Background & Aims
Pain is highly prevalent in cancer patients and can result in a high burden of opioid use with consequent adverse effects on patients’ quality of life while undergoing curative treatment, seeking end-of-life care, or living as cancer survivors. Additionally, cancer patients may be at higher risk for developing opioid dependence than the general population. Alternative effective non-opioid treatments are urgently needed. Scrambler therapy is a non-invasive neuromodulatory treatment that is theorized to desensitize peripheral pain transmission signals and has been shown in early studies to be effective for a wide range of chronic pain conditions, including cancer-related drug-resistant visceral pain, metastatic bone pain, and chemotherapy-induced peripheral neuropathy (CIPN). The aim of this study was to perform a systematic review on the strength and quality of evidence of scrambler therapy for cancer pain conditions.
Methods
This review follows Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. We conducted a systematic search of MEDLINE, Embase, Web of Science, Clinicaltrials.gov, and Cochrane Library for publications in English from January 1, 2003 to October 16, 2023. The concepts searched include “cancer”, “neuropathy”, “pain” and “scrambler therapy” etc. Inclusion criteria were human studies, pain due to cancer, and scrambler therapy as the intervention. Articles were excluded if they were reviews or trial protocols without results. Case reports and observational before-after studies were appraised using a modified Joanna Briggs Institute appraisal checklist. Non-randomized and randomized trials were appraised using the Cochrane’s Risk of Bias in Non-Randomized Studies of Interventions and Risk of Bias 2 tools, respectively. For synthesis and recommendations, we adhered to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.
Results
Out of 129 results, 37 studies were included for review. Publication types were 9 abstracts, 1 poster, 24 articles, and 3 trial registrations. Six studies contained duplicate or preliminary data; thus, there were 31 unique studies representing 637 cancer patients. Of the these, study designs were 11 case reports (of 1-5 patients), 15 observational before-after studies (10-83 patients), and 5 randomized trials (22-80 patients). Cancer pain conditions studied included pain originating from primary cancers and/or their metastases as well as pain secondary to cancer treatments (chemotherapy, surgery, radiation, etc.). The numeric symptom rating scale 0-10 was the most used outcome (22 studies). Of these 22, 8/8 case reports and 9/11 before-after studies reported >50% pain relief by end of treatment, and three randomized trials compared scrambler to medication only, TENS, and a possibly non-inert sham; endpoint arm differences of 2.4, 1.9, and 0.9 favored scrambler therapy, respectively.
Conclusions
Using the GRADE approach, we suggest there is a weak recommendation based on low-quality study evidence for scrambler therapy in treating symptomatic CIPN. Similarly, there is a weak recommendation based on very low-quality study evidence for scrambler therapy in treating other forms of cancer pain. Scrambler therapy appears to have variable small to large benefits, possibly due to being operator-dependent, but with minimal risk of harms to patients. We speculate based on limited follow-up data that those who respond to scrambler therapy may need occasional retreatment and/or maintenance sessions for ongoing relief. Limited medication data suggests that scrambler therapy may aid in reducing opioids and other pain medications. In cancer patients with refractory pain impacting function and limited treatment options, scrambler therapy may be worth consideration. Additional randomized trials with consideration of pragmatic approaches are needed to further test this intervention’s validity.
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Presenting Author
Salahadin Abdi
Poster Authors
Alice Ye
The University of Texas MD Anderson Cancer Center
Lead Author
Ahmed Butt
MD
The University of Texas Medical Branch at Galveston
Lead Author
Yimin Geng
MSIS, MS
The University of Texas MD Anderson Cancer Center
Lead Author
Salahadin Abdi
MD, PhD
The University of Texas MD Anderson Cancer Center
Lead Author