Complementary Medicine for Cancer Digest May 2016

Authors: Garland SN; Gehrman P; Barg FK; Xie SX; Mao JJ.
Title: Choosing Options for Insomnia in Cancer Effectively (CHOICE): Design of a patient centered comparative effectiveness trial of acupuncture and cognitive behavior therapy for insomnia.
Source: Contemporary Clinical Trials. 47:349-55, 2016 Mar.
Insomnia is a prevalent and persistent side effect of cancer, which if left unaddressed, can be unremitting and negatively influence physical and mental well-being. Acupuncture and Cognitive Behavioral Therapy (CBT) are commonly used non-pharmacological treatments that are efficacious for treating insomnia in cancer patients; however, little is known about the comparative effectiveness of these options. The goal of personalized medicine is to determine which treatments are most effective for which individuals, and patient preference for treatment is a particularly important contributor to adherence and outcomes. Here we describe the design of a clinical trial that begins to determine how best to personalize the treatment of insomnia for cancer survivors. This project is a randomized controlled comparative effectiveness trial with a nested qualitative study comparing acupuncture and CBT for insomnia and co-morbid symptoms in a heterogeneous sample of 160 cancer survivors. The primary aim is to determine which treatment is associated with the largest reduction in insomnia severity. The secondary aim is to examine the demographic, clinical, and psychological characteristics that predict and/or moderate treatment effect. Patients will receive ten treatments of acupuncture or 7 sessions of CBT over eight weeks and complete validated patient-reported outcome measures of sleep and co-morbid symptoms at baseline, mid-treatment, post-treatment, and at three-months to assess durability of effect. The results of the proposed study have the potential to improve healthcare outcomes by helping cancer survivors and their caregivers make informed and evidence-based decisions, leading to patient-centered and personalized care for cancer survivors with insomnia.
SIO Commentary
In a research methodology article by Garland et al3, investigators describe their unique study design of a large RCT (N=160) evaluating the effectiveness of acupuncture to reduce insomnia severity among cancer survivors compared with Cognitive Behavior Therapy for Insomnia. This will be one of the first rigorously designed comparative effectiveness trial of two integrative modalities for this problem, which is common in cancer populations and has downstream effects on function, quality of life, and recovery. The study is funded by the Patient-Centered Outcomes Research Institute (PCORI) and incorporates input from both patients and caregivers throughout the research process. The nested qualitative portion of the study (n=60) will enhance understanding of patient decision-making and experiences as they relate to these two therapies, which will help guide individualized care for cancer survivors in the future. The overall novel and rigorous design will also serve as a model for other patient-centered comparative effectiveness trials of integrative modalities going forward.
Authors: Greenlee H; Crew KD; Capodice J; Awad D; Buono D; Shi Z; Jeffres A; Wyse S; Whitman W; Trivedi MS; Kalinsky K; Hershman DL.
Title: Randomized sham-controlled pilot trial of weekly electro-acupuncture for the prevention of taxane-induced peripheral neuropathy in women with early stage breast cancer.
Source: Breast Cancer Research & Treatment. 156(3):453-64, 2016 Apr.
To investigate the effect of electro-acupuncture (EA) as a non-pharmacological intervention to prevent or reduce chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients undergoing chemotherapy of taxane. Women with stage I-III breast cancer scheduled to receive taxane therapy were randomized to receive a standardized protocol of 12 true or sham EA (SEA) weekly treatments concurrent with taxane treatment. Subjects completed the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Taxane neurotoxicity subscale (FACT-NTX), and other assessments at baseline and weeks 6, 12, and 16. A total of 180 subjects were screened, 63 enrolled and 48 completed week 16 assessments. Mean age was 50 with 25 % white, 25 % black, and 43 % Hispanic; 52 % had no prior chemotherapy. At week 12, both groups reported an increase in mean BPI-SF worst pain score, but no mean differences were found between groups (SEA 2.8 vs. EA 2.6, P = .86). By week 16, the SEA group returned to baseline, while the EA group continued to worsen (SEA 1.7 vs. EA 3.4, P = .03). The increase in BPI-SF worst pain score was 1.62 points higher in the EA group than in the SEA group at week 16 (P = .04). In a randomized, sham-controlled trial of EA for prevention of taxane-induced CIPN, there were no differences in pain or neuropathy between groups at week 12. Of concern, subjects on EA had a slower recovery than SEA subjects. Future studies should focus on EA for treatment as opposed to prevention of CIPN.
