Pain is a dominant and often debilitating symptom in patients with spinal tumors, yet its assessment and reporting remain inconsistent across disciplines. The absence of a standardized, mechanism-based classification limits clinical communication, treatment selection, and the interpretation of outcomes in spine oncology research We conducted a modified Delphi study through the AO Spine Knowledge Forum Tumor, engaging an international panel of 44 multidisciplinary experts, including neurosurgeons, orthopedic surgeons, radiation oncologists, and pain specialists. Across four iterative rounds, participants evaluated candidate domains and definitions for spine tumor pain using structured surveys, consensus thresholds, and a final consensus meeting. A mechanism-based classification framework was developed based on agreement across predefined criteria. Consensus identified three core domains—pain characteristics, clinical examination, and imaging findings—as essential for characterizing spine tumor–related pain. These elements informed a simplified, mechanism-based classification comprising six mutually exclusive categories: mechanical-axial, mechanical-radicular, inflammatory-axial, inflammatory-radicular, neuropathic-central, and neuropathic-peripheral. The framework integrates symptom quality, anatomical distribution, and radiographic correlates to infer underlying pain mechanisms. Nociplastic and chronic pain states were incorporated as modifiers. The resulting system was considered clinically intuitive, reproducible, and applicable across specialties. This international consensus establishes the first multidisciplinary, mechanism-based classification of acute spine tumor pain. The framework provides a standardized approach to pain assessment in neuro-oncology, with potential to improve clinical decision-making, enhance cross-disciplinary communication, and enable consistent pain endpoint reporting in clinical trials. Prospective validation is warranted to confirm its reliability and utility in diverse clinical settings.
Abstract Background Intraoperative neurophysiological monitoring (IONM) facilitates safe glioma resection in eloquent regions. Its effect on survival in molecularly defined IDH–wildtype glioblastoma remains uncertain. We assessed the association between IONM-supported surgery and survival outcomes in this high-risk population and explored subgroups deriving the greatest benefit. Methods We retrospectively analyzed 200 adults who underwent first-time resection for IDH–wildtype glioblastoma between 2012 and 2021. Co-primary outcomes were progression-free survival (PFS) and overall survival (OS), evaluated through Kaplan–Meier estimates and multivariable Cox models. Secondary 1:1 propensity score-matched analyses were performed based on age, preoperative KPS, MGMT methylation status, preoperative tumor volumes and localization. Volumetric analysis included contrast-enhancing (CE) and non–CE tumor components. Subgroup analyses were stratified by tumor location. Results In the unmatched cohort, IONM was independently associated with prolonged PFS (HR 0.60, 95% CI 0.45–0.84) and OS (HR 0.60, 95% CI 0.43–0.83), along with younger age, MGMT methylation, higher KPS, and smaller postoperative volumes. IONM patients had higher complete CE resection rates (64.2% vs 40.4%, P = 0.0005) and improved functional preservation (postoperative KPS 80 vs. 70, P = 0.008), despite more early deficits. In the location-matched cohort (n = 104), median PFS was 12 months with IONM vs 7 months without (P = 0.0007), and OS was 17 vs 11 months (P = 0.0018). Supramaximal resections occurred exclusively in the IONM group. The benefit was most evident in frontal, parietal, and insular tumors. Conclusions IONM-supported surgery was associated with more extensive resection, functional preservation, and longer survival in IDH–wildtype glioblastoma. IONM was more frequently used in tumors located in frontal, parietal, and insular regions, consistent with the functional complexity of these areas.
