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1.  Clinical Care Providers’ Perspectives on Body Size and Weight Management Among Long-Term Cancer Survivors 
Integrative cancer therapies  2015;14(3):240-248.
Objective
To examine clinical care providers’ perspectives on cancer survivors’ body size and weight management
Study Design
In-depth, semi-structured, qualitative interviews
Methods
Interviews were conducted with 33 providers (e.g., oncologists, surgeons, primary care providers, nurses, dietitians) across academic and community clinical settings. They were transcribed, coded, and analyzed thematically using constant comparative analysis.
Results
Providers conceptualized weight in relation to acute treatment, cancer outcomes, or overall health/comorbidities. These patterns were reflected in their reported framing of weight discussions, although providers indicated that they counsel patients on weight to varying extents. Perspectives differed based on professional roles and patient populations. Providers reported that survivors are motivated to lose weight, particularly due to comorbidity concerns, but face numerous barriers to doing so.
Conclusion
Providers described survivor-level and capacity-level factors influencing survivors’ weight management. Differences by provider type highlighted the role of provider knowledge, attitudes, and beliefs in clinical encounters. Opportunities for research and intervention include developing and disseminating evidence-based clinical resources for weight management among cancer survivors, addressing capacity barriers, and exploring communication strategies at interpersonal and population levels.
doi:10.1177/1534735415572882
PMCID: PMC4617386  PMID: 25716349
Body Size; Weight Management; Cancer Survivors; Clinicians; Health Communication
2.  Adverse events associated with complementary and alternative medicine use in ovarian cancer patients 
Integrative cancer therapies  2013;12(6):508-516.
Many women with ovarian cancer are choosing to include complementary and alternative medicine (CAM) substances in conjunction with their conventional treatment for ovarian cancer. A 2004 study by Navo et al., found between 44% and 53% of women with ovarian cancer use some form of CAM. Many oncologists express concern about the concomitant use of CAM during conventional treatment, particularly during chemotherapy. Specifically, some providers theorize that the adjunct use of CAM substances may be detrimental to the achievement of therapeutic levels of chemotherapy by inhibiting or inducing cytochrome P450 enzyme activity leading to increases in drug toxicity, under-treatment of disease or other adverse events. Chemotherapeutic agents have complex pharmacological profiles and narrow therapeutic windows and many factors can affect the pharmacodynamics of these drugs. In an effort to ascertain the extent of the potential problem with simultaneous use of CAM with conventional treatment we undertook comprehensive systematic review of published case reports describing CAM-related adverse events among ovarian cancer patients.
Study design
This article describes a systematic literature review.
Methods
The Natural Medicines Comprehensive Database (NMCD). PubMed, EMBASE® and the Cochrane Central Register of Controlled Trials (CCTR) were systematically reviewed for research articles pertaining to known CYP mediated CAM-drug interactions; case reports describing adverse events in patients, and clinical trials which examined the effects of herbs and supplements used during cancer treatment.
Results
Only one case report and one clinical trial were identified which met our inclusion criteria and were relevant to the current investigation.
Conclusion
Although there are concerns about the potential for adverse events related to concurrent use of CAM substances during conventional treatment we found few case reports and clinical trials in the literature which support this. However, CAM substances have the potential to affect the action of pharmacological agents through the modulation of elements of the P450 enzyme system. Therefore, it is prudent to assume that herbs and drugs using the same isoforms in the CYP450 pathway may be contraindicated for simultaneous use. However, there are few human studies evaluating herb-CYP interactions and additional research is needed as these precautions may not be necessary.
doi:10.1177/1534735413485815
PMCID: PMC4613776  PMID: 23625025
ovarian cancer; oncology; complementary and alternative medicine; integrative oncology; herbs; supplements; chemotherapy; CAM-drug interactions
3.  Complementary and alternative medicine (CAM) use by breast cancer patients at time of surgery which increases the potential for excessive bleeding 
Integrative cancer therapies  2014;14(2):119-124.
Objective
The use of Complementary or Alternative Medicine (CAM) has increased greatly over the last decade [1, 2]. This study describes a cross-sectional survey of women with breast cancer in order to describe their use of herbs and supplements that might have placed them at elevated risk for bleeding at the time of their primary treatment surgery for breast cancer.
Methods
We present cross-sectional survey results from a cohort of 316 women with breast cancer. The participants included a convenience sample of 98 women who received integrative oncology (IO) treatment from local providers and a larger group of women recruited from the local cancer registry who were matched on their similarity to the IO patients demographic characteristics and stage of cancer at time of diagnosis.
Results
Almost 16% of women with breast cancer report using one or more herbs or supplements thought to potentially increase their risk for adverse bleeding related outcomes at the time of their primary surgical treatment. This does not include the twenty-two percent who used fish and flax seed oils, which were at one time thought to increase risk for bleeding but for which there is now evidence to suggest that they are safe.
Conclusion
Further research is needed to better understand the risks associated with use of a variety of herbs and supplements among women approaching surgery.
doi:10.1177/1534735414555808
PMCID: PMC4586245  PMID: 25351407
4.  A Pilot Study of Acupuncture in Treating Bortezomib-Induced Peripheral Neuropathy in Patients With Multiple Myeloma 
Integrative cancer therapies  2014;13(5):396-404.
Background
Peripheral neuropathy is the dose limiting toxicity of bortezomib in patients with multiple myeloma (MM).
Objectives
To examine the safety, feasibility and efficacy of acupuncture in reducing bortezomib-induced peripheral neuropathy (BIPN) symptoms.
