Neuro-oncology最新文献

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Immunotherapy-Related Neurotoxicity in the Central Nervous System of Children with Cancer. 癌症儿童中枢神经系统与免疫疗法相关的神经毒性
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-13 DOI: 10.1093/neuonc/noae243
Jiasen He, Jeremy Connors, Andrew Meador, Shuo Xu, Heather Meador, Hong Jiang, Juan Fueyo, Candelaria Gomez-Manzano, Gregory K Friedman, Wafik Zaky, Zsila Sadighi, John M Slopis, Ali H Ahmad
{"title":"Immunotherapy-Related Neurotoxicity in the Central Nervous System of Children with Cancer.","authors":"Jiasen He, Jeremy Connors, Andrew Meador, Shuo Xu, Heather Meador, Hong Jiang, Juan Fueyo, Candelaria Gomez-Manzano, Gregory K Friedman, Wafik Zaky, Zsila Sadighi, John M Slopis, Ali H Ahmad","doi":"10.1093/neuonc/noae243","DOIUrl":"https://doi.org/10.1093/neuonc/noae243","url":null,"abstract":"<p><p>Significant gaps remain in our understanding of immunotherapy-related neurotoxicity in pediatric patients, largely because much of our knowledge comes from studies in adults. Accurately identifying the adverse effects of immunotherapy in children is also challenging, owing to variations in terminology and grading systems. Moreover, the manifestation of immunotherapy-related neurotoxicity differs greatly across different diseases, various modalities, dosages, and delivery methods. Combining immunotherapy with other treatments might improve outcomes but introduces new complexities and potential for increased toxicities. Additionally, pediatric patients with intracranial malignancy have unique responses to immunotherapies and distinct neurotoxicity compared to those with extracranial malignancy. Consequently, we must enhance our understanding of the pathophysiology, prevalence, severity, and management of immunotherapy's neurotoxic effects in this vulnerable group. This review consolidates the current knowledge of immunotherapy-related neurotoxicity in pediatric oncology, highlighting various types of neurotoxicity including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor inflammation-associated neurotoxicity (TIAN), among others. Furthermore, we examine the unique features of neurotoxicity associated with adoptive cellular therapy (ACT), antibody-based therapies, immune checkpoint inhibitors (ICIs), oncolytic viruses (OV), and cancer vaccines.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625032","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}
引用次数: 0
Using a Pre-Radiation Window to Identify Potentially Active Cytotoxic Agents in Adults with Newly Diagnosed Glioblastoma. 利用放疗前窗口识别新诊断胶质母细胞瘤成人患者中潜在的活性细胞毒性药物
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-13 DOI: 10.1093/neuonc/noae240
Danielle A Bazer, Antonio C Wolff, Stuart A Grossman
{"title":"Using a Pre-Radiation Window to Identify Potentially Active Cytotoxic Agents in Adults with Newly Diagnosed Glioblastoma.","authors":"Danielle A Bazer, Antonio C Wolff, Stuart A Grossman","doi":"10.1093/neuonc/noae240","DOIUrl":"https://doi.org/10.1093/neuonc/noae240","url":null,"abstract":"<p><strong>Background: </strong>Therapies shown to improve outcomes in patients with recurrent cancers are commonly used in the neoadjuvant setting to optimize surgery, reduce radiation fields, and treat micro-metastatic disease. While pre-radiation chemotherapy (PRC) use has flourished in systemic cancers, it has not in glioblastomas. This review documents these trajectories and highlights the potential of PRC to rapidly and safely screen cytotoxic drugs for efficacy in patients with newly diagnosed glioblastoma.</p><p><strong>Methods: </strong>Prospective trials of adults with newly diagnosed systemic and brain cancers treated with PRC published between 1980 and 2023 were identified in PubMed. NCCN guidelines were used to document the standard use of PRC in patients with systemic and brain cancers.