Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 132
Filter
2.
Acta Neurochir (Wien) ; 166(1): 253, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847921

ABSTRACT

BACKGROUND/PURPOSE: Several periprocedural adjuncts for elective surgical aneurysm treatment have been introduced over the last 20 years to increase safety and efficacy. Besides the introduction of IONM in the late-1990s, ICG-videoangiography (ICG-VAG) since the mid-2000s and intraoperative CT-angiography/-perfusion (iCT-A/-P) since the mid-2010s are available. We aimed to clarify whether the introduction of ICG-VAG and iCT-A/-P resulted in our department in a stepwise improvement in the rate of radiologically detected postoperative ischemia, complete aneurysm occlusion and postoperative new deficits. METHODS: Patients undergoing microsurgical clip occlusion for unruptured anterior circulation aneurysms between 2000 and 2019 were included, with ICG-VAG since 2009 and iCT-A/-P (for selected cases) since 2016. Baseline characteristics and treatment-related morbidity/outcome focusing on differences between the three distinct cohorts (cohort-I: pre-ICG-VAG-era, cohort-II: ICG-VAG-era, cohort-III: ICG-VAG&iCT-A/-P-era) were analyzed. RESULTS: 1391 patients were enrolled (n = 74 were excluded), 779 patients were interventionally treated, 538 patients were surgically clipped by a specialized vascular team (cohort-I n = 167, cohort-II n = 284, cohort-III n = 87). Aneurysm size was larger in cohort-I (8.9 vs. 7.5/6.8 mm; p < 0.01) without differences concerning age (mean:55years), gender distribution (m: f = 1:2.6) and aneurysm location (MCA:61%, ICA:18%, ACA/AcomA:21%). There was a stepwise improvement in the rate of radiologically detected postoperative ischemia (16.2vs.12.0vs.8.0%; p = 0.161), complete aneurysm occlusion (68.3vs.83.6vs.91.0%; p < 0.01) and postoperative new deficits (10.8vs.7.7vs.5.7%; p = 0.335) from cohort-I to -III. After a mean follow-up of 12months, a median modified Rankin scale of 0 was achieved in all cohorts. DISCUSSION: Associated with periprocedural technical achievements, surgical outcome in elective anterior circulation aneurysm surgery has improved in our service during the past 20 years.


Subject(s)
Brain Ischemia , Intracranial Aneurysm , Postoperative Complications , Humans , Intracranial Aneurysm/surgery , Intracranial Aneurysm/diagnostic imaging , Male , Female , Middle Aged , Postoperative Complications/etiology , Aged , Brain Ischemia/prevention & control , Brain Ischemia/etiology , Brain Ischemia/diagnostic imaging , Elective Surgical Procedures/methods , Neurosurgical Procedures/methods , Surgical Instruments , Adult , Treatment Outcome , Cerebral Angiography/methods , Retrospective Studies , Microsurgery/methods , Computed Tomography Angiography/methods
3.
Acta Neurochir (Wien) ; 166(1): 170, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38581569

ABSTRACT

BACKGROUND: Patients with intracranial meningiomas frequently suffer from tumor-related seizures prior to resection, impacting patients' quality of life. We aimed to elaborate on incidence and predictors for seizures in a patient cohort with meningiomas WHO grade 2 and 3. METHODS: We retrospectively searched for patients with meningioma WHO grade 2 and 3 according to the 2021 WHO classification undergoing tumor resection. Clinical, histopathological and imaging findings were collected and correlated with preoperative seizure development. Tumor and edema volumes were quantified. RESULTS: Ninety-five patients with a mean age of 59.5 ± 16.0 years were included. Most tumors (86/95, 90.5%) were classified as atypical meningioma WHO grade 2. Nine of 95 tumors (9.5%) corresponded to anaplastic meningiomas WHO grade 3, including six patients harboring TERT promoter mutations. Meningiomas were most frequently located at the convexity in 38/95 patients (40.0%). Twenty-eight of 95 patients (29.5%) experienced preoperative seizures. Peritumoral edema was detected in 62/95 patients (65.3%) with a median volume of 9 cm3 (IR: 0-54 cm3). Presence of peritumoral edema but not age, tumor localization, TERT promoter mutation, brain invasion or WHO grading was associated with incidence of preoperative seizures, as confirmed in multivariate analysis (OR: 6.61, 95% CI: 1.18, 58.12, p = *0.049). Postoperative freedom of seizures was achieved in 91/95 patients (95.8%). CONCLUSIONS: Preoperative seizures were frequently encountered in about every third patient with meningioma WHO grade 2 or 3. Patients presenting with peritumoral edema on preoperative imaging are at particular risk for developing tumor-related seizures. Tumor resection was highly effective in achieving seizure freedom.


