Cases Of High-grade Gliomas Research Articles

LINC-03. A single center retrospective analysis of current therapy and outcome of central nervous system tumors in children of Beijing

OBJECTIVE: To explore the clinical characteristics, therapy and outcome in children with central nervous system (CNS) tumors in Beijing, China. METHODS: Clinical data of 1003 patients with newly diagnosed CNS tumors under the age of 15 years admitted to Beijing Shijitan Hospital between January 2017 and December 2021 were retrospectively analyzed. The diagnoses were confirmed by pathology and/or molecular tests. RESULTS: 34 patients were lost to follow up. Medulloblastoma (n=472), ependymoma (n=79), ETMR (n=59) and pinealoblastoma (n=19) were treated according to HIT-2000/2017, 5-year progression-free survival (PFS) and overall survival (OS) were 76.4 ± 2.3%/ 84.8 ±1.9% in MB, 88.8±3.7% /89.5±3.8% in ependymoma, 49.9±7.6%/59.6±10.7% in ETMR, and 3y-PFS/OS of 11.1±10.5%, 90.0±9.5% in pinealoblastoma. The detailed histology of 59 cases of embryonal tumors included 40 cases of CNS embryonal tumor, 9 neuroblastoma, 7 ETMR, and 3 rare tumors (Intracranial mesenchymal tumor with FET-CREB fusion, CNS high-grade neuroepithelial tumor with BCOR alteration, and Melanotic neuroectodermal tumor of infancy). Among 19 cases of pinealoblastoma, two contain DICER1 mutations. Atypical teratoid/rhabdoid tumors (n=36) were treated by EU-RHAB-Protocol with 3y-PFS/OS of 42.2 ± 9.4 % and 62.8 ± 9.5 %. For low-grade gliomas (n=153, 114 cases of OPG and 39 other non-STR/NTR or progressive cases) under SIOP-LGG 2004, 5y-PFS/OS rates were 77.6±5.2% and 92.4±3.2%; Comparatively, among 63 cases of high-grade gliomas, 19 cases survived with median survival of 52 months, 44 cases died. Choroid plexus cancers (n=13) were treated according to CPT-SIOP-2009 with 5y-PFS /OS of 68.4 ± 13.1 % and 64.8±14.3 %. Among 109 germ cell tumors, 5y-PFS/OS were 93.8±2.8% and 95.5±2.2%, respectively. CONCLUSION: The prognosis of CNS tumors are related to pathology, molecular type and individualized therapy. By international multicenter cooperation and adopting advanced protocols, the survival rates of pediatric CNS tumors can be significantly improved.

High Expression of PLAGL2 is Associated With Poor Prognosis in High-Grade Glioma.

Pleomorphic adenoma gene like-2 (PLAGL2) has been implicated in the development and progression of diverse malignancies, including glioblastoma. An increasing number of studies have reported that dysregulated expression of PLAGL2 is a common phenomenon in different malignancies. However, the mechanism and biological functions of PLAGL2 in patients with high-grade glioma (HGG) remain unclear. In addition, the expression and clinical significance of PLAGL2 in HGG have not yet been reported. Herein, we investigated the expression patterns and prognostic values of PLAGL2 in patients with HGG by using various databases, including Tumor Immune Estimation Resource 2.0 (TIMER2.0), GENT2, ONCOMINE, GEPIA, Human Protein Atlas, and Gene Expression Omnibus datasets. In the present study, we analyzed the relationship between PLAGL2 mRNA expression and clinical parameters in 184 HGG cases and found that PLAGL2 presented positively high expression and was relevant to poor prognosis. Immunohistochemistry analysis confirmed the overexpression of PLAGL2 protein, which is mainly expressed in the nucleus of glioma. Additionally, a high level of expression of the PLAGL2 gene was associated with lower survival in progression-free survival and overall survival in GBM patients. The correlation analysis between PLAGL2 and immune infiltration related to the abundance of B cells, CD8+ T cells, CD4+ T cells, macrophages, DCs, and neutrophils was also performed using TIMER2.0. GSEA results showed that high PLAGL2 expression was associated with cell migration, proliferation, actin cytoskeletal, and angiogenesis. To sum up, our findings indicated that PLAGL2 could serve as an independent prognostic biomarker and might be a potential therapeutic target for HGG, which should be further investigated.

