Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear editor,

Thank you for giving me an opportunity to review this manuscript regarding dose/fractionation of RT for bone metastasis.

For me, this conclusion is reasonable and informative when we choose radiation for bone metastasis.

I would like the authors to address the following points.

1.      Bone metastasis is treated not only by radiation but also agents such as chemotherapy, hormone therapy and bone modifying agents (denosumab or zoledronic acid). I would like the authors to describe those parameters in table 1.

2.      Along with the abovementioned point, subtype of breast and lung cancers are important for effect of treatment. Specifically, Expression of Estrogen receptor / Progesterone receptor / HER2 (ie. triple negative or not) for breast cancer and the presence of EGFR mutation for lung cancer are indispensable information. The authors should mention the status of them.  

Author Response

Athens, 23/05/2024

Dear Editor,

We would like to thank you for your kind e-mail with the reviewers’ comments.

We are pleased to send you the revised manuscript along with a response cover letter answering point by point the reviewers’ comments.

Reviewer 1.

“1.      Bone metastasis is treated not only by radiation but also agents such as chemotherapy, hormone therapy and bone modifying agents (denosumab or zoledronic acid). I would like the authors to describe those parameters in table 1.”

Action: All these parameters are described and included in Table 1. Please see revised manuscript

“2.      Along with the abovementioned point, subtype of breast and lung cancers are important for effect of treatment. Specifically, Expression of Estrogen receptor / Progesterone receptor / HER2 (ie. triple negative or not) for breast cancer and the presence of EGFR mutation for lung cancer are indispensable information. The authors should mention the status of them.”

Action: Discussion about hormonal status and EGFR mutational status is included in the manuscript.

We do hope that now our manuscript would be suitable for publication in your honorable Journal

Looking  forward to hearing from you soon.

Yours truly

Dr. Zoi Liakouli (MD)

Reviewer 2 Report

Comments and Suggestions for Authors

The authors are to be commended for undertaking a randomized trial which includes objective outcome (RED), several QOL type outcomes and a patient reported outcome. This is tremendously appreciated, rather than retrospective or single cohort study which just adds to noise.

Minor comment: @104 RDE should be RED.

Minor comment: @ 70 the authors state the CTV is the "affected bone" which implies entire bone. While guidelines suggest the "entire" bone should be treated, in practice this is rarely done for ribs, femur, humerus and iliac bone because of the large volume entailed in such a treatment. The authors should clarify if they treated the whole bone or was partial bone allowed for the above sites?

Minor comment: Table 1 or sec. 2.2 should acknowledge whether bisphosphonates were in use.

Major comment: The results section is quite inadequate. Only a few outcomes are mentioned and only at 3 months. I suggest a table with columns of baseline, 3 and 6 mos and rows of RED, QLQ C30, BPI, MDAH tool and SAT mean values, in order to allow the reader a comparison across groups by tool.

Furthermore the authors mention outcomes of sub-tool @ 109 and 110. These could also be exploded from the overall tool and tabulated for ease of assessment by the reader.

The lack of commentary on 6 month outcomes is concerning and gives the reader the impression that any differences were transient and the authors are perhaps hiding later results which show nothing.

Finally the authors make no comments on whether these differences were clinically meaningful. 

Author Response

Athens, 23/05/2024

Dear Editor,

We would like to thank you for your kind e-mail with the reviewers’ comments.

We are pleased to send you the revised manuscript along with a response cover letter answering point by point the reviewers’ comments.

Reviewer 2.

“Minor comment: @104 RDE should be RED.”

Action: Done. Please see revised manuscript.

“Minor comment: @ 70 the authors state the CTV is the "affected bone" which implies entire bone. While guidelines suggest the "entire" bone should be treated, in practice this is rarely done for ribs, femur, humerus and iliac bone because of the large volume entailed in such a treatment. The authors should clarify if they treated the whole bone or was partial bone allowed for the above sites?”

Action: Done. Definitions about CTV depending on the anatomical site are included in the manuscript.

“Minor comment: Table 1 or sec. 2.2 should acknowledge whether bisphosphonates were in use.”

Action: Done. Discussion about bisphosphonates is included in the manuscript (Table 1).

“Major comment: The results section is quite inadequate. Only a few outcomes are mentioned and only at 3 months. I suggest a table with columns of baseline, 3 and 6 mos and rows of RED, QLQ C30, BPI, MDAH tool and SAT mean values, in order to allow the reader a comparison across groups by tool.”

Action: Done. Details about outcomes of treatment at 3 and 6 months are included in the manuscript.

“Furthermore the authors mention outcomes of sub-tool @ 109 and 110. These could also be exploded from the overall tool and tabulated for ease of assessment by the reader.”

Action: Done. Relative tables are included in the manuscript.

“The lack of commentary on 6 month outcomes is concerning and gives the reader the impression that any differences were transient and the authors are perhaps hiding later results which show nothing.”

Action: Details about outcomes of treatment at 3 and 6 months are included in the manuscript.

“Finally the authors make no comments on whether these differences were clinically meaningful.”

Action: Done. Please see revised manuscript.

We do hope that now our manuscript would be suitable for publication in your honorable Journal

Looking  forward to hearing from you soon.

Yours truly

Dr. Zoi Liakouli (MD)

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors addressed major points I pointed out. I think this study has some limitations but acceptable for publication.

Author Response

Athens, 28/05/2024

Dear Editor,

We would like to thank you for yourkind e-mail with your comments.

We are pleased to send you the revised manuscript along with a response cover letter answering point by point the comments.

Academic Editor notes.

“When the authors made a conclusion suggesting " Multiple fraction radiotherapy may be the preferable option for select patients with painful osteolytic bone metastasis. " I strongly ask them to specify in which patients they suggest this kind of treatment instead of single fraction?”

Action:Done. Please see the revised document with our suggestions.

Comments and Suggestions for Authors.

“The authors addressed major points I pointed out. I think this study has some limitations but acceptable for publication.”

Action: We are most grateful for your comments and suggestions.

Looking forward to hearing from you soon.

Yours truly

Dr. ZoiLiakouli (MD)

Corresponding author