Numerical analysis of TTFields distribution in patient models shows a connection between TTFields intensity in the tumor and patient outcome

Introduction:

Tumor Treating Fields (TTFields) are alternating electric fields approved for the treatment of Glioblastoma (GBM). The Phase 3 EF-14 trial showed that adding TTFields to chemoradiation improves Overall Survival (OS) and Progression Free Survival (PFS) in newly diagnosed GBM. In-vitro studies show that the efficacy of TTFields increases with field intensity, leading to the hypothesis that increasing TTFields intensity at the tumor improves OS and PFS. Here we present, preliminary results of a simulation-based study testing this hypothesis in patients treated with TTFields as part of the EF-14 trial (n=466).

Methods:

To-date, n=119 cases have been simulated, and field intensity distributions in a tumor bed comprising the Gross Tumor Volume (GTV) and a zone extending 1 cm from the GTV derived. In addition, the average compliance and average a current delivered to the patients over the first six months were extracted from the Optune output log files. To test the hypothesis that patient outcome correlates with field intensities, two quantities were derived:

E95: the value such that 95% of the combined volume of the GTV and PBZ receives field intensities (multiplied by compliance) above this value.

Eaverage: the average intensity (multiplied by compliance and average current) in the combined volume of the GTV and PBZ.

Patients were divided into two groups based on threshold values of both E95 and Eaverage, and the OS and PFS of the groups were compared. The threshold values of these parameters were chosen to yield the most statistically significant difference in OS between the groups.

Results:

When dividing the 119 patients into two groups based on E95, the median OS and PFS were superior when E95>1.3.V/cm OS (33.0 months vs. 21.9 months, p=0.009, HR=0.46) and PFS (11.9 months vs 7.5 months, p=0.06, HR=0.49). Similar results were seen when dividing the patients into two groups based on a threshold of Eaverage>1.0 V/cm. Eaverage>1.0.V/cm, OS (26.1 months vs. 21.6 months, p=0.025, HR=0.50) and PFS (9.9 months vs 6.1 months, p=0.026, HR=0.54). OS in E95≤1.3.V/cm group is superior to OS in the EF-14-control-arm (16.0 months, p=0.009), indicating that patients benefited from treatment even when field intensities were lower.

Conclusions:

These preliminary results suggest that field intensity at the tumor bed correlates with patient outcome. Analysis of the full patient group will further elucidate this connection, leading to new strategies for treatment optimization.