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  1. Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study

    International Nuclear Information System (INIS)

    Delgado, Anna F.; Nilsson, Markus; Latini, Francesco; Mårtensson, Johanna; Zetterling, Maria; Berntsson, Shala G.; Alafuzoff, Irina; Lätt, Jimmy; Larsson, Elna-Marie

    2016-01-01

    Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement

  2. A Multicenter Phase I/II Study of the BCNU Implant (Gliadel ® Wafer) for Japanese Patients with Malignant Gliomas

    Science.gov (United States)

    AOKI, Tomokazu; NISHIKAWA, Ryo; SUGIYAMA, Kazuhiko; NONOGUCHI, Naosuke; KAWABATA, Noriyuki; MISHIMA, Kazuhiko; ADACHI, Jun-ichi; KURISU, Kaoru; YAMASAKI, Fumiyuki; TOMINAGA, Teiji; KUMABE, Toshihiro; UEKI, Keisuke; HIGUCHI, Fumi; YAMAMOTO, Tetsuya; ISHIKAWA, Eiichi; TAKESHIMA, Hideo; YAMASHITA, Shinji; ARITA, Kazunori; HIRANO, Hirofumi; YAMADA, Shinobu; MATSUTANI, Masao

    2014-01-01

    Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe. PMID:24739422

  3. Randomised phase I/II study to evaluate carbon ion radiotherapy versus fractionated stereotactic radiotherapy in patients with recurrent or progressive gliomas: The CINDERELLA trial

    International Nuclear Information System (INIS)

    Combs, Stephanie E; Wick, Wolfgang; Debus, Jürgen; Burkholder, Iris; Edler, Lutz; Rieken, Stefan; Habermehl, Daniel; Jäkel, Oliver; Haberer, Thomas; Haselmann, Renate; Unterberg, Andreas

    2010-01-01

    Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cauteously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV gliomas. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons. First Japanese Data on the evaluation of carbon ion radiation therapy for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective. In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy. Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival. The Cinderella trial is the first study to evaluate carbon ion

  4. Facing Contrast-Enhancing Gliomas: Perfusion MRI in Grade III and Grade IV Gliomas according to Tumor Area

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    Anna Luisa Di Stefano

    2014-01-01

    Full Text Available Tumoral neoangiogenesis characterizes high grade gliomas. Relative Cerebral Blood Volume (rCBV, calculated with Dynamic Susceptibility Contrast (DSC Perfusion-Weighted Imaging (PWI, allows for the estimation of vascular density over the tumor bed. The aim of the study was to characterize putative tumoral neoangiogenesis via the study of maximal rCBV with a Region of Interest (ROI approach in three tumor areas—the contrast-enhancing area, the nonenhancing tumor, and the high perfusion area on CBV map—in patients affected by contrast-enhancing glioma (grades III and IV. Twenty-one patients were included: 15 were affected by grade IV and 6 by grade III glioma. Maximal rCBV values for each patient were averaged according to glioma grade. Although rCBV from contrast-enhancement and from nonenhancing tumor areas was higher in grade IV glioma than in grade III (5.58 and 2.68; 3.01 and 2.2, resp., the differences were not significant. Instead, rCBV recorded in the high perfusion area on CBV map, independently of tumor compartment, was significantly higher in grade IV glioma than in grade III (7.51 versus 3.78, P=0.036. In conclusion, neoangiogenesis encompasses different tumor compartments and CBV maps appear capable of best characterizing the degree of neovascularization. Facing contrast-enhancing brain tumors, areas of high perfusion on CBV maps should be considered as the reference areas to be targeted for glioma grading.

  5. Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma.

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    Tang, Jiaze; Huang, Ning; Zhang, Xiang; Zhou, Tao; Tan, Ying; Pi, Jiangli; Pi, Li; Cheng, Si; Zheng, Huzhi; Cheng, Yuan

    2017-01-01

    The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood-brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma

  6. Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

    Directory of Open Access Journals (Sweden)

    Tang J

    2017-05-01

    Full Text Available Jiaze Tang,1 Ning Huang,1 Xiang Zhang,1,2 Tao Zhou,3 Ying Tan,1,4 Jiangli Pi,5 Li Pi,1 Si Cheng,6 Huzhi Zheng,5 Yuan Cheng1 1Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, 3Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, 4Institute of Life Sciences, Chongqing Medical University, 5Key Laboratory on Luminescent and Real-Time Analytical Chemistry, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, 6Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Abstract: The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD-labeled aptamer (QD-Apt nanoprobe by conjugating aptamer 32 (A32 to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling

  7. TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients

    International Nuclear Information System (INIS)

    Wang, Chao; Cao, Shouqiang; Yan, Ying; Ying, Qiao; Jiang, Tao; Xu, Ke; Wu, Anhua

    2010-01-01

    Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cells in vitro. RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cells in vitro with MTT assays and matrigel transwell assay respectively. RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients(P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasion in vitro. Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy

  8. Unusual combination of Cis platinum and radiotherapy followed by a three fractions per day irradiation in splitcourse: a phase I-II study in brain glioma patients

    International Nuclear Information System (INIS)

    Ben-Hassel, M.; Lesimple, T.; Gedouin, D.; Chenal, C.; Guegan, Y.; Darcel, F.

    1992-01-01

    An unusual protocol based on a preliminary clinical study on cylindromas metastasized to the lung was proposed to brain glioma patients: Day 2 100 mg/m 2 i.v. Cis platinum (Cis P II) followed at days 3 and 5 by 6 Gy irradiation (RT) in two fractions and three days. Five cycles were scheduled at 21 days interval. On disease progression a three fractions per day radiotherapy regimen (3 FRT) in split-course (two series of 22.50 Gy in 15 fractions and five days separated by a two weeks period of rest) was then delivered to the patients. All patients had a measurable mass on the CT scan. 19 were entered into the study: 13 as first line therapy (group A) and six for salvage treatment (group B). Tolerance was globally good. Eight patients were considered responders at the end of five cycles of Cis II-RT. They were all group A patients. Median symptom-free interval was six months for the whole population. Survival was twelve months. The 3 FRT was well tolerated but does not seem to have improved the therapeutic gain of the chemoradiotherapy combination. The present study concerns patients whose prognosis was poor on inclusion: Surgery unadvisable or unsatisfactory and diagnosis mainly based on biopsy only. The number and the duration of responses justify further study into Cis P II as first line therapy as either an effective cytotoxic drug or a potential radio enhancer. (orig.) [de

  9. Epileptic seizures in patients with glioma: A single centre- based ...

    African Journals Online (AJOL)

    were used for analysis of seizure incidence differences as per WHO Grades, histology, location ... Keywords: Brain tumour, Epilepsy, Glioma, Seizures, Levetiracetam, .... glioma patients. Characteristics. N (%). Gender. Male. Female. Histology.

  10. Cortical and Subcortical Structural Plasticity Associated with the Glioma Volumes in Patients with Cerebral Gliomas Revealed by Surface-Based Morphometry

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    Jinping Xu

    2017-06-01

    Full Text Available Postlesional plasticity has been identified in patients with cerebral gliomas by inducing a large functional reshaping of brain networks. Although numerous non-invasive functional neuroimaging methods have extensively investigated the mechanisms of this functional redistribution in patients with cerebral gliomas, little effort has been made to investigate the structural plasticity of cortical and subcortical structures associated with the glioma volume. In this study, we aimed to investigate whether the contralateral cortical and subcortical structures are able to actively reorganize by themselves in these patients. The compensation mechanism following contralateral cortical and subcortical structural plasticity is considered. We adopted the surface-based morphometry to investigate the difference of cortical and subcortical gray matter (GM volumes in a cohort of 14 healthy controls and 13 patients with left-hemisphere cerebral gliomas [including 1 patients with World Health Organization (WHO I, 8 WHO II, and 4 WHO III]. The glioma volume ranges from 5.1633 to 208.165 cm2. Compared to healthy controls, we found significantly increased GM volume of the right cuneus and the left thalamus, as well as a trend toward enlargement in the right globus pallidus in patients with cerebral gliomas. Moreover, the GM volumes of these regions were positively correlated with the glioma volumes of the patients. These results provide evidence of cortical and subcortical enlargement, suggesting the usefulness of surface-based morphometry to investigate the structural plasticity. Moreover, the structural plasticity might be acted as the compensation mechanism to better fulfill its functions in patients with cerebral gliomas as the gliomas get larger.

  11. Epileptic seizures in patients with glioma: A single centrebased ...

    African Journals Online (AJOL)

    Purpose: To elucidate the outcomes of treatment and epidemiology of epilepsy related to glioma in a single center in Chinese patients. Methods: Prescription medicines usage and clinical data were collected from medical records of 119 patients with gliomas between August 2009 and September 2015. Fisher's exact and ...

  12. Tumor-infiltrating lymphocytes (TILs) from patients with glioma

    DEFF Research Database (Denmark)

    Liu, Zhenjiang; Meng, Qingda; Bartek, Jiri

    2017-01-01

    Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21...

  13. Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging

    DEFF Research Database (Denmark)

    Falk, Anna; Fahlström, Markus; Rostrup, Egill

    2014-01-01

    INTRODUCTION: Perfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging...... written informed consent in this review board-approved study. Regions of interests (ROIs) in tumour area were delineated on FLAIR images co-registered to DCE and DSC, respectively, in 25 patients with histopathological grade II (n = 18) and III (n = 7) gliomas. Statistical analysis of differences between...

  14. LuIII parvovirus selectively and efficiently targets, replicates in, and kills human glioma cells.

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    Paglino, Justin C; Ozduman, Koray; van den Pol, Anthony N

    2012-07-01

    Because productive infection by parvoviruses requires cell division and is enhanced by oncogenic transformation, some parvoviruses may have potential utility in killing cancer cells. To identify the parvovirus(es) with the optimal oncolytic effect against human glioblastomas, we screened 12 parvoviruses at a high multiplicity of infection (MOI). MVMi, MVMc, MVM-G17, tumor virus X (TVX), canine parvovirus (CPV), porcine parvovirus (PPV), rat parvovirus 1A (RPV1A), and H-3 were relatively ineffective. The four viruses with the greatest oncolytic activity, LuIII, H-1, MVMp, and MVM-G52, were tested for the ability, at a low MOI, to progressively infect the culture over time, causing cell death at a rate higher than that of cell proliferation. LuIII alone was effective in all five human glioblastomas tested. H-1 progressively infected only two of five; MVMp and MVM-G52 were ineffective in all five. To investigate the underlying mechanism of LuIII's phenotype, we used recombinant parvoviruses with the LuIII capsid replacing the MVMp capsid or with molecular alteration of the P4 promoter. The LuIII capsid enhanced efficient replication and oncolysis in MO59J gliomas cells; other gliomas tested required the entire LuIII genome to exhibit enhanced infection. LuIII selectively infected glioma cells over normal glial cells in vitro. In mouse models, human glioblastoma xenografts were selectively infected by LuIII when administered intratumorally; LuIII reduced tumor growth by 75%. LuIII also had the capacity to selectively infect subcutaneous or intracranial gliomas after intravenous inoculation. Intravenous or intracranial LuIII caused no adverse effects. Intracranial LuIII caused no infection of mature mouse neurons or glia in vivo but showed a modest infection of developing neurons.

  15. High bone sialoprotein (BSP expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients.

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    Tao Xu

    Full Text Available OBJECTIVES: To investigate the expression and prognostic value of bone sialoprotein (BSP in glioma patients. METHODS: We determined the expression of BSP using real-time RT-PCR and immunohistochemistry in tissue microarrays containing 15 normal brain and 270 glioma samples. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate analyses were performed by the stepwise forward Cox regression model. RESULTS: Both BSP mRNA and protein levels were significantly elevated in high-grade glioma tissues compared with those of normal brain and low-grade glioma tissues, and BSP expression positively correlated with tumor grade (P<0.001. Univariate and multivariate analysis showed high BSP expression was an independent prognostic factor for a shorter progression-free survival (PFS and overall survival (OS in both grade III and grade IV glioma patients [hazard ratio (HR = 2.549 and 3.154 for grade III glioma, and HR = 1.637 and 1.574 for grade IV glioma, respectively]. Patients with low BSP expression had a significantly longer median OS and PFS than those with high BSP expression. Small extent of resection and lineage of astrocyte served as independent risk factors of both shorter PFS and OS in grade III glioma patients; GBM patients without O(6-methylguanine (O(6-meG DNA methyltransferase (MGMT methylation and Karnofsky performance score (KPS less than 70 points were related to poor prognosis. Lack of radiotherapy related to shorter OS but not affect PFS in both grade III and grade IV glioma patients. CONCLUSION: High BSP expression occurs in a significant subset of high-grade glioma patients and predicts a poorer outcome. The study identifies a potentially useful molecular marker for the categorization and targeted therapy of gliomas.

  16. Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

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    Desjardins, Annick; Quinn, Jennifer A; Vredenburgh, James J; Sathornsumetee, Sith; Friedman, Allan H; Herndon, James E; McLendon, Roger E; Provenzale, James M; Rich, Jeremy N; Sampson, John H; Gururangan, Sridharan; Dowell, Jeannette M; Salvado, August; Friedman, Henry S; Reardon, David A

    2007-05-01

    Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG). Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate. Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses. Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.

  17. Seizure control following radiotherapy in patients with diffuse gliomas: a retrospective study

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    Rudà, Roberta; Magliola, Umberto; Bertero, Luca; Trevisan, Elisa; Bosa, Chiara; Mantovani, Cristina; Ricardi, Umberto; Castiglione, Anna; Monagheddu, Chiara; Soffietti, Riccardo

    2013-01-01

    Background Little information is available regarding the effect of conventional radiotherapy on glioma-related seizures. Methods In this retrospective study, we analyzed the seizure response and outcome following conventional radiotherapy in a cohort of 43 patients with glioma (33 grade II, 10 grade III) and medically intractable epilepsy. Results At 3 months after radiotherapy, seizure reduction was significant (≥50% reduction of frequency compared with baseline) in 31/43 patients (72%) of the whole series and in 25/33 patients (76%) with grade II gliomas, whereas at 12 months seizure reduction was significant in 26/34 (76%) and in 19/25 (76%) patients, respectively. Seizure reduction was observed more often among patients displaying an objective tumor response on MRI, but patients with no change on MRI also had a significant seizure reduction. Seizure freedom (Engel class I) was achieved at 12 months in 32% of all patients and in 38% of patients with grade II tumors. Timing of radiotherapy and duration of seizures prior to radiotherapy were significantly associated with seizure reduction. Conclusions This study showed that a high proportion of patients with medically intractable epilepsy from diffuse gliomas derive a significant and durable benefit from radiotherapy in terms of epilepsy control and that this positive effect is not strictly associated with tumor shrinkage as shown on MRI. Radiotherapy at tumor progression seems as effective as early radiotherapy after surgery. Prospective studies must confirm and better characterize the response to radiotherapy. PMID:23897633

  18. Cognitive impairments in patients with low grade gliomas and high grade gliomas

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    Eliane C. Miotto

    2011-08-01

    Full Text Available OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19 and high-grade glioma (G2, n=8 patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

  19. A high 18F-FDOPA uptake is associated with a slow growth rate in diffuse Grade II-III gliomas.

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    Isal, Sibel; Gauchotte, Guillaume; Rech, Fabien; Blonski, Marie; Planel, Sophie; Chawki, Mohammad B; Karcher, Gilles; Marie, Pierre-Yves; Taillandier, Luc; Verger, Antoine

    2018-04-01

    In diffuse Grade II-III gliomas, a high 3,4-dihydroxy-6-( 18 F)-fluoro-L-phenylalanine ( 18 F-FDOPA) positron emission tomography (PET) uptake, with a standardized uptake value (SUV max )/contralateral brain tissue ratio greater than 1.8, was previously found to be consistently associated with the presence of an isocitrate dehydrogenase (IDH) mutation, whereas this mutation is typically associated with a better prognosis. This pilot study was aimed to ascertain the prognostic value of this high 18 F-FDOPA uptake in diffuse Grade II-III gliomas with regard to the velocity of diameter expansion (VDE), which represents an established landmark of better prognosis when below 4 mm per year. 20 patients (42 ± 10 years, 10 female) with newly-diagnosed diffuse Grade II-III gliomas (17 with IDH mutation) were retrospectively included. All had a 18 F-FDOPA PET, quantified with SUV max ratio, along with a serial MRI enabling VDE determination. SUV max ratio was above 1.8 in 5 patients (25%) all of whom had a VDE VDE <4 mm/year in the overall population (45 vs 0%, p = 0.04) and also in the subgroup of patients with IDH mutation (45 vs 0%, p = 0.10). This pilot study shows that in diffuse Grade II-III gliomas, a high 18 F-FDOPA uptake would be predictive of low tumour growth, with a different prognostic significance than IDH mutation. Advances in knowledge: 18 F-FDOPA PET in a single session imaging could have prognostic value in initial diagnosis of diffuse Grade II-III gliomas.

  20. Current standard treatment for pediatric glioma patients

    International Nuclear Information System (INIS)

    Sonoda, Yukihiko; Kumabe, Toshihiro; Saito, Ryuta; Kanamori, Masayuki; Yamashita, Yoji; Tominaga, Teiji

    2012-01-01

    In this paper, we selected three representative disorders among pediatric gliomas and reviewed standard treatments for these diseases. The formation of this rare disease is involved with BRAF mutation as well as cerebellar pilocytic astrocytoma. Radical resection is not recommended as initial therapy due to high morbidity. Despite its good tumor control, radiotherapy is not a standard therapy due to neuroendocrine and neurocognitive dysfunction. Several papers have reported the effectiveness of platinum-based chemotherapy, which is a useful for induction therapy. Recent progress in molecular analyses has suggested that some markers might be used for staging ependymoma. While total resection is considered to be strongly correlated with patients' survival, the majority of recurrence occurs in the primary site. Despite many clinical trials, chemotherapeutic agents were not found to be effective for this disease. Since whole brain radiation cannot prevent dissemination, local radiation is recommended for adjuvant therapy. The prognosis of this disease is still dismal, and median survival time is within 1 year. Although clinical trials have been conducted to assess the efficacy of chemotherapy prior to, concomitantly with, or after radiotherapy, an effective regimen has not yet been established. Therefore, only conventional local radiotherapy is the standard regimen for this disease. A new therapeutic approach, such as convection-enhanced drug delivery, would be required for improved outcomes in patients with this disease. (author)

  1. Binding of cetuximab to the EGFRvIII deletion mutant and its biological consequences in malignant glioma cells

    International Nuclear Information System (INIS)

    Jutten, Barry; Dubois, Ludwig; Li Younan; Aerts, Hugo; Wouters, Bradly G.; Lambin, Philippe; Theys, Jan; Lammering, Guido

    2009-01-01

    Background and purpose: Despite the clinical use of cetuximab, a chimeric antibody against EGFR, little is known regarding its interaction with EGFRvIII, a frequently expressed deletion mutant of EGFR. Therefore, we investigated the interaction and the functional consequences of cetuximab treatment on glioma cells stably expressing EGFRvIII. Materials and methods: The human glioma cell line U373 genetically modified to express EGFRvIII was used to measure the binding of cetuximab and its internalization using flow cytometry and confocal microscopy. Proliferation and cell survival were analyzed by cell growth and clonogenic survival assays. Results: Cetuximab is able to bind to EGFRvIII and causes an internalization of the receptor and decreases its expression levels. Furthermore, in contrast to EGF, cetuximab was able to activate EGFRvIII which was evidenced by multiple phosphorylation sites and its downstream signaling targets. Despite this activation, the growth rate and the radiosensitivity of the EGFRvIII-expressing glioma cells were not modulated. Conclusions: Cetuximab binds to EGFRvIII and leads to the initial activation, internalization and subsequent downregulation of EGFRvIII, but it does not seem to modulate the proliferation or radiosensitivity of EGFRvIII-expressing glioma cells. Thus, approaches to treat EGFRvIII-expressing glioma cells should be evaluated more carefully.

  2. Treating malignant glioma in Chinese patients: update on temozolomide

    Directory of Open Access Journals (Sweden)

    Chang L

    2014-02-01

    Full Text Available Liang Chang,1 Jun Su,1 Xiuzhi Jia,2,3 Huan Ren2,3 1Department of Neurosurgery, The Tumor Hospital of Harbin Medical University, 2Department of Immunology, Harbin Medical University, 3Key Lab Infection and Immunity, Heilongjiang Province, Harbin, People's Republic of China Abstract: Malignant glioma, ie, anaplastic astrocytoma and glioblastoma, is the most common type of primary malignant brain tumor in the People's Republic of China, and is particularly aggressive. The median survival of patients with newly diagnosed glioblastoma is only 12–14 months despite advanced therapeutic strategies. Treatment of malignant glioma consists mainly of surgical resection followed by adjuvant radiation and chemotherapy. Temozolomide (TMZ, a second-generation oral alkylating agent, is playing an increasingly important role in the treatment of malignant glioma in Chinese patients. Since the publication of a study by Stupp et al in 2005, which used a protocol of conventional fractionated irradiation with concomitant TMZ followed by standard TMZ for six cycles, many clinical studies in the People's Republic of China have demonstrated that such a treatment strategy has significantly improved efficacy with limited side effects for newly diagnosed glioblastoma after surgery as compared with strategies that do not contain TMZ. However, as a relatively new agent, the history and development of TMZ for malignant glioma is not well documented in Chinese patients. Multicenter, randomized controlled trials including appropriately sized patient populations investigating multiple aspects of TMZ therapy and related combination therapies are warranted in patients with malignant glioma. This review provides an update on the efficacy, mechanism of action, adverse reactions, and clinical role of TMZ in the treatment of malignant glioma in Chinese patients. Keywords: malignant glioma, chemotherapy, temozolomide, efficacy, side effect, People's Republic of China

  3. Molecular Subtyping of Tumors from Patients with Familial Glioma.

    Science.gov (United States)

    Ruiz, Vanessa Y; Praska, Corinne E; Armstrong, Georgina; Kollmeyer, Thomas M; Yamada, Seiji; Decker, Paul A; Kosel, Matthew L; Eckel-Passow, Jeanette E; Consortium, The Gliogene; Lachance, Daniel H; Bainbridge, Matthew N; Melin, Beatrice S; Bondy, Melissa L; Jenkins, Robert B

    2017-10-10

    Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on IDH mutation and 1p/19q co-deletion. We hypothesized that the prevalence of molecular subtypes might differ in familial versus sporadic gliomas, and that tumors in the same family should have the same molecular subtype. Participants in the FG study (Gliogene) provided samples for germline DNA analysis. Formalin-fixed, paraffin-embedded (FFPE) tumor was obtained for a subset of FG cases, and DNA was extracted. We analyzed tissue from 75 families, including 10 families containing a second affected family member. Copy number variation (CNV) data was obtained using a first-generation Affymetrix molecular inversion probe (MIP) array. Samples from 62 of 75 (83%) FG cases could be classified into the 3 subtypes. The prevalence of the molecular subtypes was: 30 (48%) IDH-wild type, 21 (34%) IDH-mutant non-codeleted, and 11 (19%) IDH-mutant and 1p/19q-codeleted. This distribution of molecular subtypes was not statistically different from that of sporadic gliomas (p=0.54). Of 10 paired FG samples, molecular subtypes were concordant for 7 (κ=0.59): 3 IDH-mutant non-codeleted, 2 IDH-wild type, and 2 IDH-mutant and 1p/19q-codeleted gliomas. Our data suggest that within individual families, patients develop gliomas of the same molecular subtype. However, we did not observe differences in the prevalence of the molecular subtypes in FG compared with sporadic gliomas. These observations provide further insight about the distribution of molecular subtypes in FG. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  4. Multiparametric analysis of magnetic resonance images for glioma grading and patient survival time prediction

    International Nuclear Information System (INIS)

    Garzon, Benjamin; Emblem, Kyrre E.; Mouridsen, Kim; Nedregaard, Baard; Due-Toennessen, Paulina; Nome, Terje; Hald, John K.; Bjoernerud, Atle; Haaberg, Asta K.; Kvinnsland, Yngve

    2011-01-01

    Background. A systematic comparison of magnetic resonance imaging (MRI) options for glioma diagnosis is lacking. Purpose. To investigate multiple MR-derived image features with respect to diagnostic accuracy in tumor grading and survival prediction in glioma patients. Material and Methods. T1 pre- and post-contrast, T2 and dynamic susceptibility contrast scans of 74 glioma patients with histologically confirmed grade were acquired. For each patient, a set of statistical features was obtained from the parametric maps derived from the original images, in a region-of-interest encompassing the tumor volume. A forward stepwise selection procedure was used to find the best combinations of features for grade prediction with a cross-validated logistic model and survival time prediction with a cox proportional-hazards regression. Results. Presence/absence of enhancement paired with kurtosis of the FM (first moment of the first-pass curve) was the feature combination that best predicted tumor grade (grade II vs. grade III-IV; median AUC 0.96), with the main contribution being due to the first of the features. A lower predictive value (median AUC = 0.82) was obtained when grade IV tumors were excluded. Presence/absence of enhancement alone was the best predictor for survival time, and the regression was significant (P < 0.0001). Conclusion. Presence/absence of enhancement, reflecting transendothelial leakage, was the feature with highest predictive value for grade and survival time in glioma patients

  5. Multiparametric analysis of magnetic resonance images for glioma grading and patient survival time prediction

    Energy Technology Data Exchange (ETDEWEB)

    Garzon, Benjamin (Dept. of Circulation and Medical Imaging, NTNU, Trondheim (Norway)), email: benjamin.garzon@ntnu.no; Emblem, Kyrre E. (The Interventional Center, Rikshospitalet, Oslo Univ. Hospital, Oslo (Norway); Dept. of Radiology, MGH-HST AA Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston (United States)); Mouridsen, Kim (Center of Functionally Integrative Neuroscience, Aarhus Univ., Aarhus (Denmark)); Nedregaard, Baard; Due-Toennessen, Paulina; Nome, Terje; Hald, John K. (Dept. of Radiology and Nuclear Medicine, Rikshospitalet, Oslo Univ. Hospital, Oslo (Norway)); Bjoernerud, Atle (The Interventional Center, Rikshospitalet, Oslo Univ. Hospital, Oslo (Norway)); Haaberg, Asta K. (Dept. of Circulation and Medical Imaging, NTNU, Trondheim (Norway); Dept. of Medical Imaging, St Olav' s Hospital, Trondheim (Norway)); Kvinnsland, Yngve (NordicImagingLab, Bergen (Norway))

    2011-11-15

    Background. A systematic comparison of magnetic resonance imaging (MRI) options for glioma diagnosis is lacking. Purpose. To investigate multiple MR-derived image features with respect to diagnostic accuracy in tumor grading and survival prediction in glioma patients. Material and Methods. T1 pre- and post-contrast, T2 and dynamic susceptibility contrast scans of 74 glioma patients with histologically confirmed grade were acquired. For each patient, a set of statistical features was obtained from the parametric maps derived from the original images, in a region-of-interest encompassing the tumor volume. A forward stepwise selection procedure was used to find the best combinations of features for grade prediction with a cross-validated logistic model and survival time prediction with a cox proportional-hazards regression. Results. Presence/absence of enhancement paired with kurtosis of the FM (first moment of the first-pass curve) was the feature combination that best predicted tumor grade (grade II vs. grade III-IV; median AUC 0.96), with the main contribution being due to the first of the features. A lower predictive value (median AUC = 0.82) was obtained when grade IV tumors were excluded. Presence/absence of enhancement alone was the best predictor for survival time, and the regression was significant (P < 0.0001). Conclusion. Presence/absence of enhancement, reflecting transendothelial leakage, was the feature with highest predictive value for grade and survival time in glioma patients

  6. Single agent vinorelbine in pediatric patients with progressive optic pathway glioma.

    Science.gov (United States)

    Cappellano, Andrea Maria; Petrilli, Antonio Sergio; da Silva, Nasjla Saba; Silva, Frederico Adolfo; Paiva, Priscila Mendes; Cavalheiro, Sergio; Bouffet, Eric

    2015-01-01

    The management of progressive unresectable low-grade glioma remains controversial. Treatment options have included radiotherapy, and more recently chemotherapy, usually following an initial period of observation. Within this context, we evaluated vinorelbine, a semi-synthetic vinca alkaloid that has shown evidence of activity against glioma. From July 2007 an institutional protocol with vinorelbine (30 mg/m(2) days 0, 8, 22) for a total of 18 cycles, has been conducted at IOP/GRAACC/UNIFESP for children with optic pathway glioma (OPG). The main objectives were clinical and radiological response, as well as toxicity profile. Twenty-three patients with progressive OPG with a mean age of 69 months (4-179) were enrolled. Three patients had a diagnosis of neurofibromatosis type 1. Twenty-two patients were assessable for response with an overall objective response rate of 63 %, with eight patients showing stable disease. The most important toxicity was hematologic (grade III/IV neutropenia) observed in four patients. Gastrointestinal toxicity (grade I/II vomiting) was observed in seven patients and only 1 patient showed grade I peripheral neuropathy. The median progression-free survival (PFS) was 33 months (6.9-69) with a 3 and 5 year PFS of 64 ± 19 and 37 ± 20 %, respectively, for an overall 3 and 5 year-survival of 95 ± 10 %. This study suggests that vinorelbine may be an interesting option for pediatric low-grade gliomas, showing low toxicity profile and providing a good quality of life for patients with such chronic disease.

  7. Levetiracetam improves verbal memory in high-grade glioma patients

    NARCIS (Netherlands)

    de Groot, Marjolein; Douw, Linda; Sizoo, Eefje M; Bosma, Ingeborg; Froklage, Femke E; Heimans, Jan J; Postma, Tjeerd J; Klein, Martin; Reijneveld, Jaap C

    BACKGROUND: Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration. The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of

  8. Bereaved Caregivers to Patients With High-Grade Glioma

    DEFF Research Database (Denmark)

    Piil, Karin; Jarden, Mary

    2018-01-01

    PURPOSE: The disease and treatment trajectory of patients with high-grade glioma is a burdensome period for the patients' closest relatives who become informal caregivers. Caregivers experiencing this demanding shift in role are at risk of developing symptoms such as depression. Few studies have...... care planning within neuro-oncology caregiving to establish evidence-based practice guidelines and recommendations....

  9. IDH mutation is paradoxically associated with higher {sup 18}F-FDOPA PET uptake in diffuse grade II and grade III gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Verger, A. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Lorraine University, Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU Nancy, Nancy (France); Lorraine University, IADI, INSERM, UMR 947, Nancy (France); Metellus, P. [Centre Hospitalier Prive Clairval, Department of Neurosurgery, Marseille (France); Aix-Marseille University, INSERM, UMR 911, Marseille (France); Sala, Q. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Colin, C. [Aix-Marseille University, INSERM, UMR 911, Marseille (France); Bialecki, E. [Centre Hospitalier Prive Clairval, Department of Neurosurgery, Marseille (France); Taieb, D. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Aix-Marseille University, CERIMED, Marseille (France); Chinot, O. [Aix-Marseille University, INSERM, UMR 911, Marseille (France); APHM, La Timone Hospital, Department of Neuro-Oncology, Marseille (France); Figarella-Branger, D. [Aix-Marseille University, INSERM, UMR 911, Marseille (France); APHM, La Timone Hospital, Department of Anatomopathology, Marseille (France); Guedj, E. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Aix-Marseille University, CERIMED, Marseille (France); Aix-Marseille University, Institut de Neurosciences de la Timone, CNRS, UMR 7289, Marseille (France); Hopital de la Timone, Service Central de Biophysique et Medecine Nucleaire, Marseille (France)

    2017-08-15

    The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and {sup 18}F-FDOPA uptake on PET in newly diagnosed gliomas. A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone {sup 18}F-FDOPA PET at an initial stage before surgery and histological diagnosis. {sup 18}F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S). Patients with IDH mutation showed higher {sup 18}F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation (p < 0.05). This study showed paradoxically higher {sup 18}F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of {sup 18}F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation. (orig.)

  10. Neurocognitive training in patients with high-grade glioma: a pilot study.

    Science.gov (United States)

    Hassler, Marco Ronald; Elandt, Katarzyna; Preusser, Matthias; Lehrner, Johann; Binder, Petra; Dieckmann, Karin; Rottenfusser, Andrea; Marosi, Christine

    2010-03-01

    Although their neurocognitive performance is one of the major concerns of patients with high-grade gliomas (HGG) and although neurocognitive deficits have been described to be associated with negative outcome, neurocognitive rehabilitation is usually not integrated into the routine care of patients with malignant gliomas. In this pilot trial, a weekly group training session for attention, verbal, and memory skills was offered to patients with HGG with pre and post-training evaluation. Eleven patients, six with glioblastoma multiforme and five with WHO grade III gliomas, median age 50 years, with a Karnofsky performance score of 80-100 participated in ten group training sessions of 90 min. For evaluation at baseline and after the training by a neuropsychologist not involved in care or training of the patients, Trail Making Tests A and B (TMTA and TMTB), Hopkins Verbal Learning Test (HVLT), and the Controlled Oral Word Association Test (COWA) were used. Comparison of mean group differences between baseline and at post-training evaluation after 12 weeks revealed improvement across all neurocognitive variables. The patients showed a great diversity in their performances, with worsening, improvement, and stabilization. However, a significant group difference was detected only for the HVLT (score 19.6 +/- 8.9 at baseline, 23.6 +/- 8.8 after 12 weeks, P = 0.04). This pilot study shows that neurocognitive training in patients with HGG is feasible as group training with weekly sessions and might be able to induce improvements in attention and memory skills.

  11. A 12-week interdisciplinary rehabilitation trial in patients with gliomas

    DEFF Research Database (Denmark)

    Hansen, Anders; Søgaard, Karen; Minet, Lisbeth Rosenbek

    2018-01-01

    rehabilitation intervention of physical therapy and occupational therapy in the initial treatment phase of patients with gliomas whose Karnofsky performance status is ≥70 is safe and feasible, if relevant inclusion criteria and precautionary screening are made. With the revised protocol, we are confident...

  12. Prognostic Marker before Treatment of Patients with Malignant Glioma

    Directory of Open Access Journals (Sweden)

    Norbert Galldiks

    2012-11-01

    Full Text Available The purpose of this positron emission tomography (PET study was to compare the prognostic value of pretreatment volume of [11C] methionine (MET uptake and semiquantitative MET uptake ratio in patients with malignant glioma. The study population comprised 40 patients with malignant glioma. Pretreatment magnetic resonance imaging (MRI and MET-PET imaging were performed before the initiation of glioma treatment in all patients. The pretreatment MET uptake ratios and volumes were assessed. To create prognostically homogeneous subgroups, patients′ pretreatment prognostic factors were stratified according to the six classes of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA. Univariate and multivariate analyses were performed to determine significant prognostic factors. Survival analyses identified the pretreatment volume of MET uptake and a higher RTOG RPA class as significant predictors. In contrast, pretreatment maximum areas of contrast enhancement on MRI and semiquantitative MET uptake ratios could not be identified as significant prognostic factors. The patients′ outcomes and Karnofsky Performance Scale scores were significantly correlated with pretreatment volume of MET uptake but not with semiquantitative MET uptake ratio. The data suggest that pretreatment volumetry of MET uptake but not the semiquantitative MET uptake ratio is a useful biologic prognostic marker in patients with malignant glioma.

  13. Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma

    OpenAIRE

    DeLorenze, Gerald N; McCoy, Lucie; Tsai, Ai-Lin; Quesenberry, Charles P; Rice, Terri; Il'yasova, Dora; Wrensch, Margaret

    2010-01-01

    Abstract Background Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis. Methods Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire i...

  14. Differentiation of grade II/III and grade IV glioma by combining ''T1 contrast-enhanced brain perfusion imaging'' and susceptibility-weighted quantitative imaging

    International Nuclear Information System (INIS)

    Saini, Jitender; Gupta, Pradeep Kumar; Gupta, Rakesh Kumar; Sahoo, Prativa; Singh, Anup; Patir, Rana; Ahlawat, Suneeta; Beniwal, Manish; Thennarasu, K.; Santosh, Vani

    2018-01-01

    MRI is a useful method for discriminating low- and high-grade glioma using perfusion MRI and susceptibility-weighted imaging (SWI). The purpose of this study is to evaluate the usefulness of T1-perfusion MRI and SWI in discriminating among grade II, III, and IV gliomas. T1-perfusion MRI was used to measure relative cerebral blood volume (rCBV) in 129 patients with glioma (70 grade IV, 33 grade III, and 26 grade II tumors). SWI was also used to measure the intratumoral susceptibility signal intensity (ITSS) scores for each tumor in these patients. rCBV and ITSS values were compared to seek differences between grade II vs. grade III, grade III vs. grade IV, and grade III+II vs. grade IV tumors. Significant differences in rCBV values of the three grades of the tumors were noted and pairwise comparisons showed significantly higher rCBV values in grade IV tumors as compared to grade III tumors, and similarly increased rCBV was seen in the grade III tumors as compared to grade II tumors (p < 0.001). Grade IV gliomas showed significantly higher ITSS scores on SWI as compared to grade III tumors (p < 0.001) whereas insignificant difference was seen on comparing ITSS scores of grade III with grade II tumors. Combining the rCBV and ITSS resulted in significant improvement in the discrimination of grade III from grade IV tumors. The combination of rCBV values derived from T1-perfusion MRI and SWI derived ITSS scores improves the diagnostic accuracy for discrimination of grade III from grade IV gliomas. (orig.)

  15. Differentiation of grade II/III and grade IV glioma by combining ''T1 contrast-enhanced brain perfusion imaging'' and susceptibility-weighted quantitative imaging

    Energy Technology Data Exchange (ETDEWEB)

    Saini, Jitender [National Institute of Mental Health and Neurosciences, Neuroimaging and Interventional Radiology, Bangalore (India); Gupta, Pradeep Kumar; Gupta, Rakesh Kumar [Fortis Memorial Research Institute, Department of Radiology and Imaging, Gurugram (India); Sahoo, Prativa [Philips Health System, Philips India Limited, Bangalore (India); Beckman Research Institute, Mathematical Oncology, Duarte, CA (United States); Singh, Anup [Indian Institute of Technology Delhi, Center for Biomedical Engineering, Delhi (India); Patir, Rana [Fortis Memorial Research Institute, Department of Neurosurgery, Gurugram (India); Ahlawat, Suneeta [Fortis Memorial Research Institute, SRL Diagnostics, Gurugram (India); Beniwal, Manish [National Institute of Mental Health and Neurosciences, Department of Neurosurgery, Bangalore (India); Thennarasu, K. [National Institute of Mental Health and Neurosciences, Department of Biostatistics, Bangalore (India); Santosh, Vani [National Institute of Mental Health and Neurosciences, Department of Neuropathology, Bangalore (India)

    2018-01-15

    MRI is a useful method for discriminating low- and high-grade glioma using perfusion MRI and susceptibility-weighted imaging (SWI). The purpose of this study is to evaluate the usefulness of T1-perfusion MRI and SWI in discriminating among grade II, III, and IV gliomas. T1-perfusion MRI was used to measure relative cerebral blood volume (rCBV) in 129 patients with glioma (70 grade IV, 33 grade III, and 26 grade II tumors). SWI was also used to measure the intratumoral susceptibility signal intensity (ITSS) scores for each tumor in these patients. rCBV and ITSS values were compared to seek differences between grade II vs. grade III, grade III vs. grade IV, and grade III+II vs. grade IV tumors. Significant differences in rCBV values of the three grades of the tumors were noted and pairwise comparisons showed significantly higher rCBV values in grade IV tumors as compared to grade III tumors, and similarly increased rCBV was seen in the grade III tumors as compared to grade II tumors (p < 0.001). Grade IV gliomas showed significantly higher ITSS scores on SWI as compared to grade III tumors (p < 0.001) whereas insignificant difference was seen on comparing ITSS scores of grade III with grade II tumors. Combining the rCBV and ITSS resulted in significant improvement in the discrimination of grade III from grade IV tumors. The combination of rCBV values derived from T1-perfusion MRI and SWI derived ITSS scores improves the diagnostic accuracy for discrimination of grade III from grade IV gliomas. (orig.)

  16. Survival in adult patients with diagnosis of high-grade glioma located in the central nervous system, who were treated with radiotherapy and temozolamide at Hospital Mexico during the period from January 2009 to December 2011

    International Nuclear Information System (INIS)

    Chaves Porras, Jorge Alvaro

    2013-01-01

    The impact of survival is determined by the incorporation of the chemotherapeutic temozolamide into the therapy regimen of patients with high grade gliomas. Overall survival is determined in patients with high grade gliomas. The investigation is performed with the total of patients with high grade gliomas, with treatment of radiotherapy and temozolamide. Progression-free survival is determined in the population with high-grade gliomas at Hospital Mexico, from January 2009 to December 2011. The diagnosis of glioblastoma is given in 86% and astrocytoma grade III in 14% of the cases. The concomitance of radiotherapy with temozolomide is received by 33 of 37 patients. Seventy-six percent of patients completed the 6 cycles of adjuvant therapy. The overall survival rate was 14.39 months. Patients with grade III gliomas have had a better prognosis [es

  17. Innate immune functions of microglia isolated from human glioma patients

    Directory of Open Access Journals (Sweden)

    Grimm Elizabeth

    2006-03-01

    Full Text Available Abstract Background Innate immunity is considered the first line of host defense and microglia presumably play a critical role in mediating potent innate immune responses to traumatic and infectious challenges in the human brain. Fundamental impairments of the adaptive immune system in glioma patients have been investigated; however, it is unknown whether microglia are capable of innate immunity and subsequent adaptive anti-tumor immune responses within the immunosuppressive tumor micro-environment of human glioma patients. We therefore undertook a novel characterization of the innate immune phenotype and function of freshly isolated human glioma-infiltrating microglia (GIM. Methods GIM were isolated by sequential Percoll purification from patient tumors immediately after surgical resection. Flow cytometry, phagocytosis and tumor cytotoxicity assays were used to analyze the phenotype and function of these cells. Results GIM expressed significant levels of Toll-like receptors (TLRs, however they do not secrete any of the cytokines (IL-1β, IL-6, TNF-α critical in developing effective innate immune responses. Similar to innate macrophage functions, GIM can mediate phagocytosis and non-MHC restricted cytotoxicity. However, they were statistically less able to mediate tumor cytotoxicity compared to microglia isolated from normal brain. In addition, the expression of Fas ligand (FasL was low to absent, indicating that apoptosis of the incoming lymphocyte population may not be a predominant mode of immunosuppression by microglia. Conclusion We show for the first time that despite the immunosuppressive environment of human gliomas, GIM are capable of innate immune responses such as phagocytosis, cytotoxicity and TLR expression but yet are not competent in secreting key cytokines. Further understanding of these innate immune functions could play a critical role in understanding and developing effective immunotherapies to malignant human gliomas.

  18. Clinical outcomes of gamma knife radiosurgery in the salvage treatment of patients with recurrent high-grade glioma.

    Science.gov (United States)

    Elaimy, Ameer L; Mackay, Alexander R; Lamoreaux, Wayne T; Demakas, John J; Fairbanks, Robert K; Cooke, Barton S; Lamm, Andrew F; Lee, Christopher M

    2013-12-01

    Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy. Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed. After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity. Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating

  19. Immunotherapy for high-grade glioma: how to go beyond Phase I/II clinical trials.

    Science.gov (United States)

    van Gool, Stefaan

    2013-10-01

    Evaluation of: Lasky JL 3rd, Panosyan EH, Plant A et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas. Anticancer Res. 33, 2047-2056 (2013). Immunotherapy for children and adults with high-grade glioma (HGG) is an emerging innovative treatment approach, which aims at stimulating the body's own immune system against HGG by using autologous dendritic cells pulsed with autologous tumor lysate as a therapeutic vaccine. This is the third report on immunotherapy for HGG in children, bringing additional knowledge and experience to the scientific community. However, at the same time, this and other manuscripts urge for the next step in treatment development.

  20. Hypo fractionated conformal irradiation of patients with malignant glioma

    International Nuclear Information System (INIS)

    Aboziada, M.A.; Abo-Kresha, A.E.

    2012-01-01

    Purpose: The aim of the study is to evaluate the effect of a conformal irradiation in short fractionation scheme of 49.5 Gy in 15 fractions in an overall time of 3 weeks, in terms of overall survival (OAS) and progression free survival (PFS) rates in brain glioma patients. Patients and methods: A prospective study was conducted on 54 brain glioma patients and was carried out in the Radiation Oncology Department, South Egypt Cancer Institute, Assiut University during the period from April 2006 till June 2009. Patients were treated by hypo fractionated conformal irradiation (49.5 Gy/15 fractions/3 weeks). Results: The median follow up was 23 months (range: 9-39 months). Two-year OAS and PFS rates were 68% and 60%, respectively. In univariate analysis, age > 50 years, poor performance status [Karnofasky score of >40- 50 years and glioblastoma pathology were the only independent prognostic factors that were associated with poor OAS (p = 0.003 and p = 0.004, respectively), and PFS (p = 0.027 and p = 0.011, respectively). Conclusion: Hypo fractionated conformal radiotherapy was as effective as the conventional radiotherapy, with time sparing for patients, and for radiation oncology centers. Hypo fractionated radiotherapy may be considered the radiotherapy regimen of choice in clinical practice for patients with gliomas

  1. Clinical Presentation and Outcome of Patients With Optic Pathway Glioma.

    Science.gov (United States)

    Robert-Boire, Viviane; Rosca, Lorena; Samson, Yvan; Ospina, Luis H; Perreault, Sébastien

    2017-10-01

    Optic pathway gliomas (OPGs) occur sporadically or in patients with neurofibromatosis type 1 (NF1). The purpose of this study was to evaluate the clinical presentation at diagnosis and at progression of patients with OPGs. We conducted a chart review of patients with OPGs diagnosed in a single center over a period of 15 years. Demographic data including age, sex, NF1 status, clinical presentation, and outcome were collected. Of the 40 patients who were identified, 23 had sporadic tumors (57.5%) and 17 had NF1-related tumors (42.5%). Among the children with NF1, there was a significant overrepresentation of girls (82.3%) (P = 0.02), while among the children without NF1, there were slightly more boys (56.5%) than girls (43.5%). The presence of nystagmus was strongly associated with sporadic optic pathway gliomas. Poor visual outcome was related to tumor affecting both optic pathways, hydrocephalus at diagnosis, and optic nerve atrophy. Of the 40 patients, five died of OPG complications (12.5%) and all had sporadic tumors. Our cohort is one of the largest with OPGs and a detailed description of the clinical presentation both at diagnosis and at progression. We observed a significant difference between sporadic and NF1 optic pathway gliomas in terms of demographics, clinical presentation, and outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Tumor-specific binding of radiolabeled G-22 monoclonal antibody in glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Jun; Wakabayashi, Toshihiko; Mizuno, Masaaki; Sugita, Kenichiro; Oshima, Motoo; Tadokoro, Masanori; Sakuma, Sadayuki [Nagoya Univ. (Japan). Faculty of Medicine; Seo, Hisao

    1992-03-01

    Iodine-131-labeled G-22 monoclonal antibody F(ab'){sub 2} fragment reacting specifically with a glioma-associated surface glycoprotein was administered to 12 glioma patients to investigate its use in radioimaging of intracranial gliomas. No immediate or delayed side effects were attributable to antibody injection. Nine patients received the radiolabeled complex intravenously. The images of low-grade gliomas were generally poor and disappeared within 4 days. High-contrast images were obtained beyond the 7th day in high-grade gliomas except one case in the pineal region. Three patients received intraventricular or intratumoral administration. Clear images of all tumors were demonstrated from the 2nd until later than the 7th day. One patient with cerebrospinal fluid (CSF) dissemination of brainstem glioma demonstrated negative CSF cytology after intraventricular administration. (author).

  3. Symptom clusters in patients with high-grade glioma.

    Science.gov (United States)

    Fox, Sherry W; Lyon, Debra; Farace, Elana

    2007-01-01

    To describe the co-occurring symptoms (depression, fatigue, pain, sleep disturbance, and cognitive impairment), quality of life (QoL), and functional status in patients with high-grade glioma. Correlational, descriptive study of 73 participants with high-grade glioma in the U.S. Nine brief measures were obtained with a mailed survey. Participants were recruited from the online message board of The Healing Exchange BRAIN TRUST, a nonprofit organization dedicated to improving quality of life for people with brain tumors. Two symptom cluster models were examined. Four co-occurring symptoms were significantly correlated with each other and explained 29% of the variance in QoL: depression, fatigue, sleep disturbance, and cognitive impairment. Depression, fatigue, sleep disturbance, cognitive impairment, and pain were significantly correlated with each other and explained 62% of the variance in functional status. The interrelationships of the symptoms examined in this study and their relationships with QoL and functional status meet the criteria for defining a symptom cluster. The differences in the models of QoL and functional status indicates that symptom clusters may have unique characteristics in patients with gliomas.

  4. EGFRvIII promotes glioma angiogenesis and growth through the NF-κB, interleukin-8 pathway.

    Science.gov (United States)

    Bonavia, R; Inda, M M; Vandenberg, S; Cheng, S-Y; Nagane, M; Hadwiger, P; Tan, P; Sah, D W Y; Cavenee, W K; Furnari, F B

    2012-09-06

    Sustaining a high growth rate requires tumors to exploit resources in their microenvironment. One example of this is the extensive angiogenesis that is a typical feature of high-grade gliomas. Here, we show that expression of the constitutively active mutant epidermal growth factor receptor, ΔEGFR (EGFRvIII, EGFR*, de2-7EGFR) is associated with significantly higher expression levels of the pro-angiogenic factor interleukin (IL)-8 in human glioma specimens and glioma stem cells. Furthermore, the ectopic expression of ΔEGFR in different glioma cell lines caused up to 60-fold increases in the secretion of IL-8. Xenografts of these cells exhibit increased neovascularization, which is not elicited by cells overexpressing wild-type (wt)EGFR or ΔEGFR with an additional kinase domain mutation. Analysis of the regulation of IL-8 by site-directed mutagenesis of its promoter showed that ΔEGFR regulates its expression through the transcription factors nuclear factor (NF)-κB, activator protein 1 (AP-1) and CCAAT/enhancer binding protein (C/EBP). Glioma cells overexpressing ΔEGFR showed constitutive activation and DNA binding of NF-κB, overexpression of c-Jun and activation of its upstream kinase c-Jun N-terminal kinase (JNK) and overexpression of C/EBPβ. Selective pharmacological or genetic targeting of the NF-κB or AP-1 pathways efficiently blocked promoter activity and secretion of IL-8. Moreover, RNA interference-mediated knock-down of either IL-8 or the NF-κB subunit p65, in ΔEGFR-expressing cells attenuated their ability to form tumors and to induce angiogenesis when injected subcutaneously into nude mice. On the contrary, the overexpression of IL-8 in glioma cells lacking ΔEGFR potently enhanced their tumorigenicity and produced highly vascularized tumors, suggesting the importance of this cytokine and its transcription regulators in promoting glioma angiogenesis and tumor growth.

  5. Spinal metastases of malignant gliomas

    International Nuclear Information System (INIS)

    Materlik, B.; Steidle-Katic, U.; Feyerabend, T.; Richter, E.; Wauschkuhn, B.

    1998-01-01

    Purpose: Extracranial metastases of malignant gliomas are rare. We report 2 cases with spinal metastases in patients suffering from glioma. Patients and Method: Two patients (33 and 57 years old) developed spinal canal metastases of a glioblastoma multiforme and anaplastic astrocytoma Grade III respectively 25 and 9 months after surgical resection and radiotherapy. Both metastases were confirmed pathohistologically. Results: Intraspinal metastases were irradiated with a total dose of 12.6 Gy and 50 Gy. Treatment withdrawal was necessary in one patient due to reduced clinical condition. Regression of neurological symptoms was observed in the second patient. Conclusions: Spinal spread of malignant glioma should be considered during care and follow-up in glioma patients with spinal symptoms. (orig.) [de

  6. Efficacy of radiotherapy for malignant gliomas in elderly patients

    International Nuclear Information System (INIS)

    Villa, Salvador; Vinolas, Nuria; Verger, Eugenia; Yaya, Ricard; Martinez, Antonio; Gil, Miquel; Moreno, Victor; Caral, Luis; Graus, Francesc

    1998-01-01

    Purpose: Age above 65 years is a strong negative prognostic factor for survival in patients with malignant gliomas (MG) treated with radiotherapy (RT) and its value has been questioned. We analyzed the effect of RT on the survival of elderly patients with malignant gliomas. Methods and Materials: We examined 85 consecutive elderly patients with a histological diagnosis of MG. Age ranged from 65 to 81 years (median 70 years). Glioblastoma multiforme (GBM) was diagnosed in 64 patients (75.3%). Surgical treatment included needle biopsy in 32 patients (37.6%). Median postoperative Karnofsky Performance Status (KPS) was 60 (range: 30-100). Survival probability was estimated using Kaplan-Meier method and compared with the log-rank test. Crude and adjusted hazard ratios (HR) were calculated using Cox's regression models. Results: Median survival time for all patients was 18.1 weeks. In multivariate analysis, RT was the only independent prognostic variable for survival (HR: 9.1 [95% CI: 4.5-18.7]). Forty-two patients did not start RT mostly due to low KPS (<50). The median survival of the 43 patients who started RT was 45 weeks. In these patients, Cox multivariate analysis indicated that age was independently associated with prolonged survival (HR: 2.85 [95% CI 1.31-6.19]). Median survival of patients age 70 years and younger was 55 weeks compared with 34 weeks for patients older than 70 years. Conclusions: The overall survival for elderly patients with MG is poor. RT seems to improve survival in patients up to 70 years, but in older patients treated with RT the survival is significantly shorter

  7. Genetic Alterations in Glioma

    International Nuclear Information System (INIS)

    Bralten, Linda B. C.; French, Pim J.

    2011-01-01

    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes

  8. Medical decision-making capacity in patients with malignant glioma.

    Science.gov (United States)

    Triebel, Kristen L; Martin, Roy C; Nabors, Louis B; Marson, Daniel C

    2009-12-15

    Patients with malignant glioma (MG) must make ongoing medical treatment decisions concerning a progressive disease that erodes cognition. We prospectively assessed medical decision-making capacity (MDC) in patients with MG using a standardized psychometric instrument. Participants were 22 healthy controls and 26 patients with histologically verified MG. Group performance was compared on the Capacity to Consent to Treatment Instrument (CCTI), a psychometric measure of MDC incorporating 4 standards (choice, understanding, reasoning, and appreciation), and on neuropsychological and demographic variables. Capacity outcomes (capable, marginally capable, or incapable) on the CCTI standards were identified for the MG group. Within the MG group, scores on demographic, clinical, and neuropsychological variables were correlated with scores on each CCTI standard, and significant bivariate correlates were subsequently entered into exploratory stepwise regression analyses to identify multivariate cognitive predictors of the CCTI standards. Patients with MG performed significantly below controls on consent standards of understanding and reasoning, and showed a trend on appreciation. Relative to controls, more than 50% of the patients with MG demonstrated capacity compromise (marginally capable or incapable outcomes) in MDC. In the MG group, cognitive measures of verbal acquisition/recall and, to a lesser extent, semantic fluency predicted performance on the appreciation, reasoning, and understanding standards. Karnofsky score was also associated with CCTI performance. Soon after diagnosis, patients with malignant glioma (MG) have impaired capacity to make treatment decisions relative to controls. Medical decision-making capacity (MDC) impairment in MG seems to be primarily related to the effects of short-term verbal memory deficits. Ongoing assessment of MDC in patients with MG is strongly recommended.

  9. Prognostic value of preoperative dynamic contrast-enhanced MRI perfusion parameters for high-grade glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Ulyte, Agne [Vilnius University, Faculty of Medicine, Vilnius (Lithuania); Katsaros, Vasileios K. [General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Advanced Imaging Modalities - CT and MRI, Athens (Greece); University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Liouta, Evangelia; Stranjalis, Georgios [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Boskos, Christos [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Radiation Oncology, Athens (Greece); Papanikolaou, Nickolas [Champalimaud Foundation, Department of Radiology, Centre for the Unknown, Lisbon (Portugal); Usinskiene, Jurgita [National Cancer Institute, Vilnius (Lithuania); Affidea Lietuva, Vilnius (Lithuania); Bisdas, Sotirios [University College London Hospitals, Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery, London (United Kingdom)

    2016-12-15

    The prognostic value of the dynamic contrast-enhanced (DCE) MRI perfusion and its histogram analysis-derived metrics is not well established for high-grade glioma (HGG) patients. The aim of this prospective study was to investigate DCE perfusion transfer coefficient (K{sup trans}), vascular plasma volume fraction (v{sub p}), extracellular volume fraction (v{sub e}), reverse transfer constant (k{sub ep}), and initial area under gadolinium concentration time curve (IAUGC) as predictors of progression-free (PFS) and overall survival (OS) in HGG patients. Sixty-nine patients with suspected anaplastic astrocytoma or glioblastoma underwent preoperative DCE-MRI scans. DCE perfusion whole tumor region histogram parameters, clinical details, and PFS and OS data were obtained. Univariate, multivariate, and Kaplan-Meier survival analyses were conducted. Receiver operating characteristic (ROC) curve analysis was employed to identify perfusion parameters with the best differentiation performance. On univariate analysis, v{sub e} and skewness of v{sub p} had significant negative impacts, while k{sub ep} had significant positive impact on OS (P < 0.05). v{sub e} was also a negative predictor of PFS (P < 0.05). Patients with lower v{sub e} and IAUGC had longer median PFS and OS on Kaplan-Meier analysis (P < 0.05). K{sup trans} and v{sub e} could also differentiate grade III from IV gliomas (area under the curve 0.819 and 0.791, respectively). High v{sub e} is a consistent predictor of worse PFS and OS in HGG glioma patients. v{sub p} skewness and k{sub ep} are also predictive for OS. K{sup trans} and v{sub e} demonstrated the best diagnostic performance for differentiating grade III from IV gliomas. (orig.)

  10. Terahertz reflectometry imaging for low and high grade gliomas

    Science.gov (United States)

    Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

    2016-01-01

    Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes. PMID:27782153

  11. Intraoperative language localization in multilingual patients with gliomas.

    Science.gov (United States)

    Bello, Lorenzo; Acerbi, Francesco; Giussani, Carlo; Baratta, Pietro; Taccone, Paolo; Songa, Valeria; Fava, Marica; Stocchetti, Nino; Papagno, Costanza; Gaini, Sergio M

    2006-07-01

    Intraoperative localization of speech is problematic in patients who are fluent in different languages. Previous studies have generated various results depending on the series of patients studied, the type of language, and the sensitivity of the tasks applied. It is not clear whether languages are mediated by multiple and separate cortical areas or shared by common areas. Globally considered, previous studies recommended performing a multiple intraoperative mapping for all the languages in which the patient is fluent. The aim of this work was to study the feasibility of performing an intraoperative multiple language mapping in a group of multilingual patients with a glioma undergoing awake craniotomy for tumor removal and to describe the intraoperative cortical and subcortical findings in the area of craniotomy, with the final goal to maximally preserve patients' functional language. Seven late, highly proficient multilingual patients with a left frontal glioma were submitted preoperatively to a battery of tests to evaluate oral language production, comprehension, and repetition. Each language was tested serially starting from the first acquired language. Items that were correctly named during these tests were used to build personalized blocks to be used intraoperatively. Language mapping was undertaken during awake craniotomies by the use of an Ojemann cortical stimulator during counting and oral naming tasks. Subcortical stimulation by using the same current threshold was applied during tumor resection, in a back and forth fashion, and the same tests. Cortical sites essential for oral naming were found in 87.5% of patients, those for the first acquired language in one to four sites, those for the other languages in one to three sites. Sites for each language were distinct and separate. Number and location of sites were not predictable, being randomly and widely distributed in the cortex around or less frequently over the tumor area. Subcortical stimulations found

  12. Therapy of Patients with Malignant Glioma with Targeted A-Radionuclide Therapy Using 213Bi-DOTA-[Thi8, Met (Oo)11]-Substanz P

    International Nuclear Information System (INIS)

    Forrer, F.; Mueller-Brand, J.; Cordier, D.; Merlo, A.; Morgenstern, A.; Bruchertseifer, F.; Maecke, H.R.

    2009-01-01

    The prognosis of patients with malignant glioma is very poor. New therapy options are mandatory. Substance P is the main ligand of neurokinin type 1 (NK-1) receptors, which are consistently over-expressed in malignant gliomas and surrounding tumor vessels. Administration of 90 Y-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P was shown to be feasible and safe. However, in critically located tumors, the mean tissue range of 5 mm of 90 Y may lead to unacceptable damage of adjacent, functional critical areas of the brain. We report a phase I study with locally administered 213 Bi labeled DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P in patients with malignant glioma. By using a direct, intratumoral injection, the problem of the short physical half life of Bismuth-213 can be circumvent. To date, 5 patients with malignant glioma (2 Grade IV, 1 Grade III and 2 grade II) without previous treatment were included. One to three catheter systems were placed stereotactically into the tumor. After a diagnostic injection with 111 In-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P and subsequent dosimetry, totally 30 to 138 mCi of 213 Bi-DOTA-[Thi8, Met (O o ) 11 ]-Substanz P was injected intratumorally performing 3 to 4 applications over 2 days. SPECT/CT was used to assess the biodistribution. Follow up was performed clinically and with morphological imaging. Targeted radiopeptide therapy using 213 Bi-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P was very well tolerated by all patients. No additional neurological deficit was observed. Repetitive imaging is suggestive of progressive radiation-induced necrosis, which was validated by subsequent resection of the tumors. Time to progression was found to be 11 and 14 months respectively in patients with grade IV glioma. No progression is found after 18 to 23 months in patients with grade II or III glioma. We conclude that targeted loco-regional radiotherapy using 213 Bi-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P represents an innovative and effective

  13. Clinical value of CD133 and nestin in patients with glioma

    DEFF Research Database (Denmark)

    Dahlrot, Rikke H; Hansen, Steinbjørn; Jensen, Stine S

    2014-01-01

    Cancer stem cell-related (CSC) markers have been suggested to have promising potentials as novel types of prognostic and predictive markers in gliomas. However no single CSC-related marker is currently used in clinical decisions. The aim of this study was to investigate the prognostic value of CD......133 and nestin separately and in combination using a novel quantitative approach in a well-characterized population-based cohort of glioma patients. The expression of CD133 and nestin was measured by systematic random sampling in stained paraffin sections from 239 glioma patients diagnosed between...

  14. Childhood Brain Stem Glioma Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Childhood brain stem glioma can be a benign (not cancer) or malignant (cancer) condition where abnormal cells form in the tissues of the brain stem. Get information about the symptoms, diagnosis, prognosis, and treatment of newly diagnosed and recurrent childhood brain stem glioma in this expert-reviewed summary.

  15. Quality of life after radiation therapy of cerebral low-grade gliomas of the adult: results of a randomised Phase III trial on dose response (EORTC trial 22844)

    Energy Technology Data Exchange (ETDEWEB)

    Kiebert, G.M. [MEDTAP International, 27 Gilbert Street, London (United Kingdom); Curran, D. [EORTC Data Centre Brussels (Belgium); Aaronson, N.K. [The Netherlands Cancer Institute, Amsterdam (Netherlands); Bolla, M. [Centre Hospitalier Regional Universitaire, Grenoble (France); Menten, J. [University Hospital Gasthuisberg Leuven (Belgium); Rutten, E.H.J.M. [University Hospital St. Radboud, Nijmegen (Netherlands); Nordman, E. [Turku University Central Hospital, Turku (Finland); Silvestre, M.E. [Hospital Santa Maria, Lisbon (Portugal); Pierart, M. [EORTC Data Centre, Brussels (Belgium); Karim, A.B.M.F. [Free University Hospital, Amsterdam (Netherlands)

    1998-11-01

    In 1985, the EORTC Radiotherapy Co-operative Group launched a randomised phase III study comparing high-dose (59.4 Gy in 6.5 weeks) versus low-dose (45 Gy in 5 weeks) radiotherapy with conventional techniques in patients diagnosed with low-grade cerebral glioma. The primary endpoint of the study was survival. No difference in survival was observed between the two treatment strategies. A quality of life (QoL) questionnaire consisting of 47 items assessing a range of physical, psychological, social, and symptom domains was included in the trial to measure the impact of treatment over time. Patients who received high-dose radiotherapy tended to report lower levels of functioning and more symptom burden following completion of radiotherapy. These group differences were statistically significant for fatigue/malaise and insomnia immediately after radiotherapy and in leisure time and emotional functioning at 7-15 months after randomisation. These findings suggest that for conventional radiotherapy for low-grade cerebral glioma, a schedule of 45 Gy in 5 weeks not only saves valuable resources, but also spares patients a prolonged treatment at no loss of clinical efficacy. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  16. Quality of life after radiation therapy of cerebral low-grade gliomas of the adult: results of a randomised Phase III trial on dose response (EORTC trial 22844)

    International Nuclear Information System (INIS)

    Kiebert, G.M.; Curran, D.; Aaronson, N.K.; Bolla, M.; Menten, J.; Rutten, E.H.J.M.; Nordman, E.; Silvestre, M.E.; Pierart, M.; Karim, A.B.M.F.

    1998-01-01

    In 1985, the EORTC Radiotherapy Co-operative Group launched a randomised phase III study comparing high-dose (59.4 Gy in 6.5 weeks) versus low-dose (45 Gy in 5 weeks) radiotherapy with conventional techniques in patients diagnosed with low-grade cerebral glioma. The primary endpoint of the study was survival. No difference in survival was observed between the two treatment strategies. A quality of life (QoL) questionnaire consisting of 47 items assessing a range of physical, psychological, social, and symptom domains was included in the trial to measure the impact of treatment over time. Patients who received high-dose radiotherapy tended to report lower levels of functioning and more symptom burden following completion of radiotherapy. These group differences were statistically significant for fatigue/malaise and insomnia immediately after radiotherapy and in leisure time and emotional functioning at 7-15 months after randomisation. These findings suggest that for conventional radiotherapy for low-grade cerebral glioma, a schedule of 45 Gy in 5 weeks not only saves valuable resources, but also spares patients a prolonged treatment at no loss of clinical efficacy. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  17. Inter-hemispheric language functional reorganization in low-grade glioma patients after tumour surgery

    NARCIS (Netherlands)

    Kristo, Gert; Raemaekers, Mathijs; Rutten, Geert-Jan; de Gelder, Beatrice; Ramsey, Nick F.