STMO-16 The usability of Detailed pre-operative 3D simulation image for Tumor Resection of High grade glioma

IntroductionUnderstanding micro structures is important for the safety and reliable tumor resection for high grade glioma(HGG). The high-resolution 3-demension pre-operative simulation image (3D simulation imege) provides the useful information to the operators. We will report the outcome and the device of 3D simulation image at our single institute.Material and MethodFrom April 2019 to July 2021, 56 cases of HGG (grade III: 18 cases, grade IV: 38 cases, initial cases: 49 cases, recurrent cases: 7) were included retrospectively. Zedview, Horos, and Freeform were used to create 3D simulation image from conventional clinical images as CT, MRI, and angiography. The evaluations of anatomical structures were 9 items: cerebral arteries (A), cerebral veins (V), perforators (Per), passing arteries (Pass), feeders (F), drainers (D), sylvian fissure vessels (SV), brain structures (B), and ventricles (Vent). After determining the necessity of 3D visualization for operative planning and evaluating whether it was possible to create the 3D image, the consistency with the anatomical structure and the usefulness for surgery were scored (Excellent 3 points / Good 2 points / Poor 1 point) respectively.ResultA: 56 out of 56 cases (100%) was judged as necessary, and the average score was 2.73 points. V: 56/56 cases (100%), 2.70 points. Per: 7/7 cases (100%), 1.80 points. Pass: 7/7 cases (100%), 2.86 points. F: 34/36 cases (94.5%), 2.56 points. D: 22/22 cases (100%), 2.36 points. SA: 7/7 cases (100%), 2.43 points. B: 53/54 (98.1%), 2.70 points. Vent: 27/28 cases (96.5%), 2.50 points. The average score of all structures was 2.59 points.Discussion and Conclusion3D imaging of the required anatomical structures was possible in almost all cases, and consistency and usefulness in most items were highly scored. Although the evaluation of the perforators was low, the 3D simulation image seemed to be useful for surgical planning.

RADT-20. SINGLE INSTITUTION REVIEW OF LARGE VOLUME HIGH GRADE GLIOMA PATIENTS TREATED WITH RADIOTHERAPY

Abstract AIM Not uncommonly, we come across significantly large high grade glioma cases (HGGs). With standard delineation protocols, we end up irradiating a large volume of normal brain. Emami & QUANTEC data define normal brain tolerance doses, however they are often of limited use in clinic practice. Thus, we reviewed our patients with significant tumor volumes to derive a safe dose/ volume level for brain. METHODOLOGY Patients with HGGs over the last 3 years were extracted from Mosaiq™ information system. The output was sorted with respect to clinical target volumes from lowest to highest. The top 25 percentile i.e. patients with a CTV of > 412cc (n=53) were identified for this study. Data was collected with respect to clinical, tumor characteristics and radiotherapy parameters. RESULTS Median age of population was 53 and majority (n=38) were males. Nine patients had multi-focal tumors while six had bilateral extension. Majority of the study group had Glioblastoma Multiforme (n=44), whereas 6 had Grade 3 tumors. Most of the patients could only have a biopsy (n=27). Molecular profile showed 42 were Isocitrate-Dehydrogenase negative and 26 were unmethylated tumors. Stupp’s & Perry’s regimen were the commonly used protocols, however patients (n=7) with significant volumes near critical structures were treated with doses in the range of 50.4 – 55Gy in 30 fractions. The CTV volumes in the population ranged from 412 – 1223 cc while total brain volume range was 1112 – 1667 cc. Median of 43.5% of brain volume was covered in the PTV, while median of 5% of brain volume outside the PTV was treated to BED2 of 100Gy. Median survival was 12.4 months. CONCLUSION Our study shows reasonable tolerance of radiotherapy doses of > 50 Gy to larger volumes of brain. We propose a multi-center collaborative study to derive a new standardized dose volume tolerance.

