gms | German Medical Science

Objective: We recently showed that intracavitary thermotherapy with superparamagnetic iron-oxide nanoparticles can induce persistent inflammatory reactions which might lead to long-term stabilization of recurrent glioblastoma (GBM) patients.

Methods: Here, we report data from a series of ten recurrent GBM WHO IV patients (IDH WT, MGMT: methylated 30%, unmethylated 70%; median age: 59 years) who were treated with intracavitary thermotherapy after coating the resection cavity wall ("NanoPaste") with NanoTherm^® (MagForce AG, Berlin, Germany). All patients underwent six 1-hour semi-weekly hyperthermia sessions in an alternating magnetic field (mean maximum temperature 52.3° C (+/- 6.0 °C), and six patients also received concurrent radiotherapy at a dose of 39.6 Gy (5 x 1.8 Gy/week).

Results: No major side effects were observed during active treatment. However, all patients developed cerebral edema and increasing clinical symptoms during treatment follow-up (median 92 days, range 73 to 144). Patients were treated with dexamethasone and, if necessary, underwent re-surgery to remove nanoparticles (n=5). Histopathology revealed sustained necrosis and large amounts of nanoparticles without evidence for tumor activity and a proinflammatory reaction with increased T-cell and myeloid cell infiltration. Median overall survival (mOS) for the study population was 10.1 months (CI 95% 8.0 to 12.2). A survival advantage could be observed for patients who were treated at first recurrence (n=5) when compared to patients treated at the second recurrence or later (mOS = 20.6 vs 9.4 months). Patients, who received both thermotherapy and re-irradiation (n=6) had better mOS than patients treated with thermotherapy alone (17.3 vs 8.6 months). Two patients had long-lasting treatment responses > 23 months with one patient who is still alive 3.5 years after treatment without receiving any further therapy.

Conclusion: These results warrant further investigations. A European clinical registry will be set up to further evaluate the potential of "NanoPaste" therapy for patients with recurrent glioblastoma.

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