Integrative Cancer Therapies

Background: Cancer ‘patients’ are increasingly using traditional indigenous and complementary medicines (T&CM) alongside conventional medical treatments to both cure and cope with their cancer diagnoses. To date T&CM use among Indigenous cancer patients from Australia, Canada, New Zealand, and the United States has not been systematically reviewed. Methods: We systematically searched bibliographic databases to identify original research published between January 2000 and October 2017 regarding T&CM use by Indigenous cancer patients in Australia, Canada, New Zealand, and the United States. Data from records meeting eligibility criteria were extracted and appraised for quality by 2 independent reviewers. Results: Twenty-one journal articles from 18 studies across all 4 countries met our inclusion criteria. T&CM use ranged from 19% to 57.7% (differing across countries). T&CM was mostly used concurrently with conventional cancer treatments to meet their spiritual, emotional, social, and cultural needs; however, bush, traditional, and herbal medicines were used in a minority of cases as an alternative. Conclusions: Our findings highlight the importance of T&CM use to Indigenous cancer patients across these 4 countries; we identified multiple perceived spiritual, emotional and cultural benefits to its use. The patient’s perception of their health professional’s attitudes toward T&CM in some cases hindered or encouraged the patient’s disclosure. Additional research is required to further explore the use and disclosure of T&CM among Indigenous cancer patients to help inform and ensure effective, safe, coordinated care for Indigenous cancer patients that relies on shared open decision making and communication across patients, communities, and providers.

Bearing in mind the doctrine of tumor angiogenesis hypothesized by Folkman several decades ago, the fundamental strategy for alleviating numerous cancer indications may be the strengthening application of notable antiangiogenic therapies to inhibit metastasis-related tumor growth. Under physiological conditions, vascular sprouting is a relatively infrequent event unless when specifically stimulated by pathogenic factors that contribute to the accumulation of angiogenic activators such as the vascular endothelial growth factor (VEGF) family and basic fibroblast growth factor (bFGF). Since VEGFs have been identified as the principal cytokine to initiate angiogenesis in tumor growth, synthetic VEGF-targeting medicines containing bevacizumab and sorafenib have been extensively used, but prominent side effects have concomitantly emerged. Traditional Chinese medicines (TCM)–derived agents with distinctive safety profiles have shown their multitarget curative potential by impairing angiogenic stimulatory signaling pathways directly or eliciting synergistically therapeutic effects with anti-angiogenic drugs mainly targeting VEGF-dependent pathways. This review aims to summarize (a) the up-to-date understanding of the role of VEGF/VEGFR in correlation with proangiogenic mechanisms in various tissues and cells; (b) the elaboration of antitumor angiogenesis mechanisms of 4 representative TCMs, including Salvia miltiorrhiza, Curcuma longa, ginsenosides, and Scutellaria baicalensis; and (c) circumstantial clarification of TCM-driven therapeutic actions of suppressing tumor angiogenesis by targeting VEGF/VEGFRs pathway in recent years, based on network pharmacology.

Importance. Acupuncture can help reduce unpleasant side effects associated with endocrine therapy for breast cancer. Nevertheless, comprehensive evaluation of current evidence from randomized controlled trials(RCTs) is lacking. Objective. To estimate the efficacy of acupuncture for the reduction of hormone therapy-related side effects in breast cancer patients. Evidence review. RCTs of acupuncture in breast cancer patients that examined reductions in hormone therapy–related side effects were retrieved from PubMed, EMBASE, Web of Science, Ovid MEDLINE, and Cochrane Library databases through April 2016. The quality of the included studies was evaluated according to the 5.2 Cochrane Handbook standards, and CONSORT and STRICTA (Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture) statements. Intervention. Interventions included conventional acupuncture treatment compared with no treatment, placebo, or conventional pharmaceutical medication. Major outcome measures were the alleviation of frequency and symptoms and the presence of hormone therapy–related side effects. Findings/Results. A total of 17 RCTs, including a total of 810 breast cancer patients were examined. The methodological quality of the trials was relatively rigorous in terms of randomization, blinding, and sources of bias. Compared with control therapies, the pooled results suggested that acupuncture had moderate effects in improving stiffness. No significant differences were observed in hot flashes, fatigue, pain, gastrointestinal symptoms, Kupperman index, general well-being, physical well-being, tumor necrosis factor (TNF), and interleukin (IL). Conclusions. Acupuncture therapy appears to be potentially useful in relieving functional stiffness. However, further large-sample trials with evidence-based design are still needed to confirm these findings.

Introduction: Stomach cancer, historically, has a low survival rate advances in curative resection procedures. Objectives: To assess the potential benefits of traditional herbal medicines in conjunction with chemotherapy in postoperative gastric cancer patients in terms of overall survival and disease-free survival. Data Sources: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, a Chinese database (CNKI), a Korean database, a Japanese database, AMED, and CINAHL up to September 2016. We summarized survival data from all RCTs. Study Selection: All RCTs of oral traditional medicines for resectable gastric cancer compared with chemotherapy alone were eligible. Data Extraction: Thirteen eligible trials with survival data (1075 patients) were deemed eligible for inclusion. Results: There were 217 documented deaths of the 574 patients assigned to adjuvant traditional medicines groups and 319 documented deaths of the 501 patients assigned to the chemotherapy-only groups. Adjuvant traditional medicines were associated with a statistically significant benefit in terms of overall survival rate (hazard ratio = 0.56; 95% confidence interval = 0.47-0.66; P < .00001) and disease-free survival (hazard ratio = 0.54; 95% confidence interval = 0.43-0.66; P < .00001). Conclusion: Among the RCTs included, the inclusion of postoperative adjuvant traditional medicines was associated with reduced risk of death in gastric cancer patients, when survival rates were compared with the group of patients who received chemotherapy alone. However, most of the included studies utilized are thought to be of low quality, so it would certainly appear that more trials are both advisable and necessary to arrive at correct and convincing conclusions.

Purpose: To investigate the influence of music therapy on the reduction of fatigue in women with breast or gynecological malignant neoplasia during radiotherapy, since it is one of the most frequent side effects of this type of treatment, and may interfere with self-esteem, social activities, and quality of life. Experimental Design: Randomized controlled trial (control group [CG] and music therapy group [MTG]) to assess fatigue, quality of life, and symptoms of depression in women undergoing radiotherapy using the Functional Assessment of Cancer Therapy: Fatigue (FACT-F) version 4, Functional Assessment of Cancer Therapy–General (FACT-G) version 4, and Beck Depression Inventory in 3 separate times, namely, during the first week of radiotherapy, on the week of the intermediary phase, and during the last week of radiotherapy. Individual 30- to 40-minute sessions of music therapy with the presence of a trained music therapist were offered to participants. Results: In this study, 164 women were randomized and 116 (63 CG and 53 MTG) were included in the analyses, with mean age of 52.90 years (CG) and 51.85 years (MTG). Participants in the MTG had an average of 10 music therapy sessions, totaling 509 sessions throughout the study. FACT-F results were significant regarding Trial Outcome Index (P = .011), FACT-G (P = .005), and FACT-F (P = .001) for the MTG compared with the CG. Conclusions: Individual music therapy sessions may be effective to reduce fatigue related to cancer and symptoms of depression, as well as to improve quality of life for women with breast or gynecological cancer undergoing radiotherapy. Further well-designed research studies are needed to adequately determine the effects of music therapy on fatigue.

