Journal of Neuro-Oncology最新文献

{"title":"The intersection of chemokine signaling with the hallmarks of cancer in glioblastoma.","authors":"Rafal Chojak, Jillyn R Turunen, Noah B Drewes, Lara Koutah, Jawad Fares, Rebecca X Chen, Ruochen Du, Umme H Faisal, Hasaan A Kazi, Clare Kelley, Jason Miska, Amy B Heimberger, Atique U Ahmed, Maciej S Lesniak","doi":"10.1007/s11060-026-05768-0","DOIUrl":"10.1007/s11060-026-05768-0","url":null,"abstract":"<p><strong>Purpose: </strong>Glioblastoma, IDH-wildtype, is characterized by diffuse invasion, profound immunosuppression, treatment resistance, and near-inevitable recurrence. Although canonical genetic alterations establish malignant capacity, they do not fully explain how glioblastoma cells adapt to hypoxic, perivascular, invasive, immunosuppressive, metabolically constrained, and treatment-injured microenvironments. We examined how chemokine signaling contributes to these adaptive behaviors.</p><p><strong>Methods: </strong>We used the hallmarks of cancer as an organizing framework to synthesize preclinical, translational, and clinical evidence on chemokine circuits in glioblastoma. We evaluated recurrent mechanistic pathways, distinguished causal functions from context-dependent biomarker associations, and assessed their therapeutic relevance.</p><p><strong>Results: </strong>Chemokines act primarily as spatial and stress-responsive regulators rather than initiating oncogenic drivers. Recurrent circuits include CXCL12-CXCR4 in vascular repair, invasion, and stem-like persistence; CCL2 and CCL7 signaling through CCR2 in suppressive myeloid recruitment and metabolic-immune remodeling; CCL5-CCR5 in perivascular protection, invasion, and DNA-damage tolerance; and CXCL8 signaling through CXCR1 and CXCR2 in angiogenesis, immune evasion, and therapy-induced plasticity. Most chemokine-directed strategies remain preclinical or early translational.</p><p><strong>Conclusion: </strong>Therapeutic development should prioritize biomarker-defined dependencies and appropriately timed combinations that disrupt selected chemokine-dependent interactions within specific biological and treatment contexts. Clinical translation will require verification of target engagement, disruption of the relevant cellular interactions, and evidence that chemokine modulation improves treatment response or delays recurrence.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829384","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":"Therapeutic hybrid intelligence with neural and knowledge-based expert reasoning for SRS (THINKERS): an AI model for lung cancer brain metastases.","authors":"Jheremy S Reyes, Alexandros Bouras, L Dade Lunsford, Constantinos G Hadjipanayis, Ajay Niranjan","doi":"10.1007/s11060-026-05771-5","DOIUrl":"10.1007/s11060-026-05771-5","url":null,"abstract":"<p><strong>Background: </strong>Prescription dose selection for lung brain metastases treated with stereotactic radiosurgery (SRS) remains largely guided by generalized practice patterns rather than tumor-specific modeling of local failure dynamics. We developed a Therapeutic Hybrid Intelligence with Neural and Knowledge-based Expert Reasoning for SRS (THINKERS), an artificial intelligence framework for personalized dose evaluation in lung brain metastases.</p><p><strong>Methods: </strong>We performed a retrospective single-center study of lung brain metastases treated with Gamma Knife radiosurgery. Only variables available at or before treatment were included. The final model used a mixture-of-experts (MoE) deep neural network with discrete-time survival modeling. Margin dose was incorporated as an explicit input variable, allowing repeated evaluation across candidate dose levels for tumor-specific dose recommendation. Internal validation consisted of grouped 5-fold cross-validation and a grouped holdout test split by patient.</p><p><strong>Results: </strong>The final analytic cohort included 767 patients with 3,728 treated lung brain metastases. In grouped cross-validation, the MoE model achieved a mean Area Under the Curve (AUC) of 0.876 for 12-month local failure and a mean absolute error (MAE) of 0.99 months. In the grouped holdout test set, the model achieved an AUC of 0.863 (95% CI, 0.776-0.942) and an MAE of 1.26 months (95% CI, 0.44-1.49). Probabilistic performance was favorable, with a Brier score of 0.061, calibration intercept of 0.18, and calibration slope of 0.87.</p><p><strong>Conclusions: </strong>THINKERS-Lung provides an internally validated framework for tumor-specific SRS dose evaluation in lung brain metastases and supports the feasibility of AI-guided personalized radiosurgical decision support.