Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment.

Answer questions and earn CME/CNE Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194-232. © 2017 American Cancer Society.

Integrating herbal medicine into oncology care delivery: development, implementation, and evaluation of a novel program.

OBJECTIVE: To evaluate the feasibility of a novel program facilitating patient-provider communication about appropriate use of herbal medicine at a large academic cancer center and its impact on patient wellbeing. METHODS: In the Herbal Oncology Program (HOP), integrative medicine providers counseled patients about unmet symptom needs and prescribed traditional Chinese medicine (TCM) herbs when indicated, taking into consideration the clinical context, patient preference, and research evidence. To evaluate the feasibility and outcomes, we performed a retrospective analysis using medical record data (symptoms and other concerns that motivated patients to seek herbal products, types and numbers of dispensed TCM herbs, and demographic characteristics). We also conducted a survey to assess patient experience and satisfaction. RESULTS: All 851 participants were outpatients, with 712 (84%) in active treatment. HOP dispensed 1266 herbal prescriptions for a range of symptoms, most commonly GI symptoms (467, 37%); pain (353, 28%); and treatment-related fatigue, sleep, and mood disorders (346, 27%). Of 269 patients invited to the survey, 107 (40%) completed it. A majority of respondents 70.9% (73/103) were satisfied with the effectiveness of dispensed herbs in relieving their symptoms, and few 6.7% (7/104) had experienced mild adverse events that resolved after discontinuing herbal use. CONCLUSIONS: The study's findings support the feasibility of integrating herbal medicine into an academic oncology setting. Patient satisfaction with HOP was high, with limited adverse events. The patterns of herbal prescriptions in HOP suggest future areas for clinical research to strengthen the evidence base around safe and effective use.

Education Competencies for Integrative Oncology-Results of a Systematic Review and an International and Interprofessional Consensus Procedure.

Integrative oncology is a burgeoning field and typically provided by a multiprofessional team. To ensure cancer patients receive effective, appropriate, and safe care, health professionals providing integrative cancer care should have a certain set of competencies. The aim of this project was to define core competencies for different health professions involved in integrative oncology. The project consisted of two phases. A systematic literature review on published competencies was performed, and the results informed an international and interprofessional consensus procedure. The second phase consisted of three rounds of consensus procedure and included 28 experts representing 7 different professions (medical doctors, psychologists, nurses, naturopathic doctors, traditional Chinese medicine practitioners, yoga practitioners, patient navigators) as well as patient advocates, public health experts, and members of the Society for Integrative Oncology. A total of 40 integrative medicine competencies were identified in the literature review. These were further complemented by 18 core oncology competencies. The final round of the consensus procedure yielded 37 core competencies in the following categories: knowledge (n = 11), skills (n = 17), and abilities (n = 9). There was an agreement that these competencies are relevant for all participating professions. The integrative oncology core competencies combine both fundamental oncology knowledge and integrative medicine competencies that are necessary to provide effective and safe integrative oncology care for cancer patients. They can be used as a starting point for developing profession-specific learning objectives and to establish integrative oncology education and training programs to meet the needs of cancer patients and health professionals.

Fear of analgesic side effects predicts preference for acupuncture: a cross-sectional study of cancer patients with pain in the USA.

PURPOSE: Approximately one in two cancer patients globally are under-treated for pain. Opioids and other analgesics represent the mainstay of cancer pain management; however, barriers to their use are well-documented. We evaluated whether acupuncture would be a preferable treatment option among cancer patients with attitudinal barriers to pharmacological pain management. METHODS: We conducted a cross-sectional survey of cancer patients at a tertiary urban cancer center and eleven suburban/rural hospitals in the Northeastern United States. We assessed attitudinal barriers to pharmacological pain management with the Barriers Questionnaire (BQ-13). The BQ-13 consists of two subscales: pain management beliefs and analgesic side effects. We also asked patients whether they prefer acupuncture, analgesics, or have no preference between these two modalities for pain management. Covariates included sociodemographics, clinical characteristics, and attitudes/beliefs about acupuncture. We used logistic regression to examine the association between attitudinal barriers and acupuncture preference. RESULTS: Among 628 patients, 197 (31.4%) preferred acupuncture for pain management, 146 (23.3%) preferred analgesics, and 285 (45.4%) had no preference. The highest reported attitudinal barriers were fear of addiction and fear of analgesic-associated constipation and nausea. Adjusting for covariates, we found that attitudinal barriers related to fear of analgesic side effects were significantly associated with acupuncture preference (adjusted odds ratio [AOR] 1.45, 95% confidence interval [CI] 1.17-1.81), but barriers related to pain management beliefs were not (AOR 1.17, 95% CI 0.91-1.51). Attitudes/beliefs about acupuncture (i.e., greater expected benefits, fewer perceived barriers, and more positive social norms) and female gender also predicted acupuncture preference, whereas race and educational status did not. CONCLUSION: Acupuncture may be a preferable treatment option among cancer patients at risk of inadequately controlled pain due to fear of analgesic side effects. Evidence-based integration of acupuncture and analgesics, guided by patient treatment preferences, represents an essential aspect of patient-centered care and has potential to address unmet cancer pain management needs.

