Abstract CT204: Increasing Tumor Treating Fields dose at the tumor bed improves survival: Setting a framework for TTFields dosimetry based on analysis of the EF-14 Phase III trial in newly diagnosed glioblastoma
Authors: Ballo Matthew T. , Urman Noa , Bomzon Ze'ev , Lavy-Shahaf Gitit , Toms Steven 
Published: August 2019

Introduction: Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, anti-mitotic alternating electric fields that are delivered via transducer arrays placed on the shaved scalp. TTFields are approved for Glioblastoma (GBM) based on improved overall survival (OS) and progression free survival (PFS) in the Phase III EF-14 [NCT00916409] trial in newly diagnosed GBM patients. To test the hypothesis if increasing TTFields dose at the tumor bed improves patient outcomes, we performed a simulation-based study investigating the association between TTFields dose and overall survival (OS) and progression free survival (PFS) in EF-14 TTFields-treated patients.

Methods: EF-14 patients cases (N=340) were included. Realistic computational head models of the patients were derived from T1-contrast images captured at baseline. Patients who were on treatment for less than two months, or for whom MRI image quality was insufficient for the creation of a realistic head model were excluded from the analysis (N=126). The transducer array layout on each patient was obtained from EF-14 records; average compliance (fraction of time patient was on active treatment), and average electrical current delivered to the patient were derived from log files of the TTFields devices used by patients. TTFields intensity distributions and power loss densities were calculated for each patient using a Finite Elements Method. Local Minimum Dose Density (LMiDD) was defined as the product of TTFields power loss density and the average patient compliance. The average LMiDD within a tumor bed comprising the Gross Tumor Volume and the Peritumoral Boundary Zone 3 mm wide was calculated.

Results: The median OS and PFS were significantly longer when average LMiDD in the tumor bed was &gt;0.77 MmW/cm3: OS (25.2 vs. 20.4 months, p=0.003, HR=0.611) and PFS (8.5 vs 6.7 months, p=0.02, HR=0.699). The median OS and PFS were longer when average TTFields intensity was &gt;1.06 V/cm OS (24.3 vs. 21.6 months, p=0.03, HR=0.705) and PFS (8.1 vs 7.9 months, p=0.03, HR=0.721).

Conclusions: In this study we present the first reported analysis demonstrating patient-level dose responses to TTFields. Increasing Tumor Treating Fields dose at the tumor bed improves survival (OS and PFS) in newly diagnosed GBM. We provide a rigorous definition for TTFields dose, and set a conceptual framework for future work on TTFields dosimetry and treatment planning.

Citation Format: Matthew T. Ballo, Noa Urman, Ze'ev Bomzon, Gitit Lavy-Shahaf, Steven Toms. Increasing Tumor Treating Fields dose at the tumor bed improves survival: Setting a framework for TTFields dosimetry based on analysis of the EF-14 Phase III trial in newly diagnosed glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT204.