Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: A systematic review with network meta-analysis.

Aromatase inhibitor-induced arthralgia (AIA) contributes to poor adherence of aromatase inhibitor therapies in patients with breast cancer. A systematic review using network meta-analysis (NMA) was conducted to examine the clinical effectiveness of multiple therapies and rank probabilities for the management of AIA. Randomized controlled trials (RCTs) assessing treatments for AIA in postmenopausal women with stage 0-III hormone receptor-positive breast cancer were searched from inception to October 2021. The main NMA involved 1516 participants from 17 RCTs. Acupuncture was the highest ranked intervention to improve pain intensity followed by sham acupuncture, multicomponent herbal medicine, exercise, duloxetine, vitamin D, omega-3 fatty acids, physical therapy, testosterone, and inactive controls. Single natural products were inferior to controls. The current review provides new insights into the management of AIA in breast cancer survivors for increased survival and can be utilized to make evidence-based decisions regarding treatment.

Critical evaluation of reporting quality of network meta-analyses assessing the effectiveness of acupuncture.

BACKGROUND: and purpose: Network meta-analyses (NMAs) comparing the effectiveness of multiple acupuncture have been published but the key concepts underlying NMAs have not been properly reported. This critical evaluation aims to assess the completeness of reporting for NMAs of acupuncture to enhance the validity of findings. MATERIALS AND METHODS: Five databases were searched. The characteristics and reporting quality based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension Statement for reporting of NMA (PRISMA-NMA) were evaluated. NMAs were categorized into two groups according to the publication date, reporting guideline, and intervention. The group differences and correlation coefficients were calculated. RESULTS: Forty-two NMAs of acupuncture were evaluated. The reporting quality for new items in the key concepts of NMAs was low (median 70.0 % (interquartile range 60.0-80.0)). While the issue of consistency was well reported, the assumption of transitivity and network geometry showed poor reporting. Seventeen studies that followed the PRISMA-NMA guideline showed a higher reporting rate for essential concepts of NMA. The recency of publication did not guarantee clear reporting. CONCLUSION: The reporting quality of NMAs of acupuncture was low. The researchers should follow the guidelines on the reporting of NMAs.

The Effects of Tai Chi and Qigong on Immune Responses: A Systematic Review and Meta-Analysis.

Background: Effective preventative health interventions are essential to maintain well-being among healthcare professionals and the public, especially during times of health crises. Several studies have suggested that Tai Chi and Qigong (TQ) have positive impacts on the immune system and its response to inflammation. The aim of this review is to evaluate the current evidence of the effects of TQ on these parameters. Methods: Electronic searches were conducted on databases (Medline, PubMed, Embase and ScienceDirect). Searches were performed using the following keywords: "Tai Chi or Qigong" and "immune system, immune function, immunity, Immun*, inflammation and cytokines". Studies published as full-text randomized controlled trials (RCTs) in English were included. Estimates of change in the levels of immune cells and inflammatory biomarkers were pooled using a random-effects meta-analysis where randomised comparisons were available for TQ versus active controls and TQ versus non-active controls. Results: Nineteen RCTs were selected for review with a total of 1686 participants and a range of 32 to 252 participants within the studies. Overall, a random-effects meta-analysis found that, compared with control conditions, TQ has a significant small effect of increasing the levels of immune cells (SMD, 0.28; 95% CI, 0.13 to 0.43, p = 0.00), I2 = 45%, but not a significant effect on reducing the levels of inflammation (SMD, -0.15; 95% CI, -0.39 to 0.09, p = 0.21), I2 = 85%, as measured by the systemic inflammation biomarker C-reactive protein (CRP) and cell mediated biomarker cytokines. This difference in results is due to the bidirectional regulation of cytokines. An overall risk of bias assessment found three RCTs with a low risk of bias, six RCTs with some concerns of bias, and ten RCTs with a high risk of bias. Conclusions: Current evidence indicates that practising TQ has a physiologic impact on immune system functioning and inflammatory responses. Rigorous studies are needed to guide clinical guidelines and harness the power of TQ to promote health and wellbeing.

Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Aromatase inhibitor-induced arthralgia (AIA) is a major adverse event of aromatase inhibitors (AIs) and leads to premature discontinuation of AI therapy in breast cancer patients. The objective of this protocol for a systematic review and network meta-analysis (NMA) is to provide the methodology to compare the change in pain intensity between different AIA treatments and demonstrate the rank probabilities for different treatments by combining all available direct and indirect evidence. METHODS AND ANALYSIS: PubMed, the Cochrane Controlled Register of Trials (CENTRAL), EMBASE, Web of Science and ClinicalTrials.gov will be searched to identify publications in English from inception to November 2019. We will include randomised controlled trials (RCTs) assessing the effects of different treatments for AIA in postmenopausal women with stage 0-III hormone receptor-positive breast cancer. The primary endpoints will be the change in patient-reported pain intensity from baseline to post-treatment. The number of adverse events will be presented as a secondary outcome.Both pairwise meta-analysis and NMA with the Frequentist approach will be conducted. We will demonstrate summary estimates with forest plots in meta-analysis and direct and mixed evidence with a ranking of the treatments as the P-score in NMA. The revised Cochrane risk-of-bias tool for randomised trials will be used to assess the methodological quality within individual RCTs. The quality of evidence will be assessed. ETHICS AND DISSEMINATION: As this review does not involve individual patients, ethical approval is not required. The results of this systematic review and NMA will be published in a peer-reviewed journal. This review will provide valuable information on AIA therapeutic options for clinicians, health practitioners and breast cancer survivors. PROSPERO REGISTRATION NUMBER: CRD42019136967.

Integrative cancer treatment may have a survival benefit in patients with lung cancer: A retrospective cohort study from an integrative cancer center in Korea.

Integrative oncology is being increasingly adopted in mainstream cancer care to strengthen anticancer effects and to control cancer-related symptoms.The objective of this study is to identify the characteristics of patients with lung cancer treated at an integrative cancer center in Korea and to determine the effects of integrative cancer treatment (ICT) on survival outcome in traditional Korean medicine (TKM).We reviewed medical records for lung cancer patients who visited a single integrative clinical setting, East-West Cancer Center, between January 2014 and December 2015. We classified the patients into groups according to their ICT and whether or not they underwent anticancer traditional Korean Medicine treatment with a multiherbal formula containing Panax notoginseng Radix, Cordyceps militaris, P ginseng C.A.Mey., and Boswellia carterii BIRDWOOD (HangAmDan-B), with a herbal formula containing Rhus verniciflua Stoke, or with cultivated wild ginseng pharmacopuncture. A descriptive analysis of the characteristics and a survival analysis using the Kaplan-Meier curves with log rank test and a Cox proportional hazard model were performed.A total of 91 patients were included, and the majority had advanced-stage cancer. Of those patients, 45.1% were in the mono-TKM group and 39.6% were integrative group. Patients with advanced stage had significantly higher mortality than patients with early stage (crude hazard ratio [HR]: 4.41, 95% confidence interval [CI]: 1.56-12.5; adjusted HR: 6.31, 95% CI: 1.24-32.1). In the unadjusted model, for patients in the integrative group, the mortality rate was reduced by 50% compared to mono-TKM group with statistical significance. After adjusting confounders, the mortality rate of integrative group was reduced by 6% compared to mono-TKM group, suggesting positive effect on survival probability of integrative group.The results suggest that integration of TKM and conventional cancer treatment may have survival benefits in patients with lung cancer. Even though this study has limitations including heterogeneity between treatment groups, the study results suggest that ICT has positive effect on survival probability. To clarify the impacts of ICT for lung cancer and other cancers on survival outcome, further prospective study with a rigorous study design is required in multiclinical setting.

The effectiveness of anticancer traditional Korean medicine treatment on the survival in patients with lung, breast, gastric, colorectal, hepatic, uterine, or ovarian cancer: A prospective cohort study protocol.

