2000 Background: In a few years more than half of the patients with glioblastoma will be older than 65 years of age and thus be classified as elderly. The current standard of care in elderly patients with glioblastoma (GB) or anapestic astrocytoma (AA) is resection or biopsy followed by involved-field radiotherapy (RT). The role of primary chemotherapy is poorly defined. The NOA-08 trial compared efficacy and safety of RT to temozolomide (TMZ) in patients with newly diagnosed AA or GB. Methods: Patients (N=412; 39 AA, 373 GB) > 65 years with a Karnofsky performance score > 60 were randomized to receive RT or TMZ. The primary endpoint was overall survival (OS). The trial sought to demonstrate the non-inferiority of TMZ compared with RT. Results: Patient characteristics in the intention-to-treat population [N=373 (178 patients RT, 195 patients TMZ)] were balanced. All histologic diagnoses (11% AA and 89% GB) were centrally confirmed. Median OS [HR=1.09 (95% CI: 0.84-1.42)] and event-free survival (EFS) [hazard ratio (HR)=1.15 (0.92-1.43)] of TMZ versus RT did not differ between both arms. Non-inferiority of TMZ compared with RT was significant (p<0.05). Extent of resection, but not age or diagnosis of AA were associated with prolonged EFS and OS. DNA repair protein O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation in tumor tissue was associated with prolonged OS [HR=0.67 (0.38-1.29)]. Patients with MGMT promoter methylation had longer EFS when treated with TMZ (8.4 months [5.5-11.7] versus RT (4.6 [4.2-5] months) whereas patients without MGMT promoter methylation had longer EFS when treated with RT (4.6 [3.7-6.3] versus 3.3 [3-3.5] months). This effect persisted for OS. Conclusions: NOA-08 demonstrates the non-inferiority of TMZ compared with RT in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation is a strong predictive biomarker for the choice between RT and TMZ.

Today it is possible to cure more than 90 % of children and adolescents with Hodgkin's disease with a combination of radiotherapy and chemotherapy. Since the DAL-HD 82 study, the main scientific focus has been on avoiding late effects such as the OPSI syndrome, late complications involving the heart, lungs, thyroid and/or gonads particularly sterility in men and premature onset of menopause in women, and the prevention of secondary malignancies. The GPOH-HD 2003 study will introduce FDG-PET to the initial diagnostic program and the assessment of response to therapy in order to evaluate further possibilities for reducing therapy. In this context, the central review of all clinical and radiological findings, systematically done since the DAL-HD 90 study, will be increasingly relevant in maintaining standardised stage classification and therapy group assignment which was established by the preceding studies. Continuing in the direction of the earlier studies, the indications for radiotherapy will be restricted even further. In the early stages (treatment group 1) patients with CR or a negative FDG-PET at the end of chemotherapy will receive no radiotherapy in order to reduce the risk of a secondary malignancy. In a randomized comparison, procarbazine will be replaced by dacarbazine in the COPP cycles to determine whether sterility in men and premature onset of menopause in women can be avoided by elimination of procarbazine while retaining the same clinical efficacy. Finally, relapse therapy is to be tailored according to the time of relapse, the initial therapy group, and the patient's response to the relapse therapy with more patients receiving autologous transplantation in order to further improve the results of relapse treatment.

Intravenous glucocorticoids and orbital radiotherapy are effective treatments for moderate-to-severe and active Graves' orbitopathy. We examined the ophthalmological outcome in daily life activities, such as driving competency. In a retrospective case series, 23 patients with moderate-to-severe and active Graves' disease (14 women and 7 men) were consecutively treated with combined orbital radiotherapy (13 Gy) and intravenous methylprednisolone (500 mg weekly for 6 consecutive weeks and 250 mg weekly for consecutive 6 weeks). The pretreatment Clinical Activity Score of 5.2 points (SD+/-0.9) decreased significantly to 2.7 points (SD+/-1.1) in the 12-month follow-up. Inflammatory eye signs, for example, pain and pressure sensation, caruncle inflammation, eyelid swelling, and exophthalmos decreased significantly. However, there was no significant improvement of eye motility. Despite anti-inflammatory treatment, 13 patients (61.9%) were not fit to drive a car under binocular conditions and additional stabismologic therapy including strabismus surgery was required. The combined therapy of intravenous glucocorticoids and orbital radiotherapy reduced inflammatory ophthalmological signs. In most cases strabismologic intervention including eye muscle surgery was necessary to restore driving competency.

PURPOSE: This study was performed to evaluate the incidence of seizures with its implications on disease progression and the diagnostic value of post-ictal magnetic resonance images (MRI) during the management of highgrade gliomas (HGGs). PATIENTS AND METHODS: A total of 406 consecutive patients with newly diagnosed HGGs were retrospectively reviewed. The incidence of seizure attacks during the management was investigated. In patients who experienced a seizure, the causality between seizures and disease progression was assessed by pre-ictal, post-ictal (,1 month), and follow-up (,3 months) MRI. RESULTS: After a mean follow-up of 21.9 months (range, 0.1 -88.3), seizure attacks developed in 127 patients (31%). Of the 127 patients, radiological progression at the post-ictal MRI was found in 83 patients (65%) and the follow-up MRI confirmed progression in 79 patients (62%). However, other 4 patients (3%) were shown to be progression-free. Among those without radiological progression at the post-ictal MRI, the follow-up MRI confirmed progression-free in 31 patients (24%); however, 13 patients (10%) revealed eventual progression. In the patients with a seizure, absence of preoperative seizure (p ¼ 0.003), , 95% tumor resection (p ¼ 0.001), and pre-ictal Karnofski Performance Scale score ≤ 70 (p ¼ 0.025) were significantly associated with disease progression. CONCLUSION: During the management of HGG, 31% of patients experienced seizures; of these patients, 72% harbored progressive disease. The post-ictal MRI is useful for detecting disease progression; however, there are pitfalls. Clinical settings should be considered together for diagnosing disease progression in patients with seizures.

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