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

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.

Magnetic Nanoparticles for Precision Oncology: Theranostic Magnetic Iron Oxide Nanoparticles for Image-Guided and Targeted Cancer Therapy

“…For example, magnetic hyperthermia mediated by IONPs could increase the temperature at the tumor center to greater than 40°C after exposing to alternating magnetic field [106], resulting in tumor growth inhibition in a human head and neck tumor xenograft model. IONP-facilitated magnetic hyperthermia has been translated in human patients in clinical trials [107]. After received IONP-induced MNPs for precision oncology: theranostic magnetic IONPs for image-guided & targeted cancer therapy Review hyperthermia and low-dosage radiotherapy, a significant increase in survival of the patients with recurrent glioblastoma was observed in the combination treatment group comparing with control groups.…”

Magnetic Nanoparticles: Its Effect on Cellular Behaviour and Potential Applications

“…The survival after first diagnosis is 8.6 months longer in hyperthermia group compared with conventional treatment group. In addition, the adverse effect of hyperthermia is not significant according to the observation of the study (Maier-Hauff et al, 2011).…”

Nanomaterials for biomedical applications

“…These NPs can be activated either by using radiofrequency (RF) pulses or infrared light to release heat and kill the target tissue. Super paramagnetic iron oxide NP is currently being used in hyperthermia applications in vivo (Maier-Hauff et al 2011). The surface plasmon resonance of metal NPs is another property which is used for irreversible thermal ablation of tumors (Chen et al 2010).…”

“…They can be used to reduce toxicity of a therapeutic drug (Vlerken & Amiji 2006), or for pH-triggered drug release (Lim et al 2011). NPs are currently being used for hyperthermia treatment (Maier-Hauff et al 2011), and photodynamic therapy (Robertson et al 2009). For example, AuroShell is a nanoproduct that kills cells at the target tumor site by emitting heat upon absorption of near-infrared (NIR) light (Leung et al 2013).…”