Methods
Patients with MM experiencing persistent BIPN ≥grade 2 despite adequate medical intervention and discontinuation of bortezomib received 10 acupuncture treatments for 10 weeks (2×/week for 2 weeks, 1×/week for 4 weeks, and then biweekly for 4 weeks). Responses were assessed by the Clinical Total Neuropathy Score (TNSc), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) questionnaire, and the Neuropathy Pain Scale (NPS). Repeated-measures analysis of variance was used to test for monotonic decline in scores on each of the measures. Serial serum levels of proinflammatory and neurotrophic cytokines were obtained at baseline and weeks 1, 2, 4, 8, and 14.
Results
Twenty-seven patients with MM were enrolled in the trial. There were no adverse events associated with the acupuncture treatments. TNSc data were deemed invalid and therefore were not reported. At weeks 10 and 14, FACT/GOG-Ntx and NPS showed significant reduction suggesting decreased pain, and improved function (P values were <.0001 for both FACT/GOG-Ntx and NPS at weeks 10 and 14). However, nerve conduction studies did not significantly change between baseline assessment and end of study. There was no correlation in serum cytokines for responders versus none responders.
Conclusions
Acupuncture is safe, feasible and produces subjective improvements in patients’ symptoms. A follow-up randomized controlled trial is warranted.
doi:10.1177/1534735414534729
PMCID: PMC4562796  PMID: 24867959
acupuncture; bortezomib; peripheral neuropathy; multiple myeloma
5.  Dietary Quercetin Reduces Chemotherapy-Induced Fatigue in Mice 
Integrative cancer therapies  2014;13(5):417-424.
Purpose
While fatigue is the most commonly reported symptom of chemotherapy, there are currently no effective treatments for chemotherapy-induced fatigue (CIF). We used a mouse model to examine the benefits of quercetin on CIF as measured by voluntary wheel running activity and sought to determine whether quercetin may be associated with a decrease in inflammation and/or anemia.
Methods
Mice were assigned to 1 of 4 groups: placebo-vehicle (Plac-PBS), placebo-5-fluorouracil (Plac-5FU), quercetin-vehicle (Quer-PBS), or quercetin-5-fluorouracil (Quer-5FU). All mice were given a daily injection of either 60 mg/kg of 5-FU or phosphate buffered saline (PBS) for 5 days. Quercetin (0.02%) treatment was administered in the food 3 days prior to 5-FU administration and for the duration of the experiment (ie, days −2 to 14). A second group of mice was sacrificed at 5 and 14 days post initial injection for assessment of monocyte chemoattractant protein-1 (MCP-1) and anemia.
Results
Voluntary wheel running was reduced in both the Plac-5FU and Quer-5FU groups following 5-FU injection (P < .05). However, the Quer-5FU group recovered to baseline levels by approximately day 7, whereas the Plac-5FU group remained suppressed. MCP-1 was significantly elevated at 14 days in Plac-5FU (P < .001), but no changes were seen with Quer-5FU. Treatment with 5-FU resulted in anemia at both 5 days and 14 days; however, quercetin blocked this effect at 14 days (P < .001).
Conclusion
These results demonstrate the beneficial effect of quercetin on improving recovery of voluntary physical activity following 5-FU treatment, which may be linked to a decrease in inflammation and anemia.
doi:10.1177/1534735414523315
PMCID: PMC4136550  PMID: 24626097
quercetin; chemotherapy; fatigue; inflammation; anemia
6.  Vivekananda Yoga Program for Patients with Advanced Lung Cancer and their Family Caregivers 
Integrative cancer therapies  2015;14(5):446-451.
BACKGROUND
Although yoga practice may improve quality of life (QOL) in cancer patients, feasibility in patients with lung cancer is largely unknown. Moreover, previous research has excluded patients’ family caregivers. Because caregivers are vulnerable to caregiver burden, a dyadic approach targeting QOL in both patient and caregiver may be particularly beneficial. Thus, the purpose of this study was to establish the feasibility of a couple-based Vivekananda Yoga (VKC) intervention in lung cancer patients and caregivers. Vivekananda Yoga may be suitable for a dyadic approach and address the multifaceted needs (e.g., emotional, physical, spiritual, and social) common among families coping with lung cancer.
METHOD
In this single-arm feasibility trial, patients with lung cancer undergoing radiotherapy and their caregivers participated in a 15-session VKC program focused on the interconnectedness of the dyad. The program consisted of four main components: 1) joint loosening with breath synchronization; 2) postures (asanas) and a deep relaxation technique; 3) breath energization (pranayama) with sound resonance; and 4) meditation. We assessed pre/post-intervention levels of fatigue (BFI), sleep disturbances (PSQI), psychological distress (BSI), overall mental and physical QOL (SF-36), spirituality (FACT-Sp) and relational closeness. We also tracked feasibility data, and participants completed program evaluations.
RESULTS
We approached 28 eligible dyads of which 15 (53%) consented and 9 (60%) completed the intervention. No adverse events were reported. Patients (mean age: 73 years, 63% female, all stage III) and caregivers (mean age: 62 years, 38% female, 63% spouses) completed a mean of 10 sessions (range: 4–14) and 95.5% of them rated the program as very useful. Paired t-tests revealed a significant increase in patients’ mental health (d=.84, P=.04) and a significant decrease in caregivers’ sleep disturbances (d=1.44, P=.02). Although not statistically significant, for patients, effect sizes for change scores were medium for benefit finding and small for distress (d=.65 and .37, respectively). For caregivers, medium effects were found for improvement in physical functioning (d=.50).
CONCLUSION
This novel supportive care program appears to be safe, feasible, acceptable, and subjectively useful for lung cancer patients and their caregivers and lends support for further study in a larger randomized controlled trial.
doi:10.1177/1534735415583554
PMCID: PMC4537807  PMID: 25917816
Non-small cell lung cancer; mind-body medicine; family caregivers; dyadic intervention; feasibility; quality of life
7.  Sleep Quality Improves During Treatment With Bryophyllum pinnatum 
Integrative Cancer Therapies  2015;14(5):452-459.
