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1.
Clin Cancer Res ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976016

ABSTRACT

PURPOSE: Recent artificial intelligence (AI) algorithms aided intraoperative decision-making via stimulated Raman histology (SRH) during craniotomy. This study assesses deep-learning algorithms for rapid intraoperative diagnosis from SRH images in small stereotactic-guided brain biopsies. It defines a minimum tissue sample size threshold to ensure diagnostic accuracy. EXPERIMENTAL DESIGN: A prospective single-center study examined 121 SRH images from 84 patients with unclear intracranial lesions undergoing stereotactic brain biopsy. Unprocessed, label-free samples were imaged with a portable fiber-laser Raman scattering microscope. Three deep-learning models were tested to (I) identify tumorous/non-tumorous tissue as qualitative biopsy control, (II) subclassify into high-grade glioma (CNS WHO grade 4), diffuse low-grade glioma (CNS WHO grade 2-3), metastases, lymphoma, or gliosis, and (III) molecularly subtype IDH- and 1p/19q-status of adult-type diffuse gliomas. Model predictions were evaluated against frozen section analysis and final neuropathological diagnoses. RESULTS: The first model identified tumorous/non-tumorous tissue with 91.7% accuracy. Sample size on slides impacted accuracy in brain tumor subclassification (81.6%, κ=0.72 frozen section; 73.9%, κ=0.61 second model), with SRH being smaller than H&E (4.1±2.5mm² vs 16.7±8.2mm², p<0.001). SRH images with over 140 high-quality patches and a mean squeezed sample of 5.26mm² yielded 89.5% accuracy in subclassification and 93.9% in molecular subtyping of adult-type diffuse gliomas. CONCLUSIONS: AI-based SRH image analysis is non-inferior to frozen section analysis in detecting and subclassifying brain tumors during small stereotactic-guided biopsies once a critical squeezed sample size is reached. Beyond frozen section analysis, it enables valid molecular glioma subtyping, allowing faster treatment decisions in the future. Refinement is needed for long-term application.

2.
Neurointervention ; 19(2): 92-101, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38880639

ABSTRACT

PURPOSE: Multi-sac aneurysms (MSAs) are not uncommon, but studies on their management are scarce. This study aims to evaluate and compare the feasibility, safety, and efficacy of MSAs treated with either clipping or coiling after interdisciplinary case discussion at our center. MATERIALS AND METHODS: We retrospectively analyzed MSAs treated by microsurgical clipping, coiling, or stent-assisted coiling (SAC). Treatment modalities, complications, angiographic results, and clinical outcomes were evaluated. Major neurological events were defined as a safety endpoint and complete occlusion as an efficacy endpoint. RESULTS: Ninety patients (mean age, 53.2±11.0 years; 73 [81.1%] females) with MSAs met our inclusion criteria (clipping, 50; coiling, 19; SAC, 21). Most aneurysms were located in the middle cerebral artery (48.9%). All clipping procedures were technically successful, but endovascular treatment failed in 1 coiling case, and a switch from coiling to SAC was required in 2 cases. The major event rates were 4.0% after clipping (1 major stroke and 1 intracranial hemorrhage) and 0% after endovascular therapy (P=0.667). At mid-term angiographic follow-up (mean 12.0±8.9 months), all 37 followed clipped aneurysms were completely occluded, compared to 8/17 (41.7%) after coiling and 11/15 (73.3%) after SAC (P<0.001). Coiling was significantly associated with incomplete occlusion in the adjusted analysis (odds ratio, 11.7; 95% confidence interval, 2.7-52.6; P=0.001). CONCLUSION: Both endovascular and surgical treatment were feasible and safe for MSAs. As coiling was associated with comparatively high recanalization rates, endovascular treatment may be preferred with stent support.

