Tumour Treating Fields (TTFields) have anti-proliferative effects on paediatric brain tumour cell lines at clinically deliverable field settings

Abstract

Approximately 400 children in the UK are diagnosed with a CNS tumour each, which represents a quarter of childhood cancer cases in the UK. The overall 5-year survival rate of peadiatric brain tumour patients is roughly 75%, however survival still remains poor for some brain tumours, particularly high grade gliomas. Pre-clinical studies have shown efficacy of TTFields on high grade glioma cell lines, while TTFields have only been approved for adult Glioblastoma multiforme (GBM) patients in combination with the Stupp treatment protocol. The lack of overlapping toxicities associated with OptuneTM has made TTFields an attractive treatment strategy for poor prognosis brain tumours. The InovitroTM system is the laboratory testing system used to develop the clinically approved Optune system. InovitroTM was used to deliver TTFields over 72 hours at a range of clinically relevant frequencies (100-400kHz) and intensities (1-3V/cm) to a panel of paediatric GBM, Medulloblastoma and Ependymoma cell lines. The effects of TTFields on cell viability and cell cycle was assessed using metabolic viability tests (Presto blue), cell proliferation assays and cell cycle analysis using flow cytometry. TTFields treatment reduces cell viability of all paediatric brain tumour cell lines tested within the frequency titration. The optimum frequencies were between 200 and 300kHz for all cell lines tested. TTFields treatment had significant effects on cell cycling relative to control cells. This preliminary study has confirmed the efficacy of electric fields on paediatric brain tumour cell lines. The optimum frequencies for the paediatric GBM cell lines did not uniformly fall into the 200kHz range as previously reported for glioma cell lines. This report warrants further study into the potential for TTFields therapy for paediatric patients.