High-grade Glial Tumors Research Articles

FET PET to differentiate between post-treatment changes and recurrence in high-grade gliomas: a single center multidisciplinary clinic controlled study.

The clinico-radiological dilemma in post-treatment high-grade gliomas, between disease recurrence (TR) and treatment-related changes (TRC), still persists. FET (Fluoro-ethyl-tyrosine) PET has been extensively used as problem-solving modality for cases where MR imaging is inconclusive. We incorporated a systematic imaging and clinical follow-up algorithm in a multi-disciplinary clinic (MDC) setting to analyse our cohort of FET PET in post-treatment gliomas. We retrospectively analyzed 171 patients of post-treatment grade III and IV glioma with equivocal findings on MRI. 185-222 MBq of 18F-FET was injected and dedicated static imaging of brain was performed at 20min. TBR (Tumor to background ratio) was used as semi-quantitative parameter. Cutoff of 2.5 was used for image interpretation. Imaging findings were confirmed with histopathological diagnosis, wherever available or in a multidisciplinary joint clinic based on serial imaging. 121 of 171 patients showed recurrent disease on FET PET, on follow up, 109 were confirmed with recurrence; 7 patients showed TRC, whereas 5 were treated with bevacizumab, with no further clinico-radiological deterioration, thus confirming TRC. 50 patients showed TRC on FET PET, on follow up on follow up, 40 were confirmed as true-negative. 10 patients who showed TBR less than 2.5 had confirmed TR on subsequent MR imaging. The overall sensitivity and specificity was 91.6 and 76.9% respectively, with a diagnostic accuracy of 87.13%. There is potential for FET PET to be used along with MRI in the post treatment algorithm of high-grade glial tumors.

Preliminary evaluation of FAPI-04-PET/CT for differentiating recurrence and post-treatment changes in high-grade gliomas

Fibroblast-activated protein (FAP) expression in glial cells is attributed to FAP-positive foci on tumor vessels and neoplastic cells. Preclinical and pilot studies have shown FAP expression in high-grade gliomas. We aimed at comparing PET imaging with FAP-inhibitor (FAPI-PET) with current standard, i.e., fluoro-ethyl tyrosine (FET) PET in post-treatment setting to differentiate recurrence and post-treatment changes. 6 patients with WHO Grade III and IV glioma who received standard treatment underwent Ga-68-FAPI-04 PET/CT (FAPI-PET/CT). Tracer uptake greater than background was considered positive. FET PET was performed and interpreted as per institutional standards, which formed the basis of treatment decision. There was concordance between FAPI expression and FET uptake in 5 patients suggestive of disease recurrence. There was no FAPI expression seen in 1 patient, in whom FET PET was suggestive of post-treatment changes. FAPI PET uptake correlated with amino acid expression to differentiate post treatment changes from recurrence in high-grade glial tumors; further validation with prospective study and histopathological confirmation is needed.

Utilizing Radiomics of Peri-Lesional Edema in T2-FLAIR Subtraction Digital Images to Distinguish High-Grade Glial Tumors From Brain Metastasis.

Differentiating high-grade glioma (HGG) and isolated brain metastasis (BM) is important for determining appropriate treatment. Radiomics, utilizing quantitative imaging features, offers the potential for improved diagnostic accuracy in this context. To differentiate high-grade (grade 4) glioma and BM using machine learning models from radiomics data obtained from T2-FLAIR digital subtraction images and the peritumoral edema area. Retrospective. The study included 1287 patients. Of these, 602 were male and 685 were female. Of the 788 HGG patients included in the study, 702 had solitary masses. Of the 499 BM patients included in the study, 112 had solitary masses. Initially, the model was developed and tested on solitary masses. Subsequently, the model was developed and tested separately for all patients (solitary and multiple masses). Axial T2-weighted fast spin-echo sequence (T2WI) and T2-weighted fluid-attenuated inversion recovery sequence (T2-FLAIR), using 1.5-T and 3.0-T scanners. Radiomic features were extracted from digitally subtracted T2-FLAIR images in the area of peritumoral edema. The maximum relevance-minimum redundancy (mRMR) method was then used for dimensionality reduction. The naive Bayes algorithm was used in model development. The interpretability of the model was explored using SHapley Additive exPlanations (SHAP). Chi-square test, one-way analysis of variance, and Kruskal-Wallis test were performed. The P values <0.05 were considered statistically significant. The performance metrics include area under curve (AUC), sensitivity (SENS), and specificity (SPEC). The mean age of HGG patients was 61.4 ± 13.2 years and 61.7 ± 12.2 years for BM patients. In the external validation cohort, the model achieved AUC: 0.991, SENS: 0.983, and SPEC: 0.922. The external cohort results for patients with solitary lesions were AUC: 0.987, SENS: 0.950, and SPEC: 0.922. The artificial intelligence model, developed with radiomics data from the peritumoral edema area in T2-FLAIR digital subtraction images, might be able to differentiate isolated BM from HGG. 3 TECHNICAL EFFICACY: Stage 2.

