The relationship between coping strategies, quality of life, and mood in patients with incurable cancer.

BACKGROUND: Patients with incurable cancer face many physical and emotional stressors, yet little is known about their coping strategies or the relationship between their coping strategies, quality of life (QOL), and mood. METHODS: As part of a randomized trial of palliative care, this study assessed baseline QOL (Functional Assessment of Cancer Therapy-General), mood (Hospital Anxiety and Depression Scale), and coping (Brief COPE) in patients within 8 weeks of a diagnosis of incurable lung or gastrointestinal cancer and before randomization. To examine associations between coping strategies, QOL, and mood, we used linear regression, adjusting for patients' age, sex, marital status, and cancer type. RESULTS: There were 350 participants (mean age, 64.9 years), and the majority were male (54.0%), were married (70.0%), and had lung cancer (54.6%). Most reported high utilization of emotional support coping (77.0%), whereas fewer reported high utilization of acceptance (44.8%), self-blame (37.9%), and denial (28.2%). Emotional support (QOL: ß = 2.65, P < .01; depression: ß = -0.56, P = .02) and acceptance (QOL: ß = 1.55, P < .01; depression: ß = -0.37, P = .01; anxiety: ß = -0.34, P = .02) correlated with better QOL and mood. Denial (QOL: ß = -1.97, P < .01; depression: ß = 0.36, P = .01; anxiety: ß = 0.61, P < .01) and self-blame (QOL: ß = -2.31, P < .01; depression: ß = 0.58, P < .01; anxiety: ß = 0.66, P < .01) correlated with worse QOL and mood. CONCLUSIONS: Patients with newly diagnosed, incurable cancer use a variety of coping strategies. The use of emotional support and acceptance coping strategies correlated with better QOL and mood, whereas the use of denial and self-blame negatively correlated with these outcomes. Interventions to improve patients' QOL and mood should seek to cultivate the use of adaptive coping strategies. Cancer 2016;122:2110-6. © 2016 American Cancer Society.

A Systematic Review of Adherence to Oral Antineoplastic Therapies.

BACKGROUND: Oral antineoplastic therapies not only improve survival but also reduce the burden of care for patients. Yet patients and clinicians face new challenges in managing adherence to these oral therapies. We conducted a systematic literature review to assess rates and correlates of adherence to oral antineoplastic therapies and interventions aimed at improving adherence. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search of the Ovid MEDLINE database from January 1, 2003 to June 30, 2015, using relevant terminology for oral antineoplastic agents. We included observational, database, and intervention studies. At least two researchers evaluated each paper to ensure accuracy of results and determine risk of bias. RESULTS: We identified 927 records from the search and screened 214 abstracts. After conducting a full-text review of 167 papers, we included in the final sample 51 papers on rates/correlates of adherence to oral antineoplastic therapy and 12 papers on intervention studies to improve adherence. Rates of adherence varied widely, from 46% to 100%, depending on patient sample, medication type, follow-up period, assessment measure, and calculation of adherence. Of the intervention studies, only 1 of the randomized trials and 2 of the cohort studies showed benefit regarding adherence, with the majority suffering high risk of bias. CONCLUSIONS: Although no reliable estimate of adherence to oral antineoplastic therapies can be gleaned from the literature, a substantial proportion of patients struggle to adhere to these medications as prescribed. The few intervention studies for adherence have notable methodological concerns, thereby limiting the evidence to guide practice in promoting medication adherence among patients with cancer.

Postsurgical Depressive Symptoms and Proinflammatory Cytokine Elevations in Women Undergoing Primary Treatment for Breast Cancer.