Reduction of Opioid Use by Acupuncture in Patients Undergoing Hematopoietic Stem Cell Transplantation: Secondary Analysis of a Randomized, Sham-Controlled Trial.

OBJECTIVE: To evaluate acupuncture as a nonpharmacologic intervention for pain management in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan chemotherapy and autologous peripheral blood HSCT were randomized to receive either true (TA) or sham acupuncture (SA) once daily for five days starting on the day after chemotherapy. Use of pain medications and pain scores were assessed at baseline and at days 5, 15, and 30 after transplantation. RESULTS: Among 60 evaluable subjects, the SA group (vs TA) had greater than five times odds of increasing pain medication use from baseline. Among patients who were opioid nonusers at baseline, all 15 patients in the TA group remained free from opioid use at the end of the study. In contrast, 20% of those in the SA group (four of the 20 patients) started to use opioids after chemotherapy and stem cell infusion (day 5) and 40% (eight of the 20) had become opioid users by day 30 after HSCT (Fisher exact test P = 0.006). Among patients who were taking opioids at baseline, 14% in the TA group vs 10% in the SA group increased opioid intake at day 5, and 21% (TA) vs 30% (SA) at day 30 (P = 0.86). CONCLUSIONS: Acupuncture appears to significantly reduce the need for pain medications during HSCT and the number of post-HSCT opioid users among baseline opioid nonusers. It warrants further studies as an opioid-sparing intervention for pain in HSCT patients.

Virtual Reality for Pediatric Needle Procedural Pain: Two Randomized Clinical Trials.

OBJECTIVE: To assess the efficacy and safety of a virtual reality distraction for needle pain in 2 common hospital settings: the emergency department (ED) and outpatient pathology (ie, outpatient laboratory). The control was standard of care (SOC) practice. STUDY DESIGN: In 2 clinical trials, we randomized children aged 4-11 years undergoing venous needle procedures to virtual reality or SOC at 2 tertiary Australian hospitals. In the first study, we enrolled children in the ED requiring intravenous cannulation or venipuncture. In the second, we enrolled children in outpatient pathology requiring venipuncture. In the ED, 64 children were assigned to virtual reality and 59 to SOC. In pathology, 63 children were assigned to virtual reality and 68 to SOC; 2 children withdrew assent in the SOC arm, leaving 66. The primary endpoint was change from baseline pain between virtual reality and SOC on child-rated Faces Pain Scale-Revised. RESULTS: In the ED, there was no change in pain from baseline with SOC, whereas virtual reality produced a significant reduction in pain (between-group difference, -1.78; 95% CI, -3.24 to -0.317; P = .018). In pathology, both groups experienced an increase in pain from baseline, but this was significantly less in the virtual reality group (between-group difference, -1.39; 95% CI, -2.68 to -0.11; P = .034). Across both studies, 10 participants experienced minor adverse events, equally distributed between virtual reality/SOC; none required pharmacotherapy. CONCLUSIONS: In children aged 4-11 years of age undergoing intravenous cannulation or venipuncture, virtual reality was efficacious in decreasing pain and was safe. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry: ACTRN12617000285358p.

Pharmacovigilance of Alternative Medications in the Cancer Setting.

