Pathophysiological and vascular characteristics of tumours and their importance for hyperthermia: Heterogeneity is the key issue

Figures & data

Table I.  Factors characterising the hostile pathophysiological tumour microenvironment (‘crucial Ps’).

A. Increase in	B. Decrease in
Perfusion inadequacies and vascular chaos	Partial pressure of O2 (pO2)
Perfusion heterogeneities	Production of high-energy compounds
Permeability in tumour microvessels	pH of extracellular compartment
Pressure of interstitial fluid	Perfusion pressure (arterio-venous pressure difference in microvessels)
Production of lactate
Production of adenosine
Paucity of nutrients
Partial pressure of CO2 (pCO2)
Paucity of bicarbonate

All listed parameters change for the worse during tumour growth and during tumour heating. Modified from Vaupel [3].

Figure 1. Variability of tumour perfusion response to localised 44°C hyperthermia. Curves show relative red blood cell flux at three different sites within a single tumour at comparable temperatures. The shaded bar shows the time of hyperthermia application (modified from Vaupel et al. [47]).

Figure 2. Temperature dependency of the O₂ consumption rate of isolated ascites cells suspended in native ascites fluid (DS-sarcoma) (modified from Vaupel [4]).

Table II.  Chronic and acute tumour hypoxia: Classification according to different causative mechanisms (selection).

A. Acute hypoxia (cyclic, intermittent, fluctuating, transient, repetitive hypoxia)	B. Chronic hypoxia (sustained hypoxia)
1. Ischaemic hypoxia due to perfusion limitations following temporary obstruction of vessels (e.g. by tumour cells, blood cell aggregates, fibrin aggregates)	1. Diffusion-limited hypoxia due to surpassing of the maximum O2 diffusion distances, exaggerated longitudinal intravascular O2 gradients or shunt perfusion
2. Hypoxemic hypoxia due to severe reduction of intravascular O2 content (e.g. transient plasma flow, temporal fluctuations of red	2. Hypoxemic hypoxia due to anaemia (tumour-associated, therapy-induced, HbCO formation)
blood cell flux)	3. Hypoxia due to compromised perfusion through leaky microvessels (e.g. abolished perfusion pressure difference in areas with high interstitial fluid pressure)
	4. Hypoxia due to compromised perfusion as a result of a reduction in red blood cell flexibility (e.g. under hypoxia, low pH and hyperthermia)

Figure 3. Tumour pO₂ values measured continuously before, during and after 40°C, 41.8°C or 43°C hyperthermia. Each data point indicates the mean value (±SEM) for the number of tumours indicated. The shaded area indicates the time of heating (modified from Kelleher and Vaupel [93]).

Figure 4. Comparison of mean pO₂ values before, during (at t = 35 min after reaching the set temperature) and after localised hyperthermia. Each data point indicates the mean value (±SEM) for the number of tumours indicated. * = p < 0.01 (modified from Kelleher and Vaupel [93]).

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