Traditional single-reaction Arrhenius models have been successfully used for many years in burn studies[1–3] and have been adapted and used to predict quantitative histologic results in laser, RF and microwave heating at high temperatures.[4–6] The single reaction kinetics model also forms the basis for the time scaling ratio as is currently used in calculating the cumulative equivalent minutes (CEM) assessment of tumor hyperthermia treatments.[7] Recently, it has been clearly demonstrated that these models are not acceptably accurate predictors of the early stages of cell death processes in hyperthermic heating — moderate temperature rises (< ∼15 C) for times from several minutes to hours.[8, 9] A typical ensemble of cell survival curves has an initial slowly-developing shoulder region, a constant-rate region and, often, a “foot’, as it were, which has a much slower death rate. Simple first-order Arrhenius predictions are constant-rate models, only, and substantially over-estimate population cell death in the early stages of heating.

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