The impact of anaemia on outcome in cancer

Abstract

Anaemia is not an inconsequential side effect of cancer and its treatment should not be ignored. Current practice for anaemia management varies and its role in influencing outcome in cancer patients is under recognized. As a common complication of cancer, anaemia is prevalent in virtually all tumour types to varying degrees. Predictive factors for anaemia include baseline haemoglobin concentration, decrease in haemoglobin concentration within the first month of treatment, tumour type, duration of treatment and prior blood transfusions. Interest in the prognostic significance of anaemia in cancer patients has generated extensive clinical research. Data is now published in a wide range of tumour types confirming that anaemia is a negative prognostic indicator of outcome (e.g. survival, disease-free recurrence and local relapse), with the strongest association in patients receiving radiotherapy. The association has also been documented in patients undergoing chemotherapy and chemoradiation. A retrospective meta-analysis has shown an overall 65% increased risk of death associated with anaemia in cancer patients. The impact of anaemia as an independent prognostic factor for outcome may be mediated by several factors, however the emerging consensus is on the central role of tumour hypoxia. It has been nearly 50 years since R. Thomlinson and L. Gray (British Journal of Cancer 1955, 9: 539) first documented the existence of hypoxia in tumours and it is now well accepted that tumour hypoxia protects tumour cells from therapeutic damage directly by reducing the availability of oxygen-free radicals which are necessary for optimal impact of radiotherapy, certain chemotherapeutic agents and photodynamic therapy. The indirect effects include the impact of hypoxia on gene expression, which affects genetic stability, proliferation kinetics and cellular metabolism. There has been an emergence of preclinical and circumstantial data over recent years that are suggestive of the ability to correct the negative effect of anaemia on outcome by the use of repeated blood transfusions or recombinant human erythropoietin. This has led to some attempts to measure the impact on survival in cancer patients of treating anaemia, but early attempts have served to underline the complexity of the relationship and have produced unexpected results.

The severity and optimal management of iron deficiency and anaemia before radiation for cervical cancer at the University of Pretoria Academic Hospitals

“…Low haemoglobin levels predict poorer disease control and survival 5,6 and haemoglobin levels above 12 g/dl are crucial for good treatment response. 7 Survival is improved when anaemia is corrected by transfusion and is then similar to patients who do not need transfusion to maintain normal haemoglobin.…”

Anaemia is of prognostic significance in patients with oesophageal adenocarcinoma

“…Several mechanisms cause anaemia in colorectal cancer (CRC), including gastrointestinal haemorrhage, bone marrow infiltration, haemolysis, myelosuppression secondary to therapy and cancer-related anaemia (CRA). 4 Cancer-related anaemia is characterised by normochromic and normocytic red cell indices, a form of anaemia seen in chronic illness ('anaemia of chronic inflammation'). It occurs secondary to tumour-induced activation of the immune system with the subsequent release of cytokines such as neopterin, tumour necrosis factor, interleukin-1 and interferon-γ.…”

“…It occurs secondary to tumour-induced activation of the immune system with the subsequent release of cytokines such as neopterin, tumour necrosis factor, interleukin-1 and interferon-γ. 4 They inhibit red cell formation and hasten their removal through the reticuloendothelial system. Anaemia has been shown to be a negative prognostic marker of survival, independent of tumour stage in a wide range of malignant diseases including CRC.…”

“…Anaemia has been shown to be a negative prognostic marker of survival, independent of tumour stage in a wide range of malignant diseases including CRC. 4,5 The strongest association appears to occur in individuals receiving radiotherapy. 4 Proposed mechanisms included tumour hypoxia in anaemic patients that reduces the availability of oxygen free radicals to exert one of the therapeutic effects of radiotherapy.…”

“…4,5 The strongest association appears to occur in individuals receiving radiotherapy. 4 Proposed mechanisms included tumour hypoxia in anaemic patients that reduces the availability of oxygen free radicals to exert one of the therapeutic effects of radiotherapy. Tissue hypoxia also promotes tumour angiogenesis and is associated with increased tumour aggressiveness and outcome possibly independent of treatment modality.…”