With the increase in utilization of alternative medications to manage cancer treatment-related side effects, pharmacovigilance of alternative drug therapies, specifically herbal supplements, has become of increasing importance in the oncologic setting. This chapter focuses on the pharmacovigilance of herbal supplements in the setting of cancer drug therapy and explores national and international drug policies that have been employed to mitigate adverse herbal supplement events (AHEs). This chapter examines common drug-herbal supplement interactions, discusses the mechanisms behind these interactions, and investigates several common pharmacovigilance reporting methods clinicians can use to report adverse events. This chapter will also describe policies and strategies that can be employed to monitor use of these alternative drug therapies, and examines global harmonization efforts to reduce AHEs in the cancer setting. The safety of herbal medicines has emerged as an international public health priority, and we explore how oncology providers may directly apply the knowledge garnered herein to help guide their clinical management of oncology patients utilizing alternative medications.

Understanding the Benefits of Acupuncture Treatment for Cancer Pain Management.

This article summarizes the current evidence regarding the use of acupuncture for pain management in cancer patients. It includes a description of how acupuncture is thought to work and what the intervention entails, data on acupuncture for managing pain caused by cancer or by cancer treatment (radiation, chemotherapy, endocrine therapy), how acupuncture is practiced in the US medical system, discussion of safety issues, and practical tips on how to integrate acupuncture into cancer care.

Acupuncture for reduction of symptom burden in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation: a randomized sham-controlled trial.

PURPOSE: Hematopoietic stem cell transplantation (HCT) is potentially curative for a number of hematologic malignancies, but is associated with high symptom burden. We conducted a randomized sham-controlled trial (RCT) to evaluate efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan followed by autologous HCT (AHCT) were randomized to receive either true or sham acupuncture once daily for 5 days starting the day after chemotherapy. Patients and clinical evaluators, but not acupuncturists, were blinded to group assignment. Symptom burden, the primary outcome was assessed with the MD Anderson Symptom Inventory (MDASI) at baseline, during transplantation, and at 15 and 30 days post transplantation. RESULTS: Among 60 participants, true acupuncture produced nonsignificant reductions in overall MDASI core symptom scores and symptom interference scores during transplantation (P = .4 and .3, respectively), at 15 days (P = .10 and .3), and at 30 days posttransplantation (P = .2 and .4) relative to sham. However, true acupuncture was significantly more efficacious in reducing nausea, lack of appetite, and drowsiness at 15 days (P = .042, .025, and .010, respectively). Patients receiving sham acupuncture were more likely to increase pain medication use posttransplantation (odds ratio 5.31, P = .017). CONCLUSIONS: Acupuncture was well tolerated with few attributable adverse events. True acupuncture may prevent escalation of symptoms including nausea, lack of appetite, and drowsiness experienced by patients undergoing AHCT, and reduce the use of pain medications. These findings need to be confirmed in a future definitive study. TRIAL REGISTRATION: NCT01811862.

Traditional Oriental Herbal Medicine and Natural Killer Cells for Cancer Patients: A Systematic Review and Meta-analysis.

Traditional oriental herbal medicine (HM) is used by cancer patients to improve immunity. Natural killer (NK) cells are associated with development and progression of tumor and survival of cancer patients. This literature review examined randomized controlled trials (RCTs) in four electronic databases until October 2015 to evaluate the effects of oral HM on NK cells in cancer patients. Data were pooled and computed in a meta-analysis. The methodological quality was assessed according to the Cochrane risk of bias tool. Sixteen RCTs involving 1326 cancer patients were identified. Combination of HM and conventional treatment was associated with significantly higher level of NK cells compared with conventional cancer treatments (standardized mean difference, 1.218; 95% confidence interval 0.719-1.717; p < 0.001). Eight RCTs reported statistically significant improvements in the proportions or activity of NK cells in patient groups who received both HM and conventional treatment compared with patients who received conventional treatment alone, while eight RCTs reported no statistically significant differences between the two groups. Studies (n = 16) included in this review had insufficient quality of evidence with unclear (n = 1) and high (n = 15) values of the risk of bias. Although traditional oriental HM may have the positive effects on preserving the level of NK cells in cancer patients receiving conventional treatments, current evidence is inconclusive because of lack of high-quality evidence. Copyright © 2017 John Wiley & Sons, Ltd.

Development of a Suicidal Ideation Detection Tool for Primary Healthcare Settings: Using Open Access Online Psychosocial Data.

