Category: Oncology

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Petrosal Meningiomas: Factors Affecting Outcome and the Role of Intraoperative Multimodal Assistance to Microsurgery

Neurosurgery, Volume 84, Issue 6, June 2019, Pages 1313–1324

Petrous meningiomas (PMs) represent a subset of posterior fossa tumors accounting for ∼8% of all intracranial meningiomas. Surgical treatment of PMs is challenging because of their relationships with vital neurovascular structures of the cerebellopontine angle.

OBJECTIVE: To investigate independent pre- and intraoperative predictors of PM surgery outcome.

METHODS:We reviewed the surgical and outcome data of patients who underwent microsurgical resection of PMs from 1997 to 2016. From 2007 onward, a multimodal intraoperative protocol consisting of intraoperative neuromonitoring (IONM), endoscopy, and indocyanine green (ICG) videoangiography was applied. Outcome variables included extent of resection, Karnofsky performance status (KPS), overall survival, and progression-free survival (PFS).

RESULTS: A total of 54 patients were included. Independent predictors of gross total resection (GTR) included retromeatal location (P < .0175; odds ratio [OR] 4.05), absence of brainstem compression (P < .02; OR 3.55), and histological WHO grade I (P < .001; OR 3.47). Nongiant size (P < .012; OR 4.38), and WHO grade I (P < .0001; OR 7.7) were independent predictors of stable or improved KPS. The use of multimodal intraoperative tools to assist surgery independently predicted GTR (P < .002; OR 6.8) and good KPS (P < .018; OR 4.23). Nongiant size (P = .01) and WHO grade I (P = .002) were significantly associated with increased PFS.

CONCLUSION: Notwithstanding the limitations of a retrospective study, our results suggest that support of microsurgery by a combination of IONM, endoscopy, and ICG videoangiography may improve patient outcome in PM surgery.

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Early postoperative delineation of residual tumor after low-grade glioma resection by probabilistic quantification of diffusion-weighted imaging

J Neurosurg 130:2016–2024, 2019

In WHO grade II low-grade gliomas (LGGs), early postoperative MRI (epMRI) may overestimate residual tumor on FLAIR sequences. Consequently, MRI at 3–6 months follow-up (fuMRI) is used for delineation of residual tumor. This study sought to evaluate if integration of apparent diffusion coefficient (ADC) maps permits an accurate estimation of residual tumor early on epMRI.

METHODS From a consecutive cohort, 43 cases with an initial surgery for an LGG, and complete epMRI (< 72 hours after resection) and fuMRI including ADC maps, were retrospectively identified. Residual FLAIR hyperintense tumor was manually segmented on epMRI and corresponding ADC maps were coregistered. Using an expectation maximization algorithm, residual tumor segments were probabilistically clustered into areas of residual tumor, ischemia, or normal white matter (NWM) by fitting a mixture model of superimposed Gaussian curves to the ADC histogram. Tumor volumes from epMRI, clustering, and fuMRI were statistically compared and agreement analysis was performed.

RESULTS Mean FLAIR hyperintensity suggesting residual tumor was significantly larger on epMRI compared to fuMRI (19.4 ± 16.5 ml vs 8.4 ± 10.2 ml, p < 0.0001). Probabilistic clustering of corresponding ADC histograms on epMRI identified subsegments that were interpreted as mean residual tumor (7.6 ± 10.2 ml), ischemia (8.1 ± 5.9 ml), and NWM (3.7 ± 4.9 ml). Therefore, mean tumor quantification error between epMRI and fuMRI was significantly reduced (11.0 ± 10.6 ml vs -0.8 ± 3.7 ml, p < 0.0001). Mean clustered tumor volumes on epMRI were no longer significantly different from the fuMRI reference (7.6 ± 10.2 ml vs 8.4 ± 10.2 ml, p = 0.16). Correlation (Pearson r = 0.96, p < 0.0001), concordance correlation coefficient (0.89, 95% confidence interval 0.83), and Bland-Altman analysis suggested strong agreement between both measures after clustering.

CONCLUSIONS Probabilistic segmentation of ADC maps facilitates accurate assessment of residual tumor within 72 hours after LGG resection. Multiparametric image analysis detected FLAIR signal alterations attributable to surgical trauma, which led to overestimation of residual LGG on epMRI compared to fuMRI. The prognostic value and clinical impact of this method has to be evaluated in larger case series in the future.

 

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Surgical Resection With Radiation Treatment Planning of Spinal Tumors

Neurosurgery, Volume 84, Issue 6, June 2019, Pages 1242–1250

The clinical paradigm for spinal tumors with epidural involvement is challenging considering the rigid dose tolerance of the spinal cord. One effective approach involves open surgery for tumor resection, followed by stereotactic body radiotherapy (SBRT). Resection extent is often determined by the neurosurgeon’s clinical expertise, without considering optimal subsequent post-operative SBRT treatment.

