Choroid plexus tumors are uncommon brain tumors that primarily occur in children. Most of these tumors originate from the intraventricular area, and the most common clinicalpresentation is increased intracranial pressure. Dissemination through the cerebrospinal fluid space is the inevitable natural course of the disease. Here, we present 2 rare cases of adult choroid plexus carcinoma (CPC), each with distinct clinical presentation and progression. The first case was a 40-year-old male who presented with multiple intraventricular masses. After surgical biopsy, radiation and intrathecal chemotherapy failed to elicit any response. The patient progressed with spinal cord dissemination and expired 1 year later. The second case presented with visual disturbance, and brain MRI revealed a large ovoid juxtaventricular mass with peritumoral edema. This 49-year-old female patient underwent craniotomy for what was thought to be a high-grade glioma; however, the mass was connected to the choroid plexus at the operative field. Her pathology specimen was diagnosed as CPC, and adjuvant systemic chemotherapy was administered. She has now been free of recurrence for 10 months. The description of the presentation and progression of these rare adult-onset CPC provides insight for the diagnosis and treatment of other rare instances of choroid plexus tumors.
Adult ; Biopsy ; Brain ; Brain Neoplasms ; Cerebrospinal Fluid ; Child ; Choroid Plexus Neoplasms ; Choroid Plexus ; Choroid ; Craniotomy ; Diagnosis ; Drug Therapy ; Edema ; Female ; Fourth Ventricle ; Glioma ; Humans ; Intracranial Pressure ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pathology ; Recurrence ; Spinal Cord

Bilateral thalamic gliomas (BTGs) are rare brain tumors. In general, the prognosis is poor because of the involvement of bilateral thalami and limitations of surgical excision. Consequently, patients with symptoms of personality changes and memory impairment must be differentiated from others. Magnetic resonance imaging (MRI) is essential for the diagnosis of BTGs and reveals a hypo-intense lesion on T1-weighted images and a hyper-intense lesion on T2 images. We report a case of a 17-year-old female patient suffering from progressive cognitive dysfunction and personality changes and subsequent rehabilitation treatment. Brain MRI showed an enlarged bilateral thalamus, with hyperintensity on T2-weighted images and iso-intensity on T1-weighted images. A biopsy was performed, and the pathology revealed a high-grade glioma. The patient was referred for radiotherapy and chemotherapy. She also underwent rehabilitation treatment for 5 weeks and showed improvement in standing balance, endurance, and speech fluency. The patient's Modified Barthel Index scores also improved. Cancer rehabilitation is important in brain tumor patients because they have a higher incidence of neurological sequelae than others. Rehabilitation of patients with a malignant brain tumor is also important for improving health-related quality of life by maintaining the general condition and preventing complications during and after cancer treatment.
Adolescent ; Biopsy ; Brain ; Brain Neoplasms ; Diagnosis ; Drug Therapy ; Female ; Glioma ; Humans ; Incidence ; Magnetic Resonance Imaging ; Memory ; Memory Disorders ; Neurobehavioral Manifestations ; Pathology ; Prognosis ; Quality of Life ; Radiotherapy ; Rehabilitation ; Thalamus

OBJECTIVE: This study aims to determine whether gamma knife radiosurgery (GKR) improves survival in patients with recurrent highgrade gliomas.METHODS: Twenty nine patients with recurrent high-grade glioma underwent 38 GKR. The male-to-female ratio was 10 : 19, and the median age was 53.8 years (range, 20–75). GKR was performed in 11 cases of recurrent anaplastic oligodendrogliomas, five anaplastic astrocytomas, and 22 glioblastomas. The median prescription dose was 16 Gy (range, 10–24), and the median target volume was 7.0 mL (range, 1.1–15.7). Of the 29 patients, 13 (44.8%) received concurrent chemotherapy. We retrospectively analyzed the progression-free survival (PFS) and overall survival (OS) after GKR depending on the Eastern Cooperative Oncology Group (ECOG) performance status (PS), pathology, concurrent chemotherapy, radiation dose, and target tumor volume.RESULTS: Starting from when the patients underwent GKR, the median PFS and OS were 5.0 months (range, 1.1–28.1) and 13.0 months (range, 1.1–75.1), respectively. On univariate analysis, the median PFS was significantly long in patients with anaplastic oligodendroglioma, ECOG PS 1, and target tumor volume less than 10 mL (p < 0.05). Meanwhile, on multivariate analysis, patients with ECOG PS 1 and target tumor volume less than 10 mL showed improved PFS (p=0.043 and p=0.007, respectively). The median OS was significantly increased in patients with ECOG PS 1 and tumor volume less than 10 mL on univariate and multivariate analyses (p < 0.05).CONCLUSION: GKR could be an additional treatment option in recurrent high-grade glioma, particularly in patients with good PS and limited tumor volume.
Astrocytoma ; Disease-Free Survival ; Drug Therapy ; Glioblastoma ; Glioma ; Humans ; Multivariate Analysis ; Oligodendroglioma ; Pathology ; Prescriptions ; Radiosurgery ; Recurrence ; Retrospective Studies ; Tumor Burden

