Changes in tumour oxygenation during fractionated hyperthermia and radiation therapy in spontaneous canine sarcomas

Abstract

Tumour oxygenation was measured in seven canine soft tissue sarcomas being treated with a fractionated course of radiation and hyperthermia. Measurements obtained during treatment were compared to pre-treatment measurements. The most important finding was an increase in oxygenation in tumours with low pre-treatment oxygenation that persisted throughout treatment. This is an advantageous hyperthermia effect as it may lead to increased radiation cell killing at each fraction. In other tumours, potentially less advantageous changes in oxygenation may be hyperthermia fractionation related and this deserves further investigation.

Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia

“…Whereas there are recent exciting advances in the use of very high temperature thermal ablation techniques for certain localized and relatively small lesions, such as liver metastases [88,89], there is a clear recognition of the value of moderate hyperthermia in treatment of locally or regionally advanced and locally recurrent diseases. Hyperthermia can potentially rapidly and significantly alter the tumor microenvironment-alterations in hypoxia [90,91], perfusion [92], and immunological function (as summarized in this review) likely play a role in the enhance survival noted in patients who receive combination treatments that include hyperthermia [93]. There are several known beneficial effects of hyperthermia in augmenting perfusion and oxygenation within tumors which very likely mediate positive responses to radiotherapy and chemotherapy [11,90,93].…”

“…Hyperthermia can potentially rapidly and significantly alter the tumor microenvironment-alterations in hypoxia [90,91], perfusion [92], and immunological function (as summarized in this review) likely play a role in the enhance survival noted in patients who receive combination treatments that include hyperthermia [93]. There are several known beneficial effects of hyperthermia in augmenting perfusion and oxygenation within tumors which very likely mediate positive responses to radiotherapy and chemotherapy [11,90,93]. As discussed earlier, the temperatures achieved in these studies can affect many normal cells in the tumor microenvironment, including cells of the immune system.…”

Fever-range whole body hyperthermia increases the number of perfused tumor blood vessels and therapeutic efficacy of liposomally encapsulated doxorubicin

“…The basis for the benefit of combining local hyperthermia and radiation is not entirely clear, however two possibilities have been proposed: either, (1) The direct cytotoxic effects of heat on tumor cells and intratumoral vascular structures that could synergize with the cytotoxic effects of ionizing radiation [8,9] particularly when the tumor temperatures reach 43 C and the tumor microenvironment is acidic and nutrient deprived [10,11], or conversely, (2) The indirect effect of heat on tumor re-oxygenation (presumably from an increased volume of blood moving through the region to remove the excess heat) which could result in radiation-enhancing increases in intratumoral oxygen tension [12][13][14][15][16][17][18]. Recent evaluations strongly support the latter mechanism of action since intratumoral temperatures high enough to cause direct thermal killing of either tumor cells or vascular endothelium are not as commonly achieved in the clinical setting as was previously believed, at least not for the duration of time needed [9].…”

Current status of antivascular therapy and targeted treatment in the clinic

“…From experimental and clinical studies it is well known that hyperthermia has effects on blood flow, causing vascular shut down at high temperatures, but also a positive effect on tumour tissue oxygenation at mild temperatures [122,[142][143][144][145][146]. It has been clearly demonstrated that hyperthermia exhibits antiangiogenic effects, and proliferating endothelial cells in vessels from malignant tumours seem more sensitive to heat than the microvessels of normal tissues [116,[147][148][149].…”