OBJECTIVE: To quantify the effect of incremental epidural disease resection on tumor coverage for spine SBRT in an effort toworking towards integrating radiotherapy planning within the operating room.

METHODS: Ten patients having undergone spinal separation surgery with postoperative SBRTwere retrospectively reviewed. Preoperative magnetic resonance imaging was coregistered to postoperative planning computed tomography to delineate the preoperative epidural disease gross tumor volume (GTV). The GTV was digitally shrunk by a series of fixed amounts away from the cord (up to 6 mm) simulating incremental tumor resection and reflecting an optimal dosimetric endpoint. The dosimetric effect on simulated GTVs was analyzed using metrics such as minimum biologically effective dose (BED) to 95% of the simulated GTV (D95) and compared to the unresected epidural GTV.

RESULTS: Epidural GTV D95 increased at an average rate of 0.88 ± 0.09 Gy10 per mm of resected disease up to the simulated 6 mm limit. Mean BED to D95 was 5.3 Gy10 (31.2%) greater than unresected cases. Allmetrics showed strong positive correlationswith increasing tumor resection margins (R2: 0.989-0.999, P< .01).

CONCLUSION: Spine separation surgery provides division between the spinal cord and epidural disease, facilitating better disease coverage for subsequent post-operative SBRT. By quantifying the dosimetric advantage prior to surgery on actual clinical cases, targeted surgical planning can be implemented.

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Gamma Knife stereotactic radiosurgery for cavernous sinus meningioma: long-term follow-up in 200 patients

J Neurosurg 130:1799–1808, 2019

The authors of this study evaluate the long-term outcomes of stereotactic radiosurgery (SRS) for cavernous sinus meningioma (CSM).

METHODS The authors retrospectively assessed treatment outcomes 5–18 years after SRS in 200 patients with CSM. The median patient age was 57 years (range 22–83 years). In total, 120 (60%) patients underwent Gamma Knife SRS as primary management, 46 (23%) for residual tumors, and 34 (17%) for recurrent tumors after one or more surgical procedures. The median tumor target volume was 7.5 cm3 (range 0.1–37.3 cm3), and the median margin dose was 13.0 Gy (range 10–20 Gy).

RESULTS Tumor volume regressed in 121 (61%) patients, was unchanged in 49 (25%), and increased over time in 30 (15%) during a median imaging follow-up of 101 months. Actuarial tumor control rates at the 5-, 10-, and 15-year followups were 92%, 84%, and 75%, respectively. Of the 120 patients who had undergone SRS as a primary treatment (primary SRS), tumor progression was observed in 14 (11.7%) patients at a median of 48.9 months (range 4.8–120.0 months) after SRS, and actuarial tumor control rates were 98%, 93%, 85%, and 85% at the 1-, 5-, 10-, and 15-year follow-ups post-SRS. A history of tumor progression after microsurgery was an independent predictor of an unfavorable response to radiosurgery (p = 0.009, HR = 4.161, 95% CI 1.438–12.045). Forty-four (26%) of 170 patients who had presented with at least one cranial nerve (CN) deficit improved after SRS. Development of new CN deficits after initial microsurgical resection was an unfavorable factor for improvement after SRS (p = 0.014, HR = 0.169, 95% CI 0.041–0.702). Fifteen (7.5%) patients experienced permanent CN deficits without evidence of tumor progression at a median onset of 9 months (range 2.3–85 months) after SRS. Patients with larger tumor volumes (≥ 10 cm3) were more likely to develop permanent CN complications (p = 0.046, HR = 3.629, 95% CI 1.026–12.838). Three patients (1.5%) developed delayed pituitary dysfunction after SRS.

CONCLUSIONS This long-term study showed that Gamma Knife radiosurgery provided long-term tumor control for most patients with CSM. Patients who underwent SRS for progressive tumors after prior microsurgery had a greater chance of tumor growth than the patients without prior surgery or those with residual tumor treated after microsurgery.

 

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5-ALA fluorescence–guided surgery in pediatric brain tumors—a systematic review

Acta Neurochirurgica (2019) 161:1099–1108

5-Aminolevulinic acid (5-ALA)-guided resection of gliomas in adults enables better differentiation between tumor and normal brain tissue, allowing a higher degree of resection, and improves patient outcomes. In recent years, several reports have emerged regarding the use of 5-ALA in other brain tumor entities, including pediatric brains tumors. Since gross total resection (GTR) of many brain tumors in children is crucial and the role of 5-ALA-guided resection of these tumors is not clear, we sought to perform a comprehensive literature review on this topic.

Methods A systematic literature review of EMBASE and MEDLINE/PubMed databases revealed 19 eligible publications encompassing 175 5-ALA-guided operations on pediatric brain tumors. To prevent bias, publications were revised independently by two authors.