Hypothesis. Cancer patients frequently suffer from poor sleep quality. Bryophyllum pinnatum is a herbal medication used in anthroposophic medicine, which has been shown to be associated with improvements in sleep quality during pregnancy with only few and minor or moderate side-effects reported. In this study, the sleep quality of cancer patients during treatment with B pinnatum was investigated. Study Design. In this prospective, observational study, cancer patients suffering from sleep problems were treated with B pinnatum (350 mg tablets, corresponding to 50% of leaf pressed juice [Weleda AG, Arlesheim, Switzerland], dosage at physician’s consideration, but most frequently 2 tablets with evening meal and 2 before going to bed). Methods. Sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daily sleepiness (Epworth Sleeping Scale [ESS]), and fatigue (Fatigue Severity Scale [FSS]) were assessed at the beginning of the treatment and after 3 weeks. Possible adverse drug reactions perceived by the patients during the treatment were recorded. From the 28 recruited patients, 20 completed both questionnaires and were considered in the present analysis. Data are expressed as mean ± standard deviation. Results. Patients were 61 ± 10.4 years old and the majority were female (17 out of 20). During treatment with B pinnatum, the PSQI decreased from 12.2 ± 3.62 to 9.1 ± 3.61 (P < .01), and ESS changed from 8.4 ± 3.18 to 7.1 ± 3.98 (P < .05). There was no change in FSS. The treatment was well tolerated by the majority of patients, with only 6 patients reporting discomfort that might have been caused by B pinnatum (fatigue n = 3, dry throat n = 1, agitation n = 1, difficult digestion n = 1). No serious adverse drug reactions were detected. Conclusion. B pinnatum may be a suitable treatment for sleep problems of cancer patients. Controlled, randomized clinical trials of the use of B pinnatum in sleep disorders are urgently needed.
doi:10.1177/1534735415580680
PMCID: PMC4538317  PMID: 25873294
cancer; Bryophyllum pinnatum; Kalanchoe pinnata; sleep; sleep quality; sleep problems
8.  Mindfulness for the Self-Management of Fatigue, Anxiety, and Depression in Women With Metastatic Breast Cancer 
Integrative Cancer Therapies  2015;14(1):42-56.
The impact of living with metastatic breast cancer (MBC) is considerable and psychosocial support can be beneficial. Mindfulness-based stress reduction (MBSR) can help self-management of anxiety, depression, quality of life (QoL), and fatigue and has been evaluated in early-stage breast cancer but not MBC. This study investigated the acceptability and feasibility of providing MBSR for women with MBC and of introducing MBSR into a National Health Service (NHS) setting. A mixed methods convergent design was used. Eligible women with MBC, an Eastern Cooperative Oncology Group (ECOG) score of 0 to 2, stable disease, and life expectancy of at least 6 months were invited to attend (by their oncologist) an 8-week MBSR course. Qualitative interviews with patients, a focus group, and interview with NHS staff were held to explore acceptability and feasibility of MBSR. Questionnaires at baseline, during (weeks 4, 8), and after (weeks 16, 24) the course measured fatigue, anxiety and depression, mindfulness, disease-specific QoL, and generic preference based QoL. Of 100 women approached, 20 joined the study. One woman dropped out prior to the intervention due to illness progression. Nineteen women took part in 3 MBSR courses. Recruitment to 2 of the 3 courses was slow. Commitment to 8 weeks was a reason for non-participation, and proved challenging to participants during the course. Participants found the course acceptable and reported many cumulative and ongoing benefits. These included feeling less reactive to emotional distress and more accepting of the disruption to life that occurs with living with MBC. There was high attendance, completion of course sessions, adherence to home practice, excellent follow-up rates, and high questionnaire return rates. MBSR was acceptable to MBC patients, who perceived benefits such as improved anxiety and QoL; but the MBSR course requires a considerable time commitment. There is scope to tailor the intervention so that it is less intensive.
doi:10.1177/1534735414546567
PMCID: PMC4390604  PMID: 25161198
feasibility; mixed methods; metastatic breast cancer; mindfulness-based stress reduction; psychosocial support
9.  Compliance with National Nutrition Recommendations among Breast Cancer Survivors in STEPPING STONE 
Integrative cancer therapies  2013;13(2):114-120.
Introduction
Compared to White breast cancer survivors, African American survivors are more likely to be overweight and obese. Differences in weight status may be attributed to differences in dietary intake; however, there is limited research pertaining to the dietary habits of African American breast cancer survivors.
Methods
We compared baseline dietary intakes of 31 overweight and obese African American breast cancer survivors enrolled in a healthy lifestyle intervention to national dietary guidelines and also examined beverage intake habits. Dietary intake was assessed using the National Cancer Institute's Diet History Questionnaire (DHQ) and beverage intake was assessed using 3-day food intake records.
Results
Overall, the majority of survivors consumed the recommended daily servings of fruits and vegetables (71.0%) and red meat (83.9%); however, survivors exceeded national recommendations for energy intake from fat (64.5%), saturated fat (87.1%) and added sugars (77.4%). Few women met the guidelines for whole grain and fiber intake (6.5% and 35.5%, respectively). Additionally, survivors consumed ~10% of total energy intake from beverages alone and only ~3.5 cups of water daily.