Abstract Background Alkylating chemotherapy is a cornerstone of glioblastoma treatment but is frequently complicated by hematotoxicity, for which reliable predictors are limited. Sarcopenia has been linked to chemotherapy-related hematotoxicity in other malignancies. Temporal muscle thickness (TMT), a surrogate marker of sarcopenia, can be readily assessed on routine brain MRI. We evaluated the association of TMT with hematotoxicity risk in patients with glioblastoma receiving first-line alkylating chemotherapy. Methods We retrospectively analyzed 222 patients with newly diagnosed glioblastoma. Temozolomide (TMZ) monotherapy was administered to 155 patients and lomustine/TMZ to 67. Hematotoxicity was graded according to the Common Terminology Criteria for Adverse Events version 5. TMT was measured on preoperative T1-weighted MRI by three independent raters blinded to clinical data. Associations between TMT and hematotoxicity were evaluated using logistic regression analysis. Results The median age was 61 years, and the median TMT was 8.4 mm. TMT was significantly higher in male patients and in those with better postoperative functional status (Karnofsky Performance Status ≥70). Grade 3-4 hematotoxicity occurred in 37.8% of patients and was more frequent in the lomustine/TMZ group than in the TMZ-only group (76.1% vs. 21.3%). Female sex was independently associated with an increased risk of high-grade hematotoxicity (odds ratio 3.00; P = .009), while TMT was not associated with hematotoxicity in the overall cohort. Conclusions Female sex and combined lomustine/TMZ therapy were independently associated with severe hematotoxicity. TMT showed no significant association, although the low prevalence of sarcopenia limits further conclusions.
Abstract Background Adult patients with primary brain tumors experience significant cognitive sequelae yet remain underrepresented in behavioral intervention research. We present the development and preliminary evaluation of C-SMART (Cognitive Strategies, Mindfulness, and Rehabilitation Therapy), an integrated cognitive rehabilitation and mindfulness-based intervention designed for patients with primary brain tumor and mild cognitive decline. Stakeholder input was systematically incorporated prior to launching a single-arm pilot trial assessing feasibility and acceptability. Methods Following the NIH ORBIT Model, Phase Ia convened two advisory boards: one comprised of brain tumor patients and caregivers (n=4) and another of neuro-oncology professionals (n=5) to inform C-SMART intervention development. Next, feasibility and acceptability were investigated in a single-arm Phase Ib design (n = 18 patients; n = 14 caregivers), with an exploratory aim of assessing preliminary signal change on neurocognitive performance and patient-reported outcomes. Results Phase Ia results supported an individually tailored neuropsychological intervention integrating mindfulness training and caregiver involvement to address patient-centered goals. Phase Ib results met all primary aims of feasibility and acceptability, with rates of enrollment, retention, and satisfaction exceeding established benchmarks. Caregiver involvement was robust, with reported benefit. Qualitative data from exit interviews supported the benefits of C-SMART on self-efficacy and interpersonal functioning with recommendations to increase caregiver involvement. Exploratory outcomes demonstrated signal change, supporting progression to a Phase II trial. Conclusions C-SMART is the first consensus-supported, individualized, mindfulness-based, neuropsychological intervention in neuro-oncology. Evidence provides strong support for feasibility and acceptability of the tailored intervention with key recommendations for optimization, including increased structure for caregiver involvement and self-efficacy outcome measurement.
Abstract Background Supratotal resection (SpTR) has emerged as a compelling surgical target for gliomas, with a strong signal toward improved survival. However, the balance between resections extending into tumor-infiltrated normal brain and preservation of higher-order cognitive function remains poorly defined. This systematic review aims to characterize formal neuropsychological (NP) outcomes following glioma SpTR. Methods A PRISMA-adherent systematic search was conducted across six electronic databases. Inclusion criteria required patients with WHO Grade 2–4 gliomas undergoing SpTR with standardized NP assessment. Quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists. Results 55 studies reported SpTR for glioma, but only 11 (20%) utilized formal NP testing as an outcome. 80% of studies omitting NP testing focused exclusively on high-grade glioma (HGG). Cognitive data was available from 2 studies in HGG and 9 studies in LGG. Early post-operative cognitive declines were reported in 55.5% of extractable cohorts, predominantly in the domains of executive function and memory/learning. The majority of these studies report cognitive recovery after 3-6 months. Long-term permanent cognitive morbidity was indeed very low (∼1%), but critical appraisal revealed a high risk of bias. Conclusions While current evidence suggests SpTR is functionally safe, these findings are limited by high risk of bias and a lack of comparative controls. A reporting gap remains in functional-cognitive outcomes after HGG surgery. Standardized, anatomically-anchored NP testing will be essential to validate the "onco-functional balance" of supratotal margins.