Subject(s)
Brain Edema , Meningeal Neoplasms , Meningioma , Humans , Adult , Middle Aged , Aged , Meningioma/complications , Meningioma/surgery , Meningioma/pathology , Retrospective Studies , Quality of Life , Seizures/etiology , Seizures/epidemiology , Risk Factors , Edema , Meningeal Neoplasms/complications , Meningeal Neoplasms/surgery , Meningeal Neoplasms/pathology , World Health Organization , Brain Edema/etiology , Brain Edema/surgery
4.
Neuro Oncol ; 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38466087

ABSTRACT

Brain tumor diagnostics have significantly evolved with the use of PET and advanced MRI techniques. In addition to anatomical MRI, these modalities may provide valuable information for several clinical applications such as differential diagnosis, delineation of tumor extent, prognostication, differentiation between tumor relapse and treatment-related changes, and the evaluation of response to anticancer therapy. In particular, joint recommendations of the RANO group, the EANO, and major European and American Nuclear Medicine societies highlighted that the additional clinical value of radiolabeled amino acids compared to anatomical MRI alone is outstanding and that its widespread clinical use should be supported. For advanced MRI and its steadily increasing use in clinical practice, the Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition provided more recently an updated acquisition protocol for the widely used dynamic susceptibility contrast perfusion MRI. Besides amino acid PET and perfusion MRI, other PET tracers and advanced MRI techniques (e.g., MR spectroscopy) are of considerable clinical interest and are increasingly integrated into everyday clinical practice. Nevertheless, these modalities have shortcomings which should be considered in clinical routine. This comprehensive review provides an overview of potential challenges, limitations and pitfalls associated with PET imaging and advanced MRI techniques in patients with gliomas or brain metastases. Despite these issues, PET imaging and advanced MRI techniques continue to play an indispensable role in brain tumor management. Acknowledging and mitigating these challenges through interdisciplinary collaboration, standardized protocols, and continuous innovation will further enhance the utility of these modalities in guiding optimal patient care.

6.
Radiol Artif Intell ; 6(1): e230095, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38166331

ABSTRACT

Purpose To develop a fully automated device- and sequence-independent convolutional neural network (CNN) for reliable and high-throughput labeling of heterogeneous, unstructured MRI data. Materials and Methods Retrospective, multicentric brain MRI data (2179 patients with glioblastoma, 8544 examinations, 63 327 sequences) from 249 hospitals and 29 scanner types were used to develop a network based on ResNet-18 architecture to differentiate nine MRI sequence types, including T1-weighted, postcontrast T1-weighted, T2-weighted, fluid-attenuated inversion recovery, susceptibility-weighted, apparent diffusion coefficient, diffusion-weighted (low and high b value), and gradient-recalled echo T2*-weighted and dynamic susceptibility contrast-related images. The two-dimensional-midsection images from each sequence were allocated to training or validation (approximately 80%) and testing (approximately 20%) using a stratified split to ensure balanced groups across institutions, patients, and MRI sequence types. The prediction accuracy was quantified for each sequence type, and subgroup comparison of model performance was performed using χ2 tests. Results On the test set, the overall accuracy of the CNN (ResNet-18) ensemble model among all sequence types was 97.9% (95% CI: 97.6, 98.1), ranging from 84.2% for susceptibility-weighted images (95% CI: 81.8, 86.6) to 99.8% for T2-weighted images (95% CI: 99.7, 99.9). The ResNet-18 model achieved significantly better accuracy compared with ResNet-50 despite its simpler architecture (97.9% vs 97.1%; P ≤ .001). The accuracy of the ResNet-18 model was not affected by the presence versus absence of tumor on the two-dimensional-midsection images for any sequence type (P > .05). Conclusion The developed CNN (www.github.com/neuroAI-HD/HD-SEQ-ID) reliably differentiates nine types of MRI sequences within multicenter and large-scale population neuroimaging data and may enhance the speed, accuracy, and efficiency of clinical and research neuroradiologic workflows. Keywords: MR-Imaging, Neural Networks, CNS, Brain/Brain Stem, Computer Applications-General (Informatics), Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning Algorithms Supplemental material is available for this article. © RSNA, 2023.