Objective: This study sought to describe changes in the health-related quality of life (HRQOL) of women who do and do not seek naturopathic oncology (NO) complementary and alternative medicine (CAM) care during and immediately after breast cancer treatment, and to explore the predictive role of NO CAM care, demographic characteristics, and involvement in decision-making on HRQOL in breast cancer survivors. Methods: Matched cohorts of breast cancer survivors who did and did not choose to supplement their breast cancer treatment with NO care within 2 years of diagnosis participated. NO users were identified through naturopathic doctors’ clinics and usual care (UC) controls with similar prognosis were identified through a cancer registry. The registry provided information about all participants’ age, race, ethnicity, marital status, stage of cancer at time of diagnosis, date of diagnosis, and use of conventional medical treatments (surgery, chemotherapy, radiation, and endocrine therapy). Data of participants’ self-reported involvement in decision-making and HRQOL were collected at study enrollment and at 6-month follow-up. Results: At 6-month follow-up, the NO patients reported significantly more involvement in decision-making about care and better general health than did UC patients (P < .05). Self-reported involvement in decision-making about cancer treatment was associated with better role-physical, role-emotional, and social-functional well-being (P < .05). Race, age, marital status, and congruence of preferred and achieved levels of involvement also predicted aspects of HRQOL in breast cancer survivors (P < .05). Conclusions: Both NO CAM care and involvement in decision-making about cancer treatment may be associated with better HRQOL in breast cancer survivors.

Background/Aim: MK615 extracted from Prunus mume was reported to have anti-inflammatory effects. In this article, we examined the in vivo antitumor effect of MK615 (an extract from Japanese apricot) using mouse tumor xenografts and focusing on the downregulation of PD-L1 (programmed death-ligand 1), a ligand of programmed cell death-1, a surface protein of activated T cells. Materials and Methods: B16/BL6 melanoma cells were injected into C57BL/6 or BALB/c-nu/nu mice to establish lung metastasis. BALB/c-nu/nu mice (nude mice) were used as a T cell–deficient model. The mice were given MK615 or saline orally every other day for approximately 8 weeks, and their survival was observed. NF-κB (nuclear factor-κB) and PD-L1 expressions of metastatic lung tissues were also examined. Results: The survival rate was improved only in the MK615-treated C57BL/6 mice (P < .05), not in the saline-given control mice or BALB/c-nu/nu mice. The downregulations of NF-κB and PD-L1 were observed in both MK615-treated C57BL/6 and BALB/c-nu/nu mice. These results suggest that the antitumor effects of MK615 are associated with T cell–mediated immunity activated by MK-615-induced PD-L1 downregulation in tumor cells. Conclusion: MK615 is beneficial for a prolonged host survival time in the B16/BL6 melanoma xenograft model associated with T cell–mediated antitumor immunity.

Plants from the Bursera genus are widely distributed in the tropical dry forests of Mexico. In traditional medicine, extracts from different species of Bursera have been used for a wide range of biological activities, including the treatment of cancer-related symptoms. Compounds present in the Bursera genus include lignans, flavonoids, steroids, short-chain aliphatic alkanes, acetates, alcohols, ketones, and terpenoids. In some instances, secondary metabolites of these classes of compounds may induce cytotoxicity, and therefore we sought to investigate the effects of B. copallifera leaf extracts in breast cancer cell lines to evaluate their potential therapeutic value for the treatment of breast cancer, one of the most prevalent types of cancer in women worldwide. Two B. copallifera leaf extracts exerted cytotoxic effects on both the MCF7 and MDA-MB-231 breast cancer cell line models. The cytotoxic effect was more evident in the MDA-MB-231 triple negative cell line inhibiting also the migration of these cells. We identified hydroxycinnamic acid and flavonol derivatives as major phenolic components of the extracts. Our results strongly suggest a potential use of the Bursera leaf extracts rich in phenolic compounds, their individual phenolic compounds, or their combinations for the treatment of breast cancer.

Introduction: Hematopoietic stem cell transplantation has become a well-established treatment for hematologic disorders including acute leukemia. However, long-term survival rates following this procedure are still extremely low, due to posttransplantation relapse, infections, and graft-versus-host disease. We propose that adjunctive Chinese herbal medicine may benefit posttransplantation patients. In preparation for a randomized clinical trial, we conducted a pilot trial. Methods and Analysis: Between September 2015 and June 2017, 18 patients were consecutively enrolled at China Medical University Hospital and followed for up to 1 year. Fresh blood samples were obtained on a monthly basis, and immune reconstitution was analyzed. In addition to the standard-care treatment administered by their oncologist, a number of patients also received a Chinese herbal formula (Sheng-Yu-Tang) for up to 6 months. Results were used to improve on study protocol and estimate required sample size for a future randomized trial. Ethics and Dissemination: Study protocol was approved by the institutional review board of China Medical University Hospital (DMR-105-005), and all participants provided informed consent.

Malignant gliomas are the most common brain tumors with high rates of recurrence and mortality. Novel approaches are in research, and immunotherapy emerges as a promising strategy. Recently, scientific attention has been focused on Ganoderma lucidum polysaccharides (GL-PS), one of the critical bioactive components of G lucidum, which have been recognized as a promising natural source of immunomodulatory and anticancer compounds. It remains unknown whether the GL-PS have any immunomodulatory and anticancer effects on brain glioma. This study was designed to identify and characterize the antitumor action and influence of immune system of GL-PS in glioma-bearing rats. Results showed that GL-PS increased the concentration of serum interleukin-2, tumor necrosis factor-α, and interferon-γ, and enhanced the cytotoxic activity of natural killer cells and T cells, promoting the functional maturation of dendritic cells, thus resulting in the inhibition of glioma growth and prolonged survival of rats. Therefore, GL-PS may be potentially useful as part of the treatment regimen to regulate host immune responses and increase the antitumor effects of immunotherapy for glioma.

Context. Breast cancer (BC) requires a significant psychological adaptation once treatment is finished. There is growing evidence of how compassion training enhances psychological and physical well-being, however, there are very few studies analyzing the efficacy of compassion-based Interventions on BC survivors. Objective. To study the efficacy of the Cognitively-Based Compassion Training (CBCT) protocol in a BC survivor sample on quality of life, psychological well-being, fear of cancer recurrence, self-compassion, and compassion domains and mindfulness facets. Furthermore, enrollment, adherence, and satisfaction with the intervention were also analyzed. Methods. A randomized clinical trial was designed. Participants (n = 56) were randomly assigned to CBCT (n = 28) or a treatment-as-usual control group (TAU; n = 28). Pre-post intervention and 6-month follow-up measures took place to evaluate health-related quality of life, psychological well-being; psychological stress, coping strategies, and triggering cognitions; self-compassion and compassion; and mindfulness in both intervention and wait-list groups. Results. Accrual of eligible participants was high (77%), and the drop-out rate was 16%. Attendance to CBCT sessions was high and practice off sessions exceeded expectations). CBCT was effective in diminishing stress caused by FCR, fostering self-kindness and common humanity, and increasing overall self-compassion scores, mindful observation, and acting with awareness skillsets. Conclusion. CBCT could be considered a promising and potentially useful intervention to diminish stress caused by FCR and enhance self-kindness, common humanity, overall self-compassion, mindful observation, and acting with awareness skillsets. Nevertheless, future randomized trials are needed and a process of deeper cultural adaptation required.

Purpose: Integrative oncology (IO) services provide complementary/integrative medicine (CIM) therapies to patients as part of their supportive cancer care. In this study, we examine and compare the structural, operational, financial and academic/research-related aspects of IO services in Israeli oncology centers. Methods: The medical directors of seven Israeli IO programs completed questionnaires which explored the objectives and organizational features of their service within the context of supportive cancer care. Results: All participating IO services addressed patient-reported concerns related to quality of life and function, within the context of conventional supportive cancer care. The centers shared similar characteristics regarding the procedure of referral to their service and emphasized research and teaching initiatives within an academic framework, as part of their clinical practice. A number of obstacles to integration were identified, primarily those related to financial considerations, such as the need for patients to carry the cost of the CIM treatments. Conclusions: IO services situated within conventional oncology departments in Israel share a number of characteristics, as well as obstacles to their incorporation into standard care. All participating centers described both clinical and academic activities, including research initiatives and the promotion of CIM in an academic setting. Further research is needed in order to better understand the place of CIM in the oncology setting and prioritize the allocation of resources in order to advance the inclusion of CIM in standard supportive cancer care.

