Neuro-oncology Advances最新文献

{"title":"Unraveling the relations between post-traumatic stress symptoms, neurocognitive functioning and limbic white matter in pediatric brain tumor patients","authors":"Anne E M Leenders, Eva Kremer - Hooft van Huijsduijnen, Bruno Robalo, Rosa van Male, A. De Luca, Rachèl Kemps, E. Hoving, Maarten H Lequin, M. Grootenhuis, M. Partanen","doi":"10.1093/noajnl/vdae026","DOIUrl":"https://doi.org/10.1093/noajnl/vdae026","url":null,"abstract":"\u0000 \u0000 \u0000 Pediatric brain tumor patients are at risk of developing neurocognitive impairments and associated white matter alterations. In other populations, post-traumatic stress symptoms (PTSS) impact cognition and white matter. This study aims to investigate the effect of PTSS on neurocognitive functioning and limbic white matter in pediatric brain tumor patients.\u0000 \u0000 \u0000 \u0000 Sixty-six patients (6-16 years) completed neuropsychological assessment and brain MRI (one-year post-diagnosis) and parents completed PTSS proxy questionnaires (CRIES-13; 1-3 months and one-year post-diagnosis). Mean Z-scores and percentage impaired (>1SD) for attention, processing speed, executive functioning, and memory were compared to normscores (t-tests, chi-square tests). Multi-shell diffusion MRI data were analyzed for white matter tractography (fractional anisotropy/axial diffusivity). Effects of PTSS on neurocognition and white matter were explored with linear regression models (FDR correction for multiple testing), including age at diagnosis, treatment intensity, and tumor location as covariates. Neurocognition and limbic white matter associations were explored with correlations.\u0000 \u0000 \u0000 \u0000 Attention (M=-.49, 33% impaired; P<.05) and processing speed (M=-.57, 34% impaired; P<.05) were significantly lower than healthy peers. PTSS was associated with poorer processing speed (β=-0.64, P<.01). Treatment intensity, age at diagnosis, and tumor location, but not PTSS, were associated with limbic white matter metrics. Neurocognition and white matter metrics were not associated.\u0000 \u0000 \u0000 \u0000 Higher PTSS was associated with poorer processing speed, highlighting the need for monitoring and timely referrals to optimize psychological well-being and neurocognitive functioning. Future research should focus on longitudinal follow-up and explore the impact of PTSS interventions on neurocognitive performance.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"23 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139958371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-driven measurements of brain metastases’ response to SRS compare favorably with current manual standards of assessment","authors":"K. Prezelski, D. G. Hsu, L.A. del Balzo, Erica Heller, Jennifer Ma, Luke R G Pike, A. Ballangrud, M. Aristophanous","doi":"10.1093/noajnl/vdae015","DOIUrl":"https://doi.org/10.1093/noajnl/vdae015","url":null,"abstract":"\u0000 \u0000 \u0000 Evaluation of treatment response for brain metastases (BMs) following stereotactic radiosurgery (SRS) becomes complex as the number of treated BMs increases. This study uses artificial intelligence (AI) to track BMs after SRS and validates its output compared with manual measurements.\u0000 \u0000 \u0000 \u0000 Patients with BMs who received at least one course of SRS and followed up with MRI scans were retrospectively identified. A tool for automated detection, segmentation, and tracking of intracranial metastases on longitudinal imaging, MEtastasis Tracking with Repeated Observations (METRO), was applied to the dataset. The longest three-dimensional (3D) diameter identified with METRO was compared with manual measurements of maximum axial BM diameter, and their correlation was analyzed. Change in size of the measured BM identified with METRO after SRS treatment was used to classify BMs as responding, or not responding, to treatment, and its accuracy was determined relative to manual measurements.\u0000 \u0000 \u0000 \u0000 From 71 patients, 176 BMs were identified and measured with METRO and manual methods. Based on a one-to-one correlation analysis, the correlation coefficient was R2 = 0.76 (p = 0.0001). Using modified BM response classifications of BM change in size, the longest 3D diameter data identified with METRO had a sensitivity of 0.72 and a specificity of 0.95 in identifying lesions that responded to SRS, when using manual axial diameter measurements as the ground truth.