Integrative Oncology Research Update

One of the main goals of SIO’s research committee is to disseminate updated research to our members. As such, we recently started a Research Update program. We will provide bi-monthly updates of relevant literature by selecting a number of recent papers to be listed on the SIO website, based on search criteria that focus on original clinical research in human populations spanning a full range of complementary therapy modalities. For chosen papers we will include the abstract and link to the journal cite for downloads. We hope you enjoy this new feature and appreciate your comments and feedback! PhotoSIOPosterSession PhotoSIOPosterSession3 https://integrativeonc.org/recent-research-findings?platform=hootsuite Abrams DI. An Integrative Approach to Prostate Cancer. J Altern Complement Med 2018 Sep/Oct;24(9-10):872-880 PMID 30247964 OBJECTIVES: The mostly indolent natural history and long overall survival associated with a diagnosis of prostate cancer provides a unique opportunity for men to explore diet and lifestyle interventions to alter the trajectory of their disease. As many patients may be appropriate for postponing conventional therapy, the effects of various integrative interventions can be investigated. In addition, treatment of prostate cancer with surgery, radiation, or androgen deprivation therapy, all may produce physical or psychological side effects that could be amenable to complementary therapies. This article serves to review salient information in the published literature. DESIGN: A review of published research was conducted. RESULTS: A plant-based antioxidant-rich diet with an emphasis on cruciferous vegetables, tomatoes, soy, pomegranate, and marine omega 3 fatty acids while avoiding saturated fats, including dairy products is the best option. Supplementation with vitamin D3, omega 3, and some nutraceutical-based preparations may be advised. It is likely prudent to avoid vitamin E and selenium supplements. Physical activity has been shown to have multiple benefits in men diagnosed with all stages of prostate cancer from strengthening bones, improving body habitus, and enhancing overall wellbeing. Yoga, combining physical activity with a mind-body component, has been shown to have a salutogenic effect in both prostate cancer patients and their caregivers. Traditional Chinese Medicine may be particularly useful in managing side effects of conventional treatments, especially the hot flashes associated with androgen deprivation therapy. Although the long natural history, availability of a useful blood marker of disease progression and prolonged survival are overall positive features, they also combine to allow men to live for a long time with diagnosed cancer, fear of progression, or recurrence and fixation on changes in their prostate-specific antigen level. The resultant stress can be deleterious to general health as well as possibly the natural history of their disease. Mind-body interventions to reduce stress, including mindfulness-based stress reduction and support groups may be useful adjunctive therapies. CONCLUSION: Men with prostate cancer may benefit from lifestyle and complementary interventions integrated with their conventional care. Adair M, Murphy B, Yarlagadda S, Deng J, Dietrich MS, Ridner SH. Feasibility and Preliminary Efficacy of Tailored Yoga in Survivors of Head and Neck Cancer: A Pilot Study. Integr Cancer Ther 2018 Sep;17(3):774-784 PMID 29355046 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 5ng/mL are associated with substantial cognitive and psychomotor impairment. The predicted time for concentrations to drop <5ng/mL was 49days after administration. DISCUSSION: The unusual pharmacokinetic properties of the case suggest that there is a large amount unknown about cannabis pharmacokinetic properties. The pharmacokinetic properties of a large amount of a lipid soluble compound given intraperitoneally gave insights into the absorption and distribution of cannabinoids, particularly in the setting of metastatic malignancy. Maurya N, Velmurugan BK. Therapeutic applications of cannabinoids. Chem Biol Interact 2018 Sep 25;293:77-88 PMID 30040916 The psychoactive property of cannabinoids is well known and there has been a continuous controversy regarding the usage of these compounds for therapeutic purposes all over the world. Their use for medical and research purposes are restricted in various countries. However, their utility as medications should not be overshadowed by its negative physiological activities. This review article is focused on the therapeutic potential and applications of phytocannabinoids and endocannabinoids. We further highlights their mode of action, overall effects on physiology, various in vitro and in vivo studies that have been done so far and the extent to which these compounds can be useful in different disease conditions such as cancer, Alzheimer's disease, multiple sclerosis, pain, inflammation, glaucoma and many others. Thus, this work is an attempt to make the readers understand the positive implications of these compounds and indicates the significant developments of utilizing cannabinoids as therapeutic agents. Pan Y, Yang K, Shi X, Liang H, Shen X, Wang R, et al. Clinical Benefits of Acupuncture for the Reduction of Hormone Therapy-Related Side Effects in Breast Cancer Patients: A Systematic Review. Integr Cancer Ther 2018 Sep;17(3):602-618 PMID 30117343 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. Park H, Oh S, Noh Y, Kim JY, Kim JH. Heart Rate Variability as a Marker of Distress and Recovery: The Effect of Brief Supportive Expressive Group Therapy With Mindfulness in Cancer Patients. Integr Cancer Ther 2018 Sep;17(3):825-831 PMID 29417836 