Low-grade Brain Tumors Research Articles

Funktionelle Bildgebung bei Hirntumoren (Perfusion, DTI, MR-Spektroskopie)

This contribution considers the possibilities involved with using functional methods in magnetic resonance imaging (MRI) diagnostics for brain tumors. Of the functional methods available, we discuss perfusion MRI (PWI), diffusion MRI (DWI and DTI) and MR spectroscopy (H-MRS). In cases of brain tumor, PWI aids in grading and better differentiation in diagnostics as well as for pre-therapeutic planning. In addition, the course of treatment, both after chemo- as well as radiotherapy in combination with surgical treatment, can be optimized. PWI allows better estimates of biological activity and aggressiveness in low grade brain tumors, and in the case of WHO grade II astrocytoma showing anaplasically transformed tumor areas, allows more rapid visu-alization and a better prediction of the course of the disease than conventional MRI diagnostics. Diffusion MRI, due to the directional dependence of the diffusion, can illustrate the course and direction of the nerve fibers, as well as reconstructing the nerve tracts in the cerebrum, pons and cerebellum 3-dimensionally. Diffusion imaging can be used for describing brain tumors, for evaluating contralateral involvement and the course of the nerve fibers near the tumor. Due to its operator dependence, DTI based fiber tracking for defining risk structures is controversial. DWI can also not differentiate accurately between cystic and necrotic brain tumors, or between metastases and brain abscesses. H-MRS provides information on cell membrane metabolism, neuronal integrity and the function of neuronal structures, energy metabolism and the formation of tumors and brain tissue necroses. Diagnostic problems such as the differentiation between neoplastic and non-neoplastic lesions, grading cerebral glioma and distinguishing between primary brain tumors and metastases can be resolved. An additional contribution will discuss the control of the course of glial tumors after radiotherapy.

FDOPA-PET als Paradigma molekularer Bildgebung in der Onkologie

In recent years, positron emission tomography with 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) has become a wide-spread method in the diagnostics of Parkinson's disease. The amino acid is an important component in protein metabolism. As a precursor in the synthesis of catecholamines it is also of use in metabolic imaging of a variety, mostly neuroendocrine, tumors. The specific uptake mechanisms make FDOPA a paradigm of metabolic imaging. The current review assesses the value of the tracer in the diagnostics of different oncological diseases. It summarizes own experiences and the published results of oncological FDOPA PET-studies. Above all, there is a very high impact of FDOPA in the staging of pheochromocytomas and paragangliomas as well as serotonin-positive neuroendocrine tumors of the gastroentero-pancreatic system (NET-GEPs). Additionally, FDOPA extends the diagnostic possibilities in recurrent medullary thyroid cancer. In the imaging of tumors of the central nervous system, FDOPA represents an alternative to 11 C-labelled PET-tracers. First reports show a high accuracy in the differentiation of radiation induced necrosis and recurrent disease in both high and low grade brain tumors. Furthermore, there is a correlation between the uptake of FDOPA and the expression of proliferation markers. Today, the noninvasive differentiation of focal and diffuse congenital hyperinsulinism has therapeutic consequences. In cases of focal disease, the extent of pancreas resection can be limited resulting in better prognosis without diabetes mellitus.

