[Brainlife] Newsletter, Vol.4 No.38

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BRAINLIFE NEWSLETTER

Volume 4, Number 38 - 13 September 2005	Volume 4 Archive

1: Br J Neurosurg. 2005 Feb;19(1):65-8.

Cutaneous metastasis from glioblastoma.

Jain N, Mirakhur M, Flynn P, Choudhari KA.

Department of Neurosurgery, Regional Neurosciences Unit, Royal Victoria Hospital, Belfast, UK.

A rare case of glioblastoma with isolated cutaneous metastasis adjacent to the scar site is described. Its pathogenesis and clinical significance are discussed.

PMID: 16147588 [PubMed - in process]..

2: Br J Neurosurg. 2005 Feb;19(1):61-5.: Spontaneous transdural spread of glioblastoma with atypical presentation.

Shenoy SN, Raja A.

Department of Neurosurgery, Kasturba Medical College and Hospital, Manipal, India. shenoysn@yahoo.com

The dura provides an excellent protection against infiltration by malignant tumours. It is extremely rare for glial tumour cells to infiltrate the dura and subsequently invade adjacent structures. We report an interesting case of glioblastoma of the temporal lobe with spontaneous transdural spread to the skull base and infratemporal fossa. This is the first radiologically documented case of transdural spread of glioblastoma before and after the spread without previous craniotomy.

PMID: 16147587 [PubMed - in process]..

3: Br J Neurosurg. 2005 Feb;19(1):25-32.: Real-time functional magnetic resonance imaging (rt-fMRI) in patients with brain tumours: preliminary findings using motor and language paradigms.

Schwindack C, Siminotto E, Meyer M, McNamara A, Marshall I, Wardlaw JM, Whittle IR.

Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.

Functional MRI (fMRI) shows areas of the brain that are active during a task, but the standard approach (offline analysis after the imaging has finished) precludes tailoring of the imaging to the individual patient, e.g. for assessing normal function around an individual lesion. The aims of the study were to explore the technical feasibility of acquiring functional images in real-time (rt-fMRI), develop the necessary software interfaces and protocols for image acquisition, and to compare images of functional activation acquired in real-time with the standard offline statistical parametric method in patients with solitary brain tumours. Patients with a solitary supratentorial lesion were studied. The rt-fMRI paradigms were sequential finger opposition, ankle movement and language function (correct recognition of grammatically violated sentences). Datasets were analysed using AFNI software (National Institute of Mental Health, Bethesda, Maryland, USA) for the real-time analysis and SPM99 (Functional Imaging Laboratory, University College, London, UK) for the offline analysis. From 11 patients, useful data were obtained in nine. The finger tapping task produced most consistent activation between real-time and offline analysis with good anatomic localization to the primary motor cortex contralateral to the tapping finger. Ankle movement produced weaker activation and correlation with real-time analysis. For the language task the offline analysis provided reproducible activation patterns, but the real-time method showed no activation at the chosen threshold of p = 0.001. Tumourous areas of brain did not show any activation with either method of analysis during any task. rt-fMRI is feasible and could be a valuable functional evaluation tool in the planning of surgery for tumours in motor regions of the brain. Further paradigm development is required for evaluation of language, and possibly other more complex executive functions.

PMID: 16147579 [PubMed - in process]..

4: Br J Neurosurg. 2005 Feb;19(1):13-20.: The use of stereotactic radiosurgery in the management of meningiomas.

Malik I, Rowe JG, Walton L, Radatz MW, Kemeny AA.

National Centre for Stereotactic Radiosurgery, Royal Hallamshire Hospital, Sheffield, UK.

This is a systematic review of a consecutive series of 309 meningiomas treated with gamma knife stereotactic radiosurgery between 1994 and 2000. There was an extreme selection bias towards lesions unfavourable for surgery, determined by the patients referred for treatment: 70% of tumours involved the skull base, 47% specifically the cavernous sinus: 15% of patients had multiple meningiomatosis or type 2 neurofibromatosis. Tumour histology was the main determinant of growth control (p < 0.001), the 5-year actuarial control rates being 87% for typical meningiomas, 49% for atypical tumours and 0% for malignant lesions. Complications from radiosurgery were rare, occurring in 3% of tumours, and were most frequently trigeminal and eye movement disturbances treating cavernous sinus meningiomas. Given the problems inherent in managing these tumours, radiosurgery is a valuable strategy and adjuvant treatment for these meningiomas.

