Category: Oncology

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Factors associated with overall survival and 90-day mortality following resection of melanoma brain metastases

Operative Neurosurgery. 2026;31(2):270–284

Objective

To identify factors associated with early postoperative mortality and overall survival after surgical resection of melanoma brain metastases.

Methods

This retrospective single-center study included 103 patients who underwent resection as their initial treatment for melanoma brain metastases between 2009 and 2018. The primary outcomes were overall survival, 90-day mortality and development of leptomeningeal disease.

Main results

Nineteen patients (18%) died within 90 days of surgery. Elevated lactate dehydrogenase at diagnosis was independently associated with greater early mortality (OR 7.17).

Factors associated with lower 90-day mortality included:

  • Postoperative Karnofsky Performance Status ≥80: OR 0.13.
  • Brain metastasis already present at the diagnosis of stage IV disease: OR 0.11.

Better overall survival was associated with:

  • Preoperative Karnofsky score ≥80: HR 0.46.
  • Adjuvant stereotactic radiosurgery: HR 0.55.
  • Surgical reduction of total intracranial tumor burden by ≥95.6%: HR 0.47.
  • Synchronous diagnosis of brain metastasis and stage IV melanoma: HR 0.59.

No evaluated factor was significantly associated with subsequent leptomeningeal disease. PubMed abstract

Interpretation

Functional status remains central to surgical selection. The study also suggests that the value of surgery may depend not only on removing the symptomatic lesion but on achieving a major reduction in the patient’s total intracranial tumor burden.

The association between adjuvant stereotactic radiosurgery and longer survival supports a combined local-treatment strategy rather than surgery alone. Elevated LDH may help identify patients at particularly high risk of early postoperative death.

Limitations

The study was retrospective, conducted at a single tertiary cancer center and included patients treated between 2009 and 2018. Systemic melanoma therapy has evolved substantially since that period. The survival associations cannot establish that extensive resection or adjuvant radiosurgery directly caused better survival because healthier patients may have been more likely to receive these treatments.

Clinical takeaway

Surgery for melanoma brain metastases should be considered within a multimodal treatment strategy. Patients with good functional status are the most likely to benefit, while elevated LDH identifies a group with substantial early mortality risk. When safely achievable, a reduction of at least approximately 95% of total intracranial tumor burden may provide greater benefit than limited resection of the dominant lesion alone.

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Resection and permanent intracranial brachytherapy using modular, biocompatible cesium-131 implants for recurrent aggressive meningiomas: 5-year results from a prospective phase 2 trial

J Neurosurg 145:206–213, 2026

This prospective single-center phase 2 trial evaluates maximal safe resection combined with intraoperative Cs-131 collagen tile brachytherapy (R+CTBT) for 29 recurrent, aggressive meningiomas, reporting improved local control rates at long-term follow-up compared with each tumor’s prior same-site treatment. Outcomes include Kaplan–Meier local control at 36–60 months, hazard ratios from Cox models, and detailed adverse-event reporting.

The report describes patient selection, implant technique, dosimetry metrics, statistical methods, and safety considerations, highlighting a lower symptomatic radiation necrosis rate with Cs-131 tiles and acceptable surgical complications, while noting single-center design and limited sample size as study limitations.

Objective Evaluate whether maximal safe resection plus Cs-131 collagen tile brachytherapy (R+CTBT) improves control of recurrent aggressive meningiomas versus the patient’s prior same-site treatment.

Design Prospective, nonrandomized, single-center phase 2 trial enrolling patients with recurrent aggressive meningiomas (June 2013–Jan 2018), with follow-up through August 2020.

Procedure After maximal safe resection and intraoperative pathologic confirmation, Cs-131 seeds were embedded into collagen squares (“tiles”) and placed in the resection bed; postoperative CT was used for radiation planning and MRI for extent of resection assessment.

Population 29 tumors in 27 patients (median age 66); tumors at time of R+CTBT were predominantly WHO grade 2 (90%), with 3% grade 1 and 7% grade 3.

Efficacy Local control at 48 and 60 months was 73% and 48% after R+CTBT versus 21% and 17% after prior same-site treatment (HR 0.145, p < 0.001).

Outcomes detail Local progression (≤ 1.5 cm from operative bed) occurred in 8/29 (28%) implant sites over a median radiographic follow-up of 34.8 months.