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829378","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":"Contrast-enhancement-defined resection outcomes with sodium fluorescein and 5-aminolevulinic acid in glioblastoma surgery: a multicenter retrospective cohort of 1389 patients.","authors":"Salvatore Chibbaro, Charles-Henry Mallereau, Mario Ganau, Ismail Zaed, Guillaume Dannhoff, Julien Todeschi, Alex Alfieri, Julien Haemmerli, Andrea Cardia, Carmen Bruno, Nikolaos Syrmos, Antonio Romano, Giuseppe Maria Vincenzo Barbagallo, Biagio Roberto Carangelo, Alessandro Zalaffi, Franco Moruzzi, Giacomo Tiezzi, Ludovica Cellini, Giovanni Di Pietro, Maria Grazia Pluchino, Vitaliano Francesco Muzii, Laura Lippa, Nicola Montemurro, Giovanni Muscas, Alessandro Della Puppa, Alfonso Cerase, Giacomo Gualtieri, Victoria Dembour, Giuseppe Battaglia, Paolo Tini","doi":"10.1007/s11060-026-05769-z","DOIUrl":"10.1007/s11060-026-05769-z","url":null,"abstract":"<p><strong>Background: </strong>Sodium fluorescein (SF) and 5-aminolevulinic acid (5-ALA) have distinct biological mechanisms and may highlight different tumor compartments. Comparative multicenter data remain limited, and interpretation depends on the imaging endpoint used.</p><p><strong>Methods: </strong>We performed a retrospective analysis of prospectively maintained databases from 12 European neurosurgical centers, including 1389 consecutive patients with locally documented IDH-wildtype glioblastoma undergoing fluorescence-guided surgery. Patients received SF alone (n = 650), 5-ALA alone (n = 457), or dual fluorescence (n = 282). The primary endpoint was contrast-enhancement-defined gross total resection (CE-GTR); secondary endpoints were contrast-enhancing extent of resection (CE-EOR), postoperative KPS, and overall survival (OS). Conventional multivariable models were supplemented by center-clustered generalized estimating equations (GEE), center fixed-effects logistic regression, a Cox model with center-clustered robust standard errors, and a center-stratified Cox sensitivity analysis.</p><p><strong>Results: </strong>CE-GTR was achieved in 74.9% of the SF group, 62.6% of the 5-ALA group, and 68.4% of the dual-fluorescence group (overall p < 0.001). In conventional multivariable analysis, 5-ALA was associated with lower odds of CE-GTR than SF (OR 0.63, 95% CI 0.49-0.81; p < 0.001). The association persisted in the center-clustered GEE model (OR 0.57, 95% CI 0.36-0.90; p = 0.015) but was attenuated after inclusion of center fixed effects (OR 0.65, 95% CI 0.37-1.12; p = 0.121). In the adjusted center-clustered CE-EOR analysis, SF remained associated with a 6.7% points higher mean CE-EOR than 5-ALA (95% CI 3.3-10.0; Bonferroni-adjusted p = 0.003), whereas the other pairwise contrasts were not significant. Median OS was 18.2 months (95% CI 16.8-19.6) with SF, 17.9 months (95% CI 16.6-19.5) with 5-ALA, and 18.5 months (95% CI 17.5-20.2) with dual fluorescence. In the center-clustered Cox model, 5-ALA was associated with a lower hazard than SF (HR 0.84, 95% CI 0.74-0.97; p = 0.014), but this association was attenuated in the center-stratified model (HR 0.88, 95% CI 0.64-1.22; p = 0.451). Dual fluorescence was not associated with survival.</p><p><strong>Conclusions: </strong>SF was associated with higher rates of CE-defined GTR and greater resection of the contrast-enhancing tumor compartment than 5-ALA. However, attenuation in the center fixed-effects analysis indicates that institutional practices and case selection contributed to the observed difference. No consistent center-independent survival advantage was demonstrated. These findings do not establish the intrinsic superiority of SF, particularly because non-enhancing and supramaximal resection could not be assessed.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829421","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":"Clinical, radiographic, and neuropathologic characterization of peripherally hyperenhancing brain metastases: a novel radiographic entity.","authors":"Ryan M Shute, Rifaquat Rahman, Shyam Tanguturi, Paul J Catalano, Daphne A Haas-Kogan, Patrick Y Wen, David Meredith, Wenya Linda Bi, Camille Verry, Jeffrey P Guenette, Nayan Lamba, Ayal A Aizer","doi":"10.1007/s11060-026-05759-1","DOIUrl":"10.1007/s11060-026-05759-1","url":null,"abstract":"<p><strong>Purpose: </strong>Select brain metastases display peripheral hyperenhancement at the tumor-brain interface, constituting a unique radiographic entity. However, the incidence, associated clinical characteristics, pathologic correlates, and longer-term outcomes associated with this phenomenon remain largely unknown. Here, we characterize peripherally hyperenhancing brain metastases to inform clinical management.