Tumor Treating Fields Therapy Influences Patterns of Failure in Glioblastoma Patients in a Dose-Dependent Manner: A Multidisciplinary Analysis of the Randomized Phase III EF-14 Clinical Trial

Abstract

The phase 3 EF-14 trial showed that when combined with chemoradiation Tumor Treating Fields (TTFields) improve Overall Survival (OS) and Progression Free Survival (PFS) in newly diagnosed GBM. We correlated TTFields dose distributions and patient specific patterns of failure, hypothesizing that the antimitotic effects of TTFields therapy would result in measurable changes in the location of recurrence. Two hundred and twenty five patients treated on the TTFields arm of EF-14 had both MR imaging sufficient for dose calculations and radiographically measureable progression of disease. Realistic head models of patients were created with virtual transducer arrays placed on the models in a patient-specific manner. TTFields intensity distributions were calculated using a Finite Elements Method. TTFields dose (expressed as mW/cm3) was defined as the product of TTFields intensity, tissue conductivity and the average patient compliance during first 6 months of therapy. For each case, the resection cavity +/- any residual gross tumor and an expansion margin of 3, 5, 10, 15, or 20 mm was defined as the primary areas of interest. At baseline, regions of residual tumor and regions of normal brain were identified for calculation of the TTFields dose within each these regions and its relationship with subsequent recurrence. The average dose in areas of enhancing tumor that regressed to normal was higher than in the areas of normal brain that progressed to enhancing tumor (0.84 mW/cm3 vs 0.75 mW/cm3, p<0.001). Regardless of the expansion margin used for analysis, TTFields dose in areas of normal brain that remained normal (norm to norm) at the time of progression were consistently higher than in the areas of normal brain that progressed to enhancing tumor (norm to tumor). These results confirm the clinical activity of TTFields and the importance of dose intensity at the tumor bed. Higher dose was seen in areas of normal brain that remain normal at the time of progression, providing further rationale for optimizing the array placement to maximize delivery to areas at highest risk of recurrence. Efforts to improve patient-specific TTFields dose planning and optimization, similar to radiotherapy planning, are underway.Abstract 3845; Table 1Expansion margin (mm)avg Dose in norm to norm (mW/cm3)avg Dose in norm to tumor (mW/cm3)Difference (mW/cm3)p-value30.7940.7340.06<0.00150.7850.7340.051<0.001100.7690.7340.0350.011150.7600.7310.0290.026200.7560.7310.0250.048 Open table in a new tab