RECOMMENDATIONS IN the Society for Integrative Oncology (SIO) clinical practice guidelines for integrative therapies during and after breast cancer treatment “are clear, thorough, and based on the most relevant scientific evidence,” concluded an ASCO expert panel that reviewed the guidelines.^1,2 ASCO endorsed the guidelines “with a few added discussion points.” The panel’s findings were reported in the Journal of Clinical Oncology.² 

As defined by the SIO, integrative oncology “refers to the use of complementary and integrative therapies in collaboration with conventional oncology care.”¹ Complementary therapies include meditation, yoga, and natural products and “are commonly used by patients with breast cancer and survivors of breast cancer,” the ASCO expert panel wrote. 

“If patients are using these therapies in addition to effective scientifically proven cancer therapies and their doctors are aware of it, we’re comfortable with it. However, concern arises when they are not disclosed or are used instead of conventional effective therapies,” stated Gary H. Lyman, MD, MPH, FACP, FRCP (Edin), FASCO, the panel’s co-chair and lead author of the article.³ Dr. Lyman is Co-Director of the Hutchinson Institute for Cancer Outcomes Research at Fred Hutchinson Cancer Research Center and Professor of Medicine/Medical Oncology, University of Washington School of Medicine, Seattle. 

“If patients are using these therapies in addition to effective scientifically proven cancer therapies and their doctors are aware of it, we’re comfortable with it.”

— Gary H. Lyman, MD, MPH, FACP, FRCP (Edin), FASCO

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Open Dialogue 

ALTHOUGH MOST integrative therapies “are probably quite safe, with few side effects, some do potentially interact, complicate, or have their own set of side effects that the physician should know about,” Dr. Lyman said in an interview with The ASCO Post. “My biggest concern is when patients decide to rely on these nonstandard therapies instead of, and therefore replacing, conventional chemotherapy. To avoid that, it is important to have a dialogue between the clinician and the patient. That requires, of course, that the clinician know what the patient is taking,” explained Dr. Lyman. 

“Open dialogue is critical, so patients feel they can tell their oncologist about anything they are doing that could impact how they are feeling, as well as any new symptoms. And the oncologist should be as well informed and knowledgeable as possible about these therapies and should guide patients.” 

Mind and Body Practices 

IN THE RECOMMENDATION grading system used in the SIO guidelines, grade A signifies a high certainty of substantial net benefit; grade B, a high certainty of moderate net benefit or a moderate certainty of moderate to substantial net benefit; and grade C, at least a moderate certainty of small benefit for selected individuals. Grades D and below recommend against a therapy due to no benefit, harm, or insufficient data. 

Mind and body practices had the highest recommendations, with meditation receiving a grade A for reducing anxiety, treating mood disturbance and depressive symptoms, and improving quality of life. Music therapy, yoga, massage, and stress reduction (particularly longer group programs) generally received grade B recommendations for those applications. They are among the most common currently used integrative therapies and “are promoted far beyond cancer, just for general mental health and to alleviate other conditions related to anxiety,” Dr. Lyman added. “There is some evidence that they are useful and really no evidence that they do harm.” 

Key Recommendations 

AS NOTED IN the ASCO expert panel’s report, the key recommendations in the SIO guidelines include the following: 

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 because of a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related adverse effects. 

There are other proposed therapies “with insufficient evidence to form a clinical recommendation,” the ASCO panel noted, and they are listed in Table 2 of the report.² “Many integrative therapies are promoted on which we have no evidence. I have concerns about these as they could cause some side effects that may complicate treatment,” Dr. Lyman said. “We do need well-designed studies to show that these things work if the patient is going to add them to their treatment, particularly as they are likely to be paying for them out of pocket,” he noted. “It is important to have as much science brought to bear on them as possible.” 

‘Discussion Points’ 

TWO OF the three discussion points raised by the ASCO expert panel focused on safety: one on the long-term use of ginseng and the other about the ingestion of high doses of mistletoe. Although using ginseng against fatigue received a grade C recommendation in the SIO guideline, the ASCO panel “wanted to highlight that the efficacy and safety of ginseng may vary by the type of ginseng and extraction method.” The panel also noted there is “concern that some ginseng preparations, especially those derived from ethanol extracts, may have estrogenic properties; therefore, caution should be used in patients with estrogen receptor–positive breast cancer.” 

The use of mistletoe for improving quality of life also received a grade C recommendation in the SIO guideline, but the “studies cited by the SIO used subcutaneous mistletoe, which is not approved by the U.S. Food and Drug Administration,” the ASCO panel noted. “Orally available mistletoe is available in the United States, but ingestion of high doses of mistletoe berry or leaf is known to cause serious adverse reactions.” 

