After explaining the treatment plan to a recently-diagnosed patient with cancer, it is not uncommon for oncologists to hear their patients ask questions and make statements like “Should I be on an alkaline diet? I heard that alkalizing the body kills cancer cells. I've also heard sugar feeds cancer. Should I avoid sugar? How about graviola, an herb from the Amazon—does it truly cure cancer? Can I get acupuncture during chemotherapy to reduce side effects? I heard that homeopathy works and has fewer side effects than regular cancer treatment. Could I try that first?”
The remainder of this article aims to clarify the terminology, review reasons for patient interest in questionable therapies, summarize research data regarding helpful modalities and their appropriate incorporation into cancer care (integrative oncology), and review nonviable so-called “alternatives.” We also recommend means of managing patient issues in an evidence-based, compassionate way that will enhance trust and rapport, strengthen the doctor–patient relationship, and improve patient and family quality of life.
Data on the use of adjunctive complementary therapies for symptom control is often confused by the convenient acronym “CAM,” for “Complementary and Alternative Medicine,” in publications that fail to distinguish between the two. This acronym is inherently imprecise and problematic. Some therapies, such as vitamins, are mainstream medical care when prescribed for patients with vitamin deficiency or taken in appropriate amounts to maintain general health. But they are “alternative” when used in mega-doses as cancer treatment, sometimes instead of needed mainstream care. Similarly, “prayer for health” may be a useful aid during mainstream cancer care in some regions of the world, but it is used as a cancer “treatment” in others. Varying interpretations of words can interfere with accurate reporting and hinder proper interpretation of survey data.
The interest in therapies outside of mainstream oncology care is not limited geographically or among particular segments of the population. In countries where modern medicine predominates, 40% to 50% of patients with cancer use CAM.1-6 Among cancer survivors in the United States, up to 40% of patients with cancer use complementary or alternative therapies during the period following acute cancer treatment,7 and use is prevalent among members of the general public as well. The 2007 National Health Interview Survey showed that 4 in 10 adults (38.3%; 83 million) and 1 in 9 children (11.8%; 8.5 million under age 18 years) in the United States used dietary supplements and various mind-body therapy techniques.8,9
A SOLUTION TO PROBLEMS OF TERMINOLOGY AND DEFINITION
Because the term CAM conflates unrelated, often mutually contradictory concepts, it fortunately has become outdated and is no longer in common use.10 Another publication sums the terminology problem well and urges moving forward and away from the problematic term: “This controversial term should be changed, since the words “complementary” and “alternative” have different meanings and should not be connected by ‘and’. Complementary therapies are those used to complement or to be used alongside conventional methods of therapy, whereas alternative methods refer to those that are used instead of known conventional therapies. The term ‘integrative therapies’ more accurately describes the complementary treatments being used in U.S. medical settings alongside conventional practices in a therapeutic environment. Centers for integrative medicine are being established in many academic medical centers.”11
Today, the term CAM rarely is applied in legitimate settings, and virtually every National Cancer Institute-designated comprehensive cancer center in the United States has a program or department using the term “integrative medicine.” In addition, the United States Consortium of Academic Health Centers for Integrative Medicine, with a membership of 55 esteemed academic medical centers with associated medical schools, all have integrative medicine programs. The remainder of this article addresses separately the promise of complementary therapies and the problem of “alternative” cancer treatments.
CHARACTERISTICS OF PATIENTS WHO USE COMPLEMENTARY CANCER THERAPIES
Surveys indicate that patients with cancer who use complementary approaches are younger, female, better educated and more affluent than others, representing a health-conscious segment of the population that is proactive in its health care, seeks health information, and has the means to pay for services that are typically not covered by insurance. Given the increased sophistication of many patients and physicians over recent years, patients and their oncologists increasingly pursue discussions of “integrative oncology,” alert to the fact that complementary (adjunctive) therapies decrease symptoms, improve overall quality of life, and enable patients to play a role in their own care.12
Patients acquire information about complementary approaches primarily from friends (65%), family (48%), and media (21%),1,13 with information as well as misinformation facilitated by the Internet and social networks.14 Increasing amounts of supportive data over recent decades support the value of complementary (integrative) therapies and demonstrate the increase in professional and patient acceptance. The recent wellness and survivorship emphases also enhance interest in complementary modalities.
THE IMPORTANCE OF COMMUNICATION
Optimal cancer care demands addressing issues of importance to patients, issues that may be detrimental if left unstated. Proper usage, application and discussion of therapies are important. A majority of patients want to discuss the topic with their oncologists given the opportunity, yet nondisclosure remains a problem in part because the opportunity fails to arise,15 and also because patients fear physician disapproval or disinterest in what they do outside of conventional treatment, or assume incorrectly that such information is not important or relevant to their cancer treatment.16,17
Although patients attribute nondisclosure to their uncertainty of benefit and because they were not asked about what they try on their own, physicians tend to believe that nondisclosure is because of patient fears that physicians would disapprove of outside therapies, or fail to understand them.18 Given the high prevalence of complementary therapy use, raising a discussion is an excellent opportunity for the physician to demonstrate compassion, understanding, and humanity, and to provide high-quality care based on scientific data. Questions commonly asked by patients with cancer, with possible responses, can be found in Table 1.
