Magnetic resonance diffusion tensor imaging and fibertracking diffusion tensor tractography in the management of spinal astrocytomas

Some specially imaging of magnetic resonance imaging,the diffusion-weighted imaging(DWI),the diffusion tensor imaging and fractional anisotropy(FA),are useful to described,detect,and map the extent of spinal cord lesions.FA measurements may are used to predicting the outcome of patients who have spinal cord lesions.Fiber tracking enable to visualizing the integrity of white matter tracts surrounding some lesions,and this information could be used to formulating a differential diagnosis and planning biopsies or resection.In this article,we will describe the current uses for DWI and fiber tracking and speculate on others in which we believe these techniques will be useful in the future.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Low-Grade Astrocytomas—Final Report (Protocol BT-13)

Nonresectable Low-Grade Astrocytomas (LGA) can compromise function and threaten life. For the majority of patients, the most appropriate strategy is initial chemotherapy followed by Radiation Therapy (RT). Since curative treatment is not available for most of these patients, it is reasonable to conduct clinical studies to evaluate new agents. This Phase II study evaluates efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in LGA. Sixteen children diagnosed with LGA were treated. They included 12 males and 4 females, ages 1.6 - 17.4 years (median 10.6). Efficacy was evaluated in 16 patients. The majority of patients were previously treated, but 1 patient had stereotactic biopsy only. Out of the remaining 15 patients, 6 patients received chemotherapy, and 7 patients had surgery, and 2 patients received RT and chemotherapy after surgery. The patients received treatment with ANP administered daily every 4 hours (median dose of A10 was 7.71 g/kg/d and AS2-1 was 0.26 g/kg/d) until objective response or stable disease was documented and for 8 months thereafter. The duration of ANP IV ranged from 1.4 to 286 weeks with a median of 83 weeks. A complete response was documented in 25.0%, partial response in 12.5%, and stable disease in 37.5%. Overall survival was 67.7% at 5 years, and 54.2% at 10 and 15 years. Progression-free survival was 48.1%, 34.4% and 34.4% at 5, 10, and 15 years respectively. The treatment was associated with grade 3 or grade 4 Adverse Drug Experiences (ADE) in 6 patients. There were two hypernatremias of grade 4 (12%). Grade 3 ADE included urinary frequency (6%), fatigue (6%) and hypernatremia (6%). There were no chronic toxicities, and there was a high quality of survival. ANP shows efficacy with a very good toxicity profile in this cohort of children with low-grade astrocytoma.

Concise review of radiosurgery for contemporary management of pilocytic astrocytomas in children and adults

Pilocytic astrocytoma(PA)may be seen in both adults and children as a distinct histologic and biologic subset of low-grade glioma.Surgery is the principal treatment for the management of PAs;however,selected patients may benefit from irradiation particularly in the setting of inoperability,incomplete resection,or recurrent disease.While conventionally fractionated radiation therapy has been traditionally utilized for radiotherapeutic management,stereotactic irradiation strategies have been introduced more recently to improve the toxicity profile of radiation delivery without compromising tumor control.PAs may be suitable for radiosurgical management due to their typical appearance as well circumscribed lesions.Focused and precise targeting of these well-defined lesions under stereotactic immobilization and image guidance may offer great potential for achieving an improved therapeutic ratio by virtue of radiosurgical techniques.Given the high conformality along with steep dose gradients around the target volume allowing for reduced normal tissue exposure,radiosurgery may be considered a viable modality of radiotherapeutic management.Another advantage of radiosurgery may be the completion of therapy in a usually shorter overall treatment time,which may be particularly well suited for children with requirement of anesthesia during irradiation.Several studies have addressed the utility of radiosurgery particularly as an adjuvant or salvage treatment modality for PA.Nevertheless,despite the growing body of evidence supporting the use of radiosurgery,there is need for a high level of evidence to dictate treatment decisions and establish its optimal role in the management of PA.Herein,we provide a concise review of radiosurgery for PA in light of the literature.

