Effects of Structured Exercise Programs on Self-Reported Health-Related Quality of Life in Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript, titled "Effects of Structured Exercise Programs on Self-Reported Health-Related Quality of Life in Patients with Advanced Non-Small Cell Lung Cancer," presents a timely and clinically relevant systematic review and meta-analysis. It explores an important but often underrepresented aspect of cancer care: improving quality of life through non-pharmacologic interventions in patients with advanced disease.

The paper is well written, well organized, and methodologically sound. The authors adhere to current standards for systematic reviews, following PRISMA 2020 guidelines, registering the protocol in PROSPERO, and applying rigorous tools such as the Cochrane risk-of-bias tool (RoB 2), SWiM guidelines, and GRADE assessment. These choices enhance the credibility and transparency of the work.

The findings suggest that structured, supervised exercise programs can provide modest to significant improvements in health-related quality of life (HRQoL) for patients with advanced NSCLC. The qualitative synthesis indicates consistent trends across different types of exercise and various measurement tools. The meta-analysis, while limited to only three studies using the EORTC QLQ-C30, reveals a large effect size (SMD 0.81), albeit with a wide confidence interval. These results, while encouraging, must be interpreted cautiously due to the small number of studies in the pooled analysis.

A major strength of the manuscript is its nuanced discussion of limitations, including heterogeneity in interventions and outcome measures, the challenge of blinding in behavioral interventions, and the difficulty of attributing adverse events to exercise in a population with advanced disease. The authors appropriately highlight the limitations of safety reporting across studies and recommend caution in interpreting these findings.

However, some areas could be strengthened further. A clearer synthesis of the types, intensities, and durations of exercise interventions used across the included studies would help readers understand what kinds of programs are most effective. While the use of multiple HRQoL tools reflects the diversity in the literature, the variability does make comparison difficult. The inclusion of a table summarizing the intervention components and follow-up durations would be helpful. In addition, while the GRADE assessment appropriately rates safety evidence as low certainty, the manuscript would benefit from a brief recommendation on how future studies might standardize safety data collection and reporting.

Despite these minor weaknesses, the manuscript makes a valuable contribution to the field of supportive oncology. It reinforces the role of exercise as a safe and potentially impactful adjunctive therapy even in patients with advanced disease. The writing is clear and professional, and the conclusions are supported by the data.

Author Response

Effects of Structured Exercise Programs on Self-Reported Health-Related Quality of Life in Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

 

Response to Reviewer 3 Comments
1. Summary
Dear esteemed reviewer, On behalf of my co-authors, we would like to thank you for devoting your time in reviewing our manuscript. Indeed, your inputs are of valuable importance to us. Included in this document are our point-by-point response to the first round of reviews.
2. Point-by-point response to Comments and Suggestions for Authors
Comment 1: A clearer synthesis of the types, intensities, and durations of exercise interventions used across the included studies would help readers understand what kinds of programs are most effective.   Response 1: Thank you for this suggestion, we agree that a summary of the exercise characteristics is necessary in order to provide a wider perspective into our study. The authors have included a new appendix (A) to summarize the pertinent exercise interventions that were used in the study, this included the time/duration, intensity, and type of exercise (aerobic or strength-based). The summary of appendix A was discussed in lines 275-287.   Further, the authors have improved the flow of discussion to reflect the practical applications of this study to real world practice. This included analyzing the common factors among enrolled patients and included exercise regimens involved. A concise recommendation on how to apply this study to clinical practice is found on lines 403-442 and figure 5.     Comment 2: The inclusion of a table summarizing the intervention components and follow-up durations would be helpful.   Response 2: Thank you for this suggestion, we agree that a summary of the exercise characteristics is necessary in order to provide a wider perspective into our study. The authors have included a new appendix (A) to summarize the pertinent exercise interventions that were used in the study, this included the time/duration, intensity, and type of exercise (aerobic or strength-based). The summary of appendix A was discussed in lines 275-287.   Further, the authors have improved the flow of discussion to reflect the practical applications of this study to real world practice. This included analyzing the common factors among enrolled patients and included exercise regimens involved. A concise recommendation on how to apply this study to clinical practice is found on lines 403-442 and figure 5.   Comment 3: The manuscript would benefit from a brief recommendation on how future studies might standardize safety data collection and reporting.   Response 3: In relation to the GRADE analysis for safety, standardization of reporting adverse effects is essential for uniformity of interpretation of results. The authors recommend established criterion for reporting adverse events, particularly the Common Terminology Criteria for Adverse Events (CTCAE) (Lines 439-442).