PMID: 16147577 [PubMed - in process]..

5: Cancer Res. 2005 Sep 1;65(17):7674-81.: Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry.

Schwartz SA, Weil RJ, Thompson RC, Shyr Y, Moore JH, Toms SA, Johnson MD, Caprioli RM.

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8575, USA.

Clinical diagnosis and treatment decisions for a subset of primary human brain tumors, gliomas, are based almost exclusively on tissue histology. Approaches for glioma diagnosis can be highly subjective due to the heterogeneity and infiltrative nature of these tumors and depend on the skill of the neuropathologist. There is therefore a critical need to develop more precise, non-subjective, and systematic methods to classify human gliomas. To this end, mass spectrometric analysis has been applied to these tumors to determine glioma-specific protein patterns. Protein profiles have been obtained from human gliomas of various grades through direct analysis of tissue samples using matrix-assisted laser desorption ionization mass spectrometry (MS). Statistical algorithms applied to the MS profiles from tissue sections identified protein patterns that correlated with tumor histology and patient survival. Using a data set of 108 glioma patients, two patient populations, a short-term and a long-term survival group, were identified based on the tissue protein profiles. In addition, a subset of 57 patients diagnosed with high-grade, grade IV, malignant gliomas were analyzed and a novel classification scheme that segregated short-term and long-term survival patients based on the proteomic profiles was developed. The protein patterns described served as an independent indicator of patient survival. These results show that this new molecular approach to monitoring gliomas can provide clinically relevant information on tumor malignancy and is suitable for high-throughput clinical screening.

PMID: 16140934 [PubMed - in process]..

6: Cancer Res. 2005 Sep 1;65(17):7573-9.: IFN-beta down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide.

Natsume A, Ishii D, Wakabayashi T, Tsuno T, Hatano H, Mizuno M, Yoshida J.

Center for Genetic and Regenerative Medicine, Nagoya University Hospital, Japan. anatsume@med.nagoya-u.ac.jp

Alkylating agents, such as temozolomide, are among the most effective cytotoxic agents used for malignant gliomas, but responses remain very poor. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in cellular resistance to alkylating agents. IFN-beta can act as a drug sensitizer, enhancing toxicity against a variety of neoplasias, and is widely used in combination with other antitumor agents such as nitrosoureas. Here, we show that IFN-beta sensitizes glioma cells that harbor the unmethylated MGMT promoter and are resistant to temozolomide. By means of oligonucleotide microarray and RNA interference, we reveal that the sensitizing effect of IFN-beta was possibly due to attenuation of MGMT expression via induction of the protein p53. Our study suggests that clinical efficacy of temozolomide might be improved by combination with IFN-beta using appropriate doses and schedules of administration.

PMID: 16140920 [PubMed - in process]

7: Cancer Res. 2005 Jul 1;65(13):5750-60.: Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells.

Dimitroff CJ, Descheny L, Trujillo N, Kim R, Nguyen V, Huang W, Pienta KJ, Kutok JL, Rubin MA.

Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA. cdimitroff@rics.bwh.harvard.edu

Prostate tumor cells, which characteristically metastasize to bone, initiate binding interactions with bone marrow endothelium under blood flow conditions through binding interactions with E-selectin. We hypothesized that E-selectin ligands on prostate tumor cells are directly associated with bone-metastatic potential. In this report, we elucidate the identity of E-selectin ligands on human metastatic prostate tumor cells and examine their association with prostate tumor progression and metastasis in vivo. To our surprise, we found that the E-selectin-binding form of P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on the human bone-metastatic prostate tumor MDA PCa 2b cell line. Interestingly, we also found that human prostate tumor cells derived from bone, lymph node, and brain metastases expressed another leukocyte E-selectin ligand, E-selectin ligand-1 (ESL-1). Immunohistochemical analysis of PSGL-1 and ESL-1 in normal prostate tissue and in localized and metastatic prostate tumors revealed that ESL-1 was principally localized to intracellular cell membrane and expressed on all normal and malignant prostate tissue, whereas PSGL-1 was notably detected on the surfaces of bone-metastatic prostate tumor cells. These findings implicate a functional role of PSGL-1 in the bone tropism of prostate tumor cells and establish a new perspective into the molecular mechanism of human prostate tumor metastasis.

