Integrating acupuncture into cancer care.

Oncology acupuncture has become a new and promising field of research because more and more cancer patients have sought non-pharmacological alternatives for symptom management. While different mechanisms have been proposed to explain its efficacy, including theories of the neural system, endocrine cytokine or immunological regulation, its eventual role has become that of alleviating the side effects induced by chemotherapy or radiotherapy. In this paper, we have reviewed the related articles focusing on acupuncture mechanisms and applications in cancer care to provide a quick sketch of acupuncture in cancer care. A detailed search was performed to identify the randomized controlled trials (RCTs) and systematic reviews on acupuncture in oncology, using PUBMED and Cochrane. The search terms included: Acupuncture, acupressure, and cancer. Additional terms were used to target specific symptoms (i.e., breast cancer, hot flash, xerostomia, nausea, vomiting, cancer pain, insomnia, fatigue). Two authors independently extracted data for analysis and review. Ultimately, 25 articles underwent full-text review. Recent trials made efforts in studying (a) hot flashes in breast cancer, (b) xerostomia induced by radiotherapy in head and neck cancer, (c) nausea and vomiting post-chemotherapy, (d) cancer pain, and (e) fatigue and insomnia in cancer patients. Controversial results for acupuncture application in cancer care appeared in different categories, but a trend emerged that acupuncture can palliate cancer-related symptoms. The research to date certainly offers us a valid complementary therapy in treating cancer-related symptoms. Meanwhile, practical strategies with safe measures for enhancing the efficacy are needed in further interventions, as well as continuing research with a validated methodology.

INTRODUCTION

With the increasing incidence of cancer and major advances in cancer treatment in recent decades, acupuncture has become a popular complementary treatment in oncology. One European survey highlighted over a third of cancer patients are utilizing complementary therapies for treating their cancer symptoms and/or the side effects of their treatment.[1] Since different cancer patients often share similar symptoms, most complementary therapies are focused on the symptoms rather than the disease itself. Oncology acupuncture is a new field of research. Recent advances from published clinical trials have added evidence to support the use of acupuncture for management of symptoms such as pain, nausea and vomiting, xerostomia, hot flashes, fatigue, anxiety, depression, and insomnia. Acupuncture is based on the meridian theory of Traditional Chinese Medicine and stresses “Qi.” From the viewpoint of western medicine, the mechanism of acupuncture may be explained by neurotransmitter release or modulation of autonomic nervous system (ANS). Recent studies also used sham acupuncture control groups to validate the efficacy of acupuncture.[2] Applying acupuncture in oncology requires constant dialog and communication between qualified practitioners and the oncology team.

Here, we review some review articles and clinical trials including patient-administered acupuncture, electroacupuncture (EA), acupressure, and auricular acupuncture applied in cancer-related symptom treatment. Most studies indicate acupuncture has the potential to act as an adjunctive care in palliating symptoms.[2] This has encouraged deeper investigations and clinical practice to apply this technique in cancer care because of its low side-effect profile and economic cost benefits.

Theory and mechanism

In Traditional Chinese Medicine theory, acupoints are defined as the visceral reaction points on the body surface where the Qi of the viscera and meridians are transfused.

Triggering these acupuncture points promotes the flow of Qi and blood, and regulates visceral function.[3]

In the last half of the 20th century, many studies conducted in animals and humans have demonstrated multiple biological responses related to acupuncture, including (a) neural regulation, (b) endocrine regulation, and (c) immunological regulation.[4]

In neural regulation, some experiments have indicated the relationship between acupuncture and the ANS.[5] According to Traditional Chinese Medicine, “acupuncture is believed to restore the balance of Yin and Yang,” which may correspond to the modern definition that “acupuncture modulates the imbalance between the parasympathetic and sympathetic activity.”[6]