Subject(s)
Deep Learning , Humans , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Neuroimaging , Retrospective Studies , Multicenter Studies as Topic
7.
Biomedicines ; 12(1)2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38255293

ABSTRACT

BACKGROUND: The translocator protein (TSPO) has been proven to have great potential as a target for the positron emission tomography (PET) imaging of glioblastoma. However, there is an ongoing debate about the potential various sources of the TSPO PET signal. This work investigates the impact of the inoculation-driven immune response on the PET signal in experimental orthotopic glioblastoma. METHODS: Serial [18F]GE-180 and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) PET scans were performed at day 7/8 and day 14/15 after the inoculation of GL261 mouse glioblastoma cells (n = 24) or saline (sham, n = 6) into the right striatum of immunocompetent C57BL/6 mice. An additional n = 25 sham mice underwent [18F]GE-180 PET and/or autoradiography (ARG) at days 7, 14, 21, 28, 35, 50 and 90 in order to monitor potential reactive processes that were solely related to the inoculation procedure. In vivo imaging results were directly compared to tissue-based analyses including ARG and immunohistochemistry. RESULTS: We found that the inoculation process represents an immunogenic event, which significantly contributes to TSPO radioligand uptake. [18F]GE-180 uptake in GL261-bearing mice surpassed [18F]FET uptake both in the extent and the intensity, e.g., mean target-to-background ratio (TBRmean) in PET at day 7/8: 1.22 for [18F]GE-180 vs. 1.04 for [18F]FET, p < 0.001. Sham mice showed increased [18F]GE-180 uptake at the inoculation channel, which, however, continuously decreased over time (e.g., TBRmean in PET: 1.20 at day 7 vs. 1.09 at day 35, p = 0.04). At the inoculation channel, the percentage of TSPO/IBA1 co-staining decreased, whereas TSPO/GFAP (glial fibrillary acidic protein) co-staining increased over time (p < 0.001). CONCLUSION: We identify the inoculation-driven immune response to be a relevant contributor to the PET signal and add a new aspect to consider for planning PET imaging studies in orthotopic glioblastoma models.

8.
Neuro Oncol ; 26(5): 902-910, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38219019

ABSTRACT

BACKGROUND: Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in O6-methylguanine-DNA methyltransferase (MGMT) promoter-methylated glioblastoma treated with standard-of-care chemoradiotherapy with or without the integrin inhibitor cilengitide according to the modified response assessment in neuro-oncology (RANO) criteria of 2017. METHODS: Patients with ≥ 3 follow-up MRIs were included. Preliminary PD was defined as a ≥ 25% increase of the sum of products of perpendicular diameters (SPD) of a new or increasing lesion compared to baseline. PD required a second ≥25% increase of the SPD. Treatment-associated changes require stable or regressing disease after preliminary PD. RESULTS: Of the 424 evaluable patients, 221 patients (52%) were randomized into the cilengitide and 203 patients (48%) into the control arm. After chemoradiation with or without cilengitide, preliminary PD occurred in 274 patients (65%) during available follow-up, and 88 of these patients (32%) had treatment-associated changes, whereas 67 patients (25%) had PD. The remaining 119 patients (43%) had no further follow-up after preliminary PD. Treatment-associated changes were more common in the cilengitide arm than in the standard-of-care arm (24% vs. 17%; relative risk, 1.3; 95% CI, 1.004-1.795; P = .047). Treatment-associated changes occurred mainly during the first 6 months after RT (54% after 3 months vs. 13% after 6 months). CONCLUSIONS: With the modified RANO criteria, the rate of treatment-associated changes was low compared to previous studies in MGMT promoter-methylated glioblastoma. This rate was higher after cilengitide compared to standard-of-care treatment. Confirmatory scans, as recommended in the modified RANO criteria, were not always available reflecting current clinical practice.