BACKGROUND: Suicidal patients often visit healthcare professionals in their last month before suicide, but medical practitioners are unlikely to raise the issue of suicide with patients because of time constraints and uncertainty regarding an appropriate approach. INTRODUCTION: A brief tool called the e-PASS Suicidal Ideation Detector (eSID) was developed for medical practitioners to help detect the presence of suicidal ideation (SI) in their clients. If SI is detected, the system alerts medical practitioners to address this issue with a client. The eSID tool was developed due to the absence of an easy-to-use, evidence-based SI detection tool for general practice. MATERIAL AND METHODS: The tool was developed using binary logistic regression analyses of data provided by clients accessing an online psychological assessment function. Ten primary healthcare professionals provided advice regarding the use of the tool. RESULTS: The analysis identified eleven factors in addition to the Kessler-6 for inclusion in the model used to predict the probability of recent SI. The model performed well across gender and age groups 18-64 (AUR 0.834, 95% CI 0.828-0.841, N = 16,703). Healthcare professionals were interviewed; they recommended that the tool be incorporated into existing medical software systems and that additional resources be supplied, tailored to the level of risk identified. CONCLUSION: The eSID is expected to trigger risk assessments by healthcare professionals when this is necessary. Initial reactions of healthcare professionals to the tool were favorable, but further testing and in situ development are required.

Novel insights into development of diabetic bladder disorder provided by metabolomic analysis of the rat nondiabetic and diabetic detrusor and urothelial layer.

There are at present no published studies providing a global overview of changes in bladder metabolism resulting from diabetes. Such studies have the potential to provide mechanistic insight into the development of diabetic bladder disorder (DBD). In the present study, we compared the metabolome of detrusor and urothelial layer in a 1-mo streptozotocin-induced rat model of type 1 diabetes with nondiabetic controls. Our studies revealed that diabetes caused both common and differential changes in the detrusor and urothelial layer's metabolome. Diabetes resulted in similar changes in the levels of previously described diabetic markers in both tissues, such as glucose, lactate, 2-hydroxybutyrate, branched-chain amino acid degradation products, bile acids, and 1,5-anhydroglucitol, as well as markers of oxidative stress. In the detrusor (but not the urothelial layer), diabetes caused activation of the pentose-phosphate and polyol pathways, concomitant with a reduction in the TCA cycle and ß-oxidation. Changes in detrusor energy-generating pathways resulted in an accumulation of sorbitol that, through generation of advanced glycation end products, is likely to play a central role in the development of DBD. In the diabetic urothelial layer there was decreased flux of glucose via glycolysis and changes in lipid metabolism, particularly prostaglandin synthesis, which also potentially contributes to detrusor dysfunction.

ESR and X-ray Structure Investigations on the Binding and Mechanism of Inhibition of the Native State of Myeloperoxidase with Low Molecular Weight Fragments.

As an early visitor to the injured loci, neutrophil-derived human Myeloperoxidase (hMPO) offers an attractive protein target to modulate the inflammation of the host tissue through suitable inhibitors. We describe a novel methodology of using low temperature ESR spectroscopy (6 K) and FAST™ technology to screen a diverse series of small molecules that inhibit the peroxidase function through reversible binding to the native state of MPO. Our initial efforts to profile molecules on the inhibition of MPO-initiated nitration of the Apo-A1 peptide (AEYHAKATEHL) assay showed several potent (with sub-micro molar IC50s) but spurious inhibitors that either do not bind to the heme pocket in the enzyme or retain high (>50 %) anti oxidant potential. Such molecules when taken forward for X-ray did not yield inhibitor-bound co-crystals. We then used ESR to confirm direct binding to the native state enzyme, by measuring the binding-induced shift in the electronic parameter g to rank order the molecules. Molecules with a higher rank order-those with g-shift Rrelative ≥15-yielded well-formed protein-bound crystals (n = 33 structures). The co-crystal structure with the LSN217331 inhibitor reveals that the chlorophenyl group projects away from the heme along the edges of the Phe366 and Phe407 side chain phenyl rings thereby sterically restricting the access to the heme by the substrates like H2O2. Both ESR and antioxidant screens were used to derive the mechanism of action (reversibility, competitive substrate inhibition, and percent antioxidant potential). In conclusion, our results point to a viable path forward to target the native state of MPO to tame local inflammation.

A phase II, randomized, controlled trial of acupuncture for reduction of Postcolectomy Ileus.

