Category: Oncology

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A novel robot-guided minimally invasive technique for brain tumor biopsies

J Neurosurg 132:150–158, 2020

As decisions regarding tumor diagnosis and subsequent treatment are increasingly based on molecular pathology, the frequency of brain biopsies is increasing. Robotic devices overcome limitations of frame-based and frameless techniques in terms of accuracy and usability. The aim of the present study was to present a novel, minimally invasive, robot-guided biopsy technique and compare the results with those of standard burr hole biopsy.

METHODS A tubular minimally invasive instrument set was custom-designed for the iSYS-1 robot-guided biopsies. Feasibility, accuracy, duration, and outcome were compared in a consecutive series of 66 cases of robot-guided stereotactic biopsies between the minimally invasive (32 patients) and standard (34 patients) procedures.

RESULTS Application of the minimally invasive instrument set was feasible in all patients. Compared with the standard burr hole technique, accuracy was significantly higher both at entry (median 1.5 mm [range 0.2–3.2 mm] vs 1.7 mm [range 0.8–5.1 mm], p = 0.008) and at target (median 1.5 mm [range 0.4–3.4 mm] vs 2.0 mm [range 0.8–3.9 mm], p = 0.019). The incision-to-suture time was significantly shorter (median 30 minutes [range 15–50 minutes] vs 37.5 minutes [range 25–105 minutes], p < 0.001). The skin incision was significantly shorter (median 16.3 mm [range 12.7–23.4 mm] vs 28.4 mm [range 20–42.2 mm], p = 0.002). A diagnostic tissue sample was obtained in all cases.

CONCLUSIONS Application of the novel instrument set was feasible in all patients. According to the authors’ data, the minimally invasive robot-guidance procedure can significantly improve accuracy, reduce operating time, and improve the cosmetic result of stereotactic biopsies.

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5-Aminolevulinic Acid Fluorescence-Guided Resection of 18F-FET-PET Positive Tumor Beyond Gadolinium Enhancing Tumor Improves Survival in Glioblastoma

Neurosurgery 85:E1020–E1029, 2019

The value of early postoperative 18F-FET-PET in patients with glioblastoma (GBM) is unclear. Five-aminolevulinic acid (5-ALA) is used for fluorescence-guided resections in these patients and previous data suggest that fluorescence and 18F-FET-PET both demarcate larger tumor volumes than gadolinium enhanced magnet resonance imaging (MRI).

OBJECTIVE: To correlate fluorescence with enhancing volumes on postoperative MRI and 18F-FET-PET tumor volumes, and determine the value of postoperative 18F-FET-PET for predicting survival through observational study.

METHODS: GBM patients underwent fluorescence-guided resection after administration of 5-ALA followed by early postoperative MRI and 18F-FET-PET for determination of residual tissue volumes. All patients were treated with standard temozolomide radiochemotherapy and monitored for progression-free and overall survival (PFS, OS).

RESULTS: A total of 31 patients were included. For functional reasons, residual 5-ALA derived fluorescent tissue was left unresected in 18 patients with a median 18F-FETPET volume of 17.82 cm3 (interquartile range 6.50-29.19). In patients without residual fluorescence, median 18F-FET-PET volume was 1.20 cm3 (interquartile range 0.87-5.50) and complete resection of gadolinium enhancing tumor was observed in 100% of patients. A 18F-FET-PET volume of above 4.3 cm3 was associated with worse OS (logrank P-value≤.05), also in patients with no residual contrast enhancing tumor on MRI. More patients in whom fluorescencing tissue had been removed completely had postoperative 18F-FET-PET tumor volumes below 4.3 cm3.

CONCLUSION: Postoperative 18F-FET-PET volumes predict OS and PFS. Resection of 5-ALA derived fluorescence beyond gadolinium enhancing tumor tissue leads to lower postoperative 18F-FET-PET tumor volumes and improved OS and PFS without additional deficits.