\u0000 \u0000 \u0000 \u0000 Using AI to automatically measure and track BM volumes following SRS treatment, this study showed a strong correlation between AI-driven measurements and the current clinically used method: manual axial diameter measurements.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"3 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139958801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of the third-generation, bi-steric mTORC1-selective inhibitor RMC-6272 in NF2-deficient models","authors":"Srirupa Bhattacharyya, Janet L. Oblinger, R. Beauchamp, Lili Kosa, Francis Robert, S. Plotkin, Long-Sheng Chang, V. Ramesh","doi":"10.1093/noajnl/vdae024","DOIUrl":"https://doi.org/10.1093/noajnl/vdae024","url":null,"abstract":"\u0000 \u0000 \u0000 NF2-associated meningiomas are progressive, highly morbid and are non-responsive to chemotherapies, highlighting the need for improved treatments. We have established aberrant activation of mechanistic target of rapamycin (mTOR) signaling in NF2-deficient tumors, leading to clinical trials with first- and second-generation mTOR inhibitors. However, results have been mixed, showing stabilized tumor growth without shrinkage offset by adverse side-effects. To address these limitations, here we explored the potential of third-generation, bi-steric mTORC1 inhibitors using the preclinical tool compound RMC-6272.\u0000 \u0000 \u0000 \u0000 Employing human NF2-deficient meningioma lines, we compared mTOR inhibitors rapamycin (first-generation), INK128 (second-generation) and RMC-6272 (third-generation) using in vitro dose-response testing, cell-cycle analysis and immunoblotting. Furthermore, the efficacy of RMC-6272 was assessed in NF2-null 3D-spheroid meningioma models, and its in vivo potential was evaluated in two orthotopic meningioma mouse models.\u0000 \u0000 \u0000 \u0000 Treatment of meningioma cells revealed that, unlike rapamycin, RMC-6272 demonstrated superior growth inhibitory effects, cell cycle arrest, and complete inhibition of phosphorylated 4E-BP1 (mTORC1 readout). Moreover, RMC-6272 had a longer retention time than INK128 and inhibited expression of several eIF4E-sensitive targets on the protein level. RMC-6272 treatment of NF2 spheroids showed significant shrinkage in size as well as reduced proliferation. Further, in vivo studies in mice revealed effective blockage of meningioma growth by RMC-6272, compared with vehicle controls.\u0000 \u0000 \u0000 \u0000 Our study in preclinical models of NF2 supports possible future clinical evaluation of third-generation, investigational mTORC1 inhibitors, such as RMC-5552, as a potential treatment strategy for NF2.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"35 30","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139962426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential roles for efferocytosis in glioblastoma immune evasion","authors":"I. Lorimer","doi":"10.1093/noajnl/vdae012","DOIUrl":"https://doi.org/10.1093/noajnl/vdae012","url":null,"abstract":"\u0000 Glioblastoma is an aggressive and incurable brain cancer. This cancer establishes both local and systemic immunosuppression that create a major obstacle to effective immunotherapies. Many studies point to tumour resident myeloid cells (primarily microglia and macrophages) as key mediators of this immunosuppression. Myeloid cells exhibit a high level of plasticity with respect to their phenotype, and are capable of both stimulating and repressing immune responses. How glioblastomas recruit myeloid cells and exploit them to avoid the immune system is an active area of research. Macrophages can acquire an immunosuppressive phenotype as a consequence of exposure to cytokines such as TGFB1 or IL4; in addition, macrophages can acquire an immunosuppressive phenotype as a consequence of the engulfment of apoptotic cells, a process referred to as efferocytosis. There is substantial evidence that glioblastoma cells are able to secrete cytokines and other factors that induce an immunosuppressive phenotype in macrophages and microglia. However, less is known about the contribution of efferocytosis to immunosuppression in glioblastoma. Here I review the literature in this area and discuss the potential of efferocytosis inhibition to improve glioblastoma response to immunotherapy.