PURPOSE: Postoperative ileus (POI) prolongs hospital stay and increases risk of postoperative complications. We conducted a randomized, sham-controlled trial to evaluate whether acupuncture reduces POI more effectively than sham acupuncture. METHODS: Colon cancer patients undergoing elective colectomy were randomized to receive 30 min of true or sham acupuncture twice daily during their first 3 postoperative days. GI-3 (the later of the following two events: time that the patient first tolerated solid food, AND time that the patient first passed flatus OR a bowel movement) and GI-2 (the later of the following two events: time patient first tolerated solid food AND time patient first passed a bowel movement) were determined. Pain, nausea, vomiting, and use of pain medications were evaluated daily for the first 3 postoperative days. RESULTS: Ninety patients were randomized. Eighty-one received the allocated intervention: 39 in the true acupuncture group and 42 in the sham acupuncture group, all evaluated for the primary endpoint. The mean time to GI-3 was 149 h [standard deviation (SD) 71 h] and 146 (SD 62 h) after surgery for the acupuncture group and the sham acupuncture group (difference between means -2 h; 95 % confidence interval -31, 26; p = 0.9). No significant differences were found between groups for secondary endpoints. CONCLUSIONS: True acupuncture as provided in this study did not reduce POI more significantly than sham acupuncture. The study was limited by a standard deviation much larger than expected, suggesting that a study with a larger sample size might be required.

Acupuncture for the treatment of post-chemotherapy chronic fatigue: a randomized, blinded, sham-controlled trial.

PURPOSE: Many cancer patients experience persistent fatigue after the completion of chemotherapy. A previous single-arm study provided evidence for an effect of acupuncture in this population. We conducted a randomized controlled trial to determine whether acupuncture reduces post-chemotherapy chronic fatigue more effectively than sham acupuncture. METHODS: Cancer patients reporting significant fatigue persisting for at least 2 months following the completion of chemotherapy were randomized to receive once weekly true or sham acupuncture for 6 weeks. Fatigue was evaluated before and after treatment using the Brief Fatigue Inventory (BFI, the primary endpoint). Secondary endpoints included the Hospital Anxiety and Depression Scale (HADS) and Functional Assessment of Cancer Treatment-General (FACT-G) scores. RESULTS: One hundred one patients were randomized with 74 (34 true acupuncture; 40 sham control) evaluated for the primary endpoint. BFI scores fell by about one point between baseline and follow-up in both groups with no statistically significant difference between groups. HADS and FACT-G scores also improved in both groups, but there was no significant difference between groups. Patients in the sham acupuncture group crossed over to receive true acupuncture in week 7. No long-term reduction of fatigue scores was observed at the 6-month evaluation. CONCLUSIONS: True acupuncture as provided in this study did not reduce post-chemotherapy chronic fatigue more than did sham acupuncture. The study is limited by the number of patients lost to follow-up. We also cannot exclude the possibility that a more intensive treatment regimen may be more effective.

Acupuncture improves certain aspects of sleep in hematopoietic stem cell transplantation patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: High-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) is associated with a high symptom burden including sleep disturbance. Here we present the results of a secondary analysis of a randomized, sham-controlled trial assessing the effect of acupuncture on sleep quality during HSCT. METHODS: Adult multiple myeloma patients undergoing inpatient and outpatient autologous HSCT were randomized and blinded to receive either true or sham acupuncture (by licensed acupuncturists) once daily for 5 days starting the day after chemotherapy. Sleep onset, total sleep time, sleep efficiency percentage and sleep-onset latency time were assessed using an actigraphy-based sleep monitor. A multivariate regression analysis was conducted to compare the average area-under-the-curve of five acupuncture intervention days for each sleep outcome between groups, adjusted by baseline score and inpatient or outpatient chemotherapy stratum. RESULTS: Over 32 months, 63 patients were enrolled. Participants undergoing true acupuncture experienced a significant improvement in sleep efficiency when compared to sham (-6.70, 95% CI -13.15, -0.25, p = 0.042). Subgroup analysis showed that the improvement was more prominent in the inpatient setting (-9.62, 95% CI -18.76, -0.47; p = 0.040). True acupuncture tended to improve wake time after sleep onset (WASO; -10.95, p = 0.054). Between-group differences in other sleep related variables were not statistically significant. CONCLUSION: Our data suggest that true acupuncture may improve certain aspects of sleep, including sleep efficiency and possibly WASO, in multiple myeloma patients undergoing HSCT. By studying patient reported outcomes in future larger scale studies, acupuncture's role in improving sleep quality during HSCT treatment could be further elucidated. TRIAL REGISTRATION NUMBER: NCT01811862 (ClinicalTrials.gov).