In endocrine regulation, EA evokes serotonin release from the upper brain stem region and hypothalamus and stimulates endogenous opiate release (β-endorphin, enkephalin, endomorphin, and dynorphin) which then alleviates cancer pain.[7] In addition, some neurohormones like γ-aminobutyric acid and glutamate, neuropeptide Y, and brain-derived neurotrophic factors can lead to euphoric sensations and treat the psychological problems of the cancer patients.[89]

From the view point of immune modulation, EA may stimulate leukocytes’ (granulocytes and lymphocytes) growth via the hypo-thalamus–pituitary–adrenal axis.[10] Improvements in T-lymphocyte and Natural Killer cell function to promote the recovery of immune function in cancer patients were observed in some studies.[1112]

METHODS

Our search for articles of acupuncture in the management of each symptom was carried out on 15 September 2012 in the database PUBMED and in the Cochrane Central Register of Controlled Trials. Language restricted to English were applied. Key search terms were: Acupuncture, electroacupuncture, acupressure, and cancer. Additional terms were used to target specific symptoms (i.e., breast cancer, hot flashes, xerostomia, nausea, vomiting, cancer pain, insomnia, fatigue). References of all the included studies were also searched.

Selection criteria

We included only the recent reviews and randomized controlled trials (RCTs) investigating acupuncture applied in cancer-related symptoms within the past 8 years.

Data collection and analysis

Two independent reviewers screened the abstracts and titles of all the articles for eligibility. When the reviewers felt that the abstract or title was potentially useful, full copies of the article were retrieved and considered for eligibility by all reviewers.

When discrepancies occurred between reviewers, the reasons were identified and a final decision was made based on the agreement of all reviewers. In the end, 25 articles, including RCTs and systemic reviews, were retrieved for the final analysis [Figure 1]. And the major conclusions of included RCTs and systemic reviews in acupuncture applied in cancer-related symptoms would be summarized in Table 1. The common acupoints applied in oncology-related problem would be list in Table 2.

Figure 1

Reviewing process flowchart

Table 1

Recent RCT and systemic reviews in acupuncture applied in cancer-related symptoms

Table 2

Common acupoints applied in cancer care

ACUPUNCTURE APPLIED IN ONCOLOGY-RELATED PROBLEM

Hot flashes

Hot flashes are a common complaint in nearly 70% of breast cancer patients.[13] They may be related to abrupt menopause or anti-estrogen therapy (tamoxifen or aromatase inhibitors). Acupuncture (a complementary modality) plays some role in reducing the hot flashes in breast cancer patients on treatment with accompanying side effects. Two recent RCT studies showed acupuncture may decrease the frequency of hot flashes, but not to a statistically significant level when compared with sham acupuncture.[1415] Another RCT enrolled breast cancer patients who had all taken tamoxifen for more than 3 months, and compared the Kupperman index and frequency of hot flashes between the patients who received true acupuncture (TA) and those who received sham acupuncture (SA). A significant benefit was found in this study.[16] A systemic review indicated evidence from sham-controlled RCTs for the limited effects of acupuncture in treating hot flashes in breast cancer patients, and more pharmacologic agents, including megestrol acetate, clonidine, and selective serotonin reuptake inhibitors (SSRI), need to be tested.[1617] Although the mechanism is uncertain, it is hypothesized that neurotransmitters are involved in thermoregulation.[18]

Xerostomia

Radiation-induced xerostomia is a common symptom in patients with head and neck cancer (HNC) because radiotherapy fields frequently encompass the major salivary glands. Once the accumulated dose exceeds 26 Gy, the radiation damage to salivary gland tissue is difficult to reverse. The dry mouth sensation definitely influences a patient's quality of life (QoL). Thus, some conventional modalities that have been applied include (a) salivary replacement treatment, (b) mechanical and pharmacological stimulants, (c) cholinergic muscarinic agonist (pilocarpine), and (d) improved radiation dosimetry. In recent years, “acupuncture” has received much more attention stemming from a hypothesis that acupuncture may stimulate salivary flow accompanied by corresponding central nervous system (CNS) functional magnetic resonance imaging (fMRI) changes in radiation-induced xerostomia.[19] Some systemic reviews have given evidence indicating that acupuncture's benefit in irradiation-induced xerostomia is limited and further high-quality RCTs are still needed.[2021] A recent non-RCT study showed preventive acupuncture led to significantly improved salivary flow rates and decreased xerostomia-related symptoms,[22] and another RCT by David reported significant reduction in pain, dysfunction, and xerostomia with good tolerance.[23] The possible mechanism for palliating xerostomia using acupuncture may be related to the neuropeptides modulating the salivary secretion in a complex process orchestrated by both the sensory and the autonomic nervous systems.[24]