Common Questions Asked by Patients with Cancer and Examples of Possible Responses
MAJOR COMPLEMENTARY APPROACHES
Mind-body modalities focus on interactions among the brain, mind, body and behavior, with the intent to use the mind and body to improve function and promote health. Some of these therapies, such as meditation, relaxation techniques, hypnotherapy, yoga, tai chi, music therapy, and qigong have ancient roots; others, more recently developed, include the likes of guided imagery. Their common goal is to reduce the effect of anxiety, fear, phobia, anger, resentment, depression, and pain, while promoting a sense of emotional, physical, and spiritual well-being. Mind-body therapies do not treat cancer per se.
Systematic reviews and meta-analyses consistently find mind-body approaches to be beneficial. They reduce anxiety and stress, and improve sleep and overall quality of life, especially when used with other treatments.19-23 Among such therapies, mindfulness-based stress reduction techniques have been most carefully studied. This approach focuses on developing the practitioner's objective “observer role” for emotions, feelings, perceptions, and creating a nonjudgmental “mindful state” of conscious awareness.24 Its meditative components of body scan, sitting meditation, and mindful movement are taught over a period of weeks. Yoga, tai chi, and qigong, which originated in Asia, combine physical movement, postures, and breath control with meditation. These ancient practices are commonly used but are less well studied. A few small trials showed reduction in anxiety, depression, and distress, and improved emotional well-being.25-27
Mind-body therapies are generally safe. Their effectiveness requires instructors skilled in conveying appropriate technique, and regular practice by the patient. These modalities can become part of a multidisciplinary approach to reduce anxiety, mood, and sleep disturbance, and to improve quality of life in patients with cancer. An additional important result is that patients become empowered to help themselves. Major research trials are underway to elucidate the mechanisms by which mental activity exerts control over physiologic function.
An ancient technique with great contemporary interest, acupuncture involves the placement of special needles at certain body points, which may be followed by applying manual manipulation, heat or electric pulses to the needles.28 Regulated as a medical device in the United States, acupuncture needles are sterile, single-use, filiform, 32 gauge to 36 gauge, and 30 mm to 40 mm in length. Needles are inserted a few millimeters to a few centimeters into the skin. A typical treatment session is provided by a licensed or certified professional, and lasts for 20 minutes to 40 minutes.
Acupuncture is used to treat a wide variety of ailments. Its efficacy has been evaluated with rigorous scientific research methodology in the last few decades. Clinical trials show that it is safe and effective for several symptoms experienced by patients with cancer.29 A Cochrane review of 11 randomized controlled trials (RCTs), most using sham acupuncture as controls, concluded that acupuncture helps reduce chemotherapy-induced nausea and vomiting.30 The majority of acupuncture trials have been conducted to determine acupuncture's ability to reduce pain. Recent systematic reviews of RCTs support the analgesic effects of acupuncture for certain types of pain.31,32 Acupuncture shows benefit also in reducing radiation-induced xerostomia,33 mixed results in reducing hot flashes experienced by patients with breast cancer,34-36 and possible effectiveness in reducing lymphedema.37 A systematic review of 46 RCTs and a Cochrane review showed that acupuncture appears effective for insomnia, although larger, more rigorously designed RCTs are warranted.38 Acupuncture also has been shown to relieve anxiety.39-41
According to classical texts, acupuncture exerts its effect by regulating the flow of energy (called “chi” or “qi”) along meridians in the body when inserted into specific points (acupoints). Although anatomic studies indicate that acupoints tend to be located over interstitial connective tissue planes,42 current evidence does not conclusively support the claim that acupuncture points or meridians are electrically distinguishable per se.43 However, substantial data from neuroscience research suggest that acupuncture's effects may be mediated by modulation of nervous system activity.44-47
Acupuncture is generally safe when performed by qualified practitioners. After 760,000 treatments in 97,733 patients receiving acupuncture in Germany, only six cases of serious adverse events were reported.48 The most common side effects (<5%) include minor bleeding/bruising and pain or unfamiliar sensations at acupuncture sites. In patients with cancer, acupuncture should not be given to patients with severe neutropenia or thrombocytopenia, nor at the site of primary or metastatic neoplasm.
Acupuncture may not be optimal as first-line treatment for symptom relief. Rather, it can be considered when standard treatment is not satisfactory or not tolerated. In patients with severe chemotherapy-induced nausea/vomiting, pain, xerostomia, or hot flashes despite optimal medical management, acupuncture may be included as part of a multimodal management plan. Some insurance companies may cover acupuncture treatment provided by qualified therapists for certain indications.
