Category: Oncology

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Guidelines for the Treatment of Adults With WHO Grade II Diffuse Glioma: Update

Neurosurgery 98:984–991, 2026

These updated CNS evidence-based guidelines consolidate current literature on the management of WHO grade II diffuse gliomas, covering imaging, surgical strategies, neuropathology, radiotherapy, chemotherapy, and recurrence. They summarize evidence levels, provide topic-specific recommendations, and identify areas needing higher-quality research to inform clinical decisions.

The document details unchanged, updated, and new recommendations—ranging from MRI protocols and intraoperative mapping to molecular testing and adjuvant therapy—while describing methodology, conflict-of-interest procedures, and plans for periodic revision to ensure clinical relevance.

Scope: Updated evidence-based recommendations for adult WHO grade II diffuse glioma across imaging, surgery, neuropathology/molecular markers, radiotherapy, chemotherapy, and recurrence management.

Methods: Systematic search of MEDLINE/Embase/Cochrane covering Jan 1, 2013–Jan 31, 2020, with recommendations based on evidence rather than consensus.

Imaging (minimum MRI): Minimum evaluation includes T2-weighted and pre- and post-gadolinium T1-weighted MRI; serial imaging is used to detect new enhancement or significant growth suggesting higher-grade transformation.

Imaging (advanced/PET): Diffusion plus perfusion techniques (e.g., DSC/DCE/ASL) are suggested when standard MRI cannot distinguish grade II from higher-grade gliomas; amino-acid PET (FET or FDOPA) may be added when not evident on MRI to help with grading, prognosis (FET), or progression detection (FDOPA).

Surgery: When safe/feasible, resection (gross total or subtotal) is recommended over biopsy alone to reduce progression; extent of resection should be maximized when safely possible (including for IDH-mutant and IDH–wild-type tumors).

Pathology/molecular testing: Diagnosis relies on histopathology from representative tissue; IDH mutation testing is recommended for classification/prognosis, and 1p/19q loss-of-heterozygosity testing is recommended in oligodendroglial cases for prognosis/treatment planning.

Adjuvant therapy (high-risk): For high-risk grade II diffuse glioma (age >40 or <40 without gross total resection), adding chemotherapy to radiotherapy is recommended to improve overall survival (including procarbazine/PCV-based approaches) and is also recommended without decline in neurocognitive function.

Recurrence: At suspected recurrence, advanced imaging (MRS/perfusion/diffusion/PET) is suggested; temozolomide is suggested (often initial choice) and procarbazine may help (strongest evidence in oligodendroglioma); radiation is suggested if not previously given and reirradiation may be considered.

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Awake Versus Asleep Craniotomy for Glioma: A Comparison of Survival and Costs Using Time-Driven Activity-Based Costing

Operative Neurosurgery 30:653–667, 2026

Awake versus asleep (general anesthesia) craniotomy are two approaches for glioma resection, and this work compares their intraoperative costs and survival outcomes.

Key Insights and Themes

Clinical question centers on whether awake craniotomy (AC) differs from asleep craniotomy under general anesthesia (GA) in intraoperative cost and in survival for glioma patients.

Cohort identification included all glioma resections at one institution from 2017–2022: 298 GA cases and 67 AC cases.

Awake-craniotomy indication primarily involved tumors in eloquent brain regions to allow intraoperative monitoring of neural function, while noneloquent tumors typically started under GA.

Costing method (TDABC) used process maps plus automated time-stamped extraction from the electronic medical record to capture intraoperative resources and time.

Cost components were dominated by supplies and personnel, with other elements (turnover and overhead) described as relatively minor contributors.

Baseline overall intraoperative cost had a median total of $6600 (IQR $2875), largely driven by supply cost (median $3178) and personnel cost (median $3141).

Operating-room time was longer for AC (median 5.2 hours) than GA (median 4.5 hours), and AC had about 30 additional minutes of incision-to-closure time.

Patient/tumor comparability showed GA patients were older, but there were no differences in WHO grade distribution or extent of resection between groups.

Unadjusted total cost difference showed higher median intraoperative cost for AC ($8506) versus GA ($6033).

Unadjusted subcomponent differences showed AC had higher median supply cost ($4238 vs $2928) and higher median personnel cost ($4111 vs $2962) than GA.

Adjusted total cost effect found AC associated with $2175 additional intraoperative cost versus GA after accounting for confounders.

Adjusted cost drivers attributed the added AC cost to higher supply cost (+$1272) and higher personnel cost (+$970).

Supply subcomponents were higher for AC than GA across consumables, implants, sterilization, and medications in unadjusted comparisons.