OBJECTIVE: Depression and inflammation may independently promote breast cancer (BCa) disease progression and poorer clinical outcomes. Depression has been associated with increased levels of inflammatory markers in medically healthy individuals and patients with cancer. However, inconsistencies in study time frames complicate interpretation of results within specific cancer types. This study examined relationships between depressive symptoms and inflammation in women with early-stage BCa before beginning adjuvant treatment. METHODS: Women with Stage 0-III BCa were recruited approximately 4 to 8 weeks after surgery. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression, and blood samples were collected to quantify circulating levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNF-α) by enzyme-linked immunosorbent assay. Analyses of covariance were used to test for group differences (elevated versus low depressive symptoms) in levels of cytokines. Multiple regression analyses were used to examine relationships between continuous severity of depressive symptoms and levels of cytokines adjusting for relevant biobehavioral covariates. RESULTS: Thirty-six (40%) of 89 patients showed elevated levels of depressive symptoms and, in adjusted models, had marginally higher levels of IL-1ß (mean [M] = 14.49 [95% confidence interval {CI} = 6.11-32.65] versus M = 4.68 [95% CI = 1.96-9.86] and IL-6 [M = 88.74 {95% CI = 33.28-233.96} versus M = 61.52 {95% CI = 27.44-136.40}]) significantly higher levels of TNF-α (M = 17.07 [95% CI = 8.27-34.32] versus M = 6.94 [95% CI = 3.58-12.80]) than did women with low depressive symptoms. Across the spectrum of depressive symptoms, greater magnitude of depressive symptoms was related to greater levels of IL-1ß (ß = 0.06, p = .006, R = 0.25) and TNF-α (ß = 0.06, p = .003, R = 0.27). CONCLUSIONS: Postsurgery and preadjuvant treatment for early-stage BCa, depressive symptoms covary with elevated levels of multiple proinflammatory cytokines. Findings have implications for psychosocial and biological interventions concurrently focusing on depression and inflammation. TRIAL REGISTRATION: NCT01422551.

Ethnic differences in types of social support from multiple sources after breast cancer surgery.

OBJECTIVES: Diagnosis of and treatment for breast cancer (BCa) may require psychological adaptation and often involve heightened distress. Several types of social support positively relate to psychological adaptation to BCa, and negative support is associated with poorer adaptation. Although Hispanic women report greater distress than non-Hispanic White (NHW) women after diagnosis of BCa, no studies have examined ethnic differences in types of social support received from varying sources after surgery for BCa. DESIGN: Hispanic (N = 61) and NHW (N = 150) women diagnosed with early-stage BCa self-reported emotional, informational, instrumental, and negative support from five sources. Ethnic differences in levels of social support were compared using multiple regression analysis. RESULTS: When controlling for age, income, days since surgery, and stage of disease in multivariable models there were no ethnic differences in levels of emotional support from any source. Hispanic women reported greater informational support from adult women family members and children and male adult family members than did NHW women. Instrumental support from adult women family members was also greater among Hispanic than NHW women. Hispanic women reported higher negative support from husbands/partners and from children and male adult family members. When the number of years in the USA was controlled, Hispanic women showed greater informational support from adult women family members, children and male adult family members, and friends. Instrumental support from adult women family members remained greater in Hispanic women, but negative support no longer differed. CONCLUSION: Family is a greater source of informational and instrumental support for Hispanic than NHW women. Hispanic women reported higher negative support from male sources than did NHW women. Level of support from different sources may also depend on time spent in the USA. Longitudinal studies are needed to determine whether patterns and sources of social support shift over the course of BCa treatment.

Long-term psychological benefits of cognitive-behavioral stress management for women with breast cancer: 11-year follow-up of a randomized controlled trial.

BACKGROUND: Breast cancer survivors experience long-term physical and psychological sequelae after their primary treatment that negatively influence their quality of life (QOL) and increase depressive symptoms. Group-based cognitive-behavioral stress management (CBSM) delivered after surgery for early-stage breast cancer was previously associated with better QOL over a 12-month follow-up and with fewer depressive symptoms up to 5 years after study enrollment. This 8- to 15-year follow-up (median, 11 years) of a previously conducted trial (NCT01422551) evaluated whether women in this cohort receiving CBSM had fewer depressive symptoms and better QOL than controls at an 8- to 15-year follow-up. METHODS: Women with stage 0 to IIIb breast cancer were initially recruited 2 to 10 weeks after surgery and randomized to a 10-week CBSM intervention or a 1-day psychoeducational control group. One hundred women (51 CBSM patients and 49 controls) were recontacted 8 to 15 years after study enrollment to participate in a follow-up assessment. The Center for Epidemiologic Studies-Depression (CES-D) scale and the Functional Assessment of Cancer Therapy-Breast (FACT-B) were self-administered. Multiple regression was employed to evaluate group differences on the CES-D scale and FACT-B over and above effects of confounding variables. RESULTS: Participants assigned to CBSM reported significantly lower depressive symptoms (d, 0.63; 95% confidence interval [CI], 0.56-0.70) and better QOL (d, 0.58; 95% CI, 0.52-0.65) above the effects of the covariates. CONCLUSIONS: Women who received CBSM after surgery for early-stage breast cancer reported lower depressive symptoms and better QOL than the control group up to 15 years later. Early implementation of cognitive-behavioral interventions may influence long-term psychosocial functioning in breast cancer survivors.

A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up.

Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8-15 years post-enrollment. From 1998 to 2005, women (N = 240) 2-10 weeks post-surgery for non-metastatic Stage 0-IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention (n = 120) or a 1-day psychoeducational seminar control (n = 120). In 2013, 8-15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality (p = .006) and disease-free interval (p = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes.

Randomized controlled trial of cognitive behavioral stress management in breast cancer: a brief report of effects on 5-year depressive symptoms.

OBJECTIVE: Survivors of breast cancer experience stress and are at risk for depressive symptoms following primary treatment. Group-based interventions such as cognitive-behavioral stress management (CBSM) delivered postsurgery for nonmetastatic breast cancer (BCa) were previously associated with fewer depressive symptoms over a 12-month follow-up; few studies have examined the longer-term benefits of such psychosocial interventions. This 5-year follow-up study of a previously conducted trial (#NCT01422551) tested whether group-based CBSM following surgery for nonmetastatic BCa was associated with fewer depressive symptoms. METHODS: Women (N = 240) with Stage 0-IIIb BCa were recruited 2-10 weeks postsurgery and randomized to a 10-week CBSM intervention group or a 1-day psycho-educational control group. Women were recontacted 5 years poststudy enrollment and reconsented to participate in the follow-up study (N = 130). Depressive symptomatology was assessed using the Center for Epidemiologic Studies-Depression scale (CES-D). ANOVA and ANCOVA analyses were employed to test for group differences on the CES-D at 5-year follow-up accounting for relevant covariates. RESULTS: Participants assigned to CBSM reported significantly fewer depressive symptoms (M = 9.99, SE = 0.93) at the follow-up compared with those in the control group (M = 12.97, SE = 0.99), p = .030. With covariates, the group difference remained significant, p = .012. CONCLUSION: Women who received CBSM postsurgery for BCa reported fewer depressive symptoms than those in the control group in this 5-year follow-up. Psychosocial interventions early in treatment may influence long-term psychological well-being in BCa survivors.

Perceived Fatigue Interference and Depressed Mood: Comparison of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients with Fatigued Breast Cancer Survivors.

OBJECTIVE: Persistent fatigue and depressive symptoms are both highly prevalent among patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) as well as breast cancer survivors. This study aimed to assess and directly compare perceptions of fatigue as highly interfering in one's daily functioning in both patient populations to better understand their relationships with depressed mood. METHODS: Participants were 95 female CFS/ME patients and 67 females who were approximately 5 years post-treatment for stage 0-III breast cancer presenting with clinically elevated fatigue severity. Self-report measures were obtained on participants' fatigue-related interference in daily functioning and fatigue severity as well as depressed mood. Hierarchical regression was used to test effects controlling for relevant demographic, psychosocial, and medical covariates. RESULTS: CFS/ME patients endorsed greater depressed mood and fatigue interference than did fatigued breast cancer survivors, p's<.001. These factors were significantly positively correlated among CFS/ME patients (ß=.36, p<.001), but not the fatigued breast cancer survivors (ß=.18, p=.19). CONCLUSIONS: CFS/ME patients reported elevated fatigue symptoms and depression relative to fatigued breast cancer survivors. In the former group, greater depressed mood was highly and significantly associated with greater fatigue-related inference in daily activities. Potential targets for cognitive behavioral interventions are discussed.

Brief cognitive-behavioral and relaxation training interventions for breast cancer: A randomized controlled trial.

OBJECTIVE: Women with breast cancer (BCa) report elevated distress postsurgery. Group-based cognitive-behavioral stress management (CBSM) following surgery improves psychological adaptation, though its key mechanisms remain speculative. This randomized controlled dismantling trial compared 2 interventions featuring elements thought to drive CBSM effects: a 5-week cognitive-behavioral training (CBT) and 5-week relaxation training (RT) versus a 5-week health education (HE) control group. METHOD: Women with stage 0-III BCa (N = 183) were randomized to CBT, RT, or HE condition 2-10 weeks postsurgery. Psychosocial measures were collected at baseline (T1) and postintervention (T2). Repeated-measures analyses of variance (ANOVAs) tested whether CBT and RT treatments improved primary measures of psychological adaptation and secondary measures of stress management resource perceptions from pre- to postintervention relative to HE. RESULTS: Both CBT and RT groups reported reduced depressive affect. The CBT group reported improved emotional well-being/quality of life and less cancer-specific thought intrusions. The RT group reported improvements on illness-related social disruption. Regarding stress management resources, the CBT group reported increased reliability of social support networks, while the RT group reported increased confidence in relaxation skills. Psychological adaptation and stress management resource constructs were unchanged in the HE control group. CONCLUSIONS: Nonmetastatic breast cancer patients participating in 2 forms of brief, 5-week group-based stress management intervention after surgery showed improvements in psychological adaptation and stress management resources compared with an attention-matched control group. Findings provide preliminary support suggesting that using brief group-based stress management interventions may promote adaptation among nonmetastatic breast cancer patients.