</p><p><strong>Results: </strong>Over 5,000 prospective PRC trials in solid tumors were identified. These accrued >1 million patients and resulted in neoadjuvant therapies being standard-of-care in ~28 systemic cancers. Only 50 similar trials (2,206 patients) were identified in high grade gliomas. In 13 trials containing PRC temozolomide (n=846), radiographic responses ranged from 6-53% with a median survival of ~13 months. Glioblastoma PRC trials were not associated with unexpected toxicities or major negative impacts on survival.</p><p><strong>Conclusions: </strong>PRC in patients with glioblastoma appears safe and feasible. The pre-radiation window is ideally suited to rapidly screen cytotoxic agents for efficacy. It permits radiographic response as a primary outcome, small sample sizes, and initiation of standard therapies a few months after diagnosis. PRC may be most appropriate in patients with glioblastoma who are unlikely to benefit from temozolomide.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625060","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}
引用次数: 0
TRIM21-mediated ubiquitination and phosphorylation of ERK1/2 promotes cell proliferation and drug resistance in pituitary adenomas. TRIM21 介导的泛素化和 ERK1/2 磷酸化促进了垂体腺瘤的细胞增殖和抗药性。
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-13 DOI: 10.1093/neuonc/noae241
Yanting Liu, Fang Liu, Chuanbao Li, Tao Zhang, Tianyi Han, Yuting Dai, Ning Huang, Hao Tang, Xiaobin Wang, Shaojian Lin, Li Xue, Zhe Bao Wu
{"title":"TRIM21-mediated ubiquitination and phosphorylation of ERK1/2 promotes cell proliferation and drug resistance in pituitary adenomas.","authors":"Yanting Liu, Fang Liu, Chuanbao Li, Tao Zhang, Tianyi Han, Yuting Dai, Ning Huang, Hao Tang, Xiaobin Wang, Shaojian Lin, Li Xue, Zhe Bao Wu","doi":"10.1093/neuonc/noae241","DOIUrl":"https://doi.org/10.1093/neuonc/noae241","url":null,"abstract":"<p><strong>Background: </strong>Pituitary adenomas (PAs) are common intracranial tumors and TRIM family plays a crucial role in cell proliferation, and therapeutic resistance of tumors. However, the role of the TRIM family in PAs is not well recognized.</p><p><strong>Methods: </strong>CRISPR screening explored the role of TRIM family in the cell proliferation and drug resistance in PAs. In vitro and in vivo experiments were performed to evaluate the effects of Tripartite Motif Containing 21 (TRIM21). RNA-sequencing, mass spectrometry, immunoprecipitation and ubiquitination experiments were performed to explore the molecular mechanism. NanoBiT assays were used to screen the drugs reducing TRIM21 expression.</p><p><strong>Results: </strong>CRISPR-Cas9 screens identified that TRIM21 facilitated cell proliferation and drug resistance in PAs. Mechanistically, TRIM21 interacted with ERK1/2 through PRY-SPRY domain, leading to ERK1/2 K27-linked ubiquitination. The ERK1/2 ubiquitination promotes the interaction between ERK1/2 and MEK1/2, thereby facilitating the phosphorylation of ERK1/2. However, an excess presence of TRIM21 supressed the phosphorylation of ERK1/2 and cell proliferation via activating ERK1/2 negative feedback pathways. Importantly, TRIM21 was upregulated in dopamine-resistant prolactinomas and cabergoline-resistant MMQ cells. Furthermore, drug screening identified that Fimepinostat and Quisinostat, can reduce the protein levels of TRIM21, inhibit tumor progression, and increase drug sensitivity.</p><p><strong>Conclusions: </strong>TRIM21 may represent a therapeutic target for tumors, and inhibiting TRIM21 could be a potential strategy for tumor treatment.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625054","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}
引用次数: 0
The prognostic impact of CDKN2A/B hemizygous deletions in IDH-mutant glioma. IDH 突变胶质瘤中 CDKN2A/B 基因半杂合子缺失对预后的影响。
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-12 DOI: 10.1093/neuonc/noae238
Franziska M Ippen, Thomas Hielscher, Dennis Friedel, Kirsten Göbel, David Reuss, Christel Herold-Mende, Sandro Krieg, Andreas V Deimling, Wolfgang Wick, Felix Sahm, Abigail K Suwala