Personnel mix differed in that neurology attendings/fellows were included in AC but not GA at this institution, contributing to personnel-cost differences.

Unadjusted survival showed higher overall survival for AC on Kaplan–Meier analysis (log-rank P = .011), while progression-free survival did not significantly differ (log-rank P = .106).

Adjusted survival showed no significant differences between AC and GA in overall survival (HR 0.84, P = .48) or progression-free survival (HR 0.9, P = .66) after multivariable adjustment.

Key limitation (missing GA neuromonitoring costs) is that electrophysiological neuromonitoring personnel costs for GA were not captured due to EMR documentation limits.

Scope limitation (episode-of-care costs) is that the analysis focuses on intraoperative costs, and commenters note postoperative/inpatient costs could change conclusions about overall expense.

Conclusion

Awake craniotomy for glioma resection had higher intraoperative costs than asleep craniotomy, but after adjustment it showed no significant survival advantage in overall or progression-free survival.

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Prediction of Diffuse High-Grade Glioma Survival Outcomes Using Preoperative Whole-Brain Tractography–Based Resectability Metrics

Neurosurgery 98:836–847, 2026

This study presents novel whole-brain tractography (WBT)–derived resectability metrics—resectability index (RI) and unresectable tumor volume (UTV), plus modified versions mRI and mUTV—calculated from preoperative diffusion imaging to estimate how much of diffuse high-grade gliomas (HGG) can be safely resected. Metrics are derived by quantifying tumor overlap with critical white-matter tracts and deep structures, and compared with conventional postoperative measures.

Using retrospective data from 146 tumors (84 with WBT), mRI and mUTV strongly predicted biopsy versus resection and correlated with extent of resection, residual tumor, and overall survival. Accelerated failure time models incorporating mUTV/mRI provided accurate preoperative survival predictions, outperforming conventional metrics in postoperative models.

Problem: Extent of resection (EOR) predicts survival in diffuse high-grade glioma but is only measurable postoperatively, limiting preoperative decision-making.

Approach: Preoperative whole-brain tractography (WBT) was used to quantify tumor overlap with eloquent tracts and deep structures to estimate resectability before surgery.

Metrics: Unresectable tumor volume (UTV) = tumor overlap with eloquent tracts + deep structures; Resectability index (RI) = (preop tumor volume − UTV) / preop tumor volume.

Modified metrics: mUTV/mRI focused only on corticospinal tract and left arcuate fasciculus, and performed better than unmodified metrics in several analyses.

Surgical decision prediction: mRI (AUROC 0.953) and mUTV (AUROC 0.854) accurately predicted biopsy vs resection, with optimal cutoffs mRI 0.75 and mUTV 2.5 cm³.

Survival separation: Tumors with mRI > 0.65 vs ≤ 0.65 showed the largest median overall survival difference (not reached vs 82 days, P < .0001).

Best preop survival model: A log-logistic accelerated failure time (AFT) model using only preoperative covariates achieved validated C-index 0.788, with mUTV an independent predictor of overall survival (P = .008).

Overall conclusion: Preoperative WBT-based resectability metrics approximate postoperative EOR/residual tumor volume and can strongly predict survival outcomes after biopsy or resection.

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Global economic differences in modern glioblastoma care – a systematic review

Acta Neurochirurgica (2026) 168:89

This systematic review quantifies global cost and cost-effectiveness differences in contemporary glioblastoma (GBM) care, analyzing 21 studies standardized to 2024 USD. It reports extreme heterogeneity in direct medical costs—from about $18,908 in India to $356,481 in the United States—and identifies inpatient care and adjuvant therapies as primary cost drivers in high-income settings.

Economic models reveal that the full Stupp protocol often exceeds willingness-to-pay thresholds in middle- and low-income countries, while surgical resection and 5‑ALA fluorescence-guided surgery show relatively favorable cost-effectiveness. The authors call for standardized cost reporting and inclusion of societal perspectives to improve cross-country comparisons and policy decisions.

Purpose Quantified global differences in costs and cost-effectiveness of modern Stupp-protocol–based glioblastoma care via a systematic review.

Methods Searched PubMed/MEDLINE/Cochrane to Dec 1, 2025 using (Glioblastoma OR GBM) AND (costs OR cost-effectiveness OR economic burden); included studies with quantifiable economic outcomes from 2005 onward, yielding 21 eligible studies.

Standardization Converted all reported costs to 2024 USD by inflating with country-specific CPI to 2024 and converting using 2024 PPP rates.

Direct costs range Direct medical costs were highly heterogeneous, from about $356,481 (United States) to about $18,908 (India), across 15,547 real-world patients.

Cost drivers (Western systems) Adjuvant treatment and inpatient care were major contributors to direct medical costs in western countries (with inpatient care and radiotherapy prominent in US analyses).

Stupp protocol affordability The Stupp protocol exceeded willingness-to-pay thresholds in middle-income/resource-limited settings, indicating substantial financial burden in those contexts.

TTF cost-effectiveness variability Tumor treating fields (TTF) showed very high ICERs in France (≈ $862k–$940k per LYG) and $252,590 per LYG in the US, but a more favorable estimate of $45,813.91 per QALY in China.

Key implication Uniform, standardized cost reporting is needed to better compare cost-effectiveness across countries; economic findings also underscore the role of surgery as a cost-effective component of modern GBM management.

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Quantitative MRI Tractography of White Matter Tracts After Tumor Craniotomy Surgery: Comparative Analysis Between Tubular Retractor and Open Craniotomy Surgery

Operative Neurosurgery 30:525–532, 2026

This study compares quantitative diffusion MRI tractography outcomes after deep-seated brain tumor resections using tubular retraction (TR) versus open craniotomy (OC) with spatula/cottonoid retraction. In a matched cohort of 20 patients, TR achieved comparable extent of resection with improved postoperative fractional and geodesic anisotropy metrics and a greater mean increase in Karnofsky Performance Score.

Methods include pre/postoperative 1.5T DTI, autosegmented tractography of ipsilateral tracts, and statistical comparison of FA, GA, diffusivity metrics, and tract volume. Results suggest TR reduces certain retraction-related white matter distortion without worsening diffusivity markers, supporting TR as a viable technique for deep subcortical lesions with potential functional benefit.

Goal Quantitatively compare cerebral retraction–related white matter tract changes after deep-seated tumor surgery using tubular retraction (TR) vs open craniotomy (OC) with spatula retraction via diffusion MRI tractography metrics.

Design Retrospective matched-pair analysis of 20 patients (10 TR vs 10 OC), matched by tumor size, depth, and age; all surgeries performed by a single surgeon.

Tractography process/metrics Pre- and postoperative DTI tractography (1.5T MRI) autosegmented ipsilateral supratentorial tracts; quantified FA, GA, MD, RD, AD, and tract volume across specified tracts (e.g., corticospinal, arcuate/SLF, ILF, IFOF, fornix, uncinate, optic radiations).

Extent of resection Resection was comparable between groups (TR 90.4% vs OC 94.8%, P = .395).

Functional outcome Change in Karnofsky Performance Score (KPS) favored TR (mean +11 points) vs OC (no change), P = .035.

Key quantitative findings Postoperative FA and GA differed significantly in favor of TR (FA 0.322 TR vs 0.029 OC, P = .011; GA increased in TR 0.441 vs decreased in OC 0.411, P = .012).

Other imaging metrics Postoperative tract volume was higher in TR than OC (14.9 cm³ vs 10.6 cm³, P = .036), while diffusivity metrics (MD, RD, AD) were broadly comparable between cohorts.

Conclusion TR offers a viable approach for deep-seated tumors with similar resection extent while mitigating some components of retraction injury as reflected by quantitative tractography changes and improved KPS.

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The Role of Intraoperative Imaging Modalities in Surgical Resection of Supratentorial Gliomas: A Review of 300 Cases

Operative Neurosurgery 30:278–288, 2026

This retrospective study of 300 supratentorial glioma surgeries compares outcomes using intraoperative MRI (iMRI), navigated intraoperative ultrasound (iUS) and no intraoperative imaging. It reports higher gross total resection rates and greater contrast-enhancement extent with iMRI and iUS, with iMRI achieving the highest contrast-enhanced extent of resection (CE-EOR) but longer operative times.

Clinical outcomes show fewer postoperative weaknesses and better overall survival when intraoperative imaging is used. Postoperative cognitive and sensory deficits varied by modality; progression-free survival differences were not significant. Study limitations include a retrospective design, the temporal rollout of modalities and differing surgeon experience.

Gross Total Resection (GTR) Rates: GTR was significantly more common with intraoperative MRI (iMRI, 56.9%) and intraoperative ultrasound (iUS, 57.1%) than without intraoperative imaging guidance (34%) in glioma surgery.

Extent of Resection (EOR): The mean EOR of contrast enhancement was highest with iMRI (96.6%), followed by iUS (93.2%), and lowest without intraoperative imaging (92%).

Postoperative Neurological Deficits: Patients without intraoperative imaging had significantly higher rates of postoperative weakness compared to those with iMRI or iUS (odds ratio = 0.520, CI = 0.272-0.994, P = .048).