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"54 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139598683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of liquid biopsy for detection of the KIAA1549-BRAF fusion in circulating tumor DNA from children with pilocytic astrocytoma","authors":"Olha Krynina, T. Díaz de Ståhl, C. Jylhä, Geraldine Giraud, Per Nyman, Anders Fritzberg, Johanna Sandberg, E. Tham, Ulrika Sandvik","doi":"10.1093/noajnl/vdae008","DOIUrl":"https://doi.org/10.1093/noajnl/vdae008","url":null,"abstract":"\u0000 \u0000 \u0000 Low-grade gliomas (LGGs) represent children's most prevalent central nervous system tumor, necessitating molecular profiling to diagnose and determine the most suitable treatment. Developing highly sensitive screening techniques for liquid biopsy samples is particularly beneficial, as it enables the early detection and molecular characterization of tumors with minimally invasive samples.\u0000 \u0000 \u0000 \u0000 We examined CSF and plasma samples from patients with pilocytic astrocytoma (PA) using custom multiplexed droplet digital polymerase chain reaction (ddPCR) assays based on whole genome sequencing data. These assays included a screening test to analyze BRAF duplication and a targeted assay for the detection of patient-specific KIAA1549::BRAF fusion junction sequences or single nucleotide variants.\u0000 \u0000 \u0000 \u0000 Our findings revealed that 5 out of 13 individual cerebrospinal fluid (CSF) samples tested positive for circulating tumor DNA (ctDNA). Among these cases, three exhibited the KIAA1549::BRAF fusion, which was detected through copy number variation (CNV) analysis (n=1) or a fusion-specific probe (n=2), while one case each displayed the BRAF V600E mutation and the FGFR1 N577K mutation. Additionally, a quantitative analysis of cell-free DNA (cfDNA) concentrations in PA CSF samples showed that most cases had low cfDNA levels, below the limit of detection of our assay (<1.9 ng).\u0000 \u0000 \u0000 \u0000 While CNV analysis of CSF samples from LGGs still has some limitations, it has the potential to serve as a valuable complementary tool. Furthermore, it can also be multiplexed with other aberrations e.g. to the BRAF V600 test, to provide important insights into the molecular characteristics of LGGs.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"58 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139602416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing the efficacy of bevacizumab in newly diagnosed glioblastoma: a systematic review and external pseudodata-based analysis","authors":"G. Sferruzza, Massimo Malcangi, Luca Bosco, G. Finocchiaro","doi":"10.1093/noajnl/vdad174","DOIUrl":"https://doi.org/10.1093/noajnl/vdad174","url":null,"abstract":"\u0000 \u0000 \u0000 First-line use of Bevacizumab for glioblastoma (GBM) was evaluated in two Phase III randomized controlled trials (RCT), demonstrating an impact on progression-free survival (PFS) but not overall survival (OS). However, the crossover events of these trials raised concerns regarding the reliability of this latter analysis. In this study, we conducted an external control-based reassessement of the bevacizumab efficacy in newly diagnosed GBM (ndGBM) against the standard Stupp protocol.\u0000 \u0000 \u0000 \u0000 A systematic review of literature was conducted to identify the Phase III RCTs in ndGBM incorporating the Stupp protocol as an arm. For the selected studies, we extracted individual patient survival pseudodata of the Stupp protocol arm by digitizing the Kaplan-Meier plots. A comprehensive pipeline was established to select suitable control studies as external benchmarks.\u0000 \u0000 \u0000 \u0000 Among the 13 identified studies identified in our systematic review, 4 studies resulted as comparable with the AVAglio trial and 2 with the RTOG 0825. Pooled individual patient pseudodata analysis showed no differences in terms of OS when bevacizumab is added to the Stupp protocol.\u0000 \u0000 \u0000 \u0000 The external controlled-based reassessment of the bevacizumab treatment in ndGBM confirmed its lack of efficacy in extending OS. Our study includes a summary table of individual patient survival pseudodata from all Phase III RCTs in ndGBM employing the Stupp protocol and provides a pipeline that offers comprehensive guidance for conducting external control-based assessments in ndGBM.