Results We found that 5-ALA-guided resection enabled the surgeons to identify the tumor more easily and was considered helpful mainly in cases of glioblastoma (GBM, 21/27, 78%), anaplastic ependymoma WHO grade III (10/14, 71%), and anaplastic astrocytoma (4/6, 67%). In contrast, cases of pilocytic astrocytomas (PAs) and medulloblastomas 5-ALA-guided surgery did not show consistent fluorescent signals and 5-ALA was considered helpful only in 12% and 22% of cases, respectively. Accumulation of fluorescent porphyrins seems to depend on WHO tumor grading. One important finding is that when 5- ALA-guided resections were considered helpful, the degree of resection was higher than is cases where it was not helpful. The rate of adverse events related to 5-ALA was negligible, especially new postoperative sequelae.

Conclusion 5-ALA could play a role in resection of pediatric brain tumors. However, further prospective clinical trials are needed.

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Is Visible Aminolevulinic Acid-Induced Fluorescence an Independent Biomarker for Prognosis in Histologically Confirmed (World Health Organization 2016) Low-Grade Gliomas?

Neurosurgery, Volume 84, Issue 6, June 2019, Pages 1214–1224

Approximately 20% of low-grade gliomas (LGG) display visible protoporphyrin fluorescence during surgery after 5-aminolevulinic acid (5-ALA) administration.

OBJECTIVE: To determine if fluorescence represents a prognostic marker in LGG.

METHODS: Seventy-four consecutive patients with LGG (World Health Organization 2016) were operated on with 5-ALA. Fluorescent tissue was specifically biopsied. Tumor size, age, Karnofsky index, contrast-enhancement, fluorescence, and molecular factors (IDH1/IDH2-mutations, Ki67/MIB1 Index, 1p19q codeletions, ATRX, EGFR, p53 expression, and O6-methylguanine DNA methyltransferase promotor methylation), were related to progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS).

RESULTS: Sixteen of seventy-four LGGs (21.6%) fluoresced. Fluorescence was partially related to weak enhancement on magnetic resonance imaging and increased (positron emission tomography)PET-FET uptake, but not to Karnofsky Performance Score, tumor size, or age. Regarding molecular markers, only EGFR expression differed marginally (fluorescing vs nonfluorescing: 19% vs 5%; P = .057). Median follow-up was 46.4 mo (95% confidence interval [CI]: 41.8-51.1). PFS, MTFS, and OS were shorter in fluorescing tumors (PFS: median 9.8 mo, 95% CI: 1.00-27.7 vs 45.8, 31.9-59.7, MTFS: 43.0 [27.5-58.5] vs 64.6 [57.7- 71.5], median not reached, P = .015; OS: 51.6, [34.8-68.3] vs [68.2, 62.7-73.8], P = .002). IDH mutations significantly predicted PFS, MTFS, and OS. In multivariate analysis IDH status and fluorescence both independently predictedMTFS and OS. PFSwas not independently predicted by fluorescence.

CONCLUSION: This is the first report investigating the role of ALA-induced fluorescence in histologically confirmed LGG. Fluorescence appeared to be a marker for inherent malignant transformation and OS, independently of known prognostic markers. Fluorescence in LGG might be taken into account when deciding on adjuvant therapies.

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Posterior fossa meningiomas: perioperative predictors of extent of resection, overall survival and progression-free survival

Acta Neurochirurgica (2019) 161:1003–1011

Posterior fossa meningiomas (PFMs) often represent surgical challenges due to their proximity to neurovascular structures. Factors predicting the extent of resection (EOR), overall survival (OS), and progression-free survival (PFS) were identified and integrated in a prediction tool to offer evidence-based personalized therapeutic strategies.

Methods All meningiomas managed surgically from 1990 to 2010 from a single-center were reviewed. A classification tree was created using the classification and regression tree recursive partitioning analysis that incorporated patient and tumor data available before surgery in order to predict the rates of gross total resection (GTR).

Results A total of 198 patients were identified (female-to-male ratio, 2.7; mean age, 59.1 years) and compared with 1271 supratentorial meningiomas (STMs) operated in the same institution during the same time period. GTR was achieved less often (59.6% versus 81.9%; p < 0.01) in PFMs than STMs. Preoperative neurological symptoms were predictive of higher Simpson grades (OR, 2.19 [1.05; 4.58]; p = 0.04). Age was associated with reduced OS (OR, 1.08 [1.04;1.12]; p < 0.001). A KPS ≥ 70 was associated with higher survival rates (OR, 2.70 [2.19;2.92]; p = 0.02). Higher WHO grades were associated with reduced OS (OR, 3.56 [1.02;12.47]; p = 0.05). The GTR rate varies from 80% in patients without a preoperative deficit to 40% patients with a preoperative deficit, younger than 60 years old, and with adjacent bone invasion.

Conclusions This study provides a classification tree of the predictors of EOR in PFMs, based upon preoperative demographic, clinical, and radiological variables. An evidence-based management protocol with estimated EORs may guide the decision making process in PFMs.

