Tag: High-grade glioma

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

Neurosurg Focus 59(2):E10, 2025

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

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

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

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

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

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

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

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

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

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

J Neurosurg 143:323–331, 2025

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

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

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

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

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

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

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

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

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

 

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Anatomical multifocal high-grade glioma resection

Acta Neurochirurgica (2021) 163:953–957

If an awake surgery is somehow not available for gliomas at the language area, understanding the anatomy and well designed surgical strategy are important.

Method We present a case with left hemispheric multifocal high-grade gliomas located deeply at the left temporal pole, the Wernicke’s area, and mesial temporal region. Because the patient could not endure the awake surgery and obtain practicable functional magnetic resonance imaging (MRI) for eloquent cortex evaluation, we removed the lesions following the anatomical resection strategy guided by diffusion tensor imaging (DTI).

Conclusion This case demonstrates the value of DTI and the importance of anatomical resection strategies in glioma surgeries.

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The Glioma-Network Interface: A Review of the Relationship Between Glioma Molecular Subtype and Intratumoral Function

 

Neurosurgery 87:1078–1084, 2020

Gliomas are a major cause of morbidity. Direct cortical stimulation mapping offers the ability to identify functional areas within the broader neural network both cortically and subcortically. Since the World Health Organization (WHO) 2016 classification categorized gliomas into molecular subgroups with varied molecular signatures and clinical behavior, it is possible that gliomas may demonstrate rates of functional network integration.

We therefore retrospectively reviewed a data registry of 181 patients with dominant hemisphere frontal, parietal, insular, or temporal gliomas. Our goal was to test the hypothesis that WHO glioma histopathology and molecular subtype influences functional language or motor sites identified within the tumor.

Intratumoral function as determined by direct cortical and subcortical stimulation mapping was identified at the highest rate in isocitrate dehydrogenase mutant astrocytomas and oligodendrogliomas. Finally, we reviewed the emerging literature exploring the interface between functional neural networks and gliomas. These data shed light on glioma molecular and histological characteristics most commonly associated within intratumoral function.

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5-Aminolevulinic Acid and Contrast-Enhanced Ultrasound: The Combination of the 2 Techniques to Optimize the Extent of Resection in Glioblastoma Surgery

Neurosurgery 86:E529–E540, 2020

The survival benefit in maximizing resection in glioblastomas (GBMs) has been demonstrated by numerous studies. The true limit of infiltration of GBMs has been an overwhelming obstacle, and several technological advances have been introduced to improve the identification of residual tumors.

OBJECTIVE: To evaluate whether the integration of 5-aminolevulinic acid (5-ALA) with microbubble contrast-enhanced ultrasound (CEUS) improves residual tumor identification and has an impact on the extent of resection (EOR), overall survival (OS), and progressionfree survival (PFS).

METHODS: A total of 230 GBM procedures were retrospectively studied. Cases were stratified according to the surgical procedure into 4 groups: 5-ALA- and CEUS-guided surgeries, 5-ALA-guided surgeries, CEUS-guided surgeries, and conventional microsurgical procedures.

RESULTS: Patients undergoing conventional microsurgical procedures showed the worst EORs compared to the assisted techniques (5-ALA and CEUS procedures). Both 5-ALA and CEUS techniques improved the EOR compared to conventional microsurgical procedures. However, their combination gave the best results in terms of the EOR (P = .0003). The median EOR% and the number of supramarginal resections are hence superior in the 5-ALA + CEUS + group compared to the others; this observation had consequences on PFS and OS in our series.

CONCLUSION: In terms of the EOR, the best results can be achieved through a combination of both techniques,where the 5-ALA-guided procedure is followed by a final survey with CEUS. Compared with other intraoperative imaging techniques, CEUS is a real-time, readily repeatable, safe, and inexpensive technique that provides valuable information to the surgeon before, during, and after resection.

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Impact of Extent of Resection on Incidence of Postoperative Complications in PatientsWith Glioblastoma

Neurosurgery 86:625–630, 2020

Extent of resection (EOR) is well established as correlating with overall survival in patients with glioblastoma (GBM). The impact of EOR on reported quality metrics such as patient safety indicators (PSIs) and hospital-acquired conditions (HACs) is unknown.

OBJECTIVE: To perform a retrospective study to evaluate possible associations between EOR and the incidence of PSIs and HACs.

METHODS: We queried all patients diagnosed with GBM who underwent surgical resection at our institution between January 2011 and May 2017. Pre- and postoperative magnetic resonance imageswere analyzed for EOR. Each chart was reviewed to determine the incidence of PSIs and HACs.

RESULTS: A total of 284 patients met the inclusion criteria. EOR ranged from 39.00 to 100%, with a median of 99.84% and a mean of 95.7%. There were 16 PSI, and 13 HAC, events. There were no significant differences in the rates of PSIs or HACs when compared between patients stratified by gross total resection (EOR ≥ 95%) and subtotal resection (EOR < 95%). The odds of encountering a PSI or HAC were 2.5 times more likely in the subtotal resection group compared to the gross total resection group (P = .58). After adjusting for confounders, the odds of encountering a PSI or HAC in the subtotal resection group were 3.9 times greater than for the gross total resection group (P < .05).

