Primary Brain Gliomas Research Articles

Strokes in Individuals with Primary Brain Glioma After Radiation Therapy Managed with Bevacizumab: A Subgroup Analysis of a Retrospective Cohort (P6-5.019)

Strokes in Individuals with Primary Brain Glioma After Radiation Therapy Managed with Bevacizumab: A Subgroup Analysis of a Retrospective Cohort (P6-5.019)

Relaxation Along a Fictitious Field, continuous wave T1rho, adiabatic T1rho and adiabatic T2rho imaging of human gliomas at 3T: A feasibility study.

In pre-clinical models of brain gliomas, Relaxation Along a Fictitious Field in second rotating frame (TRAFF2), continues wave T1rho (T1ρcw), adiabatic T1rho (T1ρadiab), and adiabatic T2rho (T2ρadiab) relaxation time mappings have demonstrated potential to non-invasively characterize brain gliomas. Our aim was to evaluate the feasibility and potential of 4 different spin lock methods at 3T to characterize primary brain glioma. 22 patients (26-72 years) with suspected primary glioma. T1ρcw was performed using pulse peak amplitude of 500Hz and pulse train durations of 40 and 80 ms while the corresponding values for T1ρadiab, T2ρadiab, TRAFF2 were 500/500/500Hz and 48 and 96, 64 and 112, 45 and 90 ms, respectively. The parametric maps were calculated using a monoexponential model. Molecular profiles were evaluated from tissue specimens obtained during the resection. The lesion regions-of-interest were segmented from high intensity FLAIR using automatic segmentation with manual refinement. Statistical descriptors from the voxel intensity values inside each lesion and radiomic features (Pyrad MRC package) were calculated. From extracted radiomics, mRMRe R package version 2.1.0 was used to select 3 features in each modality for statistical comparisons. Of the 22 patients, 10 were found to have IDH-mutant gliomas and of those 5 patients had 1p/19q codeletion group comparisons. Following correction for effects of age and gender, at least one statistical descriptor was able to differentiate between IDH and 1p/19q codeletion status for all the parametric maps. In the radiomic analysis, corner-edge detector features with Harris-Stephens filtered signal showed significant group differences in IDH and 1p/19q codeletion groups. Spin lock imaging at 3T of human glioma was feasible and various qualitative parameters derived from the parametric maps were found to have potential to differentiate IDH and 1p19q codeletion status. Future larger prospective clinical trials are warranted to evaluate these methods further.

Abstract TP229: Stroke Rate and Associated Factors in Individuals With Primary Brain Gliomas and Brain Radiation Therapy: A Retrospective Cohort Study

Background/Objectives: The risk of stroke in individuals with brain gliomas may be increased due to several possible factors including chemotherapy, radiation-induced toxicity, and concomitant vascular risks. We report on the stroke rate and associated factors following brain tumor diagnosis and radiation therapy. Design: This is a retrospective cohort study, from a single tertiary academic brain tumor center, of patients with brain gliomas diagnosed between 2004-2021 who received brain radiation therapy during their treatment. Chi-square test was used to calculate the odds ratios. Results: Among a total of 912 patients with primary gliomas who received radiation therapy, stroke subsequently occurred in 93 patients (10.2%). Strokes were ischemic in 72.0% (N=67), intracerebral hemorrhage (ICH) in 25.8% (N=24), and subarachnoid hemorrhage in 2.2% (N=2). Individuals who sustained a stroke were 44.1% female and had a mean age of 54.2 years (range 21-84) at the time of stroke diagnosis. Of those who had a stroke, 64.5% (N=60) were also taking bevacizumab at the time of stroke. Median time from initiation of radiation therapy to stroke was 653 days (range 0-3788). Median radiation dose was 5940 cGy (range 1800-6000). The following factors were associated with a higher odd of having a stroke: radiation necrosis (OR 4.51; 95% CI 1.98-10.29, P=0.0003); hypertension (OR 1.82; 95% CI 1.17-2.82, P=0.008); hyperlipidemia (OR 5.50; 95% CI 3.45-8.78, P<0.0001); and diabetes (OR 2.19; 95% CI 1.25-3.84, P=0.007). Among stroke patients, 80.6% had strokes on the same side as radiation therapy. Those who were taking bevacizumab were more likely to have an ICH (31.7% vs. 15.1%, OR 2.60, 95% CI 0.87-7.77, P=0.09) as compared to other stroke types. Conclusions: Individuals with primary brain gliomas undergoing radiation therapy who were subsequently diagnosed with a stroke had higher rates of comorbid vascular risk factors and radiation necrosis.

