New publication of Vaupel et al. in Cancers on the multitude of mechanisms responsible for improving cancer oxygenation as radiosensitizing effect of hyperthermia
Locoregional mild hyperthermia (mHT) of 39–42°C can increase the efficacy of radiotherapy, allowing for reduced total doses and toxicity in specific clinical situations. One of the basic mHT-related radiosensitizing effects is an improved tumor oxygenation, primarily due to an enhanced microcirculatory blood flow. In this publication the authors review the relevant data and discuss additional underlying biological mechanisms including
- short-term effects. supposed to be the prime driver: “Vasodilation of co-opted vessels and upstream normal tissue vasculature, decreases in viscous resistance to flow, increasing O2 diffusivities and O2 extraction rates, and facilitated O2 unloading from oxyhemoglobin due to right-shifts of the HbO2-dissociation curve by HT per se and intensified tumor acidosis”,
- more sustained effects: “Reduction in interstitial fluid pressure and -possibly- VEGF-triggered angiogenesis”. The authors consider a significant improvement in tumor oxygenation due to an HT-related, questionable reduction in the respiratory activity of the tumor cells to be unlikely.
The mHT-related better oxygenation status of the tumor microenvironment may also improve the efficacy of anti-tumor immune responses and of oxygen-dependent chemotherapies.
Download of the open access publication: Vaupel P, Piazena H, Notter M, Thomsen AR, Grosu AL, Scholkmann F, Pockley AG, Multhoff G. From localized mild hyperthermia to improved tumor oxygenation: Physiological mechanisms critically involved in oncologic thermo-radio-immunotherapy. Cancers 2023,15,1394. https://doi.org/10.3390/cancers15051394
The conclusion of the publication greatly supports the sequence and timing of combined thermography-controlled wIRA superficial HT and re-RT as suggested by Notter et al. (2017, 2020, 2021: Hyperthermia directly before (re-)irradiation with a time gap as short as possible (< 5 minutes).