SIO Commentary
In a pilot randomized controlled trial (RCT), Greenlee et al1 evaluated the potential of electro-acupuncture (EA) to prevent chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients receiving weekly paclitaxel (n=48). This is the first CIPN prevention trial of EA, as prior studies have focused mostly on CIPN treatment, and the methods of acupuncture delivery in these studies has varied. Contrary to the investigators’ hypothesis, EA did not prevent the development of CIPN symptoms either during receipt of paclitaxel chemotherapy or at the end of the 12 weekly cycles. In addition, 4 weeks post-chemotherapy, the EA group experienced increased CIPN pain whereas the sham control group recovered, suggesting that EA may actually worsen CIPN rather than prevent its development. Several causes might explain this surprising finding. Most pilot studies demonstrating efficacy with acupuncture to reduce CIPN symptoms used manual acupuncture rather than EA. The increased stimulation that occurs with EA over manual acupuncture may not only increase blood flow, but subsequently increase chemotherapy delivery to the peripheral nerves to cause worsening CIPN. A prior study by Eckoff et al2 has shown that cryotherapy, which causes vasoconstriction, is associated with a lower incidence of CIPN. A number of clinical trials (NCT 023647260, NCT02744274, NCT02615678) are ongoing to study the effect of acupuncture in reducing CIPN symptoms during chemotherapy. Their results will be helpful to define the role of acupuncture as well as methods of acupuncture delivery in preventing or treating CIPN.

Authors: Chiu HY; Shyu YK; Chang PC; Tsai PS.
Title: Effects of Acupuncture on Menopause-Related Symptoms in Breast Cancer Survivors: A Meta-analysis of Randomized Controlled Trials.
Source: Cancer Nursing. 39(3):228-37, 2016 May-Jun.
BACKGROUND: Evidence regarding the effects of acupuncture on hot flashes in breast cancer survivors is conflicting. Little is known about the intermediate-term effects of acupuncture on hot flashes and other menopause-related symptoms in breast cancer survivors.
OBJECTIVE: The objective of this study was to evaluate the short-term and intermediate-term effects of acupuncture on menopause-related symptoms and particularly on hot flashes in breast cancer survivors.
METHODS: Electronic databases including EMBASE, PubMed, PsycINFO, Web of Science, CINAHL, Wanfang Data Chinese Database, and China Knowledge Resource Integrated Database from inception until June 15, 2014, were searched. Randomized controlled trials in which acupuncture was compared with sham controls or other interventions according to the reduction of hot flashes or menopause-related symptoms in breast cancer survivors were included.
RESULTS: We analyzed 7 studies involving 342 participants. Acupuncture significantly reduced the frequency of hot flashes and severity of menopause-related symptoms (g = -0.23 and -0.36, respectively) immediately after the completion of treatment. In comparison with sham acupuncture, effects of true acupuncture on the frequency and severity of hot flashes were not significantly different. At 1 to 3 months' follow-up, the severity of menopause-related symptoms remained significantly reduced (g = -0.56).
CONCLUSION: Acupuncture yielded small-size effects on reducing hot-flash frequency and the severity of menopause-related symptoms.
IMPLICATIONS FOR PRACTICE: Acupuncture may be used as a complementary therapy for breast cancer survivors experiencing hot flashes and other menopause-related symptoms; however, whether acupuncture exerts specific treatment effects other than needling or placebo effects needs to be further evaluated.

Authors: Tao WW; Jiang H; Tao XM; Jiang P; Sha LY; Sun XC.
Title: Effects of Acupuncture, Tuina, Tai Chi, Qigong, and Traditional Chinese Medicine Five-Element Music Therapy on Symptom Management and Quality of Life for Cancer Patients: A Meta-Analysis.
Source: Journal of Pain & Symptom Management. 51(4):728-47, 2016 Apr.
CONTEXT: Most cancer patients suffer from both the disease itself and symptoms induced by conventional treatment. Available literature on the clinical effects on cancer patients of acupuncture, Tuina, Tai Chi, Qigong, and Traditional Chinese Medicine Five-Element Music Therapy (TCM-FEMT) reports controversial results.
OBJECTIVES: The primary objective of this meta-analysis was to evaluate the effect of acupuncture, Tuina, Tai Chi, Qigong, and TCM-FEMT on various symptoms and quality of life (QOL) in patients with cancer; risk of bias for the selected trials also was assessed.
METHODS: Studies were identified by searching electronic databases (MEDLINE via both PubMed and Ovid, Cochrane Central, China National Knowledge Infrastructure, Chinese Scientific Journal Database, China Biology Medicine, and Wanfang Database). All randomized controlled trials (RCTs) using acupuncture, Tuina, Tai Chi, Qigong, or TCM-FEMT published before October 2, 2014, were selected, regardless of whether the article was published in Chinese or English.