CONCLUSION: Gross total resection of GBM is associated with a decreased incidence of PSIs and HACs, as compared to subtotal resection.

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Maximizing safe resection of low- and high-grade glioma

dti-gliomas

J Neurooncol (2016) 130:269–282

Surgical resection plays a central role in the management of gliomas. In this study, we review the evidence in support of extent of resection to improve survival, symptom management, and time to malignant transformation in low- and high-grade gliomas, and summarize the findings from our literature search regarding the role of extent of resection and intraoperative practices to maximize safety.

There is a growing body of evidence supporting improved overall survival, improved progression-free survival, and superior quality of life with greater extent of resection.

Additionally, a better understanding of central nervous system plasticity allows for a staged approach to the surgical management of low- and intermediate-grade gliomas.

A number of intraoperative techniques have been utilized to offer safer glioma surgery with greater extent of resection. Approaches such as awake brain tumor surgery can be safely performed with low failure rates and excellent long-term functional outcomes.

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A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

Combining 5-Aminolevulinic Acid Fluorescence and Intraoperative Magnetic Resonance Imaging in Glioblastoma Surgery

J Neurosurg 124:1300–1309, 2016

There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity.

Methods A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated.

Results A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%.

Conclusions The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.

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Anaplastic astrocytomas: survival and prognostic factors in a surgical series

AA

Acta Neurochir (2014) 156:1053–1061

To study patient characteristics, prognostic factors and overall survival (OS) in a consecutive, surgical series of WHO grade III anaplastic astrocytomas (AA).

Methods Patients were identified from a prospective tumor database at Oslo University Hospital, Norway, and patients undergoing surgery for an AA from 2005–2012 were included. Patients’ medical charts were retrospectively reviewed for data collection.

Results A total of 99 adult patients with histologically verified AA were included. Median age was 52 years (20–81). Biopsy was conducted in 33 % and resection in 67 %. Adjuvant treatment with radiation therapy + temozolomide or radiation therapy only was given in 63 % and 26 %, respectively. The thirty-day mortality rate was 3 %. Median OS was 19 months (95 % CI 11–27 months). Age≥65 years, KPS<70, biopsy as opposed to resection, and no adjuvant treatment were confirmed negative prognostic factors in multivariate analysis. For patients undergoing resection, presence of postoperative contrast-enhanced tumor, not volume of residual tumor, had significant impact on OS in adjusted analysis.

Conclusions Median OS following surgery was 19 months, though much variable outcome was observed among subgroups of AA (95 % CI 11–27 months). Age ≥65 years, KPS<70, biopsy as opposed to resection, and no adjuvant treatment were confirmed negative prognostic factors for OS.

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Use of intraoperative fluorescein sodium fluorescence to improve the accuracy of tissue diagnosis during stereotactic needle biopsy of high-grade gliomas

stereotactic biopsy specimen obtained under the YELLOW560

Acta Neurochir (2014) 156:1071–1075

Stereotactic needle biopsy is valuable for tissue diagnosis of suspected high-grade gliomas, but limited by a sampling error that can lead to inappropriate grading of the tumor or failure to provide diagnosis. Increasing the number of biopsy attempts can increase morbidity. The authors designed a protocol to increase safety and efficiency of the procedure.

Methods Six consecutive patients with suspected high-grade gliomas who were not candidates for cytoreductive surgery underwent fluorescein-guided stereotactic needle biopsy. All received an injection of 3 mg/kg fluorescein sodium during anesthesia induction. Samples were obtained and observed under a microscope-integrated fluorescent module. If the initial specimens were fluorescent, the procedure was complete if the pathologist confirmed diagnostic tissue. Additional specimens were obtained only at the pathologist’s request. An independent neuropathologist later analyzed and graded samples for diagnostic value, tumor, and necrosis. This information was correlated to the degree of intraoperative fluorescent signal in biopsy samples.

Results During six biopsy procedures, 26 specimens were obtained: 15 (58 %) fluorescent and 11 (42%) nonfluorescent. All fluorescent specimens contained diagnostic tissue appropriate for tumor grading. Of 11 nonfluorescent specimens, four (36 %) did not contain tumor, three (27 %) contained minor hypercellularity or gliosis, and four (36 %) contained tumor with a high proportion of necrosis. All six tumors were diagnosed as glioblastoma multiforme. The sensitivity and specificity for fluorescein fluorescence was 79 % and 100 %, respectively.

Conclusions Fluorescein fluorescence may improve diagnostic accuracy and expedite stereotactic biopsy procedures.

