Tag: Oncology

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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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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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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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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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Comparative analysis of intraoperative MRI and early postoperative MRI findings in glioma surgery patients

J Neurosurg 142:1289–1297, 2025

The study compares intraoperative MRI (iMRI) and early postoperative MRI (epMRI) in glioma surgery, highlighting iMRI’s accuracy in extent of resection (EOR) and reduced surgically induced contrast enhancement (SICE). iMRI better detects postoperative neurological deficits, with fewer diffusion-weighted imaging abnormalities than epMRI.

• Objective: The study compares intraoperative MRI (iMRI) and early postoperative MRI (epMRI) findings in glioma surgery to assess the extent of resection (EOR) and postoperative neurological deficits.

• Methods: A retrospective analysis of 43 glioma patients who underwent surgery with iMRI, with no additional resection after iMRI, was conducted.

• Results: Discrepancies in EOR were found in 11.1% of nonenhanced and 4.0% of enhanced lesions. iMRI showed more accurate EOR and less surgically induced contrast enhancement (SICE) compared to epMRI.

• Findings: The positive rate of SICE was higher on epMRI (67.9%) than iMRI (25.0%). The positive rate of diffusion-weighted imaging (DWI) abnormality was also higher on epMRI (89.2%) compared to iMRI (73%).

• Clinical Outcomes: Two patients developed new neurological deficits postoperatively, both showing DWI abnormality on both iMRI and epMRI. No deficits were observed in the late-developing group.

• Conclusion: iMRI is more reliable for assessing accurate EOR and detecting postoperative neurological deficits than epMRI, despite higher late-developing DWI abnormalities on epMRI.

• Significance: The study underscores the importance of iMRI in optimizing glioma surgery outcomes and minimizing misinterpretation of residual tumors.

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Management strategies for cervical schwannomas: a comprehensive review

J Neurosurg Spine 42:650–658, 2025

The review discusses cervical schwannomas, focusing on their pathophysiology, clinical presentation, and management strategies, including surgical resection and stereotactic body radiation therapy (SBRT). It emphasizes the importance of a multidisciplinary approach for optimal patient outcomes and highlights the need for ongoing research.

• Cervical schwannomas are benign tumors originating from Schwann cells, often occurring in the intradural, extramedullary space of the cervical spine.

• MRI is the primary imaging modality for diagnosing schwannomas, characterized by avid Gd uptake and specific radiographic features.

• Surgical resection is the main treatment approach, with gross-total resection preferred to minimize recurrence. Various surgical techniques are available depending on tumor location.

• Stereotactic body radiation therapy (SBRT) is a viable alternative for patients who are not surgical candidates, offering good local control and symptomatic relief.

• Histological analysis distinguishes schwannomas through specific features such as Antoni A and B areas and Verocay bodies. Immunohistochemical stains like S100 and SOX10 aid in diagnosis.

• Multidisciplinary management is crucial, integrating surgical and nonsurgical options to optimize patient outcomes and quality of life.

• Observation may be suitable for asymptomatic patients with slow-growing lesions, with regular monitoring to assess progression.

• Malignant transformation into peripheral nerve sheath tumors is rare but possible, particularly in patients with NF1.

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Presentation, surgical outcome, and supplementary motor area syndrome risk of posterior superior frontal gyrus tumors

J Neurosurg 142:162–173, 2025

Following resection of posterior superior frontal gyrus (PSFG) tumors, patients can experience supplementary motor area (SMA) syndrome consisting of contralateral hemiapraxia and/or speech apraxia. Given the heterogeneity of PSFG tumors, the authors sought to determine the risk of postoperative deficits and assess predictors of outcomes for all intraparenchymal PSFG tumors undergoing surgery (biopsy or resection), regardless of histology.

METHODS This was a retrospective single-center cohort study of adult PSFG-region tumors undergoing biopsy or resection by a single surgeon.