Manipulative and Body-Based Practices
Massage therapy and other manual techniques such as Swedish massage, shiatsu, tui na, reflexology, Thai massage, Ayurvedic massage, lymphatic drainage, and myofascial release are provided by massage therapists, physical therapists and occupational therapists. These practices evolved from various cultures, and all focus primarily on the musculoskeletal system and connective tissues.
Most cancer-related clinical trials of massage therapy focus on Swedish massage and reflexology (foot massage using specified parts of the sole said to relate to bodily organs or locations). Results have been summarized in two systematic reviews of 14 RCTs and 12 RCTs, respectively, with some overlap.49,50 Control interventions used in these trials include usual care, attention, or low-intensity bodywork. RCT reviewers indicate that research methodology of most trials in both reviews was poor, but conclude that data do support massage therapy as an effective adjunct in cancer supportive care to reduce anxiety and pain.
Massage therapy in patients with cancer must be provided by certified massage therapists who are also trained in working with patients with cancer to minimize risk of injury. Only light touch massage should be provided to frail patients. Strong pressure should be avoided in areas of tumor or metastasis, or to patients with bleeding tendencies. Cases of serious adverse events have been reported, usually as a result of exotic types of massage or massage delivered by lay people.51,52 When delivered appropriately, massage therapy is a valuable, soothing complementary therapy that aids symptom control in patients with cancer and on which many patients with cancer rely.
Exercise and Physical Activity
Physical activity is the only integrative oncology therapy with a survival advantage. Exercise can improve cancer-related survival.53-68 Animal and epidemiologic studies suggest that chronic stress and adrenergic activation are associated with worse cancer-related survival via pathways in angiogenesis and src activation.58-60 For several years, the American Cancer Society has continued to recommend at least 150 minutes of moderate intensity or 75 minutes of vigorous intensity activity each week.
The importance of physical activity for patients with cancer and survivors cannot be overstated. It is a preeminent goal of integrative oncology. Many leading cancer facilities, including ours, have exercise programs tailored to the needs of patients with cancer, with experienced fitness instructors who routinely work with inpatients and outpatients across a broad range of ability and disability.
”ALTERNATIVE” THERAPIES CANCER PATIENTS ASK ABOUT
The remainder of this article reviews “alternative” therapies of common interest to patients. Sidebar 1 summarizes common reasons behind the interest in “alternatives” to mainstream cancer care. Because cancer was such a dire disease with few effective treatments in past decades, patients sought more effective, more gentle treatments, real or imagined.69 Today, the primary danger of “alternative therapies” is that patients may delay or forego effective cancer treatment. For example, instead of surgical resection of an early-stage breast cancer, a patient may use an alternative “natural therapy.” By the time it becomes apparent that the therapy does not control the growth of cancer, the cancer often has metastasized, rendering it incurable.
Sidebar 1. Factors behind Patient Interest in Useless Cancer Treatment “Alternatives” to Mainstream CareExpand
Another problem is that most “alternative” therapies tend to be costly. Patients pay for them out of pocket, often depleting family resources with the false belief that they are receiving effective treatment. The subsequent financial havoc creates great distress for the patient and family. A third risk is that these therapies offer false promises to desperate patients; results they cannot deliver, representing an act of deception and betrayal. We as clinicians have a moral obligation to dissuade patients from the use of useless therapies. A few of the numerous, currently popular “alternatives” are described below.
Miraculous Alternative Cancer “Cures” for End-Stage Disease
Proponents claim to produce amazing results in patients with cancer who have not responded to conventional therapy. The treatment may be as simple as a single product from an exotic source or derived from a “breakthrough discovery” decades ago yet claimed to have been “suppressed” by mainstream medicine. Amygdalin (aka Laetrile or so-called vitamin B17, an extract from bitter apricot seed. i.e., not a vitamin) is an example of such treatment. Despite lack of efficacy in clinical studies70,71 and a risk of cyanide toxicity,72 some patients continue to seek and use it.
Another example is “Cesium Therapy” where patients ingest cesium chloride (CsCl) to alkalinize the body, which proponents claim will kill the cancer cells because “cancer cells cannot survive in an alkaline environment.” Unfortunately ingestion of CsCl can lead to torsade de pointes, a potentially lethal cardiac arrhythmia.73,74 This “treatment” also may include an elaborate regimen of special diets, detoxification techniques, and large doses of natural products. These therapies rely heavily on testimonials of purported users of the products. The promotion materials often are laden with specious scientific jargon that may be appealing to laypersons, but their misleading nature is obvious to anyone versed in cancer biology. Costing $20,000 or more, “oxygen therapy” and variations of “bioelectromagnetism” are readily available, as are various so-called “energy therapies.”75 None have any value.
A universal patient question concerns diet. Often patients pursue one of many available “anticancer” diets, an approach that has its own category of self-help books. The alkaline or pH diet is frequently cited in this category. Similar to the concept behind cesium therapy, the belief here is that acidity promotes cancer, and that cancer cells cannot survive in an alkaline environment. By drinking “alkaline water” from an expensive device hooked up to a faucet and eating “alkaline foods,” which happen to be mainly fresh vegetables, fruits, legumes and nuts, purveyors claim cures for cancer, arthritis, obesity, and more.
