Neuro-oncology最新文献

{"title":"AI differentiates radionecrosis from true progression in brain metastasis upon stereotactic radiosurgery: analysis of 124 histologically assessed lesions.","authors":"Gaia Ressa, Riccardo Levi, Giovanni Savini, Luca Raspagliesi, Elena Clerici, Luisa Bellu, Luca A Cappellini, Marco Grimaldi, Saverio Pancetti, Beatrice Bono, Andrea Franzini, Marco Riva, Bethania Fernandez, Maximilian Niyazi, Federico Pessina, Giuseppe Minniti, Pierina Navarria, Marta Scorsetti, Letterio S Politi","doi":"10.1093/neuonc/noaf090","DOIUrl":"https://doi.org/10.1093/neuonc/noaf090","url":null,"abstract":"<p><strong>Background: </strong>Differentiating radionecrosis from neoplastic progression after stereotactic radiosurgery (SRS) for brain metastases is a diagnostic challenge. Previous studies have often been limited by datasets lacking histologically confirmed diagnoses. This study aimed to develop automated models for distinguishing radionecrosis from disease progression on brain MRI, utilizing cases with definitive histopathological confirmation.</p><p><strong>Methods: </strong>This multi-center retrospective study included patients who underwent surgical resection for suspected brain metastasis progression after SRS. Presurgical FLAIR and post-contrast T1 (T1w-ce) were segmented using a convolutional neural network (CNN) and compared with manual segmentation by means of Dice score. Radiomics features were extracted from each lesion, and a Random Forest model was trained on 70% of the internal dataset and evaluated on the remaining 30% and the complete external dataset. A 3DResNet-CNN was trained on the same split dataset. Validation was performed on the external dataset. Post-surgical histology was available for all cases.</p><p><strong>Results: </strong>124 brain metastases were included (104 from center 1 and 20 from center 2). Sole radionecrosis was histologically detected in 34 cases (27.4%).In the internal dataset, univariate and multivariate analysis identified 131 significantly different radiomics features, including GLDM_DNUN and GLDM_SDE within the enhancing area on the T1w-ce. On the external test dataset, the Random Forest model and the 3DResNet-CNN yielded accurate results in terms of accuracy (80.0%, 85.0%), AUROC (0.830, 0.893) and sensitivity (92.8%, 100%) in radionecrosis prediction, respectively.</p><p><strong>Conclusion: </strong>Artificial intelligence could be employed to differentiate between radionecrosis and brain metastasis progression upon SRS, potentially reducing unnecessary surgical interventions.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764515","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":"Advancing Clinical Response Against Glioblastoma: Evaluating SHP1705 CRY2 Activator Efficacy in Preclinical Models and Safety in Phase I Trials.","authors":"Priscilla Chan, Yoshiko Nagai, Qiulian Wu, Anahit Hovsepyan, Seda Mkhitaryan, Jiarui Wang, Gevorg Karapetyan, Theodore Kamenecka, Laura A Solt, Jamie Cope, Rex A Moats, Tsuyoshi Hirota, Jeremy N Rich, Steve A Kay","doi":"10.1093/neuonc/noaf089","DOIUrl":"https://doi.org/10.1093/neuonc/noaf089","url":null,"abstract":"<p><strong>Background: </strong>It has been reported that circadian clock components, Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), are essential for glioblastoma (GBM) stem cell (GSC) biology and survival. Consequently, we developed a novel Cryptochrome (CRY) activator SHP1705, which inhibits BMAL1-CLOCK transcriptional activity.</p><p><strong>Methods: </strong>We utilized GlioVis to determine which circadian genes are differentially expressed in non-tumor versus GBM tissues. We employed in vitro and in vivo methods to test the efficacy of SHP1705 against patient-derived GSCs and xenografts in comparison to earlier CRY activator scaffolds. We applied a novel REV-ERB agonist SR29065, which inhibits BMAL1 transcription, to determine whether targeting both negative limbs of the circadian transcription-translation feedback loop (TTFL) would yield synergistic effects against various GBM cells.</p><p><strong>Results: </strong>SHP1705 is the first circadian clock-modulating compound to be found safe and well-tolerated in Phase I clinical trials. SHP1705 has increased selectivity for the CRY2 isoform and potency against GSC viability compared to previously published CRY activators, making it promising for applications in GBM where CRY2 levels are found to be low. SHP1705 prolonged survival in mice bearing GBM tumors established with GSCs. When combined with novel REV-ERB agonist SR29065, SHP1705 displayed synergy against multiple GSC lines and differentiated GSCs (DGCs).