RESULTS A total of 106 consecutive patients undergoing 123 procedures (21 biopsies, 102 resections) fulfilled inclusion and exclusion criteria. Anaplastic astrocytomas were the most frequent among resected tumors (39% vs 29%), while glioblastomas were most common among biopsies (38% vs 27%) (p < 0.0001). The biopsy cohort was more likely to have tumor involvement outside the PSFG (90% vs 62%) (p = 0.011), most commonly in the motor cortex (67% vs 31%) (p = 0.005). Seizures were the most common presenting symptom in the resection cohort (p = 0.017), while motor deficits were more common in the biopsy cohort (58% vs 29%) (p < 0.001). Immediate postoperative neurological deficits occurred in 71 cases (58%), but only 3 of the deficits were permanent at 6 months of follow-up (2%). Postoperative SMA syndrome occurred in 48 cases (47%) and was significantly associated with involvement of the motor cortex (p = 0.018) or cingulate gyrus (p = 0.023), which were also significant in multivariate analysis as risk factors for SMA syndrome. However, postoperative SMA syndrome was not significantly associated with overall survival (p = 0.51). There were no perioperative deaths, but corpus callosum involvement (p < 0.001), contrast enhancement (p = 0.003), and glioblastoma pathology (p = 0.038) predicted worse overall survival in patients undergoing resection.

CONCLUSIONS Nearly half of all patients undergoing resection of PSFG-region tumors experience a postoperative SMA syndrome. Individuals with corpus callosum and/or motor cortex involvement may be at an increased risk of experiencing SMA syndrome. However, these deficits are usually transient, and the risk of permanent new deficits is very low (3%). Preoperative characteristics including corpus callosum involvement and tumor enhancement—in addition to pathology—might serve as predictors of overall survival within this patient population.

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Long-term survivors in 976 supratentorial glioblastoma, IDH-wildtype patients

J Neurosurg 142:174–186, 2025

Glioblastoma, isocitrate dehydrogenase (IDH)–wildtype is the most aggressive glioma with poor outcomes. The authors explored survival rates and factors associated with long-term survival in patients harboring a glioblastoma, IDH-wildtype.

METHODS In an observational, retrospective, single-center study, the authors examined the medical records of 976 adults newly diagnosed with supratentorial glioblastomas, IDH-wildtype between January 2000 and January 2021. They analyzed clinical-, imaging-, and treatment-related factors associated with 2-year and 5-year survival.

RESULTS The median overall survival was 11.2 months (12.2 months for patients included after 2005 and the introduction of standard combined chemoradiotherapy). The median progression-free survival was 9.4 months (10.0 months for patients included after 2005). Overall, 17.6% of patients reached a 2-year overall survival, while 2.2% of patients reached a 5-year overall survival. Furthermore, 6.6% of patients survived 2 years without progression, while 1.1% of patients survived 5 years without progression. Two factors that were consistently associated with 2-year and 5-year survival were first-line oncological treatment with standard combined chemoradiotherapy and methylated O 6 -methylguanineDNA methyltransferase promoter. Other factors that were significantly associated with 2-year or 5-year survival were age at diagnosis ≤ 60 years, headaches or signs of raised intracranial pressure at diagnosis, cortical contact of contrast enhancement, no contrast enhancement crossing the midline on initial imaging, total or subtotal tumor resection, and a second line of oncological treatment at recurrence. Within 21 cases of 5-year survival, 18 were confirmed to be glioblastomas, IDH-wildtype, and 7 of the 5-year survivors (38.9%) had additional genetic alterations: 3 cases had an FGFR mutation or fusion, 3 cases had a PIK3CA mutation, 1 case had a PTPN11 mutation, and 1 case had a PMS2 mutation in the context of constitutional mismatch repair deficiency syndrome.

CONCLUSIONS Five-year overall survival in patients with glioblastoma, IDH-wildtype is extremely low. Predictors of a longer survival are mostly treatment factors, emphasizing the importance of a complete oncological treatment plan, when achievable. Glioblastoma, IDH-wildtype 5-year survivors could be screened for actionable targets in case of recurrence.

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Microscope-integrated optical coherence tomography for in vivo human brain tumor detection with artificial intelligence

J Neurosurg 141:1343–1351, 2024

It has been shown that optical coherence tomography (OCT) can identify brain tumor tissue and potentially be used for intraoperative margin diagnostics. However, there is limited evidence on its use in human in vivo settings, particularly in terms of its applicability and accuracy of residual brain tumor detection (RTD). For this reason, a microscope-integrated OCT system was examined to determine in vivo feasibility of RTD after resection with automated scan analysis.

