择达到全基因组显著性(PResults:在各种胶质瘤亚型中,PRS-CS 的预测性普遍高于 PRS-CT,解释方差 (R2) 的中位数增加了 24%(四分位间范围=11-30%)。PRS-CS对胶质母细胞瘤(GBM)的预测效果显著,每标准差的几率比(OR)更大(OR=1.93,P=2.0×10-54 vs. OR=1.83,P=9.4×10-50),解释方差(R2=2.82% vs. R2=2.56%)更高。PRS-CS分布第80百分位数的人与PRS平均值(0.046%,P=2.4×10-12)的人相比,60岁时罹患GBM的风险(0.107%)明显更高。PRS百分位数第95位的人患胶质瘤的终生绝对风险为1.18%,患IDH野生型肿瘤的终生绝对风险为0.76%。当加入人口统计学因素时,PRS-CS增强了病例中IDH突变状态的分类(AUC=0.839 vs. AUC=0.895,PΔAUC=6.8×10-9):结论:全基因组PRS有望提高高危人群的检测率,并有助于区分预后良好的胶质瘤亚型。
{"title":"Genome-wide polygenic risk scores predict risk of glioma and molecular subtypes.","authors":"Taishi Nakase, Geno A Guerra, Quinn T Ostrom, Tian Ge, Beatrice S Melin, Margaret Wrensch, John K Wiencke, Robert B Jenkins, Jeanette E Eckel-Passow, Melissa L Bondy, Stephen S Francis, Linda Kachuri","doi":"10.1093/neuonc/noae112","DOIUrl":"10.1093/neuonc/noae112","url":null,"abstract":"<p><strong>Background: </strong>Polygenic risk scores (PRS) aggregate the contribution of many risk variants to provide a personalized genetic susceptibility profile. Since sample sizes of glioma genome-wide association studies (GWAS) remain modest, there is a need to efficiently capture genetic risk using available data.</p><p><strong>Methods: </strong>We applied a method based on continuous shrinkage priors (PRS-CS) to model the joint effects of over 1 million common variants on disease risk and compared this to an approach (PRS-CT) that only selects a limited set of independent variants that reach genome-wide significance (P < 5 × 10-8). PRS models were trained using GWAS stratified by histological (10 346 cases and 14 687 controls) and molecular subtype (2632 cases and 2445 controls), and validated in 2 independent cohorts.</p><p><strong>Results: </strong>PRS-CS was generally more predictive than PRS-CT with a median increase in explained variance (R2) of 24% (interquartile range = 11-30%) across glioma subtypes. Improvements were pronounced for glioblastoma (GBM), with PRS-CS yielding larger odds ratios (OR) per standard deviation (SD) (OR = 1.93, P = 2.0 × 10-54 vs. OR = 1.83, P = 9.4 × 10-50) and higher explained variance (R2 = 2.82% vs. R2 = 2.56%). Individuals in the 80th percentile of the PRS-CS distribution had a significantly higher risk of GBM (0.107%) at age 60 compared to those with average PRS (0.046%, P = 2.4 × 10-12). Lifetime absolute risk reached 1.18% for glioma and 0.76% for IDH wildtype tumors for individuals in the 95th PRS percentile. PRS-CS augmented the classification of IDH mutation status in cases when added to demographic factors (AUC = 0.839 vs. AUC = 0.895, PΔAUC = 6.8 × 10-9).</p><p><strong>Conclusions: </strong>Genome-wide PRS has the potential to enhance the detection of high-risk individuals and help distinguish between prognostic glioma subtypes.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1933-1944"},"PeriodicalIF":16.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Temozolomide use in elderly patients with MGMT promoter unmethylated glioblastoma: Is it finally time to dismount a dead horse?","authors":"Ugur T Sener, Erik P Sulman, Jann N Sarkaria","doi":"10.1093/neuonc/noae143","DOIUrl":"10.1093/neuonc/noae143","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1876-1877"},"PeriodicalIF":16.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas S Cho, Viên Lam Le, Francesco Sanvito, Sonoko Oshima, Jayla Harper, Saewon Chun, Catalina Raymond, Albert Lai, Phioanh L Nghiemphu, Jingwen Yao, Richard Everson, Noriko Salamon, Timothy F Cloughesy, Benjamin M Ellingson
Typical longitudinal radiographic assessment of brain tumors relies on side-by-side qualitative visualization of serial magnetic resonance images (MRIs) aided by quantitative measurements of tumor size. However, when assessing slowly growing tumors and/or complex tumors, side-by-side visualization and quantification may be difficult or unreliable. Whole-brain, patient-specific "digital flipbooks" of longitudinal scans are a potential method to augment radiographic side-by-side reads in clinical settings by enhancing the visual perception of changes in tumor size, mass effect, and infiltration across multiple slices over time. In this approach, co-registered, consecutive MRI scans are displayed in a slide deck, where one slide displays multiple brain slices of a single timepoint in an array (eg, 3 × 5 "mosaic" view of slices). The flipbooks are viewed similarly to an animated flipbook of cartoons/photos so that subtle radiographic changes are visualized via perceived motion when scrolling through the slides. Importantly, flipbooks can be created easily with free, open-source software. This article describes the step-by-step methodology for creating flipbooks and discusses clinical scenarios for which flipbooks are particularly useful. Example flipbooks are provided in Supplementary Material.
