Relevance of oxygen in radiation oncology. Mechanisms of action, correlation to low hemoglobin levels.

At the beginning of this century Schwarz (1909) and Holthusen (1921) observed the influence of oxygen on the radiosensitivity of cells. In 1951 Hollaender et al. described that E. coli needed 3-fold higher radiation doses when treated under anoxic conditions compared to normoxic conditions. This led to the evaluation of the oxygen enhancement ratio (OER) for photons (X-rays), neutrons and heavy ions. It was found that the OER for conventional radiation therapy (RT) with photons is much higher (about 3) than the OER for neutron-RT (only 1.5) or heavy ions. According to a hypothesis free radicals which are produced by radiation are fixed in the presence of oxygen. Radicals are interacting with DNA, macromolecules and membranes. The DNA lesion can be followed by cell death. There is some evidence that tumor cells respond to hypoxia with the expression of a variety of genes coding for oxygen regulated proteins such as c-jun, VEGF or p53. Hypoxia also enhances the genetic instability of tumor cells. Oxygen tensions in malignant tumors can be determined under clinical routine conditions by using a computerized polarographic needle electrode system (Eppendorf, Hamburg, Germany). Several studies in the past years showed that tumors are in general more hypoxic than the surrounding normal tissue and that a marked variability of intra- as well as intertumoral pO2 values exist (for review see Vaupel and Höckel 1998). Moreover, it has been shown in different tumor entities that the oxygenation status influences the local control rate and overall survival. Furthermore, the oxygenation status obtained at one site (primary) is significantly related at other sites (lymph node metastases) in patients with squamous cell carcinoma of the head and neck (SCCHN). In addition, there is a significant correlation between hemoglobin level and tumor oxygenation in patients with SCCHN. There is some evidence that the oxygenation status can be improved by the correction of a low hemoglobin level and consequently, the curative chance might rise.