Publications by authors named "Julia Furtner"

79 Publications

Influence of dexamethasone on visible 5-ALA fluorescence and quantitative protoporphyrin IX accumulation measured by fluorescence lifetime imaging in glioblastomas: is pretreatment obligatory before fluorescence-guided surgery?

J Neurosurg 2021 Oct 22:1-9. Epub 2021 Oct 22.

1Department of Neurosurgery.

Objective: Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is nowadays widely applied for improved resection of glioblastomas (GBMs). Initially, pretreatment with dexamethasone was considered to be essential for optimal fluorescence effect. However, recent studies reported comparably high rates of visible fluorescence in GBMs despite absence of dexamethasone pretreatment. Recently, the authors proposed fluorescence lifetime imaging (FLIM) for the quantitative analysis of 5-ALA-induced protoporphyrin IX (PpIX) accumulation. The aim of this study was thus to investigate the influence of dexamethasone on visible fluorescence and quantitative PpIX accumulation.

Methods: The authors prospectively analyzed the presence of visible fluorescence during surgery in a cohort of patients with GBMs. In this study, patients received dexamethasone preoperatively only if clinically indicated. One representative tumor sample was collected from each GBM, and PpIX accumulation was analyzed ex vivo by FLIM. The visible fluorescence status and mean FLIM values were correlated with preoperative intake of dexamethasone.

Results: In total, two subgroups with (n = 27) and without (n = 20) pretreatment with dexamethasone were analyzed. All patients showed visible fluorescence independent from preoperative dexamethasone intake. Furthermore, the authors did not find a statistically significant difference in the mean FLIM values between patients with and without dexamethasone pretreatment (p = 0.097).

Conclusions: In this first study to date, the authors found no significant influence of dexamethasone pretreatment on either visible 5-ALA fluorescence during GBM surgery or PpIX accumulation based on FLIM. According to these preliminary data, the authors recommend administering dexamethasone prior to fluorescence-guided surgery of GBMs only when clinically indicated.
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http://dx.doi.org/10.3171/2021.6.JNS21940DOI Listing
October 2021

Trabectedin for recurrent WHO grade 2 or 3 meningioma: a randomized phase 2 study of the EORTC Brain Tumor Group (EORTC-1320-BTG).

Neuro Oncol 2021 Oct 21. Epub 2021 Oct 21.

Department of Neuropathology, Otto-von-Guericke-University, Leipziger Straße 44, 39120 Magdeburg, Germany.

Background: No systemic treatment has been established for meningioma progressing after local therapies.

Methods: This randomized, multicenter, open-label, phase 2 study included adult patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.5 mg/m 2 every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS), objective radiological response, safety, quality of life (QoL) assessment using the QLQ-C30 and QLQ-BN20 questionnaires, and we performed tissue-based exploratory molecular analyses.

Results: Ninety patients were randomized (n=29 in LOC, n=61 in trabectedin arm). With 71 events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR]=1.42; 80% CI, 1.00-2.03; p=0.294) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) and 21.1% (95% CI, 11.3%-32.9%), respectively. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR=0.98; 95% CI, 0.54-1.76; p=0.94). Grade ≥3 adverse events occurred in 44.4% patients in the LOC and 59% of patients in the trabectedin arm. Enrolled patients had impeded global QoL and overall functionality and high fatigue before initiation of systemic therapy. DNA methylation class, performance status, presence of a relevant co-morbidity, steroid use, and right hemisphere involvement at baseline were independently associated with OS.

Conclusions: Trabectedin did not improve PFS and OS and was associated with higher toxicity than LOC treatment in patients with non-benign meningioma. Tumour DNA methylation class is an independent prognostic factor for OS.
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http://dx.doi.org/10.1093/neuonc/noab243DOI Listing
October 2021

Temporal muscle thickness as a prognostic marker in newly diagnosed glioblastoma patients: translational imaging analysis of the CENTRIC EORTC 26071-22072 and CORE trials.

Clin Cancer Res 2021 Oct 19. Epub 2021 Oct 19.

Department of Internal Medicine 1, Medical University of Vienna

Purpose: To investigate the prognostic relevance of temporal muscle thickness (TMT) as a surrogate parameter of skeletal muscle status in patients with newly diagnosed glioblastoma.

Methods: We assessed TMT in cranial magnetic resonance images (MRI) of 755 patients enrolled in the CENTRIC EORTC 26071-22072 study (n=508) and CORE study (n=247). We used predefined sex-specific TMT cutoff values to categorize "patients at risk of sarcopenia" and "patients with normal muscle status" at baseline. Furthermore, we categorized patients according to the extent of TMT loss over time. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using the Cox model adjusted for other exploratory variables.

Results: Patients at risk of sarcopenia (CENTRIC; n=158/508, 31.1%; CORE; n=87/247, 35.2%) at baseline had significantly higher risk of progression and death than patients with normal muscle status in both study cohorts (CENTRIC: PFS=HR 0.16, 95% CI: 0.12, 0.21, p<0.001; OS=HR 0.341, 95% CI: 0.27, 0.44, p < 0.001; CORE: PFS=HR 0.29, 95% CI: 0.21, 0.39, p<0.001; OS=HR 0.365, 95% CI: 0.27, 0.49, p<0.001). Similar results were obtained in multivariate Cox models adjusted for other important prognostic parameters. The extent of TMT loss over time showed a significant inverse correlation with median OS times in patients at risk for sarcopenia (CENTRIC: p<0.001, CORE: p=0.005), but not in patients with normal baseline muscle mass (CENTRIC: p=0.538, CORE: p=0.28).

Conclusion: TMT identifies ambulatory patients with newly diagnosed glioblastoma at risk for progressive sarcopenia and adverse outcomes. Early intervention may prevent skeletal muscle loss and improve patient outcome.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1987DOI Listing
October 2021

Glioblastoma Surgery Imaging-Reporting and Data System: Validation and Performance of the Automated Segmentation Task.

Cancers (Basel) 2021 Sep 17;13(18). Epub 2021 Sep 17.

Department of Clinical Epidemiology and Biostatistics, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands.