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"45 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139608495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid, economical diagnostic classification of ATRT molecular subgroup using NanoString nCounter platform","authors":"B. Ho, A. Arnoldo, Y. Zhong, M. Lu, J. Torchia, F. Yao, C. Hawkins, A. Huang","doi":"10.1093/noajnl/vdae004","DOIUrl":"https://doi.org/10.1093/noajnl/vdae004","url":null,"abstract":"\u0000 \u0000 \u0000 Despite genomic simplicity, recent studies have reported at least three major Atypical Teratoid Rhabdoid Tumor (ATRT) subgroups with distinct molecular and clinical features. Reliable ATRT subgrouping in clinical settings remains challenging due to a lack of suitable biological markers, sample rarity, and relatively high cost of conventional subgrouping methods. This study aimed to develop a reliable ATRT molecular stratification method that can be implemented across clinical settings.\u0000 \u0000 \u0000 \u0000 We have developed an ATRT subgroup predictor assay using a custom genes panel for the NanoString nCounter System and a flexible machine learning classifier package. 71 ATRT primary tumors with matching gene expression array and NanoString data were used to construct a multi-algorithms ensemble classifier. Additional validation was performed using an independent gene expression array against independently generated dataset. We also analyzed 11 extra-cranial rhabdoid tumors with our classifier and compared our approach against DNA methylation classification to evaluate the result consistency with existing methods.\u0000 \u0000 \u0000 \u0000 We have demonstrated that our novel ensemble classifier has an overall average of 93.6% accuracy in the validation dataset, and a striking 98.9% accuracy was achieved with the high prediction score samples. Using our classifier, all analyzed extra-cranial rhabdoid tumors are classified as MYC subgroups. Compared with the DNA methylation classification, the results show high agreement, with 84.5% concordance and up to 95.8% concordance for high-confidence predictions.\u0000 \u0000 \u0000 \u0000 Here we present a rapid, cost-effective, and accurate ATRT subgrouping assay applicable for clinical use.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 30","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139619078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in methylation profiles between long-term survivors and short-term survivors of IDH- wildtype glioblastoma","authors":"M. van der Meulen, Ronald C Ramos, M. Voisin, V. Patil, Qingxia Wei, O. Singh, S. Climans, Navya Kalidindi, Rosemarylin Or, Ken Aldape, P. Diamandis, David G Munoz, G. Zadeh, Warren P Mason","doi":"10.1093/noajnl/vdae001","DOIUrl":"https://doi.org/10.1093/noajnl/vdae001","url":null,"abstract":"\u0000 \u0000 \u0000 Patients with glioblastoma (GBM) have a median overall survival (OS) of approximately 16 months. However, approximately 5% of patients survive >5 years. This study examines the differences in methylation profiles between long-term survivors (>5 years, LTS) and short-term survivors (<1 year, STS) with isocitrate dehydrogenase (IDH)-wildtype GBMs.\u0000 \u0000 \u0000 \u0000 In a multicenter retrospective analysis, we identified 25 LTS with a histologically confirmed GBM. They were age- and sex-matched to a STS. The methylation profiles of all 50 samples were analyzed with EPIC 850k, classified according to the DKFZ methylation classifier, and the methylation profiles of LTS versus STS were compared.\u0000 \u0000 \u0000 \u0000 After methylation profiling, 16/25 LTS and 23/25 STS were confirmed to be IDH-wildtype GBMs, all with +7/-10 signature. LTS had significantly increased MGMT promoter methylation, and higher prevalence of FGFR3-TACC3 fusion (p=0.03). STS were more likely to exhibit CDKN2A/B loss (p=0.01) and higher frequency of NF1 (p=0.02) mutation. There were no significant CpGs identified between LTS vs STS at an adjusted p-value of 0.05. Unadjusted analyses identified key pathways involved in both LTS and STS. The most common pathways were the Hippo signaling pathway and the Wnt-pathway in LTS, and GPCR ligand binding and cell-cell signaling in STS.\u0000 \u0000 \u0000 \u0000 A small group of patients with IDH-wildtype GBM survive more than 5 years. While there are few differences in the global methylation profiles of LTS compared to STS, our study highlights potential pathways involved in GBMs with a good or poor prognosis.