Differential protein expression in low-grade astrocytomas and peritumoral human brain tissues

Differential protein expression between various pathological grades of glioma has been shown in studies of glioma proteomics. However, very little data is available regarding normal brain tissues and glioma differential protein expression, because normal human brain tissues are difficult to harvest. The present study selected samples from low-grade astrocytomas and peritumoral brain tissues to analyze differential protein expression by two-dimensional （2D） electrophoresis and mass spectrometry techniques. Results revealing 36 protein spots by 2D electrophoresis, including 23 spots revealing increased expression and 13 spots revealing decreased expression. However, 25 differential proteins were identified by mass spectrometry, including 16 proteins with increased expression and 9 with decreased expression. Western blot analysis confirmed the mass spectrometry results, i.e., heat shock protein 70 （HSP70） and human transthyretin （TTR） expressions were increased, but glial fibrillary acidic protein （GFAP） was decreased, in astrocytomas. The present study constructed a 2D electrophoresis pattern between low-grade astrocytomas in the human brain and peritumoral tissues. Results demonstrated that a majority of differential proteins, such as HSP70, TTR, and GFAP, participate in malignant progression of gliomas.

STUDY OF DELETION OF P16 GENE IN THE PROGRESSION OF BRAIN ASTROCYTOMAS

Objective: To study the relationship between deletion of P16 gene and occurrence and progression of astrocytomas Methods: The techniques of polymerase chain reaction (PCR) and immunohistochemistry were used to detect the deletion of exon2 of P16 gene and expression of P16 gene in 52 cases of Brain astrocytoma Results: The deletion rate of exon2 of P16 gene in the tumors analyzed was 34 6% Most of them with deletion of exon2 of p16 gene were high grade astrocytomas (grade III 42%, grade IV 50%) 61 5% of the tumors were absent from expression of p16 and the deletion rate of p16 protein increased with the grade of astrocytoma (X 2=10 83, P <0 005) Conclusion: Deletion of p16 gene and protein may correlate with the malignant progression of astrocytoma

Updates on management of gliomas in the molecular age

Gliomas are primary brain tumors derived from glial cells of the central nervous system,afflicting both adults and children with distinct characteristics and therapeutic challenges.Recent developments have ushered in novel clinical and molecular prognostic factors,reshaping treatment paradigms based on classi-fication and grading,determined by histological attributes and cellular lineage.This review article delves into the diverse treatment modalities tailored to the specific grades and molecular classifications of gliomas that are currently being discussed and used clinically in the year 2023.For adults,the therapeutic triad typically consists of surgical resection,chemotherapy,and radiotherapy.In contrast,pediatric gliomas,due to their diversity,require a more tailored approach.Although complete tumor excision can be curative based on the location and grade of the glioma,certain non-resectable cases demand a chemotherapy approach usually involving,vincristine and carboplatin.Addi-tionally,if surgery or chemotherapy strategies are unsuccessful,Vinblastine can be used.Despite recent advancements in treatment methodologies,there remains a need of exploration in the literature,particularly concerning the efficacy of treatment regimens for isocitrate dehydrogenase type mutant astrocytomas and fine-tuned therapeutic approaches tailored for pediatric cohorts.This review article explores into the therapeutic modalities employed for both adult and pediatric gliomas in the context of their molecular classification.

Expression and significance of sonic hedgehog signaling pathway-related components in brainstem and supratentorial astrocytomas

