MRI Treatment Response Assessment Maps (TRAMs) for differentiating recurrent glioblastoma from radiation necrosis.

BACKGROUND: MRI treatment response assessment maps (TRAMs) were introduced to distinguish recurrent malignant glioma from therapy related changes. TRAMs are calculated with two contrast-enhanced T1-weighted sequences and reflect the "late" wash-out (or contrast clearance) and wash-in of gadolinium. Vital tumor cells are assumed to produce a wash-out because of their high turnover rate and the associated hypervascularization, whereas contrast medium slowly accumulates in scar tissue. To examine the real value of this method, we compared TRAMs with the pathology findings obtained after a second biopsy or surgery when recurrence was suspected. METHODS: We retrospectively evaluated TRAMs in adult patients with histologically demonstrated glioblastoma, contrast-enhancing tissue and a pre-operative MRI between January 1, 2017, and December 31, 2022. Only patients with a second biopsy or surgery were evaluated. Volumes of the residual tumor, contrast clearance and contrast accumulation before the second surgery were analyzed. RESULTS: Among 339 patients with mGBM who underwent MRI, we identified 29 repeated surgeries/biopsies in 27 patients 59 ± 12 (mean ± standard deviation) years of age. Twenty-eight biopsies were from patients with recurrent glioblastoma histology, and only one was from a patient with radiation necrosis. We volumetrically evaluated the 29 pre-surgery TRAMs. In recurrent glioblastoma, the ratio of wash-out volume to tumor volume was 36 ± 17% (range 1-73%), and the ratio of the wash-out volume to the sum of wash-out and wash-in volumes was 48 ± 21% (range 22-92%). For the one biopsy with radiation necrosis, the ratios were 42% and 54%, respectively. CONCLUSIONS: Typical recurrent glioblastoma shows a > 20%ratio of the wash-out volume to the sum of wash-out and wash-in volumes. The one biopsy with radiation necrosis indicated that such necrosis can also produce high wash-out in individual cases. Nevertheless, the additional information provided by TRAMs increases the reliability of diagnosis.

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.

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.

Essentials in intraoperative indocyanine green videoangiography assessment for intracranial aneurysm surgery: conclusions from 295 consecutively clipped aneurysms and review of the literature.

OBJECT: Indocyanine green (ICG) videoangiography (VA) in cerebral aneurysm surgery allows confirmation of blood flow in parent, branching, and perforating vessels as well as assessment of remnant aneurysm parts after clip application. A retrospective analysis and review of the literature were conducted to determine the current essential advantages of ICG-VA in aneurysm surgery. METHODS: The authors retrospectively evaluated all aneurysm cases treated with the aid of intraoperative ICG-VA at a single institution between 2007 and 2013. They also analyzed the literature published since the initial description of ICG-VA in 2003. RESULTS: Two hundred forty-six procedures were performed in 232 patients harboring 295 aneurysms. The patients, whose mean age was 54 years, consisted of 159 women and 73 men. One hundred twenty-four surgeries were performed after subarachnoid hemorrhage, and 122 were performed for incidental aneurysms. Single aneurysms were clipped in 185 patients, and multiple aneurysms were clipped in 47 (mean aneurysm diameter 6.9 mm, range 2-40 mm). No complications associated with ICG-VA occurred. Intraoperative microvascular Doppler ultrasonography was performed before ICG-VA in all patients, and postoperative digital subtraction angiography (DSA) studies were available in 121 patients (52.2%) for retrospective comparative analysis. In 22 (9%) of 246 procedures, the clip position was modified intraoperatively as a consequence of ICG-VA. Stenosis of the parent vessels (16 procedures) or occlusion of the perforators (6 procedures), not detected by micro-Doppler ultrasonography, were the most common problems demonstrated on ICG-VA. In another 11 procedures (4.5%), residual perfusion of the aneurysm was observed and one or more additional clips were applied. Vessel stenosis or a compromised perforating artery occurred independent of aneurysm location and was about equally common in middle cerebral artery and anterior communicating artery aneurysms. In 2 procedures (0.8%), aneurysm puncture revealed residual blood flow within the lesion, which had not been detected by the ICG-VA. In the postoperative DSA studies, unexpected small (< 2 mm) aneurysm neck remnants, which had not been detected on intraoperative ICG-VA, were found in 11 (9.1%) of 121 patients. However, these remnants remained without consequence except in 1 patient with a 6-mm residual aneurysm dome, which was subsequently embolized with coils. CONCLUSIONS: In a large cohort of consecutive patients, ICG-VA proved to be a helpful intraoperative tool and led to a significant intraoperative clip modification rate of 15%. However, small, < 2-mm-wide neck remnants and a 6-mm residual aneurysm were missed by intraoperative ICG-VA in up to 10% of patients. Results in this study confirm that DSA is indispensable for postoperative quality assessment in complex aneurysm surgery.

