Neuro-oncology最新文献

{"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}

{"title":"SWI/SNF complexes govern ontology-specific transcription factor function in MYC-subtype atypical teratoid rhabdoid tumor.","authors":"Cody L Nesvick, Liang Zhang, Yuqian Yan, Alexander Q Wixom, Feda H Hamdan, Jizhi Ge, Jacob B Anderson, Alexandre Gaspar-Maia, Steven A Johnsen, David J Daniels","doi":"10.1093/neuonc/noaf081","DOIUrl":"https://doi.org/10.1093/neuonc/noaf081","url":null,"abstract":"<p><strong>Background: </strong>Atypical teratoid rhabdoid tumor (ATRT) is a deadly central nervous system embryonal tumor caused by loss of SMARCB1, a core subunit of SWI/SNF chromatin remodeling complexes. SMARCB1-deficient cancers are defined by loss of cell differentiation-associated enhancers, but how SWI/SNF interacts with other arbiters of cell differentiation (specifically lineage-specific transcription factors (TFs)) remains poorly understood.</p><p><strong>Methods: </strong>We leveraged a multi-omics approach, patient-derived ATRT cells and patient-derived orthotopic xenografts to investigate the interplay of SWI/SNF with lineage-specific TFs in a clinically relevant setting.</p><p><strong>Results: </strong>We observe that an activating protein 1 (AP-1)-dependent transcriptional regulatory network is lost in ATRT, and AP-1 and lineage-specific TFs TEAD1 and ZIC2 require SMARCB1 for enhancer binding. SMARCB1-dependent SWI/SNF integrates transcriptional functions of lineage-specific TFs into a core regulatory circuit that depends on the AP-1 subunit cJUN, whose expression is determined by a SMARCB1-dependent super enhancer that is lost in ATRT-MYC. In the absence of SMARCB1, lineage-specific TFs are sequestered to promoters, where they maintain core transcriptional programs necessary for cell survival. Targeting residual, promoter-proximal TF activity by a protein degrader of the SWI/SNF ATPase SMARCA4 or small molecule inhibitors that indirectly inhibit AP-1 and TEAD activity abrogates expression of these networks, reducing cell viability in vitro and prolonging survival in an orthotopic patient-derived xenograft model.</p><p><strong>Conclusions: </strong>These results demonstrate SWI/SNF complexes are critical for lineage-specific TF binding and activity at both promoters and enhancers. In the context of ATRT, these findings reveal a previously underappreciated therapeutic vulnerability in targeting residual promoter-proximal TF function in ATRT.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692958","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":"Ototoxicity and Cognitive Outcomes among Very Young Children Treated for Brain Tumors: Findings from a Multisite, Prospective, Longitudinal Trial.","authors":"Heather M Conklin, Nicole A Salman, Johnnie K Bass, Jie Huang, Arzu Onar-Thomas, Jason M Ashford, Jennifer Harman, Jeanelle S Ali, Michelle A Swain, Lana L Harder, Bonnie L Carlson-Green, Jonathan M Miller, Joanna Wallace, Ryan J Kaner, Thomas E Merchant, Giles W Robinson, Amar Gajjar","doi":"10.1093/neuonc/noaf073","DOIUrl":"https://doi.org/10.1093/neuonc/noaf073","url":null,"abstract":"<p><strong>Background: </strong>Brain tumor treatment can result in sensorineural hearing loss (SNHL) that is associated with cognitive declines in school-age children. Young children treated for brain tumors are at heightened cognitive risk. This study examines the unique contribution of treatment-related ototoxicity to cognitive outcomes in young children treated for brain tumors.</p><p><strong>Methods: </strong>135 young children (mean age= 1.7 years) with a newly diagnosed malignant brain tumor were treated with chemotherapy, with or without focal proton or photon radiation therapy. Serial audiology and neurocognitive assessments were conducted for five years as part of a prospective, multisite, longitudinal trial (SJYC07; NCT00602667). SNHL was dichotomized as present versus not present (Chang grade ≥1a vs. 0). Neurocognitive assessments included intellectual functioning and parent ratings of adaptive functioning and attention.</p><p><strong>Results: </strong>67% of patients experienced mild-to-severe SNHL, which was associated with younger age at diagnosis (p<. 001) but not sex, treatment, or study risk arm (p> .10). Pre-treatment, higher IQ was associated with older age and higher socioeconomic status (p< .01), with a negative change in IQ trajectory after SNHL that was worse for children with supratentorial tumors. Pre-treatment, higher adaptive functioning was associated with older age (p= .0001), with a negative change in adaptive functioning trajectory after SNHL that was worse for those treated at a younger age. Attention problems increased after SNHL for the entire group (p= .0099).