Evaluation of the effectiveness of multicomponent treatment in the progression of primary low-grade brain gliomas. Own experience

BACKGROUND: Despite the improved results of treatment of brain tumors achieved over the past decade, most patients experience relapses of the disease 1–2 years after treatment. Numerous clinical studies have made it possible to obtain standard protocols for the treatment of primary brain tumors; however, protocols for the treatment of recurrent tumors have not been developed. The choice of treatment usually includes reoperation, systemic chemotherapy, and reirradiation alone or in combination. However, the treatment of recurrent glial tumors is challenging given the lack of effective treatment options and the lack of randomized controlled trials on which to base therapy.
 AIM: To determine the most important prognostic factors, as well as the most effective treatment option in patients with continued growth of primary low-grade gliomas of the brain.
 METHODS: This study included 40 patients with a confirmed diagnosis of progression of low-malignant glial brain tumors, who underwent inpatient treatment at the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine from 2007 to 2022. The ratio of men and women: 1:1.5. The mean age was 45.6±11.5 years. Patients with grade I astrocytomas predominated (n=23), oligodendroglioma was diagnosed in 8 patients.
 Reoperation was performed in 11 patients as the first stage of progression treatment. In 7 cases, monochemotherapy with temozolomide was performed. Repeated radiation therapy was performed in 29 patients, of which: 9 patients received a course of combined photon-neutron therapy; 9 patients — stereotactic radiation therapy (was performed on the CyberKnife device); 11 patients — external beam radiation therapy.
 RESULTS: The median overall survival (OS) for all patients with continued growth of low-grade cerebral gliomas after treatment was 120 months. 1-year OS — 97.3%; 3-year — 86.8%; 5-year — 78.2%. Median OS after relapse treatment was 36 months. The median OS was higher in the age group under 50 compared to the older age group: 120 and 95 months (p 0.05).
 The best results of treatment were noted in patients who underwent reoperation followed by a course of radiation therapy or chemotherapy with temozolomide for 48 months and 36 months respectively (p 0.05). When analyzing the results of treatment after a course of repeated radiation therapy in an independent variant, there were undoubted advantages in patients who underwent stereotactic radiation therapy and photon-neutron therapy for 60 months and 24 months respectively (p 0.05).
 CONCLUSIONS: The optimal approach to the treatment of patients with continued growth of primary low-grade glioma brain tumors is to perform a second operation, followed by radiation therapy or chemotherapy. The method of choice for a repeat course of radiotherapy may be photon-neutron therapy or stereotactic radiation therapy.

Results of Treatment of Patients with Progression of Primary Highly Malignant Brain Gliomas During a Repeated Course of Radiation Therapy. Own Experience

Purpose: To determine the most effective option for repeated radiation therapy in patients with continued growth of primary high-grade brain glioma, taking into account the isodose distribution during the initial course of radiation therapy. Material and methods: As a result of a retrospective analysis, the results of treatment of 100 patients with confirmed progression of high-grade glioma treated at the Chelyabinsk Regional Center for Oncology and Nuclear Medicine in the period from 2010 to 2020 were evaluated. The ratio of men and women was approximately equal (56 men and 44 women). The mean age of patients of both sexes was 47.2±11.9 years. According to the histological conclusion, patients with glioblastomas (GB) prevailed (n = 58), 42 patients were diagnosed with anaplastic astrocytoma (AA). Reoperation was performed in 26 patients. Repeated radiation therapy in an independent variant was performed in 76 patients of them: 17 patients received a course of neuronal therapy in mono mode and in 17 patients in combination with external beam radiation therapy; 23 patients underwent stereotactic radiotherapy (SRS) using the CyberKnife device; in 19 cases, remote radiation therapy. In 24 cases, a chemotherapeutic component was added in addition to radiation treatment. Results: Mean time to relapse was 23 months. The median overall survival (OS) for all patients was 35 months. (DI 26.2–43.7). Indicators of 1-year OS — 85.6 %; 3-year-old — 44.1 %, 5-year-old — 26.5 %. Depending on the type of radiation therapy: the highest progression-free survival (PFS) was found with SPLT and combined photon-neutron therapy (SPNT) as in the group of patients with recurrent EH for 15, 17, and AA 24 and 40 months, respectively. Among the patients included in our study, the majority of patients (42 people) had central recurrences (in which 95 % or more of the volume of the recurrent tumor was within 100-95 % of the initial isodose), 6 had marginal relapses (20 to 80 % of the recurrent volume is within the surface of 95 % isodose), and in 2 cases a distant recurrence was recorded (less than 20 % of the recurrent volume was within 95 % of the isodose). Distant recurrences (marginal and distant) occurred within an average of 12 months, while central recurrences were diagnosed on average 26 months after the end of the course of radiation (chemoradiation) treatment. Conclusion: Thus, when analyzing our data, in all patients with continued growth of primary high-grade brain gliomas, the method of choice for a repeated course of radiation therapy is stereotactic radiation therapy or a combined course of photon-neutron therapy, which allows to overcome the existing radioresistance.

