Response to Letter to the Editor Regarding “Efficacy of Chinese Medicine on Postoperative Rehabilitation of Non-Small Cell Lung Cancer (NSCLC), a Randomized Controlled Study” in Integrative Cancer Therapies

To the editor,

We thank Liu et al for their interest in our publication, titled “Efficacy of Chinese Medicine on Postoperative Rehabilitation of Non-Small Cell Lung Cancer (NSCLC), a Randomized Controlled Study,” in Integrative Cancer Therapies. We appreciate the opportunity to address the relevant suggestions raised by our colleagues and welcome this chance for further academic discussion. Below, we provide our responses to the issues raised.

First, currently there is no universally recognized rehabilitation exercise protocol for post-operative patient in lung cancer. To our knowledge, existing clinical guidelines do not specify a detailed, standardized exercise regimen. As mentioned in our publication, the primary recommendation for post-operative patients is early ambulation. ¹ Our further review of a 2024 supplemental report to these guidelines confirmed that the recommendations regarding a specific rehabilitation protocol remain unupdated. ² Furthermore, a 2025 guideline indicates that the utility of structured in-hospital rehabilitation exercises during the post-operative stay remains a subject of debate. The potential benefits of rehabilitation exercises appear to be limited to improving daily physical activity, while evidence supporting their efficacy in other domains remains insufficient. ³ This lack of consensus presented a challenge in designing the rehabilitation strategy for our control group. Consequently, after considering the current guideline recommendations and consulting with thoracic surgery specialists, we opted to instruct the control group patients in breathing training. In the absence of a clear, evidence-based, and effective rehabilitation strategy, assigning a mandatory, structured exercise regimen to the control group could potentially introduce unnecessary risks.

Second, the use of rehabilitation exercise as an intervention made blinding practically challenging. The present study was designed to investigate the potential benefits of an integrated protocol combining traditional Chinese medicine with rehabilitation exercises, rather than to evaluate the effects of any individual component in isolation. As noted in the discussion, a Chinese herbal medicine placebo was not employed in the control group as part of the standard study design. However, designing a credible, placebo-equivalent “sham” rehabilitation exercise for the control group presents a significant methodological hurdle. To our knowledge, no validated or widely accepted “sham exercise” protocol exists in the current literature that could be feasibly applied to a control group in this context. Consequently, it was not possible to blind participants to their group allocation, as they were inherently aware of whether they were performing the Liuzijue exercises. This is a well-recognized limitation common to many clinical trials involving physical or exercise-based interventions. We echo the need for and look forward to the future development of a feasible “sham exercise” protocol to mitigate this issue in future research.

Third, the various domains of the QLQ-C30 questionnaire represent distinct concepts. The scoring methodology of the QLQ-C30 is designed to assess a patient’s quality of life (QoL) through multiple, separate dimensions, including physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, and global QoL. It is important to note that the “Global QoL” score is one specific domain alongside others, rather than representing the patient’s overall quality of life. ⁴ Therefore, the primary objective of utilizing this instrument in our study was to identify the specific domains in which our rehabilitation protocol demonstrated improvement, rather than to present a generalized claim of enhancing overall QoL.

Finally, as acknowledged in our publication, this study has several limitations. We are currently conducting further research based on its findings. We look forward to the development of more robust study designs and high-quality research in the field of post-operative rehabilitation for lung cancer patients, which we believe will provide new insights for enhancing patient care.

We thank the Editors of Integrative Cancer Therapies for this opportunity to respond to the comments.

Yifeng Gu, MD*

Yichao Wang, MD*

Huiling Zhou, MD

Ao Qi, PhD

Guanjin Wu, MMed

Jiaqi Li, MMed

Jialin Yao, MD

Wenxiao Yang, PhD

Lingzi Su, MMed

Yi Liu, MMed

Xueqi Tian, MMed

Jiajun Song, MMed

Yabin Gong, MD

Lijing Jiao, PhD

Ling Xu, PhD
Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai University of Traditional Chinese Medicine, China

Congmeng Zhang, MMed
Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai University of Traditional Chinese Medicine, China
Fangta T.C.M. Hospital of Songjiang District, Shanghai, China

Yong Yang, MD

Xiong Qin, MD
Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
*These authors have contributed equally to this work and share first authorship.