Search Results (98)

Background/Objectives: Positron emission tomography (PET) imaging with radiolabeled amino acids is increasingly used in glioma patients for biopsy planning, tumor delineation, prognostication, and therapy response assessment. This study investigated whether baseline amino acid PET imaging could identify regions at risk of future tumor recurrence. Methods: Retrospective case series of 14 patients with high-grade glioma. Contrast-enhanced magnetic resonance imaging (MRI) data of tumor recurrence and baseline imaging (PET-MRI) were co-registered. Volumes of interest (VOIs) of the high-grade glioma were derived from contrast-enhanced MRI at baseline and follow-up and from amino acid PET at baseline. The Dice similarity coefficient (DSC) was used to assess the overlap between VOIs. Furthermore, dynamic and static PET parameters were compared between the VOIs derived from contrast-enhanced MRI at follow-up and from the region of increased amino acid transport at baseline. Results: Regions of tumor recurrence in high-grade glioma patients overlap significantly more with baseline regions of increased amino acid transport on PET compared to regions of contrast enhancement on baseline MRI (p < 0.001). However, the static and dynamic PET statistics did not differentiate between regions that would later develop tumor recurrence and other areas of increased amino acid transport at baseline. Conclusions: These findings reaffirm the ability of amino acid PET to visualize the infiltrative components of gliomas not detected by contrast-enhanced MRI. Also, this study supports the role of amino acid PET in visualizing glioma infiltration beyond the MRI-visible tumor, but also indicates that accurately predicting the specific regions of recurrence based on baseline PET remains limited. Full article

Gliomas are incurable, heterogeneous brain tumors, with rare forms often constituting diagnostic and treatment challenges. Molecular diagnostics, mainly implemented through the World Health Organization (WHO) 2021 guidelines, have refined the classification, but highlight difficulties in diagnosing rare gliomas remain. This case series analyzes four patients with rare gliomas treated at the University Hospital, Ulm, between 2002 and 2024. Patients were selected based on unique histopathological features and long-term clinical follow-up. Clinical records, imaging, and histological data were reviewed. Molecular diagnostics followed WHO 2021 guidelines. Quality of life was assessed using standardized tools including the EQ-5D-5L, EQ VAS, the Distress Thermometer, and the Montreal Cognitive Assessment (MoCA). In the first case, a 51-year-old male’s diagnosis evolved from pleomorphic xanthoastrocytoma to a high-grade glioma with pleomorphic and pseudopapillary features, later identified as a neuroepithelial tumor with a PATZ1 fusion over 12 years. Despite multiple recurrences, extensive surgical interventions led to excellent outcomes. The second case involved a young female with long-term survival of astroblastoma, demonstrating significant improvements in both longevity and quality of life through personalized care. The third case involved a patient with oligodendroglioma, later transforming into glioblastoma, emphasizing the importance of continuous diagnostic reevaluation and adaptive treatment strategies, contributing to prolonged survival and quality of life improvements. Remarkably, the patient has achieved over 20 years of survival, including 10 years of being both therapy- and progression-free. The fourth case presents a young woman with neurofibromatosis type 1, initially misdiagnosed with glioblastoma based on histopathological findings. Subsequent molecular diagnostics revealed a subependymal giant cell astrocytoma-like astrocytoma, highlighting the critical role of early advanced diagnostic techniques. These cases underscore the importance of precise molecular diagnostics, individualized treatments, and ongoing diagnostic reevaluation to optimize outcomes. They also address the psychological impact of evolving diagnoses, stressing the need for comprehensive patient support. Even in complex cases, extensive surgical interventions can yield favorable results, reinforcing the value of adaptive, multidisciplinary strategies based on evolving tumor characteristics. Full article