TEMPORAL LOBE SURGERY FOR INTRACTABLE EPILEPSY IN CHILDREN

Abstract OBJECTIVE Temporal lobectomy is a well-established neurosurgical procedure for temporal lobe epilepsy. In this study, we conducted a retrospective review of children with drug-resistant temporal lobe epilepsy to evaluate seizure outcome after temporal lobe surgery. METHODS We reviewed the medical records of 126 children who had surgery for temporal lobe epilepsy at The Hospital for Sick Children between 1983 and 2003. The records were examined for preoperative and intraoperative factors that could predict patient outcome after surgery. RESULTS The mean age at seizure onset was 5.9 years. The mean seizure duration before surgery was 5.6 years. All patients had preoperative computed tomographic scans, magnetic resonance imaging scans, or both. The mean age at the time of surgery was 13.5 years. Sixty-two patients underwent left temporal resections and 64 patients underwent right temporal resections. The histopathology of the temporal resections revealed low-grade brain tumors in 65 children (52%) and cavernous malformations in four children. Ganglioglioma and astrocytoma were the most common tumors encountered. Mesial temporal sclerosis was found in 16 patients (13%), astrogliosis in 15 patients (12%), and cortical dysplasia in eight patients (7%). Postoperative follow-up of at least 2 years was available for 106 patients and ranged up to 13.0 years. Seventy-four percent of patients had an Engel Class I or II outcome. Patients with temporal lobe lesions had better outcomes compared with those without lesions (P< 0.05). Patients without a history of secondary generalization of seizures also had a better outcome when compared with those with secondary generalization. Complications in the form of contralateral homonymous hemianopsia, dysphasia, and infection were found in 5% of patients. Twelve patients had a second temporal lobe procedure for intractable recurrent seizures. After a second procedure, seven patients returned to a seizure-free state. CONCLUSION Temporal lobe resections for epilepsy in children are effective and safe procedures, with a favorable impact on seizure control. Repeat temporal resections for recurrent seizures may also be effective in restoring a seizure-free outcome to children.

Neuropsychological status in children and young adults with benign and low-grade brain tumors treated prospectively with focal stereotactic conformal radiotherapy

Purpose: To present prospective neuropsychological data at baseline and follow-up in children and young adults with benign and low-grade gliomas treated with focal stereotactic conformal radiotherapy (SCRT). Methods and Materials: A total of 22 patients (age 4–25 years) with residual/progressive benign and low-grade brain tumors considered suitable for SCRT underwent detailed and in-depth neuropsychological and cognitive testing at baseline before SCRT. The test battery included measurement of age-adjusted intelligence quotients (IQs) and cognitive parameters of visual, spatial, visuomotor, and attention concentrations. Anxiety was measured using the State-Trait Anxiety Inventory for Children and Hamilton Anxiety Rating Scale for patients >16 years old. Patients were treated with high-precision conformal radiotherapy under stereotactic guidance to a dose of 54 Gy in 30 fractions. All neuropsychological assessments were repeated at 6 and 24 months after SCRT completion and compared with the baseline values. Results: The baseline mean full-scale IQ before starting RT for patients 16 years, the corresponding value was 72 (range, 64–129). Of 20 evaluable patients, 14 (70%) had less than average IQs at baseline, even before starting radiotherapy. The verbal IQ, performance IQ, and full-scale IQ, as well as other cognitive scores, did not change significantly at the 6- and 24-month follow-up assessments for all patients. The memory quotient in older children and young adults was maintained at 6 and 24 months after SCRT, with a mean value of 93 and 100, respectively, compared with a mean baseline value of 81 before RT. The mean anxiety score in children measured by the C1 and C2 components of the State-Trait Anxiety Inventory for Children (STAIC) was 48 and 40, respectively, which improved significantly to mean values of 30 and 26, respectively, at the 24-month follow-up assessment ( p = 0.005). The mean depression score in patients >16 years old was 23 at baseline and had improved to 17 and 14 at the 6-month and 24-month follow-up assessments, respectively. Conclusion: Our data demonstrated neuropsychological impairment in a cohort of young patients with benign and low-grade tumors even before starting radiotherapy. SCRT, however, did not result in any additional worsening. These encouraging results need to be validated in a study with a larger number of patients and longer follow-up.

