Karen K. Fields

Measurement of fatigue in cancer patients: development and validation of the Fatigue Symptom Inventory.

Although fatigue is one of the most common and debilitating symptoms experienced by cancer patients, it has received little systematic attention. This situation is due in large part to the lack of adequate instruments to measure fatigue. The primary aim of this study was to validate a newly developed measure of fatigue for use with cancer patients: the Fatigue Symptom Inventory (FSI). This 13 item self-report measure was designed to measure the intensity and duration of fatigue and its impact on quality of life. The psychometric properties of the FSI were assessed in women undergoing treatment for breast cancer, women who had completed treatment for breast cancer and women with no history of cancer. A seven-item interference subscale was found to have good internal consistency, with α coefficients above 0.90 in all three groups. The complete FSI was found to have rather weak to moderate test-retest reliability among patients in active treatment and healthy comparison subjects assessed on three separate occasions. Convergent validity was demonstrated using comparisons with existing measures of fatigue. Construct validity was demonstrated using comparisons between and within groups as well as comparisons with measures of anxiety and depression. Overall, the FSI was established as a valid and reliable measure of fatigue in cancer patients and healthy individuals. Suggestions are made for the potential application of the measure in clinical research.

The uncertainty principle and industry-sponsored research

BACKGROUND Reporting of pharmaceutical-industry-sponsored randomised clinical trials often result in biased findings, either due to selective reporting of studies with non-equivalent arms or publication of low-quality papers, wherein unfavourable results are incompletely described. A randomised trial should be conducted only if there is substantial uncertainty about the relative value of one treatment versus another. Studies in which intervention and control are thought to be non-equivalent violates the uncertainty principle. METHODS We examined the quality of 136 published randomised trials that focused on one disease category (multiple myeloma) and adherence to the uncertainty principle. To evaluate whether the uncertainty principle was upheld, we compared the number of studies favouring experimental treatments over standard ones. We analysed data according to the source of funding. FINDINGS Trials funded solely or in part by 35 profit-making organisations had a trend toward higher quality scores (mean 2.94 [SD 1.3]; median 3) than randomised trials supported by 95 governmental or other non-profit organisations (2.4 [0.8]; 2; p=0.06). Overall, the uncertainty principle was upheld, with 44% of randomised trials favouring standard treatments and 56% innovative treatments (p=0.17); mean and median preference evaluation scores were 3.7 (1.0) and 4. However, when the analysis was done according to the source of funding, studies funded by non-profit organisations maintained equipoise favouring new therapies over standard ones (47% vs 53%; p=0.608) to a greater extent than randomised trials supported solely or in part by profit-making organisations (74% vs 26%; p=0.004). INTERPRETATION The reported bias in research sponsored by the pharmaceutical industry may be a consequence of violations of the uncertainty principle. Sponsors of clinical trials should be encouraged to report all results and to choose appropriate comparative controls.

Predictors of Posttraumatic Growth Following Bone Marrow Transplantation for Cancer

There is growing recognition that the experience of cancer can have a positive as well as a negative psychological impact. This longitudinal study sought to identify predictors of posttraumatic growth among cancer patients (N=72) undergoing bone marrow transplantation. Greater posttraumatic growth in the posttransplant period was related to younger age; less education; greater use of positive reinterpretation, problem solving, and seeking alternative rewards as coping strategies in the pretransplant period; more stressful appraisal of aspects of the transplant experience; and more negatively biased recall of pretransplant levels of psychological distress. Findings partially support J. A. Schaefer and R. H. Mooss (1992) model of life crises and personal growth and also suggest that temporal self-comparisons contribute to the experience of posttraumatic growth.

Clinical significance of bone marrow metastases as detected using the polymerase chain reaction in patients with breast cancer undergoing high-dose chemotherapy and autologous bone marrow transplantation.

