Neuro-oncology最新文献

{"title":"Enhancing prognostication and treatment response evaluation in primary CNS lymphoma with 18F-FDG-PET/CT.","authors":"Minyoung Oh, Hyungwoo Cho, Ji Eun Park, Ho Sung Kim, Heounjeong Go, Chan-Sik Park, Sang-Wook Lee, Sang Woo Song, Young-Hoon Kim, Young Hyun Cho, Seok Ho Hong, Jeong Hoon Kim, Dong Yun Lee, Jin-Sook Ryu, Dok Hyun Yoon, Jae Seung Kim","doi":"10.1093/neuonc/noae146","DOIUrl":"10.1093/neuonc/noae146","url":null,"abstract":"<p><strong>Background: </strong>The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG).</p><p><strong>Results: </strong>The median age of the 268 patients was 62 years (range: 17-85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% CI: 19.9-29.1), and the median overall survival (OS) was 34.5 months (95% CI: 22.9-46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9 cm3 and 135.0 ± 152.7 g, respectively. Patients with a baseline TMTV ≥ 17.0 cm3 had significantly shorter OS (12.5 vs 74.0 months, P = .011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs 46.0 months, P = .001) and OS (median: 21.0 vs 62.0 months, P = .002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (P = .130) or OS (P = .540).</p><p><strong>Conclusion: </strong>Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2377-2387"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889804","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":"Immune landscape of isocitrate dehydrogenase-stratified primary and recurrent human gliomas.","authors":"Pravesh Gupta, Minghao Dang, Shivangi Oberai, Simona Migliozzi, Rakesh Trivedi, Gayatri Kumar, Mekenzie Peshoff, Nancy Milam, Aml Ahmed, Krishna Bojja, Tuan M Tran, Joy Gumin, Carlos Kamiya-Matsuoka, Jason Huse, Kathryn Cox, Jianzhuo Li, Huma Shehwana, Sameer A Sheth, Rodriguez Saxon, Sun Baohua, Brittany Parker Kerrigan, Atul Maheshwari, Edwin Roger Parra Cuentas, Nicholas E Navin, Amy B Heimberger, Frederick F Lang, Antonio Iavarone, Karen Clise-Dwyer, Linghua Wang, Krishna P Bhat","doi":"10.1093/neuonc/noae139","DOIUrl":"10.1093/neuonc/noae139","url":null,"abstract":"<p><strong>Background: </strong>Human gliomas are classified using isocitrate dehydrogenase (IDH) status as a prognosticator; however, the influence of genetic differences and treatment effects on ensuing immunity remains unclear.</p><p><strong>Methods: </strong>In this study, we used sequential single-cell transcriptomics on 144 678 and spectral cytometry on over 2 million immune cells encompassing 48 human gliomas to decipher their immune landscape.</p><p><strong>Results: </strong>We identified 22 distinct immune cell types that contribute to glioma immunity. Specifically, brain-resident microglia (MG) were reduced with a concomitant increase in CD8+ T lymphocytes during glioma recurrence independent of IDH status. In contrast, IDH-wild type-associated patterns, such as an abundance of antigen-presenting cell-like MG and cytotoxic CD8+ T cells, were observed. Beyond elucidating the differences in IDH, relapse, and treatment-associated immunity, we discovered novel inflammatory MG subpopulations expressing granulysin, a cytotoxic peptide that is otherwise expressed in lymphocytes only. Furthermore, we provide a robust genomic framework for defining macrophage polarization beyond M1/M2 paradigm and reference signatures of glioma-specific tumor immune microenvironment (termed GlioTIME-36) for deconvoluting transcriptomic datasets.</p><p><strong>Conclusions: </strong>This study provides advanced optics of the human pan-glioma immune contexture as a valuable guide for translational and clinical applications.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2239-2255"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913466","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":"Selumetinib for plexiform neurofibroma: advances and ongoing challenges.","authors":"Zhichao Wang, Jingxuan Huang, Qingfeng Li","doi":"10.1093/neuonc/noae180","DOIUrl":"10.1093/neuonc/noae180","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2391-2393"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372436","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":"Erratum to: Defining neuroblastoma: from origin to precision medicine.","authors":"","doi":"10.1093/neuonc/noae218","DOIUrl":"10.1093/neuonc/noae218","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2398"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504989","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":"Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases.","authors":"Rupert Bartsch, Anna Sophie Berghoff, Julia Furtner, Maximilian Marhold, Elisabeth Sophie Bergen, Sophie Roider-Schur, Maximilian Johannes Mair, Angelika Martina Starzer, Heidrun Forstner, Beate Rottenmanner, Marie-Bernadette Aretin, Karin Dieckmann, Zsuzsanna Bago-Horvath, Helmuth Haslacher, Georg Widhalm, Aysegül Ilhan-Mutlu, Christoph Minichsdorfer, Thorsten Fuereder, Thomas Szekeres, Leopold Oehler, Birgit Gruenberger, Georg Pfeiler, Christian Singer, Ansgar Weltermann, Luzia Berchtold, Matthias Preusser","doi":"10.1093/neuonc/noae123","DOIUrl":"10.1093/neuonc/noae123","url":null,"abstract":"<p><strong>Background: </strong>Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report the final PFS and OS results.</p><p><strong>Patients and methods: </strong>TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analyzed in the per-protocol population.</p><p><strong>Results: </strong>At 26.5 months median follow-up, median PFS was 21 months (95% CI: 13.3-n.r.) and median OS was not reached (95% CI: 22.2-n.r.). With longer follow-ups, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period.</p><p><strong>Conclusions: </strong>T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of antibody-drug-conjugates as systemic therapy for active BM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2305-2315"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534954","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":"Corrigendum to: Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer.","authors":"","doi":"10.1093/neuonc/noae197","DOIUrl":"10.1093/neuonc/noae197","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2396"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292328","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":"Navigating in the dark:tailoring the extent of resection in gliomas with FastGlioma.","authors":"Nico Teske, Oliver Schnell, Philipp Karschnia","doi":"10.1093/neuonc/noae263","DOIUrl":"https://doi.org/10.1093/neuonc/noae263","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829542","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}