</p><p><strong>Methods: </strong>We identified 922 patients with 2790 newly-diagnosed brain metastases between 2009 and 2022 managed with brain-directed radiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Peripheral hyperenhancement was defined as visualized contrast uptake at the periphery of the tumor exceeding background enhancement of the metastasis. Peripheral hyperenhancement was assessed at both per-patient and per-metastasis levels. Predictors and outcomes associated with peripherally hyperenhancing brain metastases were assessed using multivariable logistic and Fine-Gray models, respectively.</p><p><strong>Results: </strong>In total, 137 patients (15%) and 176 metastases (6%) demonstrated peripheral hyperenhancement. Pathologically, peripherally hyperenhancing metastases displayed tumor cells infiltrating brain parenchyma. Patients with peripheral hyperenhancement were more likely to present with neurologic symptoms (84% vs. 60%, p < 0.001) and seizures (20% vs. 12%, p = 0.008). Renal primaries (vs. the reference of non-small cell lung cancer, OR 2.54 [95% CI 1.19-5.45], p = 0.02) and larger metastasis size (OR 1.03 per 1 mm increase [95% CI 1.02-1.04], p < 0.001) were associated with peripheral hyperenhancement. Peripheral hyperenhancement was not associated with survival-based, recurrence-based, or other time-to-event outcomes after initial management.</p><p><strong>Conclusion: </strong>Peripherally hyperenhancing brain metastases represent a distinct radiographic entity associated with renal primaries, edema, and neurologic symptomatology, with implications for surgical management and target delineation during stereotactic radiation. Definitive treatment seems to mitigate the aggressive nature of such tumors.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818793","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":"Subperineural 'onion-peeling' dissection for maximizing extent of resection and facial nerve preservation for onco-functional balance in vestibular schwannoma surgery.","authors":"James K Liu, Ahmed Sabra, Yaxel Levin-Carrion, Caryn J Ha, Sraavya Anne, Arevik Abramyan, Vicente Rojas-Navas, Kevin Wong, Yu-Lan Mary Ying, Robert W Jyung","doi":"10.1007/s11060-026-05755-5","DOIUrl":"10.1007/s11060-026-05755-5","url":null,"abstract":"<p><strong>Introduction: </strong>Planned subtotal resection (STR) of vestibular schwannomas (VS) followed by stereotactic radiosurgery (SRS) has gained popularity for minimizing facial nerve injury. However, recurrence risk correlates with residual tumor volume, and long-term outcomes remain unknown. The authors report their facial nerve outcomes with planned maximal safe resection using a facial nerve-sparing subperineural \"onion-peeling\" technique, and compare their outcomes to those of the hybrid STR-SRS approach.</p><p><strong>Methods: </strong>A retrospective study was performed on 146 patients who underwent VS resection by a single surgeon using a subperineural \"onion-peeling\" technique, leaving a thin layer of perineurium as an anatomic buffer overlying the facial nerve. Tumor size, operative approach, extent of resection (EOR: GTR 100%, NTR 95-99%, STR < 95%), facial nerve outcomes by House-Brackmann (HB) grade, recovery time, recurrence, and postoperative SRS usage were analyzed.</p><p><strong>Results: </strong>Most tumors were Koos grade III-IV (69.9%), followed by grade I-II (30.2%), removed via retrosigmoid (86.3%) or translabyrinthine (13.7%) approaches. At last follow-up (mean follow-up = 89.8 months), 95.2% of patients achieved HB I-II scores while obtaining an EOR ≥ 95% (GTR/NTR) in 97.3% of patients. There was no significant difference in rates of HB I-II outcomes whether EOR was GTR or NTR (97.8% vs. 92.5%, p = 0.196). HB I-II outcomes were achieved in 100% of Koos I-II and 93.1% of Koos III-IV tumors. There was a trend of decreased GTR and increased NTR with increasing Koos grade I to IV (GTR: 93.75%, 86.2%, 76.9%, 39.5%; NTR: 6.25%, 13.8%, 23.1%, 55.3%, respectively). Postoperative CSF leak rate was 2.7%. Tumor recurrence (3.4%) was lower with GTR than NTR (1.1% vs. 7.5%, p = 0.0646).</p><p><strong>Conclusion: </strong>The subperineural \"onion-peeling\" dissection technique provides a safe, nerve-sparing approach for maximal VS resection while preserving facial nerve function thus achieving excellent onco-functional outcomes. Compared to historical hybrid STR-SRS data, our approach demonstrated favorable facial nerve outcomes with higher EOR, lower tumor recurrence, and less radiation usage.