Background Studies have shown that abnormal activation of the sonic hedgehog pathway is closely related to tumorigenesis in central nervous system. This study aimed to investigate the role of the sonic hedgehog signaling pathway in the occurrence of brainstem and supratentorial glioma. Methods Real-time quantitative reverse transcription polymerase chain reaction （qRT-PCR） and immunohistochemistry were used to detect the expression of sonic hedgehog-related components in 5 specimens of normal brain tissue, 10 of grade II brainstem glioma, and 10 of grade II supratentorial glioma. The significance of differences between two groups was determined using the Mann-Whitney U test or the two-sample test according to the results of normality distribution tests. Results The mRNA expression levels of sonic hedgehog-related genes were higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue. The level of protein patched homolog 1 （PTCH1） was significantly higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue （P 〈0.01）. Immunohistochemistry semi-quantitative analysis was consistent with the qRT-PCR result that PTCH1 expression was increased significantly in brainstem astrocytomas at the protein level （P 〈0.05）. Conclusions Enhanced PTCH1 expression and activation of the sonic hedgehog pathway are involved in brainstem glioma. This may be related to the difference in malignant biological behavior between brainstem and hemispheric glioma and could be an ideal therapeutic target in brainstem glioma.

Screening of differentially expressed genes related to differentiation and proliferation by gene expression profiling of different grade astrocytoma cell lines

BACKGROUND： The detection of differential gene expression in brain is possible by cDNA microarray technology, and the screening of differentially expressed genes might provide a biological basis for gene-targeted therapy for tumors. OBJECTIVE： To detect the differential expression of genes among astrocytoma SHG-44 （WHO grade Ⅳ）, CHG-5 （WHO grade Ⅱ）, and ATRA-treated SHG-44 cell lines by cDNA microarray. DESIGN： Laboratory experiments in vitro. SETTING： Department of Neurobiology, the Third Military Medical University. MATERIALS： The experiment was performed at the Department of Neurobiology in the Third Military Medical University of the Chinese PLA from January to October 2007. The SHG-44 cell line （WHO grade Ⅳ） was established by Prof. Ziwei Du, and the CHG-5 cell line （WHO grade Ⅱ） was set up by Prof. Xiuwu Bian from the Third Military Medical University of the Chinese PLA. The cDNA microarray containing 9182 known genes was prepared and provided by Dr. Yang Zhong at the City University of Hong Kong. METHODS： To screen differentially expressed genes from the gene expression profiles detected by cDNA microarray comparisons were made between CHG-5 and SHG-44 cells and between SHG-44 cells with or without treatment with 10 μmol/L ATRA. Some differentially expressed genes were selected randomly for Northern Blot analysis to confirm the results of the microarray. The determination criteria for differential gene expression were as follows. ① The ratio of Cy5 signal to Cy3 was greater than 2.0 or less than 0.5. ② The results of the triplicate microarray hybridizations showed the same trend in three experiments. ③ A gene appeared at least two times on the triplicate microarray hybridizations, and the 3^rd value did not show a contradictory trend. A normalized ratio of Cy5 intensity to Cy3 greater than 2.0 or less than 0.5 was considered to represent up-regulated or down-regulated gene expression, respectively. MAIN OUTCOME MEASURES： The identification of genes that were similarly regulated （overlapping） during tumor progression and differentiation, by comparison of gene expression profiles between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. RESULTS： Thirty-one overlapping genes were found to have similar regulatory effects on astrocytomas; among them, twenty genes were up-regulated and eleven were down-regulated in both comparisons between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. The four reported genes, SERPINFI, MAPKI 1, HIFIA and SOD2, were up-regulated in this study. CONCLUSION： The differentially expressed genes in different grade astrocytoma cell lines were revealed primarily by cDNA microarray; among them, five identified overlapping genes, SERPINF1, MAPK11, DCTN2, HIF1 A and SOD2, were related to the malignant progression of astrocytoma cells.

Pilomyxoid Astrocytoma in Cerebellum

Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma,and typically locates in the hypothalamic and chiasmatic region.Herein,we reported a nine-year-old boy with pilomyxoid astrocytoma in the cerebellum.MRI scanning showed a tumor involved the cerebellar vermis,tonsil,the forth ventricle and brainstem.It was homogeneous isointensity on T1WI,relative hyper-intensity on T2WI,hyper-intensity on fluid attenuated inversion recovery （FLAIR） images,and uniform enhancement on contrast T1WI.The tumor was sub-totally removed and was proved histologically to be pilomyxoid astrocytoma.Follow-up at the 5th month,MRI showed the residual tumor enlarged at the brainstem.The patient survived 10 months after the operation,and finally died of respiration failure resulting from brainstem dysfunction.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Recurrent, Refractory or Progressive Primary Brain Tumors—Final Report (Protocol BT-22)