{"title":"RNA splicing as a biomarker and phenotypic driver of meningioma DNA-methylation groups.","authors":"Nathan K Leclair, Abrar Choudury, William C Chen, Stephen T Magill, Kathleen McCortney, Craig M Horbinski, Zhenhong Chen, Ezequiel Goldschmidt, Charlotte D Eaton, Ketan R Bulsara, Wenya Linda Bi, Akash J Patel, Felix Sahm, David Raleigh, Olga Anczukow","doi":"10.1093/neuonc/noae150","DOIUrl":"10.1093/neuonc/noae150","url":null,"abstract":"<p><strong>Background: </strong>Advances in our understanding of the molecular biology of meningiomas have led to significant gains in the ability to predict patient prognosis and tumor recurrence and to identify novel targets for therapeutic design. Specifically, classification of meningiomas based on DNA methylation has greatly improved our ability to risk stratify patients, however new questions have arisen in terms of the underlying impact these DNA-methylation signatures have on meningioma biology.</p><p><strong>Methods: </strong>This study utilizes RNA-sequencing data from 486 meningioma samples corresponding to 3 meningioma DNA-methylation groups (merlin-intact, immune-enriched, and hypermitotic), followed by in vitro experiments utilizing human meningioma cell lines.</p><p><strong>Results: </strong>We identify alterations in RNA splicing between meningioma DNA-methylation groups including individual splicing events that correlate with hypermitotic meningiomas and predict tumor recurrence and overall patient prognosis and compile a set of splicing events that can accurately predict DNA-methylation classification based on RNA-seq data. Furthermore, we validate these events using reverse transcription polymerase chain reaction (RT-PCR) in patient samples and meningioma cell lines. Additionally, we identify alterations in RNA-binding proteins and splicing factors that lie upstream of RNA splicing events, including upregulation of SRSF1 in hypermitotic meningiomas which we show drives alternative RNA splicing changes. Finally, we design splice-switching antisense oligonucleotides to target RNA splicing changes in NASP and MFF observed in hypermitotic meningiomas, providing a rationale for RNA-based therapeutic design.</p><p><strong>Conclusions: </strong>RNA splicing is an important driver of meningioma phenotypes that can be useful in prognosticating patients and as a potential exploit for therapeutic vulnerabilities.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2222-2236"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879215","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":"Osimertinib-induced DNA resistance mutations in cerebrospinal fluid of epidermal growth factor receptor-mutated non-small-cell lung carcinoma patients developing leptomeningeal metastases: Osimertinib Resistance Analysis-leptomeningeal metastases study.","authors":"J W Tijmen van der Wel, Mirjam C Boelens, Merel Jebbink, Sietske A Smulders, Klaartje W Maas, Merel J A Luitse, Annette Compter, Robin P B Boltjes, Nik Sol, Kim Monkhorst, Daan van den Broek, Egbert F Smit, Adrianus J de Langen, Dieta Brandsma","doi":"10.1093/neuonc/noae138","DOIUrl":"10.1093/neuonc/noae138","url":null,"abstract":"<p><strong>Background: </strong>Diagnosis and treatment of leptomeningeal metastases (LM) in epidermal growth factor receptor mutation-positive (EGFRm +) non-small-cell lung carcinoma (NSCLC) is challenging. We aimed to identify resistance mechanisms (RM) to osimertinib in cerebrospinal fluid (CSF) and plasma.</p><p><strong>Methods: </strong>EGFRm + patients with new or progressive LM during osimertinib were enrolled. NGS Ampliseq was performed on DNA isolated from CSF. Patients were prescribed osimertinib dose escalation (DE, 160 mg QD) following lumbar puncture. Clinical and radiological response was evaluated 4 weeks after osimertinib DE.</p><p><strong>Results: </strong>Twenty-eight patients were included. The driver mutation was identified in 93% of CSF samples (n = 26). Seven (27%) harbored ≥1 RM. Twenty-five patients (89%) were prescribed osimertinib DE. Four weeks afterwards, symptoms improved in 5 patients, stabilized in 9 and worsened in 11 patients. Twenty-one (84%) patients underwent MR imaging. Four showed radiological improvement, 14 stabilization, and 3 worsening.</p><p><strong>Conclusions: </strong>In 27% of patients, an RM was found in CSF ctDNA, none of which are targetable at the time of writing, and the clinical efficacy of osimertinib DE seems limited. There is much to gain in diagnostic as well as therapeutic strategies in EGFRm + NSCLC LM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2316-2327"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897912","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":"Trastuzumab deruxtecan: Defining a novel systemic treatment standard for HER2-positive breast cancer brain metastases?","authors":"Rupert Bartsch, Matthias Preusser","doi":"10.1093/neuonc/noae202","DOIUrl":"10.1093/neuonc/noae202","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2157-2158"},"PeriodicalIF":16.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365962","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}