gms | German Medical Science

Objective: Tumor Treat­ing Fields (TTFields) intensity was shown to be related to the antimitotic effect of this new treatment modality in preclinical settings. How this finding translates to patient outcome in a clinical setting has not been established yet. This simulation based study sought to explore a hypothesized correlation of TTFields dose with patient outcome, using data collected in the EF-14 trial that showed a clinical benefit of adding TTFields therapy to chemoradiation in patients with newly diagnosed glioblastoma.

Methods: Realistic computational models of patients receiving TTFields for at least 2 months and with baseline MRIs of sufficient quality (n=340) were created. To estimate the TTFields distribution within all patients, their specific transducer array (TA) layouts, average monthly compliance (ie, fraction of time the patient received TTFields), and average electrical current each patient received (calculated from log files of the TTFields generators) were combined into numerical simulations. TTFields are administered by 2 pairs of TAs in roughly orthogonal directions. To combine the two fields into a single measure of dose we defined Local Minimum Dose Density (LMiDD), as the product of the lower of the power densities delivered by the two fields to each point in the model, and the patient’s average compliance. The average LMiDD within a tumour bed (Gross Tumour Volume +3mm Peritumoural Boundary Zone) was calculated for each patient. By choosing the threshold value with the most significant difference in median survival between the groups, the patients were separated into 2 groups depending on every patient’s average LMiDD within the tumour bed.

Results: The best threshold of average LMiDD within the tumour bed for separation was determined as 0.77 mW/cm³. Splitting the population based on this threshold produced 2 groups with comparable demographics. In the group with higher TTFields doses, OS and PFS were significantly improved (OS: 25.2 months (mo) vs 20.4 mo, p=0.003, HR=0.61; PFS: 8.5 mo vs 6.7 mo, p=0.02, HR=0.70). Moreover, an average electric field in the tumour bed >1.06 V/cm was shown to prolong median OS (24.3 mo vs 21.6 mo, p=0.03, HR=0.71) and PFS (8.1 mo vs 7.9 mo, p=0.03 HR=0.79).

Conclusion: This study is the first to provide evidence for a connection between TTFields dose and efficacy in a clinical setting. This finding underlines the necessity of proper TTFields treatment planning to improve patients’ outcome.