Journal of Neuro-Oncology最新文献

{"title":"Opportunities and challenges of artificial intelligence and digital pathology in adult CNS tumors.","authors":"Mirna Lechpammer, Jacqueline T Norrell, Jaime N Parnas, Morana Vojnic, Jonathan H Sherman","doi":"10.1007/s11060-026-05833-8","DOIUrl":"https://doi.org/10.1007/s11060-026-05833-8","url":null,"abstract":"<p><strong>Purpose: </strong>For over a century, the pathologist's interpretation at the microscope was the final word on a brain tumor's identity. The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors, 5th edition, changed that hierarchy by introducing a layered, integrated diagnosis in which molecular findings take precedence over histology when the two conflict. Artificial intelligence (AI) applied to digitized slides adds a computational layer to this framework and marks a fundamental change in diagnostic workflow. This review examines the role of AI and digital pathology in adult CNS tumors and discusses the opportunities and challenges in clinical, neuro-oncology implementation.</p><p><strong>Methods: </strong>We conducted a narrative review of relevant literature indexed in PubMed before and after the 2021 WHO classification, covering digital pathology, whole-slide imaging (WSI), and AI applications in adult neuro-oncology. We synthesized evidence on diagnostic performance, molecular prediction, prognostic modeling, workflow integration, and ethical considerations.</p><p><strong>Results: </strong>AI and digital pathology show potential to improve diagnostic consistency, shorten turnaround time, and integrate histopathological, molecular, and radiological information. AI models may support glioma grading, prediction of molecular alterations from routine histology, survival stratification, prediction of brain metastasis, and intraoperative decisions. Barriers to clinical adoption include limited generalizability, lack of transparency, data privacy, and evolving regulatory oversight.</p><p><strong>Conclusion: </strong>AI and digital pathology are transforming adult CNS tumor diagnostics and could improve precision, efficiency, and multidisciplinary decision-making. Successful implementation will require rigorous multi-institutional clinical validation, transparent governance, equitable access, and collaboration among patients and health care professionals.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of intra-axial brain metastases in Eastern Finland.","authors":"Samir Moniruzzaman, Susanna Rantala, Juhana Hakumäki, Tuomas Rauramaa","doi":"10.1007/s11060-026-05842-7","DOIUrl":"https://doi.org/10.1007/s11060-026-05842-7","url":null,"abstract":"<p><strong>Purpose: </strong>Brain metastases (BM) incidence and characteristics remain poorly defined due to registry data being often incomplete, recording only primary tumors or unspecified metastases. The objective of this study was to examine BM incidence rates and characteristics confirmed by MRI in North Savo, Finland.</p><p><strong>Methods: </strong>In this retrospective study, North Savo residents with first MRI diagnosis of BM between 1 January 2004 and 31 December 2023 were identified through the radiology information system, irrespective of primary cancer diagnosis date. Medical and histopathological records were reviewed. Population person-years were estimated by summing annual end-year counts of all North Savo residents obtained from Statistics Finland. Crude incidence rates and age-standardized incidence rates (ASIRs), standardized to the 2013 European Standard population, were calculated. Temporal trends were assessed using age-adjusted Poisson regression.</p><p><strong>Results: </strong>Among 516 patients, 474 had histopathological verification. Cancers originating from lung and breast tissue accounted for 56.8% of BM cases. Overall crude incidence was 10.22 (95% CI 9.36-11.15) and ASIR was 9.20 (95% CI 8.42-10.04) per 100,000 person years. ASIR increased from 5.8 in 2004-2008 to 11.8 in 2019-2023. Age-adjusted Poisson regression estimated a 24% increase in incidence per five-year period (incidence rate ratio 1.24; 95% CI 1.14-1.34; P < 0.001). Age-specific incidence peaked at 33.1 per 100,000 person years among patients aged 70-74 years.