Postsurgical physical activity and fatigue-related daily interference in women with non-metastatic breast cancer.

PURPOSE: Women undergoing surgery for breast cancer experience side effects, such as fatigue, reduced quality of life (QOL) and depression. Physical activity (PA) is associated with improved psychological adjustment during treatment and survivorship, yet little is known about how PA relates to fatigue, depression and QOL in the period following surgery for breast cancer. The purpose of the study was to examine the relationships between these constructs in women who recently underwent surgery for breast cancer. METHODS: At 2-10 weeks post-surgery, 240 women with non-metastatic breast cancer reported intensity and duration of moderate and vigorous PA (MVPA), fatigue (intensity and interference), depressed mood, clinician-rated depression and functional QOL. RESULTS: In the path analysis models tested, women that reported greater weekly MVPA reported less fatigue interference, greater functional QOL, less depressed mood, and lower clinician-rated depression. Tests of indirect effects suggested that fatigue interference may be an intermediate pathway by which MVPA relates to functional QOL, clinician-rated depression and depressed mood. CONCLUSION: Women who are more physically active in the months after breast cancer surgery show greater psychological adaptation in the initial phases of their treatment.

NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors.

PURPOSE: European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. DESIGN: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events related to platelets and granulocytes only [corrected]; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. RESULTS: DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1300 mg/m(2) [corrected] and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. CONCLUSION: GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

Cognitive-behavioral stress management reverses anxiety-related leukocyte transcriptional dynamics.

BACKGROUND: Chronic threat and anxiety are associated with pro-inflammatory transcriptional profiles in circulating leukocytes, but the causal direction of that relationship has not been established. This study tested whether a cognitive-behavioral stress management (CBSM) intervention targeting negative affect and cognition might counteract anxiety-related transcriptional alterations in people confronting a major medical threat. METHODS: One hundred ninety-nine women undergoing primary treatment of stage 0-III breast cancer were randomized to a 10-week CBSM protocol or an active control condition. Seventy-nine provided peripheral blood leukocyte samples for genome-wide transcriptional profiling and bioinformatic analyses at baseline, 6-month, and 12-month follow-ups. RESULTS: Baseline negative affect was associated with >50% differential expression of 201 leukocyte transcripts, including upregulated expression of pro-inflammatory and metastasis-related genes. CBSM altered leukocyte expression of 91 genes by >50% at follow-up (group × time interaction), including downregulation of pro-inflammatory and metastasis-related genes and upregulation of type I interferon response genes. Promoter-based bioinformatic analyses implicated decreased activity of NF-κB/Rel and GATA family transcription factors and increased activity of interferon response factors and the glucocorticoid receptor as potential mediators of CBSM-induced transcriptional alterations. CONCLUSIONS: In early-stage breast cancer patients, a 10-week CBSM intervention can reverse anxiety-related upregulation of pro-inflammatory gene expression in circulating leukocytes. These findings clarify the molecular signaling pathways by which behavioral interventions can influence physical health and alter peripheral inflammatory processes that may reciprocally affect brain affective and cognitive processes.

Botanicals used in complementary and alternative medicine treatment of cancer: clinical science and future perspectives.

BACKGROUND: Botanicals and herbal combinations are among the most common complementary and alternative medicine (CAM) approaches used by cancer patients both for cancer treatment and management of cancer symptoms. Despite their widespread use, however, the safety and efficacy of many botanicals has not been established in controlled clinical trials. OBJECTIVES: This article reviews the published evidence for the safety and clinical benefit of botanicals used in the treatment of cancer and cancer symptom management and describes the continuing clinical trials of botanicals with applications in oncology. METHODS: Literature searches were conducted in PubMed, EMBASE, Cochrane Clinical Trials databases, Pharmaprojects and CRISP (Computer Retrieval of Information on Scientific Projects) clinical trials databases. CONCLUSION: A number of botanicals have shown promise for cancer symptom management but need further study. A limited number of multi-agent nutritional supplement approaches are being explored in clinical trials. Botanical immunomodulators and botanical products shown to affect pathways of angiogenesis, apoptosis and cell signaling in vitro have stimulated research interest and may broaden the range of available cancer treatments.