{"title":"The prognostic impact of CDKN2A/B hemizygous deletions in IDH-mutant glioma.","authors":"Franziska M Ippen, Thomas Hielscher, Dennis Friedel, Kirsten Göbel, David Reuss, Christel Herold-Mende, Sandro Krieg, Andreas V Deimling, Wolfgang Wick, Felix Sahm, Abigail K Suwala","doi":"10.1093/neuonc/noae238","DOIUrl":"https://doi.org/10.1093/neuonc/noae238","url":null,"abstract":"<p><strong>Background: </strong>Homozygous deletions of CDKN2A/B are known to predict poor prognosis in gliomas, but the impact of hemizygous deletions is less clear. This study aimed to evaluate the prognostic significance of hemizygous CDKN2A/B deletions in IDH-mutant low-grade astrocytomas and oligodendrogliomas.</p><p><strong>Methods: </strong>Tissue samples diagnosed as astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3 were collected from the archives of the Institute of Neuropathology in Heidelberg. DNA methylation analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples. Evaluation of the CDKN2A/B locus was performed by visual inspection of copy-number plots derived from methylation-array data for each case. Hemizygous and homozygous losses were assessed in relation to whole chromosomal or larger segmental losses and gains in the chromosomal profile. Survival probabilities were assessed using the Kaplan-Meier method.</p><p><strong>Results: </strong>A total of 334 low-grade glioma cases were identified, including 173 astrocytomas and 161 oligodendrogliomas. Hemizygous deletions in CDKN2A/B (37/173 in astrocytomas, 15/161 in oligodendrogliomas) did not confer significantly worse survival outcomes compared to CDKN2A/B wildtype cases in neither low grade astrocytoma (log-rank p= 0.2556; HR 2.29, 95% CI [0.76; 6.40], p= 0.135) nor oligodendroglioma (log-rank p= 0.2760; HR 0.17; 95% CI [0.01; 5.05]; p= 0.305), regardless of CNS WHO grade, which was further demonstrated on a subgroup of astrocytoma, IDH mutant CNS WHO 4 cases (log-rank p= 0.1680; HR 4.55, 95% CI [0.88; 24.51], p= 0.0689).</p><p><strong>Conclusions: </strong>Hemizygous CDKN2A/B deletions do not significantly worsen OS or PFS in IDH-mutant astrocytomas and oligodendrogliomas, CNS WHO grade 2 and 3.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624962","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}
引用次数: 0
Point/Counterpoint: The role of reirradiation in recurrent glioblastoma. 观点/反观点:再照射在复发性胶质母细胞瘤中的作用。
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-11 DOI: 10.1093/neuonc/noae209
Rifaquat Rahman, Matthias Preusser, Christina Tsien, Emilie Le Rhun, Erik P Sulman, Patrick Y Wen, Giuseppe Minniti, Michael Weller
{"title":"Point/Counterpoint: The role of reirradiation in recurrent glioblastoma.","authors":"Rifaquat Rahman, Matthias Preusser, Christina Tsien, Emilie Le Rhun, Erik P Sulman, Patrick Y Wen, Giuseppe Minniti, Michael Weller","doi":"10.1093/neuonc/noae209","DOIUrl":"https://doi.org/10.1093/neuonc/noae209","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624961","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}
引用次数: 0
Glioma-Astrocyte connexin43 confers temozolomide resistance through activation of the E2F1/ERCC1 axis. 胶质瘤-星形胶质细胞Connexin43通过激活E2F1/ERCC1轴赋予替莫唑胺抗药性
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-08 DOI: 10.1093/neuonc/noae237
Yanping Gui, Hongkun Qin, Xinyu Zhang, Qianqian Chen, Fangyu Ye, Geng Tian, Shihe Yang, Yuting Ye, Di Pan, Jieying Zhou, Xiangshan Fan, Yajing Wang, Li Zhao
{"title":"Glioma-Astrocyte connexin43 confers temozolomide resistance through activation of the E2F1/ERCC1 axis.","authors":"Yanping Gui, Hongkun Qin, Xinyu Zhang, Qianqian Chen, Fangyu Ye, Geng Tian, Shihe Yang, Yuting Ye, Di Pan, Jieying Zhou, Xiangshan Fan, Yajing Wang, Li Zhao","doi":"10.1093/neuonc/noae237","DOIUrl":"https://doi.org/10.1093/neuonc/noae237","url":null,"abstract":"<p><strong>Background: </strong>Glioma is the most prevalent and lethal tumor of the central nervous system. Routine treatment with Temozolomide (TMZ) would unfortunately result in inevitable recurrence and therapy resistance, severely limiting therapeutic efficacy. Tumor associated astrocytes (TAAs) are key components of the tumor microenvironment and increasing evidence has demonstrated that aberrant expression of Connexin43 (Cx43) was closely associated with glioma progression and TMZ resistance. However, the specific role of Cx43 in mediating TMZ resistance through glioma and astrocyte interactions has not been fully explored.