Multimodal target point assessment for stereotactic biopsy in children with diffuse bithalamic astrocytomas.

INTRODUCTION: Diffuse glial tumors with bithalamic involvement are rare in children. Diagnostic assessment can be difficult as the radiological findings can be unspecific. MATERIALS AND METHODS: In order to enhance the diagnostic yield metabolic imaging with MRS and PET using FET ( O-(2-[(18)F]fluoroethyl)- L-tyrosine) was performed in two children (2 and 10 years of age). Co-registered images were used for image-guided biopsy, which was planned with neuronavigation and stereotaxy simultaneously. RESULTS: Biopsies from the right thalamus were planned, but locations were changed in both cases after metabolic imaging was available. MRS (thalamic voxel) was typical for a glial tumor in one child. In the older girl FET-PET revealed an unexpected lesion in the left cerebellar hemisphere, with a tumor-to-cortex ratio of 3.8, as against 1.7 in the thalamus. Accordingly, a stereotactic biopsy specimen was taken from the left cerebellar hemisphere, and a final diagnosis of anaplastic astrocytoma was made. The other patient showed a higher uptake (tumor-to-cortex ratio 1.6) in the left dorsal thalamus, compared with bilateral homogeneous hyperintensity of the thalamus structures on MRI. Stereotactic biopsy revealed a low-grade diffuse astrocytoma. CONCLUSION: Stereotactic biopsy using metabolic imaging and image fusion can enhance the diagnostic yield in cases of diffuse pediatric gliomas disclosing unexpected 'hot spots'.

Comparative follow-up of enhancement phenomena with MRI and Proton MR Spectroscopic Imaging after intralesional immunotherapy in glioblastoma--Report of two exceptional cases.

The morphologic pattern of contrast enhancement in magnetic resonance imaging (MRI) of glioblastoma patients could be non specific and metabolic investigations can be useful for the differentiation of tumorous and non tumorous enhancement. Following initial therapy secondary tissue changes can occur and non specific non tumorous enhancement phenomena have been observed after local immuno- and gene therapy strategies. Magnetic resonance spectroscopic imaging (MRSI) has the potential to give more specific information on the metabolism of the suspective tissue and to differentiate enhancing phenomena. We demonstrate two cases of patients suffering from a glioblastoma with simultaneous MRI and MRSI follow-up after multimodal treatment with surgery, radiation, intralesional immunotherapy (IL-4 toxin) and ongoing chemotherapy. MRI demonstrated extensive and increasing enhancement. This was highly suspicious of rapid progressive local tumor recurrency in both patients. Simultaneously obtained MRSI did not show the expected result of extensive and increasing choline concentration within these enhancing areas. This indicated that the enhancement did most likely not reflect vital tumor tissue. Chemotherapy treatment was continued and further MRI follow up revealed nearly complete regression of all enhancement. In pretreated glioblastoma metabolic data of MRSI seem to be potentially helpful to differentiate tumorous and non tumorous enhancement phenomena after local immunotherapy, which might be useful for further treatment decisions.

MR imaging and single-photon emission CT findings after gene therapy for human glioblastoma.

BACKGROUND AND PURPOSE: Our goal was to evaluate MR imaging findings after local intracerebral gene therapy in patients with glioblastoma and differentiate postoperative contrast enhancement phenomena. METHODS: In all, 26 patients with supratentorial single lesion glioblastoma underwent tumor resection and intracerebral injection of murine retroviral vector-producer cells for gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir system. Serial contrast-enhanced MR studies were obtained before treatment and postoperatively on day 1 or 2; weeks 2, 4, 9, 13, 17, 25, and 33; and every 8 weeks thereafter. Iodomethyltyrosine single-photon emission CT (IMT-SPECT) investigations also were performed in selected cases. RESULTS: Twelve patients showed nontumorous enhancement of various intensities after treatment, arising within 18 to 72 hours and persisting at 3 to 10 months. It was characterized by a strong local enhancement up to 20 mm thick, which was initially nodular and later linear along the resection cavity wall and surrounded by massive perifocal edema. This "flare" enhancement had features that clearly differed from those of residual tumor enhancements and benign postsurgical enhancements. The IMT-SPECT investigations showed increased amino acid uptake in patients with enhancement from residual or relapsing tumor, but not in patients with flare. CONCLUSION: After local gene therapy, a unique dynamic, transient perifocal flare enhancement can occur on MR images. IMT-SPECT may help to differentiate between tumorous and nontumorous flare enhancements in patients with enhancing tissue on MR images after gene therapy for glioblastoma.

Local inflammation and devascularization--in vivo mechanisms of the "bystander effect" in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma.

Somatic gene therapy with the herpes simplex virus type I thymidine kinase gene/ganciclovir (HSV-Tk/GCV) system and murine retroviral vector producer cells (VPCs) was introduced as a new adjuvant treatment modality to treat tumor bulk and to prevent tumor recurrence in patients harboring malignant glioma. The single-center experience after treatment of 27 patients undergoing tumor resection followed by intracerebral VPC injection for HSV-Tk suicide gene therapy will be presented focused on findings of systematic and close MRI follow-up and a few histological specimens. The data indicate that hemorrhagic necrosis due to endothelial cell transfection mediated vessel necrosis and that local inflammatory immune response occurs frequently after gene therapy. These phenomena seem to be specific because none of the patients of a control group showed any similar features. The prognosis (time to progression, survival) of the patients with "bystander effects" after gene therapy was better, but compared to those patients without bystander effects, they were also privileged by a favorable constellation of prognostic factors. Therefore, the appearance of these neuroradiologic features cannot serve as an indicator for treatment effectiveness and outcome.

Survival in malignant glioma: analysis of prognostic factors with special regard to cytoreductive surgery.

Although the question of optimal treatment for malignant gliomas has been addressed in many retrospective papers, no clear answer has been found to what extent surgical removal of tumor tissue should be performed. We conducted a retrospective analysis in 274 unselected patients, admitted to our institution with the diagnosis of malignant supratentorial glioma. Median survival time after surgery was analyzed with respect to the following defining variables: Age, pre- and postoperative Karnofsky Performance Scale (KPS), tumor location, histology, sex, pre- and postoperative tumor volume and volumetrically measured extent of resection. All these defining variables with exception of sex and preoperative tumor volume were of significant influence on the median survival time of glioma patients (Kolmogoroff-Smirnoff test, Log-Rank test, Breslow test and Tarone-Ware test p < 0,05). To exclude covariant influences of these variables on patients survival and to answer the question of the best surgical option, a matched pair analysis between 40 patients undergoing stereotactic biopsy and 40 patients undergoing cytoreductive surgery was performed. Median survival time (MST) in the biopsy group was 184 days whereas the cytoreductive surgery group had a MST of 292 days (p < 0,05). In addition median postoperative KPS at the point of discharge in patients with tumor resection was slightly better (KPS 58%) in comparison with the biopsy group (KPS 53%) but not on a significant level. It is concluded from these data that patients harbouring malignant gliomas clearly benefit from cytoreductive surgery compared with stereotactic biopsy regarding life expectancy and mildly regarding life quality.