Challenges of anemia correction during radiotherapy and chemoradiation

Abstract

Th e eff ect 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. Th e 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. Th is may be achieved with red blood cell transfusions (RBCT) or erythropoiesis stimulating agents (ESAs). However, RBCT have had negligible or even negative eff ect 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. Th is concept is supported by the fi ndings 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 eff ect of ESAs on treatment outcome. In summary, the eff ect 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.

Impact of hematologic toxicities during concurrent chemoradiation for cervical cancer

“…In cervical cancer, several studies have found low hemoglobin (Hg) levels before and during radiation therapy to be strongly prognostic for local control and survival [20,21]. Although the relationship between anemia and poor prognosis is still unclear, one explanation may be that anemic hypoxia impairs the production of cytotoxic free radicals, limiting the extent to which radiation therapy can reduce tumor size [22]. More recently, however, a number of reports have questioned the potential causality of this relationship [23,24].…”