Conclusions
Current dietary guidelines for cancer survivors recommend consuming >5 servings/day of fruits and vegetables and broad guidelines regarding limiting discretionary fat and added sugars, but do not specify beverage intake recommendations. Future dietary interventions in African American Breast cancer survivors should focus on reducing intake from dietary fat and added sugar, as well as increasing whole grain consumption as a means for increasing daily fiber intake. Furthermore, substituting caloric beverages with water or noncaloric beverages may be a strategy to decrease caloric intake in African American Breast cancer survivors. Nutrition information targeting these nutrients could be administered during treatments or doctor's visits as a means to prevent weight gain that often occurs following diagnosis.
doi:10.1177/1534735413503550
PMCID: PMC4227310  PMID: 24105362
Energy Intake; Added Sugars; Beverages; Breast Cancer; Survivors; Fiber Intake; Water
10.  Feasibility and Acceptability of a Tai Chi Chih Randomized Controlled Trial in Senior Female Cancer Survivors 
Integrative cancer therapies  2013;12(6):10.1177/1534735413485418.
Objective
Tai Chi Chih (TCC) is associated with improved physical functioning and psychological benefits in breast cancer survivors and healthy older adults; thus, may also be beneficial for senior cancer survivors with physical functioning declines. The purpose of this randomized controlled trial (RCT) was to examine the feasibility and acceptability of a Tai Chi Chih (TCC) intervention in senior female cancer survivors, with physical functioning limitations, as well as, its effects on QOL.
Design
This was a two-armed, parallel group, RCT with 12-weeks of Tai Chi Chih or Health Education Control.
Methods
Sixty-three senior (M age=67 years, SD=7.15) female cancer survivors (83% breast cancer, stages I–III) with physical functioning limitations (SF-12 Health Survey role physical & physical functioning subscales) were randomized to 12-weeks of TCC or Health Education control (HEC). Primary outcomes were feasibility and acceptability. Secondary outcomes included quality of life (SF-36 Health Survey), and participants’ qualitative feedback on intervention.
Results
Retention (TCC = 91%; HEC = 81%) and class attendance (TCC =79%; HEC = 83%) rates, and satisfaction levels for both study arms were high, but did not significantly differ from one another. At one-week post-intervention, none of the SF-36 scores differed between the TCC and HEC arms. Within-group analyses revealed significant improvements in the mental component summary score in TCC (p = 0.01), but not in HEC. Qualitative analyses indicated that the TCC group felt they received mental and physical benefits, whereas HEC group reported on social support benefits and information received.
Conclusion
A TCC intervention was found to be a feasible and acceptable modality for senior female cancer survivors. Future, larger definitive trials are needed to clarify TCC dosage effects on QOL in this vulnerable population.
doi:10.1177/1534735413485418
PMCID: PMC3831606  PMID: 23620504
Senior Female Cancer Survivors; Tai Chi Chih; Feasibility Randomized Controlled Trial; Quality of Life; Oncology
11.  Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach: Ten-Year Follow-up Data Analyzed With Marginal Structural Models and Propensity Score Methods 
Integrative cancer therapies  2011;10(3):240-259.
Although localized colon cancer is often successfully treated with surgery, advanced disease requires aggressive systemic therapy that has lower effectiveness. Approximately 30% to 75% of patients with colon cancer use complementary and alternative medicine (CAM), but there is limited formal evidence of survival efficacy. In a consecutive case series with 10-year follow-up of all colon cancer patients (n = 193) presenting at a San Francisco Bay-Area center for Chinese medicine (Pine Street Clinic, San Anselmo, CA), the authors compared survival in patients choosing short-term treatment lasting the duration of chemotherapy/radiotherapy with those continuing long-term. To put these data into the context of treatment responses seen in conventional medical practice, they also compared survival with Pan-Asian medicine + vitamins (PAM+V) with that of concurrent external controls from Kaiser Permanente Northern California and California Cancer Registries. Kaplan-Meier, traditional Cox regression, and more modern methods were used for causal inference—namely, propensity score and marginal structural models (MSMs), which have not been used before in studies of cancer survival and Chinese herbal medicine. PAM+V combined with conventional therapy, compared with conventional therapy alone, reduced the risk of death in stage I by 95%, stage II by 64%, stage III by 29%, and stage IV by 75%. There was no significant difference between short-term and long-term PAM+V. Combining PAM+V with conventional therapy improved survival, compared with conventional therapy alone, suggesting that prospective trials combining PAM+V with conventional therapy are justified.
doi:10.1177/1534735411406539
PMCID: PMC4081504  PMID: 21964510
colon cancer; survival; Chinese herbal medicine; vitamins; propensity score; marginal structural models; chemotherapy; radiotherapy
12.  Effects of a physical activity behavior change intervention on inflammation and related health outcomes in breast cancer survivors: pilot randomized trial 
Integrative cancer therapies  2012;12(4):323-335.
Background
Physical activity may provide benefits for breast cancer survivors in part by reducing systemic inflammation. Physical activity behavior change studies are a type of implementation research in which exercise efficacy information is translated into a “real world” setting, allowing determination of whether physical activity changes are sufficient to improve health outcomes. We hypothesized that breast cancer survivors (BCS) who undertook a physical activity behavior change intervention would have less systemic inflammation and improved cardiorespiratory fitness, muscle strength, body composition, fatigue, and sleep as compared with BCS receiving usual care. The goal of this pilot study was to determine the magnitude and direction of intervention effect sizes for inflammatory related serum markers and relevant health outcomes.
Methods
This randomized controlled trial enrolled 28 Stage I, II, or IIIA BCS who were post-primary treatment and were not regular exercisers. These women were assigned to either a 3-month physical activity behavior change intervention group (ING) or usual care group (UCG). Intervention included supervised aerobic (150 weekly minutes, moderate-intensity) and resistance (two sessions per week) exercise that gradually tapered to home-based exercise. At baseline and after 3 months, health outcomes and serum concentrations of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, leptin, and adiponectin were measured.
