4.1 Interventions to raise haemoglobin levels in patients with malignancies

4.1.3 Impact of correction of anaemia on radiotherapy outcome

Anaemia (using Hb thresholds of 90 –145 g/L) has been associated with a reduced response to therapy and shortened survival in cervical, bladder, bronchial, and head and neck cancers.161

Erythropoiesis-stimulating agents

ESAs reduce therapy-related anaemia and need for transfusion.95,162 However, locoregional progression- free survival was significantly worse in the treatment arm in a large multi-institutional placebo-controlled phase III trial of ESA therapy in patients undergoing radiotherapy for head and neck cancer.163

A Cochrane review164 examined the use of ESAs with radiotherapy or chemotherapy in head and neck cancer patients and demonstrated poorer survival in patients receiving ESAs, although the target Hb was higher than currently regarded as appropriate in four of the five included trials.

The Gynecologic Oncology Group (GOG) trial 0191 assessed the effect of using ESAs to maintain the Hb at 100 g/L compared with ESA treatment or transfusion to a Hb of 120 –130 g/L in women with locally advanced cervical cancer.165 The study was closed early due to increased thromboembolic events in the latter arm. The three-year progression-free survival and overall survival were inferior in the ESA treatment group.

The adverse outcomes may result from an excess of thromboembolic events among patients treated with a high Hb target. ESAs may also promote tumour progression, because erythropoietin receptors may be expressed on the surface of some tumour cell lines.

ESAs are not currently approved by the Therapeutic Goods Administration (TGA) for use in Australia for treatment of anaemia due to malignancy or chemotherapy.

Red blood cell transfusion

The view that transfusing RBCs to maintain a Hb of 125 g/L in patients undergoing radiotherapy for solid tumours is associated with a reduced local relapse rate is based on a 1978 publication.166 However, subsequent analysis of the study, based on intention to treat, demonstrated that there was no difference in disease-related mortality. A recent study evaluating the prognostic significance of anaemia and its modification by transfusion in head and neck cancer patients treated with radiotherapy showed no benefit.167 Transfusion may improve oxygen delivery in profoundly anaemic patients, but does not necessarily overcome other factors leading to tumour hypoxia.

It has been proposed that increased morbidity and mortality in transfused patients is due to immunosuppression.168-170 The review by Varlotto and Stevenson171 concluded that correction of anaemia by blood transfusions has had an adverse effect on patient survival. The authors postulated that this was due to modulation of inflammatory or immunosuppressive pathways.

The relationship between anaemia, tumour hypoxia and the effects of treatment to correct anaemia in patients with solid tumours is far more complex than initially perceived. Hypoxia is most likely predominantly related to abnormal tumour vasculature, and correction of anaemia has not been demonstrated to improve the outcome of radiotherapy. The use of ESAs, particularly with higher Hb targets, has been associated with an adverse impact on survival in patients with malignancy.

Transfusion decisions for patients undergoing radiotherapy are thus based on the principles used for other patients with cancer (see Section 3.2.4).