</p><p><strong>Methods: </strong>The expression and prognostic value of Cx43 were evaluated in tumor samples and clinical databases. ShRNA-medicated knockdown and Gfap-Cre Cx43flox/flox gene mouse were used to assessed the role and functional significance of Cx43 in vitro and in vivo. Moreover, we performed mass spectrometry analysis, chromatin immunoprecipitation, and other biochemical assays to define the molecular mechanisms by which Cx43 promotes TMZ resistance.</p><p><strong>Results: </strong>We confirmed that upregulation of Cx43 expression between TAAs and glioma cells contributed to TMZ resistance and tumor recurrence. Genetic knockdown or pharmacological inhibition of Cx43 enhanced TMZ-induced cytotoxicity. Mechanistically, elevated Cx43 expression induced β-catenin accumulation at the cell surface of glioma cells, suppressing TCF/LEF transcription, This led to impaired miR-205-5p expression and subsequent activation of E2F1/ERCC1 axis, which eventually led to chemoresistance.</p><p><strong>Conclusions: </strong>Our study reveals a novel regulatory mechanism in which the Cx43/miR-205-5p/E2F1/ERCC1 axis contributes to TMZ resistance in glioma. These findings further highlight the potential of targeting Cx43 as a therapeutic strategy in glioma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605294","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}
引用次数: 0
Validation and next-generation update of a DNA methylation-based recurrence predictor for meningioma: a multicenter prospective study. 基于DNA甲基化的脑膜瘤复发预测指标的验证和下一代更新:一项多中心前瞻性研究。
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-06 DOI: 10.1093/neuonc/noae236
Alexander P Landry, Justin Z Wang, Vikas Patil, Chloe Gui, Mamatjan Yasin, Zeel Patel, Rebecca Yakubov, Ramneet Kaloti, Parnian Habibi, Mark Wilson, Andrew Ajisebutu, Yosef Ellenbogen, Qingxia Wei, Olivia Singh, Julio Sosa, Sheila Mansouri, Christopher Wilson, Aaron A Cohen-Gadol, Piiamaria Virtanen, Noah Burket, Matthew Blackwell, Jenna Koenig, Anthony Alfonso, Joseph Davis, Mohamed A Zaazoue, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Jill S Barnholtz-Sloan, Andrew E Sloan, Silky Chotai, Lola B Chambless, Alireza Mansouri, Felix Ehret, David Capper, Derek S Tsang, Kenneth Aldape, Andrew Gao, Farshad Nassiri, Gelareh Zadeh
{"title":"Validation and next-generation update of a DNA methylation-based recurrence predictor for meningioma: a multicenter prospective study.","authors":"Alexander P Landry, Justin Z Wang, Vikas Patil, Chloe Gui, Mamatjan Yasin, Zeel Patel, Rebecca Yakubov, Ramneet Kaloti, Parnian Habibi, Mark Wilson, Andrew Ajisebutu, Yosef Ellenbogen, Qingxia Wei, Olivia Singh, Julio Sosa, Sheila Mansouri, Christopher Wilson, Aaron A Cohen-Gadol, Piiamaria Virtanen, Noah Burket, Matthew Blackwell, Jenna Koenig, Anthony Alfonso, Joseph Davis, Mohamed A Zaazoue, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Jill S Barnholtz-Sloan, Andrew E Sloan, Silky Chotai, Lola B Chambless, Alireza Mansouri, Felix Ehret, David Capper, Derek S Tsang, Kenneth Aldape, Andrew Gao, Farshad Nassiri, Gelareh Zadeh","doi":"10.1093/neuonc/noae236","DOIUrl":"10.1093/neuonc/noae236","url":null,"abstract":"<p><strong>Background: </strong>We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion since its original publication. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation predictor compatible with newer methylation arrays.</p><p><strong>Methods: </strong>Genome-wide methylation profiles were generated with the Illumina EPICArray. The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. An nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection.</p><p><strong>Results: </strong>A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and an external cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperform 2021 WHO grade in predicting early postoperative recurrence. Dichotomizing patients into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (p<0.05), while all WHO grade 3 tumours were considered high-risk. Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Finally, our next-generation predictor contains nearly 10-fold fewer features than the original model, allowing for targeted arrays.</p><p><strong>Conclusions: </strong>This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. We make this available as a point-and-click tool which will improve prognostication, inform patient selection for RT, and allow for molecularly-stratified clinical trials.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583595","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}
