Trajectories of Fatigue in Patients with Breast Cancer before, During, and after Radiation Therapy

Anand Dhruva, MD; Marylin Dodd, PhD, RN; Steven M. Paul, PhD; Bruce A. Cooper, PhD; Kathryn Lee, PhD, RN; Claudia West, MS, RN; Bradley E. Aouizerat, PhD; Patrick S. Swift, MD; William Wara, MD; Christine Miaskowski, PhD, RN, FAAN

Disclosures

Cancer Nurs. 2010;33(3):201-212. 

In This Article

Abstract and Introduction

Abstract

Background: Fatigue is a significant problem associated with radiation therapy (RT).
Objective: This study examined how evening and morning fatigue changed from the time of simulation to 4 months after the completion of RT and investigated whether specific demographic and disease characteristics and baseline severity of symptoms predicted the initial levels of fatigue and characteristics of the trajectories of fatigue.
Methods: Seventy-three women with breast cancer completed questionnaires that assessed sleep disturbance, depression, anxiety, and pain prior to the initiation of RT and the Lee Fatigue Scale, over 6 months. Descriptive statistics and hierarchical linear modeling were used for data analysis.
Results: Large amounts of interindividual variability were found in the trajectories of fatigue. Evening fatigue at baseline was negatively influenced by having children at home and depression. The trajectory of evening fatigue was worse for women who were employed. Morning fatigue at baseline was influenced by younger age, lower body mass index, and the degree of sleep disturbance and trait anxiety. Trajectories of morning fatigue were worse for patients with a higher disease stage and more medical comorbidities.
Conclusion: Interindividual and diurnal variability in fatigue found in women with breast cancer is similar to that found in men with prostate cancer. However, the predictors of interindividual variability in fatigue between these 2 cohorts were different.
Implications for Practice: Diurnal variability and different predictors for morning and evening fatigue suggest different underlying mechanisms. The various predictors of fatigue need to be considered in the design of future intervention studies.

Introduction

Fatigue is the most common and disruptive symptom reported by patients undergoing radiation therapy (RT).[1–9] Despite major advances in RT techniques, fatigue remains a significant clinical problem.[9–11] In fact, fatigue associated with RT occurs in approximately 80% of patients and has deleterious effects on their functional status and quality of life.[8,12–14]

Longitudinal Studies of RT-induced Fatigue in Patients with Breast Cancer

Several studies have evaluated for changes in fatigue in women with breast cancer during the course of RT.[4,15,16] While the exact measurement times differed across these studies, in most cases fatigue severity ratings increased significantly from the beginning to the middle of RT and remained elevated from the middle to the end of RT. In the 7 studies that evaluated for changes in fatigue in women with breast cancer following the completion of RT,[17–23] fatigue severity scores decreased to pretreatment levels within 4 to 8 weeks following the completion of treatment.

Predictors of RT-induced Fatigue in Patients with Breast Cancer

The findings across the 7 studies that evaluated for predictors of RT-induced fatigue in women with breast cancer[16–21,23] are inconsistent. For example, in 1 study,[16] fatigue severity scores were not associated with the stage of disease, type of breast cancer surgery, or pretreatment with chemotherapy (CTX). In contrast, Donovan and colleagues[15] found that women who received CTX prior to the initiation of RT reported higher fatigue severity scores that persisted throughout RT compared with women who had not received CTX. In another study,[17] while fatigue severity scores were not influenced by age, stage of disease, time since surgery, weight, or length of time since diagnosis, women with higher levels of psychological and symptom distress reported higher fatigue severity scores. This finding contrasts with that of Geinitz and colleagues,[23] who found no relationship between fatigue severity and anxiety and depression. In another study that examined factors that predicted fatigue severity at the end of RT,[19] younger age, higher level of education, increased level of treatment-related adverse effects, and living alone were associated with higher fatigue scores. In a study of women who underwent adjuvant treatment for breast cancer,[20] higher pretreatment levels of fatigue were associated with higher levels of mood disturbance, higher total network support, lower satisfaction with social support, lower morning cortisol, and higher levels of interleukin 1β. No associations were found between fatigue severity scores prior to adjuvant therapy and age, income, educational level, stage of disease, type of surgery, or type of adjuvant therapy. Finally, in a recent study of fatigue in patients with breast cancer who underwent adjuvant therapy,[21] the magnitude and correlates of response shift in the measurement of fatigue were evaluated. Of note, clinically significant response shifts in ratings of fatigue did occur over time. Larger response shifts were found in women who reported higher pretreatment ratings of fatigue, in those who received CTX, and in those who reported lower fatigue catastrophizing scores.

