Oncological hyperthermia: The correct dosing in clinical applications

Abstract

The problem with the application of conventional hyperthermia in oncology is firmly connected to the dose definition, which conventionally uses the concept of the homogeneous (isothermal) temperature of the target. Its imprecise control and complex evaluation is the primary barrier to the extensive clinical applications. The aim of this study was to show the basis of the problems of the misleading dose concept. A clear clarification of the proper dose concept must begin with the description of the limitations of the present doses in conventional hyperthermia applications. The surmounting of the limits the dose of oncologic hyperthermia has to be based on the applicability of the Eyring transition state theory on thermal effects. In order to avoid the countereffects of thermal homeostasis, the use of precise heating on the nanoscale with highly efficient energy delivery is recommended. The nano-scale heating allows for an energy-based dose to control the process. The main aspects of the method are the following: i) It is not isothermal (no homogeneous heating); ii) malignant cells are heated selectively; and iii) it employs high heating efficacy, with less energy loss. The applied rigorous thermodynamical considerations show the proper terminology and dose concept of hyperthermia, which is based on the energy-absorption (such as in the case of ionizing radiation) instead of the temperature-based ideas. On the whole, according to the present study, the appropriate dose in oncological hyperthermia must use an energy-based concept, as it is well-known in all the ionizing radiation therapies. We propose the use of Gy (J/kg) in cases of non-ionizing radiation (hyperthermia) as well.

Bevacizumab Plus FOLFOX-4 Combined With Deep Electro-Hyperthermia as First-line Therapy in Metastatic Colon Cancer: A Pilot Study

“…In fact, the electric field tends to move through the pathways with the lowest impedance, i.e. through the malignant tissue (71,(74)(75)(76)(77).…”

Quo Vadis Oncological Hyperthermia (2020)?

“…Modulated electro-hyperthermia applies capacitive coupling with impedance matching in order to maximize the absorbed energy and minimize the reflected, or lost energy (106). Due to the high efficacy of current matching (107), the absorbed energy can be used as the dose control (108,109) instead of the temperature achieved within the tumor.…”

wIRA-heating of piglet skin and subcutis in vivo: proof of accordance with ESHO criteria for superficial hyperthermia

“…To characterize heating properties, the following parameters were calculated according to [1,18,[20][21][22][23][24][25][26] as a function of exposure time and tissue depth: (a) HR; (b) SAR; (c) effective penetration depth (EPD); (d) TR after 6 min of exposure and in the thermal steady state; (e) thermal effective penetration depth (TEPD); (f) exposure time to reach a TR of 6K (ET6K); (g) 10th, 50th and 90th percentiles of temperature data, and T 90 , T 50 and T 10 as temperatures exceeded by 90%, 50% and 10% of temperature data measured during the exposure; (h) 100 th percentile and maximum temperature T max ; (i) tissue depths related to T 90 ! 40 C and by T 50 > 41 C; (j) TD expressed as cumulative thermal equivalent minutes at 43 C (CEM 43 ) calculated for tissue temperatures measured as a function of time within the exposure period; (k) TD expressed as CEM 43 T 90 calculated by using data of T 90 upon achieving thermal steady state.…”

“…CEM 43 converts the various time-temperature exposures applied during the treatment into an equivalent exposure time expressed as minutes at the reference temperature of 43 C. Calculations were performed according to [20][21][22][23][24]:…”