引用次数: 0
Potential of ex vivo organotypic slice cultures in neuro-oncology. 体外有机切片培养在神经肿瘤学中的潜力。
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-06 DOI: 10.1093/neuonc/noae195
Ariane Steindl, Manuel Valiente
{"title":"Potential of ex vivo organotypic slice cultures in neuro-oncology.","authors":"Ariane Steindl, Manuel Valiente","doi":"10.1093/neuonc/noae195","DOIUrl":"https://doi.org/10.1093/neuonc/noae195","url":null,"abstract":"<p><p>Over recent decades, in vitro and in vivo models have significantly advanced brain cancer research; however, each presents distinct challenges for accurately mimicking in situ conditions. In response, organotypic slice cultures have emerged as a promising model recapitulating precisely specific in vivo phenotypes through an ex vivo approach. Ex vivo organotypic brain slice models can integrate biological relevance and patient-specific variability early in drug discovery, thereby aiming for more precise treatment stratification. However, the challenges of obtaining representative fresh brain tissue, ensuring reproducibility, and maintaining essential central nervous system (CNS)-specific conditions reflecting the in situ situation over time have limited the direct application of ex vivo organotypic slice cultures in robust clinical trials. In this review, we explore the benefits and possible limitations of ex vivo organotypic brain slice cultures in neuro-oncological research. Additionally, we share insights from clinical experts in neuro-oncology on how to overcome these current limitations and improve the practical application of organotypic brain slice cultures beyond academic research.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591325","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}
引用次数: 0
Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis type 1 (NF1). 关于 1 型神经纤维瘤病 (NF1) 周围神经鞘瘤综合诊断方法的共识建议。
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-06 DOI: 10.1093/neuonc/noae235
Calixto-Hope G Lucas, Andrea M Gross, Carlos G Romo, Carina A Dehner, Alexander J Lazar, Markku Miettinen, Melike Pekmezci, Martha Quezado, Fausto J Rodriguez, Anat Stemmer-Rachamimov, David Viskochil, Arie Perry
{"title":"Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis type 1 (NF1).","authors":"Calixto-Hope G Lucas, Andrea M Gross, Carlos G Romo, Carina A Dehner, Alexander J Lazar, Markku Miettinen, Melike Pekmezci, Martha Quezado, Fausto J Rodriguez, Anat Stemmer-Rachamimov, David Viskochil, Arie Perry","doi":"10.1093/neuonc/noae235","DOIUrl":"https://doi.org/10.1093/neuonc/noae235","url":null,"abstract":"<p><p>Consensus recommendation published in 2017 histologically defining atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) and malignant peripheral nerve sheath tumor (MPNST) were codified in the 2021 WHO Classification of Tumors of the Central Nervous System and the 2022 WHO Classification of Tumors of Soft Tissue and Bone. However, given the shift in diagnostic pathology toward the use of integrated histopathologic and genomic approaches, the incorporation of additional molecular strata in the classification of Neurofibromatosis Type 1 (NF1)-associated peripheral nerve sheath tumors should be formalized to aid in accurate diagnosis and early identification of malignant transformation to enable appropriate intervention for affected patients. To this end, we assembled a multi-institutional expert pathology working group as part of a \"Symposium on Atypical Neurofibroma: State of the