Evolution of genomic profiles in primary and recurrent brain gliomas.

e14042 Background: Diffuse gliomas are highly heterogenous tumors with variable biological behaviors, including high intratumor and extratumor heterogeneity, and with occurrence of recurrent lesions in majority of patients. During disease progression, gliomas undergo cellular and genomic evolution with newly acquired genetic properties. However, the mechanism of this complicated process associated with treatment failure is poorly understood. In this retrospective study, we performed cytogenomic analyses of primary and recurrent tumors in five patients with diffuse glioma who underwent surgical resections or biopsies of multiple recurrences. Methods: One primary and at least two recurrent freshly resected tumor tissues from each patient were analyzed using combination of cytogenomic methods. To assess specific and random copy number alterations (CNAs), I-FISH (Abbott Molecular, MetaSystems), array CGH/SNP (Agilent) and MLPA (MRC Holland) were performed. Methylation of MGMT promoter was investigated by methylation-specific MLPA (MRC Holland) and mutations of 67 genes associated with solid tumors were assessed by target NGS (Archer VariantPlex Solid Tumor, Invitae). Results: All five patients (three men and two women) experienced recurrence with newly acquired genetic or epigenetic changes. We observed a higher frequency of CNAs in recurrent gliomas than in primary tumors. Moreover, several aberrations were not detected in recurrence despite being found in earlier samples. As a primary event we proved mutation R132H of IDH1 gene. In addition, we detected methylation of the MGMT promoter, CDKN2A/B homozygous deletion, and RB1 deletion as later events that were probably associated with higher tumor grades. Besides the typical genomic changes, we detected many aberrations with unknown or unclear prognostic relevance (e.g. inframe deletion in TP53, p.Met243_Asn247del, etc.). The progression to a higher grade of glioma occurred in four patients. Conclusions: The evolutional patterns in glioma depend on clonal selection caused by CNAs, mutations, genetic drift, intratumor heterogeneity and/or the patient’s treatment. Recurrence may arise from one major tumor clone or from one or more subclones within the primary tumor through. Integrated cytogenomic analyses of genetic/epigenetic profiles of primary and all recurrent tissues can contribute to a better understanding of mechanisms responsible for these processes and to identification of new alterations related to gliomas progression and/or resistance to treatment. These biomarkers could subsequently serve as new therapeutic targets for personalized treatment.

Brain metastases of cancer of unknown primary: presentation of clinical cases

Background. Metastases to the brain (brain metastases (BM)) are the most common intracranial tumors in adults and occur 3–10 times more frequently than primary brain tumors. In 15% of patients with BM, the primary tumor cannot be determined, which is known as BM cancer of unknown primary. Cancer of unknown primary is the seventh/eighth common malignancy and the fourth leading cause of cancer-related death, often characterized by early and aggressive metastatic spread, poor response to chemotherapy, and poor prognosis. Purpose – To study the course of brain metastases in cancer of unknown primary on the example of clinical cases. Materials and methods. Clinical observation of male patient N., 50 years old, who was diagnosed with a metachronous disease with metastatic damage to the lymph nodes, the excisional biopsy of which established a metastasis of squamous non-keratinous carcinoma and a solitary voluminous neoplasm of the brain, which during the initial examination was considered as IV glioma. Clinical observation of patient B., 40 years old, in whom the primary manifestation of the disease was a solitary neoplasm of the brain, the pathohistological examination of which was regarded as a metastasis of grade III small cell neuroendocrine carcinoma, but the localization of the primary cancer was not established. The examination and treatment were performed in the State Organization «Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine». Results. The clinical cases of BM cancer of unknown primary in two patients aged 50 and 40 years old, which according to histopathological examination were probably low-differentiated squamous cell adenocarcinoma, are presented. The difficulties of diagnostic search for primary cancer and treatment of such patients are shown. Conclusion. Brain metastases cancer of unknown primary, as well as the differential diagnosis of primary brain gliomas and solitary metastases, remain a complex diagnostic and therapeutic medical problem that is a challenge for oncologists, neurosurgeons and neurologists alike. Further study of this problem is necessary for the effective treatment of such patients.

