Eloquent Lower Grade Gliomas, a Highly Vulnerable Cohort: Assessment of Patients' Functional Outcome After Surgery Based on the LoG-Glio Registry.

Majority of lower grade glioma (LGG) are located eloquently rendering surgical resection challenging. Aim of our study was to assess rate of permanent deficits and its predisposing risk factors. We retrieved 83 patients harboring an eloquently located LGGs from the prospective LoG-Glio Database. Patients without surgery or incomplete postoperative data were excluded. Sign rank test, explorative correlations by Spearman ρ and multivariable regression for new postoperative deficits were calculated. Eloquent region involved predominantly motor (45%) and language (40%). At first follow up after 3 months permanent neuro-logical deficits (NDs) were noted in 39%. Mild deficits remained in 29% and severe deficits in 10%. Complete tumor removal (CTR) was successfully in 62% of intended cases. Postoperative and 3-month follow up National Institute of Health Stroke Score (NIHSS) showed significantly lower values than preoperatively (p<0.001). 38% cases showed a decreased NIHSS at 3-month, while occurrence was only 14% at 9-12-month follow up. 6/7 patients with mild aphasia recovered after 9-12 months, while motor deficits present at 3-month follow up were persistent in majority of patients. Eastern oncology group functional status (ECOG) significantly decreased by surgery (p < 0.001) in 31% of cases. Between 3-month and 9-12-months follow up no significant improvement was seen. In the multivariable model CTR (p=0.019, OR 31.9), and ECOG>0 (p=0.021, OR 8.5) were independent predictors for permanent postoperative deficit according to NIHSS at 3-month according to multivariable regression model. Patients harboring eloquently located LGG are highly vulnerable for permanent deficits. Almost one third of patients have a permanent reduction of their functional status based on ECOG. Risk of an extended resection has to be balanced with the respective oncological benefit. Especially, patients with impaired pre-operative status are at risk for new permanent deficits. There is a relevant improvement of neurological symptoms in the first year after surgery, especially for patients with slight aphasia.

The value of intraoperative angiography in the time of indocyanine green videoangiography in the treatment of cerebrovascular lesions: Efficacy, workflow, risk-benefit and cost analysis A prospective study.

INTRODUCTION: Intraoperative digital subtraction angiography (ioDSA) allows early treatment evaluation after neurovascular procedures. However, the value and efficiency of this procedure has been discussed controversially. We have evaluated the additional value of hybrid operating room equipped with an Artis Zeego robotic c-arm regarding cost, efficiency and workflow. Furthermore, we have performed a risk-benefit analysis and compared it with indocyanine green (ICG) angiography. METHODS: For 3 consecutive years, we examined all neurovascular patients, treated in the hybrid operating theater in a risk-benefit analysis. After using microdoppler and ICG angiography for best operative result, every patient received an additional ioDSA to look for remnants or unfavorable clip placement which might lead to a change of operating strategy or results. Furthermore, a workflow-analysis reviewing operating steps, staff positioning, costs, technical errors or complications were conducted on randomly selected cases. RESULTS: 54 patients were enrolled in the risk-benefit analysis, 22 in the workflow analysis. The average duration of a cerebrovascular operation was 4 h 58 min 2 min 35 s accounted for ICG angiography, 46 min 4 s for ioDSA. Adverse events occurred during one ioDSA. In risk-benefit analysis, ioDSA was able to detect a perfusion rest in 2 out of 43 cases (4,7%) of aneurysm surgery, which could not have been visualized by ICG angiography before. In arterio-venous-malformation (AVM) surgery, one of 11 examined patients (7,7%) showed a remnant in ioDSA and resulted in additional resection. The average cost of an ioDSA in Ulm University can be estimated with 1928,00€. CONCLUSION: According to our results ioDSA associated complications are low. Relevant findings in ioDSA can potentially avoid additional intervention, however, due to the high costs and lower availability, the main advantage might lie in the treatment of selected patients with complexes neurovascular pathologies since ICG angiography is equally safe but associated with lower costs and better availability.

