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Journal of Cancer Research and... 2022Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven...
BACKGROUND
Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven equivocal. The present study aims to evaluate the risk variables, indicating that LGA gradually differentiates to malignant astrocytoma.
METHODS
Retrospective cohort analysis of LGA patients was performed. Both univariate and multivariate studies were used to discover variables connected to MT using the Cox regression method. As a result, the cumulative incidence of MT for each covariate survival curve was built after the final model.
RESULTS
In the current study, 115 individuals with LGA were included in the analysis, and MT was found in 16.5% of cases. In the case of MT, 68.4% of patients progressed to glioblastoma, whereas 31.6% progressed to anaplastic astrocytoma. Significant factors included supratentorial tumor (hazard ratio (HR) 3.41, 95% CI 1.18-12.10), midline shift > 5 mm (HR 7.15, 95% CI 2.28-34.33), and non-total resection as follows: subtotal resection (HR 5.09, 95% CI 0.07-24.02), partial resection (HR 1.61, 95% CI 1.09-24.11), and biopsy (HR 2.80, 95% CI 1.18-32.52).
CONCLUSION
In individuals with LGA, MT dramatically altered the disease's natural history to a poor prognosis. The present study's analysis of the clinical features of patients indicated supratentorial LGA, a midline shift greater than 5 mm, and the degree of resection as risk factors for MT. The more extensive the resection, the greater the reduction in tumor load and MT. In addition, more molecular study is necessary to elucidate the pathophysiology of MT.
Topics: Humans; Retrospective Studies; Brain Neoplasms; Astrocytoma; Glioblastoma; Cell Transformation, Neoplastic
PubMed: 36412420
DOI: 10.4103/jcrt.JCRT_1469_20 -
Polish Journal of Pathology : Official... 2023Aim of the study is To investigate the effect of lentinan on proliferation and apoptosis of human astrocytoma U251 cells. Lentinan was dissolved in DMEM complete medium...
AIM OF THE STUDY
Aim of the study is To investigate the effect of lentinan on proliferation and apoptosis of human astrocytoma U251 cells. Lentinan was dissolved in DMEM complete medium to form different concentrations (0, 25, 50, 100, 200, 400, 500, 600 µg/ml). CCK8 was used to detect the effect of lentinan with different concentrations on proliferation of human astrocytoma U251 cells, and the expression of Ki-67 was detected by immunofluorescence. In addition, the effect of different concentrations of lentinan on apoptosis of human astrocytoma U251 cells was detected by flow cytometry. Compared with the blank control group, 50 and 100 µg/ml lentinan significantly promoted proliferation of human astrocytoma U251 cells. When the concentration is more than 100 µg/ml, the cell activity gradually decreases, and the cell activity is the lowest when the concentration is 600 µg/ml. In addition, the low concentration lentinan (25, 50, and 100 µg/ml) had no significant effect on apoptosis of human astrocytoma U251 cells. However, lentinan above 200 µg/ml significantly promoted apoptosis of human astrocytoma U251 cells and had a concentration gradient effect, and the highest apoptosis rate was at 600 µg/ml.
CONCLUSIONS
Lentinan can effectively inhibit proliferation and promote apoptosis of human astrocytoma U251 cells.
Topics: Humans; Lentinan; Cell Line, Tumor; Cell Proliferation; Astrocytoma; Apoptosis
PubMed: 36106424
DOI: 10.5114/pjp.2022.119264 -
Journal of Neuro-oncology Oct 2022The role of temozolomide chemotherapy alone in isocitrate dehydrogenase (IDH)-mutant astrocytomas has not been conclusively determined. Radiotherapy might be superior to...
PURPOSE
The role of temozolomide chemotherapy alone in isocitrate dehydrogenase (IDH)-mutant astrocytomas has not been conclusively determined. Radiotherapy might be superior to temozolomide. Recent studies have linked temozolomide with induction of hypermutation and poor clinical course in some IDH-mutant gliomas.
METHODS
In this retrospective study, 183 patients with astrocytoma, IDH-mutant, CNS WHO grade 2 or 3 and diagnosed between 2001 and 2019 were included. Patients initially monitored by wait-and-scan strategies or treated with radiotherapy or temozolomide alone were studied. Patient data were correlated with outcome. Matched pair and subgroup analyses were conducted.