Although anticancer traditional Korean medicine treatment (ACTKMT) is widely applied to patients with cancer together with, or in place of, conventional cancer treatment in Korea, the cohort evidence on its clinical effects is lacking. Therefore, this prospective cohort study is designed to evaluate the effect of ACTKMT on the survival and the clinical outcomes for patients being treated at an integrative oncology clinic.This is a single center, prospective cohort study of patients within 1 year after the diagnosis of primary lung, breast, gastric, colorectal, hepatic, uterine, or ovarian cancer. The event-free survival, disease-free survival/progression-free survival, the overall survival, the results of blood tests, and telomere-length information will be compared between patients receiving and patients not receiving a key ACTKMT (HangAmDan-B1, Geonchil-jung, and/or cultivated wild ginseng pharmacopuncture), and the correlation between the use of the key ACTKMT and the prognosis will be identified considering other risk factors.This study has received ethical approval from the Institutional Review Board, Dunsan Korean Medicine Hospital of Daejeon University (No. DJDSKH-16-BM-09). The results of this study will be published in a peer-reviewed journal.Clinical Research Information Service: KCT0002160.

The evaluation of changes in peripheral neuropathy and quality-of-life using low-frequency electrostimulation in patients treated with chemotherapy for breast cancer: a study protocol.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and sometimes irreversible neurotoxic symptom that occurs in 30-40% of chemotherapy-treated cancer patients. CIPN negatively affects both the patient's abilities to perform daily activities and their health-related quality of life (HRQOL) after chemotherapy treatment. Although this neuropathy has been treated with duloxetine and/or gabapentin, limited therapeutic benefits have been reported, thereby necessitating the development of an integrated approach that combines pharmacological management and complementary methods such as acupuncture and electric nerve stimulation. Therefore, this study is designed to examine the effect of a portable, low-frequency electrostimulation (ES) device on CIPN symptoms and HRQOL of female patients diagnosed with CIPN immediately after chemotherapy for breast cancer. METHODS: This study is a single-center, randomized, placebo-controlled trial with two parallel groups and a 2-week follow-up. We will enroll 80 breast cancer patients who are newly diagnosed with CIPN after chemotherapy. Duloxetine or pregabalin will be prescribed to all participants from the initial assessment. Half of the patients will be assigned into the experimental group and the other half to the control group. The CarebandR (Piomed Inc., Seoul, Korea), a wearable wristband that generates low-frequency electrostimulation, will be administered only to the experimental group. Electrostimulation will be administered on the unilateral PC6 acupoint. A numerical rating scale will be used to assess the overall intensity of CIPN symptoms. The key secondary outcome variables include patient-reported CIPN symptom distress tested by a self-rated questionnaire, physician-rated symptom severity assessed by the Total Neuropathy Score, and HRQOL. DISCUSSION: It is expected that the combination of a low-frequency electrostimulation device and pharmacological intervention (duloxetine or pregabalin) will produce synergistic effects in breast cancer patients with CIPN after treatment. To our knowledge, this is the first study to investigate the beneficial effect of a new integrated approach for CIPN management after breast cancer treatment. The study findings can expand our knowledge and understanding of the occurrence of CIPN and the efficacy of integrated intervention efforts to ameliorate CIPN symptoms. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea, ID: KCT0002357 . Registered retrospectively on 13 June 2017.

Benefit of Adjuvant Traditional Herbal Medicine With Chemotherapy for Resectable Gastric Cancer.

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.

Correlation Between Natural Killer Cell Activity and Systemic Inflammatory Markers for Heterogeneous Cancer Patients Treated With Wheel Balance Cancer Therapy.

