No abstract

Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 × 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan–Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6–16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma.

No abstract

We aimed to evaluate the feasibility and tolerability of the newly developed thermotherapy using magnetic nanoparticles on recurrent glioblastoma multiforme. Fourteen patients received 3-dimensional image guided intratumoral injection of aminosilane coated iron oxide nanoparticles. The patients were then exposed to an alternating magnetic field to induce particle heating. The amount of fluid and the spatial distribution of the depots were planned in advance by means of a specially developed treatment planning software following magnetic resonance imaging (MRI). The actually achieved magnetic fluid distribution was measured by computed tomography (CT), which after matching to pre-operative MRI data enables the calculation of the expected heat distribution within the tumor in dependence of the magnetic field strength. Patients received 4-10 (median: 6) thermotherapy treatments following instillation of 0.1-0.7 ml (median: 0.2) of magnetic fluid per ml tumor volume and single fractions (2 Gy) of a radiotherapy series of 16-70 Gy (median: 30). Thermotherapy using magnetic nanoparticles was tolerated well by all patients with minor or no side effects. Median maximum intratumoral temperatures of 44.6 degrees C (42.4-49.5 degrees C) were measured and signs of local tumor control were observed. In conclusion, deep cranial thermotherapy using magnetic nanoparticles can be safely applied on glioblastoma multiforme patients.