To treat or not to treat? A retrospective multicenter assessment of survival in patients with IDH-mutant low-grade glioma based on adjuvant treatment.

OBJECTIVE: The level of evidence for adjuvant treatment of diffuse WHO grade II glioma (low-grade glioma, LGG) is low. In so-called "high-risk" patients most centers currently apply an early aggressive adjuvant treatment after surgery. The aim of this assessment was to compare progression-free survival (PFS) and overall survival (OS) in patients receiving radiation therapy (RT) alone, chemotherapy (CT) alone, or a combined/consecutive RT+CT, with patients receiving no primary adjuvant treatment after surgery. METHODS: Based on a retrospective multicenter cohort of 288 patients (≥ 18 years old) with diffuse WHO grade II gliomas, a subgroup analysis of patients with a confirmed isocitrate dehydrogenase (IDH) mutation was performed. The influence of primary adjuvant treatment after surgery on PFS and OS was assessed using Kaplan-Meier estimates and multivariate Cox regression models, including age (≥ 40 years), complete tumor resection (CTR), recurrent surgery, and astrocytoma versus oligodendroglioma. RESULTS: One hundred forty-four patients matched the inclusion criteria. Forty patients (27.8%) received adjuvant treatment. The median follow-up duration was 6 years (95% confidence interval 4.8-6.3 years). The median overall PFS was 3.9 years and OS 16.1 years. PFS and OS were significantly longer without adjuvant treatment (p = 0.003). A significant difference in favor of no adjuvant therapy was observed even in high-risk patients (age ≥ 40 years or residual tumor, 3.9 vs 3.1 years, p = 0.025). In the multivariate model (controlled for age, CTR, oligodendroglial diagnosis, and recurrent surgery), patients who received no adjuvant therapy showed a significantly positive influence on PFS (p = 0.030) and OS (p = 0.009) compared to any other adjuvant treatment regimen. This effect was most pronounced if RT+CT was applied (p = 0.004, hazard ratio [HR] 2.7 for PFS, and p = 0.001, HR 20.2 for OS). CTR was independently associated with longer PFS (p = 0.019). Age ≥ 40 years, histopathological diagnosis, and recurrence did not achieve statistical significance. CONCLUSIONS: In this series of IDH-mutated LGGs, adjuvant treatment with RT, CT with temozolomide (TMZ), or the combination of both showed no significant advantage in terms of PFS and OS. Even in high-risk patients, the authors observed a similar significantly negative impact of adjuvant treatment on PFS and OS. These results underscore the importance of a CTR in LGG. Whether patients ≥ 40 years old should receive adjuvant treatment despite a CTR should be a matter of debate. A potential tumor dedifferentiation by administration of early TMZ, RT, or RT+CT in IDH-mutated LGG should be considered. However, these data are limited by the retrospective study design and the potentially heterogeneous indication for adjuvant treatment.

Counseling Patients with a Glioblastoma Amenable Only for Subtotal Resection: Results of a Multicenter Retrospective Assessment of Survival and Neurologic Outcome.

BACKGROUND: Patients with a glioblastoma (GB) amenable only for subtotal resection (STR) represent a challenge in patient counseling. Our objective was to assess impact of extent of resection (EoR) on survival and clinical outcome of these patients. METHODS: We performed a retrospective multicenter assessment. Patients receiving an intended STR in 3 centers with unilocular, primary, highly eloquent GB who received the same adjuvant treatment were included. We assessed EoR, neurologic outcome, and rate of complications. Progression-free survival (PFS) and overall survival (OS) were calculated with Kaplan-Meier estimations. We used 1% EoR and 1-cm3 steps to detect a threshold for a minimal EoR and residual tumor volume (RV) to be beneficial for survival and performed multivariate Cox regression models to assess its influence on PFS and OS. RESULTS: In total, 67 patients were included. EoR and RV were not significantly associated with PFS in multivariate Cox regression. Multivariate Cox regression model for OS revealed that volumetric EoR is a significant predictor for OS (P = 0.002, OR 0.982), same as RV (P = 0.007, OR 1.03), controlling for age, preoperative tumor volume, sex, and recurrent surgery. We found a significant benefit for OS if an EoR >60% or a RV <8 cm3 was reached. In the aforementioned multivariate Cox regression models, an EoR ≤60% and a RV ≥8 cm3 independently showed a significantly negative association with OS (P = 0.044, OR 1.96/P = 0.024, OR 2.07). CONCLUSIONS: In highly eloquent GB, EoR significantly matters for patients' OS. Also, potential RV should be considered when treating these patients. In cases with an expected RV above or an EoR below the aforementioned thresholds, open surgery should be carefully considered.

Evaluation of surgical decision making and resulting outcome in patients with highly eloquent glioblastoma: Results of a multicenter assessment.

INTRODUCTION: Treatment of glioblastoma(GB) patients amenable only for a subtotal resection(STR) is controversial. Since outcome of patients is affected by surgical management, our aim was to assess surgical decision making and resulting outcome in patients with highly eloquent GBs. PATIENTS AND METHODS: We retrospectively assessed GB patients with intended sub-total resection (STR) or stereotactic biopsy (STX) of 3 neurooncological centers operated between 2008 and 2013. A volumetric assessment of overall extent of resection(oEoR), presence of complications, new permanent neurological deficits(nPNDs) was performed. A central reviewer reassessed all cases blinded and gave recommendation on surgical management and on a potential EoR(pEoR) based on imaging data. We compared outcome data using Mann-Whitney-U-test and Sign-Rank-Test. Survival was assessed based on Kaplan-Meier-estimates. RESULTS: 97 patients were included. In 17 patients received STX, 70 patients a STR and 10 patients a near total resection (NTR, EoR>95%). Median OS was significantly different from STX patients only if NTR was reached (16 vs. 7 months, p=0.042). The central reviewer recommended a more aggressive strategy(NTR or STR resp.) in 41 patients and a less aggressive strategy in 13 patients. Overall, management recommendation was significantly different to clinical treatment (p<0.001). Mean pEoR was significantly higher than oEoR (85.7% vs. 71.3%, p=0.001). Regarding the different OR subgroups, no significant differences were found in the NTR group(12/13 ties, p=1) and in STX group (14/17 ties, p=0.125). In STR group, a significant difference was found (p=0.001). In 38/69 patients a NTR and in 13/77 patients a STX was recommended. CONCLUSION: Surgery in GB patients with intended STR requires precise preoperative planning since potential EoR is mainly underestimated. Especially, patients with lesions amenable for a NTR should not be missed.

Evaluating patients for psychosocial distress and supportive care needs based on health-related quality of life in primary brain tumors: a prospective multicenter analysis of patients with gliomas in an outpatient setting.

The association between health-related quality of life (HRQoL), psychosocial distress, and supportive care is in the focus of patient-centered neuro-oncology. We investigated the relationship between the aforementioned in glioma-patients to evaluate the association of these instruments and determine cut-off values for suitable HRQoL scales indicating a potential need for intervention. In an observational multi-center study, outpatients completed the Distress Thermometer (DT), EORTC Quality of Life Questionnaire (EORTC-QLQ-C30/BN20, HRQoL), and Supportive-Care-Needs-Survey-SF34-G (SCNS). Based on nine EORTC-function and selected -symptom scales items of the questionnaires were matched. Convergent validity of related single items and scores across the instruments was estimated. EORTC cut-off values were calculated. Data of 167 patients were analyzed. The strongest correlation of EORTC-QLQ-C30 and DT was found for cognitive function (cogf), global health status (GHS), emotional (emof), role function (rolef), future uncertainty (FU), fatigue, and between EORTC-QLQ-C30 and SCNS for FU, emof, rolef (r = |0.4-0.7|; p < 0.01). EORTC cut-off values of <54.2 (GHS/QoL) and <62.5 (emof) predicted a DT ≥ 6 (AUC 0.79, 0.85, p < 0.01). EORTC cut-off values of <70.8 (emof) and <52.8 (FU) predicted the need for supportive care (AUC 0.78, 0.85; p < 0.01). Worse EORTC-C30 scores correlate with higher DT and SCNS scores. With this exploratory assessment, cut-off values for EORTC-C30 subscores to predict distress and pathological SCNS-scores could be determined, which could influence patients' referral to further treatment. However, further prospective clinical trials are needed to confirm the clinical relevance of these cut-off values.