For patients with presumed glioblastoma, essential tumor characteristics are determined from preoperative MR images to optimize the treatment strategy. This procedure is time-consuming and subjective, if performed by crude eyeballing or manually. The standardized GSI-RADS aims to provide neurosurgeons with automatic tumor segmentations to extract tumor features rapidly and objectively. In this study, we improved automatic tumor segmentation and compared the agreement with manual raters, describe the technical details of the different components of GSI-RADS, and determined their speed. Two recent neural network architectures were considered for the segmentation task: nnU-Net and AGU-Net. Two preprocessing schemes were introduced to investigate the tradeoff between performance and processing speed. A summarized description of the tumor feature extraction and standardized reporting process is included. The trained architectures for automatic segmentation and the code for computing the standardized report are distributed as open-source and as open-access software. Validation studies were performed on a dataset of 1594 gadolinium-enhanced T1-weighted MRI volumes from 13 hospitals and 293 T1-weighted MRI volumes from the BraTS challenge. The glioblastoma tumor core segmentation reached a Dice score slightly below 90%, a patientwise F1-score close to 99%, and a 95th percentile Hausdorff distance slightly below 4.0 mm on average with either architecture and the heavy preprocessing scheme. A patient MRI volume can be segmented in less than one minute, and a standardized report can be generated in up to five minutes. The proposed GSI-RADS software showed robust performance on a large collection of MRI volumes from various hospitals and generated results within a reasonable runtime.
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http://dx.doi.org/10.3390/cancers13184674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465753PMC
September 2021

Prognostic factors in adult brainstem glioma: a tertiary care center analysis and review of the literature.

J Neurol 2021 Aug 3. Epub 2021 Aug 3.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Introduction: Adult brainstem gliomas (BSGs) are rare central nervous system tumours characterized by a highly heterogeneous clinical course. Median survival times range from 11 to 84 months. Beyond surgery, no treatment standard has been established. We investigated clinical and radiological data to assess prognostic features providing support for treatment decisions.

Methods: 34 BSG patients treated between 2000 and 2019 and aged ≥ 18 years at the time of diagnosis were retrospectively identified from the databases of the two largest Austrian Neuro-Oncology centres. Clinical data including baseline characteristics, clinical disease course, applied therapies, the outcome as well as neuroradiological and neuropathological findings were gathered and analysed. The tumour apparent diffusion coefficient (ADC), volumetry of contrast-enhancing and non-contrast-enhancing lesions were determined on magnetic resonance imaging scans performed at diagnosis.

Results: The median age at diagnosis was 38.5 years (range 18-71 years). Tumour progression occurred in 26/34 (76.5%) patients after a median follow up time of 19 months (range 0.9-236.2). Median overall survival (OS) and progression-free survival (PFS) was 24.1 months (range 0.9-236.2; 95% CI 18.1-30.1) and 14.5 months (range 0.7-178.5; 95% CI 5.1-23.9), respectively. Low-performance status, high body mass index (BMI) at diagnosis and WHO grading were associated with shorter PFS and OS at univariate analysis (p < 0.05, log rank test, respectively). ADC values below the median were significantly associated with shorter OS (14.9 vs 44.2 months, p = 0.018).

Conclusion: ECOG, BMI, WHO grade and ADC values were associated with the survival prognosis of BSG patients and should be included in the prognostic assessment.
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http://dx.doi.org/10.1007/s00415-021-10725-0DOI Listing
August 2021

An fMRI study of cognitive remediation in drug-naïve subjects diagnosed with first episode schizophrenia.

Wien Klin Wochenschr 2021 Jul 13. Epub 2021 Jul 13.

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Objective: The purpose of our functional magnetic resonance imaging (fMRI) study was to examine brain activity using a "1-back" paradigm as working memory task in drug-naïve subjects with first episode schizophrenia before and after cognitive remediation training.

Methods: In this study 15 drug-naïve first episode subjects who met DSM-IV criteria for schizophrenia were randomized to receive either atypical antipsychotics (AP, n = 8) or atypical antipsychotics in combination with cognitive remediation therapy (AP + CR, n = 7), 11 subjects had a follow-up fMRI examination after therapy (AP, n = 5; AP + CR, n = 6).

Results: In 4 of the 6 AP + CR subjects the number of activation clusters increased, whereas in 4 out of the 5 AP subjects the number of clusters decreased (mean number of clusters: AP + CR = 5.53, SD 12.79, AP = -5.8, SD 6.9).

Conclusion: In this randomized study the number of activation clusters during a working memory task increased after cognitive remediation training. Our data show that neurobiological effects of cognitive remediation can be identified in the very early course of schizophrenia.
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http://dx.doi.org/10.1007/s00508-021-01910-2DOI Listing
July 2021

On the cutting edge of glioblastoma surgery: where neurosurgeons agree and disagree on surgical decisions.

J Neurosurg 2021 Jul 9:1-11. Epub 2021 Jul 9.

1Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit, Cancer Center Amsterdam.

Objective: The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity. Standards are lacking for surgical decision-making, and previous studies indicate treatment variations. These shortcomings reflect the need to evaluate larger populations from different care teams. In this study, the authors used probability maps to quantify and compare surgical decision-making throughout the brain by 12 neurosurgical teams for patients with glioblastoma.

Methods: The study included all adult patients who underwent first-time glioblastoma surgery in 2012-2013 and were treated by 1 of the 12 participating neurosurgical teams. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to identify and compare patient treatment variations. Brain regions with different biopsy and resection results between teams were identified and analyzed for patient functional outcome and survival.

Results: The study cohort consisted of 1087 patients, of whom 363 underwent a biopsy and 724 a resection. Biopsy and resection decisions were generally comparable between teams, providing benchmarks for probability maps of resections and biopsies for glioblastoma. Differences in biopsy rates were identified for the right superior frontal gyrus and indicated variation in biopsy decisions. Differences in resection rates were identified for the left superior parietal lobule, indicating variations in resection decisions.

Conclusions: Probability maps of glioblastoma surgery enabled capture of clinical practice decisions and indicated that teams generally agreed on which region to biopsy or to resect. However, treatment variations reflecting clinical dilemmas were observed and pinpointed by using the probability maps, which could therefore be useful for quality-of-care discussions between surgical teams for patients with glioblastoma.
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http://dx.doi.org/10.3171/2020.11.JNS202897DOI Listing
July 2021

Glioblastoma Surgery Imaging-Reporting and Data System: Standardized Reporting of Tumor Volume, Location, and Resectability Based on Automated Segmentations.

Cancers (Basel) 2021 Jun 8;13(12). Epub 2021 Jun 8.

Department of Neurosurgery, Amsterdam University Medical Centers, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.