PURPOSE The present study evaluates the clinical significance of detection of cytokeratin 19 (K19) in the bone marrow of patients with breast cancer undergoing high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS We studied retrospectively cryopreserved bone marrow aspirates from 83 patients with high-risk stage II, III, and IV breast cancer obtained before bone marrow harvest but after induction chemotherapy. All samples were histologically negative for metastases. Polymerase chain reaction (PCR) for K19 was performed according to methods described previously and results were correlated with the probability of relapse following HDCT and ABMT. RESULTS The incidence of occult metastases as defined by PCR for K19 message was 52% for 19 stage II, 57% for 14 stage III, and 82% for 50 stage IV patients (two-tailed P = .0075, chi 2 test). The probability of relapse at 3 years after ABMT was 32% and 94% for K19-positive stage II/III and stage IV patients, respectively, versus 10% and 14% for K19-negative stage II/III and stage IV patients, respectively. The difference was significant for stage IV patients (two-tailed P = .0002). CONCLUSION It has been shown that PCR is a highly sensitive method to detect K19 message in the bone marrow. The incidence of K19 positivity in bone marrow increases significantly with advancing stage. In patients with breast cancer, especially metastatic breast cancer, undergoing HDCT and ABMT, the presence of K19 is associated with a poor prognosis.

Relation of psychological vulnerability factors to posttraumatic stress disorder symptomatology in bone marrow transplant recipients.

Objective Prior research suggests that the diagnosis and treatment of cancer can result in the development of symptoms of posttraumatic stress disorder (PTSD). Based on Lazarus and Folkman’s model of stress, the current study examined whether trauma appraisals, coping, social support, and social constraint were associated with the severity of PTSD symptoms in cancer patients who had undergone bone marrow transplantation (BMT). Methods Participants were 23 males and 79 females treated with BMT an average of 20 months previously (range = 3–62 months). Past and current psychiatric diagnoses were assessed through a structured clinical interview. PTSD symptomatology and other psychological variables were assessed using standardized self-report measures. Results Results indicated that 5% of participants met diagnostic criteria for current PTSD. Participants reported an average of three to four symptoms of PTSD (range = 0–16). Univariate analyses confirmed predictions that increased PTSD symptomatology would be associated with more negative appraisals of the BMT experience, greater use of avoidance-based coping strategies, lower levels of social support, and greater social constraint (p < .05). Regression analyses indicated that each of these variables accounted for significant (p < .05) variability in PTSD symptomatology above and beyond relevant demographic and medical variables. Conclusions Results of the present study confirm and extend prior research regarding the prevalence of PTSD and PTSD symptoms among patients treated for cancer. In addition, the study identified a set of theoretically derived psychological characteristics that seem to place patients at risk for greater PTSD symptomatology after BMT.

POSTTRAUMATIC STRESS DISORDER SYMPTOMS AFTER BONE MARROW TRANSPLANTATION FOR BREAST CANCER

Objective On the basis of revisions of DSM criteria, questions have been raised concerning the occurrence of posttraumatic stress disorder (PTSD) symptoms among adults who have been diagnosed and treated for life-threatening illnesses. The present study examined the prevalence and correlates of PTSD symptoms among women who had undergone autologous bone marrow transplantation (ABMT) for breast cancer. Methods Participants were 43 women who had undergone ABMT for breast cancer an average of 19 months previously (range = 2 to 62 months) and had no clinical evidence of disease at their most recent follow-up visit. PTSD symptoms and quality of life were assessed using standardized self-report instruments. Results Between 12% and 19% of participants were likely to meet DSM-IV criteria for the current diagnosis of PTSD. Women who were less well educated, had more advanced disease at the time of the transplantation and had longer hospital stays for the transplantation reported more symptoms of PTSD. Greater PTSD symptomatology was associated with reports of poorer physical health, mental health, and sleep quality. Conclusion Comparisons with previous research suggest that rates of PTSD are higher among women who undergo ABMT as opposed to less intensive forms of breast cancer treatment. These findings are consistent with the view that development of PTSD symptoms is associated with the degree of life threat. The clinical significance of PTSD in this patient population is underscored by findings indicating that greater PTSD symptoms are associated with poorer health-related quality of life.

