Category: Oncology

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Transcortical insular glioma resection: clinical outcome and predictors

J Neurosurg 131:706–716, 2019

OBJECTIVE Insular lobe gliomas continue to challenge neurosurgeons due to their complex anatomical position. Transcortical and transsylvian corridors remain the primary approaches for reaching the insula, but the adoption of one technique over the other remains controversial. The authors analyzed the transcortical approach of resecting insular gliomas in the context of patient tumor location based on the Berger-Sinai classification, achievable extents of resection (EORs), overall survival (OS), and postsurgical neurological outcome.

METHODS The authors studied 255 consecutive cases of insular gliomas that underwent transcortical tumor resection in their division. Tumor molecular pathology, location, EOR, postoperative neurological outcome for each insular zone, and the accompanying OS were incorporated into the analysis to determine the value of this surgical approach.

RESULTS Lower-grade insular gliomas (LGGs) were more prevalent (63.14%). Regarding location, giant tumors (involving all insular zones) were most prevalent (58.82%) followed by zone I+IV (anterior) tumors (20.39%). In LGGs, tumor location was an independent predictor of survival (p = 0.003), with giant tumors demonstrating shortest patient survival (p = 0.003). Isocitrate dehydrogenase 1 (IDH1) mutation was more likely to be associated with giant tumors (p < 0.001) than focal tumors located in a regional zone. EOR correlated with survival in both LGG (p = 0.001) and higher-grade glioma (HGG) patients (p = 0.008). The highest EORs were achieved in anterior-zone LGGs (p = 0.024). In terms of developing postoperative neurological deficits, patients with giant tumors were more susceptible (p = 0.038). Postoperative transient neurological deficit was recorded in 12.79%, and permanent deficit in 15.70% of patients. Patients who developed either transient or permanent postsurgical neurological deficits exhibited poorer survival (p < 0.001).

CONCLUSIONS The transcortical surgical approach can achieve maximal tumor resection in all insular zones. In addition, the incorporation of adjunct technologies such as multimodal brain imaging and mapping of cortical and subcortical eloquent brain regions into the transcortical approach favors postoperative neurological outcomes, and prolongs patient survival.

 

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Koos Classification of Vestibular Schwannomas: A Reliability Study

Neurosurgery, Volume 85, Issue 3, September 2019, 409–414

The Koos classification of vestibular schwannomas is designed to stratify tumors based on extrameatal extension and compression of the brainstem. While this classification system is widely reported in the literature, to date no study has assessed its reliability.

OBJECTIVE: To assess the intra- and inter-rater reliability of the Koos classification system.

METHODS: After institutional review board approval was obtained, a cross-sectional group of the Magnetic Resonance imagings of 40 patients with vestibular schwannomas varying in size comprised the study sample. Four raters were selected to assign a Koos grade to 50 total scans. Inter- and intrarater reliability were calculated and reported using Fleiss’ kappa, Kendall’s W, and Intraclass correlation coefficient (ICC).

RESULTS: Inter-rater reliability was found to be substantial when measured using Fleiss’ kappa (.71), extremely strong using Kendall’sW(.92), and excellent as calculated by ICC (.88). Intrarater reliability was perfect for 3 out of 4 raters as assessed using weighted kappa, Kendall’s W and ICC, with the intrarater agreement for the fourth rater measured as extremely high.

CONCLUSION: We have demonstrated that the Koos classification system for vestibular schwannoma is a reliable method for tumor classification. This study lends further support to the results of current literature using Koos grading system. Further studies are required to evaluate its validity and utility in counseling patients with regard to outcomes.

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Papillary Tumor of the Pineal Region: Systematic Review and Analysis of Prognostic Factors

Neurosurgery, Volume 85, Issue 3, September 2019: E420–E429

Clinical outcomes and biological behavior of papillary tumors of the pineal region (PTPR) are still under investigation. The best therapeutic strategy has not been defined.

OBJECTIVE: To perform a comprehensive patient-level analysis of all PTPR cases and identify their clinical features, treatment options, and prognostic factors.

METHODS: A search of the medical databases for case series and reports on PTPRs from January 2003 to June 2017 was performed. Data addressing PTPR’s clinical presentation, imaging, treatment, and histological features were. Variables associated with the primary outcome of 36-mo survival were identified through Cox regression models.

RESULTS: The initial search yielded 1164 studies, of which 71 were included (60 case reports and 11 case series), containing 177 patients (mean age 33.0 ± 15.3 yr and 53.2% male). Intracranial hypertension and hydrocephalus prevailed as the clinical picture. Surgery was performed on 82.0% and gross total resection (GTR) was achieved on 71.4%. A total of 56.8% recurred after a median 29-mo (quartiles 10.5-45.5). The 36-mo survival rate was 83.5% (95% confidence interval [CI] 76.2-89.2%). Good functional outcomes (Glasgow Outcome Scale 4/5) were observed in 60.0%. The variables of interest were inconsistently reported and the multivariable analysis final sample was 133 patients. After adjustment for age, tumor size (each additional centimeter, hazard ratio [HR] 1.99, 95% CI 1.12-3.53, P = .019) and surgical treatment (HR 0.16, 95% CI 0.05-0.45, P = .001) were associated with 36-mo survival.