    Despite many claims of functional reorganization following tumour surgery, empirical studies that investigate changes in functional activation patterns are rare. This study investigates whether functional recovery following surgical treatment in patients with a low-grade glioma in the left

  18. Inter-hemispheric language functional reorganization in low-grade glioma patients after tumour surgery

    NARCIS (Netherlands)

    Kristo, Gert; Raemaekers, Mathijs; Rutten, Geert Jan; de Gelder, Beatrice; Ramsey, Nick F.

    2015-01-01

    Despite many claims of functional reorganization following tumour surgery, empirical studies that investigate changes in functional activation patterns are rare. This study investigates whether functional recovery following surgical treatment in patients with a low-grade glioma in the left

  19. Epidemiology of glioma

    DEFF Research Database (Denmark)

    Rasmussen, Birthe Krogh; Hansen, Steinbjorn; Laursen, Rene J.

    2017-01-01

    in 15%. The overall male:female ratio was 3:2 and the mean age at onset was 60 years. Data for WHO grade I, II, III and IV glioma showed several important differences regarding age and sex distribution and symptomatology at presentation. The mean age increased with the grade of glioma and males...... duration, and headache rates for glioma grade I-IV showed decreasing survival with increasing grade. Glioma grade I-IV showed...

  20. EMMPRIN is an independent negative prognostic factor for patients with astrocytic glioma.

    Directory of Open Access Journals (Sweden)

    Li Tian

    Full Text Available Extracellular matrix metalloproteinase inducer (EMMPRIN, also known as CD147, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs. It has been proved to be associated with tumor invasion and metastasis in various human malignancies. In our study, the protein expression level of EMMPRIN in 306 cases of astrocytic glioma is investigated by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of EMMPRIN with clinicopathological characteristics and prognosis of patients. It was proved that EMMPRIN protein expression was increased in glioma compared with that in normal brain tissue. Moreover, EMMPRIN immunohistochemical staining was correlated with WHO grade and Karnofsky performance score for strong positive EMMPRIN staining is more frequently detected in glioma of advanced grade or low KPS score. It is also demonstrated that EMMPRIN could be an independent negative prognostic factor in glioma for patients with glioma of strong EMMPRIN staining tend to have high risk of death. These results proved that EMMPRIN is associated with prognosis of glioma, which may also suggest the potential role of EMMPRIN in glioma management.

  1. EMMPRIN is an independent negative prognostic factor for patients with astrocytic glioma.

    Science.gov (United States)

    Tian, Li; Zhang, Yang; Chen, Yu; Cai, Min; Dong, Hailong; Xiong, Lize

    2013-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as CD147, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). It has been proved to be associated with tumor invasion and metastasis in various human malignancies. In our study, the protein expression level of EMMPRIN in 306 cases of astrocytic glioma is investigated by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of EMMPRIN with clinicopathological characteristics and prognosis of patients. It was proved that EMMPRIN protein expression was increased in glioma compared with that in normal brain tissue. Moreover, EMMPRIN immunohistochemical staining was correlated with WHO grade and Karnofsky performance score for strong positive EMMPRIN staining is more frequently detected in glioma of advanced grade or low KPS score. It is also demonstrated that EMMPRIN could be an independent negative prognostic factor in glioma for patients with glioma of strong EMMPRIN staining tend to have high risk of death. These results proved that EMMPRIN is associated with prognosis of glioma, which may also suggest the potential role of EMMPRIN in glioma management.

  2. TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival

    International Nuclear Information System (INIS)

    Micale, Lucia; Fusco, Carmela; Fontana, Andrea; Barbano, Raffaela; Augello, Bartolomeo; De Nittis, Pasquelena; Copetti, Massimiliano; Pellico, Maria Teresa; Mandriani, Barbara; Cocciadiferro, Dario; Parrella, Paola; Fazio, Vito Michele; Dimitri, Lucia Maria Cecilia; D’Angelo, Vincenzo; Novielli, Chiara; Larizza, Lidia; Daga, Antonio; Merla, Giuseppe

    2015-01-01

    Human gliomas are a heterogeneous group of primary malignant brain tumors whose molecular pathogenesis is not yet solved. In this regard, a major research effort has been directed at identifying novel specific glioma-associated genes. Here, we investigated the effect of TRIM8 gene in glioma. TRIM8 transcriptional level was profiled in our own glioma cases collection by qPCR and confirmed in the independent TCGA glioma cohort. The association between TRIM8 expression and Overall Survival and Progression-free Survival in TCGA cohort was determined by using uni-multivariable Cox regression analysis. The effect of TRIM8 on patient glioma cell proliferation was evaluated by performing MTT and clonogenic assays. The mechanisms causing the reduction of TRIM8 expression were explored by using qPCR and in vitro assays. We showed that TRIM8 expression correlates with unfavorable clinical outcome in glioma patients. We found that a restored TRIM8 expression induced a significant reduction of clonogenic potential in U87MG and patient’s glioblastoma cells. Finally we provide experimental evidences showing that miR-17 directly targets the 3′ UTR of TRIM8 and post-transcriptionally represses the expression of TRIM8. Our study provides evidences that TRIM8 may participate in the carcinogenesis and progression of glioma and that the transcriptional repression of TRIM8 might have potential value for predicting poor prognosis in glioma patients. The online version of this article (doi:10.1186/s12885-015-1449-9) contains supplementary material, which is available to authorized users

  3. Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

    Directory of Open Access Journals (Sweden)

    Haidar A. Shamran

    2015-01-01

    Full Text Available Human Cytomegalovirus (HCMV is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n=50 and from benign meningioma patients (n=30 were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG compared to 72.5% among control samples (P=0.04. These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis.

  4. Longitudinal DSC-MRI for Distinguishing Tumor Recurrence From Pseudoprogression in Patients With a High-grade Glioma.

    Science.gov (United States)

    Boxerman, Jerrold L; Ellingson, Benjamin M; Jeyapalan, Suriya; Elinzano, Heinrich; Harris, Robert J; Rogg, Jeffrey M; Pope, Whitney B; Safran, Howard

    2017-06-01

    For patients with high-grade glioma on clinical trials it is important to accurately assess time of disease progression. However, differentiation between pseudoprogression (PsP) and progressive disease (PD) is unreliable with standard magnetic resonance imaging (MRI) techniques. Dynamic susceptibility contrast perfusion MRI (DSC-MRI) can measure relative cerebral blood volume (rCBV) and may help distinguish PsP from PD. A subset of patients with high-grade glioma on a phase II clinical trial with temozolomide, paclitaxel poliglumex, and concurrent radiation were assessed. Nine patients (3 grade III, 6 grade IV), with a total of 19 enhancing lesions demonstrating progressive enhancement (≥25% increase from nadir) on postchemoradiation conventional contrast-enhanced MRI, had serial DSC-MRI. Mean leakage-corrected rCBV within enhancing lesions was computed for all postchemoradiation time points. Of the 19 progressively enhancing lesions, 10 were classified as PsP and 9 as PD by biopsy/surgery or serial enhancement patterns during interval follow-up MRI. Mean rCBV at initial progressive enhancement did not differ significantly between PsP and PD (2.35 vs. 2.17; P=0.67). However, change in rCBV at first subsequent follow-up (-0.84 vs. 0.84; P=0.001) and the overall linear trend in rCBV after initial progressive enhancement (negative vs. positive slope; P=0.04) differed significantly between PsP and PD. Longitudinal trends in rCBV may be more useful than absolute rCBV in distinguishing PsP from PD in chemoradiation-treated high-grade gliomas with DSC-MRI. Further studies of DSC-MRI in high-grade glioma as a potential technique for distinguishing PsP from PD are indicated.

  5. Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

    Directory of Open Access Journals (Sweden)

    Torres-Trejo Alejandro

    2007-12-01

    received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-γ post-vaccine responses or prolonged progression-free survival in these participants. Conclusion Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines.

  6. 111Indium (DTPA-octreotide) scintigraphy in patients with cerebral gliomas

    International Nuclear Information System (INIS)

    Luyken, C.; Hildebrandt, G.; Klug, N.; Scheidhauer, K.; Schicha, H.; Krisch, B.

    1994-01-01

    Somatostatin receptors (SR) have been identified in vitro in normal brain tissue, in neuro-endocrine tumours and in cerebral gliomas WHO grade 1 or 2 by autoradiography or using somatostatin-gold conjugates. In vivo, SR detection has become possible by scintigraphy applying the somatostatin analogue octreotide, radio-labelled with 111 indium. It was supposed that expression of SR in cerebral gliomas corresponds to low grade tumour malignancy and that, in vivo, somatostatin receptor scintigraphy (SRS) could refine and improve the WHO grading system for cerebral gliomas. Nineteen patients with cerebral gliomas (grade 2: n=8, grade 3: n=3, grade 4: n=8) were examined with 111 In (DTPA-octreotide) to evaluate, whether SRS could improve the pre-operative estimation of tumour biology and the postoperative management. The results of SRS were related with the histological findings and with the in vitro demonstration of somatostatin-binding sites on cultured tumour cells incubated with a somatostatin-gold conjugate. In vivo, none of the patients with glioma grade 2 showed enhanced tracer uptake in the SRS, whereas in vitro SR were detected in cultured tumour tissue in 5 out of 5 cases. Every patient with glioma grade 3 or 4 demonstrated a high focal uptake of 111 In (DTPA-octreotide), as shown by SRS. Three patients with glioma grade 4, additionally examined with 99mTc-DTPA, showed an increased tracer uptake within the tumour area when compared with results of SRS. In vitro, SR were detected on tumour cell surface in 5 out of 6 tissue samples from patients with gliomas grade 3 or 4. One patient harbouring a cerebral abscess with a high focal tracer uptake in the SRS but with absence of somatostatin-binding sites in vitro. We conclude, that in glioma patients enhanced tracer uptake in receptor scintigraphy with 111 In (DTPA-octreotide) does not depend on the presence of SR in tumour but on the dysfunction of the blood-brain barrier. Thus, SRS dose not improve the

  7. Effect of epidermal growth factor receptor gene polymorphisms on prognosis in glioma patients

    Science.gov (United States)

    Li, Jingjie; Yan, Mengdan; Xie, Zhilan; Zhu, Yuanyuan; Chen, Chao; Jin, Tianbo

    2016-01-01

    Previous studies suggested that single nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) are associated with risk of glioma. However, the associations between these SNPs and glioma patient prognosis have not yet been fully investigated. Therefore, the present study was aimed to evaluate the effects of EGFR polymorphisms on the glioma patient prognosis. We retrospectively evaluated 269 glioma patients and investigated associations between EGFR SNPs and patient prognosis using Cox proportional hazard models and Kaplan-Meier curves. Univariate analysis revealed that age, gross-total resection and chemotherapy were associated with the prognosis of glioma patients (p < 0.05). In addition, four EGFR SNPs (rs11506105, rs3752651, rs1468727 and rs845552) correlated with overall survival (OS) (Log-rank p = 0.011, 0.020, 0.008, and 0.009, respectively) and progression-free survival PFS (Log-rank p = 0.026, 0.024, 0.019 and 0.009, respectively). Multivariate analysis indicated that the rs11506105 G/G genotype, the rs3752651 and rs1468727 C/C genotype and the rs845552 A/A genotype correlated inversely with OS and PFS. In addition, OS among patients with the rs730437 C/C genotype (p = 0.030) was significantly lower OS than among patients with A/A genotype. These data suggest that five EGFR SNPs (rs11506105, rs3752651, rs1468727, rs845552 and rs730437) correlated with glioma patient prognosis, and should be furthered validated in studies of ethnically diverse patients. PMID:27437777

  8. Long noncoding RNA CASC2 predicts the prognosis of glioma patients and functions as a suppressor for gliomas by suppressing Wnt/β-catenin signaling pathway

    Directory of Open Access Journals (Sweden)

    Wang R

    2017-07-01

    Full Text Available Ronglin Wang,1,* Yuqian Li,1,* Gang Zhu,1,* Bo Tian,1 Wen Zeng,1 Yang Yang,2 Zhihong Li1 1Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, 2Department of Neurosurgery, The 451th hospital of PLA, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Background: Previous studies have demonstrated that long noncoding RNA cancer susceptibility candidate 2 (lncRNA CASC2 is frequently downregulated in several types of tumors and functions as a tumor-suppressive factor. However, the clinical significance and function of CASC2 in human glioma remain largely unknown. The purpose of this study was to identify the clinical values of CASC2, as well as investigate the potential molecular mechanisms in glioma. Methods: This retrospective study first analyzed the expression levels of CASC2 using quantitative real-time polymerase chain reaction. Then, CASC2 expression levels were associated with various clinicopathologic characteristics and the survival rate of patients with glioma. Finally, the function and underlying molecular mechanisms of CASC2 in human glioma were investigated in U251 cell line. Results: By quantitative real-time polymerase chain reaction analysis, our data showed that CASC2 expression was significantly downregulated in glioma tissues and cell lines (U87 and U251 compared to adjacent normal brain tissues or normal human astrocytes. Moreover, its expression negatively correlated with tumor grade in glioma patients. Furthermore, Kaplan–Meier curves with log-rank analysis revealed a close correlation between downregulated CASC2 and shorter survival time in glioma patients. In addition, Cox regression analysis indicated that CASC2 could be considered as an independent risk factor for poor prognosis. Finally, in vitro experiment demonstrated that CASC2 overexpression remarkably suppressed glioma cell proliferation, migration, and invasion through suppressing Wnt

  9. Radiotherapy-induced cerebral abnormalities in patients with low-grade glioma

    NARCIS (Netherlands)

    Postma, TJ; Klein, M; Verstappen, CCP; Bromberg, JEC; Swennen, M; Langendijk, JA; Taphoorn, MJB; Scheltens, P; Slotman, BJ; van der Ploeg, HM; Aaronson, NK; Heimans, JJ

    2002-01-01

    Abnormalities on CT or MRI and neuropsychological performance in patients with low-grade glioma, with (n = 23) or without (n = 16) prior cerebral radiotherapy, were evaluated. Cerebral atrophy was observed in 14 of 23 patients (61%) treated with prior radiotherapy, and in 1 of 16 patients (6%)

  10. The End-of-Life Phase of High-Grade Glioma Patients: Dying With Dignity?

    NARCIS (Netherlands)

    Sizoo, E.M.; Taphoorn, M.J.B.; Uitdehaag, B.M.J.; Heimans, J.J.; Deliens, L.; Reijneveld, J.C.; Pasman, H.R.W.

    2013-01-01

    Background. In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with

  11. The end-of-life phase of high-grade glioma patients: dying with dignity?

    NARCIS (Netherlands)

    Sizoo, Eefje M.; Taphoorn, Martin J. B.; Uitdehaag, Bernard; Heimans, Jan J.; Deliens, Luc; Reijneveld, Jaap C.; Pasman, H. Roeline W.

    2013-01-01

    In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as

  12. The expression of cytoglobin as a prognostic factor in gliomas: a retrospective analysis of 88 patients

    International Nuclear Information System (INIS)

    Xu, Hong-Wu; Huang, Hai-Hua; Wei, Xiao-Long; Man, Kwan; Zhang, Guo-Jun; Huang, Yue-Jun; Xie, Ze-Yu; Lin, Lan; Guo, Yan-Chun; Zhuang, Ze-Rui; Lin, Xin-Peng; Zhou, Wen; Li, Mu

    2013-01-01

    Evidence suggests that cytoglobin (Cygb) may function as a tumor suppressor gene. We immunohistochemically evaluated the expression of Cygb, phosphatidylinositol-3 kinase (PI-3K), phosphorylated (p)-Akt, Interleukin-6 (IL-6), tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) in 88 patients with 41 high-grade gliomas and 47 low-grade gliomas. Intratumoral microvessel density (IMD) was also determined and associated with clinicopathological factors. Low expression of Cygb was significantly associated with the higher histological grading and tumor recurrence. A significant negative correlation emerged between Cygb expression and PI3K, p-Akt, IL-6, TNFα or VEGF expression. Cygb expression was negatively correlated with IMD. There was a positive correlation between PI3K, p-Akt, IL-6, TNFα and VEGF expression with IMD.High histologic grade, tumor recurrence, decreased Cygb expression, increased PI3K expression, increased p-Akt expression and increased VEGF expression correlated with patients’ overall survival in univariate analysis. However, only histological grading and Cygb expression exhibited a relationship with survival of patients as independent prognostic factors of glioma by multivariate analysis. Cygb loss may contribute to tumor recurrence and a worse prognosis in gliomas. Cygb may serve as an independent predictive factor for prognosis of glioma patients

  13. Neutrophilia as a biomarker for overall survival in newly diagnosed high-grade glioma patients undergoing chemoradiation

    Directory of Open Access Journals (Sweden)

    Antoine Schernberg

    2018-03-01

    Full Text Available Objective: To study the prognostic value of neutrophil disorders in a retrospective cohort of high-grade glioma patients receiving definitive concurrent temozolomide and radiation. Materials and methods: Clinical records of consecutive patients treated in our Institution between January 2005 and December 2010 with concurrent temozolomide (75 mg/m2 daily and radiation were collected. The prognostic value of pretreatment neutrophilia on survival, defined as a neutrophil count exceeding 7 G/L, was examined. Results: We identified 164 patients, all treated with concurrent temozolomide-based chemoradiotherapy. Initial surgery was achieved in most (75%, with resection > 90% in 55 patients (34%. Total 151 patients (92% had glioblastoma, and 13 patients (8% had WHO grade III glioma. Eighty-two patients (50% displayed pretreatment neutrophilia. Neutrophilia was not associated with concurrent or adjuvant temodal discontinuation (p > 0.3. The 2-year actuarial overall survival was 45%. Steroid consumption, i.e. 60 mg or more of daily prednisolone, increased pretreatment neutrophil count (p = 0.005. In univariate analysis, neutrophilia was associated with worse overall survival (p = 0.019, as well as age ≥ 65 years (p = 0.009, surgical resection < 90% (p = 0.003 and prednisolone consumption ≥ 60 mg/day (p = 0.016. In multivariate analysis, neutrophilia (p = 0.013, age ≥ 65 (p = 0.001, and surgical tumor resection < 90% (p = 0.010 independently decreased overall survival, while, steroid consumption was not (p = 0.088. Conclusion: In high-grade gliomas treated with concurrent temozolomide and radiation, pretreatment neutrophilia may be a significant prognosis factor for overall survival. In addition with previously available markers, this independent cost-effective biomarker could help identifying patients with worsened prognosis. Keywords: High grade gliomas, Glioblastoma

  14. Symptoms and problems in the end-of-life phase of high-grade glioma patients

    NARCIS (Netherlands)

    Sizoo, Eefje M.; Braam, Lies; Postma, Tjeerd J.; Pasman, H. Roeline W.; Heimans, Jan J.; Klein, Martin; Reijneveld, Jaap C.; Taphoorn, Martin J. B.

    2010-01-01

    Despite multimodal treatment, it is not possible to cure high-grade glioma (HGG) patients. Therefore, the aim of treatment is not only to prolong life, but also to prevent deterioration of health-related quality of life as much as possible. When the patient's condition declines and no further tumor

  15. Fatigue in patients with low grade glioma: systematic evaluation of assessment and prevalence

    NARCIS (Netherlands)

    E.M.P. Van Coevorden-van Loon (Ellen M. P.); Coomans, M.B. (Marijke B.); M.H. Heijenbrok-Kal (Majanka); G.M. Ribbers (Gerard); M.J. van den Bent (Martin)

    2017-01-01

    textabstractFatigue is the most prevalent and disabling symptom in cancer patients. Yet, scientific literature on this topic is scarce and reports disparate results. This study systematically reviews how fatigue is assessed in patients with low-grade glioma and evaluates its prevalence in LGG

  16. Symptoms and medication management in the end of life phase of high-grade glioma patients

    NARCIS (Netherlands)

    Koekkoek, J.A.F.; Dirven, L.; Sizoo, E.M.; Pasman, H.R.W.; Heimans, J.J.; Postma, T.J.; Deliens, L.; Grant, R.; McNamara, S.; Stockhammer, G.; Medicus, E.; Taphoorn, M.J.B.; Reijneveld, J.C.

    2014-01-01

    During the end of life (EOL) phase of high-grade glioma (HGG) patients, care is primarily aimed at reducing symptom burden while maintaining quality of life as long as possible. In this study, we evaluated the prevalence of symptoms and medication management in HGG patients during the EOL phase. We

  17. The Role of Molecular Diagnostics in the Management of Patients with Gliomas.

    Science.gov (United States)

    Wirsching, Hans-Georg; Weller, Michael

    2016-10-01

    The revised World Health Organization (WHO) classification of tumors of the central nervous system of 2016 combines biology-driven molecular marker diagnostics with classical histological cancer diagnosis. Reclassification of gliomas by molecular similarity beyond histological boundaries improves outcome prediction and will increasingly guide treatment decisions. This change in paradigms implies more personalized and eventually more efficient therapeutic approaches, but the era of molecular targeted therapies for gliomas is yet at its onset. Promising results of molecularly targeted therapies in genetically less complex gliomas with circumscribed growth such as subependymal giant cell astrocytoma or pilocytic astrocytoma support further development of molecularly targeted therapies. In diffuse gliomas, several molecular markers that predict benefit from alkylating agent chemotherapy have been identified in recent years. For example, co-deletion of chromosome arms 1p and 19q predicts benefit from polychemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) in patients with anaplastic oligodendroglioma, and the presence of 1p/19q co-deletion was integrated as a defining feature of oligodendroglial tumors in the revised WHO classification. However, the tremendous increase in knowledge of molecular drivers of diffuse gliomas on genomic, epigenetic, and gene expression levels has not yet translated into effective molecular targeted therapies. Multiple reasons account for the failure of early clinical trials of molecularly targeted therapies in diffuse gliomas, including the lack of molecular entry controls as well as pharmacokinetic and pharmacodynamics issues, but the key challenge of specifically targeting the molecular backbone of diffuse gliomas is probably extensive clonal heterogeneity. A more profound understanding of clonal selection, alternative activation of oncogenic signaling pathways, and genomic instability is warranted to identify effective

  18. Alteration of long-distance functional connectivity and network topology in patients with supratentorial gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Eun; Kim, Ho Sung; Kim, Sang Joon; Shim, Woo Hyun [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Songpa-Gu, Seoul (Korea, Republic of); Kim, Jeong Hoon [University of Ulsan College of Medicine, Department of Neurosurgery, Asan Medical Center, Seoul (Korea, Republic of)

    2016-03-15

    The need for information regarding functional alterations in patients with brain gliomas is increasing, but little is known about the functional consequences of focal brain tumors throughout the entire brain. Using resting-state functional MR imaging (rs-fMRI), this study assessed functional connectivity in patients with supratentorial brain gliomas with possible alterations in long-distance connectivity and network topology. Data from 36 patients with supratentorial brain gliomas and 12 healthy subjects were acquired using rs-fMRI. The functional connectivity matrix (FCM) was created using 32 pairs of cortical seeds on Talairach coordinates in each individual subject. Local and distant connectivity were calculated using z-scores in the individual patient's FCM, and the averaged FCM of patients was compared with that of healthy subjects. Weighted network analysis was performed by calculating local efficiency, global efficiency, clustering coefficient, and small-world topology, and compared between patients and healthy controls. When comparing the averaged FCM of patients with that of healthy controls, the patients showed decreased long-distance, inter-hemispheric connectivity (0.32 ± 0.16 in patients vs. 0. 42 ± 0.15 in healthy controls, p = 0.04). In network analysis, patients showed increased local efficiency (p < 0.05), but global efficiency, clustering coefficient, and small-world topology were relatively preserved compared to healthy subjects. Patients with supratentorial brain gliomas showed decreased long-distance connectivity while increased local efficiency and preserved small-world topology. The results of this small case series may provide a better understanding of the alterations of functional connectivity in patients with brain gliomas across the whole brain scale. (orig.)

  19. Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma

    Science.gov (United States)

    2017-10-23

    Childhood Cerebral Anaplastic Astrocytoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma

  20. Patient specific actual size 3D printed models for patient education in glioma treatment: first experiences.

    Science.gov (United States)

    van de Belt, Tom H; Nijmeijer, Hugo; Grim, David; Engelen, Lucien Jlpg; Vreeken, Rinaldo; van Gelder, Marleen Mmj; Laan, Mark Ter

    2018-06-02

    Cancer patients need high quality information about the disease stage, treatment options and side effects. High quality information can also improve health literacy, shared decision-making and satisfaction. We created patient-specific 3D models of tumours including surrounding functional areas, and assessed what patients with glioma actually value (or fear) about these models when they are used to educate them about the relation between their tumour and specific brain parts, the surgical procedure, and risks. We carried out an explorative study with adult glioma patients, who underwent functional MRI and DTi as part of the pre-operative work-up. All participants received an actual size 3D model, printed based on fMRI and DTi imaging. Semi-structured interviews were held to identify facilitators and barriers for using the model, and perceived effects. A model was successfully created for all 11 participants. A total of 18 facilitators and 8 barriers were identified. The model improved patients' understanding about their situation, that it was easier to ask questions to their neurosurgeon based on their model and that it supported their decision about the preferred treatment. A perceived barrier for using the 3D model was that it could be emotionally confronting, particularly in an early phase of the disease process. Positive effects were related to psychological domains including coping, learning effects and communication. Patient-specific 3D models are promising and simple tools that could help patients with glioma to better understand their situation, treatment options and risks. They have the potential to improve shared decision-making. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. MR-monitored LITT as a palliative concept in patients with high grade gliomas: preliminary clinical experience.

    Science.gov (United States)

    Reimer, P; Bremer, C; Horch, C; Morgenroth, C; Allkemper, T; Schuierer, G

    1998-01-01

    The purpose of this study was to evaluate the clinical utility of laser-induced thermotherapy (LITT) as a palliative treatment for patients with high-grade gliomas. Four consenting patients with recurrent high grade III/IV gliomas near the primary language or motor areas were palliatively treated with LITT (2-5 W, 3-13 minutes; Neodym YAG Laser, Dornier, Friedrichshafen, Germany). Temperature monitoring was performed by T1-weighted turbo-fast low-angle shot (FLASH) imaging at 1.5 T (Siemens Magnetom SP 4000, Siemens, Erlangen, Germany). MRI studies before LITT included contrast-enhanced conventional scans and functional activation studies to localize the primary motor cortex or language areas using an echo-planar imaging (EPI) spin-echo (SE) sequence. Follow-up studies consisted of contrast-enhanced conventional scans as well as diffusion studies (contrast-enhanced Fourier-acquired steady-state technique and EPI-SE) and perfusion studies (EPI-SE with .2 mmol of gadolinium (Gd)/kg body weight) to differentiate post-therapeutic effects from residual or recurrent tumor growth. Local tumor control was achieved in areas with laser energy deposition with clinically stable conditions > or = 6 months. Conventional contrast-enhanced scans demonstrated strong enhancement surrounding ablated tumor components, which showed a reduction in CBV/CBF. Perfusion studies were useful to discriminate granulomatous tissue enhancement from residual or recurrent tumor growth. Careful application of LITT may evolve as an alternative palliative concept for patients with end-stage high-grade cerebral gliomas reducing clinical symptoms from circumscribed areas of pathology.

  2. Improving the Quality of Care for Patients Diagnosed With Glioma During the Perioperative Period

    Science.gov (United States)

    Riblet, Natalie B.V.; Schlosser, Evelyn M.; Homa, Karen; Snide, Jennifer A.; Jarvis, Lesley A.; Simmons, Nathan E.; Sargent, David H.; Mason, Linda P.; Cooney, Tobi J.; Kennedy, Nancy L.; Fadul, Camilo E.

    2014-01-01

    Purpose: Although there is agreement on the oncologic management of patients with glioma, few guidelines exist to standardize other aspects of care, including supportive care. Methods: A quality improvement (QI) project was chartered to improve the care provided to patients with glioma. A multidisciplinary team was convened and identified 10 best-practice measures. Using a plan-do-study-act framework, the team brainstormed and implemented various improvement interventions between June 2011 and October 2012. Statistical process control charts were used to evaluate progress. A dashboard of quality measures was generated to allow for ongoing measurement and reporting. Results: The retrospective assessment phase consisted of 43 patients with diagnosis of glioma. A manual medical record review for these patients showed that compliance with 10 best-practice measures ranged from 23% to 100%. Several factors contributed to less-than-ideal process performance, including poor communication among disciplines and lack of familiarity with the larger system of care. After implementing improvement interventions, performance was measured in 96 consecutive patients with glioma. The proportion of patients who met criteria for 10 practice measures significantly improved (pre-QI work, 63%; post-QI work, 85%; P = .003). The largest improvement was observed in the measure assessing for preoperative notification of the neuro-oncology program (pre-QI work, 39%; post-QI work, 97%; P sustaining process improvements. PMID:25294392

  3. Effectiveness of interferon-[beta], ACNU, and radiation therapy in pediatric patients with brainstem glioma

    Energy Technology Data Exchange (ETDEWEB)

    Wakabayashi, Toshihiko; Yoshida, Jun; Mizuno, Masaaki; Sugita, Kenichiro [Nagoya Univ. (Japan). Faculty of Medicine; Kito, Akira

    1992-12-01

    Sixteen pediatric patients with brainstem glioma were treated with a combination of interferon-[beta], 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl -3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), and radiation therapy (IAR therapy). All patients received 1-1.5 million IU/day of interferon-[beta] intravenously for 1 week of each 6-week cycle. In addition, ACNU (2-3 mg/kg) was given on the 2nd day of each cycle. Conventional focal irradiation (1.5-2 Gy/day for 5 days to a total dosage of 40-60 Gy) was administered beginning on day 3. Patients underwent at least two 6-week cycles. Adverse effects included nausea, vomiting, and myelosuppression, but were mild and transient. Response to treatment was evaluated by the reduction in tumor size measured on postcontrast computed tomographic scans and magnetic resonance images. Responses occurred in 10 of 11 patients with the intrinsic type of brainstem glioma, including three complete and seven partial responses. Two of the five patients with exophytic type gliomas partially responded. The median survival was 15.7 months, a remarkable improvement over the natural course of this disease. These results indicate that IAR therapy is a useful primary treatment for pediatric patients with brainstem gliomas. (author).

  4. Levetiracetam-induced interstitial nephritis in a patient with glioma.

    Science.gov (United States)

    Mahta, Ali; Kim, Ryan Y; Kesari, Santosh

    2012-01-01

    A 45-year-old man with a new diagnosis of low grade glioma was started on an escalating dose of levetiracetam (Lev) for seizure management. He gradually developed intractable nausea/vomiting and a high creatinine concentration due to acute renal failure which was attributed to Lev-induced interstitial nephritis. The medication was changed and his renal function rapidly improved to his baseline. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Initial experience with locoregional radioimmunotherapy using {sup 131}I-labelled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)

    Energy Technology Data Exchange (ETDEWEB)

    Poepperl, G.; Gildehaus, F.J.; Hahn, K.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum Grosshadern, Muenchen (Germany); Goetz, C.; Reulen, H.J. [Klinik und Poliklinik fuer Neurochirurgie, Klinikum Grosshadern, Muenchen (Germany); Yousry, T.A. [Inst. fuer Neuroradiologie der LMU Muenchen, Klinikum Grosshadern, Muenchen (Germany)

    2002-06-01

    Aim: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radioimmunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. Methods: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq {sup 131}labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. Results: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse anti-bodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remain stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n=89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. Conclusions: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration

  6. An immuno-wall microdevice exhibits rapid and sensitive detection of IDH1-R132H mutation specific to grade II and III gliomas

    Science.gov (United States)

    Yamamichi, Akane; Kasama, Toshihiro; Ohka, Fumiharu; Suzuki, Hiromichi; Kato, Akira; Motomura, Kazuya; Hirano, Masaki; Ranjit, Melissa; Chalise, Lushun; Kurimoto, Michihiro; Kondo, Goro; Aoki, Kosuke; Kaji, Noritada; Tokeshi, Manabu; Matsubara, Toshio; Senga, Takeshi; Kaneko, Mika K.; Suzuki, Hidenori; Hara, Masahito; Wakabayashi, Toshihiko; Baba, Yoshinobu; Kato, Yukinari; Natsume, Atsushi

    2016-01-01

    World Health Organization grade II and III gliomas most frequently occur in the central nervous system (CNS) in adults. Gliomas are not circumscribed; tumor edges are irregular and consist of tumor cells, normal brain tissue, and hyperplastic reactive glial cells. Therefore, the tumors are not fully resectable, resulting in recurrence, malignant progression, and eventual death. Approximately 69-80% of grade II and III gliomas harbor mutations in the isocitrate dehydrogenase 1 gene (IDH1), of which 83-90% are found to be the IDH1-R132H mutation. Detection of the IDH1-R132H mutation should help in the differential diagnosis of grade II and III gliomas from other types of CNS tumors and help determine the boundary between the tumor and normal brain tissue. In this study, we established a highly sensitive antibody-based device, referred to as the immuno-wall, to detect the IDH1-R132H mutation in gliomas. The immuno-wall causes an immunoreaction in microchannels fabricated using a photo-polymerizing polymer. This microdevice enables the analysis of the IDH1 status with a small sample within 15 min with substantially high sensitivity. Our results suggested that 10% content of the IDH1-R132H mutation in a sample of 0.33 μl volume, with 500 ng protein, or from 500 cells is theoretically sufficient for the analysis. The immuno-wall device will enable the rapid and highly sensitive detection of the IDH1-R132H mutation in routine clinical practice.

  7. The end-of-life phase of high-grade glioma patients: a systematic review

    NARCIS (Netherlands)

    Sizoo, Eefje M.; Pasman, H. Roeline W.; Dirven, Linda; Marosi, Christine; Grisold, Wolfgang; Stockhammer, Günther; Egeter, Jonas; Grant, Robin; Chang, Susan; Heimans, Jan J.; Deliens, Luc; Reijneveld, Jaap C.; Taphoorn, Martin J. B.

    2014-01-01

    High-grade gliomas (HGG) are rare and incurable; yet, these neoplasms result in a disproportionate share of cancer morbidity and mortality. Treatment of HGG patients is directed not merely towards prolonging life but also towards quality of life, which becomes the major goal in the end of life

  8. The end-of-life phase of high-grade glioma patients: a systematic review

    NARCIS (Netherlands)

    Sizoo, E.M.; Pasman, H.R.W.; Dirven, L.; Marosi, C.; Grisold, W.; Stockhammer, G.; Egeter, J.; Grant, R.; Chang, S.; Heimans, J.J.; Deliens, L.; Reijneveld, J.C.; Taphoorn, M.J.B.

    2014-01-01

    Background: High-grade gliomas (HGG) are rare and incurable; yet, these neoplasms result in a disproportionate share of cancer morbidity and mortality. Treatment of HGG patients is directed not merely towards prolonging life but also towards quality of life, which becomes the major goal in the end

  9. Reirradiation and lomustine in patients with relapsed high-grade gliomas

    International Nuclear Information System (INIS)

    Arcicasa, Mauro; Roncadin, Mario; Bidoli, Ettore; Dedkov, Anatolyi; Gigante, Marco; Trovo, Mauro G.

    1999-01-01

    Purpose: The aim of this study was to evaluate the toxicity, response, and survival of patients with relapsed high-grade gliomas after radiation therapy (RT) combined with lomustine (CCNU). Methods and Materials: Thirty-one patients with relapsed gliomas at least 6 months after completion of RT were reirradiated. Twenty-four patients had a pathological diagnosis of high-grade gliomas, whereas 7 had a radiological diagnosis of relapsed malignant gliomas. The study focused on patients with high-grade relapsed gliomas. A total dose of 34.5 Gy was delivered in 23 fractions over 4.5 weeks. Oral administration of CCNU (130 mg/m 2 ) was begun at the same time as RT, and was repeated every 6 weeks until disease progression, or up to 12 courses. Results: Twelve of 24 patients had surgery before RT plus CCNU treatment. Median interval between RT courses was 14 months (range 6-73). All patients received a complete course of RT, and 22 of 24 patients received at least one course of CCNU. Objective responses were seen in 14 evaluable patients: 3 with partial response, 5 with stable disease, and 6 with progressive disease. Duration of partial response was 20, 9, and 8 months. Median time to progression and overall survival from the onset of retreatment were 8.4 months (range 1-22) and 13.7 months (range 1-63+), respectively. One case of G4 thrombocytopenia was observed. Five patients had G1 or G2 leucopenia and 3 patients had G3 leucopenia. Moderate nausea and vomiting were reported in 4 patients. One patient, after one course of CCNU, refused further chemotherapy. No significant difference in survival from relapse was found between patients who underwent surgery before RT plus CCNU and those who received only RT plus CCNU (p = 0.74). Conclusion: Overall, the acute toxicity was moderate, and patient compliance was good. Reirradiation of high-grade glioma was associated with modest subjective and objective response rates. It is remarkable that median overall survival from relapse

  10. Local injection of the 90Y-labelled peptidic vector DOTATOC to control gliomas of WHO grades II and III: an extended pilot study

    International Nuclear Information System (INIS)

    Schumacher, T.; Mueller-Brand, J.; Hofer, S.; Wasner, M.; Zimmerer, S.; Gratzl, O.; Merlo, A.; Eichhorn, K.; Freitag, P.; Probst, A.; Reubi, J.-C.; Maecke, H.R.

    2002-01-01

    We have previously presented preliminary observations on targeting somatostatin receptor-positive malignant gliomas of all grades by local injection of the radiolabelled peptidic vector 90 Y-DOTATOC. We now report on our more thorough clinical experience with this novel compound, focussing on low-grade and anaplastic gliomas. Small peptidic vectors have the potential to target invisible infiltrative disease within normal surrounding brain tissue, thereby opening a window of opportunity for early intervention. Five progressive gliomas of WHO grades II and III and five extensively debulked low-grade gliomas were treated with varying fractions of 90 Y-DOTATOC. The vectors were locally injected into the resection cavity or into solid tumour. The activity per single injection ranged from 555 to 1,875 MBq, and the cumulative activity from 555 to 7,030 MBq, according to tumour volumes and eloquence of the affected brain area, yielding dose estimates from 76±15 to 312±62 Gy. Response was assessed by the clinical status, by steroid dependence and, every 4-6 months, by magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography. In the five progressive gliomas, lasting responses were obtained for at least 13-45 months without the need for steroids. Radiopeptide brachytherapy had been the only modality applied to counter tumour progression. Interestingly, we observed the slow transformation of a solid, primarily inoperable anaplastic astrocytoma into a resectable multi-cystic lesion 2 years after radiopeptide brachytherapy. Based on these observations, we also assessed the feasibility of local radiotherapy following extensive debulking, which was well tolerated. Targeted beta-particle irradiation based on diffusible small peptidic vectors appears to be a promising modality for the treatment of malignant gliomas. (orig.)

  11. C-MET overexpression and amplification in gliomas.

    Science.gov (United States)

    Kwak, Yoonjin; Kim, Seong-Ik; Park, Chul-Kee; Paek, Sun Ha; Lee, Soon-Tae; Park, Sung-Hye

    2015-01-01

    We investigated c-Met overexpression and MET gene amplification in gliomas to determine their incidence and prognostic significance. c-Met immunohistochemistry and MET gene fluorescence in situ hybridization were carried out on tissue microarrays from 250 patients with gliomas (137 grade IV GBMs and 113 grade II and III diffuse gliomas). Clinicopathological features of these cases were reviewed. c-Met overexpression and MET gene amplification were detected in 13.1% and 5.1% of the GBMs, respectively. All the MET-amplified cases showed c-Met overexpression, but MET amplification was not always concordant with c-Met overexpression. None of grade II and III gliomas demonstrated c-Met overexpression or MET gene amplification. Mean survival of the GBM patients with MET amplification was not significantly different from patients without MET amplification (P=0.155). However, GBM patients with c-Met overexpression survived longer than patients without c-Met overexpression (P=0.035). Although MET amplification was not related to poor GBM prognosis, it is partially associated with the aggressiveness of gliomas, as MET amplification was found only in grade IV, not in grade II and III gliomas. We suggest that MET inhibitor therapy may be beneficial in about 5% GBMs, which was the incidence of MET gene amplification found in the patients included in this study.

  12. Decreased FOXD3 Expression Is Associated with Poor Prognosis in Patients with High-Grade Gliomas.

    Directory of Open Access Journals (Sweden)

    Wei Du

    Full Text Available The transcription factor forkhead box D3 (FOXD3 plays important roles in the development of neural crest and has been shown to suppress the development of various cancers. However, the expression and its potential biological roles of FOXD3 in high-grade gliomas (HGGs remain unknown.The mRNA and protein expression levels of FOXD3 were examined using real-time quantitative PCR and western blotting in 23 HGG and 13 normal brain samples, respectively. Immunohistochemistry was used to validate the expression FOXD3 protein in 184 HGG cases. The association between FOXD3 expression and the prognosis of HGG patients were analyzed using Kaplan-Meier survival curves and Cox proportional hazards regression models. In addition, we further examined the effects of FOXD3 on the proliferation and serum starvation-induced apoptosis of glioma cells.In comparison to normal brain tissues, FOXD3 expression was significantly decreased in HGG tissues at both mRNA and protein levels. Immunohistochemistry further validated the expression of FOXD3 in HGG tissues. Moreover, low FOXD3 expression was significantly associated with poor prognosis in HGG patients. Depletion of FOXD3 expression promoted glioma cell proliferation and inhibited serum starvation-induced apoptosis, whereas overexpression of FOXD3 inhibited glioma cell proliferation and promoted serum starvation-induced apoptosis.Our results indicated that FOXD3 might serve as an independent prognostic biomarker and a potential therapeutic target for HGGs, which warrant further investigation.

  13. Neural Networks Mediating High-Level Mentalizing in Patients With Right Cerebral Hemispheric Gliomas

    Directory of Open Access Journals (Sweden)

    Riho Nakajima

    2018-03-01

    Full Text Available Mentalizing is the ability to understand others’ mental state through external cues. It consists of two networks, namely low-level and high-level metalizing. Although it is an essential function in our daily social life, surgical resection of right cerebral hemisphere disturbs mentalizing processing with high possibility. In the past, little was known about the white matter related to high-level mentalizing, and the conservation of high-level mentalizing during surgery has not been a focus of attention. Therefore, the main purpose of this study was to examine the neural networks underlying high-level mentalizing and then, secondarily, investigate the usefulness of awake surgery in preserving the mentalizing network. A total of 20 patients with glioma localized in the right hemisphere who underwent awake surgery participated in this study. All patients were assigned to two groups: with or without intraoperative assessment of high-level mentalizing. Their high-level mentalizing abilities were assessed before surgery and 1 week and 3 months after surgery. At 3 months after surgery, only patients who received the intraoperative high-level mentalizing test showed the same score as normal healthy volunteers. The tract-based lesion symptom analysis was performed to confirm the severity of damage of associated fibers and high-level mentalizing accuracy. This analysis revealed the superior longitudinal fascicles (SLF III and fronto-striatal tract (FST to be associated with high-level mentalizing processing. Moreover, the voxel-based lesion symptom analysis demonstrated that resection of orbito-frontal cortex (OFC causes persistent mentalizing dysfunction. Our study indicates that damage of the OFC and structural connectivity of the SLF and FST causes the disorder of mentalizing after surgery, and assessing high-level mentalizing during surgery may be useful to preserve these pathways.

  14. EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss.

    Science.gov (United States)

    Sampson, John H; Choi, Bryan D; Sanchez-Perez, Luis; Suryadevara, Carter M; Snyder, David J; Flores, Catherine T; Schmittling, Robert J; Nair, Smita K; Reap, Elizabeth A; Norberg, Pamela K; Herndon, James E; Kuan, Chien-Tsun; Morgan, Richard A; Rosenberg, Steven A; Johnson, Laura A

    2014-02-15

    Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to significant toxicity. Preclinical studies have been limited by the use of xenograft models that do not adequately recapitulate the immune system of a clinically relevant host. A constitutively activated mutant of the naturally occurring epidermal growth factor receptor (EGFRvIII) is antigenically identical in both human and mouse glioma, but is also completely absent from any normal tissues. We developed a third-generation, EGFRvIII-specific murine CAR (mCAR), and performed tests to determine its efficacy in a fully immunocompetent mouse model of malignant glioma. At elevated doses, infusion with EGFRvIII mCAR T cells led to cures in all mice with brain tumors. In addition, antitumor efficacy was found to be dependent on lymphodepletive host conditioning. Selective blockade with EGFRvIII soluble peptide significantly abrogated the activity of EGFRvIII mCAR T cells in vitro and in vivo, and may offer a novel strategy to enhance the safety profile for CAR-based therapy. Finally, mCAR-treated, cured mice were resistant to rechallenge with EGFRvIII(NEG) tumors, suggesting generation of host immunity against additional tumor antigens. All together, these data support that third-generation, EGFRvIII-specific mCARs are effective against gliomas in the brain and highlight the importance of syngeneic, immunocompetent models in the preclinical evaluation of tumor immunotherapies. ©2013 AACR

  15. Sequential Apparent Diffusion Coefficient for Assessment of Tumor Progression in Patients with Low-Grade Glioma.

    Science.gov (United States)

    Chen, I E; Swinburne, N; Tsankova, N M; Hefti, M M; Aggarwal, A; Doshi, A H; Hormigo, A; Delman, B N; Nael, K

    2018-04-19

    Early and accurate identification of tumor progression in patients with low-grade gliomas is challenging. We aimed to assess the role of quantitative ADC analysis in the sequential follow-up of patients with low-grade gliomas as a potential imaging marker of tumor stability or progression. In this retrospective study, patients with a diagnosis of low-grade glioma with at least 12 months of imaging follow-up were retrospectively reviewed. Two neuroradiologists independently reviewed sequential MR imaging in each patient to determine tumor progression using the Response Assessment in Neuro-Oncology criteria. Normalized mean ADC (ADC mean ) and 10th percentile ADC (ADC 10 ) values from FLAIR hyperintense tumor volume were calculated for each MR image and compared between patients with stable disease versus tumor progression using univariate analysis. The interval change of ADC values between sequential scans was used to differentiate stable disease from progression using the Fisher exact test. Twenty-eight of 69 patients who were evaluated met our inclusion criteria. Fifteen patients were classified as stable versus 13 patients as having progression based on consensus reads of MRIs and the Response Assessment in Neuro-Oncology criteria. The interval change of ADC values showed greater concordance with ultimate lesion disposition than quantitative ADC values at a single time point. The interval change in ADC 10 matched the expected pattern in 12/13 patients with tumor progression (overall diagnostic accuracy of 86%, P average, the ADC 10 interval change predicted progression 8 months before conventional MR imaging. The interval change of ADC 10 values can be used to identify progression versus stability of low-grade gliomas with a diagnostic accuracy of 86% and before apparent radiologic progression on conventional MR imaging. © 2018 by American Journal of Neuroradiology.

  16. Health-related quality of life in patients with high-grade gliomas

    DEFF Research Database (Denmark)

    Piil, K; Jakobsen, J; Christensen, Karl Bang

    2015-01-01

    follow-up after 1 year. Scores of Karnofsky Performance Status (KPS), physical activity, anxiety and depression and health-related quality of life (FACT-Br) are obtained. Patients' physical activity level and KPS decrease during the disease- and treatment trajectory. The majority of patients did......The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity...... levels, prevalence and severity of anxiety and depressive symptoms and health-related quality of life among patients with a highgrade glioma. This paper is based on a longitudinal mixed methods study. Patients (n = 30) completed questionnaires at 5 time points from time of diagnosis until the final...

  17. ACE I/D sequence variants but not MTHFR C677T, is strongly linked to malignant glioma risk and its variant DD genotype may act as a promising predictive biomarker for overall survival of glioma patients.

    Science.gov (United States)

    Pandith, Arshad A; Qasim, Iqbal; Zahoor, Wani; Shah, Parveen; Bhat, Abdul R

    2018-01-10

    ACE I/D and MTHFR C677T gene polymorphisms can be seen as candidate genes for glioma on the basis of their biological functions and their involvement in different cancers. The aim of this study was to analyze potential association and overall survival between MTHFR C677T and ACE I/D polymorphism in glioma patients in our population. We tested genotype distribution of 112 glioma patients against 141 cancer-free controls from the same region. Kaplan-Meier survival analysis was performed to evaluate overall survival of patients for both genes. No significant differences were found among MTHFR C677T wild type C and variant genotypes CT/TT with glioma patients. In ACE, the distribution of variant ID and DD was found to be significantly higher in glioma cases as compared to controls (pACE DD genotypes were highly presented in glioma cases 26.8% versus 10.6% in controls (pACE DD genotypes had the least estimated overall survival of 13.4months in comparison to 21. 7 and 17.6months for ACE II and I/D genotypes respectively. We conclude ACE I/D polymorphism plays a vital role in predisposition of higher risk for glioma. We also suggest that ACE DD genotypes may act as an important predictive biomarker for overall survival of glioma patients. Copyright © 2017. Published by Elsevier B.V.

  18. Concurrent radiotherapy: fotemustine combination for newly diagnosed malignant glioma patients, a phase II study.

    Science.gov (United States)

    Beauchesne, Patrick D; Taillandier, L; Bernier, V; Carnin, C

    2009-06-01

    Fotemustine is a nitrosourea compound used for the treatment of malignant gliomas, especially in France. Recently, an EORTC-NCIC study has shown that a concomitant combination of radiotherapy plus temozolomide (an oral cytotoxic drug) improved survival in glioblastoma patients. We set out to test a concurrent combination of radiotherapy and fotemustine for newly malignant gliomas. A prospective single-center phase II study opened for accrual in September 2004. Patients over 18 years of age able to give informed consent and with histologically proven, newly diagnosed supratentorial malignant gliomas were eligible. All patients were treated by a standard cranial irradiation (conformal irradiation, tumor bulk plus a margin of 2.5 cm) and concomitant daily administration of 10 mg/m(2) of fotemustine (5 days per week, 6 weeks, 1 h 30 min before radiation therapy). Adjuvant chemotherapy, fotemustine, was administered at tumor progression as standard and classic regimen. Twenty-two patients were enrolled, 16 men and 6 women, median age 56 years (range 32-74), median Karnofsky performance status 70 (range 60-90). Histology included 16 glioblastomas, 3 anaplastic astrocytomas, 2 anaplastic oligodendrogliomas and 1 mixed glioma. Eight patients underwent surgery (three total resections). Fourteen patients had a stereotactic biopsy. The concurrent radiotherapy-fotemustine combination was well tolerated: toxicity was mild and three hematologic toxicities grade 3-4 were observed. Median survival from the initial diagnosis was 9.9 months, two patients are currently alive. Median survival was 11 months for surgery and 9 months for stereotactic biopsy. Concomitant radiotherapy-fotemustine combination is safe and well tolerated. Overall survival of over 10 months for the whole population compares favorably with other reports.

  19. Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma

    Science.gov (United States)

    2018-06-18

    Constitutional Mismatch Repair Deficiency Syndrome; Lynch Syndrome; Malignant Glioma; Progressive Ependymoma; Progressive Medulloblastoma; Recurrent Brain Neoplasm; Recurrent Childhood Ependymoma; Recurrent Diffuse Intrinsic Pontine Glioma; Recurrent Medulloblastoma; Refractory Brain Neoplasm; Refractory Diffuse Intrinsic Pontine Glioma; Refractory Ependymoma; Refractory Medulloblastoma

  20. Quality assurance in the EORTC 22033–26033/CE5 phase III randomized trial for low grade glioma: The digital individual case review

    International Nuclear Information System (INIS)

    Fairchild, Alysa; Weber, Damien C.; Bar-Deroma, Raquel; Gulyban, Akos; Fenton, Paul A.; Stupp, Roger; Baumert, Brigitta G.

    2012-01-01

    Introduction: The phase III EORTC 22033–26033/NCIC CE5 intergroup trial compares 50.4 Gy radiotherapy with up-front temozolomide in previously untreated low-grade glioma. We describe the digital EORTC individual case review (ICR) performed to evaluate protocol radiotherapy (RT) compliance. Methods: Fifty-eight institutions were asked to submit 1–2 randomly selected cases. Digital ICR datasets were uploaded to the EORTC server and accessed by three central reviewers. Twenty-seven parameters were analysed including volume delineation, treatment planning, organ at risk (OAR) dosimetry and verification. Consensus reviews were collated and summary statistics calculated. Results: Fifty-seven of seventy-two requested datasets from forty-eight institutions were technically usable. 31/57 received a major deviation for at least one section. Relocation accuracy was according to protocol in 45. Just over 30% had acceptable target volumes. OAR contours were missing in an average of 25% of cases. Up to one-third of those present were incorrectly drawn while dosimetry was largely protocol compliant. Beam energy was acceptable in 97% and 48 patients had per protocol beam arrangements. Conclusions: Digital RT plan submission and review within the EORTC 22033–26033 ICR provide a solid foundation for future quality assurance procedures. Strict evaluation resulted in overall grades of minor and major deviation for 37% and 32%, respectively.

  1. Profound tumor-specific Th2 bias in patients with malignant glioma

    International Nuclear Information System (INIS)

    Shimato, Shinji; Maier, Lisa M; Maier, Richard; Bruce, Jeffrey N; Anderson, Richard CE; Anderson, David E

    2012-01-01

    Vaccination against tumor-associated antigens is one promising approach to immunotherapy against malignant gliomas. While previous vaccine efforts have focused exclusively on HLA class I-restricted peptides, class II-restricted peptides are necessary to induce CD4 + helper T cells and sustain effective anti-tumor immunity. In this report we investigated the ability of five candidate peptide epitopes derived from glioma-associated antigens MAGE and IL-13 receptor α2 to detect and characterize CD4 + helper T cell responses in the peripheral blood of patients with malignant gliomas. Primary T cell responses were determined by stimulating freshly isolated PBMCs from patients with primary glioblastoma (GBM) (n = 8), recurrent GBM (n = 5), meningioma (n = 7), and healthy controls (n = 6) with each candidate peptide, as well as anti-CD3 monoclonal antibody (mAb) and an immunodominant peptide epitope derived from myelin basic protein (MBP) serving as positive and negative controls, respectively. ELISA was used to measure IFN-γ and IL-5 levels, and the ratio of IFN-γ/IL-5 was used to determine whether the response had a predominant Th1 or Th2 bias. We demonstrate that novel HLA Class-II restricted MAGE-A3 and IL-13Rα2 peptides can detect T cell responses in patients with GBMs as well as in healthy subjects. Stimulation with a variety of peptide antigens over-expressed by gliomas is associated with a profound reduction in the IFN-γ/IL-5 ratio in GBM patients relative to healthy subjects. This bias is more pronounced in patients with recurrent GBMs. Therapeutic vaccine strategies to shift tumor antigen-specific T cell response to a more immunostimulatory Th1 bias may be needed for immunotherapeutic trials to be more successful clinically

  2. Palliative Care Options for a Young Adult Patient with a Diffuse Intrinsic Pontine Glioma.

    Science.gov (United States)

    Sison, Julian; Tran, Hung; Margol, Ashley; Tiwari, Nishant; Garcia, Karla M; Cotter, Jennifer; Kiehna, Erin; Olch, Arthur J; Wong, Kenneth

    2017-08-18

    Diffuse intrinsic pontine gliomas (DIPGs) are rare but devastating brain tumors that occur primarily in children. These gliomas have poor prognoses and present options focus on palliation of symptoms and prolongation of life. Here, we present a case of a 16-year-old female diagnosed with a DIPG whose age group has been mostly left out of discussions regarding psychosocial support options. This report is meant to start a conversation about the different support options available at our institution that have shown promising results in the literature for palliative care applications. These options can include camps for patients with brain tumors, psychological counseling, the Ronald McDonald House, and other psychosocial programs. Many of these programs can be tailored to meet the specific needs of adolescent and young adult (AYA) patients and will hopefully be integrated into a comprehensive palliative care regimen in future studies.

  3. Inter-hemispheric language functional reorganization in low-grade glioma patients after tumour surgery.

    Science.gov (United States)

    Kristo, Gert; Raemaekers, Mathijs; Rutten, Geert-Jan; de Gelder, Beatrice; Ramsey, Nick F

    2015-03-01

    Despite many claims of functional reorganization following tumour surgery, empirical studies that investigate changes in functional activation patterns are rare. This study investigates whether functional recovery following surgical treatment in patients with a low-grade glioma in the left hemisphere is linked to inter-hemispheric reorganization. Based on literature, we hypothesized that reorganization would induce changes in the spatial pattern of activation specifically in tumour homologue brain areas in the healthy right hemisphere. An experimental group (EG) of 14 patients with a glioma in the left hemisphere near language related brain areas, and a control group of 6 patients with a glioma in the right, non-language dominant hemisphere were scanned before and after resection. In addition, an age and gender matched second control group of 18 healthy volunteers was scanned twice. A verb generation task was used to map language related areas and a novel technique was used for data analysis. Contrary to our hypothesis, we found that functional recovery following surgery of low-grade gliomas cannot be linked to functional reorganization in language homologue brain areas in the healthy, right hemisphere. Although elevated changes in the activation pattern were found in patients after surgery, these were largest in brain areas in proximity to the surgical resection, and were very similar to the spatial pattern of the brain shift following surgery. This suggests that the apparent perilesional functional reorganization is mostly caused by the brain shift as a consequence of surgery. Perilesional functional reorganization can however not be excluded. The study suggests that language recovery after transient post-surgical language deficits involves recovery of functioning of the presurgical language system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Treatment of Malignant Gliomas in Elderly Patients: A Concise Overview of the Literature

    Directory of Open Access Journals (Sweden)

    Patrizia Farina

    2014-01-01

    Full Text Available Gliomas are the most frequent primary brain tumors and the incidence data has increased in the elderly population. Unfortunately, prospective studies on this population are few and so the right treatment is unknown. In the elderly patients no standard treatment has been established and therefore the optimal treatment should be individualized. We performed a review analyzing the prognostic and predictive factors, the clinical studies, and the correct management of this population.

  5. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study.

    Science.gov (United States)

    Phuphanich, Surasak; Baker, Sharyn D; Grossman, Stuart A; Carson, Kathryn A; Gilbert, Mark R; Fisher, Joy D; Carducci, Michael A

    2005-04-01

    We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 muM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme-inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants.

  6. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: A dose escalation and pharmacologic study1

    Science.gov (United States)

    Phuphanich, Surasak; Baker, Sharyn D.; Grossman, Stuart A.; Carson, Kathryn A.; Gilbert, Mark R.; Fisher, Joy D.; Carducci, Michael A.

    2005-01-01

    We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 μM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme–inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants. PMID:15831235

  7. Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta [Humanitas Clinical and Research Hospital, Nuclear Medicine, Humanitas Cancer Center, Rozzano, MI (Italy); Riva, Marco; Raneri, Fabio; Pessina, Federico [Humanitas Clinical and Research Hospital, Neurosurgery, Rozzano, Milan (Italy); Olivari, Laura; Rossi, Marco; Alfieri, Tommaso [Universita degli Studi di Milano, Milan (Italy); Soffietti, Riccardo; Ruda, Roberta [University and City of Health and Science Hospital, Neuro-Oncology, Turin (Italy); Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine, Genova (Italy); Bizzi, Alberto [Fondazione IRCCS Istituto Neurologico Carlo Besta, Neuroradiology, Milan (Italy); Navarria, Pierina; Ascolese, Anna Maria [Humanitas Clinical and Research Hospital, Radiosurgery and Radiotherapy, Rozzano, Milan (Italy); Fernandes, Bethania [Humanitas Clinical and Research Hospital, Pathology, Rozzano, Milan (Italy); Grimaldi, Marco [Humanitas Clinical and Research Hospital, Medical Oncology, Rozzano, Milan (Italy); Simonelli, Matteo; Zucali, Paolo Andrea [Humanitas Clinical and Research Hospital, Radiology Department, Rozzano, Milan (Italy); Scorsetti, Marta [Humanitas Clinical and Research Hospital, Pathology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Bello, Lorenzo [Humanitas Clinical and Research Hospital, Neurosurgery, Rozzano, Milan (Italy); Universita degli Studi di Milano, Milan (Italy); Chiti, Arturo [Humanitas Clinical and Research Hospital, Nuclear Medicine, Humanitas Cancer Center, Rozzano, MI (Italy); Humanitas University, Rozzano, Milan (Italy)

    2017-07-15

    We evaluated the relationship between {sup 11}C-methionine PET ({sup 11}C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative {sup 11}C-METH PET were analysed. Semiquantitative evaluation of the {sup 11}C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months). In all patients, the tumour was identified on {sup 11}C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis. {sup 11}C-METH PET parameters are significantly correlated with histological grade and IDH1

  8. Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice

    Science.gov (United States)

    Weller, Michael; Stupp, Roger; Hegi, Monika E.; van den Bent, Martin; Tonn, Joerg C.; Sanson, Marc; Wick, Wolfgang; Reifenberger, Guido

    2012-01-01

    Histological subtyping and grading by malignancy are the cornerstones of the World Health Organization (WHO) classification of tumors of the central nervous system. They shall provide clinicians with guidance as to the course of disease to be expected and the choices of treatment to be made. Nonetheless, patients with histologically identical tumors may have very different outcomes, notably in patients with astrocytic and oligodendroglial gliomas of WHO grades II and III. In gliomas of adulthood, 3 molecular markers have undergone extensive studies in recent years: 1p/19q chromosomal codeletion, O6-methylguanine methyltransferase (MGMT) promoter methylation, and mutations of isocitrate dehydrogenase (IDH) 1 and 2. However, the assessment of these molecular markers has so far not been implemented in clinical routine because of the lack of therapeutic implications. In fact, these markers were considered to be prognostic irrespective of whether patients were receiving radiotherapy (RT), chemotherapy, or both (1p/19q, IDH1/2), or of limited value because testing is too complex and no chemotherapy alternative to temozolomide was available (MGMT). In 2012, this situation has changed: long-term follow-up of the Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951 trials demonstrated an overall survival benefit from the addition to RT of chemotherapy with procarbazine/CCNU/vincristine confined to patients with anaplastic oligodendroglial tumors with (vs without) 1p/19q codeletion. Furthermore, in elderly glioblastoma patients, the NOA-08 and the Nordic trial of RT alone versus temozolomide alone demonstrated a profound impact of MGMT promoter methylation on outcome by therapy and thus established MGMT as a predictive biomarker in this patient population. These recent results call for the routine implementation of 1p/19q and MGMT testing at least in subpopulations of malignant glioma patients and represent an encouraging

  9. Increased Expression of microRNA-17 Predicts Poor Prognosis in Human Glioma

    Directory of Open Access Journals (Sweden)

    Shengkui Lu

    2012-01-01

    Full Text Available Aim. To investigate the clinical significance of microRNA-17 (miR-17 expression in human gliomas. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR analysis was used to characterize the expression patterns of miR-17 in 108 glioma and 20 normal brain tissues. The associations of miR-17 expression with clinicopathological factors and prognosis of glioma patients were also statistically analyzed. Results. Compared with normal brain tissues, miR-17 expression was significantly higher in glioma tissues (P<0.001. In addition, the increased expression of miR-17 in glioma was significantly associated with advanced pathological grade (P=0.006 and low Karnofsky performance score (KPS, P=0.01. Moreover, Kaplan-Meier survival and Cox regression analyses showed that miR-17 overexpression (P=0.008 and advanced pathological grade (P=0.02 were independent factors predicting poor prognosis for gliomas. Furthermore, subgroup analyses showed that miR-17 expression was significantly associated with poor overall survival in glioma patients with high pathological grades (for grade III~IV: P<0.001. Conclusions. Our data offer the convinced evidence that the increased expression of miR-17 may have potential value for predicting poor prognosis in glioma patients with high pathological grades, indicating that miR-17 may contribute to glioma progression and be a candidate therapeutic target for this disease.

  10. Imaging of Non— or Very Subtle Contrast-Enhancing Malignant Gliomas with [11C]-Methionine Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Norbert Galldiks

    2011-11-01

    Full Text Available In patients with World Health Organization (WHO grade III glioma with a lack of or minimal (2 lesion and reached beyond it (in 10 of 12 MRIs/MET-PET scans. The present data suggest that in patients with WHO grade III glioma with minimal or a lack of contrast enhancement, MET-PET delineates metabolically active tumor tissue. These findings support the use of combined PET-MRI with radiolabeled amino acids (eg, MET for the delineating of the true extent of active tumor in the diagnosis and treatment planning of patients with gliomas.

  11. Antithrombin III for critically ill patients

    DEFF Research Database (Denmark)

    Allingstrup, Mikkel; Wetterslev, Jørn; Ravn, Frederikke B

    2016-01-01

    Background: Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation...... in critically ill patients are unknown. This review was published in 2008 and updated in 2015.  Objectives: To examine: 1. The effect of AT III on mortality in critically ill participants. 2. The benefits and harms of AT III. We investigated complications specific and not specific to the trial intervention......, bleeding events, the effect on sepsis and disseminated intravascular coagulation (DIC) and the length of stay in the intensive care unit (ICU) and in hospital in general.  Search methods: We searched the following databases from inception to 27 August 2015: Cochrane Central Register of Controlled Trials...

  12. 11C-methionine PET as a prognostic marker in patients with glioma: comparison with18F-FDG PET

    International Nuclear Information System (INIS)

    Kim, Sungeun; Chung, June-Key; Jeong, Jae Min; Im, So-Hyang; Kim, Dong Gyu; Jung, Hee Won; Lee, Dong Soo; Lee, Myung Chul

    2005-01-01

    The purpose of this study was to compare the prognostic value of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in glioma patients. The study population comprised 47 patients with gliomas (19 glioblastoma, 28 others). Pretreatment magnetic resonance imaging, MET PET and FDG PET were performed within a time interval of 2 weeks in all patients. The uptake ratio and standard uptake values were calculated. Univariate and multivariate analyses were done to determine significant prognostic factors. Ki-67 index was measured by immunohistochemical staining, and compared with FDG and MET uptake in glioma. Among the several clinicopathological prognostic factors, tumour pathology (glioblastoma or not), age (≥60 or <60 years), Karnofsky performance status (KPS) (≥70 or <70) and MET PET (higher uptake or not compared with normal cortex) were found to be significant predictors by univariate analysis. In multivariate analysis, tumour pathology, KPS and MET PET were identified as significant independent predictors. The Ki-67 proliferation index was significantly correlated with MET uptake (r=0.64), but not with FDG uptake. Compared with FDG PET in glioma, MET PET was an independent significant prognostic factor and MET uptake was correlated with cellular proliferation. MET PET may be a useful biological prognostic marker in glioma patients. (orig.)