Abstracts from the Seventh Congress of the European Association for Neuro-Oncology

BACKGROUND: Conventional interpretation of methionine PET (Met-PET) scans in suspected brain tumors uses the ratio of the tracer uptake within the lesion to the corresponding contralateral area. The precise location at which the region of interest used to calculate the reference value is placed is vital, because local variations in methionine uptake may significantly alter the calculated ratio. Identifying a precise mirror region is complicated by the distorting effect of the tumor and the need for manual realignment of the image. METHOD: Patients with low-grade primary brain tumors or benignlesions were identified on the basis of a tissue diagnosis or surveillance neuroimaging that excluded a high-grade tumor. These conditions were selected because they primarily involve a single hemisphere, with methionine uptake in the unaffected hemisphere being essentially normal. A total of 180 Met-PET scans performed during 2003 – 2005 were identified from the database at the Max Planck Institute for Neurological Research, coded, and anonymized for analysis. Scans demonstrating midline lesions, significant mass effect, or evidence of substantial previous surgery were then excluded. A methionine template was prepared using data from patients who had undergone both FDG and Met-PET scans within eight weeks, with normalization to a previously developed FDG template. Methionine scans were coregistered to the template, after masking of any tumor, and the diseased hemispheres stripped. Mean uptake maps for each hemisphere were calculated on a voxel-by-voxel basis and merged to create the normal methionine uptake map. Scans unsuitable for inclusion into the normal map were reanalyzed using the contralateral hemisphere and the normal uptake map for reference values, allowing the methods to be compared. RESULTS: Good correlation was found between uptake ratios using reference values calculated by both methods. Reference values could be reliably calculated in tumors that were previously problematic to analyze, such as those that cross the midline. Coregistration of the normal map was impaired in some cases by loss of the normal architecture, but valid reference values were obtained despite this. CONCLUSION: Use of a normal uptake may facilitate calculation of PET uptake ratios in brain tumors. Further research is required to evaluate the correlation with histological findings and the accuracy of image coregistration in the presence of distorting tumors.

Ganglioglioma: comparison with other low-grade brain tumors

Forty-two patients with low-grade brain tumor and refractory epilepsy were studied. The mean age was 22.3 years. They were divided into two groups: Group A, patients with ganglioglioma (n=19) and group B, patients with other low-grade tumors (n=23) (14 astrocytoma, 6 oligodendroglioma, 2 dysembryoplastic neuroepithelial tumor, and 1 xanthoastrocytoma). Age at seizures onset was 7 years or less in 73% of the patients in group A and in 30.4% of the patients in group B (p=0.045). Complex partial occurred frequently in group A and B (94.7% versus 82%, respectively). Seizures frequency was higher in group B (p=0.002). Computerized tomography (CT) was normal in 36.8% of group A patients and abnormal in all group B patients. Magnetic resonance imaging (MRI) was abnormal in all patients. Surgical removal was complete in 89.5% of the patients in group A and in 78.2% of the patients in group B. The association of refractory epilepsy and complex partial seizures, at a relatively low frequency, in young patients potentially normal CT and a MRI hypointense temporal lobe lesion in T1-weighed slices were habitual image findings in ganglioglioma, rather than other low-grade tumor.

Dysembryoplastic Neuroepithelial Tumor in Pregnancy

Dysembryoplastic neuroepithelial tumor is a rare, low-grade brain tumor that is characterized by intractable, partial seizures of juvenile onset. A 36-year-old pregnant woman with dichorionic, diamniotic twins temporarily lost consciousness at 27 weeks of gestation. Magnetic resonance imaging evaluation showed a 3-cm multicystic nodule in her right temporal lobe that was diagnosed, together with her history of recurrent anxiety attacks, as dysembryoplastic neuroepithelial tumor. The lesion did not enlarge during pregnancy, and healthy male infants were delivered by cesarean at 36 weeks. The tumor was successfully removed 2 months postpartum, and the patient has experienced no further seizures. Dysembryoplastic neuroepithelial tumor was conservatively managed during pregnancy without neurosurgical intervention.