Primary malignant brain tumors are a leading cause of cancer-related death in children. This Phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in children who developed progression during standard treatment. A total of 43 children were recruited to the study, but only 41 met eligibility criteria. There were twelve cases of glioblastoma multiforme (GBM), eight anaplastic astrocytomas (AA), twelve diffuse intrinsic pontine gliomas (DIPG), three supertentorial primitive neuroectodermal tumors (sPNET), three cases of medulloblastoma and one case each of anaplastic ependymoma (AE), atypical teratoid rhabdoid tumor (AT/RT), and disseminated pilocytic astrocytoma (PAD). ANP was administered intravenously daily every four hours (median dose of A10 8.74 g/kg/d and AS2-1 0.35 g/kg/d), until objective response (OR) was documented, and then a further eight months. All enrolled patients were included in safety, but only eligible patients in the efficacy evaluation. A total of 12.2% of patients obtained OR;2.4% complete response (CR) and 9.8% partial response (PR). Stable disease (SD) was determined in 17.1% and progressive disease (PD) in 43.9% of cases. There were 26.8% of nonevaluable (NE) cases due to premature discontinuation. Out of five OR cases, four patients were diagnosed with recurrent DIPG and one with recurrent AA. Median progression-free survival (PFS) was 2.5 months. Median overall survival was 4.8 months. OS at 6 months was 46.3%, one year was 12.2%, and 4.8% at two, five, and ten years. The longest survivor is a patient diagnosed with DIPG and gliosarcoma who remains alive more than 15 years. A group of eleven patients reported grade 3 and 4 toxicity including hypernatremia in eight cases, somnolence in two cases, and hypokalemia in one case. There were no chronic toxicities, and the quality of life was very good. The largest group of patients were represented by DIPG, GBM, and AA. The best results were obtained in the DIPG and AA groups. In the DIPG group, CR was in 8.3%, PR was 25%, median PFS was 4.8 months, median OS was 6.1 months, and OS at 6 months was 58.3%, at one year 25%, and 8.3% at two, five, and ten years. In the AA group, PR was 12.5%, median PFS was 3.7 months, median OS was 4.7 months, and OS at 6 months was 37.5%, and 12.5%, at one, two, five, and ten years. In conclusion, antineoplastons showed efficacy and acceptable toxicity in patients with recurrent, refractory or progressive primary brain tumors.

Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

This study was designed to investigate whether the Notch pathway is involved in the develop-ment of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133＋and CD133？ cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7–11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133＋ cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133？ cell suspension, and Notch-immunopositive expres-sion was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133＋ astro-cytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However,it should be emphasized that the sub-cortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133？ astrocytoma cells. However, these ifndings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treat-ment target for diffuse spinal cord astrocytoma.

Carbonic anhydrase VII–a potential prognostic marker in gliomas

Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII expression in a cohort of human diffuse astrocytomas, mixed oligoastrocytomas and oligodendrogliomas. CA VII immunostaining was correlated to clinico-pathologic findings, survival data, and expres-sion of other molecular factors, including Ki-67, p53 protein and epidermal growth factor receptor. CA VII-positive staining was observed in 94% of astrocytomas and 85% of oligodendrogliomas. In the tumor specimens, strong positive areas were often located in close proximity to necrosis. The CA VII immunoreactivity showed positive correlation with tumor malignancy grades of astrocytomas (p = 0.02, chi-square test). In all tumor categories, CA VII-positive staining was often seen in the en-dothelial cells of neovessels in addition to the tumor cells. CA VII intensity showed no significant association with p53 nor did it correlate with the amplification of epidermal growth factor receptor (analyzed only in astrocytomas) or cell proliferation. Our present results show that CA VII may act as a useful biomarker in histopathologic diagnostics of gliomas. The high expression of CA VII in the tumor cells and endothelium suggests important roles for the enzyme in tumor metabolism. The results also led us to conclude that CA VII might serve as a marker of poor prognosis in diffuse astrocytomas.

