Karen M. Mustian

Prevalence, Demographics, and Psychological Associations of Sleep Disruption in Patients With Cancer: University of Rochester Cancer Center―Community Clinical Oncology Program

PURPOSE Sleep disruption is prevalent in patients with cancer and survivors, but the prevalence of insomnia, a distressing sleep disorder, in these populations has yet to be determined in large-scale studies. PATIENTS AND METHODS A total of 823 patients with cancer receiving chemotherapy (mean age, 58 years; 597 female patients) reported on sleep difficulties in a prospective study. RESULTS During day 7 of cycle 1 of chemotherapy, 36.6% (n = 301) of the patients with cancer reported insomnia symptoms, and 43% (n = 362) met the diagnostic criteria for insomnia syndrome. Patients with cancer younger than 58 years were significantly more likely to experience either symptoms of insomnia or insomnia syndrome (chi(2) = 13.6; P = .0002). Patients with breast cancer had the highest number of overall insomnia complaints. A significant positive association was found between symptoms of insomnia during cycles 1 and 2 of chemotherapy (phi = .62, P < .0001), showing persistence of insomnia during the first two cycles of chemotherapy. Sixty percent of the patient sample reported that their insomnia symptoms remained unchanged from cycle 1 to cycle 2. Those with insomnia complaints had significantly more depression and fatigue than good sleepers (all P < .0001). CONCLUSION The proportions of patients with cancer in this sample reporting symptoms of insomnia and meeting diagnostic criteria for insomnia syndrome during chemotherapy are approximately three times higher than the proportions reported in the general population. Insomnia complaints persist throughout the second chemotherapy cycle for the majority of patients with cancer in this study. Insomnia is prevalent, underrecognized, undermanaged, and understudied among patients with cancer receiving chemotherapy.

Effect of paroxetine hydrochloride (Paxil®) on fatigue and depression in breast cancer patients receiving chemotherapy

SummaryBackground. Fatigue can significantly interfere with a cancer patient’s ability to fulfill daily responsibilities and enjoy life. It commonly co-exists with depression in patients undergoing chemotherapy, suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue. Methods. We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy randomly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor (SSRI) paroxetine (Paxil®, SmithKline Beecham Pharmaceuticals) or an identical-appearing placebo. Patients began their study medication seven days following their first on-study treatment and continued until seven days following their fourth on-study treatment. Seven days after each treatment, participants completed questionnaires measuring fatigue (Multidimensional Assessment of Fatigue, Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist) and depression (Profile of Mood States-Depression subscale [POMS-DD] and Center for Epidemiologic Studies-Depression [CES-D]). Results. Repeated-measures ANOVAs, after controlling for baseline measures, showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D (p=0.006) and the POMS-DD (p=0.07) but not in reducing fatigue (all measures, ps > 0.27). Conclusions. Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo, indicating that a biologically active dose was used, no significant differences between groups on any of the measures of fatigued were observed. Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment.

Falls and Physical Performance Deficits in Older Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy

OBJECTIVES Men experience a decrease in lean muscle mass and strength during the first year of androgen deprivation therapy (ADT). The prevalence of falls and physical and functional impairment in this population have not been well described. METHODS A total of 50 men aged 70 years and older (median 78) receiving ADT for systemic prostate cancer (80% biochemical recurrence) underwent functional and physical assessments. The functional assessments included Katzs Activities of Daily Living (ADLs) and Lawtons Instrumental Activities of Daily Living (IADLs). Patients completed the Vulnerable Elders Survey-13, a short screening tool of self-perceived functional and physical performance ability. Physical performance was assessed using the Short Physical Performance Battery. The history of falls was recorded. Of the 50 patients, 40 underwent follow-up assessment with the same instruments 3 months after the initial assessment. RESULTS Of the 50 men, 24% had impairment in the ADLs, 42% had impairment in the IADLs, 56% had abnormal Short Physical Performance Battery findings, and 22% reported falls within the previous 3 months. Within the Short Physical Performance Battery, deficits occurred within all subcomponents (balance, walking, and chair stands). On univariate analysis, age, deficits in ADLs and IADLs, and abnormal cognitive and functional screen findings were associated with an increased risk of abnormal physical performance. ADL deficits, the use of an assistive device, and abnormal functional screen findings were associated with an increased risk of falling. CONCLUSIONS The results of our study have shown that older men with prostate cancer receiving long-term ADT exhibit significant functional and physical impairment and are at risk of falls that is greater than that for similar-aged cohorts. Careful assessment of the functional and physical deficits in older patients receiving ADT is warranted.

