Prevalence and causes of fatigue after cancer treatment: the next generation of research.

The presence of fatigue in cancer patients is now well documented. Fatigue is recognized as the most common and distressing side effect of cancer treatment, occurring among patients undergoing radiation, chemotherapy, and treatment with biologic response modifiers. Furthermore, there is evidence that fatigue may persist for months or years after completion of successful treatment in a substantial minority of patients. Qualitative reports indicate that cancer-related fatigue differs from normal fatigue related to lack of rest or overexertion as it involves more severe and enduring mental, physical, and emotional domains. As such, cancer-related fatigue has a particularly detrimental effect on quality of life. Although research on cancer-related fatigue has become increasingly sophisticated, few longitudinal studies have been conducted that assess patients before and after treatment completion. Clearly, knowledge of a patient’s status before treatment onset (and ideally, during treatment) is critical for an accurate understanding of posttreatment fatigue. The study by Nieboer et al in this issue of the Journal of Clinical Oncology represents an important advance in this literature in its evaluation of breast cancer patients before and at yearly intervals after randomization to treatment with standardor high-dose chemotherapy. The study is also notable for the size of the sample (N 430) and the number of post-treatment assessments. The key findings from the study are as follows. First, the authors found that fatigue remained stable over the assessment period. That is, fatigue levels before treatment were comparable with those observed 1, 2, and 3 years after random assignment (all patients had completed treatment with chemotherapy and radiation therapy at the 1-year assessment). Second, women treated with standardand high-dose chemotherapy reported comparable levels of fatigue. Third, approximately 20% of women were classified as fatigued at each assessment point. This categorization was based on women’s scores on the SF-36 vitality scale; if they scored 46 on this scale (at least one standard deviation below the mean score for Dutch women in the general population), they were classified as fatigued. Fourth, fatigue was strongly correlated with mental health and with muscle and joint pain, but not with hemoglobin or menopausal status. Overall, these findings offer hope for breast cancer survivors, suggesting that most patients will recover their energy within 1 year after treatment onset and that the incidence of post-treatment fatigue is relatively low. Before these conclusions can be drawn, it is important to compare findings from the study by Nieboer et al with previous research. Studies conducted with breast cancer patients have shown consistently that fatigue levels increase during chemotherapy, but few have followed patients into the post-treatment period. In one report, fatigue declined to baseline levels after completion of treatment with chemotherapy and radiotherapy among women with early-stage breast cancer. These results are consistent with Nieboer et al, who found that fatigue levels 1 year after treatment onset were comparable with pretreatment levels among women treated with chemotherapy and radiation therapy. In contrast, previous cross-sectional studies have shown that breast cancer patients treated with radiation or chemotherapy report higher levels of fatigue than women treated with surgery alone 1 year after diagnosis. In addition, there is considerable variability in fatigue levels both during and after treatment, suggesting that some patients may experience a slower (or faster) course of recovery. Because Nieboer et al did not evaluate patterns of change in fatigue over time, it is unclear whether certain patients experienced more severe or more persistent fatigue. The percentage of patients who were categorized as fatigued in the report by Nieboer et al was quite low, and JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 33 NOVEMBER 2