Results
Cardiorespiratory fitness significantly improved in the ING versus UCG (between group difference=3.8 ml/kg/min; d=1.1; P=0.015). Self-reported sleep latency was significantly reduced in the ING versus UCG (between group difference=−0.5; d=−1.2; P=0.02) as was serum leptin (between group difference=−9.0 ng/ml; d=−1.0; P=0.031). Small to medium non-significant negative effect sizes were noted for IL-10 and TNF-alpha and ratios of IL-6:IL-10, IL-8:IL10, and TNF-alpha:IL-10, with non-significant positive effect sizes noted for IL-6 and high molecular weight adiponectin.
Conclusions
Physical activity behavior change interventions in BCS can achieve large effect size changes for several health outcomes. Although effect sizes for inflammatory markers were often small and not significant, changes were in the hypothesized direction for all except IL-6 and IL-10. These preliminary data support larger trials that would more fully examine potential inflammatory changes that accompany physical activity behavior change interventions.
doi:10.1177/1534735412449687
PMCID: PMC3909487  PMID: 22831916
exercise; intervention; oncology; cytokine; inflammation; survivorship
13.  Cancer-Specific Concerns and Physical Activity Among Recently Diagnosed Breast and Prostate Cancer Survivors 
Integrative cancer therapies  2012;12(3):206-212.
Background
Cancer treatment-related side effects may have a negative impact on quality of life among cancer survivors, and may limit participation in physical activity.
Hypothesis
Cancer-specific concerns will be reduced throughout a 10-month diet and exercise intervention among recently-diagnosed cancer survivors. Additionally, participants reporting greater levels of physical activity will also report fewer cancer-specific concerns.
Study Design
This study is an exploratory analysis of 452 recently diagnosed, early stage breast and prostate cancer survivors who participated in the FRESH START diet and exercise trial. Data were collected at baseline and 1-year follow-up via telephone administration of the Functional Assessment of Cancer Therapy (FACT) instrument and the 7-Day Physical Activity Recall.
Results
At baseline, chief concerns among prostate cancer survivors included ability to have an erection (mean score [SD]: 1.0 [1.3]) and urinary frequency (2.5 [1.4]), whereas among breast cancer survivors eminent concerns were not feeling sexually attractive (2.0 [1.3]) and worry about cancer in other members of their family (2.1 [1.3]). At 1 year, there was a significant improvement in cancer-specific concerns on breast cancer specific-concerns (p<0.01), but not on prostate cancer-specific concerns. Physical activity (PA) was generally not related to cancer-specific concerns, though at baseline women who were self-conscious about their dress had higher levels of PA, whereas men reporting issues with incontinence reported lesser increases in PA in response to the intervention.
Conclusion
While cancer survivors have several cancer-specific concerns, these concerns diminish over time, especially among breast cancer survivors. Furthermore, this reduction appears independent of changes in physical activity. Among prostate cancer survivors, incontinence is a significant barrier that hinders benefit from PA interventions. Thus, there is a need either for medical interventions to ameliorate incontinence or for behavioral interventions to address this issue among survivors, especially given the importance of PA for overall health.
doi:10.1177/1534735412449734
PMCID: PMC3764991  PMID: 22879576
breast neoplasms; prostatic neoplasms; physical activity; quality of life
14.  A Randomized Controlled Trial of Mindfulness-Based Stress Reduction for Women With Early-Stage Breast Cancer Receiving Radiotherapy 
Integrative cancer therapies  2013;12(5):404-413.
Purpose
To testthe relative effectiveness of a mindfulness-based stress reduction program (MBSR) compared with a nutrition education intervention (NEP) and usual care (UC) in women with newly diagnosed early-stage breast cancer (BrCA) undergoing radiotherapy.
Methods
Datawere available from a randomized controlled trialof 172 women, 20 to 65 years old, with stage I or II BrCA. Data from women completing the 8-week MBSR program plus 3 additional sessions focuses on special needs associated with BrCA were compared to women receiving attention control NEP and UC. Follow-up was performed at 3 post-intervention points: 4 months, and 1 and 2 years. Standardized, validated self-administered questionnaires were used to assess psychosocial variables. Descriptive analyses compared women by randomization assignment. Regression analyses, incorporating both intention-to-treat and post hoc multivariable approaches, were used to control for potential confounding variables.
Results
A subset of 120 women underwent radiotherapy; 77 completed treatment prior to the study, and 40 had radiotherapy during the MBSR intervention. Women who actively received radiotherapy (art) while participating in the MBSR intervention (MBSR-art) experienced a significant (P < .05) improvement in 16 psychosocial variables compared with the NEP-art, UC-art, or both at 4 months. These included health-related, BrCA-specific quality of life and psychosocial coping, which were the primary outcomes, and secondary measures, including meaningfulness, helplessness, cognitive avoidance, depression, paranoid ideation, hostility, anxiety, global severity, anxious preoccupation, and emotional control.
Conclusions
MBSR appears to facilitate psychosocial adjustment in BrCA patients receiving radiotherapy, suggesting applicability for MBSR as adjunctive therapy in oncological practice.
doi:10.1177/1534735412473640
PMCID: PMC3758444  PMID: 23362338
mindfulness-based stress reduction program; breast cancer; quality of life; psychosocial intervention; radiotherapy; radiation therapy
15.  A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma 
Integrative cancer therapies  2013;13(1):46-53.
Purpose
To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction.
Experimental Design
Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks.
Results
Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug.
Conclusion
Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.
doi:10.1177/1534735413490798
PMCID: PMC3866213  PMID: 23757319
phase I clinical trial; milk thistle; hepatocellular carcinoma; herbal supplement; dietary supplement
16.  Practices, Attitudes, and Beliefs associated with Complementary and Alternative Medicine (CAM) use among Cancer Patients 
Integrative cancer therapies  2012;11(3):10.1177/1534735411433832.