{"title":"Digital \"flipbooks\" for enhanced visual assessment of simple and complex brain tumors.","authors":"Nicholas S Cho, Viên Lam Le, Francesco Sanvito, Sonoko Oshima, Jayla Harper, Saewon Chun, Catalina Raymond, Albert Lai, Phioanh L Nghiemphu, Jingwen Yao, Richard Everson, Noriko Salamon, Timothy F Cloughesy, Benjamin M Ellingson","doi":"10.1093/neuonc/noae097","DOIUrl":"10.1093/neuonc/noae097","url":null,"abstract":"<p><p>Typical longitudinal radiographic assessment of brain tumors relies on side-by-side qualitative visualization of serial magnetic resonance images (MRIs) aided by quantitative measurements of tumor size. However, when assessing slowly growing tumors and/or complex tumors, side-by-side visualization and quantification may be difficult or unreliable. Whole-brain, patient-specific \"digital flipbooks\" of longitudinal scans are a potential method to augment radiographic side-by-side reads in clinical settings by enhancing the visual perception of changes in tumor size, mass effect, and infiltration across multiple slices over time. In this approach, co-registered, consecutive MRI scans are displayed in a slide deck, where one slide displays multiple brain slices of a single timepoint in an array (eg, 3 × 5 \"mosaic\" view of slices). The flipbooks are viewed similarly to an animated flipbook of cartoons/photos so that subtle radiographic changes are visualized via perceived motion when scrolling through the slides. Importantly, flipbooks can be created easily with free, open-source software. This article describes the step-by-step methodology for creating flipbooks and discusses clinical scenarios for which flipbooks are particularly useful. Example flipbooks are provided in Supplementary Material.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1823-1836"},"PeriodicalIF":16.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tools and toys beyond RANO 2.0: Digital flipbooks to monitor brain tumor growth dynamics?","authors":"Emilie Le Rhun, Michael Weller","doi":"10.1093/neuonc/noae141","DOIUrl":"10.1093/neuonc/noae141","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1837-1838"},"PeriodicalIF":16.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to the letter by Wang et al.: Selumetinib for plexiform neurofibroma: Advances and ongoing challenges.","authors":"Beom Hee Lee, Hyery Kim, Hee Mang Yoon","doi":"10.1093/neuonc/noae181","DOIUrl":"https://doi.org/10.1093/neuonc/noae181","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica A Wilcox, Ugonma N Chukwueke, Myung-Ju Ahn, Ayal A Aizer, Tejus A Bale, Dieta Brandsma, Priscilla K Brastianos, Susan Chang, Mariza Daras, Peter Forsyth, Livia Garzia, Michael Glantz, Isabella C Glitza Oliva, Priya Kumthekar, Emilie Le Rhun, Seema Nagpal, Barbara O'Brien, Elena Pentsova, Eudocia Quant Lee, Jan Remsik, Roberta Rudà, Inna Smalley, Michael D Taylor, Michael Weller, Jeffrey Wefel, Jonathan T Yang, Robert J Young, Patrick Y Wen, Adrienne A Boire
Leptomeningeal metastases (LM) are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options, and clinical research protocols for patients with LM from solid tumors have similarly evolved to improve survival within specific populations. Recent expansions in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions. These include leptomeningeal metastasis biology and preferred animal modeling, epidemiology in the modern cancer population, ensuring validation and accessibility of newer leptomeningeal metastasis diagnostics, best clinical practices with multimodality treatment options, clinical trial design and standardization of response assessments, and avenues worthy of further research. An international group of multi-disciplinary experts in the research and management of LM, supported by the Society for Neuro-Oncology and American Society of Clinical Oncology, were assembled to reach a consensus opinion on these pressing topics and provide a roadmap for future directions. Our hope is that these recommendations will accelerate collaboration and progress in the field of LM and serve as a platform for further discussion and patient advocacy.