Patients commonly are unaware that the body maintains a tight pH range and eliminates excess acid or alkaline to preserve proper pH balance and that the “treated” water has little buffering capacity, and that drinking “alkaline water” will not significantly affect blood pH levels. Likewise, glorifying “alkaline foods” really translates to pursuing a healthy diet not because of its alkalinity, but because such foods are rich in essential nutrients.
Sugar and Cancer
Patients often ask if sugar feeds cancer. This notion may not be entirely without merit, as glucose metabolism is an active area of research in anticancer drug development.76 However, it is often overblown in public perception. Some patients become paranoid about any sugar-containing food, regardless of amount. Such anxiety by itself is detrimental to patients' quality of life, and patients should be advised to keep things in perspective. There is no definitive proof that sugar promotes cancer growth, but excessive intake of refined sugar is unhealthy in general and should be minimized. A small amount of refined sugar is not harmful. Patients should be encouraged to meet their caloric requirements by consuming complex unrefined carbohydrates and unsaturated fat, unless they have a digestive tract condition that precludes those foods, instead of large amounts of foods with added sugar.
Other Anticancer Diets
Numerous “anticancer” diets with little scientific basis circulate among patients, including the Budwig diet, the Gerson diet, the raw food diet, and many others.77 In addition, detox or mono diets (such as those relying mainly on vegetable and fruit juice) may restrict or preclude important food categories that are necessary for a full range of nutrition. The high-fat, very low-carbohydrate ketogenic diet is another popular subject of inquiry. Animal studies suggest that ketogenic diets induce excessive oxidative stress and may enhance the effect of radiotherapy.78 Although clinical trials are underway to evaluate the benefits and risks of the ketogenic diet, none of the radical “anticancer” diets that employ restrictive regimens have been shown to improve survival. Moreover, patients run the risk of lacking essential nutrients when on such extreme diets.
Counseling patients who ask about “anticancer diets” provides a good opportunity to discuss an overall healthy lifestyle, which includes regular exercise79 as well as healthy nutrition. The potential for physical activity to improve outcomes is noted above including benefits to palliative care patients.80,81
Natural Products Available as Dietary Supplements
Over-the-counter dietary supplements available to patients with cancer include vitamins and trace element formulations with well-defined constituents, as well as botanical extracts and herbal products that often contain complex compositions of many compounds, some unidentified. The use of supplements is among the most frequently asked questions by patients with cancer. Indeed, natural products from botanicals, fungi, and marine sources are a rich source of anticancer therapy; chemotherapeutic agents derived from natural products include the taxanes, camptothecin analogs, vinca alkaloids, and numerous microbial compounds.82 But it takes decades of research to determine clinical safety and efficacy. Most supplements have not been subjected to rigorous clinical study.
Dietary supplements are popular and readily available. Patients often use them on their own, without informing their physicians. Patients are drawn also to natural products lacking anticancer activity, but marketed with “buzzwords” such as antioxidant, immune booster, and detox. Product claims indicating protection of good cells from damage, restoring suppressed immune function or removing “toxins” left behind by cancer treatment are not uncommon.
Some agents may indeed hold promise in cancer prevention or treatment, as shown in early clinical trials such as polyphenols extracted from green tea to treat chronic lymphocytic leukemia (CLL)83 and as chemoprevention in breast cancer84; docosahexanoic acid (DHA, an omega-3 fatty acid) in breast cancer prevention85 and treatment86; and curcumin in slowing progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma.87
However, most supplements have not shown meaningful clinical benefit when ingested orally. Many also may risk interaction with prescription medicines either pharmacokinetically or pharmacodynamically.88-91 Several herbs contain estrogen-like activity, which may not be advisable in estrogen-receptor positive patients with cancer.92 Others can alter drug metabolism, leading to serum drug levels higher or lower than that intended.93 Misconceptions held by patients after reading news reports or marketing materials need to be explained in language patients can understand. Some examples are given in Table 1.
LAST RESORT DILEMMAS FOR CLINICIANS
Although most patients use natural products hoping to reduce treatment-related side effects, support the body during cancer treatment or to prevent cancer recurrence, other patients with few or no treatment options want to try anything, including natural products that may have shown possible anticancer activity in preliminary studies. Various “anticancer regimens” are promoted. A current example is the “Bill Peeples cocktail,” which is circulating among patients with advanced sarcoma.94 Containing more than a dozen dietary supplement ingredients, this product claims antiangiogenic or antioxidant properties based primarily on laboratory studies.
This scenario presents a dilemma for the oncologist faced with a patient for whom there is neither effective treatment nor an appropriate clinical trial. How do we provide compassionate care while safeguarding our patient's best interests? We believe that the answer lies in acknowledging and meeting patients where they are. We can affirm their perseverance not to “give up,” and tolerate their use of agents that are generally safe and have shown some preliminary evidence of anticancer activity.