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. Qureshi M, Zelinski E, Carlson LE. Cancer and Complementary Therapies: Current Trends in Survivors' Interest and Use. Integr Cancer Ther 2018 Sep;17(3):844-853 PMID 29629606 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. Radl D, Vita M, Gerber N, Gracely EJ, Bradt J. The effects of Self-Book((c)) art therapy on cancer-related distress in female cancer patients during active treatment: A randomized controlled trial. Psychooncology 2018 Sep;27(9):2087-2095 PMID 29744966 OBJECTIVE: National attention on patients' cancer-related emotional distress produced a need for evidence-based, psychosocial interventions in oncology care. The purpose of this study was to evaluate the efficacy of Self-Book((c)) art therapy for emotional distress and psychological well-being of female oncology patients during active oncology treatment. METHODS: Sixty consenting women with cancer were randomly assigned to either a 6-session Self-Book((c)) art therapy program or standard care. A repeated measures randomized controlled trial design was employed. Data were collected by using the Distress Thermometer, Perceived Emotional Distress Inventory, Patient-Reported Outcomes Measurement Information System Brief Psychological Well-being test, and the Functional Assessment of Chronic Illness Therapy Spiritual Well-being. Measurements were obtained at baseline, week 3, week 6, and 1 to 2 months post intervention. RESULTS: Forty participants were included in the final analysis. No significant differences between groups were found for the primary outcome measures: emotional distress and psychological well-being. Greater improvements in Self-Book((c)) art therapy participants' spiritual well-being were found compared with the standard care control participants (P = .02). CONCLUSIONS: Although no statistically significant differences were present between the groups for the primary outcomes, several positive trends were noted. Thirty percent of Self-Book((c)) art therapy participants reported postintervention emotional distress scores that were below the abnormal range for emotional distress, compared with only 5% of standard care control participants, suggesting that Self-Book((c)) art therapy may have clinical value. Further studies are recommended to better understand the therapeutic mechanisms of Self-Book((c)) art therapy for enhancing psychological well-being. Saadeh CE, Rustem DR. Medical Marijuana Use in a Community Cancer Center. J Oncol Pract 2018 Sep;14(9):e566-e578 PMID 30205775 PURPOSE: The primary purpose of this study was to compare the incidence of marijuana use between patients with early- versus advanced-stage cancers. Differences in adverse effects, drug-drug interactions, and drug-disease interactions between those who use marijuana and those who do not were also compared. METHODS: Patients age 18 years and older who were receiving chemotherapy were asked to complete an electronic self-reported questionnaire. In addition to questions about patient demographics, current adverse effects, cancer type and stage, comorbidities, performance status, treatment regimen, and general marijuana use, those patients who used marijuana within the last 30 days (current marijuana users) were asked additional questions about the route and frequency of marijuana administration, about reason(s) for use, about possession of a marijuana card, and if they had received any counseling about marijuana. Drug-drug and drug-disease interactions were also analyzed. RESULTS: The overall incidence of marijuana use was 18.3% (32 of 175 patients). The incidence of marijuana use in patients with early- versus advanced-stage cancers was 19.6% (11 of 56 patients) versus 17.6% (21 of 119 patients; P = .75). Patients who use marijuana reported more pain, nausea, appetite issues, and anxiety. There were more drug-drug interactions associated with marijuana use, primarily with concurrent CNS depressants. The frequency of drug-disease interactions between those who use marijuana versus those who do not was similar. CONCLUSION: Approximately one in five patients with cancer who were receiving chemotherapy were using marijuana, and the frequency was equal in early- and advanced-stage cancer groups. The risks versus benefits should be discussed with all patients who use marijuana. Seely D, Ennis JK, McDonell E, Zhao L. Naturopathic Oncology Care for Thoracic Cancers: A Practice Survey. Integr Cancer Ther 2018 Sep;17(3):793-805 PMID 29558830 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. Serce S, Ovayolu O, Pirbudak L, Ovayolu N. The Effect of Acupressure on Pain in Cancer Patients With Bone Metastasis: A Nonrandomized Controlled Trial. Integr Cancer Ther 2018 Sep;17(3):728-736 PMID 29649905 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 chi(2) 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. Shaffer KM, Garland SN, Mao JJ, Applebaum AJ. Insomnia among Cancer Caregivers: A Proposal for Tailored Cognitive Behavioral Therapy. J Psychother Integr 2018 Sep;28(3):275-291 PMID 30245560 Caregivers are relatives, friends, or partners who have a significant relationship with and provide assistance (i.e., physical, emotional) to a patient with often life-threatening, serious illnesses. Between 40 and 76 percent of caregivers for people with cancer experience sleep disturbance. This is thought to be due, in part, to the unique responsibilities, stressors, and compensatory behaviors endemic to caregiving that serve as precipitating and perpetuating factors of insomnia. Sleep disturbances are associated with significant alterations in one's mental and physical health. Once chronic, insomnia does not remit naturally. Cognitive-behavioral therapy for insomnia (CBT-I) is well-suited to