Increased leucine-rich repeats and immunoglobulin- like domains 1 expression enhances chemosensitivity in glioma

Leucine-rich repeats and immunoglobulin-like domains 1 （LRIG1） is an anti-oncogene. LRIG1 is correlated with Bcl-2 in ependymomas. Decreased Bcl-2 and manganese superoxide dismutase expression can improve the chemosensitivity of glioma. In the present study, a tissue microarray of human brain astrocytomas was constructed. To investigate the relationship of LRIG1 with Bcl-2 and manganese superoxide dismutase, LRIG1, Bcl-2 and manganese superoxide dismutase expression in our tissue microarray was determined using immunohistochemistry. In addition, we constructed the LRIG1-U251 cell line, and its responses to doxorubicin and temozolomide were detected using the MTT assay. Results showed that LRIG1 expression was significantly negatively correlated with Bcl-2 and manganese superoxide dismutase expression in glioma. Also, proliferation of LRIG1-U251 cells exposed to doxorubicin or temozolomide was significantly inhibited, i.e. in the LRIG1-U251 cell line, the chemosensitivity to doxorubicin and temozolomide was increased. This indicates that increased LRIG1 expression produces a chemosensitivity in glioma.

Misdiagnosed Angioimmunoblastic T-cell Lymphoma Secondary to Cranial Astrocytoma

A case of angioimmunoblastic T-cell lymphoma （AITL） which was misdiagnosed as adult Still＇s disease was presented. The clinical and laboratory characteristics of this case and related literatures were analyzed and reviewed. The patient was finally diagnosed as AITL （Ann Arbor classification： Stage IIIB） secondary to cranial astrocytoma （WHO classification： Stage III）, complicated with severe pulmonary infection because of long time treatment of corticosteroid and misdiagnosis （about one and a half year）. It is concluded that AITL is a rare disease which was easily misdiagnosed. The diagnosis of AITL should combine the clinical manifestation with pathological biopsy as well as corresponding immunohistochemical tests.

ANALYSIS OF VARIABLES AFFECTING SURVIVAL OF PATIENTS WITH ASTRACYTOMAS

Objective: To evaluate the factors that affect the survival of patients with astrocytomas. Methods: We reviewed the clinical and radiological features of 104 patients operated during 1995~2000. The features were evaluated with univariate and multivariate analysis. Results: Univariate statistical analysis revealed that tumor localization, enhancement, edema, tumor invasion, seizure as the first symptom recurrence, edema, tumor invasion, seizure as the first symptom and recurrence of astrocytomas significantly affected the survival, In multivariate analysis four factors showed significant danger to long survival: necrosis, pathological grade, Karnofsky Performance Scale (KPS) score before operation, extent of resection. The rest factors appeared to be of no benefit to survival. Conclusion: The important factors that affect the long survival of patients with astrocytomas are necrosis, pathological grade, KPS score before operation and extent of resection.

Identification of tumor invasion-related differentially expressed genes in different grades and all-trans retinoic acid-treated astrocytoma cell lines