PMID: 15994950 [PubMed - indexed for MEDLINE]

8: Cancer Res. 2005 Jul 1;65(13):5493-7.: Ionizing radiation-induced adenovirus infection is mediated by Dynamin 2.

Qian J, Yang J, Dragovic AF, Abu-Isa E, Lawrence TS, Zhang M.

Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.

Specific viral targeting into intrahepatic tumors remains critical for adenovirus gene therapy in liver cancer. We previously showed that ionizing radiation increases adenovirus uptake and transgene expression in cells and colon cancer xenografts. Here, we tested whether radiation induces viral uptake through virus-cell membrane interaction. We found that radiation (8 Gy) induced adenoviral gene transfer in rat hepatocytes (WB) and human colon carcinoma cells (LoVo). This induction (24.4- and 6.5-fold, respectively) and viral uptake were significantly diminished by preincubation with antibody for Dynamin 2 but not for Coxsackie adenovirus receptor or for integrin alpha(v). Radiation-induced Dynamin 2 expression was detected by immunohistochemical staining and by increased mRNA levels for Dynamin 2 in WB (1.5-fold) and LoVo (2.2-fold) cells. Specific small interference RNA (siRNA) transfection significantly inhibited Dynamin 2 expression in various tumor cell lines (LoVo, D54, and MCF-7) and abolished the radiation induction of Dynamin 2. Likewise, radiation-induced viral gene transfer in these cells (6.5-, 5.5-, and 9.0-fold, respectively) was significantly reduced in siRNA-transfected cells (2.7-, 3.7-, and 5.0-fold, respectively). Moreover, viral uptake in LoVo tumor xenografts was significantly increased in s.c. tumors (10.9-fold) when adenovirus was given i.v. at 24 hours after tumor irradiation, coincident with an elevated Dynamin 2 expression in irradiated tumors. These data suggest that ionizing radiation induces adenovirus gene transfer in cells and tumor xenografts by regulating viral uptake, potentially through interaction with cellular Dynamin 2 and thus should provide insight into improving adenovirus targeting in tumors.

PMID: 15994918 [PubMed - indexed for MEDLINE]

9: Int J Cancer. 2005 Sep 8; [Epub ahead of print]: Hormonal and reproductive factors and risk of glioma: A prospective cohort study.

Silvera SA, Miller AB, Rohan TE.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, USA.

The etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. Given the lower incidence rate of glioma in women than in men, it has been hypothesized that reproductive and hormonal factors may be involved in the etiology of glioma. We conducted a secondary analysis of data from the National Breast Screening Study, which included 89,835 Canadian women, aged 40-59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between hormonal and reproductive factors and risk of glioma. During a mean of 16.4 years of follow-up, we observed 120 incident glioma cases. Compared with women with a relatively early age at menarche (</=12 years), women who were 13-14 years of age at menarche had a 64% increased risk of glioma (95% CI = 1.01-2.65), and women who were older than 14 years of age at menarche had a 66% increased risk of glioma (95% CI = 0.86-3.20, p(trend) = 0.06). Age at first live birth, parity, menopausal status, use of oral contraceptive and use of hormone replacement therapy were not associated with altered glioma risk in our study population. Additional prospective studies are needed to confirm our findings. (c) 2005 Wiley-Liss, Inc.

PMID: 16152609 [PubMed - as supplied by publisher]

10: Int J Cancer. 2005 Sep 8; [Epub ahead of print]: Identification of a glioma antigen, GARC-1, using cytotoxic T lymphocytes induced by HSV cancer vaccine.

Iizuka Y, Kojima H, Kobata T, Kawase T, Kawakami Y, Toda M.