</p><p><strong>Conclusions: </strong>We demonstrate the efficacy of SHP1705 against GSCs, which pose as a major source of chemoradiation resistance leading to poor GBM patient prognosis. Novel circadian clock compounds have high potential for targeting GBM as single agents or in combination with each other or current standard-of-care.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764493","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":"Rethinking Tumor Purity Estimation in the Era of AI.","authors":"Dana Silverbush","doi":"10.1093/neuonc/noaf091","DOIUrl":"https://doi.org/10.1093/neuonc/noaf091","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764453","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":"The impact of therapeutic radiation on drug distribution across the blood-brain barrier in normal mouse brain and orthotopic GBM tumors.","authors":"Wenjuan Zhang, Michael P Grams, Rajneet K Oberoi, Ju-Hee Oh, Paul A Decker, Terence T Sio, Surabhi Talele, Zac C Wilson, Margaret A Connors, Katrina K Bakken, Brett L Carlson, Lauren L Ott, Danielle M Burgenske, Erik J Tryggestad, Jeanette E Eckel Passow, William F Elmquist, Jann N Sarkaria","doi":"10.1093/neuonc/noaf093","DOIUrl":"https://doi.org/10.1093/neuonc/noaf093","url":null,"abstract":"<p><strong>Background: </strong>Most oncology therapeutics have limited distribution into the brain, and developing strategies to overcome this limitation would be clinically impactful. While therapeutic radiation is often cited as a strategy accomplish this, there are no published studies demonstrating the effect of radiation on drug distribution into the brain or brain tumors.</p><p><strong>Methods: </strong>Mice were treated with brain radiation (6 Gy × 5, 4 Gy × 10; 40 Gy × 1) and dosed with drugs (levetiracetam, cefazolin, nedisertib, brigimadlin, apitolisib, or GNE-317) at times ranging from just prior to months after radiation. Plasma and tissue drug concentrations were measured by LC-MS/MS.</p><p><strong>Results: </strong>Radiation did not significantly enhance drug delivery into brain tissue for levetiracetam, cefazolin, GNE-317, apitolisib, or nedisertib at any times post-radiation. Even a single, supra-therapeutic dose of radiation (40 Gy) did not significantly affect brain distribution of GNE-317 or apitolisib (P ≥ 0.07) from 16 to 160 hours post-radiation. For brigimadlin, radiation (6 Gy × 5) was associated with a modest but significant increase on drug accumulation only at 72 hours post-radiation (brain-to-plasma ratio 0.014±0.006 vs. 0.025±0.010, respectively; P = 0.04), but not at any other timepoint (24 hr, 15, 28, 94, 133, 183 days; P > 0.05). Similarly, radiation (6 Gy × 5) of orthotopic tumors did not increase levels of brigimadlin in GBM10 or GBM108 or nedisertib in GBM108 (P > 0.05).</p><p><strong>Conclusions: </strong>Radiation had no meaningful impact of drug delivery into brain or brain tumors for the drugs tested.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753428","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":"Erratum to: Metadherin/Astrocyte elevated gene-1 positively regulates the stability and function of forkhead box M1 during tumorigenesis.","authors":"","doi":"10.1093/neuonc/noaf060","DOIUrl":"https://doi.org/10.1093/neuonc/noaf060","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743212","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":"Co-occurrence of congenital anomalies and childhood brain tumors in 22 million live births.","authors":"Thanh T Hoang, Jeremy M Schraw, Charles Shumate, Tania A Desrosiers, Wendy N Nembhard, Mahsa Yazdy, Eirini Nestoridi, Amanda E Janitz, Russell S Kirby, Jason L Salemi, J P Tanner, Tiffany M Chambers, Michael D Taylor, Chad D Huff, Sharon E Plon, Philip J Lupo, Michael E Scheurer","doi":"10.1093/neuonc/noaf087","DOIUrl":"https://doi.org/10.1093/neuonc/noaf087","url":null,"abstract":"<p><strong>Background: </strong>Children born with a congenital anomaly have a higher risk of developing a brain tumor during childhood or adolescence, but the co-occurrence between specific types of congenital anomalies and specific types of childhood brain tumors (CBTs) is not well described. This study characterized the associations between specific congenital anomalies and CBTs.