Low-grade Glioma Surgery in Intraoperative Magnetic Resonance Imaging: Results of a Multicenter Retrospective Assessment of the German Study Group for Intraoperative Magnetic Resonance Imaging.

BACKGROUND: The ideal treatment strategy for low-grade gliomas (LGGs) is a controversial topic. Additionally, only smaller single-center series dealing with the concept of intraoperative magnetic resonance imaging (iMRI) have been published. OBJECTIVE: To investigate determinants for patient outcome and progression-free-survival (PFS) after iMRI-guided surgery for LGGs in a multicenter retrospective study initiated by the German Study Group for Intraoperative Magnetic Resonance Imaging. METHODS: A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and field-strength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment. RESULTS: A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P < .01), whereas "failed" GTR did not differ significantly from intended subtotal-resection. Combined radiochemotherapy as adjuvant therapy was a negative prognostic factor (hazard ratio: 2.84, P < .01). Field strength of iMRI was not associated with PFS. In the binary logistic regression model, use of high-field iMRI (odds ratio: 0.51, P < .01) was positively and eloquent location (odds ratio: 1.99, P < .01) was negatively associated with GTR. GTR was not associated with increased rates of new permanent neurological deficits. CONCLUSION: GTR was an independent positive prognostic factor for PFS in LGG surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS. ABBREVIATIONS: EoR, extent of resectionFLAIR, fluid-attenuated inversion recoveryGTR, gross total resectionIDH1, isocitrate dehydrogenase 1iMRI, intraoperative magnetic resonance imagingLGG, low-grade gliomaMGMT, methylguanine-deoxyribonucleic acid methyltransferasenPND, new permanent neurological deficitOS, overall survivalPFS, progression-free survivalSTR, subtotal resectionWHO, World Health Organization.

Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA-enhanced intraoperative MRI at the border of contrast-enhancing lesions: a prospective study based on histopathological assessment.

OBJECT: High-grade gliomas (HGGs) and metastasis (MET) are the most common intracranial lesions in neurosurgical routine. Both of them show an invasive growth pattern extending into neural tissue beyond the margins of contrast enhancement on MRI. These "undetected" areas might be the origin of early tumor recurrence. The aim of the present study was to evaluate whether 5-aminolevulinic acid (5-ALA) fluorescence provides an additional benefit in detection of invasive tumor compared with intraoperative MRI (iMRI). METHODS: The authors prospectively enrolled 45 patients harboring contrast-enhancing lesions, in whom gross-total resection was intended. All patients had surgery in which iMRI and 5-ALA-guided resection were used following a specific protocol. First, a typical white light tumor resection was performed. Then, spatial location of residual fluorescence was marked. After that, an iMRI was performed and residual uptake of contrast was marked. Navigated biopsy samples were taken from all marked areas and from additional sites according to the surgeon's judgment. Cross tables and receiver operating characteristic curves were calculated, assessing performance of the imaging methods for tumor detection alone and for combined detection of infiltration zone and solid tumor (pathological tissue). Also, correlations of histopathological findings with imaging results were tested using Spearman rho. RESULTS: Thirty-four patients with HGGs and 11 with METs were enrolled. Three patients harboring a MET showed no 5-ALA enhancement and were excluded; 127 histopathological samples were harvested in the remaining patients. In HGG, sensitivity for tumor detection was significantly higher (p < 0.001) in 5-ALA (0.85) than in iMRI (0.41). Specificity was significantly lower (p < 0.001) in 5-ALA (0.43) than in iMRI (0.70). For detection of pathological tissue, 5-ALA significantly exceeded iMRI in specificity (0.80 vs 0.60) and sensitivity (0.91 vs 0.66) (p < 0.001). Imaging results of iMRI and 5-ALA did not correlate significantly; only 5-ALA showed a significant correlation with final histopathological diagnosis of the specimen and with typical histopathological features of HGGs. In METs, sensitivity and specificity for tumor detection were equal in 5-ALA and iMRI. Both techniques showed high values for sensitivity (0.75) and specificity (0.80). The odds ratio for detection of tumor tissue was 12 for both techniques. Concerning pathological tissue, no statistically significant difference was found either. Imaging results of iMRI and 5-ALA correlated significantly (p < 0.022), as with final histopathological diagnosis in METs. CONCLUSIONS: In METs, due to the rate of nonenhancing lesions, the authors found no additional benefit of 5-ALA compared with iMRI. In HGG, imaging results of 5-ALA and iMRI are significantly different at the border zone; 5-ALA has a higher sensitivity and a lower specificity for tumor detection than Gd-DTPA-enhanced iMRI. For detection of infiltrating tumor at the border of the resection cavity, 5-ALA is superior to Gd-DTPA-enhanced iMRI concerning both sensitivity and specificity. Thus, use of 5-ALA in addition to iMRI might be beneficial to maximize extent of resection. Clinical synergistic effects will be evaluated in a prospective randomized trial.

