Abstract
Dear Editor,
We read with great interest the systematic review and meta-analysis by Lee et al 1 evaluating herbal medicine combined with chemotherapy in advanced non-small cell lung cancer (NSCLC). Synthesizing evidence from 81 randomized controlled trials (RCTs) represents a significant undertaking and provides a valuable overview of the potential role of Fuzheng-Based Qi and Yin Therapy (FBQYT) in the integrative management of advanced lung cancer. The authors are to be commended for their detailed work.
While the review rigorously addresses study quality and heterogeneity, we wish to highlight a fundamental methodological consideration embedded in its core eligibility criterion—the definition of the intervention itself. This consideration substantially influences the interpretation of the results and the design of future studies.
The authors defined FBQYT based on the reported therapeutic intent of the original trials, requiring explicit mention of a “Fuzheng” strategy or the treatment of “Qi deficiency” or “Yin deficiency” patterns. This approach, which prioritizes the traditional diagnostic framework over specific pharmacological composition, is philosophically sound within the paradigm of Traditional Asian Medicine (TAM) and successfully groups studies by their underlying theoretical rationale. 2 However, this classification strategy may inadvertently introduce a layer of interpretive heterogeneity distinct from, and potentially additive to, the clinical and methodological heterogeneity already discussed. The same core combination of herbs could be employed in different studies: one might explicitly frame it within a “Qi and Yin tonification” protocol for lung cancer, while another might use an identical formula described simply as an “adjuvant to mitigate chemotherapy toxicity” without invoking specific TAM pattern terminology. Conversely, 2 formulas with divergent herb compositions might both be labeled as “Fuzheng” by their respective authors. Relying on author-reported intent alone creates a classification system sensitive to variability in reporting conventions rather than one anchored to a reproducible, compositional standard.
This raises a pivotal question for the field of integrative oncology evidence synthesis: Should the classification of herbal interventions in meta-analyses be based primarily on reported traditional principles, on standardized formula compositions, or on a hybrid model? The choice defines the construct being evaluated—whether it is the efficacy of a specific herbal combination or the efficacy of a treatment strategy guided by a specific TAM principle. The authors’ frequency and network analyses identify a core set of commonly used herbs, suggesting a de facto compositional convergence. Yet, the review’s primary inclusion criterion was not based on this composition.
This disconnect between the classification method and the subsequent compositional analysis highlights an area ripe for methodological refinement.
To enhance precision and reproducibility, we propose that future systematic reviews in this domain consider adopting a dual-anchored eligibility and classification framework. First, they could maintain the inclusion of studies that explicitly report treatment based on recognized TAM patterns, as done effectively by Lee et al. Second, they could simultaneously code all included interventions using a standardized, ontology-driven system for herbal formulas. This would allow for complementary subgroup analyses: one based on the stated therapeutic principle and another based on the presence of core herbal components. Such an approach could help disentangle whether observed effects are more strongly associated with a documented TCM diagnosis or with specific phytochemical profiles. Furthermore, we echo the authors’ call for improved reporting and encourage future primary RCTs to mandatorily report both the TCM pattern diagnosis and the complete formula composition with dosages, in line with the CONSORT extension for Chinese Herbal Medicine Formulas. 2 Future trials should also explore biomarker correlates that might objectively define subsets of patients who respond to “Qi-tonifying” or “Yin-nourishing” regimens, as exemplified by studies that have identified distinct metabolic profiles for Qi and Yin deficiency patterns in other diseases, 3 thereby building a bridge between traditional concepts and modern pathophysiology.
Lee et al’s review makes a substantial contribution by consolidating a large body of literature under the FBQYT framework. By openly discussing and further developing methodologies for defining and classifying complex herbal interventions, the integrative oncology community can strengthen the validity of its conclusions and accelerate the translation of promising therapies into clearer clinical guidelines.
Footnotes
Author Contributions
Xiaoyu Han: conceptualization, writing—original draft, writing—review and editing. Yujin Liu: writing—original draft, writing—review and editing. All authors contributed to the study conception and design.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.