P.126 An unlikely impersonator of primary brain tumours: Illustrative case report and literature review of primary angiitis of the central nervous system

Background: Primary angiitis of the central nervous system (PACNS) is a rare inflammatory condition affecting the parenchymal and leptomeningeal vessels of the CNS. PACNS presenting as a solitary mass lesion (ML-PACNS) constitutes a rare subtype of this pathology. Herein we present the first case reported in Canada of ML-PACNS, presenting with clinical and radiographic findings consistent with a high grade glial neoplasm, as well as a review of the literature on ML-PACNS. Methods: Review of the literature from 1987-2023 was conducted using PubMed to identify features of ML-PACNS and possible treatment paradigms. Results: A number of case reports of ML-PACNS were identified, as well as 6 retrospective analyses of a total of 67 patients. Features such as faster rate of symptom onset, and investigations such as MRI vessel-wall imaging and MR spectroscopy were suggested for identification of ML-PACNS. Treatment was highly variable, but followed guidelines for other neuroinflammatory disorders. Conclusions: Preoperative differentiation between ML-PACNS and CNS neoplasms is difficult due to their similar clinical and radiographic features. However, making this distinction is crucial as PACNS mass lesions can regress entirely with immunosuppressive therapy, potentially obviating the requirement for surgical intervention. Beyond diagnostics, further research is required to establish and validate a treatment paradigm.

Clinical, pathologic, and genomic characteristics of two pediatric glioneuronal tumors with a CLIP2::MET fusion

Integration of molecular data with histologic, radiologic, and clinical features is imperative for accurate diagnosis of pediatric central nervous system (CNS) tumors. Whole transcriptome RNA sequencing (RNAseq), a genome-wide and non-targeted approach, allows for the detection of novel or rare oncogenic fusion events that contribute to the tumorigenesis of a substantial portion of pediatric low- and high-grade glial and glioneuronal tumors. We present two cases of pediatric glioneuronal tumors occurring in the occipital region with a CLIP2::MET fusion detected by RNAseq. Chromosomal microarray studies revealed copy number alterations involving chromosomes 1, 7, and 22 in both tumors, with Case 2 having an interstitial deletion breakpoint in the CLIP2 gene. By methylation profiling, neither tumor had a match result, but both clustered with the low-grade glial/glioneuronal tumors in the UMAP. Histologically, in both instances, our cases displayed characteristics of a low-grade tumor, notably the absence of mitotic activity, low Ki-67 labeling index and the lack of necrosis and microvascular proliferation. Glial and neuronal markers were positive for both tumors. Clinically, both patients achieved clinical stability post-tumor resection and remain under regular surveillance imaging without adjuvant therapy at the last follow-up, 6 months and 3 years, respectively. This is the first case report demonstrating the presence of a CLIP2::MET fusion in two pediatric low-grade glioneuronal tumors (GNT). Conservative clinical management may be considered for patients with GNT and CLIP2:MET fusion in the context of histologically low-grade features.

EGFR/CEP7 high polysomy is separate and distinct from EGFR amplification in glioblastoma as determined by fluorescence in situ hybridization.