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Upfront Magnetic Resonance Imaging-Guided Stereotactic Laser-Ablation in Newly Diagnosed Glioblastoma: A Multicenter Review of Survival Outcomes Compared to a Matched Cohort of Biopsy-Only Patients

Neurosurgery. 2019 Dec 1;85(6):762-772

Laser ablation (LA) is used as an upfront treatment in patients with deep seated newly diagnosed Glioblastoma (nGBM).

OBJECTIVE: To evaluate the outcomes of LA in patients with nGBM and compare them with a matched biopsy-only cohort.

METHODS: Twenty-four nGBM patients underwent upfront LA at Cleveland clinic, Washington University in St. Louis, and Yale University (6/2011-12/2014) followed by chemo/radiotherapy. Also, 24 out of 171 nGBM patients with biopsy followed by chemo/radiotherapy were matched based on age (< 70 vs ≥ 70), gender, tumor location (deep vs lobar), and volume (<11 cc vs ≥11 cc). Progression-free survival (PFS), overall survival (OS), and disease-specific PFS and OS were outcome measures. Three prognostic groups were identified based on extent of tumor ablation by thermal-damage-threshold (TDT)-lines.

RESULTS: The median tumor volume in LA (n = 24) and biopsy only (n = 24) groups was 9.3 cm3 and 8.2 cm3 respectively. Overall, median estimate of OS and PFS in LA cohort was 14.4 and 4.3 mo compared to 15.8 mo and 5.9 mo for biopsy only cohort. On multivariate analysis, favorable TDT-line prognostic groups were associated with lower incidence of disease specific death (P = .03) and progression (P = .05) compared to other groups including biopsy only cohort. Only age (<70 yr, P=.02) and tumor volume (<11 cc, P=.03) were favorable prognostic factors for OS.

CONCLUSION: Themaximum tumor coverage by LA followed by radiation/chemotherapy is an effective treatment modality in patientswith nGBM, compared to biopsy only cohort. The TDT-line prognostic groups were independent predictor of disease specific death and progression after LA.

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Risk factors associated with postoperative recurrence in atypical intracranial meningioma

Acta Neurochirurgica (2019) 161:2563–2570

Atypical meningioma (AM) has a high rate of local recurrence after surgery, and the role of adjuvant radiotherapy in AM remains controversial. We analysed progression-free survival (PFS) and identified the factors associated with postoperative recurrence in AM patients.

Methods Data were obtained from 263 AM patients who underwent surgery at our institution between October 2009 and September 2018. Analyses included factors such as the extent of surgical resection, MIB-1 labelling index, brain invasion and therapy modality. Univariate and multivariate analyses were used to assess recurrence-related prognostic factors.

Result The median follow-up duration was 41 months, and the median PFS was 28 months. Gross total resection (GTR) was achieved in 213 (81.0%) patients, and 86 (32.7%) patients received postoperative radiation therapy (RT). During follow-up, there were 61 (23.2%) tumour recurrences. In a Cox multivariate analysis, MIB-1 labelling index (hazard ratio = 2.637; p < 0.001), secondary tumour (hazard ratio = 3.541; p < 0.001), tumour size (hazard ratio = 1.818; p = 0.032) and extent of resection (hazard ratio = 2.861; p < 0.001) were independent significant predictors of tumour recurrence. RTwas associated with reduced tumour recurrence in subtotal resection (STR) (p = 0.023) but not GTR (p = 0.923). An analysis of 6 meningioma patients who underwent more than 3 operations suggested that the recurrence time became shorter and the MIB-1 labelling index increased as the number of recurrences increased.

Conclusions MIB-1 labelling index, secondary tumour, tumour size and extent of resection were powerful predictors of recurrence in AM patients. Postoperative RT did not decrease the risk of recurrence in GTR patients.

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Prospective clinical validation of a meningioma consistency grading scheme

J Neurosurg 131:1356–1360, 2019

The present study aims to assess the clinical utility of a previously validated intraoperative meningioma consistency grading scale and its association with extent of resection (EOR) and various surgical outcomes.

