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Frontiers in Oncology 2024Glioma is the most common primary intracranial neoplasm with a relatively poor prognosis.
INTRODUCTION
Glioma is the most common primary intracranial neoplasm with a relatively poor prognosis.
CASE PRESENTATION
Here, we present a unique case of a 53-year-old woman with two histopathologically distinct gliomas at the initial diagnosis. She presented with headaches and left limb weakness before admission, and magnetic resonance imaging (MRI) showed right frontal and basal ganglia area involvement combined with hemorrhage. The patient underwent a navigation-guided craniotomy for tumor removal. Pathological examination revealed the right frontal lobe lesion as a WHO grade II IDH-NOS astrocytoma, but the right parietal lobe lesion was a WHO grade IV IDH-mutant diffuse astrocytoma. Molecular detection of the parietal lesion revealed a point mutation at the R132 locus of the gene, no mutation in the promoter, amplification of the epidermal growth factor receptor, and a non-homozygous deletion.
DISCUSSION
In-depth epigenomic analysis and molecular examination revealed that one patient had two different brain tumors, underscoring the importance of performing a comprehensive brain tumor workup.
CONCLUSION
This unique case confirms that adjacent astrocytomas may have different molecular pathogenesis and provides novel insights into the development of gliomas.
PubMed: 38919539
DOI: 10.3389/fonc.2024.1308497 -
Medical Oncology (Northwood, London,... Jun 2024Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an... (Review)
Review
Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an incurable disease. GBM has a poor prognosis with a median survival of 12-15 months, and its aggressive clinical course is related to rapid growth, extensive infiltration of adjacent tissues, resistance to chemotherapy, radiotherapy and immunotherapy, and frequent relapse. Currently, several molecular biomarkers are used in clinical practice to predict patient prognosis and response to treatment. However, due to the overall unsatisfactory efficacy of standard multimodal treatment and the remaining poor prognosis, there is an urgent need for new biomarkers and therapeutic strategies for GBM. Recent evidence suggests that GBM tumorigenesis is associated with crosstalk between cancer, immune and stromal cells mediated by various cytokines. One of the key factors involved in this process appears to be interleukin-17 (IL-17), a pro-inflammatory cytokine that is significantly upregulated in the serum and tissue of GBM patients. IL-17 plays a key role in tumorigenesis, angiogenesis, and recurrence of GBM by activating pro-oncogenic signaling pathways and promoting cell survival, proliferation, and invasion. IL-17 facilitates the immunomodulation of the tumor microenvironment by promoting immune cells infiltration and cytokine secretion. In this article we review the latest scientific reports to provide an update on the role of IL-17 role in tumorigenesis, tumor microenvironment, diagnosis, prognosis, and treatment of GBM.
Topics: Humans; Glioblastoma; Brain Neoplasms; Interleukin-17; Tumor Microenvironment; Biomarkers, Tumor; Prognosis
PubMed: 38918274
DOI: 10.1007/s12032-024-02434-1 -
Frontiers in Immunology 2024Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong... (Review)
Review
Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong patient survival. With the deepening of research, it has been found that gut microbiota plays a certain role in GBM, and can directly or indirectly affect the efficacy of immune checkpoint inhibitors (ICIs) in various ways. (1) The metabolites produced by gut microbiota directly affect the host's immune homeostasis, and these metabolites can affect the function and distribution of immune cells, promote or inhibit inflammatory responses, affect the phenotype, angiogenesis, inflammatory response, and immune cell infiltration of GBM cells, thereby affecting the effectiveness of ICIs. (2) Some members of the gut microbiota may reverse T cell function inhibition, increase T cell anti-tumor activity, and ultimately improve the efficacy of ICIs by targeting specific immunosuppressive metabolites and cytokines. (3) Some members of the gut microbiota directly participate in the metabolic process of drugs, which can degrade, transform, or produce metabolites, affecting the effective concentration and bioavailability of drugs. Optimizing the structure of the gut microbiota may help improve the efficacy of ICIs. (4) The gut microbiota can also regulate immune cell function and inflammatory status in the brain through gut brain axis communication, indirectly affecting the progression of GBM and the therapeutic response to ICIs. (5) Given the importance of gut microbiota for ICI therapy, researchers have begun exploring the use of fecal microbiota transplantation (FMT) to transplant healthy or optimized gut microbiota to GBM patients, in order to improve their immune status and enhance their response to ICI therapy. Preliminary studies suggest that FMT may enhance the efficacy of ICI therapy in some patients. In summary, gut microbiota plays a crucial role in regulating ICIs in GBM, and with a deeper understanding of the relationship between gut microbiota and tumor immunity, it is expected to develop more precise and effective personalized ICI therapy strategies for GBM, in order to improve patient prognosis.