METHODS Healthy and diseased brain was 3D scanned at the resection edge in 18 brain tumor patients and investigated for its informative value in regard to intraoperative tissue classification. Biopsies were taken at these locations and labeled by a neuropathologist for further analysis as ground truth. Optical OCT properties were obtained, compared, and used for separation with machine learning. In addition, two artificial intelligence–assisted methods were utilized for scan classification, and all approaches were examined for RTD accuracy and compared to standard techniques.

RESULTS In vivo OCT tissue scanning was feasible and easily integrable into the surgical workflow. Measured backscattered light signal intensity, signal attenuation, and signal homogeneity were significantly distinctive in the comparison of scanned white matter to increasing levels of scanned tumor infiltration (p < 0.001) and achieved high values of accuracy (85%) for the detection of diseased brain in the tumor margin with support vector machine separation. A neuronal network approach achieved 82% accuracy and an autoencoder approach 85% accuracy in the detection of diseased brain in the tumor margin. Differentiating cortical gray matter from tumor tissue was not technically feasible in vivo.

CONCLUSIONS In vivo OCT scanning of the human brain has been shown to contain significant value for intraoperative RTD, supporting what has previously been discussed for ex vivo OCT brain tumor scanning, with the perspective of complementing current intraoperative methods for this purpose, especially when deciding to withdraw from further resection toward the end of the surgery.

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Longitudinal brain volumetrics in glioma survivors

J Neurosurg 141:634–641, 2024

Radiation therapy (RT) is used selectively for patients with low-grade glioma (LGG) given the concerns for potential cognitive effects in survivors, but prior cognitive outcome studies among LGG survivors have had inconsistent findings. Translational studies that characterize changes in brain anatomy and physiology after treatment of LGG may help to both contextualize cognitive findings and improve the overall understanding of radiation effects in normal brain tissue. This study aimed to investigate the hypothesis that patients with LGG who are treated with RT will experience greater brain volume loss than those who do not receive RT.

METHODS This retrospective longitudinal study included all patients with WHO grade 2 glioma who received posttreatment surveillance MRI at the University of Alabama at Birmingham. Volumetric analysis of contralateral cortical white matter (WM), cortical gray matter (GM), and hippocampus was performed on all posttreatment T1-weighted MRI sequences using the SynthSeg script. The effect of clinical and treatment variables on brain volumes was assessed using two-level hierarchical linear models.

RESULTS The final study cohort consisted of 105 patients with 1974 time points analyzed. The median length of imaging follow-up was 4.6 years (range 0.36–18.9 years), and the median number of time points analyzed per patient was 12 (range 2–40). Resection was performed in 79 (75.2%) patients, RT was administered to 61 (58.1%) patients, and chemotherapy was administered to 66 (62.9%) patients. Age at diagnosis (β = −0.06, p < 0.001) and use of RT (β = −1.12, p = 0.002) were associated with the slope of the contralateral cortical GM volume model (i.e., change in GM over time). Age at diagnosis (β = −0.08, p < 0.001), midline involvement (β = 1.31, p = 0.006), and use of RT (β = −1.45, p = 0.001) were associated with slope of the contralateral cortical WM volume model. Age (β = −0.0027, p = 0.001), tumor resection (β = −0.069, p < 0.001), use of chemotherapy (β = −0.0597, p = 0.003), and use of RT (β = −0.0589, p < 0.001) were associated with the slope of the contralateral hippocampus volume model.

CONCLUSIONS This study demonstrated volume loss in contralateral brain structures among LGG survivors, and patients who received RT experienced greater volume loss than those who did not. The results of this study may help to provide context for cognitive outcome research in LGG survivors and inform the design of future strategies to preserve cognition.

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Olfactory groove meningiomas: supraorbital keyhole versus orbitofrontal, frontotemporal, or bifrontal approaches

J Neurosurg 140:1568–1575, 2024

Olfactory groove meningiomas (OGMs) often require surgical removal. The introduction of recent keyhole approaches raises the question of whether these tumors may be better treated through a smaller cranial opening. One such approach, the supraorbital keyhole craniotomy, has never been compared with more traditional open transcranial approaches with regard to outcome. In this study, the authors compared clinical, radiographic, and functional quality of life (QOL) outcomes between the keyhole supraorbital approach (SOA) and traditional transcranial approach (TTA) for OGMs. They sought to examine the potential advantages and disadvantages of open/TTA versus keyhole SOA for the resection of OGMs in a relatively case-matched series of patients.