</p><p><strong>Conclusions: </strong>SNHL is associated with IQ decline and worsening adaptive functioning and attention in young children treated for brain tumors. These findings have important implications for treatment modifications, interventions, and caregiver education.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692953","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":"Diffusion and contrast-enhancement MRI phenotypes associated with immune checkpoint inhibitor exposure and with immune cell infiltration in brain metastases.","authors":"Francesco Sanvito, Gianluca Nocera, Zexi Wang, Eileen Shiuan, Lu Sun, Sonoko Oshima, Asher Kim, Irina Kryukov, Guowen Shao, Nicholas S Cho, Noriko Salamon, Benjamin M Ellingson, Robert Prins, Won Kim, Jingwen Yao","doi":"10.1093/neuonc/noaf084","DOIUrl":"https://doi.org/10.1093/neuonc/noaf084","url":null,"abstract":"<p><strong>Background: </strong>MRI-derived apparent diffusion coefficient (ADC) and contrast-enhancement (CE) may represent non-invasive biomarkers to evaluate microstructural tissue changes and histopathological immune cell infiltration induced by immune checkpoint inhibitors (ICI).</p><p><strong>Methods: </strong>125 lesions across 93 patients were analyzed. ADC (reflecting water diffusivity) and CE T1-subtraction maps (reflecting blood-brain barrier permeability) tumor values were used for bivariate histograms of ADC and CE, and to quantify voxel fractions belonging to highADC-highCE and lowADC-lowCE quadrants. The association between ICI exposure and voxel frequency in ADC-CE quadrants was evaluated with multivariate mixed-effects models accounting for corticosteroid exposure and other variables. In a subset of patients (n=23), the association between immune cell counts (CD45+ cell density) from tissue samples and ADC-CE phenotypes was tested.</p><p><strong>Results: </strong>ICI and corticosteroid exposure were associated with distinct ADC-CE phenotypes on bivariate histograms. ICI-exposed lesions showed significantly higher voxel frequency in the highADC-highCE quadrant (p<0.001) and lower voxel frequency in the lowADC-lowCE quadrant (p<0.01), compared to ICI-naïve lesions. Multivariate analyses confirmed that ICI exposure was an independent determinant of higher voxel frequency in the highADC-highCE quadrant (p=0.001) and lower voxel frequency in the lowADC-lowCE quadrant (p=0.01) in absence of corticosteroid treatment. Corticosteroid usage significantly influenced the relationship between ADC-CE phenotypes and ICI exposure. Voxel frequency in ADC-CE quadrants was correlated with CD45+ cell density in histopathology (partial ρ=0.56 p=0.01 for highADC-highCE, partial ρ=-0.64 p<0.01 for lowADC-lowCE).</p><p><strong>Conclusions: </strong>ADC-CE phenotypes are associated with ICI exposure and immune cell infiltration in BM, representing potential non-invasive markers to monitor ICI-induced pathophysiological changes.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677092","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":"Characterizing long-term neurocognitive outcomes through diffusion tensor imaging in childhood brain tumor survivors.","authors":"Ryan T Oglesby, Chathurangi H Pathiravasan, Elizabeth Olatunji, Leslie Chang, Jill Chotiyanonta, Yuto Uchida, Junghoon Lee, Kenichi Oishi, Rachel Peterson, Sahaja Acharya","doi":"10.1093/neuonc/noaf083","DOIUrl":"https://doi.org/10.1093/neuonc/noaf083","url":null,"abstract":"<p><strong>Background: </strong>Diffusion tensor imaging (DTI) can probe the longitudinal microstructural integrity and development of the brain. This study characterizes the relationship between long-term neurocognition and changes in fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum and hippocampus in childhood brain tumor survivors.</p><p><strong>Methods: </strong>Patients diagnosed with a brain tumor at < 18 years of age with ≥ 2 neurocognitive assessments retrospectively paired with DTI were eligible. Multi-trajectory modeling clustered patients into distinct neurocognitive trajectories based on intelligent quotient, processing speed index and working memory. Linear mixed models were used to determine whether patient clusters were associated with change in MD and FA. Patient clusters were compared to healthy subjects.