NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality.

Purpose: NovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division.

Methods: Phase III trial of chemotherapy-free treatment of NovoTTF (20-24h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma.

Treatment of high-grade glioma with radiolabeled peptides.

The management of high-grade glioma (HGG) patients in clinical routine represents a challenging task. HGG has a poor prognosis because of early recurrence or therapy-refractory disease following first-line standard therapy, which includes a multidisciplinary approach involving radical surgical resection followed by external beam radiation therapy in combination with chemotherapy. Glioma cells are known to express specific receptors or glycoproteins on their surface which can be used as biological targets for treatment.

O-(2-18F-fluoroethyl)-L-tyrosine PET predicts failure of antiangiogenic treatment in patients with recurrent high-grade glioma.

Unlabelled: The objective of this study was to compare MRI response assessment with metabolic O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET response evaluation during antiangiogenic treatment in patients with recurrent high-grade glioma (rHGG).

Methods: Eleven patients with rHGG were treated biweekly with bevacizumab-irinotecan. MR images and (18)F-FET PET scans were obtained at baseline and at follow-up 8-12 wk after treatment onset.

Management of recurrent malignant glioma--neurosurgical strategies.

There is currently no standard for neurosurgical interventions in patients with recurrent high grade gliomas. An individualized approach is recommended as well for decision-making as for planning an intervention with resection of the outmost possible amount of tumor tissue while preserving neurological function and thus quality of life. Recent technical developments of imaging and of neuronavigation and visualization of tumor tissue with in vivo fluorescence with 5-Ala have proved helpful in improving symptoms and prolonging survival times also for patients with recurrent malignant gliomas.

ADC histograms predict response to anti-angiogenic therapy in patients with recurrent high-grade glioma.

Introduction: The purpose of this study is to evaluate apparent diffusion coefficient (ADC) maps to distinguish anti-vascular and anti-tumor effects in the course of anti-angiogenic treatment of recurrent high-grade gliomas (rHGG) as compared to standard magnetic resonance imaging (MRI).

Methods: This retrospective study analyzed ADC maps from diffusion-weighted MRI in 14 rHGG patients during bevacizumab/irinotecan (B/I) therapy. Applying image segmentation, volumes of contrast-enhanced lesions in T1 sequences and of hyperintense T2 lesions (hT2) were calculated.

Photodynamic diagnosis and therapy and the brain.

Photodynamic techniques such as photodynamic diagnosis (PDD), fluorescence-guided tumour resection (FGR) and photodynamic therapy (PDT) are currently undergoing intensive clinical investigations as adjuvant treatment for malignant brain tumours. The following chapter provides an overview on the current clinical data and trials of PDT as well as photosensitizers, technical developments and indications for photodynamic application in neurosurgery. Besides many clinical phase I/II trials for PDT for malignant brain tumours, there are only few controlled clinical trials following tumour resection.

Response of recurrent high-grade glioma to treatment with (90)Y-DOTATOC.

Unlabelled: The treatment of patients with high-grade malignant glioma still represents an unsolved clinical problem. We report the treatment of 3 patients who had World Health Organization grade IV recurrent glioblastoma: a 23-y-old woman and 2 men aged 61 and 62 y.

Methods: All 3 patients were treated with the somatostatin receptor radiopharmaceutical (90)Y-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid(0)-d-Phe(1),Tyr(3)]octreotide (DOTATOC).

Axl and growth arrest-specific gene 6 are frequently overexpressed in human gliomas and predict poor prognosis in patients with glioblastoma multiforme.

Purpose: The receptor tyrosine kinase Axl has recently been identified as a critical element in the invasive properties of glioma cell lines. However, the effect of Axl and its ligand growth arrest--specific gene 6 (Gas6) in human gliomas is still unknown.

Experimental Design: Axl and Gas6 expression was studied in 42 fresh-frozen and 79 paraffin-embedded glioma specimens by means of reverse transcription-PCR and immunohistochemistry.

[Surgical intervention in patients with malignant glioma].

Glial tumors occur at an incidence from 2 to 10/ 100.000 (Japan vs. Sweden) and building up to 50 % of all patients suffering from brain tumors.

Basic fibroblast growth factor isoforms promote axonal elongation and branching of adult sensory neurons in vitro.

Synthesis of the multifunctional cytokine basic fibroblast growth factor (FGF-2) is up-regulated after sciatic nerve lesion. In this study, the effects of low and high molecular weight FGF-2 isoforms on axonal elongation and branching of dissociated rat sensory neurons derived from adult lumbar dorsal root ganglia were investigated. These neurons express FGF receptor (FGFR) type I in the cytoplasmic/membrane compartment and in nuclear speckles.

In vitro investigation on the pH dependence of the absorption and fluorescence properties of the photosensitizer mTHPC.

Fluorescence excitation efficiency is of great importance for photodynamic diagnosis. Because usually a difference in the interstitial pH between normal and tumor tissue occurs, it is necessary to assess the impact of pH on the fluorescence emission intensity of the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) in this context. The results obtained by in vitro fluorescence measurements clearly indicate that pH values below 6 lead to a significant decrease in the fluorescence intensity.

mTHPC-mediated photodynamic diagnosis of malignant brain tumors.

Radical tumor resection is the basis for the prolonged survival of patients suffering from malignant brain tumors such as glioblastoma multiforme. We have carried out a phase-II study involving 22 patients with malignant brain tumors to assess the feasibility and the effectiveness of the combination of intraoperative photodynamic diagnosis and fluorescence-guided resection (FGR) mediated by the second-generation photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). In addition, intraoperative photodynamic therapy (PDT) was performed.

Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and correlates with tumor progression.

Vascular endothelial growth factor (VEGF), a key regulatory protein in neoangiogenesis, is strongly expressed in a variety of primary brain tumors, particularly malignant gliomas. In previous studies, high levels of VEGF were also reported in tumor cysts of glioblastomas. Using an ELISA method we measured the concentration of VEGF in matched samples of aspiration fluid from tumor cysts and serum.

Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GFR-alpha 1) are strongly expressed in human gliomas.

Glial cell line-derived neurotrophic factor (GDNF), a sequence-related factor of the transforming growth factor-beta family, has been identified as a potent neurotrophic factor for a variety of neuronal cell populations. At present, it is still unknown whether human gliomas in vivo are also capable of producing GDNF. We studied the expression of GDNF in 14 human glioblastomas, 1 gliosarcoma and 5 astrocytomas.

Photodynamic therapy for recurrent gynecologic malignancy: a report on 4 cases.

4 patients with recurrent gynecological malignancy were treated photodynamically, 4 d after sensitisation with intravenous meso-tetra(hydroxyphenyl)-chlorin (m-THPC) at a dose of 0.15 mg/kg bodyweight (total dose ranged from 12-15 mg). Light at 652 nm was derived from a KTP-Dye laser (Diasonic) and delivered superficially at a total light dose of 20 J/cm2 (power density of 100 mW/sec).

Uptake and kinetics of 14C-labelled meta-tetrahydroxyphenylchlorin and 5-aminolaevulinic acid in the C6 rat glioma model.

Meta-tetrahydroxyphenylchlorin (m-THPC) and 5-aminolaevulinic acid (5-ALA) are two second-generation photosensitizers which are currently under investigation for photodynamic therapy (PDT) and photodynamic diagnosis (PDD). So far, the experience with these photosensitizers for use within brain tumours is limited. We examined the distribution and retention of 14C-labelled m-THPC and [14C]5-ALA in the rat C6 glioma brain tumour model.

Transcutaneous pressure-adjustable valves and magnetic resonance imaging: an ex vivo examination of the Codman-Medos programmable valve and the Sophy adjustable pressure valve.

Objective: We investigated the compatibility of magnetically adjustable cerebrospinal fluid valves with clinical magnetic resonance imaging. Torque acting on the valves, subjective sensations of valve-carrying volunteers, extension of artifacts on acquired images, changes in valve pressure setting, and accurate valve function after repeated exposure to the magnetic field were tested.

Methods: Two externally adjustable differential pressure valves, i.

Electromotive diffusion (EMD) and photodynamic therapy with delta-aminolaevulinic acid (delta-ALA) for superficial bladder cancer.

Recent reports have shown that topical application of delta-aminolaevulinic acid (delta-ALA) can be used for the photodynamic diagnosis and therapy of superficial bladder tumours. Electromotive diffusion (EMD) increases the cellular uptake of polar substances. In six patients with biopsy-proven recurrent carcinoma in situ of the bladder after Bacillus Calmette-Guérin (BCG) treatment, 100 cm3 of a 0.

Unusual adverse reaction in a patient sensitized with Photosan 3.

Serious side effects of photodynamic therapy (PDT) are rare (A.L. Abramson, M.

Photodynamic therapy in neurosurgery: a review.

Photodynamic therapy (PDT) has been investigated extensively, both experimentally and clinically, as an adjunctive treatment in the neuro-oncological field. It is based on the more selective accumulation of a photosensitizer in malignant than normal tissue with low systemic toxicity. Subsequent light activation induces photo-oxidation, followed by selective tumour destruction via vascular and direct cellular mechanisms.

Therapy of glioblastoma multiforme: a cumulative experience of 10 years.

Purpose: Comparison of the effect of different therapeutic modalities on survival time of patients with glioblastoma multiforme operated on during the last decade (1980-1990).

Patients And Methods: The records of 157 consecutive patients with the histological diagnosis of glioblastoma multiforme were analysed for survival with respect to age of patients, extent of surgery, influence of re-operation and adjuvant postoperative treatment. The latter included fractionated radiotherapy, chemotherapy (BCNU.

Treatment of patients with severe head injury by triamcinolone: a prospective, controlled multicenter clinical trial of 396 cases.

The present studies were conducted to test whether the outcome of severe head injury is improved by early administration of the synthetic corticosteroid triamcinolone. In a prospective, double-blind, multicenter clinical trial, 396 patients with severe head injury were randomized to a steroid group (n = 187) receiving 200 mg triamcinolone acetonide (Volon A soluble) i.v.

[Photodynamic therapy in patients with recurrent gynecologic cancers].

Patients with recurrent gynaecological carcinomas have a poor prognosis, with a survival of a few months. Three patients with a recurrent vulva carcinoma, one patient with a recurrent cervical carcinoma, one patient with a recurrent endometrial carcinoma, and one patient with a recurrent breast carcinoma underwent PDT after parenteral or topical sensitisation with Photosan 3. From these patients, two of them showed a complete response with no evidence of disease for 32 and 29 months.

[Intraoperative radiotherapy of brain gliomas].

11 patients with recurrent brain tumours underwent intraoperative radiotherapy (IORT) at a dosage of 15-25 Gy of fast electrons (17-20 MEV). IORT allows a higher dose of irradiation to be delivered to a well-defined target than is possible with external radiation, in anticipation of favourable results. However, tumour growth was not influenced in 7 out of the 11 patients and these patients died between 2 and 10 months following IORT.