Background: Syndrome (ZHENG in Chinese) in traditional Chinese medicine (TCM) refers to the intrinsic characteristics of a pathological process at a certain stage; these characteristics are influenced by internal and external environments and reveal the nature of a disease. Proper syndrome differentiation is the basic principle that guides clinical treatment. Objective: To have a good understanding of tumor progression and the different mechanisms related to ZHENG that have occurred before and after tumor development and to explore the valid evaluation criteria of different pancreatic cancer syndromes to improve the guiding role of TCM syndrome differentiation in pancreatic cancer treatment. Methods: In this study, we established mouse subcutaneous pancreatic cancer models, namely, Con (control), Pi-Xu (Spleen-Deficiency), Shi-Re (Dampness-Heat), and Xue-Yu (Blood-Stasis). Then, for the first time, we compared the different effects of “ZHENG-first” (referring to a different disease status that occurred before tumor occurrence) and “Tumor-first” (referring to the change in the tumor microenvironment and the resulting changes in the state of the body) conditions on tumor progression and evaluated the associated molecular mechanisms. Results: We found that tumor growth in the “ZHENG-first” and “Tumor-first” conditions was different. In the “Tumor-first” model, the tumor growth in the Pi-Xu group was faster than that in the other groups. However, in the “ZHENG-first” model, the tumor growth trend was most obvious in the Shi-Re group. There was a difference in tumor-associated macrophage infiltration between the 2 models. The expression levels of the inflammatory cytokines IL-6, IL-10, and P-STAT3 were also differentially altered. Conclusion: The emergence of ZHENG conditions before or after tumor occurrence had different impacts on pancreatic cancer development, and these impacts may be related to differences in tumor-associated macrophage infiltration and the involved inflammatory cytokines IL-6, IL-10, and P-STAT3. The study results uncovered the molecular basis of syndrome differentiation in pancreatic cancer progression, which might provide more specific guidance for TCM treatment of pancreatic cancer.

Background: Pain is a serious and common problem in bone metastases. For this purpose, complementary and supportive practices are also applied along with medical treatment. This study was conducted for the purpose of evaluating the effect of acupressure on pain in cancer patients with bone metastasis. Methods: The study was conducted in a nonrandomized controlled trial with patients who applied to the radiotherapy unit of an oncology hospital. The data of the study were collected by using a questionnaire and the Visual Analog Scale. A total of 8 acupressure sessions, which lasted for approximately 10 minutes each (with warming and acupressure periods), was applied to the intervention group. The data were analyzed by using χ² test, paired t test, and Pearson’s correlation coefficient. Results: It was determined that the pain mean score of the intervention group was 7.6 ± 1.9 before the acupressure and decreased to 6.8 ± 1.9 after the acupressure and this result was statistically significant. On the other hand, no significant difference was determined in the pain mean score of the control group. Conclusions: Acupressure is applicable for cancer patients with bone metastasis by nursing staff after receiving brief training and may make a difference in relieving pain of the patients. Further well-designed trials should be conducted.

Background: Among women in China, gynecological cancers are the second most common cancers after breast cancer. Cancer-related cognitive impairment (CRCI) has emerged as a significant problem affecting gynecological cancer survivors. While acupuncture has been used in different aspects of cancer care, the possible positive effects of acupuncture on cognitive impairment have received little attention. This study hypothesized that patients would demonstrate lower neurocognitive performance and lower structural connectivity compared to healthy controls. This pilot study also hypothesized that acupuncture may potentially be effective in treating CRCI of cancer patients by increasing brain structural connectivity and integrity. Methods: This prospective cohort study consisted of 3 stages: the first stage included a group of gynecological cancer patients and a group of age-matched healthy controls. This baseline stage used a core set of neurocognitive tests to screen patients with cognitive impairment and used a multimodal approach of brain magnetic resonance imaging (MRI) to explore the possible neurobiological mechanism of cognitive impairment in cancer patients, comparing the results with a group of noncancer controls. The second stage involved assigning CRCI patients into the acupuncture intervention group, while patients without CRCI were assigned into the cancer control group. The third stage was a postintervention assessment of neurocognitive function by the same set of neurocognitive tests at baseline. To explore the possible neurobiological basis of acupuncture for treating CRCI, this study also used a multimodal MRI approach to assess changes in brain structural connectivity, and neurochemical properties in patients at pre- and postacupuncture intervention. Results: This study found that the prevalence of cognitive impairment in Chinese gynecological cancer patients at diagnosis was 26.67%. When investigating the microstructural white matter in the brain, diffusion tensor imaging data in this study indicated that premorbid cognitive functioning (before clinical manifestations become evident) has already existed, as the global and local connectome properties in the entire patient group were lower than in the healthy control group. Using magnetic resonance spectroscopy, this study indicated there was a significant reduction of relative concentration of NAA (N-acetyl aspartate) in the left hippocampus, comparing these results with healthy controls. Regarding the effects of acupuncture on reducing CRCI, patients in the acupuncture group reported better neurocognitive test performance after matching for age, menopausal status, cancer stage, and chemotherapy regimen dosage. On a microstructural level, acupuncture’s ability to reduce CRCI may be attributed to a reduction in demyelination and an enhancement of the neuronal viability of white matter in the hippocampus. Conclusion: This pilot study indicates that acupuncture is a promising intervention in treating CRCI in gynecological cancer patients undergoing chemotherapy; however, it requires evaluation in larger randomized controlled studies to definitively assess its benefit. By using a multimodal imaging approach, this pilot study also provides novel insights into the neurobiological basis of cognitive impairment on the human brain that has been induced by cancer and/or its treatment.

Nausea and vomiting are among the most common and distressing side effects of chemotherapy. Additional antiemetic drugs are urgently needed to effectively manage and ameliorate chemotherapy-induced nausea and vomiting (CINV). The efficacy of ginger as an antiemetic modality for ameliorating CINV has not been established in previous studies. The aim of this study was to examine the efficacy of ginger, as an adjuvant drug to standard antiemetic therapy, in ameliorating acute and delayed CINV in patients with lung cancer receiving cisplatin-based regimens. In this randomized, double-blind, placebo-controlled clinical trial, 140 patients with lung cancer receiving cisplatin-based regimens were enrolled and allocated to receive either ginger root powder or a placebo. Ginger root powder was administered orally (0.5 g, 2 capsules per day, 0.25 g per capsule, every 12 hours) for 5 days beginning on the first day of chemotherapy. The incidence and severity of acute and delayed nausea and vomiting were assessed using the MASCC (Multinational Association for Supportive Care in Cancer) Antiemesis Tool (MAT). Adverse effects and patient adherence were also assessed in this study. No significant difference was observed between the ginger and control groups in the reduction of the incidence and severity of nausea and vomiting (P > .05). No significant difference in adverse events was observed between the 2 groups (P > .05). No study-treatment-related adverse events were observed in this study. As an adjuvant drug to standard antiemetic therapy, ginger had no additional efficacy in ameliorating CINV in patients with lung cancer receiving cisplatin-based regimens.