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Brain invasion and the risk of seizures in patients with meningioma

J Neurosurg 130:789–796, 2019

Identification of risk factors for perioperative epilepsy remains crucial in the care of patients with meningioma. Moreover, associations of brain invasion with clinical and radiological variables have been largely unexplored. The authors hypothesized that invasion of the cortex and subsequent increased edema facilitate seizures, and they compared radiological data and perioperative seizures in patients with brain-invasive or noninvasive meningioma.

METHODS Correlations of brain invasion with tumor and edema volumes and preoperative and postoperative seizures were analyzed in univariate and multivariate analyses.

RESULTS Totals of 108 (61%) females and 68 (39%) males with a median age of 60 years and harboring totals of 92 (52%) grade I, 79 (45%) grade II, and 5 (3%) grade III tumors were included. Brain invasion was found in 38 (22%) patients and was absent in 138 (78%) patients. The tumors were located at the convexity in 72 (41%) patients, at the falx cerebri in 26 (15%), at the skull base in 69 (39%), in the posterior fossa in 7 (4%), and in the ventricle in 2 (1%); the median tumor and edema volumes were 13.73 cm3 (range 0.81–162.22 cm3) and 1.38 cm3 (range 0.00–355.80 cm3), respectively. As expected, edema volume increased with rising tumor volume (p < 0.001). Brain invasion was independent of tumor volume (p = 0.176) but strongly correlated with edema volume (p < 0.001). The mean edema volume in noninvasive tumors was 33.0 cm3, but in invasive tumors, it was 130.7 cm3 (p = 0.008). The frequency of preoperative seizures was independent of the patients’ age, sex, and tumor location; however, the frequency was 32% (n = 12) in patients with invasive meningioma and 15% (n = 21) in those with noninvasive meningioma (p = 0.033). In contrast, the probability of detecting brain invasion microscopically was increased more than 2-fold in patients with a history of preoperative seizures (OR 2.57, 95% CI 1.13–5.88; p = 0.025). In univariate analyses, the rate of preoperative seizures correlated slightly with tumor volume (p = 0.049) but strongly with edema volume (p = 0.014), whereas seizure semiology was found to be independent of brain invasion (p = 0.211). In multivariate analyses adjusted for age, sex, tumor location, tumor and edema volumes, and WHO grade, rising tumor volume (OR 1.02, 95% CI 1.00–1.03; p = 0.042) and especially brain invasion (OR 5.26, 95% CI 1.52–18.15; p = 0.009) were identified as independent predictors of preoperative seizures. Nine (5%) patients developed new seizures within a median follow-up time of 15 months after surgery. Development of postoperative epilepsy was independent of all clinical variables, including Simpson grade (p = 0.133), tumor location (p = 0.936), brain invasion (p = 0.408), and preoperative edema volume (p = 0.081), but was correlated with increasing preoperative tumor volume (p = 0.004). Postoperative seizure-free rates were similar among patients with invasive and those with noninvasive meningioma (p = 0.372).

CONCLUSIONS Brain invasion was identified as a new and strong predictor for preoperative, but not postoperative, seizures. Although also associated with increased peritumoral edema, seizures in patients with invasive meningioma might be facilitated substantially by cortical invasion itself. Consideration of seizures in consultations between the neurosurgeon and neuropathologist can improve the microscopic detection of brain invasion.

 

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Utility of preoperative meningioma consistency measurement with magnetic resonance elastography (MRE)

Neurosurg Rev (2019) 42:1–7

Meningioma consistency is a critical factor that influences preoperative planning for surgical resection. Recent studies have investigated the utility of preoperative magnetic resonance elastography (MRE) in predicting meningioma consistency. However, it is unclear whether existing methods are optimal for application to clinical practice.

The results and conclusions of these studies are limited by their imaging acquisition methods, such as the use of a single MRE frequency and the use of shear modulus as the final measurement variable, rather than its storage and loss modulus components. In addition, existing studies do not account for the effects of cranial anatomy, which have been shown to significantly distort the MRE signal.

Given the interaction of meningiomas with these anatomic structures and the lack of supporting evidence with more accurate imaging parameters, MRE may not yet be reliable for use in clinical practice

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Parietal association deficits in patients harboring parietal lobe gliomas

J Neurosurg 130:773–779, 2019

Although the parietal lobe is a common site for glioma formation, current literature is scarce, consists of retrospective studies, and lacks consistency with regard to the incidence, nature, and severity of parietal association deficits (PADs).

The aim of this study was to assess the characteristics and incidence of PADs in patients suffering from parietal lobe gliomas through a prospective study and a battery of comprehensive neuropsychological tests.