Cognitive training for improving executive function in chemotherapy-treated breast cancer survivors.

BACKGROUND A majority of breast cancer (BC) survivors, particularly those treated with chemotherapy, experience long-term cognitive deficits that significantly reduce quality of life. Among the cognitive domains most commonly affected include executive functions (EF), such as working memory, cognitive flexibility, multitasking, planning, and attention. Previous studies in other populations have shown that cognitive training, a behavioral method for treating cognitive deficits, can result in significant improvements in a number of cognitive skills, including EF. MATERIALS AND METHODS In this study, we conducted a randomized controlled trial to investigate the feasibility and preliminary effectiveness of a novel, online EF training program in long-term BC survivors. A total of 41 BC survivors (21 active, 20 wait list) completed the 48 session training program over 12 weeks. The participants were, on average, 6 years after therapy. RESULTS Cognitive training led to significant improvements in cognitive flexibility, verbal fluency and processing speed, with marginally significant downstream improvements in verbal memory as assessed via standardized measures. Self-ratings of EF skills, including planning, organizing, and task monitoring, also were improved in the active group compared with the wait list group. CONCLUSIONS Our findings suggest that EF skills may be improved even in long-term survivors by using a computerized, home-based intervention program. These improvements may potentially include subjective EF skills, which suggest a transfer of the training program to real-world behaviors.

Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors

Many survivors of breast cancer show significant cognitive impairments, including memory deficits. Inflammation induced by chemotherapy may contribute to hippocampal changes that underlie these deficits. In this cross-sectional study, we measured bilateral hippocampal volumes from high-resolution magnetic resonance images in 42 chemotherapy-treated breast cancer survivors and 35 healthy female controls. Patients with breast cancer were, on average, 4.8 ± 3.4 years off-therapy. In a subset of these participants (20 breast cancer, 23 controls), we quantified serum cytokine levels. Left hippocampal volumes and memory performance were significantly reduced and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα) concentrations were significantly elevated in the breast cancer group compared to controls. In the breast cancer group, lower left hippocampal volume was associated with higher levels of TNFα and lower levels of IL-6 with a significant interaction between these two cytokines suggesting a potential modulatory effect of IL-6 on TNFα. Verbal memory performance was associated with cytokine levels and left hippocampal volume in both groups. These findings provide evidence of altered hippocampal volume and verbal memory difficulties following breast cancer chemotherapy that may be mediated by TNFα and IL-6.

Multicenter, Randomized Controlled Trial of Yoga for Sleep Quality Among Cancer Survivors

PURPOSE Thirty percent to 90% of cancer survivors report impaired sleep quality post-treatment, which can be severe enough to increase morbidity and mortality. Lifestyle interventions, such as exercise, are recommended in conjunction with drugs and cognitive behavioral therapy for the treatment of impaired sleep. Preliminary evidence indicates that yoga-a mind-body practice and form of exercise-may improve sleep among cancer survivors. The primary aim of this randomized, controlled clinical trial was to determine the efficacy of a standardized yoga intervention compared with standard care for improving global sleep quality (primary outcome) among post-treatment cancer survivors. PATIENTS AND METHODS In all, 410 survivors suffering from moderate or greater sleep disruption between 2 and 24 months after surgery, chemotherapy, and/or radiation therapy were randomly assigned to standard care or standard care plus the 4-week yoga intervention. The yoga intervention used the Yoga for Cancer Survivors (YOCAS) program consisting of pranayama (breathing exercises), 16 Gentle Hatha and Restorative yoga asanas (postures), and meditation. Participants attended two 75-minute sessions per week. Sleep quality was assessed by using the Pittsburgh Sleep Quality Index and actigraphy pre- and postintervention. RESULTS In all, 410 survivors were accrued (96% female; mean age, 54 years; 75% had breast cancer). Yoga participants demonstrated greater improvements in global sleep quality and, secondarily, subjective sleep quality, daytime dysfunction, wake after sleep onset, sleep efficiency, and medication use at postintervention (all P ≤ .05) compared with standard care participants. CONCLUSION Yoga, specifically the YOCAS program, is a useful treatment for improving sleep quality and reducing sleep medication use among cancer survivors.

