Tumor Oxygenation Under Normobaric and Hyperbaric Hyperoxia

Abstract

Tumor hypoxia is an important factor limiting the efficiency of sparsely ionizing ra-diation and O₂-dependent chemotherapy. Since the tumor pO₂ is the result of a dynamic steady state between oxygen supply and O₂ consumption of the tumor tissue, hypoxia could be reduced either by increasing the O₂-supply or by reducing the O₂ demand of the tumor cells. The O₂ supply can be improved for instance by (i) increasing the arterial oxy-gen partial pressure, (ii) improving (and homogenizing) the tumor perfusion, or (iii) en-hancing the O₂ release from blood into the tissue by right-shifting the HbO₂ dissociation curve. Theoretically, it should also be possible to improve tumor oxygenation by a rela-tively small decrease in O₂ consumption rate of the tumor cells. However, at present in-creasing the arterial pO₂ by breathing hyperoxic gas mixtures seems to be the most effective method to improve tumor oxygenation and, thus, to enhance the efficiency of standard radio- and chemotherapy in experimental malignancies [1,7,10,11,15,24] as well as in human tumors [3,9,12,14,22,29,30]. However, since in some tumor entities oxygena-tion is inadequate and anisotropic [27], normobaric hyperoxia is often not sufficient to completely eradicate tumor hypoxia [6,16,18,26]. In these cases only breathing of hyper-oxic gases under hyperbaric conditions may be sufficient to lead to therapeutic results. On the other hand, studies on experimental tumors in animals as well as clinical trials in pa-tients showed non-uniform results concerning the therapeutic benefit of inspiratory hyper-oxia ranging from clear improvement of radiosensitivity [3,4,20,30] to no effect on therapeutic outcome [3,4]. Finally, enhancement of tumor growth by hyperbaric oxygenation has been discussed [13,23].

Supported by the Deutsche Krebshilfe (Grant M 40/91 Va 1) and the Dr.med.h.c. Erwin Braun Foundation, Basel (Grant 5.5)