</p><p><strong>Results: </strong>From 2014 to 2022, 68 patients with 464 neurocognitive assessments paired with DTI and 80 healthy subjects were included. Multi-trajectory modeling identified two patient clusters: (1) low-performance, with declining scores below the normative mean, and (2) normal-performance. Compared to the low-performance group, the normal-performance group demonstrated greater increase in FA and greater decrease in MD within the corpus callosum and hippocampus, respectively. This pattern was consistent across multiple white matter tracts, highlighting global differences between the groups. Directional change of FA and MD observed in healthy subjects mirrored that of the normal-performance group, but was opposite to that of the low-performance group.</p><p><strong>Conclusion: </strong>Compared to the normal performance group, the low-performance group demonstrated reduced white matter microstructural integrity and higher mean diffusivity in the hippocampus over time, opposite to what is observed in normally developing children. This suggests aberrant neurodevelopment may contribute to late neurocognitive impairment.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677067","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":"A multi-institutional phase 1 clinical trial exploring upfront multimodal standard of care and combined immunotherapies for newly diagnosed glioblastoma.","authors":"Patrick Y Wen, Andrea Manzanera, Caroline Duault, Edgar Gonzalez-Kozlova, Lenika Lopez, Stuart A Grossman, Xiaobu Ye, Joy Fisher, Ian Lee, Tobias Walbert, James Snyder, Steven Brem, Arati Desai, Stephen J Bagley, Chandana Kakani, Roy Strowd, Stephen Tatter, Adrian Laxton, Glenn Lesser, Nduka Amankulor, Frank Lieberman, Jan Drappatz, Megan Mantica, Dan Triggs, Cara Haymaker, Ignacio I Wistuba, Gheath Al-Atrash, Julia Mendoza Perez, Andrew Futreal, Latasha D Little, M D Habibul Islam, Dzifa Duose, Peixin Jiang, Alexandre Reuben, Sean E Lawler, Mina Pichavant, Andrew Gentles, Sean Bendall, Alex Kong, Christine Camacho, Diane Del Valle, Seunghee Kim-Schulze, Sacha Gnjatic, Elad Sharon, M Oskar Nowicki, Pierpaolo Peruzzi, Doug Lane, Estuardo Aguilar-Cordova, Laura K Aguilar, Garrett Nichols, Jessica Dwyer, Paul Peter Tak, Holden Maecker, Francesca Barone, E Antonio Chiocca","doi":"10.1093/neuonc/noaf079","DOIUrl":"https://doi.org/10.1093/neuonc/noaf079","url":null,"abstract":"<p><strong>Background: </strong>For newly diagnosed glioblastoma (GBM), combination of surgical upfront immunotherapy with aglatimagene besadenovec (CAN-2409), followed by chemoradiation and then adjuvant nivolumab has not been tested. The aim of this study was to test the safety of this regimen and determine metrics of immune activation that may correlate with clinical outcomes.</p><p><strong>Methods: </strong>41 patients with suspected newly diagnosed GBM by imaging were enrolled in this multi-institutional, open label, phase 1b clinical trial before surgical resection. Frozen section confirmation of high-grade glioma was required for administration of aglatimagene besadenovec. This was then followed with chemoradiation and adjuvant nivolumab. Tumor and blood were assayed for genetic and immune markers before and during treatment.</p><p><strong>Results: </strong>The regimen was well tolerated and generated measurable immune activation. Factors linked to survival were identified, such as baseline mutated gene pairs (e.g. MED15/ HRC), tumor immune cell composition, and changes in systemic cytokine, immune cells, and T cell diversity. The most significant serial systemic immune changes were observed in a long-term survivor subset of patients with gross total resection (GTR)/ methylated methylguanine methyltransferase (MGMT) promoter tumors. Median overall survival (mOS) in these patients was 30.6 months, while it was less for patients with unmethylated or subtotal resections.</p><p><strong>Conclusions: </strong>These findings suggest the opportunity for patient stratification and the potential for more durable antitumor immune responses in future clinical trials of this multimodal standard of care and combined immunotherapy regimen. ClinicalTrials.gov identifier: NCT03576612.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692949","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":"Histopathological and molecular characteristics of IDH-wildtype glioblastoma without contrast enhancement: implications for clinical outcomes.","authors":"Martha Foltyn-Dumitru, Rouzbeh Banan, Marianne Schell, Mustafa Ahmed Mahmutoglu, Tobias Kessler, Wolfgang Wick, Gianluca Brugnara, Martin Bendszus, Felix Sahm, Philipp Vollmuth","doi":"10.1093/neuonc/noaf070","DOIUrl":"https://doi.org/10.1093/neuonc/noaf070","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GB) heterogeneity poses substantial challenges for diagnosis and treatment. IDH-wildtype GB may lack contrast enhancement on MRI and exhibit a \"low-grade radiologic appearance\" (non-CE GB), a phenomenon with unclear clinical implications. This study investigates the histopathological and molecular differences and survival outcomes between contrast-enhancing (CE) and non-CE GB.