At the same time, we need also to help patients work toward accepting whatever outcome they may face, despite everyone's best efforts. Palliative care often begins too late in clinical practice.95 Patients' options, goals and preferences should be assessed early in the course of cancer treatment. Personalized care should be tailored to the physical, psychologic, social and spiritual consequences of cancer for the individual patient.96 Using some of these agents may help patients feel that they have tried everything, help them to accept the futility of further treatment, and enable closure. A compassionate approach accepting patients' decisions may be appropriate, along with efforts to minimize physical, emotional and financial burdens, discussion and close monitoring for adverse reactions, and a redoubled effort to prepare the patient and family for end-of-life issues.
MOVING FORWARD: INTEGRATIVE ONCOLOGY PROGRAMS, PRACTICES, AND GUIDELINES
Combining helpful complementary therapies with mainstream cancer care to reduce symptoms and improve quality of life constitutes the practice of integrative oncology. Most cancer centers now have integrative oncology departments or programs to provide complementary therapies and to counsel patients against potentially problematic “alternative therapies.”
Counseling by trained and experienced physicians should guide patients away from potentially harmful therapies and address their underlying needs. Referral to a qualified specialist often is the best way to connect the patient to solid sources of facts and sound advice. As patients gain information about additional symptom management techniques, they also experience positive interactions with their physicians, improve self-care skills, and enhance their physical, emotional and overall well-being.97,98
Suggestions for doctor-patient discussion throughout the cancer continuum.
A structured approach to discussing complementary and alternative medicine with patients in general was described in 1997 and updated later.75,99 An article by oncologists addressed these issues for patients with cancer.100 More recently, comprehensive guidelines for discussion were proposed for discussion of complementary modalities.101 These provide a framework for counseling patients with cancer about complementary and alternative approaches.
At the authors' institution, every new patient receives a packet reminding them to discuss any self-prescribed supplements or medications with their physicians, and patients are asked at each visit to disclose any herbs and other dietary supplements they are taking on a “home medication list.” Patients who raise questions that require discussion, and those on supplements that might interact with prescription medicines, are referred to the authors' Integrative Medicine Service for comprehensive counseling.
Counseling by physicians who are well versed in both oncology and integrative medicine optimally can develop a comprehensive assessment of the patient's needs, and address related issues from both the cancer care perspective and the patient's specific concerns. Sidebar 2 summarizes the steps taken in counseling patients. Practice models of integrative oncology vary according to patient demographics and the societal environment of the medical facility. Counseling is not always easy. It can be hampered by the oncologist's lack of awareness or insufficient understanding of what is important to the patient, by the paucity of physicians who are properly trained and knowledgeable about both cancer medicine and complementary therapies, lack of trust between physicians and non-MD practitioners, or insufficient funds. An investigation of six integrative oncology programs across four continents identified several essential elements for a successful program.102
Sidebar 2. Steps in Advising PatientsExpand
A candid and open-minded discussion of patients' needs and interests helps build enduring physician-patient relationships and improves the overall quality of cancer care.103 An effective discussion is facilitated with strong communication skills, knowledge of common complementary therapies and awareness of the “alternative” therapies promoted to patients with cancer. For busy oncologists, it is difficult to stay abreast of new complementary medicine research results and of the ever-expanding world of Internet-promoted “alternatives” to mainstream cancer treatment.
Many excellent continuing education materials are available from reputable sources (Sidebar 3). In addition, the expertise of integrative oncology colleagues can be helpful, especially those dual-trained in mainstream oncology and integrative medicine. National and international efforts offer helpful information for practicing oncologists. A multidisciplinary nonprofit organization, the Society for Integrative Oncology, was formed by clinicians, researchers and patient advocates to provide a platform for the advancement of evidence-based, comprehensive, integrative health care to improve the lives of people affected by cancer (www.integrativeonc.org). Using the standard methodology for developing practice guidelines, including systematic reviews of current literature and multiple rounds of peer reviews, the authors et al have evaluated the strength of evidence for common complementary therapies, as well as potential risks or burdens. The resultant recommendations were graded, peer-reviewed, and adapted by the American College of Chest Physicians104 and the Society for Integrative Oncology.105
Sidebar 3. Reputable Resources for Information about Integrative Oncology and Complementary TherapiesExpand
Complementary or alternative medicine topics are of substantial interest to patients with cancer. Safe and beneficial complementary therapies should be integrated into regular cancer care to improve patient's quality of life and clinical outcome. Patients should be steered away from “alternative” cancer therapies that are risky and without clinical value. Integrative oncology combines evidence-based complementary therapies with mainstream care, optimizing physical, psychologic and spiritual well-being, taking into consideration each patient's values and priorities. A robust integrative oncology program should be part of cancer care in hospitals, as it is for virtually all NCI-designated comprehensive cancer centers.
By understanding and addressing issues that patients with cancer see as important, compassionate care can be tailored to each patient, and oncology will reach the noble goal of treating each patient as a person with cancer, rather than treating only the cancer in a patient.