EPID-06. ASSOCIATIONS BETWEEN GERMLINE GENETIC VARIANTS AND OVERALL SURVIVAL IN PATIENTS WITH GLIOMA

Abstract BACKGROUND In addition to somatic genetic variation in tumors, germline genetic variation can better define cancer susceptibility risk, guide therapy, and predict survival. Most prior research into associations between germline genetic variants and survival outcomes in patients with glioma has been limited by small sample sizes and to high-grade glioma only. This study is the first to use data from Brigham and Women’s Hospital (BWH) and to include both low-grade and high-grade glioma cases to explore associations between germline genetic variants and overall survival. METHODS This study included 211 patients enrolled at BWH from April 2010 to January 2020. Ninety-two candidate germline genetic variants were identified via literature review. Fifty-five variants with minor allele frequency >0.05 were included preliminarily, for which bivariate Cox proportional hazards regression models were employed. Twenty-two variants with P< 0.5 were included in the final multivariable model, adjusted for patient sex, age, race, and glioma grade. Stratified sub-analyses were also conducted by sex. Associations were considered statistically significant at P< 0.05. RESULTS Among all patients, homozygous C/C genotype at rs17655 (ERCC5 gene) was significantly associated with worse overall survival (hazard ratio=2.61, P=0.0095). Among females only, worse survival was associated with homozygous T/T genotype at rs1381057 (POLQ, hazard ratio=2.58, P=0.046). Among males only, heterozygous status for the A genotype at rs487848 (POLQ, hazard ratio=0.31, P=0.018) and the A genotype at rs1468923 variant (PIK3CA, hazard ratio=0.51, P=0.016) were associated with improved survival. CONCLUSION We identified statistically significant associations between overall survival and four variants in genes involved in DNA repair and the PIK3 pathway, three of which were sex-specific. Our results contribute to improving patient stratification in glioma and may lead to increased targeting of treatment strategies.

CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA

Pediatric high grade gliomas(HGG) have dismal prognosis with median survival of 9-15 months after standard radio-chemptherapy. Recent molecular investigations revealed a missmatch repair defect called Constitutional Mismatch Repair Deficiency (CMMRD), which induce pediatric HGG. In CMMRD, there are mutations at least one of the mismatch repair(MMR) genes in both tumoral and non-tumoral DNA. Patients generally have cafe au lait spots resembling the ones in NF-1. Forty-four pediatric high-grade glioma cases operated in our clinic between 2015-2021 were included in the study. PMS2, MLH1, MSH6, MSH2 immunohistochemical antibodies were applied to the sections prepared from paraffin blocks with tumors of these 44 cases. Next generation Sequencing (NGS) Custom Panel for Brain Tumors was performed with DNA and RNA obtained from neoplastic tissue of 2 cases and germline NGS analysis was performed with DNA obtained from peripheral blood in 1 case. MMR protein expression loss was detected in 11 (25%) cases. In 5 (45%) of these 11 cases, MMR protein loss was detected in both neoplastic and non-neoplastic tissue, and these cases were considered as CMMRD. NGS performed in 2 of these 5 cases revealed a hypermutant profile. At least one MMR protein loss was found only in the neoplastic tissue in 6 (55%) of 11 cases, and PMS2 deficiency was the most common. In 1 of these 6 cases, MSH6 deficiency was shown as germline by NGS. CMMRD and MMRD, are disorders with close relationship with pediatric high grade gliomas. Since CMMRD cases also may have cafe au lait spots, they should not be misdiagnosed as NF 1. Temozolomide induce more aggressive tumors in CMMRD ve MMRD, therefore its use is not suggested in those cases. Preliminary literature data advocate use of immunotherapy instead. All pediatric HGG cases should be evaluated for CMMRD and MMRD with molecular investigations to understand their biology.

Classification and Treatment of Pediatric Gliomas in the Molecular Era.