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818873","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":"Machine learning for functional outcome prediction after vestibular schwannoma surgery: a systematic review and diagnostic test accuracy meta-analysis.","authors":"Shiva A Nischal, Shaan Patel, Musa China, Kush M Kale, Yi Hein Chai, Santosh Guru, William R Muirhead, Patrick Grover","doi":"10.1007/s11060-026-05747-5","DOIUrl":"10.1007/s11060-026-05747-5","url":null,"abstract":"<p><strong>Purpose: </strong>Machine learning (ML) models have been increasingly applied to predict postoperative facial nerve dysfunction and hearing preservation after vestibular schwannoma (VS) surgery. However, reported performance varies substantially, and the overall diagnostic accuracy and clinical reliability of these models remain uncertain. We conducted a systematic review and diagnostic test accuracy meta-analysis to characterise the current state and methodological readiness of ML-based prediction of these outcomes.</p><p><strong>Methods: </strong>PubMed, Embase, and CENTRAL were searched from inception to February 2026. Studies evaluating ML-based prediction of facial nerve function or hearing preservation following VS surgery were included. Diagnostic performance metrics were pooled using random-effects generalised linear mixed models. Sensitivity, specificity, diagnostic odds ratio, and AUC were synthesised, and SROC curves were constructed. The prespecified primary synthesis pooled the single best model per study; small-study effects were assessed with Deeks' test. Risk of bias (PROBAST) and certainty of evidence (GRADE) were assessed.</p><p><strong>Results: </strong>Ten retrospective cohort studies encompassing 1270 patients and 56 ML models met inclusion criteria. In the prespecified primary analysis pooling the single best model per study, the summary AUC was 0.91 for facial nerve dysfunction (sensitivity 0.89, specificity 0.86) and 0.92 for hearing preservation (sensitivity 0.88, specificity 0.96). Pooling all models on held-out test data gave a facial nerve AUC of 0.81; test-set data were too sparse for a stable hearing estimate, for which only training performance could be pooled (AUC 0.79). Tumour size, age, tumour location, and baseline hearing status were the most frequently identified influential predictors. Most studies were at unclear or high risk of bias (PROBAST has no intermediate \"moderate\" category), and certainty of evidence was moderate for facial nerve dysfunction and low for hearing preservation, the latter reflecting significant small-study effects (Deeks' p = 0.004).</p><p><strong>Conclusion: </strong>ML-based models demonstrate promising discrimination for predicting postoperative facial nerve and hearing outcomes after VS surgery. However, heterogeneity, limited external validation, and inconsistent reporting of calibration constrain inference regarding transportability and clinical implementation.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813274","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":"Molecular features of intratumoral hemorrhage in glioblastoma isocitrate dehydrogenase-wildtype.","authors":"Angel Bueno, Antonio Dono, Oscar Alcantar, Christian Amezquita-Contreras, Laura Ocasio, Sigmund Hsu, Mark Amsbaugh, Jay-Jiguang Zhu, Angel I Blanco, Roy F Riascos, Leomar Y Ballester, Nitin Tandon, Yoshua Esquenazi","doi":"10.1007/s11060-026-05749-3","DOIUrl":"10.1007/s11060-026-05749-3","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma isocitrate dehydrogenase (IDH)-wildtype (GBM) has been reclassified based on molecular and phenotypic features. Intratumoral hemorrhage is a phenotypic subtype with poorly understood molecular and clinical characteristics. We aimed to characterize the molecular profile and outcomes of hemorrhagic glioblastoma (hGBM) compared with non-hGBM.</p><p><strong>Methods: </strong>A retrospective analysis of GBMs with pre-operative and post-operative MRI and comprehensive next-generation sequencing of 205 genes was performed. Patients were classified as hGBM or non-hGBM using the Visually Accessible Rembrandt Images criteria. Univariable and multivariable survival analyses were performed. Genes were compared using the Fisher-exact test and corrected for multiple comparisons with the Benjamini-Hochberg method.