Objective: To determine the activity of fucoidan from Undaria pinnatifida (UPF) and Fucus vesiculosus (FVF) when given in combination of chemotherapy drugs using selected human breast or ovarian cancer orthotopic mouse models. Methods: Mice were inoculated with 1 × 10⁶ cells of TOV-112d, MCF-7, or ZR-75 subcutaneously or SKOV₃-GFP-Luc intraperitoneally on day 0. MCF-7 and ZR-75 mice were administered with estradiol valerate 2 mg/kg in 0.2 mL castor oil subcutaneously two days prior to cell inoculation. Mice were randomized to one of six arms (N = 10/arm) paclitaxel, UPF/paclitaxel, FVF/paclitaxel, tamoxifen, UPF/tamoxifen, or FVF/tamoxifen. Tumors were measured three times per week for 28 days. Results: Improved activity was observed with UPF or FVF in combination with tamoxifen in both the MCF-7 and ZR-75D breast cancer mouse models. Decreased activity of paclitaxel was observed when given in combination with UPF or FVF in both breast cancer mouse models. The combination of FVF/tamoxifen in the TOV-112d ovarian cancer mouse model had improved activity but no there was difference observed with the UPF/tamoxifen in either ovarian cancer mouse model. No difference was observed with combination of UPF or FVF with paclitaxel in human ovarian cancer SKOV₃ or TOV-112d orthotopic mouse models. Conclusion: This study did confirm that UPF/FVF in combination with tamoxifen did not decrease tamoxifen activity in both breast and ovarian cancer, with some potential to improve activity compared to tamoxifen alone in breast cancers. Previous in vitro studies had suggested UPF and FVF had overall synergistic activity with paclitaxel; however, in the current in vivo human cancer mouse model studies there was no change in paclitaxel activity when given in combination with UPF or FVF in either of the two human ovarian cancer models. Furthermore, this study demonstrated that UPF or FVF given in combination with paclitaxel had a potential antagonistic effect in breast cancer models. Additional studies are warranted to delineate mechanisms contributing to variation in the in vivo activity when given in combination with paclitaxel. As a first step, a clinical pharmacokinetic study evaluating impact of FVF/UPF given in combination with chemotherapy in patients with solid tumors is underway.

Background: Although cancer-related fatigue (CRF) has gained increased attention in the past decade, it remains difficult to treat. An integrative approach combining conventional and complementary medicine interventions seems highly promising. Treatment programs are more likely to be effective if the needs and interests of the people involved are well represented. This can be achieved through stakeholder engagement. Objectives: The aim of the study was to develop an integrative CRF treatment program using stakeholder engagement and to compare it to an expert version. Method: In a qualitative study, a total of 22 stakeholders (4 oncologists, 1 radiation-oncologist, 1 psycho-oncologist, 5 nurses/nurse experts, 9 patients, 1 patient family member, 1 representative of a local Swiss Cancer League) were interviewed either face-to-face or in a focus group setting. For data analysis, qualitative content analysis was used. Results: With stakeholder engagement, the integrative CRF treatment program was adapted to usual care using a prioritizing approach and allowing more patient choice. Unlike the expert version, in which all intervention options were on the same level, the stakeholder engagement process resulted in a program with 3 different levels. The first level includes mandatory nonpharmacological interventions, the second includes nonpharmacological choice-based interventions, and the third includes pharmacological interventions for severe CRF. The resulting stakeholder based integrative CRF treatment program was implemented as clinical practice guideline at our clinic (Institute for Complementary and Integrative Medicine, University Hospital Zurich). Conclusion: Through the stakeholder engagement approach, we integrated the needs and preferences of people who are directly affected by CRF. This resulted in an integrative CRF treatment program with graded recommendations for interventions and therefore potentially greater sustainability in a usual care setting.

Purpose: Treatment for head and neck cancer (HNC) results in long-term toxicities and increased physical and psychosocial survivor burden. There are a limited number of treatments for these late effects. Yoga postures, breath work, relaxation, and meditation, may improve these late effects. The purpose of this study was to examine the feasibility of a tailored yoga program in HNC survivors and obtain preliminary efficacy data. Methods: This was a randomized wait-list control study of yoga-naive HNC survivors who were >3 months post–cancer treatment. Baseline data were collected. Participants were randomized to either an 8-week hatha yoga intervention group or a wait-list group. Feasibility and efficacy data were collected. At 4 and 8 weeks, patients underwent a repeat assessment of health. Wait-list control group participants were offered the yoga program after data collection. Descriptive statistics evaluated feasibility. Mixed effects general linear models were used to generate estimates of the efficacy outcomes. Results: Seventy-three individuals were screened and 40 were eligible. All eligible individuals consented and enrolled. Five of the intervention group discontinued early and none in the wait-list control group. Feasibility was affirmed as participants were recruited and retained in the study, there were no adverse events, fidelity to protocol was demonstrated, and satisfaction rates were high. Efficacy measures indicated potential benefit for shoulder range of motion (d = 0.57-0.86, P < .05), pain (d = 0.67-0.90, P ≤ .005), and anxiety (d = 0.59, P = .015). Conclusion: A tailored hatha yoga program is feasible and potentially efficacious for HNC survivors. Preliminary data supports further investigation of yoga in this population is needed.

Purpose: Many cancer survivors seek complementary therapies (CTs) to improve their quality of life. While it is well-known that women who are younger, more highly educated, and have higher incomes are more likely to use CTs, individual differences such as personality factors have been largely unexplored as predictors of CT use. Methods: In a secondary analysis of a larger study, 270 women with stage I to III breast cancer completed self-report measures of demographic and illness-related information, personality variables, and use of several different types of CTs. A series of logistic regression models were used to explore whether demographic, illness-related, and personality variables predicted different types of CT use. Results: Prior relationships between education and CT use were replicated. There were no significant relationships between illness-related variables and different types of CT use. Of the 5 personality factors, only openness to experience was a significant predictor of multiple types of CT use. Conclusions: Openness to experience may represent an individual difference variable that predicts CT use among cancer survivors. CTs themselves may represent a form of intellectual curiosity and novelty seeking. Further studies are needed to replicate and examine the generalizability of the relationship between openness to experience and CT use in oncology populations.

Background and Objectives: There is a lack of information on therapies recommended by naturopathic doctors (NDs) for lung and gastroesophageal cancer care. Study objectives were to: (1) identify the most common interventions considered for use by NDs; (2) identify interventions NDs recommend to support key therapeutic goals; and (3) identify potential contraindications between integrative and conventional therapies. Methods: Oncology Association of Naturopathic Physicians (OncANP) members (n = 351) were invited to complete an electronic survey. Respondents provided information on interventions considered for thoracic cancer pre- and postoperatively across 4 therapeutic domains (supplemental natural health products, physical, mental/emotional, and nutritional), therapeutic goals, and contraindications. This survey was part of the development of the Thoracic Perioperative Integrative Surgical Evaluation trial. Results: Forty-four NDs completed the survey (12.5% response rate), all of whom were trained at accredited colleges in North America and the majority of whom were Fellows of the American Board of Naturopathic Oncology (FABNO) (56.8%). NDs identified significantly more interventions in the postoperative compared to preoperative setting. The most frequently identified interventions included modified citrus pectin, arnica, omega-3 fatty acids, vitamin D, probiotics, exercise, acupuncture, meditation, stress reduction, low glycemic index diet, and Mediterranean diet. Potential contraindications with conventional treatment (surgery, chemotherapy, radiotherapy) differed across natural health products. Conclusions: These findings highlight naturopathic interventions with a high level of use in thoracic cancer care, describe and characterize therapeutic goals and the interventions used to achieve these goals, and provide insight on how practice changes relative to conventional cancer treatment phase.

Background: The blood-brain barrier (BBB) is the greatest challenge in the treatment of intracranial malignant tumors. Objective: The aim of this study is to determine the role of borneol in opening the BBB and elucidate the underlying mechanisms. Materials and Methods: Twenty Sprague-Dawley (SD) rats were randomized into borneol group intragastrically administered with 10% borneol corn oil (2 mL/kg) and control group. After 30 minutes, 2% Evans blue (4 mL/kg) was injected. Thirty minutes later, brain tissue was analyzed using the Evans blue standard curve. Another 40 SD rats were randomized into high-, medium-, and low-dose borneol groups and a control group. Each rat in the experimental groups was intragastrically administered with 10% borneol corn oil (2 mL/kg, 1.25 mL/kg, and 0.5 mL/kg, respectively). The control group was injected with corn oil of 1.25 mL/kg. After 30 minutes, the rats were killed, and the brain tissues were collected. The expression of occludin, occludens-1, nitric oxide synthase, P-glycoprotein, and intercellular cell adhesion molecule-1 (ICAM-1) was detected by immunohistochemy. Results: The concentration of Evans blue in the borneol group was higher than in the control group (P < .05). The mean density of ICAM-1 expression was higher in the experimental group than in the control group (P < .05). In contrast, significant differences of positive area and total density of ICAM-1 were shown only between the high-dose group and the control group (P < .05). Conclusion: Borneol can open the BBB, which might be related with the increased expression of ICAM-1.