Background and Objectives: Gliomas are characterized by high disability rates, frequent recurrence, and low survival rates, posing a significant threat to human health. Accurate grading of gliomas is crucial for treatment plan selection and prognostic assessment. Previous studies have primarily focused on the binary classification (i.e., high grade vs. low grade) of gliomas. In order to perform the four-grade (grades I, II, III, and IV) glioma classification preoperatively, we constructed an artificial neural network (ANN) model using magnetic resonance imaging data. Materials and Methods: We reviewed and included patients with gliomas who underwent preoperative MRI examinations. Radiomics features were derived from contrast-enhanced T1-weighted images (CE-T₁WI) using Pyradiomics and were selected based on their Spearman’s rank correlation with glioma grades. We developed an ANN model to classify the four pathological grades of glioma, assigning training and validation sets at a 3:1 ratio. A diagnostic confusion matrix was employed to demonstrate the model’s diagnostic performance intuitively. Results: Among the 362-patient cohort, the ANN model’s diagnostic performance plateaued after incorporating the first 19 of the 530 extracted radiomic features. At this point, the average overall diagnostic accuracy ratings for the training and validation sets were 91.28% and 87.04%, respectively, with corresponding coefficients of variation (CVs) of 0.0190 and 0.0272. The diagnostic accuracies for grades I, II, III, and IV in the training set were 91.9%, 89.9%, 92.1%, and 90.7%, respectively. The diagnostic accuracies for grades I, II, III, and IV in the validation set were 88.7%, 87.1%, 86.5%, and 86.9%, respectively. Conclusions: The MRI radiomics-based ANN model shows promising potential for the four-type classification of glioma grading, offering an objective and noninvasive method for more refined glioma grading. This model could aid in clinical decision making regarding the treatment of patients with various grades of gliomas. Full article

Background: High-grade gliomas (HGGs), particularly glioblastoma (GBM), are associated with exceptionally high mortality and inevitable recurrence. In considering novel treatment options for these devastating diseases, immunotherapies represent promising candidates. Immunotherapies have demonstrated efficacy for several advanced tumors outside the central nervous system, highlighting a potential role for these agents in treating HGGs. However, multiple challenges to immunotherapy efficacy have tempered therapeutic benefit in practice, including local and systemic immunosuppression, intratumoral heterogeneity, and various mechanisms of intrinsic and acquired resistance. In the past 30 years, diverse immunotherapeutic subclasses have been assessed for benefit against HGGs. Methods: We performed a PubMed search for randomized clinical trials performed within the last 30 years evaluating the following immunotherapy agents for high-grade gliomas: immune checkpoint inhibitors, vaccines, oncologic viruses, cytokines, and CAR T-cells. The present review offers a critical analysis of key pre-clinical and clinical trials that have shaped the immunotherapy landscape for high-grade gliomas over the past two decades. Results/Conclusions: Across the different immunotherapeutic methods and modalities explored thus far, a recurring theme emerges: while therapeutic strategies with a compelling conceptual basis are continually under development and even demonstrate a benefit in preclinical and early-phase trials, larger and later-phase trials consistently fail to produce concordantly significant outcomes. To date, no large-scale clinical trial has demonstrated a benefit of sufficient consequence to change practice. Continued critical appraisal of the strengths and pitfalls of prior investigative work, optimization of treatment development and delivery, and innovative approaches to combination therapy design will collectively be integral to future therapeutic advancement. Full article

Brain tumors are among the most common malignant tumors of the central nervous system, with high mortality and recurrence rates. Radiomics extracts quantitative features from medical images, converting them into predictive biomarkers for tumor diagnosis, prognosis, and survival analysis. Despite the invasiveness and heterogeneity of brain tumors, even with timely treatment, the overall survival time or survival probability is not necessarily favorable. Therefore, accurate prediction of brain tumor grade and survival outcomes is important for personalized treatment. In this study, we propose a radiomic model for the non-invasive prediction of brain tumor grade and patient survival outcomes. We used four magnetic resonance imaging (MRI) sequences from 159 patients with glioma. Four classifiers were employed based on whether feature selection was applied. The features were derived from regions of interest identified and corrected either manually or automatically. The extreme gradient boosting (XGB) model with 3860 radiomic features achieved the highest classification performance, with an AUC of 98.20%, in distinguishing LGG from GBM images using manually corrected labels. Similarly, the Random Forest (RF) model exhibits the best discrimination between short-term and long-term survival groups with a p-value < 0.0003, a hazard ratio (HR) value of 3.24, and a 95% confidence interval (CI) of 1.63–4.43 based on the ICC features. The experimental findings demonstrate strong classification accuracy and effectively predict survival outcomes in glioma patients. Full article

Glioblastoma in patients affected by NF1 germline mutation (NF1-associated GBM) represents a unique heterogeneous clinical and pathological entity. We have reviewed the few cases reported in the literature and they seem to have a better response to standard therapy and overall survival than GBM in the non-NF1 population. We present two cases of long-survival NF1 patients with GBM. Case 1 was a 38-year-old woman with cerebellar GBM who underwent surgical asportation and the Stupp protocol many times with an overall survival of 117 months. Case 2 was a 47-year-old woman with GBM in the eloquent area of the right frontal lobe; she underwent surgical asportation and the Stupp protocol with an overall survival of 25 months. The data analysis demonstrates that NF1-associated GBM patients could be considered long-term survivors. Full article