BACKGROUND： Although several genetic aberrations and gene expressional changes have been shown to exist in tumors and different grades of astrocytomas, as well as in normal tissues, the gene profiling and genetic pathways associated with malignant transformation and progression remain unclear. OBJECTIVE： To identify differentially expressed genes related to tumor invasion from various grades and all-trans retinoic acid （ATRA）-treated astrocytoma cell lines by cDNA microarray. DESIGN, TIME AND SETTING： In vitro gene experiment was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA from January to October 2007. MATERIALS： Two different grades of astrocytoma cell lines CHG-5 （WHO grade II ） and SHG-44 （WHO grade IV） were developed by our laboratory; a cell differentiation-inducing agent ATRA and a human cDNA microarray technology were used to determine differentially expressed genes （City University of Hong Kong）. METHODS： Total RNA was extracted using the Trizol test kit. Reverse transcription was performed using Superscript 11 reverse transcriptase. The cDNA product （target DNA） was marked with fluorochromes Cy3 （normal SHG-44） and Cy5 （CHG-5 or ATRA-treated SHG-44）, followed by chip hybridization. MAIN OUTCOME MEASURES： Gene expression profiles of CHG-5 vs. SHG-44 and ATRA-treated vs. normal SHG-44 were performed to identify differentially expressed genes. Several of these genes were randomly selected for Northern Blot analysis. The identification of genes that were similarly regulated （overlapping） was performed by comparing gene expression profiles between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. RESULTS： No significant differences were observed between CHG5 and SHG-44 cell line morphology. Under confocal microscopy, GFAP staining intensity of CHG5 cells was greater than SHG-44 cells （t = 6.078 P = 0.004）. Growth curve analysis demonstrated that the speed of SHG-44 cell growth was greater than CHG5 cells. Flow cytometry analysis showed that the number of ATRA-treated SHG-44 cells at G0/G1 stage increased by 15%, compared with normal SHG-44 cells （P 〈 0.05）. A total of 31 known genes with altered expression were identified in this study. Among them, 20 genes were upregulated and 11 were downregulated in CHG-5 compared with SHG-44 cells, and ATRA-treated SHG-44 compared with untreated SHG-44 ceils. Four of these reported genes （CD151, G3BP, UGB, and CSTB） were shown to be involved in tumor invasion. Validation of a selection of differentially expressed genes was perfonlaed by Northern blot. CONCLUSION： A total of 31 known genes were demonstrated by cDNA microarray to relate to the malignant progression of astrocytomas, and four differentially expressed genes （CD151, G3BP, UGB, and CSTB） were shown to relate to tumor invasion.

A Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Primary Brain Tumors—Final Report (Protocol BT-09)

Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine, and phenylacetic acid. In 1993, a phase II clinical trial program began according to protocols based on the initial protocol, BT-06, which was transferred from the National Institutes of Health (NIH). Protocol BT-09 was designed for different types of primary brain tumors in adults that were not curable by standard treatment. The study was designed as a single arm, two-stage, phase II trial of ANP as a monotherapy in a high-risk, poor-prognosis population. The total number of registered subjects was 40. The majority of patients were diagnosed with high-grade tumors (N = 33). In this group, 12 patients carried diagnosis of anaplastic astrocytoma (AA) and 11 patients of glioblastoma. In the group of low-grade tumors (N = 7), there were 6 cases of low-grade glioma, and 1 neurocytoma grade 2. A group of 12 patients did not receive any prior treatment, 12 patients had surgical resection only, 5 patients received radiation therapy (RT) only, and 11 patients received both RT and chemotherapy. The median duration of ANP was 16.6 weeks. The median dosage of A10 was 7.16 g/kg/d and AS2-1 was 0.27 g/kg/d. Responses were accessed by gadolinium-enhanced magnetic resonance imaging (MRI). Objective responses (OR) in all patients were 22.5% and in the AA group were 41.7% of patients. The median progression-free survival (PFS) in the AA group was 5.4 months. The median overall survival (OS) was 12.7 months and OS at 1 and 2 years was 54.5% and 45.5% correspondingly. The treatment was well-tolerated with reversible grade 3 and 4 toxicities in 35% of all patients (N = 40). In conclusion, the study reached efficacy endpoint and ANP was well-tolerated and compared favorably to the current treatment of AA.