Seizures in children with low-grade tumors: outcome after tumor resection and risk factors for uncontrolled seizures

The goals of this study were to define the incidence of seizures in children with low-grade tumors, study seizure outcome after lesionectomy in these children, and identify risk factors for poor seizure outcome. The authors performed a retrospective chart review of children who harbored low-grade brain tumors, experienced seizures, and were treated in a single institution. Statistical analyses included step-wise as well as single-variable binary logistic regression analyses. Fifty-five children (20%) with seizures were identified in a cohort of 280 children with low-grade tumors. Of these 55 children, 35 harbored cortical cerebral tumors and 20 had noncortical lesions, including six whose tumors were in the posterior fossa. Seizures were defined as controlled if there was no seizure in the 12 months preceding the last clinic visit. All cortical tumors were treated by lesionectomy as an initial procedure. Of the 27 children with cortical tumors whose seizures began before tumor diagnosis, 23 had complete resection and 52% of these 23 experienced no further seizures after surgery. Seizures are presently controlled in 84% of the total 55 patients at a median follow-up time of 4.5 years after the first seizure (range 1-17.4 years). Only two variables, a pericavity hyperintense signal on T2-weighted magnetic resonance (MR) images and at least 10 seizures prior to therapy for seizures, were associated with uncontrolled seizures. Lesionectomy may be appropriate in children with low-grade brain tumors. A large number of seizures before therapy and a hyperintense area around the tumor cavity on postresection MR images are associated with uncontrolled seizures. Medical therapy and tumor resection will control seizures in the majority of children with low-grade tumors.

Neuropsychological Status in Children and Young Adults with Benign and Low-Grade Brain Tumors Treated Prospectively with Focal Stereotactic Conformal Radiotherapy

Purpose/Objective: To present prospective neuropsychological data at baseline and follow up in children and young adults with benign and low-grade gliomas treated with focal stereotactic conformal radiotherapy (SCRT). Materials/Methods: Twenty-two patients (age: 4 to 25 years) with residual/progressive benign and low-grade brain tumors considered suitable for SCRT underwent a detailed and in-depth neuropsychological and cognitive testing at baseline before radiotherapy. The test battery included measurement of age-adjusted intelligence quotients (IQ), cognitive parameters of visual, spatial, visuomotor and attention concentrations. Anxiety was measured by State-Trait Anxiety Inventory for Children (STAIC) and Hamilton Anxiety rating Scale (HARS) for patients more than 16 years of age. Patients were treated with high precision conformal radiotherapy under stereotactic guidance to a dose of 54Gy in 30 fractions. All neuropsychological assessments were repeated at 6 and 24 month after the completion of SCRT and compared with the baseline values. Results: The baseline mean full scale IQ before starting RT for patients less than 16 years was 82 (range 33–105) and for those older than 16 years, the corresponding value was 72 (range 64–129). 14 out of 20 evaluable patients (70%) had less than average IQ′s at baseline, even before starting radiotherapy. Verbal IQ, performance IQ and full scale IQ′s as well as other cognitive scores did not change significantly at 6 and 24 months follow up assessments for all patients. Memory quotient in older children and young adults remained maintained at 6 months and 2 years after SCRT with mean values of 93 and 100 compared to mean baseline value of 81 before RT. Mean anxiety score in children measured by C1 of STAIC was 48 and 40 respectively, which improved significantly to mean values of 30 and 26, respectively at 24 month follow up assessment (p=0.005). Mean depression score in patients aged more than 16 years was 23 at baseline, which improved to 17 and 14 at 6 and 24 months follow up assessments, respectively. Conclusions: Our data demonstrates neuropsychological impairment in a cohort of young patients with benign and low-grade tumors even before starting radiotherapy. SCRT however did not result in any further worsening, the encouraging results of which need to be validated in larger number of patients at a longer follow up.

Multisection 1H Magnetic Resonance Spectroscopic Imaging Assessment of Glioma Response to Chemotherapy

This study evaluated the role of proton magnetic resonance spectroscopic imaging (1H MRSI) in assessing the response of low-grade brain tumors to a chemotherapy-only treatment regimen. Specifically, it was of interest to assess if 1H 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 1H 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 1H 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.

