P14.69 Evaluation of electric field intensity delivered by Tumor-Treating Fields therapy to PET-defined metabolic volumes in recurrent glioblastomas

Abstract

Abstract BACKGROUND Tumor-Treating Fields (TTFields) therapy is a clinical treatment option for patients with newly-diagnosed and recurrent glioblastomas. Electric field intensities (EFIs) delivered to the tumor mass may affect treatment responses. In this study, we used the patients’ neuroimaging data to create realistic head models and evaluate: (i) the magnitude of EFIs delivered to the tumor mass; (ii) factors affecting the EFI values; and (iii) factors affecting treatment responses as assessed by amino acid PET. MATERIAL AND METHODS Fourteen recurrent glioblastomas in 9 patients were evaluated with α-[11C]-methyl-L-tryptophan (AMT)-PET before and up to 3 months after TTFields therapy (mean follow-up: 2.3 months). Individual MRI and CT scans were used to create patient-specific realistic head models and simulate TTFields delivery to the tumors. For each direction of treatment (antero-posterior, left-right), two 9-disk transducer arrays were simulated using disks placed according to the patients’ NovoTAL System™ based treatment plan. To generate TTFields, an alternating voltage difference (200V peak-to-peak, 200 kHz) was imposed on the outer surfaces of the disks. The simulations were performed using the Sim4Life V3.0 (ZMT-Zurich) quasi-electrostatic solver. The field intensities were normalized to simulate 2A peak-to-peak current supplied by the device. 3D EFI maps were created and fused with the pre- and post-TTFields PET images to measure EFIs delivered to the PET-defined metabolic tumor volume. Interval changes of static AMT uptake and kinetic PET variables were also evaluated. RESULTS The mean EFI delivered to the tumors varied between 1.34–2.43 V/cm (mean: 1.86 V/cm). Fronto-parietal tumors received higher mean EFI than temporal lobe tumors (p=0.05). Most tumors showed decreasing (n=9) or stable (n=4) AMT uptake on follow-up PET imaging after TTFields therapy. Higher EFIs delivered to the tumors (r=-0.56, p=0.04) and concomitant bevacizumab treatment (n=7, p=0.01) were associated with a greater PET response. On tracer kinetic analysis, the AMT uptake responses correlated with transport rate changes (p=0.04). CONCLUSION TTFields treatment of recurrent glioblastomas delivers variable EFIs to the metabolic tumor volume. Treatment responses on PET are driven by decreased amino acid transport rates, whose magnitude is associated with higher EFIs delivered to the tumor mass and also with concomitant antiangiogenic treatment in those with combined therapy. (The cost of the PET scans was supported by a grant from NovoCure Ltd., Haifa, Israel)