METHODS The previously validated grading system was prospectively assessed in 127 consecutive patients undergoing open craniotomy for meningioma by multiple neurosurgeons at two high-volume academic hospitals from 2013 to 2016. Consistency grading scores ranging from 1 (soft) to 5 (firm/calcified) were retrospectively analyzed to test for association with surgical outcomes and EOR, categorized as gross-total resection (GTR) or subtotal resection, defined by postoperative MRI.

RESULTS One hundred twenty-seven patients were included in the analysis with a tumor consistency distribution as follows: grade 1, 3.1%; grade 2, 14.2%; grade 3, 44.1%; grade 4, 32.3%; and grade 5, 6.3%. The mean tumor diameter was 3.6 ± 1.7 cm. Tumor consistency grades were grouped into soft (grades 1 and 2), average (grade 3), and firm (grades 4 and 5) groups for statistical analysis with distributions of 17.3%, 44.1%, and 38.6%, respectively. There was no association between meningioma consistency and maximal tumor diameter, or location. Mean duration of surgery was longer for tumors with higher consistency: grades 1 and 2, 186 minutes; grade 3, 219 minutes; and grades 4 and 5, 299 minutes (p = 0.000028). There was a trend toward higher perioperative complication rates for tumors of increased consistency: grades 1 and 2, 4.5%; grade 3, 7.0%; and grades 4 and 5, 20.8% (p = 0.047). The proportion of GTR for each consistency group was as follows: grades 1 and 2, 77%; grade 3, 68%; and grades 4 and 5, 43% (p = 0.0062).

CONCLUSIONS In addition to other important meningioma characteristics such as invasiveness, tumor consistency is a key determinant of surgical outcomes, including operative duration and EOR. Future studies predicting tumor consistency based on preoperative neuroimaging will help considerably with preoperative planning for meningiomas.

 

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Comparative Analysis of Subventricular Zone Glioblastoma Contact and Ventricular Entry During Resection in Predicting Dissemination, Hydrocephalus, and Survival

Neurosurgery, Volume 85, Issue 5, November 2019, Pages E924–E932

Ventricular entry during glioblastoma resection and tumor contact with the subventricular zone (SVZ) have both been shown to associate with development of hydrocephalus, leptomeningeal dissemination, distant parenchymal recurrence, and decreased survival. However, prior studies did not analyze these variables together in a single-patient population; therefore, it is unknown which is an independent predictor of these outcomes.

OBJECTIVE: To conduct a comparative outcome analysis of surgical ventricular entry and SVZ contact by glioblastoma in a retrospective cohort of 232 patients.

METHODS: Outcomes studied included hydrocephalus, leptomeningeal dissemination, distant tumor recurrences, and progression-free (PFS) and overall (OS) survival. The Cox proportional regression analyses were adjusted for age at diagnosis, preoperative Karnofsky performance status score, extent of resection, temozolomide and radiation treatments, and tumor molecular status (specifically, IDH1/2 mutation and MGMT promoter methylation).

RESULTS: Surgical ventricular entry, SVZ-contacting glioblastoma, hydrocephalus, leptomeningeal dissemination, and distant recurrences were observed in 85 (36.6%), 114 (49.1%), 19 (8.2%), 78 (33.6%), and 59 (25.4%) patients, respectively. Multivariate, adjusted analysis revealed SVZ tumor contact—but not ventricular entry—associated with hydrocephalus (hazard ratio, HR, 4.20 [1.13-15.7], P = .03), leptomeningeal dissemination (HR 1.93 [1.14-3.28], P = .01), PFS (HR 2.10 [1.53-2.88], P < .001), and OS (HR 1.90 [1.35-2.67], P < .001). Distant recurrences were not associated with either. No interaction between the 2 variables was statistically noted.

CONCLUSION: SVZ contact by glioblastoma was independently associated with the development of hydrocephalus, leptomeningeal dissemination, and decreased survival. SVZ tumor contact was associated with ventricular entry during surgical resections, which did not independently correlate with these outcomes.

