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This article discusses the identification of a molecular subtype of adult-type diffuse astrocytoma with recurrent MAPK pathway alterations. Adult-type diffuse gliomas are the most common malignant primary tumors of the central nervous system, and they are classified based on the isocitrate dehydrogenase (IDH1/2) mutation status. Through DNA methylation analysis and next-generation sequencing, a distinct cluster of diffuse gliomas was identified, characterized by high-level amplification of PDGFRA and alterations in the MAPK pathway. These findings suggest potential targeted therapeutic interventions for this newly identified tumor subgroup. Further research is needed to fully understand the clinical implications of this molecular subtype. [Extracted from the article]

Simple Summary: The European Network for Rare Cancers (EURACAN) Task Force on Ultra-Rare Brain Tumors (domain 10, subdomain 10) has reviewed the literature extensively regarding primary meningeal melanocytic tumors, which are ultra-rare entities that affect primarily children and young adults and represent an unmet need in neuro-oncology. The review covers the main histological and molecular factors, radiological findings, clinical features, and therapeutic challenges. Further efforts are needed to collect more knowledge on these rare brain tumors to improve the diagnostic tools and provide novel treatment strategies. Background: Primary meningeal melanocytic tumors are ultra-rare entities with distinct histological and molecular features compared with other melanocytic or pigmented lesions, such as brain and leptomeningeal metastases from metastatic melanoma. Methods: The European Network for Rare Cancers (EURACAN) Task Force on Ultra-Rare Brain Tumors (domain 10, subdomain 10) performed a literature review from January 1985 to December 2023 regarding the epidemiologic and clinical characteristics, histological and molecular features, radiological findings, and efficacy of local treatments (surgery and radiotherapy) and systemic treatments for these entities. Results: Molecular analysis can detect specific mutations, including GNAQ, GNA11, SF3B1, EIF1AX, BAP1, that are typically found in circumscribed primary meningeal melanocytic tumors and not in other melanocytic lesions, whereas NRAS and BRAF mutations are typical for diffuse primary meningeal melanocytic tumors. The neuroimaging of the whole neuroaxis suggests a melanocytic nature of a lesion, depicts its circumscribed or diffuse nature, but cannot predict the tumor's aggressiveness. Gross-total resection is the first choice in the case of circumscribed meningeal melanocytoma and melanoma; conversely, meningeal biopsy may be reserved for patients with diffuse and multinodular leptomeningeal spread to achieve a definitive diagnosis. High-dose radiotherapy is rarely indicated in diffuse melanocytic tumors except as palliative treatment to alleviate symptoms. Last, a definitive advantage of a specific systemic treatment could not be concluded, as most of the data available derive from case reports or small cohorts. Conclusions: As primary meningeal melanocytic tumors are extremely rare, the correlations between the clinical characteristics, molecular profile, radiological findings at diagnosis and progression are weak, and poor evidence on the best therapeutic approach is available. There is a need to develop shared platforms and registries to capture more knowledge regarding these ultra-rare entities. [ABSTRACT FROM AUTHOR]

Purpose: Amide proton transfer‐weighted (APTw) MRI at 3T provides a unique contrast for brain tumor imaging. However, APTw imaging suffers from hyperintensities in liquid compartments such as cystic or necrotic structures and provides a distorted APTw signal intensity. Recently, it has been shown that heuristically motivated fluid suppression can remove such artifacts and significantly improve the readability of APTw imaging. Theory and Methods: In this work, we show that the fluid suppression can actually be understood by the known concept of spillover dilution, which itself can be derived from the Bloch‐McConnell equations in comparison to the heuristic approach. Therefore, we derive a novel post‐processing formula that efficiently removes fluid artifact, and explains previous approaches. We demonstrate the utility of this APTw assessment in silico, in vitro, and in vivo in brain tumor patients acquired at MR scanners from different vendors. Results: Our results show a reduction of the CEST signals from fluid environments while keeping the APTw‐CEST signal intensity almost unchanged for semi‐solid tissue structures such as the contralateral normal appearing white matter. This further allows us to use the same color bar settings as for conventional APTw imaging. Conclusion: Fluid suppression has considerable value in improving the readability of APTw maps in the neuro‐oncological field. In this work, we derive a novel post‐processing formula from the underlying Bloch‐McConnell equations that efficiently removes fluid artifact, and explains previous approaches which justify the derivation of this metric from a theoretical point of view, to reassure the scientific and medical field about its use. [ABSTRACT FROM AUTHOR]