Treatment decisions for patients with presumed glioblastoma are based on tumor characteristics available from a preoperative MR scan. Tumor characteristics, including volume, location, and resectability, are often estimated or manually delineated. This process is time consuming and subjective. Hence, comparison across cohorts, trials, or registries are subject to assessment bias. In this study, we propose a standardized Glioblastoma Surgery Imaging Reporting and Data System (GSI-RADS) based on an automated method of tumor segmentation that provides standard reports on tumor features that are potentially relevant for glioblastoma surgery. As clinical validation, we determine the agreement in extracted tumor features between the automated method and the current standard of manual segmentations from routine clinical MR scans before treatment. In an observational consecutive cohort of 1596 adult patients with a first time surgery of a glioblastoma from 13 institutions, we segmented gadolinium-enhanced tumor parts both by a human rater and by an automated algorithm. Tumor features were extracted from segmentations of both methods and compared to assess differences, concordance, and equivalence. The laterality, contralateral infiltration, and the laterality indices were in excellent agreement. The native and normalized tumor volumes had excellent agreement, consistency, and equivalence. Multifocality, but not the number of foci, had good agreement and equivalence. The location profiles of cortical and subcortical structures were in excellent agreement. The expected residual tumor volumes and resectability indices had excellent agreement, consistency, and equivalence. Tumor probability maps were in good agreement. In conclusion, automated segmentations are in excellent agreement with manual segmentations and practically equivalent regarding tumor features that are potentially relevant for neurosurgical purposes. Standard GSI-RADS reports can be generated by open access software.
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http://dx.doi.org/10.3390/cancers13122854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229389PMC
June 2021

5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Neurosurgery, Medical University of Vienna, 1090 Vienna, Austria.

The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered.
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http://dx.doi.org/10.3390/cancers13112540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196836PMC
May 2021

Timing of glioblastoma surgery and patient outcomes: a multicenter cohort study.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab053. Epub 2021 Apr 8.

Amsterdam University Medical Centers, location VU University Medical Center, Neurosurgical Center Amsterdam, Amsterdam, Netherlands.

Background: The impact of time-to-surgery on clinical outcome for patients with glioblastoma has not been determined. Any delay in treatment is perceived as detrimental, but guidelines do not specify acceptable timings. In this study, we relate the time to glioblastoma surgery with the extent of resection and residual tumor volume, performance change, and survival, and we explore the identification of patients for urgent surgery.

Methods: Adults with first-time surgery in 2012-2013 treated by 12 neuro-oncological teams were included in this study. We defined time-to-surgery as the number of days between the diagnostic MR scan and surgery. The relation between time-to-surgery and patient and tumor characteristics was explored in time-to-event analysis and proportional hazard models. Outcome according to time-to-surgery was analyzed by volumetric measurements, changes in performance status, and survival analysis with patient and tumor characteristics as modifiers.

Results: Included were 1033 patients of whom 729 had a resection and 304 a biopsy. The overall median time-to-surgery was 13 days. Surgery was within 3 days for 235 (23%) patients, and within a month for 889 (86%). The median volumetric doubling time was 22 days. Lower performance status (hazard ratio [HR] 0.942, 95% confidence interval [CI] 0.893-0.994) and larger tumor volume (HR 1.012, 95% CI 1.010-1.014) were independently associated with a shorter time-to-surgery. Extent of resection, residual tumor volume, postoperative performance change, and overall survival were not associated with time-to-surgery.

Conclusions: With current decision-making for urgent surgery in selected patients with glioblastoma and surgery typically within 1 month, we found equal extent of resection, residual tumor volume, performance status, and survival after longer times-to-surgery.
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http://dx.doi.org/10.1093/noajnl/vdab053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156977PMC
April 2021

Favourable outcome of patients with breast cancer brain metastases treated with dual HER2 blockade of trastuzumab and pertuzumab.

Ther Adv Med Oncol 2021 22;13:17588359211009002. Epub 2021 Apr 22.

Division of Oncology, Department of Medicine 1, Medical University of Vienna, Austria.

Background: Dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab (TP) is a standard therapy of metastatic and localized HER2-positive breast cancer (BC), but its activity in breast cancer brain metastases (BCBM) is unknown.

Methods: Patients with HER2-positive BCBM were identified from the Vienna Brain Metastasis Registry and clinical data including patient characteristics, therapies and overall survival (OS) were obtained. Patients were grouped into 'TP', 'other-HER2-targeted therapy' and 'no-HER2-targeted therapy' according to received first-line systemic therapy after diagnosis of BCBM. Radiological re-assessment of intracranial lesions was performed in patients treated with TP as systemic first-line therapy according to RANO response criteria for brain metastases (BM).

Results: A total of 252 HER2-positive BC patients with BM were available for this analysis. Patients treated with TP as systemic first-line therapy after diagnosis of BM had a significantly longer OS compared with treatment with other-HER2-targeted therapy and no-HER2-targeted therapy (44 17 3 months,  < 0.001; log-rank test). Among radiologically re-assessed patients treated with TP as systemic first-line therapy after diagnosis of BM, 5/14 patients (35.7%) had complete intracranial remission (CR), 8/14 patients (57.1%) partial intracranial remission (PR), 1/14 patients (7.1%) stable intracranial disease (SD) and 0/14 patients (0.0%) progressive intracranial disease (PD) as best response resulting in an intracranial objective response rate (iORR) of 92.9% and an intracranial clinical benefit rate (iCBR) of 100.0%.

Conclusion: First-line therapy with dual HER2-inhibition of TP after BM diagnosis was associated with the longest median OS times in patients with BCBM.
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http://dx.doi.org/10.1177/17588359211009002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072867PMC
April 2021

Robust Deep Learning-based Segmentation of Glioblastoma on Routine Clinical MRI Scans Using Sparsified Training.

Radiol Artif Intell 2020 Sep 30;2(5):e190103. Epub 2020 Sep 30.

Department of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (R.S.E., M.v.H., M.G.W.); Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands (M.V., F.B., H.V., J.C.d.M.); Neurosurgical Center Amsterdam, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands (D.M.J.M., P.C.D.W.H.); Institutes of Neurology & Healthcare Engineering, University College London, London, England (F.B.); Faculty of Biology, Medicine & Health, Division of Cancer Sciences, University of Manchester and Christie NHS Trust, Manchester, England (M.v.H.); Neurosurgical Oncology Unit, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Humanitas Research Hospital, IRCCS, Milan, Italy (L.B., M.C.N., M.R., T.S.); Department of Neurologic Surgery, University of California-San Francisco, San Francisco, Calif (M.S.B., S.H.J.); Department of Neurosurgery, Medical University Vienna, Vienna, Austria (B.K., G.W.); Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Austria (J.F.); Department of Neurology & Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands (P.A.J.T.R.); and Department of Neurologic Surgery, Hôpital Lariboisière, Paris, France (E.M.).

