{'fraction_non_alphanumeric': 0.014400677678949597, 'fraction_numerical': 0.00042354934349851756, 'mean_word_length': 5.425850340136054, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Tumour perfusion and associated physiology: Characterization and significance for hyperthermia

There is a clear association between the vascular and pathophysiological characteristics of solid tumours and hyperthermia. Such an association involves both an effect of the tumour vasculature and pathophysiology on heating and the influence of heat on these tumour characteristics. Of the parameters involved in this interaction it is probably blood flow/perfusion that plays the most critical role. The vascular supply is one of the major vehicles by which heat is dissipated, and as such it will significantly influence the ability to heat tumours. Typically, the lower the blood flow rate the easier it becomes to heat. It is also important in determining the microenvironment that exists within tumours; a poor microvascular blood supply results in the development of large areas that are nutrient deprived, low in oxygen (hypoxic) and highly acidic, and cells exposed to such adverse conditions, especially low pH, are more sensitive to the killing effect of heat. When tumours are heated the tumour pathophysiology and vascularity change, and do so in a temperature-dependent fashion. At mild clinically relevant tumour temperatures blood flow transiently increases. There is also a corresponding improvement in oxyhaemoglobin saturation of the individual red blood cells within tumour microvessels, and these changes combine to increase overall oxygen availability with a subsequent improvement in tumour oxygenation status. With higher tissue temperatures one may see a transient increase in tumour blood flow during the heating period, but vascular damage soon occurs leading to a rapid decrease in flow. There are again corresponding changes in other pathophysiological factors including oxyhaemoglobin saturation, energy status, and pH, which ultimately lead to ischemia and cell death. Historically there have been a number of reviews dealing with the significance of the tumour vasculature and pathophysiology for hyperthermia [1–4]. However, in recent years it has become clear that the issue is far more complex than was earlier thought. In order to expand and update our knowledge it was suggested that a volume of the International Journal of Hyperthermia be dedicated to this aspect. The eight papers included in this special issue under the general title of ‘Tumour perfusion and associated physiology: Characterization and significance for hyperthermia’ were the result. The first article in this issue is a comprehensive updated overview by Vaupel and Kelleher on how tumour pathophysiology and vasculature are important for hyperthermia. They show that there are controversial experimental and clinical data which substantially deviate with respect to the extent, the time course, and even the direction of changes in pathophysiological parameters upon (mild) hyperthermia. These effects probably reflect the heterogeneity that exists in tumours, making it difficult to actually predict how tumours will respond to heating. Thus, several of the ‘consensus’ opinions regarding the tumour vascular and pathophysiological effects of heat may not be true with heating in the clinical situation, and that this is a critical issue requiring further clarification. One characteristic feature of most solid tumours is hypoxia. Its presence in tumours is known to have a negative impact on local tumour control and overall survival in patients due to a decrease in the efficacy of radiation and chemotherapy, as well as driving malignant progression. The next paper in this issue, by Sun et al., concentrates on the use of mild temperature hyperthermia to increase tumour blood perfusion and thus decrease the level of tumour hypoxia. They summarise the various studies that show these effects and further demonstrate it using results from their own studies with dual marker immunohistochemistry. The kinetics of these mild temperature hyperthermia-induced changes and how this approach can be exploited to enhance radiation and chemotherapy are also discussed. They also briefly review how mild temperature hyperthermia can be further exploited to improve radiation sensitivity by combining it with drugs that induce damage to the tumour vasculature, and which are currently undergoing clinical testing. Apart from the effect of hypoxia on tumour response to conventional therapies and malignancy, there is now evidence that hypoxia suppresses antitumour effector cells and can enhance tumour escape from immune surveillance. This aspect is the basis of the review by Lee et al. These authors further suggest that by using mild temperature hyperthermia to alter tumour vascular perfusion and oxygenation status