Manuscript title: Integrative Medicine for Pain Management in Oncology: Society for Integrative Oncology-ASCO Guideline
Pain is one of the most common, disabling, and feared symptoms experienced by patients diagnosed with cancer. Among patients with advanced cancer, pain can be a result of tumor burden or invasion of bones, muscles, or nerves. In addition, many conventional cancer treatments such as surgery, chemotherapy, radiotherapy, immunotherapy, or hormonal therapy can result in both acute and chronic pain conditions such as aromatase inhibitor (AI)-Induced joint pain or chemotherapy-induced peripheral neuropathy (CIPN) pain. With improved oncologic treatment, many patients diagnosed with advanced cancer now live longer with symptomatic illness and ongoing oncologic treatment. Additionally, increasing numbers of patients experience remission and join the 16.9 million cancer survivors in the United States alone. Many survivors, however, continue to experience chronic pain resulting from their cancer treatment that not only negatively affects their quality of life, but also their daily functions. Chronic pain may also lead to nonadherence to oncologic treatment such as hormonal therapies, thus, potentially compromising overall survival. Therefore, effective pain management is of critical importance throughout the cancer care trajectory.
As pain in patients and survivors of cancer is complex with different etiologies (eg, tumor burden, treatment-related, and non–cancer-related) and varying presentations (eg, neuropathic and Musculoskeletal) and duration (eg, acute and chronic), pain management requires an interdisciplinary approach and should include both pharmacologic and nonpharmacologic treatments, where appropriate. Integrative medicine, defined as the coordinated use of evidence-based complementary practices and conventional care treatments, includes interventions such as acupuncture, massage, meditation, and yoga, which are increasingly available in cancer centers and are recommended for symptom and pain management. An estimated 40% of patients with cancer use integrative medicine on an annual basis. The key guiding principle of integrative medicine is to use these interventions along with conventional pain management approaches (eg, medications, radiation, injections, and physical therapies) and it is not intended to replace conventional interventions.
Patients often seek integrative medicine because they perceive that conventional medical treatment is not completely meeting their needs, fear side effects from pharmacotherapies, prefer a holistic approach, or because it has been recommended by their family or health care providers. A growing number of well-conducted randomized controlled trials (RCTs) have found that interventions such as acupuncture or massage can alleviate pain in patients and survivors of cancer. However, for many other interventions, trials are small and are often limited by a lack of methodologic rigor. Ideally studies should not only report the statistical significance of their findings but also the clinically meaningful change in pain severity (a two-point reduction on a 0-10 scale).
Both the Society for Integrative Oncology (SIO) and American Society of Clinical Oncology (ASCO) regularly engage in the development and dissemination of clinical practice guidelines. SIO’s mission is to advance evidence-based, comprehensive, integrative health care to improve the lives of people affected by cancer. ASCO’s mission is to conquer cancer through research, education, and promotion of the highest-quality, equitable patient care. For this guideline, SIO and ASCO joined efforts to develop a guideline focused on the use of integrative therapies to manage oncology-related pain to provide evidence-based recommendations to patients and clinicians to inform clinical decisions. This guideline builds upon the existing ASCO guidelines on pain management, the growing body of research in this area, and the emphasis from the Centers for Disease Control and Prevention to use nonpharmacologic approaches for pain management.
This systematic review (SR)-based guideline product was developed by an international multidisciplinary Expert Panel, which included a patient representative and a health research methodologist. The Expert Panel met via video conferences and corresponded through e-mail. Based upon the consideration of the evidence, the authors were asked to contribute to the development of the guideline, provide critical review, and finalize the guideline recommendations. The guideline recommendations were sent for an open comment period of two weeks allowing the public to review and comment on the recommendations after submitting a confidentiality agreement. These comments were taken into consideration while finalizing the recommendations. Members of the Expert Panel were responsible for reviewing and approving the penultimate version of the guideline, which was then submitted to the Journal of Clinical Oncology (JCO) for editorial review and consideration for publication. All SIO-ASCO guidelines are ultimately reviewed and approved by the Expert Panel, the SIO Clinical Practice Guidelines Committee, and the ASCO Evidence Based Medicine Committee before publication. All funding for the administration of the project was provided by SIO.