Amin M, Glynn F, Rowley S, et al. Complementary medicine use in patients with head and neck cancer in Ireland. Eur Arch Othorhnolaryngol
Navo MA, Phan J, Vaughan C, et al. An assessment of the utilization of complementary and alternative medication in women with gynecologic or breast malignancies. J Clin Oncol
Vapiwala N, Mick R, Hampshire MK, et al. Patient initiation of complementary and alternative medical therapies (CAM) following cancer diagnosis. Cancer J
Molassiotis A, Fernadez-Ortega P, Pud D, et al. Use of complementary and alternative medicine in cancer patients: A European survey. Ann Oncol
Hyodo I, Amano N, Eguchi K, et al. Nationwide survey on complementary and alternative medicine in cancer patients in Japan. J Clin Oncol
Moran MS, Ma S, Jagsi R, et al. A prospective, multicenter study of complementary/alternative medicine (CAM) utilization during definitive radiation for breast cancer. Int J Radiat Oncol Biol Phys
Gansler T, Kaw C, Crammer C, et al. A population-based study of prevalence of complementary methods use by cancer survivors: A report from the American Cancer
Society's studies of cancer survivors. Cancer
Nahin RL, Barnes PM, Stussman BJ, et al. Costs of complementary and alternative medicine (CAM) and frequency of visits to CAM practitioners: United States, 2007. Natl Health Stat Report
Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report
Rosenthal DS, Doherty-Gilman AM. Integrative medicine and cancer care. Virtual Mentor
12. Verhoef MJ, Rose MS, White M, et al. Declining conventional cancer treatment and using complementary and alternative medicine: A problem or a challenge? Curr Oncol. 2008;Suppl 2:s101-s106.
Verhoef MJ, Balneaves LG, Boon HS, Vroegindewey A. Reasons for and characteristics associated with complementary and alternative medicine use among adult cancer patients: A systematic review. Integr Cancer Ther
Page SA, Mannion C, Bell LH, et al. CAM information online: An audit of Internet information on the “Bill Henderson Protocol”. Complement Ther Med
Saxe GA, Madlensky L, Kealey S, Wu DP, Freeman KL, Pierce JP. Disclosure to physicians of CAM use by breast cancer patients: Findings from the Women's Healthy Eating and Living Study. Integr Cancer Ther
Tasaki K, Maskarinec G, Shumay DM, Tatsumura Y, Kakai H. Communication between physicians and cancer patients about complementary and alternative medicine: Exploring patients' perspectives. Psychooncology
Robinson A, McGrail MR. Disclosure of CAM use to medical practitioners: A review of qualitative and quantitative studies. Complement Ther Med
Richardson MA, Masse LC, Nanny K, et al. Discrepant views of oncologists and cancer patients on complementary/alternative medicine. Support Care Cancer
Shennan C, Payne S, Fenlon D. What is the evidence for the use of mindfulness-based interventions in cancer care? A review. Psychooncology
Ledesma D, Kumano H. Mindfulness-based stress reduction and cancer: A meta-analysis. Psychooncology
Cramer H, Lauche R, Paul A, Dobos G. Mindfulness-based stress reduction for breast cancer-a systematic review and meta-analysis. Curr Oncol
Zainal NZ, Booth S, Huppert FA. The efficacy of mindfulness-based stress reduction on mental health of breast cancer patients: A meta-analysis. Psychooncology
. 2013;22:1457-1465. Epub 2012 Sep 7.PubMed
Piet J, Wurtzen H, Zachariae R. The effect of mindfulness-based therapy on symptoms of anxiety and depression in adult cancer patients and survivors: A systematic review and meta-analysis. J Consult Clin Psychol
Fjorback LO, Arendt M, Ornbol E, et al. Mindfulness-based stress reduction and mindfulness-based cognitive therapy: A systematic review of randomized controlled trials. Acta Psychiatr Scand
Lin KY, Hu YT, Chang KJ, Lin HF, Tsauo JY. Effects of yoga on psychological health, quality of life, and physical health of patients with cancer: a meta-analysis. Evid Based Complement Alternat Med
Smith KB, Pukall CF. An evidence-based review of yoga as a complementary intervention for patients with cancer. Psychooncology
Chan CL, Wang CW, Ho RT, et al. A systematic review of the effectiveness of qigong exercise in supportive cancer care. Support Care Cancer
Kaptchuk TJ. Acupuncture: theory, efficacy, and practice. Ann Intern Med
Garcia MK, McQuade J, Haddad R, et al. Systematic review of acupuncture in cancer care: A synthesis of the evidence. J Clin Oncol
Ezzo JM, Richardson MA, Vickers A, et al. Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting. Cochrane Database Syst Rev
Vickers AJ, Cronin AM, Maschino AC, et al. Acupuncture for chronic pain: Individual patient data meta-analysis. Arch Intern Med
Lee MS, Ernst E. Acupuncture for pain: An overview of Cochrane reviews. Chin J Integr Med
Pfister DG, Cassileth BR, Deng GE, et al. Acupuncture for pain and dysfunction after neck dissection: Results of a randomized controlled trial. J Clin Oncol