</p><p><strong>Conclusions: </strong>MRI-confirmed BM incidence increased over 20 years, despite age standardization. Incidence was highest among older adults. These findings provide contemporary population-based epidemiological data of BM incidence.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postoperative DWI morphology and neurological worsening after eloquent-area glioma surgery: a retrospective cohort study.","authors":"Francesco Guerrini, Federico D'Agata, Valeria Musella, Agostina Vitali, Antonio Giuri, Maria Claudia Caporrimo, Luisa Chiapparini, Giannantonio Spena","doi":"10.1007/s11060-026-05837-4","DOIUrl":"https://doi.org/10.1007/s11060-026-05837-4","url":null,"abstract":"<p><strong>Purpose: </strong>To assess whether the association between postoperative diffusion-weighted imaging (DWI) and neurological worsening after eloquent-area glioma surgery differs according to lesion morphology.</p><p><strong>Methods: </strong>We retrospectively analyzed 139 consecutive patients undergoing resection of eloquent-area supratentorial gliomas (WHO 2-4). Postoperative MRI (< 48 h) classified lesions as sector- or rim-shaped. Neurological status was assessed at discharge and 4-6 months.</p><p><strong>Results: </strong>DWI lesions occurred in 44/139 patients (31.7%; 31 sector-shaped, 13 rim-shaped); 59 (42.4%) worsened at discharge. Overall, DWI positivity alone was not associated with worsening. Sector-shaped DWI lesions were associated with neurological worsening (positive predictive value, PPV of 58.1%) and remained associated after multivariable adjustment (OR 3.83, 95% CI 1.30-11.29), although the confidence interval was wide and the unadjusted association was borderline. Rim-shaped lesions carried a PPV of 38.5%, comparable to the risk in DWI-negative patients (37.9%), and the two morphologies did not differ significantly in direct comparison. Awake craniotomy was also independently associated with worsening, and frontal site with a lower risk. 61% of worsening occurred with negative DWI. A deficit was present at the 4-6 month follow-up in 9 patients (6.5%), all with IDH-wildtype glioblastoma, and was associated with a ≥ 50% evoked-potential decrease.</p><p><strong>Conclusion: </strong>In this cohort, postoperative DWI positivity was associated with neurological worsening mainly when the lesion was sector-shaped, a finding that requires confirmation in larger series. Rim-shaped lesions showed a risk of worsening similar to that of a negative scan. Most worsening occurs without DWI ischemia, suggesting non-ischemic mechanisms of function-guided surgery. A deficit at follow-up occurred only in IDH-wildtype glioblastoma and was associated with intraoperative neurophysiological changes.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotactic body radiation therapy in elderly patients with spinal metastases.","authors":"Brock J Gjesdal, Samuel Adida, Suchet Taori, Andrew H Zureick, Serah Choi, John C Flickinger, Pascal O Zinn, James C Bayley, Peter C Gerszten, Roberta K Sefcik","doi":"10.1007/s11060-026-05838-3","DOIUrl":"10.1007/s11060-026-05838-3","url":null,"abstract":"<p><strong>Purpose: </strong>Elderly patients with spinal metastases are often considered poor candidates for aggressive local therapy, due in part to medical comorbidity and limited evidence to guide treatment selection. This study evaluated outcomes following spine stereotactic body radiation therapy (SBRT) in this patient population and examined predictors of local failure (LF) and vertebral compression fracture (VCF).