Which clinical variable influences health-related quality of life the most after spontaneous subarachnoid hemorrhage? Hunt and Hess scale, Fisher score, World Federation of Neurosurgeons score, Brussels coma score, and Glasgow coma score compared.

OBJECTIVE: To determine the strength of the correlation between the Hunt and Hess scale, Fisher score, Brussels coma score, World Federation of Neurosurgeons score, and Glasgow coma score and health-related quality of life. METHODS: Evaluable questionnaires from 236 patients (5.6 years [± standard deviation, 2.854 years] on average after hemorrhage) were included in the analysis. Quality of life was documented using the MOS-36 item short form health survey. Because of the ordinal nature of the variables, Kendall tau was used for calculation. Significance was established as P ≤ 0.05. RESULTS: Weak and very weak correlations were found in general (r ≤ 0.28). The strongest correlations were found between the Glasgow coma score and quality of life (r = 0.236, P = 0.0001). In particular, the "best verbal response" achieved the strongest correlations in the comparison, at r = 0.28/P = 0.0001. The Fisher score showed very weak correlations (r = -0.148/P = 0.012). The Brussels coma score (r = -0.216/P = 0.0001), Hunt and Hess scale (r = -0.197/P = 0.0001), and the World Federation of Neurosurgeons score (r = -0.185/P = 0.0001) revealed stronger correlations, especially in terms of the physical aspects of quality of life. CONCLUSIONS: The Glasgow coma scale revealed the strongest, and the Fisher score showed the weakest correlations. Thus the Fisher score, as an indicator of the severity of a hemorrhage, has little significance in terms of health-related quality of life.

Comparative study of application accuracy of two frameless neuronavigation systems: experimental error assessment quantifying registration methods and clinically influencing factors.

This study aimed at comparing the accuracy of two commercial neuronavigation systems. Error assessment and quantification of clinical factors and surface registration, often resulting in decreased accuracy, were intended. Active (Stryker Navigation) and passive (VectorVision Sky, BrainLAB) neuronavigation systems were tested with an anthropomorphic phantom with a deformable layer, simulating skin and soft tissue. True coordinates measured by computer numerical control were compared with coordinates on image data and during navigation, to calculate software and system accuracy respectively. Comparison of image and navigation coordinates was used to evaluate navigation accuracy. Both systems achieved an overall accuracy of <1.5 mm. Stryker achieved better software accuracy, whereas BrainLAB better system and navigation accuracy. Factors with conspicuous influence (P<0.01) were imaging, instrument replacement, sterile cover drape and geometry of instruments. Precision data indicated by the systems did not reflect measured accuracy in general. Surface matching resulted in no improvement of accuracy, confirming former studies. Laser registration showed no differences compared to conventional pointers. Differences between the two systems were limited. Surface registration may improve inaccurate point-based registrations but does not in general affect overall accuracy. Accuracy feedback by the systems does not always match with true target accuracy and requires critical evaluation from the surgeon.