RESULTS: We identified 67 RCTs (5465 patients) that met our inclusion criteria to perform this meta-analysis. Analysis results showed that a significant combined effect was observed for QOL change in patients with terminal cancer in favor of acupuncture and Tuina (Cohen's d: 0.21-4.55, P < 0.05), whereas Tai Chi and Qigong had no effect on QOL of breast cancer survivors (P > 0.05). The meta-analysis also demonstrated that acupuncture produced small-to-large effects on adverse symptoms including pain, fatigue, sleep disturbance, and some gastrointestinal discomfort; however, no significant effect was found on the frequency of hot flashes (Cohen's d = -0.02; 95% CI = -1.49 to 1.45; P = 0.97; I(2) = 36%) and mood distress (P > 0.05). Tuina relieved gastrointestinal discomfort. TCM-FEMT lowered depression level. Tai Chi improved vital capacity of breast cancer patients. High risk of bias was present in 74.63% of the selected RCTs. Major sources of risk of bias were lack of blinding, allocation concealment, and incomplete outcome data.
CONCLUSION: Taken together, although there are some clear limitations regarding the body of research reviewed in this study, a tentative conclusion can be reached that acupuncture, Tuina, Tai Chi, Qigong, or TCM-FEMT represent beneficial adjunctive therapies. Future study reporting in this field should be improved regarding both method and content of interventions and research methods.

Authors: Greenlee H; Sardo Molmenti CL; Falci L; Ulmer R; Deming-Halverson S; DeRoo LA; Sandler DP.
Title: High use of complementary and alternative medicine among a large cohort of women with a family history of breast cancer: the Sister Study.
Source: Breast Cancer Research & Treatment. 156(3):527-38, 2016 Apr.
Use of complementary and alternative medicine (CAM) is high among U.S. women, yet information is limited on use among women at increased breast cancer risk. We analyzed CAM use among women with a family history of breast cancer. CAM use was analyzed among women enrolled 2003-2009 in the Sister Study cohort. Eligible women were aged 35-74, U.S. or Puerto Rican residents, no personal history of breast cancer, and had >1 sister with breast cancer. Baseline data on CAM use in the past year were available for 49,734 women. Logistic regression models examined the association between CAM use and Gail Model breast cancer risk score. Results were compared to female participants in the 2007 National Health Interview Survey (n = 7965). Among Sister Study participants, there was high use of vitamin/mineral supplements (79 %), mind-body practices (41 %), manipulative/body-based practices (32 %), and botanicals (23 %). Overall use was higher than the U.S. female population. No association was observed between familial breast cancer risk and CAM use. Black women were more likely to use spirituality/meditation-based CAM modalities, while non-Hispanic white and Asian women were high users of dietary supplements. In a cohort of women with increased breast cancer risk due to family history, CAM use is higher than women in the general U.S. population and is associated with race/ethnicity. Use was not associated with breast cancer risk. Given the high prevalence of CAM use among women at risk for breast cancer, research on the effectiveness of CAM use for disease prevention is needed.
Authors: Siegel P; da Motta PM; da Silva LG; Stephan C; Lima CS; de Barros NF.
Title: Reiki for Cancer Patients Undergoing Chemotherapy in a Brazilian Hospital:A Pilot Study.
Source: Holistic Nursing Practice. 30(3):174-82, 2016 May-Jun.
The purpose of this pilot study was to explore whether individualized Reiki given to cancer patients at a Brazilian hospital improved symptoms and well-being. Data from 36 patients who received 5 Reiki sessions were collected using the MYMOP and were compared before and after their treatment and also with 14 patients who did not receive Reiki and who acted as a comparison group. Twenty-one patients reported feeling better, 12 felt worse, and 3 reported no change. Of the comparison group, 6 patients reported feeling better and 8 felt worse. The Reiki practice delivered as part of the integrative care in oncology did produce clinically significant effects, although not statistically significant results, for more than half of the patients undergoing cancer treatment.
Authors: Carr T; Quinlan E; Robertson S; Duggleby W; Thomas R; Holtslander L.
Title: Yoga as palliation in women with advanced cancer: a pilot study.
Source: International Journal of Palliative Nursing. 22(3):111-7, 2016 Mar 2.
OBJECTIVE: The purpose of this pilot study was to investigate the palliative potential of home-based yoga sessions provided to women with advanced cancer.