Subject(s)
Brain Neoplasms , Chemoradiotherapy , DNA Methylation , DNA Modification Methylases , DNA Repair Enzymes , Glioblastoma , Promoter Regions, Genetic , Snake Venoms , Tumor Suppressor Proteins , Humans , Glioblastoma/genetics , Glioblastoma/diagnostic imaging , Glioblastoma/therapy , Glioblastoma/pathology , Glioblastoma/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Brain Neoplasms/therapy , Brain Neoplasms/pathology , DNA Modification Methylases/genetics , Chemoradiotherapy/methods , Female , Male , DNA Repair Enzymes/genetics , Middle Aged , Aged , Tumor Suppressor Proteins/genetics , Adult , Magnetic Resonance Imaging , Follow-Up Studies , Disease Progression , Prognosis , Aged, 80 and over
9.
Lancet Oncol ; 25(1): e29-e41, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38181810

ABSTRACT

Response Assessment in Neuro-Oncology (RANO) response criteria have been established and were updated in 2023 for MRI-based response evaluation of diffuse gliomas in clinical trials. In addition, PET-based imaging with amino acid tracers is increasingly considered for disease monitoring in both clinical practice and clinical trials. So far, a standardised framework defining timepoints for baseline and follow-up investigations and response evaluation criteria for PET imaging of diffuse gliomas has not been established. Therefore, in this Policy Review, we propose a set of criteria for response assessment based on amino acid PET imaging in clinical trials enrolling participants with diffuse gliomas as defined in the 2021 WHO classification of tumours of the central nervous system. These proposed PET RANO criteria provide a conceptual framework that facilitates the structured implementation of PET imaging into clinical research and, ultimately, clinical routine. To this end, the PET RANO 1.0 criteria are intended to encourage specific investigations of amino acid PET imaging of gliomas.


Subject(s)
Glioma , Neurology , Humans , Glioma/diagnostic imaging , Glioma/therapy , Amino Acids , Internal Medicine , Positron-Emission Tomography , Transcription Factors
10.
J Neurosurg Spine ; 40(2): 248-254, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37948685

ABSTRACT

OBJECTIVE: While adhesive incision drapes are widely used for reducing surgical site infection (SSI), evidence remains scarce on whether impregnated adhesive incision draping can further reduce the rate of SSI in spine surgery. METHODS: All patients treated surgically in the authors' high-volume university spine center from January 2018 to December 2021 were retrospectively evaluated and divided into cohorts treated before (the control cohort) and after (the study cohort) introduction of an iodophor-impregnated adhesive incision drape (instead of a standard nonimpregnated adhesive incision drape) at their institute. Epidemiological aspects, baseline characteristics, operative records, and rate and characteristics of postoperative SSI were analyzed and compared between cohorts. RESULTS: Two thousand two hundred seventy-nine consecutively treated patients were included, with an overall SSI rate of 0.5%. Baseline patient findings and surgical characteristics (including indication, localization, procedure, and duration of surgery) did not significantly differ between the 1125 patients in the control cohort and the 1154 patients in the study cohort. Uni- and multivariate analyses showed that use of an iodophor-impregnated adhesive incision drape was the only factor significantly associated with a lower risk of SSI. The SSI rate was significantly lower in the study cohort (0.2% vs 0.8%, p = 0.036). While germs of the skin microbiome such as Staphylococcus epidermidis and S. aureus were predominantly prevalent in both cohorts, fecal germs such as Enterococcus/Enterobacter species were found only in the control cohort and not in the study cohort. CONCLUSIONS: The use of iodophor-impregnated adhesive incision drapes in spine surgery can help to lower the rate of postoperative SSI and aid in reducing the risk of fecal germ infections.