Magnetic Resonance Spectroscopy

Magnetic resonance spectroscopy (MRS) complements magnetic resonance imaging (MRI) as a non-invasive means for the characterization of tissue. While MRI uses the signal from hydrogen protons to form anatomic images, proton MRS uses this information to determine the concentration of brain metabolites such as N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate in the tissue examined. The most widely used clinical application of MRS has been in the evaluation of central nervous system disorders.MRS has its limitations and is not always specific but, with good technique and in combination with clinical information and conventional MRI, can be very helpful in diagnosing certain entities. For example, a specific pattern of metabolites can be seen in disorders such as Canavan's disease, creatine deficiency, and untreated bacterial brain abscess. MRS may also be helpful in the differentiation of high grade from low grade brain tumors, and perhaps in separating recurrent brain neoplasm from radiation injury.

Maximal Resection of Low-grade Intrinsic Brain Tumors Using “Awake” Craniotomy and Multiple Marginal Smear Biopsies: Operative Complication Rates and 10-year Survival Data

Maximal Resection of Low-grade Intrinsic Brain Tumors Using “Awake” Craniotomy and Multiple Marginal Smear Biopsies: Operative Complication Rates and 10-year Survival Data

Integration of [11C]Methionine-Positron Emission Tomographic and Magnetic Resonance Imaging for Image-guided Surgical Resection of Infiltrative Low-grade Brain Tumors in Children

To evaluate the interest of integrating positron emission tomography (PET) images with the radiolabeled tracer [(11)C]methionine (Met) into the image-guided navigation planning of infiltrative low-grade brain tumors (LGBTs) in children. Twenty-two children underwent combined Met-PET with magnetic resonance imaging (MRI) scans in the planning of a navigation procedure. These children presented an LGBT (astrocytomas, 10; oligodendrogliomas, 4; ependymomas, 4; gangliogliomas, 4) located close to functional areas. Tumor boundaries were ill-defined on MRI (including T2-weighted and fluid-attenuated inversion-recovery scans) and could not be clearly identified for allowing a complete, or at least a large, image-guided resection. The PET tracer Met was chosen because of its higher sensitivity and specificity than MRI to detect tumor tissue. The level and extension of MET uptake were analyzed to define the PET contour, subsequently projected onto MRI scans to define a final target contour for volumetric resection. The quality of tumor resection was assessed by an early postoperative MRI and Met-PET workup. In 20 of the 22 children with ill-defined LGBTs, PET improved tumor delineation and contributed to define a final target contour different from that obtained with MRI alone. Met-PET guidance allowed a total resection of Met uptake in 17 cases that were considered total tumor resections because the operative margin left in place contained nontumor tissue. These data suggested that Met-PET guidance could help to improve the number of total resections and the amount of tumor removed in infiltrative LGBTs in children.

MRI changes due to early-delayed conformal radiotherapy and postsurgical effects in patients with brain tumors

Discernment of radiotherapy (XRT) effects vs. tumor activity is difficult in brain tumor patients during the months after XRT when white matter hyperintensities sometimes emerge. We examined brain scans in XRT-treated vs. untreated patients for early-delayed post-XRT effects. Brain regions susceptible to XRT injury were examined on magnetic resonance imaging (MRI) for T2-weighted hyperintensities and atrophy in 37 adults with low-grade primary brain tumors (13 nonirradiated and 24 irradiated). Cases evidencing recurrence/growth over the study period were censored. Interactions with age, mood, fatigue, medications, tumor type and grade, extent of resection, and laterality of MRI changes were examined. Hyperintensity and atrophy ratings over time for the treated and untreated groups were not significantly different. White matter atrophy increased unrelated to XRT. In all patients combined, white matter atrophy and hyperintensities were greater at all time points and more lateralized in surgically treated patients. Radiotherapy status was not related to changes in MRI ratings during the weeks/months after XRT. Findings contradict assumptions about radiographically evidenced early-delayed XRT effects. Increases in T2-weighted hyperintensities during the 1-6-month period post-conformal radiotherapy for low-grade tumors are likely not related to early-delayed XRT effects.

