Abstract
Dear Editor,
We read with great interest the systematic review and meta-analysis by Lee et al. 1 evaluating the efficacy of herbal medicine therapy combined with palliative chemotherapy in patients with unresectable advanced non-small cell lung cancer (NSCLC). By synthesizing evidence from a large number of randomized controlled trials, the authors provide valuable insights into the potential role of Fuzheng-based Qi and Yin therapy as an adjunctive treatment in integrative oncology. Their findings suggesting improvements in tumor response, quality of life, and several chemotherapy-related adverse events are noteworthy and contribute to the ongoing discussion regarding complementary therapeutic strategies for advanced NSCLC. While we appreciate the contribution of this work, several methodological aspects may warrant further clarification to facilitate interpretation of the pooled results.
First, the definition of the target population appears somewhat heterogeneous. The review focuses on patients with unresectable advanced NSCLC, generally corresponding to stage III–IV disease receiving palliative chemotherapy. However, examination of the included trials indicates that some studies enrolled patients with earlier disease stages or did not clearly specify staging information. Because prognosis and therapeutic strategies can vary considerably across disease stages, 2 the inclusion of mixed-stage populations may introduce clinical heterogeneity and influence pooled outcomes such as tumor response or quality-of-life measures.
Second, variability in the definition of the comparator across included trials may also deserve attention. Although the review is framed as a comparison between herbal medicine plus palliative chemotherapy and chemotherapy alone, several studies appear to have used different background regimens in the control arm, including chemoradiotherapy, targeted therapy, or other supportive interventions. Such heterogeneity in background treatment may complicate interpretation of the pooled estimates and potentially contribute to variability in treatment effects. Clarification regarding the consistency of comparator regimens or additional subgroup analyses may further strengthen the robustness of the conclusions.
Third, interpretation of patient-centered outcomes should consider the potential influence of methodological limitations in the included trials. The risk-of-bias assessment indicates that allocation concealment and blinding were frequently unclear or not implemented. This issue may be particularly relevant for subjective outcomes such as Karnofsky Performance Status (KPS) and quality-of-life scales (eg, QLQ-C30), which can be susceptible to expectation or assessment bias when blinding is absent. 3 Although the reported improvements in these measures are encouraging, sensitivity analyses focusing on trials with more rigorous methodological reporting could provide additional reassurance regarding the reliability of the findings.
Despite these considerations, the study by Lee et al. represents a valuable effort to synthesize available evidence on integrative approaches for advanced NSCLC. Future randomized trials with standardized disease staging, clearer comparator definitions, and improved methodological transparency will be important to further clarify the clinical value of herbal medicine as an adjunct to conventional cancer therapy. We commend the authors for their contribution and hope these comments may help support continued methodological refinement in this evolving area of integrative oncology research.
