Clarifying the Survival Benefits of Moxibustion in Advanced Pulmonary Adenocarcinoma: Methodological Considerations

Dear Editor,

We read with great interest the recent study by Li et al, ¹ which investigates the potential survival benefit of adding moxibustion (Moxa) treatment to conventional Western and Chinese herbal therapies in patients with stage-IV pulmonary adenocarcinoma (PUAD-IV). The authors reported a significant, dose-dependent improvement in median survival time (MST) associated with moxibustion treatment. Given the limited therapeutic options and prognosis for patients with advanced adenocarcinoma, this study provides valuable evidence that supports the integrative use of traditional Chinese medicine (TCM) alongside conventional therapies. Despite the important clinical implications, several methodological issues need further clarification to better interpret the reported findings.

First, the authors applied propensity score analysis (PSA) to adjust for baseline covariate imbalances between groups receiving different moxibustion dosages. However, the classification of moxibustion exposure as “none,” “1-4 times,” and “>4 times” remains broad and potentially imprecise. The study did not specify exact intervals or frequencies clearly for each dosage group. Given that therapeutic efficacy and physiological responses to moxibustion may vary substantially with even small changes in dosage frequency or timing, ² providing more precise data on treatment intervals could significantly enhance clinical applicability and reproducibility of findings. A previous meta-analysis has indicated that the therapeutic effectiveness of acupuncture and related TCM modalities is closely related to precise dosing regimens. ³

Second, while the study adjusted for baseline covariates through PSA, it remains unclear whether and how the changes in patients’ conditions during follow-up were addressed analytically. Given that patients received Moxa treatments based on evolving TCM syndromes, it is plausible that those receiving more treatments were inherently different, potentially biasing survival outcomes. Thus, incorporating a time-dependent analysis might have provided more robust insights into the effectiveness of Moxa treatments relative to patient status changes over the follow-up period.

Lastly, although the authors reported promising survival improvements, the precise biological mechanisms underpinning the beneficial effects of moxibustion in PUAD-IV remain speculative. While previous research highlighted potential immunological mechanisms, including modulation of natural killer cells and inflammatory cytokines,^4,5 it would have been informative for the authors to discuss how their findings could translate into actionable clinical practice or guide mechanistic studies more clearly.

In summary, Li et al’s work provides encouraging evidence supporting moxibustion as an adjunctive treatment in advanced pulmonary adenocarcinoma. However, addressing these methodological concerns, particularly regarding dosage precision, time-dependent treatment assignment, and mechanistic clarification, will substantially enhance the reliability, validity, and translational value of their findings. We look forward to future randomized controlled trials designed to rigorously test these hypotheses.

Xingjian Wang, MDDepartment of Respiratory Medicine, Chongqing General Hospital of the Chinese People’s Armed Police Force, China Keyuan Liu, MDDepartment of Respiratory Medicine, Chongqing General Hospital of the Chinese People’s Armed Police Force, China Jie Zhao, MDDepartment of Respiratory Medicine, Chongqing General Hospital of the Chinese People’s Armed Police Force, China Xinglong Li, MD Ping Gan, MDDepartment of Respiratory Medicine, Chongqing General Hospital of the Chinese People’s Armed Police Force, China