Age-related degradation in the central nervous system: assessment with diffusion-tensor imaging and quantitative fiber tracking.

PURPOSE: To prospectively quantify differences in age-related changes in the diffusivity parameters and fiber characteristics between association, callosal, and projection fibers. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained. Diffusion-tensor imaging data with an isotropic voxel size of 1.9 mm(3) were acquired at 3 T in 38 healthy volunteers (age range, 18-88 years; 18 women). Quantitative fiber tracking was used to calculate fractional anisotropy (FA) and mean diffusivity values, eigenvalues (lambda(1), lambda(2), and lambda(3)), the number of fiber projections, and the number of fiber projections per voxel for three-dimensional reconstructed association, callosal, projection, and total brain fibers. Bivariate linear regression models were used to analyze correlations. Significant differences between correlations were assessed with the Hotelling-Williams test. RESULTS: For FA, the strongest degradation in association fibers and no significant changes in projection fibers were observed. The difference in correlation was significant (P = .002). The number of fiber projections and the number of fiber projections per voxel showed strong to moderate negative correlations that were dependent on age (P < .001) in the three fiber structures and total brain fibers, with the exception of the number of fiber projections per voxel in projection fibers, which showed no significant correlation. The decrease in the number of fiber projections was significantly greater (P = .043) in projection fibers than in total brain fibers, whereas the decrease in the number of fiber projections per voxel was significantly weaker (P = .005). Association fibers showed the largest changes per decade of age for FA (-1.13%) and for the number of fiber projections per voxel (-4.7%), whereas callosal fibers showed the largest changes per decade of age for the number of fiber projections (-10.4%). CONCLUSION: Quantitative fiber tracking enables identification of differences in diffusivity and fiber characteristics due to normal aging.

Volumetric assessment of glioma removal by intraoperative high-field magnetic resonance imaging.

OBJECTIVE: To investigate the contribution of high-field intraoperative magnetic resonance imaging (iMRI) for further reduction of tumor volume in glioma surgery. METHODS: From April 2002 to June 2003, 182 neurosurgical procedures were performed with a 1.5-T magnetic resonance system. Among patients who underwent these procedures, 47 patients with gliomas (14 with World Health Organization Grade I or II glioma, and 33 with World Health Organization Grade III or IV glioma) who underwent craniotomy were investigated retrospectively. Completeness of tumor resection and volumetric analysis were assessed with intraoperative imaging data. RESULTS: Surgical procedures were influenced by iMRI in 36.2% of operations, and surgery was continued to remove residual tumor. Additional further resection significantly reduced the percentage of final tumor volume compared with first iMRI scan (6.9% +/- 10.3% versus 21.4% +/- 13.8%; P < 0.001). Percentages of final tumor volume also were significantly reduced in both low-grade (10.3% +/- 11.5% versus 25.8% +/- 16.3%; P < 0.05) and high-grade gliomas (5.4% +/- 9.9% versus 19.5% +/- 13.0%; P < 0.001). Complete resection was achieved finally in 36.2% of all patients (low-grade, 57.1%; high-grade, 27.3%). Among the 17 patients in whom complete tumor resection was achieved, 7 complete resections (41.2%) were attributable to further tumor removal after iMRI. We did not encounter unexpected events attributable to high-field iMRI, and standard neurosurgical equipment could be used safely. CONCLUSION: Despite extended resections, introduction of high-field iMRI in conjunction with functional navigation did not translate into an increased risk of postoperative deficits. The use of high-field iMRI increased radicality in glioma surgery without additional morbidity.