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Neurobiology of Disease Jan 2016Glioblastoma (GBM, Grade IV astrocytoma) is the most common and most aggressive of the primary malignant brain tumors in adults. Hypoxia is a distinct feature in GBM and... (Review)
Review
Glioblastoma (GBM, Grade IV astrocytoma) is the most common and most aggressive of the primary malignant brain tumors in adults. Hypoxia is a distinct feature in GBM and plays a significant role in tumor progression, resistance to treatment and poor outcomes. This review considers the effects of hypoxia on astrocytic tumors and the mechanisms that contribute to tumor progression and therapeutic resistance, with a focus on the vascular changes, chemotaxic signaling pathways and metabolic alterations involved.
Topics: Animals; Astrocytoma; Brain Neoplasms; Humans; Hypoxia
PubMed: 26094595
DOI: 10.1016/j.nbd.2015.06.007 -
Cancer Reports (Hoboken, N.J.) Aug 2022Pilocytic astrocytoma is the most common brain tumour type in childhood located in the posterior fossa, and treated mainly with surgery. These tumours have low...
BACKGROUND
Pilocytic astrocytoma is the most common brain tumour type in childhood located in the posterior fossa, and treated mainly with surgery. These tumours have low mortality, but knowledge concerning its long-term outcome is sparse.
AIMS
The aim was to investigate if patients treated for pilocytic astrocytoma in the posterior fossa had motor complications, including balance, motor and process skills.
METHODS AND RESULTS
This descriptive single-centre study includes eight children and 12 adults, treated for pilocytic astrocytoma as children. Motor performance was investigated with Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, and dynamic balance with the mini-balance evaluation systems test. Physiological cost index, six-minute walk test, hand grip strength and assessment of motor and process skills were also evaluated. Ten patients reported motor difficulties, mainly from the upper limbs. The motor performance test showed results within normal limits except for manual dexterity, which was significantly below mean (p = .008). In the dynamic balance test patients had significantly lower results compared with controls (p = .036). Physiological cost index, six-minute walk tests and hand grip strength showed results within normal limits. In the Assessment of Motor and Process Skills, patients over 16 years had significantly lower results compared with test norms for motor activities of daily living (ADL) and 30% of all patients scored below the cut-off level for difficulties with motor skills.
CONCLUSIONS
Motor performance for patients treated for pilocytic astrocytoma in the posterior fossa in childhood is satisfactory but some patients display difficulties with balance, manual dexterity and ADL motor skills. Thus, it is important to identify those in need of motor follow-up and training.
Topics: Activities of Daily Living; Adult; Astrocytoma; Brain Neoplasms; Child; Hand Strength; Humans
PubMed: 34643060
DOI: 10.1002/cnr2.1548 -
Frontiers in Pediatrics 2020Arterial Spin Labeling (ASL), a perfusion assessment without using gadolinium-based contrast agents, is outstandingly advantageous for pediatric patients. The...
Arterial Spin Labeling (ASL), a perfusion assessment without using gadolinium-based contrast agents, is outstandingly advantageous for pediatric patients. The differentiation of medulloblastomas from pilocytic astrocytomas in children plays a significant role in determining treatment strategies and prognosis. This study aimed to assess the use of ASL parameters during the differentiation between pediatric medulloblastoma and pilocytic astrocytoma. The institutional review board of Children's Hospital 2 approved this prospective study. The brain magnetic resonance imaging (MRI) protocol, including axial three-dimensional (3D) pseudo-continuous ASL, was evaluated in 33 patients, who were divided into a medulloblastoma group ( = 25) and a pilocytic astrocytoma group ( = 8). The quantified region of interest (ROI) values for the tumors and the tumor to parenchyma ratios were collected and compared between the two groups. Receiver operating characteristic (ROC) curve analysis and the Youden index were utilized to identify the best cut-off, sensitivity, specificity, and area under the curve (AUC) values for significant ASL parameters. The cerebral blood flow (CBF) and the ratio between the CBF of the tumor relative to that of the parenchyma (rCBF) values for medulloblastomas were significantly higher than those for pilocytic astrocytomas ( < 0.05). A cut-off value of 0.51 for rCBF was able to discriminate between medulloblastoma and pilocytic astrocytoma, generating a sensitivity of 88%, a specificity of 75%, and an AUC of 83.5%. The rCBF measurement, obtained during MRI with 3D pseudo-continuous ASL, plays a supplemental role in the differentiation of medulloblastoma from pilocytic astrocytoma.
PubMed: 33763392
DOI: 10.3389/fped.2020.598190 -
BMC Medical Imaging May 2022The accurate grading of IDH-mutant astrocytoma is essential to make therapeutic strategies and assess the prognosis of patients. The purpose of this study was to...