Although methyltransferase has been recognized as a major element that governs the epigenetic regulation of the genome during temozolomide (TMZ) chemotherapy in glioblastoma multiforme (GBM) patients, its regulatory effect on glioblastoma chemoresistance has not been well defined. This study investigated whether DNA methyltransferase (DNMT) expression was associated with TMZ sensitivity in glioma cells and elucidated the underlying mechanism. DNMT expression was analyzed by western blotting. miR-20a promoter methylation was evaluated by methylation-specific PCR. Cell viability and apoptosis were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and TdT-mediated dUTP-biotin nick end labeling assays, respectively. The results showed that compared with parental U251 cells, DNMT1 expression was downregulated, miR-20a promoter methylation was attenuated and miR-20a levels were elevated in TMZ-resistant U251 cells. Methyltransferase inhibition by 5-aza-2\'-deoxycytidine treatment reduced TMZ sensitivity in U251 cells. In U251/TM cells, DNMT1 expression was negatively correlated with miR-20a expression and positively correlated with TMZ sensitivity and leucine-rich repeats and immunoglobulin-like domains 1 expression; these effects were reversed by changes in miR-20a expression. DNMT1 overexpression induced an increase in U251/TM cell apoptosis that was inhibited by the miR-20a mimic, whereas DNMT1 silencing attenuated U251/TM cell apoptosis in a manner that was abrogated by miR-20a inhibitor treatment. Tumor growth of the U251/TM xenograft was inhibited by pcDNA-DNMT1 pretreatment and boosted by DNMT1-small hairpin RNA pretreatment. In summary, DNMT1 mediated chemosensitivity by reducing methylation of the microRNA-20a promoter in glioma cells.
Animals ; Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use ; Apoptosis/drug effects ; Brain/drug effects/metabolism/pathology ; Brain Neoplasms/drug therapy/*genetics/pathology ; DNA (Cytosine-5-)-Methyltransferase/antagonists & inhibitors/*genetics/metabolism ; DNA Methylation ; Dacarbazine/*analogs & derivatives/pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Glioma/drug therapy/*genetics/pathology ; Humans ; Mice, Inbred C57BL ; MicroRNAs/*genetics ; Promoter Regions, Genetic

Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.
Aminolevulinic Acid ; pharmacology ; therapeutic use ; Animals ; Brain Neoplasms ; blood supply ; drug therapy ; pathology ; Cell Line, Tumor ; Glioma ; blood supply ; drug therapy ; pathology ; Microvessels ; drug effects ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Xenograft Model Antitumor Assays

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited familial tumor syndrome. Benign tumors such as pilocytic astrocytoma, optic glioma make up the majority of intracranial neoplasms in patients with NF1. There have only been a handful of cases in which adult glioblastoma presented with NF1. A 32-year-old male presented with headache and radiological studies showing a high grade intra-axial tumor. The patient underwent gross total surgical excision and the pathology revealed glioblastoma. After the surgery, he received concomitant chemo-radiotherapy with temozolomide and adjuvant temozolomide chemotherapy. We report a NF1 patient who developed glioblastoma and reviewed related articles.
Adult ; Astrocytoma ; Brain Neoplasms ; Drug Therapy ; Glioblastoma* ; Hand ; Headache ; Humans ; Male ; Neurofibromatosis 1* ; Optic Nerve Glioma ; Pathology