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Growth prediction in asymptomatic meningiomas: the utility of the AIMSS score

Acta Neurochirurgica (2019) 161:2233–2240

Management of asymptomatic meningiomas represents a challenge due to the absence of a solid consensus on which is the best management strategy. There are various known factors predicting meningiomas growth risk. However, the Asian Intracranial Meningioma Scoring System (AIMSS) is the only described score to quantify such risk thus emerging as a potential tool for management decisions. This study aims to validate this score on our series of asymptomatic meningiomas.

Method We performed a retrospective review of asymptomatic meningiomas diagnosed at our institution between January 2008 and October 2016 and followed by an annual cerebral Magnetic Resonance Imaging (MRI). For each lesion, the AIMSS score was calculated thus classifying them in low (0–2), intermediate (3–6) or high risk (7–11) of rapid growth (>2cm 3 /year). We investigated the correlation between the expected Average Growth Rate (AGR) according to the score and the one obtained in our study. The mean growth velocity over the different risk groups was also compared.

Results Overall, 69 asymptomatic meningiomas found incidentally in 46 patients were included in the study; 31 were assigned to the low-risk group, 34 to the intermediate-risk group and 4 to the high-risk group. Attending to the AGR, 0% showed rapid growth in the low-risk group, 12% in the intermediate-risk group, and 25% in the high-risk group. The mean growth velocity showed a significant difference over the different risk groups (p < 0,001).

Conclusions According to our finding, the AIMSS score is a valid tool to estimate the risk of rapid growth of asymptomatic meningiomas. It is especially useful distinguishing between low- and intermediate-risk meningiomas. This feature would allow physicians to adjust the periodicity of radiological and clinical controls. Adding more known risk factors of rapid growth to the score might improve its predictive capabilities with the high-risk group.

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Surgical outcomes after reoperation for recurrent non–skull base meningiomas

J Neurosurg 131:1179–1187, 2019

Recurrent meningiomas are primarily managed with radiation therapy or repeat resection. Surgical morbidity after reoperation for recurrent meningiomas is poorly understood. Thus, the objective of this study was to report surgical outcomes after reoperation for recurrent non–skull base meningiomas.

METHODS A retrospective review of patients was performed. Inclusion criteria were patients with recurrent meningioma who had prior resection and supratentorial non–skull base location. Univariate and multivariate logistic regression and recursive partitioning analysis were used to identify risk factors for surgical complications.

RESULTS The authors identified 67 patients who underwent 111 reoperations for recurrent supratentorial non–skull base meningiomas. The median age was 53 years, 49% were female, and the median follow-up was 9.8 years. The most common presenting symptoms were headache, weakness, and seizure. The WHO grade after the last reoperation was grade I in 22% of cases, grade II in 51%, and grade III in 27%. The tumor grade increased at reoperation in 22% of cases. Tumors were located on the convexity (52%), parasagittal (33%), falx (31%), and multifocal (19%) locations. Tumors involved the middle third of the sagittal plane in 52% of cases. In the 111 reoperations, 48 complications occurred in 32 patients (48%). There were 26 (54%) complications requiring surgical intervention. There was no perioperative mortality. Complications included neurological deficits (14% total, 8% permanent), wound dehiscence/infection (14%), and CSF leak/pseudomeningocele/hydrocephalus (9%). Tumors that involved the middle third of the sagittal plane (OR 6.97, 95% CI 1.5–32.0, p = 0.006) and presentation with cognitive changes (OR 20.7, 95% CI 2.3–182.7, p = 0.001) were significantly associated with complication occurrence on multivariate analysis. The median survival after the first reoperation was 11.5 years, and the 2-, 5-, and 10-year Kaplan-Meier survival rates were 91.0%, 68.8%, and 50.0%, respectively.

CONCLUSIONS Reoperation for recurrent supratentorial non–skull base meningioma is associated with a high rate of complications. Patients with cognitive changes and tumors that overlap the middle third of the sagittal plane are at increased risk of complications. Nevertheless, excellent long-term survival can be achieved without perioperative mortality.

