Challenges of anemia correction during radiotherapy and chemoradiation

The effect of radiotherapy depends on optimal tumour oxygenation, as tumour hypoxia impairs the production of radiation-induced cytotoxic free radicals resulting in less tumour cell kill. The range of haemoglobin levels optimal for tumour oxygenation is 12-14 g/dl in women and 13-15 g/dl in men. It appears reasonable to elevate the haemoglobin level in anaemic cancer patients into this optimal range. This may be achieved with red blood cell transfusions (RBCT) or erythropoiesis stimulating agents (ESAs). However, RBCT have had negligible or even negative effect on patient outcome, possibly because RBCT induce immunosuppression or result in haemoglobin levels too high for optimal tumour oxygenation. Several randomized trials have demonstrated that patients irradiated for head-and-neck cancer had worse outcomes with ESAs than the control group. However, in the majority of these trials, over-treatment with ESAs resulted in haemoglobin levels above the optimal range. Tumour oxygenation is impaired by inappropriately high haemoglobin levels due to increased blood viscosity and decreased tumour cell perfusion. This concept is supported by the findings of prospective studies in cervix cancer and esophageal cancer patients. In these studies the ESA administration was withheld at a haemoglobin level of 14 g/dl resulting in a positive effect of ESAs on treatment outcome. In summary, the effect of RBCT and particularly of ESAs during radiotherapy remains unclear. Further randomized trials are required. Until such trials are available, one should follow the ASCO and ESMO guidelines that are very conservative regarding the administration of ESAs during radiotherapy and chemoradiation.