Subject(s)
Adhesives , Surgical Wound Infection , Humans , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Retrospective Studies , Staphylococcus aureus , Iodophors
11.
Neuro Oncol ; 26(1): 166-177, 2024 01 05.
Article in English | MEDLINE | ID: mdl-37665776

ABSTRACT

BACKGROUND: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement. METHODS: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement. RESULTS: Among 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller postoperative tumor volumes were associated with more favorable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had a more favorable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables. CONCLUSIONS: The absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favorable outcome.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/diagnostic imaging , Glioblastoma/surgery , Glioblastoma/pathology , Retrospective Studies , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Prognosis , Magnetic Resonance Imaging/methods
12.
J Pain ; 25(2): 497-507, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37742905

ABSTRACT

Development of back pain is multifactorial, and it is not well understood which factors are the main drivers of the disease. We therefore applied a machine-learning approach to an existing large cohort study data set and sought to identify and rank the most important contributors to the presence of back pain amongst the documented parameters of the cohort. Data from 399 participants in the KORA-MRI (Cooperative health research in the region Augsburg-magnetic resonance imaging) (Cooperative Health Research in the Region Augsburg) study was analyzed. The data set included MRI images of the whole body, including the spine, metabolic, sociodemographic, anthropometric, and cardiovascular data. The presence of back pain was one of the documented items in this data set. Applying a machine-learning approach to this preexisting data set, we sought to identify the variables that were most strongly associated with back pain. Mediation analysis was performed to evaluate the underlying mechanisms of the identified associations. We found that depression and anxiety were the 2 most selected predictors for back pain in our model. Additionally, body mass index, spinal canal width and disc generation, medium and heavy physical work as well as cardiovascular factors were among the top 10 most selected predictors. Using mediation analysis, we found that the effects of anxiety and depression on the presence of back pain were mainly direct effects that were not mediated by spinal imaging. In summary, we found that psychological factors were the most important predictors of back pain in our cohort. This supports the notion that back pain should be treated in a personalized multidimensional framework. PERSPECTIVE: This article presents a wholistic approach to the problem of back pain. We found that depression and anxiety were the top predictors of back pain in our cohort. This strengthens the case for a multidimensional treatment approach to back pain, possibly with a special emphasis on psychological factors.


Subject(s)
Low Back Pain , Humans , Cohort Studies , Low Back Pain/psychology , Depression/diagnostic imaging , Back Pain/diagnostic imaging , Back Pain/epidemiology , Magnetic Resonance Imaging , Anxiety/diagnostic imaging , Anxiety/epidemiology , Lumbar Vertebrae/pathology
13.
Lancet Oncol ; 24(11): e438-e450, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37922934

ABSTRACT

Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.


Subject(s)
Brain Neoplasms , Glioma , Humans , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Prospective Studies , Biological Specimen Banks , Neoplasm Recurrence, Local/surgery , Glioma/diagnostic imaging , Glioma/surgery
14.
Neurooncol Adv ; 5(1): vdad135, 2023.
Article in English | MEDLINE | ID: mdl-38024243