Science\". Herein, we provide a suggested framework for adequate interventional radiology and surgical sampling, and recommend molecular profiling for clinically or radiologically worrisome non-cutaneous lesions in patients with NF1 to identify diagnostically-relevant molecular features, including CDKN2A/B inactivation for ANNUBP, as well as SUZ12, EED, or TP53 inactivating mutations, or significant aneuploidy for MPNST. We also propose renaming \"low-grade MPNST\" to \"ANNUBP with increased proliferation\" to avoid the use of the \"malignant\" term in this group of tumors with persistent unknown biologic potential. This refined integrated diagnostic approach for NF1-associated peripheral nerve sheath tumors should continue to evolve in concert with our understanding of these neoplasms.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583591","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}
引用次数: 0
Automated segmentation of brain metastases with deep learning: A multi-center, randomized crossover, multi-reader evaluation study. 利用深度学习自动分割脑转移瘤:一项多中心、随机交叉、多阅读器评估研究。
IF 16.4 1区 医学
Neuro-oncology Pub Date : 2024-11-04 DOI: 10.1093/neuonc/noae113
Xiao Luo, Yadi Yang, Shaohan Yin, Hui Li, Ying Shao, Dechun Zheng, Xinchun Li, Jianpeng Li, Weixiong Fan, Jing Li, Xiaohua Ban, Shanshan Lian, Yun Zhang, Qiuxia Yang, Weijing Zhang, Cheng Zhang, Lidi Ma, Yingwei Luo, Fan Zhou, Shiyuan Wang, Cuiping Lin, Jiao Li, Ma Luo, Jianxun He, Guixiao Xu, Yaozong Gao, Dinggang Shen, Ying Sun, Yonggao Mou, Rong Zhang, Chuanmiao Xie
{"title":"Automated segmentation of brain metastases with deep learning: A multi-center, randomized crossover, multi-reader evaluation study.","authors":"Xiao Luo, Yadi Yang, Shaohan Yin, Hui Li, Ying Shao, Dechun Zheng, Xinchun Li, Jianpeng Li, Weixiong Fan, Jing Li, Xiaohua Ban, Shanshan Lian, Yun Zhang, Qiuxia Yang, Weijing Zhang, Cheng Zhang, Lidi Ma, Yingwei Luo, Fan Zhou, Shiyuan Wang, Cuiping Lin, Jiao Li, Ma Luo, Jianxun He, Guixiao Xu, Yaozong Gao, Dinggang Shen, Ying Sun, Yonggao Mou, Rong Zhang, Chuanmiao Xie","doi":"10.1093/neuonc/noae113","DOIUrl":"10.1093/neuonc/noae113","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence has been proposed for brain metastasis (BM) segmentation but it has not been fully clinically validated. The aim of this study was to develop and evaluate a system for BM segmentation.</p><p><strong>Methods: </strong>A deep-learning-based BM segmentation system (BMSS) was developed using contrast-enhanced MR images from 488 patients with 10338 brain metastases. A randomized crossover, multi-reader study was then conducted to evaluate the performance of the BMSS for BM segmentation using data prospectively collected from 50 patients with 203 metastases at 5 centers. Five radiology residents and 5 attending radiologists were randomly assigned to contour the same prospective set in assisted and unassisted modes. Aided and unaided Dice similarity coefficients (DSCs) and contouring times per lesion were compared.</p><p><strong>Results: </strong>The BMSS alone yielded a median DSC of 0.91 (95% confidence interval, 0.90-0.92) in the multi-center set and showed comparable performance between the internal and external sets (P = .67). With BMSS assistance, the readers increased the median DSC from 0.87 (0.87-0.88) to 0.92 (0.92-0.92) (P < .001) with a median time saving of 42% (40-45%) per lesion. Resident readers showed a greater improvement than attending readers in contouring accuracy (improved median DSC, 0.05 [0.05-0.05] vs 0.03 [0.03-0.03]; P < .001), but a similar time reduction (reduced median time, 44% [40-47%] vs 40% [37-44%]; P = .92) with BMSS assistance.</p><p><strong>Conclusions: </strong>The BMSS can be optimally applied to improve the efficiency of brain metastasis delineation in clinical practice.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2140-2151"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11639187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590872","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}
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