3.
Anticancer Res ; 44(7): 3005-3011, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38925840

ABSTRACT

BACKGROUND/AIM: Glioblastoma multiforme (GBM) is one of the most lethal types of brain cancer with a median survival of only 12 months due to its aggressiveness and lack of effective treatment options. Astrocytomas and oligodendrogliomas are classified as low-grade gliomas (LGG) and have the potential to progress into secondary GBM. YAP1 and TAZ are transcriptional co-activators of the hippo pathway and play an important role in tumorigenesis by controlling cell proliferation and differentiation. The aim of this study was to analyze whether YAP1 and TAZ influence the survival in patients with astrocytoma and oligodendroglioma. PATIENTS AND METHODS: A total of 22 patient samples of astrocytoma and 11 samples of oligodendroglioma were analyzed using real-time PCR. We utilized open-access data from The Cancer Genome Atlas (TCGA) focusing on "brain lower grade glioma". mRNA expression rates were used to validate our findings on survival analysis. RESULTS: Expression of YAP1 was twice as high in astrocytoma than in oligodendroglioma, whereas there was no difference in TAZ. In oligodendrogliomas, the expression of TAZ was higher in relapsed than in primary tumors. Patients with astrocytoma having a high YAP1 expression had a significantly shorter overall survival than patients with lower expression (median survival 161 vs. 86 months, p=0.0248). These findings were validated with survival analysis of TCGA data. CONCLUSION: High YAP1 expression shows a high correlation with poorer overall survival in LGG. YAP1 has higher levels of expression in astrocytomas than in oligodendrogliomas.


Subject(s)
Adaptor Proteins, Signal Transducing , Astrocytoma , Brain Neoplasms , Transcription Factors , YAP-Signaling Proteins , Humans , YAP-Signaling Proteins/metabolism , Astrocytoma/metabolism , Astrocytoma/genetics , Astrocytoma/pathology , Astrocytoma/mortality , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Female , Male , Transcription Factors/genetics , Transcription Factors/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/mortality , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Middle Aged , Adult , Neoplasm Grading , Oligodendroglioma/genetics , Oligodendroglioma/metabolism , Oligodendroglioma/pathology , Oligodendroglioma/mortality , Phosphoproteins/metabolism , Phosphoproteins/genetics , Aged , Prognosis , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Transcriptional Coactivator with PDZ-Binding Motif Proteins , Trans-Activators/genetics , Trans-Activators/metabolism , Young Adult
4.
Aging (Albany NY) ; 16(10): 9023-9046, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38809507

ABSTRACT

Intracerebral hemorrhage (ICH) can induce intensive oxidative stress, neuroinflammation, and brain cell apoptosis. However, conventional methods for ICH treatment have many disadvantages. There is an urgent need for alternative, effective therapies with minimal side effects. Pharmacodynamics experiment, molecular docking, network pharmacology, and metabolomics were adopted to investigate the treatment and its mechanism of Jingfang Granules (JFG) in ICH. In this study, we investigated the therapeutic effects of JFG on ICH using behavioral, brain water content and Magnetic resonance imaging experiments. However, the key active component and targets of JFG remain unknown. Here we verified that JFG was beneficial to improve brain injury after ICH. A network pharmacology analysis revealed that the anti-inflammatory effect of JFG is predominantly mediated by its activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway through Luteolin, (+)-Anomalin and Phaseol and their targeting of AKT1, tumor necrosis factorα (TNF-α), and interleukin-1ß (IL-1ß). Molecular docking analyses revealed an average affinity of -8.633 kcal/mol, indicating a binding strength of less than -5 kcal/mol. Metabolomic analysis showed that JFG exerted its therapeutic effect on ICH by regulating metabolic pathways, such as the metabolism of taurine and hypotaurine, biosynthesis of valine, leucine, and isoleucine. In conclusion, we demonstrated that JFG attenuated neuroinflammation and BBB injury subsequent to ICH by activating the PI3K/Akt signaling pathway.