Purpose: To improve the robustness of deep learning-based glioblastoma segmentation in a clinical setting with sparsified datasets.

Materials And Methods: In this retrospective study, preoperative T1-weighted, T2-weighted, T2-weighted fluid-attenuated inversion recovery, and postcontrast T1-weighted MRI from 117 patients (median age, 64 years; interquartile range [IQR], 55-73 years; 76 men) included within the Multimodal Brain Tumor Image Segmentation (BraTS) dataset plus a clinical dataset (2012-2013) with similar imaging modalities of 634 patients (median age, 59 years; IQR, 49-69 years; 382 men) with glioblastoma from six hospitals were used. Expert tumor delineations on the postcontrast images were available, but for various clinical datasets, one or more sequences were missing. The convolutional neural network, DeepMedic, was trained on combinations of complete and incomplete data with and without site-specific data. Sparsified training was introduced, which randomly simulated missing sequences during training. The effects of sparsified training and center-specific training were tested using Wilcoxon signed rank tests for paired measurements.

Results: A model trained exclusively on BraTS data reached a median Dice score of 0.81 for segmentation on BraTS test data but only 0.49 on the clinical data. Sparsified training improved performance (adjusted < .05), even when excluding test data with missing sequences, to median Dice score of 0.67. Inclusion of site-specific data during sparsified training led to higher model performance Dice scores greater than 0.8, on par with a model based on all complete and incomplete data. For the model using BraTS and clinical training data, inclusion of site-specific data or sparsified training was of no consequence.

Conclusion: Accurate and automatic segmentation of glioblastoma on clinical scans is feasible using a model based on large, heterogeneous, and partially incomplete datasets. Sparsified training may boost the performance of a smaller model based on public and site-specific data.Published under a CC BY 4.0 license.
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http://dx.doi.org/10.1148/ryai.2020190103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082349PMC
September 2020

How to predict the consistency and vascularity of meningiomas by MRI: an institutional experience.

Neurol Res 2021 Aug 27;43(8):693-699. Epub 2021 Apr 27.

Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.

Objective: In surgery for meningiomas tumor location and extension is currently the only MRI characteristic used to predict the feasibility and difficulty of the resection. Key surgical tumor characteristics such as consistency and vascularity remain obscured until the tumor is exposed. We therefore aimed to identify MRI sequences able to predict these crucial meningioma features.

Methods: We retrospectively reviewed our imaging database on cranial meningiomas and correlated MRI T2W, T1W, and FLAIR images with the consistency and vascularity reported by the surgeon in the operative notes. The reported consistency was classified into three grades [°I (soft) to °III (hard)]. Vascularity was grouped into little (°I) versus strong (°II). MRI signal intensity (SI) ratios were calculated with ROIs in the meningioma, the buccinator muscle and the frontal white matter.

Results: Of the 172 reviewed patients, 44 met the strict inclusion criteria with respect to the quality of the OR notes. The included meningiomas were located at the convexity (11/44), falcine (3/44), skull base (14/44), and posterior fossa (16/44). Twenty-four meningiomas (54.5%) were classified as consistency grade (°)I, seven (15.9%) °II, and thirteen (29.5%) °III. The grade of vascularization was little in 12 and strong in 14. The higher the ratio on T2W images the softer (p = 0.020) and the more vascularized (p = 0.001) the tumor presented.

Discussion: T2W MR images may be helpful to characterize meningiomas with regard to the expected consistency and grade of vascularization.
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http://dx.doi.org/10.1080/01616412.2021.1922171DOI Listing
August 2021

Tumor DNA methylation profiles correlate with response to anti-PD-1 immune checkpoint inhibitor monotherapy in sarcoma patients.

J Immunother Cancer 2021 03;9(3)

Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Background: Some sarcomas respond to immune checkpoint inhibition, but predictive biomarkers are unknown. We analyzed tumor DNA methylation profiles in relation to immunological parameters and response to anti-programmed cell death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy in patients with sarcoma.

Patients And Methods: We retrospectively identified adult patients who had received anti-PD-1 ICI therapy for recurrent sarcoma in two independent centers. We performed (1) blinded radiological response evaluation according to immune response evaluation criteria in solid tumors (iRECIST) ; (2) tumor DNA methylation profiling of >850,000 probes using Infinium MethylationEPIC microarrays; (3) analysis of tumor-infiltrating immune cell subsets (CD3, CD8, CD45RO, FOXP3) and intratumoral expression of immune checkpoint molecules (PD-L1, PD-1, LAG-3) using immunohistochemistry; and (4) evaluation of blood-based systemic inflammation scores (neutrophil-to-lymphocyte ratio, leucocyte-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio). Response to anti-PD-1 ICI therapy was bioinformatically and statistically correlated with DNA methylation profiles and immunological data.

Results: 35 patients (median age of 50 (23-81) years; 18 females, 17 males; 27 soft tissue sarcomas; 8 osteosarcomas) were included in this study. The objective response rate to anti-PD-1 ICI therapy was 22.9% with complete responses in 3 out of 35 and partial responses in 5 out of 35 patients. Adjustment of DNA methylation data for tumor-infiltrating immune cells resulted in identification of methylation differences between responders and non-responders to anti-PD-1 ICI. 2453 differentially methylated CpG sites (DMPs; 2043 with decreased and 410 with increased methylation) were identified. Clustering of sarcoma samples based on these DMPs revealed two main clusters: methylation cluster 1 (MC1) consisted of 73% responders and methylation cluster 2 (MC2) contained only non-responders to anti-PD-1 ICI. Median progression-free survival from anti-PD-1 therapy start of MC1 and MC2 patients was 16.5 and 1.9 months, respectively (p=0.001). Median overall survival of these patients was 34.4 and 8.0 months, respectively (p=0.029). The most prominent DNA methylation differences were found in pathways implicated in Rap1 signaling, focal adhesion, adherens junction Phosphoinositide 3-kinase (PI3K)-Akt signaling and extracellular matrix (ECM)-receptor interaction.

Conclusions: Our data demonstrate that tumor DNA methylation profiles may serve as a predictive marker for response to anti-PD-1 ICI therapy in sarcoma.
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http://dx.doi.org/10.1136/jitc-2020-001458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993298PMC
March 2021

Neuroimaging in dementia.

Wien Med Wochenschr 2021 Sep 3;171(11-12):274-281. Epub 2021 Mar 3.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Waehringerguertel 18-20, 1090, Vienna, Austria.