Complications Surgery-related complications requiring intervention occurred in 4/29 (14%) (1 early infection; 3 delayed wound breakdown/infection).

Radiation injury Symptomatic radiation brain injury/radiation necrosis occurred in 4/29 (14%), and all cases resolved with medical therapy.

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Resectability of White Matter Tracts in Patients With Language-Critical Gliomas

Neurosurgery 99:140–148, 2026

This study evaluates how resections of language-associated white matter tracts (WMTs) predict persistent postoperative language deficits (PLDs) in 68 glioma patients using tractography, intraoperative mapping, and outcome assessments. Results show WMT resection strongly predicts PLDs with high negative predictive value but modest positive predictive value, and temporal/parietal segments carry the greatest risk.

Anatomic clustering localized high-risk resections to the temporoparietal junction and middle temporal lobe, while frontal operculum and orbitofrontal tracts were often resectable without lasting deficits. Anatomically stratifying tracts (parietal/temporal) improved positive predictive value, supporting tractography-informed surgical planning alongside intraoperative mapping.

Goal Identify predictors of permanent postoperative language deficits (PLDs) in language-eloquent glioma surgery by analyzing which language-associated white matter tract (WMT) segments are resected.

Cohort & approach Retrospective analysis of consecutive adults undergoing awake craniotomy with intraoperative language mapping; WMT tractography reconstructed 6 language-related tracts and parcellated by anatomic location; outcomes based on formal language testing pre-op vs 1–3 months post-op (with clinical follow-up to 6 months for persistence).

Overall predictive signal Any WMT resection strongly increased odds of PLDs (odds ratio 16.0, P = .0115) with high NPV 97.4% but low PPV 29.6%.

Anatomic vulnerability Resections associated with PLDs clustered in the temporoparietal junction (TPJ) and middle temporal lobe (MTL), while resections without PLDs were more diffuse and concentrated in frontal/anterior regions.

Resectability by region Frontal tract segments showed near-complete resectability (PPV = 0 across reported frontal segments), whereas parietal/temporal segments had higher PPVs (eg, parietal AF 0.4, temporal AF 1, temporal IFOF 0.5, temporal ILF 0.5).

Stratified model Focusing only on parietal and temporal tract segment resections improved prediction of PLDs (odds ratio 29.4, P < .001) and increased PPV to 50% (NPV 96.7%).

Resection volume The volume of tract resected did not differ by functional outcome (U = 84.0, P = .70), suggesting location/segment matters more than amount.

Clinical implication WMT resections in orbitofrontal, anterior temporal, and frontal operculum regions were often tolerated, while parietal/temporal WMT injuries substantially increased PLD risk.

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Speech mapping in awake high-grade glioma resection: subcortical tract proximity as a predictor of language outcomes

J Neurosurg 145:179–189, 2026

This clinical study evaluates intraoperative predictors of postoperative language decline in awake resections of language-eloquent high-grade gliomas using diffusion tractography, 5-ALA, and subcortical stimulation with standardized language testing. It reports rates of transient and permanent deficits, correlates specific white matter tracts (IFOF, ILF, AF/SLF) with domain-specific impairments, and presents stimulation thresholds predictive of decline.

The paper emphasizes that preoperative deficits and positive stimulation of multiple tracts increase risk of lasting language impairment, while most single-tract-related declines tend to recover by three months; proposed SCS amplitude cutoffs are offered as practical guidance to balance maximal resection and language preservation.

Objective Identify intraoperative predictors of postoperative language decline and predictors of temporal language recovery after awake resection of language-eloquent high-grade glioma (HGG).

Methods Single-center cohort (Jan 2017–Nov 2024) undergoing awake craniotomy with diffusion tractography, 5-ALA, subcortical stimulation (SCS), and intraoperative language testing; language outcomes assessed at 48 hours, 2 weeks, and 3 months.

Outcomes New or worsened postoperative language deficit occurred in 53.1% (69/130) and was permanent (>3 months) in 9.2% (12/130).

Key intraoperative predictor (domain-specific) Clinical deterioration during awake testing predicted short-term decline in semantic processing (IFOF) (RR 3.47), reading (ILF) (RR 21.4), and auditory naming/repetition (AF/SLF) (RR 6.98).