ABSTRACT

Background: Treatment of hematological malignancies with chimeric antigen receptor modified T cells (CART) is highly efficient, but often limited by an immune effector cell-associated neurotoxicity syndrome (ICANS). As conventional MRI is often unremarkable during ICANS, we aimed to examine whether resting-state functional MRI (rsfMRI) is suitable to depict and quantify brain network alterations underlying ICANS in the individual patient. Methods: The dysconnectivity index (DCI) based on rsfMRI was longitudinally assessed in systemic lymphoma patients and 1 melanoma patient during ICANS and before or after clinical resolution of ICANS. Results: Seven lymphoma patients and 1 melanoma patient (19-77 years; 2 female) were included. DCI was significantly increased during ICANS with normalization after recovery (P = .0039). Higher ICANS grades were significantly correlated with increased DCI scores (r = 0.7807; P = .0222). DCI increase was most prominent in the inferior frontal gyrus and the frontal operculum (ie, Broca's area) and in the posterior parts of the superior temporal gyrus and the temporoparietal junction (ie, Wernicke's area) of the language-dominant hemisphere, thus reflecting the major clinical symptoms of nonfluent dysphasia and dyspraxia. Conclusions: RsfMRI-based DCI might be suitable to directly quantify the severity of ICANS in individual patients undergoing CAR T-transfusion. Besides ICANS, DCI seems a promising diagnostic tool to quantify functional brain network alterations during encephalopathies of different etiologies, in general.

15.
Curr Opin Neurol ; 36(6): 564-570, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37865849

ABSTRACT

PURPOSE OF REVIEW: Maximal safe tumor resection represents the current standard of care for patients with newly diagnosed diffuse gliomas. Recent efforts have highlighted the prognostic value of extent of resection measured as residual tumor volume in patients with isocitrate dehydrogenase (IDH)-wildtype and -mutant gliomas. Accurate assessment of such information therefore appears essential in the context of clinical trials as well as patient management. RECENT FINDINGS: Current recommendations for evaluation of extent of resection rest upon standardized postoperative MRI including contrast-enhanced T1-weighted sequences, T2-weighted/fluid-attenuated-inversion-recovery sequences, and diffusion-weighted imaging to differentiate postoperative tumor volumes from ischemia and nonspecific imaging findings. In this context, correct timing of postoperative imaging within the postoperative period is of utmost importance. Advanced MRI techniques including perfusion-weighted MRI and MR-spectroscopy may add further insight when evaluating residual tumor remnants. Positron emission tomography (PET) using amino acid tracers proves beneficial in identifying metabolically active tumor beyond anatomical findings on conventional MRI. SUMMARY: Future efforts will have to refine recommendations on postoperative assessment of residual tumor burden in respect to differences between IDH-wildtype and -mutant gliomas, and incorporate the emerging role of advanced imaging modalities like amino acid PET.


Subject(s)
Brain Neoplasms , Glioma , Humans , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Brain Neoplasms/surgery , Neoplasm, Residual/diagnostic imaging , Glioma/diagnostic imaging , Glioma/genetics , Glioma/surgery , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Amino Acids
16.
Acta Neuropathol Commun ; 11(1): 147, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37697350

ABSTRACT

TSPO is a promising novel tracer target for positron-emission tomography (PET) imaging of brain tumors. However, due to the heterogeneity of cell populations that contribute to the TSPO-PET signal, imaging interpretation may be challenging. We therefore evaluated TSPO enrichment/expression in connection with its underlying histopathological and molecular features in gliomas. We analyzed TSPO expression and its regulatory mechanisms in large in silico datasets and by performing direct bisulfite sequencing of the TSPO promotor. In glioblastoma tissue samples of our TSPO-PET imaging study cohort, we dissected the association of TSPO tracer enrichment and protein labeling with the expression of cell lineage markers by immunohistochemistry and fluorescence multiplex stains. Furthermore, we identified relevant TSPO-associated signaling pathways by RNA sequencing.We found that TSPO expression is associated with prognostically unfavorable glioma phenotypes and that TSPO promotor hypermethylation is linked to IDH mutation. Careful histological analysis revealed that TSPO immunohistochemistry correlates with the TSPO-PET signal and that TSPO is expressed by diverse cell populations. While tumor core areas are the major contributor to the overall TSPO signal, TSPO signals in the tumor rim are mainly driven by CD68-positive microglia/macrophages. Molecularly, high TSPO expression marks prognostically unfavorable glioblastoma cell subpopulations characterized by an enrichment of mesenchymal gene sets and higher amounts of tumor-associated macrophages.In conclusion, our study improves the understanding of TSPO as an imaging marker in gliomas by unveiling IDH-dependent differences in TSPO expression/regulation, regional heterogeneity of the TSPO PET signal and functional implications of TSPO in terms of tumor immune cell interactions.