Results of multicomponent treatment of patients with progression of primary brain glioma

The aim of this study was to determine the most effective approach to the treatment of patients with continuous growth of brain glioma.Material and Methods. The study included 200 patients with progression of primary brain glioma, who were treated at the Chelyabinsk Regional Center of Oncology and Nuclear Medicine in the period from 2001 to 2021. The average age of patients was 47.86 ± 11.47 years. The ratio of men to women was 1:1. The continuous growth of high-grade glioma was detected in 125 cases. The progression of lowgrade glioma was observed in 40 patients. Transformation of low-grade glioma into high-grade glioma was found in 35 patients. Re-surgery was performed in 92 patients. Repeated radiation therapy was given to 140 patients. Chemotherapy as the method of choice was administered to 60 patients.Results. The median overall survival (OS) time was 36 months. The 1and 2-year survival rates were 96.0 % and 59.4 %, respectively. The method-specific overall survival time was 15 months. There was a tendency towards an increase in OS in all subgroups of patients who underwent re-surgery. The highest method-specific overall survival rates were observed in patients who received stereotactic radiation therapy (STRT) and combined photon-neutron therapy (CPNT): 23 and 47 months in patients with high-grade glioma and 60 and 72 months in patients with continuous growth of low-grade glioma, respectively (p>0.05). In patients with the transformation of low-grade glioma into high-grade glioma, the method-specific OS was higher in patients who received combination of chemotherapy and radiation therapy compared to those who received chemotherapy or radiation therapy alone: 32, 12, and 24 months, respectively (p>0.05).Conclusion. Repeated surgery is the optimal treatment approach for patients with continuous growth of primary brain glioma. In cases with repeated radiotherapy courses, CPNT or STRT can be the methods of choice. Treatment of patients with transformation of low-grade gliomas into high-grade gliomas should include repeated course of chemoradiotherapy.

DISP-12. RACIAL DISPARITY IN LENGTH OF STAY FOLLOWING CRANIOTOMY FOR PRIMARY BRAIN GLIOMA

Abstract Introduction The racial disparities of opportunity to receive the appropriate surgical intervention and insurance coverage for adjuvant care may result in surgical outcome and survival disparities among different races. Length of stay (LOS) is an important quality metric measure for determining the distribution of medical resources and their consumption. This study aims to provide a perspective on racial disparities in the overall length of stay and complications for patients undergoing craniotomy for primary brain glioma. METHODS The authors performed a retrospective chart review of all patients who underwent craniotomies for resection of primary brain tumors at the Moffitt Cancer Center from 2004-2018. Patients age, race, tumor type, comorbidities, length of stay and complications were reviewed. RESULTS A total of 701 patients underwent craniotomies for primary brain glioma, but 66 were excluded due to insufficient follow-up or incomplete records. The racial categories include Caucasians, African American, Asian, Hispanic, and other. Due to the prevalence of Caucasians, the minorities groups were pooled as non-Caucasians. Both cohorts were similar in baseline comorbidities, KPS, tumor characteristics, and surgical factors. Mean LOS remained lower for Caucasians versus non-Caucasians (3.6 vs. 5.5 d). The differences in LOS remain among different tumor types, including GBM (4 vs. 6.7 d), anaplastic astrocytoma (2 vs. 4.4 d), and oligodendroglioma (2.3 vs. 3.7 d). Interestingly, among astrocytoma, Caucasians had a longer LOS (3 vs 1.2 d). CONCLUSION Our results highlight disparate treatment patterns that reflect in LOS among patients undergoing craniotomies for primary brain gliomas. These findings warrant further investigation regarding current health-care practices and policies.

Construction of a novel blood brain barrier-glioma microfluidic chip model: Applications in the evaluation of permeability and anti-glioma activity of traditional Chinese medicine components

