Effect of True and Sham Acupuncture on Radiation-Induced Xerostomia Among Patients With Head and Neck Cancer: A Randomized Clinical Trial

Radiation-induced xerostomia (RIX) is a common and debilitating adverse effect of radiotherapy in patients with head and neck cancer, affecting quality of life and difficult to treat. This phase 3 randomized controlled trial investigated whether acupuncture can prevent RIX when administered during the course of radiotherapy. The study was conducted at two leading cancer centers: MD Anderson Cancer Center (Houston, USA) and Fudan University Cancer Center (Shanghai, China), between December 2011 and July 2015. A total of 399 patients with oropharyngeal or nasopharyngeal carcinoma scheduled to receive radiotherapy with a mean dose of at least 24 Gy to the parotid glands were randomized.

Participants were divided into three groups: true acupuncture (TA), sham acupuncture (SA), and standard care control (SCC). The acupuncture protocol consisted of three sessions per week for 6-7 weeks of radiotherapy, for a total of approximately 18 sessions. The true acupuncture group received specific xerostomia-validated points, while the sham group used a combination of non-specific points and validated placebo needling devices. The primary outcome was measured using the Xerostomia Questionnaire (XQ), a validated 0-100 point scale where higher scores indicate more severe symptoms.

Follow-up was conducted at the end of radiotherapy and at 3, 6, and 12 months post-treatment. Of the 399 patients randomized, 339 completed the 12-month assessment (85% adherence rate). Mean age was 51.3 years, with 77.6% men. Adherence to acupuncture treatment was excellent (95.9%).

Results showed that, at 12 months, the mean adjusted xerostomia score in the TA group was significantly lower than in the SCC group (26.6 vs 34.8; P=0.001; effect size = -0.44). The difference between TA and SA was marginally significant (26.6 vs 31.3; P=0.06). The incidence of clinically significant xerostomia (score >30) was lower in the TA group (34.6%) compared with the SA group (47.8%) and the SCC group (55.1%) (P=0.009). Exploratory analyses revealed interesting differences between centers.

In China, true acupuncture was superior to both sham and control, whereas in the USA, both true and sham acupuncture were superior to control, with no significant difference between them. This difference may be related to cultural factors, differences in the treatment setting (inpatient vs outpatient), or variations in the placebo response. The safety profile of acupuncture was excellent, with only one treatment-related adverse event (mild pain at the needle site). Adverse events did not differ between groups or centers.

Limitations include differences in the treatment setting between centers, possible unblinding among Chinese patients due to greater cultural familiarity with acupuncture, and variations in the clinical context that may have influenced the placebo effect. The authors did not systematically control verbal interactions or relaxation factors during treatment. This is the first phase 3 study to demonstrate that acupuncture may be effective in preventing radiation-induced xerostomia, offering a safe and low-cost therapeutic option for at-risk patients. The results suggest that acupuncture should be considered as adjuvant therapy for interested patients, although additional studies are needed to confirm the clinical relevance and generalizability of the findings, particularly given the inconsistencies observed across different populations and treatment centers.