Subject(s)
Blood-Brain Barrier , Cerebral Hemorrhage , Drugs, Chinese Herbal , Molecular Docking Simulation , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/metabolism , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Drugs, Chinese Herbal/pharmacology , Male , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , Neuroprotective Agents/pharmacology , Signal Transduction/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Mice , Rats , Anti-Inflammatory Agents/pharmacology , Network Pharmacology , Disease Models, Animal
5.
J Neurooncol ; 168(2): 333-343, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38696050

ABSTRACT

PURPOSE: To benchmark palliative care practices in neurooncology centers across Germany, evaluating the variability in palliative care integration, timing, and involvement in tumor board discussions. This study aims to identify gaps in care and contribute to the discourse on optimal palliative care strategies. METHODS: A survey targeting both German Cancer Society-certified and non-certified university neurooncology centers was conducted to explore palliative care frameworks and practices for neurooncological patients. The survey included questions on palliative care department availability, involvement in tumor boards, timing of palliative care integration, and use of standardized screening tools for assessing palliative burden and psycho-oncological distress. RESULTS: Of 57 centers contacted, 46 responded (81% response rate). Results indicate a dedicated palliative care department in 76.1% of centers, with palliative specialists participating in tumor board discussions at 34.8% of centers. Variability was noted in the initiation of palliative care, with early integration at the diagnosis stage in only 30.4% of centers. The survey highlighted a significant lack of standardized spiritual care assessments and minimal use of advanced care planning. Discrepancies were observed in the documentation and treatment of palliative care symptoms and social complaints, underscoring the need for comprehensive care approaches. CONCLUSION: The study highlights a diverse landscape of palliative care provision within German neurooncology centers, underscoring the need for more standardized practices and early integration of palliative care. It suggests the necessity for standardized protocols and guidelines to enhance palliative care's quality and uniformity, ultimately improving patient-centered care in neurooncology.


Subject(s)
Benchmarking , Palliative Care , Humans , Palliative Care/standards , Germany , Medical Oncology/standards , Surveys and Questionnaires , Brain Neoplasms/therapy , Practice Patterns, Physicians'/standards , Practice Patterns, Physicians'/statistics & numerical data
6.
Neuro Oncol ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695575

ABSTRACT

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and the rising availability of neuroimaging. While most exhibit non-malignant behaviour, a subset of meningiomas are biologically aggressive and lead to significant neurological morbidity and mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) working group. There also remains clinical equipoise on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas (ICOM) including field-leading experts, have prepared a comprehensive consensus narrative review directed towards clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality of life studies, and management strategies for unique meningioma patient populations. In each section we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

7.
J Clin Neurosci ; 124: 94-101, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38678972

ABSTRACT

OBJECTIVE: Overdrainage and frequent reprogramming are common problems with programmable valves after ventriculoperitoneal shunt surgery for idiopathic normal pressure hydrocephalus (iNPH). Non-adjustable, flow-regulated valves offer a potential solution to these problems, but there is limited data on their efficacy. This study will evaluate neurological improvement and overdrainage rates within one year of treatment with a flow-regulated valve. PATIENTS AND METHODS: This prospective study analyzes 45 iNPH patients (median age: 73 years) treated with a flow-regulated valve. Clinical evaluations were performed at baseline, postoperatively, and at 3, 6, and 12 months after surgery. The primary efficacy endpoint was improvement of at least 5 points on the iNPH grading scale at follow-up. The safety endpoint was radiographic evidence of overdrainage. RESULTS: All patients presented with gait disturbance, 35 (78 %) had cognitive impairment, and 35 (78 %) had urinary incontinence. The median duration of symptoms was 24 months. The total iNPH score improved in 33/41 (81 %) at 3 months, in 29/34 (85 %) at 6 months, and in 22/29 (64 %) at 12 months. Overall, 40/45 (89 %) patients had a significant improvement on the iNPH scale. Secondary worsening of symptoms after initial improvement was observed in 5 (11 %) patients. Overdrainage occurred in one patient (2 %) requiring surgical evacuation. CONCLUSION: Treatment of iNPH patients with flow-regulated valves resulted in a good neurological outcome with minimal rates of overdrainage. These results are encouraging and justify the clinical use of these valve types.