BACKGROUND AND OBJECTIVE: Natural killer (NK) cells are known to have an effect on the prevention of tumorigenesis for the initial cancer, as well as the metastatic cancer. For the past several years, the relationship between cancer and inflammation has been actively studied in preclinical and clinical settings, but there are no reports on alterations in and correlation for NK cell activity (NKA) and systemic inflammatory markers. Accordingly, this study aimed to measure correlation between NKA and the levels of other systemic inflammatory markers in patients with gastric, breast, and pancreatic cancer who received Wheel Balance Cancer Therapy (WBCT). METHODS: Forty-two electronic charts of patients with gastric, breast, and pancreatic cancer treated with WBCT from February 1, 2015 to September 30, 2015, were reviewed retrospectively. These charts were statistically analyzed, looking for alterations of and correlation for NKA and the expressions of systemic inflammatory markers. RESULTS: Patients with a NKA of under 300 pg/mL at admission showed significantly higher erythrocyte sedimentation rate (ESR) and neutrophil-to-lymphocyte ratio (NLR) values and decreasing NLR values due to WBCT than patients with an NKA greater than 300 pg/mL. As a result of the correlation analysis between NKA and the levels of the systemic inflammatory markers, NKA showed significant negative correlation with NLR, ESR, and fibrinogen values. CONCLUSIONS: Negative correlation was identified between NKA and NLR, NKA and ESR, and NKA and fibrinogen in patients with heterogeneous cancer patients.

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.

A Case Series of Snake Venom Pharmacopuncture for Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Observational Study.

OBJECTIVE: This case series aims to report the efficacy and the safety of using snake venom pharmacopuncture (SVP) for chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Three heterogeneous cancer (1 endometrium, 1 cervix, and 1 prostate cancer) patients were referred to the East-West Cancer Center (EWCC), Dunsan Korean Medicine Hospital of Daejeon University, from August 02, 2017, to September 15, 2017, for treatment with SVP, and they were treated with SVP 4 times, 6 times, and 8 times, respectively. During the treatment period, the efficacy of SVP therapy was assessed by using the Numerical Rating Scale (NRS) and the Common Terminology Criteria for Adverse Events (CTCAE), and the stability was evaluated by using blood tests. Following each session, all patients were examined closely for any allergenic responses or adverse effects. RESULTS: All patients showed noticeable improvements of their NRS and CTCAE scores. Except for bleeding and bruising at the SVP injection site, no major side effects were noted. One of the patients reported mild chilling and a sore throat after receiving the second treatment; those symptoms went away after a few hours. No hematologic toxicity, hepatotoxicity, or nephrotoxicity was found on the blood test. CONCLUSION: The results of this research suggest positive potential benefits of using SVP for treating patients with CIPN. Also, the excellent safety results of SVP seen in this research should lead to larger clinical trials aimed at developing SVP into a potential intervention for managing patients with the symptoms of CIPN.

Acupuncture for Aromatase Inhibitor-Induced Arthralgia: A Systematic Review.

BACKGROUND: Aromatase inhibitors (AIs) are commonly used as adjunctive hormone treatment for early breast cancer patients. The major side effect of AIs is arthralgia, which affects adherence. Previous reviews suggested that acupuncture is effective in the management of cancer-related pain. The aim of this review is to evaluate the effects of acupuncture on arthralgia caused by AIs. METHODS: This article examined randomized controlled trials (RCTs) measuring the effects of acupuncture on joint symptoms caused by AIs within 8 medical databases till May 2014. The quality of the articles was evaluated according to the Cochrane risk of bias (ROB) tool. RESULTS: Four RCTs were identified in medical journals. Two studies were conducted with manual acupuncture and 2 studies were electroacupuncture. The range of sample size was between 32 and 67. One RCT showed significant improvement in the acupuncture group compared with the sham control group and another RCT showed a statistical difference between the electroacupuncture and waitlist group. The other 2 studies showed no statistical differences between control and acupuncture groups. Two studies conducted blood analysis to elucidate the mechanism of efficacy of acupuncture for arthralgia. The 2 positive studies had a lower ROB and 2 studies had a high ROB. CONCLUSIONS: The systematic review suggests that acupuncture has potential benefits to improve arthralgia caused by AIs. However, further trials of adequate sample size, appropriate control group, and longer follow-up are necessary to investigate the efficacy of acupuncture in AI-induced arthralgia.