Subject(s)
Glioblastoma , Glioma , Mesenchymal Stem Cells , Humans , Glioblastoma/diagnostic imaging , Glioblastoma/genetics , Tumor-Associated Macrophages , Macrophages , Receptors, GABA/genetics
17.
Nat Med ; 29(10): 2586-2592, 2023 10.
Article in English | MEDLINE | ID: mdl-37735561

ABSTRACT

Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype of diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses that control H3K27M+ tumors in major histocompatibility complex-humanized mice. Here we describe a first-in-human treatment with H3K27M-vac of eight adult patients with progressive H3K27M+ diffuse midline glioma on a compassionate use basis. Five patients received H3K27M-vac combined with anti-PD-1 treatment based on physician's discretion. Repeat vaccinations with H3K27M-vac were safe and induced CD4+ T cell-dominated, mutation-specific immune responses in five of eight patients across multiple human leukocyte antigen types. Median progression-free survival after vaccination was 6.2 months and median overall survival was 12.8 months. One patient with a strong mutation-specific T cell response after H3K27M-vac showed pseudoprogression followed by sustained complete remission for >31 months. Our data demonstrate safety and immunogenicity of H3K27M-vac in patients with progressive H3K27M+ diffuse midline glioma.


Subject(s)
Brain Neoplasms , Glioma , Vaccines , Humans , Adult , Animals , Mice , Brain Neoplasms/genetics , Brain Neoplasms/therapy , Histones/genetics , Glioma/genetics , Glioma/therapy , Mutation/genetics
18.
Eur J Nucl Med Mol Imaging ; 51(1): 206-217, 2023 12.
Article in English | MEDLINE | ID: mdl-37642702

ABSTRACT

PURPOSE: Tumor resection represents the first-line treatment for symptomatic meningiomas, and the extent of resection has been shown to be of prognostic importance. Assessment of tumor remnants with somatostatin receptor PET proves to be superior to intraoperative estimation with Simpson grading or MRI. In this preliminary study, we evaluate the prognostic relevance of postoperative PET for progression-free survival in meningiomas. METHODS: We conducted a post hoc analysis on a prospective patient cohort with resected meningioma WHO grade 1. Patients received postoperative MRI and [68Ga]Ga-DOTA-TATE PET/CT and were followed regularly with MRI surveillance scans for detection of tumor recurrence/progression. RESULTS: We included 46 patients with 49 tumors. The mean age at diagnosis was 57.8 ± 1.7 years with a male-to-female ratio of 1:1.7. Local tumor progression occurred in 7/49 patients (14%) after a median follow-up of 52 months. Positive PET was associated with an increased risk for progression (*p = 0.015) and a lower progression-free survival (*p = 0.029), whereas MRI was not. 20 out of 20 patients (100%) with negative PET findings remained recurrence-free. The location of recurrence/progression on MRI was adjacent to regions where postoperative PET indicated tumor remnants in all cases. Gross tumor volumes were higher on PET compared to MRI (*p = 0.032). CONCLUSION: Our data show that [68Ga]Ga-DOTA-TATE PET/CT is highly sensitive in revealing tumor remnants in patients with meningioma WHO grade 1. Negative PET findings were associated with a higher progression-free survival, thus improving surveillance. In patients with tumor remnants, additional PET can optimize adjuvant radiotherapy target planning of surgically resected meningiomas.


Subject(s)
Meningeal Neoplasms , Meningioma , Organometallic Compounds , Humans , Male , Female , Middle Aged , Positron Emission Tomography Computed Tomography , Meningioma/diagnostic imaging , Meningioma/surgery , Prognosis , Gallium Radioisotopes , Progression-Free Survival , Prospective Studies , Neoplasm Recurrence, Local/diagnostic imaging , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/surgery , World Health Organization , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL
...