Subject(s)
Hydrocephalus, Normal Pressure , Ventriculoperitoneal Shunt , Humans , Hydrocephalus, Normal Pressure/surgery , Aged , Female , Male , Prospective Studies , Aged, 80 and over , Ventriculoperitoneal Shunt/methods , Treatment Outcome , Middle Aged , Follow-Up Studies
8.
Neurosurgery ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587396

ABSTRACT

BACKGROUND AND OBJECTIVES: Surgical treatment is an integral component of multimodality management of metastatic spine disease but must be balanced against the risk of surgery-related morbidity and mortality, making tailored surgical counseling a clinical challenge. The aim of this study was to investigate the potential predictive value of the preoperative performance status for surgical outcome in patients with spinal metastases. METHODS: Performance status was determined using the Karnofsky Performance Scale (KPS), and surgical outcome was classified as "favorable" or "unfavorable" based on postoperative changes in neurological function and perioperative complications. The correlation between preoperative performance status and surgical outcome was assessed to determine a KPS-related performance threshold. RESULTS: A total of 463 patients were included. The mean age was 63 years (range: 22-87), and the mean preoperative KPS was 70 (range: 30-100). Analysis of clinical outcome in relation to the preoperative performance status revealed a KPS threshold between 40% and 50% with a relative risk of an unfavorable outcome of 65.7% in KPS ≤40% compared with the relative chance for a favorable outcome of 77.1% in KPS ≥50%. Accordingly, we found significantly higher rates of preserved or restored ambulatory function in KPS ≥50% (85.7%) than in KPS ≤40% (48.6%; P < .001) as opposed to a significantly higher risk of perioperative mortality in KPS ≤40% (11.4%) than in KPS ≥50% (2.1%, P = .012). CONCLUSION: Our results underline the predictive value of the KPS in metastatic spine patients for counseling and decision-making. The study suggests an overall clinical benefit of surgical treatment of spinal metastases in patients with a preoperative KPS score ≥50%, while a high risk of unfavorable outcome outweighing the potential clinical benefit from surgery is encountered in patients with a KPS score ≤40%.

10.
Chirurgie (Heidelb) ; 95(4): 274-279, 2024 Apr.
Article in German | MEDLINE | ID: mdl-38334774

ABSTRACT

BACKGROUND: In brain tumor surgery a personalized surgical approach is crucial to achieve a maximum safe tumor resection. The extent of resection decisively depends on the histological diagnosis. Stimulated Raman histology (SRH), a fiber laser-based optical imaging method, offers the possibility for evaluation of an intraoperative diagnosis in a few minutes. OBJECTIVE: To provide an overview on the applications of SRH in neurosurgery and transference of the technique to other surgical disciplines. METHODS: Description of the technique and review of the current literature on SRH. RESULTS: The SRH technique was successfully used in multiple neuro-oncological tumor entities. Initial pilot projects showed the potential for analysis of extracranial tumors. CONCLUSION: The use of SRH provides a near real-time diagnosis with high diagnostic accuracy and provides further developmental potential to improve personalized tumor surgery.


