Research on Fatigue

Fatigue – a common problem in patients who are recovering from various cancers and related surgeries and therapies – is associated with depression and reduced physical performance and not, as previously suggested, with anaemia, a flagging immune system or other physiological conditions.

That is the conclusion of a German research team, reported July 2004, in Annals of Oncology.

Cancer related fatigue – defined as an unusual and persistent sense of tiredness that can occur during or after treatment, may affect physical and mental ability and is not relieved by rest – is the most common and distressing problem for cancer patients after treatment. For many patients it is so severe that it limits normal daily activity.

Lead researcher Dr. Fernando Dimeo said that no one fully understood the origins of this extreme fatigue: among the factors proposed as possible causes were anaemia, impaired nutritional status, sleep disturbances, changes in the concentrations of cytokines (small proteins released by cells that affect the behaviour of other cells) due to the interaction between the tumour and the immune system, impaired thyroid, liver or kidney function, mental and social status and a reduced level of activity.

Dr. Dimeo and colleagues from the Charité University Medical Center in Berlin, studied over 70 patients in remission who had been free of treatment for at least three months. They all underwent physical examinations, answered questionnaires and had a range of blood tests after undertaking a series of physical activities.

“We evaluated possible biological and immunological mechanisms of fatigue. We could find no correlation between fatigue, diagnosis, time since surgery or chemotherapy, renal, hepatic or thyroid function, severity of anaemia, serum albumin concentration, cytokine activity or other inflammatory or immune system markers,” he said.

“However, the scores for depression and physical performance in those patients with highest and lowest fatigue scores were significantly different even though there was no difference in the values of laboratory tests for the two groups. The mean depression score of those who scored highly for fatigue was 10 times higher than those with low fatigue scores. The mean performance score of those scoring highly for fatigue was five times lower than those with low fatigue scores.”

Dr. Dimeo said that there were some limitations to the study. For example, the information from questionnaires may be biased because of patients’ subjective feelings and expectations about physical limitations and may not reflect their actual experience. Also, levels of fatigue can fluctuate in patients with cancer, so longer-term studies may provide better understanding of the causes. However, any patients with side effects or signs of infection that might have been responsible for fatigue were excluded from the study.

“Impaired physical performance and depression seem to be critical components in cancer-related fatigue although we have not yet clarified the association between the two factors. Impaired performance can result in increased dependence, lower self-esteem, reduced social activities, restricted family life and a pessimistic mood. The patient can also interpret poor performance as a sign of poor health and this increases psychological distress. On the other hand, depressed and anxious patients are more likely to limit outdoor activities and resort to a passive lifestyle, which can result in loss of muscle condition and physical performance.”

So, the question now facing the researchers is – is the depression the cause of the poor physical performance or is it the other way round? Or could it be that both these problems are related to a third, as yet unknown factor?

They now plan a larger study. “Although patients who have had major surgery ... may have fatigue that can be related more to nutritional deficits or poor lung function, we feel that our findings may apply to most cancer patients, so we will be examining the correlates of fatigue in further groups of patients,” said Dr. Dimeo.

Meanwhile, he added, their existing findings already have implications in the clinic. The diagnostic work-up of patients should include evaluating their workload, psychological status and physical performance.

“There are also treatment implications. In the recent past several publications have underlined the role of anaemia as a major cause of fatigue in patients undergoing chemotherapy. Erythropoetin (EPO) is sometimes given to stimulate the production of red blood cells. But, our findings and those of other studies, show that chronic fatigue in patients who are free of relapse may not be related to haemoglobin concentrations. While all patients with severe anaemia feel tired, a low percentage of patients with chronic fatigue are anaemic.”

Source: “Physical performance, depression, immune status and fatigue in patients with hematological malignancies after treatment.” Annals of Oncology. 15: 1237-1242.2004.

Annals of Oncology is the monthly journal of the European Society for Medical Oncology. www.annonc.oupjournals.org