Introduction
The high prevalence of complementary and alternative medicine (CAM) use among cancer patients (40 – 83%) receiving conventional treatment and the complex relationship between the psychosocial factors that may contribute to or result from CAM use requires further understanding. We conducted a descriptive mixed-methods pilot study to understand CAM practices, attitudes and beliefs among cancer patients at the Loma Linda University Medical Center (LLUMC).
Methods
This was the qualitative phase of the study and no hypotheses were set. Twenty-three face-to-face interviews were conducted and thematic coding was used to analyze 22 interview transcriptions. There were fourteen CAM users (64%) and eight non-users (36%).
Findings
The themes present among those who used CAM were: physicians viewed as one aspect of health care options, a holistic view on wellbeing, satisfaction with CAM use, and three key coping methods (confrontive, supportive, and optimistic) to confront cancer. Themes were not independent of each other. Two themes were present among nonusers; nonusers trusted their physician and were more likely to express evasive coping methods.
Discussion
Perceptions and behavioral patterns are complex predictors of CAM use. A better understanding of CAM, medical pluralism, and the perceptions of patients would help health care providers deliver a better quality of care. The promotion of integrative care may help health care providers better identify medical pluralism and would shift focus to patient-centered care.
doi:10.1177/1534735411433832
PMCID: PMC3873860  PMID: 22313741
CAM; medical pluralism; integrative medicine; perceptions among cancer patients; coping methods; thematic coding
17.  Effect of Coenzyme Q10 on Doxorubicin Cytotoxicity in Breast Cancer Cell Cultures 
Integrative cancer therapies  2012;11(3):10.1177/1534735412439749.
Background/hypotheses
Doxorubicin is a standard adjuvant therapy for early-stage breast cancer and it significantly improves disease-free and overall survival. However, 3-20% of breast cancer patients develop chronic cardiomyopathic changes and congestive heart failure due to doxorubicin therapy. Doxorubicin-induced cardiotoxicity is thought to be due to increased generation of reactive oxygen species (ROS) within cardiac myocyte mitochondria. Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant that may protect against mitochondrial ROS, and thus prevent doxorubicin-induced cardiotoxicity. Despite the potential benefits of CoQ10 in preventing cardiotoxicity, it is unknown if CoQ10 diminishes the antineoplastic effects of doxorubicin therapy.
Study design
In vitro cell culture experiments.
Methods
Breast cancer cell lines (MDA-MB-468 and BT549) were tested for their ability to uptake exogenous CoQ10 using high performance liquid chromatography (HPLC). Breast cancer cell lines were then treated with doxorubicin and a range of CoQ10 concentrations to determine the effect of CoQ10 on doxorubicin’s cytotoxicity.
Results
This study demonstrated that intracellular and mitochondrial CoQ10 concentrations increased substantially as higher exogenous concentrations are administered to breast cancer cells. CoQ10 had no effect on the ability of doxorubicin to induce apoptosis or inhibit growth or colony formation in both cell lines tested when CoQ10 was applied over a wide dose range, which encompassed typical basal plasma levels as well as plasma levels above those typically achieved by supplemented patients.
Conclusion
The clinical testing of CoQ10 as supplement to prevent doxorubicin induced cardiotoxicity requires confidence that it does not decrease chemotherapy efficacy. These results support the hypothesis that CoQ10 does not alter the antineoplastic properties of doxorubicin. Further in vivo studies, as well as combination chemotherapy studies, would be reassuring before large scale clinical testing of CoQ10 as a cardioprotective drug.
doi:10.1177/1534735412439749
PMCID: PMC3840161  PMID: 22544232
Doxorubicin; Adriamycin; Coenzyme Q10; cytotoxicity; breast cancer; in vitro
18.  The Role of Religion and Spirituality in Psychological Distress Prior to Surgery for Urologic Cancer 
Integrative cancer therapies  2011;11(3):212-220.
The present study examined the associations between religion and spirituality (R/S), presurgical distress, and other psychosocial factors such as engagement coping, avoidant coping, and social support. Participants were 115 men scheduled for surgery for urologic cancer. Before surgery, participants completed scales measuring intrinsic religiosity, organized religious activity, and nonorganized religious activity (IR, ORA, NORA); social support (Medical Outcomes Study Social Support Survey); and distress (Impact of Event Scale [IES], Perceived Stress Scale [PSS], Brief Symptom Inventory-18 [BSI-18], and Profile of Mood States [POMS]). R/S was positively associated with engagement coping. Social support was positively associated with engagement coping and inversely associated with POMS and PSS scores. Engagement coping was positively associated with IES and BSI scores, and avoidant coping was positively associated with all distress measures. R/S moderated the association between engagement coping and IES scores, such that the association between engagement coping and IES was not significant for men with high R/S scores (greater religious belief). R/S moderated the association between social support and distress; the inverse association between social support and PSS and POMS scores was only significant for men who scored high on R/S. This study replicated findings from previous studies suggesting that engagement and avoidant types of coping can lead to increased distress prior to surgery. Although R/S was associated with engagement coping, it was not associated with any of the distress measures. The finding that R/S moderated the associations between engagement coping and distress and social support and distress suggests that the association between R/S, coping style, social support, and adjustment to stressful life situations is not simplistic, and indirect associations should be explored.
doi:10.1177/1534735411416456
PMCID: PMC3746331  PMID: 21964511
oncology; cancer; spirituality; religion; distress; surgery
19.  Feasibility Trial of Electro-acupuncture for Aromatase Inhibitor Related Arthralgia in Breast Cancer Survivors 
Integrative cancer therapies  2009;8(2):123-129.