The recommendations were developed by using a SR of evidence identified through online searches of PubMed (1990-2021) and Cochrane Library (1990-2021) of RCTs, SRs, and meta-analyses. Articles were selected for inclusion in the SR on the basis of the following criteria:
• Population: Adults and pediatric patients experiencing pain during any stage of their cancer care trajectory
• Interventions: Integrative interventions for pain management, including acupuncture, acupressure, mind body therapies, and natural products (note: see details in the Data Supplement, online only; therapies focused on pain prevention were not included)
• Comparisons: No intervention, waitlist, usual care (UC) or standard care, guideline-based care, active control, attention control, placebo, or sham interventions
• Outcomes: Pain intensity, reduction, or change in symptoms reported as the primary outcome in published manuscript
• Sample size: Minimum total sample size of 20
Articles were excluded from the SR if they were (1) meeting abstracts not subsequently published in peer-reviewed journals; (2) editorials, commentaries, letters, news articles, case reports, and narrative reviews; or (3) published in a non-English language.
A total of 1,346 articles were identified in the literature search. After applying the eligibility criteria, 227 articles (26 SRs, 181 RCTs) remained, forming the evidentiary basis for the guideline recommendations.
Study Quality Assessment
Study design aspects related to individual study quality, quality of evidence, strength of recommendations, and risk of bias were assessed for the 227 intervention studies identified. SRs and meta-analyses were assessed for quality using the assessment of multiple systematic reviews (AMSTAR) tool. Design elements, such as blinding, allocation concealment, sufficient sample size, intention-to treat, and funding sources, were assessed for RCTs using the Cochrane Risk-of-Bias tool. Overall, the included SRs were conducted using established methods; however, many of the primary studies included in these reviews suffered from flaws and/or limitations in study design. Ultimately, we used the SRs as one of the means to identify relevant primary studies. Additional RCTs identified and included in this guideline ranged from low to high overall risk of bias in one or more key domains. Some of the flaws in the study design included lack of blinding; incomparable control arms, small sample sizes and/or high attrition rates; and limited statistical power, all of which lowered the confidence in the findings. The included studies were also heterogeneous with respect to patient populations, sample size, methodologic quality, treatment duration, and outcome measures. The primary outcomes varied across studies and, in most cases, were not directly comparable because of different outcomes, measurements, and instruments used at different time points. This diversity precluded a quantitative analysis and, as such, only a descriptive review was performed. Refer to the Data Supplement for quality rating scores and the Methodology Manual for more information and for definitions of ratings for overall potential risk of bias.
Aromatase Inhibitor–Related Joint Pain
Recommendation 1.1. Acupuncture should be offered to patients experiencing AI-related joint pain in breast cancer (Type: Evidence based, benefits outweigh harms; Evidence quality: Intermediate; Strength of recommendation: Moderate).
Clinical interpretation. Since AI-related joint pain affects up to 50% of women on this class of drugs and negatively affects quality of life and adherence to hormonal treatment, we recommend that acupuncture should be used for management of this painful condition. Our recommendation is based on the available evidence for managing this challenging condition and clinical importance of this issue. Many studies showed joint pain results in nonadherence to Ais and such behavior can lead to increased recurrence and mortality for women with breast cancer. Funding to study nonpharmacologic approaches to pain and symptom management is highly limited partly because of the lack of industry support. To date, only acupuncture, duloxetine, and supervised exercise have been found to improve AI-induced pain in large RCTs but only one large definitive trial for each intervention has been conducted. Despite the recommendation, the decision to use acupuncture with other treatments for AI-related pain needs to be based on patient preference, benefit versus risk for each therapy, and availability of and access to the treatment modality. Yoga, other mind-body therapies, and natural products require additional well-conducted RCTs to increase the quality of evidence to inform a change in the level of recommendation, if warranted.
General Cancer Pain or Musculoskeletal Pain
Recommendation 1.3. Acupuncture may be offered to patients experiencing general pain or musculoskeletal pain from cancer (Type: Evidence based, benefits outweigh harms; Evidence quality: Intermediate; Strength of recommendation: Moderate).
This is an official clinical guideline for management of cancer pain, with integrative medicine, recommended by a society of conventional medicine, and published by a highly impacted oncology journal, which indicates a milestone in the conventional medical system. However, acupuncture and Chinese medicine can not only improve cancer associated symptoms such as pain, fatigue, nauseas/vomitus and diarrhea, but also the cancer itself. The more we try, the more evidence will show up. This is how innovation advances our society, and human health.
1. Mao J et al. Integrative Medicine for Pain Management in Oncology: Society for Integrative Oncology-ASCO Guideline. J Clin Oncol. 2022 Sep 19;JCO2201357. doi: 10.1200/JCO.22.01357. https://ascopubs.org/doi/full/10.1200/JCO.22.01357
2. Mao J et al. Integrative Medicine for Pain Management in Oncology: Society for Integrative Oncology-ASCO Guideline Summary and Q&A. JCO Oncology Practice. DOI https://doi.org/10.1200/OP.22.00622 . https://ascopubs.org/doi/full/10.1200/OP.22.00622