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Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT methylation, EGFR status and pretreatment MRI in determining response and survival

Recurrent GBM and bevacizumab

J Neurooncol (2013) 115:267–276

Although bevacizumab represented an important advance in treatment of recurrent high-grade gliomas (HGG), responses occur in fewer than half of patients. There are no validated biomarkers for anti-angiogenic therapy that are available for routine clinical use.

We assessed the prognostic values of imaging and molecular markers in this patient population. MRI scans from 191 patients with recurrent HGG obtained prior to initiating bevacizumab were reviewed for areas of enhancement, necrosis, T2/FLAIR abnormality, and ADC values. Serial MRI scans following the initiation of bevacizumab were evaluated for response and progression. Non-radiographic markers including EGFR and MGMT status were also assessed with respect to response and patient survival.

65 of 191 patients (34 %) showed complete or partial response at the time of their best response MRI and demonstrated longer progression free survival (PFS) and overall survival (OS) compared to the group without response (PFS: 6.9 vs 3.5 months, OS: 10.9 vs 6.1 months). Minimum ADC values within enhancing and non-enhancing regions were lower in responders compared to those of nonresponders (1,099 vs 984 x 10-6 mm2/s, p = 0.006). Smaller enhancing area was associated with longer OS (HR = 1.99, p = 0.017). The ratio of T2/FLAIR to enhancing area was prognostic of OS for only the Grade III HGG subgroup (HR = 0.14, p = 0.004).

Area of enhancing tumor at baseline can stratify survival in patients with recurrent HGG treated with bevacizumab. The extent of edema relative to enhancing area may have a prognostic role specific to Grade III HGG.

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5-aminolevulinic acid (5-ALA) fluorescence guided surgery of high-grade gliomas in eloquent areas assisted by functional mapping

5ALA and functional mapping

Acta Neurochir (2013) 155:965–972

Only few data are available on the specific topic of 5-aminolevulinic acid (5-ALA) guided surgery of high-grade gliomas (HGG) located in eloquent areas. Studies focusing specifically on the post-operative clinical outcome of such patients are yet not available, and it has not been so far explored whether such approach could be more suitable for some particular subgroups of patients.

Methods Patients affected by HGG in eloquent areas who underwent surgery assisted by 5-ALA fluorescence and intra-operative monitoring were prospectively recruited in our Department between June 2011 and August 2012. Resection rate was reported as complete resection of enhancing tumor (CRET), gross total resection (GTR) >98 % and GTR>90 %. Clinical outcome was evaluated at 7, 30, and 90 days after surgery.

Results Thirty-one patients were enrolled. Resection was complete (CRET) in 74 % of patients. Tumor removal was stopped to avoid neurological impairment in 26 % of cases. GTR>98 % and GTR>90 % was achieved in 93 % and 100 % of cases, respectively. First surgery and awake surgery had a CRET rate of 80 % and 83 %, respectively. Even though at the first-week assessment 64 % of patients presented neurological impairment, there was a 3 % rate of severe morbidity at the 90th day assessment. Newly diagnosed patients had a significantly lower morbidity (0 %) and post-operative higher median KPS. Both pre-operative neurological condition and improvement after corticosteroids resulted significantly predictive of post-operative functional outcome.

Conclusions 5-ALA surgery assisted by functional mapping makes high HGG resection in eloquent areas feasible , through a reasonable rate of late morbidity. This emerges even more remarkably for selected patients.

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Prognostic factors and survival in a prospective cohort of patients with high-grade glioma treated with carmustine wafers or temozolomide on an intention-to-treat basis

Acta Neurochir (2012) 154:211–222.DOI 10.1007/s00701-011-1199-7

Patients with high-grade glioma can be treated with carmustine wafers or following the Stupp protocol. As far as we are aware, no scientific evidence has been published comparing the two treatments. The primary objective of this study was to analyse the survival of groups of patients with each of these treatment modalities. The secondary objective was to assess the influence of the usual prognostic factors on the patients in our hospital.

Methods A prospective cohort of 110 patients with single, supratentorial high-grade glioma treated by craniotomy and tumour resection was retrospectively studied. Half of the patients had carmustine wafers placed during this operation while the others (55) did not, the latter group receiving firstline systemic chemotherapy on an intention-to-treat basis.

Findings Patients treated with carmustine wafers had a median survival of 13.414 months compared with 11.047 in the group without implants (p=0.856). For the overall cohort of patients, the following factors were found to influence survival: age (p<0.0001), postoperative KPS score (p=0.001), histological grade (p=0.004), RPA class (p=0.001), extent of resection (p=0.002) and salvage surgery (p=0.028).

Conclusions In this prospective cohort of patients, analysed on the basis of intention-to-treat at the time of the first surgery, no statistically significant differences in survival were found between the two treatment modalities (carmustine wafers vs. first-line systemic chemotherapy). On the other hand, age, preoperative KPS, histological grade, and RPA class were confirmed to be prognostic factors in this cohort. Finally, the extent of resection was also found to influence survival.

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