</p><p><strong>Methods: </strong>A prospectively maintained database of consecutive patients aged ≥ 70 years with available imaging who underwent spine SBRT at a quaternary referral center from 2002 to 2024 was analyzed. The median single-fraction dose was 16 Gy (range: 12-18 Gy), and multi-fraction regimens ranged from 18 to 35 Gy in 2-5 fractions.</p><p><strong>Results: </strong>Of 208 metastases in 161 patients (median age: 75 years, range: 70-94 years), 72% had prior conventional radiotherapy and 76% received a single fraction. The 6-, 12-, 24-, and 36-month cumulative incidence rates were 6%, 9%, 9%, and 10% for LF and 4%, 7%, 8%, and 9% for VCF (median follow-up: 9 months, range: 1-132 months). Gross tumor volume > 37 cc (subdistribution hazard ratio [sHR]: 6.27, 95% confidence interval [CI]: 1.48-26.63, P = 0.013) and Spinal Instability Neoplastic Score (SINS, per-point sHR: 1.23, 95% CI: 1.07-1.42, P = 0.005) were independently associated with LF; only SINS was independently associated with VCF (per-point sHR: 1.19, 95% CI: 1.06-1.34, P = 0.003), and 11 of 17 VCFs required cement augmentation or surgery. Age was associated with overall survival (hazard ratio: 1.05 per year, 95% CI: 1.01-1.09, P = 0.018); no statistically significant association was detected with LF or VCF when age was analyzed continuously, at thresholds of 75 or 80 years, or by exploratory maximally selected rank statistical analysis. Complete or partial pain response followed 61 of 148 evaluable treatments (41%) among 186 symptomatic metastases, and 18% of patients had grade 1-2 radiation toxicity.</p><p><strong>Conclusion: </strong>Spine SBRT, predominantly single-fraction reirradiation, was associated with low rates of LF and VCF; chronologic age alone should not preclude its use in appropriately selected elderly patients.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal motor recovery trajectories in brainstem glioma associated with preoperative DTI-based corticospinal tract involvement patterns.","authors":"Mingxin Zhang, Luyang Xie, Hang Zhou, Kai Jiang, Zhuang Jiang, Wenhao Wu, Tao Sun, Liang Wang, Zhen Wu, Junting Zhang, Peng Zhang, Liwei Zhang","doi":"10.1007/s11060-026-05829-4","DOIUrl":"https://doi.org/10.1007/s11060-026-05829-4","url":null,"abstract":"<p><strong>Purpose: </strong>Despite the high risk of postoperative motor dysfunction from corticospinal tract (CST) involvement, no preoperative system integrates CST-tumor interactions to stratify the prognosis in brainstem gliomas (BSGs).</p><p><strong>Methods: </strong>We enrolled 180 BSG patients who underwent craniotomy between 2020 and 2023. Preoperative DTI tractography classified CST-tumor relationships as displacement, infiltration, and traverse types. Clinical, pathological, and follow-up data (KPS, mRS, MRC, OS) were systematically collected at predefined intervals. Longitudinal outcomes were analyzed using linear mixed-effects models; survival was assessed by Kaplan-Meier.</p><p><strong>Results: </strong>The cohort comprised 51 displacement (28.3%), 83 infiltration (46.1%), and 46 traverse (25.6%) cases, with excellent inter-rater reliability (κ = 0.93). Tumor biology, CST fractional anisotropy (FA), and preoperative functional status demonstrated clear gradients across subtypes. The traverse type was predominantly high-grade (97.8%), exhibited the lowest FA (0.424 ± 0.055), and had the poorest preoperative KPS/mRS (all P < 0.001). Conversely, the displacement type was mostly low-grade (74.5%), showed the highest FA (0.45 ± 0.038), and had superior functional status; infiltration was intermediate. FA correlated positively with preoperative muscle strength (ρ = 0.238, P = 0.001). Longitudinal trajectories differed significantly (P_FDR < 0.05): displacement patients recovered rapidly, traverse patients showed minimal recovery with late decline, and infiltration was intermediate. Median OS was not reached for displacement, versus 15.3 months for infiltration and 12.0 months for traverse; all pairwise comparisons were significant.