人们日益认识到,脑膜转移是晚期癌症的一种可治疗但通常无法治愈的并发症。随着现代癌症疗法延长了转移性癌症患者的生命,特别是脑实质转移患者的生命,针对实体瘤脑膜转移患者的治疗方案和临床研究方案也同样得到了发展,以提高特定人群的生存率。近来,临床研究、早期诊断和药物开发领域的扩展引发了新的未解之谜。这些问题包括脑膜转移生物学和首选动物模型、现代癌症人群的流行病学、确保更新的脑膜转移诊断方法的有效性和可及性、多模式治疗方案的最佳临床实践、临床试验设计和反应评估的标准化,以及值得进一步研究的途径。在神经肿瘤学会(Society for Neuro-Oncology)和美国临床肿瘤学会(American Society of Clinical Oncology)的支持下,研究和治疗脑转移瘤的多学科专家组成了一个国际小组,就这些紧迫的课题达成了共识,并为未来的发展方向提供了路线图。我们希望这些建议能加快脑膜外转移领域的合作与进步,并为进一步的讨论和患者权益维护提供一个平台。
{"title":"Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions.","authors":"Jessica A Wilcox, Ugonma N Chukwueke, Myung-Ju Ahn, Ayal A Aizer, Tejus A Bale, Dieta Brandsma, Priscilla K Brastianos, Susan Chang, Mariza Daras, Peter Forsyth, Livia Garzia, Michael Glantz, Isabella C Glitza Oliva, Priya Kumthekar, Emilie Le Rhun, Seema Nagpal, Barbara O'Brien, Elena Pentsova, Eudocia Quant Lee, Jan Remsik, Roberta Rudà, Inna Smalley, Michael D Taylor, Michael Weller, Jeffrey Wefel, Jonathan T Yang, Robert J Young, Patrick Y Wen, Adrienne A Boire","doi":"10.1093/neuonc/noae103","DOIUrl":"10.1093/neuonc/noae103","url":null,"abstract":"<p><p>Leptomeningeal metastases (LM) are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options, and clinical research protocols for patients with LM from solid tumors have similarly evolved to improve survival within specific populations. Recent expansions in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions. These include leptomeningeal metastasis biology and preferred animal modeling, epidemiology in the modern cancer population, ensuring validation and accessibility of newer leptomeningeal metastasis diagnostics, best clinical practices with multimodality treatment options, clinical trial design and standardization of response assessments, and avenues worthy of further research. An international group of multi-disciplinary experts in the research and management of LM, supported by the Society for Neuro-Oncology and American Society of Clinical Oncology, were assembled to reach a consensus opinion on these pressing topics and provide a roadmap for future directions. Our hope is that these recommendations will accelerate collaboration and progress in the field of LM and serve as a platform for further discussion and patient advocacy.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1781-1804"},"PeriodicalIF":16.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martin J van den Bent, Pim J French, Daniel Brat, Joerg C Tonn, Mehdi Touat, Benjamin M Ellingson, Robert J Young, Johan Pallud, Andreas von Deimling, Felix Sahm, Dominique Figarella Branger, Raymond Y Huang, Michael Weller, Ingo K Mellinghoff, Tim F Cloughsey, Jason T Huse, Kenneth Aldape, Guido Reifenberger, Gilbert Youssef, Philipp Karschnia, Houtan Noushmehr, Katherine B Peters, Francois Ducray, Matthias Preusser, Patrick Y Wen
The 2016 and 2021 World Health Organization 2021 Classification of central nervous system tumors have resulted in a major improvement in the classification of isocitrate dehydrogenase (IDH)-mutant gliomas. With more effective treatments many patients experience prolonged survival. However, treatment guidelines are often still based on information from historical series comprising both patients with IDH wild-type and IDH-mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological, and molecular factors associated with the outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with IDH-mutant grades 2 and 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize the overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment.