EGFR amplification in gliomas is commonly defined by an EGFR/CEP7 ratio of ≥2. In testing performed at a major reference laboratory, a small subset of patients had ≥5 copies of both EGFR and CEP7 yet were not amplified by the EGFR/CEP7 ratio and were designated high polysomy cases. To determine whether these tumors are more closely related to traditionally defined EGFR-amplified or nonamplified gliomas, a retrospective search identified 22 out of 1143 (1.9%) gliomas with an average of ≥5 copies/cell of EGFR and CEP7 with an EGFR/CEP7 ratio of <2 displaying high polysomy. Of these cases, 4 had insufficient clinicopathologic data to include in additional analysis, 15 were glioblastomas, 2 were IDH-mutant astrocytomas, and 1 was a high-grade glial neoplasm, NOS. Next-generation sequencing available on 3 cases demonstrated one with a TERT promoter mutation, TP53 mutations in all cases, and no EGFR mutations or amplifications, which most closely matched the nonamplified cases. The median overall survival times were 42.86, 66.07, and 41.14 weeks for amplified, highly polysomic, and nonamplified, respectively, and were not significantly different (p = 0.3410). High chromosome 7 polysomic gliomas are rare but our data suggest that they may be biologically similar to nonamplified gliomas.

Rapid Vision Loss Due to Multifocal Glioma: A Diagnostic Challenge.

This is a unique case report in medical literature for its detailing of diagnostics of an uncommon presentation of a rapid unexplained bilateral vision loss of a 73-year-old male diabetic patient. This report highlights the crucial role of advanced molecular diagnostics in difficult neurological cases and also elucidates the difficulties involved in diagnosing optic nerve glioblastoma, an exceptionally rare and aggressive tumour. Slow and progressive loss of vision over 2 months, ultimately developing almost complete visual impairment in both eyes and a defect of right eye field of vision conclusively highlighted that the likely etiology was neuro-ophthalmic. Initially, the conditions were suspected to be an extended spectrum of diabetic eye disease complications but further deterioration was a hint towards something more substantive. This entailed in-depth diagnosis processes that included an MRI and the analysis of cerebrospinal fluid. The important discovery was through stereotactic biopsies of the optic nerve revealing a high-grade glial neoplasm. Next generation sequencing confirmed the pathology as IDH-wildtype glioblastoma. Despite management, his vision continued to deteriorate. Hence, an aggressive clinical course was followed. This case highlights the important learning need in considering glioblastoma of the optic chiasm as part of the differential diagnosis of rapid vision loss, which may present as multifocal brain lesions, especially in casesof rapid loss of vision where initial workup is negative. Quite a useful lesson that can be drawn from this case relates to the diagnostic process with advanced molecular profiling, more attention given to clinical suspicion and cutting-edge diagnostic tools applied in atypical presentation of neurological conditions.

First person – Tanja Müller

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Tanja Müller is first author on ‘ The neuronal transcription factor MEIS2 is a calpain-2 protease target’, published in JCS. Tanja conducted the research described in this article while a PhD student in Prof. Dr Dorothea Schulte's lab at the Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Germany. She is now a postdoc and co-lead of the Translational Neurooncology Junior Group in the lab of Dr Ann-Christin Hau at the Translational Neurooncology Group at the University Hospital Frankfurt, Germany. Her current research focuses on the identification of invasion-promoting genes in high-grade glial tumors.

Сравнение липидных изменений в астроцитомах по мере роста их злокачественности

The use of ambient ionization mass spectrometry methods is one of the promising approaches to the impovement of glial tumor resection completeness by using an additional method to improve the tumor margin identification accuracy during the neurosurgical intervention itself. The amounts of data accumulated when testing such techniques can be also used in fundamental research to identify metabolic alterations associated with the tumor growth. The study was aimed to assess changes in the cell membrane lipid composition of diffuse and anaplastic astrocytomas based on the data acquired by ambient ionization mass spectrometry profiling of the tissues excised during the elective neurosurgical intervention. The lipid profiles obtained when assessing the tumor tissue samples (n = 43) by flow microextraction in a cartridge were subjected to shrinkage linear discriminant analysis enabling extraction of a number of lipids, the levels of which changed with increasing tumor grade. The lipid diversity decreased with increasing grade. Thus, the levels of 13 phospholipids belonging to six different subclasses turned out to be decreased in anaplastic tumors compared to diffuse ones. Both average size of the polar lipid fatty acid residues and their degree of unsaturation decrease with increasing tumor grade. The findings agree well with the data of the earlier study of high-grade glial tumors and confirm the biochemical view of metabolic reprogramming associated with malignant transformation of neuroglia.