</p><p><strong>Methods: </strong>We leveraged a population-based registry linkage study of births (1990-2018), congenital anomalies, and cancer from nine states (n=22,599,099 births). Congenital anomalies were classified as major structural without a known chromosomal or genetic syndrome, chromosomal, neurofibromatosis, and/or tuberous sclerosis complex. CBT classification was based on the International Classification of Childhood Cancer for children diagnosed <20 years. Cox regression analyses were conducted separately by congenital anomaly for anomaly-CBT combinations with at least 5 co-occurring cases. We conducted analyses for any CBT and separately for astrocytoma, atypical teratoid/rhabdoid tumor, ependymoma, medulloblastoma, mixed and unspecified gliomas, and primitive neuroectodermal tumors.</p><p><strong>Results: </strong>There were 6,247 children diagnosed with a CBT. Having any major structural anomaly was associated with risk of any CBT and across all subgroups (aHR range: 1.48-3.69) except ependymoma, particularly among children diagnosed with a tumor by 1 year of age. Of the 66 anomaly-CBT combinations analyzed, 42 were significant (p<0.05), including 25 in an earlier version of this study and 16 novel associations (aHR range: 1.46-525). Anomaly-CBT associations also differed by astrocytoma histology.</p><p><strong>Conclusions: </strong>We observed consistent evidence that having a structural congenital anomaly increases risk of developing a CBT, particularly in infancy, which may provide insights into etiology.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730871","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":"SOX2 commands LIM homeobox transcription factors in choroid plexus development and tumorigenesis.","authors":"Lukas J Faltings, Fengjuan Lin, Mariam Zahran, Heena Jalili, Anjali Siluveru, Mahek Chaudry, Leah M Wachsmuth, Navjot Guru, Melanie Schoof, Ping Cao, Yuan Huang, Noreen Mian, Sohyun Moon, Asmaa Zahran, Kristen Green, Siddhi Modi, Maheen Umer, James Q Virga, Ying-Tao Zhao, Ulrich Schüller, Qun Li, Haotian Zhao","doi":"10.1093/neuonc/noaf085","DOIUrl":"https://doi.org/10.1093/neuonc/noaf085","url":null,"abstract":"<p><strong>Background: </strong>Choroid plexus (CP) tumors are rare brain neoplasms that mainly affect the pediatric population. Unlike benign CP papilloma (CPP), CP carcinoma (CPC) is an aggressive cancer with a dismal survival rate. Despite chromosome-wide rearrangements, drivers of most CP tumors remain elusive except recurrent alterations in TP53. Studies of signaling dysregulation may bring biological understanding of these malignancies. Previous studies implicated NOTCH signaling in CP tumors; we developed mouse models of CP tumors driven by NOTCH activation and Trp53 loss, respectively. This work examined the role of the transcription factor SOX2 in CP development and tumorigenesis.</p><p><strong>Methods: </strong>Multi-omics approaches were used to characterize cellular heterogeneity in NOTCH-driven CP tumors. SOX2 functions in the molecular signature of tumor cells were investigated.</p><p><strong>Results: </strong>Single-cell transcriptomics and epigenetics methods identified diverse cell populations in tumors that resemble normal CP, such as epithelial and glial groups. Pseudo-time trajectory analysis indicated that NOTCH-driven CP tumor arises from bi-potential glial progenitors and retains a progenitor-like signature characterized by an enhanced SOX2 profile. SOX2 inactivation attenuated progenitor-like features and blunted tumor growth. Integrative omics studies revealed SOX2 binding to genes expressed in progenitors in the rhombic lip, including LIM homeobox transcription factors LMX1A and LMX1B. Consistently, SOX2 maintains progenitor identity through regulating their expression in CP tumors and during development, whereas LMX1A and LMX1B support SOX2 functions in tumor cell proliferation. Furthermore, spatial transcriptomics revealed aberrant SOX2 and LMX1A expression in human CP tumors.</p><p><strong>Conclusions: </strong>SOX2-LMX1 signaling maintains progenitor identity in CP development and tumor formation.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701122","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":"Targeting PDGFRA-SHP2 Signaling Enhances Radiotherapy in IDH1-Mutant Glioma.","authors":"Xiaozhou Yu, Xiao Song, Deanna Tiek, Runxin Wu, Maya Walker, Craig Horbinski, Bo Hu, Shi-Yuan Cheng","doi":"10.1093/neuonc/noaf086","DOIUrl":"https://doi.org/10.1093/neuonc/noaf086","url":null,"abstract":"<p><strong>Background: </strong>Isocitrate dehydrogenase mutant (IDH-mut) gliomas represent a distinct subtype of glioma, characterized by a relatively better prognosis compared to IDH wildtype (wt) glioblastoma (GBM). Despite this advantage, these tumors remain incurable due to the limited availability of effective treatments. Targeting SHP2, a non-receptor protein tyrosine phosphatase, is a promising therapeutic strategy for several types of human cancers. In this study, we aim to determine the efficacy of SHP inhibition in IDH-mut gliomas.