Subject(s)
Brain Neoplasms , Neurosurgery , Humans , Neurosurgical Procedures/methods , Optical Imaging , Histological Techniques , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery
11.
Cureus ; 16(1): e52474, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38371129

ABSTRACT

INTRODUCTION: Seizures are a common symptom of supratentorial meningiomas with pre- and postoperative seizure rates of approximately 30% and 12%, respectively, especially in parasagittal and convexity meningiomas. Less is known about the association between seizures and posterior fossa meningiomas. This study evaluates the prevalence, potential causes, and outcomes of seizures in patients who have undergone surgery for posterior fossa meningioma. METHODS: This is a retrospective, observational, single-center study of consecutive patients who underwent surgical resection of posterior fossa meningiomas between 2009 and 2017. We retrospectively identified patients with seizures and analyzed patient demographics, tumor characteristics, and procedural characteristics. RESULTS: A total of 44 patients (mean age: 59.8 ± 13.5 years) were included. Twenty-six tumors were located at the cerebellar convexity and tentorium (59.1%), 12 at the cerebellopontine angle (27.3%), four at the clivus (9.1%), and two at the foramen magnum (4.5%). Seizures were the presenting symptom of cerebellar meningioma in two patients. Patients were seizure-free after surgery. Three patients had their first seizure after surgery (interval between surgery and first seizure: two days to 17 months). Analysis of these three patients revealed possible causes of postoperative seizures: radiation necrosis and edema, hyponatremia, and preoperative hydrocephalus. In all patients with postoperative seizures, long-term seizure control was achieved with the administration of antiepileptic drugs. CONCLUSIONS: The incidence of seizures in patients with posterior fossa meningiomas is relatively low. Antiepileptic drugs can help to achieve seizure control.

12.
J Neurosci Res ; 102(1): e25283, 2024 01.
Article in English | MEDLINE | ID: mdl-38284859

ABSTRACT

Spinal cord injury (SCI) is a highly disabling neurological disorder that is difficult to treat due to its complex pathophysiology and nerve regeneration difficulties. Hence, effective SCI treatments are necessary. Olfactory ensheathing cells (OECs), glial cells derived from the olfactory bulb or mucosa, are ideal candidates for SCI treatment because of their neuroprotective and regenerative properties, ample supply, and convenience. In vitro, animal model, and human trial studies have reported discoveries on OEC transplantation; however, shortcomings have also been demonstrated. Recent studies have optimized various OEC transplantation strategies, including drug integration, biomaterials, and gene editing. This review aims to introduce OECs mechanisms in repairing SCI, summarize the research progress of OEC transplantation-optimized strategies, and provide novel research ideas for SCI treatment.


Subject(s)
Gene Editing , Spinal Cord Injuries , Animals , Humans , Nerve Regeneration , Neuroglia , Neuroprotection , Spinal Cord Injuries/therapy
13.
Laryngorhinootologie ; 103(3): 176-186, 2024 03.
Article in German | MEDLINE | ID: mdl-38128578

ABSTRACT

The treatment of vestibular schwannomas (VS) has always posed a challenge for physicians. Three essential treatment principles are available: wait-and-scan, surgery, and stereotactic radiotherapy. In addition to the type of treatment, decisions must be made regarding the optimal timing of therapy, the combination of different treatment modalities, the potential surgical approach, and the type and intensity of radiation. Factors influencing the therapy decision include tumor location and size or stage, patient age, comorbidities, symptoms, postoperative hearing rehabilitation options, patient preferences, and, not least, the experience of the surgeons and the personnel and technical capabilities of the clinical site. This article begins with a brief overview of vestibular schwannomas, then outlines the fundamental interdisciplinary treatment options, and finally discusses the ENT (ear, nose, and throat)-relevant factors in the therapy decision.


Subject(s)
Neuroma, Acoustic , Radiosurgery , Humans , Hearing , Neuroma, Acoustic/diagnosis , Neuroma, Acoustic/therapy , Treatment Outcome
14.
Analyst ; 148(23): 6109-6119, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37927114

