Clinical Study – Patient Study

Journal of Neuro-Oncology

, Volume 103, Issue 2, pp 317-324

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme

  • Klaus Maier-HauffAffiliated withDepartment of Neurosurgery, Bundeswehrkrankenhaus Berlin Email author 
  • , Frank UlrichAffiliated withClinic for Neurosurgery, Helios Klinikum Krefeld
  • , Dirk NestlerAffiliated withDepartment of Neurosurgery, Bundeswehrkrankenhaus Berlin
  • , Hendrik NiehoffAffiliated withClinic for Neurosurgery, Helios Klinikum Krefeld
  • , Peter WustAffiliated withDepartment of Radiotherapy, Charité—Universitätsmedizin Berlin
  • , Burghard ThiesenAffiliated withMagForce Nanotechnologies AG
  • , Helmut OrawaAffiliated withCoordination Centre for Clinical Studies (KKS), Charité—Universitätsmedizin Berlin
  • , Volker BudachAffiliated withDepartment of Radiotherapy, Charité—Universitätsmedizin Berlin
  • , Andreas JordanAffiliated withDepartment of Radiotherapy, Charité—Universitätsmedizin BerlinMagForce Nanotechnologies AG


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.


Glioblastoma Magnetic nanoparticles Radiotherapy Recurrence Thermotherapy