Nausea/vomiting

Both ASCO (American Society of Clinical Oncology) and NCCN (National Comprehensive Cancer Network) state the 5-hydroxytryptamine (5HT3) antagonists and neurokinin 1 (NK1)-receptor antagonist can reduce chemotherapy-induced nausea/vomiting (CINV). However, there are still many patients who cannot tolerate these symptoms because they deeply impair the patients’ QoL and delay the chemotherapy course.[25] Application of acupuncture in cancer-related nausea/vomiting has been studied since 1990s.[26] In 1998, the National Institutes of Health Consensus Statement on Acupuncture noted that promising results have emerged showing the efficacy of acupuncture in adult postoperative and chemotherapy-induced nausea and vomiting. A review article indicated the benefits of EA in chemotherapy-induced acute vomiting, but studies combining EA with state-of-the-art antiemetics and in patients with refractory symptoms are needed to determine the clinical relevance.[27] The most popular acupoints applied in this problem are P6 and S36, both of which belong to the Chinese stomach meridian.[28] Improving vagal modulation and HRV (Heart rate variability) change were observed to be related to reducing post-chemotherapy nausea/vomiting.[29] Several acupuncture studies have applied different chemotherapy regimes such as cisplatin or cyclophosphamide. They revealed that acupuncture combined with antiemetics can effectively decrease the incidence and degree of cisplatin- and cyclophosphamide-induced delayed nausea and vomiting and that the effect of acupuncture is better than that of sham acupuncture.[3031] Two multicenter longitudinal RCTs have also shown significant benefits of acupuncture in alleviating the severity of both acute and delayed vomiting.[3233]

However, there have still been negative results of acupuncture on CINV. A randomized controlled single-blind trial that focused on high-dose chemotherapy and autologous peripheral blood stem cell transplantation showed no benefit from acupuncture.[34]

Therefore, the effect in radiotherapy-induced nausea/vomiting is not conclusive, as there are both positive and negative results.[3536]

Cancer pain

Cancer pain is a refractory symptom in oncology. The World Health Organization suggested managing pain should begin with the use of time-honored opioids, but it also recommends the use of adjuvant therapies such as acupuncture and other complementary and alternative modalities early in the management process.[37] The main mechanism of the analgesic effect of acupuncture may be related to its effect in decreased substance P and upregulating plasma β-endorphin levels.[38] Since there are various manual approaches to acupuncture, there is no definite conclusion as to its effectiveness. A systemic review of RCTs evaluating any type of invasive acupuncture for cancer pain indicated insufficient evidence to judge whether acupuncture is effective, due to methodological limitations, small sample sizes, poor reporting, and inadequate analysis.[39] Meanwhile, a meta-analysis showed Transcutaneous Electric Nerve Stimulation (TENS) may have a role in pain management, but there was insufficient available evidence to determine its effectiveness in treating cancer-related pain.[4041] However, closer inspection shows positive results, for example, a randomized controlled blind study with 90 patients found auricular acupuncture may significantly reduce pain intensity from cancer patients who are in pain, despite stable analgesic treatment.[42] Providing massage and acupuncture in addition to usual care also resulted in decreased pain among postoperative cancer patients, when compared with usual care alone.[43] Similar significant benefits were also observed in RCTs comparing true body and auricular acupuncture with the sham group, concluding acupuncture can relieve Aromatase inhibitors induced arthralgia and joint stiffness.[4445] This is because cancer pain may arise not only from cancer itself, but also from cytokine or other related treatments. More focused and rigorous, methodological quality studies are necessary to assess the clinical efficacy of acupuncture for cancer pain.[46]