Responsible Position in Between 

SO FAR, DR. LYMAN has received positive feedback from the publication of the ASCO endorsement of the SIO guidelines. “Many oncologists feel they need more information. They have not been trained on these types of interventions while they know from surveys and their own experience that patients are often using these interventions. Most oncologists want to be prepared to guide patients, and I think patients are looking for that engagement as well,” Dr. Lyman shared. 

“There certainly will be some pushback from those who think either we have gone too far or haven’t gone far enough. We recognize this is a sensitive area, and there are clinicians who just think we shouldn’t recommend any of this if we don’t have large randomized controlled trials proving efficacy and safety, as we do for cancer drugs,” noted Dr. Lyman. 

“My biggest concern is when patients decide to rely on these nonstandard therapies instead of, and therefore replacing, conventional chemotherapy.”

— Gary H. Lyman, MD, MPH, FACP, FRCP (Edin), FASCO

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“There are others who think these things are fine and they don’t cause any harm, so why not just let patients take what they want. We really thought a responsible position was in between by pointing out where we have sufficient information on both benefit and safety and to say when it is probably reasonable to consider if standard therapies are not working. For a few things, we saw there was real evidence of harm. In the end, of course, for many integrative approaches, we just don’t have much evidence at all.” 

Educational Efforts 

“HOPEFULLY, ONE of the things that will come out of our guidelines will be education for oncologists enabling them to be better prepared to answer questions patients may have about integrative therapies—what works, what doesn’t work, and what we don’t have any information about,” Dr. Lyman said. 

There have been some local efforts, such as conferences, to educate physicians and other health-care professionals about integrative therapies. “We’ve had discussions about integrating some of this information into the fellowship training program for oncologists. That is in the works here at Fred Hutch and the Seattle Cancer Care Alliance,” Dr. Lyman noted, adding that he suspects it is happening at other major centers as well. “As part of a balanced training of oncology specialists, it would be good to have better exposure to and understanding of integrative therapies are and what potential side effects to look for.” 

Dr. Lyman said there could potentially be an educational session on the SIO guideline and ASCO’s endorsement at next year’s ASCO meeting. “We often provide educational programs when we release a new guideline to update attendees about the guidelines and new evidence that may have come along.” 

Closer Cooperation 

ASCO’S ENDORSEMENT “reinforces the recommendations provided by the SIO guideline and acknowledges the effort put forth by SIO to inform practitioners who care for patients with breast cancer,” the panel wrote. 

Following publication of the endorsement, the SIO issued a statement quoting Dr. Lyman’s colleague at Fred Hutchinson and coauthor, Heather Greenlee, ND, PhD, MPH, who called the ASCO endorsement a “very important step for the field of integrative oncology.”⁴ Dr. Greenlee is Co-Chair of the SIO Guideline Task Force and Past President of the SIO. 

Heather Greenlee, ND, PhD, MPH

Lynn Balneaves, PhD, RN

The current SIO President, Lynn Balneaves, PhD, RN, also expressed appreciation for the ASCO endorsement: “This furthers our goal to provide clinicians and patients with practical information and tools to make informed decisions on whether and how to use a specific integrative therapy for a specific clinical application during and after breast cancer treatment.⁴” 

Asked whether it also signals closer cooperation with providers of complementary therapies, Dr. Lyman said, “I think so. If it is being viewed as helpful, then I think there is mutual interest in doing such things together,” he added. 

Dr. Lyman continued: “This guideline is focused on integrative therapies in breast cancer, and that was primarily because it is the most common cancer in women and also where we have the most evidence on some of these interventions. As Chair of the ASCO Guideline Methodology Subcommittee, I encourage a rigorous process for guideline development. One of the reasons we were particularly inclined to endorse this is that SIO followed an ASCO type of rigorous systematic review, evidence summary, with guideline recommendations coming out of that.” 

“This is a good start and a possible gateway to a series of related guidelines in the future,” he concluded. ■

DISCLOSURE: Dr. Lyman reported no conflicts of interest. 

REFERENCES 

1. Greenlee H, DuPont-Reyes MJ, Balneaves LG, et al: Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment. CA Cancer J Clin 67:194-232, 2017. 

2. Lyman GH, Greenlee H, Bohlke K, et al: Integrative therapies during and after breast cancer treatment: ASCO endorsement of the SIO clinical practice guideline. J Clin Oncol. June 11, 2018 (early release online). 

3. Mapes D: ASCO endorses integrative oncology guidelines for breast cancer patients. Fred Hutch News Service, June 11, 2018. Available at https://www. fredhutch.org/en/news/center-news/2018/06/asco-endorses-integrative-oncology-guidelines-for-breast-cancer-patients.html. Accessed June 29, 2018. 

4. ASCO endorses SIO Breast Cancer Guideline. Society for Integrative Oncology news release, June 13, 2013. Available at https://integrativeonc.org/news/sio-news/261-asco-endorses-sio-breast-cancer-guideline. Accessed June 29, 2018.