Permanent-deficit risk factors Higher risk of persistent language decline was associated with preoperative speech deficit (RR 2.65), intraoperative ILF-related reading deterioration (RR 8.92), and positive SCS of multiple language tracts.

Tract sensitivity & recovery Posterior ILF–related reading function showed the greatest sensitivity to decline and the lowest propensity for recovery; all observed reading deficits were linked to tumors near the posterior ILF.

SCS threshold cutoffs ROC/Youden-derived SCS amplitudes predictive of postoperative deficits were reported per tract: IFOF 5.5 mA (48h/2w), 4.5 mA (3m); ILF (reading) 7.0 mA (48h/2w), 4.5 mA (3m); AF/SLF 5.5 mA (48h/2w), 2.5 mA (3m).

Multiple-tract involvement At 3 months, deficits occurred in 7.4% (5/68) with single-tract positive SCS versus 75.0% (9/12) with two tracts; both patients with all three tracts stimulated had persistent deficits beyond 3 months.

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Corticosteroid Use Before Stereotactic Brain Biopsy for Suspected Lymphoma

Neurosurgery 99:30–39, 2026

This retrospective cohort study evaluates whether preoperative corticosteroid therapy (CST) affects the diagnostic yield of stereotactic brain biopsy (SBB) in 104 patients with pathologically confirmed primary central nervous system lymphoma (PCNSL). The analysis stratifies patients by steroid timing, duration, and cumulative dexamethasone-equivalent dose, reporting diagnostic rates, radiographic features, and complications.

Results show a 92.3% overall diagnostic yield that remained high regardless of CST exposure, dose, or timing, with comparable postoperative complication rates. The authors conclude short-course CST for symptom control appears safe before SBB, while emphasizing multidisciplinary coordination and need for prospective standardized protocols.

Clinical question Whether preoperative corticosteroid therapy (CST) (timing, dose, duration) reduces stereotactic brain biopsy (SBB) diagnostic yield in suspected primary CNS lymphoma (PCNSL), and whether it affects postoperative complications

Cohort & design Retrospective review of 725 SBBs (2014–2025) identifying 104 pathologically confirmed PCNSL cases; CST-naive vs CST-exposed with stratification by last-dose timing, cumulative dexamethasone-equivalent dose, and duration

Overall yield Initial SBB diagnostic yield for PCNSL was 92.3% (96/104), with 8 nondiagnostic initial biopsies

CST vs no CST yield Diagnostic yield was 95.3% with CST (41/43) vs 90.2% without CST (55/61), not significant (P = .46)

Timing of last CST dose Yield remained high across intervals: ≤48 h 96.4%, 48–72 h 91.7%, >72 h 100% (P = .66)

Cumulative dose & duration Yield did not differ by cumulative dexamethasone dose (≤20 mg 95.5%, 21–40 mg 100%, >40 mg 100%, P = 1.0) or by duration (≤5 days 94.6% vs >5 days 100%, P = 1.0)

Complications Postoperative complications occurred in 4.8% of PCNSL cases, with no significant difference between CST-exposed and CST-naive patients (P = .84)

Nondiagnostic biopsies & next steps Only 2/8 initially nondiagnostic cases had prebiopsy CST; all 8 were ultimately confirmed PCNSL via repeat SBB, CSF cytology, or postmortem, supporting repeat/alternative diagnostic approaches when initial biopsy is nondiagnostic

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Multi-Institutional Assessment of Circulating Cell-Free DNA in Cerebrospinal Fluid Facilitates Central Nervous System Lymphoma Diagnosis and Treatment Initiation

Neurosurgery 99:40–49, 2026

This multi-institutional clinical study evaluates a CLIA-certified rapid PCR assay detecting the MYD88 L265P variant in cell-free DNA from cerebrospinal fluid to diagnose central nervous system (CNS) lymphoma. The assay demonstrated 100% specificity, 40% sensitivity, and facilitated earlier treatment initiation, sometimes obviating the need for risky CNS tissue biopsy.

The report details prospective implementation across 19 hospitals, methods for CSF processing and qPCR, diagnostic performance metrics, clinical trajectories of MYD88-positive patients, and implications for using CSF liquid biopsy to accelerate safe, targeted CNS lymphoma therapy.

Clinical need CNS lymphoma diagnosis has historically relied on CNS tissue biopsy, which can delay treatment and carries neurological morbidity risk.