CONCLUSION: Tumor size and surgery are associated with improvement in 36-mo survival. We did not observe any significant benefits from GTR or adjuvant treatments.

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The Impact of Early Corticosteroid Pretreatment Before Initiation of Chemotherapy in Patients With Primary Central Nervous System Lymphoma

Neurosurgery, Volume 85, Issue 2, August 2019, Pages 264–272

The optimal timing of corticosteroid (CS) treatment in patients with primary central nervous system (CNS) lymphoma (PCNSL) remains controversial. While poor clinical presentation may justify early treatment with CS, this may ultimately result in reduced concentrations of chemotherapeutic agents via perturbations in the permeability of the blood-brain barrier.

OBJECTIVE: To investigate whether early CS exposure is associated with beneficial outcomes and/or reduced occurrence of adverse events as opposed to delayed/concomitant administration.

METHODS: Herein we performed a retrospective observational analysis using patients that were prospectively entered into a database. All patients whom were admitted to the University Hospital between 2009 and 2015 with newly diagnosed PCNSL were included within our study.

RESULTS: Our cohort included 50 consecutive patients diagnosed with PCNSL; of these, in 30 patients CS administration was initiated prior to chemotherapy (early), whilst in the remaining 20 patientsCS administrationwas initiated concomitantly with their chemotherapeutic regimen (concomitant).Within the early vs concomitant CS administration groups, no significant differences were observed with regard to progression-free survival (PFS) (P=.81), overall survival (OS) (P=.75), or remission (P=.68; odds ratio 0.76 and confidence interval [95%] 0.22-2.71). Critically, the timing of CS initiation was not associated with either PFS (P = .81) or PFS (P = .75).

CONCLUSION: Early CS administration was not associated with a deterioration in response to chemotherapy, PFS, or OS. As such, administration of CS prior to initiation of chemotherapy is both reasonable and safe for patients with newly diagnosed PCNSL

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Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patients With 5 to 15 Brain Metastases

Neurosurgery, Volume 85, Issue 2, August 2019, Pages 257–263

The role of primary stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) remains controversial.

OBJECTIVE: To compare the outcomes of patients treated with upfront SRS alone for 1, 2 to 4, and 5 to 15 BM and assess for predictors of clinical outcomes in the 5 to 15 BM group.

METHODS: A total of 478 patients treated with upfront SRS were stratified by number of lesions: 220 had 1 BM, 190 had 2 to 4 BM, and 68 patients had 5 to 15 BM. Overall survival and whole brain radiotherapy-free survival were estimated using the Kaplan–Meier method. The cumulative incidences of local failure and distant brain failure (DBF) were estimated using competing risks methodology. Clinicopathologic and dosimetric parameters were evaluated as predictors of survival and DBF in patients with 5 to 15 BM using Cox propor- tional hazards.

RESULTS: Median overall survival was 8.0, 6.3, and 4.7 mo for patients with 1, 2 to 4, and 5 to 15 BM, respectively (P = .14). One-year DBF was 27%, 44%, and 40%, respec- tively (P = .01). Salvage SRS and whole brain radiotherapy rates did not differ. Progressive extracranial disease and gastrointestinal primary were associated with poor survival while RCC primary was associated with increased risk of DBF. No evaluated dose-volume param- eters predicted for death, neurologic death or toxicity.

CONCLUSION: SRS for 5 to 15 BM is well tolerated without evidence of an associated increase in toxicity, treatment failure, or salvage therapy. Further prospective, randomized studies are warranted to clarify the role of SRS for these patients.

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Iterative Surgical Resections of Diffuse Glioma With Awake Mapping: How to Deal With Cortical Plasticity and Connectomal Constraints?

Neurosurgery 85(1):105–116. 2019

In diffuse glioma, a multistage approach with iterative tailored surgical resections can be considered.
OBJECTIVE: To compare results of iterative intrasurgical brain mappings to investigate the potential and limitation of neuroplasticity at the individual stage, and to highlight to what extent it can influence the therapeutic strategy.
METHODS: Glioma patients who underwent 2 consecutive awake surgeries with cortical and subcortical stimulation were classified into group 1 (n = 23) if cortical mappings exhibited high level of plasticity (displacement of ≥2 sites) or into group 2 (n = 19) with low level of plasticity.
RESULTS: Clinical characteristics did not differ significantly between both groups. The borders of the tumors were mostly sharp in group 1 (82.6%) and rather indistinct in group 2 (84.2%), (P = .00001). Tumor remnants were more often cortical (± subcortical) in group 1 (39.1%) and more often purely subcortical in group 2 (68.4%; P = .009). In group 1, the time needed to recover independence was significantly shorter at reoperation (37.6 h vs 78.3 h after the first surgery, P = .00003) while this difference was not significant in group 2. The iterative extents of resection (EOR) remain comparable in group 1 (94% vs 92%, P = .40) but were significantly smaller in group 2 at reoperation (94% vs 88%, P = .05).
CONCLUSION: More efficient plasticity mechanisms are facilitated by cortical tumors with sharp borders, are associated with an increase of EOR at reoperation and with earlier functional recovery. Tumoral invasion of the white matter tracts represents the main limitation of neuroplasticity: this connectomal constraint limits EOR during second surgery.

