Abstract 472: What electric field strength is necessary for maximum tumor-treating fields efficacy

Abstract Why Is 4 V/cm Electric Field Strength Necessary for Maximum Tumor-Treating Fields Efficacy? INTRODUCTION: Tumor Treating Fields (TTFields) extend overall survival in glioblastoma patients. Threshold field strength for TTFields is typically cited as 2V/cm. Yet plots of cell death vs. field strength in vitro indicate a power law relationship asymptotic to 4 V/cm for 100% efficacy. The mechanisms of action (MoA) of TTFields underlying this relationship are currently under investigation. TTFields are suspected of disrupting critical mitotic processes performed by large polar cellular molecules such as microtubules (MT). METHODS: Using the power law relationship for the energy (intensity, I) carried by an electric field and its amplitude (Eq. 1), we calculated energy vs. TTFields amplitude. (1) RESULTS: We suggest Eq. 1 is a likely source of the relationship between TTFields' amplitude and cell death proportion that has been demonstrated empirically. Further, Table 1 shows energy transmitted per unit MT surface area per TTFields cycle, specifically, the energy per MT dimer band around an MT helix per TTFields period of 5 µs. TTFields Field Strength (V/cm)Radiant Flux Density (W/nm2)Energy/(Cycle-Area) (J/nm2)Energy/MT Dimer/Cycle (J)Energy/MT Dimer Band/Cycle (J)113.3 × 10−186.63 × 10−234.01 × 10−224.17 × 10−20253.1 × 10−1826.6 × 10−231.60 × 10−211.67 × 10−193119 × 10−1859.7 × 10−233.61 × 10−213.75 × 10−194212 × 10−18106 × 10−236.42 × 10−216.67 × 10−195332 × 10−18166 × 10−231.00 × 10−201.04 × 10−186478 × 10−18239 × 10−231.44 × 10−201.50 × 10−18 A metric for disruption of cellular processes is 1-2 orders of magnitude greater than the thermal background energy in the cell, kT = 4.3 × 10−21 J. Table 1 shows that the energy absorbed by a MT dimer is insufficient to disrupt cellular processes at 2 V/cm, while due to energy increasing with square of field strength, at 5 V/cm it may be disruptive. For an entire dimer band around the MT helix, 2 V/cm appears to be sufficient, while 4 V/cm seems amply strong to disrupt MT function, in accordance with in vitro experiments. CONCLUSION: Assuming the power law of energy vs. electric field strength and the resulting energy absorbed by microtubule components, we found a correlation between typical TTFields' amplitudes and estimated disruption thresholds of MT function. TTFields MoA. 4 V/cm, not 2V/cm, should be the target field strength to realize the full efficacy of TTFields. Citation Format: Kristen W. Carlson, Jack A. Tuszynski, Socrates Dokos, Nirmal Paudel, Zeev Bomzon. What electric field strength is necessary for maximum tumor-treating fields efficacy [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 472.

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