ABSTRACT

Label-free identification of tumor cells using spectroscopic assays has emerged as a technological innovation with a proven ability for rapid implementation in clinical care. Machine learning facilitates the optimization of processing and interpretation of extensive data, such as various spectroscopy data obtained from surgical samples. The here-described preclinical work investigates the potential of machine learning algorithms combining confocal Raman spectroscopy to distinguish non-differentiated glioblastoma cells and their respective isogenic differentiated phenotype by means of confocal ultra-rapid measurements. For this purpose, we measured and correlated modalities of 1146 intracellular single-point measurements and sustainingly clustered cell components to predict tumor stem cell existence. By further narrowing a few selected peaks, we found indicative evidence that using our computational imaging technology is a powerful approach to detect tumor stem cells in vitro with an accuracy of 91.7% in distinct cell compartments, mainly because of greater lipid content and putative different protein structures. We also demonstrate that the presented technology can overcome intra- and intertumoral cellular heterogeneity of our disease models, verifying the elevated physiological relevance of our applied disease modeling technology despite intracellular noise limitations for future translational evaluation.


Subject(s)
Glioblastoma , Spectrum Analysis, Raman , Humans , Cell Differentiation , Algorithms , Machine Learning
16.
J Neurooncol ; 164(3): 749-755, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37787906

ABSTRACT

PURPOSE: The AVAglio trial reported a significant survival benefit for first line bevacizumab treatment in patients with IDH wildtype glioblastoma of the proneural gene expression subtype. We here aim to replicate these findings in an independent trial cohort. METHODS: We evaluate the treatment benefit of bevacizumab according to gene expression subtypes of pretreatment tumor samples (n = 123) in the GLARIUS trial (NCT00967330) for MGMT unmethylated glioblastoma patients with Kaplan-Meier analyses, log-rank tests and Cox regression models. RESULTS: Employing the Phillips classifier, bevacizumab conferred a significant PFS advantage in patients with proneural IDH wild-type tumors (10.4 vs. 6.0 months, p = 0.002), but no OS advantage (16.4 vs. 17.4 months, p = 0.6). Multivariable analysis adjusting for prognostic covariates confirmed the absence of a significant OS advantage from bevacizumab (hazard ratio, 1.05, 95% CI, 0.42 to 2.64; p = 0.14). Further, there was no interaction between the proneural subtype and treatment arm (p = 0.15). These results were confirmed in analyses of tumor subgroups according to the Verhaak classifier. CONCLUSION: In contrast to AVAglio, glioblastoma gene expression subgroups were not associated with a differential OS benefit from first-line bevacizumab in the GLARIUS trial.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Bevacizumab/therapeutic use , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/pathology , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Kaplan-Meier Estimate , Prognosis
17.
Nat Commun ; 14(1): 6279, 2023 10 07.
Article in English | MEDLINE | ID: mdl-37805627

ABSTRACT

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway  in neoplasia.


Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Meningioma/genetics , Ligands , Signal Transduction , Meningeal Neoplasms/genetics
18.
J Neurooncol ; 164(3): 607-616, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37728779

ABSTRACT

PURPOSE: In the randomized CeTeG/NOA-09 trial, lomustine/temozolomide (CCNU/TMZ) was superior to TMZ therapy regarding overall survival (OS) in MGMT promotor-methylated glioblastoma. Progression-free survival (PFS) and pseudoprogression rates (about 10%) were similar in both arms. Further evaluating this discrepancy, we analyzed patterns of postprogression survival (PPS) and MRI features at first progression according to modified RANO criteria (mRANO). METHODS: We classified the patients of the CeTeG/NOA-09 trial according to long vs. short PPS employing a cut-off of 18 months and compared baseline characteristics and survival times. In patients with available MRIs and confirmed progression, the increase in T1-enhancing, FLAIR hyperintense lesion volume and the change in ADC mean value of contrast-enhancing tumor upon progression were determined. RESULTS: Patients with long PPS in the CCNU/TMZ arm had a particularly short PFS (5.6 months). PFS in this subgroup was shorter than in the long PPS subgroup of the TMZ arm (11.1 months, p = 0.01). At mRANO-defined progression, patients of the CCNU/TMZ long PPS subgroup had a significantly higher increase of mean ADC values (p = 0.015) and a tendency to a stronger volumetric increase in T1-enhancement (p = 0.22) as compared to long PPS patients of the TMZ arm. CONCLUSION: The combination of survival and MRI analyses identified a subgroup of CCNU/TMZ-treated patients with features that sets them apart from other patients in the trial: short first PFS despite long PPS and significant increase in mean ADC values upon mRANO-defined progression. The observed pattern is compatible with the features commonly observed in pseudoprogression suggesting mRANO-undetected pseudoprogressions in the CCNU/TMZ arm of CeTeG/NOA-09.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Dacarbazine/therapeutic use , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Temozolomide/therapeutic use , Glioblastoma/diagnostic imaging , Glioblastoma/drug therapy , Glioblastoma/pathology , Lomustine/therapeutic use , Magnetic Resonance Imaging , Antineoplastic Agents, Alkylating/therapeutic use
19.
Adv Exp Med Biol ; 1416: 1-4, 2023.
Article in English | MEDLINE | ID: mdl-37432615

