NovoTTF™-100A System (Tumor Treating Fields) transducer array layout planning for glioblastoma: a NovoTAL™ system user study

Abstract

Background: Optune™, previously known as the NovoTTF-100A System™, generates Tumor Treating Fields (TTFields), an effective anti-mitotic therapy for glioblastoma. The system delivers intermediate frequency, alternating electric fields to the supratentorial brain. Patient therapy is personalized by configuring transducer array layout placement on the scalp to the tumor site using MRI measurements and the NovoTAL System. Transducer array layout mapping optimizes therapy by maximizing electric field intensity to the tumor site. This study evaluated physician performance in conducting transducer array layout mapping using the NovoTAL System compared with mapping performed by the Novocure in-house clinical team.

Methods: Fourteen physicians (7 neuro-oncologists, 4 medical oncologists, and 3 neurosurgeons) evaluated five blinded cases of recurrent glioblastoma and performed head size and tumor location measurements using a standard Digital Imaging and Communications in Medicine reader. Concordance with Novocure measurement and intra- and inter-rater reliability were assessed using relevant correlation coefficients. The study criterion for success was a concordance correlation coefficient (CCC) >0.80.

Results: CCC for each physician versus Novocure on 20 MRI measurements was 0.96 (standard deviation, SD ± 0.03, range 0.90-1.00), indicating very high agreement between the two groups. Intra- and inter-rater reliability correlation coefficients were similarly high: 0.83 (SD ±0.15, range 0.54-1.00) and 0.80 (SD ±0.18, range 0.48-1.00), respectively.

Conclusions: This user study demonstrated an excellent level of concordance between prescribing physicians and Novocure in-house clinical teams in performing transducer array layout planning. Intra-rater reliability was very high, indicating reproducible performance. Physicians prescribing TTFields, when trained on the NovoTAL System, can independently perform transducer array layout mapping required for the initiation and maintenance of patients on TTFields therapy.

Figures

Fig. 1

Electric field magnitude and distribution (in V/cm) shown in coronal view from a finite element method simulation model. This simulation employs a left-right paired transducer array configuration. Reprinted with permission from Miranda et al. [5]

Fig. 2

Sample transducer array layout map guiding placement of transducer arrays on the scalp

Fig. 3

Magnetic resonance imaging. a Axial T1 sequence slice containing most apical image, including orbits used to measure head size. b Coronal T1 sequence slice selecting image at level of ear canal used to measure head size. c Postcontrast T1 axial image shows maximal enhancing tumor diameter used to measure tumor location. d Postcontrast T1 coronal image shows maximal enhancing tumor diameter used to measure tumor location

Fig. 4

Scatterplots and linear correlation between Novocure and physician magnetic resonance imaging (MRI) measurement for MRI cases 1 to 5. Error bars represent ±7.5 mm from Novocure measurements. Each color represents a set of measurements made by a different physician (n = 14). Mean (SD) R2 linear correlations for all physicians versus Novocure were a case 1, 0.9966 (0.0039); b case 2, 0.9954 (0.0041); c case 3, 0.9967 (0.0050); d case 4, 0.9963 (0.0037); and e case 5, 0.9935 (0.0066)