METHODS Between 2012 and 2016 the authors recruited 38 patients with glioma confined in the parietal lobe. Patients were examined for primary and secondary association deficits with a dedicated battery of neuropsychological tests. The PADs were grouped into 5 categories: visuospatial attention, gnosis, praxis, upper-limb coordination, and language. For descriptive analysis tumors were divided into high- and low-grade gliomas and also according to patient age and tumor size.

RESULTS Parietal association deficits were elicited in 80% of patients, thus being more common than primary deficits (50%). Apraxia was the most common PAD (47.4%), followed by anomic aphasia and subcomponents of Gerstmann’s syndrome (34.2% each). Other deficits such as hemineglect, stereoagnosia, extinction, and visuomotor ataxia were also detected, albeit at lower rates. There was a statistically nonsignificant difference between PADs and sex (72.2% males, 85% females) and age (77.8% at ≤ 60 years, 80% at age > 60 years), but a statistically significant difference between the > 4 cm and the ≤ 4 cm diameter group (p = 0.02, 94.7% vs 63.2%, respectively). There was a tendency (p = 0.094) for low-grade gliomas to present with fewer PADs (50%) than high-grade gliomas (85.7%). Tumor laterality showed a strong correlation with hemineglect (p = 0.004, predilection for right hemisphere), anomia (p = 0.001), and Gerstmann’s symptoms (p = 0.01); the last 2 deficits showed a left (dominant) hemispheric preponderance.

CONCLUSIONS This is the first study to prospectively evaluate the incidence and nature of PADs in patients with parietal gliomas. It could be that the current literature may have underestimated the true incidence of deficits. Dedicated neuropsychological examination detects a high frequency of PADs, the most common being apraxia, followed by anomia and subcomponents of Gerstmann’s syndrome. Nevertheless, a direct correlation between the clinical deficit and its anatomical substrate is only possible to a limited extent, highlighting the need for intraoperative cortical and subcortical functional mapping.

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The transcortical equatorial approach for gliomas of the mesial temporal lobe

J Neurosurg 130:822–830, 2019

Many surgical approaches have been described for lesions within the mesial temporal lobe (MTL), but there are limited reports on the transcortical approach for the resection of tumors within this region. Here, the authors describe the technical considerations and functional outcomes in patients undergoing transcortical resection of gliomas of the MTL.

METHODS Patients with a glioma (WHO grades I–IV) located within the MTL who had undergone the transcortical approach in the period between 1998 and 2016 were identified through the University of California, San Francisco (UCSF) tumor registry and were classified according to tumor location: preuncus, uncus, hippocampus/parahippocampus, and various combinations of the former groups. Patient and tumor characteristics and outcomes were determined from operative, radiology, pathology, and other clinical reports that were available through the UCSF electronic medical record.

RESULTS Fifty patients with low- or high-grade glioma were identified. The mean patient age was 46.8 years, and the mean follow-up was 3 years. Seizures were the presenting symptom in 82% of cases. Schramm types A, C, and D represented 34%, 28%, and 38% of the tumors, and the majority of lesions were located at least in part within the hippocampus/ parahippocampus. For preuncus and preuncus/uncus tumors, a transcortical approach through the temporal pole allowed for resection. For most tumors of the uncus and those extending into the hippocampus/parahippocampus, a corticectomy was performed within the middle and/or inferior temporal gyri to approach the lesion. To locate the safest corridor for the corticectomy, language mapping was performed in 96.9% of the left-sided tumor cases, and subcortical motor mapping was performed in 52% of all cases. The mean volumetric extent of resection of low- and high-grade tumors was 89.5% and 96.0%, respectively, and did not differ by tumor location or Schramm type. By 3 months’ followup, 12 patients (24%) had residual deficits, most of which were visual field deficits. Three patients with left-sided tumors (9.4% of dominant-cortex lesions) experienced word-finding difficulty at 3 months after resection, but 2 of these patients demonstrated complete resolution of symptoms by 1 year.

CONCLUSIONS Mesial temporal lobe gliomas, including larger Schramm type C and D tumors, can be safely and aggressively resected via a transcortical equatorial approach when used in conjunction with cortical and subcortical mapping.

 

 

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Surgical management of spinal meningiomas

J Neurosurg Spine 30:308–313, 2019

Spinal meningiomas (sMNGs) are relatively rare in comparison to intracranial MNGs. sMNGs localized anterior to the denticulate ligament (aMNGs) represent a surgically challenging subgroup. A high perioperative complication rate due to the need for complex surgical approaches has been described. In the present study, the authors report on their surgical experience that involves two institutions in which 207 patients underwent surgery for sMNGs. Special focus was placed on patients with aMNGs that were treated via a unilateral posterior approach (ULPA).

METHODS Between 2005 and 2017, 207 patients underwent resection of sMNGs at one of two institutions. The following characteristics were assessed: tumor size and localization, surgical approach, duration of surgery, grade of resection, peri- and postoperative complication rates, and neurological outcome. Data were compared between the subgroups of patients according to the lesion’s relationship to the denticulate ligament and to surgical approach.

