A Prospective, International, Multicentre Registry of Patients Undergoing Segmental Mandibular Defect Reconstruction After Mandibular Resection for Tumours and Drug-Induced Osteonecrosis: A Study Protocol

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a well-designed and carefully planned study, and I congratulate the authors on conducting it. The topic is highly relevant and timely, given the considerable variability of available treatment options and the lack of large-scale “real-world” data. The manuscript is well-structured, with clearly defined objectives, methodology, and a discussion of strengths and weaknesses. Despite the many positive aspects, there are several issues and questions that could be improved.

The inclusion criteria are very broad: this will facilitate patient recruitment but may complicate data analysis and reduce the accuracy of conclusions. There is a high risk of confounding due to differences in comorbidities, surgeon experience, and institutional resources.

The planned enrollment of 300 patients is realistic, but it is not based on a statistical hypothesis. It would be desirable to clarify what subgroup analyses can realistically be performed. I would also like the authors to define more clearly the hierarchy of endpoints (e.g., successful reconstruction → implant-based rehabilitation → quality of life).

The manuscript states that segmental defects arise from resection procedures and congenital anomalies. However, defects resulting from high-energy trauma are overlooked. Currently, due to ongoing armed conflicts in many parts of the world (Palestine, Ukraine, etc.), the number of such patients is extremely high, and in some countries, trauma is the dominant cause of mandibular defects.

A two-year follow-up may be insufficient to evaluate long-term outcomes, particularly implant survival, especially if dental implantation is highlighted as an important issue in the introduction. At minimum, the authors should explain why the follow-up was limited to two years.

In general, the Introduction is too long and should be limited to 2–3 short paragraphs, with about two-thirds of the current text moved to the Discussion.

The manuscript states that only 15–20% of patients receive implants after reconstruction, citing the study by Pogrel et al. However, this statement is based on a single study that is nearly 30 years old. This trend may have changed, so the assertion is not entirely accurate.

The authors plan to use the Brown classification; however, despite its wide adoption, this system does not take into account the condition of perimandibular soft tissues. This is not critical, but the authors might consider alternative systems, such as the Urken et al. CRBS classification.

Could the authors clarify which specific software platforms will be used for virtual surgical planning (VSP)? This information would be important for reproducibility and for understanding the comparability of results across different centers.

The data collection section does not mention harmful habits and addictions. According to many studies, smoking can significantly affect reconstruction outcomes. The authors should indicate whether such information will be collected.

Some methodological sections are overly detailed and cumbersome (for example, the description of VSP, 3D biomodels, and cutting guides). I recommend presenting part of this information in the form of a diagram, table, or figure in order to reduce the text volume and improve clarity and conciseness.

Finally, the manuscript should be carefully checked for grammatical errors. For example, there are overly long sentences that are difficult to read, as well as clear mistakes such as “patients meeting all the inclusion and none of the inclusion criteria” and “osseus reconstruction”, among others.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This is a very interesting and important study. The creation of an international repository, particularly for rare mandibular conditions, has the potential to significantly aid experts worldwide in determining optimal treatment modalities.

Abstract
The abstract presents the trial protocol and rationale for a study on mandibular defect reconstruction in a non-trauma context. Consider clarifying the study objectives and emphasizing the significance of establishing an international database for rare mandibular conditions.

Introduction
The introduction would benefit from a discussion of priorities in treating mandibular defects, including:

• Addressing the primary disease
• Reconstruction of the defect
• Restoration of functionality

(an image/figure could be used to display this information in a nice format for the reader)

Although high-velocity trauma is less common, it would be important to mention other causes of mandibular defects, as these require different treatment algorithms and planning. May also provide some more insight why these cases are not suitable for the current database. 

Additionally, a brief discussion of modern treatment planning techniques could be included, such as:

• CAD (computer-aided design)
• Imaging software
• Segmentation
• Customizable implants
• 3D models

Methods
The study includes sites across Europe, the United States, and one centre in Asia. Will this change and be open to other centres in the future?

• Will any additional patient-reported outcome measures (PROMs) be utilized, particularly for head and neck outcomes? For example: MDASI or equivalents, quality-of-life metrics assessing functionality (swallowing, oral mucositis, performance status), UQQOL, HRQOL, HADS, etc. Are all the QOL/PROMS translated? 
• Are trauma defects excluded and why?
• Are there any criteria that could warrant early termination of the study?
• The schedule of events and data collection at each visit is very thorough.
• It would be helpful to include the recruitment strategy, ideally with a flow diagram. Will additional sites be added over time?

Overall Considerations

• What are the standard-of-care procedures, investigations, and assessments to be performed during the study? Which visits coincide with standard-of-care assessments in this context?
• Will a treatment algorithm be developed or suggested based on the study findings?

Summary
Overall, this is a highly interesting and well-conceived study proposal. With minor revisions to include additional details on treatment priorities, patient-reported outcomes, recruitment strategy, and standard-of-care procedures, this study has the potential to make a meaningful contribution to the field of mandibular reconstruction.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the thorough answers. The manuscript can be published and is of interest to the reader. I wish you success with the planned study and look forward to the results.