Introduction: The pivotal phase 3 EF-14 trial revealed extended Overall Survival (OS) and Progression Free Survival (PFS) in newly Diagnosed Glioblastoma (ndGBM) patients that received Tumor Treating Fields + chemoradiation vs. patients that received chemoradiation alone. The effect of TTFields is dose-dependent, with improved outcomes for patients who received higher doses of TTFields to the tumor bed . Recent studies have also shown that TTFields influences tumor progression patterns in patients in a dose-dependent manner, with recurrence more likely to occur in regions of the brain in which field intensities are lower. This study also revealed that distal progressions are more common in ndGBM patients treated with TTFields_chemoradiation vs. patients treated with chemoradiation alone . Thus it seems that a major influence of TTFields is to enhance local control of the primary lesion. Here we present an analysis testing this hypothesis by analyzing tumor growth rates in patients who participated in the EF-14 trial.
Methods: Biopsy patients of the EF-14 trial who exhibited radiological progression were included in this study (treatment: N=37/60, control: N=12/29). Volumes of enhancing tumor were segmented on T1-contrast MRIs at baseline and at progression. The tumor Specific Growth Rate (SGR) was calculated as: Specific_Growth_Rate=(ln(v0)-ln(v1))/dt. Here, v0 represents tumor volume at baseline, v1 represents tumor volume at progression, and dt represents the time to progression. This equation models tumor volume as increasing exponentially over time . The distribution of growth rates in the treatment and control arms were compared. The analysis was restricted to biopsy-only patients since the definition of tumor volume is ambiguous in patients that underwent resection, as a large portion of the tumor has been removed.
Results: The median growth rate was lower in the treatment arm than in the control. (control: 0.14±0.12 mL/month, TTFields -0.011±0.11 mL/month, p<0.008 Wilcoxon rank-sum).
Discussion and conclusions: This study suggests that TTFields does indeed enhance local control of the tumor, significantly inhibiting the growth rate of the primary lesion. In this context, is worth noting that standard practice is to plan placement of the transducer arrays used to deliver TTFields in order to maximize dose delivered to the tumor. Thus, the results of this study support the hypothesis that adaptive treatment planning, in which the transducer array layout is periodically changed in order to dynamically target regions in which progression is observed, may help to improve patient outcomes.
References:  Ballo, Matthew, et al. IJRBOP (2019)  S. Jeyapalan et. al., presented at ASTRO 2019  Stensjøen, Anne Line, et al. Neuro-oncology (2015)
Citation Format: Ze'ev Bomzon, Noa Urman, Shay Levi, Gitit Lavy-Shahaf. TTFields dose distribution alters tumor growth patterns: An imaging-based analysis of the randomized phase 3 EF-14 trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 44.