Since most anti-glioma drug candidates hardly permeate through the blood-brain barrier (BBB), preclinical models that can integrate the complexity of the tumor microenvironment and the structure and function of the BBB is urgently needed for the treatment of glioma. Herein, we constructed an in vitro BBB-glioma microfluidic chip model lined by primary human brain microvascular endothelial cells, pericytes, astrocytes and glioma cells, which could recapitulate the high level of barrier function of the in vivo human BBB and glioma microenvironment. The BBB unit in BBB-glioma microfluidic chip (BBB–U251 chip) displayed selective permeability to fluorescein isothiocyanate isomer-dextran (FITC-dextran) with different molecular weights and three model drugs with different permeability behavior across BBB, which indicated that this glioma model included a functional barrier. Six potential anti-glioma components in traditional Chinese medicine (TCM) were delivered into the blood channel and the permeated amount was quantified by high-performance liquid chromatography combined with ultraviolet (HPLC-UV). The permeated drugs then directly acted on 3D cultured glioma cells (U251) to evaluate the drug efficacy. The results of permeability coefficients of drugs showed that the data were closer to the in vivo data of traditional Transwell model. The effect of the drugs on U251 cells in the BBB-U251 chip was significantly lower due to the existence of BBB. Drug responses on glioma demonstrated the necessity to take BBB into account during the development of anti-glioma new drugs. Therefore, this 3D glioma microfluidic models integrating the BBB functionality can be a useful platform for screening the anticancer drug for brain tumors.

Anticancer Activities of 9-chloro-6-(piperazin-1-yl)-11H-indeno[1,2-c] quinolin-11-one (SJ10) in Glioblastoma Multiforme (GBM) Chemoradioresistant Cell Cycle-Related Oncogenic Signatures.

Simple SummaryGlioblastoma multiforme (GBM) remains to be the most frequent malignant tumor of the central nervous system (CNS), which accounts for approximately 54% of all primary brain gliomas. Current treatment modalities for GBM include surgical resection, followed by radiotherapy and chemotherapy with temozolomide (TMZ). However, due to its genetic heterogeneity, GBM tumors always recur, due to treatment reasistance. The aim of this study was to identify molecular gene signatures, responsible for cancer initiation, progression, resistances and to treatment, metastasis, and also evaluate the potency of our novel compounds SJ10 as potential target for CCNB1/CDC42/MAPK7/CD44 oncogenic signatures. Accordingly, we used computational simulation and identify these signatures as regulators of the cell cycle in GBM, which leads to cancer development and metastasis. We also showed the antiproliferative and cytotoxic effects of SJ10 compound against a panel of NCI-60 cancer cell lines. This suggests the potential of the compounds to inhibit CCNB1/CDC42/MAPK7/CD44 in GBM.Current anticancer treatments are inefficient against glioblastoma multiforme (GBM), which remains one of the most aggressive and lethal cancers. Evidence has shown the presence of glioblastoma stem cells (GSCs), which are chemoradioresistant and associated with high invasive capabilities in normal brain tissues. Moreover, accumulating studies have indicated that radiotherapy contributes to abnormalities in cell cycle checkpoints, including the G1/S and S phases, which may potentially lead to resistance to radiation. Through computational simulations using bioinformatics, we identified several GBM oncogenes that are involved in regulating the cell cycle. Cyclin B1 (CCNB1) is one of the cell cycle-related genes that was found to be upregulated in GBM. Overexpression of CCNB1 was demonstrated to be associated with higher grades, proliferation, and metastasis of GBM. Additionally, increased expression levels of CCNB1 were reported to regulate activation of mitogen-activated protein kinase 7 (MAPK7) in the G2/M phase, which consequently modulates mitosis; additionally, in clinical settings, MAPK7 was demonstrated to promote resistance to temozolomide (TMZ) and poor patient survival. Therefore, MAPK7 is a potential novel drug target due to its dysregulation and association with TMZ resistance in GBM. Herein, we identified MAPK7/extracellular regulated kinase 5 (ERK5) genes as being overexpressed in GBM tumors compared to normal tissues. Moreover, our analysis revealed increased levels of the cell division control protein homolog (CDC42), a protein which is also involved in regulating the cell cycle through the G1 phase in GBM tissues. This therefore suggests crosstalk among CCNB1/CDC42/MAPK7/cluster of differentiation 44 (CD44) oncogenic signatures in GBM through the cell cycle. We further evaluated a newly synthesized small molecule, SJ10, as a potential target agent of the CCNB1/CDC42/MAPK7/CD44 genes through target prediction tools and found that SJ10 was indeed a target compound for the above-mentioned genes; in addition, it displayed inhibitory activities against these oncogenes as observed from molecular docking analysis.