D-methionine is a sulfur-containing amino acid that can act as a potent antioxidant. Anorexia and nephrotoxicity are side effects of cisplatin. The protective effects of D-methionine on cisplatin-induced anorexia and renal injury were investigated. The model of chronic cisplatin administration (5 mg/kg body weight) involved intraperitoneal injection on days 1, 8, and 15 and oral D-methionine (300 mg/kg body weight) coadministration daily for 20 days. On the 21st day of treatment, food intake and body weight in the cisplatin-treated group significantly decreased by 52% and 31%, respectively, when compared with a control group. D-methionine coadministration with cisplatin decreased food intake and body weight by 29% and 8%, respectively. In cisplatin-treated rats, white blood cell, mean corpuscular volume, and platelet values significantly decreased, while mean corpuscular hemoglobin concentration significantly increased by 8.6% when compared with control rats. Cisplatin administration resulted in significantly decreased feeding efficiency, elevated renal oxidative stress, and reduced antioxidative activity. Leukocyte infiltration, tubule vacuolization, tubular expansion, and swelling were observed in the kidneys of cisplatin-treated rats. Oral D-methionine exhibited an antianorexic effect, with improvement in food intake, feeding efficiency, and hematological toxicities, as well as a protective effect against nephrotoxicity by elevated antioxidative activity. D-methionine may serve as a chemoprotectant in patients receiving cisplatin as part of a chemotherapy regimen.

Objectives. We aimed to investigate the effects of brief supportive expressive group therapy with mindfulness for cancer patients and to assess the utility of heart rate variability (HRV) as a biomarker of distress and treatment effect. Methods. A total of 28 female patients with nonmetastatic cancer at a university hospital in South Korea received a 4-week modified group therapy for distress reduction. The BESTMIND (Brief Expression and Support Therapy with Mindfulness) program consisted of supportive–expressive group therapy and mindfulness-based stress reduction. The subjective outcomes of distress, anger, sleep quality, and sense of well-being and the physiological outcome of HRV were assessed before and after the program. Results. After the program, patients showed significantly reduced distress, perceived stress, anger, and sleep disturbance and increased quality of life. No significant change was observed in the degree of mindfulness. A significantly increased SD in the normal beat-to-beat intervals and normalized high-frequency (HF 0.15-0.4 Hz) power from spectral analysis were observed after treatment. According to the correlation analyses, HF power correlated with depression scores, and normalized HF power was associated with depression, anxiety, perceived stress, and anger at baseline. The pretreatment and posttreatment comparison indicated that an increase in HF power was associated with a decrease in anger. Conclusions. These results suggest the effectiveness of this modified group-based program for distress reduction and also provide preliminary evidence for the use of HRV as a biomarker of distress and recovery. HF power from HRV variables may serve as a quantitative biomarker of the treatment response of distress management, including anger.

Background: Inonotus obliquus, also known as Chaga, is a parasitic fungus growing on birches and used in traditional medicine (especially by Khanty people) to treat various health problems. In this study, we aimed to quantify the 3 metabolites frequently cited in literature, that is, betulin, betulinic acid, and inotodiol in the Chaga recently discovered in forests located in Normandy (France), and to compare their concentrations with Ukrainian and Canadian Chaga. This study also explores the cytotoxicity of the French Chaga against cancer-derived cells and transformed cells. Methods: A quantification method by HPLC-MS-MS (high-performance liquid chromatography–tandem mass spectrometry) of betulin, betulinic acid, and inotodiol was developed to study the French Chaga and compare the concentration of these metabolites with extracts provided from Chaga growing in Canada and Ukraine. This method was also used to identify and quantify those 3 compounds in other traditional preparations of Chaga (aqueous extract, infusion, and decoction). Among these preparations, the aqueous extract that contains betulin, betulinic acid, and inotodiol was chosen to evaluate and compare its cytotoxic activity toward human lung adenocarcinoma cells (A549 line) and human bronchial epithelial cells (BEAS-2B line). Results: French Chaga contains betulin and betulinic acid at higher levels than in other Chaga, whereas the concentration of inotodiol is greater in the Canadian Chaga. Moreover, the results highlighted a cytotoxic activity of the Chaga’s aqueous extract after 48 and 72 hours of exposure with a higher effect on cancer-derived cells A549 than on normal transformed cells BEAS-2B (P = 0.025 after 48 hours of exposure and P = 0.004 after 72 hours of exposure).

Background. Cancer survivors use complementary therapies (CTs) for a variety of reasons; however, with interest and use reportedly on the rise and a widening range of products and practices available, there is a need to establish trends in and drivers of interest. We aimed to determine (1) frequencies of use, level of interest, and barriers for 30 specific CTs and (2) whether physical symptoms, perceived stress (PS), or spiritual well-being were related to interest levels. Method. A total of 212 cancer outpatients were surveyed at the Tom Baker Cancer Centre in Calgary, Canada. Results. Overall, up to 75% of survivors already used some form of CTs since their diagnosis. The most highly used were the following: vitamins B12 and D, multivitamins, calcium, and breathing and relaxation exercises. Those who had not used CTs indicated highest interest in massage, vitamin B12, breathing and relaxation, mindfulness-based stress reduction, and antioxidants. The most frequently reported barriers for all CTs were not knowing enough about what a therapy was and not having enough evidence on whether it worked. High PS predicted higher interest for all CTs, but spirituality was not significantly related to any. Physical symptoms, anxiety, and depression were significant predictors of interest for some CTs. Conclusion. These findings provide a blueprint for future clinical efficacy trials and highlight the need for clinical practice guidelines.

Introduction: Increasing evidence suggests that acupuncture may be helpful to manage common symptoms and treatment side effects among breast cancer (BC) survivors. Acupuncture usage among BC survivors remains low with little known about the barriers to its utilization. We evaluated perceived barriers to acupuncture use among BC survivors and explored the sociodemographic variations of such barriers. Methods: We conducted a cross-sectional analysis at an urban academic cancer center on 593 postmenopausal women with a history of stage I-III hormone receptor-positive BC who were taking or had taken an aromatase inhibitor. We used the modified Attitudes and Beliefs about Complementary and Alternative Medicine instrument to evaluate patients’ perceived barriers to acupuncture. Multiple linear regression analysis was performed to determine sociodemographic factors associated with perceived barrier scores. Results: The most common barriers were lack of knowledge about acupuncture (41.6%), concern for lack of insurance coverage (25.0%), cost (22.3%), and difficulty finding qualified acupuncturists (18.6%). Compared with whites, minority patients had higher perceived barriers to use acupuncture (β coefficient = 1.63, 95% confidence interval = 0.3-2.9, P = .013). Patients with lower education had higher barriers to use acupuncture (β coefficient = 4.23, 95% confidence interval = 3.0-5.4, P < .001) compared with patients with college education or above. Conclusion: Lack of knowledge and concerns for insurance coverage and cost are the common barriers to acupuncture use among BC survivors, especially among minority patients with lower education. Addressing these barriers may lead to more equitable access to acupuncture treatment for BC survivors from diverse backgrounds.