Despite the fact that the diagnosis of dementia is mainly based on clinical criteria, the role of neuroimaging is still expanding. Among other imaging techniques, magnetic resonance imaging (MRI) plays a core role in assisting with the differentiation between various dementia syndromes and excluding other underlying pathologies that cause dementia, such as brain tumors and subdural hemorrhages. This article gives an overview of the standard MRI protocol and of structural radiological reporting systems in patients who suffer from dementia. Moreover, it presents characteristic MRI features of the most common dementia subtypes.
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http://dx.doi.org/10.1007/s10354-021-00825-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397686PMC
September 2021

Prognostic Value of 5-ALA Fluorescence, Tumor Cell Infiltration and Angiogenesis in the Peritumoral Brain Tissue of Brain Metastases.

Cancers (Basel) 2021 Feb 3;13(4). Epub 2021 Feb 3.

Department of Neurosurgery, Medical University Vienna, Vienna General Hospital, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Complete resection is an indispensable treatment option in the management of brain metastases (BM). 5-aminolevulinic acid (5-ALA) fluorescence is used for improved intraoperative visualization of tumor tissue in gliomas and was recently observed in BM. We investigated the potential of 5-ALA fluorescence to visualize the infiltrative growth of BM in the peritumoral brain tissue and its histopathological correlate. Patients with BM resection after 5-ALA administration and collection of tissue samples from peritumoral brain tissue were included. Each tissue sample was histopathologically investigated for tumor cell infiltration and angiogenesis. Altogether, 88 samples were collected from the peritumoral brain tissue in 58 BM of 55 patients. Visible 5-ALA fluorescence was found in 61 (69%) of the samples, tumor infiltration in 19 (22%) and angiogenesis in 13 (15%) of samples. Angiogenesis showed a significant correlation with presence of fluorescence ( = 0.008). Moreover, angiogenesis was related to visible 5-ALA fluorescence and showed an association with patient prognosis since it was significantly correlated to shorter time to local progression/recurrence ( = 0.001) and lower one-year survival ( = 0.031). Consequently, angiogenesis in the peritumoral brain tissue of BM might be a novel prognostic marker for individualized perioperative treatment concepts in the future.
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http://dx.doi.org/10.3390/cancers13040603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913757PMC
February 2021

Evaluation of the Temporal Muscle Thickness as an Independent Prognostic Biomarker in Patients with Primary Central Nervous System Lymphoma.

Cancers (Basel) 2021 Feb 2;13(3). Epub 2021 Feb 2.

Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.

In this study, we assessed the prognostic relevance of temporal muscle thickness (TMT), likely reflecting patient's frailty, in patients with primary central nervous system lymphoma (PCNSL). In 128 newly diagnosed PCNSL patients TMT was analyzed on cranial magnetic resonance images. Predefined sex-specific TMT cutoff values were used to categorize the patient cohort. Survival analyses, using a log-rank test as well as Cox models adjusted for further prognostic parameters, were performed. The risk of death was significantly increased for PCNSL patients with reduced muscle thickness (hazard ratio of 3.189, 95% CI: 2-097-4.848, < 0.001). Importantly, the results confirmed that TMT could be used as an independent prognostic marker upon multivariate Cox modeling (hazard ratio of 2.504, 95% CI: 1.608-3.911, < 0.001) adjusting for sex, age at time of diagnosis, deep brain involvement of the PCNSL lesions, Eastern Cooperative Oncology Group (ECOG) performance status, and methotrexate-based chemotherapy. A TMT value below the sex-related cutoff value at the time of diagnosis is an independent adverse marker in patients with PCNSL. Thus, our results suggest the systematic inclusion of TMT in further translational and clinical studies designed to help validate its role as a prognostic biomarker.
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http://dx.doi.org/10.3390/cancers13030566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867149PMC
February 2021

5-ALA fluorescence for intraoperative visualization of spinal ependymal tumors and identification of unexpected residual tumor tissue: experience in 31 patients.

J Neurosurg Spine 2020 Dec 4:1-9. Epub 2020 Dec 4.

1Department of Neurosurgery.

Objective: Gross-total resection (GTR) is the treatment of choice in the majority of patients suffering from spinal ependymal tumors. In such tumors, the extent of resection (EOR) is considered the key factor for tumor recurrence and thus patient prognosis. However, incomplete resection is not uncommon and leads to increased risk of tumor recurrence. One important cause of incomplete resection is insufficient intraoperative visualization of tumor tissue as well as residual tumor tissue. Therefore, the authors investigated the value of 5-aminolevulinic acid (5-ALA)-induced fluorescence in a series of spinal ependymal tumors for improved tumor visualization.

Methods: Adult patients who underwent preoperative 5-ALA administration and surgery for a spinal ependymal tumor were included in this study. For each tumor, a conventional white-light microsurgical resection was performed. Additionally, the fluorescence status (strong, vague, or no fluorescence) and fluorescence homogeneity (homogenous or inhomogeneous) of the spinal ependymal tumors were evaluated during surgery using a modified neurosurgical microscope. In intramedullary tumor cases with assumed GTR, the resection cavity was investigated for potential residual fluorescing foci under white-light microscopy. In cases with residual fluorescing foci, these areas were safely resected and the corresponding samples were histopathologically screened for the presence of tumor tissue.

Results: In total, 31 spinal ependymal tumors, including 27 intramedullary tumors and 4 intradural extramedullary tumors, were included in this study. Visible fluorescence was observed in the majority of spinal ependymal tumors (n = 25, 81%). Of those, strong fluorescence was noted in 23 of these cases (92%), whereas vague fluorescence was present in 2 cases (8%). In contrast, no fluorescence was observed in the remaining 6 tumors (19%). Most ependymal tumors demonstrated an inhomogeneous fluorescence effect (17 of 25 cases, 68%). After assumed GTR in intramedullary tumors (n = 15), unexpected residual fluorescing foci within the resection cavity could be detected in 5 tumors (33%). These residual fluorescing foci histopathologically corresponded to residual tumor tissue in all cases.

Conclusions: This study indicates that 5-ALA fluorescence makes it possible to visualize the majority of spinal ependymal tumors during surgery. Unexpected residual tumor tissue could be detected with the assistance of 5-ALA fluorescence in approximately one-third of analyzed intramedullary tumors. Thus, 5-ALA fluorescence might be useful to increase the EOR, particularly in intramedullary ependymal tumors, in order to reduce the risk of tumor recurrence.
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http://dx.doi.org/10.3171/2020.6.SPINE20506DOI Listing
December 2020

Distributed changes of the functional connectome in patients with glioblastoma.