The first experience of application of remote radiotherapy in combination with hyperthermia and electrotherapy (oncothermia) in the treatment of patients with primary gliomas of the brain of a high degree of malignancy

High-grade brain gliomas are characterized by a rapid clinical course and a 2-year survival rate of 8-12%. Despite the improvement of methods of surgery, radiotherapy( RT), and systemic drug therapy, it is still not possible to significantly increase the overall and relapse-free survival in patients with this neuro-oncological pathology, and the combination of RT and CT with hyperthermic electrotherapy (oncothermy) (OT) looks like a promising method that helps to increase the effectiveness of special treatment.
 At the same time, oncothermia does not cause brain edema and does not worsen the quality of life of neuro-oncological patients. At the same time, a possible alternative to further progress in improving the results of treatment of primary brain gliomas (WHO Grade III-IV) is not only to optimize the radiotherapy program, but also to combine standard methods of radical treatment with hyperthermic electrotherapy.
 This article presents preliminary immediate results of treatment of 20 patients who received special treatment in the RSCRR with an assessment of the toxicity and safety of its implementation and with an assessment of the likely resumption of continued tumor growth 1.5 and 3 months after the end of treatment. In General, the data obtained indicate the safety of the developed method of special treatment of this category of neuro-oncological patients,
 which confirms the results obtained in 28.09.2019 patent for an invention. However, for final conclusions, further clinical studies are required on a larger group of patients with longer follow-up periods, followed by a thorough analysis of the results.

ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА ГЛИОМ ГОЛОВНОГО МОЗГА: ВОЗМОЖНОСТИ ДИНАМИЧЕСКОЙ ПЭТ/КТ С 18F- ФТОРДЕЗОКСИГЛЮКОЗОЙ

Purpose. The aim of this prospective study, which included the analysis of data from 52 patients with primary brain gliomas, was to look for additional PET-CT biomarkers determined on the basis of the analysis of the first minute of dynamic PET scanning in order to increase the specificity and sensitivity of differential diagnosis of gliomas. 18F-FDG was administered simultaneously with the data collection began. Materials and methods. The study group included data of 52 patients, 27 men, 25 women, age 18-80 years, median 48 years + 12. Histologically, these were glioblastomas (n= 19), anaplastic astrocytomas (n=9), anaplastic oligodendrogliomas (n= 6), benign oligodendrogliomas (n= 6), and diffuse astrocytomas (n=9). Each patient underwent a standard brain MR- study (T2, T2-FLAIR, T1, 3D T1 with contrast enhancement). The selected patients then underwent PET-CT examination (Siemens Truepoint scanner, Siemens Medical Solutions, USA) with radiopharmaceutical 18F-FDG according to the dynamic protocol developed in the our department. Data collection started simultaneously with intravenous administration of radiotracer for the next 40 minutes. 34 frames of 6X10 sec, 6x20 sec, 6x30 sec, 4x60 sec and 12x150 sec were reconstructed. Results. Among the proposed new PET parameters, T/N60s (accumulation index averaged over the first 60 seconds after the administration of 18 F-FDG) turned out to be the most successful, which made it possible to statistically reliably separate glioblastomas from all other histological subtypes of gliomas. Thus, for glioblastomas, T/N60s = 1.6 ± 0.4, and for anaplastic oligodendrogliomas, it was 1.1 ± 0.2, p<0.01. Moreover, T/N60s made it possible to reliably differentiate not only Gr. II from gliomas Gr.III + Gr.IV, but also to differentiate glioblastomas from anaplastic astrocytomas (p<0.01) and glioblastomas from anaplastic and benign oligodendrogliomas (p<0.05 and p<0.01, respectively). All types of gliomas had an T/N60s>1.0, while its final accumulation could be lower than in intact tissue. A possible reason for this phenomenon may be tumor neoangiogenesis, which develops even in the case of low-grade gliomas. Conclusion. The use of the proposed technique for studying patients with brain gliomas and analyzing the data obtained with the new PET biomarkers significantly improves the quality of differential diagnosis of gliomas using 18F-FDG. It also allows reducing the study time for one patient without losing the specificity and sensitivity of diagnosis.

Perfusion and permeability MRI in glioma grading

BackgroundMRI is successful in showing the anatomy of probable pathologies of the central nervous system. Although it may not be sufficient to reveal physiological and metabolic changes, advanced MRI techniques, such as perfusion and permeability MRI, are the key to overcoming these limitations. The aim of this study was to detect the efficacy of permeability and perfusion MRI techniques.ResultsThe study included 38 patients with a pathology result of primary brain glioma. The permeability MRI (Ktrans, Ve), perfusion MRI values (CBV, CBF), and pathology results were evaluated. The high-grade group included 22 patients, and the low-grade group, 16 patients. Mean CBV and CBF, median Ktrans, and Ve values were higher in the high-grade group. All parameters tended to elevate with grade and had a positive correlation. CBV > 2.25, with sensitivity and specificity of 100%, CBF > 2.02, with sensitivity and specificity of 100%, Ktrans > 0.043, with sensitivity of 81.82% and specificity of 100%, and Ve > 0.255, with sensitivity and specificity of 100%, can predict high grade.ConclusionPerfusion and permeability MRI can be used safely for the differentiation of high- and low-grade gliomas and for the prediction of glioma grades.

