Selective Internal Radiation Combined with Chemotherapy Maintains the Quality of Life in Intrahepatic Cholangiocarcinomas

Round 1

Reviewer 1 Report

This is a very well written paper, which I cannot improve by any comments.

Author Response

We thank the reviewer for his/her nice comment. No revision was required.

Reviewer 2 Report

Well written manuscript. Addressed an important research question for SIRT in ICC in the MISPHEC trial.

The limitations are mentioned correctly. Given those limitations, the data and interpretations and clinical implications are nicely described. Hopefully this will be expanded to the stage III trial.

I suggest to include SD or CI in the figures (at least for Fig 1 and 4) for clarity. And also to show difference between male and female patients.

Minor suggestion: To delete the last sentence from the conclusion - "This result is also true and all the more important in patients undergoing secondary resection".

Author Response

We thank the reviewer for the nice comments.

We were not able to modify the figures, as the limited number of patients could not allow us to do subgroup analyses between female and male patients.

We agree for the suggestion of deleting the last sentence.

Reviewer 3 Report

The authors conducted an ad hoc analysis of the MISPHEC trial on the quality of life in patients with advanced intrahepatic cholangiocarcinoma underwent selective internal radiation combined with chemotherapy. They concluded that QoL is maintained in patients underwent combination of SIRT and Gem Cis chemotherapy as first of treatment. I have the following comments:

1. Essentially, this is a case series ad hoc analysis of patients in the previously reported MISPHEC trial. The trial was powered for the primary end point of response rate. As such it is difficult to know whether there is enough patients to reach meaningful QoL data for this treatment regimen.
2. The toxicities of chemotherapy are often the determining factor for patients’ QoL during treatment. SIRT tends to cause immediate side effects, but not commonly long term toxicities. Therefore QoL treatment outcomes can be biased based on treatment related factors. Please elaborate.
3. Overall, a concise, well-written study but fairly limited by the ad hoc data analysis case series study design.
4. Minor comment:
   1. Figure 1B – Valeur du Score needs to be translated to Score value
   2. Would be helpful to include the QLQ-C30 questionnaire as supplemental materials

Author Response

1. We thank the reviewer for his/her comment. The analysis was preplanned. However we agree that the question of the limited number of patients is important. We reinforced the statement in the “limitations” section of the discussion: “As the number of patients included is relatively low and because of the number of missing data, statistical power is limited, and uncertainties remain as regards to the QoL data with this regimen.”
2. We thank the reviewer for his/her comment. Indeed, QoL analysis results from both treatments and disease. We added discussion on this point.
3. We agree with the comment, however, limitations are described in the “limitations” section of the discussion.
4. We corrected figure 1B. QLQ-C30 is a property of the EORTC and we did not have permission for republication. However, the QLQ-C30 is available freely on demand to the EORTC for academic researcher.

Reviewer 4 Report

Overall a limited analysis due to small numbers of patients.  Application of data is limited and we cannot draw significant conclusions from the analysis due to lack of power.  But I think study is still worthy of publishing as there is a lack of QoL data.

Major comments:

• Please specify in the methods that patients with limited extrahepatic metastases were also enrolled.
• Would disagree with your statement in conclusion that 'we can assume that the treatment helps to maintain QoL', as the dataset is small.

Minor: please see the attached file with my edits and suggestions for improving writing style.

Comments for author File: Comments.pdf

Author Response

We thank the reviewer for the comments and edits. We agreed and changed the phrase at the conclusion. We also accepted the edits and revised accordingly.