The aim of the present study was to investigate whether fraction from Lycium barbarum polysaccharide (LBP) could reduce immunotoxicity and enhance antitumor activity of doxorubicin (Dox) in mice. A water-soluble LBP fraction, designated LBP3, was isolated from edible Chinese herbal Lycium barbarum and used in this study. To investigate the effect of LBP3 on Dox-induced immunotoxicity, tumor-free mice were used and treated with either normal saline, Dox, or Dox plus LBP3. To investigate the effect of LBP3 on antitumor activity of Dox, H22 tumor-bearing mice were used and treated with either normal saline, Dox, LBP3, or Dox plus LBP3. The results showed that LBP3 did not protect against the body weight loss caused by Dox, but it promoted the recovery of body weight starting at day 5 after Dox treatment in tumor-free mice. LBP3 also improved peripheral blood lymphocyte counts, promoted cell cycle recovery in bone marrow cells, and restored the cytotoxicity of natural killer cells. Furthermore, in H22 tumor-bearing mice, LBP3 enhanced antitumor activity of Dox and improved peripheral blood lymphocyte counts and the cytotoxicity of splenocytes. In brief, our results demonstrated that LBP3 could reduce the immunotoxicity and enhance antitumor activity of Dox.

Besides honey, honeybees make a sticky substance (called propolis/bee glue) by mixing saliva with poplar tree resin and other botanical sources. It is known to be rich in bioactivities of which the anticancer activity is most studied. Caffeic acid phenethyl ester (CAPE) is a key anticancer component in New Zealand propolis. We have earlier investigated the molecular mechanism of anticancer activity in CAPE and reported that it activates DNA damage signaling in cancer cells. CAPE-induced growth arrest of cells was mediated by downregulation of mortalin and activation of p53 tumor suppressor protein. When antitumor and antimetastasis activities of CAPE were examined in vitro and in vivo, we failed to find significant activities, which was contrary to our expectations. On careful examination, it was revealed that CAPE is unstable and rather gets easily degraded into caffeic acid by secreted esterases. Interestingly, when CAPE was complexed with γ-cyclodextrin (γCD) the activities were significantly enhanced. In the present study, we report that the CAPE-γCD complex with higher cytotoxicity to a wide range of cancer cells is stable in acidic milieu and therefore recommended as an anticancer amalgam. We also report a method for preparation of stable and less-pungent powder of propolis that could be conveniently used for health and therapeutic benefits.

Purpose: To determine if women with breast cancer who choose adjunctive naturopathic oncology (NO) specialty care receive different standard oncologic treatment when compared with breast cancer patients who receive only standard care. Participants: Women with breast cancer stages 0 to 4, aged 18+ who spoke English and sought care from outpatient naturopathic doctor clinics were enrolled in an observational study of clinical and quality of life outcomes. Women who sought NO care 2 or more times within the first 2 years postdiagnosis were identified as NO cases. A matched comparison group of breast cancer patients were identified using the Western Washington Cancer Surveillance System(CSS). Methods: A longitudinal cohort design. In addition to self-report data, the CSS provided data on demographics, stage at the time of diagnosis, and initial treatment. Oncology medical records were abstracted in order to provide additional information on standard oncologic treatment for all participants. Results: Cohorts were well matched with regard to demographic, histologic, and prognostic indicators at the time of diagnosis. Approximately 70% of women in both cohorts received standard oncologic care that met the National Comprehensive Cancer Network guidelines. There were no statistically significant differences between the cohorts in treatment received. Fewer women in the NO cohort with estrogen receptor–positive breast cancer appear to have received antiestrogen therapy. Conclusions: Women in both cohorts appear to receive guideline-concordant care. However, women who receive adjunctive NO care may be less likely to receive antiestrogen therapy.

Background: Traditional Chinese medicine (TCM) is widely used among Chinese cancer patients. However, little is known about Chinese patients’ expectations and barriers toward using TCM for cancer. Methods: We conducted a cross-sectional survey within a patient-support group, the Beijing Anti-Cancer Association. We measured the outcome, Chinese cancer survivors’ expectations and barriers toward TCM utilization, using a modified version of ABCAM (Attitudes and Beliefs towards Complementary and Alternative Medicine), the ABTCM (Attitudes and Beliefs towards Traditional Chinese Medicine). We used multivariate models to evaluate the impact of socioeconomic status and clinical factors on their expectations and barriers (including treatment concerns and logistical challenges domain) toward TCM. Results: Among 590 participants, most patients expected TCM to boost their immune system (96%), improve their physical health (96%), and reduce symptoms (94%). Many had logistical challenges (difficulty decocting herbs (58%) and finding a good TCM physician (55%)). A few were concerned that TCM might interfere with conventional treatments (7.6%), and that many TCM treatments are not based on scientific research (9.1%). In the multivariable regression model, age ≤60 years was independently associated with higher expectation score (P = .031). Age ≤60 years (coefficient 5.0, P = .003) and localized disease (coefficient 9.5, P = .001) were both associated with higher treatment concerns. Active employment status (coefficient 9.0, P = .008) and localized disease (coefficient 7.5, P = .030) were related to more logistical challenges. Conclusion: Age and cancer stage were related to Chinese cancer patients’ perceived expectations and barriers toward TCM use. Understanding these attitudes is important for reshaping the role that TCM plays in China’s patient-centered comprehensive cancer care model.

Objectives. Triphala is a herbal medicine that has been widely used for treating a variety of ailments. This study aims to systematically analyze the antitumor effects of Triphala on gynecological cancers. Methods. The antineoplastic activities of Triphala on gynecological cancers were analyzed using network pharmacology-based strategies. Afterward, the human ovarian cancer cell line SK-OV-3, cervical cancer cell line HeLa, and endometrial cancer cell line HEC-1-B were selected for experimetal valification. Results. Network pharmacology analysis suggested that Triphala could comprehensively intervene in proliferation and apoptosis through diverse signaling pathways, mainly including MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53. The Cell Counting Kit 8 (CCK-8) assay illustrated that Triphala was able to inhibit cell proliferation with half inhibition concentration (IC₅₀) values of 98.28 ± 13.71, 95.56 ± 8.94, and 101.23 ± 7.76 µg/mL against SK-OV-3, HeLa, and HEC-1-B cells, respectively. The ELISA experiment demonstrated that Triphala was capable of promoting programmed cell death, with dosage correlations. The antiproliferative and proapoptotic activities were confirmed by flow cytometric analysis using Ki67 antibody and Annexin V/propidium iodide (PI) dual staining. Western blotting revealed a decrease in expression levels of phospho-Akt, phospho-p44/42, and phospho-NF-κB p56 in cells administered Triphala, which indicated that the possible mechanism could involve downregulation of MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53 signaling pathways, as was predicted. Conclusion. Triphala holds great promise for treating gynecological cancers. Although the favorable pharmacological properties have been preliminarily investigated in this study, further studies are still needed to uncover the sophisticated mechanism of Triphala in cancer therapy.

Background. Hepatocellular carcinoma (HCC) is one of the major malignancies associated with high mortality rates. Chinese herbal medicine (CHM) alone, or in combination with conventional therapies (CT), has been widely used for patients with HCC in China. This study aims to explore how integrative therapy (IT) through the combination of CHM and CT affects the survival of patients with intermediate-advanced HCC. Methods. A retrospective cohort study was performed at the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Data of consecutive patients diagnosed with intermediate-advanced HCC and a specific traditional Chinese medicine diagnostic pattern between January 2006 and December 2013 were retrieved from the electronic medical record system at the hospital. Patients were divided into 3 groups based on the therapies used, that is, IT, CHM alone, and CT alone, and the survival times of these patients was compared. Results. A total of 328 patients were included in this study. Median follow-up period was 26.4 months (95% confidence interval [CI] = 22.7-38.9). Median overall survival was 11.0 months for IT, 8.6 months for CHM, and 9.4 months for CT groups (P < .001). The adjusted hazard ratio (HR) of death for the IT group was 0.55 (95% CI = 0.38-0.79, P = .001) relative to the CT group and 0.68 (95% CI = 0.52-0.90, P = .007) relative to the CHM group, after adjusting for the factors that impact prognosis. Stratified analysis shows that IT can significantly lower the risk of death, especially for patients with good performance status (PS) and Child-Pugh class A. Conclusions. It was indicated that the integrative approach with combination of CHM and CT might improve survival for patients with intermediate-advanced HCC, especially for patients with good PS and Child-Pugh class A. However, a randomized controlled trial is warranted for a conclusive statement.