BACKGROUND
The accurate grading of IDH-mutant astrocytoma is essential to make therapeutic strategies and assess the prognosis of patients. The purpose of this study was to investigate the usefulness of DWI, SWI and DSC-PWI in grading IDH-mutant astrocytoma.
METHODS
One hundred and seven patients with IDH-mutant astrocytoma who underwent DWI, SWI and DSC-PWI were retrospectively reviewed. Minimum apparent diffusion coefficient (ADC), intratumoral susceptibility signal intensity(ITSS) and maximum relative cerebral blood volume (rCBV) values were assessed. ADC, ITSS and rCBV values were compared between grade 2 vs. grade 3, grade 3 vs. grade 4 and grade 2 + 3 vs. grade 4 tumors. Logistic regression, tenfold cross-validation,and receiver operating characteristic (ROC) curve analyses were used to assess their diagnostic performances.
RESULTS
Grade 4 IDH-mutant astrocytomas showed significantly lower ADC and higher rCBV as compared to grade 3 tumors (adjusted P < 0.001). IDH-mutant grade 3 astrocytomas showed significantly lower ITSS levels as compared with grade 4 tumors (adjusted P < 0.001). ITSS levels between IDH-mutant grade 2 and grade 3 astrocytomas were significantly different (adjusted P = 0.002). Combined the ADC, ITSS and rCBV resulted in the highest AUC for differentiation grade 2 and grade 3 tumors from grade 4 tumors.
CONCLUSION
ADC rCBV and ITSS can be used for grading the IDH-mutant astrocytomas. The combination of ADC ITSS and rCBV could improve the diagnostic performance in grading of IDH-mutant astrocytoma.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Humans; Magnetic Resonance Imaging; Perfusion; Retrospective Studies
PubMed: 35644621
DOI: 10.1186/s12880-022-00832-3 -
Clinical and Translational Medicine Feb 2024Paediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and... (Review)
Review
Paediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and these treatments lead to adverse long-term health concerns. Integrative omics-based studies have shown the pathology and fundamental molecular characteristics differ significantly and cannot be extrapolated from the more widely studied adult disease. Recent clinical advances in our understanding of paediatric astrocytomas, with the aid of next-generation sequencing and epigenome-wide profiling, have led to the identification of key canonical mutations that vary based on the tumour location and age of onset. These driver mutations, in particular the identification of the recurrent histone H3 mutations in high-grade tumours, have confirmed the important role epigenetic dysregulations play in cancer progression. This review summarises the current updates of the classification, epidemiology, pathogenesis and clinical management of paediatric astrocytoma based on their grades and the ongoing clinical trials. It also provides novel insights on genetic and epigenetic alterations as diagnostic biomarkers, highlighting the potential of targeting these pathways as therapeutics for this devastating childhood cancer.
Topics: Adult; Humans; Child; Brain Neoplasms; Astrocytoma; Histones; Epigenesis, Genetic; Epigenomics
PubMed: 38299304
DOI: 10.1002/ctm2.1560 -
JCO Precision Oncology Apr 2022
Topics: Astrocytoma; Humans; Morpholines; Mutation; Pyrimidines; Pyrroles; Receptor, Fibroblast Growth Factor, Type 1
PubMed: 35507888
DOI: 10.1200/PO.21.00371 -
European Journal of Medical Genetics Jan 2020Mutations in LZTR1, already known to be causal in familial schwannomatosis type 2, have been recently involved in a small proportion of patients with autosomal dominant...
Mutations in LZTR1, already known to be causal in familial schwannomatosis type 2, have been recently involved in a small proportion of patients with autosomal dominant and autosomal recessive Noonan syndrome. LZTR1 is also a driver gene in non syndromal glioblastoma. We report a 26-year-old patient with typical Noonan syndrome, and the dominantly transmitted c.850C > T (p.(Arg284Cys)) variant in LZTR1. An oligoastrocytoma was diagnosed in the patient at the age of 22 years; recurrence of the tumor occurred at age 26, as a ganglioblastoma. The patient had been transiently treated with growth hormone between ages 15 and 17. Considering the implication of LZTR1 in sporadic tumors of the nervous system, we hypothesize that gliomas are a possible complication of LZTR1-related Noonan syndrome. This report also supports a possible link between occurrence of a cerebral tumor in Noonan syndrome and a previous treatment with growth hormone.
Topics: Adolescent; Adult; Astrocytoma; Female; Genetic Predisposition to Disease; Glioblastoma; Humans; Male; Mutation; Noonan Syndrome; Pedigree; Transcription Factors
PubMed: 30664951
DOI: 10.1016/j.ejmg.2019.01.007 -
Orphanet Journal of Rare Diseases Dec 2023The randomised double-blinded placebo-controlled EXIST-1-3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms... (Clinical Trial)
Clinical Trial
BACKGROUND
The randomised double-blinded placebo-controlled EXIST-1-3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms in patients with tuberous sclerosis complex (TSC), although evidence of outcomes in clinical practice remains limited. This study aimed to investigate, in clinical practice, the effectiveness and safety of everolimus for epilepsy, renal angiomyolipoma (rAML), and subependymal giant cell astrocytoma (SEGA) in patients with TSC.