</p><p><strong>Results: </strong>176 patients were included, of whom 105 had hGBM. Compared to non-hGBMs, hGBMs were more likely Hispanic (20.0% vs. 7.0%, p = 0.018), presented with motor deficits (38.0% vs. 21.1%, p = 0.020), and had larger tumors (147.6 cm³ vs. 122.2 cm³, p = 0.034). In addition, hGBMs harbored less frequently PDGFRA (13.3% vs. 26.8%, p = 0.031), KIT (8.5% vs. 19.7%, p = 0.040), KDR (6.6% vs. 18.3%, p = 0.027), or PIK3R1 (2.8% vs. 11.3%, p = 0.030) alterations, and a higher frequency of SETD2 alterations (8.5% vs. 1.4%, p = 0.050). These differences were not significant after multiple comparison corrections. No differences in progression-free survival (8.2 vs. 8.3 months, p = 0.337) or overall survival (18.4 vs. 19.7 months, p = 0.800) were identified by hemorrhagic status.</p><p><strong>Conclusions: </strong>hGBMs might be associated with lower frequencies of PDGFRA, KIT, KDR, and PIK3R1 alterations and higher frequencies of SETD2 alterations compared to non-hGBMs. No outcome differences were observed by intratumoral hemorrhage status in this cohort.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813370","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":"Trends and disparities in mortality due to secondary malignant neoplasm of the brain and cerebral meninges in the United States (1999-2024).","authors":"Vishan Das, Abdul Moeez Awais, Eshal Atif, Kaneez Fatima, Asad Ullah Farooq, Pari Kotak, Fatima Sohail, Sadia Qazi, Chanchal Kumari, Sandesh Kumar, Muhammad Atif Mazhar","doi":"10.1007/s11060-026-05763-5","DOIUrl":"10.1007/s11060-026-05763-5","url":null,"abstract":"<p><strong>Introduction: </strong>Secondary malignant neoplasms of the brain and cerebral meninges are among the most common intracranial malignancies in adults and a major contributor to cancer-related death. Despite substantial therapeutic advances, national mortality trends and the disparities within them have not previously been characterized.</p><p><strong>Methods: </strong>We obtained mortality data for U.S. adults aged 25 years and older from the CDC WONDER Multiple Cause of Death database for 1999 through 2024. Deaths were identified using ICD-10 code C79.3 (secondary malignant neoplasm of brain and cerebral meninges) recorded as a multiple cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated overall and by sex, age group, race and ethnicity, census region, state, urbanization level, and place of death. Temporal trends were assessed by Joinpoint regression, yielding annual and average annual percent changes (APCs and AAPCs) with 95% confidence intervals (CIs). A sensitivity analysis restricted to the 4.3% of deaths in which C79.3 was the underlying cause was performed.</p><p><strong>Results: </strong>A total of 447,724 deaths were recorded, most occurring at the decedent's home (42.85%). The overall AAMR declined from 9.65 in 1999 to 8.01 in 2024 (AAPC - 0.69; 95% CI - 1.23 to - 0.16; p = 0.012). Rates fell steeply through 2007 (APC - 4.41; p < 0.001), changed little to 2013 (APC - 0.71; 95% CI - 1.75 to 0.35), rose non-significantly to 2016 (APC 4.11; 95% CI - 0.07 to 8.46), and then increased significantly through 2024 (APC 1.36; 95% CI 0.94 to 1.78). Adults aged 65 years and older had the highest average AAMR and adults aged 25-44 years the lowest (23.27 vs. 0.85). Mortality was higher in males than females (8.13 vs. 7.20). The Midwest had the highest average AAMR and the Northeast the lowest (8.13 vs. 6.42). Non-Hispanic (NH) White individuals had the highest average AAMR and Hispanic or Latino individuals the lowest (8.10 vs. 4.26). Non-metropolitan areas exceeded metropolitan areas (9.12 vs. 7.12; 1999-2020). Arkansas had the highest state-level AAMR in both periods (14.79 in 1999-2020; 14.90 in 2021-2024).</p><p><strong>Conclusion: </strong>Mortality from secondary malignant neoplasm of the brain and cerebral meninges fell substantially in the first decade of the study period but has risen since the mid-2010s, a reversal evident across sexes, most age groups, and most regions. The burden remains concentrated among older adults, males, NH White individuals, and non-metropolitan populations. Because brain metastasis is a complication of systemic cancer rather than a directly preventable condition, these findings argue for improved control of the primary malignancies alongside timely neuro-oncologic diagnosis and equitable access to specialized care.