Seroprevalence to herpesviruses in patients with primary brain gliomas

Purpose of the study . The purpose of the study was to assess the level of seroprevalence and the frequency of detection of serological markers of acute herpesvirus infection in patients with PGBT in comparison with those in patients with chronic non-tumor diseases. Materials and methods . Before conducting antitumor therapy, the blood serum of 42 patients with PGBT (the main group) was studied. The comparison group consisted of 137 patients with chronic non-tumor diseases. Antibodies of classes M and G to herpes simplex virus types 1, 2 (HSV-1,2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus type 6 (HHV-6) were determined by ELISA using JSC Vector-Best reagent kits. Results . Among patients with PGBT, seropositive for HSV-1,2 were 95.2%, CMV — 92.9%, EBV — 100%, HHV-6-40.5% of patients. No statistically significant differences in seroprevalence and the presence of markers of acute infection (IgM) were found either in comparison with non-tumor diseases or depending on the malignancy grade. Antibodies to HSV-1,2, CMV and EBV in patients with gliomas were significantly more often found in the medium range, and in the comparison group — in the high values of coefficient of positivity (CP) for IgG. In all the studied groups, antibodies to HHV-6 were determined statistically significantly less frequently than to other herpes viruses. Conclusion . The absence of statistically significant differences in seropositivity between groups of patients and their presence between pathogens is most likely a reflection of general trends in the population, and the question of the involvement of various representatives of the Herpesviridae family in neuro-oncogenesis of primary glial brain tumors still remains open.

MLTI-18. PRECISION IMAGING OF METASTATIC AND PRIMARY BRAIN TUMORS AFTER RADIATION WITH 18F-FDOPA PET-MRI IS FEASIBLE AND COST EFFECT

PURPOSE: Post-radiation changes in the brain can mimic tumor recurrence on MRI, requiring multiple short term follow-ups to differentiate tumor progression from radiation necrosis. We propose combining functional and anatomic imaging with FDOPA PET tracer in hybrid PET-MRI to improve detection of tumor recurrence. MATERIALS AND METHODS: Seventeen adult patients treated with radiation therapy were identified - four with metastatic disease from breast and lung cancer and thirteen with primary brain glioma (11 IDH wildtype glioblastoma and 2 astrocytoma). Patients were scanned on hybrid PET-MRI (GE Healthcare) with clinical MRI brain sequences and dynamic FDOPA uptake. Dynamic FDOPA uptake within these tumors over 45 minutes after tracer injection was analyzed and compared to ADC histogram analysis. RESULTS: For each of the patients, clinical multi sequence gadolinium enhanced MRI and dynamic PET imaging for up to 45 minutes with 18F-FDOPA amino acid tracer was obtained. The total cost savings of scanning 17 patients in groups was 51.4% ($28,321), as opposed to the cost of individual radiosynthesis performed for each study. Quantitative analysis of tracer uptake in striatum, internal carotid artery, and superior sagittal sinus were performed with appropriate accumulation and subsequent washout of tracer respectively. Successful dynamic FDOPA uptake within the tumor was seen in all patients and ratio of tumor to contralateral ROI were found to range from 1.8–4.5. While raw SUV values did not differentiate between recurrent tumor and radiation changes, T/C SUVmax ratios were elevated to 4.5 in recurrent glioblastoma, 2.5 in hypoxic treated glioblastoma, and 1.8 in non-recurrent metastatic breast cancer after gamma knife treatment. CONCLUSION: Batch imaging of patients with [18F]FDOPA PET-MRI is feasible and cost effective. Understanding radionuclide synthesis process is critical for increasing accessibility of novel PET tracers to patients and results in significant cost savings.

Sodium Fluorescein Guided Excision of High Grade Gliomas: A Tool for Total Excision

