The Relevance of High Temperatures and Short Time Intervals Between Radiation Therapy and Hyperthermia: Insights in Terms of Predicted Equivalent Enhanced Radiation Dose.

Abstract

The radiosensitization effect of hyperthermia can be considered and quantified as an enhanced equivalent radiation dose (EQD_RT), that is, the dose needed to achieve the same effect without hyperthermia. EQD_RT can be predicted using an extended linear quadratic model, with temperature-dependent parameters. Clinical data show that both the achieved temperature and time interval between radiation therapy and hyperthermia correlate with clinical outcome, but their effect on expected EQD_RT is unknown and was therefore evaluated in this study. Biological modeling was performed using our in-house developed software (X-Term), considering a 23- × 2-Gy external beam radiation scheme, as applied for patients with locally advanced cervical cancer. First, the EQD_RT was calculated for homogeneous temperature levels, evaluating time intervals between 0 and 4 hours. Next, realistic heterogeneous hyperthermia treatment plans were combined with radiation therapy plans and the EQD_RT was calculated for 10 patients. Furthermore, the effect of achieving 0.5°C to 1°C lower or higher temperatures was evaluated. EQD_RT increases substantially with both increasing temperature and decreasing time interval. The effect of the time interval is most pronounced at higher temperatures (>41°C). At a typical hyperthermic temperature level of 41.5°C, an enhancement of ∼10 Gy can be realized with a 0-hour time interval, which is decreased to only ∼4 Gy enhancement with a 4-hour time interval. Most enhancement is already lost after 1 hour. Evaluation in patients predicted an average additional EQD_RT (D95%) of 2.2 and 6.3 Gy for 4- and 0-hour time intervals, respectively. The effect of 0.5°C to 1°C lower or higher temperatures is most pronounced at high temperature levels and short time intervals. The additional EQD_RT (D95%) ranged between 1.5 and 3.3 Gy and between 4.5 and 8.5 Gy for 4- and 0-hour time intervals, respectively. Biological modeling provides relevant insight into the relationship between treatment parameters and expected EQD_RT. Both high temperatures and short time intervals are essential to maximize EQD_RT.