address the multifaceted contributing factors unique to caregivers' sleep disturbance, yet only one intervention has tested a CBT-I informed intervention among cancer caregivers. Toward the goal of developing effective, tailored treatments for insomnia in caregivers, we address the distinct presentation of insomnia among cancer caregivers and describe key modifications to standard CBT-I that address these specific needs and enhance sensitivity and feasibility, modeled in a demonstrative case vignette. Future research must seek to provide a wide range of effective treatment options for this population, including internet-based, dyadic, and alternative integrative medicine treatments. Applicability of key modifications for caregivers of patients with other chronic illnesses is discussed. Establishing empirically-supported interventions for insomnia among cancer caregivers has the potential to enhance their quality of life and care provided, lead to improved bereavement outcomes, and attenuate the notable mental and physical health disparities present in this vulnerable population. Sikorskii A, Victorson D, O'Connor P, Hankin V, Safikhani A, Crane T, et al. PROMIS and legacy measures compared in a supportive care intervention for breast cancer patients and caregivers: Experience from a randomized trial. Psychooncology 2018 Sep;27(9):2265-2273 PMID 29956396 OBJECTIVE: Accurate and efficient measurement of patient-reported outcomes is key in cancer symptom management trials. The newer Patient Reported Outcomes Measurement Information System (PROMIS) and previously developed measures of similar conceptual content (legacy) are available to measure symptoms and functioning. This report compares the performance of two sets of measures, PROMIS and legacy, in a recently completed trial of a supportive care intervention that enrolled breast cancer patients and their friend or family caregivers. METHODS: Patient-caregiver dyads (N = 256) were randomized to either reflexology delivered by caregivers or usual care control. Post-intervention, PROMIS and legacy measures of symptoms and functioning were analyzed in relation to trial arm, while adjusting for baseline values. Responsiveness of the two sets of measures was assessed using effect sizes and P-values for the effect of trial arm on patients' and caregivers' symptom and functioning outcomes. RESULTS: Similar conclusions about intervention effects were found using PROMIS and legacy measures for pain, fatigue, sleep, anxiety, physical, and social functioning. Different conclusions were obtained for patient and caregiver depression: legacy measures indicated the efficacy of reflexology, while PROMIS depression measure did not. CONCLUSION: Evidence of similar responsiveness supports the use of either set of measures for symptoms and functioning in clinical and general populations. Differences between PROMIS and legacy measures of depression need to be considered when choosing instruments for use in trials of supportive care interventions and in clinical practice. Stan DL, Wahner-Roedler DL, Yost KJ, O'Byrne TJ, Branda ME, Leppin AL, et al. Absent and Discordant Electronic Health Record Documentation of Complementary and Alternative Medicine in Cancer Care. J Altern Complement Med 2018 Sep/Oct;24(9-10):988-995 PMID 30247970 OBJECTIVES: Many patients with cancer use complementary and alternative medicine (CAM), but the quality of CAM documentation in their electronic health records (EHRs) is unknown. The authors aimed to describe (i) the prevalence and types of CAM used after cancer diagnosis and the influence of oncologists on CAM use, as per patients' self-report, and (ii) the prevalence of CAM documentation in the EHR and its consistency with self-reported usage. DESIGN: Patient and provider surveys and chart review. SETTINGS/LOCATION: Medical oncology practices at one institution. SUBJECTS: Patients with cancer at oncologist visits. OUTCOME MEASURES: Patient self-reported rate of 3-month postvisit CAM use; provider EHR documentation of CAM use or discussion and its concordance with patient self-report. RESULTS: Among 327 patients enrolled, 248 responded to the 3-month postvisit survey. Of these, 158 reported CAM use after diagnosis (63.7%). CAM users were younger (p < 0.001) and had a higher percentage of women (p = 0.03) than nonusers. Modalities most commonly used were supplements (62.6%), special diets (38.6%), chiropractor (28.4%), and massage (28.4%). CAM was used to improve well-being (68.7%), manage adverse effects (35.5%), and fight cancer (22.9%). Oncologists suggested CAM in 22.5% of instances of use. CAM use/discussion was documented for 58.2% of self-reported CAM users. Of the documented modalities, EHR and self-report were concordant for only 8.2%. CAM documentation was associated with physician provider (p = 0.03), older patients (p = 0.01), and treatment with radiation (p = 0.03) or surgery (p = 0.001). After adjusting for other factors, patients with breast cancer or "other" tumor category were four times more likely than patients with gastrointestinal cancer to have CAM use documentation (odds ratio [95% confidence interval]: 4.41 [1.48-13.10]; 3.76 [1.42-9.99], respectively). CONCLUSIONS: Most patients with cancer use CAM after diagnosis, yet EHR documentation is complete for very few. Oncologists should inquire about, document, and discuss CAM benefits and harm or refer patients to CAM specialists. Sun L, Mao JJ, Vertosick E, Seluzicki C, Yang Y. Evaluating Cancer Patients' Expectations and Barriers Toward Traditional Chinese Medicine Utilization in China: A Patient-Support Group-Based Cross-Sectional Survey. Integr Cancer Ther 2018 Sep;17(3):885-893 PMID 29888609 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