Application of WHO CNS Fifth Edition Criteria for Glioblastoma Multiforme Diagnosis: A single center study

Abstract Introduction/Objective The fifth edition of the WHO classification of the tumors of the central nervous system (WHO CNS 5) published in 2021 introduced major changes that incorporate molecular diagnostics in CNS tumor classification along with histology and immunohistochemistry. Glioblastomas (GBM) were diagnosed based on the histologic features of diffuse and astrocytic glioma in adults, if there is microvascular proliferation and /or necrosis. Isocitrate dehydrogenase 1 (IDH) R132 H immunohistochemical stain expression and /or mutation analysis results were used to further classify GBMs as IDH mutant or IDH wild type. In WHO CNS 5 all IDH mutant diffuse astrocytic tumors are considered a single type (Astrocytoma, IDH mutant) and graded 2, 3, or 4. Glioblastoma IDH wild type is diagnosed in the setting of an IDH wild type diffuse and astrocytic glioma with microvascular proliferation or necrosis or TERT promoter mutation or EGFR gene amplification or +7/-10 chromosome copy number changes. In this study, we analyze how the change in diagnostic criterion would affect the classification of GBMs diagnosed in our institution retrospectively. Methods/Case Report The pathology database was searched for all diffuse gliomas diagnosed as GBM between 01/2019 and 12/2021. Age of the patient, gender, location of tumor, histologic features, IDH status and molecular alterations ( Onkosight Advanced solid tumor panel, 50 genes) were reviewed. Results (if a Case Study enter NA) A total of 74 adult high grade glial neoplasms were identified out of which 25 were GBMs. The age of the patients ranged from 40 to 87 years. 14 were men and 11 were females. All tumors had histologic features of GBM such as necrosis and microvascular proliferation. 24 (96%) tumors were IDH negative by immunohistochemistry and mutation analysis, and 1 (4%) was IDH strongly positive by immunohistochemistry. Molecular studies were not performed on this tumor. Conclusion 96% of GBMS diagnosed during the time period conformed to the WHO CNS 5 diagnostic criteria. The one IDH positive tumor would be reclassified as diffuse astrocytoma, IDH mutant, Grade 4. Like previous WHO classifications, WHO CNS 5 is a work in progress attempting to introduce new knowledge into the classification hoping to provide practical guidance to pathologists and neuro-oncologists and to benefit the patients with CNS tumors.

Deep Learning-Assisted Segmentation and Classification of Brain Tumor Types on Magnetic Resonance and Surgical Microscope Images

The primary aim of this research was to harness the capabilities of deep learning to enhance neurosurgical procedures, focusing on accurate tumor boundary delineation and classification. Through advanced diagnostic tools, we aimed to offer surgeons a more insightful perspective during surgeries, improving surgical outcomes and patient care. The study deployed the Mask R-convolutional neural network (CNN) architecture, leveraging its sophisticated features to process and analyze data from surgical microscope videos and preoperative magnetic resonance images. Resnet101 and Resnet50 backbone networks are used in the Mask R-CNN method, and experimental results are given. We subsequently tested its performance across various metrics, such as accuracy, precision, recall, dice coefficient (DICE), and Jaccard index. Deep learning models were trained from magnetic resonance imaging and surgical microscope images, and the classification result obtained for each patient was combined with the weighted average. The algorithm exhibited remarkable capabilities in distinguishing among meningiomas, metastases, and high-grade glial tumors. Specifically, for the Mask R-CNN Resnet 101 architecture, precision, recall, DICE, and Jaccard index values were recorded as 96%, 93%, 91%, and 84%, respectively. Conversely, for the Mask R-CNN Resnet 50 architecture, these values stood at 94%, 89%, 89%, and 82%. Additionally, the model achieved an impressive DICE score range of 94%-95% and an accuracy of 98% in pathology estimation. As illustrated in our study, the confluence of deep learning with neurosurgical procedures marks a transformative phase in medical science. The results are promising but underscore diverse data sets' significance for training and refining these deep learning models.