METHODS A retrospective, single-institution review of 57 patients undergoing a keyhole SOA or larger traditional transcranial (frontotemporal, pterional, or bifrontal) craniotomy for newly diagnosed OGMs between 2005 and 2023 was performed. Extent of resection, olfaction, length of stay (LOS), radiographic volumetric assessment of postoperative vasogenic and cytotoxic edema, and QOL (using the Anterior Skull Base Questionnaire) were assessed.

RESULTS Thirty-two SOA and 25 TTA patients were included. The mean EOR was not significantly different by approach (TTA: 99.1% vs SOA: 98.4%, p = 0.91). Olfaction was preserved or improved at similar rates (TTA: 47% vs SOA: 43%, p = 0.99). The mean LOS was significantly shorter for SOA patients (4.1 ± 2.8 days) than for TTA patients (9.4 ± 11.2 days) (p = 0.002). The authors found an association between an increase in postoperative FLAIR cerebral edema and TTA (p = 0.031). QOL as assessed by the ASQB at last follow-up did not differ significantly between groups (p = 0.74).

CONCLUSIONS The keyhole SOA was associated with a statistically significant decrease in LOS and less postoperative edema relative to traditional open approaches.

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A modern approach to olfactory groove meningiomas

J Neurosurg 140:1215–1222, 2024

Management of olfactory groove meningiomas (OGMs) has changed significantly with the advances in extended endoscopic endonasal approaches (EEAs), which is an excellent approach for patients with anosmia since it allows early devascularization and minimizes retraction on the frontal lobes. Craniotomy is best suited for preservation of olfaction. However, not infrequently, a tumor presents after extending outside the reach of an EEA and a solely transcranial approach would require manipulation and retraction of the frontal lobes. These OGMs may best be treated by a staged EEA-craniotomy approach. In this study the authors’ goal was to present their case series of patients with OGMs treated with their surgical approach algorithm.

METHODS The authors conducted an IRB-approved, nonrandomized historic cohort including all consecutive cases of OGMs treated surgically between 2010 and 2020. Patient demographic information, presenting symptoms, operative details, and complications data were collected. Preoperative and postoperative tumor and T2/FLAIR intensity volumes were calculated using Visage Imaging software.

RESULTS Thirty-one patients with OGMs were treated (14 craniotomy only, 11 EEA only, and 6 staged). There was a significant difference in the distribution of patients presenting with anosmia and visual disturbance by approach. Tumor size was significantly correlated with preoperative vasogenic edema. Gross-total resection was achieved in 90% of cases, with near-total resection occurring twice with EEA and once with a staged approach. T2/FLAIR hyperintensity completely resolved in 90% of cases and rates did not differ by approach. Complication rates were not significantly different by approach and included 4 CSF leaks (p = 0.68).

CONCLUSIONS A staged approach for the management of large OGMs with associated anosmia and significant lateral extension is a safe and effective option for surgical management. Through utilization of the described algorithm, the authors achieved a high rate of GTR, and this strategy may be considered for large OGMs.

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Use of 5-ALA fluorescence–guided surgery versus white-light conventional microsurgery for the resection of newly diagnosed glioblastomas (RESECT study): a French multicenter randomized phase III study

J Neurosurg 140:987–1000, 2024

Only one phase III prospective randomized study, published in 2006, has assessed the performance of 5-aminolevulinic acid (5-ALA) fluorescence–guided surgery (FGS) for glioblastoma resection. The aim of the RESECT study was to compare the onco-functional results associated with 5-ALA fluorescence and with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care.

METHODS This was a phase III prospective randomized single-blinded study, involving 21 French neurosurgical centers, comparing 5-ALA FGS with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care, including neuronavigation use and postoperative radiochemotherapy. Randomization was performed in a 1:1 ratio stratified by institution. 5-ALA (20 mg/kg) or placebo (ascorbic acid) was administered orally 3–5 hours before the incision. The primary endpoint was the rate of gross-total resection (GTR) blindly assessed by an independent committee. Patients without a confirmed pathological diagnosis of glioblastoma or with unavailable postoperative MRI studies were excluded from the per-protocol analysis.