{"title":"The biological significance of tumor grade, age, enhancement, and extent of resection in IDH-mutant gliomas: How should they inform treatment decisions in the era of IDH inhibitors?","authors":"Martin J van den Bent, Pim J French, Daniel Brat, Joerg C Tonn, Mehdi Touat, Benjamin M Ellingson, Robert J Young, Johan Pallud, Andreas von Deimling, Felix Sahm, Dominique Figarella Branger, Raymond Y Huang, Michael Weller, Ingo K Mellinghoff, Tim F Cloughsey, Jason T Huse, Kenneth Aldape, Guido Reifenberger, Gilbert Youssef, Philipp Karschnia, Houtan Noushmehr, Katherine B Peters, Francois Ducray, Matthias Preusser, Patrick Y Wen","doi":"10.1093/neuonc/noae107","DOIUrl":"10.1093/neuonc/noae107","url":null,"abstract":"<p><p>The 2016 and 2021 World Health Organization 2021 Classification of central nervous system tumors have resulted in a major improvement in the classification of isocitrate dehydrogenase (IDH)-mutant gliomas. With more effective treatments many patients experience prolonged survival. However, treatment guidelines are often still based on information from historical series comprising both patients with IDH wild-type and IDH-mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological, and molecular factors associated with the outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with IDH-mutant grades 2 and 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize the overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1805-1822"},"PeriodicalIF":16.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin Z Wang, Alexander P Landry, David R Raleigh, Felix Sahm, Kyle M Walsh, Roland Goldbrunner, Leeor S Yefet, Jörg C Tonn, Chloe Gui, Quinn T Ostrom, Jill Barnholtz-Sloan, Arie Perry, Yosef Ellenbogen, C Oliver Hanemann, Gerhard Jungwirth, Michael D Jenkinson, Ghazaleh Tabatabai, Tiit I Mathiesen, Michael W McDermott, Marcos Tatagiba, Christian la Fougère, Sybren L N Maas, Norbert Galldiks, Nathalie L Albert, Priscilla K Brastianos, Felix Ehret, Giuseppe Minniti, Katrin Lamszus, Franz L Ricklefs, Jens Schittenhelm, Katharine J Drummond, Ian F Dunn, Omar N Pathmanaban, Aaron A Cohen-Gadol, Erik P Sulman, Emeline Tabouret, Emelie Le Rhun, Christian Mawrin, Jennifer Moliterno, Michael Weller, Wenya Linda Bi, Andrew Gao, Stephen Yip, Maximilian Niyazi, Kenneth Aldape, Patrick Y Wen, Susan Short, Matthias Preusser, Farshad Nassiri, Gelareh Zadeh
Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and increased access to neuroimaging. While most exhibit nonmalignant behavior, a subset of meningiomas are biologically aggressive and are associated with treatment resistance, resulting in significant neurologic morbidity and even mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system (CNS) tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official World Health Organization (cIMPACT-NOW) working group. Additionally, clinical equipoise still remains on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas including field-leading experts, have prepared this comprehensive consensus narrative review directed toward clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality-of-life studies, and management strategies for unique meningioma patient populations. In each section, we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.
{"title":"Meningioma: International Consortium on Meningiomas consensus review on scientific advances and treatment paradigms for clinicians, researchers, and patients.","authors":"Justin Z Wang, Alexander P Landry, David R Raleigh, Felix Sahm, Kyle M Walsh, Roland Goldbrunner, Leeor S Yefet, Jörg C Tonn, Chloe Gui, Quinn T Ostrom, Jill Barnholtz-Sloan, Arie Perry, Yosef Ellenbogen, C Oliver Hanemann, Gerhard Jungwirth, Michael D Jenkinson, Ghazaleh Tabatabai, Tiit I Mathiesen, Michael W McDermott, Marcos Tatagiba, Christian la Fougère, Sybren L N Maas, Norbert Galldiks, Nathalie L Albert, Priscilla K Brastianos, Felix Ehret, Giuseppe Minniti, Katrin Lamszus, Franz L Ricklefs, Jens Schittenhelm, Katharine J Drummond, Ian F Dunn, Omar N Pathmanaban, Aaron A Cohen-Gadol, Erik P Sulman, Emeline Tabouret, Emelie Le Rhun, Christian Mawrin, Jennifer Moliterno, Michael Weller, Wenya Linda Bi, Andrew Gao, Stephen Yip, Maximilian Niyazi, Kenneth Aldape, Patrick Y Wen, Susan Short, Matthias Preusser, Farshad Nassiri, Gelareh Zadeh","doi":"10.1093/neuonc/noae082","DOIUrl":"10.1093/neuonc/noae082","url":null,"abstract":"<p><p>Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and increased access to neuroimaging. While most exhibit nonmalignant behavior, a subset of meningiomas are biologically aggressive and are associated with treatment resistance, resulting in significant neurologic morbidity and even mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system (CNS) tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official World Health Organization (cIMPACT-NOW) working group. Additionally, clinical equipoise still remains on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas including field-leading experts, have prepared this comprehensive consensus narrative review directed toward clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality-of-life studies, and management strategies for unique meningioma patient populations. In each section, we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1742-1780"},"PeriodicalIF":16.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}