Overall Survival (OS): Overall survival was significantly worse in patients without intraoperative imaging guidance (odds ratio = 1.534, CI = 1.058-2.225, P = .024) than in those with iMRI or iUS.

Progression-Free Survival (PFS): No significant differences in progression-free survival were found between the subgroups using iMRI, iUS, or no intraoperative imaging.

Surgery Duration: Mean surgery duration was longest with iMRI (260 minutes), intermediate with iUS (194 minutes), and shortest without intraoperative imaging (175 minutes).

Postoperative Functional Status: Karnofsky Performance Status (KPS) at 1 year was lowest in patients without intraoperative imaging guidance, indicating worse functional outcomes.

Study Limitations: The retrospective design, differing periods of iMRI and iUS use, learning curves, and unequal subgroup sizes limit the ability to fully compare all factors and may affect recurrence rate assessments.

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Determinants of survival after re-resection for recurrent glioblastoma: a meta-analysis

Acta Neurochirurgica (2026) 168:11

This systematic review and meta-analysis examines prognostic factors affecting survival after re-resection for recurrent glioblastoma, synthesizing data from 30 studies (1,741 pooled patients). Key findings identify gross total resection and MGMT promoter methylation as strong positive predictors, while age and low preoperative KPS associate with poorer outcomes; adjuvant therapies and time to re-resection showed inconsistent effects.

The paper details search methods, risk-of-bias assessment, statistical approaches, sensitivity analyses for IDH status, and study heterogeneity limitations. Conclusions emphasize patient selection for re-resection based on functional status and molecular markers and call for prospective, standardized trials and individual-patient data analyses to refine management of recurrent glioblastoma.

Gross Total Resection (GTR): Achieving GTR at re-resection for recurrent glioblastoma is significantly associated with improved survival compared to subtotal resection (pooled HR ~0.52–0.70, p < 0.001).

MGMT Promoter Methylation: Patients with methylated MGMT promoter status at recurrence have significantly better survival following re-resection (multivariate HR = 0.45, 95% CI: 0.27–0.76, p < 0.01).

Preoperative Karnofsky Performance Status (KPS): A KPS score <70 before re-resection is strongly associated with poorer survival outcomes (HR = 2.25, 95% CI: 1.59–3.19, p < 0.001).

Age: Older age is modestly associated with worse survival after re-resection, but the effect size is small (HR = 1.02, 95% CI: 1.01–1.03, p < 0.001); age alone should not preclude aggressive treatment.

Adjuvant Chemotherapy and Radiotherapy: No significant survival benefit was found for adjuvant chemotherapy (HR = 0.69, p = 0.33), radiotherapy (HR = 0.62, p = 0.50), or combined chemoradiotherapy after re-resection.

Time to Re-resection: Longer time intervals between initial surgery and re-resection did not show a statistically significant association with improved survival (HR = 0.69, p = 0.16).

Personalized Approach: Selection for re-resection should prioritize patients with good performance status, favorable tumor characteristics, and methylated MGMT promoter, with GTR as a key goal.

Evidence Limitations: Most included studies were retrospective with heterogeneity in definitions and reporting; high-quality prospective trials are needed to refine prognostic assessments and treatment strategies.

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Functional status in long-term survivors after mapping-guided surgery for diffuse low-grade glioma

J Neurosurg 144:139–150, 2026

This clinical study reports long-term functional outcomes in 103 consecutive patients with diffuse low-grade glioma who underwent mapping-guided resections and were followed for at least 15 years. Key findings include high overall survival (83.5%), mean postoperative KPS of 94.8, and 90% return-to-work rate, with low permanent neurological morbidity across 205 resections.

Comparative analysis shows patients who sustained employment had smaller pre/postoperative tumor volumes, greater extent of resection (including more supratotal resections), and less exposure to radiotherapy. The data support early maximal safe resection and postponement of radiotherapy to preserve long-term functional status and professional activity.

Functional Preservation: Long-term survivors of diffuse low-grade glioma (LGG) surgery had high rates of preserved functional status, with 90.7% of surviving patients maintaining a Karnofsky Performance Scale (KPS) score ≥ 80 after an average of 18.2 years follow-up.

Return to Work: 90% of patients were able to return to work after mapping-guided resection, and maintaining professional activity was strongly associated with higher preoperative KPS and greater extent of resection (EOR).

Extent of Resection (EOR): Greater EOR, particularly supratotal or total resections, correlated with better long-term functional outcomes and higher rates of continued employment.

Radiation Therapy Impact: Early or any radiotherapy (RT) was linked to lower rates of return to work and a reduced proportion of patients with KPS ≥ 80 at last follow-up, while chemotherapy did not show this negative association.