RESULTS The authors identified 48 patients with aMNGs, 86 patients with lateral MNGs, and 76 patients with posterior MNGs (pMNGs). Overall, 66.6% of aMNGs and 64% of pMNGs were reached via a ULPA. aMNGs that were approached via a ULPA showed reduced duration of surgery (131 vs 224 minutes, p < 0.0001) and had surgical complication rates and neurological outcomes comparable to those of lesions that were approached via a bilateral approach. No significant differences in complication rate, outcomes, and extent of resection were seen between aMNGs and pMNGs.

CONCLUSIONS The duration of surgery, extent of resection, and outcomes are comparable between aMNGs and pMNGs when removed via a ULPA. Thus, ULPA represents a safe route to achieve a gross-total resection, even in cases of aMNG.

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Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for the Treatment of Adults With Metastatic Brain Tumors: Executive Summary

Neurosurgery 84:550–552, 2019

The Congress of Neurological Surgeons systematic review and evidencebased clinical practice parameter guidelines for the treatment of adults with metastatic brain tumorswas first published in 2010. Because of the time elapsed since that publication, an update of this set of guidelines based on literature published since is now indicated.

OBJECTIVE: To establish the best evidence-based management of metastatic brain tumors over all commonly used diagnostic and treatment modalities in regularly encountered clinical situations.

METHODS: Literature searches regarding management of metastatic brain tumors with whole brain radiation therapy, surgery, stereotactic radiosurgery, chemotherapy, prophylactic anticonvulsants, steroids, instances of multiple brain metastases, and emerging and investigational therapies were carried out to answer questions designed by consensus of a multidisciplinary writing group.

RESULTS: Recommendations were created and their strength linked to the quality of the literature data available thus creating an evidence-based guideline. Importantly, shortcomings and biases to the literature data are brought out so as to provide guidance for future investigation and improvements in the management of patients with metastatic brain tumors.

CONCLUSION: This series of guidelines was constructed to assess the most current and clinically relevant evidence for management of metastatic brain tumors. They set a benchmark regarding the current evidence base for this management while also highlighting important key areas for future basic and clinical research, particularly on those topics for which no recommendations could be formulated.

The full guideline can be found here.

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The diagnostic accuracy of detecting malignant transformation of low-grade glioma using O-(2-[18F]fluoroethyl)-l-tyrosine positron emission tomography

J Neurosurg 130:451–464, 2019

The diagnostic accuracy of O-(2-[18F]fluoroethyl)-l-tyrosine (FET) PET scanning in detecting the malignant transformation of low-grade gliomas (LGGs) is controversial. In this study, the authors retrospectively assessed the diagnostic potential of FET PET in patients with MRI-suspected malignant progression of LGGs that had previously been treated and the relationship between FET uptake and MRI and molecular biomarkers.

METHODS Forty-two patients who had previously undergone surgical or multimodal treatment for a histologically verified LGG were referred for FET PET assessment because of clinical signs and/or MRI findings suggestive of tumor progression. Maximal and mean tumor-to-brain ratios (TBRmax and TBRmean, respectively) on FET PET as well as kinetic FET PET parameters (time to peak [TTP] and time-activity curve [TAC]) were determined. Final diagnoses were confirmed histologically. The diagnostic accuracy of FET parameters, separately and combined, for the detection of malignant progression was evaluated using receiver operating characteristic (ROC) curve analysis. Possible predictors that might influence the diagnostic accuracy of FET PET were assessed using multiple linear regression analysis. Spearman’s rank correlation r method was applied to determine the correlation between TBRmax and TAC, and molecular biomarkers from tumor tissues.

RESULTS A total of 47 FET PET scans were obtained and showed no significant association between FET parameters and contrast enhancement on MRI. ROC curve analyses overall were unable to demonstrate any significant differentiation between nontransformed LGGs and LGGs that had transformed to high-grade gliomas when evaluating FET parameters separately or combined. After excluding the oligodendroglial subgroup, a significant difference was observed between nontransformed and transformed LGGs when combining FET parameters (i.e., TBRmax > 1.6, TAC describing a plateau or decreasing pattern, and TTP < 25 minutes), with the best result yielded by a combined analysis of TBRmax > 1.6 and TAC with a plateau or decreasing pattern (sensitivity 75% and specificity 83%, p = 0.003). The difference was even greater when patients who had previously undergone oncological treatment were also excluded (sensitivity 93% and specificity 100%, p = 0.001). Multiple linear regression analysis revealed that the presence of an oligodendroglial component (p = 0.029), previous oncological treatment (p = 0.039), and the combined FET parameters (p = 0.027) were significant confounding factors in the detection of malignant progression. TBRmax was positively correlated with increasing cell density (p = 0.040) and inversely correlated with IDH1 mutation (p = 0.006).