The current standards in radiotherapy of high-grade gliomas (HGG) are based on anatomic imaging techniques, usually computed tomography (CT) scanning and magnetic resonance imaging (MRI). The guidelines vary depending on whether the HGG is a histological grade 3 anaplastic glioma (AG) or a grade 4 glioblastoma multiforme (GBM). For AG, T2-weighted MRI sequences plus the region of contrast enhancement in T1 are considered for the delineation of the gross tumor volume (GTV), and an isotropic expansion of 15 to 20 mm is recommended for the clinical target volume (CTV). For GBM, the Radiation Therapy Oncology Group favors a two-step technique, with an initial phase (CTV1) including any T2 hyperintensity area (edema) plus a 20 mm margin treated with up to 46 Gy in 23 fractions, followed by a reduction in CTV2 to the contrast enhancement region in T1 with an additional 25 mm margin. The European Organisation of Research and Treatment of Cancer recommends a single-phase technique with a unique GTV, which comprises the T1 contrast enhancement region plus a margin of 20 to 30 mm. A total dose of 60 Gy in 30 fractions is usually delivered for GBM, and a dose of 59.4 Gy in 33 fractions is typically given for AG. As more than 85% of HGGs recur in field, dose-escalation studies have shown that 70 to 75 Gy can be delivered in 6 weeks with relevant toxicities developing in <10% of the patients. However, the only randomized dose-escalation trial, in which the boost dose was guided by conventional MRI, did not show any survival advantage of this treatment over the reference arm. HGGs are amongst the most infiltrative and heterogeneous tumors, and it was hypothesized that the most highly aggressive areas were missed; thus, better visualization of these high-risk regions for radiation boost could decrease the recurrence rate. Innovations in imaging and linear accelerators (LINAC) could help deliver the right doses of radiation to the right subvolumes according to the dose-painting concept. Advanced imaging techniques provide functional information on cellular density (diffusion MRI), angiogenesis (perfusion MRI), metabolic activity and cellular proliferation [positron emission tomography (PET) and magnetic resonance spectroscopy (MRS)]. All of these non-invasive techniques demonstrated good association between the images and histology, with up to 40% of HGGs functionally presenting a high activity within the non-contrast-enhanced areas in T1. New LINAC technologies, such as intensity-modulated and stereotactic radiotherapy, help to deliver a simultaneous integrated boost (SIB) > 60 Gy. Trials delivering a SIB into a biological GTV showed the feasibility of this treatment, but the final results, in terms of clinical benefits for HGG patients, are still pending. Many issues have been identified: the variety of MRI and PET machines (and amino-acid tracers), the heterogeneity of the protocols used for image acquisition and post-treatment, the geometric distortion and the unreliable algorithms for co-registration of brain anatomy with functional maps, and the semi-quiescent but highly invasive HGG cells. These issues could be solved by the homogenization of the protocols and software applications, the simultaneous acquisition of anatomic and functional images (PET-MRI machines), the combination of complementary imaging tools (perfusion and diffusion MRI), and the concomitant addition of some ad hoc targeted drugs against angiogenesis and invasiveness to chemoradiotherapy. The integration of these hybrid data will construct new synthetic metrics for fully individualized treatments.
Antineoplastic Agents, Alkylating ; therapeutic use ; Brain Neoplasms ; diagnosis ; pathology ; radiotherapy ; Dacarbazine ; analogs & derivatives ; therapeutic use ; Diffusion Tensor Imaging ; Glioblastoma ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Glioma ; diagnosis ; pathology ; radiotherapy ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Neoplasm Grading ; Particle Accelerators ; Positron-Emission Tomography ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; methods