O-(2-[18F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours

The aim of this study was to evaluate the differential uptake of O-(2-[18F]fluorethyl)-L-tyrosine (FET) in suspected primary brain tumours. Positron emission tomography (PET) was performed in 44 patients referred for the evaluation of a suspected brain tumour. Acquisition consisted of four 10-min frames starting upon i.v. injection of FET. Tumour uptake was calculated as the ratio of maximal tumour intensity to mean activity within a reference region (FETmax). FET uptake above the cortical level was observed in 35/44 lesions. All histologically confirmed gliomas and many other lesions showed FET uptake to a variable extent. No uptake was observed in nine lesions (one inflammatory lesion, one dysembryoplastic neuroepithelial tumour, one mature teratoma, six lesions without histological confirmation). An analysis of uptake dynamics was done in the patients with increased FET uptake (22 gliomas, three lymphomas, three non-neoplastic lesions, three lesions with unknown histology and four other primaries). Upon classification of tumours into low (i.e. WHO I and II) and high grade (i.e. WHO III and IV), a significant difference in FETmax between the two categories was observed only in the first image frame (0-10 min p.i.), with FETmax=2.0 in low-grade and 3.2 in high-grade tumours (p<0.05); no significant differences were found in frame 4 (30-40 min p.i.), with FETmax=2.4 vs 2.7. Similar results were obtained when the analysis was applied only to astrocytic tumours (2.0 vs 3.1 in the first frame; 2.4 vs 2.6 in the fourth frame). These initial results indicate that FET PET is a useful method to identify malignant brain lesions. It appears that high- and low-grade brain tumours exhibit a different uptake kinetics of FET. A kinetic analysis of FET PET may provide additional information in the differentiation of suspected brain lesions.

Conformal radiotherapy in children with low-grade brain tumours: treatment results and toxicity

Summary Background The conformal radiotherapy technique is a particularly important method for the treatment of children with localized low-grade brain tumours, whose prognosis, with regard to long-term survival is often excellent and should be accompanied by the smallest possible risk of toxicity. Aim The results of 3-D conformal radiotherapy in children with low-grade astrocytoma and craniopharyngioma, treated in our department to present. Materials/Methods Between 1997–2001, 20 children, aged between 3.5 and 18 years, with low-grade brain tumours (8 craniopharyngioma and 12 low-grade astrocytoma) were treated with conformal radiotherapy. In the craniopharyngioma group, all patients were irradiated owing to tumour recurrence, after multiple surgeries, and were seriously handicapped before the commencement of radiotherapy. Patients with astrocytoma were treated after chemotherapy, partial surgery or biopsy only. Results All patients with craniopharyngioma survived with no recurrence (5) or with a stable disease state (3). Radiation related complications were not observed. Four patients with astrocytoma died, due to progressive disease (3) or chemotherapy related complications (1). Two patients are living with dissemination to the CNS, 4 with no recurrence and 2 have stabilized. Late complications after radiotherapy were not observed. Conclusions Three-dimensional radiation therapy is a safe and successful method for the combined treatment of children with low-grade brain tumours. The risk of radiotherapy related complications is relatively low.

High precision conformal radiotherapy employing conservative margins in childhood benign and low-grade brain tumours