</p><p><strong>Methods: </strong>This retrospective study at Heidelberg University Hospital analyzed 457 IDH-wildtype GB cases (09/2009-01/2021). Contrast enhancement on preoperative MRI was volumetrically assessed, classifying tumors as non-CE/CE GB using a 1 cm³ cut-off. Molecular and histopathological features, including microvascular proliferation, necrosis, and overall survival (OS), were compared between the groups.</p><p><strong>Results: </strong>Of the initial cohort, 352 (77%) patients met the inclusion criteria, with 44 (12.5%) non-CE and 308 (87.5%) CE GB. The histopathological assessment revealed that non-CE GB was less likely to present traditional hallmarks of glioblastoma, such as microvascular proliferation (39% vs. 94%) and necrosis (25% vs. 92%) (p<0.001). In the non-CE group, 24 patients (55%) were diagnosed as molecular-GB, compared to only 8 patients (3%) in the CE group (p < 0.001). A significant difference was observed in Ki-67 levels, with non-CE GBs having a lower mean Ki-67 index of 18 ± 12% compared to 26 ± 13% in CE tumors (p<0.001). The median OS was 27.2 months (95%CI 19.8-NA) for non-CE and 14.7 months (95% CI, 13.2-17.1) for CE GB (p=0.0049).</p><p><strong>Conclusions: </strong>IDH-wildtype GBs without contrast enhancement are often diagnosed based on molecular criteria due to less frequent histopathological hallmarks and are associated with prolonged OS.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663881","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":"Dual role of WNT10A in promoting the malignancy of glioblastoma and remodeling the tumor microenvironment.","authors":"Zhiwei Xue, Xuehai Zhang, Bo Mao, Guangjing Mu, Yan Zhang, Junzhi Liu, Jiangli Zhao, Xuchen Liu, Yanfei Sun, Guo Xiang, Hongwei Wang, Wenzhe Xu, Zheng Jiang, Shuai Wang, Rolf Bjerkvig, Jian Wang, Donghai Wang, Xingang Li, Bin Huang, Mingzhi Han","doi":"10.1093/neuonc/noaf075","DOIUrl":"https://doi.org/10.1093/neuonc/noaf075","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) represents a complex ecosystem characterized by numerous interactions between tumor cells and the surrounding tumor microenvironment (TME). Here, we show that WNT10A, a member of the WNT family, plays an important role in GBM growth where its influence is mediated via both autocrine and paracrine pathways thereby stimulating not only the tumor cells but also normal cell types within the tumor microenvironment (TME).</p><p><strong>Methods: </strong>In silico analysis was performed to identify high-expressing WNT family members in GBM. Knockdown and overexpression methods were used to examine the function of WNT10A in GBM cells and in orthotopic GBM xenografts in vivo. Co-immunoprecipitation (Co-IP) was used to confirm receptor binding and chromatin immunoprecipitation (ChIP) was performed to analyze transcriptional activation of downstream genes.</p><p><strong>Results: </strong>WNT10A was found to be highly expressed in GBMs and its knockdown significantly suppressed GBM malignant behavior in vitro and in vivo. Co-IP assays confirmed an interaction between WNT10A and FZD1, which activated the JNK/c-Jun/FOSB signaling pathway and enhanced the transcription of FOSB. Importantly, GBM cells secreted WNT10A into the tumor microenvironment, leading to an activation of the PI3K-AKT pathway in tumor-associated macrophages (TAMs) and the JNK pathway in tumor-associated astrocytes. The latter caused a secretion of tumor-promoting cytokines IL-6, MCP-1, and angiogenin. LGK974, a PORCN inhibitor, inhibited the secretion of WNT10A to suppress the malignant GBM phenotype.</p><p><strong>Conclusion: </strong>Our findings revealed that WNT10A is a critical factor promoting GBM progression through both autocrine and paracrine mechanisms. Thus, our findings provide the foundation for WNT-targeted clinical GBM treatment.