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139624192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult Neuro-Oncology Trials in the United States over Five Decades: Analysis of Trials Completion Rate to Guide the Path Forward","authors":"Emily J Smith, A. Naik, Mahima Goel, Patrick Y. Wen, Michael Lim, Susan M Chang, Isabelle M Germano","doi":"10.1093/noajnl/vdad169","DOIUrl":"https://doi.org/10.1093/noajnl/vdad169","url":null,"abstract":"\u0000 \u0000 \u0000 Clinical trials are important to close the gap between therapeutic unmet needs and scientific advances in neuro-oncology. This study analyzes the landscape of neuro-oncology trials to identify completion rates and guide strategies for the path forward.\u0000 \u0000 \u0000 \u0000 US-registered adult neuro-oncology clinical trials were extracted from www .clinicaltrials.gov (1966-2019), including funding source, trial type, scope, phase, and subjects’ demographics. Completed trials, defined as those that had completed participants’ examinations or intervention administration for the purpose of the final collection of data for the primary outcome were dichotomized against those that failed to reach completion. Univariate and multivariate analysis were used to detect differences across factors and comparing the last two decades (2000-2009, 2010-2019).\u0000 \u0000 \u0000 \u0000 Our search yielded 4522 trials, 1257 eligible for this study. In 25 US states, neuro-oncology trial availability is <0.85/100,000 population. Comparing the past two decades, trial completion rate decreased from 88% to 64% (p<0.001) and NIH funding decreased from 47% to 24% (p<0.001). Inclusion of subjects >65-year-old and women increased while inclusion of Hispanic subjects decreased (p< 0.001). The top two reasons for lack of completion included accrual and operational difficulties. A larger proportion of women, non-Hispanic subjects, and older adults were enrolled in completed trials than in those that failed completion.\u0000 \u0000 \u0000 \u0000 Our study is the first report on the neuro-oncology clinical trial landscape in the US and supports the development of strategies to further improve access to these trials. Additionally, attention is needed to identify and modify other factors contributing to lack of completion.\u0000","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139440320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De Ritis ratio in elderly glioblastoma patients treated with chemoradiation: a comprehensive analysis of serum biomarkers","authors":"Jina Kim, Hye In Lee, In Ah Kim, J. Lee, Jaeho Cho, C. W. Wee, H. I. Yoon","doi":"10.1093/noajnl/vdad173","DOIUrl":"https://doi.org/10.1093/noajnl/vdad173","url":null,"abstract":"We aimed to comprehensively investigate the prognostic value of pre-treatment laboratory parameters in elderly patients with glioblastoma treated with temozolomide (TMZ)-based chemoradiation. Patients aged ≥65 years from four institutions with newly diagnosed IDH-wild-type glioblastoma who received radiotherapy (RT) with concurrent TMZ between 2006 and 2021 were included. Patient factors (age, Karnofsky performance status (KPS), temporalis muscle thickness (TMT)), molecular factors (MGMT promoter methylation, EGFR amplification, TERT promoter mutation, and TP53 mutation status), treatment factors (extent of resection, and RT dose), and pre-treatment laboratory parameters (serum De Ritis ratio, glucose level, neutrophil-to-lymphocyte ratio, platelet count, and systemic immune-inflammation index) were included in the analysis. The primary endpoint was overall survival (OS). In total, 490 patients were included in the analysis. The median follow-up period was 12.3 months (range, 1.6–149.9 months). Median OS was significantly prolonged in patients with De Ritis ratio <1.2 (18.2 months vs. 15.3 months, p = 0.022) and in patients with glucose level <150 mg/dL (18.7 months vs. 16.5 months, p = 0.034) per univariate analysis. In multivariate analysis, KPS ≥70, MGMT promoter methylation, extent of resection greater than partial resection, De Ritis ratio <1.2, and glucose level <150mg/dL were significant prognostic factors for improved OS. Along with well-known prognostic factors, pre-RT serum biomarkers, including the De Ritis ratio and glucose level, also had prognostic value in elderly patients with glioblastoma treated with TMZ-based chemoradiation.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":"23 41","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139148340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}