Sci Rep 2020 10 27;10(1):18312. Epub 2020 Oct 27.

Computational Imaging Research Lab, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.

Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resting-state functional magnetic resonance imaging to evaluate changes in global functional connectivity patterns in 15 patients with glioblastoma. For six patients we followed longitudinal trajectories of their functional connectome and structural tumour evolution using bi-monthly follow-up scans throughout treatment and disease progression. In all patients, unilateral tumour lesions were associated with inter-hemispherically symmetric network alterations, and functional proximity of tumour location was stronger linked to distributed network deterioration than anatomical distance. In the longitudinal subcohort of six patients, we observed patterns of network alterations with initial transient deterioration followed by recovery at first follow-up, and local network deterioration to precede structural tumour recurrence by two months. In summary, the impact of focal glioblastoma lesions on the functional connectome is global and linked to functional proximity rather than anatomical distance to tumour regions. Our findings further suggest a relevance for functional network trajectories as a possible means supporting early detection of tumour recurrence.
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http://dx.doi.org/10.1038/s41598-020-74726-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591862PMC
October 2020

High-resolution metabolic imaging of high-grade gliomas using 7T-CRT-FID-MRSI.

Neuroimage Clin 2020 15;28:102433. Epub 2020 Sep 15.

High-field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.

Objectives: Successful neurosurgical intervention in gliomas depends on the precision of the preoperative definition of the tumor and its margins since a safe maximum resection translates into a better patient outcome. Metabolic high-resolution imaging might result in improved presurgical tumor characterization, and thus optimized glioma resection. To this end, we validated the performance of a fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in a patient cohort of 23 high-grade gliomas (HGG).

Materials And Methods: We preoperatively measured 23 patients with histologically verified HGGs (17 male, 8 female, age 53 ± 15) with an MRSI sequence based on concentric ring trajectories with a 64 × 64 × 39 measurement matrix, and a 3.4 × 3.4 × 3.4 mm nominal voxel volume in 15 min. Quantification used a basis-set of 17 components including N-acetyl-aspartate (NAA), total choline (tCho), total creatine (tCr), glutamate (Glu), glutamine (Gln), glycine (Gly) and 2-hydroxyglutarate (2HG). The resultant metabolic images were evaluated for their reliability as well as their quality and compared to spatially segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast enhanced + edema, peritumoral) based on clinical data and also compared to histopathology (e.g., grade, IDH-status).

Results: Eighteen of the patient measurements were considered usable. In these patients, ten metabolites were quantified with acceptable quality. Gln, Gly, and tCho were increased and NAA and tCr decreased in nearly all tumor regions, with other metabolites such as serine, showing mixed trends. Overall, there was a reliable characterization of metabolic tumor areas. We also found heterogeneity in the metabolic images often continued into the peritumoral region. While 2HG could not be satisfyingly quantified, we found an increase of Glu in the contrast-enhancing region of IDH-wildtype HGGs and a decrease of Glu in IDH1-mutant HGGs.

Conclusions: We successfully demonstrated high-resolution 7T 3D-MRSI in HGG patients, showing metabolic differences between tumor regions and peritumoral tissue for multiple metabolites. Increases of tCho, Gln (related to tumor metabolism), Gly (related to tumor proliferation), as well as decreases in NAA, tCr, and others, corresponded very well to clinical tumor segmentation, but were more heterogeneous and often extended into the peritumoral region.
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http://dx.doi.org/10.1016/j.nicl.2020.102433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511769PMC
June 2021

Coronary artery bypass grafting and perioperative stroke: imaging of atherosclerotic plaques in the ascending aorta with ungated high-pitch CT-angiography.

Sci Rep 2020 08 17;10(1):13909. Epub 2020 Aug 17.

Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.

Perioperative stroke is a devastating complication after coronary artery bypass graft (CABG) surgery, with atherosclerosis of the ascending aorta as important risk factor. During surgical manipulation, detachment of plaques can lead to consecutive embolization into brain-supplying arteries. High-pitch computed tomography angiography (HP-CTA) represents a non-invasive imaging modality, which provides the opportunity for comprehensive imaging of the ascending aorta, including plaque detection and advanced characterization. In our present retrospective study on 719 individuals, who had undergone HP-CTA within 6 months prior to CABG, atherosclerotic disease of the ascending aorta was evaluated with respect to perioperative stroke rates. For image analysis, the ascending aorta was divided into a proximal and distal part, consisting of four segments, and evaluated for presence and distribution of calcified and mixed plaques. All patients with perioperative stroke presented with atherosclerotic disease of the ascending aorta. The stroke rate was significantly associated with the presence and extent of atherosclerotic disease. Patients burdened with mixed plaques presented with significantly higher perioperative stroke rates. This study demonstrates that HP-CTA allows accurate evaluation of plaque extent and composition in the ascending aorta, and therefore may improve risk stratification of stroke prior to CABG.
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http://dx.doi.org/10.1038/s41598-020-70830-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431556PMC
August 2020

Postoperative Magnetic Resonance Imaging After Surgery of Brain Metastases: Analysis of Extent of Resection and Potential Risk Factors for Incomplete Resection.

World Neurosurg 2020 11 27;143:e365-e373. Epub 2020 Jul 27.

Department of Neurosurgery, Medical University Vienna, Vienna, Austria; Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria. Electronic address:

Background: Extent of resection (EOR) constitutes a crucial factor for patient prognosis in surgery of brain metastases (BMs). According to early studies using postoperative magnetic resonance imaging (MRI), an unexpected residual tumor was not uncommon. Knowledge of potential risk factors for incomplete BM resection would be of major importance to optimize surgical strategies. The aim of this study was to evaluate EOR in a large cohort and analyze potential risk factors for incomplete BM resection.

Methods: Patients with BM resection and available postoperative MRI were included. Intraoperative estimation of EOR by the neurosurgeon was noted. Additionally, EOR was determined by postoperative MRI. Potential risk factors for incomplete resection were investigated.

Results: There were 145 patients with 163 BMs included. According to postoperative MRI, complete resection was achieved in 103 (63%) BMs, and resection was incomplete in 44 (27%) BMs. Postoperative MRI detected unexpected residual tumor in 32 (25%) BMs, and a misjudgment of the EOR by the neurosurgeon was found in 29% of cases. Regarding risk factors for incomplete resection, preoperative tumor volume was significantly larger in incompletely resected BMs compared with completely resected BMs (P = 0.011). All other analyzed risk factors had no significant influence on EOR.