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658057","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":"Post-operative Fluid Restriction to Prevent Delayed Hyponatremia after Endoscopic Transsphenoidal Surgery.","authors":"Doriann Klassen, Shinghei Mok, Jenie Y Hwang, Sydney L Blount, Kelley J Williams, Brendan M Fong, Michael R Chicoine, Ralph G Dacey, Nyssa F Farrell, Joshua W Osbun, Keith M Rich, Lauren T Roland, John S Schneider, Gregory J Zipfel, Chongliang Luo, Albert H Kim, Julie M Silverstein","doi":"10.1093/neuonc/noaf069","DOIUrl":"https://doi.org/10.1093/neuonc/noaf069","url":null,"abstract":"<p><strong>Background: </strong>Readmission following endoscopic endonasal transsphenoidal surgery (EETS) for pituitary neuroendocrine tumor (PitNET) and other sellar pathology is most commonly due to delayed hyponatremia. Studies suggest post-operative fluid restriction (FR) reduces delayed hyponatremia. We present a prospective randomized controlled study evaluating post-EETS FR.</p><p><strong>Methods: </strong>300 participants were scheduled for EETS (2016-2023) at a single institution. Patients with CKD, CHF, arginine vasopressin deficiency on post-operative day (POD) 3, chronic hyponatremia, and untreated adrenal insufficiency or hypothyroidism were excluded. Groups included control (ad-lib, n=94), moderate FR (1.8 L/day or 2 L/day weight >100 kg, n=39), and strict FR (1 L/day or 1.2 L/day weight >100 kg, n=62) from POD 3-14. Incidence of overall, moderate, and severe hyponatremia (Na <135, 125-129, and <125 mEq/L), readmission rates, fluid intake, and thirst were evaluated.</p><p><strong>Results: </strong>The incidence of overall hyponatremia was 31.9%, 28.2%, and 21.0% in control, moderate FR, and strict FR groups, and the incidence of severe hyponatremia was 7.4%, 5.1%, and 0% in control, moderate FR, and strict FR groups. Nadir Na level was higher (1.81 mEq/L; 95% CI, 0.34 to 3.27; P=0.02) and severe hyponatremia occurred less frequently (95% CI, 0.00 to 1.02; P=0.04) in the strict FR vs. control group. Readmission was lower in the strict FR (1.6%, n=1) vs. control group (6.4%, n=6).</p><p><strong>Conclusion: </strong>Post-operative FR decreases rates of delayed hyponatremia and related readmission compared to patients drinking ad-lib. Further studies are needed to assess the optimal volume and duration of FR after EETS.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625536","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":"Dual Inhibition of MAPK and TORC1 Signaling Retards Development of Radiation Resistance in Pediatric BRAFV600E Glioma Models.","authors":"Fuyang Li, Kathryn M Bondra, Hanzhou Wang, Dias Kurmashev, Bipasha Mukherjee, Suman Kanji, Amyn A Habib, Yidong Chen, Siyuan Zheng, Sandeep Burma, Peter J Houghton","doi":"10.1093/neuonc/noaf068","DOIUrl":"https://doi.org/10.1093/neuonc/noaf068","url":null,"abstract":"<p><strong>Background: </strong>MAPK pathway inhibitors (MAPKi) have shown significant efficacy in treating childhood BRAF-activated brain tumors. For tumors harboring BRAFV600E mutations, the drugs are rarely curative, and patients can become refractory to treatment. MAPKi combining X-radiation therapy (XRT) may improve cure rate, but development of XRT-resistance is a challenge.</p><p><strong>Methods: </strong>XRT-resistance was induced by multiple XRT cycles in pediatric BRAFV600E glioma patient-derived xenograft (PDX) models. RNA sequencing was performed to identify differentially expressed genes and pathways potentially contributing to XRT-resistance. Cells isolated from PDXs were used to test the contribution of specific genes and pathways to XRT-resistance. PDX models were used to evaluate the efficacy of targeted treatments combined with XRT.</p><p><strong>Results: </strong>Tumors developed resistance after multiple cycles of XRT. MEK inhibition combining XRT significantly improved tumor control, compared to XRT alone, but resistance to combined therapy developed rapidly. RNA-sequencing analysis revealed up-regulation of MAPK and PI3K-mTOR signaling in the XRT-resistant tumors. Isolated cells showed in vitro resistance to XRT, which was partially reversed by inhibiting PI3K-mTOR. Up-regulation of TORC1 signaling in XRT naïve tumor cells, via constitutively active AKT or TSC2 deletion, conferred in vitro XRT-resistance.The pro-survival gene BIRC5 (Survivin), a target of TORC1 signaling, contributed to XRT-resistance. Combining trametinib-rapamycin with XRT significantly enhanced therapeutic efficacy in PDX models and prevented or delayed resistance development.</p><p><strong>Conclusion: </strong>PI3K-mTOR activation promotes the development of XRT-resistance in pediatric BRAFV600E glioma. Dual targeting of MAPK and TORC1 signaling significantly enhances the therapeutic efficacy of XRT, and can potentially prevent the development of XRT-resistance. (250 words).</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625535","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}