Clinical Evidence for Thermometric Parameters to Guide Hyperthermia Treatment

Abstract

Hyperthermia (HT) is a cancer treatment modality which targets malignant tissues by heating to 40–43 °C. In addition to its direct antitumor effects, HT potently sensitizes the tumor to radiotherapy (RT) and chemotherapy (CT), thereby enabling complete eradication of some tumor entities as shown in randomized clinical trials. Despite the proven efficacy of HT in combination with classic cancer treatments, there are limited international standards for the delivery of HT in the clinical setting. Consequently, there is a large variability in reported data on thermometric parameters, including the temperature obtained from multiple reference points, heating duration, thermal dose, time interval, and sequence between HT and other treatment modalities. Evidence from some clinical trials indicates that thermal dose, which correlates with heating time and temperature achieved, could be used as a predictive marker for treatment efficacy in future studies. Similarly, other thermometric parameters when chosen optimally are associated with increased antitumor efficacy. This review summarizes the existing clinical evidence for the prognostic and predictive role of the most important thermometric parameters to guide the combined treatment of RT and CT with HT. In conclusion, we call for the standardization of thermometric parameters and stress the importance for their validation in future prospective clinical studies

Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy

“…It is also important to note that many other factors, independent of reoxygenation or thermal dose, per se, may influence treatment response to thermoradiotherapy. Examples include: (1) technical variations in application of HT [ 19 , 78 ], (2) variations in sequence and/or time interval between HT and radiotherapy [ 19 ], (3) rate of heating [ 54 ]; other physiologic factors such as pH, perfusion and/or metabolism and patient specific factors such as age [ 140 , 141 ], smoking history [ 142 , 143 ] and genomic variation [ 112 , 144 ]. Thus, as we have attempted to tease out how hypoxia and reoxygenation influence treatment outcome, it is important to keep in mind that many factors can play into the ultimate outcome for a specific patient.…”

“…Retrospective analysis of the impact of time interval between HT and radiotherapy has been controversial for cervix cancer [ 15 , 16 , 17 , 18 ]. A call for standardization of methods and results reporting has been recently published [ 19 ]. Standardization of reporting will contribute significantly toward understanding how to optimize thermoradiotherapy from the perspective of methods of delivery and documentation of results.…”

Oncologic Thermoradiotherapy: Need for Evidence, Harmonisation, and Innovation

“…As each technology involves advantages and disadvantages, it is most important to consciously use it for appropriate clinical indications, preferably within prospective clinical trials. It is not primarily the choice of technology but rather the commonly observed unreasonable and mostly undocumented use of the method as explained by Ademaj et al [9], that has dragged the collective success of thermoradiotherapy. An excellent example on how to introduce hyperthermia in a harmonized way at a national level is presented by Stutz et al [10].…”

“…As reported by various papers improved efficiency can be achieved by innovating the heating and improved patient selection to fit with the correct level (complexity) of technology (Kroesen et al [11], Poni et al [12], Androulakis et al [13]) enhanced understanding of the biological principles, either by experimental or clinical research (Dewhirst et al [6], Sengedorj et al [7]) or through building new more advanced biological models (Scheidegger et al [14]) and supported by adequate computer modelling to predict the temperature distribution in the tissue (Kok et al [15]). At the same time the contribution of Ademaj et al [9] makes it crystal clear that to better understand which mechanisms are dominant to maximize treatment outcome during the clinical application of thermoradiotherapy, we still have a world to gain in accurate and complete documentation of the quality of the thermal therapy delivered to the patient. Improved documentation will open the gate way for further exploitation of thermal therapy using new technology to guide treatment quality and hence making thermal therapy more effective and efficient.…”

Radiofrequency Electromagnetic Fields Cause Non-Temperature-Induced Physical and Biological Effects in Cancer Cells

“…According to the prevailing opinion, the therapeutic effect of RF was attributed only to the temperature increase induced by RF [ 1 ]. Due to the technical demands and limitations in achieving the required temperatures of >41 °C for tumor therapy [ 5 , 6 ], this therapeutic approach was only established for a few oncological indications.…”