</p><p><strong>Conclusion: </strong>This DTI-based CST-tumor classification system effectively stratifies BSG patients preoperatively and is associated with distinct recovery trajectories, providing a hypothesis-generating framework for surgical planning.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-based preoperative WHO grade prediction in meningioma: development and comparison of deep learning, radiomics, clinical, and combined models in multicenter data.","authors":"Cagin Huryol, Umid Sulaimanov, Murat Yuce, Nafiye Sanlier, Fikret Ozturk, Oyku Ozturk, Irem Altun, Gular Ismayilova, Huseyin Bozkurt, Taha Yasin Altunkaya, Ferdi Afsin, Abdullah Soydan Mahmutoglu, Amine Durmus, Burak Karaaslan, Ilhan Aydin, Mehmet Sabri Gurbuz, Ahmet Tan Cimilli, Okan Turk, Ufuk Erginoglu, Mustafa K Baskaya","doi":"10.1007/s11060-026-05827-6","DOIUrl":"10.1007/s11060-026-05827-6","url":null,"abstract":"<p><strong>Purpose: </strong>The objective of this study was to develop and externally validate complementary magnetic resonance imaging (MRI)-based models and their stacked combinations for preoperative World Health Organization (WHO) grading of intracranial meningioma.</p><p><strong>Methods: </strong>This retrospective multicenter study included 455 histopathologically confirmed meningiomas: a four-center development cohort (n = 346) with leave-one-center-out cross-validation and an external cohort (n = 109). Four base models used contrast-enhanced T1-weighted MRI: tumor + peritumoral radiomics, an nnU-Net segmentation-based classifier, frozen DINOv3 transfer-learning features, and clinical variables. All 15 combinations were prespecified and stacked using a linear meta-learner trained on development out-of-fold predictions. Frozen models were externally evaluated without modification.</p><p><strong>Results: </strong>WHO 2-3 tumors comprised 24.6% overall (112/455; development 20.5%; external 37.6%). External AUCs were 0.732 for nnU-Net, 0.703 for DINOv3, 0.645 for clinical, 0.628 for radiomics. The multimodal ensemble (nnU-Net+DINOv3+Clinical) achieved the highest external AUC (0.742), exceeding radiomics (ΔAUC +0.114, p = 0.008) but not nnU-Net (ΔAUC +0.011, p = 0.737). Compared with the clinical model, discrimination was higher but nonsignificant at the prespecified threshold (ΔAUC +0.098, p = 0.050), while reclassification improved (IDI +0.109, p < 0.001). Radiomics-containing combinations performed strongly in development but lost most discrimination externally. The multimodal ensemble had an external calibration slope of 1.32 (Brier 0.190) and net benefit above default strategies at thresholds ≥ 0.23.</p><p><strong>Conclusion: </strong>The multimodal ensemble achieved the highest external AUC but did not significantly exceed nnU-Net, which was the most transportable single predictor of meningioma grade. Clinical variables did not improve discrimination but enabled interpretable feature-level attribution. Handcrafted radiomics lacked external transportability.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long term outcomes and predictors of recurrence in central neurocytomas: a 35-year multi-institutional experience.","authors":"Yufan Yang, James L Leenstra, Paul D Brown, Nitin Wadhwani, Alexander Ho, Sean Sachdev","doi":"10.1007/s11060-026-05825-8","DOIUrl":"10.1007/s11060-026-05825-8","url":null,"abstract":"<p><strong>Introduction: </strong>Central neurocytomas (CNs) are rare, WHO grade 2 brain tumors that have relatively high recurrence rates following resection. The present collaboration between Northwestern University and the Mayo Clinic describes long-term outcomes of CN as it relates to potential prognostic variables that entail recurrence risk, such as RT timing, tumor proliferation index (Ki-67), and age at diagnosis.</p><p><strong>Methods: </strong>Patients established between 1990 and 2025 with a tissue diagnosis of CN were reviewed. Recurrence free survival (RFS) and overall survival (OS) were calculated according to the Kaplan Meier-method. Multivariate cox regression analysis was performed with pre-planned variables.