Timing of Surgery: Early surgery at diagnosis, especially in patients with higher KPS and smaller tumor volume, increased the chance for maximal resection and long-term preservation of functional status.

Low Neurological Morbidity: Permanent postoperative neurological deficits were rare (1.5% after 205 resections), supporting the safety of maximal resection with intraoperative mapping.

Malignant Transformation: The risk of malignant transformation was lower in patients with greater EOR and those who continued to work, suggesting oncological benefit from radical resection.

Adjuvant Therapy Strategy: A wait-and-watch strategy after maximal safe resection, postponing adjuvant treatments unless necessary, helped preserve long-term quality of life and autonomy.

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Operative Microscope In-Field Visualization of Confocal Laser Endomicroscopy Interface (Zeiss CONVIVO )

Operative Neurosurgery 29:860–864, 2025

This study evaluates integrating the Zeiss CONVIVO confocal laser endomicroscopy interface into the operative microscope heads-up display to allow simultaneous visualization of the surgical field and real-time confocal laser endomicroscopy (CLE) images. A randomized cohort of 22 intra-axial tumor surgeries showed shorter CLE usage times, fewer total captures, and a trend toward higher usable-image proportion with heads-up integration.

The integration improved intraoperative ergonomics by reducing probe motion artifacts and image noninterpretability, streamlining workflow, and decreasing operative time while preserving diagnostic utility of CLE for margin assessment in gliomas and other brain lesions.

Confocal Laser Endomicroscopy (CLE): Provides real-time, in vivo microscopic imaging of brain tumors during neurosurgery, enabling identification of tumor margins without the need for traditional tissue extraction or frozen section analysis.

Zeiss CONVIVO® System: A CLE device recently introduced in neurosurgery, proven reliable for both ex vivo and in vivo applications, and undergoing further clinical refinement.

Technical Challenge: Standard CLE use requires the surgeon to shift attention from the operative field to a separate screen to assess image quality, potentially causing motion artifacts, prolonging surgery, and increasing the number of unusable images.

Heads-Up Display Integration: Visualization of the CONVIVO® interface was integrated as a picture-in-picture display inside the operative microscope, allowing simultaneous monitoring of the surgical field and CLE images without diverting gaze.

Study Findings: Use of the heads-up display significantly reduced CLE employment time (mean 61.1 vs. 201.6 seconds; P = .01), decreased the total number of images acquired, and increased the proportion of usable images, though the latter was not statistically significant (P = .06).

Workflow Efficiency: Direct intraoperative feedback enabled by the heads-up display led to fewer motion artifacts, more efficient image acquisition, and reduced overall operative time.

Clinical Implications: The integration supports more efficient and accurate intraoperative tumor assessment, potentially improving the extent of resection, especially in gliomas, and reducing reliance on frozen sections.

Limitations and Future Directions: Further refinement is needed for effortless image acquisition; artificial intelligence for artifact reduction and real-time interpretation by neurosurgeons are potential future improvements.

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Integrated insular phenotype (IIP) versus Berger–Sanai and Yasargil classifications: comparative prognostic value in surgery of insular gliomas

Acta Neurochirurgica (2025) 167:324

This study compares the Integrated Insular Phenotype (IIP), a three-level ordinal topographic classification of insular gliomas, with Berger–Sanai and Yasargil systems to evaluate prognostic performance for extent of resection, seizure control, and persistent neurological deficit at 90 days. Using retrospective analysis of 167 surgically treated patients, logistic regression and model metrics (AUC, AIC, LR χ2) assessed associations between classification complexity and outcomes.

Results show increasing IIP complexity strongly predicted lower resectability, poorer seizure control, and higher persistent deficit risk; IIP produced more stable odds ratios, lower AIC, and higher LR χ2 than traditional systems. The authors propose IIP as a practical risk-stratification tool to balance oncological radicality and functional safety, recommending multicenter prospective validation and integration with molecular and intraoperative technologies.

Integrated Insular Phenotype (IIP): An ordinal classification system for insular gliomas that incorporates tumor topographic complexity and multizonal involvement, outperforming traditional Berger–Sanai and Yasargil systems in prognostic accuracy for surgical outcomes.

Prognostic Value: IIP demonstrates superior and more stable associations with key surgical outcomes—extent of resection, seizure control, and persistent neurological deficit at 90 days—compared to Berger–Sanai and Yasargil classifications, as shown by higher informativeness, lower AIC, and more reproducible odds ratios.

Surgical Complexity: Higher IIP complexity (IIP-M) is linked to reduced likelihood of total/subtotal resection, poorer seizure control, and increased risk of persistent neurological deficits, while simpler phenotypes (IIP-L) are associated with more favorable outcomes.