Background
Arthralgia affects postmenopausal women receiving aromatase inhibitors (AI) for breast cancer. Given the existing evidence for electro-acupuncture (EA) for treatment of osteoarthritis in the general population, this study aims to establish the feasibility of studying EA for treating AI-related arthralgia.
Patients and Methods
Postmenopausal women with stage I-III breast cancer who reported AI-related arthralgia were enrolled in a single arm feasibility trial. EA was provided twice a week for two weeks followed by six weekly treatments. The protocol was based on Chinese medicine diagnosis of “Bi” syndrome with electro-stimulation of needles around the painful joint(s). Pain severity of the modified Brief Pain Inventory was used as the primary outcome. Joint stiffness, Joint interference, and Patient Global Impression of Change (PGIC) were secondary outcomes. Paired-t tests were used for analysis.
Results
Twelve women were enrolled and all provided data for analysis. From baseline to the end of intervention, patients reported reduction in pain severity (5.3 to 1.9), stiffness (6.9 to 2.4), and joint symptom interference (4.7 to 0.8), all P<0.001; 11/12 considered joint symptoms “very much better” based on PGIC. Subjects also reported significant decrease in fatigue (4.4 to 1.9, p=0.005) and anxiety (7.1 to 4.8, p=0.01). No infection or development or worsening of lymphedema was observed.
Conclusion
Preliminary data establishes the feasibility of recruitment and acceptance as well as promising preliminary safety and effectiveness. A randomized controlled trial is warranted to establish the efficacy of EA for AI-related arthralgia in breast cancer survivors.
doi:10.1177/1534735409332903
PMCID: PMC3569528  PMID: 19679620
Acupuncture; breast neoplasm; clinical trial; Aromatase inhibitors/*adverse effects; joint diseases
20.  Prevalence and Correlates of Vitamin and Supplement Usage among Men with a Family History of Prostate Cancer 
Integrative Cancer Therapies  2011;11(2):83-89.
Hypotheses
Men who have a brother with prostate cancer have a two-fold increased risk of being diagnosed with prostate cancer. Strategies employed by these men to reduce prostate cancer risk are not well understood. Preliminary studies have shown that men with a family history of prostate cancer have a high rate of vitamin and supplement usage aimed at the prevention of prostate cancer.
Study Design
We analyzed data from a cross-sectional study of men with familial and hereditary prostate cancer and their unaffected brothers. We interviewed 542 unaffected men who had at least one brother who had been diagnosed with prostate cancer regarding their use of vitamins and supplements, as well as the motivation for use.
Methods
The associations between subject characteristics and vitamin and supplement use were evaluated using an unconditional logistic regression modeling approach.
Results
Overall, 59.2 and 36.5 percent of men reported ever using and currently using, respectively, one or more vitamins or supplements (including multivitamins). One-third of men took a vitamin or supplement that has been targeted for prostate health or cancer prevention, including green tea, magnesium, male hormones, saw palmetto, selenium, soy, vitamins A, C, E and zinc. Increasing age at time of survey was associated with vitamin/supplement use (OR=1.03; 95% CI=1.01–1.0). After adjusting for age at time of survey, being younger than an affected brother was associated with vitamin and supplement use (OR=1.51; 95% CI=1.01–2.25). 25% of men reported obtaining information from books or articles as the most common source of information.
Conclusions
Our findings indicate that men at an increased risk for prostate cancer report a high rate of vitamin and supplement use, including supplements targeted for prostate cancer prevention. Men with a family history of prostate cancer represent a target population for future chemopreventative agents.
doi:10.1177/1534735411413262
PMCID: PMC3213317  PMID: 21821653
Prostate Cancer Chemoprevention; Family History; Complementary and Alternative Medicine
21.  Classification of CAM Use and its Correlates in Early Stage Breast Cancer Patients 
Integrative cancer therapies  2011;10(2):138-147.
Hypothesis
Self-reported use of complementary and alternative medicine (CAM) has been shown to increase following a cancer diagnosis, and breast cancer survivors are the heaviest users among cancer survivors. The aim of this study was to determine whether the prevalence estimate of CAM use varied according to classification of CAM. We used a comprehensive system to classify CAM users and test differences in demographic, lifestyle, quality of life, and cancer characteristics among them.
Study Design and Methods
Participants were 2562 breast cancer survivors participating in the Women's Healthy Eating and Living (WHEL) Study, aged 28-74 years. A structured telephone interview assessed CAM use, questioning about specific CAM practices, and whether use was related to cancer. We examined CAM use in relation to demographics, health behaviors, and quality of life.
Results
Approximately 80% of the women used CAM for general purposes but only 50% reported CAM use for cancer purposes. Visual imagery, spiritual healing, and meditation were the most frequently used practices for cancer purposes. CAM use, defined as consulting a CAM practitioner and regular use, was significantly related to younger age, higher education, increased fruit & vegetable intake, and lower body mass index (p < .05). CAM users who had seen a practitioner were also more likely to report poor physical and mental health than non-CAM users (p < .05). CAM use was not associated with changes in physical and mental health between study baseline and 1-year follow-up.
Conclusion
This study addressed important differences in the classification of CAM use among breast cancer survivors. Future studies need to further test the potential benefits and risks associated with CAM use.
doi:10.1177/1534735410392578
PMCID: PMC3126886  PMID: 21382963
22.  Polarity Therapy for Cancer-Related Fatigue in Patients With Breast Cancer Receiving Radiation Therapy: A Randomized Controlled Pilot Study 
Integrative Cancer Therapies  2011;10(1):27-37.