Maximal safe surgical resection is the gold standard in brain tumor surgery. Fluorescence-guided surgery (FGS) is one of many intraoperative techniques that have been designed with the intention of accomplishing this goal. 5-aminolevulinic acid (5-ALA) is one of the main fluorophores that facilitates FGS in neurosurgical oncology. Multiple different types of brain tumors can take in and metabolize 5-ALA into protoporphyrin IX (PpIX) through the mitochondria heme biosynthesis pathway. PpIX then selectively accumulates in brain tumor cells due to decreased ferrochelatase activity and emits red fluorescence (630–720 nm) when excited with blue light (375–440 nm). This mechanism allows neurosurgeons to better visualize tumor burden and increase extent of resection while preserving non-cancerous brain parenchyma and, specifically, eloquent white matter tracts, if combined with mapping techniques, thereby minimizing morbidity while improving survival. While 5-ALA use is well established in the treatment of high-grade gliomas, its applicability in recurrent high-grade and non-enhancing IDH-mutant low-grade gliomas, as well as non-glial tumors, is less established or limited by certain features of their cellular and molecular biology. This review aims to discuss the current landscape of 5-ALA utility across the diverse range of brain tumors, practical considerations that optimize its current use in neurosurgery, modern clinical limitations of 5-ALA, and how its application can be expanded by combining its use with other techniques that overcome current limitations. Full article

High-grade gliomas are aggressive, primary, central nervous system tumors with low survival rates due to recurrence and resistance to current therapy models. Recent studies have highlighted the importance between the interaction of glioma cancer cells and cells of the tumor microenvironment (TME). Cancer stem cells and immune cells play a critical role in the TME of gliomas. TMEs in glioma include the perivascular TME, hypoxic TME, and invasive TME, each of which have evolved as our understanding of the involved cellular players has improved. This review discusses the multidimensional aspects of the current targeted therapies and interactions between glioma cells and the TME with specific focus on targeted immunotherapies. Understanding the complexities of the TME and elucidating the various tumor-cell interactions will be critical for facilitating the development of novel precision strategies, ultimately enabling better patient outcomes. Full article

Background/Objectives: Tumor interactions with their surrounding environment, particularly in the case of peritumoral edema, play a significant role in tumor behavior and progression. While most studies focus on the radiomic features of the tumor core, this work investigates whether peritumoral edema exhibits distinct radiomic fingerprints specific to glioma (GLI), meningioma (MEN), and metastasis (MET). By analyzing these patterns, we aim to deepen our understanding of the tumor microenvironment’s role in tumor development and progression. Methods: Radiomic features were extracted from peritumoral edema regions in T1-weighted (T1), post-gadolinium T1-weighted (T1-c), T2-weighted (T2), and T2 Fluid-Attenuated Inversion Recovery (T2-FLAIR) sequences. Three classification tasks using those features were then conducted: differentiating between Low-Grade Glioma (LGG) and High-Grade Glioma (HGG), distinguishing GLI from MET and MEN, and examining all four tumor types, i.e., LGG, HGG, MET, and MEN, to observe how tumor-specific signatures manifest in peritumoral edema. Model performance was assessed using balanced accuracy derived from 10-fold cross-validation. Results: The radiomic fingerprints specific to tumor types were more distinct in the peritumoral regions of T1-c images compared to other modalities. The best models, utilizing all features extracted from the peritumoral regions of T1-c images, achieved balanced accuracies of 0.86, 0.81, and 0.76 for the LGG-HGG, GLI-MET-MEN, and LGG-HGG-MET-MEN tasks, respectively. Conclusions: This study demonstrates that peritumoral edema, as characterized by radiomic features extracted from MRIs, contains fingerprints specific to tumor type, providing a non-invasive approach to understanding tumor-brain interactions. The results of this study hold the potential for predicting recurrence, distinguishing progression from pseudo-progression, and assessing treatment-induced changes, particularly in gliomas. Full article