  13. Needs and preferences among patients with high-grade glioma and their caregivers - A longitudinal mixed methods study

    DEFF Research Database (Denmark)

    Piil, K; Jakobsen, J; Christensen, K B

    2018-01-01

    Previous reports on the patient perspective of daily life during a 1-year high-grade glioma (HGG) trajectory from the time of diagnosis are sparse. The aim of this longitudinal mixed methods study is to identify the specific needs and preferences for rehabilitation and supportive care and how...... it links with physical activity, psychological measures and health quality longitudinally over the first year after diagnosis among patients with HGG and their caregivers by integrating qualitative and quantitative findings. Using a longitudinal mixed methods design, patients with malignant glioma (n = 30...

  14. Increased seroreactivity to glioma-expressed antigen 2 in brain tumor patients under radiation.

    Directory of Open Access Journals (Sweden)

    Sabrina M Heisel

    Full Text Available BACKGROUND: Surgery and radiation are the mainstays of therapy for human gliomas that are the most common primary brain tumors. Most recently, cell culture and animal studies provided the first convincing evidence that radiation not only eliminates tumor cells, but also modulates the immune response and likely improves anti-tumor immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: We present an in vivo study that analyzes the effects of radiation on the immune response in tumor patients. As readout system, we utilized the reactivity of glioma patients' sera against antigen GLEA2 as the most frequent antigen immunogenic in glioblastoma patients. We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months. As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients. We compared the course of GLEA2 seroreactivity at different times prior, during and after radiation. The GLEA2 seroreactivity was increased by the time of surgery, decreased after surgery, increased again under radiation, and slightly decreased after radiation. CONCLUSIONS/SIGNIFICANCE: Our results provide in vivo evidence for an increased antibody response against tumor antigens under radiation. Antigens that become immunogenic with an increased antibody response as result of radiation can serve as ideal targets for immunotherapy of human tumors.

  15. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    Science.gov (United States)

    2017-11-07

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  16. Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab.

    Science.gov (United States)

    Bahrami, N; Piccioni, D; Karunamuni, R; Chang, Y-H; White, N; Delfanti, R; Seibert, T M; Hattangadi-Gluth, J A; Dale, A; Farid, N; McDonald, C R

    2018-04-05

    Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis-edge contrast-improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival ( P = .009) and overall survival ( P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ 2 = 8.3, P = .003) and overall survival (log-rank χ 2 = 5.5, P = .019). Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas. © 2018 by American Journal of Neuroradiology.

  17. {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography for grading and estimation of prognosis in patients with intracranial gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Gempt, Jens, E-mail: jens.gempt@tum.de [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Bette, Stefanie; Ryang, Yu-Mi; Buchmann, Niels; Peschke, Patrick [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Pyka, Thomas; Wester, Hans-Jürgen; Förster, Stefan [Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Meyer, Bernhard; Ringel, Florian [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany)

    2015-05-15

    Highlights: • The aim of the present study was to evaluate the use of {sup 18}F-FET-PET (FET-PET) for the grading and estimation of prognosis in newly diagnosed patients with intracranial gliomas in a clinical setting. • One hundred fifty-two patients (39 WHO II, 26 WHO III, 87 WHO IV) were included. The median T/N ratio of low-grade glioma patients was 1.65 (1.1–3.7), and 3.14 (1.61–8.1, p < 0.001) in high-grade glioma patients. • The test of the maximally selected log-rank statistic resulted in a T/N ratio of 1.88 as the cut-off value, with the greatest difference in overall survival between patients with longer and shorter survival. • Regarding the prognostic validity for overall survival ROC-curves display an AUC of 0.847 for the 48-month survival for T/N ratio and MRI contrast-enhancement. • Our study suggests that FET-PET can predict prognosis and survival in patients harboring intracranial gliomas. - Abstract: Introduction: Histopathological examination is the standard for grading and determination of diagnosis in intrinsic brain tumors though the possibility of malignization and tumor heterogeneity always bears the possibility of tumor under-grading or misjudgement regarding the estimation of prognosis. The aim of the present study was to evaluate the use of {sup 18}F-FET-PET (FET-PET) for the grading and estimation of prognosis in newly diagnosed patients with intracranial gliomas in a clinical setting. Methods: Patients who were treated for a newly diagnosed intracranial glioma between January 2007 and May 2012, and had a preoperative FET-PET and MRI scan between were included. The ratio of counts in a tumor VOI (volume of interest) with maximum uptake to the respective counts in a background VOI was calculated to provide the tumor-to-normal (T/N) ratio. The clinical and histopathological data (tumor grading, pre- and postoperative neurological status, Karnofsky Performance Status Scale scores, and overall survival rates) were recorded

  18. Neutron capture therapy of epidermal growth factor receptor (EGFR)vIII positive gliomas using boronated monoclonal antibody L8A4

    International Nuclear Information System (INIS)

    Yang, Weilian; Barth, Rolf F.; Wu, Gong

    2006-01-01

    The purpose of the present study was to evaluate the EGFRvIII specific monoclonal antibody, L8A4 as a boron delivery agent for NCT of the receptor (+) rat glioma, F98 npEGFRvIII . A heavily boronated polyamidoamine (PAMAM) dendrimer (BD) was linked to L8A4 by means of heterobifunctional reagents. Wild type (F98 WT ) receptor(-) or EGFRvIII human gene transfected receptor(+) F98 npEGFRvIII glioma cells were implanted into the brains of Fischer rats. Biodistribution studies were initiated 14 d later. Animals received 125 I-labeled BD-L8A4 by either convection enhanced delivery (CED) or intratumoral(i.t.) injection and were euthanized 6, 12, 24 or 48 h later. At 6 h following CED, equivalent amounts of the bioconjugate were detected in receptor(+) and (-) tumors, but by 24 h the amounts retained by receptor(+) gliomas were 60.1% following CED and 43.7% following i.t. injection, compared to 14.6% ID/g by receptor(-) tumors. Tumor boron concentrations were 32.7 and 44.5 μg/g, respectively, for BD-L8A4 alone or in combination with i.v. BPA. BNCT was carried out at the MITR-II Reactor 24 h after CED of BD-L8A4 (∼40 μg 10 B/∼750 μg protein) and 2.5 h after i.v. injection of BPA (500 mg/kg). Rats that received BD-L8A4 alone or in combination with BPA had mean survival times of 70.4 and 85d, respectively, with 20% and 10% long term survivors, respectively, compared to 40.1 d for i.v. BPA and 30.3 and 26.3 d for irradiated and untreated controls, respectively. These data convincingly demonstrate the therapeutic efficacy of molecular targeting of EGFRvIII and should provide a platform for the future development of combinations of high and low molecular weight delivery agents for BNCT of brain tumors. (author)

  19. Description of selected characteristics of familial glioma patients – Results from the Gliogene Consortium

    DEFF Research Database (Denmark)

    Sadetzki, Siegal; Bruchim, Revital; Oberman, Bernice

    2013-01-01

    While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained ...

  20. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  1. NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma

    DEFF Research Database (Denmark)

    Liu, Zhenjiang; Poiret, Thomas; Persson, Oscar

    2018-01-01

    The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO...

  2. High-grade glioma in a patient with breast cancer

    Directory of Open Access Journals (Sweden)

    Che-Chao Chang

    2014-07-01

    Full Text Available Breast cancer is one of the most common origins of metastatic lesions in the central nervous system. Many patients with a breast cancer and concurrent brain tumor(s were diagnosed to have a metastatic lesion or lesions in the brain, based exclusively on their image findings without further pathologic verification, and received radiotherapy alone thereafter. It is, however, possible that a different pathology such as primary brain malignancy, which actually warrants a specific treatment modality, may occur in such patients with an already known malignancy. We, herein, reported a 61-year-old female patient who suffered from an anaplastic oligodendroglioma 1 year after her diagnosis of breast cancer. Demographic data, characteristic imaging findings, treatment, and outcome of the patient were discussed.

  3. Functional Connectivity in Frontoparietal Network: Indicator of Preoperative Cognitive Function and Cognitive Outcome Following Surgery in Patients with Glioma.

    Science.gov (United States)

    Lang, Stefan; Gaxiola-Valdez, Ismael; Opoku-Darko, Michael; Partlo, Lisa A; Goodyear, Bradley G; Kelly, John J P; Federico, Paolo

    2017-09-01

    Patients with diffuse glioma are known to have impaired cognitive functions preoperatively. However, the mechanism of these cognitive deficits remains unclear. Resting-state functional connectivity in the frontoparietal network (FPN) is associated with cognitive performance in healthy subjects. For this reason, it was hypothesized that functional connectivity of the FPN would be related to cognitive functioning in patients with glioma. To assess this relationship, preoperative cognitive status was correlated to patient-specific connectivity within the FPN. Further, we assessed whether connectivity could predict neuropsychologic outcome following surgery. Sixteen patients with diffuse glioma underwent neuropsychologic assessment and preoperative functional magnetic resonance imaging using task (n-back) and resting-state scans. Thirteen patients had postoperative cognitive assessment. An index of patient-specific functional connectivity in the FPN was derived by averaging connectivity values between 2 prefrontal and 2 parietal cortex regions defined by activation during the n-back task. The relationship of these indices with cognitive performance was assessed. Higher average connectivity within the FPN is associated with lower composite cognitive scores. Higher connectivity of the parietal region of the tumor-affected hemisphere is associated specifically with lower fluid cognition. Lower connectivity of the parietal region of the nontumor hemisphere is associated with worse neuropsychologic outcome 1 month after surgery. Resting-state functional connectivity between key regions of the FPN is associated with cognitive performance in patients with glioma and is related to cognitive outcome following surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. High expression of cystine-glutamate antiporter xCT (SLC7A11) is an independent biomarker for epileptic seizures at diagnosis in glioma

    DEFF Research Database (Denmark)

    Sørensen, Mai Froberg; Heimisdóttir, Sólborg Berglind; Sørensen, Mia Dahl

    2018-01-01

    Epileptic seizures are an important cause of morbidity in glioma patients. Substantial lines of evidence support the concept of the excitatory neurotransmitter glutamate being a crucial mediator of glioma-associated seizures. In gliomas, non-vesicular secretion of glutamate via the cystine...... tumor using tissue microarrays. In addition to histological grading of the tumors, isocitrate dehydrogenase 1 (IDH1) R132H mutational status was determined by immunohistochemistry. 215 consecutive glioma patients were included in the study (7.4% grade II, 7.0% grade III, 85.6% grade IV). High x...

  5. The use of dynamic O-(2-18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma.

    Science.gov (United States)

    Galldiks, Norbert; Stoffels, Gabriele; Filss, Christian; Rapp, Marion; Blau, Tobias; Tscherpel, Caroline; Ceccon, Garry; Dunkl, Veronika; Weinzierl, Martin; Stoffel, Michael; Sabel, Michael; Fink, Gereon R; Shah, Nadim J; Langen, Karl-Josef

    2015-09-01

    We evaluated the diagnostic value of static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET parameters in patients with progressive or recurrent glioma. We retrospectively analyzed 132 dynamic (18)F-FET PET and conventional MRI scans of 124 glioma patients (primary World Health Organization grade II, n = 55; grade III, n = 19; grade IV, n = 50; mean age, 52 ± 14 y). Patients had been referred for PET assessment with clinical signs and/or MRI findings suggestive of tumor progression or recurrence based on Response Assessment in Neuro-Oncology criteria. Maximum and mean tumor/brain ratios of (18)F-FET uptake were determined (20-40 min post-injection) as well as tracer uptake kinetics (ie, time to peak and patterns of the time-activity curves). Diagnoses were confirmed histologically (95%) or by clinical follow-up (5%). Diagnostic accuracies of PET and MR parameters for the detection of tumor progression or recurrence were evaluated by receiver operating characteristic analyses/chi-square test. Tumor progression or recurrence could be diagnosed in 121 of 132 cases (92%). MRI and (18)F-FET PET findings were concordant in 84% and discordant in 16%. Compared with the diagnostic accuracy of conventional MRI to diagnose tumor progression or recurrence (85%), a higher accuracy (93%) was achieved by (18)F-FET PET when a mean tumor/brain ratio ≥2.0 or time to peak dynamic (18)F-FET PET parameters differentiate progressive or recurrent glioma from treatment-related nonneoplastic changes with higher accuracy than conventional MRI. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. [Identification of emotions in patients with low-grade gliomas versus cerebrovascular accidents].

    Science.gov (United States)

    du Boullay, V; Plaza, M; Capelle, L; Chaby, L

    2013-03-01

    Facial and vocal emotions contribute to sustain efficient social relationships. Brain disease may impair their identification. In the case of slow-growth tumors (Low Grade Gliomas [LGG]) or sudden stroke (cerebrovascular accidents [CVA]), the lesions induce contrasted plasticity and reorganisation processes. We compared the facial, vocal and intermodal identification of six emotions (happiness, fear, angriness, sadness, disgust and neutral) of three groups: patients with LGG before and after tumor resection, patients with CVA and control subjects. In LGG patients, the results revealed less efficient performances after tumor resection and in CVA patients weak performances regarding negative emotions. The intermodal condition (simultaneous visual and vocal association) improved performances in all groups and enabled equivalent performance in CVA subjects compared with control subjects. The intergroup differences may be related to variable brain plasticity as a function of type and rapidity of brain injury. Intermodal processing appears to be a compensatory condition. Copyright © 2012. Published by Elsevier Masson SAS.

  7. Clinical Study Preoperative Evaluation with f MRI of Patients with Intracranial Gliomas Ioannis

    International Nuclear Information System (INIS)

    Kapsalakis, Z.; Hadjigeorgiou, G.; Papadimitriou, A.; Kapsalaki, E.Z.; Fezoulidis, I.; Gotsis, E.D.; Verganelakis, D.; Toulas, P.; Chung, I.; Robinson, J.S.; Lee, J.P.; Fountas, K.N.; Fountas, K.N.

    2012-01-01

    Aggressive surgical resection constitutes the optimal treatment for intracranial gliomas. However, the proximity of a tumor to eloquent areas requires exact knowledge of its anatomic relationships to functional cortex. The purpose of our study was to evaluate f MRI’s accuracy by comparing it to intraoperative cortical stimulation (DCS) mapping. Material and Methods. Eighty-seven patients, with presumed glioma diagnosis, underwent preoperative fMRI and intraoperative DCS for cortical mapping during tumor resection. Findings of fMRI and DCS were considered concordant if the identified cortical centers were less than 5 mm apart. Pre and postoperative Karnofsky Performance Scale and Spitzer scores were recorded. A postoperative MRI was obtained for assessing the extent of resection. Results. The areas of interest were identified by f MRI and DCS in all participants. The concordance between f MRI and Dncs was 91.9% regarding sensory-motor cortex, 100% for visual cortex, and 85.4% for language. Data analysis showed that patients with better functional condition demonstrated higher concordance rates, while there also was a weak association between tumor grade and concordance rate. The mean extent of tumor resection was 96.7%. Conclusions. Functional MRI is a highly accurate preoperative methodology for sensory-motor mapping. However, in language mapping, DCS remains necessary for accurate localization

  8. Working memory and the identification of facial expression in patients with left frontal glioma.

    Science.gov (United States)

    Mu, Yong-Gao; Huang, Ling-Juan; Li, Shi-Yun; Ke, Chao; Chen, Yu; Jin, Yu; Chen, Zhong-Ping

    2012-09-01

    Patients with brain tumors may have cognitive dysfunctions including memory deterioration, such as working memory, that affect quality of life. This study was to explore the presence of defects in working memory and the identification of facial expressions in patients with left frontal glioma. This case-control study recruited 11 matched pairs of patients and healthy control subjects (mean age ± standard deviation, 37.00 ± 10.96 years vs 36.73 ± 11.20 years; 7 male and 4 female) from March through December 2011. The psychological tests contained tests that estimate verbal/visual-spatial working memory, executive function, and the identification of facial expressions. According to the paired samples analysis, there were no differences in the anxiety and depression scores or in the intelligence quotients between the 2 groups (P > .05). All indices of the Digit Span Test were significantly worse in patients than in control subjects (P patient and control groups. Of all 7 Wisconsin Card Sorting Test (WCST) indexes, only the Preservative Response was significantly different between patients and control subjects (P Patients were significantly less accurate in detecting angry facial expressions than were control subjects (30.3% vs 57.6%; P identification of other expressions. The backward indexes of the Digit Span Test were associated with emotion scores and tumor size and grade (P Patients with left frontal glioma had deficits in verbal working memory and the ability to identify anger. These may have resulted from damage to functional frontal cortex regions, in which roles in these 2 capabilities have not been confirmed. However, verbal working memory performance might be affected by emotional and tumor-related factors.

  9. Bereaved caregivers of patients with high-grade glioma

    DEFF Research Database (Denmark)

    Piil, Karin; Nordentoft, Sara; Larsen, Anders

    2018-01-01

    )) experience and manage their life situation after the death of the patient. METHODS: A systematic literature search was carried out in December 2016 and revised in September 2017. The following six databases were searched: PubMed, Cumulative Index of Nursing and Allied Health Literature, Excerpta Medica...... and their role as caregiver. Moreover, they experienced depressive symptoms and fatigue, resulting in a reduced work capability and social network. CONCLUSIONS: We conclude that bereaved informal caregivers experience psychosocial consequences and emotional reactions after bereavement, resulting in feelings...

  10. Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

    International Nuclear Information System (INIS)

    Kuwert, T.; Morgenroth, C.; Woesler, B.; Matheja, P.; Palkovic, S.; Vollet, B.; Samnick, S.; Maasjosthusmann, U.; Lerch, H.; Gildehaus, F.J.; Wassmann, H.; Schober, O.

    1996-01-01

    Using single-photon emission tomography (SPET), the radiopharmaceutical L-3-iodine-123-α-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating higc-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours. (orig.)

  11. Correlation of Tumor Immunohistochemistry with Dynamic Contrast-Enhanced and DSC-MRI Parameters in Patients with Gliomas

    NARCIS (Netherlands)

    Nguyen, T.B.; Cron, G.O.; Bezzina, K.; Perdrizet, K.; Torres, C.H.; Chakraborty, S.; Woulfe, J.; Jansen, G.H.; Thornhill, R.E.; Zanette, B.; Cameron, I.G.M.

    2016-01-01

    BACKGROUND AND PURPOSE: Tumor CBV is a prognostic and predictive marker for patients with gliomas. Tumor CBV can be measured noninvasively with different MR imaging techniques; however, it is not clear which of these techniques most closely reflects histologically-measured tumor CBV. Our aim was to

  12. Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide).

    Science.gov (United States)

    Pandith, Arshad A; Qasim, Iqbal; Zahoor, Wani; Shah, Parveen; Bhat, Abdul R; Sanadhya, Dheera; Shah, Zafar A; Naikoo, Niyaz A

    2018-04-30

    O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Methylation status of MGMT and loss of protein expression showed a very high concordant association with better survival and progression free survival (PFS) (p < 0.0001). Multivariate Cox regression analysis showed both MGMT methylation and loss of protein as significant independent prognostic factors in glioma patients with respect to lower Hazard Ratio (HR) for better OS and PFS) [p < 0.05]. Interestingly concordant MGMT methylation and lack of protein showed better response in TMZ therapy treated patient subgroups with HR of 2.02 and 0.76 (p < 0.05). We found the merits of prognostication of MGMT parameters, methylation as well as loss of its protein as predictive factors for favorable outcome in terms of better survival for TMZ therapy.

  13. The end-of-life phase of high-grade glioma patients: dying with dignity?

    Science.gov (United States)

    Sizoo, Eefje M; Taphoorn, Martin J B; Uitdehaag, Bernard; Heimans, Jan J; Deliens, Luc; Reijneveld, Jaap C; Pasman, H Roeline W

    2013-01-01

    In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as perceived by their relatives and (b) identify disease and care factors correlated with dying with dignity in HGG patients. We approached relatives of a cohort of 155 deceased HGG patients for the study. Participants completed a questionnaire concerning the EOL phase of the patient, covering several subthemes: (a) symptoms and signs, (b) health-related quality of life, (c) decision making, (d) place and quality of EOL care, and (e) dying with dignity. Relatives of 81 patients participated and 75% indicated that the patient died with dignity. These patients had fewer communication deficits, experienced fewer transitions between health care settings in the EOL phase, and more frequently died at their preferred place of death. Relatives were more satisfied with the physician providing EOL care and reported that the physician adequately explained treatment options. Multivariate analysis identified satisfaction with the physician, the ability to communicate, and the absence of transitions between settings as most predictive of a dignified death. Physicians caring for HGG patients in the EOL phase should timely focus on explaining possible treatment options, because patients experience communication deficits toward death. Physicians should strive to allow patients to die at their preferred place and avoid transitions during the last month of life.

  14. Integrated analysis of dynamic FET PET/CT parameters, histology, and methylation profiling of 44 gliomas.

    Science.gov (United States)

    Röhrich, Manuel; Huang, Kristin; Schrimpf, Daniel; Albert, Nathalie L; Hielscher, Thomas; von Deimling, Andreas; Schüller, Ulrich; Dimitrakopoulou-Strauss, Antonia; Haberkorn, Uwe

    2018-05-07

    Dynamic 18 F-FET PET/CT is a powerful tool for the diagnosis of gliomas. 18 F-FET PET time-activity curves (TAC) allow differentiation between histological low-grade gliomas (LGG) and high-grade gliomas (HGG). Molecular methods such as epigenetic profiling are of rising importance for glioma grading and subclassification. Here, we analysed dynamic 18 F-FET PET data, and the histological and epigenetic features of 44 gliomas. Dynamic 18 F-FET PET was performed in 44 patients with newly diagnosed, untreated glioma: 10 WHO grade II glioma, 13 WHO grade III glioma and 21 glioblastoma (GBM). All patients underwent stereotactic biopsy or tumour resection after 18 F-FET PET imaging. As well as histological analysis of tissue samples, DNA was subjected to epigenetic analysis using the Illumina 850 K methylation array. TACs, standardized uptake values corrected for background uptake in healthy tissue (SUVmax/BG), time to peak (TTP) and kinetic modelling parameters were correlated with histological diagnoses and with epigenetic signatures. Multivariate analyses were performed to evaluate the diagnostic accuracy of 18 F-FET PET in relation to the tumour groups identified by histological and methylation-based analysis. Epigenetic profiling led to substantial tumour reclassification, with six grade II/III gliomas reclassified as GBM. Overlap of HGG-typical TACs and LGG-typical TACs was dramatically reduced when tumours were clustered on the basis of their methylation profile. SUVmax/BG values of GBM were higher than those of LGGs following both histological diagnosis and methylation-based diagnosis. The differences in TTP between GBMs and grade II/III gliomas were greater following methylation-based diagnosis than following histological diagnosis. Kinetic modeling showed that relative K1 and fractal dimension (FD) values significantly differed in histology- and methylation-based GBM and grade II/III glioma between those diagnosed histologically and those diagnosed by

  15. Molecular Alterations of KIT Oncogene in Gliomas

    Directory of Open Access Journals (Sweden)

    Ana L. Gomes

    2007-01-01

    Full Text Available Gliomas are the most common and devastating primary brain tumours. Despite therapeutic advances, the majority of gliomas do not respond either to chemo or radiotherapy. KIT, a class III receptor tyrosine kinase (RTK, is frequently involved in tumourigenic processes. Currently, KIT constitutes an attractive therapeutic target. In the present study we assessed the frequency of KIT overexpression in gliomas and investigated the genetic mechanisms underlying KIT overexpression. KIT (CD117 immunohistochemistry was performed in a series of 179 gliomas of various grades. KIT activating gene mutations (exons 9, 11, 13 and 17 and gene amplification analysis, as defined by chromogenic in situ hybridization (CISH and quantitative real-time PCR (qRT-PCR were performed in CD117 positive cases. Tumour cell immunopositivity was detected in 15.6% (28/179 of cases, namely in 25% (1/4 of pilocytic astrocytomas, 25% (5/20 of diffuse astrocytomas, 20% (1/5 of anaplastic astrocytomas, 19.5% (15/77 of glioblastomas and one third (3/9 of anaplastic oligoastrocytomas. Only 5.7% (2/35 of anaplastic oligodendrogliomas showed CD117 immunoreactivity. No association was found between tumour CD117 overexpression and patient survival. In addition, we also observed CD117 overexpression in endothelial cells, which varied from 0–22.2% of cases, being more frequent in high-grade lesions. No KIT activating mutations were identified. Interestingly, CISH and/or qRT-PCR analysis revealed the presence of KIT gene amplification in 6 glioblastomas and 2 anaplastic oligoastrocytomas, corresponding to 33% (8/24 of CD117 positive cases. In conclusion, our results demonstrate that KIT gene amplification rather than gene mutation is a common genetic mechanism underlying KIT expression in subset of malignant gliomas. Further studies are warranted to determine whether glioma patients exhibiting KIT overexpression and KIT gene amplification may benefit from therapy with anti-KIT RTK

  16. Increasing feasibility and utility of 18F-FDOPA PET for the management of glioma

    International Nuclear Information System (INIS)

    Bell, Christopher; Dowson, Nicholas; Puttick, Simon; Gal, Yaniv; Thomas, Paul; Fay, Mike; Smith, Jye; Rose, Stephen

    2015-01-01

    Introduction: Despite radical treatment therapies, glioma continues to carry with it a uniformly poor prognosis. Patients diagnosed with WHO Grade IV glioma (glioblastomas; GBM) generally succumb within two years, even those with WHO Grade III anaplastic gliomas and WHO Grade II gliomas carry prognoses of 2–5 and 2 years, respectively. PET imaging with 18 F-FDOPA allows in vivo assessment of the metabolism of glioma relative to surrounding tissues. The high sensitivity of 18 F-DOPA imaging grants utility for a number of clinical applications. Methods: A collection of published work about 18 F-FDOPA PET was made and a critical review was discussed and written. Results: A number of research papers have been published demonstrating that in conjunction with MRI, 18 F-FDOPA PET provides greater sensitivity and specificity than these modalities in detection, grading, prognosis and validation of treatment success in both primary and recurrent gliomas. In further comparisons with 11 C-MET, 18 F-FLT, 18 F-FET and MRI, 18 F-FDOPA has shown similar or better efficacy. Recently synthesis cassettes have become available, making 18 F-FDOPA more accessible. Conclusions: According to the available data, 18 F-FDOPA PET is a viable radiotracer for imaging and treatment planning of gliomas. Advances in knowledge and implication for patient care: 18 F-FDOPA PET appears to be a viable radiopharmaceutical for the diagnosis and treatment planning of gliomas cases, improving on that of MRI and 18 F-FDG PET

  17. The relationship between Cho/NAA and glioma metabolism: implementation for margin delineation of cerebral gliomas.

    Science.gov (United States)

    Guo, Jun; Yao, Chengjun; Chen, Hong; Zhuang, Dongxiao; Tang, Weijun; Ren, Guang; Wang, Yin; Wu, Jinsong; Huang, Fengping; Zhou, Liangfu

    2012-08-01

    The marginal delineation of gliomas cannot be defined by conventional imaging due to their infiltrative growth pattern. Here we investigate the relationship between changes in glioma metabolism by proton magnetic resonance spectroscopic imaging ((1)H-MRSI) and histopathological findings in order to determine an optimal threshold value of choline/N-acetyl-aspartate (Cho/NAA) that can be used to define the extent of glioma spread. Eighteen patients with different grades of glioma were examined using (1)H-MRSI. Needle biopsies were performed under the guidance of neuronavigation prior to craniotomy. Intraoperative magnetic resonance imaging (MRI) was performed to evaluate the accuracy of sampling. Haematoxylin and eosin, and immunohistochemical staining with IDH1, MIB-1, p53, CD34 and glial fibrillary acidic protein (GFAP) antibodies were performed on all samples. Logistic regression analysis was used to determine the relationship between Cho/NAA and MIB-1, p53, CD34, and the degree of tumour infiltration. The clinical threshold ratio distinguishing tumour tissue in high-grade (grades III and IV) glioma (HGG) and low-grade (grade II) glioma (LGG) was calculated. In HGG, higher Cho/NAA ratios were associated with a greater probability of higher MIB-1 counts, stronger CD34 expression, and tumour infiltration. Ratio threshold values of 0.5, 1.0, 1.5 and 2.0 appeared to predict the specimens containing the tumour with respective probabilities of 0.38, 0.60, 0.79, 0.90 in HGG and 0.16, 0.39, 0.67, 0.87 in LGG. HGG and LGG exhibit different spectroscopic patterns. Using (1)H-MRSI to guide the extent of resection has the potential to improve the clinical outcome of glioma surgery.

  18. EPID-28. PROGNOSTIC AND PREDICTIVE BIOMARKERS IN RECURRENT WHO GRADE 3 GLIOMA PATIENTS TREATED WITH BEVACIZUMAB AND IRINOTECAN

    DEFF Research Database (Denmark)

    Toft, Anders; Urup, Thomas; Grunnet, Kirsten

    2015-01-01

    BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients. The prim......BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients...... response MRI (RANO criteria). Responders had significantly prolonged OS (p ¼ 0.007) and trended toward longer PFS (p ¼ 0.067) as compared to non-responders (OS: 12.4 vs 4.3 months, PFS: 5.6 vs 3.2 months). A favorable WHO performance status (PS) and absence of necrosis were significantly more common...... in responders than nonresponders. Multivariate analysis also identified a poor PS as the only prognostic factor for PFS, while an unfavorable PS and immunohistochemical p53 accumulation were prognostic of reducedOS.CONCLUSIONS:Apoor baseline PS and the presence of necrosis were negatively associated...

  19. Prognostic effects of O6-Methylguanine DNA methyltransferase promoter hypermethylation in high-grade glioma patients with carmustine wafer implants

    Directory of Open Access Journals (Sweden)

    Mao-Yu Chen

    2017-01-01

    Results and Conclusion: BCNU wafer implantation was performed in 18 patients with newly diagnosed gliomas and in 14 with recurrent gliomas. All patients had a Karnofsky performance status of ≥70. The median age was 51 years. At a median follow-up of 31 months, the 1- and 2-year overall survival (OS rate was 43% and 22%, respectively. OS rates did not significantly differ between the newly diagnosed and recurrent patients. Gross total tumor resection was achieved in 19 (59% patients, and MGMT hypermethylation was noted in 13 (41% tumor specimens. Multivariate analysis demonstrated that patients with MGMT hypermethylation in their tumors and gross total tumor removal have more favorable survival rates (P = 0.03.

  20. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

    Science.gov (United States)

    Brat, Daniel J; Verhaak, Roel G W; Aldape, Kenneth D; Yung, W K Alfred; Salama, Sofie R; Cooper, Lee A D; Rheinbay, Esther; Miller, C Ryan; Vitucci, Mark; Morozova, Olena; Robertson, A Gordon; Noushmehr, Houtan; Laird, Peter W; Cherniack, Andrew D; Akbani, Rehan; Huse, Jason T; Ciriello, Giovanni; Poisson, Laila M; Barnholtz-Sloan, Jill S; Berger, Mitchel S; Brennan, Cameron; Colen, Rivka R; Colman, Howard; Flanders, Adam E; Giannini, Caterina; Grifford, Mia; Iavarone, Antonio; Jain, Rajan; Joseph, Isaac; Kim, Jaegil; Kasaian, Katayoon; Mikkelsen, Tom; Murray, Bradley A; O'Neill, Brian Patrick; Pachter, Lior; Parsons, Donald W; Sougnez, Carrie; Sulman, Erik P; Vandenberg, Scott R; Van Meir, Erwin G; von Deimling, Andreas; Zhang, Hailei; Crain, Daniel; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Troy; Sherman, Mark; Yena, Peggy; Black, Aaron; Bowen, Jay; Dicostanzo, Katie; Gastier-Foster, Julie; Leraas, Kristen M; Lichtenberg, Tara M; Pierson, Christopher R; Ramirez, Nilsa C; Taylor, Cynthia; Weaver, Stephanie; Wise, Lisa; Zmuda, Erik; Davidsen, Tanja; Demchok, John A; Eley, Greg; Ferguson, Martin L; Hutter, Carolyn M; Mills Shaw, Kenna R; Ozenberger, Bradley A; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Jensen, Mark A; Liu, Jia; Pihl, Todd; Raman, Rohini; Wan, Yunhu; Wu, Ye; Ally, Adrian; Auman, J Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B; Beroukhim, Rameen; Bootwalla, Moiz S; Bowlby, Reanne; Bristow, Christopher A; Brooks, Denise; Butterfield, Yaron; Carlsen, Rebecca; Carter, Scott; Chin, Lynda; Chu, Andy; Chuah, Eric; Cibulskis, Kristian; Clarke, Amanda; Coetzee, Simon G; Dhalla, Noreen; Fennell, Tim; Fisher, Sheila; Gabriel, Stacey; Getz, Gad; Gibbs, Richard; Guin, Ranabir; Hadjipanayis, Angela; Hayes, D Neil; Hinoue, Toshinori; Hoadley, Katherine; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven; Jones, Corbin D; Kucherlapati, Raju; Lai, Phillip H; Lander, Eric; Lee, Semin; Lichtenstein, Lee; Ma, Yussanne; Maglinte, Dennis T; Mahadeshwar, Harshad S; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew L; Mieczkowski, Piotr A; Moore, Richard A; Mose, Lisle E; Mungall, Andrew J; Pantazi, Angeliki; Parfenov, Michael; Park, Peter J; Parker, Joel S; Perou, Charles M; Protopopov, Alexei; Ren, Xiaojia; Roach, Jeffrey; Sabedot, Thaís S; Schein, Jacqueline; Schumacher, Steven E; Seidman, Jonathan G; Seth, Sahil; Shen, Hui; Simons, Janae V; Sipahimalani, Payal; Soloway, Matthew G; Song, Xingzhi; Sun, Huandong; Tabak, Barbara; Tam, Angela; Tan, Donghui; Tang, Jiabin; Thiessen, Nina; Triche, Timothy; Van Den Berg, David J; Veluvolu, Umadevi; Waring, Scot; Weisenberger, Daniel J; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Xu, Andrew W; Yang, Lixing; Zack, Travis I; Zhang, Jianhua; Aksoy, B Arman; Arachchi, Harindra; Benz, Chris; Bernard, Brady; Carlin, Daniel; Cho, Juok; DiCara, Daniel; Frazer, Scott; Fuller, Gregory N; Gao, JianJiong; Gehlenborg, Nils; Haussler, David; Heiman, David I; Iype, Lisa; Jacobsen, Anders; Ju, Zhenlin; Katzman, Sol; Kim, Hoon; Knijnenburg, Theo; Kreisberg, Richard Bailey; Lawrence, Michael S; Lee, William; Leinonen, Kalle; Lin, Pei; Ling, Shiyun; Liu, Wenbin; Liu, Yingchun; Liu, Yuexin; Lu, Yiling; Mills, Gordon; Ng, Sam; Noble, Michael S; Paull, Evan; Rao, Arvind; Reynolds, Sheila; Saksena, Gordon; Sanborn, Zack; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Shen, Ronglai; Shmulevich, Ilya; Sinha, Rileen; Stuart, Josh; Sumer, S Onur; Sun, Yichao; Tasman, Natalie; Taylor, Barry S; Voet, Doug; Weinhold, Nils; Weinstein, John N; Yang, Da; Yoshihara, Kosuke; Zheng, Siyuan; Zhang, Wei; Zou, Lihua; Abel, Ty; Sadeghi, Sara; Cohen, Mark L; Eschbacher, Jenny; Hattab, Eyas M; Raghunathan, Aditya; Schniederjan, Matthew J; Aziz, Dina; Barnett, Gene; Barrett, Wendi; Bigner, Darell D; Boice, Lori; Brewer, Cathy; Calatozzolo, Chiara; Campos, Benito; Carlotti, Carlos Gilberto; Chan, Timothy A; Cuppini, Lucia; Curley, Erin; Cuzzubbo, Stefania; Devine, Karen; DiMeco, Francesco; Duell, Rebecca; Elder, J Bradley; Fehrenbach, Ashley; Finocchiaro, Gaetano; Friedman, William; Fulop, Jordonna; Gardner, Johanna; Hermes, Beth; Herold-Mende, Christel; Jungk, Christine; Kendler, Ady; Lehman, Norman L; Lipp, Eric; Liu, Ouida; Mandt, Randy; McGraw, Mary; Mclendon, Roger; McPherson, Christopher; Neder, Luciano; Nguyen, Phuong; Noss, Ardene; Nunziata, Raffaele; Ostrom, Quinn T; Palmer, Cheryl; Perin, Alessandro; Pollo, Bianca; Potapov, Alexander; Potapova, Olga; Rathmell, W Kimryn; Rotin, Daniil; Scarpace, Lisa; Schilero, Cathy; Senecal, Kelly; Shimmel, Kristen; Shurkhay, Vsevolod; Sifri, Suzanne; Singh, Rosy; Sloan, Andrew E; Smolenski, Kathy; Staugaitis, Susan M; Steele, Ruth; Thorne, Leigh; Tirapelli, Daniela P C; Unterberg, Andreas; Vallurupalli, Mahitha; Wang, Yun; Warnick, Ronald; Williams, Felicia; Wolinsky, Yingli; Bell, Sue; Rosenberg, Mara; Stewart, Chip; Huang, Franklin; Grimsby, Jonna L; Radenbaugh, Amie J; Zhang, Jianan

    2015-06-25

    Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most

  1. Patient-specific metrics of invasiveness reveal significant prognostic benefit of resection in a predictable subset of gliomas.

    Directory of Open Access Journals (Sweden)

    Anne L Baldock

    Full Text Available Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas.In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness.We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532 from gross total resection over subtotal/biopsy, while those with nodular (less diffuse tumors showed a significant benefit (P = 0.00142 with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors.These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection.

  2. Reirradiation in progressive high-grade gliomas: outcome, role of concurrent chemotherapy, prognostic factors and validation of a new prognostic score with an independent patient cohort

    International Nuclear Information System (INIS)

    Scholtyssek, Felix; Kortmann, Rolf-Dieter; Müller, Klaus; Zwiener, Isabella; Schlamann, Annika; Seidel, Clemens; Meixensberger, Jürgen; Bauer, Manfred; Hoffmann, Karl-Titus; Combs, Stephanie E; Bueren, André O von

    2013-01-01

    First, to evaluate outcome, the benefit of concurrent chemotherapy and prognostic factors in a cohort of sixty-four high-grade glioma patients who underwent a second course of radiation therapy at progression. Second, to validate a new prognostic score for overall survival after reirradiation of progressive gliomas with an independent patient cohort. All patients underwent fractionated reirradiation with a median physical dose of 36 Gy. Median planned target volume was 110.4 ml. Thirty-six patients received concurrent chemotherapy consisting in 24/36 cases (67%) of carboplatin and etoposide and in 12/36 cases (33%) of temozolomide. We used the Kaplan Meier method, log rank test and proportional hazards regression analysis for statistical assessment. Median overall survival from the start of reirradiation was 7.7 ± 0.7 months. Overall survival rates at 6 and 12 months were 60 ± 6% and 24 ± 6%, respectively. Despite relatively large target volumes we did not observe any major acute toxicity. Concurrent chemotherapy did not appear to improve outcome. In contrast, female gender, young age, WHO grade III histology, favorable Karnofsky performance score and complete resection of the tumor prior to reirradiation were identified as positive prognostic factors for overall survival. We finally validated a recent suggestion for a prognostic score with our independent but small patient cohort. Our preliminary findings suggest that its ability to discriminate between different prognostic groups is limited. Outcome of our patients was comparable to previous studies. Even in case of large target volumes reirradiation seems to be feasible without observing major toxicity. The benefit of concurrent chemotherapy is still elusive. A reassessment of the prognostic score, tested in this study, using a larger patient cohort is needed

  3. The effect of an interdisciplinary rehabilitation intervention comparing HRQoL, symptom burden and physical function among patients with primary glioma

    DEFF Research Database (Denmark)

    Hansen, Anders; Rosenbek Minet, Lisbeth Kirstine; Søgaard, Karen

    2014-01-01

    INTRODUCTION: Gliomas are among the biggest challenges in neurological and oncology rehabilitation and optimising treatment is of major clinical importance in this population. Although inpatient rehabilitation among glioma patients' results in improved functional measures, rehabilitation efforts...... of literature investigating the potential role of exercise as a supportive therapeutic intervention for a patient with cancer. ETHICS AND DISSEMINATION: The project is approved by the Regional Scientific Ethical Committees for Southern Denmark under Project-ID: (S-20140108) and by the Danish Data Protection...

  4. Malignant gliomas (MG) in the elderly. A study of 85 consecutive patients in two institutions

    International Nuclear Information System (INIS)

    Villa, S.; Vinolas, N.; Verger, E.; Gil, M.; Caralt, L.; Moreno, V.; Graus, F.

    1997-01-01

    Purpose: The treatment of MG in old patients is controversial and not well established. Some authors consider that adjuvant radiotherapy (RT) is not useful to improve survival. Our aim was to identify which group of patients older than 65 years might benefit of adjuvant radiotherapy (RT). Patients and Methods: A total of 85 consecutive patients were analyzed from two Institutions diagnosed during the period 1987-1995. Forty six were male and 39 female. The median age was 70 (r 65-81). The extent of surgery (S) was analyzed by neurosurgeons reports or postoperative CT scan (32 p. underwent biopsy, 25 partial resection, 28 complete resection). Glioblastoma Multiforme was observed in 64 patients (75%) and anaplastic gliomas in 21 patients (25%). Postoperative Karnofsky Index (KI) was as follows: in 47 p 60% (for 2 p was unknown). Survival probability was estimated using Kaplan-Meier method and compared with log-rank test. Crude and adjusted hazard ratios (HR) were calculated using Cox's regression models. Results: Forty four patients were treated by adjuvant RT and 41 patients were not. Median survival time for all patients was 18.3 weeks. In multivariate analysis we found that the most powerful independent variable was not to receive RT with a hazard ratio of 8.5 (CI 4.55-16.06). Reasons for not RT were: in 7 p. postsurgical complications, in 17 p. KI 40%. Multivariate analysis showed that the most significant independent variable was age ( 71 y) with a HR of 2.85 (CI 1.31-6.19). Conclusions: 1- Patients who did not received RT, due to several reasons, had poorer evolution. 2-In patients who received adjuvant treatment, it was suggested that age is the first variable to consider, although patients older than 71 can benefit of RT (see table)

  5. Molecular markers in glioma.

    Science.gov (United States)

    Ludwig, Kirsten; Kornblum, Harley I

    2017-09-01

    Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.

  6. Structured Evaluation of Glioma Patients by an Occupational Therapist-Is Our Clinical Examination Enough?

    Science.gov (United States)

    Freyschlag, Christian Franz; Kerschbaumer, Johannes; Pinggera, Daniel; Bacher, Gabriele; Mur, Erich; Thomé, Claudius

    2017-07-01

    Preservation of neurologic function is mandatory when offering a surgical intervention to patients with low-grade gliomas (LGGs), given that the goal of any treatment is the patient's return to their normal everyday life. To determine whether a structured evaluation by an occupational therapist can reveal deficits that might be overseen in routine clinical examination of patients with a surgically treated LGG. A total of 20 patients with radiographically suspected LGG were examined in a standardized fashion at 3 stages: preoperatively, postoperatively, and 3 months thereafter. Results were analyzed descriptively. A total of 19 patients (95%) showed no postoperative motor deficit; one suffered from akinesia due to supplementary motor area involvement and demonstrated a transient deficit with manifestation on the first postoperative day. Patients with eloquent LGGs, involving speech (n = 6, 30%), exhibited different transient speech disturbances according to the location of the lesion. Structured testing revealed a postoperative worsening of movement mirroring (upper extremity) and finger discrimination (sensory) in 5 of 20 patients (25%). Force meter evaluation of the upper extremity was decreased significantly postoperatively for the affected hemisphere, even though motor deficits were absent in most patients. The action research arm test detected deterioration in more than one half of the patients postoperatively. Patients recovered from these deficits within the first 3 months. Routine clinical examination and neuropsychological evaluation fail to detect mild deficits in sensory function, reactivity, and apraxia, which may have a serious impact on patients' ability to return to their normal lives and work. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Palliative care at the end-of-life in glioma patients.

    Science.gov (United States)

    Koekkoek, Johan A F; Chang, Susan; Taphoorn, Martin J B

    2016-01-01

    The end-of-life (EOL) phase of patients with a glioma starts when symptom prevalence increases and antitumor treatment is no longer effective. During the EOL phase, care is primarily aimed at reducing symptom burden while maintaining quality of life as long as possible without inappropriate prolongation of life. Palliative care during the EOL phase also involves complex medical decisions for the prevention and relief of suffering. We discuss the prevalence and treatment of the most common EOL symptoms, decision making in the EOL phase, the organization of EOL care, and the role of the patient's caregiver. Treating disease-specific symptoms, such as impaired consciousness, seizures, focal neurologic deficits and cognitive disturbances, is a major concern during the EOL phase, as these symptoms may interfere with EOL decision making. Advance care planning is aimed at reaching consensus about possible EOL decisions between all participants, respecting the values of patients and their informal caregivers. In order to prevent the possibility that the patient becomes incompetent to make informed decisions, we recommend initiating EOL conversations at a relatively early stage in the disease course. © 2016 Elsevier B.V. All rights reserved.

  8. Atypical nuclear localization of VIP receptors in glioma cell lines and patients

    Energy Technology Data Exchange (ETDEWEB)

    Barbarin, Alice; Séité, Paule [Equipe Récepteurs, Régulations et Cellules Tumorales, Université de Poitiers, PBS bât 36, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9 (France); Godet, Julie [Laboratoire d’anatomie et de cytologie pathologiques, CHU de Poitiers, 2 rue de la Milétrie, 86000 Poitiers (France); Bensalma, Souheyla; Muller, Jean-Marc [Equipe Récepteurs, Régulations et Cellules Tumorales, Université de Poitiers, PBS bât 36, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9 (France); Chadéneau, Corinne, E-mail: corinne.chadeneau@univ-poitiers.fr [Equipe Récepteurs, Régulations et Cellules Tumorales, Université de Poitiers, PBS bât 36, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9 (France)

    2014-11-28

    Highlights: • The VIP receptor VPAC1 contains a putative NLS signal. • VPAC1 is predominantly nuclear in GBM cell lines but not VPAC2. • Non-nuclear VPAC1/2 protein expression is correlated with glioma grade. • Nuclear VPAC1 is observed in 50% of stage IV glioma (GBM). - Abstract: An increasing number of G protein-coupled receptors, like receptors for vasoactive intestinal peptide (VIP), are found in cell nucleus. As VIP receptors are involved in the regulation of glioma cell proliferation and migration, we investigated the expression and the nuclear localization of the VIP receptors VPAC1 and VPAC2 in this cancer. First, by applying Western blot and immunofluorescence detection in three human glioblastoma (GBM) cell lines, we observed a strong nuclear staining for the VPAC1 receptor and a weak nuclear VPAC2 receptor staining. Second, immunohistochemical staining of VPAC1 and VPAC2 on tissue microarrays (TMA) showed that the two receptors were expressed in normal brain and glioma tissues. Expression in the non-nuclear compartment of the two receptors significantly increased with the grade of the tumors. Analysis of nuclear staining revealed a significant increase of VPAC1 staining with glioma grade, with up to 50% of GBM displaying strong VPAC1 nuclear staining, whereas nuclear VPAC2 staining remained marginal. The increase in VPAC receptor expression with glioma grades and the enhanced nuclear localization of the VPAC1 receptors in GBM might be of importance for glioma progression.

  9. Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients.

    Science.gov (United States)

    Jansen, Nathalie L; Suchorska, Bogdana; Wenter, Vera; Eigenbrod, Sabina; Schmid-Tannwald, Christine; Zwergal, Andreas; Niyazi, Maximilian; Drexler, Mark; Bartenstein, Peter; Schnell, Oliver; Tonn, Jörg-Christian; Thon, Niklas; Kreth, Friedrich-Wilhelm; la Fougère, Christian

    2014-02-01

    Because the clinical course of low-grade gliomas in the individual adult patient varies considerably and is unpredictable, we investigated the prognostic value of dynamic (18)F-fluorethyltyrosine ((18)F-FET) PET in the early diagnosis of astrocytic low-grade glioma (World Health Organization grade II). Fifty-nine patients with newly diagnosed low-grade glioma and dynamic (18)F-FET PET before histopathologic assessment were retrospectively investigated. (18)F-FET PET analysis comprised a qualitative visual classification of lesions; assessment of the semiquantitative parameters maximal, mean, and total standardized uptake value as ratio to background and biologic tumor volume; and dynamic analysis of intratumoral (18)F-FET uptake over time (increasing vs. decreasing time-activity curves). The correlation between PET parameters and progression-free survival, overall survival, and time to malignant transformation was investigated. (18)F-FET uptake greater than the background level was found in 34 of 59 tumors. Dynamic (18)F-FET uptake analysis was available for 30 of these 34 patients. Increasing and decreasing time-activity curves were found in 18 and 12 patients, respectively. Neither the qualitative factor presence or absence of (18)F-FET uptake nor any of the semiquantitative uptake parameters significantly influenced clinical outcome. In contrast, decreasing time-activity curves in the kinetic analysis were highly prognostic for shorter progression-free survival and time to malignant transformation (P dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.

  10. Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Pyka, Thomas; Hiob, Daniela; Wester, Hans-Juergen [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Klinikum Rechts der Isar der TU Muenchen, Neurosurgic Department, Munich (Germany); Schlegel, Juergen [Klinikum Rechts der Isar der TU Muenchen, Institute of Pathology and Neuropathology, Munich (Germany); Bette, Stefanie [Klinikum Rechts der Isar der TU Muenchen, Neuroradiologic department, Munich (Germany); Foerster, Stefan [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Klinikum Rechts der Isar der TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Munich (Germany)

    2016-01-15

    Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not

  11. The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients.

    Science.gov (United States)

    Chen, Jian-Wu; Zhou, Chang-Fu; Lin, Zhi-Xiong

    2015-09-15

    Although age is thought to correlate with the prognosis of glioma patients, the most appropriate age-group classification standard to evaluate prognosis had not been fully studied. This study aimed to investigate the influence of age-group classification standards on the prognosis of patients with high-grade hemispheric glioma (HGG). This retrospective study of 125 HGG patients used three different classification standards of age-groups (≤ 50 and >50 years old, ≤ 60 and >60 years old, ≤ 45 and 45-65 and ≥ 65 years old) to evaluate the impact of age on prognosis. The primary end-point was overall survival (OS). The Kaplan-Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. Univariate analysis showed a significant correlation between OS and all three classification standards of age-groups as well as between OS and pathological grade, gender, location of glioma, and regular chemotherapy and radiotherapy treatment. Multivariate analysis showed that the only independent predictors of OS were classification standard of age-groups ≤ 50 and > 50 years old, pathological grade and regular chemotherapy. In summary, the most appropriate classification standard of age-groups as an independent prognostic factor was ≤ 50 and > 50 years old. Pathological grade and chemotherapy were also independent predictors of OS in post-operative HGG patients. Copyright © 2015. Published by Elsevier B.V.

  12. Controlled rehabilitative and supportive care intervention trials in patients with high-grade gliomas and their caregivers

    DEFF Research Database (Denmark)

    Piil, K; Juhler, M; Jakobsen, J

    2016-01-01

    and Embase were searched for literature published from 1995 to May 2013. Data from eight studies were reviewed for substantive methods and results. Methodological quality was described and assessed using the scoring system for appraising mixed methods research and concomitantly appraising qualitative......, quantitative and mixed methods primary studies in mixed study reviews. RESULTS: The search yielded 914 unique publications, of which 9 were classified eligible for this review. There is preliminary evidence that cognitive group therapy improves memory skills in patients with high-grade gliomas, early physical....... CONCLUSIONS: As evidence is beginning to emerge, there is a need for well-designed longitudinal and randomised controlled trials of non-pharmacological interventions in high-grade glioma patients and their caregivers in order to develop clinical guidelines for supportive and rehabilitative approaches...

  13. Successful Insular Glioma Removal in a Deaf Signer Patient During an Awake Craniotomy Procedure.

    Science.gov (United States)

    Metellus, Philippe; Boussen, Salah; Guye, Maxime; Trebuchon, Agnes

    2017-02-01

    Resection of tumors located within the insula of the dominant hemisphere represents a technical challenge because of the complex anatomy, including the surrounding vasculature, and the relationship to functional (motor and language) structures. We report here the case of a successful resection of a left insular glioma in a native deaf signer during an awake craniotomy. The patient, a congenitally deaf right-handed patient who is a native user of sign language, presented with a seizure 1 week before he was referred to our department. Magnetic resonance imaging revealed a left heterogeneous insular tumor enhanced after intravenous gadolinium infusion. Because of its deep and dominant hemisphere location, an awake craniotomy was decided. The patient was evaluated intraoperatively using object naming, text reading, and sign repetition tasks. An isolated inferior frontal gyrus site evoked repeated object naming errors. A transopercular parietal approach was performed and allowed the successful removal of the tumor under direct electric stimulation and electrocorticography. To our knowledge, this is the first report of successful removal of a left insular tumor without any functional sequelae in a native deaf signer using intraoperative direct cerebral stimulation during an awake craniotomy. The methodology used also provides the first evidence of the actual anatomo-functional organization of language in deaf signers. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide

    Science.gov (United States)

    Wick, Wolfgang; Roth, Patrick; Hartmann, Christian; Hau, Peter; Nakamura, Makoto; Stockhammer, Florian; Sabel, Michael C.; Wick, Antje; Koeppen, Susanne; Ketter, Ralf; Vajkoczy, Peter; Eyupoglu, Ilker; Kalff, Rolf; Pietsch, Torsten; Happold, Caroline; Galldiks, Norbert; Schmidt-Graf, Friederike; Bamberg, Michael; Reifenberger, Guido; Platten, Michael; von Deimling, Andreas; Meisner, Christoph; Wiestler, Benedikt; Weller, Michael

    2016-01-01

    Background Optimal treatment and precise classification for anaplastic glioma are needed. Methods The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). Results Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6–10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4–5.1] y vs 4.4 [3.3–5.3) y), PFS (2.5 [1.3–3.5] y vs 2.7 [1.9–3.2] y), and OS (8 [5.5–10.3] y vs 6.5 [5.4–8.3] y). Oligodendroglial versus astrocytic histology—but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status—revealed a strong prognostic value of CIMPpos with (CIMPcodel) versus without 1p/19 co-deletion (CIMPnon-codel) versus CIMPneg. but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMPcodel tumors (HR B1 vs B2 0.39 [0.17–0.92], P = .031). In CIMPneg. tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy. Conclusions There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology. Trial Registration: clinicaltrials.gov Identifier: NCT00717210. PMID:27370396

  15. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide.

    Science.gov (United States)

    Wick, Wolfgang; Roth, Patrick; Hartmann, Christian; Hau, Peter; Nakamura, Makoto; Stockhammer, Florian; Sabel, Michael C; Wick, Antje; Koeppen, Susanne; Ketter, Ralf; Vajkoczy, Peter; Eyupoglu, Ilker; Kalff, Rolf; Pietsch, Torsten; Happold, Caroline; Galldiks, Norbert; Schmidt-Graf, Friederike; Bamberg, Michael; Reifenberger, Guido; Platten, Michael; von Deimling, Andreas; Meisner, Christoph; Wiestler, Benedikt; Weller, Michael

    2016-11-01

    Optimal treatment and precise classification for anaplastic glioma are needed. The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6-10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4-5.1] y vs 4.4 [3.3-5.3) y), PFS (2.5 [1.3-3.5] y vs 2.7 [1.9-3.2] y), and OS (8 [5.5-10.3] y vs 6.5 [5.4-8.3] y). Oligodendroglial versus astrocytic histology-but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status-revealed a strong prognostic value of CIMP pos with (CIMP codel ) versus without 1p/19 co-deletion (CIMP non-codel ) versus CIMP neg . but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMP codel tumors (HR B1 vs B2 0.39 [0.17-0.92], P = .031). In CIMP neg . tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy. There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology. clinicaltrials.gov Identifier: NCT00717210. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Postoperative modified stereotactic radiotherapy using a micro-multileaf collimator in patients with malignant glioma.

    Science.gov (United States)

    Isaka, Toshihiko; Nishiyama, Kinji; Nakagawa, Hidemitsu; Suzuki, Tsuyoshi; Wada, Kouichi

    2002-06-01

    To achieve local control of malignant glioma, we designed a postoperative stereotactic radiotherapy using a micro-multileaf collimator (micro-MLC). The purpose of this study was to clarify the feasibility of this treatment. The treatment was performed in six patients who met the following eligibility criteria: (1) supratentorial tumor, (2) residual tumor volume or = 70. The three planning target volumes (PTVs), which consisted of restricted PTV (RPTV), intermediate PTV (IPTV), and extended PTV (EPTV), defined as the residual tumor plus a 1 cm, 2 cm, and 3 cm margins, respectively, and total dose delivery of 60-68 Gy, 52-60 Gy, and 44-52 Gy to the isocenters of RPTV, IPTV, and EPTV, respectively, in 4 Gy per fraction at five fractions per week, were established. The beam arrangement and the conformal blockade with a micro-MLC for the optimal treatment plan were designed. The treatment plans showed the high dose conformation to EPTV, the appropriate dose gradients in the three PTVs with the high dose homogeneity to RPTV, and the tolerated dose to critical structures. Following the plans, treatment was performed. The clinical findings more than 12 months after the treatment supported its possible use. We conclude that this treatment is feasible at least in selected patients.

  17. Glioma Indian scenario: Is there a human leucocyte antigen association?

    Science.gov (United States)

    Shankarkumar, U; Sridharan, B

    2011-07-01

    The central nervous system tumors are a rare neoplasm with little knowledge with Human Leukocyte Antigen (HLA) involvement. Primary brain tumors are cancers that originate in brain classified according to their appearance under a microscope as low grade (grade I and II) with diffuse astrocytomas, pliocytic astrocytomas, oligodendrogliomas, gangliogliomas, and mixed gliomas as common subtypes and high grade (grade III and IV). HLA associations in common glioma are reported from other parts of the world. The normal cancer treatment is surgery, followed by radiotherapy, and chemotherapy; nowadays immunotherapy is advised. HLA distribution in a Glioma patient was done based on serology and molecular techniques. The immune response gene studies have implicated the HLA allele association in most of the common diseases from India. Considerable variations are noted in HLA association with cancers; hence, we have summarized the HLA involvement in Glioma with respect to the literature. HLA A*030101, A*310102, B*350101, B*4406, Cw*040101, Cw*070101, DRB1*070101, and DRB1*1001. Ethnic diversity and HLA polymorphism precipitate differential immune response genes involved in variable disease manifestations. Therefore, caste-specific HLA allelic specificity needs to be identified, which may help in early identification of the associated HLA allele and establishing clinical practices among glioma patients.

  18. Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

    Science.gov (United States)

    Xu, Sen-Lin; Liu, Sha; Cui, Wei; Shi, Yu; Liu, Qin; Duan, Jiang-Jie; Yu, Shi-Cang; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Bian, Xiu-Wu

    2015-01-01

    Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1+ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1+ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1+ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma. PMID:26101711

  19. Validation and predictive power of radiation therapy oncology group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06

    International Nuclear Information System (INIS)

    Scott, Charles B.; Scarantino, Charles; Urtasun, Raul; Movsas, Benjamin; Jones, Christopher U.; Simpson, Joseph R.; Fischbach, A. Jennifer; Curran, Walter J.

    1996-01-01

    Background/Purpose: The recursive partitioning analysis (RPA) classes for malignant glioma patients were previously established by Curran et al. (JNCI 85:704-10, 1993) using data on over 1500 patients from the Radiation Therapy Oncology Group (RTOG). The current analysis was to validate the RPA classes on a new dataset (RTOG 90-06) and determine the predictive power of the RPA classes. Patients and Methods: There are six RPA classes for malignant glioma patients that comprise distinct groups of patients with significantly different survival outcome. RTOG 90-06 is a randomized phase III study of 712 patients accrued from 1990 to 1994. The minimum potential follow-up is 18 months. The treatment arms were combined for the purpose of this analysis. There were 84, 13, 105, 240, 150, and 23 patients in the six RPA classes from RTOG 90-06. Results: The median survival times (MST) and two-year survivals for the six RPA classes in RTOG 90-06 are compared to those published by Curran et al. (JNCI 1993). The RPA classes appear in descending order in the following table. The MST and 2-year survivals for the RTOG RPA classes were within 95% confidence intervals of the 90-06 estimates for classes I, III, IV, and V. The RPA classes explained 43% of the variation (squared error loss). By comparison, a model containing only histology explains only 13% of the variation. The RPA classes are statistically distinct with all comparisons exceeding 0.0001, except those involving class II. Conclusion: The validity of the model is verified by the reliability of the RPA classes to define distinct groups with respect to survival. Further evidence is given by prediction of MST and 2-year survival for all classes except class II. The RPA classes explained a good portion of the variation in the data. RPA class II did not perform well which may be an artifact of the small sample size or an indication that this class is not distinct. The validation of the RPA classes attests to their usefulness as

  20. Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: A report using RTOG 90-06

    International Nuclear Information System (INIS)

    Scott, Charles B.; Scarantino, Charles; Urtasun, Raul; Movsas, Benjamin; Jones, Christopher U.; Simpson, Joseph R.; Fischbach, A. Jennifer; Curran, Walter J.

    1998-01-01

    Purpose: The recursive partitioning analysis (RPA) classes for malignant glioma patients were previously established using data on over 1500 patients entered on Radiation Therapy Oncology Group (RTOG) clinical trials. The purpose of the current analysis was to validate the RPA classes with a new dataset (RTOG 90-06), determine the predictive power of the RPA classes, and establish the usefulness of the database norms for the RPA classes. Patients and Methods: There are six RPA classes for malignant glioma patients that comprise distinct groups of patients with significantly different survival outcome. RTOG 90-06 is a randomized Phase III study of 712 patients accrued from 1990 to 1994. The minimum potential follow-up is 18 months. The treatment arms were combined for the purpose of this analysis. There were 84, 13, 105, 240, 150, and 23 patients in the RPA Classes I-VI from RTOG 90-06, respectively. Results: The median survival times (MST) and 2-year survival rates for the six RPA classes in RTOG 90-06 are compared to those previously published. The MST and 2-year survival rates for the RTOG RPA classes were within 95% confidence intervals of the 90-06 estimates for Classes I, III, IV, and V. The RPA classes explained 43% of the variation (squared error loss). By comparison, a Cox model explains 30% of the variation. The RPA classes within RTOG 90-06 are statistically distinct with all comparisons exceeding 0.0001, except those involving Class II. A survival analysis from a prior RTOG study indicated that 72.0 Gy had superior outcome to literature controls; analysis of this data by RPA classes indicates the survival results were not superior to the RTOG database norms. Conclusion: The validity of the model is verified by the reliability of the RPA classes to define distinct groups with respect to survival. Further evidence is given by prediction of MST and 2-year survival for all classes except Class II. The RPA classes explained a good portion of the variation in

  1. Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET and MRI in patients with recurrent gliomas.

    Science.gov (United States)

    Youland, Ryan S; Pafundi, Deanna H; Brinkmann, Debra H; Lowe, Val J; Morris, Jonathan M; Kemp, Bradley J; Hunt, Christopher H; Giannini, Caterina; Parney, Ian F; Laack, Nadia N

    2018-05-01

    Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M-P- in 16%, M-P+ in 32%, M+P+ in 46% and M+P- in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning.

  2. Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma.

    Science.gov (United States)

    Quinn, Jennifer A; Pluda, James; Dolan, M Eileen; Delaney, Shannon; Kaplan, Richard; Rich, Jeremy N; Friedman, Allan H; Reardon, David A; Sampson, John H; Colvin, O Michael; Haglund, Michael M; Pegg, Anthony E; Moschel, Robert C; McLendon, Roger E; Provenzale, James M; Gururangan, Sridharan; Tourt-Uhlig, Sandra; Herndon, James E; Bigner, Darell D; Friedman, Henry S

    2002-05-01

    We conducted a phase II trial of carmustine (BCNU) plus the O(6)-alkylguanine-DNA alkyltransferase inhibitor O(6)-benzylguanine (O(6)-BG) to define the activity and toxicity of this regimen in the treatment of adults with progressive or recurrent malignant glioma resistant to nitrosoureas. Patients were treated with O(6)-BG at an intravenous dose of 120 mg/m(2) followed 1 hour later by 40 mg/m(2) of BCNU, with cycles repeated at 6-week intervals. Eighteen patients were treated (15 with glioblastoma multiforme, two with anaplastic astrocytoma, and one with malignant glioma). None of the 18 patients demonstrated a partial or complete response. Two patients exhibited stable disease for 12 weeks before their tumors progressed. Three patients demonstrated stable disease for 6, 12, and 18 weeks before discontinuing therapy because of hematopoietic toxicity. Twelve patients experienced reversible > or = grade 3 hematopoietic toxicity. There was no difference in half-lives (0.56 +/- 0.21 hour v 0.54 +/- 0.20 hour) or area under the curve values (4.8 +/- 1.7 microg/mL/h v 5.0 +/- 1.3 microg/mL/h) of O(6)-BG for patients receiving phenytoin and those not treated with this drug. These results indicate that O(6)-BG plus BCNU at the dose schedule used in this trial is unsuccessful in producing tumor regression in patients with nitrosourea-resistant malignant glioma, although stable disease was seen in five patients for 6, 12, 12, 12, and 18 weeks. Future use of this approach will require strategies to minimize dose-limiting toxicity of BCNU such as regional delivery or hematopoietic stem-cell protection.