Topics: Humans; Gastrointestinal Microbiome; Glioblastoma; Immune Checkpoint Inhibitors; Brain Neoplasms; Animals; Brain-Gut Axis; Fecal Microbiota Transplantation; Tumor Microenvironment
PubMed: 38915399
DOI: 10.3389/fimmu.2024.1401967 -
Frontiers in Microbiology 2024Herpes Simplex Virus type 1 (HSV-1) 1 is a neurotropic virus that has been associated with neurodegenerative disorders. The dysregulation of autophagy by HSV-1 has been...
Herpes Simplex Virus type 1 (HSV-1) 1 is a neurotropic virus that has been associated with neurodegenerative disorders. The dysregulation of autophagy by HSV-1 has been proposed as a potential cause of neurodegeneration. While studies have extensively tackled the interaction between autophagy and HSV-1 in neurons, research in glial cells is currently limited. Our studies demonstrate that HSV-1 inhibits, but not completely blocks, the formation of autophagosomes in human oligodendroglioma- and astrocytoma- derived cell lines. These findings have been confirmed in murine oligodendrocyte precursor cells (OPCs). Finally, this study investigates the impact of autophagy on HSV-1 infection in glial cells. While the lack of basal autophagy in LC3B knockout glial cells does not have a significant effect on viral infection, cells without the autophagy-related protein ATG5 exhibit reduced viral production. The absence of ATG5 leads to a decrease in the transcription and replication of viral genes, as well as a delay in the initial stages of the formation of HSV-1 replication compartments. These findings indicate that while autophagy may not play a significant role in antiviral defense in glial cells, HSV-1 may be inhibiting autophagy to exploit non-canonical functions of certain components of the autophagic machinery, such as ATG5, to benefit its lifecycle.
PubMed: 38915300
DOI: 10.3389/fmicb.2024.1411655 -
Scientific Data Jun 2024Hyperspectral (HS) imaging (HSI) technology combines the main features of two existing technologies: imaging and spectroscopy. This allows to analyse simultaneously the...
Hyperspectral (HS) imaging (HSI) technology combines the main features of two existing technologies: imaging and spectroscopy. This allows to analyse simultaneously the morphological and chemical attributes of the objects captured by a HS camera. In recent years, the use of HSI provides valuable insights into the interaction between light and biological tissues, and makes it possible to detect patterns, cells, or biomarkers, thus, being able to identify diseases. This work presents the HistologyHSI-GB dataset, which contains 469 HS images from 13 patients diagnosed with brain tumours, specifically glioblastoma. The slides were stained with haematoxylin and eosin (H&E) and captured using a microscope at 20× power magnification. Skilled histopathologists diagnosed the slides and provided image-level annotations. The dataset was acquired using custom HSI instrumentation, consisting of a microscope equipped with an HS camera covering the spectral range from 400 to 1000 nm.
Topics: Humans; Glioblastoma; Brain Neoplasms; Hyperspectral Imaging; Microscopy
PubMed: 38914542
DOI: 10.1038/s41597-024-03510-x -
AJNR. American Journal of Neuroradiology Jun 2024Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors...
BACKGROUND AND PURPOSE
Hemangioblastoma is a rare vascular tumor that occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors can be challenging on imaging, and preoperative diagnosis can change the neurosurgical approach. We hypothesize that a 'lightbulb sign' on the ASL sequence (diffuse homogenous intense hyperperfusion within the solid component of the tumor) will provide additional imaging finding to differentiate hemangioblastoma from other posterior fossa tumors.
