Normo- and hyperbaric oxygenation of tumors: from bench to bedside

Tumor hypoxia is an important factor limiting the efficacy of sparsely ionizing radiation and O₂-dependent chemotherapy.Because the tumor pO₂ is the result of a dynamic steady state between oxygen supply and O₂ consumption of the tumor cells,hypoxia could be reduced by improving the O₂ supply for instance by breathing hyperoxic gas mixtures to increase the arterial oxygen partial pressure. This technique seems to be the most effective method to improve tumor oxygenation, and thus to enhance the efficacy of standard radiotherapy and chemotherapy in experimental malignancies, as well as in human tumors. However, the role of varying inspiratory pCO₂ on tumor oxygenation has been discussed controversially. Although carbogen (95% O₂ + 5% CO₂) is used in the clinical setting, it remains unclear whether the beneficial therapeutic effects are more pronounced than with pure oxygen. Because insome tumor entities oxygenation is inadequate and anisotropic, normobaric hyperoxia is often not sufficient to completely eradicate tumor hypoxia. In these cases, breathing of hyperoxic gases under hyperbaric conditions (2-3 atm) may be sufficient to lead to therapeutic results. However, studies on experimental tumors in animals as well as clinical trials in patients showed nonuniform results concerning the therapeutic benefit of hyperbaric hyperoxia, depending on the tumor entity, site of growth, or tumor vascularization. Especially, squamous cell carcinomas of the head and neck region seem to benefit from additional HBO therapy during radiotherapy, although several technical problems of irradiation during hyperbaric conditions are presently not satisfactorily resolved.