Background: Dihydroxy‐6‐[18F]fluoro‐L‐phenylalanine (18F‐FDOPA) positron emission tomography (PET) is a valuable tool for managing high‐grade gliomas (HGGs), but there is a lack of literature on its relationship with glioma subtypes since the 2021 reclassification of brain tumors. There is also debate surrounding the mechanism of 18F‐FDOPA uptake, particularly after chemoradiation therapy. This study aimed to investigate the correlation between 18F‐FDOPA uptake and histomolecular characteristics, particularly L‐amino acid transporter 1 (LAT1) expression, in recurrent gliomas, and examine their impact on survival in HGGs. Methods: Thirty‐nine patients with recurrent HGGs (14 isocitrate dehydrogenase [IDH]‐mutant, 25 IDH‐wildtype) who underwent a brain 18F‐FDOPA PET/computed tomography (CT) or PET/magnetic resonance imaging (MRI) followed by surgical resection of the 18F‐FDOPA‐avid lesion within 6 months, were retrospectively reviewed. PET results were compared with histological examination and for SCL7A5/LAT1 immunostaining. The study also examined the relationship between PET parameters, LAT1 expression, and survival outcomes. Results: Astrocytoma IDH‐mutant G4 had higher 18F‐FDOPA uptake than glioblastoma IDH‐wildtype G4 (maximum tumor‐to‐normal brain ratio [TBRmax] 5 [3.4–9] vs. 3.8 [2.8–5.9], p = 0.02). IDH‐mutant gliomas had higher LAT1 expression than IDH‐wildtype gliomas (100 [14–273] vs. 15.5 [0–137], p < 0.05) as well as higher TBRmax (5 [2.4–9] vs. 3.8 [2.8–6], p < 0.05). In survival analysis, LAT1 score >100 was a predictor for longer progression‐free survival in IDH‐mutant HGGs. Conclusions: To our knowledge, our study is the first to suggest a link between LAT1 expression and IDH mutation status. We showed that higher TBRmax was associated with higher LAT1 expression and IDH mutation status. Further studies are needed to better understand the mechanisms underlying amino acid PET tracers uptake, especially in the post‐radiation and chemotherapy settings. [ABSTRACT FROM AUTHOR]

Lower-grade (grade 2–3) gliomas (LGGs) constitutes a group of primary brain tumors with variable clinical behaviors and treatment responses. Recent advancements in molecular biology have redefined their classification, and novel imaging modalities emerged for the noninvasive diagnosis and follow-up. This review comprehensively analyses the current knowledge on molecular and imaging biomarkers in LGGs. Key molecular alterations, such as IDH mutations and 1p/19q codeletion, are discussed for their prognostic and predictive implications in guiding treatment decisions. Moreover, the authors explore theranostic biomarkers for the potential of tailored therapies. Additionally, they also describe the utility of advanced imaging modalities, including widely available techniques, as dynamic susceptibility contrast perfusion-weighted imaging and less validated, emerging approaches, for the noninvasive LGGs characterization and follow-up. The integration of molecular markers enhanced the stratification of LGGs, leading to the new concept of integrated histomolecular classification. While the IDH mutation is an established key prognostic and predictive marker, recent results from IDH inhibitors trials showed its potential value as a theranostic marker. In this setting, advanced MRI techniques such as 2-D-hydroxyglutarate spectroscopy are very promising for the noninvasive diagnosis and monitoring of LGGs. This progress offers exciting prospects for personalized medicine and improved treatment outcomes in LGGs. [ABSTRACT FROM AUTHOR]

It has been well described during the first waves of this disease that COVID-19, the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is associated with worse outcomes (i.e. higher risk of death or intensive care unit [ICU] admission) in patients with cancer [[1]], especially those with hematological malignancies [[3], [5]]. Sixteen patients (64%, among whom 2 patients just received their last treatment before being tested positive for SARS-CoV-2) were receiving first-line treatment. The five remaining patients were a- or pauci-symptomatic since a median of 15 days from the diagnosis of SARS-COV-2 at the time of scheduled chemotherapy (which included rituximab for one patient) and therefore did not have a delay in treatment. Twenty-one patients (84%) were symptomatic for a median duration of 13 days (range 2-43), the most frequent symptoms being cough (16 patients, 64%) and fever (11 patients, 44%). [Extracted from the article]