Traditional Classifications: Berger–Sanai and Yasargil systems provide limited prognostic value; Berger–Sanai yields high but unstable odds ratios with wide confidence intervals, while Yasargil offers consistent but less discriminative results.

Clinical Implications: IIP can guide individualized surgical strategies by balancing oncological radicality against functional safety, supporting the principle of maximal safe resection and informing risk stratification.

Seizure Outcomes: Multizonal and widespread IIP phenotypes (IIP-M) are associated with poorer postoperative seizure control, reflecting the challenge of eliminating diffuse epileptogenic networks.

Study Limitations: The findings are based on a single-center retrospective cohort; external validation and integration with molecular, histopathological, and neurocognitive factors are needed for broader applicability.

Future Directions: Prospective multicenter validation, integration with intraoperative technologies, and use of AI/ML for risk stratification and personalized planning are recommended to enhance the utility of IIP in clinical practice

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Indirect cognitive mapping in glioma surgery in patients not eligible for awake craniotomy

Acta Neurochirurgica (2025) 167:289

This article presents a neurosurgical technique for indirectly mapping cognitive subcortical white matter pathways during glioma resection in patients who cannot undergo awake craniotomy. Using preoperative DTI and fMRI to create a 3D functional map, the team employs intraoperative monopolar subcortical motor stimulation as a live landmark to infer and protect nearby cognitive tracts like the arcuate fasciculus and IFOF.

Three illustrative cases demonstrate planning limits based on measured motor stimulation thresholds (approx. 1 mA ≈ 1 mm) and show safe resections with preserved cognitive and motor function. The report discusses indications, limitations versus awake mapping, importance of patient counselling about transient deficits, and integration of neuronavigation, tractography, and intraoperative motor mapping.

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Awake surgery for IDH-mutant grade 2 glioma involving the corpus callosum: long-term onco-functional results after callosectomy in 157 consecutive patients

J Neurosurg 143:1280–1289, 2025

This clinical study reports outcomes from 157 consecutive patients with IDH‑mutant grade 2 gliomas infiltrating the corpus callosum who underwent connectome-guided awake surgery with callosectomy. It summarizes surgical technique, extent of resection, complication rates, return-to-work statistics, histology, adjuvant treatments, reoperations, and long-term overall survival.

Comparative analysis contrasts complete (total/supratotal) versus incomplete resections, showing higher extent of resection, greater reoperation potential, and longer median overall survival when callosal tumor was fully removed, while preserved function and a 96.8% return-to-work rate underline favorable onco-functional balance.

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Factors associated with poor prognosis in elderly biopsy‑only glioblastoma patients

Acta Neurochirurgica (2025) 167:273

In elderly glioblastoma patients undergoing biopsy only, poor preoperative performance status, central tumor location, and larger tumor volume were associated with reduced three-month survival and lower treatment completion rates, highlighting the need for careful preoperative assessment and personalized counseling in this vulnerable group.

Study investigated elderly patients (>65 years) with glioblastoma (GBM) who underwent biopsy only, not surgical resection.

• Median overall survival (OS) was 4.6 months; only half completed oncological treatment.

• Poor preoperative performance status (PS), central tumor location, and larger tumor volume were independently associated with reduced three-month survival.

• Poor PS was the only independent predictor for not completing oncological treatment; these patients had very poor survival (median OS 1.6 months).

• Completion of treatment was linked to longer survival (median OS 8.3 months for completers vs. 3.5 months for non-completers).

• Findings suggest limited benefit of biopsy and oncological treatment in elderly GBM patients with poor PS.

• Results can help guide preoperative counseling and decision-making for this vulnerable patient group.

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The neuronal reserve in glioma surgery: functional reorganization of the motor network examined by navigated transcranial magnetic stimulation and diffusion tensor imaging tractography

J Neurosurg 143:793–804, 2025

This study demonstrates that glioma-induced reorganization of the motor cortex, measured by navigated transcranial magnetic stimulation and diffusion tensor imaging, is linked to functional recovery. Individual neuronal reserve—reflected in motor area resizing, excitability, and tract integrity—may explain differences in disease progression and surgical outcomes.

• Glioma surgery outcomes vary due to individual differences in motor network compensation and adaptation.

• This study used navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging (DTI) tractography to measure motor cortex reorganization in glioma patients.

• Motor area relocation, resizing, and changes in excitability were observed in both affected and unaffected hemispheres, indicating bilateral reorganization.

• Greater preoperative motor area size and excitability were associated with better postoperative motor function and recovery.

