A clinical study evaluated the efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy in patients with recurrent glioblastoma multiforme. The study involved 66 patients, of whom 59 had recurrent glioblastoma. Patients received neuronavigation-guided intratumoral instillation of an aqueous dispersion of iron-oxide nanoparticles, followed by heating in an alternating magnetic field. This was combined with fractionated stereotactic radiotherapy (median dose 30 Gy). The primary endpoint was overall survival following first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary diagnosis (OS-1). The median OS-2 was 13.4 months, and the median OS-1 was 23.2 months. Only tumor volume at study entry was significantly correlated with survival. The treatment had moderate side effects, with no serious complications. Thermotherapy using magnetic nanoparticles combined with reduced radiation dose was safe and effective, leading to longer OS-2 compared to conventional therapies. The study demonstrated that the combination of thermotherapy and radiotherapy improved survival in patients with recurrent glioblastoma. The approach showed promising results, with no significant differences in survival between patients who had prior treatment and those who had not. The study also highlighted the potential of this combined approach for future clinical applications, including combination with chemotherapy. The results suggest a favorable risk-benefit ratio for patients with recurrent glioblastoma. The study was conducted in two centers and approved by institutional review boards. The findings indicate that intratumoral thermotherapy using magnetic nanoparticles combined with radiotherapy is a promising treatment option for recurrent glioblastoma.A clinical study evaluated the efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy in patients with recurrent glioblastoma multiforme. The study involved 66 patients, of whom 59 had recurrent glioblastoma. Patients received neuronavigation-guided intratumoral instillation of an aqueous dispersion of iron-oxide nanoparticles, followed by heating in an alternating magnetic field. This was combined with fractionated stereotactic radiotherapy (median dose 30 Gy). The primary endpoint was overall survival following first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary diagnosis (OS-1). The median OS-2 was 13.4 months, and the median OS-1 was 23.2 months. Only tumor volume at study entry was significantly correlated with survival. The treatment had moderate side effects, with no serious complications. Thermotherapy using magnetic nanoparticles combined with reduced radiation dose was safe and effective, leading to longer OS-2 compared to conventional therapies. The study demonstrated that the combination of thermotherapy and radiotherapy improved survival in patients with recurrent glioblastoma. The approach showed promising results, with no significant differences in survival between patients who had prior treatment and those who had not. The study also highlighted the potential of this combined approach for future clinical applications, including combination with chemotherapy. The results suggest a favorable risk-benefit ratio for patients with recurrent glioblastoma. The study was conducted in two centers and approved by institutional review boards. The findings indicate that intratumoral thermotherapy using magnetic nanoparticles combined with radiotherapy is a promising treatment option for recurrent glioblastoma.