Background. Intravenous ascorbic acid (IV AA) has been used extensively in cancer patients throughout the United States. Currently, there are limited data on the safety and clinical effects of IV AA. The purpose of this study was to expand the current literature using a retrospective analysis of adverse events and symptomatic changes of IV AA in a large sample of cancer patients. Methods. We conducted a retrospective chart review of all patients receiving IV AA for cancer at the Thomas Jefferson University Hospital over a 7-year period. We assessed all reports of adverse events, laboratory findings, and hospital or emergency department admissions. We also reviewed quality-of-life data, including fatigue, nausea, pain, appetite, and mood. Results. There were 86 patients who received a total of 3034 doses of IV AA ranging from 50 to 150g. In all, 32 patients received only ascorbic acid as part of their cancer management (1197 doses), whereas 54 patients received ascorbic acid in conjunction with chemotherapy (1837 doses). The most common adverse events related to ascorbic acid were temporary nausea and discomfort at the injection site. All events reported in the ascorbic acid alone group were associated with less than 3% of the total number of infusions. Patients, overall, reported improvements in fatigue, pain, and mood while receiving ascorbic acid. Conclusions. The results of this retrospective analysis support the growing evidence that IV AA is generally safe and well tolerated in patients with cancer, and may be useful in symptom management and improving quality of life.

Introduction: Physical activity (PA) is a potential therapy to improve quality of life in patients with advanced-stage lung cancer (LC), but no PA regimen has been shown to be beneficial, clinically practical, and sustainable. We sought to test the hypothesis that a patient-centered activity regimen (PCAR) will improve patient participation and PA more effectively than weekly phone calls. Methods: In patients with advanced-stage LC, we implemented a walking-based activity regimen and motivated patients via either weekly phone calls (n = 29; FitBit Zip accelerometer) or PCAR (n = 15; FitBit Flex, an educational session, and twice-daily gain-framed text messages). Data collection over a 4-week period was compared, and a repeated-measures, mixed-effects model for activity level was constructed. Results: Subjects receiving PCAR more frequently used the device (100% vs 79%) and less frequently had missing data (11% vs 38%). “More active” and “less active” groups were created based on mean step count in the first week. “Less active” patients in the PCAR group increased their PA level, whereas PA level fell in the “more active” group. Most subjects found PCAR helpful (92%) and would participate in another activity study (85%). Discussion: Compared with weekly phone calls, PCAR has higher patient participation, is more likely to improve PA in “less active” subjects, and has high patient satisfaction. A multifaceted PA regimen may be a more efficacious mechanism to study PA in advanced LC. PCAR should be used in a randomized controlled trial to evaluate for improvements in symptom burden, quality of life, and mood.

Background: Pediatric cancer patients experience different psychological processes during hospitalization that may regulate the immune response and affect recovery and response to cancer treatment. In this study, we aimed to examine the feasibility of longitudinal testing of psychophysiological parameters of stress and fatigue in pediatric osteosarcoma patients hospitalized for chemotherapy submitted to clown intervention; and to investigate whether changes in the levels of biomarkers are associated with psychological stress and fatigue levels in these patients after the clown intervention. Methods: A pretest-posttest quasi-experimental pilot study was conducted at the pediatric oncology inpatient unit in a comprehensive cancer care center in Brazil including children and adolescents with osteosarcoma hospitalized for chemotherapy. Eight saliva samples were collected, comprising 4 at baseline (pre-intervention) and 4 after the clown intervention (+1, +4, +9, and +13 hours post-awakening). Salivary cortisol, α-amylase (sAA), cytokines, and matrix metalloproteinase-9 (MMP-9) levels were determined using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Stress and fatigue were measured by Child Stress Scale–ESI and PedsQL Multidimensional Fatigue Scale respectively. Bivariate association analysis between stress and fatigue scores and biomarker levels were investigated using nonparametric statistics. Effect sizes were calculated for each outcome variable. Results: Six pediatric osteosarcoma patients were enrolled with no missing data. No significant effects sizes were observed for psychophysiological outcomes. Effect sizes ranged from 0.54 (cortisol) to 0 (interleukin-1β [IL-1β]). Decreasing overall trends were observed for cortisol levels for all 6 pediatric osteosarcoma patients over time. In addition, a similar pattern of tumor necrosis factor–α (TNF-α) levels over time was found for all 6 patients. Patients with metastatic osteosarcoma showed a linear trend for a decrease in MMP-9 levels between 1 and 9 hours after the clown intervention and restoration to basal levels after 13 hours. Conclusions: The results of this pilot study suggest that it is feasible longitudinally measure psychophysiological outcomes in the pediatric osteosarcoma inpatients for chemotherapy. Clown intervention merits further study as a way to reduce stress as well as fatigue, since that the stress and cytokines measurements are feasible based on our work.

Purpose. Although the demand from patients for integrative medicine is increasing, complementary medicine services are still quite heterogeneous and have not been incorporated into clinical routine. The aim of this study was to systematically evaluate improvements in side effects and quality of life associated with a hospital-based integrative medicine program in the modern breast cancer patient care setting. Methods. In a cross-sectional study, integrative health counseling and treatment were evaluated in women with breast cancer. Over a 15-month period, data for 75 patients from an integrative medicine consultancy service with standardized operating procedures were collected at the University Breast Center for Franconia. At baseline, the patients answered a questionnaire on their medical history, symptoms, and the treatment goals they were hoping to achieve with integrative medicine. In the follow-up, patient-reported outcomes related to side effects of conventional cancer treatment and patients’ quality of life were analyzed. Results. Among 60 patients with the therapy goal of reducing the side effects of conventional treatment, 46 (76.7%) were successful. Among 57 patients hoping to improve disease-related quality of life, 46 (82%) reported success. Whereas patients with metastatic disease achieved a reduction in the side effects of conventional therapy, quality-of-life improvements were predominantly achieved by patients with a good treatment prognosis. Conclusions. Breast cancer patients benefit from the counseling and treatment provided with integrative medicine in all phases of tumor disease. Integrative treatment services should be included as part of patient care in clinical routine work to offer patients the maximum quality of care and safety with complementary therapies.

Background: Neoadjuvant chemoradiation treatment (CRT) in rectal cancer patients is associated with a reduction in physical capacity, lean mass and increased fatigue. As a countermeasure to these treatment-related adverse effects, we examined the feasibility and preliminary efficacy of a 10-week exercise program during CRT. Methods: Ten rectal cancer patients (7 men, aged 27-70 years, body mass index = 26.4 ± 3.8 kg/m²) receiving CRT undertook supervised resistance and aerobic exercise twice weekly. Assessments were undertaken pre- and post-intervention for upper and lower body muscle strength by 1-RM, muscle endurance, physical performance tests, body composition by dual X-ray absorptiometry, quality of life, and fatigue. Results: There was a significant loss in appendicular skeletal muscle (−1.1 kg, P = .012), and fat mass (−0.8 kg, P = .029) following CRT. Despite the loss in skeletal muscle, leg press (P = .030) and leg extension (P = .046) strength improved by 27.2% and 22.7%, respectively, and leg press endurance by 76.7% (P = .007). Changes in strength were accompanied by improved performance (P < .05) in 6-m fast walking speed (6.9%) and dynamic balance as determined by the 6-m backwards walk (15.5%). There was minimal change in quality of life and fatigue, and no adverse events related to training. Conclusions: Exercise during neoadjuvant CRT appears to be feasible and well tolerated in rectal cancer patients and may enhance physical function while minimizing adverse changes in body composition and cancer-related fatigue. These initial findings need to be confirmed in randomized controlled trials.

