Drs. Shasha and Harrison provide an excellent review of the problem of anemia in patients receiving definitive radiotherapy. They also summarize their own original research on the prevalence of anemia in a typical radiation oncology practice. Their study confirms that there is an "epidemic" of anemia among oncology patients and suggests that the issue requires far more attention than it has received.
A Prognostic Indicator
It is well recognized that anemia is associated with decreased response, local control, and/or survival after radiotherapy, and the authors supply numerous references to support this premise. Many of these studies addressed the condition in the setting of radiotherapy alone, but is anemia still an important prognostic factor now that concurrent chemoradiation has supplanted radiotherapy alone for manyif not mostepithelial cancers? The Austrian experience cited by Drs. Shasha and Harrison is thus very important in support of this hypothesis.
At the University of Pennsylvania Medical Center, we have observed a strong relationship between hemoglobin level and response to preoperative chemoradiation in patients with bulky stage IIIA non-small-cell lung carcinoma. We treated 41 patients (all with mediastinoscopy-proven bulky stage IIIA disease) with neoadjuvant radiotherapy (45-50 Gy) and concurrent chemotherapy (either etoposide(Drug information on etoposide)/cisplatin [Platinol] or carboplatin(Drug information on carboplatin) [Paraplatin]/paclitaxel [Taxol]). Our results are listed in Table 1. Pathologic complete or near-complete (only tiny microscopic residual foci) responses were seen in 12 of 23 patients with hemoglobin levels of 12.5 g/dL or more vs 3 of 18 responses in patients with hemoglobin levels < 12.5 g/dL. More studies are needed to determine the significance of anemia in the setting of concurrent chemoradiation.
A Frequently Uncorrected Problem
In light of the strong evidence of a relationship between anemia and outcome, why isn’t more emphasis placed on the correction of anemia? Drs. Shasha and Harrison provide several possible reasons, including:
- A lack of recognition of the problem;
- The perception that the problem of anemia pales in comparison with other treatment toxicities, such as infection and esophagitis;
- The well-known infectious and immunologic risks of transfusion; and
- The cost and logistical difficulties associated with the use of recombinant human erythropoietin(Drug information on erythropoietin) (epoetin alfa, Epogen, Procrit), including the modest rate at which it increases hemoglobin.
Perhaps the most significant reason why the correction of anemia is still not a standard intervention is the failure of the academic and clinical research communities to prove that there is indeed a cause-and-effect relationship between anemia and poor tumor control. In Figure 1 of their article, Drs. Shasha and Harrison describe the traditional hypothesis that anemia leads to hypoxia, which, in turn, leads to radioresistance and poor outcome. However, an alternative explanation is that anemia/hypoxiawhich may be present for months to years prior to cancer diagnosis and treatmentstimulates angiogenesis and, thus, tumor invasion and metastasis. In the angiogenesis model, correcting anemia at this late stage in a cancer’s natural history may be ineffective.