Conclusions: Our data indicate that postoperative MRI is able to detect a high portion of unexpected residual tumors after surgery of BMs. Preoperative tumor volume in particular represents an important risk factor for incomplete resection, and hence neurosurgeons should pay special attention to avoid residual tumor tissue.
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http://dx.doi.org/10.1016/j.wneu.2020.07.150DOI Listing
November 2020

Bevacizumab-based treatment as salvage therapy in patients with recurrent symptomatic brain metastases.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa038. Epub 2020 Mar 16.

Clinical Cooperation Unit Neuro-Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: Salvage treatment for recurrent brain metastases (BM) of solid cancers is challenging due to the high symptomatic burden and the limited local treatment options.

Methods: Patients with recurrent BM with no option for further local therapies were retrospectively identified from BM databases. Bevacizumab-based treatment was initiated as a salvage treatment. Radiological imaging before and after bevacizumab-based treatment was reevaluated for treatment response using the Response Assessment in Neuro-Oncology (RANO) BM criteria.

Results: Twenty-two patients (36.4% male) with recurrent BM from breast cancer (40.9%), colorectal cancer (31.8%), or lung cancer (27.3%) were identified. Previous BM-directed therapies were radiosurgery in 16/22 (72.7%) patients, whole-brain radiotherapy in 8/22 (36.4%), and neurosurgical resection in 11/22 (50.0%). Time since BM diagnosis to initiation of bevacizumab treatment was 16.5 months. Of 22 patients 14 (63.6%) received concurrent systemic therapies. Neurological symptom improvement could be achieved in 14/22 (63.6%) and stabilization in 6/22 (27.3%) patients, resulting in a clinical benefit in 20/22 (90.9%) patients. Steroids could be reduced or stopped in 15/22 (68.2%) patients. Rate of improvement on T1-weighted imaging was 15/19 (78.9%; median reduction: -26.0% ± 32.9) and 19/20 (95%; median reduction: -36.2% ± 22.2) on T2-weighted FLAIR imaging. According to RANO-BM best response was partial response in 7/19 (36.8%), stable disease in 9/19 (47.3%), and progressive disease in 3/19 (15.7%) patients. Median CNS-specific progression-free survival was 8 months and median overall survival after initiation of bevacizumab treatment was 17 months.

Conclusions: Bevacizumab-based treatment had clinically relevant intracranial activity in the vast majority of patients suffering from recurrent, symptomatic BM. The data supports a prospective clinical trial of bevacizumab as a salvage treatment in BM.
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http://dx.doi.org/10.1093/noajnl/vdaa038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212911PMC
March 2020

Multi-Habitat Radiomics Unravels Distinct Phenotypic Subtypes of Glioblastoma with Clinical and Genomic Significance.

Cancers (Basel) 2020 Jun 27;12(7). Epub 2020 Jun 27.

Centerfor Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon 16419, Korea.

We aimed to evaluate the potential of radiomics as an imaging biomarker for glioblastoma (GBM) patients and explore the molecular rationale behind radiomics using a radio-genomics approach. A total of 144 primary GBM patients were included in this study (training cohort). Using multi-parametric MR images, radiomics features were extracted from multi-habitats of the tumor. We applied Cox-LASSO algorithm to build a survival prediction model, which we validated using an independent validation cohort. GBM patients were consensus clustered to reveal inherent phenotypic subtypes. GBM patients were successfully stratified by the radiomics risk score, a weighted sum of radiomics features, corroborating the potential of radiomics as a prognostic biomarker. Using consensus clustering, we identified three distinct subtypes which significantly differed in the prognosis ("heterogenous enhancing", "rim-enhancing necrotic", and "cystic" subtypes). Transcriptomic traits enriched in individual subtypes were in accordance with imaging phenotypes summarized by radiomics. For example, rim-enhancing necrotic subtype was well described by radiomics profiling (T2 autocorrelation and flat shape) and highlighted by the inflammatory genomic signatures, which well correlated to its phenotypic peculiarity (necrosis). This study showed that imaging subtypes derived from radiomics successfully recapitulated the genomic underpinnings of GBMs and thereby confirmed the feasibility of radiomics as an imaging biomarker for GBM patients with comprehensible biologic annotation.
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http://dx.doi.org/10.3390/cancers12071707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408408PMC
June 2020

Sex-Specific Differences in Primary CNS Lymphoma.

Cancers (Basel) 2020 Jun 16;12(6). Epub 2020 Jun 16.

Division of Neuropathology & Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria.

Sex-specific differences have been increasingly recognized in many human diseases including brain cancer, namely glioblastoma. Primary CNS lymphoma (PCNSL) is an exceedingly rare type of brain cancer that tends to have a higher incidence and worse outcomes in male patients. Yet, relatively little is known about the reasons that contribute to these observed sex-specific differences. Using a population-representative cohort of patients with PCNSL with dense magnetic resonance (MR) imaging and digital pathology annotation ( = 74), we performed sex-specific cluster and survival analyses to explore possible associations. We found three prognostically relevant clusters for females and two for males, characterized by differences in (i) patient demographics, (ii) tumor-associated immune response, and (iii) MR imaging phenotypes. Upon a multivariable analysis, an enhanced FoxP3+ lymphocyte-driven immune response was associated with a shorter overall survival particularly in female patients (HR 1.65, = 0.035), while an increased extent of contrast enhancement emerged as an adverse predictor of outcomes in male patients (HR 1.05, < 0.01). In conclusion, we found divergent prognostic constellations between female and male patients with PCNSL that suggest differential roles of tumor-associated immune response and MR imaging phenotypes. Our results further underline the importance of continued sex-specific analyses in the field of brain cancer.
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http://dx.doi.org/10.3390/cancers12061593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352658PMC
June 2020

Perioperative imaging in patients treated with resection of brain metastases: a survey by the European Association of Neuro-Oncology (EANO) Youngsters committee.

BMC Cancer 2020 May 12;20(1):410. Epub 2020 May 12.

Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Background: Neurosurgical resection represents an important treatment option in the modern, multimodal therapy approach of brain metastases (BM). Guidelines for perioperative imaging exist for primary brain tumors to guide postsurgical treatment. Optimal perioperative imaging of BM patients is so far a matter of debate as no structured guidelines exist.

Methods: A comprehensive questionnaire about perioperative imaging was designed by the European Association of Neuro-Oncology (EANO) Youngsters Committee. The survey was distributed to physicians via the EANO network to perform a descriptive overview on the current habits and their variability on perioperative imaging. Chi square test was used for dichotomous variables.