• Reduced integrity of the corticospinal tract correlated with motor impairment and limited reorganization capacity.

• Functional recovery was linked to increased motor area size, excitability, and area relocation, supporting the concept of an individual neuronal reserve.

• Reorganization patterns were independent of tumor grade, highlighting the importance of personalized risk stratification and treatment planning.

• The study recommends using nTMS data for tailored preoperative risk assessment and patient counseling in glioma surgery.

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Dynamic Tumor in Situ Fluid Circulating Tumor DNA Postsurgery Effectively Predicts Recurrence and Clinical Benefits for Glioblastomas

Neurosurgery 97:671–680, 2025

Dynamic monitoring of tumor in situ fluid circulating tumor DNA (TISF-ctDNA) after glioblastoma surgery predicts recurrence earlier than imaging, effectively identifies molecular residual disease, and serves as a robust prognostic biomarker. TISF-ctDNA status guides treatment response assessment and may enable more personalized, timely interventions for GBM patients.

• TISF-ctDNA (tumor in situ fluid circulating tumor DNA) is a promising biomarker for monitoring molecular residual disease (MRD) and recurrence in glioblastoma (GBM) patients after surgery.

• In a prospective study of 37 GBM patients, TISF-ctDNA positivity after surgery was detected in 62.2% of cases and predicted a higher risk of recurrence and shorter progression-free survival (PFS).

• TISF-ctDNA positivity preceded imaging-detected recurrence by a median of 71 days, allowing for earlier intervention.

• Conversion from TISF-ctDNA positive to negative during adjuvant therapy was associated with improved overall survival.

• TISF-ctDNA showed high sensitivity (86.2%) and specificity (100%) in detecting postsurgical MRD recurrence.

• Common tumor gene mutations (EGFR, TP53, PTEN, NF1) did not significantly impact prognosis in this cohort.

• TISF-ctDNA monitoring is less effective for detecting distant tumor recurrences.

• The study supports TISF-ctDNA as an early, noninvasive tool for personalized GBM management, though larger studies are needed for validation.

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Ventricular Entry During Glioblastoma Resection is Associated With Reduced Survival and Increased Risk of Distant Recurrence

Neurosurgery 97:601–611, 2025

Ventricular entry (VE) during glioblastoma resection is an independent risk factor for reduced overall survival and increased distant recurrence, including leptomeningeal dissemination. VE may diminish the survival benefit of gross-total resection, especially in tumors contacting the subventricular zone. Surgical strategies should weigh VE risks against maximal tumor removal.

• Ventricular entry (VE) during glioblastoma (GBM) resection is associated with significantly reduced overall survival (OS) and increased risk of distant recurrence and leptomeningeal dissemination (LMD), independent of other prognostic factors.

• Patients with VE had a median OS of 12 months versus 18 months for non-VE, and higher rates of distant recurrence (63.9% vs 39.7%).

• VE is more common in tumors contacting the subventricular zone (SVZ), and even among these, VE further reduces survival (12 vs 17 months).

• Gross-total resection (GTR) without VE provides the longest survival; GTR with VE does not significantly improve survival over less extensive resections with VE.

• VE is also associated with higher rates of postoperative hydrocephalus and need for external ventricular drains.

• Mechanistically, VE may facilitate tumor cell seeding into cerebrospinal fluid, promoting multifocal recurrences and LMD.

• Neurosurgeons should carefully weigh the risks of VE against the benefits of maximal tumor resection in surgical planning.

• Further prospective, multicenter studies are needed to clarify the risks and guide surgical strategies for GBM involving the SVZ.

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Laser interstitial thermal therapy for high-grade glioma: a systematic review, meta-analysis, and meta-regression

Neurosurg Focus 59(2):E10, 2025

Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for high-grade glioma (HGG) showing mean overall survival of 11.7 months and progression-free survival of 5.3 months. LITT offers acceptable safety, especially for deep or unresectable tumors, but further randomized studies are needed to confirm long-term efficacy.

• Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for high-grade glioma (HGG), especially in deep-seated or unresectable tumors.

• A systematic review and meta-analysis of 21 studies including 602 patients found mean overall survival (OS) after LITT was 11.74 months and mean progression-free survival (PFS) was 5.3 months.

• 6-, 12-, and 24-month OS rates were 77.0%, 48.9%, and 16.1%; PFS rates were 37.1%, 12.8%, and 4.3%, respectively.

• Permanent postoperative deficits occurred in 5.7% of patients, with higher rates in newly diagnosed HGG than recurrent cases (4.15% vs 0.02%).

• Tumor progression after LITT was observed in about 80% of patients, and overall mortality was 67.7%.