MATERIALS AND METHODS
In this retrospective comparative observational study, we only included pathology-proven cases of hemangioblastoma, while the control group consisted of other randomly selected pathology-proven posterior fossa tumors from January 2022 to January 2024. Two blinded neuroradiologists analyzed all applicable MRI sequences, including ASL sequence if available. ASL was analyzed for the 'lightbulb sign'. Disagreements between the radiologists were resolved by a third pediatric neuroradiologist. Chi-square and Fisher's exact test were used to analyze the data.
RESULTS
95 patients were enrolled in the study; 57 (60%) were male. The median age at diagnosis was 8 years old (IQR: 3-14). Out of the enrolled patients, 8 had hemangioblastoma, and 87 had other posterior fossa tumors, including medulloblastoma (n=31), pilocytic astrocytoma (n=23), posterior fossa ependymoma type A (n=16), and other tumors (n=17). The comparison of hemangioblastoma vs non-hemangioblastoma showed that peripheral edema (p=0.02) and T2 flow void (p=0.02) favors hemangioblastoma, whereas reduced diffusion (low ADC) (p=0.002) and ventricular system extension (p=0.001) favors nonhemangioblastoma tumors.Forty-two cases also had ASL perfusion sequences. While high perfusion favors hemangioblastoma (p=0.03), the lightbulb sign shows a complete distinction since all the ASL series of hemangioblastoma cases (n=4) showed the lightbulb sign, whereas none of the nonhemangioblastoma cases (n=38) showed the sign (p<0.001).
CONCLUSIONS
Lightbulb-like intense and homogenous hyperperfusion patterns on ASL are helpful in diagnosing posterior fossa hemangioblastoma in children.ABBREVIATIONS ASL = Arterial spin labelling; pASL = Pulsed arterial spin labelling; pCASL = Pseudocontinuous arterial spin labelling; DCE = Dynamic contrast-enhanced; DSC = Dynamic susceptibility contrast; VHL = Von Hippel Lindau.
PubMed: 38914433
DOI: 10.3174/ajnr.A8391 -
Neuro-oncology Jun 2024The 2016 and 2021 World Health Organization (WHO) 2021 Classification of Central Nervous System (CNS) tumors have resulted in a major improvement of the classification...
The biological significance of tumor grade, age, enhancement and extent of resection in IDH mutant gliomas: how should they inform treatment decision in the era of IDH inhibitors? Invited review.
The 2016 and 2021 World Health Organization (WHO) 2021 Classification of Central Nervous System (CNS) tumors have resulted in a major improvement of the classification of IDH-mutant gliomas. With more effective treatments many patients experience prolonged survival . However, treatment guidelines are often still based on information from historical series comprising both patients with IDHwt and IDH mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological and molecular factors associated with outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with an IDH-mutant grade 2 and grade 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment.
PubMed: 38912846
DOI: 10.1093/neuonc/noae107 -
Frontiers in Oncology 2024Pediatric low-grade gliomas (pLGG) are the most common brain tumor in children and encompass a wide range of histologies. Treatment may pose challenges, especially in...
INTRODUCTION
Pediatric low-grade gliomas (pLGG) are the most common brain tumor in children and encompass a wide range of histologies. Treatment may pose challenges, especially in those incompletely resected or those with multiple recurrence or progression.
CASE DESCRIPTION
We report the clinical course of a girl diagnosed with pilocytic astrocytoma and profound hydrocephalus at age 12 years treated with subtotal resection, vinblastine chemotherapy, and focal proton radiotherapy. After radiotherapy the tumor increased in enhancement temporarily with subsequent resolution consistent with pseudoprogression. Despite improvement in imaging and radiographic local control, the patient continues to have challenges with headaches, visual and auditory concerns, stroke-like symptoms, and poor quality of life.