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Transcortical insular glioma resection: clinical outcome and predictors

J Neurosurg 131:706–716, 2019

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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Comparison of Motor Outcome in Patients Undergoing Awake vs General Anesthesia Surgery for Brain Tumors Located Within or Adjacent to the Motor Pathways

Neurosurgery, Volume 85, Issue 3, September 2019: E470–E476

Surgical removal of intra-axial brain tumors aims at maximal tumor resection while preserving function. The potential benefit of awake craniotomy over craniotomy under general anesthesia (GA) for motor preservation is yet unknown.

OBJECTIVE: To compare the clinical outcomes of patients who underwent surgery for perirolandic tumors while either awake or under GA.

METHODS: Between 2004 and 2015, 1126 patients underwent surgical resection of newly diagnosed intra-axial tumors in a single institution. Data from 85 patients (44 awake, 41 GA) with full dataset who underwent resections for perirolandic tumors were retrospectively analyzed.

RESULTS: Identification of the motor cortex required significantly higher stimulation thresholds in anesthetized patients (9.1 ± 4 vs 6.2 ± 2.7 mA for awake patients, P = .0008). There was no group difference in the subcortical threshold for motor response used to assess the proximity of the lesion to the corticospinal (pyramidal) tract. High-grade gliomas were the most commonly treated pathology. The extent of resection and residual tumor volume were not different between groups. Postoperative motor deficits were more common in the anesthetized patients at 1 wk (P = .046), but no difference between the groups was detected at 3 mo. Patients in the GA group had a longer mean length of hospitalization (10.3 vs 6.7 d for the awake group, P = .003).

CONCLUSION: Awake craniotomy results in a better early postoperative motor outcome and shorter hospitalization compared with patients who underwent the same surgery under GA. The finding of higher cortical thresholds for the identification of the motor cortex in anesthetized patients may suggest an inhibitory effect of anesthetic agents on motor function.

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Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma

J Neurosurg 131:724–734, 2019

The use of the optical contrast agent sodium fluorescein (NaFl) to guide resection of gliomas has been under investigation for decades. Although this imaging strategy assumes the agent remains confined to the vasculature except in regions of blood-brain barrier (BBB) disruption, clinical studies have reported significant NaFl signal in normal brain tissue, limiting tumor-to-normal contrast. A possible explanation arises from earlier studies, which reported that NaFl exists in both pure and protein-bound forms in the blood, the former being small enough to cross the BBB. This study aims to elucidate the kinetic binding behavior of NaFl in circulating blood and its effect on NaFl accumulation in brain tissue and tumor contrast. Additionally, the authors examined the blood and tissue kinetics, as well as tumor uptake, of a pegylated form of fluorescein selected as a potential optical analog of gadolinium-based MRI contrast agents.

METHODS Cohorts of mice were administered one of the following doses/forms of NaFl: 1) high human equivalent dose (HED) of NaFl, 2) low HED of NaFl, or 3) pegylated form of fluorescein. In each cohort, groups of animals were euthanized 15, 30, 60, and 120 minutes after administration for ex vivo analysis of fluorescein fluorescence. Using gel electrophoresis and fluorescence imaging of blood and brain specimens, the authors quantified the temporal kinetics of bound NaFl, unbound NaFl, and pegylated fluorescein in the blood and normal brain tissue. Finally, they compared tumor-to-normal contrast for NaFl and pegylated-fluorescein in U251 glioma xenografts.

RESULTS Administration of NaFl resulted in the presence of unbound and protein-bound NaFl in the circulation, with unbound NaFl constituting up to 70% of the signal. While protein-bound NaFl was undetectable in brain tissue, unbound NaFl was observed throughout the brain. The observed behavior was time and dose dependent. The pegylated form of fluorescein showed minimal uptake in brain tissue and improved tumor-to-normal contrast by 38%.

CONCLUSIONS Unbound NaFl in the blood crosses the BBB, limiting the achievable tumor-to-normal contrast and undermining the inherent advantage of tumor imaging in the brain. Dosing and incubation time should be considered carefully for NaFl-based fluorescence-guided surgery (FGS) of glioma. A pegylated form of fluorescein showed more favorable normal tissue kinetics that translated to higher tumor-to-normal contrast. These results warrant further development of pegylated-fluorescein for FGS of glioma.

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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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