RESULTS
Radiotherapy was associated with longer progression-free survival than temozolomide (6.2 vs 3.4 years, p = 0.02) and wait-and-scan strategies (6.2 vs 4 years, p = 0.03). Patients treated with radiotherapy lived longer than patients treated with temozolomide (14.4 vs 10.7 years, p = 0.02). Survival was longer in the wait-and-scan cohort than in the temozolomide cohort (not reached vs 10.7 years, p < 0.01). Patients from the wait-and-scan cohort receiving temozolomide at first progression had significantly shorter survival times than patients treated with any other therapy at first progression (p < 0.01). Post-surgical T2 tumor volume, contrast enhancement on MRI and WHO grade were associated with overall survival in univariate analyses (p < 0.01).
CONCLUSION
The results suggest superiority of radiotherapy over temozolomide and wait-and-scan strategies regarding progression-free survival and superiority of radiotherapy over temozolomide regarding overall survival. Our results are consistent with the notion that early temozolomide might compromise outcome in some patients.
Topics: Humans; Temozolomide; Isocitrate Dehydrogenase; Dacarbazine; Retrospective Studies; Antineoplastic Agents, Alkylating; Brain Neoplasms; Astrocytoma; World Health Organization; Mutation
PubMed: 36112301
DOI: 10.1007/s11060-022-04128-y -
Modern Pathology : An Official Journal... Jul 2021WHO 2016 classified glioblastomas into IDH-mutant and IDH-wildtype with the former having a better prognosis but there was no study on IDH-mutant primary glioblastomas...
WHO 2016 classified glioblastomas into IDH-mutant and IDH-wildtype with the former having a better prognosis but there was no study on IDH-mutant primary glioblastomas only, as previous series included secondary glioblastomas. We recruited a series of 67 IDH-mutant primary glioblastomas/astrocytoma IV without a prior low-grade astrocytoma and examined them using DNA-methylation profiling, targeted sequencing, RNA sequencing and TERT promoter sequencing, and correlated the molecular findings with clinical parameters. The median OS of 39.4 months of 64 cases and PFS of 25.9 months of 57 cases were better than the survival data of IDH-wildtype glioblastomas and IDH-mutant secondary glioblastomas retrieved from datasets. The molecular features often seen in glioblastomas, such as EGFR amplification, combined +7/-10, and TERT promoter mutations were only observed in 6/53 (11.3%), 4/53 (7.5%), and 2/67 (3.0%) cases, respectively, and gene fusions were found only in two cases. The main mechanism for telomere maintenance appeared to be alternative lengthening of telomeres as ATRX mutation was found in 34/53 (64.2%) cases. In t-SNE analyses of DNA-methylation profiles, with an exceptional of one case, a majority of our cases clustered to IDH-mutant high-grade astrocytoma subclass (40/53; 75.5%) and the rest to IDH-mutant astrocytoma subclass (12/53; 22.6%). The latter was also enriched with G-CIMP high cases (12/12; 100%). G-CIMP-high status and MGMT promoter methylation were independent good prognosticators for OS (p = 0.022 and p = 0.002, respectively) and TP53 mutation was an independent poor prognosticator (p = 0.013) when correlated with other clinical parameters. Homozygous deletion of CDKN2A/B was not correlated with OS (p = 0.197) and PFS (p = 0.278). PDGFRA amplification or mutation was found in 16/59 (27.1%) of cases and was correlated with G-CIMP-low status (p = 0.010). Aside from the three well-known pathways of pathogenesis in glioblastomas, chromatin modifying and mismatch repair pathways were common aberrations (88.7% and 20.8%, respectively), the former due to high frequency of ATRX involvement. We conclude that IDH-mutant primary glioblastomas have better prognosis than secondary glioblastomas and have major molecular differences from other commoner glioblastomas. G-CIMP subgroups, MGMT promoter methylation, and TP53 mutation are useful prognostic adjuncts.
Topics: Adult; Astrocytoma; Brain Neoplasms; DNA Mutational Analysis; Female; Glioblastoma; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Prognosis
PubMed: 33692446
DOI: 10.1038/s41379-021-00778-x -
Frontiers in Neurology 2022The differential diagnosis between autoimmune encephalitis and low-grade diffuse astrocytoma remains challenging. We aim to develop a quantitative model integrating...