The overall survival of pediatric gliomas varies over a wide spectrum depending on the tumor grade. Low-grade gliomas have an excellent long-term survival, with a possible burden of surgery, irradiation, and chemotherapy; in contrast, high-grade gliomas generally have a short-term, devastating lethal outcome. Recent advances in understanding their molecular background will transform the classification and therapeutic approaches of pediatric gliomas. Molecularly targeted treatments may acquire a leading role in the primary treatment of low-grade gliomas and may provide alternative therapeutic strategies for high-grade glioma cases in the attempt to avoid the highly unsuccessful conventional therapeutic approaches. This review aims to overview this progress.

Expression of YAP1 and pSTAT3-S727 and their prognostic value in glioma

AimsA growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on...

A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature.

Li-Fraumeni syndrome (LFS) is a rare high-penetrance and autosomal-dominant pathological condition caused by the germline mutation of the TP53 gene, predisposing to the development of tumors from pediatric age. We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms “Li-Fraumeni” AND “pediatric high-grade glioma (HGG)”, identifying six cases of HGGs in pediatric patients with LFS. We added a further case with peculiar features such as no familiar history of LFS, association of embryonal rhabdomyosarcoma and bithalamic HGG, whose immunohistochemical profile was accurately defined by Next Generation Sequencing. Knowledge synthesis and case analysis grounded the discussion about challenges in the management of this pathology in pediatric age.

Assessment of Isocitrate Dehydrogenase 1 Mutation by Immunohistochemistry in Egyptian Patients with High-grade Gliomas

BACKGROUND: At present, the classification of central nervous system tumors relies on molecular factors in addition to histologic features to identify many tumor types. This should subsequently results in more accurate diagnosis as well as addressing specific markers of potential prognostic and predictive value. AIM: This study was conducted to emphasize the importance of including isocitrate dehydrogenase 1 (IDH1) evaluation as a crucial part of the diagnosis and categorization of high-grade glioma cases. This also may help to individualize the treatment of high-grade glioma patients. MATERIALS AND METHODS: The current study included 60 cases of high-grade gliomas, studied histologically and immunohistochemically for the detection of IDH1 mutation. The results were correlated with different clinicopathologic variables and course of the disease. RESULTS: IDH1 immunohistochemical expression was positive in 46.67% of the studied high-grade glioma cases. A statistically significant relationship was detected between IDH1 expression and tumor histologic grade as 100% of Grade III anaplastic oligodendroglioma cases and 80% of the Grade III anaplastic astrocytoma cases were IDH1 positive while only 40.4% of Grade IV glioblastoma cases were IDH1 positive (p = 0.03). In addition, patients who were IDH1 mutant were in a better category of response to radiotherapy (p = 0.019) and also to chemotherapy (p < 0.001). Moreover, patients who expressed IDH1 had prolonged overall survival (OS) and progression-free survival than those who showed negative IDH1expression (p < 0.001). On the other hand, no statistically significant relationship was detected between IDH1 expression and patients age, sex, tumor site, tumor size, motor symptoms, sensory symptoms, and increased intracranial tension (p > 0.05). CONCLUSIONS: It is suggested that IDH1 is a good prognostic marker for gliomas and is a good predictive marker for response to treatment. IDH1 is a promising target for therapy in high-grade gliomas through the emerging IDH1 inhibitors. Immunohistochemical testing for IDH1 is a practical and cost-effective method that should be applied in all glioma cases. Further study on a larger sample size is recommended to validate the current results. Moreover, applying molecular analysis to detect IDH1 mutation is recommended to be able to precisely detect the IDH1 wild-type tumor

Improving the Usability of 5-Aminolevulinic Acid Fluorescence-Guided Surgery by Adding an Optimized Secondary Light Source