Summary and Rationale for the Proposed Study

While the number of longitudinal studies of RT-related fatigue in women with breast cancer has increased, additional research is warranted because of the inconsistent findings across these studies. While some of these inconsistencies may be related to the measures used to assess fatigue, the timing of the measures, large variations in sample size, and/or the number and types of predictor variables tested, clinical experience and the findings reported, to date, suggest that a large amount of interindividual variability exists in patients' experiences of fatigue during and following RT.

Another factor that may contribute to the inconsistent findings is the time of day that fatigue was assessed. While diurnal variations in fatigue were reported in the general population,[24–26] only 2 studies have assessed for diurnal variations in fatigue in oncology patients.[27,28] In the only study of women with breast cancer,[27] their ratings of fatigue were compared with those of age-matched groups of healthy women and women with benign breast disease. While breast cancer survivors reported higher levels of fatigue relative to the other 2 groups of women, no group differences in the diurnal pattern of fatigue were evident. Fatigue scores were lowest at 10 AM and highest at 9 PM. An evaluation of diurnal variations in fatigue severity might provide insights into its etiology or mechanisms.[27–29]

In an attempt to overcome some of the limitations noted above, as part of a larger study of symptoms in patients who underwent RT and their family caregivers (FCs), evening and morning fatigue trajectories were evaluated in patients with prostate cancer[13] and in their FCs[30] using a more sophisticated method for longitudinal data analysis (ie, hierarchical linear modeling [HLM]).

In this study, patients and their FCs were taught to complete the fatigue measure before going to bed each night (evening fatigue) and upon arising each morning (morning fatigue). Assessments were done prior to the initiation of RT, weekly during the course of RT, every 2 weeks for 2 months, and once a month for 2 months. While mean evening and morning fatigue scores were in the moderate range, a large amount of interindividual variability was found in the trajectories of morning and evening fatigue reported by both patients and their FCs.[13,30]

Younger men and those with higher levels of sleep disturbance reported higher levels of evening fatigue at the initiation of RT. In terms of predictors of the trajectories of evening fatigue, younger age, lower baseline levels of evening fatigue, and higher baseline levels of sleep disturbance were associated with the worst evening fatigue trajectory. In terms of morning fatigue, the 2 variables that predicted higher baseline levels of morning fatigue in these patients with prostate cancer were younger age and higher baseline levels of depression and sleep disturbance. In terms of predictors of the trajectories of morning fatigue, younger age, lower baseline levels of morning fatigue, and higher baseline levels of sleep disturbance and depression were associated with the worst morning fatigue trajectory.[13]

In terms of the FCs,[30] the 2 predictors of higher baseline levels of evening fatigue were higher baseline levels of sleep disturbance in the FC and higher baseline levels of evening fatigue in the patient. Family caregivers with the worst evening fatigue trajectory were those who reported lower baseline levels of evening fatigue and higher baseline levels of sleep disturbance and who cared for a patient who reported higher baseline levels of evening fatigue. The 3 predictors of higher baseline levels of morning fatigue in these FCs were higher baseline levels of trait anxiety in the FC, lower baseline levels of family support, and higher baseline levels of morning fatigue in the patient. Family caregivers with the worst morning fatigue trajectory were those who reported higher baseline levels of anxiety and lower baseline levels of family support and who cared for a patient who reported higher baseline levels of morning fatigue.

Findings from these 2 studies suggest that diurnal variation exists in patients' and FCs' ratings of evening and morning fatigue, that evening and morning fatigue scores in both groups were in the moderate range, and that a large amount of interindividual variability exists in ratings of evening and morning fatigue. However, the predictors of baseline levels of evening and morning fatigue, as well as the predictors of changes in fatigue trajectories over time, were different between the 2 measures of fatigue, as well as between patients and their FCs.[13,30] Based on these findings and because this type of longitudinal analysis is lacking in women with breast cancer, the purposes of this study, in a sample of women who underwent RT for breast cancer, were to examine how ratings of evening and morning fatigue changed from the time of simulation to 4 months after the completion of RT and to investigate whether specific patient, disease, and symptom characteristics predicted the initial levels of fatigue and/or characteristics of the trajectories of evening and morning fatigue.

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