Photodynamic therapy of malignant brain tumors (literature review

Primary brain malignancies are among the 17 most common tumor types worldwide, and about 77 % of them are glial tumors. An integrated approach to the treatment of these pathologies, including total resection of tumor tissue and postoperative chemotherapy and radiation therapy, is aimed at prolonging the patient’s life as much as possible. However, even when using the «gold standard» in treatment, the average life expectancy of patients with glioblastoma is 14.6 months, and of patients with diffuse astrocytoma — 50.5 months. The use of selective methods of influencing tumor cells, including photodynamic therapy, is a current trend in neuro-oncology. Several controlled studies have demonstrated a statistically significant effect of photodynamic therapy in increasing the life expectancy of patients with high-grade gliomas compared with conventional treatment. This review is devoted to the analysis of the effectiveness of photodynamic therapy and fluorescence-guided resection in the treatment of high-grade glial tumors for further search for ways to improve these treatment methods in order to enhance the radicality of tumor removal and increase the duration and quality of life of patients.

Evaluating interleukin-16 expression in patients with grade-3 and grade-4 glial cell tumors and healthy individuals.

This study evaluated the change in IL-16 levels in patients with high-grade glial tumors undergoing radiotherapy (RT) and healthy individuals (control group). Serum IL-16 levels of 35 high-grade glioma patients receiving radiotherapy (RT) and 30 healthy individuals were compared. We compared the IL-16 levels before (RT0) and after the (RT1) and IL-16 levels were measured and the relationship of this change with other characteristics such as age, gender, weight, height, and blood test results. The RT0-IL-16 level was approximately 15 pg/ml higher than the RT1 measurement in the patient group. The mean RT0-IL-16 levels in the patient group were approximately 10 pg/ml higher than the mean IL-16 levels in the control group. Likewise, at the RT1 time-point, the mean IL-16 levels for the patient group were approximately 5 pg/ml lower than the mean IL-16 for the control group. The mean RT0-RT1-IL-16 value tended to be higher in female patients than in male patients. The application of RT reduces the overall IL-16 levels, suggesting the efficacy of RT, as well as the role of IL-16 in tumorigenesis.

Prognostic value of indoleamine 2, 3-dioxygenase-1 expression in glial tumors.

<p>Gliomas are the most common primary malignant central nervous system tumors in adults, exhibiting a poor prognosis. Indoleamine 2, 3-dioxygenase-1 (IDO-1) has important functions in cancer immunotherapy due to its role in escaping cancer cells from the immune system. In this study we purposed to evaluate the correlation between IDO-1 expression and clinicopathological parameters in gliomas, and whether IDO-1 can be a prognostic marker.</p>. <p>n=75 patients in total, n=25 patients with low grade glial tumors (LGG, grade 1-2), n=25 patients with high grade glial tumors (HGG, grade 3-4), and n=25 persons with normal brain tissue as control group were included in this study. IDO-1 expression was categorized by using immunohistochemical staining in biopsy specimens as high (H) and low (L) groups among the patients with gliomas. We used a 95% percent confidence interval and p &lt;0.05 to analyze the association between the degree of IDO-1 expression, clinicopathological characteristics, and survival rates in glioma patients.&nbsp;</p>. <p>In HGG, IDO-1 levels were higher than in control brain tissue and LGG (p&lt; 0.001). The mean overall survival (OS) was longer in the L-IDO-1 group (64.53 &plusmn; 3.34) in months (95% CI: 57.969-71.098) compared to the H-IDO-1 group (43.74 &plusmn; 4.36) in months, (95% CI: 35.218-52.330) (p&lt; 0.05).</p>. <p>IDO-1 expression is an in&shy;de&shy;pendent prognostic biomarker to predict&nbsp;<br>OS and progression in HGG. IDO-1 can be&nbsp;evaluated as an alternative instrument for precision medicine in the treatment of gliomas.</p>.