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794259","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":"Cyst wall enhancement is associated with local recurrence after resection of intracranial hemangioblastoma: an exploratory retrospective cohort study.","authors":"Hyeong-Cheol Oh, Jihwan Yoo, Sung Jun Ahn, Chang-Ki Hong, Kyu Sung Lee, Hun Ho Park","doi":"10.1007/s11060-026-05766-2","DOIUrl":"10.1007/s11060-026-05766-2","url":null,"abstract":"<p><strong>Purpose: </strong>Central nervous system hemangioblastomas usually achieve durable local control after gross-total resection (GTR), yet recurrence can occur even after apparently complete removal. We evaluated whether preoperative MRI-defined radiologic subtypes, particularly cyst wall enhancement (CWE), are associated with local recurrence in surgically treated intracranial hemangioblastomas.</p><p><strong>Methods: </strong>We retrospectively reviewed 52 surgically treated intracranial hemangioblastomas in 49 patients between 2010 and 2025. Tumors were classified as solid (S), extratumoral cystic (Ce), intratumoral cystic (Ci), or mixed cystic (Cm) type. Primary analysis was restricted to 47 first resections, including 44 tumors treated with gross-total resection (GTR). Local recurrence after GTR was evaluated primarily using Kaplan-Meier analysis and the log-rank test. Because no recurrence occurred among CWE-negative GTR tumors, exploratory odds ratios were estimated using Firth bias-reduced penalized logistic regression.</p><p><strong>Results: </strong>Among the 44 primary tumors treated with GTR, local recurrence occurred in 8 of 14 CWE-positive tumors (57.1%) and in none of 30 CWE-negative tumors (0%; Fisher exact p < 0.001). CWE-positive tumors showed significantly shorter recurrence-free survival than CWE-negative tumors (log-rank p < 0.0001). Exploratory univariable Firth regression yielded an OR of 79.77 (95% CI 8.22-10,812.87) for the association between CWE and local recurrence.</p><p><strong>Conclusions: </strong>CWE was associated with local recurrence after GTR in this exploratory retrospective cohort. CWE may provide a simple and surgically interpretable imaging feature, but its prognostic value requires validation in larger independent cohorts.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794287","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":"Five-year changes in health-related quality of life after proton therapy in a primarily meningioma cohort: a prospective study.","authors":"Per Fessé, Linda Åkeflo, Karin Ahlberg, Emelie Blomqvist, Per Fransson, Ingrid Kristensen, Kristin Kunni, Ulrica Langegård, Emma Ohlsson-Nevo, Katarina Sjövall","doi":"10.1007/s11060-026-05767-1","DOIUrl":"10.1007/s11060-026-05767-1","url":null,"abstract":"<p><strong>Purpose: </strong>Long-term patient-reported outcomes after Proton beam therapy (PBT) remain insufficiently described for patients with benign intracranial and seller-region tumors. The aim of this study was to evaluate health-related quality of life (HRQoL) and brain tumor-specific symptoms over five years after PBT in a primarily meningioma cohort.</p><p><strong>Methods: </strong>In this prospective cohort study, adults treated with PBT completed the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-BN20 questionnaires from baseline through 5 years. Mixed models for repeated measures estimated mean scores and change from baseline with 95% confidence intervals. Baseline-to-five-year change analyses included participants with available data at both time points. Exploratory analyses evaluated associations between sociodemographic factors and changes over five-years.</p><p><strong>Results: </strong>Seventy-seven of 126 participants (61%) completed the 5-year assessment. Global health status did not change significantly, whereas the QLQ-C30 summary score declined modestly. Clinically meaningful worsening was observed for fatigue and insomnia, with smaller increases in pain, dyspnoea, and constipation. Physical and cognitive functioning declined, while emotional functioning improved. On the QLQ-BN20, hair loss increased to a clinically meaningful extent and drowsiness, bladder control difficulties, motor dysfunction, communication deficits, and leg weakness worsened, whereas headaches decreased. No associations were observed between the investigated sociodemographic factors and change in fatigue or insomnia.</p><p><strong>Conclusions: </strong>Five-year outcomes demonstrated a mixed pattern with stable global health status despite a modest decline in overall HROoL and worsening in several symptom and functioning domains. Clinically meaningful increases in fatigue and insomnia, alongside smaller functional and brain tumor-specific changes, support structured long-term follow-up and rehabilitation. These findings reflect long-term outcomes following PBT, while treatment-specific contribution remains uncertain.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794328","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}