Objective: This study was designed to assess the feasibility of using the Jaw Dynasplint System as an adjunct to conventional stretching exercises as a preventative measure against trismus in patients undergoing radiotherapy. Methods: Study participants (n = 40) were randomized using a permuted block design to conventional stretching or stretching plus use of the Jaw Dynasplint 3 times per day for 30 minutes. Patients were instructed to record maximum interincisal opening each day as well as logging use of the Jaw Dynasplint. Results: At 6 months after initiation of the preventative regimen, 50% of patients in the Dynasplint arm and 75% in the conventional stretching arm remained on their assigned therapy. Trismus was diagnosed in 2 patients in the control arm and in 4 patients in the Dynasplint arm. Only 25% (95% confidence interval = 11.1, 46.9) of patients in the Dynasplint arm used the device as prescribed. Conclusions: The addition of the Jaw Dynasplint decreased compliance compared with conventional stretching. It is unlikely that the prescribed regimen will prove efficacious as a preventative measure due to low compliance.

Introduction: Women with breast cancer are often prescribed aromatase inhibitors, which can cause rapid loss of bone mass leading to significant potential for morbidity. Vibration training has been shown to be helpful in reducing bone turnover in postmenopausal women without cancer. Aim: To examine the effect of vibration stimulus on markers of bone turnover in breast cancer patients receiving aromatase inhibitors. Methods: Thirty-one breast cancer survivors undergoing treatment with aromatase inhibitors were randomized to vibration stimulus (n = 14) or usual care control (n = 17). Low-frequency and low-magnitude vibration stimulus (27-32 Hz, 0.3g) was delivered in supervised sessions via standing on a vibration platform for 20 minutes, 3 times per week for 12 weeks. The primary outcome was blood markers of bone resorption (serum N-telopeptide X/creatine) and formation (serum type 1 procollagen N-terminal propeptide; P1NP). Other study outcomes body composition as well as measures of physical functioning. Outcomes were compared between groups using analysis of covariance adjusted for baseline values as well as time on aromatase inhibitors. Outcomes: On average, participants were 61.5 years old and overweight (ie, body mass index = 28.5 kg/m²). Following vibration training, there was no significant difference between groups for bone resorption (adjusted group difference 0.5, P = .929) or formation (adjusted group difference 5.3, P = .286). There were also no changes in any measure of physical functioning body composition. Conclusions: Short-term low-magnitude vibration stimulus does not appear to be useful for reducing markers of bone turnover secondary to aromatase inhibitors in breast cancer patients; nor is it useful in improving physical function or symptoms. However, further investigations with larger samples and higher doses of vibration are warranted. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12611001094965).

Introduction: Complementary medicine (CM) use has been found to influence the uptake of conventional cancer treatment. This study examines associations between CM use and cancer screening rates. Methods: Women aged 62 to 67 years from the Australian Longitudinal Study on Women’s Health were surveyed regarding their use of cancer screening initiatives. Associations between cancer screening behavior and visits to CM practitioners were analyzed. Results: Of the 9151 women, 9049 (98.9%) completed questions about cancer screening. A total of 65.1% of women had received a clinical skin examination, 54.3% colorectal cancer screening, 56.2% Pap test (within past 2 years), 83.3% mammogram (within past 2 years), 55.8% clinical breast examination, and 55.8% had conducted breast self-examination. Women who had consulted a massage therapist were more likely to undergo clinical skin examination (P = .002), clinical breast examination (P = .018), and mammogram (P = .001). Women who had consulted a chiropractor were more likely to undergo a clinical skin examination (P = .001), colorectal cancer screening (P = .020), and mammogram (P = .011). Women who had consulted an acupuncturist were more likely to undergo colorectal cancer screening (P = .019), and those who consulted with an osteopath were more liable to have a Pap test (P = .049). Conclusion: Women who visit CM practitioners are more likely to participate in cancer screening initiatives. Research is required to understand the current and potential role that CM practitioners (can) have as public health advocates, recommending preventative health measures such as cancer screening. Such an examination will help ensure optimal screening utilization and effective, timely care for all cancer patients.

In this case report, we describe the treatment of a 64-year-old male patient diagnosed with metastatic renal cell carcinoma (RCC) in June of 2008. In spite of a left nephrectomy and the standard oncological protocols, the patient developed a solitary left lung metastasis that continued to grow. He was informed that given his diagnosis and poor response to conventional therapy, any further treatment would, at best, be palliative. The patient arrived at the Integrative Medical Center of New Mexico in August of 2010. He was in very poor health, weak, and cachectic. An integrative program—developed by one of the authors using intravenous (IV) α-lipoic acid, IV vitamin C, low-dose naltrexone, and hydroxycitrate, and a healthy life style program—was initiated. From August 2010 to August 2015, the patient’s RCC with left lung metastasis was followed closely using computed tomography and positron emission tomography/computed tomography imaging. His most recent positron emission tomography scan demonstrated no residual increased glucose uptake in his left lung. After only a few treatments of IV α-lipoic acid and IV vitamin C, his symptoms began to improve, and the patient regained his baseline weight. His energy and outlook improved, and he returned to work. The patient had stable disease with disappearance of the signs and symptoms of stage IV RCC, a full 9 years following diagnosis, with a gentle integrative program, which is essentially free of side effects. As of November 2017 the patient feels well and is working at his full-time job.

Pancreatic cancer (PC) has a very low average survival, but its prognosis is further reduced in the case of metastatic spread. Medical therapy in these cases is the only applicable methodology in the international guidelines. During anticancer treatments, common side effects are nausea, vomiting, arthralgia, neuropathy, and alopecia as well as a myelosuppressive effect. The toxicity of various drugs not only affects the quality of life of the patient, but often its severity requires a reduction in if not the termination of drug administration. Scientific studies have shown that a combined use of chemotherapy and certain natural substances, in the form of standardized extracts, can lead to an enhancement of the action of the chemotherapy. Here, we describe 2 cases of metastatic PC. The first case concerns the integrated treatment of a patient with cancer of the pancreas tail with metastatic involvement ab initio of peripancreatic lymph nodes and liver parenchyma, with numerous secondary lesions greater than 9.5 cm. The second case concerns the integrated treatment of a patient with cancer of the pancreatic body with metastatic involvement of the liver parenchyma, with a small secondary lesion. In both cases, an integrated cancer treatment approach, combining chemotherapy with natural remedies, extracts, and hyperthermia, induced a notable remission of primary and metastatic lesions.

Cachexia has been recognized for a long time as an adverse effect of cancer. It is associated with reduced physical function, reduced tolerance to anticancer therapy, and reduced survival. This wasting syndrome is mainly known for an ongoing loss of skeletal muscle leading to progressive functional impairment and is driven by a variable combination of reduced food intake and abnormal metabolism. Cytokines derived from host immune system or the tumor itself is believed to play a role in promoting cancer cachexia. Circulating levels of cytokines, including IL-1α, IL-6, and TNFα have been identified in cancer patients but they probably only represent a small part of a changed and abnormal metabolism. Murine models have shown that browning of white adipose tissue (WAT) takes place early in the progression of cancer cachexia. Thus, browning of white adipose tissue is believed to be a strong contributor to the increased energy expenditure common in cachectic patients. Despite the severe implications of cancer cachexia for the patients and extensive research efforts, a more coherent and mechanistic explanation of the syndrome is lacking, and for many clinicians, cancer cachexia is still a vague concept. From a lung cancer perspective this commentary reviews the current knowledge on cancer cachexia mechanisms and identifies specific ways of clinical management regarding food intake, systemic inflammation, and muscular dysfunction. Much of what we know comes from preclinical studies. More translational research is needed for a future cancer cachexia screening tool to guide clinicians, and here possible variables for a cancer cachexia screening tool are considered.