Mistletoe Extracts during the Oncological Perioperative Period: A Systematic Review and Meta-Analysis of Human Randomized Controlled Trials

Round 1

Reviewer 1 Report

This is a systematic review and meta-analysis of human randomized controlled trials (RCTs) evaluating the safety and efficacy of mistletoe extract (ME) use during the oncological perioperative period. The review included 7 RCTs and 3 non-randomized studies. The RCTs had sample sizes ranging from 20 to 204 participants, and the publication dates ranged from 2001 to 2020. The methodological quality of the included studies was assessed, and it was found that all RCTs had a substantial risk of bias, with none judged to have a low risk of bias overall. The main limitations of the studies were the lack of blinding and placebo/sham controls. The meta-analysis suggested a possible benefit of ME use for patients with cancer undergoing surgery, particularly in terms of immune function and quality of life. However, the evidence was limited and further investigation is needed to address the methodological limitations. The non-randomized studies also had varying methodological quality, and the review acknowledged the limitations of excluding non-English reports and not searching Asian databases. Overall, the review provides insights into the use of ME during the perioperative period in cancer patients but highlights the need for more rigorous studies.

The major concerns about this review are related to the methodological limitations and the risk of bias in the included studies.

 Risk of Bias: The review found that all the included RCTs had a substantial risk of bias, with none judged to have a low risk of bias overall. The elements that scored worst were related to blinding, as none of the RCTs reported being double-blinded, which suggests potential performance and detection bias. Additionally, the majority of the studies were unclear for selective reporting, as trial registration or an accessible protocol was not cited, indicating possible reporting bias. These biases can affect the validity and reliability of the study results.

 

Methodological Limitations: The review acknowledges several methodological limitations of the included studies. One major limitation is the lack of blinding and placebo/sham controls in the RCTs, which can introduce bias and affect the interpretation of the results. Another limitation is the short follow-up times and inadequate control for confounding in the non-randomized studies, which can limit the reliability of the findings. Additionally, the review excluded non-English reports and did not search Asian databases, which introduces a language bias and may have missed relevant studies.

 

Sparse Evidence: The review highlights that the evidence for the efficacy of mistletoe extract during the perioperative period is fairly sparse. The number of included studies was limited, and the methodological limitations of these studies weaken the strength of the findings. Therefore, further investigation with more rigorous study designs is needed to provide more robust evidence.

 

 

Poor Reporting of Adverse Events: The review mentions that the details of adverse events were poorly reported across the RCTs. While there were no significant concerning side effects, serious adverse events, or post-operative complications reported, the lack of comprehensive reporting raises concerns about the safety profile of mistletoe extract use during the perioperative period.

Overall, the concerns about this review mainly revolve around the risk of bias in the included studies.

 

no comments

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Regarding the manuscript (curroncol-2539458) entitled:

“Mistletoe extracts during the oncological perioperative period: A systematic review and meta-analysis of human randomized controlled trials”

 

General comment

 

The manuscript describes the systemic review of the safety and efficacy of mistletoe extract (ME) use during the oncological perioperative period where 12 reports had been used for the study. I have a few comments to be considered before publication: 

- 1. Introduction: More description about bioactive components should be added.

2- Figure 2: This is a table not a figure. So,  Figure 2 should be Table 3. Besides color code should be added

3- Figure 3  should be added 4- Table 3: Meaning of the number of stars should be added  

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

No more comments

no more comments

Reviewer 2 Report

no comment