Assay approach A CLIA-certified rapid PCR test was implemented to detect the MYD88 L265P variant in cell-free DNA (cfDNA) from CSF as a minimally invasive diagnostic method.

Deployment scale Prospective testing was conducted over 16 months across 19 hospitals: 201 samples from 184 patients; 19 samples (18 patients) were MYD88 L265P positive, with 2 test failures from inadequate DNA.

Performance characteristics In patients with available records, the assay showed specificity 100%, sensitivity 40%, PPV 100%, NPV 83% (positive LR ∞; negative LR 0.6).

Clinical utility Positive MYD88 results enabled CNS lymphoma–directed treatment initiation, including cases treated without CNS tissue confirmation, with 100% concordance between CSF and CNS tissue biopsy among contemporaneous paired cases (N=8).

Time impact MYD88-positive results often returned before biopsy (median 5.5 vs 10.5 days from admission), and time to treatment was shorter when LP/CSF testing avoided CNS biopsy (7 vs 9 days, P=.048).

Predictors/limitations Detection was more likely with leptomeningeal disease (multivariable P=.017) and DLBCL histology (multivariable P=.027); sensitivity remained modest, implying negative tests still require further workup such as biopsy.

Practice caveat (annotation) Because of modest sensitivity and concerns about spectrum bias/loss to follow-up, MYD88 CSF testing can supplement or obviate biopsy in selected cases, but generally does not replace the need for tissue-based molecular profiling.

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Isocitrate Dehydrogenase Wild-type Glioblastoma Resection Under Fluorescein Sodium and White Light Guidance Based on Response Assessment in Neuro-Oncology Resect Criteria

Operative Neurosurgery 30:861–869, 2026

This study evaluates sodium fluorescein–guided resection versus white‑light surgery in isocitrate dehydrogenase wild‑type glioblastoma, using RANO resection classes and quantitative MRI volumes to compare residual contrast‑enhanced tumor burden. The retrospective analysis of 162 patients shows significantly lower postoperative CE residual volume and higher complete CE resection rates with fluorescein guidance.

The paper also correlates molecular markers with resection outcomes, finding MGMT promoter methylation associated with higher complete CE resection rates and suggesting fluorescein guidance may particularly improve CE resection across molecular subgroups, while survival differences require longer follow‑up and larger cohorts.

Objective Increase extent of resection of the contrast-enhanced (CE) portion of IDH–wild-type glioblastoma, using the RANO absolute residual-volume resection classes to quantify what sodium fluorescein guidance achieves vs white light (WL) surgery.

Design/measurement Retrospective comparative study of 162 patients (fluorescein 82 vs WL 80), with pre/post-op MRI volumetrics outlined in Brainlab and categorized by RANO EOR classes.

Key EOR result Residual CE tumor volume was lower with fluorescein guidance than WL (median 0.0 cm³ vs 0.5 cm³, P = .023).

Complete CE resection rate Proportion with 0 cm³ residual CE (RANO I + IIA) was higher with fluorescein (62.2%) than WL (42.5%), P = .012.

RANO distribution shift RANO class distribution differed between groups (P = .015), with more IIA and fewer IIB resections under fluorescein guidance.

Non-CE resection No significant between-group differences were found in preoperative CE/NCE volumes or postoperative NCE residual volumes, consistent with fluorescein primarily highlighting BBB-disrupted (enhancing) tissue.

MGMT association MGMT promoter methylation was associated with higher likelihood of achieving nonresidual CE (complete CE resection), P = .005; fluorescein guidance and MGMT status were significant predictors of nonresidual CE.

Survival Overall survival did not significantly differ between fluorescein-guided and WL groups (log-rank P = .15), while MGMT-methylated patients had significantly better survival than unmethylated (P = .019; HR = 0.52).

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Relationships Between Surgical Approach, Tumor Classification Scheme, and Early Neurocognitive Outcome After Awake Craniotomy for Resection of Insular Glioma

Operative Neurosurgery 30:880–889, 2026

This study evaluates early postoperative neurocognitive outcomes after awake craniotomy for insular glioma resection, comparing transcortical and transsylvian approaches and examining tumor classification schemes. It reports frequent, domain-specific declines—most notably in memory and verbal fluency—and analyzes relationships with tumor hemisphere, insular zone, and extension.