Integrin ß3 directly inhibits the Gα13-p115RhoGEF interaction to regulate G protein signaling and platelet exocytosis.

The integrins and G protein-coupled receptors are both fundamental in cell biology. The cross talk between these two, however, is unclear. Here we show that ß3 integrins negatively regulate G protein-coupled signaling by directly inhibiting the Gα13-p115RhoGEF interaction. Furthermore, whereas ß3 deficiency or integrin antagonists inhibit integrin-dependent platelet aggregation and exocytosis (granule secretion), they enhance G protein-coupled RhoA activation and integrin-independent secretion. In contrast, a ß3-derived Gα13-binding peptide or Gα13 knockout inhibits G protein-coupled RhoA activation and both integrin-independent and dependent platelet secretion without affecting primary platelet aggregation. In a mouse model of myocardial ischemia/reperfusion injury in vivo, the ß3-derived Gα13-binding peptide inhibits platelet secretion of granule constituents, which exacerbates inflammation and ischemia/reperfusion injury. These data establish crucial integrin-G protein crosstalk, providing a rationale for therapeutic approaches that inhibit exocytosis in platelets and possibly other cells without adverse effects associated with loss of cell adhesion.

Acupuncture vs Massage for Pain in Patients Living With Advanced Cancer: The IMPACT Randomized Clinical Trial.

Importance: Pain is challenging for patients with advanced cancer. While recent guidelines recommend acupuncture and massage for cancer pain, their comparative effectiveness is unknown. Objective: To compare the effects of acupuncture and massage on musculoskeletal pain among patients with advanced cancer. Design, Setting, and Participants: A multicenter pragmatic randomized clinical trial was conducted at US cancer care centers consisting of a northeastern comprehensive cancer center and a southeastern cancer institute from September 19, 2019, through February 23, 2022. The principal investigator and study statisticians were blinded to treatment assignments. The duration of follow-up was 26 weeks. Intention-to-treat analyses were performed (linear mixed models). Participants included patients with advanced cancer with moderate to severe pain and clinician-estimated life expectancy of 6 months or more. Patient recruitment strategy was multipronged (eg, patient database queries, mailings, referrals, community outreach). Eligible patients had English or Spanish as their first language, were older than 18 years, and had a Karnofsky score greater than or equal to 60 (range, 0-100; higher scores indicating less functional impairment). Interventions: Weekly acupuncture or massage for 10 weeks with monthly booster sessions up to 26 weeks. Main Outcomes and Measures: The primary end point was the change in worst pain intensity score from baseline to 26 weeks. The secondary outcomes included fatigue, insomnia, and quality of life. The Brief Pain Inventory (range, 0-10; higher numbers indicate worse pain intensity or interference) was used to measure the primary outcome. The secondary outcomes included fatigue, insomnia, and quality of life. Results: A total of 298 participants were enrolled (mean [SD] age, 58.7 [14.1] years, 200 [67.1%] were women, 33 [11.1%] Black, 220 [74.1%] White, 46 [15.4%] Hispanic, and 78.5% with solid tumors). The mean (SD) baseline worst pain score was 6.9 (1.5). During 26 weeks, acupuncture reduced the worst pain score, with a mean change of -2.53 (95% CI, -2.92 to -2.15) points, and massage reduced the Brief Pain Inventory worst pain score, with a mean change of -3.01 (95% CI, -3.38 to -2.63) points; the between-group difference was not significant (-0.48; 95% CI, -0.98 to 0.03; P = .07). Both treatments also improved fatigue, insomnia, and quality of life without significant between-group differences. Adverse events were mild and included bruising (6.5% of patients receiving acupuncture) and transient soreness (15.1% patients receiving massage). Conclusions and Relevance: In this randomized clinical trial among patients with advanced cancer, both acupuncture and massage were associated with pain reduction and improved fatigue, insomnia, and quality of life over 26 weeks; however, there was no significant different between the treatments. More research is needed to evaluate how best to integrate these approaches into pain treatment to optimize symptom management for the growing population of people living with advanced cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT04095234.