A panel of glial tumors consisting of 11 low grade gliomas, 9 anaplastic gliomas, and 29 glioblastomas were analyzed for loss of heterozygosity by examining at least one locus for each chromosome. The frequency of allele loss was highest among the glioblastomas, suggesting that genetic alterations accumulate during glial tumor development. The most common genetic alteration detected involved allele losses of chromosome 10 loci; these losses were observed in all glioblastomas and in three of the anaplastic gliomas. In order to delineate which chromosome 10 region or regions were deleted in association with glial tumor development, a deletion mapping analysis was performed, and this revealed the partial loss of chromosome 10 in eight glioblastomas and two of the anaplastic gliomas. Among these cases, three distinct regions of chromosome 10 were indicated as being targeted for deletion: one telomeric region on 10p and both telomeric and centromeric locations on 10q. These data suggest the existence of multiple chromosome 10 tumor suppressor gene loci whose inactivation is involved in the malignant progression of glioma.
Thalamotomy aiming at the CM-Pf complex and using stereotactic gamma irradiation has been performed in a series of 52 patients with severe pain due to malignancy. Lesions were produced either contra- or ipsilaterally to the side of the pain as well as bilaterally. Eight patients experienced good pain relief, 18 had moderate relief, and in 24 the operation did not significantly influence the pain. A second operation following recurrence of pain was rarely of value. There was a tendency towards more efficient relief of pain located in the face or in the arm and shoulder than of pain in the lower part of the body. Although contralateral lesions seem to be most effective, ipsilateral operations may also give some relief. The best results were obtained when the lesions were placed close to the wall of the third ventricle and at the level of the posterior commissure. Postmortem examination of 21 brains disclosed that the mean error in the placing of the lesions was about 1 mm. It is concluded that medial thalamotomy may be tried as a last resort in the treatment of cancer pain in selected patients with a short life expectancy.
Malignant glioblastoma may over-express the epidermal-growth-factor receptor (EGF-R). Normal brain cells show a low or no expression of EGF-R. A mouse monoclonal antibody (IgG2A) (mAb 425) (EMD55900) (Merck KGaA, Bernstadt, Germany) directed against EGF-R was produced for therapeutic use. Eight patients with primary or recurrent, EGF-R-positive glioblastomas entered the study, which was designed to evaluate the clinical effect of the mAb. In order to achieve a high tumor cell saturation, the mAb was injected intratumorally twice weekly through an implantable catheter. The total administered dose varied between 4 mg and 120 mg. In 3 patients with solid tumors, a massive tumor necrosis was noted, with infiltration of macrophages, granulocytes and T cells. A further 3 patients developed clinical and radiological signs of an intense, local, inflammatory reaction. There may be a relation between the mAb dosage and the antitumor effect, insofar as higher doses seemed to cause a more pronounced, inflammatory reaction. Of the 8 patients, 6 developed human, anti-(mouse Ig) antibodies. This anti-EGF-R mAb may induce an intense, inflammatory reaction and a considerable necrosis in glioblastoma. However, the planned schedule could not be completed, even after the dose level was re-adjusted, owing to inflammatory reactions, which were severe without prior tumor debulking.
Object. The authors report on the follow-up studies in patients treated at the Karolinska Hospital to evaluate the efficacy of gamma knife radiosurgery (GKS) for pilocytic astrocytoma. Methods. Twelve male and seven female patients were treated (mean age 10.6 years [range 2–60 years]). Sixteen of these patients were children in whom GKS was performed to treat residual tumor after surgery. Most tumors were treated with a prescription dose of 10 to 12 Gy (range 9–20 Gy). The corresponding maximum dose varied between 22 and 30 Gy (range 10–50 Gy). The median clinical follow-up time was 7 years and mean clinical follow-up time 8.5 years. Median radiological follow-up time was 4.7 years and the mean radiological follow-up time was 5.9 years. Tumor control was achieved in all patients. In 85% of the cases a moderate tumor volume reduction was observed after GKS. This result occurred despite the low prescription dose administered. The radiological follow-up studies showed adverse radiation effects in 25% of patients with increasing contrast enhancement and some edema. These effects generally appeared within 7 months and resolved later. Cyst development occurred in two patients, which may have been treatment related. Conclusions. It appears that small pilocytic astrocytomas may be treated with low-prescription-dose GKS, resulting in satisfactory clinical outcomes and only minor side effects. There were a certain number of radiologically demonstrated side effects that appeared relatively early but subsequently resolved. This study should be regarded as a preliminary one because the number of patients is small and the follow-up period is short compared with the natural time course of the disease.
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