Background/Objectives: Multiple immune-modulatory strategies have been tested in efforts to mitigate the pro-tumor microenvironment in pediatric high-grade glioma. HSV1716 is an oncolytic virus that previously demonstrated evidence of response in adult and pediatric patients. PBTC-037 was a single-center phase I trial developed and performed by the Pediatric Brain Tumor Consortium (PBTC) to estimate the maximum tolerated dose or recommended phase II dose of HSV1716 administered during surgical resection. Methods: Patients aged 12 to 21 years with recurrent or refractory high-grade glioma for whom surgical resection was clinically indicated were eligible. After maximal tumor resection, patients received one intraoperative dose of HSV1716. Results: Two patients were enrolled; one was later deemed ineligible yet was continued in follow up for safety. Both patients underwent complete tumor resection with the administration of HSV1716. Shortly after the enrollment of the two patients, this study was closed to accrual due to a change in the sponsor’s investment focus. One patient completed the 8-week reporting period without toxicity. The second patient who was later deemed ineligible had no evidence of dose-limiting toxicity. The two patients had progressive disease at 1.9 and 2.9 months after enrollment; both eventually died due to progressive disease at 7.5 months. Conclusion: We describe the administration of HSV1716 to two pediatric patients with recurrent high-grade glioma, without evidence of dose-limiting toxicity. Oncolytic viruses are currently being tested in pediatric patients in larger combinatorial trials. Despite the limited numbers, the data presented here will hopefully provide incremental steps toward improved immunovirotherapy of pediatric brain tumors. Full article

Background/Objectives: 5-aminulevulinic acid (5-ALA)-guided surgery for high-grade gliomas remains a challenge in neuro-oncological surgery. Inconsistent fluorescence visualisation, subjective quantification and false negatives due to blood, haemostatic agents or optical impediments from the external light source are some of the limitations of the present technology. Methods: The preliminary results from this single-centre retrospective study are presented from the first 35 patients operated upon with the novel Nico Myriad Spectra System©. The microdebrider (Myriad) with an additional in situ light system (Spectra) can alternately provide white and blue light (405 nm) to within 15 mm of the tissue surface to enhance the morphology of the anatomical structures and the fluorescence of the pathological tissues. Results: A total of 35 patients were operated upon with this new technology. Eight patients (22.85%) underwent tubular retractor-assisted minimally invasive parafascicular surgery (tr-MIPS). The majority had high-grade gliomas (68.57%). Fluorescence was identified in 30 cases (85.71%), with residual fluorescence in 11 (36.66%). The main applications were better white–blue light alternation and visualisation during tr-MIPS, increase in the extent of resection at the border of the cavity, identification of satellite lesions in multifocal pathology, the differentiation between radionecrosis and tumour recurrence in redo surgery and the demarcation between normal ependyma versus pathological ependyma in tumours infiltrating the subventricular zone. Conclusions: This proof-of-concept study confirms that the novel in situ light-source delivery technology integrated with the usual intraoperative armamentarium provides a spatially, functionally and oncologically informed framework for glioblastoma surgery. It allows for the enhancement of the morphology of anatomical structures and the fluorescence of pathological tissues, increasing the extent of resection and, possibly, the prognosis for patients with high-grade gliomas. Full article

Background: Diffuse midline glioma (DMG), H3 K27-altered, is a WHO grade 4 malignant glioma located at midline structures, including the thalamus, brainstem and spinal cord. While H3 K27-altered DMG is more common in pediatric age in which it shows a uniformly aggressive clinical behavior, its occurrence is relatively unusual among adults, and its clinico–pathological and prognostic features are not fully characterized in this age group. Methods: In this present paper, a review of the literature, including all cases of adult H3 K27-altered DMG published from January 2010 to December 2023 was performed, and the following clinical parameters were evaluated: sex, age (median and range), anatomic site, median follow-up, leptomeningeal dissemination, local recurrence and treatment. In addition, the clinico–pathological features of three additional adult cases from our retrospective series were also reported and discussed. Results: All tumors from our series exhibited a high-grade morphology with brisk mitotic activity; microvascular proliferation and necrosis were seen only in one case. The immunohistochemical loss of H3 K27me3 along with diffuse and strong immunoreactivity for H3 K27M was found in all cases, leading to the diagnosis of H3 K27-altered DMG. Conclusions: The literature review showed that adult H3 K27-altered DMG more frequently occurred in males aged between 18 and 40 years. The thalamus was the most affected site, followed by the brainstem and spinal cord, in both sex groups. Adult tumors exhibited less aggressive clinical behavior, with leptomeningeal dissemination and local recurrence reported in only 23.78% and 37.75% of cases, respectively. Full article

