Influence of acute tumor hypoxia on radiation therapy outcome

One of the most important factors that influence the outcome of cancer treatment is tumor hypoxia that is caused by a deficient vascular network and an increased interstitial pressure. Tumor hypoxia can be divided into two types depending on the underlying mechanism. Thus, chronic hypoxia is caused mainly by the limited diffusion of oxygen into tissue due to cellular consumption and might also be influenced by a high interstitial pressure, and changes very slowly in time. Acute hypoxia might also appear in tumors due to transient perfusion-related events such as the temporary closure of blood vessels and has a finite lifetime ranging from minutes to hours. The temporal variation of acute hypoxia influences the treatment outcome in a more complex way than the chronic hypoxia. The aim of this study is to simulate the influences of various amounts of acute hypoxia on the treatment outcome. The present model for tumor oxygenation allows the simulation of the two forms of tumor hypoxia. We have studied the reduced tumor oxygenations resulting from the temporary shutting down of a given fraction of tumor blood vessels at every radiation fraction throughout the treatment. The particular effect of acute hypoxia on the treatment outcome was evaluated by calculating the effective tumor control probability with or without acute hypoxia. The results suggest that the presence of acute hypoxia during every treatment fraction reduces the tumor control probability significantly. As consequence, higher and higher doses are needed to achieve a certain level of local control in tumors when the fraction of closed vessels increases. These results therefore show that acute hypoxia has to be taken into consideration for accurate simulations of radiation treatments and that an individual approach for each patient might be desirable for maximum improvement of outcome.