SDPS-11 IMPACT OF MOLECULAR MARKERS USING FISH TECHNIQUE ON GOS/SURVIVAL IN HIGH GRADE GLIOMAS IN INDIAN SCENARIO

Abstract Aims Molecular markers (MGMT, IDH and 1p/19q, MIB-1 index, TP53) are used for present day diagnosis of high-grade glial tumours. This study evaluates outcome parameters [e.g., GOS, progression free (PFS) and overall survival(OS)] in treated high grade gliomas in Indian context using FISH technique for molecular characterisation. MATERIALS AND METHODS This study used FISH techniques for IDH, MGMT and other IHC markers prospectively on 10 patients with high-grade gliomas, after safe maximal resection. Outcomes were noted for PFS and OS. A GOS of 1-3 (considered unfavourable); 4-5 (favourable), was documented at every 3-monthly follow-up for 2 years. The standardised detection of IDH (by FISH) and methylation profiles of tumours is the strength of the study. RESULTS Most (80%) patients had a GOS &amp;gt; 13 post operatively, and none were less than 9. There was no statistically significant effect of gender, extent of resection or tumour location. IDH-1 positivity was recorded in 10%, MGMT methylation in 40%, intermediate to low MIB-1 index in 83.3%. TP53 mutations were noted in 30% cohort who had adverse outcome. The median PFS was 8.60 months. Mean survival was 12.70 months, with no molecular marker having statistically significant effects on PFS or OS. GOS of 13-15 conferred the best OS in contrast to GOS of 9-12 (16.2 months versus 7.5 months); (p = 0.001). CONCLUSION GOS is an easy-to-use, validated scoring system with broad applicability and high reproducibility as a quantitative benchmark for clinical assessment. Since IHC lacks standardisation, FISH, despite being costlier, was used as a diagnostic benchmark. Further research on the impact of genomic profiling, extent of resection, especially in geriatric age groups is needed, to formulate an algorithm for optimal management.

Re-irradiation with stereotactic radiotherapy for recurrent high-grade glial tumors.

Despite the radical treatments applied, recurrence is encountered in the majority of high-grade gliomas (HGG). There is no standard treatment when recurrence is detected, but stereotactic radiotherapy (SRT) is a preferable alternative. The aim of this retrospective study is to evaluate the efficacy of SRT for recurrent HGG, and to investigate the factors that affect survival. From 2013 to 2021, a total of 59 patients with 64 lesions were re-irradiated in a single center with the CyberKnife Robotic Radiosurgery System. The primary endpoints of the study were overall survival (OS), progression free survival (PFS) and local control rates (LCR). The median time to first recurrence was 13 (4-85) months. SRT was performed as a median prescription dose of 30 Gy (range 15-30), with a median of 5 fractions (1-5). The median follow-up time was 4 months (range 1-57). The median OS was 8 (95% CI: 4.66-11.33) months. Age, grade 3, tumor size were associated with better survival. The median PFS was 5 [95% confidence interval (CI): 3.39-6.60] months. Age, grade 3 and time to recurrence > 9 months were associated with improved PFS. Grade 3 gliomas (p = 0.027), size of tumor < 2 cm (p = 0.008) remained independent prognostic factors for OS in multivariate analysis. SRT is a viable treatment modality with significant survival contribution. Since it may have a favorable prognostic effect on survival in patients with tumor size < 2 cm, we recommend early diagnosis of recurrence and a decision to re-irradiate a smaller tumor during follow-up.

Anaplastic oligodendroglioma WHO grade 3: Rare brain tumor

The anaplastic oligodendrogliomas are uncommon gliomas. It is clinically significant to know this entity as they have unique clinical, histopathological and molecular features. We present a 43 year female having complaint of headache, tingling numbness, giddiness. Which was of 2 year duration, off and on, and was increased in last 15 days. MRI brain (plain + contrast) showed a large heterogenously enhancing cortical based solid-cystic lesion with surrounding edema in left frontal lobe with mass effects and midline shift. On radiological features impression was suggestive of high grade glial neoplasm and advised biopsy. In our case on histopathology reported as anaplastic oligodendrogliomas WHO CNS grade 3 of left frontal lobe. Patient was treated with surgery, and chemotherapy. We are presenting this rare case of anaplastic oligodendrogliomas for it’s clinical, Histopathological and radiological findings.