Background: 5-Aminolevulinic acid-guided surgery for adult gliomas has been approved by the European Medicines Agency and the US Food and Drug Administration, becoming a reliable tool for improving gross total resection rates and patient outcomes. This has led several medical centers to explore the off-label use of 5-ALA in the resection of pediatric brain tumors, assessing its efficacy and safety across various tumor types. However, given the differences between children and adults, the appropriateness of 5-ALA use in pediatric populations has not yet been fully established. Methods: We collected eligible publications from Embase, Scopus, PubMed, and Proquest, ultimately selecting 27 studies. Data extraction and retrospective analysis of 249 surgical cases were conducted to determine the current efficacy and safety of 5-ALA in pediatric brain tumors. The fluorescence rate and utility stratified by several clinical features, including WHO grade, tumor classification, and tumor location, were analyzed. Results: Most studies suggest that 5-ALA can enhance tumor identification in high-grade tumors, including glioblastomas and anaplastic astrocytomas. Changes in survival or recurrence rates associated with 5-ALA-guided resection have not been reported. None of the cases reported significant postoperative complications related to the use of 5-ALA. Conclusions: 5-ALA can aid in the resection of high-grade gliomas in pediatric patients. The efficacy of 5-ALA in low-grade gliomas and other tumors may require enhancement with additional tools or modified administration protocols. The safety of 5-ALA has reached a preliminary consensus, although further randomized controlled trials and data on survival and molecular characteristics are needed. Full article

Background: High-grade gliomas remain a virtually incurable form of brain cancer. Current therapies are unable to completely eradicate the tumor, and the tumor cells that survive chemotherapy or radiation therapy often become more aggressive and resistant to further treatment, leading to inevitable relapses. While the antiproliferative effects of new therapeutic molecules are typically the primary focus of research, less attention is given to their influence on tumor cell migratory activity, which can play a significant role in recurrence. A potential solution may lie in the synergistic effects of multiple drugs on the tumor. Objectives: In this study, we investigated the effect of combined exposure to bi-(AID-1-T), an anti-proliferative aptamer, and its analog bi-(AID-1-C), on the migratory activity of human GBM cells. Results: We examined the effects of various sequences of adding bi-(AID-1-T) and bi-(AID-1-C) on five human GBM cell cultures. Our findings indicate that certain sequences significantly reduced the ability of tumor cells to migrate and proliferate. Additionally, the expression of Nestin, PARP1, L1CAM, Caveolin-1, and c-Myc was downregulated in human GBM cells that survived exposure, suggesting that the treatment had a persistent antitumor effect on these cells. Full article

Background/Objectives: High-grade gliomas are the most common primary malignant brain tumors in adults. These neoplasms remain predominantly incurable due to the genetic diversity within each tumor, leading to varied responses to specific drug therapies. With the advent of new targeted and immune therapies, which have demonstrated promising outcomes in clinical trials, there is a growing need for image-based techniques to enable early prediction of treatment response. This study aimed to evaluate the potential of radiomics and artificial intelligence implementation in predicting progression-free survival (PFS) in patients with highest-grade glioma (CNS WHO 4) undergoing a standard treatment plan. Methods: In this retrospective study, prediction models were developed in a cohort of 51 patients with pathologically confirmed highest-grade glioma (CNS WHO 4) from the authors’ institution and the repository of the Cancer Imaging Archive (TCIA). Only patients with confirmed recurrence after complete tumor resection with adjuvant radiotherapy and chemotherapy with temozolomide were included. For each patient, 109 radiomic features of the tumor were obtained from a preoperative magnetic resonance imaging (MRI) examination. Four clinical features were added manually—sex, weight, age at the time of diagnosis, and the lobe of the brain where the tumor was located. The data label was the time to recurrence, which was determined based on follow-up MRI scans. Artificial intelligence algorithms were built to predict PFS in the training set (n = 75%) and then validate it in the test set (n = 25%). The performance of each model in both the training and test datasets was assessed using mean absolute percentage error (MAPE). Results: In the test set, the random forest model showed the highest predictive performance with 1-MAPE = 92.27% and a C-index of 0.9544. The decision tree, gradient booster, and artificial neural network models showed slightly lower effectiveness with 1-MAPE of 88.31%, 80.21%, and 91.29%, respectively. Conclusions: Four of the six models built gave satisfactory results. These results show that artificial intelligence models combined with radiomic features could be useful for predicting the progression-free survival of high-grade glioma patients. This could be beneficial for risk stratification of patients, enhancing the potential for personalized treatment plans and improving overall survival. Further investigation is necessary with an expanded sample size and external multicenter validation. Full article