RESULTS Between March 2013 and August 2016, a total of 171 patients were assigned to the 5-ALA fluorescence group (n = 88) or to the placebo group (n = 83). Twenty-four cases were excluded because the WHO histological criteria of grade 4 glioma were not met. The proportion of GTR was significantly higher in the 5-ALA fluorescence group (53/67, 79.1%) than in the placebo group (33/69, 47.8%; p = 0.0002). After adjustment for age, preoperative Karnofsky Performance Scale score, and tumor location, GTR was still associated with 5-ALA fluorescence (OR 4.13 [95% CI 1.94–8.79]). The mean 7-day postoperative Karnofsky Performance Scale score (≥ 80% in 49/71, 69.0% [5-ALA group]; 50/71, 70.4% [placebo group], p = 0.86) and the proportion of patients with a worsened neurological status 3 months postoperatively (9/68, 13.2% [5-ALA group]; 9/70, 12.9% [placebo group], p = 0.95) were similar between groups. Adverse events related to 5-ALA intake were rare and consisted of photosensitization in 4/87 (4.6%) patients and hepatic cytolysis in 1/87 (1.1%) patients. The 6-month PFS (70.2% [95% CI 57.7%–79.6%] and 68.4% [95% CI 55.7%–78.1%]; p =0.39) and 24-month OS (30.1% [95% CI 18.9%–42.0%] and 37.7% [95% CI 25.8%–49.5%]; p = 0.89) did not significantly differ. In multivariate analysis, GTR was an independent predictor of PFS (hazard ratio 0.56 [95% CI 0.36–0.86], p =0.008) and OS (hazard ratio 0.65 [95% CI 0.42–1.01], p = 0.05). The use of 5-ALA FGS generates a significant extra cost of 2732.36€ (95% CI 1658.40€–3794.11€).

CONCLUSIONS The authors found that 5-ALA FGS is an easy-to-use, cost-effective, and minimally time-consuming technique that safely optimizes the extent of resection in patients harboring glioblastoma amenable to a large resection.

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Asleep triple-modality motor mapping for perirolandic gliomas: an update on outcomes

J Neurosurg 140:1029–1037, 2024

Maximal safe resection of gliomas near motor pathways is facilitated by intraoperative mapping. Here, the authors review their results with triple-modality asleep motor mapping with motor evoked potentials and bipolar and monopolar stimulation for cortical and subcortical mapping during glioma surgery in an expanded cohort.

METHODS This was a retrospective analysis of patients who underwent resection of a perirolandic glioma near motor pathways. Clinical and neuromonitoring data were extracted from the electronic medical records for review. All patients with new or worsened postoperative motor deficits were followed for at least 6 months. Regression analyses were performed to assess factors associated with a persistent motor deficit.

RESULTS Between January 2018 and December 2021, 160 operations were performed in 151 patients with perirolandic glioma. Sixty-four patients (40%) had preoperative motor deficits, and the median extent of resection was 98%. Overall, patients in 38 cases (23.8%) had new or worse immediate postoperative deficits by discharge, and persistent deficits by 6 months were seen in 6 cases (3.8%), all in patients with high-grade gliomas. There were no new persistent deficits in low-grade glioma patients (0%). The risk factors for a persistent deficit included an insular tumor component (OR 8.6, p = 0.01), preoperative motor weakness (OR 8.1, p = 0.03), intraoperative motor evoked potential (MEP) changes (OR 36.5, p < 0.0001), and peri–resection cavity ischemia (OR 7.5, p = 0.04). Most persistent deficits were attributable to ischemic injury despite structural preservation of the descending motor tracts. For patients with persistent motor deficits, there were 3 cases (50%) in which a change in MEP was noted but subsequent subcortical monopolar stimulation still elicited a response in the corresponding muscle groups, suggesting axonal activation distal to a point of injury.

CONCLUSIONS Asleep triple motor mapping results in a low rate of permanent deficits, especially for low-grade gliomas. Peri–resection cavity ischemia continues to be a significant risk factor for permanent deficit despite maintaining appropriate distance for subcortical tracts based on monopolar feedback.