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Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases

Neurosurgery, Volume 85, Issue 1, July 2019, Pages 117–125

Twenty percent of all brain metastases (BM) occur in the posterior fossa (PF). Radiotherapy sometimes associated with surgical resection remains the therapeutic option, while Karnovsky performance status and graded prognostic assessment (GPA) are the best preoperative survival prognostic factors.

OBJECTIVE: To explore the prognostic role of peritumoral brain edema in the PF, which has never been explored though its role in supratentorial BM has been debated.

METHODS: A total of 120 patients diagnosed with PF metastasis who underwent surgical resection were included retrospectively in this analysis. Clinical data were retrieved from electronic patient medical files. The tumor volumes and their associated edema were calculated via manual delineation; subsequently the edema/tumor volume ratio was determined.

RESULTS: In multivariate analysis with Cox multivariate proportional hazard model, the edema to tumor volumes ratio (hazard ratio [HR]: 1.727, 95% confidence interval [CI] 1.427- 2.083; P < .0001) was identified as a new strong independent prognosis factor on overall survival (OS) whereas edema volume alone was not (P = .469). Moreover, BM complete resection (HR: 0.447, 95% CI 0.277-0.719; P < .001), low (0-1) World Health Organization status at diagnosis (HR: 2.109, 95% CI 1.481-3.015; P < .0001), high GPA class at diagnosis (HR: 1.77, 95% CI 0.9-2.9; P < .04), and postoperative brain irradiation (HR: 2.019, 95% CI 1.213-3.361; P < .007] were all confirmed as independent predictive factors for survival.

CONCLUSION: The edema/tumor ratio appears to greatly influence OS in patients suffering from PF metastases unlike the extent of edema alone. This easily determined as well as strong prognostic factor could be used as an interesting tool in clinical practice to help the management of these patients.

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Pediatric Supratentorial Ependymoma: Surgical, Clinical, and Molecular Analysis

Neurosurgery 85:41–49, 2019

Pediatric supratentorial ependymomas (SEs) have distinct molecular and behavioral differences from their infratentorial counterparts.

OBJECTIVE: To present our experience with pediatric SEs over a 24-yr period.

METHODS: Clinical, operative, and radiographic information was abstracted retrospectively. Our primary outcomes were progression-free survival (PFS) and overall survival (OS). Detection of C11or f95-RELA rearrangement was performed using interphase fluorescence in situ hybridization (iFISH).

RESULTS: Seventy-three patients were identified (41 female, 32 male); median age was 6.7 yrs (range, 1 mo-18.8 yr); median follow-up was 8.3 yrs (range, 2.0-26.3). Fifty-eight (79.5%) of 73 patients underwent gross total resection (GTR); no patient with subtotal resection had greater than 1 cm3 of residual tumor; 42 patients (57.5%) experienced subsequent disease progression with 17 patients ultimately dying of their disease. Median PFS was 3.7 yrs. Molecular analysis was available for 51 patients (70%). On bivariate analysis, PFS and OS were not statistically affected by age, tumor grade, or extent of resection, although there was a clinically significant trend for the latter in favor of aggressive resection on PFS (P = .061). Children with RELA fusion had significantly higher PFS (P = .013) than those without, although there was no difference in OS when compared with those with no C11orf95-RELA fusion or C11orf95 gene rearrangement alone.

CONCLUSION: In our series, GTR may be associated with better PFS, but did not impact OS. Surprisingly, RELA fusion was not found to be a negative prognostic factor, raising the possibility that the deleterious effects may be overcome by aggressive resection.

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MRI combined with PET-CT of different tracers to improve the accuracy of glioma diagnosis

Neurosurg Rev (2019) 42:185–195

Based on studies focusing on positron emission tomography (PET)-computed tomography (CT) combined with magnetic resonance imaging (MRI) in the diagnosis of glioma, we conducted a systematic review and meta-analysis evaluating the pros and cons and the accuracy of different examinations. PubMed and Cochrane Library were searched. The search was conducted until April 2017. Two reviewers independently conducted the literature search according to the criteria set initially. Based on the exclusion criteria, 15 articles are included in this study.

Of all studies that used MRI examination, there are five involving 18F-fluorodeoxyglucose- PET, five involving 11C-methionine-PET, five involving 18F-fluoro-ethyl-tyrosine-PET, and three involving 18Ffluorothymidine- PET. Due to the limitations such as lack of data, small sample size, and unrepresentative studies, we use a non-quantitative methodology.

MRI examination can provide the anatomy information of glioma more clearly. PET-CT examinations based on tumor metabolism using different tracers have more advantages in determining the degree of glioma malignancy and boundaries. However, information provided by PET-Craneotomía of different tracers is not the same. With respect to the novel hybrid MRI/PET examination equipment proposed in recent years, the combination of MRI and PET-CT can definitively improve the diagnostic accuracy of glioma.

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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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