DIPG-12. OUTCOMES IN PEDIATRIC MALIGNANT CENTRAL NERVOUS SYSTEM TUMORS UTILIZING TEMOZOLOMIDE, BEVACIZUMAB, AND IRINOTECAN

Abstract High-grade glioma (HGG) and diffuse intrinsic pontine glioma (DIPG) are the most common high-grade glial tumors in pediatrics. Hummel et al. assessed the feasibility of bevacizumab (BVZ) ± temozolomide (TEM) with radiation, followed by BVZ, irinotecan (IRO) ± TEM. The regimen conferred no survival benefit to patients with DIPG. The study was limited by sample size. Further defining efficacy of this therapy is important. We aimed to examine the outcomes of patients with HGG and DIPG treated with BVZ, IRO, and TEM. This is a retrospective review of patients treated at Cincinnati Children’s Hospital from 03/2005 to 10/2022. We examined progression-free survival (PFS) and overall survival (OS). Descriptive analyses were used to examine age, sex, diagnosis, and tumor location. 47 patients were treated with BVZ, IRO ± TEM. Patients were 55% female and 45% male. Average age at diagnosis was 12 years. The diagnoses included patients with HGG (45%), DIPG (51%), and other tumor types (4%). 79% of patients were treated at initial diagnosis with the regimen of BVZ in addition to IRO ± TEM. 21% of patients were treated at progression. Median OS for patients with DIPG and HGG was 12.4 months and 35.9 months, respectively. 3-year OS for DIPG was 10.8% (SE 7.2%) and for HGG it was 48.6% (SE 11.0%). Median PFS for DIPG and HGG was 7.7 and 19.0 months, respectively. 1-year PFS for DIPG was 31.9% (SE 10.7%). For HGG it was 65.6% (SE 10.6%). 3-year PFS for HGG was 20.2% (SE 9.0%). The limitations of this study are that newly diagnosed and recurrent patients are included and the study does not examine radiologic and biologic data. Results from this study show promising data for OS and PFS. Additional studies are needed to further examine larger cohorts of patients to demonstrate survival benefit from this regimen.

Role of cyclin D1 in glial tumors-A retrospective and observational study.

High-grade glial tumors remain as one of the most lethal malignancies. Cyclin D1 is expressed in some human malignancies and is the potential target of intervention. The present study aims to determine the relationship of cyclin D1 expression with other clinicopathological parameters. A cross-sectional study was carried out in a tertiary care center. Biopsy proven 66 cases of glial tumor patients were included in the study. The patients with incomplete clinical details were excluded from the study. Immunohistochemistry using antibodies for IDH 1 and cyclin d1 was done in all the cases. Glial tumors were reclassified according to WHO 2016 classification. Data analysis was performed using SPSS 26.0 for the windows. Among 66 patients, 49 (74.3%) were males and 17 (25.7%) were females. The age of the patients ranged from 20 years to 70 years. Overall, 6.02% were of grade I Glial tumors, 22.7% were of grade II Glial tumors, 19.6% patients were of grade III Glial tumors, and 51.6% patients were of grade IV Glial tumors. Of 66 samples tested cyclin D1 was positive in 25 (37.87%) as high expressers and 7 (10.60%) were low expressers. Our study showed a significant correlation between the expression of cyclin D1 with grade and IDH mutation status, No significant correlation of cyclin D1 was noted with age or sex of the patient. Cyclin D1 was associated with a higher grade of the glial tumor. It can be a potential marker both for prognosis and treatment of glial tumors.

Intracerebral de novo arterio-venous malformations as a side effect of bevacizumab

Bevacizumab is a monoclonal antibody for the vascular endothelial growth factor receptor and is utilized in the treatment of various tumors. Gastrointestinal perforation/fistula, heart failure, hemorrhage, hypertension, proteinuria/nephrotic syndrome, thromboembolism, posterior reversible encephalopathy syndrome, and necrotizing fasciitis are serious side effects of bevacizumab. Bevacizumab associated de novo brain arterio-venous malformation formation has not been documented in the literature. Here, we presented a 35-year-old female patient with recurrent high-grade glial tumor who developed multiple supra- and infratentorial de novo arterio-venous malformations after receiving the last dose of bevacizumab. Intervention options for the adverse effect were limited. In fact, there was no chance of intervention because the patient died for another reason. Based on this experience, it can be hypothesized that bevacizumab may induce de novo arterio-venous malformations in the brain as a result of arterial and venous thrombotic effects. Additional studies should be done to clarify the causal relationship between bevacizumab and arterio-venous malformations in primary brain tumors.