  3. Concurrent radiotherapy with temozolomide vs. concurrent radiotherapy with a cisplatinum-based polychemotherapy regimen. Acute toxicity in pediatric high-grade glioma patients

    International Nuclear Information System (INIS)

    Seidel, Clemens; Kortmann, Rolf D.; Bueren, Andre O. von; Bojko, Sabrina; Hoffmann, Marion; Kramm, Christof M.; Pietsch, Torsten; Gielen, Gerrit H.; Warmuth-Metz, Monika; Bison, Brigitte

    2018-01-01

    As the efficacy of all pediatric high-grade glioma (HGG) treatments is similar and still disappointing, it is essential to also investigate the toxicity of available treatments. Prospectively recorded hematologic and nonhematologic toxicities of children treated with radiochemotherapy in the HIT GBM-C/D and HIT-HGG-2007 trials were compared. Children aged 3-18 years with histologically proven HGG (WHO grade III and IV tumors) or unequivocal radiologic diagnosis of diffuse intrinsic pontine glioma (DIPG) were included in these trials. The HIT-HGG-2007 protocol comprised concomitant radiochemotherapy with temozolomide, while cisplatinum/etoposide (PE) and PE plus ifosfamide (PEI) in combination with weekly vincristine injections were applied during radiochemotherapy in the HIT GBM-C/D protocol. Regular blood counts and information about cellular nadirs were available from 304 patients (leukocytes) and 306 patients (thrombocytes), respectively. Grade 3-4 leukopenia was much more frequent in the HIT GBM-C/D cohort (n = 88, 52%) vs. HIT-HGG-2007 (n = 13, 10%; P <0.001). Grade 3-4 thrombopenia was also more likely in the HIT GBM-C/D cohort (n = 21, 12% vs. n = 3,2%; P <0.001). Grade 3-4 leukopenia appeared more often in children aged 3-7 years (n = 38/85, 45%) than in children aged 8-12 years (n = 39/120, 33%) and 13-18 years (24/100, 24%; P =0.034). In addition, sickness was more frequent in the HIT GBM-C/D cohort (grade 1-2: 44%, grade 3-4: 6% vs. grade 1-2: 28%, grade 3-4: 1%; P <0.001). Radiochemotherapy involving cisplatinum-based polychemotherapy is more toxic than radiotherapy in combination with temozolomide. Without evidence of differences in therapeutic efficacy, the treatment with lower toxicity, i. e., radiotherapy with temozolomide should be used. (orig.) [de

  4. A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain

    International Nuclear Information System (INIS)

    Halperin, Edward C.; Herndon, James; Schold, S. Clifford; Brown, Mark; Vick, Nicholas; Cairncross, J. Gregory; Macdonald, David R.; Gaspar, Laurie; Fischer, Barbara; Dropcho, Edward; Rosenfeld, Steven; Morowitz, Richard; Piepmeier, Joseph; Hait, William; Byrne, Thomas; Salter, Merle; Imperato, Joseph; Khandekar, Janardan; Paleologos, Nina; Burger, Peter; Bentel, Gunilla C.; Friedman, Allan

    1996-01-01

    Purpose: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were ≥ 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) ≥ 60%. Methods and Materials: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m 2 ) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m 2 ) given at 6-week intervals or 6-mercaptopurine (6-MP, 750 mg/m 2 IV daily for 3 days every 6 weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average age 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS ≥ 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age ≥ 45 years (b) KPS < 90%; (c) GBM/Gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). Conclusions: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a

  5. Single- and Multivoxel Proton Spectroscopy in Pediatric Patients With Diffuse Intrinsic Pontine Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Steffen-Smith, Emilie A. [Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Venzon, David J. [Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Bent, Robyn S. [Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Hipp, Sean J. [Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, Maryland (United States); Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Warren, Katherine E., E-mail: warrenk@mail.nih.gov [Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States)

    2012-11-01

    Purpose: To determine the feasibility of two magnetic resonance spectroscopy (MRS) techniques for treating pediatric patients with diffuse intrinsic pontine gliomas (DIPGs) and to evaluate the relationship of metabolic profiles determined by each technique. Utility of each technique for improving patient management is also discussed. Methods and Materials: Children with DIPG (n = 36) were evaluated using single-voxel spectroscopy (SVS) and magnetic resonance spectroscopic imaging (MRSI) during the same imaging session. Patients were followed longitudinally (n = 150 total studies). Technical feasibility was defined by sufficient water and lipid suppression for detection of metabolites. Correlation of metabolic data obtained by SVS and MRSI was determined using the Spearman rank method. Metabolite ratios, including choline:N-acetyl-aspartate (Cho:NAA) and Cho:creatine (Cho:Cr), were obtained from SVS and MRSI. Results: SVS and MRSI acquisitions were feasible in >90% of studies. Maximum Cho:NAA and Cho:Cr from MRSI analysis were strongly associated with Cho:NAA and Cho:Cr obtained by SVS (r = 0.67 and 0.76, respectively). MRSI Cho:NAA values were more heterogeneous than Cho:Cr values within the same lesion, and a strong linear relationship between the range and maximum Cho:NAA values was observed. Conclusions: SVS and MRSI acquisitions were feasible, with a strong correlation in metabolic data. Both techniques may improve diagnostic evaluation and management of DIPG. SVS is recommended for global assessment of tumor metabolism before and after therapy. MRSI showed heterogeneous patterns of metabolic activity within these tumors and is recommended for planning and monitoring targeted therapies and evaluating nearby tissue for tumor invasion.

  6. 18F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience

    International Nuclear Information System (INIS)

    Ledezma, Carlos J.; Chen, Wei; Sai, Victor; Freitas, Bonnie; Cloughesy, Tim; Czernin, Johannes; Pope, Whitney

    2009-01-01

    Background and purpose: 18 F-FDOPA PET demonstrates higher sensitivity and specificity for gliomas than traditional [ 18 F] FDG PET imaging. However, PET provides limited anatomic localization. The purpose of this study was to determine whether 18 F-FDOPA PET/MRI fusion can provide precise anatomic localization of abnormal tracer uptake and how this activity corresponds to MR signal abnormality. Methods: Two groups of patients were analyzed. Group I consisted of 21 patients who underwent 18 F-FDOPA PET and MRI followed by craniotomy for tumor resection. Group II consisted of 70 patients with a pathological diagnosis of glioma that had 18 F-FDOPA PET and MRI but lacked additional pathologic follow-up. Fused 18 F-FDOPA PET and MRI images were analyzed for concordance and correlated with histopathologic data. Results: Fusion technology facilitated precise anatomical localization of 18 F-FDOPA activity. In group I, all 21 cases showed pathology-confirmed tumor. Of these, 18 F-FDOPA scans were positive in 9/10 (90%) previously unresected tumors, and 11/11 (100%) of recurrent tumors. Of the 70 patients in group II, concordance between MRI and 18 F-FDOPA was found in 49/54 (90.1%) of patients with sufficient follow-up; in the remaining 16 patients concordance could not be determined due to lack of follow-up. 18 F-FDOPA labeling was comparable in both high- and low-grade gliomas and identified both enhancing and non-enhancing tumor equally well. In some cases, 18 F-FDOPA activity preceded tumor detection on MRI. Conclusion: 18 F-FDOPA PET/MRI fusion provides precise anatomic localization of tracer uptake and labels enhancing and non-enhancing tumor well. In a small minority of cases, 18 F-FDOPA activity may identify tumor not visible on MRI.

  7. [A correlation between diffusion kurtosis imaging and the proliferative activity of brain glioma].

    Science.gov (United States)

    Tonoyan, A S; Pronin, I N; Pitshelauri, D I; Shishkina, L V; Fadeeva, L M; Pogosbekyan, E L; Zakharova, N E; Shults, E I; Khachanova, N V; Kornienko, V N; Potapov, A A

    2015-01-01

    The aim of the study was to assess the capabilities of diffusion kurtosis imaging (DKI) in diagnosis of the glioma proliferative activity and to evaluate a relationship between the glioma proliferative activity index and diffusion parameters of the contralateral normal appearing white matter (CNAWM). The study included 47 patients with newly diagnosed brain gliomas (23 low grade, 13 grade III, and 11 grade IV gliomas). We determined a relationship between absolute and normalized parameters of the diffusion tensor (mean (MD), axial (AD), and radial (RD) diffusivities; fractional (FA) and relative (RA) anisotropies) and diffusion kurtosis (mean (MK), axial (AK), and radial (RK) kurtosis; kurtosis anisotropy (KA)) and the proliferative activity index in the most malignant glioma parts (pAK, and RK) and anisotropy (KA, FA, RA) values increased, and diffusivity (MD, AD, RD) values decreased as the glioma proliferative activity index increased. A strong correlation between the proliferative activity index and absolute RK (r=0,71; p=0.000001) and normalized values of MK (r=0.8; p=0.000001), AK (r=0.71; p=0.000001), RK (r=0.81; p=0.000001), and RD (r=-0.71; p=0.000001) was found. A weak, but statistically significant correlation between the glioma proliferative activity index and diffusion values RK (r=-0.36; p=0.014), KA (r=-0.39; p=0.007), RD (r=0.35; p=0.017), FA (r=-0.42; p=0.003), and RA (r=-0.41; p=0.004) of CNAWM was found. DKI has good capabilities to detect immunohistochemical changes in gliomas. DKI demonstrated a high sensitivity in detection of microstructural changes in the contralateral normal appearing white matter in patients with brain gliomas.

  8. Low grade gliomas: preliminary analysis of failure patterns among patients treated using 3D conformal external beam irradiation

    International Nuclear Information System (INIS)

    Pu, Anthony T.; Sandler, Howard M.; Radany, Eric H.; Blaivas, Mila; Page, Michaelyn A.; Greenberg, Harry S.; Junck, Larry; Ross, Donald A.

    1995-01-01

    Purpose: The pattern of failure of low grade gliomas following radiotherapy is less well known than that of the high grade gliomas. Stereotactic histologic studies have suggested that tumor cells extend beyond imaging abnormalities, and that large margins would be required for radiotherapy target volumes to encompass all of the neoplasm. Our experience using computerized tomography (CT)- and magnetic resonance (MR)-planned irradiation of low grade gliomas was reviewed to determine the pattern of tumor recurrence, in an effort to clinically define the minimum margin required. Methods and Materials: Forty-six patients with low grade supratentorial gliomas were treated between April 1985 and November 1992 using three-dimensional (3D) conformal CT- or MR-planned external beam radiotherapy. Fields were designed to encompass a target volume created by adding a margin to the tumor in three dimensions. Generally, patients were treated using shrinking fields with an initial target (tumor plus a 1 to 3 cm margin) treated to a dose of 45 to 50.4 (median 50.4) Gy, and a boost (tumor plus a 0 to 2 cm margin) treated to a total of 54 to 59.4 (median 59.4) Gy. Median follow-up was 32.9 months. Results: There have been 11 failures; all of these occurred within the radiographic abnormality (either T2 prolongation or CT hypodensity) visualized at the time of treatment planning (i.e., all failures were within the boost volume). Median time to failure was 53 months. Because all failures were local, there was no relationship between the amount by which the tumor volumes were expanded to create target volumes and the eventual outcome. Conclusion: Despite pathologic data suggesting that low grade glioma cells can be found outside the MR T2-signal abnormality in many cases, our results demonstrate that conformal external beam radiotherapy, in which the high dose volume is limited, does not result in increased marginal or out-of-field failures. Until control of tumor within the

  9. Benefits of adjuvant chemotherapy in high-grade gliomas.

    Science.gov (United States)

    DeAngelis, Lisa M

    2003-12-01

    The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

  10. Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis.

    Science.gov (United States)

    Walsh, Kyle M; Rice, Terri; Decker, Paul A; Kosel, Matthew L; Kollmeyer, Thomas; Hansen, Helen M; Zheng, Shichun; McCoy, Lucie S; Bracci, Paige M; Anderson, Erik; Hsuang, George; Wiemels, Joe L; Pico, Alexander R; Smirnov, Ivan; Molinaro, Annette M; Tihan, Tarik; Berger, Mitchell S; Chang, Susan M; Prados, Michael D; Lachance, Daniel H; Sicotte, Hugues; Eckel-Passow, Jeanette E; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

    2013-08-01

    Genome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. We examined associations of these 7 established glioma risk loci with age at diagnosis among patients with glioma. SNP genotype data were available for 2286 Caucasian glioma patients from the University of California, San Francisco (n = 1434) and the Mayo Clinic (n = 852). Regression analyses were performed to test for associations between "number of risk alleles" and "age at diagnosis," adjusted for sex and study site and stratified by tumor grade/histology where appropriate. Four SNPs were significantly associated with age at diagnosis. Carrying a greater number of risk alleles at rs55705857 (CCDC26) and at rs498872 (PHLDB1) was associated with younger age at diagnosis (P = 1.4 × 10(-22) and P = 9.5 × 10(-7), respectively). These SNPs are stronger risk factors for oligodendroglial tumors, which tend to occur in younger patients, and their association with age at diagnosis varied across tumor subtypes. In contrast, carrying more risk alleles at rs2736100 (TERT) and at rs6010620 (RTEL1) was associated with older age at diagnosis (P = 6.2 × 10(-4) and P = 2.5 × 10(-4), respectively). These SNPs are risk factors for all glioma grades/histologies, and their association with age at diagnosis was consistent across tumor subgroups. Carrying a greater number of risk alleles might be expected to decrease age at diagnosis. However, glioma susceptibility conferred by variation in telomerase-related genes did not follow this pattern. This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres).

  11. 12 years' experience with intraoperative radiotherapy (IORT) of malignant gliomas

    International Nuclear Information System (INIS)

    Schueller, P.; Micke, O.; Moustakis, C.; Bruns, F.; Schuck, A.; Willich, N.; Palkovic, S.; Schroeder, J.; Wassmann, H.

    2005-01-01

    Background: Even after surgery and radiotherapy, malignant gliomas still have a poor prognosis. The authors report on their experience with IORT in 71 patients. Patients and methods: From May 1992 to February 2004, 71 patients with malignant gliomas were treated with IORT. 26 patients suffered from grade III gliomas, 45 patients from glioblastomas (GBM). IORT was carried out using a standard electron tube and 9- to 18-MeV electrons. 52/71 patients who were primarily treated received 20 Gy IORT + 60 Gy postoperative radiotherapy, 19/71 patients with recurrences only received IORT (20-25 Gy). Results: The complication rates were 1.4% for wound infections and 5.6% for hemorrhage. Median disease-specific survival amounted to 14.9 months (gliomass III) and 14.2 months (GBM). The 2-year survival rates amounted to 26.9% (gliomas III) and 6.8% (GBM; p=0.0296). Total versus subtotal resection had no significant influence on survival (p=0.0741), nor had age, sex, tumor site, performance status, size, primary versus recurrence, and radiation dose. A comparison to a conventionally treated patient group did not show a significant survival improvement. 3 months after treatment, initial symptoms had improved in 59% (hemiparesis), 50% (aphasia), 50% (hemianopsia), and 60% (convulsions). Conclusion: IORT has been shown to be feasible; perioperative complication rates were not increased. Survival was generally not improved compared to a historical control group. Recurrences achieved the same survival as primary tumors, and GBM also had a slightly increased survival, thus being possible indications for IORT. (orig.)

  12. Prognostic implications of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET/CT in patients with glioma.

    Science.gov (United States)

    Toriihara, Akira; Ohtake, Makoto; Tateishi, Kensuke; Hino-Shishikura, Ayako; Yoneyama, Tomohiro; Kitazume, Yoshio; Inoue, Tomio; Kawahara, Nobutaka; Tateishi, Ukihide

    2018-05-01

    The potential of positron emission tomography/computed tomography using 62 Cu-diacetyl-bis (N 4 -methylthiosemicarbazone) ( 62 Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of 62 Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[ 18 F]fluoro-D-glucose ( 18 F-FDG). 56 patients with glioma of World Health Organization grade 2-4 were enrolled. All participants had undergone both 62 Cu-ATSM PET/CT and 18 F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox's proportional hazards model. Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using 62 Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using 62 Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p PET/CT showed significant difference of progression-free survival (p PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to 18 F-FDG PET/CT.

  13. Angiogenesis in gliomas.

    Directory of Open Access Journals (Sweden)

    Elzbieta Czykier

    2008-02-01

    Full Text Available Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination has a great prognostic value. The aim of the study was to assess the vascularisation of chosen brain gliomas and to estimate how it is correlated with tumour histological type, malignancy grade, location and size, and with age and sex of patients. Tumour vascularisation analysis was based on the determination of microvascular proliferation (MVP and microvessel density (MVD. Microvascular proliferation was measured with immunohistochemical methods using mouse monoclonal antibodies to detect cell proliferation antigens. The following antibodies were used Ki-67 and PCNA (DAKO. Identification of vessels was performed by CD31 antibody and anti-human von Willebrand factor (DAKO. The highest microvascular proliferation and microvascular density were observed in multiform glioblastomas and the lowest in oligodendrogliomas. Significant correlation was observed between the vascularisation and malignancy grade.

  14. Cognitive functioning early after surgery of gliomas in eloquent areas

    NARCIS (Netherlands)

    Satoer, Djaina; Vork, Judith; Visch-Brink, Evy; Smits, Marion; Dirven, Clemens; Vincent, Arnaud

    2012-01-01

    OBJECT: Patients with gliomas frequently have cognitive deficits, and surgery can exacerbate these deficits. Preoperative assessment is therefore crucial in patients undergoing surgery for glioma in eloquent areas, because the proximity of functional areas increases the risk of permanent

  15. Retrospective analysis of 104 histologically proven adult brainstem gliomas: clinical symptoms, therapeutic approaches and prognostic factors

    International Nuclear Information System (INIS)

    Reithmeier, Thomas; Kuzeawu, Aanyo; Hentschel, Bettina; Loeffler, Markus; Trippel, Michael; Nikkhah, Guido

    2014-01-01

    Adult brainstem gliomas are rare primary brain tumors (<2% of gliomas). The goal of this study was to analyze clinical, prognostic and therapeutic factors in a large series of histologically proven brainstem gliomas. Between 1997 and 2007, 104 patients with a histologically proven brainstem glioma were retrospectively analyzed. Data about clinical course of disease, neuropathological findings and therapeutic approaches were analyzed. The median age at diagnosis was 41 years (range 18-89 years), median KPS before any operative procedure was 80 (range 20-100) and median survival for the whole cohort was 18.8 months. Histopathological examinations revealed 16 grade I, 31 grade II, 42 grade III and 14 grade IV gliomas. Grading was not possible in 1 patient. Therapeutic concepts differed according to the histopathology of the disease. Median overall survival for grade II tumors was 26.4 months, for grade III tumors 12.9 months and for grade IV tumors 9.8 months. On multivariate analysis the relative risk to die increased with a KPS ≤ 70 by factor 6.7, with grade III/IV gliomas by the factor 1.8 and for age ≥ 40 by the factor 1.7. External beam radiation reduced the risk to die by factor 0.4. Adult brainstem gliomas present with a wide variety of neurological symptoms and postoperative radiation remains the cornerstone of therapy with no proven benefit of adding chemotherapy. Low KPS, age ≥ 40 and higher tumor grade have a negative impact on overall survival

  16. Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma

    DEFF Research Database (Denmark)

    Tietze, Anna; Mouridsen, Kim; Lassen-Ramshad, Yasmin

    2015-01-01

    Objectives: Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI) based indices of microvascular flow control provide more information on tumor grade and patient outcome...... than does the established PWI angiogenesis marker, cerebral blood volume (CBV). Material and Methods: Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas) were included. Capillary transit time heterogeneity (CTH) and COV, its ratio to blood mean transit time, provide indices...... of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival...

  17. Antithrombin III for critically ill patients

    DEFF Research Database (Denmark)

    Allingstrup, Mikkel; Wetterslev, Jørn; Ravn, Frederikke B

    2016-01-01

    PURPOSE: Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients. METHODS: We searched from inception to 27 August 2015 in CENTRAL, MEDLINE, EMBASE, CAB, BIOSIS and CINAHL. We included randomized...... participants). However, for all other outcome measures and analyses, the results did not reach statistical significance. CONCLUSIONS: There is insufficient evidence to support AT III substitution in any category of critically ill participants including those with sepsis and DIC. AT III did not show an impact...

  18. A software package for patient-specific dosimetry in the locoregional RIT of gliomas using 188Re labelled NIMOTUZUMAB

    International Nuclear Information System (INIS)

    Torres, L.A.; Coca, M.A.; Sanchez, Y.; Cornejo, N.; Catasus, C.; Denaro, M. de

    2008-01-01

    Full text: The locoregional treatment of high-grade gliomas using beta emitter compounds allows delivering high radiation doses in the tumor bed and the brain adjacent tissues of patients suffering these aggressive malignancies. The main goal of this work was to implement patient-specific dosimetry procedures using a voxel-based methodology in order to compute and analyze the three-dimensional doses distributions received by the patients undergoing loco-regional treatment of gliomas with the 188 Re labeled MAb NIMOTUZUMAB. A software package called TRIDOSE has been developed to perform the image managing, volume registration, dose calculations and qualitative and quantitative analysis of the results, including dose-volume histograms and isodose curves. The dosimetric factors at voxel level for 188 Re ('S' values) were estimated using two different methods, Monte Carlo simulations of energy transport and deposition and the integration of the dose kernel functions. A quality control module was also implemented in order to test the software using well-known 3D distribution of activities or counts. The TRIDOSE outputs were compared with other commercial software showing relative differences lower than 1.10% for different sphere sizes. The established dosimetric procedures constitute a useful tool to compute the absorbed doses received by patients undergoing radioimmunotherapy of brain tumors with 188 Re-NIMOTUZUMAB. (author)

  19. Nitrosourea efficacy in high-grade glioma: a survival gain analysis summarizing 504 cohorts with 24193 patients.

    Science.gov (United States)

    Wolff, Johannes E A; Berrak, Su; Koontz Webb, Susannah E; Zhang, Ming

    2008-05-01

    Even though past studies have suggested efficacy of nitrosourea drugs in patients with high-grade glioma and temozolomide has recently been shown significantly to be beneficial, no conclusive comparisons between these agents have been published. We performed a survival gain analysis of 364 studies describing 24,193 patients with high-grade glioma treated in 504 cohorts, and compared the effects of drugs. The most frequent diagnoses were glioblastoma multiforme (GBM) (72%) and anaplastic astrocytoma (22%). The mean overall survival (mOS) was 14.1 months. The outcome was influenced by several of the known prognostic factors including the histological grade, if the tumors were newly diagnosed or recurrent, the completeness of resection, patients' age, and gender. This information allowed the calculation of a predicted mOS for each cohort based on their prognostic factors independent of treatment. Survival gain to characterize the influence of treatment was subsequently defined and validated as the difference between the observed and the predicted mOS. In 62 CCNU-treated cohorts and 15 ACNU-treated cohorts the survival gain was 5.3 months and 8.9 months (P < 0.0005), respectively. No detectable survival gain for patients treated with various BCNU-containing regimens was found. Conclusion CCNU- and ACNU-containing regimens were superior to BCNU containing regiments.

  20. Characterization of the serum metabolome following radiation treatment in patients with high-grade gliomas

    International Nuclear Information System (INIS)

    Mörén, Lina; Wibom, Carl; Bergström, Per; Johansson, Mikael; Antti, Henrik; Bergenheim, A. Tommy

    2016-01-01

    Glioblastomas progress rapidly making response evaluation using MRI insufficient since treatment effects are not detectable until months after initiation of treatment. Thus, there is a strong need for supplementary biomarkers that could provide reliable and early assessment of treatment efficacy. Analysis of alterations in the metabolome may be a source for identification of new biomarker patterns harboring predictive information. Ideally, the biomarkers should be found within an easily accessible compartment such as the blood. Using gas-chromatographic- time-of-flight-mass spectroscopy we have analyzed serum samples from 11 patients with glioblastoma during the initial phase of radiotherapy. Fasting serum samples were collected at admittance, on the same day as, but before first treatment and in the morning after the second and fifth dose of radiation. The acquired data was analyzed and evaluated by chemometrics based bioinformatics methods. Our findings were compared and discussed in relation to previous data from microdialysis in tumor tissue, i.e. the extracellular compartment, from the same patients. We found a significant change in metabolite pattern in serum comparing samples taken before radiotherapy to samples taken during early radiotherapy. In all, 68 metabolites were lowered in concentration following treatment while 16 metabolites were elevated in concentration. All detected and identified amino acids and fatty acids together with myo-inositol, creatinine, and urea were among the metabolites that decreased in concentration during treatment, while citric acid was among the metabolites that increased in concentration. Furthermore, when comparing results from the serum analysis with findings in tumor extracellular fluid we found a common change in metabolite patterns in both compartments on an individual patient level. On an individual metabolite level similar changes in ornithine, tyrosine and urea were detected. However, in serum, glutamine and

  1. Model-based, semiquantitative and time intensity curve shape analysis of dynamic contrast-enhanced MRI: a comparison in patients undergoing antiangiogenic treatment for recurrent glioma

    NARCIS (Netherlands)

    Lavini, Cristina; Verhoeff, Joost J. C.; Majoie, Charles B.; Stalpers, Lukas J. A.; Richel, Dick J.; Maas, Mario

    2011-01-01

    To compare time intensity curve (TIC)-shape analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data with model-based analysis and semiquantitative analysis in patients with high-grade glioma treated with the antiangiogenic drug bevacizumab. Fifteen patients had a pretreatment

  2. Gliomas: Application of Cumulative Histogram Analysis of Normalized Cerebral Blood Volume on 3 T MRI to Tumor Grading

    Science.gov (United States)

    Kim, Hyungjin; Choi, Seung Hong; Kim, Ji-Hoon; Ryoo, Inseon; Kim, Soo Chin; Yeom, Jeong A.; Shin, Hwaseon; Jung, Seung Chai; Lee, A. Leum; Yun, Tae Jin; Park, Chul-Kee; Sohn, Chul-Ho; Park, Sung-Hye

    2013-01-01

    Background Glioma grading assumes significant importance in that low- and high-grade gliomas display different prognoses and are treated with dissimilar therapeutic strategies. The objective of our study was to retrospectively assess the usefulness of a cumulative normalized cerebral blood volume (nCBV) histogram for glioma grading based on 3 T MRI. Methods From February 2010 to April 2012, 63 patients with astrocytic tumors underwent 3 T MRI with dynamic susceptibility contrast perfusion-weighted imaging. Regions of interest containing the entire tumor volume were drawn on every section of the co-registered relative CBV (rCBV) maps and T2-weighted images. The percentile values from the cumulative nCBV histograms and the other histogram parameters were correlated with tumor grades. Cochran’s Q test and the McNemar test were used to compare the diagnostic accuracies of the histogram parameters after the receiver operating characteristic curve analysis. Using the parameter offering the highest diagnostic accuracy, a validation process was performed with an independent test set of nine patients. Results The 99th percentile of the cumulative nCBV histogram (nCBV C99), mean and peak height differed significantly between low- and high-grade gliomas (P = histogram analysis of nCBV using 3 T MRI can be a useful method for preoperative glioma grading. The nCBV C99 value is helpful in distinguishing high- from low-grade gliomas and grade IV from III gliomas. PMID:23704910

  3. Elevation of the correlation between cerebral blood volume and permeability surface from CT perfusion images with glioma grade

    International Nuclear Information System (INIS)

    Ding Bei; Ling Huawei; Zhang Huan; Song Qi; Dong Haipeng; Chen Kemin

    2007-01-01

    Objective: To evaluate the correlation between cerebral blood volume and permeability surface by using multislice CT perfusion imaging with glioma grade. Methods: Ninteen patients with gliomas underwent conventional MR and multislice CT perfusion imaging preoperatively. These patients were divided into low grade and high grade groups which were correspond to WHO II grade gliomas and WHO III or IV grade gliomas respectively. CT data were transferred to on-line working station and processed to obtain time-signal curves, color perfusion maps and calculated perfusion parameters, including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTF) and permeability surfaces (PS) in tumoral parenchyma. Kruskal-Wallis test and correlation of CBV and PS was assessed by using SPSS 11.0 software. Results: The median of CBV and PS in low-grade and high-grade glioma were 2.7, 6.5 ml/100 g; 0.389, 12.810 ml·100 g -1 ·min -1 respectively, corresponding t value were 12.907 13.500 with P<0.05. Pearson correlations between CBV and PS were as follows: in low-grade group, r=-0.058, in high-grade group, r=0.648. Conclusion: Both CBV and PS have obvious correlation with glioma grade. The correlation between CBV and PS in low-grade glioma was weaker, probably because of the focal high vascularity in oligodendroglioma. (authors)

  4. Optimizing a machine learning based glioma grading system using multi-parametric MRI histogram and texture features.

    Science.gov (United States)

    Zhang, Xin; Yan, Lin-Feng; Hu, Yu-Chuan; Li, Gang; Yang, Yang; Han, Yu; Sun, Ying-Zhi; Liu, Zhi-Cheng; Tian, Qiang; Han, Zi-Yang; Liu, Le-De; Hu, Bin-Quan; Qiu, Zi-Yu; Wang, Wen; Cui, Guang-Bin

    2017-07-18

    Current machine learning techniques provide the opportunity to develop noninvasive and automated glioma grading tools, by utilizing quantitative parameters derived from multi-modal magnetic resonance imaging (MRI) data. However, the efficacies of different machine learning methods in glioma grading have not been investigated.A comprehensive comparison of varied machine learning methods in differentiating low-grade gliomas (LGGs) and high-grade gliomas (HGGs) as well as WHO grade II, III and IV gliomas based on multi-parametric MRI images was proposed in the current study. The parametric histogram and image texture attributes of 120 glioma patients were extracted from the perfusion, diffusion and permeability parametric maps of preoperative MRI. Then, 25 commonly used machine learning classifiers combined with 8 independent attribute selection methods were applied and evaluated using leave-one-out cross validation (LOOCV) strategy. Besides, the influences of parameter selection on the classifying performances were investigated. We found that support vector machine (SVM) exhibited superior performance to other classifiers. By combining all tumor attributes with synthetic minority over-sampling technique (SMOTE), the highest classifying accuracy of 0.945 or 0.961 for LGG and HGG or grade II, III and IV gliomas was achieved. Application of Recursive Feature Elimination (RFE) attribute selection strategy further improved the classifying accuracies. Besides, the performances of LibSVM, SMO, IBk classifiers were influenced by some key parameters such as kernel type, c, gama, K, etc. SVM is a promising tool in developing automated preoperative glioma grading system, especially when being combined with RFE strategy. Model parameters should be considered in glioma grading model optimization.

  5. High grade glioma: Imaging combined with pathological grade defines management and predicts prognosis

    International Nuclear Information System (INIS)

    Burnet, Neil G.; Lynch, Andrew G.; Jefferies, Sarah J.; Price, Stephen J.; Jones, Phil H.; Antoun, Nagui M.; Xuereb, John H.; Pohl, Ute

    2007-01-01

    Introduction: There is ambiguity in pathological grading of high grade gliomas within the WHO 2000 classification, especially those with predominant oligodendroglial differentiation. Patients and methods: All adult high grade gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was grade III but radiology suggested glioblastoma (GBM) were classified as 'grade III/IV'; their pathology was reviewed. Results: Data from 245 patients (52 grade III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards model. On pathology review, features suggestive of more aggressive behaviour were found in all 18 grade III/IV tumours. Oligodendroglial components with both necrosis and microvascular proliferation were present in 7. MIB-1 counts for the last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months, grade III/IV 10 months, GBM 11 months. Survival was not significantly different between grade III/IV and GBM. Patients with grade III/IV tumours had significantly worse outcome than grade III, with a hazard of death 3.7 times higher. Conclusions: The results highlight the current inconsistency in pathological grading of high grade tumours, especially those with oligodendroglial elements. Patients with histological grade III tumours but radiological appearances suggestive of GBM should be managed as glioblastoma

  6. Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era

    Science.gov (United States)

    Perry, Christina; Agarwal, Devika; Abdel-Fatah, Tarek M.A.; Lourdusamy, Anbarasu; Grundy, Richard; Auer, Dorothee T.; Walker, David; Lakhani, Ravi; Scott, Ian S.; Chan, Stephen; Ball, Graham; Madhusudan, Srinivasan

    2014-01-01

    Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in ‘The Cancer Genome Atlas’ (TCGA) cohort (n=508). A DNA repair prognostic index model was generated. Artificial neural network analysis (ANN) was conducted to investigate global gene interactions. Protein expression by immunohistochemistry was conducted in 61 tumours. A fourteen DNA repair gene expression panel was associated with poor survival in Test and TCGA cohorts. A Cox multivariate model revealed APE1, NBN, PMS2, MGMT and PTEN as independently associated with poor prognosis. A DNA repair prognostic index incorporating APE1, NBN, PMS2, MGMT and PTEN stratified patients in to three prognostic sub-groups with worsening survival. APE1, NBN, PMS2, MGMT and PTEN also have predictive significance in patients who received chemotherapy and/or radiotherapy. ANN analysis of APE1, NBN, PMS2, MGMT and PTEN revealed interactions with genes involved in transcription, hypoxia and metabolic regulation. At the protein level, low APE1 and low PTEN remain associated with poor prognosis. In conclusion, multiple DNA repair pathways operate to influence biology and clinical outcomes in adult high grade gliomas. PMID:25026297

  7. The prevalence of human cytomegalovirus DNA in gliomas of Brazilian patients

    Directory of Open Access Journals (Sweden)

    Renata Fragelli Fonseca

    2012-11-01

    Full Text Available Members of the Herpesviridae family have been implicated in a number of tumours in humans. At least 75% of the human population has had contact with cytomegalovirus (HCMV. In this work, we screened 75 Brazilian glioma biopsies for the presence of HCMV DNA sequences. HCMV DNA was detected in 36% (27/75 of the biopsies. It is possible that HCMV could be a co-factor in the evolution of brain tumours.

  8. Malignant gliomas of the brain managed by radiotherapy after surgery

    Energy Technology Data Exchange (ETDEWEB)

    Fichardt, T.; Sandison, A.G. (Pretoria Univ. (South Africa). Dept. of Radiotherapy)

    The article reviews the literature and gives an account of the authors' experience during a 20-year period (1960-1980) of the value of radiotherapy after surgery in the management of 76 patients suffering from brain gliomas classified into 3 grades according to the degree of anaplasia present in the histological sections, viz. grades II, III and IV. Radiotherapy was not given to grade I malignant gliomas as they are treated by surgery only. The period is divided into 2 subperiods. The first is from 1960-1972 when part-brain, high-dose irradiation following surgery was used on 33 patients in various age groups. The second period covers whole-brain, low-dose irradiation following surgery and was used on 43 patients in various age groups.

  9. Intratumoral heterogeneity of 18F-FLT uptake predicts proliferation and survival in patients with newly diagnosed gliomas

    International Nuclear Information System (INIS)

    Mitamura, Katsuya; Yamamoto, Yuka; Kudomi, Nobuyuki; Norikane, Takashi; Miyake, Keisuke; Nishiyama, Yoshihiro; Maeda, Yukito

    2017-01-01

    The nucleoside analog 3'-deoxy-3'- 18 F-fluorothymidine (FLT) has been investigated for evaluating tumor proliferating activity in brain tumors. We evaluated FLT uptake heterogeneity using textural features from the histogram analysis in patients with newly diagnosed gliomas and examined correlation of the results with proliferative activity and patient prognosis, in comparison with the conventional PET parameters. FLT PET was investigated in 37 patients with newly diagnosed gliomas. The conventional parameters [tumor-to-contralateral normal brain tissue (T/N) ratio and metabolic tumor volume (MTV)] and textural parameters (standard deviation, skewness, kurtosis, entropy, and uniformity) were derived from FLT PET images. Linear regression analysis was used to compare PET parameters and the proliferative activity as indicated by the Ki-67 index. The associations between parameters and overall survival (OS) were tested by Cox regression analysis. Median OS was 662 days. For the conventional parameters, linear regression analysis indicated a significant correlation between T/N ratio and Ki-67 index (p = 0.02) and MTV and Ki-67 index (p = 0.02). Among textural parameters, linear regression analysis indicated a significant correlation for kurtosis (p = 0.003), entropy (p < 0.001), and uniformity (p < 0.001) as compared to Ki-67 index, exceeding those of the conventional parameters. The results of univariate analysis suggested that skewness and kurtosis were associated with OS (p = 0.03 and 0.02, respectively). Mean survival for patients with skewness values less than 0.65 was 1462 days, compared with 917 days for those with values greater than 0.65 (p = 0.02). Mean survival for patients with kurtosis values less than 6.16 was 1616 days, compared with 882 days for those with values greater than 6.16 (p = 0.006). Based on the results of this preliminary study in a small patient population, textural features reflecting heterogeneity on FLT PET images seem to be

  10. A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

    International Nuclear Information System (INIS)

    Wuthrick, Evan J.; Curran, Walter J.; Camphausen, Kevin; Lin, Alexander; Glass, Jon; Evans, James; Andrews, David W.; Axelrod, Rita; Shi, Wenyin; Werner-Wasik, Maria; Haacke, E. Mark; Hillman, Gilda G.; Dicker, Adam P.

    2014-01-01

    Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival

  11. A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Wuthrick, Evan J., E-mail: evan.wuthrick@osumc.edu [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Curran, Walter J. [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Camphausen, Kevin [Department of Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland (United States); Lin, Alexander [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Glass, Jon; Evans, James; Andrews, David W. [Department of Neurological Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Axelrod, Rita [Department of Medical Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Shi, Wenyin; Werner-Wasik, Maria [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Haacke, E. Mark [Department of Radiology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Department of Biomedical Engineering, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Hillman, Gilda G. [Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Dicker, Adam P. [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-10-01

    Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival.

  12. Motor Cortex Reorganization in Patients with Glioma Assessed by Repeated Navigated Transcranial Magnetic Stimulation-A Longitudinal Study.

    Science.gov (United States)

    Barz, Anne; Noack, Anika; Baumgarten, Peter; Seifert, Volker; Forster, Marie-Therese

    2018-04-01

    Evidence for cerebral reorganization after resection of low-grade glioma has mainly been obtained by serial intraoperative cerebral mapping. Noninvasively collected data on cortical plasticity in tumor patients over a surgery-free period are still scarce. The present study therefore aimed at evaluating motor cortex reorganization by navigated transcranial magnetic stimulation (nTMS) in patients after perirolandic glioma surgery. nTMS was performed preoperatively and postoperatively in 20 patients, separated by 26.1 ± 24.8 months. Further nTMS mapping was conducted in 14 patients, resulting in a total follow-up period of 46.3 ± 25.4 months. Centers of gravity (CoGs) were calculated for every muscle representation area, and Euclidian distances between CoGs over time were defined. Results were compared with data from 12 healthy individuals, who underwent motor cortex mapping by nTMS in 2 sessions. Preoperatively and postoperatively pooled CoGs from the area of the dominant abductor pollicis brevis muscle and of the nondominant leg area differed significantly compared with healthy individuals (P < 0.05). Most remarkably, during the ensuing follow-up period, a reorganization of all representation areas was observed in 3 patients, and a significant shift of hand representation areas was identified in further 3 patients. Complete functional recovery of postoperative motor deficits was exclusively associated with cortical reorganization. Despite the low potential of remodeling within the somatosensory region, long-term reorganization of cortical motor function can be observed. nTMS is best suited for a noninvasive evaluation of this reorganization. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Measuring health-related quality of life in high-grade glioma patients at the end of life using a proxy-reported retrospective questionnaire

    NARCIS (Netherlands)

    Sizoo, E.M.; Dirven, L.; Reijneveld, J.C.; Postma, T.J.; Heimans, J.J.; Deliens, L.; Pasman, H.R.W.; Taphoorn, M.J.B.

    2014-01-01

    To develop, validate, and report on the use of a retrospective proxy-reported questionnaire measuring health-related quality of life (HRQoL) in the end-of-life (EOL) phase of high-grade glioma (HGG) patients. Items relevant for the defined construct were selected using existing questionnaires,

  14. Prospective study of p-[{sup 123}I]iodo-L-phenylalanine and SPECT for the evaluation of newly diagnosed cerebral lesions: specific confirmation of glioma

    Energy Technology Data Exchange (ETDEWEB)

    Hellwig, Dirk; Schaefer, Andrea; Farmakis, Georgios; Grgic, Aleksandar; Kirsch, Carl-Martin [Saarland University Medical Center, Department of Nuclear Medicine, Homburg/Saar (Germany); Ketter, Ralf; Moringlane, Jean R.; Steudel, Wolf-Ingo [Saarland University Medical Center, Department of Neurosurgery, Homburg (Germany); Romeike, Bernd F.M. [Saarland University Medical Center, Institute of Neuropathology, Homburg (Germany); Friedrich-Schiller-University, Department of Neuropathology, Jena (Germany); Samnick, Samuel [Saarland University Medical Center, Department of Nuclear Medicine, Homburg/Saar (Germany); University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany)

    2010-12-15

    The differentiation between gliomas, metastases and gliotic or inflammatory lesions by imaging techniques remains a challenge. Gliomas frequently exhibit increased uptake of radiolabelled amino acids and are thus amenable to PET or SPECT imaging. Recently, p-[{sup 123}I]iodo-L-phenylalanine (IPA) was validated for the visualization of glioma by SPECT and received orphan drug status. Here we investigated its diagnostic performance for differentiating indeterminate brain lesions. This prospective open study included 67 patients with newly diagnosed brain lesions suspicious for glioma (34 without and 33 with contrast enhancement in the MRI scan). Patients received 250 MBq IPA intravenously after overnight fasting. SPECT images at 30 min and 3 h post-injection were iteratively reconstructed and visually interpreted after image fusion with an MRI brain scan (fluid-attenuated inversion recovery sequence or T1-weighted contrast-enhanced image). Findings were correlated with results of stereotactic or open biopsies or serial imaging. Twenty-seven low-grade (2 WHO I, 25 WHO II) and 24 high-grade gliomas (1 WHO III, 23 WHO IV), 3 metastases originating from lung cancer as well as 13 non-neoplastic lesions were proven. All non-neoplastic lesions and all metastases were negative with IPA SPECT. Forty gliomas were true-positive (TP) and 11 false-negative (FN) findings (8 WHO II, 1 WHO III, 2 WHO IV) occurred. There were no false-positive (FP) findings. For the differentiation of primary brain tumours and non-neoplastic lesions, sensitivity and specificity were 78 and 100%. In 34 lesions without contrast enhancement in MRI, IPA SPECT resulted in 17 TP, 8 true-negative, 9 FN and no FP findings (sensitivity 65%, specificity 100%). In patients with suspected glioma, IPA SPECT shows a high specificity, but especially in low-grade gliomas FN findings may occur. Due to the high positive predictive value a positive finding allows a suspected glioma to be confirmed. (orig.)

  15. Concurrent radiotherapy with temozolomide vs. concurrent radiotherapy with a cisplatinum-based polychemotherapy regimen : Acute toxicity in pediatric high-grade glioma patients.

    Science.gov (United States)

    Seidel, Clemens; von Bueren, André O; Bojko, Sabrina; Hoffmann, Marion; Pietsch, Torsten; Gielen, Gerrit H; Warmuth-Metz, Monika; Bison, Brigitte; Kortmann, Rolf-D; Kramm, Christof M

    2018-03-01

    As the efficacy of all pediatric high-grade glioma (HGG) treatments is similar and still disappointing, it is essential to also investigate the toxicity of available treatments. Prospectively recorded hematologic and nonhematologic toxicities of children treated with radiochemotherapy in the HIT GBM-C/D and HIT-HGG-2007 trials were compared. Children aged 3-18 years with histologically proven HGG (WHO grade III and IV tumors) or unequivocal radiologic diagnosis of diffuse intrinsic pontine glioma (DIPG) were included in these trials. The HIT-HGG-2007 protocol comprised concomitant radiochemotherapy with temozolomide, while cisplatinum/etoposide (PE) and PE plus ifosfamide (PEI) in combination with weekly vincristine injections were applied during radiochemotherapy in the HIT GBM-C/D protocol. Regular blood counts and information about cellular nadirs were available from 304 patients (leukocytes) and 306 patients (thrombocytes), respectively. Grade 3-4 leukopenia was much more frequent in the HIT GBM-C/D cohort (n = 88, 52%) vs. HIT-HGG-2007 (n = 13, 10%; P <0.001). Grade 3-4 thrombopenia was also more likely in the HIT GBM-C/D cohort (n = 21, 12% vs. n = 3,2%; P <0.001). Grade 3-4 leukopenia appeared more often in children aged 3-7 years (n = 38/85, 45%) than in children aged 8-12 years (n = 39/120, 33%) and 13-18 years (24/100, 24%; P =0.034). In addition, sickness was more frequent in the HIT GBM-C/D cohort (grade 1-2: 44%, grade 3-4: 6% vs. grade 1-2: 28%, grade 3-4: 1%; P <0.001). Radiochemotherapy involving cisplatinum-based polychemotherapy is more toxic than radiotherapy in combination with temozolomide. Without evidence of differences in therapeutic efficacy, the treatment with lower toxicity, i. e., radiotherapy with temozolomide should be used.

  16. Spinal metastases of malignant gliomas; Spinale Metastasierung bei malignen Gliomen. Zwei Fallbeschreibungen

    Energy Technology Data Exchange (ETDEWEB)

    Materlik, B; Steidle-Katic, U; Feyerabend, T; Richter, E [Medizinische Univ. Luebeck (Germany). Klinik fuer Strahlentherapie und Nuklearmedizin; Wauschkuhn, B [Medizinische Univ. Luebeck (Germany). Klinik fuer Neurologie

    1998-09-01

    Purpose: Extracranial metastases of malignant gliomas are rare. We report 2 cases with spinal metastases in patients suffering from glioma. Patients and Method: Two patients (33 and 57 years old) developed spinal canal metastases of a glioblastoma multiforme and anaplastic astrocytoma Grade III respectively 25 and 9 months after surgical resection and radiotherapy. Both metastases were confirmed pathohistologically. Results: Intraspinal metastases were irradiated with a total dose of 12.6 Gy and 50 Gy. Treatment withdrawal was necessary in one patient due to reduced clinical condition. Regression of neurological symptoms was observed in the second patient. Conclusions: Spinal spread of malignant glioma should be considered during care and follow-up in glioma patients with spinal symptoms. (orig.) [Deutsch] Hintergrund: Maligne Gliome metastasieren aeusserst selten extrakraniell. Wir stellen zwei Faelle einer spinalen Filialisierung bei Gliompatienten vor. Patientengut und Methode: Zwei Patienten (33 und 57 Jahre alt) entwickelten 25 bzw. neun Monate nach Resektion und postoperativer Radiatio eines Glioblastoma multiforme und eines anaplastischen Astrozytoms WHO-Grad III histologisch gesicherte intraspinale Metastasen, welche durch Sensibilitaetsstoerungen der Beine symptomatisch wurden. Ergebnisse: Die intraspinalen Filiae wurden mit 12,6 Gy bzw. 50 Gy bestrahlt. Bei einem Patienten musste die Radiatio wegen zunehmender Verschlechterung des Allgemeinzustandes abgebrochen werden, bei dem zweiten Patienten besserte sich die neurologische Symptomatik. Schlussfolgerung: Bei der Betreuung von Gliompatienten sollte, insbesondere in der Nachsorge, an die Moeglichkeit der spinalen Metastasierung mit entsprechender Symptomatik gedacht werden. (orig.)

  17. Use of peri-operative anti-epileptic drugs in patients with newly diagnosed high grade malignant glioma: a single center experience.

    Science.gov (United States)

    Lwu, Shelly; Hamilton, Mark G; Forsyth, Peter A; Cairncross, J Gregory; Parney, Ian F

    2010-02-01

    An American Academy of Neurology practice parameter recommends that long-term prophylactic anti-epileptic drugs (AED) should not be routine in patients with newly diagnosed brain tumors. However, prospective multi-center North American data shows that most newly diagnosed glioma patients receive prophylactic AED. We examined our own peri-operative AED practice patterns in newly-diagnosed patients with malignant glioma to determine if we deviate from published guidelines. A retrospective chart review was performed in adult patients with newly diagnosed malignant gliomas undergoing surgery in southern Alberta between January 2003 and December 2005. Demographic information, AED use, seizure incidence, adverse effects, tumor size, and tumor location were recorded. Of 164 eligible patients, 54 (33%) presented with seizures and all received AED. Prophylactic AED were given to 44 patients (27%). Peri-operative seizures (within 1 week) occurred in two patients without (3%) and no patients with seizure prophylaxis. Adverse AED reactions and adverse effects attributable to seizures were both rare. Prophylactic AED were continued >1 week post-op in 30 patients (18%). Patients receiving prophylactic AED were more likely to have had tumors involving the temporal lobe than those who did not (50 vs. 20%; P < 0.01). Patients receiving peri-operative AED prophylaxis were common, had a trend to reduced peri-operative seizures, and had few adverse effects. However, most of these patients were maintained on prophylactic AED continued beyond the first peri-operative week, contradicting published guidelines. Increased awareness of practice guidelines may help modify AED prescription patterns in malignant glioma patients.

  18. SVM-based glioma grading. Optimization by feature reduction analysis

    International Nuclear Information System (INIS)

    Zoellner, Frank G.; Schad, Lothar R.; Emblem, Kyrre E.; Harvard Medical School, Boston, MA; Oslo Univ. Hospital

    2012-01-01

    We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CBV) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity = 89%, specificity = 84%) when reducing the feature vector from 101 (100-bins rCBV histogram + age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values (∝87%) while reducing the number of features by up to 98%. (orig.)

  19. 18F-fluoromisonidazole (FMISO) and 18F-fluorodeoxyglucose (FDG) PET in patients undergoing radiotherapy or chemotherapy following surgery for high-grade glioma

    International Nuclear Information System (INIS)

    Lee, S. T.

    2009-01-01

    Full text:Background: Tumour hypoxia is associated with disease progression and resistance to therapy. High grade cerebral gliomas have a poor outcome despite advancements in chemotherapy and radiotherapy. 18F-fluoromisonidazole (18F-FMISO) concentrates in hypoxic cells and is associated with tumour grade in gliomas. The aim of this study was to compare the patterns of uptake of 18F-FDG PET and 18F-FMISO PET post-surgery with MRI and areas of recurrence post-radiotherapy. Methods: Patients with high grade cerebral glioma were recruited into this prospective study. All patients had post-surgical, pre-radiotherapy 18F-FDG, 18F-FMISO and MRI scans, which were all repeated 4-6 weeks post-completion to radiotherapy. The patients were followed-up clinically three monthly and re-imaged if indicated. Results: Ten patients were enrolled in this study, mean age 62 years (range 55-69 years), who all had pre-radiotherapy scans performed. Seven patients had scans done pre- and post-radiotherapy, with 3 patients with only pre-therapy scans. Nine patients had significant FMISO uptake and 8 patients demonstrated abnormal FDG uptake. The areas of FMISO uptake on pre-radiotherapy scans correlated with the most abnormal areas of contrast-enhancement on pre-treatment MRI and areas of locally recurrent disease on post-treatment MRI in eight patients. Nine patients had locally recurrent disease on follow-up MRI. FMISO was more predictive of tumour recurrence compared to FDG. Conclusion: Post-surgical 18F-FMISO PET in patients with cerebral glioma is more predictive of areas of recurrent disease compared to 18F-FDG PET.

  20. A prospective multicenter study of venous thromboembolism in patients with newly-diagnosed high-grade glioma: hazard rate and risk factors.

    Science.gov (United States)

    Streiff, Michael B; Ye, Xiaobu; Kickler, Thomas S; Desideri, Serena; Jani, Jayesh; Fisher, Joy; Grossman, Stuart A

    2015-09-01

    Venous thromboembolism (VTE) is a common complication in patients with high-grade gliomas. The purpose of this prospective multicenter study was to determine the hazard rate of first symptomatic VTE in newly-diagnosed glioma patients and identify clinical and laboratory risk factors. On enrollment, demographic and clinical information were recorded and a comprehensive coagulation evaluation was performed. Patients were followed until death. The study end point was objectively-documented symptomatic VTE. One hundred seven patients were enrolled with a median age of 57 years (range 29-85) between June 2005 and April 2008. Ninety-one (85 %) had glioblastoma multiforme (GBM). During an average survival of 17.7 months, 26 patients (24 %) (95 % CI 17-34 %) developed VTE (hazard rate 0.15 per person-year) and 94 patients (88 %) died. Median time to VTE was 14.2 weeks post-operation (range 3-126). Patients with an initial tumor biopsy were 3.0 fold more likely to suffer VTE (p = 0.02). Patients with an elevated factor VIII activity (>147 %) were 2.1-fold more likely to develop VTE. ABO blood group, D dimer and thrombin generation were not associated with VTE. No fatal VTE occurred. VTE is a common complication in patients with newly-diagnosed high grade gliomas, particularly in the first six months after diagnosis. Patients with an initial tumor biopsy and elevated factor VIII levels are at increased risk. However, VTE was not judged to be primarily responsible for any patient deaths. Therefore, outpatient primary VTE prophylaxis remains investigational until more effective primary prophylaxis strategies and therapies for glioma are identified.

  1. Is it time to rethink the role of hyperfractionated radiotherapy in the management of children with newly-diagnosed brainstem glioma?: Results of a Pediatric Oncology Group Phase III trial comparing conventional VS. hyperfractionated radiotherapy

    International Nuclear Information System (INIS)

    Mandell, L.; Kadota, R.; Douglass, E.C.; Fontanesi, J.; Freeman, C.; Cohen, M.; Kovnar, E.; Burger, P.; Sanford, R.A.; Kepner, J.; Friedman, H.; Kun, L.

    1997-01-01

    Purposes/Objective: In June 1992, POG began accrual to a Phase III study, POG 9239, designed to compare the time to disease progression, overall survival, and toxicities observed in children with newly diagnosed brainstem glioma treated with 100 mg/m 2 of infusional Cisplatin and randomized to either conventional vs. hyperfractionated radiotherapy. The trial was closed in March 1996, having achieved its accrual goal. Materials and Methods: Patients (pts) eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the pons. Histologic confirmation of diagnosis was not mandatory, provided that the clinical and MRI scan findings were typical for diffusely infiltrating pontine glioma. Treatment (Rx) consisted of a six-week course of local field radiotherapy with either once a day treatment (Rx 1) of 180 cGy per fraction to a total dose of 5400 cGy or a twice a day regimen (Rx 2) of 117 cGy per fraction to a total dose of 7020 cGy (the second of the three hyperfractionated dose escalation levels of POG 8495). Because of previously reported poor results with conventional radiotherapy alone, Cisplatin was included as a potential radiosensitizer in an attempt to improve progression-free and ultimate survival rates. Based on results of the Phase I Cisplatin dose escalation trial, POG 9139, 100 mg/m 2 was chosen for this trial and was delivered by continuous infusion over a 120-hour period, beginning on the first day of radiotherapy and repeated during Weeks 3 and 5. Of the 132 pts accrued to the study, 94 are eligible for review based upon time since entry, 47 in each Rx arm. In Rx 1, there were 23 males and 24 females, ranging in age from 40 to 161 mo (median, 77 mo); in Rx 2, there were 20 males and 27 females, ranging in age from 41 to 212 mo (median, 77 mo). As of 4/18/96, the study coordinator had not yet verified eligibility and assessed the evaluability of the remaining pts. Results: All results are from time of diagnosis

  2. Intraoperative radiation therapy for malignant glioma

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    Sakai, Noboru; Yamada, Hiromu; Andoh, Takashi; Hirata, Toshifumi; Nishimura, Yasuaki; Miwa, Yoshiaki; Shimizu, Kotoyuki; Yanagawa, Shigeo [Gifu Univ. (Japan). Faculty of Medicine

    1991-11-01

    Intraoperative radiation therapy (IORT) was used as part of the initial therapy for malignant glioma in 32 of 73 patients with histologically verified anaplastic astrocytoma (grade III astrocytoma) and glioblastoma multiforme. The initial treatment for all cases was subtotal or total tumor resection combined with external irradiation and chemotherapy. IORT was performed 1 week after tumor resection, with doses of 10-50 Gy (mean 26.7 Gy) in one session. Fourteen of 32 cases had IORT two times because of tumor recurrence. The IORT patients had survival rates at 24 and 36 months after initial treatment of 57.1 and 33.5% (median survival 26.2 months). The other 41 patients had 23.6 and 13.1% survivals (median survival 20.7 months), which were significantly lower (p<0.01). Tumor recurrence within the original lesion site was suspected because of clinical condition, computed tomography, and magnetic resonance imaging studies in 65.6% of the IORT group (21 cases) 12 months after initial treatment. Twenty cases of death in the IORT group, including five autopsy cases, demonstrated regional tumor recurrence with a high incidence of intraventricular tumor invasion. The authors consider IORT is beneficial for selected malignant glioma patients, including tumor recurrence, because of prolonged survival. (author).

  3. The progress of radiosensitive genes of human brain glioma

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    Wang Xi; Liu Qiang

    2008-01-01

    Human gliomas are one of the most aggressive tumors in brain which grow infiltrativly. Surgery is the mainstay of treatment. But as the tumor could not be entirely cut off, it is easy to relapse. Radiotherapy plays an important role for patients with gliomas after surgery. The efficacy of radiotherapy is associated with radio sensitivity of human gliomas. This paper makes a summary of current situation and progress for radiosensitive genes of human brain gliomas. (authors)

  4. Advanced magnetic resonance imaging methods for planning and monitoring radiation therapy in patients with high-grade glioma.

    Science.gov (United States)

    Lupo, Janine M; Nelson, Sarah J

    2014-10-01

    This review explores how the integration of advanced imaging methods with high-quality anatomical images significantly improves the characterization, target definition, assessment of response to therapy, and overall management of patients with high-grade glioma. Metrics derived from diffusion-, perfusion-, and susceptibility-weighted magnetic resonance imaging in conjunction with magnetic resonance spectroscopic imaging, allows us to characterize regions of edema, hypoxia, increased cellularity, and necrosis within heterogeneous tumor and surrounding brain tissue. Quantification of such measures may provide a more reliable initial representation of tumor delineation and response to therapy than changes in the contrast-enhancing or T2 lesion alone and have a significant effect on targeting resection, planning radiation, and assessing treatment effectiveness. In the long term, implementation of these imaging methodologies can also aid in the identification of recurrent tumor and its differentiation from treatment-related confounds and facilitate the detection of radiationinduced vascular injury in otherwise normal-appearing brain tissue.

  5. DDX3X Biomarker Correlates with Poor Survival in Human Gliomas

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    Dueng-Yuan Hueng

    2015-07-01

    Full Text Available Primary high-grade gliomas possess invasive growth and lead to unfavorable survival outcome. The investigation of biomarkers for prediction of survival outcome in patients with gliomas is important for clinical assessment. The DEAD (Asp-Glu-Ala-Asp box helicase 3, X-linked (DDX3X controls tumor migration, proliferation, and progression. However, the role of DDX3X in defining the pathological grading and survival outcome in patients with human gliomas is not yet clarified. We analyzed the DDX3X gene expression, WHO pathological grading, and overall survival from de-linked data. Further validation was done using quantitative RT-PCR of cDNA from normal brain and glioma, and immunohistochemical (IHC staining of tissue microarray. Statistical analysis of GEO datasets showed that DDX3X mRNA expression demonstrated statistically higher in WHO grade IV (n = 81 than in non-tumor controls (n = 23, p = 1.13 × 10−10. Moreover, DDX3X level was also higher in WHO grade III (n = 19 than in non-tumor controls (p = 2.43 × 10−5. Kaplan–Meier survival analysis showed poor survival in patients with high DDX3X mRNA levels (n = 24 than in those with low DDX3X expression (n = 53 (median survival, 115 vs. 58 weeks, p = 0.0009, by log-rank test, hazard ratio: 0.3507, 95% CI: 0.1893–0.6496. Furthermore, DDX3X mRNA expression and protein production significantly increased in glioma cells compared with normal brain tissue examined by quantitative RT-PCR, and Western blot. IHC staining showed highly staining of high-grade glioma in comparison with normal brain tissue. Taken together, DDX3X expression level positively correlates with WHO pathologic grading and poor survival outcome, indicating that DDX3X is a valuable biomarker in human gliomas.

  6. A comparative study of MR imaging scores and MR perfusion imaging in pre-operative grading of intracranial gliomas

    International Nuclear Information System (INIS)

    Wu Honglin; Chen Junkun; Zhang Zongjun; Lu Guangming; Chen Ziqian; Wang Wei; Ji Xueman; Tang Xiaojun; Li Lin

    2005-01-01

    Objective: To compare the accuracy of MR imaging scores with MR perfusion imaging in pre-operative grading of intracranial gliomas. Methods: Thirty patients with intracranial gliomas (8 low-grade and 22 high-grade, according to WHO criteria) were examined with MR perfusion imaging pre-operatively. The lesions were evaluated by using an MR imaging score based on nine criteria. rCBV of the lesions were calculated by comparing the CBV of the lesion and that of contralateral normal white matter. The scores and ratios in high-grade and low-grade tumours were compared. Results: The MR imaging score of low grade (grades I and II) gliomas (0.67±0.29) were significantly lower than that of grades III (1.32 ± 0.47) (t=-3.48, P=0.003) and IV (1.56 ± 0.20) (t=-7.36, P=0.000) gliomas. There was no statistical difference when MR imaging scores of grades III and IV gliomas (t=-1.39, P=0.182) were compared. The maximum rCBV ratio of low grade (grades I and II) gliomas (2.38 ± 0.66 ) were significantly lower than that of grades III (5.81 ± 3.20) (t=-3.57, P=0.003) and IV (6.99 ± 2.47) (t=-5.09, P=0.001). There was no statistical difference when rCBV ratios of grades III and IV (t =-0.93, P=0.365) gliomas were compared. The accuracy of MR imaging scores in the noninvasive grading of untreated gliomas was all most the same as that of MR perfusion imaging (90.00% vs 89.29%). Conclusion: The MR imaging scores and MR perfusion imaging are two very useful tools in the evaluation of the histopathologic grade of cerebral gliomas. The overall accuracy in the noninvasive grading of gliomas may be imp roved if MR imaging scores and MR perfusion imaging are combined. (authors)

  7. Effect of Rituximab in Patients With Leucine-Rich, Glioma-Inactivated 1 Antibody–Associated Encephalopathy

    Science.gov (United States)

    Irani, Sarosh R.; Gelfand, Jeffrey M.; Bettcher, Brianne M.; Singhal, Neel S.; Geschwind, Michael D.

    2015-01-01

    IMPORTANCE This observational study describes the efficacy and safety of rituximab in 5 patients with voltage-gated potassium channel (VGKC)–complex/leucine-rich, glioma-inactivated 1 (LGI1) antibody–associated encephalopathy. Rituximab is a monoclonal antibody that targets CD20 and is used to treat other neurologic and nonneurologic diseases. OBSERVATIONS This case series reports sequential seizure frequencies, modified Rankin Scale scores, and VGKC-complex antibody titers in 5 adult patients (median age, 65 years; range, 48–73 years) treated with rituximab. Median time from symptom onset to rituximab initiation was 414 days (range, 312–851 days). One patient showed a rapid clinical improvement after treatment with rituximab alone and experienced a rituximab-responsive clinical relapse. Another showed possible improvement on neuropsychometric memory indexes after rituximab therapy. In contrast, all patients showed robust responses to treatment with glucocorticoids, intravenous immunoglobulins, and/or plasma exchange at some point in their illness. Treatment with glucocorticoids—less so with intravenous immunoglobulins and plasma exchange—was associated with the most marked reductions in VGKC-complex antibodies. The only patient who did not receive glucocorticoids showed the poorest clinical and serologic responses. CONCLUSIONS AND RELEVANCE Rituximab was well tolerated in this predominantly older adult patient population and may be an effective option for some patients with LGI1 antibody–associated encephalopathy. Glucocorticoid therapy appears particularly efficacious. Earlier rituximab administration and randomized trials are required to formally assess efficacy. PMID:24842754

  8. Imaging response is highly predictive of survival of malignant glioma patients treated with standard or hyperfractionated RT and carmustine in RTOG 9006

    International Nuclear Information System (INIS)

    Curran, Walter J.; Scott, Charles B.; Yung, W.K. Alfred; Scarantino, Charles; Urtasun, Raul; Movsas, Benjamin; Jones, Christopher; Simpson, Joseph; Fischbach, A. Jennifer; Petito, Carol; Nelson, James

    1996-01-01

    Objectives: Limited information is available correlating response to initial therapy and survival outcome among malignant glioma patients. This analysis was conducted to determine the response rate of malignant glioma patients to either standard (STN) or hyperfractionated (HFX) RT and carmustine and to correlate the tumor response status with survival. Patients and Methods: From (11(90)) to (3(94)), 712 newly diagnosed malignant glioma patients were registered on RTOG 9006 and randomized between hyperfractionated RT of 72.0 Gy in 1.2 Gy twice-daily fractions and 60.0 Gy in 2.0 Gy daily fractions. All patients received 80 mg/m-2 of carmustine D 1-3 q 8 wks. As reported in the 1996 Proceedings of the Amer Soc Clin Oncol (Abstr no. 280), there was no survival benefit observed for the HFX regimen. 529 of the 686 eligible patients had pre-operative, post-operative, and post-RT contrast-enhanced MR and/or CT scans available for central review of tumor and peritumoral edema measurements. Response status was judged by applying standard response criteria to a comparison of tumor measurements on follow-up and post-operative films. Results: Of the 529 patients evaluated for imaging response, the complete and partial response rates were 14% and 20%, respectively. A significant correlation between response and survival was observed (P<0.0001). Variables which predicted for a better tumor response were anaplastic astrocytoma vs glioblastoma multiforme histology, better performance status, more extensive resection, and a more favorable Recursive Partitioning and Amalgamation class assignment (JNCI 85:704-710, 1993). Conclusion: The objective response rate for malignant glioma patients to RTOG 9006 therapy was 34%, and survival outcome is strongly correlated with tumor response status. These observations justify the testing of aggressive salvage strategies for patients without imaging evidence of response following initial therapy

  9. Immunohistochemical detection and correlation between MHC antigen and cell-mediated immune system in recurrent glioma by APAAP method.

    Science.gov (United States)

    Miyagi, K; Ingram, M; Techy, G B; Jacques, D B; Freshwater, D B; Sheldon, H

    1990-09-01

    As part of an on-going clinical trial of immunotherapy for recurrent malignant gliomas, using alkaline phosphatase-anti-alkaline phosphatase method with monoclonal antibodies, we investigated the correlation between expression of the major histocompatibility complex (MHC) and the subpopulation of tumor-infiltrating lymphocytes (TILs) in 38 glioma specimens (20 grade IV, 11 grade III, and 7 grade II) from 33 patients. Thirty specimens (78.9%) were positive to class I MHC antigen and 20 (52.6%) were positive to class II MHC antigen. The correlations between class I MHC antigen expression and the number of infiltrating T8 (p less than 0.01), and also between class II MHC antigen expression and the number of infiltrating T4 (p less than 0.05) were significant. We conclude that TILs are the result of immunoreaction (host-defense mechanism). 31.6% of specimens had perivascular infiltration of T cells. The main infiltrating lymphocyte subset in moderate to marked perivascular cuffing was T4. Our results may indicate that lack of MHC antigen on the glioma cell surface has a share in the poor immunogenicity in glioma-bearing patients. In addition, considering the effector/target ratio, the number of infiltrating lymphocytes against glioma cells was too small, so the immunological intervention seems to be essential in glioma therapy. Previous radiation therapy and chemotherapy, including steroid therapy, did not influence lymphocyte and macrophage infiltration.

  10. Reliability of tumor volume estimation from MR images in patients with malignant glioma. Results from the American College of Radiology Imaging Network (ACRIN) 6662 Trial

    International Nuclear Information System (INIS)

    Ertl-Wagner, Birgit B.; Blume, Jeffrey D.; Herman, Benjamin; Peck, Donald; Udupa, Jayaram K.; Levering, Anthony; Schmalfuss, Ilona M.