Neuroimmunology Research Group, Keio University School of Medicine, Tokyo, Japan.

Despite several ongoing clinical trials of immunotherapies against glioma, few glioma-specific antigens recognized by cytotoxic T lymphocytes (CTLs) have been identified. We recently demonstrated that intratumoral inoculation with herpes simplex virus (HSV) as a cancer vaccine activates tumor-specific CTLs. To identify glioma antigens recognized by CTLs, we used the HSV cancer vaccine to vaccinate mice harboring a syngeneic mouse glioma cell line, GL261. From the splenocytes of the immunized mice, we generated an H-2D(b)-restricted CTL line, GCL-1, that was specific for GL261. Then, a cDNA expression library generated from GL261 was screened with GCL-1, and a new gene encoding glioma antigen, GARC-1, was isolated. Sequence analysis revealed that the GARC-1 gene isolated from GL261 had a point mutation causing an amino acid change (Asp to Asn at position 81). T-cell epitope analysis revealed that the mutated peptide GARC-1(77-85) (AALLNKLYA) but not the wild-type peptide (AALLDKLYA), was recognized by GCL-1. These results suggest that HSV cancer vaccination may be a useful method for inducing tumor-specific CTLs and identifying tumor antigens. Furthermore, this GL261/GARC-1 murine glioma model may be useful for the development of immunotherapy for brain tumors. (c) 2005 Wiley-Liss, Inc.

PMID: 16152596 [PubMed - as supplied by publisher]

11: J Neurooncol. 2005 Sep 2; [Epub ahead of print]: Multisection (1)H Magnetic Resonance Spectroscopic Imaging Assessment of Glioma Response to Chemotherapy.

Balmaceda C, Critchell D, Mao X, Cheung K, Pannullo S, Delapaz RL, Shungu DC.

Departments of Neurology, College of Physicians and Surgeons, Columbia University, USA.

This study evaluated the role of proton magnetic resonance spectroscopic imaging ((1)H MRSI) in assessing the response of low-grade brain tumors to a chemotherapy-only treatment regimen. Specifically, it was of interest to assess if (1)H MRSI could detect early tumor response to therapy prior to magnetic resonance imaging (MRI) changes, and to establish which spectral markers were sensitive to regional changes within and around a heterogeneous tumor mass. A total of 14 patients with lower-grade gliomas were evaluated by multislice (1)H MRSI, MRI and clinical examination. Changes associated with chemotherapy were assessed by longitudinal comparisons of regional levels of choline (Cho), N-acetyl-L: -aspartate (NAA), and lactate (Lac) relative to total creatine. These changes were, in turn, compared to changes on pre- and post-contrast MR images and to each patient's clinical status. In enhancing tumor regions, there was a significant association between an increase in Lac/Cr during treatment and decreased progression-free survival time. At baseline, a low NAA/Cr in normal-appearing brain tissue adjacent to non-enhancing tumor was associated with decreased progression-free survival time, as was an increase in Cho/Cr during chemotherapy. An increase in Cho/Cr and Lac/Cr in normal-appearing brain regions next to non-enhancing tumor in one patient was noted 2 months before MRI showed progressive disease. These results suggest that (1)H MRSI can be a powerful adjunct to MRI in the assessment of tumor response to chemotherapy, and that Cho/Cr and Lac/Cr appear to be the most reliable markers of tumor progression and may predict response prior to MRI changes.

PMID: 16151595 [PubMed - as supplied by publisher]

12: J Neuropathol Exp Neurol. 2005 Sep;64(9):754-762.: Microglia Stimulate the Invasiveness of Glioma Cells by Increasing the Activity of Metalloprotease-2.

Markovic DS, Glass R, Synowitz M, Rooijen NV, Kettenmann H.

From the Cellular Neuroscience Group (DSM, RG, MS, HK), Max Delbruck Center for Molecular Medicine (MDC), Berlin, Germany; the Department of Neurosurgery (MS), Helios Hospital Berlin, Berlin, Germany; and the Department of Molecular Cell Biology (NvR), Faculty of Medicine, Amsterdam, The Netherlands.