Results: One hundred twenty physicians worldwide responded to the survey. MRI was the preferred preoperative imaging method (93.3%). Overall 106/120 (88.3%) physicians performed postsurgical imaging routinely including MRI alone (62/120 [51.7%]), postoperative CT (29/120 [24.2%]) and MRI + CT (15/120 [12.5%]). No correlation of postsurgical MRI utilization in academic vs. non-academic hospitals (58/89 [65.2%] vs. 19/31 [61.3%], p = 0.698) was found. Early postoperative MRI within ≤72 h after resection is obtained by 60.8% of the participants. The most frequent reason for postsurgical imaging was to evaluate the extent of tumor resection (73/120 [60.8%]). In case of residual tumor, 32/120 (26.7%) participants indicated to adjust radiotherapy, 34/120 (28.3%) to consider re-surgery to achieve complete resection and 8/120 (6.7%) to evaluate both.

Conclusions: MRI was the preferred imaging method in the preoperative setting. In the postoperative course, imaging modalities and timing showed high variability. International guidelines for perioperative imaging with special focus on postoperative MRI to assess residual tumor are warranted to optimize standardized management and adjuvant treatment decisions for BM patients.
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http://dx.doi.org/10.1186/s12885-020-06897-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216695PMC
May 2020

Sarcopenia in Neurological Patients: Standard Values for Temporal Muscle Thickness and Muscle Strength Evaluation.

J Clin Med 2020 Apr 28;9(5). Epub 2020 Apr 28.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, 1090 Vienna, Austria.

Temporal muscle thickness (TMT) was investigated as a novel surrogate marker on MRI examinations of the brain, to detect patients who may be at risk for sarcopenia. TMT was analyzed in a retrospective, normal collective cohort ( = 624), to establish standard reference values. These reference values were correlated with grip strength measurements and body mass index (BMI) in 422 healthy volunteers and validated in a prospective cohort ( = 130) of patients with various neurological disorders. Pearson correlation revealed a strong association between TMT and grip strength (retrospective cohort, ρ = 0.746; < 0.001; prospective cohort, ρ = 0.649; < 0.001). A low or no association was found between TMT and age (retrospective cohort, R correlation coefficient 0.20; < 0.001; prospective cohort, ρ = -0.199; = 0.023), or BMI (retrospective cohort, ρ = 0.116; = 0.042; prospective cohort, ρ = 0.227; = 0.009), respectively. Male patients with temporal wasting and unintended weight loss, respectively, showed significantly lower TMT values ( = 0.04 and = 0.015, unpaired -test). TMT showed a high correlation with muscle strength in healthy individuals and in patients with various neurological disorders. Therefore, TMT should be integrated into the diagnostic workup of neurological patients, to prevent, delay, or treat sarcopenia.
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http://dx.doi.org/10.3390/jcm9051272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288067PMC
April 2020

Clinical characteristics and prognostic factors of adult patients with pilocytic astrocytoma.

J Neurooncol 2020 May 27;148(1):187-198. Epub 2020 Apr 27.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Introduction: Pilocytic astrocytoma (PA) is the most common primary brain neoplasm in children and treated in curative intent with gross total resection (GTR). However, PA is rare in adults, resulting in limited knowledge on the natural clinical course. This study aimed to describe the clinical course and identify prognostic factors of adult patients with PA.

Methods: 46 patients ≥ 18 years at diagnosis of PA and neurosurgical resection or biopsy between 2000 and 2018 were identified from the Neuro-Biobank of the Medical University of Vienna. In two cases with differing histopathological diagnosis at recurrence, DNA methylation analysis was performed using Illumina Infinium HumanMethylation850 BeadChip (850 k) arrays and the Molecular Neuropathology classifier. Clinico-pathological features were correlated with patient outcomes.

Results: Median age at diagnosis was 32.5 years (range: 19-75) and median Ki67 proliferation index was 2.8% (0.5-13.4%). Tumor location significantly correlated with resectability (p < 0.001). Tumor progression or recurrence was observed in 9/46 (19.6%) patients after a median follow up time of 53.0 months (range 0.5-300). 5-year overall and progression-free survival rates were 85.3% and 70.0%, respectively. 2/9 (22.2%) patients presented with histological changes in the recurrent tumor specimen. In detail, methylation classification redefined the histological diagnosis to anaplastic astrocytoma with piloid features and glioma in one patient, each. Age > 40 and higher body mass index (BMI) were associated with impaired progression-free and overall survival (p < 0.05).

Conclusions: Tumor recurrence or progression in adult PA patients was higher than the one reported in pediatric patients. Higher age and BMI were associated with impaired prognosis.
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http://dx.doi.org/10.1007/s11060-020-03513-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280326PMC
May 2020

Quantifying eloquent locations for glioblastoma surgery using resection probability maps.

J Neurosurg 2020 Apr 3;134(3):1091-1101. Epub 2020 Apr 3.

1Brain Tumor Center & Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands.

Objective: Decisions in glioblastoma surgery are often guided by presumed eloquence of the tumor location. The authors introduce the "expected residual tumor volume" (eRV) and the "expected resectability index" (eRI) based on previous decisions aggregated in resection probability maps. The diagnostic accuracy of eRV and eRI to predict biopsy decisions, resectability, functional outcome, and survival was determined.

Methods: Consecutive patients with first-time glioblastoma surgery in 2012-2013 were included from 12 hospitals. The eRV was calculated from the preoperative MR images of each patient using a resection probability map, and the eRI was derived from the tumor volume. As reference, Sawaya's tumor location eloquence grades (EGs) were classified. Resectability was measured as observed extent of resection (EOR) and residual volume, and functional outcome as change in Karnofsky Performance Scale score. Receiver operating characteristic curves and multivariable logistic regression were applied.

Results: Of 915 patients, 674 (74%) underwent a resection with a median EOR of 97%, functional improvement in 71 (8%), functional decline in 78 (9%), and median survival of 12.8 months. The eRI and eRV identified biopsies and EORs of at least 80%, 90%, or 98% better than EG. The eRV and eRI predicted observed residual volumes under 10, 5, and 1 ml better than EG. The eRV, eRI, and EG had low diagnostic accuracy for functional outcome changes. Higher eRV and lower eRI were strongly associated with shorter survival, independent of known prognostic factors.

Conclusions: The eRV and eRI predict biopsy decisions, resectability, and survival better than eloquence grading and may be useful preoperative indices to support surgical decisions.
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http://dx.doi.org/10.3171/2020.1.JNS193049DOI Listing
April 2020
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