    2009-01-01

    Reliable assessment of tumor growth in malignant glioma poses a common problem both clinically and when studying novel therapeutic agents. We aimed to evaluate two software-systems in their ability to estimate volume change of tumor and/or edema on magnetic resonance (MR) images of malignant gliomas. Twenty patients with malignant glioma were included from different sites. Serial post-operative MR images were assessed with two software systems representative of the two fundamental segmentation methods, single-image fuzzy analysis (3DVIEWNIX-TV) and multi-spectral-image analysis (Eigentool), and with a manual method by 16 independent readers (eight MR-certified technologists, four neuroradiology fellows, four neuroradiologists). Enhancing tumor volume and tumor volume plus edema were assessed independently by each reader. Intraclass correlation coefficients (ICCs), variance components, and prediction intervals were estimated. There were no significant differences in the average tumor volume change over time between the software systems (p > 0.05). Both software systems were much more reliable and yielded smaller prediction intervals than manual measurements. No significant differences were observed between the volume changes determined by fellows/neuroradiologists or technologists.Semi-automated software systems are reliable tools to serve as outcome parameters in clinical studies and the basis for therapeutic decision-making for malignant gliomas, whereas manual measurements are less reliable and should not be the basis for clinical or research outcome studies. (orig.)

  11. The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors.

    Science.gov (United States)

    Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias; Stummer, Walter

    2016-03-01

    Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

  12. Concordance of patient and caregiver reports in evaluating quality of life in patients with malignant gliomas and an assessment of caregiver burden

    Science.gov (United States)

    Jacobs, Daniel I.; Kumthekar, Priya; Stell, Becky V.; Grimm, Sean A.; Rademaker, Alfred W.; Rice, Laurie; Chandler, James P.; Muro, Kenji; Marymont, MaryAnne; Helenowski, Irene B.; Wagner, Lynne I.; Raizer, Jeffrey J.

    2014-01-01

    Background Given the neurocognitive impairment experienced by many patients with malignant gliomas, caregiver reports can be critical in assessing the quality of life (QOL) of these patients. In this study, we explored whether assessment of patient QOL by the primary caregiver shows concordance with the patient's self-reported QOL, and we quantified the burden faced by caregivers. Methods QOL of 45 patients was evaluated by both the patient and primary caregiver on 3 or more separate occasions using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) instrument, and concordance between the 2 reports was evaluated. Caregiver burden was measured using the Caregiver Quality of Life Index-Cancer (CQOL-C) instrument. Results Overall, good concordance was observed between the patient and caregiver FACT-Br reports (intraclass correlation coefficient = 0.74). Patient-reported FACT-Br scores were 4.75 (95% CI, 1.44–8.05) points higher than paired caregiver reports on the 200-point scale (P = .008); however, this difference did not achieve clinical significance. Caregiver burden, as measured by the CQOL-C, was significantly greater among caregivers in this study than those previously reported for caregivers of patients with lung, breast, or prostate cancer (P < .001). Conclusions Despite minor discrepancies in caregiver assessments of patient QOL relative to patient self-reports, our results suggest that the caregiver assessments can serve as adequate proxies for patient reports. Our results also illustrate the particularly heavy burden faced by caregivers of patients with malignant glioma. Further research into both of these areas is warranted. PMID:26034616

  13. [Orthodontic treatment of Class III patients with mandibular asymmetry].

    Science.gov (United States)

    Duan, Yin-Zhong; Huo, Na; Chen, Lei; Chen, Xue-Peng; Lin, Yang

    2008-12-01

    To investigate the treatment outcome of Class III patients with dental, functional and mild skeletal mandibular asymmetry. Thirty-five patients (14 males and 21 females) with dental, functional and mild skeletal mandibular asymmetry were selected. The age range of the patients was 7 - 22 years with a mean age of 16.5 years. Dental mandibular asymmetry was treated with expansion of maxillary arch to help the mandible returning to normal position. Functional mandibular asymmetry was treated with activator or asymmetrical protraction and Class III elastics. Mild skeletal mandibular asymmetry was treated with camouflage treatment. Good occlusal relationships were achieved and facial esthetics was greatly improved after orthodontic treatment in patients with dental and functional mandibular asymmetry. However, patients with skeletal mandibular asymmetry should be treated with both extraction and genioplasty. Orthodontic treatment was suitable for patients with dental and functional mandibular asymmetry, while combined orthodontics and surgery could get good results in patients with skeletal mandibular asymmetry.

  14. FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients

    Directory of Open Access Journals (Sweden)

    Hagedorn Martin

    2007-02-01

    Full Text Available Abstract Background In the quest for novel molecular mediators of glioma progression, we studied the regulation of FBXW7 (hCDC4/hAGO/SEL10, its association with survival of patients with glioblastoma and its potential role as a tumor suppressor gene in glioma cells. The F-box protein Fbxw7 is a component of SCFFbxw7, a Skp1-Cul1-F-box E3 ubiquitin ligase complex that tags specific proteins for proteasome degradation. FBXW7 is mutated in several human cancers and functions as a haploinsufficient tumor suppressor in mice. Any of the identified targets, Cyclin E, c-Myc, c-Jun, Notch1/4 and Aurora-A may have oncogenic properties when accumulated in tumors with FBXW7 loss. Results We tested the expression of FBXW7 in human glioma biopsies by quantitative PCR and compared the transcript levels of grade IV glioma (glioblastoma, G-IV with those of grade II tumors (G-II. In more than 80% G-IV, expression of FBXW7 was significantly reduced. In addition, levels of FBXW7 were correlated with survival indicating a possible implication in tumor aggressiveness. Locus 4q31.3 which carries FBXW7 was investigated by in situ hybridization on biopsy touchprints. This excluded allelic loss as the principal cause for low expression of FBXW7 in G-IV tumors. Two targets of Fbxw7, Aurora-A and Notch4 were preferentially immunodetected in G-IV biopsies. Next, we investigated the effects of FBXW7 misregulation in glioma cells. U87 cells overexpressing nuclear isoforms of Fbxw7 lose the expression of the proliferation markers PCNA and Ki-67, and get counterselected in vitro. This observation fits well with the hypothesis that Fbxw7 functions as a tumor suppressor in astroglial cells. Finally, FBXW7 knockdown in U87 cells leads to defects in mitosis that may promote aneuploidy in progressing glioma. Conclusion Our results show that FBXW7 expression is a prognostic marker for patients with glioblastoma. We suggest that loss of FBXW7 plays an important role in glioma

  15. Phase I study of vorinostat in combination with temozolomide in patients with high-grade gliomas: North American Brain Tumor Consortium Study 04-03.

    Science.gov (United States)

    Lee, Eudocia Q; Puduvalli, Vinay K; Reid, Joel M; Kuhn, John G; Lamborn, Kathleen R; Cloughesy, Timothy F; Chang, Susan M; Drappatz, Jan; Yung, W K Alfred; Gilbert, Mark R; Robins, H Ian; Lieberman, Frank S; Lassman, Andrew B; McGovern, Renee M; Xu, Jihong; Desideri, Serena; Ye, Xiabu; Ames, Matthew M; Espinoza-Delgado, Igor; Prados, Michael D; Wen, Patrick Y

    2012-11-01

    A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG). This phase I, dose-finding, investigational study was conducted in two parts. Part 1 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days every 28 days. Part 2 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days of the first cycle and 200 mg/m(2)/day for 5 days of the subsequent 28-day cycles. In part 1, the MTD of vorinostat administered on days 1 to 7 and 15 to 21 of every 28-day cycle, in combination with TMZ, was 500 mg daily. Dose-limiting toxicities (DLT) included grade 3 anorexia, grade 3 ALT, and grade 5 hemorrhage in the setting of grade 4 thrombocytopenia. In part 2, the MTD of vorinostat on days 1 to 7 and 15 to 21 of every 28-day cycle, combined with TMZ, was 400 mg daily. No DLTs were encountered, but vorinostat dosing could not be escalated further due to thrombocytopenia. The most common serious adverse events were fatigue, lymphopenia, thrombocytopenia, and thromboembolic events. There were no apparent pharmacokinetic interactions between vorinostat and TMZ. Vorinostat treatment resulted in hyperacetylation of histones H3 and H4 in peripheral mononuclear cells. Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway. ©2012 AACR.

  16. Psychological consideration in patients with cerebral gliomas candidates for intra-operative radiation therapy based on tumor location.

    Science.gov (United States)

    Seddighi, Afsoun; Akbari, Mohammad Esmaeil; Seddighi, Amir Saied; Nikouei, Amir

    2017-01-01

    Intra-operative Radiation Therapy (IORT) is gaining popularity as an adjuvant option to surgical resection, in treatment of glioblastoma multiforme (GBM) for increasing survival rate, which a highly aggressive cerebral tumor with poor prognosis. Τhe authors plan to investigate the effects of IORT combined with surgical resection on the psychological status of these patients based on tumor location. From December 2013 to February 2017, we have enrolled 109 patients with high grade cerebral gliomas, documented by Magnetic Resonance Spectroscopy (MRS). Patients with previous history of brain surgery or radiation, altered mental status and psychological content and patients diagnosed with metastases were excluded. Demographic data, tumor volume based on pre-operative Magnetic Resonance Imaging (MRI) and psychological status were recorded based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The remaining 56 patients, were equally randomized into conventional (surgical resection-group A), and trial (surgical resection with IORT-group B) who underwent IORT using the 50kV INTRABEAM® system (Carl Zeiss Meditec AG, Germany). Psychological profiles of both groups were re-evaluated in the 3 rd post-operative month. Group A consisted of 18 males and 10 females with mean age of 54.4 years, while group B consisted of 16 males and 12 females with mean age of 57.8 years. Tumor volumetry revealed mean 81.52cc and 82.8cc for group A and B respectively. (P value 0.14) Patients were classified based on glioma location on pre-operative MRI: a) left parietal lobe (6 in group A, 5 in group B); b) left temporal lobe (7 in group A, 5 in group B); c) right parietal lobe (5 in group A, 6 in group B); d) left fronto-temporal lobe (4 in group A, 6 in group B); e) left parieto-temporal lobe (4 in group A, 5 in group B); and, f) right frontal lobe (2 in group A, 1 in group B). Group B received mean 8.05 Gy radiation for mean 11.2 minutes. Post

  17. Isocitrate dehydrogenase 1 and 2 genes mutations and MGMT methylation in gliomas

    Directory of Open Access Journals (Sweden)

    D. V. Tabakov

    2017-01-01

    Full Text Available Gliomas are the most common brain tumors. It is difficult to detect them at early stages of disease and there is a few available therapies providing significant improvement in survival. Mutations of isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2 play significant role in gliomogenesis, diagnostics and selection of patient therapy. We tested the distribution of IDH1 and IDH2 mutations in gliomas of different histological types and grades of malignancy by DNA melting analysis using our protocol with a sensitivity of 5 %. The results of this assay were confirmed by conventional Sanger sequencing. IDH1/2 mutations were detected in 74 % of lower grade gliomas (II and III, World Health Organization and in 14 % of glioblastomas (IV, World Health Organization. Mutation rate in gliomas with oligodendroglioma component were significantly higher then in other glioma types (р = 0.014. The IDH1 mutations was the most common (79 % of general mutation number. IDH1/2 mutations can induce aberrant gene methylation. Detection of methylation rate of the gene encoding for O6-methylguanine-DNA-methyltransferase (MGMT, predictive biomarker for treatment of gliomas with the alkylating agents, has demonstrated a partial association with IDH1/2 mutations. In 73 % of IDH1/2-mutant tumors MGMT promoter methylation were observed. At the same time IDH1/2 mutations were not revealed in 67 % tumors with MGMT promoter methylation. These results indicate existence of another mechanism of MGMT methylation in gliomas. Our data strong support for necessity of both markers testing when patient therapy is selected.

  18. Radiochemotherapy of malignant glioma in adults. Clinical experiences

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    Kortmann, R.D.; Jeremic, B.; Plasswilm, L.; Bamberg, M. [Dept. for Radiation Oncology, Univ. of Tuebingen (Germany); Weller, M. [Dept. of Neurology, Univ. of Tuebingen (Germany)

    2003-04-01

    Background: Standard treatment in patients with malignant glioma consists of surgery and postoperative radiotherapy. A high early recurrence rate, particularly in glioblastoma, has led to the investigation of additional chemotherapy. Material and Methods: Recent results of radiochemotherapy published in the literature were reviewed with respect to outcome in phase II and III trials. Based on these experiences, aspects of future strategies were discussed. Results: 3 decades of intensive research had, unfortunately, little impact on the overall results. While early prospective studies established adjuvant nitrosoureas, particularly BCNU, as suitable adjuvant to surgery and postoperative radiotherapy, further studies largely concentrated on combined chemotherapeutic protocols, mostly procarbazine, CCNU and vincristine (PCV), which was shown to prolong survival in anaplastic astrocytoma. The recent MRC study, however, showed no effect for adjuvant PCV in grade III and IV malignant glioma. Only in high-grade glioma with an oligodendroglial component, additional chemotherapy may be of a decisive benefit. The introduction of newer drugs such as paclitaxel, temozolomide, or gemcitabine demonstrated no decisive advantage. Different modes of application and sequencing of radiotherapy and chemotherapy are presently actively investigated, but failed to substantially improve outcome. Conclusions: Therefore, search for newer and more effective drugs continues, as well as for ''optimal'' administration and sequencing, especially from the standpoint of accompanying acute and late toxicity. Finally, recent endeavors focused on basic research such as angiogenesis, migration and invasion, or induction of cell differentiation, but these strategies are still away from broader clinical investigation. (orig.)

  19. Radiochemotherapy of malignant glioma in adults. Clinical experiences

    International Nuclear Information System (INIS)

    Kortmann, R.D.; Jeremic, B.; Plasswilm, L.; Bamberg, M.; Weller, M.

    2003-01-01

    Background: Standard treatment in patients with malignant glioma consists of surgery and postoperative radiotherapy. A high early recurrence rate, particularly in glioblastoma, has led to the investigation of additional chemotherapy. Material and Methods: Recent results of radiochemotherapy published in the literature were reviewed with respect to outcome in phase II and III trials. Based on these experiences, aspects of future strategies were discussed. Results: 3 decades of intensive research had, unfortunately, little impact on the overall results. While early prospective studies established adjuvant nitrosoureas, particularly BCNU, as suitable adjuvant to surgery and postoperative radiotherapy, further studies largely concentrated on combined chemotherapeutic protocols, mostly procarbazine, CCNU and vincristine (PCV), which was shown to prolong survival in anaplastic astrocytoma. The recent MRC study, however, showed no effect for adjuvant PCV in grade III and IV malignant glioma. Only in high-grade glioma with an oligodendroglial component, additional chemotherapy may be of a decisive benefit. The introduction of newer drugs such as paclitaxel, temozolomide, or gemcitabine demonstrated no decisive advantage. Different modes of application and sequencing of radiotherapy and chemotherapy are presently actively investigated, but failed to substantially improve outcome. Conclusions: Therefore, search for newer and more effective drugs continues, as well as for ''optimal'' administration and sequencing, especially from the standpoint of accompanying acute and late toxicity. Finally, recent endeavors focused on basic research such as angiogenesis, migration and invasion, or induction of cell differentiation, but these strategies are still away from broader clinical investigation. (orig.)

  20. Paediatric and adult malignant glioma

    DEFF Research Database (Denmark)

    Jones, Chris; Perryman, Lara; Hargrave, Darren

    2012-01-01

    Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although rare in the paediatric population, patients with high-grade gliomas have, for the most part, a comparably dismal clinical outcome...... to older patients with morphologically similar lesions. Molecular profiling data have begun to reveal the major genetic alterations underpinning these malignant tumours in children. Indeed, the accumulation of large datasets on adult high-grade glioma has revealed key biological differences between...... the adult and paediatric disease. Furthermore, subclassifications within the childhood age group can be made depending on age at diagnosis and tumour site. However, challenges remain on how to reconcile clinical data from adult patients to tailor novel treatment strategies specifically for paediatric...

  1. [18F]-fluoro-l-thymidine PET and advanced MRI for preoperative grading of gliomas

    Directory of Open Access Journals (Sweden)

    S. Collet

    2015-01-01

    Conclusion: Whereas advanced MRI parameters give indications for the grading of gliomas, the addition of [18F]-FLT-PET could be of interest for the accurate preoperative classification of diffuse gliomas, particularly for identification of doubtful grade III and IV gliomas.

  2. Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with high-grade glioma, a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Dijken, Bart R.J. van [University of Groningen, University Medical Center Groningen Department of Radiology, Groningen (Netherlands); Laar, Peter Jan van; Hoorn, Anouk van der [University of Groningen, University Medical Center Groningen Department of Radiology, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Holtman, Gea A. [University of Groningen, University Medical Center Groningen, Department of General Practice, Groningen (Netherlands)

    2017-10-15

    Treatment response assessment in high-grade gliomas uses contrast enhanced T1-weighted MRI, but is unreliable. Novel advanced MRI techniques have been studied, but the accuracy is not well known. Therefore, we performed a systematic meta-analysis to assess the diagnostic accuracy of anatomical and advanced MRI for treatment response in high-grade gliomas. Databases were searched systematically. Study selection and data extraction were done by two authors independently. Meta-analysis was performed using a bivariate random effects model when ≥5 studies were included. Anatomical MRI (five studies, 166 patients) showed a pooled sensitivity and specificity of 68% (95%CI 51-81) and 77% (45-93), respectively. Pooled apparent diffusion coefficients (seven studies, 204 patients) demonstrated a sensitivity of 71% (60-80) and specificity of 87% (77-93). DSC-perfusion (18 studies, 708 patients) sensitivity was 87% (82-91) with a specificity of 86% (77-91). DCE-perfusion (five studies, 207 patients) sensitivity was 92% (73-98) and specificity was 85% (76-92). The sensitivity of spectroscopy (nine studies, 203 patients) was 91% (79-97) and specificity was 95% (65-99). Advanced techniques showed higher diagnostic accuracy than anatomical MRI, the highest for spectroscopy, supporting the use in treatment response assessment in high-grade gliomas. (orig.)

  3. Effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: secondary analysis of RTOG 98-02.

    Science.gov (United States)

    Prabhu, Roshan S; Won, Minhee; Shaw, Edward G; Hu, Chen; Brachman, David G; Buckner, Jan C; Stelzer, Keith J; Barger, Geoffrey R; Brown, Paul D; Gilbert, Mark R; Mehta, Minesh P

    2014-02-20

    The addition of PCV (procarbazine, lomustine, and vincristine) chemotherapy to radiotherapy (RT) for patients with WHO grade 2 glioma improves progression-free survival (PFS). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long-term survival. A total of 251 patients with WHO grade 2 glioma age ≥ 40 years with any extent of resection or age point. Both study arms experienced a significant gain in average MMSE score longitudinally over time, with no difference between arms. The MMSE is a relatively insensitive tool, and subtle changes in CF may have been missed. However, the addition of PCV to RT did not result in significantly higher rates of MMSE score decline than RT alone through 5 years of follow-up. Patients in both randomly assigned arms experienced a statistically significant average MMSE score increase over time, with no difference between arms. The addition of PCV chemotherapy to RT improves PFS without excessive CF detriment over RT alone for patients with low-grade glioma.

  4. Long-Term Cognitive Functioning and Psychological Well-Being in Surgically Treated Patients with Low-Grade Glioma.

    Science.gov (United States)

    Campanella, Fabio; Palese, Alvisa; Del Missier, Fabio; Moreale, Renzo; Ius, Tamara; Shallice, Tim; Fabbro, Franco; Skrap, Miran

    2017-07-01

    The aim of this work is to provide an in-depth investigation of the impact of low-grade gliomas (LGG) and their surgery on patients' cognitive and emotional functioning and well-being, carried out via a comprehensive and multiple-measure psychological and neuropsychological assessment. Fifty surgically treated patients with LGG were evaluated 40 months after surgery on their functioning over 6 different cognitive domains, 3 core affective/emotional aspects, and 3 different psychological well-being measures to obtain a clearer picture of the long-term impact of illness and surgery on their psychological and relational world. Close relatives were also involved to obtain an independent measure of the psychological dimensions investigated. Cognitive status was satisfactory, with only mild short-term memory difficulties. The affective and well-being profile was characterized by mild signs of depression, good satisfaction with life and psychological well-being, and good personality development, with patients perceiving themselves as stronger and better persons after illness. However, patients showed higher emotional reactivity, and psychological well-being measures were negatively affected by epileptic burden. Well-being was related to positive affective/emotional functioning and unrelated to cognitive functioning. Good agreement between patients and relatives was found. In the long-term, patients operated on for LGG showed good cognitive functioning, with no significant long-term cognitive sequelae for the extensive surgical approach. Psychologically, patients appear to experience a deep psychological change and maturation, closely resembling that of so-called posttraumatic growth, which, to our knowledge, is for the first time described and quantified in patients with LGG. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Comparison of 18F-FET PET and 5-ALA fluorescence in cerebral gliomas

    International Nuclear Information System (INIS)

    Floeth, Frank Willi; Sabel, Michael; Steiger, Hans Jakob; Ewelt, Christian; Stummer, Walter; Felsberg, Joerg; Reifenberger, Guido; Stoffels, Gabriele; Langen, Karl-Josef; Coenen, Heinz Hubert

    2011-01-01

    The aim of the study was to compare presurgical 18 F-fluoroethyl-L-tyrosine ( 18 F-FET) uptake and Gd-diethylenetriaminepentaacetic acid (DTPA) enhancement on MRI (Gd) with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in cerebral gliomas. 18 F-FET positron emission tomography (PET) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI. PET and MRI data were coregistered to guide neuronavigated biopsies before resection. After oral application of 5-ALA, 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for 18 F-FET or Gd and checked for 5-ALA fluorescence. 18 F-FET uptake with a mean tumour to brain ratio ≥1.6 was rated as positive. Of 38 biopsies, 21 corresponded to high-grade glioma tissue (HGG) of WHO grade III (n = 19) or IV (n = 2) and 17 biopsies to low-grade glioma tissue (LGG) of WHO grade II. In biopsies corresponding to HGG, 18 F-FET PET was positive in 86% (18/21), but 5-ALA and Gd in only 57% (12/21). A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy samples (3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive). In biopsies corresponding to LGG, 18 F-FET was positive in 41% (7/17), while 5-ALA and Gd were negative in all but one instance. All tumour areas with 5-ALA fluorescence were positive on 18 F-FET PET. There are differences between 18 F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG. 18 F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning. (orig.)

  6. Small gliomas; Metabolism and blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Masaru; Shibasaki, Takashi; Horikoshi, Satoru; Ono, Nobuo; Zama, Akira; Kakegawa, Tohru; Ishiuchi, Shogo [Gunma Univ., Maebashi (Japan). School of Medicine

    1994-02-01

    Eight patients with small gliomas (6 low-grade and 2 high-grade) localized in a single gyrus or less than 2 cm diameter were investigated using positron tomography and single photon emission computed tomography. All three tumors examined demonstrated hypermetabolism of amino acids. High-grade gliomas demonstrated hypermetabolism of glucose and high blood flow, but normal or low oxygen metabolism. High-grade gliomas also showed accumulation of [sup 201]Tl chloride and high or low accumulation of [sup 123]I-isopropyl iodoamphetamine. These indications allow preoperative diagnosis of the malignancy of small gliomas, which is important because small gliomas with high-grade malignancy need more extensive removal and adjuvant therapy. (author).

  7. Short-echo 3D H-1 Magnetic Resonance Spectroscopic Imaging of patients with glioma at 7T for characterization of differences in metabolite levels

    Science.gov (United States)

    Li, Yan; Larson, Peder; Chen, Albert P.; Lupo, Janine M.; Ozhinsky, Eugene; Kelley, Douglas; Chang, Susan M.; Nelson, Sarah J.

    2014-01-01

    Purpose The purpose of this study was to evaluate the feasibility of using a short echo time, 3D H-1 magnetic resonance spectroscopic imaging (MRSI) sequence at 7T to assess the metabolic signature of lesions for patients with glioma. Materials and Methods 29 patients with glioma were studied. MRSI data were obtained using CHESS water suppression, spectrally-selective adiabatic inversion-recovery pulses and automatically prescribed outer-volume-suppression for lipid suppression, and spin echo slice selection (TE=30ms). An interleaved flyback echo-planar trajectory was applied to shorten the total acquisition time (~10min). Relative metabolite ratios were estimated in tumor and in normal-appearing white and gray matter (NAWM, GM). Results Levels of glutamine, myo-inositol, glycine and glutathione relative to total creatine (tCr) were significantly increased in the T2 lesions for all tumor grades compared to those in the NAWM (p < 0.05), while N-acetyl aspartate to tCr were significantly decreased (p < 0.05). In grade 2 gliomas, level of total choline-containing-compounds to tCr was significantly increased (p = 0.0137), while glutamate to tCr was significantly reduced (p = 0.0012). Conclusion The improved sensitivity of MRSI and the increased number of metabolites that can be evaluated using 7T MR scanners is of interest for evaluating patients with glioma. This study has successfully demonstrated the application of a short-echo spin-echo MRSI sequence to detect characteristic differences in regions of tumor versus normal appearing brain. PMID:24935758

  8. Exploring the regulatory role of isocitrate dehydrogenase mutant protein on glioma stem cell proliferation.

    Science.gov (United States)

    Lu, H-C; Ma, J; Zhuang, Z; Qiu, F; Cheng, H-L; Shi, J-X

    2016-08-01

    Glioma is the most lethal form of cancer that originates mostly from the brain and less frequently from the spine. Glioma is characterized by abnormal regulation of glial cell differentiation. The severity of the glioma was found to be relaxed in isocitrate dehydrogenase 1 (IDH1) mutant. The present study focused on histological discrimination and regulation of cancer stem cell between IDH1 mutant and in non-IDH1 mutant glioma tissue. Histology, immunohistochemistry and Western blotting techniques are used to analyze the glioma nature and variation in glioma stem cells that differ between IDH1 mutant and in non-IDH1 mutant glioma tissue. The aggressive form of non-IDH1 mutant glioma shows abnormal cellular histological variation with prominent larger nucleus along with abnormal clustering of cells. The longer survival form of IDH1 mutant glioma has a control over glioma stem cell proliferation. Immunohistochemistry with stem cell markers, CD133 and EGFRvIII are used to demonstrate that the IDH1 mutant glioma shows limited dependence on cancer stem cells and it shows marked apoptotic signals in TUNEL assay to regulate abnormal cells. The non-IDH1 mutant glioma failed to regulate misbehaving cells and it promotes cancer stem cell proliferation. Our finding supports that the IDH1 mutant glioma has a regulatory role in glioma stem cells and their survival.

  9. 12 years' experience with intraoperative radiotherapy (IORT) of malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Schueller, P.; Micke, O.; Moustakis, C.; Bruns, F.; Schuck, A.; Willich, N. [University Hospital Muenster (Germany). Dept. of Radiotherapy and Radiation Oncology; Palkovic, S.; Schroeder, J.; Wassmann, H. [University Hospital Muenster (Germany). Dept. of Neurosurgery

    2005-08-01

    Background: Even after surgery and radiotherapy, malignant gliomas still have a poor prognosis. The authors report on their experience with IORT in 71 patients. Patients and methods: From May 1992 to February 2004, 71 patients with malignant gliomas were treated with IORT. 26 patients suffered from grade III gliomas, 45 patients from glioblastomas (GBM). IORT was carried out using a standard electron tube and 9- to 18-MeV electrons. 52/71 patients who were primarily treated received 20 Gy IORT + 60 Gy postoperative radiotherapy, 19/71 patients with recurrences only received IORT (20-25 Gy). Results: The complication rates were 1.4% for wound infections and 5.6% for hemorrhage. Median disease-specific survival amounted to 14.9 months (gliomass III) and 14.2 months (GBM). The 2-year survival rates amounted to 26.9% (gliomas III) and 6.8% (GBM; p=0.0296). Total versus subtotal resection had no significant influence on survival (p=0.0741), nor had age, sex, tumor site, performance status, size, primary versus recurrence, and radiation dose. A comparison to a conventionally treated patient group did not show a significant survival improvement. 3 months after treatment, initial symptoms had improved in 59% (hemiparesis), 50% (aphasia), 50% (hemianopsia), and 60% (convulsions). Conclusion: IORT has been shown to be feasible; perioperative complication rates were not increased. Survival was generally not improved compared to a historical control group. Recurrences achieved the same survival as primary tumors, and GBM also had a slightly increased survival, thus being possible indications for IORT. (orig.)

  10. [Class III surgical patients facilitated by accelerated osteogenic orthodontic treatment].

    Science.gov (United States)

    Wu, Jia-qi; Xu, Li; Liang, Cheng; Zou, Wei; Bai, Yun-yang; Jiang, Jiu-hui

    2013-10-01

    To evaluate the treatment time and the anterior and posterior teeth movement pattern as closing extraction space for the Class III surgical patients facilitated by accelerated osteogenic orthodontic treatment. There were 10 skeletal Class III patients in accelerated osteogenic orthodontic group (AOO) and 10 patients in control group. Upper first premolars were extracted in all patients. After leveling and alignment (T2), corticotomy was performed in the area of maxillary anterior teeth to accelerate space closing.Study models of upper dentition were taken before orthodontic treatment (T1) and after space closing (T3). All the casts were laser scanned, and the distances of the movement of incisors and molars were digitally measured. The distances of tooth movement in two groups were recorded and analyzed. The alignment time between two groups was not statistically significant. The treatment time in AOO group from T2 to T3 was less than that in the control group (less than 9.1 ± 4.1 months). The treatment time in AOO group from T1 to T3 was less than that in the control group (less than 6.3 ± 4.8 months), and the differences were significant (P 0.05). Accelerated osteogenic orthodontic treatment could accelerate space closing in Class III surgical patients and shorten preoperative orthodontic time. There were no influence on the movement pattern of anterior and posterior teeth during pre-surgical orthodontic treatment.

  11. BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient Serum and Cerebrospinal Fluid Extracellular Vesicles

    Directory of Open Access Journals (Sweden)

    Walter W Chen

    2013-01-01

    Full Text Available Development of biofluid-based molecular diagnostic tests for cancer is an important step towards tumor characterization and real-time monitoring in a minimally invasive fashion. Extracellular vesicles (EVs are released from tumor cells into body fluids and can provide a powerful platform for tumor biomarkers because they carry tumor proteins and nucleic acids. Detecting rare point mutations in the background of wild-type sequences in biofluids such as blood and cerebrospinal fluid (CSF remains a major challenge. Techniques such as BEAMing (beads, emulsion, amplification, magnetics PCR and droplet digital PCR (ddPCR are substantially more sensitive than many other assays for mutant sequence detection. Here, we describe a novel approach that combines biofluid EV RNA and BEAMing RT-PCR (EV-BEAMing, as well droplet digital PCR to interrogate mutations from glioma tumors. EVs from CSF of patients with glioma were shown to contain mutant IDH1 transcripts, and we were able to reliably detect and quantify mutant and wild-type IDH1 RNA transcripts in CSF of patients with gliomas. EV-BEAMing and EV-ddPCR represent a valuable new strategy for cancer diagnostics, which can be applied to a variety of biofluids and neoplasms.

  12. The impact of reliable prebolus T 1 measurements or a fixed T 1 value in the assessment of glioma patients with dynamic contrast enhancing MRI.

    Science.gov (United States)

    Tietze, Anna; Mouridsen, Kim; Mikkelsen, Irene Klærke

    2015-06-01

    Accurate quantification of hemodynamic parameters using dynamic contrast enhanced (DCE) MRI requires a measurement of tissue T 1 prior to contrast injection (T 1). We evaluate (i) T 1 estimation using the variable flip angle (VFA) and the saturation recovery (SR) techniques and (ii) investigate if accurate estimation of DCE parameters outperform a time-saving approach with a predefined T 1 value when differentiating high- from low-grade gliomas. The accuracy and precision of T 1 measurements, acquired by VFA and SR, were investigated by computer simulations and in glioma patients using an equivalence test (p > 0.05 showing significant difference). The permeability measure, K trans, cerebral blood flow (CBF), and - volume, V p, were calculated in 42 glioma patients, using fixed T 1 of 1500 ms or an individual T 1 measurement, using SR. The areas under the receiver operating characteristic curves (AUCs) were used as measures for accuracy to differentiate tumor grade. The T 1 values obtained by VFA showed larger variation compared to those obtained using SR both in the digital phantom and the human data (p > 0.05). Although a fixed T 1 introduced a bias into the DCE calculation, this had only minor impact on the accuracy differentiating high-grade from low-grade gliomas, (AUCfix = 0.906 and AUCind = 0.884 for K trans; AUCfix = 0.863 and AUCind = 0.856 for V p; p for AUC comparison > 0.05). T 1 measurements by VFA were less precise, and the SR method is preferable, when accurate parameter estimation is required. Semiquantitative DCE values, based on predefined T 1 values, were sufficient to perform tumor grading in our study.

  13. Right inferior frontal gyrus activation is associated with memory improvement in patients with left frontal low-grade glioma resection.

    Directory of Open Access Journals (Sweden)

    Eliane C Miotto

    Full Text Available Patients with low-grade glioma (LGG have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR, related-non-structured (RNS, and related-structured words (RS, allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG and middle frontal gyrus (MFG during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.

  14. Motor network plasticity and low-frequency oscillations abnormalities in patients with brain gliomas: a functional MRI study.

    Directory of Open Access Journals (Sweden)

    Chen Niu

    Full Text Available Brain plasticity is often associated with the process of slow-growing tumor formation, which remodels neural organization and optimizes brain network function. In this study, we aimed to investigate whether motor function plasticity would display deficits in patients with slow-growing brain tumors located in or near motor areas, but who were without motor neurological deficits. We used resting-state functional magnetic resonance imaging to probe motor networks in 15 patients with histopathologically confirmed brain gliomas and 15 age-matched healthy controls. All subjects performed a motor task to help identify individual motor activity in the bilateral primary motor cortex (PMC and supplementary motor area (SMA. Frequency-based analysis at three different frequencies was then used to investigate possible alterations in the power spectral density (PSD of low-frequency oscillations. For each group, the average PSD was determined for each brain region and a nonparametric test was performed to determine the difference in power between the two groups. Significantly reduced inter-hemispheric functional connectivity between the left and right PMC was observed in patients compared with controls (P<0.05. We also found significantly decreased PSD in patients compared to that in controls, in all three frequency bands (low: 0.01-0.02 Hz; middle: 0.02-0.06 Hz; and high: 0.06-0.1 Hz, at three key motor regions. These findings suggest that in asymptomatic patients with brain tumors located in eloquent regions, inter-hemispheric connection may be more vulnerable. A comparison of the two approaches indicated that power spectral analysis is more sensitive than functional connectivity analysis for identifying the neurological abnormalities underlying motor function plasticity induced by slow-growing tumors.

  15. Right inferior frontal gyrus activation is associated with memory improvement in patients with left frontal low-grade glioma resection.

    Science.gov (United States)

    Miotto, Eliane C; Balardin, Joana B; Vieira, Gilson; Sato, Joao R; Martin, Maria da Graça M; Scaff, Milberto; Teixeira, Manoel J; Junior, Edson Amaro

    2014-01-01

    Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.

  16. The effects of gene polymorphisms on glioma prognosis.

    Science.gov (United States)

    Cui, Ying; Li, Guolin; Yan, Mengdan; Li, Jing; Jin, Tianbo; Li, Shanqu; Mu, Shijie

    2017-11-01

    Malignant gliomas are the most common primary brain tumors. Various genetic factors play important roles in the development and prognosis of glioma. The present study focuses on the impact of MPHOSPH6, TNIP1 and several other genes (ACYP2, NAF1, TERC, TERT, OBFC1, ZNF208 and RTEL1) on telomere length and how this affects the prognosis of glioma. Forty-three polymorphisms in nine genes from 605 glioma patients were selected. The association between genotype and survival outcome was analyzed using the Kaplan-Meier method, Cox regression analysis and the log-rank test. The 1-year overall survival (OS) rates of patients younger than 40 years of age was higher compared to those in patients older than 40 years of age. The 1-year OS rate of patients who underwent total resection was higher than that of patients whose gliomas were not completely resected. The 1-year OS rates of patients undergoing chemotherapy and of patients who did not undergo chemotherapy were 39.90% and 26.80%, respectively. Univariate analyses showed that ACYP2 rs12615793 and TERT rs2853676 loci affected progression-free survival in glioma patients; both ZNF208 rs8105767 and ACYP2 rs843720 affected the OS of patients with low-grade gliomas. Multivariate analyses suggested that MPHOSPH6 rs1056629 and rs1056654, and TERT rs2853676 loci were associated with good prognoses of patients with glioma or high-grade gliomas, whereas ZNF208 rs8105767 was associated with good prognosis of patients with low-grade glioma. Age, surgical resection and chemotherapy influenced the survival rates of glioma patients. TERT, MPHOSPH6, ACYP2 and ZNF208 genes were found to affect glioma prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

  17. SU-F-T-497: Spatiotemporally Optimal, Personalized Prescription Scheme for Glioblastoma Patients Using the Proliferation and Invasion Glioma Model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, M; Rockhill, J; Phillips, M [University Washington, Seattle, WA (United States)

    2016-06-15

    Purpose: To investigate a spatiotemporally optimal radiotherapy prescription scheme and its potential benefit for glioblastoma (GBM) patients using the proliferation and invasion (PI) glioma model. Methods: Standard prescription for GBM was assumed to deliver 46Gy in 23 fractions to GTV1+2cm margin and additional 14Gy in 7 fractions to GTV2+2cm margin. We simulated the tumor proliferation and invasion in 2D according to the PI glioma model with a moving velocity of 0.029(slow-move), 0.079(average-move), and 0.13(fast-move) mm/day for GTV2 with a radius of 1 and 2cm. For each tumor, the margin around GTV1 and GTV2 was varied to 0–6 cm and 1–3 cm respectively. Total dose to GTV1 was constrained such that the equivalent uniform dose (EUD) to normal brain equals EUD with the standard prescription. A non-stationary dose policy, where the fractional dose varies, was investigated to estimate the temporal effect of the radiation dose. The efficacy of an optimal prescription scheme was evaluated by tumor cell-surviving fraction (SF), EUD, and the expected survival time. Results: Optimal prescription for the slow-move tumors was to use 3.0(small)-3.5(large) cm margins to GTV1, and 1.5cm margin to GTV2. For the average- and fast-move tumors, it was optimal to use 6.0cm margin for GTV1 suggesting that whole brain therapy is optimal, and then 1.5cm (average-move) and 1.5–3.0cm (fast-move, small-large) margins for GTV2. It was optimal to deliver the boost sequentially using a linearly decreasing fractional dose for all tumors. Optimal prescription led to 0.001–0.465% of the tumor SF resulted from using the standard prescription, and increased tumor EUD by 25.3–49.3% and the estimated survival time by 7.6–22.2 months. Conclusion: It is feasible to optimize a prescription scheme depending on the individual tumor characteristics. A personalized prescription scheme could potentially increase tumor EUD and the expected survival time significantly without increasing EUD to

  18. Molecular Diagnostics of Gliomas Using Next Generation Sequencing of a Glioma-Tailored Gene Panel.

    Science.gov (United States)

    Zacher, Angela; Kaulich, Kerstin; Stepanow, Stefanie; Wolter, Marietta; Köhrer, Karl; Felsberg, Jörg; Malzkorn, Bastian; Reifenberger, Guido

    2017-03-01

    Current classification of gliomas is based on histological criteria according to the World Health Organization (WHO) classification of tumors of the central nervous system. Over the past years, characteristic genetic profiles have been identified in various glioma types. These can refine tumor diagnostics and provide important prognostic and predictive information. We report on the establishment and validation of gene panel next generation sequencing (NGS) for the molecular diagnostics of gliomas. We designed a glioma-tailored gene panel covering 660 amplicons derived from 20 genes frequently aberrant in different glioma types. Sensitivity and specificity of glioma gene panel NGS for detection of DNA sequence variants and copy number changes were validated by single gene analyses. NGS-based mutation detection was optimized for application on formalin-fixed paraffin-embedded tissue specimens including small stereotactic biopsy samples. NGS data obtained in a retrospective analysis of 121 gliomas allowed for their molecular classification into distinct biological groups, including (i) isocitrate dehydrogenase gene (IDH) 1 or 2 mutant astrocytic gliomas with frequent α-thalassemia/mental retardation syndrome X-linked (ATRX) and tumor protein p53 (TP53) gene mutations, (ii) IDH mutant oligodendroglial tumors with 1p/19q codeletion, telomerase reverse transcriptase (TERT) promoter mutation and frequent Drosophila homolog of capicua (CIC) gene mutation, as well as (iii) IDH wildtype glioblastomas with frequent TERT promoter mutation, phosphatase and tensin homolog (PTEN) mutation and/or epidermal growth factor receptor (EGFR) amplification. Oligoastrocytic gliomas were genetically assigned to either of these groups. Our findings implicate gene panel NGS as a promising diagnostic technique that may facilitate integrated histological and molecular glioma classification. © 2016 International Society of Neuropathology.

  19. Signal intensity in T2' magnetic resonance imaging is related to brain glioma grade

    International Nuclear Information System (INIS)

    Saitta, Laura; Castellan, Lucio; Heese, Oliver; Westphal, Manfred; Foerster, Ann-Freya; Siemonsen, Susanne; Fiehler, Jens; Goebell, Einar; Matschke, Jakob

    2011-01-01

    T2' values reflect the presence of deoxyhaemoglobin related to high local oxygen extraction. We assessed the feasibility of T2' imaging to display regions with high metabolic activity in brain gliomas. MRI was performed in 25 patients (12 female; median age 46 years; range 2-69) with brain gliomas with additional T2 and T2* sequences. T2' maps were derived from T2 and T2*. Dynamic susceptibility weighted contrast (DSC) perfusion was performed in 12/25 patients. Images were visually assessed by two readers and five ROIs were evaluated for each patient. Pearson correlation, Mann-Whitney and Kruskal-Wallis tests were applied for statistical analysis. Three patients were not further evaluated because of artefacts. Mean values of high-grade (III-IV) gliomas showed significantly lower T2' values than low-grade (II) gliomas (p < 0.001). An inverse relationship was observed between rCBV and sqr (T2') (r = -0.463, p < 0.001). No correlation was observed between T2' and rCBV for grade II tumours (r = 0.038; p = 0.875). High-grade tumours revealed lower T2' values, presumably because of higher oxygen consumption in proliferating tissue. Our results indicate that T2' imaging can be used as an alternative to DSC perfusion in the detection of subtle deviations in tumour metabolism. (orig.)

  20. Concurrent radiotherapy with temozolomide vs. concurrent radiotherapy with a cisplatinum-based polychemotherapy regimen. Acute toxicity in pediatric high-grade glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, Clemens; Kortmann, Rolf D. [University of Leipzig Medical Center, Department of Radiotherapy and Radiation Oncology, Leipzig (Germany); Bueren, Andre O. von [University Medical Center Goettingen, Division of Pediatric Hematology and Oncology, Goettingen (Germany); University Hospital of Geneva, Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Geneva (Switzerland); University of Geneva, Department of Pediatrics, CANSEARCH Research Laboratory, Faculty of Medicine, Geneva (Switzerland); Bojko, Sabrina; Hoffmann, Marion; Kramm, Christof M. [University Medical Center Goettingen, Division of Pediatric Hematology and Oncology, Goettingen (Germany); Pietsch, Torsten; Gielen, Gerrit H. [University of Bonn Medical Center, Department of Neuropathology, Brain Tumor Reference Center of the DGNN, Bonn (Germany); Warmuth-Metz, Monika; Bison, Brigitte [University Hospital Wuerzburg, Department of Neuroradiology, Wuerzburg (Germany)

    2018-03-15

    As the efficacy of all pediatric high-grade glioma (HGG) treatments is similar and still disappointing, it is essential to also investigate the toxicity of available treatments. Prospectively recorded hematologic and nonhematologic toxicities of children treated with radiochemotherapy in the HIT GBM-C/D and HIT-HGG-2007 trials were compared. Children aged 3-18 years with histologically proven HGG (WHO grade III and IV tumors) or unequivocal radiologic diagnosis of diffuse intrinsic pontine glioma (DIPG) were included in these trials. The HIT-HGG-2007 protocol comprised concomitant radiochemotherapy with temozolomide, while cisplatinum/etoposide (PE) and PE plus ifosfamide (PEI) in combination with weekly vincristine injections were applied during radiochemotherapy in the HIT GBM-C/D protocol. Regular blood counts and information about cellular nadirs were available from 304 patients (leukocytes) and 306 patients (thrombocytes), respectively. Grade 3-4 leukopenia was much more frequent in the HIT GBM-C/D cohort (n = 88, 52%) vs. HIT-HGG-2007 (n = 13, 10%; P <0.001). Grade 3-4 thrombopenia was also more likely in the HIT GBM-C/D cohort (n = 21, 12% vs. n = 3,2%; P <0.001). Grade 3-4 leukopenia appeared more often in children aged 3-7 years (n = 38/85, 45%) than in children aged 8-12 years (n = 39/120, 33%) and 13-18 years (24/100, 24%; P =0.034). In addition, sickness was more frequent in the HIT GBM-C/D cohort (grade 1-2: 44%, grade 3-4: 6% vs. grade 1-2: 28%, grade 3-4: 1%; P <0.001). Radiochemotherapy involving cisplatinum-based polychemotherapy is more toxic than radiotherapy in combination with temozolomide. Without evidence of differences in therapeutic efficacy, the treatment with lower toxicity, i. e., radiotherapy with temozolomide should be used. (orig.) [German] Die Wirksamkeit verschiedener Protokolle zur Radiochemotherapie bei Kindern mit hochmalignen Gliomen (''high-grade glioma'', HGG) ist aehnlich und leider noch enttaeuschend. Es

  1. Neuronavigator-guided glioma surgery.

    Science.gov (United States)

    Du, Guhong; Zhou, Liangfu; Mao, Ying

    2003-10-01

    To evaluate the effectiveness of neuronavigator-guided surgery for the resection of gliomas. A total of 80 patients with gliomas underwent surgical treatment under the StealthStation neuronavigator to estimate the extent of the tumors. In 27 cases, the measurements of brain shifts at the dura, cortical surface and lesion margin were recorded during the operations. A technique termed "micro-catheter fence post" was used in superficial gliomas to compensate for brain shift. Mean fiducial error and predicted accuracy in the 80 cases were 2.03 mm +/- 0.89 mm and 2.43 mm +/- 0.99 mm, respectively. The shifts at the dura, cortical surface and lesion margin were 3.44 mm +/- 2.39 mm, 7.58 mm +/- 3.75 mm, and 6.55 mm +/- 3.19 mm, respectively. Although neuronavigation revealed residual tumors, operations were discontinued in 5 cases of deep-seated gliomas. In the other 75 cases, total tumor removals were achieved in 62 (82.7%), and subtotal removals were achieved in 13 (17.3%). Post-operation, neurological symptoms were improved or unchanged in 68 cases (85.0%), and worsened in 12 (15.0%). No deaths occurred during the operations and post-operations. Intraoperative brain shifts mainly contribute to the fail of spatial accuracy during neuronavigator-guided glioma surgery. The "micro-catheter fence post" technique used for glioma surgery is shown to be useful for compensating for intraoperative brain shifts. This technique, thus, contributes to an increase in total tumor removal and a decrease in surgical complications.

  2. A Preliminary Experience with Use of Intraoperative Magnetic Resonance Imaging in Thalamic Glioma Surgery: A Case Series of 38 Patients.

    Science.gov (United States)

    Zheng, Xuan; Xu, Xinghua; Zhang, Hui; Wang, Qun; Ma, Xiaodong; Chen, Xiaolei; Sun, Guochen; Zhang, Jiashu; Jiang, Jinli; Xu, Bainan; Zhang, Jun

    2016-05-01

    Thalamic gliomas are rare tumors that constitute 1%-5% of all central nervous system tumors. Despite advanced techniques and equipment, surgical resection remains challenging because of the vital structures adjacent to the tumor. Intraoperative magnetic resonance imaging (MRI) might play an active role during brain tumor surgery because it compensates for brain shift or operation-induced hemorrhage, which are challenging issues for neurosurgeons. We reviewed 38 patients treated surgically under intraoperative MRI guidance between January 2008 and July 2015 at our center. Preoperative, intraoperative, and postoperative MRI scans were reviewed. Preoperative and postoperative motor power, morbidity and mortality, resection rate, surgical approach, pathologic results, and patient demographics were also reviewed. Mean patient age was 37 years ± 18; 12 patients were included in the low-grade group, and 26 patients were included in the high-grade group. Under intraoperative MRI guidance, the gross total resection rate was increased from 16 (42.1%) to 26 (68.4%), and the near-total or subtotal resection rate was increased from 5 (13.2%) to 9 (23.7%). Hematoma formation was discovered in 3 patients on intraoperative MRI scan; each patient underwent a hemostatic operation immediately. With improvements in neurosurgical techniques and equipment, surgical resection is considered feasible in patients with thalamic gliomas. Intraoperative MRI may be helpful in achieving the maximal resection rate with minimal surgical-related morbidity. However, because of severe disease progression, the overall prognosis is unfavorable. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Reorganization of Language Areas in Patient with a Frontal Lobe Low Grade Glioma – fMRI Case Study

    International Nuclear Information System (INIS)

    Kośla, Katarzyna; Bryszewski, Bartosz; Jaskólski, Dariusz; Błasiak-Kołacińska, Nina; Stefańczyk, Ludomir; Majos, Agata

    2015-01-01

    Functional magnetic resonance (fMRI) studies results in case of an adult patient with low grade glioma (LGG) in dominant hemisphere suggest brain plasticity process with acquisition of language functions by the non-dominant hemisphere speech regions. A 36-years old right-handed woman was admitted to the Department of Neurosurgery for surgical treatment of brain tumor. An MRI examination revealed a pathological mass in the left frontal lobe, in close topographical relationship to the Broca’s area. A left fronto-parietal craniotomy was performed, with an intraoperative awake language mapping procedure. A total resection of the pathological mass was achieved. The tumor was examined histologically as LGG. In the follow-up MRI exam 32 months after the operation a tumor recurrence was suggested. The fMRI exams performed preoperative and 3, 32 and 41 months after the operation showed changes in language regions activation patterns, with a progressive right-sided activation of Broca’s and Wernicke’s areas. Pre- and postoperative cognitive evaluation by a neuropsychologist did not detect any language impairment. We present a running process of reorganization of language areas in a patient after brain tumor resection, from strong left-sided to symmetrical lateralization. 1. FMRI results in comparison with the psychological status of the patient proved contribution of functional reorganization to the preservation of language performance. 2. A slow growing LGG as well as the recurrence of the tumor near the left Broca’s area might be the factors leading to reorganization of language-related areas by recruiting the right hemisphe

  4. An Interindividual Comparison of O-(2- [18F]Fluoroethyl)-L-Tyrosine (FET)– and L-[Methyl-11C]Methionine (MET)–PET in Patients With Brain Gliomas and Metastases

    International Nuclear Information System (INIS)

    Grosu, Anca-Ligia; Astner, Sabrina T.; Riedel, Eva; Nieder, Carsten; Wiedenmann, Nicole; Heinemann, Felix; Schwaiger, Markus

    2011-01-01

    Purpose: L-[methyl- 11 C]methionine (MET)–positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of 11 C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2- [ 18 F]fluoroethyl)-L-tyrosine (FET) is labeled with 18 F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI). Methods and Materials: We examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion–to–gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up. Results: There was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p 18 F]fluoroethyl)-L-tyrosine–PET and MET-PET provide comparable diagnostic information on gliomas and brain metastases. Like MET-PET, FET-PET can be used for differentiation of residual or recurrent tumor from treatment-related changes/pseudoprogression, as well as for delineation of gliomas.

  5. Hypofractionated stereotactic radiotherapy combined with topotecan in recurrent malignant glioma

    International Nuclear Information System (INIS)

    Wurm, Reinhard E.; Kuczer, David A.; Schlenger, Lorenz; Matnjani, Gesa; Scheffler, Dirk; Cosgrove, Vivian P.; Ahlswede, Julia; Woiciechowsky, Christian; Budach, Volker

    2006-01-01

    Purpose: To assess hypofractionated stereotactic radiotherapy (H-SRT) with concurrent topotecan in patients with recurrent malignant glioma. Methods and Materials: Between February 1998 and December 2001, 25 patients with recurrent malignant glioma were treated in a phase I-II study (8 females and 17 males; median age, 45 years; range, 11-66 years; median Karnofsky performance status, 80%, range, 50-100%; median Mini Mental Standard Examination score, 25 points; range, 10-30 points). Of the 25 patients, 20% had World Health Organization Grade III and 80% World Health Organization Grade IV glioma. All patients had been treated previously by external beam radiotherapy with 54.4 Gy in 34 fractions twice daily, at least 6 h apart, within 3.5 weeks or 60 Gy in 30 fractions within 6 weeks. In addition, 84% had already received at least one chemotherapy regimen for recurrence. The median H-SRT dose at the 80% isodose was 25 Gy, and the maximal dose was 30 Gy delivered in five to six fractions on consecutive days. Topotecan (1.1 mg/m 2 /d) was given as a continuous i.v. infusion during H-SRT. Depending on the toxicity and compliance, patients received an additional 48 topotecan courses. Results: For all patients, the actuarial median progression-free survival was 10.5 months (range, 1.4-47.8 months), the median functional survival was 12.6 months (range, 1.6-49.5 months), and the median overall survival was 14.5 months (range, 3-56.4 months). Twelve percent of patients developed presumed adverse radiation effects (Radiation Therapy Oncology Group Grade 2). According to the Common Toxicity Criteria, version 2.0, no topotecan-related Grade 4 toxicity was noted. Grade 3 neutropenia was documented after 14 and Grade 3 thrombopenia after 12 courses. Conclusion: H-SRT with topotecan is feasible and well-tolerated in patients with recurrent high-grade glioma and results in similar survival compared with other repeat treatment modalities

  6. Intraoperative radiation therapy for malignant glioma

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Noboru; Yamada, Hiromu; Andoh, Takashi; Takada, Mitsuaki; Hirata, Toshifumi; Funakoshi, Takashi; Doi, Hidetaka; Yanagawa, Shigeo [Gifu Univ. (Japan). Faculty of Medicine

    1989-04-01

    Intraoperative radiation therapy (IOR) is an ideal means of exterminating residual tumor after surgical resection. In this study, the clinical results of IOR using a Scanditronix Microtron MM-22 were evaluated in 14 patients with malignant glioma, five of whom had recurrent tumors. Between July, 1985 and October, 1986, 11 patients with glioblastoma multiforme (GB) were irradiated 18 times (mean, 1.6 times/case), and three with astrocytoma (Kernohan grade III) underwent IOR once each. The target-absorbed dose at 1 to 2 cm deeper than the tumor resection surface was 15 to 50 Gy. During irradiation, a cotton bolus was placed in the dead space after over 91% of the tumor had been resected. As a rule, external irradiation therapy was also given postoperatively at a dose of 30 to 52 Gy. One patient died of pneumonia and disseminated intravascular coagulation syndrome 1 month postoperatively. The 1- and 2-year survival rates of the ramaining 13 patients were 84.6% and 61.5%, respectively; among the 10 with GB, they were 80% and 50%. Generally, the smaller the tumor size, the better the results. There were no adverse effects, despite the dose 15 to 50 Gy applied temporally to the tumor bed. IOR was especially effective against small, localized tumors, but was not always beneficial in cases of large tumors, particularly those with a contralateral focus. The improved survival rate in this series demonstrates that IOR is significantly effective in the 'induction of remission' following surgical excision of malignant gliomas. (author).

  7. Valproic acid reduces hair loss and improves survival in patients receiving temozolomide-based radiation therapy for high-grade glioma.

    Science.gov (United States)

    Watanabe, Shinichi; Kuwabara, Yui; Suehiro, Satoshi; Yamashita, Daisuke; Tanaka, Mamoru; Tanaka, Akihiro; Ohue, Shiro; Araki, Hiroaki

    2017-03-01

    Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma. The purpose of this study was to determine whether VPA use during radiotherapy for high-grade glioma is associated with decreased side effects of radiotherapy and an improvement in overall survival (OS) and progression-free survival (PFS). Medical records of 112 patients with high-grade glioma were retrospectively reviewed. We grouped patients by VPA use or non-use during radiotherapy, and evaluated hair loss, OS, and PFS. The radiation dose and fractionation at the onset of hair loss were 4 Gy and two fractions higher, respectively, in the VPA group compared with the VPA non-use group (P hair loss and improvement in survival. Hair loss prevention benefits patients suffering from the deleterious effects of radiation.

  8. 7-Tesla Susceptibility-Weighted Imaging to Assess the Effects of Radiotherapy on Normal-Appearing Brain in Patients With Glioma

    International Nuclear Information System (INIS)

    Lupo, Janine M.; Chuang, Cynthia F.; Chang, Susan M.; Barani, Igor J.; Jimenez, Bert; Hess, Christopher P.; Nelson, Sarah J.

    2012-01-01

    Purpose: To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials: SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results: Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation. These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions: High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.

  9. Functional magnetic resonance imaging (fMRI) in patients with gliomas adjacent to classical language areas. Lateralization of activated prefrontal cortex is important in determining the dominant hemisphere

    International Nuclear Information System (INIS)

    Karibe, Hiroshi; Kumabe, Toshihiro; Shirane, Reizo; Yoshimoto, Takashi

    2003-01-01

    In patients with gliomas adjacent to classical language areas, lateralized activation of prefrontal cortex was assessed to determine language dominant hemisphere using functional magnetic resonance imaging (fMRI). Twelve patients presented with aphasias were studied. In all patients, either the left frontal operculum or left superior temporal gyri were adjacent to gliomas, suggesting all patients had left lateralization in hemispheric language dominance. Functional MRI was performed with a 1.5T scanner, with the sequence of gradient-echo type echo-planar imaging. As specific language tasks, verb, word, and capping generations were used. Using a cross-correlation analysis method, primary activation maps were generated using pixels with a correlation coefficient of >0.7. The lateralized activation of frontal operculum, superior temporal gyrus, and prefrontal cortex were assessed by calculating laterality index. Successful activation of frontal operculum was imaged in 11 of 12, in the superior temporal gyrus or prefrontal cortex. Three out of 11 cases had apparent activation lateralized in the right frontal operculum on fMRI, while 3 out of 12 cases showed activation in the superior temporal gyrus. On the other hand, all cases had apparent activation lateralized to the left prefrontal cortex. Significant activation of true language area may not be obtained in some cases with gliomas adjacent to classical language areas. In such cases, lateralization of apparent activation of prefrontal cortex may reflect lateralization in the dominant hemisphere. These result suggest that the assessment of apparent activation of prefrontal cortex lateralization is useful to determine the language dominant hemisphere. (author)

  10. Immunotherapy for recurrent malignant glioma: an interim report on survival.

    Science.gov (United States)

    Ingram, M; Buckwalter, J G; Jacques, D B; Freshwater, D B; Abts, R M; Techy, G B; Miyagi, K; Shelden, C H; Rand, R W; English, L W

    1990-12-01

    We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.

  11. Radiosensitivity of Patient-Derived Glioma Stem Cell 3-Dimensional Cultures to Photon, Proton, and Carbon Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chiblak, Sara; Tang, Zili [German Cancer Consortium, Heidelberg (Germany); Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg (Germany); Campos, Benito; Gal, Zoltan; Unterberg, Andreas [Division of Neurological Research, Department of Neurosurgery, University of Heidelberg Medical School, Heidelberg (Germany); Debus, Jürgen [German Cancer Consortium, Heidelberg (Germany); Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg (Germany); Herold-Mende, Christel [Division of Neurological Research, Department of Neurosurgery, University of Heidelberg Medical School, Heidelberg (Germany); Abdollahi, Amir, E-mail: a.amir@dkfz.de [German Cancer Consortium, Heidelberg (Germany); Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg (Germany)

    2016-05-01

    Purpose: To investigate the radiosensitivity of primary glioma stem cell (GSC) cultures with different CD133 status in a 3-dimensional (3D) model after photon versus proton versus carbon irradiation. Methods and Materials: Human primary GSC spheroid cultures were established from tumor specimens of six consented glioblastoma patients. Human U87MG was used as a classical glioblastoma radioresistant cell line. Cell suspensions were generated by mechanical dissociation of GSC spheroids and embedded in a semi-solid 3D matrix before irradiation. Spheroid-like colonies were manually counted by microscopy. Cells were also recovered and quantified by fluorescence. CD133 expression and DNA damage were evaluated by flow cytometry. Results: The fraction of CD133{sup +} cells varied between 0.014% and 96% in the six GSC cultures and showed a nonsignificant correlation with plating efficiency and survival fractions. The 4 most photon-radioresistant GSC cultures were NCH644, NCH421k, NCH441, and NCH636. Clonogenic survival for proton irradiation revealed relative biologic effectiveness (RBE) in the range of 0.7-1.20. However, carbon irradiation rendered the photon-resistant GSC cultures sensitive, with average RBE of 1.87-3.44. This effect was partly attributed to impaired capability of GSC to repair carbon ion–induced DNA double-strand breaks as determined by residual DNA repair foci. Interestingly, radiosensitivity of U87 cells was comparable to GSC cultures using clonogenic survival as the standard readout. Conclusions: Carbon irradiation is effective in GSC eradication with similar RBE ranges approximately 2-3 as compared with non-stem GSC cultures (U87). Our data strongly suggest further exploration of GSC using classic radiobiology endpoints such as the here-used 3D clonogenic survival assay and integration of additional GSC-specific markers.

  12. Radiosensitivity of Patient-Derived Glioma Stem Cell 3-Dimensional Cultures to Photon, Proton, and Carbon Irradiation

    International Nuclear Information System (INIS)

    Chiblak, Sara; Tang, Zili; Campos, Benito; Gal, Zoltan; Unterberg, Andreas; Debus, Jürgen; Herold-Mende, Christel; Abdollahi, Amir

    2016-01-01

    Purpose: To investigate the radiosensitivity of primary glioma stem cell (GSC) cultures with different CD133 status in a 3-dimensional (3D) model after photon versus proton versus carbon irradiation. Methods and Materials: Human primary GSC spheroid cultures were established from tumor specimens of six consented glioblastoma patients. Human U87MG was used as a classical glioblastoma radioresistant cell line. Cell suspensions were generated by mechanical dissociation of GSC spheroids and embedded in a semi-solid 3D matrix before irradiation. Spheroid-like colonies were manually counted by microscopy. Cells were also recovered and quantified by fluorescence. CD133 expression and DNA damage were evaluated by flow cytometry. Results: The fraction of CD133"+ cells varied between 0.014% and 96% in the six GSC cultures and showed a nonsignificant correlation with plating efficiency and survival fractions. The 4 most photon-radioresistant GSC cultures were NCH644, NCH421k, NCH441, and NCH636. Clonogenic survival for proton irradiation revealed relative biologic effectiveness (RBE) in the range of 0.7-1.20. However, carbon irradiation rendered the photon-resistant GSC cultures sensitive, with average RBE of 1.87-3.44. This effect was partly attributed to impaired capability of GSC to repair carbon ion–induced DNA double-strand breaks as determined by residual DNA repair foci. Interestingly, radiosensitivity of U87 cells was comparable to GSC cultures using clonogenic survival as the standard readout. Conclusions: Carbon irradiation is effective in GSC eradication with similar RBE ranges approximately 2-3 as compared with non-stem GSC cultures (U87). Our data strongly suggest further exploration of GSC using classic radiobiology endpoints such as the here-used 3D clonogenic survival assay and integration of additional GSC-specific markers.

  13. Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment.

    Science.gov (United States)

    Yamasaki, Fumiyuki; Kurisu, Kaoru; Aoki, Tomokazu; Yamanaka, Masami; Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi; Akiyama, Yuji; Sugiyama, Kazuhiko

    2012-10-01

    The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6-65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan-Meier survival curves (log-rank test). It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment

    International Nuclear Information System (INIS)

    Yamasaki, Fumiyuki; Kurisu, Kaoru; Aoki, Tomokazu; Yamanaka, Masami; Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi; Akiyama, Yuji; Sugiyama, Kazuhiko

    2012-01-01

    Background: The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Materials and methods: Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6–65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan–Meier survival curves (log-rank test). Results: It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. Discussion and conclusion: High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab

  15. Deep RF-hyperthermia: an effective treatment of advanced gliomas

    International Nuclear Information System (INIS)

    Sahinbas, H.; Groenemeyer, D.H.W.

    2005-01-01

    Full text: Contrary to the enormous efforts, results of conventional treatments of high-grade malignant gliomas are unsatisfactory. The prognosis of that tumor type is poor, its overall median survival time (MST) less than a year. Most of the cases are inoperable or only partially resectable, and their response to the various chemotherapies and/or radiotherapy is poor. The chemo-therapies which are successful for other locations often fail due to the effective brain-blood barrier (BBB). Probably the modification of the BBB by electromagnetic fields together with the direct electromagnetic-field heating are the main factors for the success of electro-hyperthermia. Primary aim of this study was to present the therapy tolerance for patients of electro-hyperthermia (EHY) for advanced malignant gliomas and as main intention to show the increase of the median survival time (MST). Our study was performed between 2000 - 2004; for patients with inoperable, partially resected or recurrent gliomas (WHO grade III and IV) with progression after radio- and/or chemotherapy and a Karnofsky Performance Score ≤30-40 %. 105 pts were involved in this study: 38 astrocytoma pts, 56 glioblastoma pts and 12 pts with other brain malignancies. All patients were heavily and unsatisfactory pretreated. EHY was applied over 4 weeks, 3 times a week over 1 hour in average by 100 Watt, as mono- or combined therapy (chemotherapy, irradiation therapy). The set of patients as well as the frequency of EHY was well documented for future evaluations. The historic reference of the MST from the first diagnosis for gliomas grade III and IV in our institute is 11.42 months (range 1-62), which is in good agreement with the relevant literature. The median survival time (MST) in our institute with EHY increases to 44.2 m, 23.2 m and 61.0 m for astrocytoma, glioblastoma and other brain malignancies, respectively. The therapy results were controlled by MRI images. EHY is a feasible treatment for advanced

  16. The accuracy of survival time prediction for patients with glioma is improved by measuring mitotic spindle checkpoint gene expression.