The authors found similar overall neurocognitive change across surgical corridors but identified higher verbal fluency decline with transcortical approaches and greater domain-specific risk linked to left-sided tumors, extra-insular extension, and anterior or inferior insular involvement.

Study aim: Assessed how surgical approach (transsylvian vs transcortical) and tumor classification/location relate to early postoperative neurocognitive function (NCF) after awake resection of insular glioma.

Cohort & design: Retrospective series of 53 newly diagnosed insular glioma patients (47% high-grade; 75% left hemisphere) treated with awake craniotomy, with neuropsychological testing pre-op and within 60 days post-op.

Classification schemes: Tumors were categorized by Berger–Sanai zones (collapsed to anterior/posterior/superior/inferior) and Pitskhelauri extension groups (insula only; insula + extension; predominantly extra-insular).

Overall NCF change: Postoperative decline occurred across multiple domains, with the largest effects most often in memory and verbal fluency (executive function).

Frequency of clinically meaningful decline: 85% declined on ≥1 test (Δz ≤ −1.0), 52% on ≥2 tests, and 22% on ≥5 tests; decline was most frequent/severe in memory and also common in executive function, attention, and processing speed.

Surgical approach comparison: Mean NCF change generally did not differ by approach, but the transcortical approach showed a higher rate of verbal fluency decline than transsylvian (61% vs 26%).

Tumor hemisphere & localization effects: Left-hemisphere tumors were linked to poorer outcomes on multiple tests (notably memory, verbal fluency, naming, and token comprehension), while anterior tumors had worse executive function (mental flexibility) than posterior, and inferior lesions had worse recognition memory than superior.

Tumor extent/size associations: Predominantly extra-insular tumors had greater fluency reduction than insula-only; more Berger–Sanai quadrants involved correlated with worse executive function change; larger tumor volume and higher postoperative FLAIR volume related to worse processing speed and comprehension outcomes.

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Early Initiation of Radiation Therapy Improves Survival in Elderly Patients With Glioblastoma

Neurosurgery 98:1402–1412, 2026

This clinical study evaluates the effect of early postoperative radiation therapy (RT) initiation on survival in patients aged 65 and older with IDH‑wildtype glioblastoma, analyzing outcomes from a prospective registry of 56 patients treated between 2020–2024. Survival analyses, including Kaplan‑Meier curves and Cox regression, compare outcomes for RT started <20 days versus ≥20 days after surgery and examine RT fractionation and temozolomide use.

Results show that initiating RT within 20 days post‑surgery is associated with improved overall survival and progression‑free survival on univariate analysis, while multivariate models indicate confounding by performance status and adjuvant temozolomide; adjuvant TMZ remains a strong positive predictor of survival. The authors conclude early RT may benefit elderly GBM patients and call for prospective randomized trials to confirm timing effects.

Study aim: Evaluate whether earlier start of postoperative radiation therapy (RT) improves survival in elderly (≥65) patients with newly diagnosed IDH-wildtype glioblastoma.

Cohort & design: Retrospective cohort using a prospective registry (2020–2024), 56 patients, comparing RT start <20 days vs ≥20 days after surgery; endpoints were overall survival (OS) and progression-free survival (PFS).

Univariate survival finding: Starting RT <20 days after surgery was associated with improved OS (P=.0460) and PFS (P=.0075) versus ≥20 days.

Adjusted (multivariate) finding: After adjustment (including KPS and adjuvant temozolomide), RT timing was not statistically significant for OS (P=.2962) or PFS (P=.0670), indicating likely confounding.

Temozolomide effect: Adjuvant temozolomide was a significant predictor of better outcomes on multivariate analysis for both OS (P=.0038; HR 0.16) and PFS (P=.0133; HR 0.27).

Fractionation nuance: Among those starting RT early (<20 days), conventionally fractionated RT (60 Gy/30 fx) showed significantly improved PFS (P=.0164), while hypofractionated RT (40 Gy/15 fx) did not reach significance (P=.0509).

Baseline group differences: The <20-day RT group had better performance status (higher KPS, lower ECOG) and higher rates of receiving adjuvant temozolomide, which may influence observed survival differences.

Clinical implication noted: Timely initiation of adjuvant therapy (RT and chemotherapy) may be particularly important in elderly patients, but stronger evidence (e.g., prospective randomized trial) is needed to define optimal timing and account for confounding/logistical delays.