ABSTRACT

Meningiomas are the most common brain tumor in adults with rising incidence rates due to an aging population globally, increased availability of neuroimaging, and increased awareness of this condition by treating clinicians and primary care physicians. Surgical resection remains the mainstay of treatment, with adjuvant radiotherapy reserved for higher grade meningiomas or tumors that undergo incomplete resections. Whereas these tumors were classically defined by their histopathological features and subtypes, recent work has uncovered the molecular alterations that may lead to tumor development and have important prognostic implications. However, there remain important clinical questions regarding the management of meningiomas and current clinical guidelines continue to evolve as additional studies add onto the growing body of work that enables us to better understand these tumors.


Subject(s)
Brain Neoplasms , Meningeal Neoplasms , Meningioma , Adult , Humans , Aged , Meningioma/therapy , Aging , Neuroimaging , Meningeal Neoplasms/therapy
20.
J Neurooncol ; 163(3): 597-605, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37382806

ABSTRACT

BACKGROUND: The expression level of the programmed cell death ligand 1 (PD-L1) appears to be a predictor for response to immunotherapy using checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC). As differences in terms of PD-L1 expression levels in the extracranial primary tumor and the brain metastases may occur, a reliable method for the non-invasive assessment of the intracranial PD-L1 expression is, therefore of clinical value. Here, we evaluated the potential of radiomics for a non-invasive prediction of PD-L1 expression in patients with brain metastases secondary to NSCLC. PATIENTS AND METHODS: Fifty-three NSCLC patients with brain metastases from two academic neuro-oncological centers (group 1, n = 36 patients; group 2, n = 17 patients) underwent tumor resection with a subsequent immunohistochemical evaluation of the PD-L1 expression. Brain metastases were manually segmented on preoperative T1-weighted contrast-enhanced MRI. Group 1 was used for model training and validation, group 2 for model testing. After image pre-processing and radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. The radiomics model was trained and validated using random stratified cross-validation. Finally, the best-performing radiomics model was applied to the test data. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analyses. RESULTS: An intracranial PD-L1 expression (i.e., staining of at least 1% or more of tumor cells) was present in 18 of 36 patients (50%) in group 1, and 7 of 17 patients (41%) in group 2. Univariate analysis identified the contrast-enhancing tumor volume as a significant predictor for PD-L1 expression (area under the ROC curve (AUC), 0.77). A random forest classifier using a four-parameter radiomics signature, including tumor volume, yielded an AUC of 0.83 ± 0.18 in the training data (group 1), and an AUC of 0.84 in the external test data (group 2). CONCLUSION: The developed radiomics classifiers allows for a non-invasive assessment of the intracranial PD-L1 expression in patients with brain metastases secondary to NSCLC with high accuracy.


Subject(s)
Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , B7-H1 Antigen , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Retrospective Studies , ROC Curve
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