    Directory of Open Access Journals (Sweden)

    Li Bie

    Full Text Available Identification of gene expression changes that improve prediction of survival time across all glioma grades would be clinically useful. Four Affymetrix GeneChip datasets from the literature, containing data from 771 glioma samples representing all WHO grades and eight normal brain samples, were used in an ANOVA model to screen for transcript changes that correlated with grade. Observations were confirmed and extended using qPCR assays on RNA derived from 38 additional glioma samples and eight normal samples for which survival data were available. RNA levels of eight major mitotic spindle assembly checkpoint (SAC genes (BUB1, BUB1B, BUB3, CENPE, MAD1L1, MAD2L1, CDC20, TTK significantly correlated with glioma grade and six also significantly correlated with survival time. In particular, the level of BUB1B expression was highly correlated with survival time (p<0.0001, and significantly outperformed all other measured parameters, including two standards; WHO grade and MIB-1 (Ki-67 labeling index. Measurement of the expression levels of a small set of SAC genes may complement histological grade and other clinical parameters for predicting survival time.

  17. Evaluation of the risk of liver damage from the use of 5-aminolevulinic acid for intra-operative identification and resection in patients with malignant gliomas

    DEFF Research Database (Denmark)

    Offersen, Cecilie Mørck; Skjoeth-Rasmussen, Jane

    2017-01-01

    BACKGROUND: The clinical efficacy of 5-aminolevulinic acid (5-ALA) for fluorescence-guided surgery of malignant gliomas is evident from several studies; however, as post-operative elevations of liver enzymes have been seen, there is a potential risk of liver damage upon administration. The aim...... (September 2012-September 2014) at the University Hospital of Copenhagen, Rigshospitalet, was conducted. All patients received a pre-operative dose of 20 mg/kg bodyweight 5-ALA. The pre- and post-operative enzyme levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase...

  18. Expression of Zonulin, c-kit, and Glial Fibrillary Acidic Protein in Human Gliomas.

    Science.gov (United States)

    Skardelly, Marco; Armbruster, Franz Paul; Meixensberger, Jürgen; Hilbig, Heidegard

    2009-08-18

    The hallmarks of human malignant gliomas are their marked invasiveness and vascularity. Because angiogenesis and tumor invasion have been associated with extracellular matrix degradation and intercellular tight junctions, the involvement of zonulin in glioma biology is in the focus. We selected for histological examination five cases of glioblastoma WHO IV (nomenclature of the World Health Organization) and one case each from astrocytoma WHO III, meningioma WHO III, and meningioma WHO I as control samples. The meningioma WHO I is regarded as benign, whereas the meningioma WHO III is recognized as the transition form of malignant tumors in humans. The visualization of a newly designed antibody against human zonulin was studied in triple-labeling studies using fluorescence immunocytochemistry and compared with the expression of c-kit and glial fibrillary acidic protein in differently developed human gliomas. We found that increasing the expression of c-kit is accompanied by an increase of zonulin expression. Both are correlated to the degree of malignancy of human brain tumors. The expression of zonulin is correlated to the degradation of the blood-brain barrier as revealed by Griffonia simplicifolia lectin. In differently graded tumors, we found differently graded involvement of blood vessels in the tumor development, explaining patients' survival.

  19. Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma

    Energy Technology Data Exchange (ETDEWEB)

    Goettler, Jens; Preibisch, Christine [TU Muenchen, Department of Neuroradiology, Klinikum rechts der Isar, Munich (Germany); TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Munich (Germany); Lukas, Mathias; Mustafa, Mona; Schwaiger, Markus; Pyka, Thomas [TU Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kluge, Anne; Kaczmarz, Stephan; Zimmer, Claus [TU Muenchen, Department of Neuroradiology, Klinikum rechts der Isar, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [TU Muenchen, Department of Neurosurgery, Klinikum rechts der Isar, Munich (Germany); Foerster, Stefan [TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Munich (Germany); TU Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Klinikum Bayreuth, Department of Nuclear Medicine, Bayreuth (Germany)

    2017-03-15

    {sup 18}F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV. Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined. While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p < 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average. Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology. (orig.)

  20. Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma.

    Science.gov (United States)

    Göttler, Jens; Lukas, Mathias; Kluge, Anne; Kaczmarz, Stephan; Gempt, Jens; Ringel, Florian; Mustafa, Mona; Meyer, Bernhard; Zimmer, Claus; Schwaiger, Markus; Förster, Stefan; Preibisch, Christine; Pyka, Thomas

    2017-03-01

    18 F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV. Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined. While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average. Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.

  1. Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Bin [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Hu, Zhiqiang, E-mail: zhiqhutg@126.com [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Huang, Hui; Zhu, Guangtong; Xiao, Zhiyong [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Wan, Weiqing; Zhang, Peng; Jia, Wang; Zhang, Liwei [Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050 (China)

    2014-11-07

    Highlights: • KDM5B is overexpressed in glioma samples. • KDM5B stimulated proliferation of glioma cells. • Inhibition of p21contributes to KDM5B-induced proliferation. - Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.

  2. Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study.

    Science.gov (United States)

    Berntsson, Shala G; Merrell, Ryan T; Amirian, E Susan; Armstrong, Georgina N; Lachance, Daniel; Smits, Anja; Zhou, Renke; Jacobs, Daniel I; Wrensch, Margaret R; Olson, Sara H; Il'yasova, Dora; Claus, Elizabeth B; Barnholtz-Sloan, Jill S; Schildkraut, Joellen; Sadetzki, Siegal; Johansen, Christoffer; Houlston, Richard S; Jenkins, Robert B; Bernstein, Jonine L; Lai, Rose; Shete, Sanjay; Amos, Christopher I; Bondy, Melissa L; Melin, Beatrice S

    2018-04-23

    The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls. The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n = 4533) and controls (n = 4171) were also asked about seizures less than 2 years from diagnosis and previous seizure history more than 2 years prior to tumor diagnosis, including childhood seizures. Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.

  3. Compensatory canine angulation in angle Class II and III patients

    Directory of Open Access Journals (Sweden)

    Mauro Carlos Agner Busato

    2009-09-01

    Full Text Available The aim of this study was to evaluate the occurence of compensation in mesiodistal axial inclinations of canines in skeletal malocclusions patients. The sample consisted of 25 Angle Class II, division 1 malocclusion (group 1 and 19 Angle Class III malocclusion patients (group 2. After measurement of dental angulations through a method that associates plaster model photography and AutoCad software, comparisons between the groups were performed by T-test for independent samples. Results showed that there was no statistically significant difference (p < 0.05 between groups, when maxillary canine angulations were compared. Regarding the mandibular canines, there was a statistically significant difference in dental angulation, expressed by 3.2° for group 1 and 0.15° for group 2. An upright position tendency for mandibular canines was observed in the Angle Class III sample. This configures a pattern of compensatory coronary positioning, since the angulation of these teeth makes them occupy less space in the dental arch and consequently mandibular incisors can be in a more retracted position in the sagittal plane.

  4. Polifeprosan 20, 3.85% carmustine slow release wafer in malignant glioma: patient selection and perspectives on a low-burden therapy

    Directory of Open Access Journals (Sweden)

    Kleinberg L

    2016-11-01

    Full Text Available Lawrence Kleinberg Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, USA Abstract: Polifeprosan 20 with carmustine (GLIADEL® polymer implant wafer is a biodegradable compound containing 3.85% carmustine (BCNU, bischloroethylnitrosourea implanted in the brain at the time of planned tumor surgery, which then slowly degrades to release the BCNU chemotherapy directly into the brain thereby bypassing the blood–brain barrier. Carmustine implant wafers were demonstrated to improve survival in randomized placebo-controlled trials in patients undergoing a near total resection of newly diagnosed or recurrent malignant glioma. Based on these trials and other supporting data, carmustine wafer therapy was approved for use for newly diagnosed and recurrent malignant glioma in the United States and the European Union. Adverse events are uncommon, and as this therapy is placed at the time of surgery, it does not add to patient treatment burden. Nevertheless, this therapy appears to be underutilized. This article reviews the evidence for a favorable therapeutic ratio for the patient and the potential barriers. Consideration of these issues is important for optimal use of this therapeutic approach and may be important as this technology and other local therapies are further developed in the future. Keywords: carmustine, wafer, gliadel, glioblastoma

  5. Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients.

    Science.gov (United States)

    Vees, Hansjörg; Senthamizhchelvan, Srinivasan; Miralbell, Raymond; Weber, Damien C; Ratib, Osman; Zaidi, Habib

    2009-02-01

    The purpose of the study is to assess the contribution of (18)F-fluoro-ethyl-tyrosine ((18)F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone. The study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate (18)F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTV(MRI)). PET image segmentation techniques included manual delineation of contours (GTV(man)), a 2.5 standardized uptake value (SUV) cutoff (GTV(2.5)), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV(40%) and GTV(50%)), signal-to-background ratio (SBR)-based adaptive thresholding (GTV(SBR)), gradient find (GTV(GF)), and region growing (GTV(RG)). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques. Contours defined using GTV(2.5) failed to provide successful delineation technically in three patients (18% of cases) as SUV(max) segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineation.

  6. Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin

    International Nuclear Information System (INIS)

    Paganelli, G.; Grana, C.; Chinol, M.; Cremonesi, M.; De Cicco, C.; Zoboli, S.; De Braud, F.; Robertson, C.; Zurrida, S.; Veronesi, U.; Casadio, C.; Siccardi, A.G.

    1999-01-01

    While the incidence of brain tumours seems to be increasing, median survival in patients with glioblastoma remains less than 1 year, despite improved diagnostic imaging and neurosurgical techniques, and innovations in treatment. We have developed an avidin-biotin pre-targeting approach for delivering therapeutic radionuclides to gliomas, using anti-tenascin monoclonal antibodies, which seems potentially effective for treating these tumours. We treated 48 eligible patients with histologically confirmed grade III or IV glioma and documented residual disease or recurrence after conventional treatment. Three-step radionuclide therapy was performed by intravenous administration of 35 mg/m 2 of biotinylated anti-tenascin monoclonal antibody (1st step), followed 36 h later by 30 mg of avidin and 50 mg of streptavidin (2nd step), and 18-24 h later by 1-2 mg of yttrium-90-labelled biotin (3rd step). 90 Y doses of 2.22-2.96 GBq/m 2 were administered; maximum tolerated dose (MTD) was determined at 2.96 GBq/m 2 . Tumour mass reduction (>25%-100%), documented by computed tomography or magnetic resonance imaging, occurred in 12/48 patients (25%), with 8/48 having a duration of response of at least 12 months. At present, 12 patients are still in remission, comprising four with a complete response, two with a parital response, two with a minor response and four with stable disease. Median survival from 90 Y treatment is 11 months for grade IV glioblastoma and 19 months for grade III anaplastic gliomas. Avidin-biotin based three-step radionuclide therapy is well tolerated at the dose of 2.2 GBq/m 2 , allowing the injection of 90 Y-biotin without bone marrow transplantation. This new approach interferes with the progression of high-grade glioma and may produce tumour regression in patients no longer responsive to other therapies. (orig.)

  7. Dosimetric advantages of proton therapy over conventional radiotherapy with photons in young patients and adults with low-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Harrabi, S.B.; Herfarth, K. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); Bougatf, N. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); University Hospital Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Department of Medical Physics in Radiation Oncology, Heidelberg (Germany); Mohr, A. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); University Hospital Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); Haberer, T. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Combs, S.E. [Helmholtz Zentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovative Radiotherapy (iRT), Oberschleissheim (Germany); Deutsches Konsortium fuer Translationale Krebsforschung (dktk), Partner Site Munich, Munich (Germany); Debus, J.; Adeberg, S. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany)

    2016-11-15

    Low-grade glioma (LGG) is a very common brain tumor in pediatric patients typically associated with a very good prognosis. This prognosis makes it imperative that the risk of long-term treatment-related side effects be kept at an absolute minimum. Proton therapy (PRT) provides a radiation technique that has the potential to further reduce the genesis of radiogenic impairment. We retrospectively assessed 74 patients with LGG who underwent PRT. Conventional three-dimensional photon and PRT plans were generated after contouring structures of neurogenesis, crucial neuronal structures, and areas susceptible to secondary malignancies. Target volume coverage was evaluated using the homogeneity index (HI) and inhomogeneity coefficient (IC). Results were compared using the Wilcoxon-signed rank test, with p < 0.05 being statistically significant. Target volume coverage was comparable for the photon and proton plans. Overall, we could show an essential reduction in maximal, mean, and integral doses in critical neurologic structures, areas of neurogenesis, and structures of neurocognitive function. The study indicated specifically how contralaterally located structures could be spared with PRT. PRT is a highly conformal radiation technique offering superior dosimetric advantages over conventional radiotherapy by allowing significant dose reduction for organs at risk (OAR) that are essential for neurologic function, neurocognition, and quality of life, thus demonstrating the potential of this technique for minimizing long-term sequelae. (orig.) [German] Niedriggradige Gliome (LGG) zaehlen zu den haeufigsten Hirntumoren im Kindesalter und sind ueblicherweise mit einer sehr guten Prognose vergesellschaftet. Es gilt daher, das Risiko fuer therapieassoziierte Spaetfolgen so gering wie moeglich zu halten. Mit der Protonenbestrahlung steht eine Bestrahlungsmodalitaet zur Verfuegung, mit der das Auftreten radiogener Spaetfolgen im Vergleich zu konventionellen Bestrahlungstechniken

  8. TSPO PET for glioma imaging using the novel ligand {sup 18}F-GE-180. First results in patients with glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Albert, Nathalie L.; Bartenstein, P. [Munich Univ. (Germany). Dept. of Nuclear Medicine; German Cancer Consortium (DKTK), Munich (Germany); Munich Cluster for Systems Neurology (SyNergy), Munich (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); Unterrainer, M.; Lindner, S.; Vettermann, F.; Brunegraf, A.; Vomacka, L.; Brendel, M.; Wenter, V. [Munich Univ. (Germany). Dept. of Nuclear Medicine; Fleischmann, D.F.; Belka, C.; Niyazi, M. [German Cancer Consortium (DKTK), Munich (Germany); Munich Univ. (Germany). Dept. of Radiation Oncology; German Cancer Research Center (DKFZ), Heidelberg (Germany); Wetzel, C.; Rupprecht, R. [Regensburg Univ. (Germany). Dept. of Psychatry and Psychotherapy; Tonn, J.C. [German Cancer Consortium (DKTK), Munich (Germany); Munich Univ. (Germany). Dept. of Neurosurgery; German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2017-12-15

    The 18-kDa mitochondrial translocator protein (TSPO) was reported to be upregulated in gliomas. {sup 18}F-GE-180 is a novel 3rd generation TSPO receptor ligand with improved target-to-background contrast compared to previous tracers. In this pilot study, we compared PET imaging with {sup 18}F-GE-180 and MRI of patients with untreated and recurrent pretreated glioblastoma. Eleven patients with histologically confirmed IDH wildtype gliomas (10 glioblastomas, 1 anaplastic astrocytoma) underwent {sup 18}F-GE-180 PET at initial diagnosis or recurrence. The PET parameters mean background uptake (SUV{sub BG}), maximal tumour-to-background ratio (TBR{sub max}) and PET volume using different thresholds (SUV{sub BG} x 1.6, 1.8 and 2.0) were evaluated in the 60-80 min p.i. summation images. The different PET volumes were compared to the contrast-enhancing tumour volume on MRI. All gliomas were positive on {sup 18}F-GE-180 PET and were depicted with extraordinarily high tumour-to-background contrast (median SUV{sub BG} 0.47 (0.37-0.93), TBR{sub max} 6.61 (3.88-9.07)). {sup 18}F-GE-180 uptake could be found even in areas without contrast enhancement on MRI, leading to significantly larger PET volumes than MRI-based volumes (median 90.5, 74.5, and 63.8 mL vs. 31.0 mL; p = 0.003, 0.004, 0.013). In percentage difference, the PET volumes were on average 179%, 135%, and 90% larger than the respective MRI volumes. The median spatial volumetric correlation (Soerensen-Dice coefficient) of PET volumes and MRI volumes prior to radiotherapy was 0.48, 0.54, and 0.58. {sup 18}F-GE-180 PET provides a remarkably high tumour-to-background contrast in untreated and pretreated glioblastoma and shows tracer uptake even beyond contrast enhancement on MRI. To what extent {sup 18}F-GE-180 uptake reflects the tumour extent of human gliomas and inflammatory cells remains to be evaluated in future prospective studies with guided stereotactic biopsies and correlation of histopathological results. (orig.)

  9. MGMT promoter methylation determined by HRM in comparison to MSP and pyrosequencing for predicting high-grade glioma response.

    Science.gov (United States)

    Switzeny, Olivier J; Christmann, Markus; Renovanz, Mirjam; Giese, Alf; Sommer, Clemens; Kaina, Bernd

    2016-01-01

    The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) causes resistance of cancer cells to alkylating agents and, therefore, is a well-established predictive marker for high-grade gliomas that are routinely treated with alkylating drugs. Since MGMT is highly epigenetically regulated, the MGMT promoter methylation status is taken as an indicator of MGMT silencing, predicting the outcome of glioma therapy. MGMT promoter methylation is usually determined by methylation specific PCR (MSP), which is a labor intensive and error-prone method often used semi-quantitatively. Searching for alternatives, we used closed-tube high resolution melt (HRM) analysis, which is a quantitative method, and compared it with MSP and pyrosequencing regarding its predictive value. We analyzed glioblastoma cell lines with known MGMT activity and formalin-fixed samples from IDH1 wild-type high-grade glioma patients (WHO grade III/IV) treated with radiation and temozolomide by HRM, MSP, and pyrosequencing. The data were compared as to progression-free survival (PFS) and overall survival (OS) of patients exhibiting the methylated and unmethylated MGMT status. A promoter methylation cut-off level relevant for PFS and OS was determined. In a multivariate Cox regression model, methylation of MGMT promoter of high-grade gliomas analyzed by HRM, but not MSP, was found to be an independent predictive marker for OS. Univariate Kaplan-Meier analyses revealed for PFS and OS a significant and better discrimination between methylated and unmethylated tumors when quantitative HRM was used instead of MSP. Compared to MSP and pyrosequencing, the HRM method is simple, cost effective, highly accurate and fast. HRM is at least equivalent to pyrosequencing in quantifying the methylation level. It is superior in predicting PFS and OS of high-grade glioma patients compared to MSP and, therefore, can be recommended being used routinely for determination of the MGMT status of gliomas.

  10. FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading

    International Nuclear Information System (INIS)

    Poepperl, Gabriele; Koch, Walter; Gildehaus, Franz J.; Tatsch, Klaus; Kreth, Friedrich W.; Mehrkens, Jan H.; Tonn, Joerg C.; Herms, Jochen; Kretzschmar, Hans A.; Seelos, Klaus

    2007-01-01

    Treatment and prognosis of gliomas depend on their histological tumour grade. The aim of the study was to evaluate the potential of [ 18 F]fluoroethyltyrosine (FET) PET for non-invasive tumour grading in untreated patients. Dynamic FET PET studies were performed in 54 patients who, based on MRI, were estimated to have low grade (LG; n = 20), intermediate (WHO II-III; n = 4) or high grade (HG; n = 30) tumours. For standard evaluation, tumour SUV max and the ratio to background (SUV max /BG) were calculated (sum image: 20-40 min). For dynamic evaluation, mean SUV values within a 90% isocontour ROI (SUV90) and the SUV90/BG ratios were determined for each time frame to evaluate the course of FET uptake. Results were correlated with histopathological findings from PET-guided stereotactic biopsies. Histology revealed gliomas in all patients. Using the standard method a statistically significant difference (p = 0.001) was found between LG (n = 20; SUV max /BG: 2.16 ± 0.98) and HG (n = 34; SUV max /BG: 3.29 ± 1.06) gliomas (opt. threshold 2.58: SN71%/SP85%/area under ROC curve [AUC]:0.798), however, with a marked overlap between WHO II to IV tumours. Time activity curves showed slight increase in LG, whereas HG tumours presented with an early peak (10-20 min) followed by a decrease. Dynamic evaluation successfully separated LG from HG gliomas with higher diagnostic accuracy (SN94%/SP100%/AUC:0.967). Based on the ratio-based method, a statistically significant difference was found between LG and HG gliomas. Due to the interindividual variability, however, no reliable individual grading was possible. In contrast, dynamic evaluation allowed LG and HG gliomas to be differentiated with high diagnostic power and, thus, should supplement the conventional method. (orig.)

  11. Current status of cerebral glioma surgery in China.

    Science.gov (United States)

    Wu, Jin-song; Zhang, Jie; Zhuang, Dong-xiao; Yao, Cheng-jun; Qiu, Tian-ming; Lu, Jun-feng; Zhu, Feng-ping; Mao, Ying; Zhou, Liang-fu

    2011-09-01

    The treatment of gliomas is highly individualized. Surgery for gliomas is essentially for histological diagnosis, to alleviate mass effect, and most importantly, to favor longer survival expectancy. During the past two decades, many surgical techniques and adjuvants have been applied to glioma surgery in China, which lead to a rapid development in the field of cerebral glioma surgery. This article broadly and critically reviewed the existing studies on cerebral glioma surgery and to portrait the current status of glioma surgery in China. A literature search was conducted covering major innovative surgical techniques and adjuvants for glioma surgery in China. The following databases were searched: the Pubmed (January 1995 to date); China Knowledge Resource Integrated Database (January 1995 to date) and VIP Database for Chinese Technical Periodicals (January 1995 to date). A selection criterion was established to exclude duplicates and irrelevant studies. The outcome measures were extracted from included studies. A total of 3307 articles were initially searched. After excluded by abstracts and full texts, 69 studies conducted in the mainland of China were included and went through further analysis. The philosophy of surgical strategies for cerebral gliomas in China is undergoing tremendous change. Nowadays Chinese neurosurgeons pay more attention to the postoperative neurofunctional status of the patients. The aim of the glioma surgery is not only the more extensive tumor resection but also the maximal safety of intervention. The well balance of longer overall survival and higher quality of life should be judged with respect to each individual patient.

  12. Glioma cells on the run – the migratory transcriptome of 10 human glioma cell lines

    Directory of Open Access Journals (Sweden)

    Holz David

    2008-01-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common primary intracranial tumor and despite recent advances in treatment regimens, prognosis for affected patients remains poor. Active cell migration and invasion of GBM cells ultimately lead to ubiquitous tumor recurrence and patient death. To further understand the genetic mechanisms underlying the ability of glioma cells to migrate, we compared the matched transcriptional profiles of migratory and stationary populations of human glioma cells. Using a monolayer radial migration assay, motile and stationary cell populations from seven human long term glioma cell lines and three primary GBM cultures were isolated and prepared for expression analysis. Results Gene expression signatures of stationary and migratory populations across all cell lines were identified using a pattern recognition approach that integrates a priori knowledge with expression data. Principal component analysis (PCA revealed two discriminating patterns between migrating and stationary glioma cells: i global down-regulation and ii global up-regulation profiles that were used in a proband-based rule function implemented in GABRIEL to find subsets of genes having similar expression patterns. Genes with up-regulation pattern in migrating glioma cells were found to be overexpressed in 75% of human GBM biopsy specimens compared to normal brain. A 22 gene signature capable of classifying glioma cultures based on their migration rate was developed. Fidelity of this discovery algorithm was assessed by validation of the invasion candidate gene, connective tissue growth factor (CTGF. siRNA mediated knockdown yielded reduced in vitro migration and ex vivo invasion; immunohistochemistry on glioma invasion tissue microarray confirmed up-regulation of CTGF in invasive glioma cells. Conclusion Gene expression profiling of migratory glioma cells induced to disperse in vitro affords discovery of genomic signatures; selected

  13. Correlation between {sup 18}F-fluoromisonidazole PET and expression of HIF-1α and VEGF in newly diagnosed and recurrent malignant gliomas

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    Kawai, Nobuyuki; Ogawa, Daisuke; Miyake, Keisuke; Tamiya, Takashi [Kagawa University, Department of Neurological Surgery, Faculty of Medicine, Kagawa (Japan); Lin, Wei [Kagawa University, Department of Neurological Surgery, Faculty of Medicine, Kagawa (Japan); Fourth Military Medical University, Department of Neurosurgery, Xijing Hospital, Xi' an (China); Cao, Wei-Dong [Fourth Military Medical University, Department of Neurosurgery, Xijing Hospital, Xi' an (China); Haba, Reiji [Kagawa University, Department of Diagnostic Pathology, Faculty of Medicine, Kagawa (Japan); Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro [Kagawa University, Department of Radiology, Faculty of Medicine, Kagawa (Japan)

    2014-10-15

    Hypoxia and its consequences at the molecular level promote tumour progression and affect patient prognosis. One of the main early cellular events evoked by hypoxia is induction of hypoxia-inducible factor 1 (HIF-1) and subsequent upregulation of vascular endothelial growth factor (VEGF). In this study we sought to determine whether hypoxia detected by {sup 18}F-fluoromisonidazole (FMISO) PET accurately reflects the expression of HIF-1α and VEGF in the tumour and can be used as a biomarker of antiangiogenic treatment and as a prognostic factor in newly diagnosed and recurrent malignant gliomas. Enrolled in this study were 32 patients with newly diagnosed glioma and 16 with recurrent glioma of grade III or grade IV. All the patients had undergone FMISO PET preoperatively. The maximum tumour-to-blood FMISO activity ratio (T/B{sub max}) was used to evaluate the degree of tumour hypoxia and the hypoxic volume (HV) was calculated using a tumour-to-blood FMISO uptake ratio of ≥1.2. Immunohistochemical expressions of HIF-1α and VEGF were evaluated semiquantitatively using the immunoreactivity score (IRS, scores 0 to 12) and the correlation was examined between IRS of HIF-1α or VEGF and FMISO uptake of the tumour (SUV{sub tumour}) using navigation-based sampling. Survival was estimated using the Kaplan-Meier method in relation to the T/B{sub max} and the HV. The T/B{sub max} and the HV in grade IV gliomas were significantly higher than in grade III gliomas (P < 0.01 and P < 0.01, respectively). Moderate to strong HIF-1α and VEGF expression was observed in the majority of malignant gliomas. The IRS of HIF-1α and VEGF in the tumour were not significantly different between grade III and grade IV gliomas. The IRS of HIF-1α in the tumour did not correlate with the SUV{sub tumour} of FMISO in either newly diagnosed or recurrent glioma. There was a significant but weak correlation between the IRS of VEGF and the SUV{sub tumour} of FMISO in newly diagnosed glioma, but not

  14. Usefulness of {sup 18}F-FDG-PET/CT in Evaluating a Brainstem Glioma in an Adult Patient with Neurofibromatosis Type 1

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    Treglia, Giorgio [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Muoio, Barbara; Del Ciello, Annemilia [Univ. of the Sacred, Rome (Italy); Bertagna, Francesco [Univ. of Brescia, Brescia (Italy)

    2013-09-15

    We describe a case of a brainstem glioma (BSG) occurred in an adult patient with neurofibromatosis type 1 (NF1) and evaluated by Flourine-18-Fluorodeoxyglucose-positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT). A 32-year-old male patient with NF1 underwent brain magnetic resonance imaging (MRI) for the onset of diplopia, facial paresis and cerebellar signs and symptoms. MRI showed a brainstem lesion compatible with BSG. Biopsy was not performed. {sup 18}F-FDG-PET/CT demonstrated intense {sup 18}F-FDG uptake in the brainstem lesion, suggesting an aggressive neoplasm. The patient was referred to radiotherapy but he developed rapid disease progression. In this case, {sup 18}F-FDG-PET/CT provided useful information about this rare NF1-associated tumor. Subsequently, the patient was referred to radiotherapy, but he developed rapid disease progression and died 3 months later. NF-1 is an autosomal dominant disorder characterized by multiple cafe-au-lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, and iris Lisch nodules. NF-1 is also characterized by low-grade tumors of the central and peripheral nervous system. There is also an increased risk of developing malignant tumors such as malignant peripheral nerve sheath tumors or central nervous system high-grade gliomas. NF1-associated BSGs are less common than NF1-associated optic gliomas (OGs) and seem to represent a particular entity which tend, as a whole, to have a more favorable prognosis and a more indolent course than BSGs in patients without NF1; nevertheless, some NF1-associted BSG may rapidly progress. {sup 18}F-FDG-PET/CT has demonstrated to provide useful information to the surveillance of OGs in children with NF1, particularly to identify progressive, symptomatic tumors. To the best of our knowledge, there are no data about the usefulness of {sup 18}F-FDG-PET/CT in adult patients with NF1-associated BSG. In our case, {sup 18}F-FDG-PET/CT has been useful in

  15. Evaluation of a deep learning architecture for MR imaging prediction of ATRX in glioma patients

    Science.gov (United States)

    Korfiatis, Panagiotis; Kline, Timothy L.; Erickson, Bradley J.

    2018-02-01

    Predicting mutation/loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) gene utilizing MR imaging is of high importance since it is a predictor of response and prognosis in brain tumors. In this study, we compare a deep neural network approach based on a residual deep neural network (ResNet) architecture and one based on a classical machine learning approach and evaluate their ability in predicting ATRX mutation status without the need for a distinct tumor segmentation step. We found that the ResNet50 (50 layers) architecture, pre trained on ImageNet data was the best performing model, achieving an accuracy of 0.91 for the test set (classification of a slice as no tumor, ATRX mutated, or mutated) in terms of f1 score in a test set of 35 cases. The SVM classifier achieved 0.63 for differentiating the Flair signal abnormality regions from the test patients based on their mutation status. We report a method that alleviates the need for extensive preprocessing and acts as a proof of concept that deep neural network architectures can be used to predict molecular biomarkers from routine medical images.

  16. Repeating hemorrhage after radiotherapy for glioma. Radiological and histological observations

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    Kawano, Hirokazu [Miyakonojo Medical Association Hospital, Miyazaki (Japan); Wakisaka, Shinichiro; Kubota, Toshihiko; Hosotani, Kazuo

    1998-02-01

    A case of radiation necrosis which was observed six years after radiotherapy for a glioma in the right parietal lobe is reported. This patient developed hemiparesis, and radiological examinations showed similar findings consisted with recurrent glioma. Histological examination disclosed that the lesion is correspond to the radiation necrosis. (author)

  17. O-(2-[18F]fluoroethyl)-L-tyrosine uptake is an independent prognostic determinant in patients with glioma referred for radiation therapy

    International Nuclear Information System (INIS)

    Sweeney, Reinhart; Polat, Bülent; Flentje, Michael; Samnick, Samuel; Reiners, Christoph; Verburg, Frederik A.

    2014-01-01

    To evaluate the prognostic value of O-(2-[ 18 F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organization (WHO) tumor grade II-IV gliomas. We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40% of the SUVmax. Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40% SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality (p=0.005) and progression-free survival (p=0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade (p=0.001) and SUVmax ≥ 2.6 (p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 (p=0.007) and being treated for a recurrence rather than for a primary tumor manifestation (p=0.014) were predictors for progression-free survival, but not TBRmax or TBRmean. In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval. (author)

  18. TH-E-BRF-05: Comparison of Survival-Time Prediction Models After Radiotherapy for High-Grade Glioma Patients Based On Clinical and DVH Features

    International Nuclear Information System (INIS)

    Magome, T; Haga, A; Igaki, H; Sekiya, N; Masutani, Y; Sakumi, A; Mukasa, A; Nakagawa, K

    2014-01-01

    Purpose: Although many outcome prediction models based on dose-volume information have been proposed, it is well known that the prognosis may be affected also by multiple clinical factors. The purpose of this study is to predict the survival time after radiotherapy for high-grade glioma patients based on features including clinical and dose-volume histogram (DVH) information. Methods: A total of 35 patients with high-grade glioma (oligodendroglioma: 2, anaplastic astrocytoma: 3, glioblastoma: 30) were selected in this study. All patients were treated with prescribed dose of 30–80 Gy after surgical resection or biopsy from 2006 to 2013 at The University of Tokyo Hospital. All cases were randomly separated into training dataset (30 cases) and test dataset (5 cases). The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. The candidate features included the 12 clinical features (tumor location, extent of surgical resection, treatment duration of radiotherapy, etc.), and the 192 DVH features (maximum dose, minimum dose, D95, V60, etc.). The effective features for the prediction were selected according to a step-wise method by using 30 training cases. The prediction accuracy was evaluated by a coefficient of determination (R 2 ) between the predicted and actual survival time for the training and test dataset. Results: In the multiple regression analysis, the value of R 2 between the predicted and actual survival time was 0.460 for the training dataset and 0.375 for the test dataset. On the other hand, in the ANN analysis, the value of R 2 was 0.806 for the training dataset and 0.811 for the test dataset. Conclusion: Although a large number of patients would be needed for more accurate and robust prediction, our preliminary Result showed the potential to predict the outcome in the patients with high-grade glioma. This work was partly supported by the JSPS Core

  19. Beyond Alkylating Agents for Gliomas: Quo Vadimus?

    Science.gov (United States)

    Puduvalli, Vinay K; Chaudhary, Rekha; McClugage, Samuel G; Markert, James

    2017-01-01

    Recent advances in therapies have yielded notable success in terms of improved survival in several cancers. However, such treatments have failed to improve outcome in patients with gliomas for whom surgery followed by radiation therapy and chemotherapy with alkylating agents remain the standard of care. Genetic and epigenetic studies have helped identify several alterations specific to gliomas. Attempts to target these altered pathways have been unsuccessful due to various factors, including tumor heterogeneity, adaptive resistance of tumor cells, and limitations of access across the blood-brain barrier. Novel therapies that circumvent such limitations have been the focus of intense study and include approaches such as immunotherapy, targeting of signaling hubs and metabolic pathways, and use of biologic agents. Immunotherapeutic approaches including tumor-targeted vaccines, immune checkpoint blockade, antibody-drug conjugates, and chimeric antigen receptor-expressing cell therapies are in various stages of clinical trials. Similarly, identification of key metabolic pathways or converging hubs of signaling pathways that are tumor specific have yielded novel targets for therapy of gliomas. In addition, the failure of conventional therapies against gliomas has led to a growing interest among patients in the use of alternative therapies, which in turn has necessitated developing evidence-based approaches to the application of such therapies in clinical studies. The development of these novel approaches bears potential for providing breakthroughs in treatment of more meaningful and improved outcomes for patients with gliomas.

  20. Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients

    International Nuclear Information System (INIS)

    Vees, Hansjoerg; Senthamizhchelvan, Srinivasan; Ratib, Osman; Miralbell, Raymond; Weber, Damien C.; Zaidi, Habib

    2009-01-01

    The purpose of the study is to assess the contribution of 18 F-fluoro-ethyl-tyrosine ( 18 F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone. The study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate 18 F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTV MRI ). PET image segmentation techniques included manual delineation of contours (GTV man ), a 2.5 standardized uptake value (SUV) cutoff (GTV 2.5 ), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV 40% and GTV 50% ), signal-to-background ratio (SBR)-based adaptive thresholding (GTV SBR ), gradient find (GTV GF ), and region growing (GTV RG ). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques. Contours defined using GTV 2.5 failed to provide successful delineation technically in three patients (18% of cases) as SUV max MRI (67% of cases). Yet, PET detected frequently tumors that are not visible on MRI and added substantially tumor extension outside the GTV MRI in six patients (33% of cases). The selection of the most appropriate 18 F-FET PET-based segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineation. (orig.)

  1. SEMI–MATURE DENDRITIC CELLS AS A POTENTIAL BASIS FOR THE INDUCTION OF ANTI–TUMOR RESPONSE IN PATIENTS WITH MALIGNANT GLIOMAS

    Directory of Open Access Journals (Sweden)

    O. Yu. Leplina

    2005-01-01

    Full Text Available Abstract. The comparative analysis of phenotypical and functional features of dendritic cells (DCs, generated in presence of GM–CSF and IFNα from blood monocytes of patients with malignant gliomas (MG and healthy donors, was carried out in this research. The potential value of the DC–based immunotherapy in the induction of anti–tumor response in patients with MG was also examined. Our results show that within generated DCs of healthy donors 90 and 52% cells expressed correspondingly HLA–DR and CD86, only 17–18% cells were CD14+monocytes, whereas 38% cells exhibited the phenotype of mature CD83+ dendritic cells. The both monocyte conditioned medium (MCM, 30% v/v and Leukinferon® (250 IU of IFNα were comparably efficient as maturation–induced stimuli. Despite monocyte’s disturbances in malignant gliomas, the analogous population of DCs was efficiently generated in all examined patients with MG. However, the percentage of mature CD83+DCs was significantly decreased compared to that in healthy donors (24 vs 38%, and these data strongly suggest the delay maturation of DCs in MG. Nevertheless the patient’s DCs showed the allostimulatory activity, comparable with healthy donor’s DCs, and 52–62% cells maintained the ability for the receptor–dependent en–docytosis. Moreover, the patient’s DCs effectively presented bacterial and tumor–associated antigens (TAA. Immunotherapy with autologous DCs allowed to induce the TAA–specific immune reactions, both in skin test in vivo and in vitro, in 50% patients with MG. (Med. Immunol., 2005, vol.7, № 4, pp. 365–374

  2. Use of the functional imaging modalities, f MRI r CBV and PET FDG, alters radiation therapy 3-D treatment planning in patients with malignant gliomas

    International Nuclear Information System (INIS)

    Fitzek, M.; Pardo, F.S.; Busierre, M.; Lev, M.; Fischman, A.; Denny, N.; Hanser, B.; Rosen, B.R.; Smith, A.; Aronen, H.

    1995-01-01

    Background: Malignant gliomas present one of the most difficult challenges to definitive radiation therapy, not only with respect to local control, but also with respect to clinical functional status. While tumor target volume definitions for malignant gliomas are often based on CT and conventional MRI, the functional imaging modalities, echo planar r CBV (regional cerebral blood volume mapping) and 18F-fluorodeoxyglucose PET, are more sensitive modalities for the detection of neovascularization, perhaps one of the earliest signs of glial tumor initiation and progression. Methods: In order to address the clinical utility of functional imaging in radiation therapy 3-D treatment planning, we compared tumor target volume definitions and overall dosimetry in patients either undergoing co-registration of conventional Gadolinium-enhanced MRI, or co-registration of functional imaging modalities, prior to radiation therapy 3-D treatment planning. Fourteen patients were planned using 3-D radiation therapy treatment planning, either with or without inclusion of data on functional imaging. All patients received proton beam, as well as megavoltage x-ray radiation therapy, with the ratio of photon:proton optimized to the individual clinical case at hand. Both PET FDG and f MRI scans were obtained postoperatively pre-radiation, during radiation therapy, one month following completion of radiation therapy, and at three month follow-up intervals. Dose volume histograms were constructed in order to assess dose optimization, not only with respect to tumor, but also with respect to normal tissue tolerance (e.g., motor strip, dominant speech area, brainstem, optic nerves). Results: In 5 of 14 cases, functional imaging modalities, as compared with conventional MRI and CT, contributed additional information that was useful in radiation therapy treatment planning. In general, both fMRI rCBV and PET FDG uptake decreased during the course of radiation therapy. In 1 patient, however, fMRI r

  3. RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas.

    Science.gov (United States)

    Bao, Zhao-Shi; Chen, Hui-Min; Yang, Ming-Yu; Zhang, Chuan-Bao; Yu, Kai; Ye, Wan-Lu; Hu, Bo-Qiang; Yan, Wei; Zhang, Wei; Akers, Johnny; Ramakrishnan, Valya; Li, Jie; Carter, Bob; Liu, Yan-Wei; Hu, Hui-Min; Wang, Zheng; Li, Ming-Yang; Yao, Kun; Qiu, Xiao-Guang; Kang, Chun-Sheng; You, Yong-Ping; Fan, Xiao-Long; Song, Wei Sonya; Li, Rui-Qiang; Su, Xiao-Dong; Chen, Clark C; Jiang, Tao

    2014-11-01

    Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs. © 2014 Bao et al.; Published by Cold Spring Harbor Laboratory Press.

  4. Molecular subtypes of glioblastoma are relevant to lower grade glioma.

    Directory of Open Access Journals (Sweden)

    Xiaowei Guan

    Full Text Available Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas.Gene expression array, single nucleotide polymorphism (SNP array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson. Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP was assigned using prediction models by Fine et al.Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs.GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.

  5. Surgical management of thalamic gliomas: case selection, technical considerations, and review of literature.

    Science.gov (United States)

    Sai Kiran, Narayanam Anantha; Thakar, Sumit; Dadlani, Ravi; Mohan, Dilip; Furtado, Sunil Valentine; Ghosal, Nandita; Aryan, Saritha; Hegde, Alangar S

    2013-07-01

    This study aimed to identify (1) the thalamic gliomas suitable for surgical resection and (2) the appropriate surgical approach based on their location and the displacement of the posterior limb of the internal capsule (PLIC). A retrospective study over a 5-year period (from 2006 to 2010) was performed in 41 patients with thalamic gliomas. The mean age of these patients was 20.4 years (range, 2-65 years). Twenty (49 %) tumors were thalamic, 19 (46 %) were thalamopeduncular, and 2 (5 %) were bilateral. The PLIC, based on T2-weighted magnetic resonance axial sections, was displaced anterolaterally in 23 (56 %) cases and laterally in 6 (14 %) cases. It was involved by lesion in eight (20 %) cases and could not be identified in four (10 %) cases. Resection, favored in patients with well-defined, contrast-enhancing lesions, was performed in 34 (83 %) cases, while a biopsy was resorted to in 7 (17 %) cases. A gross total resection or near total resection (>90 %) could be achieved in 26 (63 %) cases. The middle temporal gyrus approach, used when the PLIC was displaced anterolaterally, was the commonly used approach (63.5 %). Common pathologies were pilocytic astrocytoma (58 %) in children and grade III/IV astrocytomas (86 %) in adults. Preoperative motor deficits improved in 64 % of the patients with pilocytic lesions as compared to 0 % in patients with grade III/IV lesions (P value, 0.001). Postoperatively, two patients (5 %) had marginal worsening of motor power, two patients developed visual field defects, and one patient developed a third nerve paresis. Radical resection of thalamic gliomas is a useful treatment modality in a select subset of patients and is the treatment of choice for pilocytic astrocytomas. Tailoring the surgical approach, depending on the relative position of the PLIC, has an important bearing on outcome.

  6. SVM-based glioma grading. Optimization by feature reduction analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zoellner, Frank G.; Schad, Lothar R. [University Medical Center Mannheim, Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Emblem, Kyrre E. [Massachusetts General Hospital, Charlestown, A.A. Martinos Center for Biomedical Imaging, Boston MA (United States). Dept. of Radiology; Harvard Medical School, Boston, MA (United States); Oslo Univ. Hospital (Norway). The Intervention Center

    2012-11-01

    We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CBV) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity = 89%, specificity = 84%) when reducing the feature vector from 101 (100-bins rCBV histogram + age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values ({proportional_to}87%) while reducing the number of features by up to 98%. (orig.)

  7. Intensity of adjuvant chemotherapy regimens and grade III-V toxicities among elderly stage III colon cancer patients.

    Science.gov (United States)

    van Erning, F N; Razenberg, L G E M; Lemmens, V E P P; Creemers, G J; Pruijt, J F M; Maas, H A A M; Janssen-Heijnen, M L G

    2016-07-01

    The aim of this study was to provide insight in the use, intensity and toxicity of therapy with capecitabine and oxaliplatin (CAPOX) and capecitabine monotherapy (CapMono) among elderly stage III colon cancer patients treated in everyday clinical practice. Data from the Netherlands Cancer Registry were used. All stage III colon cancer patients aged ≥70 years diagnosed in the southeastern part between 2005 and 2012 and treated with CAPOX or CapMono were included. Differences in completion of all planned cycles, cumulative dosages and toxicity between both regimens were evaluated. One hundred ninety-three patients received CAPOX and 164 patients received CapMono; 33% (n = 63) of the patients receiving CAPOX completed all planned cycles of both agents, whereas 55% (n = 90) of the patients receiving CapMono completed all planned cycles (P characteristics, CapMono was associated with a lower odds of developing grade III-V toxicity than CAPOX (odds ratio 0.54, 95% confidence interval 0.33-0.89). For patients treated with CAPOX, the most common toxicities were gastrointestinal (29%), haematological (14%), neurological (11%) and other toxicity (13%). For patients treated with CapMono, dermatological (17%), gastrointestinal (13%) and other toxicity (11%) were the most common. CAPOX is associated with significantly more grade III-V toxicities than CapMono, which had a pronounced impact on the cumulative dosage received and completion of all planned cycles. In this light, CapMono seems preferable over CAPOX. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Immune Response Generated With the Administration of Autologous Dendritic Cells Pulsed With an Allogenic Tumoral Cell-Lines Lysate in Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

    Directory of Open Access Journals (Sweden)

    Daniel Benitez-Ribas

    2018-04-01

    Full Text Available Background and objectiveDiffuse intrinsic pontine glioma (DIPG is a lethal brainstem tumor in children. Dendritic cells (DCs have T-cell stimulatory capacity and, therefore, potential antitumor activity for disease control. DCs vaccines have been shown to reactivate tumor-specific T cells in both clinical and preclinical settings. We designed a phase Ib immunotherapy (IT clinical trial with the use of autologous dendritic cells (ADCs pulsed with an allogeneic tumors cell-lines lysate in patients with newly diagnosed DIPG after irradiation (radiation therapy.MethodsNine patients with newly diagnosed DIPG met enrollment criteria. Autologous dendritic cell vaccines (ADCV were prepared from monocytes obtained by leukapheresis. Five ADCV doses were administered intradermally during induction phase. In the absence of tumor progression, patients received three boosts of tumor lysate every 3 months during the maintenance phase.ResultsVaccine fabrication was feasible in all patients included in the study. Non-specific KLH (9/9 patients and specific (8/9 patients antitumor response was identified by immunologic studies in peripheral blood mononuclear cells (PBMC. Immunological responses were also confirmed in the T lymphocytes isolated from the cerebrospinal fluid (CSF of two patients. Vaccine administration resulted safe in all patients treated with this schema.ConclusionThese preliminary results demonstrate that ADCV preparation is feasible, safe, and generate a DIPG-specific immune response detected in PBMC and CSF. This strategy shows a promising backbone for future schemas of combination IT.

  9. Optic pathway glioma as part of a constitutional mismatch-repair deficiency syndrome in a patient meeting the criteria for neurofibromatosis type 1.

    Science.gov (United States)

    Yeung, Jacky T; Pollack, Ian F; Shah, Sapana; Jaffe, Ronald; Nikiforova, Marina; Jakacki, Regina I

    2013-01-01

    Patients with constitutional mismatch repair-deficiency (CMMR-D) caused by the biallelic deletions of mismatch repair (MMR) genes have a high likelihood of developing malignancies of the bone marrow, bowel, and brain. Affected individuals often have phenotypic features of neurofibromatosis type 1 (NF-1), including café-au-lait spots. Optic pathway gliomas (OPGs), a common manifestation of NF-1, have not been reported. We report the case of a 3-year-old male with an extensive OPG who met the diagnostic criteria for NF-1. He was subsequently found to have multiple colonic polyps and bi-allelic loss of PMS2. Testing for NF-1 was negative. Copyright © 2012 Wiley Periodicals, Inc.

  10. Automated Grading of Gliomas using Deep Learning in Digital Pathology Images: A modular approach with ensemble of convolutional neural networks.

    Science.gov (United States)

    Ertosun, Mehmet Günhan; Rubin, Daniel L

    2015-01-01

    Brain glioma is the most common primary malignant brain tumors in adults with different pathologic subtypes: Lower Grade Glioma (LGG) Grade II, Lower Grade Glioma (LGG) Grade III, and Glioblastoma Multiforme (GBM) Grade IV. The survival and treatment options are highly dependent of this glioma grade. We propose a deep learning-based, modular classification pipeline for automated grading of gliomas using digital pathology images. Whole tissue digitized images of pathology slides obtained from The Cancer Genome Atlas (TCGA) were used to train our deep learning modules. Our modular pipeline provides diagnostic quality statistics, such as precision, sensitivity and specificity, of the individual deep learning modules, and (1) facilitates training given the limited data in this domain, (2) enables exploration of different deep learning structures for each module, (3) leads to developing less complex modules that are simpler to analyze, and (4) provides flexibility, permitting use of single modules within the framework or use of other modeling or machine learning applications, such as probabilistic graphical models or support vector machines. Our modular approach helps us meet the requirements of minimum accuracy levels that are demanded by the context of different decision points within a multi-class classification scheme. Convolutional Neural Networks are trained for each module for each sub-task with more than 90% classification accuracies on validation data set, and achieved classification accuracy of 96% for the task of GBM vs LGG classification, 71% for further identifying the grade of LGG into Grade II or Grade III on independent data set coming from new patients from the multi-institutional repository.

  11. Early experience with formalin-fixed paraffin-embedded (FFPE) based commercial clinical genomic profiling of gliomas-robust and informative with caveats.

    Science.gov (United States)

    Movassaghi, Masoud; Shabihkhani, Maryam; Hojat, Seyed A; Williams, Ryan R; Chung, Lawrance K; Im, Kyuseok; Lucey, Gregory M; Wei, Bowen; Mareninov, Sergey; Wang, Michael W; Ng, Denise W; Tashjian, Randy S; Magaki, Shino; Perez-Rosendahl, Mari; Yang, Isaac; Khanlou, Negar; Vinters, Harry V; Liau, Linda M; Nghiemphu, Phioanh L; Lai, Albert; Cloughesy, Timothy F; Yong, William H

    2017-08-01

    Commercial targeted genomic profiling with next generation sequencing using formalin-fixed paraffin embedded (FFPE) tissue has recently entered into clinical use for diagnosis and for the guiding of therapy. However, there is limited independent data regarding the accuracy or robustness of commercial genomic profiling in gliomas. As part of patient care, FFPE samples of gliomas from 71 patients were submitted for targeted genomic profiling to one commonly used commercial vendor, Foundation Medicine. Genomic alterations were determined for the following grades or groups of gliomas; Grade I/II, Grade III, primary glioblastomas (GBMs), recurrent primary GBMs, and secondary GBMs. In addition, FFPE samples from the same patients were independently assessed with conventional methods such as immunohistochemistry (IHC), Quantitative real-time PCR (qRT-PCR), or Fluorescence in situ hybridization (FISH) for three genetic alterations: IDH1 mutations, EGFR amplification, and EGFRvIII expression. A total of 100 altered genes were detected by the aforementioned targeted genomic profiling assay. The number of different genomic alterations was significantly different between the five groups of gliomas and consistent with the literature. CDKN2A/B, TP53, and TERT were the most common genomic alterations seen in primary GBMs, whereas IDH1, TP53, and PIK3CA were the most common in secondary GBMs. Targeted genomic profiling demonstrated 92.3%-100% concordance with conventional methods. The targeted genomic profiling report provided an average of 5.5 drugs, and listed an average of 8.4 clinical trials for the 71 glioma patients studied but only a third of the trials were appropriate for glioma patients. In this limited comparison study, this commercial next generation sequencing based-targeted genomic profiling showed a high concordance rate with conventional methods for the 3 genetic alterations and identified mutations expected for the type of glioma. While it may not be feasible to

  12. Simultaneous occurrence of a supra- and an infratentorial glioma in a patient with Ollier's disease : more evidence for non-mesodermal tumor predisposition in multiple enchondromatosis

    NARCIS (Netherlands)

    Heeg, M; Klein, JP; Krikke, AP

    1998-01-01

    A case is presented in which two neuro-ectodermal tumors, an infra- and a supratentorial glioma, developed in a young man with multiple enchondromatosis of Ollier's disease. This is the third such case of multifocal low-grade glioma in Ollier's disease, suggesting a predisposition for non-mesodermal

  13. 18F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas

    International Nuclear Information System (INIS)

    Hirata, Kenji; Shiga, Tohru; Tamaki, Nagara; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Yamaguchi, Shigeru; Houkin, Kiyohiro; Hattori, Naoya; Magota, Keiichi; Tanaka, Shinya; Kuge, Yuji

    2012-01-01

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that 18 F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and 18 F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p ≤ 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 ± 0.60, range 1.71-3.81) than in non-GBM patients (1.22 ± 0.06, range 1.09-1.29, p ≤ 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also higher in GBM

  14. {sup 18}F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Kenji; Shiga, Tohru; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki; Yamaguchi, Shigeru; Houkin, Kiyohiro [Graduate School of Medicine, Hokkaido University, Department of Neurosurgery, Sapporo (Japan); Hattori, Naoya [Graduate School of Medicine, Hokkaido University, Department of Molecular Imaging, Sapporo (Japan); Magota, Keiichi [Hokkaido University Hospital, Department of Radiology, Sapporo (Japan); Tanaka, Shinya [Graduate School of Medicine, Hokkaido University, Department of Cancer Pathology, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan)

    2012-05-15

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that {sup 18}F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and {sup 18}F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p {<=} 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 {+-} 0.60, range 1.71-3.81) than in non-GBM patients (1.22 {+-} 0.06, range 1.09-1.29, p {<=} 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also

  15. [Multidisciplinar approach to the management of gliomas].

    Science.gov (United States)

    Moura, Bianca; Migliorini, Denis; Bourhis, Jean; Daniel, Roy; Levivier, Marc; Hottinger, Andreas F

    2016-04-27

    Gliomas represent two thirds of all primary brain tumors. Their prognosis depends directly upon their level of differentiation. On MRI, tumoral aggressivity is highlighted by contrast uptake and the infiltrative nature of the lesion. Clinical suspicion must however be confirmed by histology and molecular markers become essential to refine the diagnosis and tailor the treatment. Isocytrate dehydrogenase (IDH) mutations, codeletion of 1p and 19q and the presence of methylation of the MGMT promoter identify a subgroup of gliomas with better prognosis and may help predict response to treatment. Management of patients with primary brain tumors should always be defined in multidisciplinar tumor boards involving neurosurgeons, oncologists, radiation oncologists, neuropathologists and neuroradiologists.

  16. [Guidelines for the radiotherapy of gliomas].

    Science.gov (United States)

    Feuvret, L; Antoni, D; Biau, J; Truc, G; Noël, G; Mazeron, J-J

    2016-09-01

    Gliomas are the most frequent primary brain tumours. Treating these tumours is difficult because of the proximity of organs at risk, infiltrating nature, and radioresistance. Clinical prognostic factors such as age, Karnofsky performance status, tumour location, and treatments such as surgery, radiation therapy, and chemotherapy have long been recognized in the management of patients with gliomas. Molecular biomarkers are increasingly evolving as additional factors that facilitate diagnosis and therapeutic decision-making. These practice guidelines aim at helping in choosing the best treatment, in particular radiation therapy. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  17. Contemporary management of high-grade gliomas.

    Science.gov (United States)

    Sim, Hao-Wen; Morgan, Erin R; Mason, Warren P

    2018-01-01

    High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases, treatment options remain limited and prognosis is poor. Recently, there have been important advances in our understanding of the molecular basis of glioma, leading to refinements in our diagnostic and management approach. There is new evidence to guide the treatment of elderly patients. A multitude of new agents have been investigated, including targeted therapies, immunotherapeutics and tumor-treating fields. This review summarizes the key findings from this research, and presents a perspective on future opportunities to advance the field.

  18. TCGA_LowerGradeGliomas

    Science.gov (United States)

    TCGA researchers analyzed nearly 300 cases of diffuse low- and intermediate-grade gliomas, which together comprise lower-grade gliomas. LGGs occur mainly in adults and include astrocytomas, oligodendrogliomas and oligoastrocytomas.

  19. The value of intraoperative sonography in low grade glioma surgery.

    Science.gov (United States)

    Petridis, Athanasios K; Anokhin, Maxim; Vavruska, Jan; Mahvash, Mehran; Scholz, Martin

    2015-04-01

    There is a number of different methods to localize a glioma intraoperatively. Neuronavigation, intraoperative MRI, 5-aminolevulinic acid, as well as intraoperative sonography. Every method has its advantages and disadvantages. Low grade gliomas do not show a specific signal with 5-aminolevulinic acid and are difficult to distinguish macroscopically from normal tissue. In the present study we stress out the importance of intraoperative diagnostic ultrasound for localization of low grade gliomas. We retrospectively evaluated the charts and MRIs of 34 patients with low grade gliomas operated in our department from 2011 until December 2014. The efficacy of ultrasound as an intraoperative navigational tool was assessed. In 15 patients ultrasound was used and in 19 not. Only histologically proven low grades gliomas (astrocytomas grade II) were evaluated. In none of the patients where ultrasound (combined with neuronavigation) was used (N=15) to find the tumors, the target was missed, whereas the exclusive use of neuronavigation missed the target in 5 of 19 cases of small subcortical low grade gliomas. Intraoperative ultrasound is an excellent tool in localizing low grade gliomas intraoperatively. It is an inexpensive, real time neuronavigational tool, which overcomes brain shift. Even when identifying the tumors with ultrasound is very reliable, the extend of resection and the decision to remove any residual tumor with the help of ultrasound is at the moment unreliable. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. T-lymphokine-activated killer cell-originated protein kinase (TOPK) as a prognostic factor and a potential therapeutic target in glioma

    Science.gov (United States)

    Duan, Qiuhong; Yuan, Ping; Xue, Peipei; Lu, Hui; Yan, Meng; Guo, Dongsheng; Xu, Sanpeng; Zhang, Xiaohui; Lin, Xuan; Wang, Yong; Dogan, Soner; Zhang, Jianmin; Zhu, Feng; Ke, Changshu; Liu, Lin

    2018-01-01

    TOPK is overexpressed in various types of cancer and associated with poor outcomes in different types of cancer. In this study, we first found that the expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was significantly higher in Grade III or Grade IV than that in Grade II in glioma (P = 0.007 and P < 0.001, respectively). Expression of TOPK was positively correlated with Ki67 (P < 0.001). Knockdown of TOPK significantly inhibited cell growth, colony formation and increased sensitivities to temozolomide (TMZ) in U-87 MG or U-251 cells, while TOPK overexpression promoted cell growth and colony formation in Hs 683 or A-172 cells. Glioma patients expressing high levels of TOPK have poor survival compared with those expressing low levels of TOPK in high-grade or low-grade gliomas (hazard ratio = 0.2995; 95% CI, 0.1262 to 0.7108; P = 0.0063 and hazard ratio = 0.1509; 95% CI, 0.05928 to 0.3842; P < 0.0001, respectively). The level of TOPK was low in TMZ-sensitive patients compared with TMZ-resistant patients (P = 0.0056). In TMZ-resistant population, patients expressing high TOPK have two months’ shorter survival time than those expressing low TOPK. Our findings demonstrated that TOPK might represent as a promising prognostic and predictive factor and potential therapeutic target for glioma. PMID:29487691

  1. Protein tyrosine phosphatases in glioma biology.

    NARCIS (Netherlands)

    Navis, A.C.; Eijnden, M. van den; Schepens, J.T.G.; Hooft van Huijsduijnen, R.; Wesseling, P.; Hendriks, W.J.A.J.

    2010-01-01

    Gliomas are a diverse group of brain tumors of glial origin. Most are characterized by diffuse infiltrative growth in the surrounding brain. In combination with their refractive nature to chemotherapy this makes it almost impossible to cure patients using combinations of conventional therapeutic

  2. Radiosurgery in gliomas (middle-line tumors)

    International Nuclear Information System (INIS)

    Betti, O.O.; Rosler, R.

    1989-01-01

    The clinical experience is presented obtained from treatment with high-energy linac radiosurgery of 22 patients with stereotactically biopsed gliomas located in middle-line, from thalamus to brain stem and from infundibulum to pineo-tectal regions, during the period 1982-1987. (H.W.). 10 refs

  3. A Novel Candidate Molecule in Pathological Grading Of Gliomas: ELABELA.

    Science.gov (United States)

    Artas, Gokhan; Ozturk, Sait; Kuloglu, Tuncay; Dagli, Adile Ferda; Gonen, Murat; Artas, Hakan; Aydin, Suleyman; Erol, Fatih Serhat

    2018-04-06

    This study aimed to investigate the possible role of ELABELA (ELA) in the histopathological grading of gliomas. We retrospectively assessed pathological specimens of patients who underwent surgery for intracranial space-occupying lesions. Only primary glioma specimens were included in this study. We enrolled 11 patients histologically diagnosed with low-grade glioma and 22 patients with high-grade glioma. The ELA antibody was applied to 4-6-µm-thick sections obtained from paraffin blocks. Histoscores were calculated using the distribution and intensity of staining immunoreactivity. An independent sample t-test was used for two-point inter-group assessments, whereas one-way analysis of variance was used for the other assessments. P 0.05 was considered statistically significant. The histoscores of the control brain, low-grade glioma, and high-grade glioma tissues were found to be 0.08, 0.37, and 0.92, respectively. The difference in ELA immunoreactivity between the control brain tissue and glioma tissue was statistically significant (p 0.05). In addition, a statistically significant increase was observed in ELA immunoreactivity in high-grade glioma tissues compared with that in low-grade glioma tissues (p 0.05). ELA has an angiogenetic role in the progression of glial tumors. ELA, which is an endogenous ligand of the apelin receptor, activates the apelinergic system and causes the progression of glial tumors. Further studies with a large number of patients are necessary to investigate the angiogenetic role of ELA in glial tumors.

  4. Strategies to finish orthodontic treatment with a Class III molar relationship: three patient reports.

    Science.gov (United States)

    Farret, Milton M B; Farret, Marcel M; Farret, Alessandro M

    2009-01-01

    The purpose of this article is to review treatment concepts for patients with congenitally missing teeth in the mandible, for patients in whom teeth in only the mandibular arch were extracted, or for patients with Class III camouflage treatment. The therapy result in these situations is a Class III molar relationship. With this type of intercuspation, esthetic and functional aspects must be observed. © 2009 BY QUINTESSENCE PUBLISHING CO, INC.

  5. Non-Gaussian diffusion MR imaging of glioma: comparisons of multiple diffusion parameters and correlation with histologic grade and MIB-1 (Ki-67 labeling) index

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Ren; Haopeng, Pang; Xiaoyuan, Feng; Jiawen, Zhang; Zhenwei, Yao [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Jinsong, Wu; Chengjun, Yao; Tianming, Qiu [Fudan University, Department of Neurosurgery, Huashan Hospital, Shanghai (China); Ji, Xiong [Fudan University, Department of Neuropathology, Huashan Hospital, Shanghai (China); Mao, Sheng; Yueyue, Ding [Department of Imaging, Suzhou Children' s Hospital, Suzhou, Jiangsu (China); Yong, Zhang [MR Research, GE Healthcare, Shanghai (China); Jianfeng, Luo [Fudan University, Department of Biostatistics, Public Health School, Shanghai (China)

    2016-02-15

    This study was conducted to compare the association of Gaussian and non-Gaussian magnetic resonance imaging (MRI)-derived parameters with histologic grade and MIB-1 (Ki-67 labeling) index (MI) in brain glioma. Sixty-five patients with pathologically confirmed glioma, who underwent diffusion-weighted MRI with 2 b values (0, 1000 s/mm{sup 2}) and 22 b values (≤5000 s/mm{sup 2}), respectively, were divided into three groups of grade II (n = 35), grade III (n = 8), and grade IV (n = 22). Comparisons by two groups were made for apparent diffusion coefficient (ADC), slow diffusion coefficient (Dslow), distributed diffusion coefficient (DDC), and heterogeneity index α. Analyses of receiver operating characteristic (ROC) curve were performed to maximize the area under the curve (AUC) for differentiating grade III + IV (high-grade glioma, HGG) from grade II (low-grade glioma, LGG) and grade IV (glioblastoma multiforme, GBM) from grade II + III (other grade glioma, OGG). Correlations with MI were analyzed for the MRI parameters. On tumor regions, the values of ADC, Dslow, DDC, and α were significantly higher in grade II [(1.37 ± 0.29, 0.70 ± 0.11, 1.39 ± 0.34) (x 10{sup -3} mm{sup 2}/s) and 0.88 ± 0.05, respectively] than in grade III [(0.99 ± 0.13, 0.55 ± 0.07, 1.04 ± 0.20) (x 10{sup -3} mm{sup 2}/s) and 0.80 ± 0.03, respectively] and grade IV [(1.03 ± 0.14, 0.50 ± 0.05, 1.02 ± 0.16) (x 10{sup -3} mm{sup 2}/s) and 0.76 ± 0.04, respectively] (all P < 0.001). The parameter α showed the highest AUCs of 0.950 and 0.922 in discriminating HGG from LGG and GBM from OGG, respectively. Significant correlations with histologic grade and MI were observed for the MRI parameters. The non-Gaussian MRI-derived parameters α and Dslow are superior to ADC in glioma grading, which are comparable with ADC as reliable biomarkers in noninvasively predicting the proliferation level of glioma malignancy. (orig.)

  6. Non-Gaussian diffusion MR imaging of glioma: comparisons of multiple diffusion parameters and correlation with histologic grade and MIB-1 (Ki-67 labeling) index

    International Nuclear Information System (INIS)

    Yan, Ren; Haopeng, Pang; Xiaoyuan, Feng; Jiawen, Zhang; Zhenwei, Yao; Jinsong, Wu; Chengjun, Yao; Tianming, Qiu; Ji, Xiong; Mao, Sheng; Yueyue, Ding; Yong, Zhang; Jianfeng, Luo

    2016-01-01

    This study was conducted to compare the association of Gaussian and non-Gaussian magnetic resonance imaging (MRI)-derived parameters with histologic grade and MIB-1 (Ki-67 labeling) index (MI) in brain glioma. Sixty-five patients with pathologically confirmed glioma, who underwent diffusion-weighted MRI with 2 b values (0, 1000 s/mm 2 ) and 22 b values (≤5000 s/mm 2 ), respectively, were divided into three groups of grade II (n = 35), grade III (n = 8), and grade IV (n = 22). Comparisons by two groups were made for apparent diffusion coefficient (ADC), slow diffusion coefficient (Dslow), distributed diffusion coefficient (DDC), and heterogeneity index α. Analyses of receiver operating characteristic (ROC) curve were performed to maximize the area under the curve (AUC) for differentiating grade III + IV (high-grade glioma, HGG) from grade II (low-grade glioma, LGG) and grade IV (glioblastoma multiforme, GBM) from grade II + III (other grade glioma, OGG). Correlations with MI were analyzed for the MRI parameters. On tumor regions, the values of ADC, Dslow, DDC, and α were significantly higher in grade II [(1.37 ± 0.29, 0.70 ± 0.11, 1.39 ± 0.34) (x 10 -3 mm 2 /s) and 0.88 ± 0.05, respectively] than in grade III [(0.99 ± 0.13, 0.55 ± 0.07, 1.04 ± 0.20) (x 10 -3 mm 2 /s) and 0.80 ± 0.03, respectively] and grade IV [(1.03 ± 0.14, 0.50 ± 0.05, 1.02 ± 0.16) (x 10 -3 mm 2 /s) and 0.76 ± 0.04, respectively] (all P < 0.001). The parameter α showed the highest AUCs of 0.950 and 0.922 in discriminating HGG from LGG and GBM from OGG, respectively. Significant correlations with histologic grade and MI were observed for the MRI parameters. The non-Gaussian MRI-derived parameters α and Dslow are superior to ADC in glioma grading, which are comparable with ADC as reliable biomarkers in noninvasively predicting the proliferation level of glioma malignancy. (orig.)