Fatigue/insomnia

Cancer-related fatigue is a multidimensional phenomenon that is self-perceived, and includes physical, emotional, cognitive, and behavioral components. It is usually accompanied by symptoms such as depression and insomnia. As part of complementary therapy, acupuncture has been studied in this field for several decades. A methodologically feasible RCT compared acupuncture, acupressure, and sham acupressure in post-chemotherapy fatigue patients and found positive results in enhancing patients’ general fatigue (P < 0.001), physical fatigue (P = 0.016), activity (P = 0.004), and motivation (P = 0.024).[47] A single-arm, phase II pilot study showed clinically meaningful results in improving post-chemotherapy fatigue with acupuncture.[48] On the other hand, insomnia may lead to fatigue and depression, which are also commonly observed in cancer patients. A recent RCT evaluated 80 patients and revealed acupuncture can effectively reduce malignant-related depression and improve the sleep quality of cancer patients.[49] A meta-analysis also indicated auricular acupuncture may improve sleep quality better than medications such as diazepam.[50] However, studies focused on cancer-related fatigue and insomnia are difficult to clearly understand because many confounding factors need to be considered. A Cochrane systematic review of acupuncture for insomnia concluded, “The current evidence is not sufficiently extensive or rigorous enough to support the use of any form of acupuncture for treating insomnia.”[51] The data so far show acupuncture causes sedative and hypnotic effects in cancer patients when used for treating nervousness and insomnia. Further methodologically strong, randomized controlled studies with a large sample size are needed to assess the usefulness of acupuncture for cancer-related fatigue and insomnia.

Side effects and complication management

The safety issues concerning oncology acupuncture practice have become imperative, since cancer patients usually have a more complicated medical status and are at higher risk of developing adverse reactions from acupuncture. Patients with coagulation dysfunction or severe thrombocytopenia with a bleeding tendency should be paid special attention. In patients with a cardiac pacemaker or intracardiac defibrillator, EA should be avoided. Direct insertion of needle into a tumor nodule or ulcerated wound, as well as lymphedematous limbs should be avoided. Sterile needles are obligatory. Severe adverse effects of acupuncture are rare and easily handled, such as a small hemorrhage, fainting, or syncope, bruising, dizziness, needle breakage, pneumothorax, or nerve damage. A multicentric survey from Germany observed that if it is used according to the established safety rules and carefully at appropriate anatomic regions, it is a safe treatment method.[52]

Based on our experience, patients with sepsis or those in shock are unsuitable for acupuncture. Other conditions caused due to treatment, such as cancer-related neutropenia [absolute neutrophil count (ANC) <500/μl] or thrombocytopenia (platelet < 20,000/μl), as well as immune-compromised condition or major co-morbidities should always be kept in mind. Before the first visit, approval and communication should be obtained from the patients and the primary oncologist.

THE PERSPECTIVE ROLE OF ACUPUNCTURE IN ONCOLOGY

The increase in the overall survival of cancer patients is attributed to the rapid progress of cancer treatment modalities. More and more attention has been focused on complementary and alternative medicine. Acupuncture is a well-established technique in this field. Many studies showed benefits of the technique to multiple cancer-related symptoms, as discussed above. Note, however, that the study design with respect to the study population, sample size, methodological quality, mode of TENS, treatment duration, method of administration, and outcome measures used was not uniform and some equivocal conclusions were reached. Based on the holistic cancer care viewpoint and current RCT data, the clinical application and study of acupuncture in oncology should be simultaneously evaluated. To be more persuasive, standardized clinical protocols, and the types and points of acupuncture for each symptom should be elucidated and investigated further. As encouraging evidence continues to emerge, acupuncture could play a more prominent role in integrative cancer care.