• Deep/unresectable tumors and IDH-wildtype mutations were associated with worse outcomes; smaller tumor size and higher baseline KPS predicted better survival.

• LITT showed acceptable safety and feasibility, but randomized prospective studies are needed to confirm long-term efficacy.

• Common complications included hemiparesis, weakness, and temporary neurological deficits.

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High-grade glioma: combined use of 5-aminolevulinic acid and intraoperative ultrasound for resection and a predictor algorithm for detection

J Neurosurg 143:323–331, 2025

Combining 5-aminolevulinic acid (5-ALA) fluorescence and intraoperative ultrasound (ioUS) significantly improved the sensitivity and specificity for detecting high-grade glioma during surgery, compared to either technique alone. A machine learning algorithm (HGGPredictor) further enhanced intraoperative tumor margin prediction, suggesting a new standard for safer, more effective resections.

• Combining 5-ALA fluorescence and intraoperative ultrasound (ioUS) improves the accuracy of high-grade glioma (HGG) resection compared to using either method alone.

• 5-ALA shows higher sensitivity (84.9%), while ioUS provides higher specificity (84.5%); combined, they reach sensitivity of 91% and specificity of 86%.

• The combined approach is especially valuable for maximizing tumor removal while minimizing neurological damage, particularly near eloquent brain regions.

• A machine learning algorithm (HGGPredictor) was developed to predict tumor presence during surgery based on 5-ALA and ioUS results.

• The study included 72 patients and 301 biopsies, with histological analysis as the reference standard.

• The benefit of combination is greatest for strong fluorescence or hyperechogenicity; ioUS is particularly helpful when 5-ALA fluorescence is weak.

• The combined method is accessible and can be integrated into existing surgical protocols without major additional costs.

• Limitations include single-center design and lack of a control group, but results suggest a new standard for HGG resection.

 

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Intraoperative brain tumor classification via laser-induced fluorescence spectroscopy and machine learning

J Neurosurg 143:313–322, 2025

A laser-based device, TumorID, combined with machine learning, rapidly and nondestructively classifies brain tumor tissue intraoperatively. Tested on 46 patients, it distinguished glioma, meningioma, pituitary adenoma, and normal tissue with high accuracy, offering potential to improve neurosurgical decision-making and outcomes

• TumorID is a laser-induced endogenous fluorescence spectroscopy device paired with machine learning for rapid intraoperative brain tumor classification.

• It distinguishes glioma, meningioma, pituitary adenoma, and nonneoplastic tissue in near real time using a 405-nm laser and support vector machine (SVM) algorithm.

• The device requires only 0.5 seconds per scan and does not damage tissue.

• In a study of 46 patients and 761 scans, TumorID achieved a multiclass AUROC of 0.809, demonstrating high classification accuracy.

• Neutral porphyrin emission regions were most significant for tissue differentiation.

• TumorID offers objective, fast, and nondestructive tissue diagnostics, potentially improving surgical decision-making and resection outcomes.

• Future directions include in vivo use, prediction of tumor subtypes and genetics, and integration with other data sources for improved accuracy.

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Is FLAIRectomy Directly Correlated with Prolonged Survival in Glioblastoma? A Prospective National Multicenter Study on Correlation Between Extent of Tumor Resection and Clinical Outcome

Neurosurgery 97:489–500, 2025

This multicenter prospective study shows that the extent of FLAIRectomy (resection of FLAIR-positive areas) in glioblastoma is a stronger predictor of survival than traditional resection, with higher EOFR significantly improving progression-free and overall survival, especially in IDH-mutant tumors, without increasing neurological complications.

• FLAIRectomy, or resection of FLAIR-MRI hyperintense regions beyond the contrast-enhancing tumor, was studied in a prospective multicenter cohort of 150 glioblastoma patients.

• A higher extent of FLAIR resection (EOFR) was associated with significantly improved overall survival (OS) and progression-free survival (PFS), more so than resection of contrast-enhancing tumor alone.

• Each 1% increase in EOFR correlated with a 6.8% reduction in mortality risk for IDH-wildtype and 12.1% for IDH-mutant tumors.

• Mean OS was 28.4 months and mean PFS was 16.3 months in the study cohort.

• IDH1 mutation status was also associated with longer survival, but EOFR remained an independent predictor after adjustment.

• AI analysis confirmed that patients with higher EOFR clustered with longer survival.

• Neurological safety was addressed with intraoperative neuromonitoring and careful planning; permanent deficits occurred in 9/150 patients.

• The study concludes that FLAIR-based supramarginal resection may be a more reliable predictor of survival in glioblastoma than conventional imaging-guided resection.

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