CONCLUSIONS A single FET PET scan obtained at the time of radiological and/or clinical progression seems to be of limited value in distinguishing transformed from nontransformed LGGs, especially if knowledge of the primary tumor histopathology is not known. Therefore, FET PET imaging alone is not adequate to replace histological confirmation, but it may provide valuable information on the location and delineation of active tumor tissue, as well as an assessment of tumor biology in a subgroup of LGGs.

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Awake craniotomy versus craniotomy under general anesthesia without surgery adjuncts for supratentorial glioblastoma in eloquent areas

Acta Neurochirurgica (2019) 161:307–315

Awake craniotomy with electrocortical and subcortical mapping (AC) has become the mainstay of surgical treat- ment of supratentorial low-grade gliomas in eloquent areas, but not as much for glioblastomas.

Objective This retrospective controlled-matched study aims to determine whether AC increases gross total resections (GTR) and decreases neurological morbidity in glioblastoma patients as compared to resection under general anesthesia (GA, conventional). Methods Thirty-seven patients with glioblastoma undergoing AC were 1:3 controlled-matched with 111 patients undergoing GA for glioblastoma resection. The two groups were matched for age, gender, preoperative Karnofsky Performance Score (KPS), preoperative tumor volume, tumor location, and type of adjuvant treatment. Primary outcomes were extent of resection and the rate of postoperative complications. The secondary outcome was overall postoperative survival.

Results After matching, there were no significant differences in clinical variables between groups. Extent of resection was significantly higher in the AC group: mean extent of resection in the AC group was 94.89% (SD = 10.57) as compared to 70.30% (SD = 28.37) in the GA group (p = 0.0001). Furthermore, the mean rate of late minor postoperative complications in the AC group (0.03; SD = − 0.16) was significantly lower than in the GA group (0.15; SD = 0.39) (p = 0.05). No significant differences between groups were found for the other subgroups of postoperative complications. Moreover, overall postoperative survival did not differ between groups (p = 0.297).

Conclusion These findings suggest that resection of glioblastoma using AC is associated with significantly greater extent of resection and less late minor postoperative complications as compared with craniotomy under GA without the use of surgery adjuncts. However, due to certain limitations inherent to our study design (selection bias) and the absence of the use of surgery adjuncts in the GA group, we advocate for a prospective study to further build upon this evidence and study the use of AC in glioblastoma patients.

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Stereotactic Radiosurgery for Intracranial Ependymomas: An International Multicenter Study

Neurosurgery 84:227–234, 2019

Stereotactic radiosurgery (SRS) is a potentially important option for intracranial ependymoma patients.

OBJECTIVE: To analyze the outcomes of intracranial ependymoma patients who underwent SRS as a part of multimodality management.

METHODS: Seven centers participating in the International Gamma Knife Research Foundation identified 89 intracranial ependymoma patients who underwent SRS (113 tumors). The median patient age was 16.3 yr (2.9-80). All patients underwent previous surgical resection and radiation therapy (RT) of their ependymomas and 40 underwent previous chemotherapy. Grade 2 ependymomas were present in 42 patients (52 tumors) and grade 3 ependymomas in 48 patients (61 tumors). The median tumor volume was 2.2 cc (0.03-36.8) and the median margin dose was 15 Gy (9-24).

RESULTS: Forty-seven (53%) patients were alive and 42 (47%) patients died at the last follow-up. The overall survival after SRSwas 86% at 1 yr, 50% at 3 yr, and 44% at 5 yr. Smaller total tumor volume was associated with longer overall survival (P = .006). Twenty-two patients (grade 2: n = 9, grade 3: n = 13) developed additional recurrent ependymomas in the craniospinal axis. The progression-free survival after SRSwas 71%at 1 yr, 56% at 3 yr, and 48% at 5 yr. Adult age, female sex, and smaller tumor volume indicated significantly better progression-free survival. Symptomatic adverse radiation effects were seen in 7 patients (8%).

CONCLUSION: SRS provides another management option for residual or recurrent progressive intracranial ependymoma patients who have failed initial surgery and RT.

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Prognostic Importance of Age, Tumor Location, and Tumor Grade in Grade II Astrocytomas

World Neurosurg. (2019) 121:e411-e418

Previous work in anaplastic astrocytoma (AA) demonstrated that the survival benefit from gross total resection (GTR) is modified by age and tumor location. Here, we determined the influence of age and tumor location on survival benefit from GTR in diffuse astrocytoma (DA).

METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database (1999-2010). We used Kaplan- Meier curves and Cox survival models to determine the survival benefit from GTR in populations stratified by age and tumor location. We determined the prevalence of the mutated isocitrate dehydrogenase (mIDH) using The Cancer Genome Atlas (TCGA).