BACKGROUND
The differential diagnosis between autoimmune encephalitis and low-grade diffuse astrocytoma remains challenging. We aim to develop a quantitative model integrating radiomics and spatial distribution features derived from MRI for discriminating these two conditions.
METHODS
In our study, we included 188 patients with confirmed autoimmune encephalitis ( = 81) and WHO grade II diffuse astrocytoma ( = 107). Patients with autoimmune encephalitis (AE, = 59) and WHO grade II diffuse astrocytoma (AS, = 79) were divided into training and test sets, using stratified sampling according to MRI scanners. We further included an independent validation set (22 patients with AE and 28 patients with AS). Hyperintensity fluid-attenuated inversion recovery (FLAIR) lesions were segmented for each subject. Ten radiomics and eight spatial distribution features were selected the least absolute shrinkage and selection operator (LASSO), and joint models were constructed by logistic regression for disease classification. Model performance was measured in the test set using the area under the receiver operating characteristic (ROC) curve (AUC). The discrimination performance of the joint model was compared with neuroradiologists.
RESULTS
The joint model achieved better performance (AUC 0.957/0.908, accuracy 0.914/0.840 for test and independent validation sets, respectively) than the radiomics and spatial distribution models. The joint model achieved lower performance than a senior neuroradiologist (AUC 0.917/0.875) but higher performance than a junior neuroradiologist (AUC 0.692/0.745) in the test and independent validation sets.
CONCLUSION
The joint model of radiomics and spatial distribution from a single FLAIR could effectively classify AE and AS, providing clinical decision support for the differential diagnosis between the two conditions.
PubMed: 36408523
DOI: 10.3389/fneur.2022.998279 -
Diagnostic and Interventional Radiology... Nov 2021The reliability and reproducibility of T2-weighted imaging/ fluid-attenuated inversion recovery (T2/FLAIR) mismatch were investigated in the diagnosis of isocitrate...
PURPOSE
The reliability and reproducibility of T2-weighted imaging/ fluid-attenuated inversion recovery (T2/FLAIR) mismatch were investigated in the diagnosis of isocitrate dehydrogenase (IDH) mutant astrocytoma between WHO grade II and III diffuse hemispheric gliomas.
METHODS
WHO grade II and grade III diffuse hemispheric gliomas (n=133) treated in our institute were included in the study. Pathological findings and molecular markers of the cases were reviewed with the criteria of WHO 2016. The finding of mismatch between T2-weighted and FLAIR images in preoperative magnetic resonance imaging (MRI) of the cases was evaluated by two different radiologists. The readers reviewed MRIs independently, blinded to the histopathologic diagnosis or molecular subset of tumors. The cases were classified as IDH-mutant astrocytoma, oligodendroglioma and IDH-wildtype (IDH-wt) astrocytoma according to molecular and genetic features.
RESULTS
T2/FLAIR mismatch positivity was observed in 46 patients (34.6%). T2/FLAIR mismatch positivity was observed in 42 of 75 IDH-mutant astrocytomas (56%) and 4 of 43 oligodendrogliomas (9.30%), while it was not seen among IDH-wt astrocytomas (0/15, 0%). The T2/FLAIR mismatch ratio was significantly different between IDH-mutant astrocytomas (WHO grade II and grade III) and oligodendrogliomas (chi-square, p <0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of T2/FLAIR mismatch in predicting IDH-mutant astrocytomas were 58.7%, 90.7%, 91.7%, 61.4%, and 70.3% respectively. Radiologist 1 diagnosed T2/FLAIR mismatch in 48 of 133 cases (36.1%) and Radiologist 2 in 66 of 133 cases (49.6%). The interrater agreement for the T2/FLAIR mismatch sign was 0.61 (p <0.05), 95% CI (0.55, 0.67).
CONCLUSION
T2/FLAIR mismatch appears to be an important MRI finding in distinguishing IDH-mutant astrocytomas from other diffuse hemispheric gliomas. However, it should be kept in mind that T2/FLAIR mismatch sign can be seen in a minority of oligodendrogliomas besides IDH-mutant astrocytomas.
