Modulated electrohyperthermia as part of immunogenic cell death treatment in pediatric neuro-oncology

Introduction The induction of immunogenic cell death (ICD) becomes an important treatment methodology in cancer. Convincing data demonstrate that modulated electrohyperthermia (mEHT) contribute to ICD. No data have been reported about the use of mEHT in a large pediatric brain cancer population. METHODS. We retrospectively analyzed a series of 76 children treated at IOZK with multimodal immunotherapy consisting of the combination of Newcastle Disease Virus (NDV) injections with mEHT and autologous dendritic cell vaccines IO-VAC. RESULTS. There were 46 females and 30 males with a median age of 6.5 resp. 9.5 years (range 1 – 19y resp. 2 – 18y). Diagnoses were anaplastic astrocytoma (6), Brain stem glioma (1), chordoma (1), DIPG (45), Ependymoma (4), GBM (12), medulloblastoma (3), pilocytic astrocytoma (1), pineoblastoma (1), choroid plexus carcinoma (1), unspecified (1). In total 811 mEHT sessions were given. Median number of mEHT sessions per child were 15, ranging up to 53. In all cases, mEHT doses were 40 Watt during 40 minutes. Treatments were feasible without sedation. There were no intervention-related side effects. NDV injections were associated to the mEHT sessions. Multimodal immunotherapy included the DC vaccinations with IO-VAC. In total 77 IO-VAC vaccines were produced, and in median 2 (range 0 – 4) IO-VAC vaccines were given per child. The use of PanTum Detect tests seemed reliable to monitor on daily basis the response to ICD treatment and over the treatment course. Median overall survival of 28 DIPG children treated with multimodal immunotherapy as part of their primary treatment showed a median overall survival of 14 months. Remarkable long-term remissions were also observed in a child with relapsed pineoblastoma and a child with metastasized Myc-amplified medulloblastoma group 3. CONCLUSION. Modulated electrohyperthermia for children with brain cancer as part of multimodal immunotherapy is feasible and safe. Response to treatment could be monitored. Multimodal immunotherapy contributed to improved tumor control and overall survival.