Tumors that take up and metabolize 5-aminolevulinic acid emit bright pink fluorescence when illuminated with blue light, aiding surgeons in identifying the margin of resection. The adoption of this method is hindered by the blue light illumination, which is too dim to safely operate under and therefore necessitates switching back and forth from white-light mode. The aim of this study was to examine the addition of an optimized secondary illuminant adapter to improve usability of blue-light mode without degrading tumor contrast. Color science methods were used to evaluate the color of the secondary illuminant and its impact on color rendering index as well as the tumor-to-background color contrast in data collected from 7 patients with high-grade gliomas (World Health Organization grade III and IV). A secondary illuminant adapter was built to provide 475-600 nm light the intensity of which can be controlled by the surgeon and was evaluated in 2 additional patients. Secondary illuminant color had opposing effects on color rendering index and tumor-to-background color contrast; providing surgeon control of intensity allows this trade-off to be balanced in real time. Demonstration in 2 high-grade glioma cases confirms this, showing that additional visibility adds value when intensity can be controlled by the surgeon. Addition of a secondary illuminant may mitigate surgeon complaints that the operative field is too dark under the blue light illumination required for 5-aminolevulinic acid fluorescence guidance by providing improved color rendering index without completely sacrificing tumor-to-background color contrast.

Genetic signature and treatment of pediatric high-grade glioma.

Pediatric high-grade glioma (HGG) is a type of malignancy that carries a poor prognosis. The genetic analysis of HGGs has previously identified useful mutations, the targeting of which has improved prognosis. Thus, further research into the more common mutations, such as H3 histone variants (HIST1H3B and H3F3A) and BRAF V600E, may be useful in identifying tumors with different prognoses, as the mutations are considered to drive two distinct oncogenic programs. The present study performed a retrospective analysis of pediatric HGGs. In total, 42 cases of HGG, including 32 cases (76.1%) of anaplastic astrocytoma and 10 cases (23.8%) of glioblastoma multiforme (GBM), were assessed. The median age of the patients was 7 years (range, 0-32 years). Mutations on histone H3, in particular the K27M and G34R mutations in the distinct variants HIST1H3B and H3F3A, in addition to the presence of the BRAF V600E mutation, were analyzed in 24 patients. The H3F3A K27M mutation was identified in 7 patients (29.1%), while the HIST1H3B K27M mutation was only observed in 1 patient with GBM. In addition, 5 patients harbored a BRAF V600E mutation (21%), while the H3F3A G34R mutation was not recorded in any of the patients. The overall survival of the wild-type patients at 20 months was 68% [confidence interval (CI): 38-85%] compared with 28% (CI: 0.4-60%) in patients with the H3F3A K27M mutation. These results suggested that patients with the H3F3A K27M mutation had a worse prognosis compared with wild-type patients (P=0.0045). Moreover, 3/5 patients with the BRAF V600E mutation had HGGs that were derived from a previous low-grade glioma (LGG; P=0.001). In conclusion, these results suggested that histone H3 mutations may help predict the outcome in patients with HGG. In addition, the BRAF V600E mutation was found to be associated with an increased risk of anaplastic progression. The novel data of the present study may help better define the clinical and radiological characteristics of glioma.

High-grade gliomas with H3 G34R mutation: a clinicopathological study

Objective: To analyze the clinicopathological features and probable mechanisms of high-grade gliomas with H3 G34R mutation. Methods: Five cases of high-grade gliomas with H3 G34R mutation were collected at Xuanwu Hospital, Capital Medical University, Beijing, China, from 2016 to 2019. The clinical and pathological data for each case was retrospectively reviewed. Results: The 5 patients (2 males and 3 females) aged from 15 to 45 years (mean 23 years), and had a history of headache or motor weakness. Four of them were younger than 20 years of age. Magnetic resonance imaging showed that the lesions of 3 cases were seen separately in frontal lobe, parietal lobe or temporal lobe, 1 case involved both frontal lobe and parietal lobe, and otherwise multiple lobes were involved in 1 case. Contrast enhancement could be observed in 2 cases. Pathological examination showed that glioblastoma was the most common entity, with or without primitive neuronal component. All 5 cases showed that H3 G34R was diffusely positive in tumor nuclei with ATRX loss. Moreover, p53 was overexpressed in 4 cases. None of them showed Olig2 expression. Two patients showed disease progression after surgery at 18 months and 24 months, respectively. The latter of the two deceased 3 months after tumor progression. Conclusions: The clinicopathological and molecular genetics features of high-grade gliomas with H3 G34R mutation have relatively similar clinicopathological and genetic features, and more commonly seen in young adults (vs. older adults). Thus, these tumors may be discussed further as a distinct tumor entity.