  7. Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide, and accelerated radiation therapy in patients with high-grade glioma

    International Nuclear Information System (INIS)

    Rajkumar, S. Vincent; Buckner, Jan C.; Schomberg, Paula J.; Reid, Joel M.; Bagniewski, Pamela J.; Ames, Matthew M.; Cascino, Terrence L.; Marks, Randolph S.

    1998-01-01

    Purpose: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high-grade glioma. Pharmacokinetic studies of oral etoposide were also done. Methods and Materials: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily x 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m 2 days 1-3, cisplatin 30 mg/m 2 days 1-3 and 29-31, and etoposide 50 mg orally days 1-14 and 29-42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m 2 every 8 weeks x 4 cycles was given after radiation therapy. Results: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3-4 leukopenia (38%) and thrombocytopenia (31%) were dose-limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m 2 days 1-3, cisplatin 20 mg/m 2 days 1-3 and 29-31, and oral etoposide 50 mg days 1-21 and 29-49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m 2 every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 μg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean ± SD 2 hr and 6 hr plasma concentrations were 0.92 ± 0.43 μg/ml and 0.36 ± 0.12 μg/ml, respectively. Estimated duration of exposure to >0.1 μg/ml etoposide was 10-17 hr. Conclusions: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high-grade gliomas is feasible and merits further investigation. Sustained

  8. Glioma epidemiology in the central Tunisian population: 1993-2012.

    Science.gov (United States)

    Trabelsi, Saoussen; Brahim, Dorra H'mida-Ben; Ladib, Mohamed; Mama, Nadia; Harrabi, Imed; Tlili, Kalthoum; Yacoubi, Mohamed Tahar; Krifa, Hedi; Hmissa, Sihem; Saad, Ali; Mokni, Moncef

    2014-01-01

    Glioma is a heterogeneous central nervous system (CNS) tumor group that encompasses different histological subtypes with high variability in prognosis. The lesions account for almost 80% of primary malignant brain tumors. The aim of this study is to extend our understanding of the glioma epidemiology in the central Tunisian region. We analyzed 393 gliomas recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence rates (CR) and world age-standardized rates (ASR) were estimated using annual population data size and age structure. Statistic correlations were established using Chi-square and Kaplan-Meier test. Tunisian glioma patients were identified with a mean age at diagnosis of 48 years and 1.5 sex ratio (male/female). During the 19 years period of study the highest incidence value was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence results underline increasing high grade glioma occurring in the adulthood in the last period (2007-2012). Median survival was 27 months, with 1-, 2- and 5-year survival rates of 42%, 30% and 26%, respectively. Survival was greater in patients with younger age, lower tumor grade, infratentrial tumor location and undergoing a palliative treatment. This central Tunisia gliomas registry study provides important information that could improve glioma management and healthcare practice.

  9. Generation and validation of a prognostic score to predict outcome after re-irradiation of recurrent glioma

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E.; Welzel, Thomas; Debus, Juergen [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)], E-mail: Stephanie.combs@med.uni-heidelberg.de; Edler, Lutz; Rausch, Renate [German Cancer Research Center (dkfz), Dept. of Biostatistics, Heidelberg (Germany); Wick, Wolfgang [Univ. Hospital of Heidelberg, Dept. of Neurooncology, Heidelberg (Germany)

    2013-01-15

    Re-irradiation using high-precision radiation techniques has been established within the clinical routine for patients with recurrent gliomas. In the present work, we developed a practical prognostic score to predict survival outcome after re-irradiation. Patients and methods. Fractionated stereotactic radiotherapy (FSRT) was applied in 233 patients. Primary histology included glioblastoma (n = 89; 38%), WHO Grade III gliomas (n = 52; 22%) and low-grade glioma (n = 92; 40%). FSRT was applied with a median dose of 36 Gy in 2 Gy single fractions. We evaluated survival after re-irradiation as well as progression-free survival after re-irradiation; prognostic factors analyzed included age, tumor volume at re-irradiation, histology, time between initial radiotherapy and re-irradiation, age and Karnofsky Performance Score. Results. Median survival after FSRT was 8 months for glioblastoma, 20 months for anaplastic gliomas, and 24 months for recurrent low-grade patients. The strongest prognostic factors significantly impacting survival after re-irradiation were histology (p <0.0001) and age (<50 vs. ={>=}50, p < 0.0001) at diagnosis and the time between initial radiotherapy and re-irradiation {<=}12 vs. >12 months (p < 0.0001). We generated a four-class prognostic score to distinguish patients with excellent (0 points), good (1 point), moderate (2 points) and poor (3-4 points) survival after re-irradiation. The difference in outcome was highly significant (p < 0.0001). Conclusion. We generated a practical prognostic score index based on three clinically relevant factors to predict the benefit of patients from re-irradiation. This score index can be helpful in patient counseling, and for the design of further clinical trials. However, individual treatment decisions may include other patient-related factors not directly influencing outcome.

  10. Generation and validation of a prognostic score to predict outcome after re-irradiation of recurrent glioma

    International Nuclear Information System (INIS)

    Combs, Stephanie E.; Welzel, Thomas; Debus, Juergen; Edler, Lutz; Rausch, Renate; Wick, Wolfgang

    2013-01-01

    Re-irradiation using high-precision radiation techniques has been established within the clinical routine for patients with recurrent gliomas. In the present work, we developed a practical prognostic score to predict survival outcome after re-irradiation. Patients and methods. Fractionated stereotactic radiotherapy (FSRT) was applied in 233 patients. Primary histology included glioblastoma (n = 89; 38%), WHO Grade III gliomas (n = 52; 22%) and low-grade glioma (n = 92; 40%). FSRT was applied with a median dose of 36 Gy in 2 Gy single fractions. We evaluated survival after re-irradiation as well as progression-free survival after re-irradiation; prognostic factors analyzed included age, tumor volume at re-irradiation, histology, time between initial radiotherapy and re-irradiation, age and Karnofsky Performance Score. Results. Median survival after FSRT was 8 months for glioblastoma, 20 months for anaplastic gliomas, and 24 months for recurrent low-grade patients. The strongest prognostic factors significantly impacting survival after re-irradiation were histology (p 12 months (p < 0.0001). We generated a four-class prognostic score to distinguish patients with excellent (0 points), good (1 point), moderate (2 points) and poor (3-4 points) survival after re-irradiation. The difference in outcome was highly significant (p < 0.0001). Conclusion. We generated a practical prognostic score index based on three clinically relevant factors to predict the benefit of patients from re-irradiation. This score index can be helpful in patient counseling, and for the design of further clinical trials. However, individual treatment decisions may include other patient-related factors not directly influencing outcome.

  11. The value of level III clearance in patients with axillary and sentinel node positive breast cancer.

    LENUS (Irish Health Repository)

    Dillon, Mary F

    2012-02-01

    BACKGROUND: The value of level III axillary clearance is contentious, with great variance worldwide in the extent and levels of clearance performed. OBJECTIVE: To determine rates of level III positivity in patients undergoing level I-III axillary clearance, and identify which patients are at highest risk of involved level III nodes. METHODS: From a database of 2850 patients derived from symptomatic and population-based screening service, 1179 patients who underwent level I-III clearance between the years 1999-2007 were identified. The pathology, surgical details, and prior sentinel nodes biopsies of patients were recorded. RESULTS: Eleven hundred seventy nine patients had level I-III axillary clearance. Of the patients, 63% (n = 747) were node positive. Of patients with node positive disease, 23% (n = 168) were level II positive and 19% (n = 141) were level III positive. Two hundred fifty patients had positive sentinel node biopsies prior to axillary clearance. Of these, 12% (n = 30) and 9% (n = 22) were level II and level III positive, respectively. On multivariate analysis, factors predictive of level III involvement in patients with node positive disease were tumor size (P < 0.001, OR = 1.36; 95% CI: 1.2-1.5), invasive lobular disease (P < 0.001, OR = 3.6; 95% CI: 1.9-6.95), extranodal extension (P < 0.001, OR = 0.27; 95% CI: 0.18-0.4), and lymphovascular invasion (P = 0.04, OR = 0.58; 95% CI: 0.35-1). Lobular invasive disease (P = 0.049, OR = 4.1; 95% CI: 1-16.8), extranodal spread (P = 0.003, OR = 0.18; 95% CI: 0.06-0.57), and having more than one positive sentinel node (P = 0.009, OR = 4.9; 95% CI: 1.5-16.1) were predictive of level III involvement in patients with sentinel node positive disease. CONCLUSION: Level III clearance has a selective but definite role to play in patients who have node positive breast carcinoma. Pathological characteristics of the primary tumor are of particular use in identifying those who are at various risk of level III nodal

  12. Do Class III patients have a different growth spurt than the general population?

    Science.gov (United States)

    Lee, Yun-Sik; Lee, Shin-Jae; An, Hongseok; Donatelli, Richard E; Kim, Soo-Hwan

    2012-11-01

    Understanding the timing and length of the growth spurt of Class III prognathic patients is fundamental to the strategy of interceptive orthopedic orthodontics as well as to the timing of orthognathic surgery. Consequently, this study was undertaken to determine whether there are any significant differences in the stature growth pattern of Class III subjects compared with non-Class III subjects and the general population. Twelve-year longitudinal stature growth data were collected for 402 randomly selected adolescents in the general population, 55 Class III mandibular prognathic patients, and 37 non-Class III patients. The growth data were analyzed by using the traditional linear interpolation method and nonlinear growth functions. The 6 stature growth parameters were measured: age at takeoff, stature at takeoff, velocity at takeoff, age at peak height velocity, stature at peak height velocity, and velocity at peak height velocity. Comparisons in the stature growth parameters and 15 cephalometric variables among the general population, Class III subjects, and non-Class III subjects were made with multivariate analysis. Patients with Class III prognathism did not have different growth parameters compared with Class II subjects or the general population. This study does not allow meaningful conclusions with regard to the relationship of mandibular size and stature growth pattern. The application of nonlinear growth curves vs the traditional linear interpolation method was also discussed. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  13. Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient.

    Science.gov (United States)

    Garcia, P A; Pancotto, T; Rossmeisl, J H; Henao-Guerrero, N; Gustafson, N R; Daniel, G B; Robertson, J L; Ellis, T L; Davalos, R V

    2011-02-01

    Non-thermal irreversible electroporation (N-TIRE) has shown promise as an ablative therapy for a variety of soft-tissue neoplasms. Here we describe the therapeutic planning aspects and first clinical application of N-TIRE for the treatment of an inoperable, spontaneous malignant intracranial glioma in a canine patient. The N-TIRE ablation was performed safely, effectively reduced the tumor volume and associated intracranial hypertension, and provided sufficient improvement in neurological function of the patient to safely undergo adjunctive fractionated radiotherapy (RT) according to current standards of care. Complete remission was achieved based on serial magnetic resonance imaging examinations of the brain, although progressive radiation encephalopathy resulted in the death of the dog 149 days after N-TIRE therapy. The length of survival of this patient was comparable to dogs with intracranial tumors treated via standard excisional surgery and adjunctive fractionated external beam RT. Our results illustrate the potential benefits of N-TIRE for in vivo ablation of undesirable brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal, and highlight the potential radiosensitizing effects of N-TIRE on the brain.

  14. Boron neutron capture therapy using mixed epithermal and thermal neutron beams in patients with malignant glioma-correlation between radiation dose and radiation injury and clinical outcome

    International Nuclear Information System (INIS)

    Kageji, Teruyoshi; Nagahiro, Shinji; Matsuzaki, Kazuhito; Mizobuchi, Yoshifumi; Toi, Hiroyuki; Nakagawa, Yoshinobu; Kumada, Hiroaki

    2006-01-01

    Purpose: To clarify the correlation between the radiation dose and clinical outcome of sodium borocaptate-based intraoperative boron neutron capture therapy in patients with malignant glioma. Methods and Materials: The first protocol (P1998, n = 8) prescribed a maximal gross tumor volume (GTV) dose of 15 Gy. In 2001, a dose-escalated protocol was introduced (P2001, n 11), which prescribed a maximal vascular volume dose of 15 Gy or, alternatively, a clinical target volume (CTV) dose of 18 Gy. Results: The GTV and CTV doses in P2001 were 1.1-1.3 times greater than those in P1998. The maximal vascular volume dose of those with acute radiation injury was 15.8 Gy. The mean GTV and CTV dose in long-term survivors with glioblastoma was 26.4 and 16.5 Gy, respectively. A statistically significant correlation between the GTV dose and median survival time was found. In the 11 glioblastoma patients in P2001, the median survival time was 19.5 months and 1- and 2-year survival rate was 60.6% and 37.9%, respectively. Conclusion: Dose escalation contributed to the improvement in clinical outcome. To avoid radiation injury, the maximal vascular volume dose should be <12 Gy. For long-term survival in patients with glioblastoma after boron neutron capture therapy, the optimal mean dose of the GTV and CTV was 26 and 16 Gy, respectively

  15. Cr(III) reactivity and foot dermatitis in Cr(VI) positive patients

    DEFF Research Database (Denmark)

    Hansen, Malene Barré; Menné, Torkil; Johansen, Jeanne Duus

    2006-01-01

    Chromium allergy has become synonymous with Cr(VI) allergy. However, real exposure to chromium from leather products may include both Cr(III) and Cr(VI). In this study, we investigate the reactivity to both Cr(VI) and Cr(III) in consecutive patients to analyse the relation between foot eczema/leather...... to Cr(III). The increased risk was not due to a higher degree of sensitivity to Cr(VI). Leather was reported most frequently as the suspected cause of chromium dermatitis (54%). However, Cr(VI) allergics having foot eczema and positive or doubtful Cr(III) reactions often had positive reactions to other...

  16. CD147 and glioma: a meta-analysis.

    Science.gov (United States)

    Li, Hui; Xi, Zhouhuan; Dai, Xuejiao; Wu, Wenyue; Li, Yanwen; Liu, Yanting; Zhang, Hanwen

    2017-08-01

    Gliomas are the most common primary brain tumors. This meta-analysis aimed to systematically evaluate the relationship between CD147 expression in tissues and the clinicopathological features of patients with glioma. We searched PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wan Fang databases (1988-2016). Quality assessment of the literature was performed using the Newcastle-Ottawa Scale, with Revman 5.3 and Stata 14.0 for analysis. In total, 1806 glioma patients from 19 studies were included, and patients with CD147 overexpression had poorer overall survival [hazard ratio (HR) = 2.211, P CD147 expression when comparing glioma tissues versus non-cancerous brain tissues (OR 20.42; 95% CI 13.94-29.91; P CD147 expression did not differ based on patient's age (young vs. old, P = 0.89) or gender (female vs. male, P = 0.57). CD147 expression may be a potential prognostic biomarker for poorer overall and relapse-free survival, and may affect the 5-year survival rate in glioma patients. CD147 expression is also closely correlated with poor clinical characteristics in glioma patients.

  17. Nasal Glioma: Case report

    Directory of Open Access Journals (Sweden)

    Ozgur Surmelioglu

    2011-02-01

    Full Text Available Nasal gliomas are rare, benign, congenital tumors that are thought to be result of abnormality in embryonic development. Three types of clinical presentations have been recognized; extranasal, intranasal and combined. Clinically, these masses are non-pulsatile, gray or purple lesions that obstruct the nasal cavity and cause deformity extranasaly. Histologically, they are made up of astrocytic cells, fibrous and vascular connective tissue that is covered with nasal respiratory mucosa. Treatment of the nasal glioma requires a multidisciplinary approach including an radiologist, neurosurgeon and otorhinolaryngologist. Radiological investigation should be performed to describe intracranial extension. In this case, a 2 years old boy with nasal mass that was diagnosed as nasal glioma is reported. . [Cukurova Med J 2011; 36(1.000: 34-36

  18. Nasal Glioma: Case report

    Directory of Open Access Journals (Sweden)

    Ozgur Surmelioglu

    2011-03-01

    Full Text Available Nasal gliomas are rare, benign, congenital tumors that are thought to be result of abnormality in embryonic development. Three types of clinical presentations have been recognized; extranasal, intranasal and combined. Clinically, these masses are non-pulsatile, gray or purple lesions that obstruct the nasal cavity and cause deformity extranasaly. Histologically, they are made up of astrocytic cells, fibrous and vascular connective tissue that is covered with nasal respiratory mucosa. Treatment of the nasal glioma requires a multidisciplinary approach including an radiologist, neurosurgeon and otorhinolaryngologist. Radiological investigation should be performed to describe intracranial extension. In this case, a 2 years old boy with nasal mass that was diagnosed as nasal glioma is reported. . [Cukurova Med J 2011; 36(1: 34-36

  19. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogeno...... of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  20. Resection of deep-seated brain glioma by microsurgery assisted with neuronavigation

    International Nuclear Information System (INIS)

    Feng Ming; Zhou Youxin; Sun Chunming; Zhang Shiming

    2009-01-01

    Objective: To investigate the clinical value of neuronavigator assisted microsurgery for deep-seated brain glioma. Methods: The electromagnetic neuronavigation system had been applied for microsurgery of deep-seated brain glioma in fifteen cases. Results: Ten from 15 patients were totally removed, 2 were subtotally removed and 3 were partial removed.All patients had no new neurological deficit. Conclusion: The neuronavigator assisted microsurgery for deep-seated brain glioma is of characters including accurate location, minimal invasiveness, and can enhance the rate of total resection and decrease the operative complications in the patients with deep-seated brain glioma. (authors)

  1. Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

    Science.gov (United States)

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymoma

  2. Reconstruction of white matter fibre tracts using diffusion kurtosis tensor imaging at 1.5T: Pre-surgical planning in patients with gliomas.

    Science.gov (United States)

    Leote, Joao; Nunes, Rita G; Cerqueira, Luis; Loução, Ricardo; Ferreira, Hugo A

    2018-01-01

    Tractography studies for pre-surgical planning of primary brain tumors is typically done using diffusion tensor imaging (DTI), which cannot resolve crossing, kissing or highly angulated fibres. Tractography based on the estimation of the diffusion kurtosis (DK) tensor was recently demonstrated to enable tackling these limitations. However, its use in the clinical context at low 1.5T field has not yet been reported. To evaluate if the estimation of whole-brain tractography using the DK tensor is feasible for pre-surgical investigation of patients with brain tumors at 1.5T. Eight healthy subjects and 3 patients with brain tumors were scanned at 1.5T using a 12-channel head coil. Diffusion-weighted images were acquired with repetition/echo times of 5800/107 ms, 82 × 82 resolution, 3 × 3 × 3 mm 3 voxel size, b-values of 0, 1000, 2000 s/mm 2 and 64 gradient sensitising directions. Whole-brain tractography was estimated using the DK tensor and corticospinal tracts (CST) were isolated using regions-of-interest placed at the cerebral peduncles and motor gyrus. Tract size, DK metrics and CST deviation index (highest curvature point) were compared between healthy subjects and patients. Tract sizes did not differ between groups. The CST deviation index was significantly higher in patients compared to healthy subjects. Fractional anisotropy was significantly lower in patients, with higher mean kurtosis asymmetry index at the highest curvature point in patients. Corticospinal fibre bundles estimated using DK tensor in a 1.5T scanner presented similar properties in patients with brain gliomas as those reported in the literature using DTI-based tractography.

  3. Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas.

    Science.gov (United States)

    Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred W K; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

    2017-03-01

    Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks.

  4. Management of Primary Tectal Plate Low-Grade Glioma in Pediatric Patients: Results of the Multicenter Treatment Study SIOP-LGG 2004.

    Science.gov (United States)

    Kaufmann, Ariane; Gerber, Nicolas U; Kandels, Daniela; Azizi, Amedeo A; Schmidt, Rene; Warmuth-Metz, Monika; Pietsch, Torsten; Kortmann, Rolf-Dieter; Gnekow, Astrid K; Grotzer, Michael A

    2018-06-11

     Tectal plate low-grade gliomas (LGGs) most often present with increased intracranial pressure and sometimes as incidental findings from brain imaging. Prognostic factors predicting outcome are largely unknown.  From 2004 until 2012, 71 patients with tectal plate LGG from Germany and Switzerland were followed within the SIOP-LGG 2004 study. Median age at diagnosis was 9.7 (range: 0.1-17.5) years, and median follow-up time of surviving patients was 6.3 (interquartile range: 4.9-8.3) years.  A total of 41 out of 71 patients received no tumor treatment (12 with and 29 without biopsy). The 10-year event-free survival (EFS) rate (± standard error ) for patients with an initial tumor volume of ≤3 cm 3 was 56% (±7%), as opposed to 12% (±8%) for those with tumors >3 cm 3 ( p  < 0.001). The 10-year EFS for patients without contrast enhancement on initial magnetic resonance imaging (MRI) was 52% (±9%), and for those with enhancement, it was 23% (±9%) ( p  = 0.003). The 10-year overall survival rate was 96% (±3%) (death due to disease, 1; ventriculoperitoneal shunt infection, 1). Sixty-three (89%) patients had at least one cerebrospinal fluid diversion procedure.  More than half of patients were managed without tumor treatment. Favorable prognostic factors for EFS were small initial tumor volume (≤3cm 3 ) and the absence of initial contrast enhancement on MRI. Overall survival was excellent. Georg Thieme Verlag KG Stuttgart · New York.

  5. Salvage immunotherapy of malignant glioma.

    Science.gov (United States)

    Ingram, M; Jacques, S; Freshwater, D B; Techy, G B; Shelden, C H; Helsper, J T

    1987-12-01

    We present the preliminary results of a phase I trial of adoptive immunotherapy for recurrent or residual malignant glioma. The protocol is based on surgical debulking followed by implantation into the tumor bed of autologous lymphocytes that have been stimulated with phytohemagglutinin-P and then cultured in vitro in the presence of interleukin 2. Fifty-five patients with a mean Karnofsky rating of 64 were treated between February 1985 and March 1987. No significant toxicity was associated with the immunotherapy. Fifty patients had a positive initial response to therapy, nine patients had early recurrence (two to four months after treatment), and 22 patients died. We comment on major differences between the protocol described and other immunotherapy protocols.

  6. Overexpression of NIMA-related kinase 2 is associated with poor prognoses in malignant glioma.

    Science.gov (United States)

    Liu, Huajie; Liu, Bin; Hou, Xianzeng; Pang, Bo; Guo, Pengbo; Jiang, Wanli; Ding, Qian; Zhang, Rui; Xin, Tao; Guo, Hua; Xu, Shangchen; Pang, Qi

    2017-05-01

    Eleated expression of NIMA-related kinase 2 (NEK2) was frequently observed in a variety of malignant cancers, and it appears to be involved in the initiation, maintenance, progression, metastasis of cancer and is positively associated with poor prognosis. We sought to investigate NEK2 expression and its predictive roles in malignant gliomas, and study the correlation of NEK2 protein expression with proliferation, clinical parameters, overall survival and some other parameters. We investigate NEK2 protein expression in 99 samples of malignant gliomas, including 35 WHO grade II, 22 grade III, and 42 grade IV gliomas, by immunohistochemistry and western blot (n = 50). We then made correlative analysis of protein overexpression using the Kaplan-Meier method, Log rank test, and Cox proportional-hazards model analysis. NEK2 protein was overexpressed in malignant gliomas, but not in normal brain tissues. Overexpression of NEK2 correlated with malignancy, proliferation and adverse overall survival in gliomas. Moreover, chemotherapy, resection extent and WHO grade also correlate with overall survival in gliomas. However, within WHO grade II glioma subgroup, NEK2 overexpression showed no impact on overall survival. The present study firstly reveals that NEK2 protein is widely overexpressed in gliomas. NEK2 overexpression correlates significantly with malignancy (WHO grades), proliferation (Ki-67) and prognosis in malignant gliomas. NEK2 is a potential gene therapy target and prognostic indicator.

  7. 测定脑胶质瘤患者神经肽、神经降压素的含量变化及意义%Clinical Significance and Detection of Neuro- Peptide and Neurotensin in Patients with Brain Glioma

    Institute of Scientific and Technical Information of China (English)

    尹秋霞; 司永兵; 齐法莲

    2001-01-01

    Objective To investigate the change of neuropeptide Y(NPY)and neurotensin(NT)in pqtients with brain glioma.Method The concentration of NPY and NT in and around brain glioma tissue and plasma were detected with inequilibrant radio- imunology method.Result NPY concentrqtion in brain glioma tissue was obviously higher than that in tissue around the tumor(P<0.01).The Concentration of NT in brain glioma tissue was obviously higher that in tissue around the glioma(P<0.01).Conclusion Detection of NPY and NTin brain glion aprovides basis for further study on brain glioma and explainning dlinical and imaginal symiptom of brain glioma.

  8. Noninvasive quantification of 18F-FLT human brain PET for the assessment of tumour proliferation in patients with high-grade glioma

    International Nuclear Information System (INIS)

    Backes, Heiko; Ullrich, Roland; Neumaier, Bernd; Kracht, Lutz; Wienhard, Klaus; Jacobs, Andreas H.

    2009-01-01

    Compartmental modelling of 3 ' -deoxy-3 ' -[ 18 F]-fluorothymidine ( 18 F-FLT) PET-derived kinetics provides a method for noninvasive assessment of the proliferation rate of gliomas. Such analyses, however, require an input function generally derived by serial blood sampling and counting. In the current study, 18 F-FLT kinetic parameters obtained from image-derived input functions were compared with those from input functions derived from arterialized blood samples. Based on the analysis of 11 patients with glioma (WHO grade II-IV) a procedure for the automated extraction of an input function from 18 F-FLT brain PET data was derived. The time-activity curve of the volume of interest with the maximum difference in 18 F-FLT uptake during the first 5 min after injection and the period from 60 to 90 min was corrected for partial-volume effects and in vivo metabolism of 18 F-FLT. For each patient a two-compartment kinetic model was applied to the tumour tissue using the image-derived input function. The resulting kinetic rate constants K 1 (transport across the blood-brain barrier) and K i (metabolic rate constant or net influx constant) were compared with those obtained from the same data using the input function derived from blood samples. Additionally, the metabolic rate constant was correlated with the frequency of tumour cells stained with Ki-67, a widely used immunohistochemical marker of cell proliferation. The rate constants from kinetic modelling were comparable when the blood sample-derived input functions were replaced by the image-derived functions (K 1,img and K 1,sample , r = 0.95, p -5 ; K i,img and K i,sample , r = 0.86, p 1,img and K 1,sample , p = 0.20; K i,img and K i,sample , p = 0.92). Furthermore, a significant correlation between K i,img and the percentage of Ki-67-positive cells was observed (r = 0.73, p = 0.01). Kinetic modelling of 18 F-FLT brain PET data using image-derived input functions extracted from human brain PET data with the practical

  9. Antiangiogenic Therapy and Mechanisms of Tumor Resistance in Malignant Glioma

    Directory of Open Access Journals (Sweden)

    Ruman Rahman

    2010-01-01

    Full Text Available Despite advances in surgery, radiation therapy, and chemotherapeutics, patients with malignant glioma have a dismal prognosis. The formations of aberrant tumour vasculature and glioma cell invasion are major obstacles for effective treatment. Angiogenesis is a key event in the progression of malignant gliomas, a process involving endothelial cell proliferation, migration, reorganization of extracellular matrix and tube formation. Such processes are regulated by the homeostatic balance between proangiogenic and antiangiogenic factors, most notably vascular endothelial growth factors (VEGFs produced by glioma cells. Current strategies targeting VEGF-VEGF receptor signal transduction pathways, though effective in normalizing abnormal tumor vasculature, eventually result in tumor resistance whereby a highly infiltrative and invasive phenotype may be adopted. Here we review recent anti-angiogenic therapy for malignant glioma and highlight implantable devices and nano/microparticles as next-generation methods for chemotherapeutic delivery. Intrinsic and adaptive modes of glioma resistance to anti-angiogenic therapy will be discussed with particular focus on the glioma stem cell paradigm.

  10. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    International Nuclear Information System (INIS)

    Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

    2010-01-01

    Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

  11. Prognostic impact of hemoglobin level and other factors in patients with high-grade gliomas treated with postoperative radiochemotherapy and sequential chemotherapy based on temozolomide. A 10-year experience at a single institution

    International Nuclear Information System (INIS)

    Ausili Cefaro, Giampiero; Genovesi, Domenico; Vinciguerra, Annamaria; Trignani, Marianna; Taraborrelli, Maria; Augurio, Antonietta; Buonaguidi, Roberto; Galzio, Renato J.; Di Nicola, Marta

    2011-01-01

    To evaluate the influence of serum hemoglobin level prior to radiotherapy and other prognostic factors on survival in patients with high-grade gliomas. From 2001-2010, we retrospectively evaluated a total of 48 patients with malignant glioma treated with surgery and postoperative radiochemotherapy with temozolomide. A total of 37 of 48 patients received sequential temozolomide. Hemoglobin levels were assayed before radiotherapy in all patients. The Kaplan-Meier method was applied to estimate the overall survival, while the log-rank test was applied to evaluate the differences on survival probability between prognostic subgroups. Results were assessed in 43 patients. The median overall survival time was 18 months (95% confidence interval: 12-40 months). The 1- and 2-year survival rates were 62.2% and 36.3%, respectively. The prognostic factors analyzed were gender, age, extent of surgery, performance status before and after radiotherapy, sequential chemotherapy, hemoglobin level, and methylation of the O-6-methylguanine-DNA methyltransferase gene (MGMT). In univariate analysis, the variables significantly related to survival were performance status before and after radiotherapy, sequential chemotherapy, and hemoglobin level. The median overall survival in patients with a hemoglobin level ≤ 12 g/dl was 12 months and 23 months in patients with a hemoglobin level > 12 g/dl. The 1- and 2-year survival rates were 46.7% and 20.0%, respectively, for patients with a hemoglobin level ≤ 12 mg/dl and 69.6% and 45.7%, respectively, for patients with a hemoglobin level > 12 g/dl. Our results confirm the impact of well-known prognostic factors on survival. In this research, it was found that a low hemoglobin level before radiotherapy can adversely influence the prognosis of patients with malignant gliomas.

  12. Immunotherapy Approaches for Malignant Glioma From 2007 to 2009

    Science.gov (United States)

    Sampson, John H.

    2012-01-01

    Malignant glioma is a deadly disease for which there have been few therapeutic advances over the past century. Although previous treatments were largely unsuccessful, glioma may be an ideal target for immune-based therapy. Recently, translational research led to several clinical trials based on tumor immunotherapy to treat patients with malignant glioma. Here we review 17 recent glioma immunotherapy clinical trials, published over the past 3 years. Various approaches were used, including passive transfer of naked and radiolabeled antibodies, tumor antigen-specific peptide immunization, and the use of patient tumor cells with or without dendritic cells as vaccines. We compare and discuss the current state of the art of clinical immunotherapy treatment, as well as its limited successes, pitfalls, and future potential. PMID:20424975

  13. Clinical characteristics associated with the intracranial dissemination of gliomas.

    Science.gov (United States)

    Cai, Xu; Qin, Jun-Jie; Hao, Shu-Yu; Li, Huan; Zeng, Chun; Sun, Sheng-Jun; Yu, Lan-Bing; Gao, Zhi-Xian; Xie, Jian

    2018-03-01

    Glioma is the most common malignant tumor of the brain and the intracranial dissemination of gliomas is the late stage of the development of the tumor. However, there is little research in literature on the occurrence of intracranial dissemination of gliomas. In order to provide a reference for clinical work, we carried out this study on intracranial dissemination of glioma. A total of 629 patients with gliomas received tumor resection by the same surgeon from August 2010 to September 2015 were included in this study. The authors performed a retrospective review of the patients and the information regarding clinical features, histopathological results, molecular pathologic results and clinical outcomes was collected and analyzed. In this retrospective study, we found that the intracranial dissemination phenomenon occurred in 53 patients (8.43%). We analyzed the clinical characteristics of patients and found that the age at diagnosis (P = 0.011), WHO grade of the tumor (P dissemination. The higher grade of the tumor, the more prone to disseminate. Deletion of 1p/19q had no significant correlation with the intracranial dissemination. MMP9, Ki-67, and EGFR were highly expressed in tumor cells that caused dissemination, and the level of Ki-67 expression had significance in statistics (P 40 years), high pathological grade, invasion of the corpus callosum and high levels of Ki-67 expression were risk factors associated with the intracranial dissemination of gliomas. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Cruickshank, G.S. [University of Birmingham and University Hospital Birmingham, Birmingham (United Kingdom)], E-mail: garth.cruickshank@uhb.nhs.uk; Ngoga, D.; Detta, A.; Green, S.; James, N.D.; Wojnecki, C.; Doran, J.; Hardie, J.; Chester, M.; Graham, N.; Ghani, Z. [University of Birmingham and University Hospital Birmingham, Birmingham (United Kingdom); Halbert, G.; Elliot, M.; Ford, S. [CR-UK Formulation Unit, University of Strathclyde, Glasgow (United Kingdom); Braithwaite, R.; Sheehan, T.M.T. [Regional Laboratory for Toxicology, Sandwell and West Birmingham Hospitals Trust, Birmingham (United Kingdom); Vickerman, J.; Lockyer, N. [Surface Analysis Research Centre, University of Manchester, Manchester (United Kingdom); Steinfeldt, H.; Croswell, G. [CR-UK Drug Development Office, London (United Kingdom)] (and others)

    2009-07-15

    This paper describes results to-date from a human pharmacokinetic study which began recruitment in December 2007. Results are presented for a single patient recruited in December 2007. A second patient was recruited in July 2008 but detailed data are not available at the time of writing. The trial is an open-label, non-comparative, non-therapeutic study of BPA-mannitol in patients with high-grade glioma, who will be undergoing stereotactic brain biopsy as part of the diagnostic process before definitive treatment. The study investigates the route of infusion (intra-venous (IV) or intra-carotid artery) and in each case will assess the effect of administration of mannitol as a blood-brain barrier disrupter. All cohorts will receive a 2 h infusion of BPA-mannitol, and for some cohorts an additional mannitol bolus will be administered at the beginning of this infusion. Measurements are made by inductively coupled plasma mass spectrometry (ICP-MS) of {sup 10}B concentration in samples of blood, urine, extra-cellular fluid in normal brain (via a dialysis probe), brain tissue around tumour and tumour tissue. Additional analysis of the tumour tissue is performed using secondary ion mass spectrometry (SIMS). The first patient was part of the cohort having intra-venous infusion without mannitol bolus. No serious clinical problems were experienced and the assay results can be compared with available patient data from other BNCT centres. In particular we note that the peak {sup 10}B concentration in blood was 28.1 mg/ml for a total BPA administration of 350 mg/kg which is very consistent with the previous experience with BPA-fructose reported by the Helsinki group.

  15. A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT

    International Nuclear Information System (INIS)

    Cruickshank, G.S.; Ngoga, D.; Detta, A.; Green, S.; James, N.D.; Wojnecki, C.; Doran, J.; Hardie, J.; Chester, M.; Graham, N.; Ghani, Z.; Halbert, G.; Elliot, M.; Ford, S.; Braithwaite, R.; Sheehan, T.M.T.; Vickerman, J.; Lockyer, N.; Steinfeldt, H.; Croswell, G.

    2009-01-01

    This paper describes results to-date from a human pharmacokinetic study which began recruitment in December 2007. Results are presented for a single patient recruited in December 2007. A second patient was recruited in July 2008 but detailed data are not available at the time of writing. The trial is an open-label, non-comparative, non-therapeutic study of BPA-mannitol in patients with high-grade glioma, who will be undergoing stereotactic brain biopsy as part of the diagnostic process before definitive treatment. The study investigates the route of infusion (intra-venous (IV) or intra-carotid artery) and in each case will assess the effect of administration of mannitol as a blood-brain barrier disrupter. All cohorts will receive a 2 h infusion of BPA-mannitol, and for some cohorts an additional mannitol bolus will be administered at the beginning of this infusion. Measurements are made by inductively coupled plasma mass spectrometry (ICP-MS) of 10 B concentration in samples of blood, urine, extra-cellular fluid in normal brain (via a dialysis probe), brain tissue around tumour and tumour tissue. Additional analysis of the tumour tissue is performed using secondary ion mass spectrometry (SIMS). The first patient was part of the cohort having intra-venous infusion without mannitol bolus. No serious clinical problems were experienced and the assay results can be compared with available patient data from other BNCT centres. In particular we note that the peak 10 B concentration in blood was 28.1 mg/ml for a total BPA administration of 350 mg/kg which is very consistent with the previous experience with BPA-fructose reported by the Helsinki group.

  16. Epstein–Barr Virus in Gliomas: Cause, Association, or Artifact?

    Directory of Open Access Journals (Sweden)

    Saghir Akhtar

    2018-04-01

    Full Text Available Gliomas are the most common malignant brain tumors and account for around 60% of all primary central nervous system cancers. Glioblastoma multiforme (GBM is a grade IV glioma associated with a poor outcome despite recent advances in chemotherapy. The etiology of gliomas is unknown, but neurotropic viruses including the Epstein–Barr virus (EBV that is transmitted via salivary and genital fluids have been implicated recently. EBV is a member of the gamma herpes simplex family of DNA viruses that is known to cause infectious mononucleosis (glandular fever and is strongly linked with the oncogenesis of several cancers, including B-cell lymphomas, nasopharyngeal, and gastric carcinomas. The fact that EBV is thought to be the causative agent for primary central nervous system (CNS lymphomas in immune-deficient patients has led to its investigations in other brain tumors including gliomas. Here, we provide a review of the clinical literature pertaining to EBV in gliomas and discuss the possibilities of this virus being simply associative, causative, or even an experimental artifact. We searched the PubMed/MEDLINE databases using the following key words such as: glioma(s, glioblastoma multiforme, brain tumors/cancers, EBV, and neurotropic viruses. Our literature analysis indicates conflicting results on the presence and role of EBV in gliomas. Further comprehensive studies are needed to fully implicate EBV in gliomagenesis and oncomodulation. Understanding the role of EBV and other oncoviruses in the etiology of gliomas, would likely open up new avenues for the treatment and management of these, often fatal, CNS tumors.

  17. Intraoperative subcortical mapping of a language-associated deep frontal tract connecting the superior frontal gyrus to Broca's area in the dominant hemisphere of patients with glioma.

    Science.gov (United States)

    Fujii, Masazumi; Maesawa, Satoshi; Motomura, Kazuya; Futamura, Miyako; Hayashi, Yuichiro; Koba, Itsuko; Wakabayashi, Toshihiko

    2015-06-01

    The deep frontal pathway connecting the superior frontal gyrus to Broca's area, recently named the frontal aslant tract (FAT), is assumed to be associated with language functions, especially speech initiation and spontaneity. Injury to the deep frontal lobe is known to cause aphasia that mimics the aphasia caused by damage to the supplementary motor area. Although fiber dissection and tractography have revealed the existence of the tract, little is known about its function. The aim of this study was to determine the function of the FAT via electrical stimulation in patients with glioma who underwent awake surgery. The authors analyzed the data from subcortical mapping with electrical stimulation in 5 consecutive cases (3 males and 2 females, age range 40-54 years) with gliomas in the left frontal lobe. Diffusion tensor imaging (DTI) and tractography of the FAT were performed in all cases. A navigation system and intraoperative MRI were used in all cases. During the awake phase of the surgery, cortical mapping was performed to find the precentral gyrus and Broca's area, followed by tumor resection. After the cortical layer was removed, subcortical mapping was performed to assess language-associated fibers in the white matter. In all 5 cases, positive responses were obtained at the stimulation sites in the subcortical area adjacent to the FAT, which was visualized by the navigation system. Speech arrest was observed in 4 cases, and remarkably slow speech and conversation was observed in 1 case. The location of these sites was also determined on intraoperative MR images and estimated on preoperative MR images with DTI tractography, confirming the spatial relationships among the stimulation sites and white matter tracts. Tumor removal was successfully performed without damage to this tract, and language function did not deteriorate in any of the cases postoperatively. The authors identified the left FAT and confirmed that it was associated with language functions. This

  18. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  19. Mitochondrial Dysfunction in Gliomas

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Anni, H.; Dráber, Pavel

    2013-01-01

    Roč. 20, č. 3 (2013), s. 216-227 ISSN 1071-9091 R&D Projects: GA MŠk LH12050 Institutional support: RVO:68378050 Keywords : gliomas * mitochondrial dysfunction * microtubule proteins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.883, year: 2013

  20. Detection of HTLV-III RNA in lungs of patients with AIDS and pulmonary involvement

    International Nuclear Information System (INIS)

    Chayt, K.J.; Harper, M.E.; Marselle, L.M.; Lewin, E.B.; Rose, R.M.; Oleske, J.M.; Epstein, L.G.; Wong-Staal, F.; Gallo, R.C.

    1986-01-01

    A majority of pediatric patients and rare adult patients with the acquired immunodeficiency syndrome (AIDS) develop a chronic respiratory disorder referred to as lymphocytic interstitial pneumonitis (LIP). Efforts to identify an infectious agent responsible for this process so far have failed. In this study, frozen sections of lungs from patients with AIDS and pulmonary disease were tested by in situ molecular hybridization for the presence of cells infected with human T-cell lymphotropic virus type III (HTLV-III) and expressing viral RNA. In the case of an infant with LIP, a relatively high frequency (0.1%) of cells in the lung were found to be positive for HTLV-III RNA. This number is the lower limit of total cells infected since the in situ hybridization technique as applied in this study depends on expression of HTLV-III genes, and previous evidence indicates that a proportion of cells infected with HTLV-III may not express viral RNA. Moreover, this degree of infection of the lung is likely limited to LIP, since in ten patients with AIDS and pulmonary diseases other than LIP, only 0% to 0.002% of cells in lung were positive for viral RNA expression. Thus, HTLV-III may play a direct causal role in the development of LIP in infected patients, implicating its involvement in yet another of the diverse clinical diseases associated with this virus

  1. Ring enhancement in recurrent gliomas

    International Nuclear Information System (INIS)

    Ogashiwa, Motohide; Takeuchi, Kazuo; Akai, Keiichiro

    1981-01-01

    The clinical courses,CT scans, and postmortem reports for 6 glioma patients treated by surgery, radiation, and chemotherapy were reviewed. They underwent reoperation and/or retreatment with radiation or chemotherapy for recurrent tumors. CT scans taken at the time of recurrence or about one month prior to death showed ring enhancement of varied size and form after intensive treatment. The cases were examined histologically in correlation with the CT features and divided into two groups based on the pathological findings in the centers surrounded by areas of ring enhancement. The 1st group demonstrated a large necrotic area in the center, and the 2nd group, a cystic tumor. Tumor cells were found to have spread throughout the high-density areas around the necrotic area or cyst. However, gross differentiation between tumor and necrosis was difficult. In addition to an increase in cellularity, all cases demonstrated vascular proliferation, and dilatation of vessels in the sulci or sulci adjacent to gyri invaded by the tumor. The contrast enhancement corresponded well with the vascular proliferation in these areas. It is concluded that vascular proliferation or dilatation of vessels in and around the tumor is an important factor in demonstrating high-density areas in ring enhancement, while a cyst or necrosis in the tumor center is revealed as a low-density area in the CT scan of recurrent gliomas. (author)

  2. Ring enhancement in recurrent gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Ogashiwa, M; Takeuchi, K; Akai, K [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

    1981-08-01

    The clinical courses,CT scans, and postmortem reports for 6 glioma patients treated by surgery, radiation, and chemotherapy were reviewed. They underwent reoperation and/or retreatment with radiation or chemotherapy for recurrent tumors. CT scans taken at the time of recurrence or about one month prior to death showed ring enhancement of varied size and form after intensive treatment. The cases were examined histologically in correlation with the CT features and divided into two groups based on the pathological findings in the centers surrounded by areas of ring enhancement. The 1st group demonstrated a large necrotic area in the center, and the 2nd group, a cystic tumor. Tumor cells were found to have spread throughout the high-density areas around the necrotic area or cyst. However, gross differentiation between tumor and necrosis was difficult. In addition to an increase in cellularity, all cases demonstrated vascular proliferation, and dilatation of vessels in the sulci or sulci adjacent to gyri invaded by the tumor. The contrast enhancement corresponded well with the vascular proliferation in these areas. It is concluded that vascular proliferation or dilatation of vessels in and around the tumor is an important factor in demonstrating high-density areas in ring enhancement, while a cyst or necrosis in the tumor center is revealed as a low-density area in the CT scan of recurrent gliomas.

  3. Economics of Malignant Gliomas: A Critical Review.

    Science.gov (United States)

    Raizer, Jeffrey J; Fitzner, Karen A; Jacobs, Daniel I; Bennett, Charles L; Liebling, Dustin B; Luu, Thanh Ha; Trifilio, Steven M; Grimm, Sean A; Fisher, Matthew J; Haleem, Meraaj S; Ray, Paul S; McKoy, Judith M; DeBoer, Rebecca; Tulas, Katrina-Marie E; Deeb, Mohammed; McKoy, June M

    2015-01-01

    Approximately 18,500 persons are diagnosed with malignant glioma in the United States annually. Few studies have investigated the comprehensive economic costs. We reviewed the literature to examine costs to patients with malignant glioma and their families, payers, and society. A total of 18 fully extracted studies were included. Data were collected on direct and indirect costs, and cost estimates were converted to US dollars using the conversion rate calculated from the study's publication date, and updated to 2011 values after adjustment for inflation. A standardized data abstraction form was used. Data were extracted by one reviewer and checked by another. Before approval of effective chemotherapeutic agents for malignant gliomas, estimated total direct medical costs in the United States for surgery and radiation therapy per patient ranged from $50,600 to $92,700. The addition of temozolomide (TMZ) and bevacizumab to glioblastoma treatment regimens has resulted in increased overall costs for glioma care. Although health care costs are now less front-loaded, they have increased over the course of illness. Analysis using a willingness-to-pay threshold of $50,000 per quality-adjusted life-year suggests that the benefits of TMZ fall on the edge of acceptable therapies. Furthermore, indirect medical costs, such as productivity losses, are not trivial. With increased chemotherapy use for malignant glioma, the paradigm for treatment and associated out-of-pocket and total medical costs continue to evolve. Larger out-of-pocket costs may influence the choice of chemotherapeutic agents, the economic implications of which should be evaluated prospectively. Copyright © 2015 by American Society of Clinical Oncology.

  4. Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication.

    Science.gov (United States)

    Lin, Qingtang; Liu, Zhao; Ling, Feng; Xu, Geng

    2016-02-01

    Gliomas are the most common type of primary brain tumor. Using current standard treatment regimens, the prognosis of patients with gliomas remains poor, which is predominantly due to the resistance of glioma cells to chemotherapy. The organ microenvironment has been implicated in the pathogenesis and survival of tumor cells. Thus, the aim of the present study was to test the hypothesis that astrocytes (the housekeeping cells of the brain microenvironment) may protect glioma cells from chemotherapy and to investigate the underlying mechanism. Immunofluorescent and scanning electron microscopy demonstrated that glioma cells were surrounded and infiltrated by activated astrocytes. In vitro co-culture of glioma cells with astrocytes significantly reduced the cytotoxic effects on glioma cells caused by various chemotherapeutic agents, as demonstrated by fluorescein isothiocyanate-propidium iodide flow cytometry. Transwell experiments indicated that this protective effect was dependent on physical contact and the gap junctional communication (GJC) between astrocytes and glioma cells. Microarray expression profiling further revealed that astrocytes upregulated the expression levels of various critical survival genes in the glioma cells via GJC. The results of the present study indicated that the organ microenvironment may affect the biological behavior of tumor cells and suggest a novel mechanism of resistance in glioma cells, which may be of therapeutic relevance clinically.

  5. Microglia immunophenotyping in gliomas

    Science.gov (United States)

    Annovazzi, Laura; Mellai, Marta; Bovio, Enrica; Mazzetti, Samanta; Pollo, Bianca; Schiffer, Davide

    2018-01-01

    Microglia, once assimilated to peripheral macrophages, in gliomas has long been discussed and currently it is hypothesized to play a pro-tumor role in tumor progression. Uncertain between M1 and M2 polarization, it exchanges signals with glioma cells to create an immunosuppressive microenvironment and stimulates cell proliferation and migration. Four antibodies are currently used for microglia/macrophage identification in tissues that exhibit different cell forms and cell localization. The aim of the present work was to describe the distribution of the different cell forms and to deduce their significance on the basis of what is known on their function from the literature. Normal resting microglia, reactive microglia, intermediate and bumpy forms and macrophage-like cells can be distinguished by Iba1, CD68, CD16 and CD163 and further categorized by CD11b, CD45, c-MAF and CD98. The number of microglia/macrophages strongly increased from normal cortex and white matter to infiltrating and solid tumors. The ramified microglia accumulated in infiltration areas of both high- and low-grade gliomas, when hypertrophy and hyperplasia occur. In solid tumors, intermediate and bumpy forms prevailed and there is a large increase of macrophage-like cells in glioblastoma. The total number of microglia cells did not vary among the three grades of malignancy, but macrophage-like cells definitely prevailed in high-grade gliomas and frequently expressed CD45 and c-MAF. CD98+ cells were present. Microglia favors tumor progression, but many aspects suggest that the phagocytosing function is maintained. CD98+ cells can be the product of fusion, but also of phagocytosis. Microglia correlated with poorer survival in glioblastoma, when considering CD163+ cells, whereas it did not change prognosis in isocitrate dehydrogenase-mutant low grade gliomas. PMID:29399160

  6. The 18-kDa mitochondrial translocator protein in gliomas: from the bench to bedside.

    OpenAIRE

    Janczar, Karolina; Su, Zhangjie; Raccagni, Isabella; Anfosso, Andrea; Kelly, Charlotte; Durrenberger, Pascal F; Gerhard, Alexander; Roncaroli, Federic

    2015-01-01

    The 18-kDa mitochondrial translocator protein (TSPO) is known to be highly expressed in several types of cancer, including gliomas, whereas expression in normal brain is low. TSPO functions in glioma are still incompletely understood. The TSPO can be quantified pre-operatively with molecular imaging making it an ideal candidate for personalized treatment of patient with glioma. Studies have proposed to exploit the TSPO as a transporter of chemotherapics to selectively target tumour cells in t...

  7. Neoadjuvant chemotherapy in patients with stages III/IV breast ...

    African Journals Online (AJOL)

    The aim of this study was to determine disease response, recurrence and development of distant metastasis with the use of chemotherapy in the form of neoadjuvant chemotherapy. Patients and methods: This was a prospective study that had enrolled a total of 57 patients with locally advanced breast cancer disease ...

  8. Concurrent thermochemoradiotherapy for brain high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ryabova, A. I., E-mail: ranigor@mail.ru; Novikov, V. A.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Choinzonov, E. L. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Siberian State Medical University, Tomsk, 634050 (Russian Federation); Gribova, O. V. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Baranova, A. V. [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  9. Upregulation of B23 promotes tumor cell proliferation and predicts poor prognosis in glioma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jianguo [Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu Province (China); Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province (China); Sun, Jie; Yang, Liu; Yan, Yaohua; Shi, Wei; Shi, Jinlong; Huang, Qingfeng; Chen, Jian [Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province (China); Lan, Qing, E-mail: lanqingsj@163.com [Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu Province (China)

    2015-10-09

    B23 (also known as Nucleophosmin, NPM, numatrin or NO38) is a ubiquitously expressed phosphoprotein belonging to the nucleoplasmin family of chaperones. In this study we intended to investigate the clinical significance of B23 expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that B23 was overexpressed in glioma tissues and glioma cell lines. In addition, the expression level of B23 was positively correlated with glioma pathological grade and Ki-67 expression. Kaplan–Meier analysis revealed that a higher B23 expression in patients with glioma was associated with a poorer prognosis. In vitro, after the release of glioma cell lines from serum starvation, the expression of B23 was upregulated, as well as PCNA (Proliferating Cell Nuclear Antigen) and cyclin A. In addition, knockdown of B23 by small interfering RNA transfection diminished the expression of PCNA, cyclin D1 and arrested cell growth at G1 phase. Taken together, our results implied that B23 could be a candidate prognostic biomarker as well as a potential therapeutical target of glioma. - Highlights: • B23 expression increased as the malignant degree of glioma increased, which was consistent with Ki-67 expression. • High expression of B23 could be a strong determinant of poor prognosis in glioma. • B23 may be involved in the proliferation of glioma in a cell-cycle-dependent pathway. • Knockdown of B23 expression by siRNA could affect the progression of glioma. • B23 may be a potential prognosis biomarker and a possible therapeutic target for glioma.

  10. Patterns of Pelvic Radiotherapy in Patients with Stage II/III Rectal Cancer

    International Nuclear Information System (INIS)

    Fitzgerald, T. L.; Zervos, E.; Wong, J. H.; Fitzgerald, T. L.; Zervos, E.; Wong, J. H.; Fitzgerald, T. L.; Zervos, E.; Wong, J. H.

    2013-01-01

    High-level evidence supports adjuvant radiotherapy for rectal cancer. We examined the influence of socio demographic factors on patterns of adjuvant radiotherapy for resected Stage II/III rectal cancer. Methods. Patients undergoing surgical resection for stage II/III rectal cancer were identified in SEER registry. Results. A total of 21,683 patients were identified. Majority of patients were male (58.8%), white (83%), and with stage III (54.9%) and received radiotherapy (66%). On univariate analysis, male gender, stage III, younger age, year of diagnosis, and higher socioeconomic status (SES) were associated with radiotherapy. Radiotherapy was delivered in 84.4% of patients <50; however, only 32.8% of those are >80 years. Logistic regression demonstrated a significant increase in the use of radiotherapy in younger patients who are 50 (OR, 10.3), with stage III (OR, 1.21), males (OR, 1.18), and with higher SES. Conclusions. There is a failure to conform to standard adjuvant radiotherapy in one-third of patients, and this is associated with older age, stage II, area-level of socioeconomic deprivation, and female sex.

  11. Performance on the Wechsler Adult Intelligence Scale-III in Japanese patients with schizophrenia.

    Science.gov (United States)

    Fujino, Haruo; Sumiyoshi, Chika; Sumiyoshi, Tomiki; Yasuda, Yuka; Yamamori, Hidenaga; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Higuchi, Arisa; Hibi, Yumiko; Matsuura, Yukako; Hashimoto, Ryota; Takeda, Masatoshi; Imura, Osamu

    2014-07-01

    Patients with schizophrenia have been reported to perform worse than non-schizophrenic populations on neuropsychological tests, which may be affected by cultural factors. The aim of this study was to examine the performance of a sizable number of patients with schizophrenia on the Japanese version of the Wechsler Adult Intelligence Scale-III (WAIS-III) compared with healthy controls. Performance on the WAIS-III was evaluated in 157 Japanese patients with schizophrenia and in 264 healthy control subjects. All IQ scores and four indices from the WAIS-III were impaired for patients with schizophrenia compared with healthy controls. Processing Speed was markedly disturbed, approximately 2 SD below that of the healthy control group. Among the 13 subtests, Comprehension (z = -1.70, d = 1.55), Digit Symbol Coding (z = -1.84, d = 1.88), and Symbol Search (z = -1.85, d = 1.77) were profoundly impaired relative to the healthy controls. These results indicate that the pattern and degree of impairment, as evaluated by the WAIS-III, in Japanese patients are similar to those previously reported in English-speaking patients and that the deficits of some neuropsychological domains relevant to functional outcomes are universally characteristic of schizophrenia. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  12. MRI in Glioma Immunotherapy: Evidence, Pitfalls, and Perspectives

    Directory of Open Access Journals (Sweden)

    Domenico Aquino

    2017-01-01

    Full Text Available Pseudophenomena, that is, imaging alterations due to therapy rather than tumor evolution, have an important impact on the management of glioma patients and the results of clinical trials. RANO (response assessment in neurooncology criteria, including conventional MRI (cMRI, addressed the issues of pseudoprogression after radiotherapy and concomitant chemotherapy and pseudoresponse during antiangiogenic therapy of glioblastomas (GBM and other gliomas. The development of cancer immunotherapy forced the identification of further relevant response criteria, summarized by the iRANO working group in 2015. In spite of this, the unequivocal definition of glioma progression by cMRI remains difficult particularly in the setting of immunotherapy approaches provided by checkpoint inhibitors and dendritic cells. Advanced MRI (aMRI may in principle address this unmet clinical need. Here, we discuss the potential contribution of different aMRI techniques and their indications and pitfalls in relation to biological and imaging features of glioma and immune system interactions.

  13. Computation of reliable textural indices from multimodal brain MRI: suggestions based on a study of patients with diffuse intrinsic pontine glioma

    Science.gov (United States)

    Goya-Outi, Jessica; Orlhac, Fanny; Calmon, Raphael; Alentorn, Agusti; Nioche, Christophe; Philippe, Cathy; Puget, Stéphanie; Boddaert, Nathalie; Buvat, Irène; Grill, Jacques; Frouin, Vincent; Frouin, Frederique

    2018-05-01

    Few methodological studies regarding widely used textural indices robustness in MRI have been reported. In this context, this study aims to propose some rules to compute reliable textural indices from multimodal 3D brain MRI. Diagnosis and post-biopsy MR scans including T1, post-contrast T1, T2 and FLAIR images from thirty children with diffuse intrinsic pontine glioma (DIPG) were considered. The hybrid white stripe method was adapted to standardize MR intensities. Sixty textural indices were then computed for each modality in different regions of interest (ROI), including tumor and white matter (WM). Three types of intensity binning were compared : constant bin width and relative bounds; constant number of bins and relative bounds; constant number of bins and absolute bounds. The impact of the volume of the region was also tested within the WM. First, the mean Hellinger distance between patient-based intensity distributions decreased by a factor greater than 10 in WM and greater than 2.5 in gray matter after standardization. Regarding the binning strategy, the ranking of patients was highly correlated for 188/240 features when comparing with , but for only 20 when comparing with , and nine when comparing with . Furthermore, when using or texture indices reflected tumor heterogeneity as assessed visually by experts. Last, 41 features presented statistically significant differences between contralateral WM regions when ROI size slightly varies across patients, and none when using ROI of the same size. For regions with similar size, 224 features were significantly different between WM and tumor. Valuable information from texture indices can be biased by methodological choices. Recommendations are to standardize intensities in MR brain volumes, to use intensity binning with constant bin width, and to define regions with the same volumes to get reliable textural indices.

  14. [Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease].

    Science.gov (United States)

    Mantilla, Carolina; Toro, Mónica; Sepúlveda, María Elsy; Insuasty, Margarita; Di Filippo, Diana; López, Juan Álvaro; Baquero, Carolina; Navas, María Cristina; Arias, Andrés Augusto

    2018-05-01

    Type III glycogen storage disease (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. The disease is characterized by fasting hypoglycemia, hepatomegaly and progressive myopathy. Molecular analyses of AGL have indicated heterogeneity depending on ethnic groups. The full spectrum of AGL mutations in Colombia remains unclear. To describe the clinical and molecular characteristics of ten Colombian patients diagnosed with GSD III. We recruited ten Colombian children with a clinical and biochemical diagnosis of GSD III to undergo genetic testing. The full coding exons and the relevant exon-intron boundaries of the AGL underwent Sanger sequencing to identify mutation. All patients had the classic phenotype of the GSD III. Genetic analysis revealed a mutation p.Arg910X in two patients. One patient had the mutation p.Glu1072AspfsX36, and one case showed a compound heterozygosity with p.Arg910X and p.Glu1072AspfsX36 mutations. We also detected the deletion of AGL gene 3, 4, 5, and 6 exons in three patients. The in silico studies predicted that these defects are pathogenic. No mutations were detected in the amplified regions in three patients. We found mutations and deletions that explain the clinical phenotype of GSD III patients. This is the first report with a description of the clinical phenotype and the spectrum of AGL mutations in Colombian patients. This is important to provide appropriate prognosis and genetic counseling to the patient and their relatives.

  15. Analogous Three-Dimensional Constructive Interference in Steady State Sequences Enhance the Utility of Three-Dimensional Time of Flight Magnetic Resonance Angiography in Delineating Lenticulostriate Arteries in Insular Gliomas: Evidence from a Prospective Clinicoradiologic Analysis of 48 Patients.

    Science.gov (United States)

    Rao, Arun S; Thakar, Sumit; Sai Kiran, Narayanam Anantha; Aryan, Saritha; Mohan, Dilip; Hegde, Alangar S

    2018-01-01

    Three-dimensional (3D) time of flight (TOF) imaging is the current gold standard for noninvasive, preoperative localization of lenticulostriate arteries (LSAs) in insular gliomas; however, the utility of this modality depends on tumor intensity. Over a 3-year period, 48 consecutive patients with insular gliomas were prospectively evaluated. Location of LSAs and their relationship with the tumor were determined using a combination of contrast-enhanced coronal 3D TOF magnetic resonance angiography and coronal 3D constructive interference in steady state (CISS) sequences. These findings were analyzed with respect to extent of tumor resection and early postoperative motor outcome. Tumor was clearly visualized in 29 (60.4%) patients with T1-hypointense tumors using 3D TOF and in all patients using CISS sequences. Using combined 3D TOF and CISS, LSA-tumor interface was well seen in 47 patients, including all patients with T1-heterointense or T1-isointense tumors. Extent of resection was higher in the LSA-pushed group compared with the LSA-encased group. In the LSA-encased group, 6 (12.5%) patients developed postoperative hemiparesis; 2 (4.2%) cases were attributed to LSA injury. Contrast-enhanced 3D TOF can delineate LSAs in almost all insular gliomas but is limited in identifying the LSA-tumor interface. This limitation can be overcome by addition of analogous CISS sequences that delineate the LSA-tumor interface regardless of tumor intensity. Combined 3D TOF and 3D CISS is a useful tool for surgical planning and safer resections of insular tumors and may have added surgical relevance when included as an intraoperative adjunct. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Near-infrared spectroscopic study and the Wada test for presurgical evaluation of expressive and receptive language functions in glioma patients: with a case report of dissociated language functions.

    Science.gov (United States)

    Sato, Yosuke; Uzuka, Takeo; Aoki, Hiroshi; Natsumeda, Manabu; Oishi, Makoto; Fukuda, Masafumi; Fujii, Yukihiko

    2012-02-29

    Near-infrared spectroscopy (NIRS) has proven to be useful for the evaluation of language lateralization in healthy subjects, infants, and epileptic patients. This study for the first time investigated the expressive and receptive language functions separately, using NIRS in presurgical glioma patients. We also describe a special case with dissociated pattern of language functions. Ten glioma patients were examined. Using NIRS, the hemodynamic changes during a verb generation task or story listening task were measured in the cerebral hemisphere on either side covering the language areas. Following the NIRS study, the Wada test was performed in all the patients. The NIRS study revealed increases of oxyhemoglobin and decreases of deoxyhemoglobin in the language areas elicited by both tasks. In 9 patients, who were all right-handed, the expressive and receptive language functions were lateralized to the left hemisphere. The results of the NIRS study were completely consistent with those of the Wada test. In the remaining 1 patient with a right sided insular glioma, who was right-handed, the NIRS study revealed stronger activation of the right inferior frontal region during the verb generation task, and stronger activation of the left superior temporal region during the story listening task. This dissociated language function was validated by the Wada test and the postoperative neurological course. These results demonstrate that a NIRS study using our technique is extremely valuable for preoperative assessment of the language functions and exemplifies how a preoperative NIRS study can allow detection of unforeseen language lateralization. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. BCNU wafer placement with temozolomide (TMZ) in the immediate postoperative period after tumor resection followed by radiation therapy with TMZ in patients with newly diagnosed high grade glioma: final results of a prospective, multi-institutional, phase II trial.

    Science.gov (United States)

    Burri, Stuart H; Prabhu, Roshan S; Sumrall, Ashley L; Brick, Wendy; Blaker, Brian D; Heideman, Brent E; Boltes, Peggy; Kelly, Renee; Symanowski, James T; Wiggins, Walter F; Ashby, Lynn; Norton, H James; Judy, Kevin; Asher, Anthony L

    2015-06-01

    Temozolomide (TMZ) and BCNU have demonstrated anti-glioma synergism in preclinical models. We report final data from a prospective, multi-institutional study of BCNU wafers and early TMZ followed by radiation therapy with TMZ in patients with newly diagnosed malignant glioma. 65 patients were consented in 4 institutions, and 46 patients (43 GBM, 3 AA) were eligible for analysis. After resection and BCNU wafer placement, TMZ began on day four postoperatively. Radiation and TMZ (RT/TMZ) were then administered, followed by monthly TMZ at 200 mg/m2 for the first 26 patients, which was reduced to 150 mg/m2 for the remaining 20 patients. Non-hematologic toxicities were minimal. Nine of 27 patients (33 %) who received 200 mg/m2 TMZ, but only 1 of 20 (5 %) who received 150 mg/m2, experienced grade 3/4 thrombocytopenia. Median progression free survival (PFS) and overall survival (OS) period was 8.5 and 18 months, respectively. The 1-year OS rate was 76 %, which is a significant improvement compared with the historical control 1-year OS rate of 59 % (p = 0.023). However, there was no difference in 1-year OS compared with standard RT/TMZ (p = 0.12) or BCNU wafer followed by RT/TMZ (p = 0.87) in post hoc analyses. Early post-operative TMZ can be safely administered with BCNU wafers following resection of malignant glioma at the 150 mg/m2 dose level. Although there was an OS benefit compared to historical control, there was no indication of benefit for BCNU wafers and early TMZ in addition to standard RT/TMZ or early TMZ in addition to regimens of BCNU wafers followed by RT/TMZ.

  18. Quality of life in patients with different constipation subtypes based on the Rome III criteria

    OpenAIRE

    M.C. Ruiz-López; E. Coss-Adame

    2015-01-01

    Background: Functional constipation and irritable bowel syndrome with constipation are highly prevalent and affect the quality of life of those who suffer from them. Aims: To evaluate quality of life in patients with functional constipation and irritable bowel disease in accordance with the Rome III criteria, using the PAC-QOL and SF-36 questionnaires. Materials and methods: A cross-sectional study was conducted using self-administered questionnaires. The PAC-QOL, SF-36, and Rome III co...