</p><p><strong>Results: </strong>Fifty-one patients with CN with a median age of 26 years and 9.7 years median follow-up were included. OS at 10 years for the cohort was 94%. Without adjuvant RT, 5-year RFS for post-GTR was 61% versus 46% for post-STR (P value = 0.18). Multivariate analysis found omission of adjuvant RT (HR: 9.0, P = 0.003), subtotal resection (HR:5.7, P = 0.017), younger age at diagnosis (HR3.1, P = 0.002), and higher Ki-67 (HR 1.13, P = 0.017) were associated with worse RFS. Salvage RT after first recurrence (n = 17) had a 5-year RFS of 83%, with a median follow-up of 4.8 years.</p><p><strong>Conclusions: </strong>We report one of the largest and most comprehensive cohorts of CN with long-term follow-up. Contrary to previous reports, recurrences were frequent after GTR. Higher Ki-67 and age at diagnosis were associated with worse RFS in our cohort. Salvage RT at recurrence achieved durable long-term tumor control, and 10-year mortality was low.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Volumetric discordance between ¹⁸F-FET-PET/MRI and MRI-based radiotherapy target volumes in high-grade glioma: a prospective pilot study (FETSMaRT).","authors":"Amit Singnurkar, Arjun Sahgal, Eli Lechtman, Mary-Jane Lim-Fat, Simon J Graham, Nir Lipsman, Pejman Maralani, Gregory Pond, Jay S Detsky","doi":"10.1007/s11060-026-05831-w","DOIUrl":"10.1007/s11060-026-05831-w","url":null,"abstract":"<p><strong>Purpose: </strong>High-grade gliomas carry a poor prognosis, and MRI-based radiotherapy (RT) planning may inadequately capture metabolically active tumor infiltration. ¹⁸F-fluoroethyl-tyrosine (FET) PET provides superior tumor delineation, yet prospective North American evidence supporting integration with RT planning remains limited.</p><p><strong>Methods: </strong>FETSMaRT enrolled 30 patients with WHO grade 3 or 4 high-grade glioma receiving post-operative RT. FET-PET/MRI was acquired before RT with the radiation oncologist blinded to PET, enabling retrospective quantification of discordance between MRI-based and FET-PET/MRI-derived gross tumor (GTV), clinical target (CTV), and planning target (PTV) volumes. In the glioblastoma subgroup (n = 23), Kaplan-Meier and Cox analyses related GTV and CTV discordance to time to progression.</p><p><strong>Results: </strong>Median age was 60 years; 77% had glioblastoma and 60% MGMT promoter methylation. GTV discordance occurred in 17/30 patients (56.7%) and CTV discordance in 15/30 (50.0%). FET-PET/MRI-derived volumes significantly exceeded MRI-based volumes for GTV (43.6 vs. 38.6 cc; p < 0.0001), CTV (119.2 vs. 110.8 cc; p = 0.0045), and PTV (171.1 vs. 159.6 cc; p = 0.0003). Larger GTV∆ and CTV∆ change values were associated with numerically shorter median time to progression, but neither association was statistically significant. Radiation treatment failures were predominantly central (60.0%).</p><p><strong>Conclusion: </strong>FET-PET/MRI-derived target volumes were significantly larger than MRI-based volumes, confirming systematic underestimation of metabolically active tumor extent by anatomical MRI. While not meeting significance in this pilot study, directional CTV and GTV discordance suggests a possible association with progression; the hypothesis generating exploratory pilot data nonetheless justify a prospective trial of FET-PET-guided RT in high-grade glioma. NCT06499831.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocytic resilience during chemoradiotherapy is independently associated with survival in IDH-Wildtype glioblastoma.","authors":"Flavio Donnini, Pierpaolo Pastina, Giuseppe Battaglia, Salvatore Chibbaro, Alfonso Cerase, Valerio Nardone, Isacco Desideri, Francesco Pasqualetti, Alessandra Pascucci, Vincenzo D'Alonzo, Maria Antonietta Mazzei, Giuseppe Minniti, Anna Maria Di Giacomo, Paolo Tini","doi":"10.1007/s11060-026-05830-x","DOIUrl":"10.1007/s11060-026-05830-x","url":null,"abstract":"<p><strong>Purpose: </strong>Routine blood counts may capture treatment-related host immune perturbation in glioblastoma, but most studies rely on static pretreatment values. We investigated whether the intra-individual preservation of circulating monocytes during chemoradiotherapy provides prognostic information beyond established clinical factors and other hematologic trajectories.