Background
Cancer-related fatigue (CRF) is the most frequently reported side effect of cancer and its treatment. In previous research, Polarity Therapy (PT), an energy therapy, was shown to reduce CRF in patients receiving radiation. This study reports on a small randomized clinical trial designed to collect preliminary data on the efficacy of PT compared with an active control (massage) and passive control (standard care) for CRF among cancer patients receiving radiation therapy.
Methods
Forty-five women undergoing radiation therapy for breast cancer were randomized to I of 3 weekly treatment conditions. Patients received standard clinical care, 3 modified massages, or 3 PT treatments. CRF and healthrelated quality of life (HRQL) were assessed during baseline and the 3 intervention weeks.
Results
TResults show CRF ratings were reduced after PT. The effect sizes for PT versus modified massage and versus standard care were small when using the primary measure of CRF (Brief Fatigue Inventory) and large when using the secondary measure of CRF (Daily CRF Diaries).The effect size was medium when assessing the benefit of PT on maintaining HRQL compared with standard care with very little difference between the PT and modified massage conditions. Patients’ feedback showed that both the modified massage and PT treatments were deemed useful by radiation patients. Conclusion. The present pilot randomized clinical trial supports previous experimental research showing that PT, a noninvasive and gentle energy therapy, may be effective in controlling CRF. Further confirmatory studies as well as investigations of the possible mechanisms of PT are warranted.
doi:10.1177/1534735410397044
PMCID: PMC3085180  PMID: 21382958
cancer-related fatigue; radiation; Polarity Therapy; massage; quality of life; complementary and integrative medicine
23.  A Mineral-Rich Red Algae Extract Inhibits Polyp Formation and Inflammation in the Gastrointestinal Tract of Mice on a High-Fat Diet 
Integrative cancer therapies  2010;9(1):93-99.
The purpose of this study was to determine whether a mineral-rich extract derived from the red marine algae, Lithothamnion calcareum (Pallas), could be used as a dietary supplement for chemoprevention against colon polyp formation. Sixty C57bl/6 mice were divided into three groups based on diet. One group received a low-fat, rodent chow diet (AIN76A). The second group received a high-fat “Western style” diet (HFWD). The third group was fed the same HFWD with the mineral-rich extract included as a dietary supplement. Mice were maintained on the respective diets for 15 months. Autopsies were performed at the time of death or at the completion of the study. To summarize, the cumulative mortality rate was higher in mice on the HFWD during the 15 month period (55%) than in mice from the low-fat diet or the extract-supplemented high-fat diet groups (20% and 30%, respectively; p<0.05 with respect to both). Autopsies revealed colon polyps in 20% of the animals on the HFWD and none in animals of the other two groups (p<0.05). In addition to the grossly visible polyps, areas of hyperplasia in the colonic mucosa and inflammatory foci throughout the gastrointestinal tract were observed histologically in animals on the high-fat diet. Both were significantly reduced in animals on the low-fat diet and animals on the extract-supplemented HFWD. These data suggest that the mineral-rich algae extract may provide a novel approach to chemoprevention in the colon.
doi:10.1177/1534735409360360
PMCID: PMC2861409  PMID: 20150219
colorectal cancer; chemoprevention; epithelial cell differentiation; extracellular calcium-sensing receptor; mineral-rich red algae extract; Aquamin®
24.  Acupuncture for Dysphagia after Chemoradiation Therapy in Head and Neck Cancer: A Case Series Report* 
Integrative cancer therapies  2010;9(3):284-290.
Background
Dysphagia is a common side effect following chemoradiation therapy (CRT) in head and neck cancer (HNC) patients.
Methods
In this retrospective case series, ten HNC patients were treated with acupuncture for radiation-induced dysphagia and xerostomia. All patients were diagnosed with stage III/IV squamous cell carcinoma. Seven of 10 patients were percutaneous endoscopic gastrostomy (PEG) tube-dependent when they began acupuncture. Manual acupuncture and electroacupuncture were used once a week.
Results
Nine of 10 patients reported various degrees of subjective improvement in swallowing functions, xerostomia, pain and fatigue levels. Six (86%) of 7 PEG tube-dependent patients had their feeding tubes removed after acupuncture, with a median duration of 114 days (range 49–368) post CRT. One typical case is described in detail.
Conclusions
A relatively short PEG tube duration and reduced symptom severity following CRT were observed in these patients. Formal clinical trials are required to determine the causality of our observations.
doi:10.1177/1534735410378856
PMCID: PMC3014053  PMID: 20713374
acupuncture; chemoradiation therapy; radiation therapy; head and neck cancer; dysphagia; percutaneous endoscopic gastrostomy (PEG) tube
25.  Circadian Disruption, Per3, and Human Cytokine Secretion 
Integrative cancer therapies  2009;8(4):329-336.
Circadian disruption has been linked with inflammation, an established cancer risk factor. Per3 clock gene polymorphisms have also been associated with circadian disruption and with increased cancer risk. Patients completed a questionnaire and provided a blood sample prior to undergoing a colonoscopy (n = 70). Adjusted mean serum cytokine concentrations (IL-6, TNF-alpha, gamma-INF, IL-I ra, IL-I-beta, VEGF) were compared among patients with high and low scores for fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory II), or sleep disruption (Pittsburgh Sleep Quality Index), or among patients with different Per3 clock gene variants. Poor sleep was associated with elevated VEGF, and fatigue-related reduced activity was associated with elevated TNF-alpha concentrations. Participants with the 4/5 or 5/5 Per3 variable tandem repeat sequence had elevated IL-6 concentrations compared to those with the 4/4 genotype. Biological processes linking circadian disruption with cancer remain to be elucidated. Increased inflammatory cytokine secretion may playa role.
doi:10.1177/1534735409352029
PMCID: PMC2959170  PMID: 19926609
circadian rhythm; clock gene; cytokine; inflammation

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