  19. Extra-Neural Metastases of Malignant Gliomas: Myth or Reality?

    Energy Technology Data Exchange (ETDEWEB)

    Beauchesne, Patrick [Neuro-Oncology, CHU de NANCY, Hôpital Central, CO n°34, 54035 Nancy Cedex (France)

    2011-01-27

    Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years— despite debulking surgery, radiotherapy and cytotoxic chemotherapy—with a median survival of 9–12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra-cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma metastases usually involve the regional lymph nodes, lungs and pleural cavity, and occasionally the bone and liver. In this review, we present three cases of extra-neural metastasis of malignant gliomas from our department, summarize the main reported cases in literature, and try to understand the mechanisms underlying these systemic metastases.

  20. Extra-Neural Metastases of Malignant Gliomas: Myth or Reality?

    International Nuclear Information System (INIS)

    Beauchesne, Patrick

    2011-01-01

    Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years— despite debulking surgery, radiotherapy and cytotoxic chemotherapy—with a median survival of 9–12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra-cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma metastases usually involve the regional lymph nodes, lungs and pleural cavity, and occasionally the bone and liver. In this review, we present three cases of extra-neural metastasis of malignant gliomas from our department, summarize the main reported cases in literature, and try to understand the mechanisms underlying these systemic metastases

  1. Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase

    International Nuclear Information System (INIS)

    Kalofonos, H.P.; Pawlikowska, T.R.; Hemingway, A.

    1989-01-01

    Twenty-seven patients with brain glioma were scanned using 123 I-labeled monoclonal antibodies against epidermal growth factor receptor (EGFR1) or placental alkaline phosphatase (H17E2). Successful localization was achieved in 18 out of 27 patients. Eleven out of 27 patients were also studied using a nonspecific control antibody (11.4.1) of the same immunoglobulin subclass and observable tumor localization was also achieved in five patients. The specificity of targeting was assessed by comparing images obtained with specific and nonspecific antibodies and by examining tumor and normal tissue biopsies after dual antibody administration. Ten patients with recurrent grade III or IV glioma who showed good localization of radiolabeled antibody were treated with 40-140 mCi of 131 I-labeled antibody delivered to the tumor area intravenously (n = 5) or by infusion into the internal carotid artery (n = 5). Six patients showed clinical improvement lasting from 6 mo to 3 yr. One patient continues in remission (3 yr after therapy), but the other five who responded initially relapsed 6-9 mo after therapy and died. No major toxicity was attributable to antibody-guided irradiation. Targeted irradiation by monoclonal antibody may be clinically useful and should be explored further in the treatment of brain gliomas resistant to conventional forms of treatment

  2. Craniofacial stability in patients with Crouzon or Apert syndrome after Le Fort III distraction osteogenesis

    NARCIS (Netherlands)

    Reitsma, J.H.; Ongkosuwito, E.M.; Buschang, P.H.; van Adrichem, L.N.A.; Prahl-Andersen, B.

    2013-01-01

    Objective: Le Fort III osteotomy with distraction osteogenesis (DO) is used to improve the retruded midface in patients with Crouzon or Apert syndrome. This study aimed to evaluate sagittal and vertical preoperative and postoperative cephalometric changes of DO of the midface in patients with

  3. Craniofacial stability in patients with crouzon or apert syndrome after le fort III distraction osteogenesis

    NARCIS (Netherlands)

    J.H. Reitsma (Jacobus Harmen); E.M. Ongkosuwito (Edwin); P.H. Buschang (Peter); L.N.A. V Adrichem (Léon); B. Prahl-Andersen (Birte)

    2013-01-01

    textabstractObjective: Le Fort III osteotomy with distraction osteogenesis (DO) is used to improve the retruded midface in patients with Crouzon or Apert syndrome. This study aimed to evaluate sagittal and vertical preoperative and postoperative cephalometric changes of DO of the midface in patients

  4. Risk of recurrence in patients with colon cancer stage II and III

    DEFF Research Database (Denmark)

    Bockelman, C.; Engelmann, Bodil E.; Kaprio, T.

    2015-01-01

    Background. Adjuvant chemotherapy is established routine therapy for colon cancer (CC) patients with radically resected stage III and 'high-risk' stage II disease. The decision on recommending adjuvant chemotherapy, however, is based on data from older patient cohorts not reflecting improvements...

  5. Crown-root morphology of lower incisors in patients with class III malocclusion.

    Science.gov (United States)

    Wang, Bo; Shen, Guofang; Fang, Bing; Zhang, Li

    2012-07-01

    The purpose of this study was to investigate the crown-root morphology of lower incisors in patients with class III malocclusion using cone-beam computed tomography. Cone-beam computed tomography images were analyzed from 53 adult class I patients (group 1), 37 preadolescent class III patients (group 2), and 66 adult class III patients (group 3) comprising 3 divisions (divisions 1, 2, and 3 corresponded to mild, moderate, and severe class III malocclusions). The size and crown-root angulations of lower incisors in different groups and divisions were statistically appraised with group 1 used as the control group. No significant differences were found for the size of lower incisors among different groups and divisions (P > 0.05). Compared with group 1, the crown-root angulations of lower incisors in groups 2 and 3 were significantly larger (P lower incisors of division 3 rather than divisions 2 and 3 exhibited larger crown-root angulations (P lower incisors in class III patients during orthodontic and orthognathic treatment, especially in severe ones.

  6. Glioma cell fate decisions mediated by Dll1-Jag1-Fringe in Notch1 signaling pathway.

    Science.gov (United States)

    Shi, Xiaofei; Wang, Ruiqi

    2017-09-21

    The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition. This paper presents a computational model for Notch1 signaling pathway in glioma cells. Based on the bifurcation analysis of the model, we show that how the glioma cell fate decisions are modulated by both trans-activation and cis-inhibition mediated by the Fringe protein, providing insight into the design and control principles of the Notch signaling system and the gliomas. This paper presents a computational model for Notch1 signaling pathway in glioma cells based on intertwined dynamics with cis-inhibition and trans-activation involving the proteins Notch1, Dll1, Jag1, and Fringe. The results show that how the glioma cell fate transitions are performed by the Notch1 signaling. Transition from grade III ∼ IV with significantly high Notch1 to grade I ∼ II with high Notch1, and then to normal cells by repressing the Fringe levels or decreasing the strength of enhancement induced by Fringe.

  7. Mutant IDH1 Promotes Glioma Formation In Vivo

    Directory of Open Access Journals (Sweden)

    Beatrice Philip

    2018-05-01

    Full Text Available Summary: Isocitrate dehydrogenase 1 (IDH1 is the most commonly mutated gene in grade II–III glioma and secondary glioblastoma (GBM. A causal role for IDH1R132H in gliomagenesis has been proposed, but functional validation in vivo has not been demonstrated. In this study, we assessed the role of IDH1R132H in glioma development in the context of clinically relevant cooperating genetic alterations in vitro and in vivo. Immortal astrocytes expressing IDH1R132H exhibited elevated (R-2-hydroxyglutarate levels, reduced NADPH, increased proliferation, and anchorage-independent growth. Although not sufficient on its own, IDH1R132H cooperated with PDGFA and loss of Cdkn2a, Atrx, and Pten to promote glioma development in vivo. These tumors resembled proneural human mutant IDH1 GBM genetically, histologically, and functionally. Our findings support the hypothesis that IDH1R132H promotes glioma development. This model enhances our understanding of the biology of IDH1R132H-driven gliomas and facilitates testing of therapeutic strategies designed to combat this deadly disease. : Philip et al. show that mutant IDH1 cooperates with PDGFA and loss of Cdkn2a, Atrx, and Pten to promote gliomagenesis in vivo in a mouse model of glioma. These tumors resemble proneural human mutant IDH1 glioblastoma and exhibit enhanced sensitivity to PARP inhibition in combination with chemotherapy. Keywords: IDH1, Cdkn2a, Atrx, Pten, glioma, mouse model, RCAS/TVA

  8. EGFR and EGFRvIII Promote Angiogenesis and Cell Invasion in Glioblastoma: Combination Therapies for an Effective Treatment

    Directory of Open Access Journals (Sweden)

    Stefanie Keller

    2017-06-01

    Full Text Available Epidermal growth factor receptor (EGFR and the mutant EGFRvIII are major focal points in current concepts of targeted cancer therapy for glioblastoma multiforme (GBM, the most malignant primary brain tumor. The receptors participate in the key processes of tumor cell invasion and tumor-related angiogenesis and their upregulation correlates with the poor prognosis of glioma patients. Glioma cell invasion and increased angiogenesis share mechanisms of the degradation of the extracellular matrix (ECM through upregulation of ECM-degrading proteases as well as the activation of aberrant signaling pathways. This review describes the role of EGFR and EGFRvIII in those mechanisms which might offer new combined therapeutic approaches targeting EGFR or EGFRvIII together with drug treatments against proteases of the ECM or downstream signaling to increase the inhibitory effects of mono-therapies.

  9. Time to Treatment in Patients With Stage III Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Wang Li; Correa, Candace R.; Hayman, James A.; Zhao Lujun; Cease, Kemp; Brenner, Dean; Arenberg, Doug; Curtis, Jeffery; Kalemkerian, Gregory P.; Kong, F.-M.

    2009-01-01

    Purpose: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. Methods and Materials: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. Results: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived ≥ 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). Conclusion: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.

  10. Evaluation of Patients' Satisfaction after Class III Orthognathic Surgery.

    Science.gov (United States)

    Magro-Filho, Osvaldo; Goiato, Marcelo Coelho; Oliveira, Derly Tescaro Narcizo; Martins, Lidia Pimenta; Salazar, Marcio; Medeiros, Rodrigo Antonio De; Santos, Daniela Micheline Dos

    2015-10-01

    Well-planned orthognathic surgery improves psychological health, aesthetics and function of patients. The present study aimed to investigate patients' satisfaction after orthognathic surgery by means of a satisfaction questionnaire before and after surgery. A total of 29 patients was selected (17 women and 12 men), with a mean age of 28 years, randomly selected from a private clinic at Araçatuba - São Paulo by two investigators. Anamnesis and clinical examination were performed. Subjects with facial deformities submitted to orthodontic treatment before and after orthognathic surgery with a minimum post-surgery period of 6 months, answered a satisfaction questionnaire composed of 10 questions regarding dental and facial aesthetics. In this study, the maximum satisfaction score was 10. Regarding aesthetics, two satisfaction parameters were investigated: dental and facial. For all indices, the average satisfaction was up to score 7. According to the results, it can be concluded that orthognathic surgery has been an effective treatment for dentofacial deformities, aesthetics and functional problems, what was verified by pre and postoperative questionnaire application.

  11. Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide.

    Science.gov (United States)

    Kaloshi, Gentian; Sierra del Rio, Monica; Ducray, François; Psimaras, Dimitri; Idbaih, Ahmed; Laigle-Donadey, Florence; Taillibert, Sophie; Houillier, Caroline; Dehais, Caroline; Omuro, Antonio; Sanson, Marc; Delattre, Jean-Yves; Hoang-Xuan, Khe

    2010-12-01

    There is a growing evidence of using Temozolomide as upfront therapy for progressive low grade gliomas. No data exist on the efficacy of nitrosoureas as an alternative to radiotherapy in those patients who progress after Temozolomide. We retrospectively reviewed 30 patients with median age of 46 years. Twenty-one patients had pure oligodendrogliomas. Thirteen patients had a non-enhancing tumor at progression after Temozolomide. The chromosomes 1p/19q were co-deleted in 5 cases and retained in 10 cases. Response rate was 10% (3 minor responses achieved in non-enhancing tumors). Tolerance was acceptable (17% grade III and IV myelosupression). Median PFS was 6.5 months. Median OS from start of salvage treatment was 23.4 months. Tumors without contrast enhancement demonstrated a better prognosis than those with contrast enhancement both in term of PFS (P = 0.0003) and OS (P = 0.0006). Chromosomes 1p/19q codeletion was not predictive for objective response to salvage treatment but correlated with a better PFS (P = 0.02). In conclusion, salvage NU chemotherapy provide disappointing results in TMZ-pretreated low grade gliomas (LGG), which should be treated in priority by conventional radiotherapy especially in LGG that display contrast enhancement at progression.

  12. Type I and III procollagen propeptides in growth hormone-deficient patients

    DEFF Research Database (Denmark)

    Jensen, L T; Jørgensen, J O; Risteli, J

    1991-01-01

    The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal...... propeptide of type III procollagen. Type I collagen is mainly found in bone and type III collagen in loose connective tissue. We observed a GH dose dependency of both procollagen propeptides. Serum type I procollagen propeptide was significantly higher following GH doses of 4 and 6 IU/day for 14 days...... procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective...

  13. Intraoperative Cerebral Glioma Characterization with Contrast Enhanced Ultrasound

    Directory of Open Access Journals (Sweden)

    Francesco Prada

    2014-01-01

    Full Text Available Background. Contrast enhanced ultrasound (CEUS is a dynamic and continuous modality providing real-time view of vascularization and flow distribution patterns of different organs and tumors. Nevertheless its intraoperative use for brain tumors visualization has been performed few times, and a thorough characterization of cerebral glioma had never been performed before. Aim. To perform the first characterization of cerebral glioma using CEUS and to possibly achieve an intraoperative differentiation of different gliomas. Methods. We performed CEUS in an off-label setting in 69 patients undergoing surgery for cerebral glioma. An intraoperative qualitative analysis was performed comparing iCEUS with B-mode imaging. A postprocedural semiquantitative analysis was then performed for each case, according to EFSUMB criteria. Results were related to histopathology. Results. We observed different CE patterns: LGG show a mild, dotted CE with diffuse appearance and slower, delayed arterial and venous phase. HGG have a high CE with a more nodular, nonhomogeneous appearance and fast perfusion patterns. Conclusion. Our study characterizes for the first time human brain glioma with CEUS, providing further insight regarding these tumors’ biology. CEUS is a fast, safe, dynamic, real-time, and economic tool that might be helpful during surgery in differentiating malignant and benign gliomas and refining surgical strategy.

  14. Utility of multiparametric 3-T MRI for glioma characterization

    International Nuclear Information System (INIS)

    Roy, Bhaswati; Gupta, Rakesh K.; Maudsley, Andrew A.; Sheriff, Sulaiman; Awasthi, Rishi; Mohakud, Sudipta; Gu, Meng; Spielman, Daniel M.; Husain, Nuzhat; Behari, Sanjay; Pandey, Chandra M.; Rathore, Ram K.S.; Alger, Jeffry R.

    2013-01-01

    Accurate grading of cerebral glioma using conventional structural imaging techniques remains challenging due to the relatively poor sensitivity and specificity of these methods. The purpose of this study was to evaluate the relative sensitivity and specificity of structural magnetic resonance imaging and MR measurements of perfusion, diffusion, and whole-brain spectroscopic parameters for glioma grading. Fifty-six patients with radiologically suspected untreated glioma were studied with T1- and T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, diffusion tensor imaging, and volumetric whole-brain MR spectroscopic imaging. Receiver-operating characteristic analysis was performed using the relative cerebral blood volume (rCBV), apparent diffusion coefficient, fractional anisotropy, and multiple spectroscopic parameters to determine optimum thresholds for tumor grading and to obtain the sensitivity, specificity, and positive and negative predictive values for identifying high-grade gliomas. Logistic regression was performed to analyze all the parameters together. The rCBV individually classified glioma as low and high grade with a sensitivity and specificity of 100 and 88 %, respectively, based on a threshold value of 3.34. On combining all parameters under consideration, the classification was achieved with 2 % error and sensitivity and specificity of 100 and 96 %, respectively. Individually, CBV measurement provides the greatest diagnostic performance for predicting glioma grade; however, the most accurate classification can be achieved by combining all of the imaging parameters. (orig.)

  15. Gene expression of manganese superoxide dismutase in human glioma cells

    Directory of Open Access Journals (Sweden)

    Novi S. Hardiany

    2010-02-01

    Full Text Available Aim This study analyze the MnSOD gene expression as endogenous antioxidant in human glioma cells compared with leucocyte cells as control.Methods MnSOD gene expression of 20 glioma patients was analyzed by measuring the relative expression of mRNA and enzyme activity of MnSOD in brain and leucocyte cells. The relative expression of mRNA MnSOD was determined by using quantitative Real Time RT-PCR and the enzyme activity of MnSOD using biochemical kit assay (xantine oxidase inhibition. Statistic analysis for mRNA and enzyme activity of MnSOD was performed using Kruskal Wallis test.Results mRNA of MnSOD in glioma cells of 70% sample was 0.015–0.627 lower, 10% was 1.002-1.059 and 20% was 1.409-6.915 higher than in leucocyte cells. Also the specific activity of MnSOD enzyme in glioma cells of 80% sample showed 0,064-0,506 lower and 20% sample was 1.249-2.718 higher than in leucocyte cells.Conclusion MnSOD gene expression in human glioma cells are significantly lower than its expression in leucocytes cells. (Med J Indones 2010; 19:21-5Keywords : MnSOD, glioma, gene expression

  16. A new anti-glioma therapy, AG119: pre-clinical assessment in a mouse GL261 glioma model.

    Science.gov (United States)

    Towner, Rheal A; Ihnat, Michael; Saunders, Debra; Bastian, Anja; Smith, Nataliya; Pavana, Roheeth Kumar; Gangjee, Aleem

    2015-07-17

    High grade gliomas (HGGs; grades III and IV) are the most common primary brain tumors in adults, and their malignant nature ranks them fourth in incidence of cancer death. Standard treatment for glioblastomas (GBM), involving surgical resection followed by radiation and chemotherapy with temozolomide (TMZ) and the anti-angiogenic therapy bevacizumab, have not substantially improved overall survival. New therapeutic agents are desperately needed for this devastating disease. Here we study the potential therapeutic agent AG119 in a pre-clinical model for gliomas. AG119 possesses both anti-angiogenic (RTK inhibition) and antimicrotubule cytotoxic activity in a single molecule. GL261 glioma-bearing mice were either treated with AG119, anti-VEGF (vascular endothelial growth factor) antibody, anti c-Met antibody or TMZ, and compared to untreated tumor-bearing mice. Animal survival was assessed, and tumor volumes and vascular alterations were monitored with morphological magnetic resonance imaging (MRI) and perfusion-weighted imaging, respectively. Percent survival of GL261 HGG-bearing mice treated with AG119 was significantly higher (p mouse GL261 glioma model, and that AG119 is also not subject to methyl guanine transferase (MGMT) mediated resistance, as is the case with TMZ, indicating that AG119 may be potentially useful in treating resistant gliomas.

  17. Report of a randomised pilot study of the treatment of patients with supratentorial gliomas using neutron irradiation

    International Nuclear Information System (INIS)

    Duncan, W.; McLelland, J.; Jack, W.J.L.; Arnott, S.J.; Kerr, G.R.; Williams, J.R.; Gordon, A.

    1986-01-01

    A randomised pilot study is reported of d(15) + Be neutrons compared with 4 MV photons in the treatment of patients with astrocytoma. Sixteen patients were treated by photons and 18 by neutrons. Both treatments were well tolerated by patients. The median survival after photons was 11 months and after neutrons, 7 months. It was demonstrated that four of nine patients treated by neutrons had evidence at autopsy of radiation-induced brain damage. All had residual cancer. No patient treated by photons had signs of radiation-related morbidity. The trial was, therefore, discontinued prematurely. (author)

  18. A longitudinal, qualitative and quantitative exploration of daily life and need for rehabilitation among patients with high-grade gliomas and their caregivers

    DEFF Research Database (Denmark)

    Piil, K; Jarden, Mary Ellen; Jakobsen, J

    2013-01-01

    High-grade gliomas (HGGs) are the most malignant type of brain tumours. The 5-year survival is 10% and a significant part of the ongoing research aims to increase survival through surgical and oncological treatments. Accordingly, there is an increasing need for investigating the HGG trajectory...

  19. The Role of Radiation Therapy in the Treatment of Intracranial Glioma : Retrospective Analysis of 96 Cases

    International Nuclear Information System (INIS)

    Kim, Yeon Sil; Kang, Ki Mun; Choi, Byung Ock; Yoon, Sei Chul; Shinn, Kyung Sub; Kang, Jun Gi

    1993-01-01

    Between March 1983 and December 1989, ninety-six patients with intracranial glioma were treated in the Department of Therapeutic Radiology, Kangnam St. Mary Hospital, Catholic University Medical College. We retrospectively reviewed each case to evaluate variable factors influencing the treatment results and to develop an optimal therapy Policy. Median follow-up is 57 months(range:31-133 months). Of the 96 patients, 60(63%) were males and 36(37%) were females. Ages ranged from 3 to 69 years (median 42 years). The most common presenting symptoms were headache(67%) followed by cerebral motor and sensory discrepancy(54%), nausea and vomiting(34%), seizure (19%), mental change(10%) and memory and calculation impairment(8%). Eighty five(88.5%) patients all, except 11(11.5%) brain stem lesions, were biopsy proven intracranial glioma. The distribution by histologic type was 64 astrocytomas(75%), 4 mixed oligoastrocytomas(5%), and 17 oligodendrogliomas(20%). Fourty nine patients (58% were grade I, II histology and 36 (42%) patients were grade III, IV histology. Of the 96 patients, 64(67%) received postoperative RT and 32(33%) were treated with primary radiotherapy. Gross total resection was performed in 14(16%) patients, subtotal resection in 29(34%), partial resection in 21(25%), and biopsy only in 21(25%). Median survival time was 53 months(range 21-133 months), and 2- and, 5-year survival rate were 69%, 49% respectively. 5-year survival rate by histologic grade was grade I, 70%, grade II, 58%, grade III, 28%, and grade IV, 15%. Multivariated analysis demonstrate that age at diagnosis (p=0.121), Karnofsky performance Status(KPS)(p=0.0002), histologic grade(p=0.0001), postoperative radiation therapy(p=0.0278), surgical extent(p=0.024), cerebellar location of tumor(p=0.0095) were significant prognostic factors influencing on survival

  20. Patients with High-Grade Gliomas Harboring Deletions of Chromosomes 9p and 10q Benefit from Temozolomide Treatment

    Directory of Open Access Journals (Sweden)

    Silke Wemmert

    2005-10-01

    Full Text Available Surgical cure of glioblastomas is virtually impossible and their clinical course is mainly determined by the biologic behavior of the tumor cells and their response to radiation and chemotherapy. We investigated whether response to temozolomide (TMZ chemotherapy differs in subsets of malignant glioblastomas defined by genetic lesions. Eighty patients with newly diagnosed glioblastoma were analyzed with comparative genomic hybridization and loss of heterozygosity. All patients underwent radical resection. Fifty patients received TMZ after radiotherapy (TMZ group and 30 patients received radiotherapy alone (RT group. The most common aberrations detected were gains of parts of chromosome 7 and losses of 10% 9p, or 13q. The spectrum of genetic aberrations did not differ between the TMZ and RT groups. Patients treated with TMZ showed significantly better survival than patients treated with radiotherapy alone (19.5 vs 9.3 months. Genomic deletions on chromosomes 9 and 10 are typical for glioblastoma and associated with poor prognosis. However, patients with these aberrations benefited significantly from TMZ in univariate analysis. In multivariate analysis, this effect was pronounced for 9p deletion and for elderly patients with 10q deletions, respectively. This study demonstrates that molecular genetic and cytogenetic analyses potentially predict responses to chemotherapy in patients with newly diagnosed glioblastomas.

  1. Radiosensitivity and TP 53, EGFR amplification and LOH10 analysis of primary glioma cell cultures

    NARCIS (Netherlands)

    Gerlach, Bärbel; Harder, Anna H.; Hulsebos, Theo J. M.; Leenstra, Sieger; Slotman, Berend J.; Vandertop, W. Peter; Hartmann, Karl-Axel; Sminia, Peter

    2002-01-01

    Aim: Determination of in-vitro radiosensitivity and genetic alterations of cell cultures derived from human glioma biopsy tissue and established glioma cell lines. Material and Methods: Fresh brain tumor specimens of six patients were processed to early passage cell cultures. In addition the cell

  2. Identification of Predictive Response Markers and Novel Treatment Targets for Gliomas

    NARCIS (Netherlands)

    L. Erdem-Eraslan (Lale)

    2016-01-01

    markdownabstractGliomas are the most frequent primary brain tumors in adults. Despite multimodality treatment strategies, the survival of patients with a diffuse glioma remains poor. There has been an increasing use of molecular markers to assist diagnosis and predict prognosis and response to

  3. Ectopic High Expression of E2-EPF Ubiquitin Carrier Protein Indicates a More Unfavorable Prognosis in Brain Glioma.

    Science.gov (United States)

    Zhang, Xiaohui; Zhao, Fangbo; Zhang, Shujun; Song, Yichun

    2017-04-01

    Ubiquitination of proteins meant for elimination is a primary method of eukaryotic cellular protein degradation. The ubiquitin carrier protein E2-EPF is a key degradation enzyme that is highly expressed in many tumors. However, its expression and prognostic significance in brain glioma are still unclear. The aim of this study was to reveal how the level of E2-EPF relates to prognosis in brain glioma. Thirty low-grade and 30 high-grade brain glioma samples were divided into two tissue microarrays each. Levels of E2-EPF protein were examined by immunohistochemistry and immunofluorescence. Quantitative real-time polymerase chain reaction was used to analyze the level of E2-EPF in 60 glioma and 3 normal brain tissue samples. The relationship between E2-EPF levels and prognosis was analyzed by Kaplan-Meier survival curves. E2-EPF levels were low in normal brain tissue samples but high in glioma nuclei. E2-EPF levels gradually increased as glioma grade increased (p EPF levels in high-grade glioma were significantly higher than in low-grade glioma (p EPF levels was shorter than in patients with low expression (p EPF was significantly shorter than patients with only nuclear E2-EPF (p EPF levels, especially ectopic, are associated with higher grade glioma and shorter survival. E2-EPF levels may play a key role in predicting the prognosis for patients with brain glioma.

  4. Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

    International Nuclear Information System (INIS)

    Patel, Samir; Portelance, Lorraine; Gilbert, Lucy; Tan, Leonard; Stanimir, Gerald; Duclos, Marie; Souhami, Luis

    2007-01-01

    Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) compared with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients

  5. Minimally invasive neuronavigator-guided microsurgery and photodynamic therapy for gliomas.

    Science.gov (United States)

    Wang, Yezhong; Lei, Ting; Wang, Zhi

    2009-06-01

    In order to evaluate the effectiveness of neuronavigator-guided microsurgery and keyhole technique for the resection of gliomas, a total of 60 patients with gliomas were exactly located by using neuronavigator during microsurgery. Forty deep-seated gliomas were resected through a keyhole operative approach. Thirty out of the 60 cases were subjected to photodynamic therapy (PDT) after tumor resection. The therapeutic effectiveness of all the cases was recorded and analyzed. The results showed that glioma was totally resected in 52 cases (86.7%), subtotally in 5 (8.3%), and most partially in 3 (5%). Neurological deficits occurred postoperatively in 4 cases. One patient died of multiple system organ failure 4 days after operation. It was concluded that the application of minimally invasive technique could dramatically decrease surgical complications following resection of glioma, and its combination with PDT could obviously improve the quality of life of patients and prolong the survival time.

  6. Perspectives in Intraoperative Diagnostics of Human Gliomas

    Directory of Open Access Journals (Sweden)

    O. Tyurikova

    2015-01-01

    Full Text Available Amongst large a variety of oncological diseases, malignant gliomas represent one of the most severe types of tumors. They are also the most common type of the brain tumors and account for over half of the astrocytic tumors. According to different sources, the average life expectancy of patients with various glioblastomas varies between 10 and 12 months and that of patients with anaplastic astrocytic tumors between 20 and 24 months. Therefore, studies of the physiology of transformed glial cells are critical for the development of treatment methods. Modern medical approaches offer complex procedures, including the microsurgical tumor removal, radiotherapy, and chemotherapy, supplemented with photodynamic therapy and immunotherapy. The most radical of them is surgical resection, which allows removing the largest part of the tumor, reduces the intracranial hypertension, and minimizes the degree of neurological deficit. However, complete removal of the tumor remains impossible. The main limitations are insufficient visualization of glioma boundaries, due to its infiltrative growth, and the necessity to preserve healthy tissue. This review is devoted to the description of advantages and disadvantages of modern intraoperative diagnostics of human gliomas and highlights potential perspectives for development of their treatment.

  7. Mandibular condyle dimensions in Peruvian patients with Class II and Class III skeletal patterns.

    Directory of Open Access Journals (Sweden)

    Hugo Zegarra-Baquerizo

    2017-10-01

    Full Text Available Objective: To compare condylar dimensions of young adults with Class II and Class III skeletal patterns using cone-beam computed tomography (CBCT. Materials and methods: 124 CBCTs from 18-30 year-old patients, divided into 2 groups according to skeletal patterns (Class II and Class III were evaluated. Skeletal patterns were classified by measuring the ANB angle of each patient. The anteroposterior diameter (A and P of the right and left mandibular condyle was assessed from a sagittal view by a line drawn from point A (anterior to P (posterior. The coronal plane allowed the evaluation of the medio-lateral diameter by drawing a line from point M (medium to L (lateral; all distances were measured in mm. Results: In Class II the A-P diameter was 9.06±1.33 and 8.86±1.56 for the right and left condyles respectively, in Class III these values were 8.71±1.2 and 8.84±1.42. In Class II the M-L diameter was 17.94±2.68 and 17.67±2.44 for the right and left condyles respectively, in Class III these values were 19.16±2.75 and 19.16±2.54. Conclusion: Class III M-L dimensions showed higher values than Class II, whereas these differences were minimal in A-P.

  8. In vivo detection of inducible nitric oxide synthase in rodent gliomas.

    Science.gov (United States)

    Towner, Rheal A; Smith, Nataliya; Doblas, Sabrina; Garteiser, Philippe; Watanabe, Yasuko; He, Ting; Saunders, Debra; Herlea, Oana; Silasi-Mansat, Robert; Lupu, Florea

    2010-03-01

    Increased iNOS expression is often found in brain tumors, such as gliomas. The goal of this study was to develop and assess a novel molecular MRI (mMRI) probe for in vivo detection of iNOS in rodent models for gliomas (intracerebral implantation of rat C6 or RG2 cells or ethyl nitrosourea-induced glioma). The probe we used incorporated a Gd-DTPA (gadolinium(III) complex of diethylenetriamine-N,N,N',N'',N''-pentaacetate) backbone with albumin and biotin moieties and covalent binding of an anti-iNOS antibody (Ab) to albumin (anti-iNOS probe). We used mMRI with the anti-iNOS probe to detect in vivo iNOS levels in gliomas. Nonimmune normal rat IgG coupled to albumin-Gd-DTPA-biotin was used as a control nonspecific contrast agent. By targeting the biotin component of the anti-iNOS probe with streptavidin Cy3, fluorescence imaging confirmed the specificity of the probe for iNOS in glioma tissue. iNOS levels in glioma tumors were also confirmed via Western blots and immunohistochemistry. The presence of plasma membrane-associated iNOS in glioma cells was established by transmission electron microscopy and gold-labeled anti-iNOS Ab. The more aggressive RG2 glioma was not found to have higher levels of iNOS compared to C6. Differences in glioma vascularization and blood-brain barrier permeability between the C6 and the RG2 gliomas are discussed. In vivo assessment of iNOS levels associated with tumor development is quite feasible in heterogeneous tissues with mMRI. (c) 2009 Elsevier Inc. All rights reserved.

  9. Introduction of a standardized multimodality image protocol for navigation-guided surgery of suspected low-grade gliomas.

    Science.gov (United States)

    Mert, Aygül; Kiesel, Barbara; Wöhrer, Adelheid; Martínez-Moreno, Mauricio; Minchev, Georgi; Furtner, Julia; Knosp, Engelbert; Wolfsberger, Stefan; Widhalm, Georg

    2015-01-01

    visualization. This new protocol was feasible and was estimated to be surgically relevant during navigation-guided surgery in all 11 patients. According to the authors' predefined surgical outcome parameters, they observed a complete resection in all resectable gliomas (n = 5) by using contour visualization with T2-weighted or FLAIR images. Additionally, tumor tissue derived from the metabolic hotspot showed the presence of malignant tissue in all WHO Grade III or IV gliomas (n = 5). Moreover, no permanent postoperative neurological deficits occurred in any of these patients, and fiber tracking and/or intraoperative monitoring were applied during surgery in the vast majority of cases (n = 10). Furthermore, the authors found a significant intraoperative topographical correlation of 3D brain surface and vessel models with gyral anatomy and superficial vessels. Finally, real-time navigation with multimodality imaging data using the advanced electromagnetic navigation system was found to be useful for precise guidance to surgical targets, such as the tumor margin or the metabolic hotspot. CONCLUSIONS In this study, the authors defined a specific protocol for multimodality imaging data in suspected LGGs, and they propose the application of this new protocol for advanced navigation-guided procedures optimally in conjunction with continuous electromagnetic instrument tracking to optimize glioma surgery.

  10. Radiotherapy in supratentorial gliomas. A study of 821 cases

    International Nuclear Information System (INIS)

    Heesters, M.; Molenaar, W.; Go, G.K.

    2003-01-01

    Purpose: Analysis of the results of radiotherapy in a large group of cerebral gliomas with identification of prognostic factors and the outcome with respect to different decades of treatment. Patients and Methods: Two decades (1979-1999) of radiotherapy in supratentorial astrocytic and oligodendroglial tumors (n = 821) at the University Hospital Groningen were retrospectively evaluated. Prognostic factors for survival were analyzed. Two decades of radiotherapy treatment were compared with respect to radiotherapy dose and treatment-field design. Results: Glioblastoma multiforme, including gliosarcoma, was the most frequent supratentorial glioma (n = 442) with a poor survival, i.e., median survival time (MST) 7 months, especially in patients > 50 years of age and with poor performance. Patients with good performance were selected for radiotherapy with an optimum dose of 60 Gy local-field irradiation. However, in patients with poor prognosis, no radiotherapy was applied or a shorter treatment scheme was given. Anaplastic astrocytomas (n = 131) were treated in the same way as glioblastoma multiforme. Over time, a decrease in radiation dose (from 60 to 45 Gy) and from whole brain irradiation to local-field treatment was observed, following the literature. In low-grade gliomas, prognostic factors for survival were age, performance, and extent of resection. Gemistocytic astrocytoma (n = 15) had an inferior survival compared to astrocytoma (MST 46 vs. 54 months), but a superior survival compared to anaplastic astrocytoma (MST 10 months). The presence of an oligodendroglial component in a glioma implied a superior survival compared to the astrocytic gliomas. The inherent biology of the glioma is reflected by the study of recurrent tumors with progression to higher grades of malignancy in 32-40% and by the histology of recurrent oligodendroglial tumors. In comparing two decades of radiotherapy in gliomas, no differences in survival were observed despite the technological

  11. Radiotherapy in supratentorial gliomas. A study of 821 cases

    Energy Technology Data Exchange (ETDEWEB)

    Heesters, M. [Dept. of Radiotherapy, Groningen Univ. Hospital (Netherlands); Molenaar, W. [Dept. of Pathology, Groningen Univ. Hospital (Netherlands); Go, G.K. [Dept. of Neurosurgery, Groningen Univ. Hospital (Netherlands)

    2003-09-01

    Purpose: Analysis of the results of radiotherapy in a large group of cerebral gliomas with identification of prognostic factors and the outcome with respect to different decades of treatment. Patients and Methods: Two decades (1979-1999) of radiotherapy in supratentorial astrocytic and oligodendroglial tumors (n = 821) at the University Hospital Groningen were retrospectively evaluated. Prognostic factors for survival were analyzed. Two decades of radiotherapy treatment were compared with respect to radiotherapy dose and treatment-field design. Results: Glioblastoma multiforme, including gliosarcoma, was the most frequent supratentorial glioma (n = 442) with a poor survival, i.e., median survival time (MST) 7 months, especially in patients > 50 years of age and with poor performance. Patients with good performance were selected for radiotherapy with an optimum dose of 60 Gy local-field irradiation. However, in patients with poor prognosis, no radiotherapy was applied or a shorter treatment scheme was given. Anaplastic astrocytomas (n = 131) were treated in the same way as glioblastoma multiforme. Over time, a decrease in radiation dose (from 60 to 45 Gy) and from whole brain irradiation to local-field treatment was observed, following the literature. In low-grade gliomas, prognostic factors for survival were age, performance, and extent of resection. Gemistocytic astrocytoma (n = 15) had an inferior survival compared to astrocytoma (MST 46 vs. 54 months), but a superior survival compared to anaplastic astrocytoma (MST 10 months). The presence of an oligodendroglial component in a glioma implied a superior survival compared to the astrocytic gliomas. The inherent biology of the glioma is reflected by the study of recurrent tumors with progression to higher grades of malignancy in 32-40% and by the histology of recurrent oligodendroglial tumors. In comparing two decades of radiotherapy in gliomas, no differences in survival were observed despite the technological

  12. Cortical GABAergic excitation contributes to epileptic activities around human glioma

    Science.gov (United States)

    Pallud, Johan; Varlet, Pascale; Cresto, Noemie; Baulac, Michel; Duyckaerts, Charles; Kourdougli, Nazim; Chazal, Geneviève; Devaux, Bertrand; Rivera, Claudio; Miles, Richard; Capelle, Laurent; Huberfeld, Gilles

    2015-01-01

    Rationale Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study. Objective We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities. Results Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. Conclusions Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients. PMID:25009229

  13. Glioma in a goat

    International Nuclear Information System (INIS)

    Marshall, C.L.; Weinstock, D.; Kramer, R.W.; Bagley, R.S.

    1995-01-01

    An adult goat was examined because of behavioral changes and circling. Results of neurologic examination, CSF analysis, hematologic evaluation, and computed tomography of the brain were suggestive of an intra-axial mass. The goat was euthanatized because of worsening neurologic condition and poor prognosis. Necropsy revealed a large mass in the right cerebral hemisphere and caudal brain herniation through the foramen magnum. The mass was diagnosed as a glioma, with oligodendrocyte differentiation. Results of immunohistochemical evaluation were compatible with a malignant, poorly differentiated tumor

  14. The majority of patients with metastatic melanoma are not represented in pivotal phase III immunotherapy trials

    DEFF Research Database (Denmark)

    Donia, Marco; Kimper-Karl, Marie Louise; Høyer, Katrine Lundby

    2017-01-01

    BACKGROUND: Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of 'real-world' patients diag...... a huge knowledge gap regarding the usefulness of new immunotherapies in the 'real-world' patient population, and urge additional testing of known regimens in selected poor prognosis cohorts.......BACKGROUND: Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of 'real-world' patients...... in 2014, were included in the analysis. Seven pre-defined eligibility criteria, all used to select patients for enrolment in five recent randomised phase III immunotherapy trials, were analysed. RESULTS: Fifty-five percent of the total population with MM did not meet one or more eligibility criteria ('not...

  15. Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Tao Fu

    Full Text Available O6-methylguanine-DNA methyltransferase (MGMT methylation status has not been extensively investigated in duodenal adenocarcinoma (DA. The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA.Demographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP, microsatellite instability (MSI, and KRAS mutations.MGMT methylation was detected in 17 of 64 (26.6% patients, and was not correlated with sex, age, tumor differentiation, CIMP, MSI, or KRAS mutations. MGMT methylation was the only one factor associated with both overall survival (OS and disease-free survival (DFS on both univariate and multivariate analyses. In patients treated with surgery alone, MGMT-methylated group had worse OS and DFS when compared with MGMT-unmethylated group. However, in patients treated with chemotherapy/radiotherapy, outcomes became comparable between the two groups.Our results demonstrate MGMT methylation is a reliable and independent prognostic factor in DAs. Methylation of MGMT is associated with poor prognosis in patients with stage III DAs.

  16. Awake Craniotomy with Noninvasive Brain Mapping by 3-Tesla Functional Magnetic Resonance Imaging for Excision of Low-grade Glioma: A Case of a Young Patient from Pakistan.

    Science.gov (United States)

    Aleem Bhatti, Atta Ul; Jakhrani, Nasir Khan; Parekh, Maria Adnan

    2018-01-01

    The past few years have seen increasing support for gross total resection in the management of low-grade gliomas (LGGs), with a greater extent of resection correlated with better overall survival, progression-free survival, and time to malignant transformation. There is consistent evidence in literature supporting extent of safe resection as a good prognostic indicator as well as positively affecting seizure control, symptomatic relief in pressure symptoms, and longer progression-free and total survival. The operative goal in most LGG cases is to maximize the extent of resection for these benefits while avoiding postoperative neurologic deficits. Several advanced invasive and noninvasive surgical techniques such as intraoperative magnetic resonance imaging (MRI), fluorescence-guided surgery, intraoperative functional pathway mapping, and neuronavigation have been developed in an attempt to better achieve maximal safe resection. We present a case of LGG in a young patient with a 5-year history of refractory seizures and gradual onset walking difficulty. Serial MRI brain scans revealed a progressive increase in right frontal tumor size with substantial edema and parafalcine herniation. Noninvasive brain mapping by functional MRI (fMRI) and sleep-awake-sleep type of anesthesia with endotracheal tube insertion was utilized during an awake craniotomy. Histopathology confirmed a Grade II oligodendroglioma, and genetic analysis revealed no codeletion at 1p/19q. Neurological improvement was remarkable in terms of immediate motor improvement, and the patient remained completely seizure free on a single antiepileptic drug. There is no radiologic or clinical evidence of recurrence 6 months postoperatively. This is the first published report of an awake craniotomy for LGG in Pakistan. The contemporary concept of supratotal resection in LGGs advocates generous functional resection even beyond MRI findings rather than mere excision of oncological boundaries. This relatively

  17. “...those left behind.” Biology and Oncology of Invasive Glioma Cells

    Directory of Open Access Journals (Sweden)

    Michael E Berens

    1999-08-01

    Full Text Available Although significant technical advances in surgical and radiation treatment for brain tumors have emerged in recent years, their impact on clinical outcome for patients has been disappointing. A fundamental source of the management challenge presented by glioma patients is the insidious propensity of the malignant cells to invade into adjacent normal brain. Invasive tumor cells escape surgical removal and geographically dodge lethal radiation exposure. Recent improved understanding of the biochemistry and molecular determinants of glioma cell invasion provide valuable insight to the underlying biological features of the disease, as well as illuminating possible new therapeutic targets. Heightened commitment to migrate and invade is accompanied by a glioma cell's reduced proliferative activity. The microenvironmental manipulations coincident to invasion and migration may also impact the glioma cell's response to cytotoxic treatments. These collateral aspects of the glioma cell invasive phenotype should be further explored and exploited as novel antiglioma therapies.

  18. Response assessment of bevacizumab in patients with recurrent malignant glioma using [{sup 18}F]Fluoroethyl-l-tyrosine PET in comparison to MRI

    Energy Technology Data Exchange (ETDEWEB)

    Galldiks, Norbert; Fink, Gereon R. [Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Juelich, Juelich (Germany); University of Cologne, Department of Neurology, Cologne (Germany); Rapp, Marion; Sabel, Michael [University of Duesseldorf, Department of Neurosurgery, Duesseldorf (Germany); Stoffels, Gabriele; Shah, Nadim J.; Coenen, Heinz H.; Langen, Karl-Josef [Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Juelich, Juelich (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Aachen (Germany)

    2013-01-15

    To investigate prospectively the potential of O-(2-[{sup 18}F]fluoroethyl)-l-tyrosine ({sup 18}F-FET) PET in comparison to MRI for the assessment of the response of patients with recurrent high-grade glioma (rHGG) to antiangiogenic treatment. Ten patients with rHGG were treated biweekly with bevacizumab/irinotecan (BEV/IR). MR images and dynamic {sup 18}F-FET PET scans were obtained at baseline and at follow-up after the start of treatment (median 4.9 weeks). Using MRI treatment response was evaluated according to RANO (Response Assessment in Neuro-Oncology) criteria. For {sup 18}F-FET PET evaluation, a reduction >45 % of the metabolically active tumour volume was considered as a treatment response, with the metabolically active tumour being defined as a tumour-to-brain ratio (TBR) of {>=}1.6. The results of the treatment assessments were related to progression-free survival (PFS) and overall survival (OS). For further evaluation of PET data, maximum and mean TBR were calculated using region-of-interest analysis at baseline and at follow-up. Additionally, {sup 18}F-FET uptake kinetic studies were performed at baseline and at follow-up in all patients. Time-activity curves were generated and the times to peak (TTP) uptake (in minutes from the beginning of the dynamic acquisition to the maximum uptake) were calculated. At follow-up, MRI showed a complete response according to RANO criteria in one of the ten patients (10 %), a partial response in five patients (50 %), and stable disease in four patients (40 %). Thus, MRI did not detect tumour progression. In contrast, {sup 18}F-FET PET revealed six metabolic responders (60 %) and four nonresponders (40 %). In the univariate survival analyses, a response detected by {sup 18}F-FET PET predicted a significantly longer PFS (median PFS, 9 vs. 3 months; P = 0.001) and OS (median OS 23.0 months vs. 3.5 months; P = 0.001). Furthermore, in four patients (40 %), diagnosis according to RANO criteria and by {sup 18}F-FET PET was

  19. Spectrum of bone marrow changes in patients of chronic kidney disease (stage iii, iv and v)

    International Nuclear Information System (INIS)

    Latif, R.K.; Khan, S.A.; Ahmad, S.Q.; Arshad, U.

    2017-01-01

    To see the various hematological changes in the bone marrow of patients with chronic kidney disease (CKD) stage III, IV and V. Study Design: Cross sectional observational study.Place and Duration of Study: Study was conducted in the department of haematology (Pathology), Army Medical College, Rawalpindi and duration was one year, from Mar 2015 to Feb 2016. Material and Methods: Patients of both sexes and all age groups with CKD stage III, IV and V were included in this study. Patients' histories were recorded. Complete blood counts, bone marrow aspiration and trephine biopsy were done and evaluated microscopically. Mean blood counts of the patients in three groups of CKD were compared. Frequencies of various bone marrow (BM) findings in patients of CKD were calculated. Results: Out of 57 patients, 41 (71.9%) were males while 16 (28%) were females. Mean age was 60 years. There was no statistically significant difference between the mean hemoglobin, mean white cell count and mean platelets count of the patients in three groups of CKD. Reactive changes due to underlying CKD and inflammation were the most frequent findings in the BM of the patients. Conclusion: Anaemia of mild to moderate severity and reactive changes in the BM are the most frequent haematological findings encountered in patients suffering from advanced stage CKD. Since CKD is predominantly a disease of the elderly so it is not rare to find the co-morbidities including plasmacytosis, malignancies and their effects on the BM in patients of CKD. (author)

  20. Survival after stereotactic biopsy of malignant gliomas

    International Nuclear Information System (INIS)

    Coffey, R.J.; Lunsford, L.D.; Taylor, F.H.

    1988-01-01

    For many patients with malignant gliomas in inaccessible or functionally important locations, stereotactic biopsy followed by radiation therapy (RT) may be a more appropriate initial treatment than craniotomy and tumor resection. We studied the long term survival in 91 consecutive patients with malignant gliomas diagnosed by stereotactic biopsy: 64 had glioblastoma multiforme (GBM) and 27 had anaplastic astrocytoma (AA). Sixty-four per cent of the GBMs and 33% of the AAs involved deep or midline cerebral structures. The treatment prescribed after biopsy, the tumor location, the histological findings, and the patient's age at presentation (for AAs) were statistically important factors determining patient survival. If adequate RT (tumor dose of 5000 to 6000 cGy) was not prescribed, the median survival was less than or equal to 11 weeks regardless of tumor histology or location. The median survival for patients with deep or midline tumors who completed RT was similar in AA (19.4 weeks) and GBM (27 weeks) cases. Histology was an important predictor of survival only for patients with adequately treated lobar tumors. The median survival in lobar GBM patients who completed RT was 46.9 weeks, and that in lobar AA patients who completed RT was 129 weeks. Cytoreductive surgery had no statistically significant effect on survival. Among the clinical factors examined, age of less than 40 years at presentation was associated with prolonged survival only in AA patients. Constellations of clinical features, tumor location, histological diagnosis, and treatment prescribed were related to survival time

  1. CURRENT APPROACHES TO CHEMORADIOTHERAPY FOR MALIGNANT GLIOMAS

    Directory of Open Access Journals (Sweden)

    Ye. L. Choinzonov

    2014-01-01

    Full Text Available High-grade malignant gliomas (WHO grade G III–IV account for more than 50% of all primary brain tumors. Despite aggressive treatment, survival rates are still very low with a median reported survival of no more than 1.5 years.Radiation therapy is an integral part of the combined treatment, but often does not influence lethally on resistant tumor cells. Thereby, in recent decades there has been an active search for novel approaches to the treatment of malignant gliomas (chemotherapeutic drugs, biological modifiers, local hyperthermia. Experimental data showed that the effect of high temperatures has both a direct damaging effect on tumor cells and a sensitizing effect. Significant advantages are achieved when the complex treatment of different malignant tumorsincludes local hyperthermia. However data on the treatment of patients with primary and recurrent gliomas G III–IV using local hyperthermia are scarce.The literature review is given in the article provides an overview of the existing treatment methods for brain tumors.

  2. Meningiomas, dicentric chromosomes, gliomas, and telomerase activity.

    Science.gov (United States)

    Carroll, T; Maltby, E; Brock, I; Royds, J; Timperley, W; Jellinek, D

    1999-08-01

    Lack of telomere maintenance during cell replication leads to telomere erosion and loss of function. This can result in telomere associations which probably cause the dicentric chromosomes seen in some tumour cells. One mechanism of telomere maintenance in dividing cells is the action of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening during cell division. Over 90 per cent of extracranial malignant neoplasms have been found to have telomerase activity. This study sought to determine if there was a relationship between absence of telomerase activity and presence of dicentric chromosomes in meningiomas and to what extent the other main group of central nervous system tumours, the gliomas, expressed telomerase activity. Telomerase activity was measured on 25 meningiomas and 29 gliomas. Four of the meningiomas were atypical variants and 11 were positive for dicentric chromosomes. Twenty-five of 29 gliomas were glioblastoma multiforme tumours. Measures were taken to ensure absence of false positives due to primer-dimer interaction and false negatives due to protein degradation or the presence of Taq polymerase inhibitors. All 25 meningiomas and the four low-grade gliomas (WHO grade II) were telomerase activity-negative. Seven (28 per cent) of the 25 glioblastoma multiforme tumours showed telomerase activity. The absence of telomerase activity in meningiomas and the high frequency of telomere associations support the hypothesis that these tumours are benign, transformed but pre-crisis. The relatively low frequency of telomerase activity in the malignant glioblastoma multiforme suggests that most of these tumours may have other mechanisms of telomere maintenance and that the potentially therapeutic telomerase inhibitors will not be of great value in the future management of the majority of patients suffering from these tumours. Copyright 1999 John Wiley & Sons, Ltd.

  3. Object-action dissociation: A voxel-based lesion-symptom mapping study on 102 patients after glioma removal

    Directory of Open Access Journals (Sweden)

    Alberto Pisoni

    Full Text Available Data concerning the neural basis of noun and verb processing are inconsistent. Some authors assume that action-verb processing is based on frontal areas while nouns processing relies on temporal regions; others argue that the circuits processing verbs and nouns are closely interconnected in a predominantly left-lateralized fronto-temporal-parietal network; yet, other researchers consider that the primary motor cortex plays a crucial role in processing action verbs. In the present study, one hundred and two patients with a tumour either in the right or left hemisphere were submitted to picture naming of objects and actions before and after surgery. To test the effect of specific brain regions in object and action naming, patients' lesions were mapped and voxel-lesion-symptom mapping (VLSM was computed. Behavioural results showed that left-brain damaged patients were significantly more impaired than right brain-damaged patients. The VLSM showed that these two grammatical classes are segregated in the left hemisphere. In particular, scores in naming of objects correlated with damage to the anterior temporal region, while scores in naming of actions correlated with lesions in the parietal areas and in the posterior temporal cortex. In addition, VLSM analyses carried out on non-linguistic tasks were not significant, confirming that the regions associated with deficits in object and action naming were not generally engaged in all cognitive tasks. Finally, the involvement of subcortical pathways was investigated and the inferior longitudinal fasciculus proved to play a role in object naming, while no specific bundle was identified for actions. Keywords: Object action dissociation, Temporal lesion, Frontal lesion, Voxel-based lesion symptom mapping

  4. Hypothalamic glioma masquerading as craniopharyngioma

    Directory of Open Access Journals (Sweden)

    Sameer Vyas

    2013-01-01

    Full Text Available Hypothalamic glioma account for 10-15% of supratentorial tumors in children. They usually present earlier (first 5 years of age than craniopharyngioma. Hypothalamic glioma poses a diagnostic dilemma with craniopharyngioma and other hypothalamic region tumors, when they present with atypical clinical or imaging patterns. Neuroimaging modalities especially MRI plays a very important role in scrutinizing the lesions in the hypothalamic region. We report a case of a hypothalamic glioma masquerading as a craniopharyngioma on imaging along with brief review of both the tumors.

  5. Evaluation of temporomandibular disorders in Class III patients treated with mandibular cervical headgear and fixed appliances.

    Science.gov (United States)

    Rey, Diego; Oberti, Giovanni; Baccetti, Tiziano

    2008-03-01

    Our aim in this study was to evaluate the prevalence of temporomandibular disorders (TMD) in Class III patients treated with mandibular cervical headgear (MCH) and fixed appliances. The sample of 75 patients included 25 patients with no previous orthodontic treatment, 25 Class I patients who had undergone orthodontic treatment with fixed appliances and without extractions, and 25 patients with dentoskeletal Class III disharmonies treated with MCH and fixed appliances. The Helkimo index was used to test the prevalence of TMD symptoms in the 3 groups. The prevalence rates of the Helkimo index in the 3 groups were compared with the z score on proportions. No statistically significant differences in the prevalence rates of the Helkimo index scores in the 3 groups were found (P = .367). Most subjects in the 3 groups had an Helkimo index of zero (66.7%). Subjects with Class III malocclusions treated with MCH and fixed appliances do not have greater prevalence of TMD symptoms than do Class I subjects treated with fixed appliances or untreated subjects.

  6. The impact of reliable pre-bolus T1 measurements or a fixed T1 value in the assessment of glioma patients with Dynamic Contrast Enhancing MRI

    DEFF Research Database (Denmark)

    Tietze, Anna; Mouridsen, Kim; Mikkelsen, Irene Klærke

    2015-01-01

    ) investigate if accurate estimation of DCE parameters outperform a time-saving approach with a pre-defined T1 value when differentiating high- from low-grade gliomas. Methods: (i) The accuracy and precision of T1 measurements, acquired by VFA and SR was investigated by computer simulations and in glioma...... to differentiate tumor grade. Results: The T1 values obtained by VFA showed larger variation compared to those obtained using SR both in the digital phantom and the human data (p > 0.05). Although a fixed T1 introduced a bias into the DCE calculation, this had only minor impact on the accuracy differentiating high......-quantitative DCE values, based on pre-defined T1 values, were sufficient to perform tumor grading in our study....

  7. Tricyclic Neovibsanin Scaffold Inhibits Glioma by Targeting Glioma ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. ... median survival time of mice bearing glioma to 34 days compared to 22 days in untreated mice. .... CX22 microscope (Olympus Corp, Inc, Tokyo,.

  8. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma

    NARCIS (Netherlands)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J. A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-01-01

    In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with

  9. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

    NARCIS (Netherlands)

    Ribas, A.; Kefford, R.; Marshall, Martin; Punt, C.J.A.; Haanen, J.B.; Marmol, M.; Garbe, C.; Gogas, H.; Schachter, J.; Linette, G.; Lorigan, P.; Kendra, K.L.; Maio, M.; Trefzer, U.; Smylie, M.; McArthur, G.A.; Dreno, B.; Nathan, P.D.; Mackiewicz, J.; Kirkwood, J.M.; Gomez-Navarro, J.; Huang, B.; Pavlov, D.; Hauschild, A.

    2013-01-01

    PURPOSE: In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients

  10. Preliminary clinical trial of immunotherapy for malignant glioma.

    Science.gov (United States)

    Ingram, M; Shelden, C H; Jacques, S; Skillen, R G; Bradley, W G; Techy, G B; Freshwater, D B; Abts, R M; Rand, R W

    1987-10-01

    An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

  11. Regrowth patterns of supratentorial gliomas: estimation from computed tomographic scans

    Energy Technology Data Exchange (ETDEWEB)

    Tsuboi, K.; Yoshii, Y.; Nakagawa, K.; Maki, Y.

    1986-12-01

    To clarify the regrowth patterns of benign and malignant gliomas, we chose 27 intervals (between two operations or between an operation and autopsy) from 21 patients with pathologically verified recurrent supratentorial gliomas. Serial computed tomographic (CT) scans of these cases were analyzed to determine the doubling time (Td) calculated from the change in volume of enhanced and low density areas, the enhancement effect graded from 0 to 4 according to the Hounsfield number, and the presence of dissemination and contralateral extension. We studied 5 benign gliomas (including 1 case of radiation necrosis), 8 malignant astrocytomas, and 8 glioblastomas. The Td's of enhanced areas on CT scans of benign gliomas, malignant astrocytomas, and glioblastomas were 937 +/- 66.5 days, 65.1 +/- 29.4 days, and 48.1 +/- 20.9 days, respectively. The Td's of low density areas were 895 +/- 130.6 days, 70.8 +/- 22.2 days, and 50.5 +/- 14.7 days. There was a significant correlation between the Td's of the enhanced and low density areas (0.97). The enhancement effect increased at recurrence in 55% of the cases, with an average increase of 1.1 grades. The increase in enhancement effect at recurrence showed a tendency to become smaller as the tumor's degree of anaplasia increased. Radiotherapy was effective in significantly retarding the growth rate of malignant gliomas, whose Td's were doubled. Although the Td's of both enhanced and low density areas of benign gliomas were significantly longer than those of malignant gliomas, there was no significant difference in the Td's of enhanced areas between malignant astrocytomas and glioblastomas.

  12. Regrowth patterns of supratentorial gliomas: estimation from computed tomographic scans

    International Nuclear Information System (INIS)

    Tsuboi, K.; Yoshii, Y.; Nakagawa, K.; Maki, Y.

    1986-01-01

    To clarify the regrowth patterns of benign and malignant gliomas, we chose 27 intervals (between two operations or between an operation and autopsy) from 21 patients with pathologically verified recurrent supratentorial gliomas. Serial computed tomographic (CT) scans of these cases were analyzed to determine the doubling time (Td) calculated from the change in volume of enhanced and low density areas, the enhancement effect graded from 0 to 4 according to the Hounsfield number, and the presence of dissemination and contralateral extension. We studied 5 benign gliomas (including 1 case of radiation necrosis), 8 malignant astrocytomas, and 8 glioblastomas. The Td's of enhanced areas on CT scans of benign gliomas, malignant astrocytomas, and glioblastomas were 937 +/- 66.5 days, 65.1 +/- 29.4 days, and 48.1 +/- 20.9 days, respectively. The Td's of low density areas were 895 +/- 130.6 days, 70.8 +/- 22.2 days, and 50.5 +/- 14.7 days. There was a significant correlation between the Td's of the enhanced and low density areas (0.97). The enhancement effect increased at recurrence in 55% of the cases, with an average increase of 1.1 grades. The increase in enhancement effect at recurrence showed a tendency to become smaller as the tumor's degree of anaplasia increased. Radiotherapy was effective in significantly retarding the growth rate of malignant gliomas, whose Td's were doubled. Although the Td's of both enhanced and low density areas of benign gliomas were significantly longer than those of malignant gliomas, there was no significant difference in the Td's of enhanced areas between malignant astrocytomas and glioblastomas

  13. Normalization of ADC does not improve correlation with overall survival in patients with high-grade glioma (HGG).

    Science.gov (United States)

    Qin, Lei; Li, Angie; Qu, Jinrong; Reinshagen, Katherine; Li, Xiang; Cheng, Su-Chun; Bryant, Annie; Young, Geoffrey S

    2018-04-01

    Mixed reports leave uncertainty about whether normalization of apparent diffusion coefficient (ADC) to a within-subject white matter reference is necessary for assessment of tumor cellularity. We tested whether normalization improves the previously reported correlation of resection margin ADC with 15-month overall survival (OS) in HGG patients. Spin-echo echo-planar DWI was retrieved from 3 T MRI acquired between maximal resection and radiation in 37 adults with new-onset HGG (25 glioblastoma; 12 anaplastic astrocytoma). ADC maps were produced with the FSL DTIFIT tool (Oxford Centre for Functional MRI). 3 neuroradiologists manually selected regions of interest (ROI) in normal appearing white matter (NAWM) and in non-enhancing tumor (NT) Normalized ADC (nADC) was computed as the ratio of absolute NT ADC to NAWM ADC. Reproducibility of nADC and absolute ADC among the readers' ROI was assessed using intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wCV). Correlations of ADC and nADC with OS were compared using receiver operating characteristics (ROC) analysis. A p value 0.05 was considered statistically significant. Both mean ADC and nADC differed significantly between patients subgrouped by 15-month OS (p = 0.0014 and 0.0073 respectively). wCV and ICC among the readers were similar for absolute and normalized ADC. In ROC analysis of correlation with OS, nADC did not perform significantly better than absolute ADC. Normalization does not significantly improve the correlation of absolute ADC with OS in HGG, suggesting that normalization is not necessary for clinical or research ADC analysis in HGG patients.

  14. Shift of microRNA profile upon glioma cell migration using patient-derived spheroids and serum-free conditions

    DEFF Research Database (Denmark)

    Munthe, Sune; Halle, Bo; Boldt, Henning B

    2017-01-01

    Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being...... therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM...... cells using serum-free stem cell conditions. We used patient-derived GBM spheroid cultures for a novel serum-free migration assay. MiRNA expression of migrating tumor cells isolated at maximum migration speed was compared with corresponding spheroids using an OpenArray Real-Time PCR System. The mi...

  15. A pilot clinical study of Class III surgical patients facilitated by improved accelerated osteogenic orthodontic treatments.

    Science.gov (United States)

    Wu, JiaQi; Jiang, Jiu-Hui; Xu, Li; Liang, Cheng; Bai, YunYang; Zou, Wei

    2015-07-01

    To evaluate if the improved accelerated osteogenic orthodontics (IAOO) procedure could speed Class III surgical patients' preoperative orthodontic treatment duration and, if yes, to what extent. This study was also designed to determine whether or not an IAOO procedure affects the tooth-moving pattern during extraction space closure. The samples in this study consisted of 24 Class III surgical patients. Twelve skeletal Class III surgery patients served as an experimental group (group 1) and the others as a control group (group 2). Before treatment, the maxillary first premolars were removed. For group 1, after the maxillary dental arch was aligned and leveled (T2), IAOO procedures were performed in the maxillary alveolar bone. Except for this IAOO procedure in group 1, all 24 patients experienced similar combined orthodontic and orthognathic treatment. Study casts of the maxillary dentitions were made before orthodontic treatment (T1) and after extraction space closure (T3). All of the casts were laser scanned, and the amount of movement of the maxillary central incisor, canine, and first molar, as well as arch widths, were digitally measured and analyzed by using the three-dimensional model superimposition method. The time durations T3-T2 were significantly reduced in group 1 by 8.65 ± 2.67 months and for T3-T1 were reduced by 6.39 ± 2.00 months (P teeth movement in the sagittal, vertical, and transverse dimensions between the two groups (P > .05). The IAOO can reduce the surgical orthodontic treatment time for the skeletal Class III surgical patient by more than half a year on average. The IAOO procedures do not save anchorage.

  16. Elevated levels of CXC chemokine connective tissue activating peptide (CTAP)-III in lung cancer patients.

    Science.gov (United States)

    Lee, Gina; Gardner, Brian K; Elashoff, David A; Purcell, Colleen M; Sandha, Harpavan S; Mao, Jenny T; Krysan, Kostyantyn; Lee, Jay M; Dubinett, Steven M

    2011-05-15

    Despite advances in treatments, lung cancer has been the leading cause of cancer-related deaths in the United States for the past several decades. Recent findings from the National Lung Screening Trial reveal that low-dose helical computed tomography (CT) scan screening of high-risk individuals reduces lung cancer mortality. This suggests that early detection is of key importance to improving patient outcome. However, of those screened with CT scans, 25% had positive scans that require further follow-up studies which often involve more radiation exposure and invasive tests to reduce false positive results. The purpose of this study was to identify candidate plasma biomarkers to aid in diagnosis of lung cancer in at-risk individuals. We found increased expression of the CXC chemokine connective tissue-activating peptide (CTAP)-III from plasma specimens of lung cancer patients compared to at-risk control subjects. Identification of the peptide was confirmed by the addition of an anti-NAP-2 antibody that recognizes CTAP-III and NAP-2. We also quantified and verified the increased levels of plasma CTAP-III with ELISA in patients with lung cancer (mean ± SD, 1859 ± 1219 ng/mL) compared to controls (698 ± 434 ng/mL; Pcancer patients. Further studies are required to determine if this chemokine could be utilized in a blood-based biomarker panel for the diagnosis of lung cancer.

  17. KDM2B overexpression correlates with poor prognosis and regulates glioma cell growth

    Directory of Open Access Journals (Sweden)

    Wang Y

    2018-01-01

    Full Text Available Yiwei Wang,1 Jin Zang,1 Dongyong Zhang,2 Zhenxiang Sun,1 Bo Qiu,2 Xiaojie Wang1 1Department of Human Anatomy, Shenyang Medical College, Huanggu District, Shenyang City, 2Department of Neurosurgery, First Affiliated Hospital of China Medical University, Heping District, Shenyang City, Liaoning Province, ChinaBackground: Gliomas are one of the most lethal cancers in the human central nervous system. Despite clinical treatment advancements, the prognosis of patients with glioma remains poor. KDM2B is a histone lysine demethylase, which has been observed in multiple tumors. But the concrete role of KDM2B in gliomas remains to be further illustrated.Methods: The KDM2B expression in gliomas was detected with immunohistochemistry and Western blot assay. Furthermore, knockdown of KDM2B in U87 and U251 glioma cell lines, the proliferation capacity was evaluated by cell viability assay, colon formation assay and flow cytometry in vitro. Western blot assay was used to analyze the p21, EZH2 and cyclinD1 changes followed by knockdown of KDM2B.Results: KDM2B was upregulated in tissues of glioma patients, and the expression was correlated to cancer progression. Downregulation of KDM2B in U87 and U251 glioma cell lines inhibited cell proliferation and arrested cell cycle in G0/G1 phase. In addition, silencing KDM2B promoted the upregulation of p21 while reduced the expression of EZH2 and cyclinD1.Conclusion: Taken together, our results revealed that KDM2B might influence gliomas growth and act as a novel therapeutic target for glioma patients.Keywords: EZH2, glioma, KDM2B, P21