Reviewer 2 Report

Comments and Suggestions for Authors

This article presents a systematic review and meta-analysis of randomized controlled trials assessing the impact of structured exercise programs on health-related quality of life (HRQoL) in patients with advanced non-small cell lung cancer (NSCLC). The primary objective was to determine the effectiveness of these interventions, with a secondary aim of evaluating their safety. Thirteen studies were included in the review, and three were suitable for meta-analysis.

The methodology followed Cochrane, PRISMA, and SWiM guidelines. The selection of studies, inclusion criteria, and data analysis process were described in detail. The risk of bias was assessed using the RoB2 tool, and safety evidence was evaluated using GRADE. Meta-analysis using the EORTC-C30 tool showed a favorable effect of exercise (SMD = 0.81).

Results suggest that structured exercise programs can enhance HRQoL, especially with longer interventions. Some studies also reported reductions in fatigue and improvements in physical functioning. Most interventions were well tolerated, although a few studies reported mild adverse events such as muscle soreness.

Limitations include small pooled sample size, heterogeneity of HRQoL tools, and inconsistent safety reporting. In lines 301–306, these concerns are correctly acknowledged but could be emphasized more strongly in the discussion.

Authors are encouraged to expand the practical implications section – for instance, how to implement such programs within standard oncology care. Lines 343–349 could be shortened in favor of clinical recommendations.

While figures are clear, Figure 4 could benefit from clearer axis labeling.

The authors appropriately identify the relevance of their findings to both clinical practice and health policy, emphasizing the need for longer interventions and better standardization. These findings may inform non-pharmacological strategies supporting NSCLC treatment.

Congratz to the authors on writing a well-designed and meaningful paper. This is a strong manuscript that deserves publication after minor editorial revision.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this very interesting manuscript titled: “Effects of Structured Exercise Programs on Self-Reported 2 Health-Related Quality of Life in Patients with Advanced Non-3 Small Cell Lung Cancer: A Systematic Review and Meta-Analy-4 sis of Randomized Controlled Trials”

 

The content of the article is very interesting e very well written, but it will be necessary some minor adjustments for it to be suitable for publication

 

1. Lack of a summary of the results in the abstract (something like the first paragraph of discussion will work)

 

2. Table 1 is very low quality, and you must remove the lateral limits in order to be a table (not a board). Additionally, it does not comprise with the journal rules.

 

3. Figure 2 is missing

 

4. The discussion is poor. Authors should discuss the key limitations and practical challenges for advanced NSCLC patients in performing structured exercise programs. The authors need to address issues such as treatment-related fatigue and comorbidities that might impede exercise adherence, and explore alternative strategies like home-based or low-impact activities. They should also include clear recommendations on tailoring exercise intensity, frequency, and duration according to patient fitness and treatment response, along with a basic framework for a training plan that ensures safety and ongoing monitoring.

Author Response

Effects of Structured Exercise Programs on Self-Reported Health-Related Quality of Life in Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

 

Response to Reviewer 3 Comments
1. Summary
Dear esteemed reviewer, On behalf of my co-authors, we would like to thank you for devoting your time in reviewing our manuscript. Indeed, your inputs are of valuable importance to us. Included in this document are our point-by-point response to the first round of reviews.
2. Point-by-point response to Comments and Suggestions for Authors
Comment 1: Lack of a summary of the results in the abstract (something like the first paragraph of discussion will work) Response 1: The summary of findings (SWiM, meta-analysis, and GRADE analysis) are now placed at the abstract page (line 31-37).   Comment 2: Table 1 is very low quality, and you must remove the lateral limits in order to be a table (not a board). Additionally, it does not comprise with the journal rules. Response 2: We have revised the presentation of the table of the journal to fit the recommended format. Likewise, we have renamed it as figure 2 (line 250).   Comment 3: Figure 2 is missing Response: Thank you for pointing out of clerical error, the missing “figure 2” has been attributed to the risk of bias section (3.1; line 247). Comment 4:  The discussion is poor. Authors should discuss the key limitations and practical challenges for advanced NSCLC patients in performing structured exercise programs. The authors need to address issues such as treatment-related fatigue and comorbidities that might impede exercise adherence, and explore alternative strategies like home-based or low-impact activities. They should also include clear recommendations on tailoring exercise intensity, frequency, and duration according to patient fitness and treatment response, along with a basic framework for a training plan that ensures safety and ongoing monitoring.   Response 4: The authors have improved the flow of discussion to reflect the practical applications of this study to real world practice. This included analyzing the common factors among enrolled patients and included exercise regimens involved. A concise recommendation on how to apply this study to clinical practice is found on lines 403-442 and figure 5.