PATH-10. PROGNOSTIC RELEVANT IMMUNOPHENOTYPES OF PEDIATRIC HIGH-GRADE NON-BRAINSTEM GLIOMAS

Pediatric diffuse astrocytomas comprise a wide range of malignancies with variable prognosis. The 4th grading system used now not always correctly characterizes the biological behavior of these tumors. We collected 24 pediatric supratentorial non-brainstem high grade glioma cases. Patient age ranged from 1 to 18 years old (median 11y). Main tumor locations were as follows: parietal lobe 8 cases; temporal lobe, 10 cases; frontal lobe, 3 cases; occipital lobe 3 cases. Eight of them were totally removed. All patients were treated with standard CT and RT. The main objective was to assess the prognostic impact of histopathological and molecular criteria on progression‐free(PFS) and overall survival (OS) of high grade gliomas. The following criteria were analyzed: IDH1 R132H, BRAF V600E expression, ALT-phenotype, CDKN2A deletion, 1p/19q co-deletion, glial and neuronal markers expression. RESULTS: IDHR132H mutation was identified in 3 cases. 4 cases carried BRAFV600E mutation with CDKN2A deletion and displayed PXA phenotype. 5 cases showed undifferentiated glial morphology and ALT–phenotype. Also there was a group of tumors without any of the above mentioned genetic changes. Interestingly 3 of them were post radiation tumors. Statistical analysis showed that low OS correlated with ALT-phenotype(p-0.015), absence of neuronal markers expression and absence of molecular changes (p-0.03). Mutation of IDH1R132H was a favorable prognostic factor as in the adult population. PFS was affected only by the presence of neuronal expression (p-0.015). Employing immunohistochemical analysis with surrogate molecular markers in complex with FISH can provide additional prognostic information in case of pediatric high grade gliomas.

HGG-12. A CASE OF PEDIATRIC SPINAL HIGH-GRADE GLIOMA WITH NTRK1 GENE FUSION

INTRODUCTIONTumors arising from the spinal cord are uncommon, especially high-grade tumors in pediatric patients. We report a case of high-grade glioma in the spinal cord harboring NTRK1 gene fusion, who received effective entrectinib therapy. CASE REPORT: A 5-year-old boy presented right hemiparesis and MR imaging revealed an intramedullary enhancing mass at the vertebral body level between C3 and Th1. He underwent microsurgical partial resection and the histological diagnosis was low-grade astrocytoma. After the first-line chemotherapy with vincristine and carboplatin, his right hemiparesis deteriorated and recurrent MR imaging showed growth of the tumor. He underwent microsurgical partial resection again and the histological examination was high-grade glioma with endothelial proliferation and necrosis. The chemoradiotherapy with temozolomide and focal irradiation of 50.4 Gy were given, and his neurological symptom slightly improved. One month later, he presented respiratory disturbance and required assisted ventilation with tracheostomy. MR imaging showed tumor progression invading upward to medulla oblongata. NTRK1 gene fusion was detected in the previous surgical specimen by a gene panel testing, and he received entrectinib, a potent inhibitor of tropomyosin receptor kinase (TRK). Since then, no tumor progression has been demonstrated for several months by MRI and he has been stable neurologically.CONCLUSIONHigh-grade spinal cord tumors are rare and effective treatment strategies have not been addressed. Although the frequency of the gene fusion is very low in pediatric gliomas, identification of the driver gene aberration like in this case by a gene panel can provide potential targeted therapies for selected patients.