Background and purpose To report local control and follow up outcome data of high precision conformal radiotherapy in childhood brain tumours. Materials and methods Between December 1999 and December 2002, 26 children (17 boys and 9 girls, median age 11.5 years) with incompletely excised or recurrent benign and low-grade brain tumours [13 craniopharyngiomas, 11 low-grade gliomas (LGG) and 2 others] were treated with three-dimensional (3D) conformal radiotherapy (CRT) (12 patients) and stereotactic conformal radiotherapy (SCRT) (14 patients). Gross tumour volume (GTV) included neuro-imaging based visible tumour and/or resected tumour bed. Clinical target volume (CTV) consisted of GTV+ 5 mm margin and planning target volume (PTV) consisted of additional 5 mm margin for CRT and 2 mm for SCRT. Treatment was delivered with 3–9 conformal fixed fields to a median dose of 54 Gy/30 fractions. Results The actuarial 2 and 3 year disease free and overall survival was 96 and 100%, respectively (median follow up: 25 months, range 12–47 months). Radiological follow up available in 25 patients revealed complete response in 1, partial regression in 10, stable disease in 13 and progression in 1 patient (within the CTV). One patient with craniopharyngioma on a routine imaging revealed a mild asymptomatic cyst enlargement, which resolved with conservative management. A patient with chiasmatic glioma developed cystic degeneration and hydrocephalus 9 months after SCRT requiring cyst drainage and placement of a ventriculoperitoneal shunt. Conclusion High-precision conformal techniques delivering irradiation to a computer generated target volume employing 7–10 mm 3D margins beyond the visible tumour and/or resected tumour bed appear to be safe in children with incompletely resected or recurrent benign and low-grade brain tumours, based on these data.

588 poster 3-D conformal radiotherapy in children with low-grade brain tumours

588 poster 3-D conformal radiotherapy in children with low-grade brain tumours

The Impact of Low-Grade Brain Tumors on Verbal Fluency Performance Bram Goldstein

Verbal fluency has traditionally represented left hemispheric function, based on large acquired lesion studies. However, recent functional imaging studies have demonstrated bilateral hemispheric activation during phonemic and semantic word generation tasks. We examined 25 left hemisphere (LH) and 26 right hemisphere (RH) low-grade brain tumor patients on semantic and phonemic fluency. Patients were also assigned to a combined anterior (left and right) group (n=26) or a combined posterior (left and right) group (n=20) and compared with normal controls (NC; n=57). We hypothesized that there would be greater left than right hemispheric phonemic and semantic fluency impairments. We also hypothesized that there would be greater anterior, specifically left anterior, than posterior impairments on phonemic fluency given their respective retrieval and initiation requirements. Finally, it was predicted that the LH patients, particularly the left posterior group, would exhibit the greatest semantic fluency impairments. Results indicated that on semantic fluency, the LH group produced significantly fewer semantic fluency responses compared to the RH group, but the expected left posterior and left frontal group differences were not found. There were no significant patient group differences associated with phonemic fluency. While we encountered semantic fluency impairments in this brain tumor population, we did not find the extensive deficits associated with the distinct or localized brain regions previously reported in the literature.

Functional measurement of local proteolytic activity in living cells of invasive and non-invasive tumors.

Proteolytic cleavage of extracellular matrix (ECM) and disruption of tissue architecture are fundamental features of tumor cell invasion. The proteolytic activity is focused in close proximity to the tumor cells. Here, we describe the possibility to quantify local proteolytic activity in the microenvironment of larger cell populations by the electrical resistance breakdown assay. The assay utilizes the transepithelial electrical resistance (TEER) of an epithelial monolayer as a sensitive indicator of monolayer integrity and permeability. Local destruction of ECM by single tumor cells was demonstrated by a second assay, based on a fluorescent matrix coating on cover slides. Local digestion of the matrix results in a reduction of fluorescence. Primary cells derived from high and low grade brain tumors as well as established cell lines of malignant gliomas and non-neural tumors of different origin (melanoma, cervical carcinoma, and breast carcinoma) were compared. Differences in proteolytic activity between tumor entities were demonstrated in both assays. Primary cells of high grade gliomas and cell lines showed TEER breakdown and local matrix destruction, while low grade brain tumors lacked matrix disintegration and disruption of cell monolayers. Taken together, both assays are capable of demonstrating local proteolytic activity and thus are versatile tools for distinguishing high and low invasive tumor cells with a potential application as diagnostic and prognostic markers in clinical investigations. The advantage of the matrix digestion assay is the requirement of only very low tumor cell numbers, whereas measurement of TEER enables precise quantification of local proteolytic processes in large and even heterogeneous tumor cultures.