RESULTS
The study included 64 patients with TSC (median age: 19, range 0.9-54 years) receiving everolimus treatment (Norway: n = 35; Denmark: n = 29). Among 45 patients with epilepsy, 14 (31%) were responders experiencing ≥ 50% reduction in seizure frequency in the last 3 months of treatment compared with the last 3 months before treatment. Nineteen (42%) patients changed their anti-seizure medications (ASMs). Responders were more common among patients < 18 years (46%) than among patients ≥ 18 years (14%, p = 0.03). In 29 patients with rAML, everolimus reduced (≥ 30% decrease) and stabilized (< 20% increase, ≤ 30% decrease) longest diameter of rAML in 38% and 59%, respectively, after a mean treatment duration of 37 months. SEGA volume was reduced in three patients by 71%, 43%, and 48% after 39, 34, and 82 months. Adverse effects were reported in 61 of 64 patients (95%) after a median treatment duration of 31 months (range 0-106), with oral ulceration/stomatitis (63%) and upper respiratory tract infections (38%) being the most common. The most common laboratory abnormalities were increased cholesterol (41%), anaemia (30%), and leucopoenia (25%). Grade 3-4 adverse effects were reported in 36% of cases, and life-threatening conditions were reported in two patients. Nine patients discontinued everolimus treatment.
CONCLUSIONS
Seizure reduction in this study sample was consistent with results from EXIST, but might be lower than expected, given that changes in concomitant ASMs are part of clinical practice. Seizure reduction was associated with younger age. As with EXIST, everolimus reduced or stabilised rAML size in most patients. SEGA volume was reduced in all three patients. Close follow-up is needed for this group, especially for children and patients who may not be able to report adverse effects.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Middle Aged; Young Adult; Angiomyolipoma; Antineoplastic Agents; Astrocytoma; Epilepsy; Everolimus; Kidney Neoplasms; Seizures; Tuberous Sclerosis
PubMed: 38042867
DOI: 10.1186/s13023-023-02982-1 -
Brain Pathology (Zurich, Switzerland) Jan 2021Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a...
Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a cohort of 67 patients with histologically defined PXA (n = 53, 79%) or anaplastic PXA (A-PXA, n = 14, 21%), including copy number analysis (ThermoFisher Oncoscan, n = 67), methylation profiling (Illumina EPIC array, n = 43) and targeted next generation sequencing (n = 32). The most frequent alterations were CDKN2A/B deletion (n = 63; 94%) and BRAF p.V600E (n = 51, 76.1%). In 7 BRAF p.V600 wild-type cases, alternative driver alterations were identified involving BRAF, RAF1 and NF1. Downstream phosphorylation of ERK kinase was uniformly present. Additional pathogenic alterations were rare, with TERT, ATRX and TP53 mutations identified in a small number of tumors, predominantly A-PXA. Methylation-based classification of 46 cases utilizing a comprehensive reference tumor allowed assignment to the PXA methylation class in 40 cases. A minority grouped with the methylation classes of ganglioglioma or pilocytic astrocytoma (n = 2), anaplastic pilocytic astrocytoma (n = 2) or control tissues (n = 2). In 9 cases, tissue was available from matched primary and recurrent tumors, including 8 with anaplastic transformation. At recurrence, two tumors acquired TERT promoter mutations and the majority demonstrated additional non-recurrent copy number alterations. Methylation class was preserved at recurrence. For 62 patients (92.5%), clinical follow-up data were available (median follow-up, 5.4 years). Overall survival was significantly different between PXA and A-PXA (5-year OS 80.8% vs. 47.6%; P = 0.0009) but not progression-free survival (5-year PFS 59.9% vs. 39.8%; P = 0.05). WHO grade remained a strong predictor of overall survival when limited to 38 cases defined as PXA by methylation-based classification. Our data confirm the importance of WHO grading in histologically and epigenetically defined PXA. Methylation-based classification may be helpful in cases with ambiguous morphology, but is largely confirmatory in PXA with well-defined morphology.
Topics: Adolescent; Adult; Aged; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Cohort Studies; DNA Methylation; Female; Humans; Male; Middle Aged; Neoplasm Grading; Young Adult
PubMed: 32619305
DOI: 10.1111/bpa.12874 -
Arquivos de Neuro-psiquiatria Dec 2023Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or...
Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma or altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome.
Topics: Adolescent; Young Adult; Humans; Child; Epilepsy; Glioma; Brain Neoplasms; Ganglioglioma; Astrocytoma; Neoplasms, Neuroepithelial
PubMed: 38157880
DOI: 10.1055/s-0043-1777730