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Sodium fluorescein uptake by the tumor microenvironment in human gliomas and brain metastases

J Neurosurg 140:958–967, 2024

Intravenous sodium fluorescein (SF) is increasingly used during surgery of gliomas and brain metastases to improve tumor resection. Currently, SF is believed to permeate the brain regions where the blood-brain barrier (BBB) is damaged and to accumulate in the extracellular space but not in tumor or healthy cells, making it possible to demarcate tumor margins to guide resection. By evaluating the immune contexture of a number of freshly resected gliomas and brain metastases from patients undergoing SF-guided surgery, the authors recurrently observed fluorescence-positive cells. Therefore, the aim of this study was to determine if SF accumulates inside the cells of the tumor microenvironment (TME), and if so, in which type of cells, and whether incorporation can also be observed in the leukocytes of peripheral blood.

METHODS Freshly resected tumor specimens were dissociated to single cells and analyzed by multiparametric flow cytometry. Peripheral blood leukocytes, macrophages, and a glioma cell line were treated with SF in vitro, and their cell uptake was assessed by multiparametric and imaging flow cytometry and by confocal microscopy.

RESULTS The ex vivo and in vitro analyses revealed that SF accumulates intracellularly in leukocytes as well as in tumor cells, but with a high variability of incorporation in the different cell subsets analyzed. Myeloid cells showed the highest level of fluorescence. In vitro uptake experiments showed that SF accumulation increases over time. The imaging analyses confirmed the internalization of the compound inside the cells.

CONCLUSIONS SF is not just a marker of BBB damage, but its intracellular detection suggests that it selectively accumulates intracellularly. Future efforts should target the mechanisms of its differential uptake by the different TME cell types in depth.

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Minimally invasive keyhole approach for supramaximal frontal glioma resections

J Neurosurg 140:949–957, 2024

The authors aimed to review the frontal lobe’s surgical anatomy, describe their keyhole frontal lobectomy technique, and analyze the surgical results.

METHODS Patients with newly diagnosed frontal gliomas treated using a keyhole approach with supramaximal resection (SMR) from 2016 to 2022 were retrospectively reviewed. Surgeries were performed on patients asleep and awake. A human donor head was dissected to demonstrate the surgical anatomy. Kaplan-Meier curves were used for survival analysis.

RESULTS Of the 790 craniotomies performed during the study period, those in 47 patients met our inclusion criteria. The minimally invasive approach involved four steps: 1) debulking the frontal pole; 2) subpial dissection identifying the sphenoid ridge, olfactory nerve, and optic nerve; 3) medial dissection to expose the falx cerebri and interhemispheric structures; and 4) posterior dissection guided by motor mapping, avoiding crossing the inferior plane defined by the corpus callosum. A fifth step could be added for nondominant lesions by resecting the inferior frontal gyrus. Perioperative complications were recorded in 5 cases (10.6%). The average hospital length of stay was 3.3 days. High-grade gliomas had a median progression-free survival of 14.8 months and overall survival of 23.9 months.

CONCLUSIONS Keyhole approaches enabled successful SMR of frontal gliomas without added risks. Robust anatomical knowledge and meticulous surgical technique are paramount for obtaining successful resections.

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Nonenhancing motor eloquent gliomas: navigated transcranial magnetic stimulation oncobiological signature

J Neurosurg 140:909–919, 2024

Preoperative grading of nonenhancing motor eloquent gliomas is hampered by a lack of specific imaging surrogates. Tumor grading is crucial for the informed consent discussion before tumor resection. In this paper, the authors hypothesized that navigated transcranial magnetic stimulation (nTMS)–derived metrics could provide significant information to distinguish between high- and low-grade motor eloquent gliomas that present as nonenhancing tumors and therefore contribute to improving patient counseling, timing of treatment, preoperative planning, and intraoperative strategies.

METHODS The authors conducted a retrospective single-center cohort study of patients admitted for tumor surgery between January 2018 and April 2022 with a nonenhancing motor eloquent glioma and preoperative bilateral nTMS mapping. nTMS data including resting motor threshold (RMT), interhemispheric RMT ratio (iRMTr), Cortical Excitability Score (CES), area and volume of cortical activation, and motor evoked potential (MEP) characteristics were obtained and integrated with demographic and clinical data.