Gliomas represent the most frequent type of human brain tumor, and their strong invasiveness is a significant clinical problem. Microglia, the immunocompetent cells of the brain, contribute significantly to the tumor and are potential interaction partners of the glioma cells. We studied the impact of the presence of microglia on tumor cell invasion in cultured brain slices. To selectively deplete microglia, the slices were treated with clodronate-filled liposomes. When glioma cells were injected into slices devoid of endogenous microglia, the invasiveness of the tumors was significantly decreased as compared with controls. Inoculation of exogenous microglia together with glioma cells into cultured brain slices increased the infiltrative behavior of the tumor depending on the microglia/glioma cell ratio. Cell culture experiments revealed that soluble factors released from glioma cells strongly stimulate metalloprotease-2 activity in microglia. In the brain slices inoculated with glioma cells, increased activity of metalloprotease-2 was directly correlated with the abundance of microglia. Our data indicate that glioma cells stimulate microglial cells to increase breakdown of extracellular matrix and thereby promote tumor invasiveness.

PMID: 16141784 [PubMed - as supplied by publisher]

13: Neuroradiology. 2005 Sep 2; [Epub ahead of print]: Follow-up gliomas after radiotherapy: (1)H MR spectroscopic imaging for increasing diagnostic accuracy.

Lichy MP, Plathow C, Schulz-Ertner D, Kauczor HU, Schlemmer HP.

Department of Radiology, German Cancer Research Center, Heidelberg, Germany.

We evaluated the value of magnetic resonance imaging (MRI) and the additional benefit of proton MR spectroscopic imaging ((1)H SI) in patients with a new suspicious lesion after fractionated stereotactic radiotherapy (FSRT) of a glioma. Thirty-four patients with histologically proven astrocytoma WHO II-IV after treatment by FSRT and a new suspect lesion in the follow-up were included in this study. Data were analysed by three independent radiologists with different experience in (1)H SI: Data were verified by clinical follow-up (PT, progressive tumour; nPT, non-progressive tumour) and a kappa analysis was performed. Sensitivity and specificity of T(1) weighted (w) and T(2)w MRI was compared (imaging at radiotherapy and follow-up) using further follow-up controls as gold standard and the additional benefit of (1)H SI (imaging at follow-up) was calculated. Mean interval between last irradiation and detection of a suspicious lesion was 37 +/- 32 months. Time to clinical evaluation was 13 +/- 8 months. Interobserver agreement was significantly high in all analyses (kappa always >0.8, P < 0.05). T(2)w imaging proved to be superior to contrast enhanced T(1)w imaging in sensitivity (87.5 vs 81.25%) and specificity (85.7 vs 57.1%). Solitary (1)H SI had similar results as T(2)w (sensitivity 87.5%, specificity 71.4%). Taking all techniques into account, all PT were correctly diagnosed. Radiologists' experience had no significant influence on correct interpretation of a suspicious lesion. We conclude that ( 1)H SI is helpful in characterising new suspicious lesions in irradiated gliomas, particularly if pre-MRI is not available for evaluating follow-up.

PMID: 16142479 [PubMed - as supplied by publisher]

14: Neurosurgery. 2005 Sep;57(3):551-7; discussion 551-7.: CD68 and CR3/43 immunohistochemical expression in secretory meningiomas.

Caffo M, Caruso G, Germano A, Galatioto S, Meli F, Tomasello F.

Neurosurgical Clinic, Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina School of Medicine, Messina, Italy.