CONCLUSION
pLGG have excellent long-term survival; thus, treatments should focus on maintaining disease control and limiting long-term toxicities. Various treatment options exist including surgery, chemotherapy, targeted agents, and radiation therapy. Given the morbidity associated with pLGG, individualized treatment approaches are necessary, with a multi-disciplinary approach to care focused on minimizing treatment side effects, and promoting optimal quality of life for patients.
PubMed: 38912055
DOI: 10.3389/fonc.2024.1366251 -
World Neurosurgery Jun 2024Anaplastic astrocytoma (AA) is an uncommon primary brain tumor with highly variable clinical outcomes. Our study aimed to develop practical tools for clinical...
OBJECTIVE
Anaplastic astrocytoma (AA) is an uncommon primary brain tumor with highly variable clinical outcomes. Our study aimed to develop practical tools for clinical decision-making in a population-based cohort study.
METHODS
Data from 2997 patients diagnosed with AA between 2004 and 2015 were retrospectively extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The LASSO and multivariate Cox regression analyses were applied to select factors and establish prognostic nomograms. The discriminatory ability of these nomogram models was evaluated using the concordance index (C-index) and receiver operating characteristic curve (ROC). Risk stratifications were established based on the nomograms.
RESULTS
Selected 2997 AA patients were distributed into the training cohort (70%, 2097) and the validation cohort (30%, 900). Age, household income, tumor site, extension, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors for both overall survival (OS) and cancer-specific survival (CSS). In the training cohort, our nomograms for OS and CSS exhibited good predictive accuracy with C-index values of 0.752 (95% CI: 0.741-0.764) and 0.753 (95% CI: 0.741-0.765), respectively. Calibration and DCA curves showed that the nomograms demonstrated considerable consistency and satisfactory clinical utilities. With the establishment of nomograms, we stratified AA patients into high- and low-risk groups, and constructed risk stratification systems for OS and CSS.
CONCLUSIONS
We constructed two predictive nomograms and risk classification systems to effectively predict the OS and CSS rates in AA patients. These models were internally validated with considerable accuracy and reliability and might be helpful in future clinical practices.
PubMed: 38909753
DOI: 10.1016/j.wneu.2024.06.076 -
Journal of Neuro-oncology Jun 2024The introduction of molecular markers in to the diagnosis of gliomas has changed the therapeutic approach to this tumors. The aim of this study was to examine the impact...
PURPOSE
The introduction of molecular markers in to the diagnosis of gliomas has changed the therapeutic approach to this tumors. The aim of this study was to examine the impact of surgery on anaplastic astrocytomas (AA), which has not previously been fully elucidated.
METHODS
This was a retrospective study involving a total of 143 patients who underwent surgery for primary AA in our department between 1995 and 2020.
RESULTS
Total tumor resection was achieved more often in patients with IDH-mutant tumors (41.09%) than in patients with IDH-wildtype tumors (30.76%). The median PFS was 1876 days for patients with IDH1 mutations and 238 days for patients with IDH-wildtype tumors. The 1-, 3-, 5- and 10-year PFS were longer in patients with total tumor resection and IDH-mutant AA (86.2%, 69%, 65.5% and 44.8%, respectively) than in patients with subtotal tumor resection and IDH-mutant AA (83.3%, 55.6%, 41.7% and 25%, respectively) and even longer compared to all IDH-wildtype tumors. The median OS was 2472 days for patients with IDH1 mutations and 434 days for patients with IDH-wildtype tumors. The 3-, 5- and 10-year OS times were longer in patients with total tumor resection and IDH-mutant AA (89.2%, 85.2% and 72.6%, respectively) than in patients with subtotal tumor resection and IDH-mutant AA (85.9%, 73.7% and 52.6%, respectively) and were even longer compared to all IDH-wildtype tumors.
CONCLUSION
Total tumor resection is more common with IDH-mutant AA than with IDH-wildtype tumors. Patients with IDH-mutant AA had significantly better PFS and OS after total tumor resection than after subtotal tumor resection and biopsy.
PubMed: 38909340
DOI: 10.1007/s11060-024-04743-x