Deng G, Vickers A, Yeung S, et al. Randomized, controlled trial of acupuncture for the treatment of hot flashes in breast cancer patients. J Clin Oncol
Carpenter JS, Neal JG. Other complementary and alternative medicine modalities: Acupuncture, magnets, reflexology, and homeopathy. Am J Med
. 2005;118 Suppl 12B:109-117.PubMed
Lee MS, Shin BC, Ernst E. Acupuncture for treating menopausal hot flushes: A systematic review. Climacteric
Cassileth BR, Van Zee KJ, Yeung KS, et al. Acupuncture in the treatment of upper-limb lymphedema: Results of a pilot study. Cancer
. 2013;119:2455-2461. Epub 2013 Apr 10.PubMed
Cao H, Pan X, Li H, Liu J. Acupuncture for treatment of insomnia: A systematic review of randomized controlled trials. J Altern Complement Med
Pilkington K, Kirkwood G, Rampes H, et al. Acupuncture for anxiety and anxiety disorders-a systematic literature review. Acupunct Med
Wang SM, Kain ZN. Auricular acupuncture: A potential treatment for anxiety. Anesth Analg
Eich H, Agelink MW, Lehmann E, et al. [Acupuncture in patients with minor depressive episodes and generalized anxiety. Results of an experimental study]. Fortschritte der Neurologie-Psychiatrie
Langevin HM, Yandow JA. Relationship of acupuncture points and meridians to connective tissue planes. Anat Rec
Ahn AC, Colbert AP, Anderson BJ, et al. Electrical properties of acupuncture points and meridians: A systematic review. Bioelectromagnetics
Huang W, Pach D, Napadow V, et al. Characterizing acupuncture stimuli using brain imaging with FMRI-a systematic review and meta-analysis of the literature. PloS One
Han JS. Acupuncture analgesia: Areas of consensus and controversy. Pain
Moffet HH. How might acupuncture work? A systematic review of physiologic rationales from clinical trials. BMC Aomplement Altern Med
Stone JA, Johnstone PA. Mechanisms of action for acupuncture in the oncology setting. Curr Treat Options Oncol
Melchart D, Weidenhammer W, Streng A, et al. Prospective investigation of adverse effects of acupuncture in 97 733 patients. Arch Intern Med
Ernst E. Massage therapy for cancer palliation and supportive care: A systematic review of randomised clinical trials. Support Care Cancer
Wilkinson S, Barnes K, Storey L. Massage for symptom relief in patients with cancer: Systematic review. J Adv Nurs
Ernst E. The safety of massage therapy. Rheumatology (Oxford)
Corbin L. Safety and efficacy of massage therapy for patients with cancer. Cancer Control
Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity and survival after breast cancer diagnosis. JAMA
Schmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc
Holick CN, Newcomb PA, Trentham-Dietz A, et al. Physical activity and survival after diagnosis of invasive breast cancer. Cancer Epidemiol Biomarkers Prev
Haskell WL, Lee IM, Pate RR, et al. Physical activity and public health: Updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc
Doyle C, Kushi LH, Byers T, et al. Nutrition and physical activity during and after cancer treatment: An American Cancer Society guide for informed choices. CA Cancer J Clin
Antoni MH, Lutgendorf SK, Cole SW, et al. The influence of bio-behavioural factors on tumour biology: Pathways and mechanisms. Nat Rev Cancer
Thaker PH, Han LY, Kamat AA, et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med
Armaiz-Pena GN, Allen JK, Cruz A, et al. Src activation by beta-adrenoreceptors is a key switch for tumour metastasis. Nat Commun
61. D'Andrea AP, Fernandez CA, Tannenbaum SL, et al. Correlates of leisure time physical activity compliance in colorectal cancer survivors. Prev Med. Feb 10 2014.
Wanner M, Tarnutzer S, Martin BW, et al. Impact of different domains of physical activity on cause-specific mortality: A longitudinal study. Prev Med
Magbanua MJ, Richman EL, Sosa EV, et al. Physical activity and prostate gene expression in men with low-risk prostate cancer. Cancer Causes Control
Seguin R, Buchner DM, Liu J, et al. Sedentary Behavior and Mortality in Older Women: The Women's Health Initiative. Am J Prev Med
Thomson CA, McCullough ML, Wertheim BC, et al. Nutrition and Physical Activity Cancer Prevention Guidelines, Cancer Risk, and Mortality in the Women's Health Initiative. Cancer Prev Res (Phila)
Carmichael AR. Physical activity as an adjuvant treatment for breast cancer; is it time for guidelines? Eur J Surg Oncol
Speed-Andrews AE, McGowan EL, Rhodes RE, et al. Identification and evaluation of the salient physical activity beliefs of colorectal cancer survivors. Cancer Nurs
Lee IM, Wolin KY, Freeman SE, Sattlemair J, Sesso HD. Physical activity and survival after cancer diagnosis in men. J Phys Act Health
Cassileth BR. Sounding boards. After laetrile, what? N Engl J Med
70. Milazzo S, Ernst E, Lejeune S, Boehm K, Horneber M. Laetrile treatment for cancer. Cochrane Database Syst Rev. 2011;(11):CD005476.