RESULTS: We identified 1980 patients with DA. For frontal DAs, GTR resulted in improved survival relative to subtotal resection in all ages (age ≤50 years hazard ratio [HR], 0.56; P [ 0.002; age >50 years HR, 0.41; P < 0.001). For nonfrontal DAs, only patients ≤50 years experienced improved survival with GTR (age ≤50 years HR, 0.55; P [ 0.002; age >50 years HR, 0.78; P [ 0.114). For patients ≤50 years with frontal tumors, survival was comparable between DA and AA after GTR (75% survival DA: 80 months, AA: 89 months, P [ 0.973). In TCGA, these tumors were nearly uniformly mIDH (DA: 98%; AA: 90%, P [ 0.11). However, for patients ≤50 years with nonfrontal tumors, there was a survival difference after GTR (75% survival DA: 80 months, AA: 30 months, P [ 0.001) despite comparable mIDH prevalence (DA: 82%, AA: 75%, P [ 0.49).

CONCLUSIONS: Age and tumor location modify the survival benefit derived from GTR in DA. Survival patterns in SEER imperfectly correlated with mIDH prevalence in TCGA, suggesting that tumor grade and mIDH status convey nonredundant prognostic information in select clinical contexts

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Insular glioma surgery: an evolution of thought and practice


J Neurosurg 130:9–16, 2019

The goal of this article is to review the history of surgery for low- and high-grade gliomas located within the insula with particular focus on microsurgical technique, anatomical considerations, survival, and postoperative morbidity.

METHODS The authors reviewed the literature for published reports focused on insular region anatomy, neurophysiol- ogy, surgical approaches, and outcomes for adults with World Health Organization grade II–IV gliomas.

RESULTS While originally considered to pose too great a risk, insular glioma surgery can be performed safely due to the collective efforts of many individuals. Similar to resection of gliomas located within other cortical regions, maximal resection of gliomas within the insula offers patients greater survival time and superior seizure control for both newly diagnosed and recurrent tumors in this region. The identification and the preservation of M2 perforating and lateral len- ticulostriate arteries are critical steps to preventing internal capsule stroke and hemiparesis. The transcortical approach and intraoperative mapping are useful tools to maximize safety.

CONCLUSIONS The insula’s proximity to middle cerebral and lenticulostriate arteries, primary motor areas, and perisyl- vian language areas makes accessing and resecting gliomas in this region challenging. Maximal safe resection of insular gliomas not only is possible but also is associated with excellent outcomes and should be considered for all patients with low- and high-grade gliomas in this area.

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Thirty-Day Outcomes After Craniotomy for Primary Malignant Brain Tumors

Neurosurgery 83:1249–1259, 2018

Despite improved perioperative management, the rate of postoperative morbidity and mortality after brain tumor resection remains considerably high.

OBJECTIVE: To assess the rates, causes, timing, and predictors of major complication, extended length of stay (>10 d), reoperation, readmission, and death within 30 d after craniotomy for primary malignant brain tumors.

METHODS: Patients were extracted from the National Surgical Quality Improvement Program registry (2005-2015) and analyzed using multivariable logistic regression.

RESULTS: A total of 7376 patientswere identified, ofwhich 948 (12.9%) experienced a major complication. The most common major complications were reoperation (5.1%), venous thromboembolism (3.5%), and death (2.6%). Furthermore, 15.6% stayed longer than 10 d, and 11.5% were readmitted within 30 d after surgery. The most common reasons for reoperation and readmission were intracranial hemorrhage (18.5%) and wound-related complications (11.9%), respectively. Multivariable analysis identified older age, higher body mass index, higher American Society of Anesthesiologists (ASA) classification, dependent functional status, elevated preoperative white blood cell count (white blood cell count [WBC], >12 000 cells/mm3), and longer operative time as predictors of major complication (all P < .001). Higher ASA classification, dependent functional status, elevated WBC, and ventilator dependence were predictors of extended length of stay (all P < .001). Higher ASA classification and elevatedWBCwere predictors of reoperation (both P<.001). Higher ASA classification and dependent functional status were predictors of readmission (both P < .001). Older age, higher ASA classification, and dependent functional status were predictors of death (all P< .001).

CONCLUSION: This study provides a descriptive analysis and identifies predictors for short term complications, including death, after craniotomy for primary malignant brain tumors.

 

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Enhancement of antitumor activity by using 5-ALA–mediated sonodynamic therapy to induce apoptosis in malignant gliomas

J Neurosurg 129:1416–1428, 2018

High invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA–mediated SDT (5-ALA-SDT).

METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry and TUNEL staining. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined by analysis of the effect of pretreatment with the radical scavenger edaravone. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated.

RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology, inducing cell shrinkage, vacuolization, and swelling. Flow cytometric analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the control group, and inhibition of ROS generation by edaravone completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. The proliferative activity of the entire tumor was markedly decreased. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact.

CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field, whereas the surrounding brain tissue remained normal, resulting in longer survival of the HIFU-treated mice compared with that of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

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