Fatigue in women treated with bone marrow transplantation for breast cancer: A comparison with women with no history of cancer

As more individuals undergo autologous bone marrow transplantation (BMT), there is growing interest in the impact of treatment side effects on quality of life. Fatigue is a potentially disruptive treatment side effect that has not been systematically assessed following BMT. The primary aim of this study was to determine whether the severity of fatigue and its impact on quality of life is significantly greater in women who had undergone BMT for breast cancer than in women of similar age with no history of cancer. Another aim was to identify the medical and psychosocial correlates of fatigue in women who had completed BMT. A group of women treated with autologous BMT for breast cancer (n = 43; mean age = 44; mean time since BMT = 20 months) and a group of women of similar age with no history of cancer (n = 43; mean age = 46) participated in this study. Subjects completed measures of fatigue, anxiety, depression, and sleep habits. Medical data were obtained from computerized patient records. Women who had completed BMT for breast cancer reported significantly more frequent and severe fatigue than women with no cancer history. In addition, fatigue had a significantly greater impact on daily functioning and quality of life in BMT recipients than in women with no cancer history. Fatigue following BMT for breast cancer was related to both medical factors (i.e., time since BMT) and psychosocial factors (i.e., anxiety, depressive symptoms and sleep difficulties). Following BMT for breast cancer, women may experience fatigue that is worse than might “normally” be expected and can interfere with daily functioning and quality of life. Future research should focus on identifying the biological correlates of fatigue, psychological and physiological mechanisms by which fatigue is produced, and interventions to alleviate fatigue.

Predictors of posttraumatic stress disorder symptomatology following bone marrow transplantation for cancer.

This study examined the prevalence and predictors of posttraumatic stress disorder (PTSD) symptoms in 70 men and women treated with bone marrow transplantation for cancer. Findings indicated that the number of symptoms present ranged from 0 to a possible high of 17 (M = 3.0, SD = 3.9). As predicted. lower social support and higher avoidance coping I month pretransplant predicted greater PTSD symptom severity an average of 7 months posttransplant. These variables remained significant predictors of symptom severity even after accounting for pretransplant levels of psychological distress. Additional analyses indicated the presence of a significant interaction between social support and avoidance coping, with patients high in avoidance coping and low in social support reporting the most severe symptoms. These findings identify patients at risk for psychological disturbance posttransplant and can serve to guide future intervention efforts.

Pilot study of a home-based aerobic exercise program for sedentary cancer survivors treated with hematopoietic stem cell transplantation

Summary:We report a pilot study of a home-based aerobic exercise program in a group of 17 adult hematopoietic stem cell transplant (HSCT) recipients. Participants had received no cancer treatment for at least 6 months and reported leisure time physical activity less than 20 min per day and fewer than three times a week during the previous month. Following baseline assessments of aerobic fitness, fatigue symptoms, and quality of life, participants were placed on home-based aerobic exercise programs consisting of 20–40 min of activity in the target heart rate zone (40–60% predicted heart rate reserve) delivered in three to five sessions per week for 12 weeks. Subjects were supplied with electronic heart rate monitors and we encouraged program adherence using weekly telephone contacts and exercise diaries. In all, 32 of the 42 qualified candidates consented (acceptance=76%). Of these, 17 kept appointments for baseline assessments, four did not complete the study (attrition=46%), and no exercise-related adverse events were reported. Scores on measures of aerobic fitness, fatigue severity, and physical well-being improved (signed ranks test; P<0.05) during program participation. Our findings suggest that individually prescribed, home-based aerobic exercise is an acceptable, safe, and potentially effective intervention for improving physical functioning and fatigue in sedentary HSCT recipients.

Preliminary evaluation of a clinical syndrome approach to assessing cancer-related fatigue.

The objectives of this study were to evaluate the reliability, validity, and utility of a newly developed clinical syndrome approach to assessing cancer-related fatigue. Fifty-one patients who underwent blood or marrow transplantation an average of 6.9 months previously were administered a standardized interview designed to identify the presence of a clinical syndrome of cancer-related fatigue. Patients also completed self-report measures of fatigue, depression, and health-related quality of life. Comparisons among independent raters demonstrated high rates of reliability for the presence or absence of a cancer-related fatigue syndrome and its symptoms. Twenty-one percent of patients (n = 11) were found to meet criteria for diagnosis of a cancer-related fatigue syndrome. Compared to patients not meeting the diagnostic criteria, patients meeting the criteria reported fatigue that was greater (P < or = 0.05) in its severity, frequency, pervasiveness, and interference with quality of life. Patients who met criteria also demonstrated poorer role functioning, less vitality, and more depressive symptomatology (P < or = 0.05). These findings provide preliminary evidence of the reliability and validity of the methods used to assess the proposed clinical syndrome and suggest their utility in identifying patients experiencing clinically significant cancer-related fatigue.