Association of Cancer With Geriatric Syndromes in Older Medicare Beneficiaries

PURPOSE To identify whether a history of cancer is associated with specific geriatric syndromes in older patients. PATIENTS AND METHODS; Using the 2003 Medicare Current Beneficiary Survey, we analyzed a national sample of 12,480 community-based elders. Differences in prevalence of geriatric syndromes between those with and without cancer were estimated. Multivariable logistic regressions were used to evaluate whether cancer was independently associated with geriatric syndromes. RESULTS Two thousand three hundred forty-nine (18%) reported a history of cancer. Among those with cancer, 60.3% reported one or more geriatric syndromes as compared with 53.2% of those without cancer (P < .001). Those with cancer overall had a statistically significantly higher prevalence of hearing trouble, urinary incontinence, falls, depression, and osteoporosis than those without cancer. Adjusting for possible confounders, those with a history of cancer were more likely to experience depression (adjusted odds ratio [OR], 1.15; 95% CI, 1.02 to 1.30; P = .023), falls (adjusted OR, 1.17; 95% CI, 1.04 to 1.32; P = .010), osteoporosis (adjusted OR, 1.21; 95% CI, 1.06 to 1.38; P = .004), hearing trouble (adjusted OR, 1.28; 95% CI, 1.08 to 1.52; P = .005), and urinary incontinence (adjusted OR, 1.42; 95% CI, 1.20 to 1.69; P < .001). Analysis of specific cancer subtypes showed that lung cancer was associated with vision, hearing, and eating trouble; prostate cancer was associated with incontinence and falls; cervical/uterine cancer was associated with falls and osteoporosis; and colon cancer was associated with depression and osteoporosis. CONCLUSION Elderly patients with cancer experience a higher prevalence of geriatric syndromes than those without cancer. Prospective studies that establish the causal relationships between cancer and geriatric syndromes are necessary.

Frequency, Severity, Clinical Course, and Correlates of Fatigue in 372 Patients during 5 Weeks of Radiotherapy for Cancer

Patients often describe fatigue as the most distressing of the symptoms they experienced during their cancer treatment. Fatigue may increase from initial levels experienced during cancer treatment with the addition of radiotherapy (RT).

Effects of Tai Chi Chuan on Insulin and Cytokine Levels in a Randomized Controlled Pilot Study on Breast Cancer Survivors

BACKGROUND Tai Chi Chuan (TCC) is an integrative medicine mind-body practice with a physical activity component that has positive effects on aerobic capacity, muscular strength, and quality of life among cancer survivors, similar to the effects elicited by other modes of moderate-intensity exercise. Inflammatory cytokines and insulin and insulin-related signaling molecules may contribute to weight gain and affect cancer recurrence rates and survival; exercise can curb cancer- and treatment-related weight gain, increase survival, and reduce levels of insulin and inflammatory cytokines. Despite knowing the beneficial effects of conventional exercise interventions on these mediators, little is known about the physiologic effects of TCC on these pathways in breast cancer survivors. METHODS We assessed the effects of a 12-week, moderately intense, TCC intervention (n = 9) compared with a non-physical activity control (n = 10) consisting of psychosocial support therapy (PST), on levels of insulin, insulin-like growth factor (IGF)-1, insulin growth factor-like binding protein (IGFBP)-1, IGFBP-3, and cytokines interleukin (IL)-6, IL-2, and interferon (IFN)-γ in breast cancer survivors. RESULTS Levels of insulin are significantly different in TCC and PST groups; levels remained stable in the TCC group but increased in the PST control group (P = .099). Bivariate analysis revealed novel and significant correlations (all r > 0.45, all P ≤ .05) of both decreased fat mass and increased fat-free mass with increased IL-6 and decreased IL-2 levels. CONCLUSIONS This pilot study shows that TCC may be associated with maintenance of insulin levels and changes in cytokine levels that may be important for maintenance of lean body mass in breast cancer survivors.

Recommendations for High-Priority Research on Cancer-Related Fatigue in Children and Adults

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current case definition to reflect more rigorous criteria, adopting the Patient Reported Outcomes Measurement Information System fatigue scales as standard measures of CRF, and linking legacy measures to the scales. With regard to the biology of CRF, the group identified the need for longitudinal research to examine biobehavioral mechanisms underlying CRF and testing mechanistic hypotheses within the context of intervention research. To address clinical trial issues, recommendations included using only placebo-controlled trial designs. setting eligibility to minimize sample heterogeneity or enable subgroup analysis, establishing a CRF severity threshold for participation in clinical trials, conducting dissemination trials of efficacious interventions (such as exercise), and combining nonpharmacologic and pharmacologic interventions to exploit the potential synergy between these approaches. Accomplishing these goals has the potential to advance the science of CRF and improve the clinical management of this troubling symptom.