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. Primary end-point was improvement of overall survival. RESULTS: Patients (median age 54 years (range 23-80), Karnofsky performance status 80% (range 50-100) were randomised to TTF alone (n=120) or active chemotherapy control (n=117). Number of prior treatments was two (range 1-6). Median survival was 6.6 versus 6.0 months (hazard ratio 0.86 [95% CI 0.66-1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6 months was 21.4% and 15.1% (p=0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains. CONCLUSIONS: This is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.

Neurosarcoidosis mimicry of multiple sclerosis: clinical, laboratory, and imaging characteristics.

OBJECTIVE: To characterize the clinical and laboratory features of neurosarcoidosis (NS), presenting with findings consistent with multiple sclerosis (MS). METHODS: Retrospective chart review of our entire NS database was undertaken. Patients initially diagnosed with MS but who were subsequently diagnosed as having both systemic and neurologic sarcoidosis years later were selected for more detailed review. RESULTS: Seven patients were identified who were diagnosed with MS (although only 4 of these met McDonald criteria for MS during chart review) and 1 patient with optic neuritis who had a diagnosis of likely MS. These patients maintained the diagnosis of MS for a mean of 107 months (median 50 mo, range 23 to 262 mo) before the diagnosis was changed to NS, concomitant with the discovery of biopsy-proven systemic sarcoidosis in 4 cases. Neurologic manifestations included relapsing-remitting optic neuritis, myelopathy, dystonic spasms, sensory abnormalities, paraparesis, and hemiparesis. Patients appeared to improve or stabilize by treatment with corticosteroids or alternative immunosuppressants. MRIs demonstrated rounded or ovoid periventricular white matter changes typical for MS. CONCLUSION: Patients with NS are frequently diagnosed initially with MS because of a considerable overlap of clinical and laboratory features. However, due to the relative rarity of NS, a misdiagnosis of NS as MS occurred only infrequently in our MS clinic.

Visually enhanced vestibulo-ocular reflex: a diagnostic tool for migraine vestibulopathy.

OBJECTIVES: 1) To compare the incidence of elevated visually enhanced vestibular-ocular reflex (VVOR) rotational gain during rotational chair testing in a normal control group versus a group of patients diagnosed with migraine vestibulopathy; 2) to discuss the possible application of VVOR gain during rotational chair testing for diagnosing migraine vestibulopathy. STUDY DESIGN: Prospective normal control group and retrospective cohort comparison. METHODS: 1) Prospective rotational chair studies including VVOR in 20 normal control patients; 2) retrospective review of vestibular studies including VVOR in 100 consecutive patients with migraine vestibulopathy. RESULTS: Twenty of the normal controls and 69 of the migraine vestibulopathy patients met all inclusion criteria. One of 20 (5%) normal control patients had elevated VVOR gain, whereas 49 of 69 (71%) of migraine vestibulopathy patients had elevated VVOR gain. CONCLUSIONS: VVOR gain normal criteria were appropriate in 95% of our normal control test group. VVOR gain was more frequently elevated in migraine vestibulopathy patients than in the normal controls, and the difference was significant (P < .001). VVOR gain elevation was the most common vestibular test abnormality in this cohort of patients with migraine vestibulopathy. Because VVOR measures visual-vestibular interaction and its central connections, this parameter may be a useful diagnostic tool for migraine vestibulopathy in patients manifesting disequilibrium and motion sensitivity.

CI-980 for the treatment of recurrent or progressive malignant gliomas: national central nervous system consortium phase I-II evaluation of CI-980.

OBJECTIVE: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma. BACKGROUND: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses. METHODS: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m2, given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m2 per cycle. Treatment response was based on serial MRI imaging characteristics. RESULTS: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95% CI = 0-14%. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95% CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen. CONCLUSIONS: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma.