Background and purpose: With the recent development of hemopoietic growth f
actors and alternatives to transfusion, there has been a renewed interest i
n the relationships between anemia, tumor hypoxia and treatment outcome in
a number of human malignancies. This review is intended to provoke a recons
ideration of these issues and their effect on clinical trials, aimed at imp
roving treatment outcome in patients with cervix cancer.
Materials and methods: Using data from the literature and from our own pros
pective series of tumor oxygenation in cervix cancer, we modeled the impact
of anemia on tumor blood flow and hypoxia in animal models and human tumor
s, examined the relationship between anemia and hypoxia and treatment outco
me in patients, and reviewed the impact of transfusion on tumor hypoxia and
treatment outcome in cervix cancer.
Results: Anemia may result in a significant reduction in oxygen delivery to
tumors, but compensatory mechanisms reduce the impact on tumor oxygenation
. Anemia is associated with inferior treatment outcome in cervix cancer, bu
t hemoglobin levels prior to and during treatment are strongly correlated w
ith tumor size, and this may explain the prognostic impact of anemia in old
er studies. Transfusion and erythropoietin ameliorate hypoxia in only a pro
portion of anemic patients. Critical analysis of the published data from th
e Princess Margaret Hospital randomized trial of transfusion in cervix canc
er reveals that, when analyzed by intention-to-treat, transfusion did not r
esult in a benefit to patients.
Conclusions: This review suggests that the relationships among anemia, hypo
xia, transfusion and treatment outcome are complex. Further study of anemia
as an independent prognostic factor is required and randomized studies of
transfusion alternatives, such as erythropoietin, must be of sufficient siz
e to detect small treatment effects. (C) 2000 Elsevier Science Ireland Ltd.
All rights reserved.