OBJECTIVE: Secretory meningiomas (SMs) are unusual benign meningiomas. SMs are highly vascularized lesions, with angiomatous features and a perivascular arrangement, and they are accompanied frequently by massive peritumoral edema. Microglia have been called the brain's immune system, although the specific role and prognostic significance of microglia remain uncertain. The objective of this study was to analyze the expression of CD68, a macrophage marker specific for resting microglia, and the expression of major histocompatibility complex Class II CR3/43 in SMs. METHODS: From 1995 to 2002, six patients with SMs were treated surgically at our institution. Immunohistochemistry was used to analyze the expression of CD68 and CR3/43 in tumor specimens. The intensity of expression was graded semiquantitatively. A correlation between immunohistochemical expression and the occurrence of brain edema was studied. RESULTS: CD68-positive mononuclear cells were observed in neoplastic tissue or around pseudopsammoma bodies and in perivascular areas, with minimal expression in one patient and moderate expression in three patients. CR3/43-positive complexes were detected in mononuclear elongated elements with ameboid extensions, presumably referable to cells at different stages of immunological activation phenomena, with minimal expression in two patients, moderate expression in one patient, and marked expression in one patient. Edema was severe in all patients. Therefore, it may be indirectly hypothesized that edema may not be correlated with the CD68 and CR3/43 immunohistochemical expression. CONCLUSION: Macrophage infiltration and major histocompatibility complex Class II immunoreactivity in this subtype of meningioma suggest the occurrence of an immune response in the presence of SM.

PMID: 16145535 [PubMed - in process]

15: Neurosurgery. 2005 Sep;57(3):538-50; discussion 538-50.: Diagnosis and treatment of atypical and anaplastic meningiomas: a review.

Modha A, Gutin PH.

Memorial Sloan-Kettering Cancer Center, Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York, USA.

Atypical and anaplastic meningiomas are uncommon tumors with a poorer prognosis than benign meningiomas. We reviewed the current literature and attempted to integrate and summarize available information to determine a logical approach to these tumors. Both tumors are rare and are often integrated with benign meningiomas when treatments are evaluated. In addition, because there has not been one histopathological classification scheme for atypical and anaplastic meningiomas in the past, there are numerous inconsistencies in the literature. Malignant progression with accumulation of mutations in a benign meningioma can result in an atypical and/or anaplastic meningioma. Both tumors are difficult to manage and have high recurrence and poor survival rates. The extent of tumor resection and histological grade are the key determinants for recurrence. In addition, metastases are unusual, but they do occur. We also review the evidence available that has resulted in the current World Health Organization classification. Radiation therapy can be used as an adjunctive treatment after both total and subtotal resection. In addition, the role of stereotactic radiosurgery is increasing, along with a possible role for brachytherapy. There are no effective chemotherapeutic agents available. A treatment algorithm is suggested.

PMID: 16145534 [PubMed - in process]

16: Neurosurgery. 2005 Sep;57(3):512-7; discussion 512-7.: Radiosurgery in the treatment of malignant gliomas: the University of Florida experience.

Ulm AJ 3rd, Friedman WA, Bradshaw P, Foote KD, Bova FJ.

Department of Neurological Surgery, University of Florida, Gainesville, Florida 32610, USA.

OBJECTIVE: To review a single-institution's 12-year experience of treating malignant gliomas with linear accelerator-based radiosurgery. METHODS: One hundred patients were treated for malignant gliomas at the University of Florida between May 1, 1989, and June 12, 2002. Patient variables were entered into a radiosurgery database in a prospective manner. The endpoint of the study was length of survival from the time of diagnosis. The minimum length of follow-up was 18 months or until death. In an attempt to control for selection bias, we used the Radiation Oncology Therapy Group's (RTOG) recursive partitioning categories to compare survival in our group of radiosurgically boosted patients with the RTOG historical database. RESULTS: Recursive partitioning analysis classification was significantly associated with survival. Compared with historical controls, this cohort of patients demonstrated a decreased survival for recursive partitioning analysis Class I and II patients, similar survival for Class III and IV patients, and increased median survival for Class V patients. Other variables demonstrating a statistically significant impact on survival were eloquent location and recurrent disease. CONCLUSION: The results of this study and those of RTOG 93-05 suggest that the reported benefit of upfront radiosurgical boost for malignant gliomas is the result of selection bias. The possibility remains that radiosurgical boost is of benefit in recurrent tumors, especially those in RTOG Class V.

PMID: 16145530 [PubMed - in process]

17: Neurosurgery. 2005 Sep;57(3):505-11; discussion 505-11.: Positron emission tomography with O-(2-[18F]fluoroethyl)-l-tyrosine versus magnetic resonance imaging in the diagnosis of recurrent gliomas.