Neural Fiber Integrity in High- Versus Low-Grade Glioma using Probabilistic Fiber Tracking

Gliomatous tumors are known to affect neural fiber integrity, either by displacement or destruction. The aim of this study is to investigate the integrity and distribution of the white matter tracts within and around the glioma regions using probabilistic fiber tracking. Forty-two glioma patients were subjected to MRI using a standard tumor protocol with diffusion tensor imaging (DTI). The tumor and peritumor regions were delineated using snake model with reference to structural and diffusion MRI. A preprocessing pipeline of the structural MRI image, DTI data, and tumor regions was implemented. Tractography was performed to delineate the white matter (WM) tracts in the selected tumor regions via probabilistic fiber tracking. DTI indices were investigated through comparative mapping of WM tracts and tumor regions in low-grade gliomas (LGG) and high-grade gliomas (HGG). Significant differences were seen in the planar tensor (Cp) in peritumor regions; mean diffusivity, axial diffusivity and pure isotropic diffusion in solid-enhancing tumor regions; and fractional anisotropy, axial diffusivity, pure anisotropic diffusion (q), total magnitude of diffusion tensor (L), relative anisotropy, Cp and spherical tensor (Cs) in solid nonenhancing tumor regions for affected WM tracts. In most cases of HGG, the WM tracts were not completely destroyed, but found intact inside the tumor. Probabilistic fiber tracking revealed the existence and distribution of WM tracts inside tumor core for both LGG and HGG groups. There were more DTI indices in the solid nonenhancing tumor region, which showed significant differences between LGG and HGG.

Brain Glioma Localization Diagnosis Based on Magnetic Resonance Imaging

We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technology and its perfusion parameters to diagnose central glioma high-grade glioma (HGG), primary central nervous system glioma low-grade glioma (LGG), brain metastases, and meningioma and make differential diagnoses. Forty-one cases of brain tumors (8 cases of LGG, 17 cases of HGG, 5 cases of "primary central nervous system lymphoma" [PCNSL], 6 cases of brain metastases, and 5 cases of meningiomas) were subjected to routine and DCE-MRI scans. The DCE-MRI quantitative parameters of the tumor parenchymal area and peripheral enema area of each tumor were measured and recorded as t-Ktrans value, t-Ve value, t-Vp value, t-Kep value and p-Ktrans value, p-Ve value, p-Vp value, and p-Kep value. Compared with other tumor types, LGG showed lower t-Ktrans value (P < 0.01, sensitivity= 89%, specificity= 99%) and low t-Ve value (P < 0.01, sensitivity= 94%, specificity= 100%); PCNSL showed a high t-Ve value (P < 0.01, sensitivity= 100%, specificity= 88%), but other perfusion parameters overlap more obviously with other tumors. Compared with LGG, the difference between t-Ktrans value, t-Ve value, and t-Kep value is statistically significant. Among them, t-Ktrans value distinguishes the highest sensitivity and specificity (when t-Ktrans value= when 0.154 is the cutoff value, the area under the curve is 1.000, P= 0.000, specificity= 100%, sensitivity= 94.1%); compared with PCNSL, the difference of t-Ve value between HGG and PCNSL is statistically significant, t-Ve of PCNSL. The value is slightly higher, and its specificity and sensitivity are not high. DCE-MRI can distinguish HGG and LGG more accurately, of which t-Ktrans value has higher specificity and sensitivity, although the difference of t-Ve value between PCNSL and HGG is statistically significant but the sensitivity and specificity are not high; the p-Ktrans value and p-Kep value of metastatic tumors are lower than HGG and have higher specificity, but meningiomas and HGG and PCNSL, meningiomas and metastases are not accurate identification.