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Exploring the Diagnostic Test Accuracy of MicroRNAs as Potential Biomarkers for Glioblastoma

Neurosurgery 98:1221–1230, 2026

This systematic review and meta-analysis evaluates microRNA (miRNA)–based liquid biopsies for diagnosing glioblastoma (GBM), synthesizing data from 15 studies and 28 biomarker evaluations across 868 samples. Key diagnostic metrics—pooled sensitivity 0.84 and specificity 0.89—indicate strong potential, with miR-21 showing the highest accuracy among single-miRNA assays.

The report details search strategy, inclusion criteria, statistical methods, subgroup analyses (miRNA type, biofluid source, control type), and study quality assessment. Limitations include methodological heterogeneity, high risk of bias in patient selection, inconsistent reporting (CSF source, IDH status), and small cohort sizes, underscoring need for standardized clinical validation.

Aim Evaluate the diagnostic accuracy of microRNA (miRNA) liquid biopsies (blood/serum/plasma/CSF) for diagnosing glioblastoma (GBM) via systematic review and meta-analysis.

Methods PRISMA-guided searches of Ovid Medline and Embase (updated through Oct 16, 2024); included studies had histologic GBM confirmation and extractable 2×2 diagnostic data; pooled estimates generated using a random-effects bivariate model.

Evidence base 15 included articles (published 2011–2022) provided 28 miRNA evaluations, totaling 868 samples from 551 GBM patients and 811 samples from 578 controls.

Overall accuracy Pooled sensitivity 0.84 and specificity 0.89, with heterogeneity of 66% (sensitivity) and 39% (specificity); pooled AUC 0.89.

Likelihood ratios Pooled PLR 7.26, NLR 0.19, and DOR 40.17, indicating strong overall discriminatory performance.

Key biomarker miR-21 showed the highest pooled performance among assessed groupings (sensitivity 0.90, specificity 0.95).

Subgroups Single miRNAs had higher specificity than multi-miRNA panels, while diagnostic capability did not differ clearly by biofluid source (CSF vs blood) in this dataset.

Limitations All included studies had high risk of bias in patient selection, and many had bias in index test interpretation/flow-timing; limited CSF comparisons and inconsistent qPCR thresholds/normalization contributed to heterogeneity and constrain clinical translation without standardization and validation.

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The role of salvage stereotactic radiosurgery for tumor progression following incomplete microsurgical resection of vestibular schwannoma

J Neurosurg 144:1403–1409, 2026

This clinical study evaluates salvage stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) that progresses after incomplete microsurgical resection, reporting long-term tumor control, freedom from additional treatment (FFAT), and complication rates in a 64-patient cohort. Key outcomes include 10- and 15-year tumor control of 87.5% and 84.4%, and FFAT of 95.3% and 92.2%, respectively.

The methods describe retrospective selection, radiosurgical dosimetry (median margin 12.5 Gy), imaging and follow-up protocols, and statistical analyses using Kaplan–Meier and Cox models; no factors significantly predicted control or FFAT, and common complications included trigeminal neuropathy and hearing worsening.

Objective Assess safety/efficacy of salvage stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) that progresses after incomplete microsurgical resection, including factors affecting tumor control and freedom from additional treatment (FFAT).

Cohort Retrospective series of 64 adults treated with salvage SRS for post-resection tumor progression; median age 51.5 years and 46.9% male.

Treatment parameters Median marginal dose 12.5 Gy (median isodose 50%); median tumor volume 1.6 cm³; median time from surgery to salvage SRS 38.8 months.

Long-term control Tumor control rates after salvage SRS were 87.5% at 10 years and 84.4% at 15 years.

Durability (FFAT) FFAT rates were 95.3% at 10 years and 92.2% at 15 years, indicating most patients avoided further intervention long term.

Predictors No evaluated factors (e.g., Koos grade, age/sex, cranial nerve neuropathies, marginal dose, extent of resection, tumor volume) were significantly associated with tumor control or FFAT in Cox modeling.

Complications Most common post-SRS issue was worsening/new trigeminal neuropathy (15.6% total); hearing worsened in 14.1% (Gardner-Robertson class), and facial nerve function worsened in 4.7% (House-Brackmann).

Conclusion Salvage SRS is a safe and effective long-term strategy for VS tumor progression after incomplete resection, supporting continued monitoring and consideration of SRS once progression is documented.

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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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