AbstractBackground: The best management of high grade gliomas starts with adequate cytoreductive surgery followed by adjuvant therapies. The extent of tumor resection is an important prognostic factor, and it directly affects the tumor progression and the median survival period. Sodium Fluorescein is a fluorescent tracer that crosses the disrupted blood brain barrier, making it suitable for intraoperative visualization of malignant gliomas.Aim: To evaluate the effectiveness of Na Fluorescein to demarcate tumor tissue from brain tissue.Material and Methods: This study was conducted on 30 patients who were indicated for surgical excision of radiolog-ically diagnosed high grade gliomas. All cases had pre and immediate post-operative imaging with contrast to detect the amount of tumor excision. In all our cases at the time of opening the dura, after doing sensitivity testing, 15-20mg/Kg Na Fluorescein was administrated intravenously. The visible yellow stained tumor was then excised using the standard microscopic procedure.Results: All cases had primary brain gliomas (21 were WHO grade IV and 9 cases were grade III). Post-operative imaging showed gross total excision in 23 cases (77%), near total excision (>80% of tumor removed) in 6 cases (20%), and subtotal excision (<80% of tumor removed) in 1 case (3%). None of our cases showed any complications related to reaction from Fluorescein, while 2 cases (6.7%) had transient post-operative motor weakness, and 1 case (3%) had postop-erative dysphasia.Conclusion: The use of Sodium Fluorescein has proven to be an effective tool for demarcation of tumoral tissue from brain tissue; this demarcation was evident using the naked eye, as well as the non-filtered white microscopic light. It is a simple, safe technique, and can be used in economically limited centers; in which Neuronavigation isn't available. The use of Fluorescein increases the chances of safe gross total excision of high grade gliomas, which is reflected on increasing the survival rates as well as decreasing the tumor progression.

Prucalopride inhibits the glioma cells proliferation and induces autophagy via AKT-mTOR pathway

BackgroundsGlioma is the most fatal primary brain glioma in central nervous system mainly attributed to its high invasion. Prucalopride, a Serotonin-4 (5-HT4) receptor agonist, has been reported to regulate neurodevelopment. This study aimed to investigate the influence of the Prucalopride on glioma cells and unveil underlying mechanism.MethodsIn this study, glioma cells proliferation was evaluated by Cell counting kit-8 (CCK8). Wound healing and transwell assay were used to test cellular migration and invasion. Flow cytometry was utilized to determine cellular apoptosis rate. Apoptosis related markers, autophagy markers, and protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway key molecules were detected using western blot assay.ResultsAs a result, the proliferation, migration and invasiveness of glioma cells were impaired by Prucalopride treatment, the apoptosis rate of glioma cells was enhanced by Prucalopride stimulation, accompanied by the increased pro-apoptosis proteins Bax and Cleaved caspase-3 and decreased anti-apoptosis protein Bcl-2. Prucalopride significantly promoted autophagy by increased expression level of Beclin 1 and LC3-II, while decreased expression level of p62. Prucalopride administration resulted in obvious inhibitions of key molecules of AKT-mTOR pathway, including phosphorylated- (p-) AKT, p-mTOR and phosphorylated-ribosomal p70S6 kinase (p-P70S6K).ConclusionsTaking together, these results indicate that Prucalopride may be likely to play an anti-tumor role in glioma cells, which suggests potential implications for glioma promising therapy alternation in the further clinics.

18F-methylcholine PET/CT, in vivo magnetic resonance spectroscopy imaging and tissue enzyme biomarkers of choline metabolism in primary brain gliomas

18F-methylcholine PET/CT, in vivo magnetic resonance spectroscopy imaging and tissue enzyme biomarkers of choline metabolism in primary brain gliomas

HCP-22TOPICALLY APPLIED VANCOMYCIN POWDER REDUCES THE RATE OF SURGICAL SITE INFECTION IN PATIENTS UNDERGOING CRANIOTOMIES FOR PRIMARY BRAIN TUMORS

BACKGROUND: Surgical site infections (SSI) can increase postoperative morbidity, mortality and lead to increased health care costs. The rates of SSI can be as high as 5.8% in patients undergoing craniotomies for tumors. Local application of vancomycin powder has been shown to be effective in reducing SSI in spine surgery; however, the effectiveness and safety of vancomycin powder in craniotomy in unclear. METHODS: The authors performed a retrospective chart review of all patients who underwent craniotomies for resection of primary brain glioma at the Moffitt Cancer Center from 2004-2014. A protocol consisting of 1 g of intrawound vancomycin powder application was initiated at our institution in 2010. Patient demographics (age, gender), clinical characteristics (comorbidities, steroid dose, KPS), tumor characteristics (tumor type, location), surgical factors (primary or redo, length of surgery, blood loss), SSI rates were assessed. Multivariate analysis was performed to determine risk factors associated with SSI and rates. RESULTS: A total of 864 patients underwent craniotomies for primary brain tumors. The cohorts were similar in demographics and baseline comorbidities, KPS, tumor characteristics, and surgical factors. SSI rates at 90 days were reduced after the implementation of vancomycin powder. CONCLUSIONS: The use of vancomycin powder application in craniotomy led to a reduction in SSI. No significant adverse events were observed.