Rachinger W, Goetz C, Popperl G, Gildehaus FJ, Kreth FW, Holtmannspotter M, Herms J, Koch W, Tatsch K, Tonn JC.

Department of Neurosurgery, University of Munich, Munich, Germany. walter.rachinger@med.uni-muenchen.de

OBJECTIVE: New treatment modalities are available for patients with glioma, which may lead to unspecific changes in posttherapeutic magnetic resonance imaging (MRI) findings. Differentiation between tumor- and therapy-associated contrast enhancement on MRI scans after treatment may be difficult. The aim of this study was to analyze the diagnostic value of O-(2-[F]fluoroethyl)-l-tyrosine (FET)-positron emission tomography (PET) and MRI in the detection of tumor recurrence in patients with glioma after radiotherapy, radiosurgery, or multimodal treatment. METHODS: The study included 36 patients with gliomas and neuroradiological diagnosis of tumor recurrence and 9 patients who had undergone radioimmunotherapy. Patients were consecutively treated between September 2001 and May 2003. A contemporary FET-PET investigation was performed in all patients. A tissue diagnosis was made for comparative analysis in all patients with progressive neuroradiological or clinical findings (32 of 45 patients). In patients with transient neuroradiological or clinical deterioration (13 of 45 patients), clinical follow-up was used to support or contradict the imaging-based diagnosis. RESULTS: Tumor recurrence was documented in 31 of 45 patients, and 14 of 45 patients were tumor free. FET-PET and MRI revealed a correct diagnosis in 44 and 36 patients, respectively. The difference was statistically significant (P < 0.01). Concordant findings after MRI and FET-PET were documented in 37 patients and discordant findings in 8 patients. The difference was statistically significant (P < 0.01). Specificity of FET-PET was 92.9%, and sensitivity was 100% (in patients suspected of having recurrent tumor as revealed by MRI). Sensitivity of MRI was 93.5%, and specificity was 50% (P < 0.05). CONCLUSION: For patients with gliomas undergoing multimodal treatment or various forms of irradiation, conventional follow-up with MRI is insufficient to distinguish between benign side effects of therapy and tumor recurrence. FET-PET is a powerful tool to improve the differential diagnosis in these patients.

PMID: 16145529 [PubMed - in process]

18: Neurosurgery. 2005 Sep;57(3):495-504; discussion 495-504.: A prospective study of quality of life in adults with newly diagnosed high-grade gliomas: the impact of the extent of resection on quality of life and survival.

Brown PD, Maurer MJ, Rummans TA, Pollock BE, Ballman KV, Sloan JA, Boeve BF, Arusell RM, Clark MM, Buckner JC.

Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA.

OBJECTIVE: To describe the quality of life (QOL) over time for adults with newly diagnosed high-grade gliomas and to examine the relationship between QOL and outcome data collected in three prospective cooperative group clinical trials. METHODS: The QOL study was a companion protocol for three Phase II high-grade glioma protocols. Five self-administered forms were completed by patients to assess QOL at study entry, 2 months, and 4 months after enrollment. RESULTS: QOL data were available for baseline, first, and second subsequent follow-up evaluations for 89%, 71%, and 69% of patients, respectively. A significant proportion of patients (47.1%) experienced impaired QOL (QOL < or = 50) in at least one measure at subsequent evaluations, whereas most patients (88%) with impaired QOL at baseline continued to have impaired QOL at subsequent evaluations. On multivariable analyses, baseline QOL measures were predictive of QOL at the time of follow-up. In addition, patients who underwent a gross total resection were much less likely to have impaired QOL (P = 0.006), were less likely to experience worsening depression (P = 0.0008), and were more likely to have improved QOL (P = 0.003) at their first follow-up evaluation. Changes in QOL measures over time were not found to be associated with survival in multivariable analyses that adjusted for known prognostic variables; variables that were independently associated with improved survival were better performance status (P < 0.001), younger age (P < 0.001), and greater extent of resection (P < 0.001). CONCLUSION: Baseline QOL was predictive of QOL over time. Gross total resection was associated with longer survival and improved QOL over time for patients with high-grade gliomas.

PMID: 16145528 [PubMed - in process]