High-Dose-Rate Three-Dimensional Image-Guided Adaptive Brachytherapy (3D IGABT) for Locally Advanced Cervical Cancer (LACC): A Narrative Review on Imaging Modality and Clinical Evidence

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The paper is an extensive review on the present treatment of cervical cancer.

Title: please add "a narrative review"

 Abstract section: Matherial and methods should be more clear. Results and Conclusions should be presented separately.

Comments on the Quality of English Language

The English of this paper is in need of a minor correction by a Medical Editor.

Author Response

Dear Reviewer,

Thank you for appreciating our efforts to address your constructive comments, which really helped us improve the manuscript.

1. We have modified the title.
2. We have revised the abstract. Additional texts to the manuscript are indicated by yellow highlight. Meanwhile,  I have deleted some texts （in track change mode) for the word limit reason.

Thank you again for your valuable suggestions.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Congratulations on your hard work. The manuscript addresses a crucial gap by discussing the role of different imaging techniques in IGABT and their impact on treatment outcomes. The methodology section is well-structured, but some areas could benefit from improvement. Specific recommendations include incorporating dosimetric studies like:

1 Georgescu, M.T.; Moldoveanu, V.; Ileanu, B.-V.; Anghel, R. Dosimetric influence of uterus position in cervix cancer high-dose-rate brachytherapy. Rom. J. Phys. 2016, 61, 1557–1566

2 Holloway CL, Racine ML, Cormack RA, O'Farrell DA, Viswanathan AN. Sigmoid dose using 3D imaging in cervical-cancer brachytherapy. Radiother Oncol. 2009 Nov;93(2):307-10. doi: 10.1016/j.radonc.2009.06.032. Epub 2009 Aug 6. PMID: 19665244; PMCID: PMC2867463.

3 Sapienza L, Aiza A, Gomes M, et al. Bladder (ICRU) dose point does not predict urinary acute toxicity in adjuvant isolated vaginal vault high-dose-rate brachytherapy for intermediate-risk endometrial cancer. Journal of Contemporary Brachytherapy. 2015;7(5):357-362. doi:10.5114/jcb.2015.54952.

And suggest evaluating the dosimetric differences between conventional and 3D conformal brachytherapy as outlined in the provided study (e.g. https://rrp.nipne.ro/2017/AN608.pdf). More comparative analyses between imaging modalities and their impact on dosimetry would enhance the manuscript. Also, the references provided are comprehensive and relevant to the subject area. However, the inclusion of additional dosimetric studies and comparative analyses, as mentioned earlier, could further strengthen the references. The addition of figures illustrating dosimetric comparisons or procedural steps could enhance the visual representation and comprehension of the content.

In conclusion, this manuscript serves as an informative and detailed review of IGABT techniques for LACC. Improvements in methodology, particularly incorporating dosimetric studies, and expanding the comparative analysis between imaging modalities would enrich the manuscript's depth. Additionally, visual aids and figures could improve the presentation of complex information.

Author Response

Dear reviewer,

Thank you for your insightful comments and suggestions on our manuscript. We have made corresponding changes to the manuscript that we believe would make it clearer and more complete.