</p><p><strong>Methods: </strong>Bioinformatic and biological analyses revealed increased expression and activation of the PDGFRA-SHP2-ERK pathway in clinical IDH-mut gliomas and patient-derived IDH-mut glioma stem-like cells (GSCs). The effects of SHP2 inhibition, alone or with radiation therapy (RT), were assessed through assays including cell growth, sphere formation, cell differentiation markers, flow cytometry, immunoblotting, immunohistochemistry, and orthotopic brain tumor xenografts.</p><p><strong>Results: </strong>PDGFRA expression was elevated in IDH-mut gliomas and GSCs, activating the SHP2-ERK pathway. SHP099, a SHP2 inhibitor, reduced GSC tumorigenicity in vitro and in vivo by disrupting SHP2-ERK signaling and promoting differentiation. SHP099 also enhanced cytotoxicity of RT, the standard treatment for IDH-mut glioma, in IDH-mut GSCs and orthotopic glioma models. Mechanistically, the PDGFRA-SHP2-ERK axis is activated in IDH-mut gliomas and RT further activates this pathway. Targeting SHP2 suppressed ERK signaling thereby enhancing the therapeutic effect of RT.</p><p><strong>Conclusion: </strong>Combining SHP2 inhibition with RT is a promising therapeutic avenue for IDH-mut glioma by suppressing the activated SHP2-ERK axis.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701128","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":"An in-depth survey of immunosuppressive myeloid cell heterogeneity in GBM.","authors":"Brandon Emanuel León, Defne Bayik","doi":"10.1093/neuonc/noaf080","DOIUrl":"https://doi.org/10.1093/neuonc/noaf080","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701055","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":"Differentiation of Tumor vs. Peritumoral Cortex in Gliomas by Intraoperative Electrocorticography.","authors":"Belén Díaz-Fernández, David Henao-Herreno, Juan Nieto, Alesya Evstratova, Silvia Cases-Cunillera, Louise Deboeuf, Alexandre Roux, Edouard Dezamis, Marc Zanello, Bertrand Mathon, Carine Karachi, Alexandre Carpentier, Pascale Varlet, Johan Pallud, Laurent Capelle, Catalina Alvarado-Rojas, Michel Le Van Quyen, Gilles Huberfeld","doi":"10.1093/neuonc/noaf082","DOIUrl":"https://doi.org/10.1093/neuonc/noaf082","url":null,"abstract":"<p><strong>Background: </strong>Brain diffuse gliomas are highly epileptic and infiltrative tumors. Glioma surgery consists in the resection of the tumor core and the maximum of the peritumoral zone, infiltrated by tumor cells, guided by the intraoperative assessment of brain functionality and connectivity. However, its electrophysiological characteristics are poorly characterized.</p><p><strong>Methods: </strong>We studied the characteristics of Electrocorticographic (ECoG) signals, in the context of glioma surgery in awake condition on 29 patients, using EEG activity sampled on the tumor itself versus on its borders and in healthy areas. We assessed the features of frequency bands and aperiodic components (offset and slope) of ECoG power spectra during awake glioma surgery, according to cortical tumoral vs peritumoral and healthy status.</p><p><strong>Results: </strong>We found that tumor contacts present a decrease in activity for all the frequency bands except for delta activity, which was increased. Second, the peritumoral cortex was characterized by an increase in relative beta activity and slopes between 20-40 Hz. Low cortical tumor cell infiltration was directly correlated with a reduction in the production of physiological brain rhythms. Finally, an automatic classifier based on neural networks allowed the classification of the electrodes based on their power spectrum characteristics.</p><p><strong>Conclusions: </strong>This intraoperative study shows that ECoG during glioma surgery in awake condition may characterize the peritumoral cortices, key for pathophysiology and therapy, and deepens our knowledge of the effects of tumor cells infiltration on nervous tissue activity. Its assessment during the surgical procedure should better delineation of the cortical areas to be removed.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701117","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}