Diagnostic Accuracy of Differentiation between Primary Central Nervous System Lymphoma and High-Grade Glioma Using Dynamic Susceptibility Contrast Perfusion Curve Analysis

Objective: To determine diagnostic accuracy of visualized dynamic susceptibility contrast (DSC) perfusion curve pattern in differentiation between primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG). Materials and Methods: Forty-one patients (nineteen cases of PCNSL and twenty-two cases of HGG) acquired between January 2010 and November 2017 were included in the present study. The DSC perfusion curve patterns were retrospectively reviewed by two neuroradiologists, divided into two patterns as 1) return of time-intensity curve above the baseline after initial drop, and 2) return of time-intensity curve below or equal to baseline. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were analyzed. Results: Return of time-intensity curve above the baseline on DSC perfusion was found in 15 of 19 (78.9%) PCNSL cases, and only two of 22 (9.1%) HGG cases, p-value&lt;0.001; whereas return of time-intensity curve below or equal to baseline was found in only four of 19 (21.1%) PCNSL cases and 20 of 22 (90.9%) HGG cases, p-value&lt;0.001. Return of time-intensity signal curve above the baseline pattern had sensitivity of 78.9%, specificity of 90.9%, PPV of 88.2%, NPV of 88.3%, and accuracy of 85.4% for diagnosis of PCNSL, respectively. Conclusion: Visualized DSC curve pattern has a role in differentiation between PCNSL and HGG. Presence of return of time-signal intensity curve above the baseline could suggest the diagnosis of PCNSL. Keywords: PCNSL, HGG, DSC perfusion, Curve analysis, Return curve above baseline

Magnetic resonance imaging evaluation of brain glioma before postoperative radiotherapy

To investigate the magnetic resonance imaging (MRI) images of brain glioma before postoperative radiotherapy, and to provide reference for the delineation of postoperative radiotherapy target area. Retrospective analysis was performed on 106 cases of brain glioma confirmed by surgery and pathology in our hospital, including 70 cases of high-grade glioma (HGG) and 36 cases of low-grade glioma (LGG). The MRI images of the lesions within 1month before and after surgery were analyzed, the apparent diffusion coefficient (ADC) values in the near and far tumor areas were measured, respectively, and the corresponding rADC values were calculated. The incidence of residual tumors of postoperative HGG and LGG was 0, 15.7% (0/36, 11/70), respectively. The incidence of postoperative reactive enhancement was 11.0% and 52.9% (4/36 and 37/70), respectively. About 30.6% and 81.4% (11/36 and 57/70) of patients with adjacent meningeal enhancement were found in the operative area. The MRI images of HGG and LGG before postoperative radiotherapy had certain characteristics, providing a favorable guidance for the delineation of the target area of radiotherapy and the formulation of treatment plan.

Evaluating H3F3A K27M and G34R/V somatic mutations in a cohort of pediatric brain tumors of different and rare histologies.

Somatic mutations on H3 histone are currently considered a genetic hallmark for midline pediatric high-grade gliomas (HGGs). Yet, different tumor histologies have been occasionally described to carry these mutations. Since histone modifications can lead to major epigenetic changes with direct impact on prognosis and treatment, we thought to investigate the occurrence of H3F3A K27M and G34R/V mutations in a cohort of pediatric tumors which included HGGs, low-grade gliomas, ependymomas, medulloblastomas, and a series of rare brain tumor lesions of different histologies. A total of 82 fresh-frozen pediatric brain tumor samples were evaluated. PCR or RT-PCR followed by Sanger sequencing for the exon 2 of H3F3A (containing both K27 and G34 hotspots) were obtained and aligned to human genome. Loss of trimethylation mark (H3K27me3) in H3F3A/K27M-mutant samples was confirmed by immunohistochemistry. We found H3F3A/K27M mutation in 2 out of 9 cases of HGGs; no H3F3A/K27M mutations were detected in low-grade gliomas (27), ependymomas (n = 10), medulloblastomas (n = 21), or a series of rare pediatric brain tumors which included meningiomas, dysembryoplastic neuroepithelial tumors (DNETs), central nervous system (CNS) germ-cell tumors, choroid plexus tumors, cortical hamartoma, subcortical tubers, and schwannomas (n = 15). H3F3A/G34R/V mutation was not observed in any of the samples. Our investigation reinforces the low frequency of H3F3A somatic mutations outside the HGG setting. Interestingly, an atypical focal brainstem glioma carrying H3F3A K27M mutation that showed protracted clinical course with late-onset tumor progression was identified.