RESULTS Thirty patients met the inclusion criteria, and 10 healthy participants were recruited for comparison. Seizures were the most common presenting symptom (25 patients) and WHO grade 3 the most common tumor grade (21 patients). The area and volume of functional cortical activation of both the abductor pollicis brevis and first dorsal interosseous muscles were decreased in healthy participants compared with patients with WHO grade 3 glioma (p < 0.05). An abnormal iRMTr for the lower limbs (16.7% [1/6] WHO grade 2, 76.2% [16/21] WHO grade 3, 100% [3/3] WHO grade 4; p = 0.015) and a higher CES (maximal abnormal CES: 0% [0/6] WHO grade 2, 38% [8/21] WHO grade 3, 66.7% [2/3] WHO grade 4; p = 0.010) were associated with the prediction of high-grade lesions. A total of 7280 MEPs were analyzed. A significant increase in the amplitude and a significant decrease in latency in the MEPs for the first dorsal interosseous and abductor digiti minimi muscles (p < 0.0001) were identified in healthy participants compared with WHO grade 3 glioma patients.

CONCLUSIONS Nonenhancing motor eloquent gliomas have a different impact on both anatomical and functional reorganization of motor areas according to their WHO grading.

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Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?

J Neurosurg 140:357–366, 2024

Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration–cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied.

METHODS Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0–2) and a high tumor probability (HTP) group (scores 3–5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated.

RESULTS Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86–0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40–0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40–0.83]) and HTP group (0.68 [0.39–0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group.

CONCLUSIONS CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE.

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Decoding the clinical effects of low-grade glioma–induced cortical excitability

J Neurosurg 140:18–26, 2024

Patients with low-grade glioma (LGG) in eloquent regions often present with seizures, and findings on detailed neuropsychological testing are often abnormal. This study evaluated the association between cortical excitability, seizures, and cognitive function in patients with LGG.

METHODS LGG patients who underwent transcranial magnetic stimulation (TMS) from January 2021 to December 2022 were studied. Cortical excitability was measured using the resting motor thresholds (RMTs) of the upper and lower extremities. Early postoperative seizures served as the seizure endpoint. Neuropsychological assessment was completed prior to surgery contemporaneous with the TMS studies.

RESULTS A total of 31 patients were analyzed for seizure outcome. Median (interquartile range [IQR]) upper-extremity RMT was 39% (34%–46%) of maximum stimulator output, and the median (IQR) lower-extremity RMT was 69% (51%79%). Lower-extremity RMT was higher in patients with early postoperative seizures, especially in those with motor region tumors (p = 0.02); however, RMT was not associated with seizures at presentation or long-term seizure control. A total of 26 patients completed neuropsychological assessment. There were significant negative correlations between upper-extremity RMT and psychomotor processing speed (Wechsler Adult Intelligence Scale–Fourth Edition [WAIS-IV] Processing Speed Index r = −0.42, p = 0.031; WAIS-IV Coding r = −0.41, p = 0.036; WAIS-IV Symbol Search r = −0.39, p = 0.048), executive function (Trail Making Test Part B r = −0.41, p = 0.036), and hand dexterity (Grooved Pegboard Test r = −0.50, p = 0.047).

CONCLUSIONS RMT was positively correlated with early postoperative seizure risk and negatively correlated with psychomotor processing speed, executive function, and hand dexterity. These findings support the theory of local and regional resting oscillatory network dysfunction from a glioma-brain network.

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Unique molecular, clinical, and treatment aspects of gliomas in adolescents and young adults

J Neurosurg 139:1619–1627, 2023

Adolescent and young adult (AYA) patients with glioma have historically had poorer outcomes than similar patients of younger or older age, a disparity thought to be attributable to the social and economic challenges faced by this group in the transition from childhood to adult life, delays in diagnosis, low participation of AYA patients in clinical trials, and the lack of standardized treatment approaches specific to this patient group.

Recent work from many groups has informed a revision of the World Health Organization classification schema for gliomas to identify biologically divergent pediatric and adult-type tumors, both types of which may occur in AYA patients, and revealed exciting opportunities for the use of targeted therapies for many of these patients. In this review, the authors focus on the glioma types of specific concern to practitioners caring for AYA patients and the factors that should be considered in the development of multidisciplinary teams to facilitate their care.

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