This study evaluated the toxicity profiles of temozolomide in the treatment of malignant glioma as either concurrent or adjuvant chemotherapy. We retrospectively reviewed the medical records of 300 malignant glioma patients treated with temozolomide in two medical institutions in Korea between 2004 and 2010. Two hundred nine patients experienced a total of 618 toxicities during temozolomide therapy. A total of 84.8% of the 618 toxicities were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three most common toxicities. There was no mortality due to temozolomide. Although temozolomide showed many types of toxicities, the majority of the toxicities were tolerable and of lower grade. Gastrointestinal troubles are the most common toxicities in Korean patients treated with temozolomide.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anorexia/etiology ; Antineoplastic Agents, Alkylating/adverse effects/*therapeutic use ; Brain Neoplasms/*drug therapy/pathology/radiotherapy ; Dacarbazine/adverse effects/*analogs & derivatives/therapeutic use/toxicity ; Female ; Glioma/*drug therapy/pathology/radiotherapy ; Hematologic Diseases/etiology ; Humans ; Male ; Middle Aged ; Nausea/drug therapy/etiology ; Neoplasm Staging ; Republic of Korea ; Retrospective Studies ; Severity of Illness Index ; Sex Factors ; Vomiting/drug therapy/etiology ; Young Adult

Gliomas are extremely aggressive brain tumors with a very poor prognosis. One of the more promising strategies for the treatment of human gliomas is targeted immunotherapy where antigens that are unique to the tumors are exploited to generate vaccines. The approach, however, is complicated by the fact that human gliomas escape immune surveillance by creating an immune suppressed microenvironment. In order to oppose the glioma imposed immune suppression, molecules and pathways involved in immune cell maturation, expansion, and migration are under intensive clinical investigation as adjuvant therapy. Toll-like receptors (TLRs) mediate many of these functions in immune cell types, and TLR agonists, thus, are currently primary candidate molecules to be used as important adjuvants in a variety of cancers. In animal models for glioma, TLR agonists have exhibited antitumor properties by facilitating antigen presentation and stimulating innate and adaptive immunity. In clinical trials, several TLR agonists have achieved survival benefit, and many more trials are recruiting or ongoing. However, a second complicating factor is that TLRs are also expressed on cancer cells where they can participate instead in a variety of tumor promoting activities including cell growth, proliferation, invasion, migration, and even stem cell maintenance. TLR agonists can, therefore, possibly play dual roles in tumor biology. Here, how TLRs and TLR agonists function in glioma biology and in anti-glioma therapies is summarized in an effort to provide a current picture of the sophisticated relationship of glioma with the immune system and the implications for immunotherapy.
Animals ; Antigens, Neoplasm ; chemistry ; immunology ; Antineoplastic Agents ; chemistry ; immunology ; therapeutic use ; Brain Neoplasms ; genetics ; immunology ; pathology ; therapy ; Chemotherapy, Adjuvant ; Clinical Trials as Topic ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic ; drug effects ; immunology ; Glioma ; genetics ; immunology ; pathology ; therapy ; Humans ; Immunotherapy ; methods ; Signal Transduction ; Toll-Like Receptors ; agonists ; genetics ; immunology

Glioma-related edema (GRE) is a significant contributor to morbidity and mortality from glioma. GRE is a complicated process involving not only peritumoral edema but also the water content of the tumor body. In terms of etiology, this condition derives from both GRE in the untreated state and GRE secondary to clinical intervention, and different cell types contribute to distinct components of GRE. Peritumoral edema was previously believed to loosen glioma tissue, facilitating tumor-cell invasion; however, the nutrition hypothesis of the tumor microecosystem suggests that tumor cells invade for the sake of nutrition. Edema is the pathologic consequence of the reconstructed trophic linkage within the tumor microecosystem. Glioma cells induce peritumoral brain edema via an active process that supplies a suitable niche for peritumoral invasive cells, suggesting that glioma-related peritumoral brain edema is determined by the invasive property of tumor cells. There are differences between pivotal molecular events and reactive molecular events in the development of GRE. Molecular therapy should target the former, as targeting reactive molecular events will produce undesired or even adverse results. At present, brain glioma angiogenesis models have not been translated into a new understanding of the features of brain images. The effect of these models on peritumoral brain edema is unclear. Clinical approaches should be transformed on the basis of new knowledge of the molecular mechanism underlying GRE. Exploring clinical assessment methods, optimizing the existing control strategy of GRE, and simultaneously developing new treatments are essential.
Brain Edema ; diagnosis ; drug therapy ; metabolism ; pathology ; Brain Neoplasms ; diagnosis ; drug therapy ; metabolism ; pathology ; Glioma ; diagnosis ; drug therapy ; metabolism ; pathology ; Humans ; Magnetic Resonance Imaging ; Molecular Targeted Therapy ; Vascular Endothelial Growth Factor A ; metabolism