</p><p><strong>Methods: </strong>We retrospectively analyzed adults with histologically confirmed IDH-wildtype glioblastoma treated with radiotherapy and concurrent temozolomide. Absolute monocyte counts obtained before and at the end of chemoradiotherapy were used to define monocytic resilience as log2(post-treatment/pre-treatment monocyte ratio). Overall survival (OS) was the primary endpoint. Cox models adjusted for MGMT promoter methylation, gross total resection, Karnofsky Performance Status, and age. The ratio was analyzed continuously for primary inference. A post/pre ratio of 0.75 was additionally evaluated as an exploratory, clinically interpretable threshold for two-group Kaplan-Meier visualization and sensitivity analysis.</p><p><strong>Results: </strong>Among 127 patients, 115 had complete monocyte trajectories and OS data. The primary adjusted model included 102 patients and 86 deaths. The continuous monocyte post/pre ratio was independently associated with OS (HR 0.53 per doubling, 95% CI 0.37-0.76; p = 0.00051). Using the exploratory 0.75 threshold, 52 patients had low resilience (< 0.75) and 63 had preserved resilience (≥ 0.75), with median OS of 10.2 and 17.3 months, respectively (log-rank p = 0.00064). Preserved resilience was associated with lower mortality in univariable Cox analysis (HR 0.50, 95% CI 0.34-0.75; p = 0.00080). Bootstrap resampling showed that outcome-optimized cut-points clustered around this region (median 0.74; IQR 0.70-0.81), although the threshold remains exploratory and requires external validation.</p><p><strong>Conclusions: </strong>Preservation or recovery of circulating monocytes during chemoradiotherapy was associated with a favorable host-response phenotype in IDH-wildtype glioblastoma. This dynamic signal remained associated with survival after adjustment for established clinical factors, baseline monocyte burden, lymphocyte change, systemic inflammatory imbalance, and measured corticosteroid exposure. External prospective validation, medication-level confounder assessment, and immune phenotyping are required before clinical use.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MGMT promoter methylation as a molecular biomarker in neuro-oncology: current practices, challenges, and future directions.","authors":"Truman J Do, Shameel Shafqat, Sani H Kizilbash, Cristiane M Ida","doi":"10.1007/s11060-026-05821-y","DOIUrl":"10.1007/s11060-026-05821-y","url":null,"abstract":"<p><strong>Purpose: </strong>MGMT promoter methylation (MGMTpm) is a well-established molecular biomarker in neuro-oncology. We review current practices, challenges, and future directions for MGMTpm as a biomarker in central nervous system (CNS) tumors.</p><p><strong>Methods: </strong>The literature on MGMT function, and MGMTpm clinical significance and testing in CNS tumors was reviewed.</p><p><strong>Results: </strong>We discuss the biological role of MGMT in DNA repair and the mechanisms by which MGMTpm leads to increased tumor sensitivity to alkylating agents. We summarize the clinical significance of MGMTpm in glioblastoma and its emerging relevance in other CNS tumors. Testing practices using methylation-specific PCR, pyrosequencing, and genome-wide methylation array-based approaches are discussed, along with challenges related to testing variability and \"gray-zone\" methylation, and emerging technologies such as nanopore sequencing.</p><p><strong>Conclusions: </strong>Despite ongoing technical and interpretative challenges, MGMTpm remains a robust and clinically valuable biomarker in neuro-oncology.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}