1. We have included dosimetric studies evaluating dosimetry between traditional 2D and 3D brachytherapy (Introduction part, Line 49). There have been sufficient evidence supporting the transition to 3D IGABT, and in this review we mainly discuss the topic “3D IGABT Imaging Modality” So we hope this modify  to manuscript would be adequate for reasons of length.
2. You suggested that more comparative analyses between imaging modalities and their impact on dosimetry were necessary. We are thankful for your constructive comments. After a systematic search, we found several comparative studies between imaging modalities.
   1. For the “CT-guided BT” part, we enrolled two retrospective studies comparing CT- and MRI-guided BT in terms of the dosimetry and clinical outcomes. (Line 181-190)
   2. For the “CT/MRI-guided BT” part, one study reported CT/MRI hybrid approach and MRI approach and showed comparable results. But selection bias remained in this study. (Line 223-228)
   3. For the “US-guided BT", we added two studies. The first were dosimetric studies on TAUS-based planning and 2D MRI imaging. (Line 296-298)The second were a real-world study to compare TAUS- and CT-guided BT. (Line 305-307) There currently are limited data to directly compare different planning strategies. The longer-term clinical outcomes associated with these approaches also require further elucidation. So we modified the enrolled studies based on current results and hoped this would enhance the depth. We appreciate the comments that contributed to a significant improvement of the manuscript.
3. Thank you for your comments on adding illustrating figures to improve the visual representation. We agree with the opinion for better presentation. But for the short time reason, it is difficult for us to obtain the copyright from the original researcher. Also, the procedural steps vary a lot among different approaches, it would take a hard effort. We will work towards this in the future.

Thank you again for your valuable suggestions.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors presented a paper about "High-dose-rate Three-dimensional Image-guided Adaptive Brachytherapy (3D IGABT) for Locally Advanced Cervical Cancer (LACC): Imaging modality and Clinical Evidence".

The topic is absolutely interesting and even though we are a dealing with a very vast topic the overall structure of the article is concise and well defined.

I have a few suggestions that I would like the authors to consider as follows:

1) in the introduction section there is a description of the old technique 2D and then the transition to the new 3D but no mention is given to the concept of 4D which is only shown in figure 1. Please add a paragraph explaining the definition of 4D brachytherapy

2) in the section for MRI, which the authors correctly define the gold standard it would be an addition to add the concept that also in the radiochemotherapy phase just before BT MRI has become relevant due to hybrid MRI-Linac machines and there is emerging clinical evidence about cervical cancer (see PMID: 32066345 for a detailed reference)

3) I appreciate the great effort to provide a vast literature overview however I firmly believe that the key messages should be clear and also the conclusions as well. With regard to the contouring phase please state clearly that MRI is the gold standard and that CT could just be considered in a combined fashion with MRI (either fusion, asynchronous etc as reported in table 2), whereas the other modalities are just under investigation (US and PET).

With regard to the insertion of the tandem as well I believe it should be more clearly stated that US is the gold standard that should be followed to reduce the risk of perforation and the other imaging modalities (MIR, 3D printing) are just under investigation

Author Response

Dear reviewer,

Thank you for your valuable review and suggestions about our manuscript. We have modified the manuscript regarding to your comments as follows.

1. We have added a paragraph explaining the definition of 4D brachytherapy for “2.1. MRI-guided contouring and planning”part (Line 82-83). Considering GTV and IR-CTV are only visible on MRI, the definifiton of 4D IGABT is applied under the MRI situation. So we added this in the MRI part.
2. We also added the concept of MRI-Linac machines in “MRI-guided contouring and planning”part (Line 71-73.)
3. You suggested that the key messages should be clear. We are thankful for your constructive comments.
   1. In “Conclusions”phase, we clarified that “CT is the most wildly applied modality, and it is considered to be combined with MRI or US to improve its contouring precision. There are also several preclinical and early phase studies reporting PET- and US-guided BT. ”(Line 421-424). For insertion parts, we added “Real-time US guidance is recommended as the gold standard to assist tandem insertion. Other techniques, like real-time MRI-guidance and 3D printing applicators and templates are under investigation. ”(Line 428-431) We also modified the abstract to make it more clear.
   2. In the “US-guided applicator implantation” part, we added “as the gold standard to assist tandem insertion to prevent perforation” to state the importance of US to assist tandem implantation". (Line 331) With regard to the contouring phase, we have discuss that “enhanced CT and/or ultrasound may also reduce the variations and dose impacts of target delineation” in the original manuscript.(Line 158-159)

Thank you again for your valuable suggestions. We hope these revisions will improve the manuscript.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

I agree with the current form of the mansucript.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors have satisfactorily addressed all of my previous comments.