Synthesis of Amine Terminated Pegylated Iron Oxide Nanoparticles for Prospective Astrocytoma Resection Grade Improvement

Having a survival rate to 5 years of only 3%,Glioblastoma’s(GBM)main treatment is surgical excision.Iron oxide nanoparticles have been proved to be a magnetic resonance imaging contrast agent and,if synthesized and tuned correctly,could be used to improve complete GBM resection.In this work monodisperse iron oxide nanoparticles were synthesized using thermal decomposition method,then a ligand exchange reaction with 3-aminopropyl trimethoxysilane(APS)was performed,following Pegylation of the particles using dicarboxylic acid PEG(PEG-diacid)and finally aminating with 2,2’-(ethylenedioxy)bis(ethylamine),last two by amide reactions.STEM and DLS demonstrate monodispersity(log σ<0.2)and desired size range to penetrate the blood-brain barrier(BBB);FT-IR shows the reactions were executed correctly and finally stability in deionized water,0.07 M NaCl and PBS 1X,as a function of 0-30 days,was tested.Results revealed the importance that the oleic acid/iron oleate molar ratio and the growth stage time represents for determining iron oxide nanoparticles’ size;as well as APS concentration and nucleation time influence on silica coating when performing the ligand exchange reaction.The produced iron oxide nanoparticles exhibit stability and proper amine terminated groups which are needed to allow easy incorporation of Chlorotoxin,a 36-amino acid peptide that binds specifically to astrocytoma cells,and a fluorescent molecule,which enables real time visualization of the tumor during surgery.

Case Report: Anaplastic Astrocytoma Treated with Postoperative Radiotherapy Using Flattening Filter-Free Volumetric Arc Therapy (FFF-VMAT) during Pregnancy—Acceptable Fetal Dosimetry

Background: Postoperative irradiation for brain tumor in pregnant women is a matter of concern. Aim: We aimed to assess the safety of radiotherapy for brain tumors in pregnancy. We here report a successful treatment for anaplastic astrocytoma during pregnancy: surgery + postoperative irradiation. We wish to emphasize how we devised irradiation procedure to achieve both therapeutic effectiveness and safety to the fetus/infant. Case Presentation: A 34-year-old pregnant woman suffered with brain anaplastic astrocytoma. Tumor resection under craniotomy was performed with success. We decided to conduct postoperative radiotherapy at 25 weeks of gestation to reduce the risk of recurrence. We used a flattening filter-free volumetric arc therapy (FFF-VMAT) technique, which can achieve lower out-of-field dose than VMAT with a flattening filter or helical tomotherapy. We prescribed 60 Gy over 30 fractions. During actual beam delivery, surface and rectal dose to the patient (mother) were measured. The total fetal dose was estimated at 0.006 - 0.018 Gy, which is under the threshold set by the ICRP. A male healthy infant was born vaginally at the 37th week of pregnancy. The patient (mother) and the infant are healthy at the time of writing. Conclusion: FFF-VMAT is a good choice for brain tumors during pregnancy.

Volumetric Assessment of Corticospinal Tract Infiltration by Astrocytoma Using Diffusion Tensor Tractography

Objectives: The aim of the study is to assess volumetric Corticospinal Tract infiltration by Astro-cytoma using Diffusion Tensor Tractography. Material and Methods: Preoperative, anatomic (T1- and T2-weighted) and diffusion tensor MRI were performed in 9 patients with supratentorial gliomas (WHO grade II and III). The tumors were manually segmented from the T1- and T2-weighted MRI, and their volume calculated. A three-dimensional tractography was performed in each case. A second segmentation and volume measurement was performed on the tumor regions intersecting adjacent white matter fiber tracts. Results: We identified that white matter tracts were infiltrated by 6 Astrocytoma tumors. The median tumor volume (±standard deviation) in our patient population was 33 ± 26.82 ml. The median tumor volume (±standard deviation) infiltrating white matter fiber tracts was 4.15 ± 9.23 ml. The median fraction of tumor volume infiltrating white matter fiber tracts was 26.3% ± 10.1%. Conclusions: Diffusion tensor MR Tractography is a reliable preoperative assessment tool since it detects extensive white matter infiltration by Astrocytoma irrespective of brain tumors volume. Recommendations: Prospective large population studies are required to clarify how infiltration relates to tumor location.