Topics: Astrocytoma; Brain Neoplasms; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Mutation; Reproducibility of Results; Retrospective Studies
PubMed: 34792037
DOI: 10.5152/dir.2021.20624 -
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 -
CMAJ : Canadian Medical Association... Sep 2021
Topics: Astrocytoma; Brain Neoplasms; Female; Humans; Mothers; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome
PubMed: 34544784
DOI: 10.1503/cmaj.210901 -
Neuro-oncology Nov 2022Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness...
BACKGROUND
Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types.
METHODS
Brain tumor patients with histopathologically confirmed diagnosis in 2018 were identified within the Central Brain Tumor Registry of the United States and NCI's Surveillance, Epidemiology, and End Results Incidence databases. The brain molecular markers (BMM) site-specific data item was assessed for coding completeness and validity. 1p/19q status, MGMT promoter methylation, WHO grade data items, and new ICD-O-3 codes were additionally evaluated. These data were used to profile the characteristics and age-adjusted incidence rates per 100 000 population of molecularly defined brain tumors with 95% confidence intervals (95% CI).
RESULTS
BMM completeness across the applicable tumor types was 75%-92% and demonstrated favorable coding validity. IDH-wildtype glioblastomas' incidence rate was 1.74 (95% CI: 1.69-1.78), as compared to 0.14 for WHO grade 2 (95% CI: 0.12-0.15), 0.15 for grade 3 (95% CI: 0.14-0.16), and 0.07 for grade 4 (95% CI: 0.06-0.08) IDH-mutant astrocytomas. Irrespective of WHO grade, IDH mutation prevalence was highest in adolescent and young adult patients, and IDH-mutant astrocytomas were more frequently MGMT promoter methylated. Among pediatric-type tumors, the incidence rate was 0.06 for H3K27M-mutant diffuse midline gliomas (95% CI: 0.05-0.07), 0.03 for SHH-activated/TP53-wildtype medulloblastomas (95% CI: 0.02-0.03), and <0.01 for both C19MC-altered embryonal tumor with multilayered rosettes and RELA-fusion ependymomas.
CONCLUSIONS
Our findings illustrate the success of developing a dedicated, integrated diagnosis variable, which provides critical molecular information about brain tumors related to accurate diagnosis.
Topics: Young Adult; Adolescent; Child; Humans; United States; Brain Neoplasms; Glioma; Astrocytoma; Glioblastoma; Biomarkers; Isocitrate Dehydrogenase; Mutation
PubMed: 35460555
DOI: 10.1093/neuonc/noac113 -
Veterinary Pathology Sep 2021Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain...
Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain tumors. Hitherto, there is relatively little prognostic data for canine gliomas and none on outcome related to specific histological features. Histologic sections of tumor biopsies from 33 dogs with glioma treated with surgical resection and immunotherapy and 21 whole brains obtained postmortem were reviewed. Tumors were diagnosed as astrocytic, oligodendroglial, or undefined glioma using Comparative Brain Tumor Consortium criteria. Putative features of malignancy were evaluated, namely, mitotic counts, glomeruloid vascularization, and necrosis. For biopsies, dogs with astrocytic tumors lived longer than those with oligodendroglial or undefined tumor types (median survival 743, 205, and 144 days, respectively). Dogs with low-grade gliomas lived longer than those with high-grade gliomas (median survival 734 and 194 days, respectively). Based on analysis of tumor biopsies, low mitotic counts, absence of glomeruloid vascularization, and absence of necrosis correlated with increased survival (median 293, 223, and 220 days, respectively), whereas high mitotic counts, glomeruloid vascularization, and necrosis correlated with poor survival (median 190, 170, and 154 days, respectively). Mitotic count was the only histological feature in biopsy samples that significantly correlated with survival ( < .05). Whole-brain analyses for those same histologic features had similar and more robust correlations, and were statistically significant for all features ( < .05). The small size of biopsy samples may explain differences between biopsy and whole-brain tumor data. These findings will allow more accurate prognosis for gliomas.
Topics: Animals; Astrocytoma; Brain Neoplasms; Dog Diseases; Dogs; Glioma; Prognosis; Retrospective Studies
PubMed: 34219560
DOI: 10.1177/03009858211025795