Milazzo S, Lejeune S, Ernst E. Laetrile for cancer: A systematic review of the clinical evidence. Support Care Cancer
Kalyanaraman UP, Kalyanaraman K, Cullinan SA, McLean JM. Neuromyopathy of cyanide intoxication due to ”laetrile“ (amygdalin). A clinicopathologic study. Cancer
Wiens M, Gordon W, Baulcomb D, Mattman A, Mock T, Brown R. Cesium chloride-induced torsades de pointes. Can J Cardiol
Pinter A, Dorian P, Newman D. Cesium-induced torsades de pointes. N Engl J Med
Weiger WA, Smith M, Boon H, Richardson MA, Kaptchuk TJ, Eisenberg DM. Advising patients who seek complementary and alternative medical therapies for cancer. Ann Intern Med
Kaelin WG, Jr., Thompson CB. Q&A: Cancer: Clues from cell metabolism. Nature
77. The Complete Guide to Complementary Therapies in Cancer Care: Essential Information for Patients, Survivors and Health Professionals. Hackensack, NJ:World Scientific Publishing Company;2011.
Abdelwahab MG, Fenton KE, Preul MC, et al. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PloS One
Demark-Wahnefried W, Rock CL, Patrick K, Byers T. Lifestyle interventions to reduce cancer risk and improve outcomes. Am Fam Physician
Lin MR, Hwang HF, Wang YW, Chang SH, Wolf SL. Community-based tai chi and its effect on injurious falls, balance, gait, and fear of falling in older people. Phys Ther
Faber MJ, Bosscher RJ, Chin APMJ, van Wieringen PC. Effects of exercise programs on falls and mobility in frail and pre-frail older adults: A multicenter randomized controlled trial. Arch Phys Med Rehabil
Mann J. Natural products in cancer chemotherapy: Past, present and future. Nat Rev Cancer
Shanafelt TD, Call TG, Zent CS, et al. Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. Cancer
Crew KD, Brown P, Greenlee H, et al. Phase IB randomized, double-blinded, placebo-controlled, dose escalation study of polyphenon E in women with hormone receptor-negative breast cancer. Cancer Prev Res (Phila)
Yee LD, Lester JL, Cole RM, et al. Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition. Am J Clin Nutr
Bougnoux P, Hajjaji N, Ferrasson MN, et al. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: A phase II trial. Br J Cancer
Golombick T, Diamond TH, Manoharan A, et al. Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and curcumin: A randomized, double-blind placebo-controlled cross-over 4g study and an open-label 8g extension study. Am J Hematol
Mathijssen RH, Verweij J, de Bruijn P, Loos WJ, Sparreboom A. Effects of St. John's wort on irinotecan metabolism. J Natl Cancer Inst
Klein EA, Thompson IM, Jr., Tangen CM, et al. Vitamin E and the risk of prostate cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA
Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA
Bairati I, Meyer F, Gelinas M, et al. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J Clin Oncol
Deng G, Davatgarzadeh A, Yeung S, Cassileth B. Phytoestrogens: Science, evidence, and advice for breast cancer patients. J Soc Integr Oncol
Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: An updated systematic review. Drugs
Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med
Peppercorn JM, Smith TJ, Helft PR, et al. American society of clinical oncology statement: Toward individualized care for patients with advanced cancer. J Clin Oncol
Koithan M, Bell IR, Caspi O, et al. Patients' experiences and perceptions of a consultative model integrative medicine clinic: A qualitative study. Integr Cancer Ther
Verhoef MJ, Mulkins A, Boon H. Integrative health care: How can we determine whether patients benefit? J Altern Complement Med
. 2005;11 Suppl 1:S57-S65.PubMed
Eisenberg DM. Advising patients who seek alternative medical therapies. Ann Intern Med
Cohen L, Cohen MH, Kirkwood C, et al. Discussing complementary therapies in an oncology setting. J Soc Integr Oncol
Schofield P, Diggens J, Charleson C, et al. Effectively discussing complementary and alternative medicine in a conventional oncology setting: Communication recommendations for clinicians. Patient Educ Couns
Ben-Arye E, Schiff E, Zollman C, et al. Integrating complementary medicine in supportive cancer care models across four continents. Med Oncol
Verhoef MJ, Boon HS, Page SA. Talking to cancer patients about complementary therapies: Is it the physician's responsibility? Curr Oncol
. 2008; 15 Suppl 2:s88-s93.PubMed
Cassileth BR, Deng GE, Gomez JE, et al. Complementary therapies and integrative oncology in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest
. 2007;132(3 Suppl):340S-354S.PubMed
Deng GE, Frenkel M, Cohen L, et al. Evidence-based clinical practice guidelines for integrative oncology: Complementary therapies and botanicals. J Soc Integr Oncol