METHOD: Personalised 45-minute yoga sessions were offered to three women with advanced cancer by an experienced yoga teacher. Each woman took part in a one-to-one interview after the completion of the yoga programme and was asked to describe her experiences of the programme's impact.
RESULTS: The personalised nature of the yoga sessions resulted in similar positive physical and psychosocial effects comparable to those demonstrated in other studies with cancer patients. Participants described physical, mental, and emotional benefits as well as the alleviation of illness impacts. The enhancement of mind-body and body-spirit connections were also noted.
CONCLUSION: Personalised home-based yoga programmes for people with advanced cancer may produce similar benefits, including palliation, as those institutionally-based programmes for people with non-advanced cancer.

Authors: Lotzke D; Wiedemann F; Rodrigues Recchia D; Ostermann T; Sattler D; Ettl J; Kiechle M; Bussing A.
Title: Iyengar-Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Therapy in Women with Stage I-III Breast Cancer: Health-Related Quality of Life, Mindfulness, Spirituality, Life Satisfaction, and Cancer-Related Fatigue.
Source: Evidence-Based Complementary & Alternative Medicine: eCAM. 2016:5931816, 2016.
Abstract: This study aims to test the effects of yoga on health-related quality of life, life satisfaction, cancer-related fatigue, mindfulness, and spirituality compared to conventional therapeutic exercises during (neo)adjuvant cytotoxic and endocrine therapy in women with breast cancer. In a randomized controlled trial 92 women with breast cancer undergoing oncological treatment were randomly enrolled for a yoga intervention (YI) (n = 45) or for a physical exercise intervention (PEI) (n = 47). Measurements were obtained before (t 0) and after the intervention (t 1) as well as 3 months after finishing intervention (t 2) using standardized questionnaires. Life satisfaction and fatigue improved under PEI (p < 0.05) but not under YI (t 0 to t 2). Regarding quality of life (EORTC QLQ-C30) a direct effect (t 0 to t 1; p < 0.001) of YI was found on role and emotional functioning, while under PEI only emotional functioning improved. Significant improvements (p < 0.001) were observed at both t 1 and t 2 also for symptom scales in both groups: dyspnea, appetite loss, constipation, and diarrhea. There was no significant difference between therapies for none of the analyzed variables neither for t 1 nor for t 2. During chemotherapy, yoga was not seen as more helpful than conventional therapeutic exercises. This does not argue against its use in the recovery phase.

Authors: Cramer H; Pokhrel B; Fester C; Meier B; Gass F; Lauche R; Eggleston B; Walz M; Michalsen A; Kunz R; Dobos G; Langhorst J.
Title: A randomized controlled bicenter trial of yoga for patients with colorectal cancer.
Source: Psycho-Oncology. 25(4):412-20, 2016 Apr.
OBJECTIVE: The aim of this trial was to evaluate the effects of yoga on health-related quality of life in patients with colorectal cancer.
METHODS: Patients with non-metastatic colorectal cancer were randomly assigned to a 10-week yoga intervention (90 min once weekly) or a waitlist control group. Primary outcome measure was disease-specific quality of life (Functional Assessment of Cancer Therapy - Colorectal [FACT-C]) at week 10. Secondary outcome measures included FACT-C subscales: spiritual well-being (FACT - Spirituality); fatigue (FACT - Fatigue); sleep disturbances (Pittsburgh Sleep Quality Inventory); depression and anxiety (Hospital Anxiety and Depression Scale); body awareness (Scale of Body Connection); and body-efficacy expectations (Body-Efficacy Expectations Scale). Outcomes were assessed at week 10 and week 22 after randomization.
RESULTS: Fifty-four patients (mean age 68.3+/-9.7 years) were randomized to yoga (n=27; attrition rate 22.2%) and control group (n=27; attrition rate 18.5%). Patients in the yoga group attended a mean of 5.3+/-4.0 yoga classes. No significant group differences for the FACT-C total score were found. Group differences were found for emotional well-being at week 22 (=1.59; 95% CI=0.27,2.90; p=0.019), sleep disturbances at week 22 (=-1.08; 95% CI=-2.13, -0.03; p=0.043), anxiety at week 10 (=-1.14; 95% CI=-2.20, -0.09; p=0.043), and depression at week 10 (=-1.34; 95% CI=-2.61, -0.8; p=0.038). No serious adverse events occurred in the yoga group, while liver metastases were diagnosed in one patient in the control group.
CONCLUSION: This randomized trial found no effects of yoga on health-related quality of life in patients with colorectal cancer. Given the high attrition rate and low intervention adherence, no definite conclusions can be drawn from this trial.