PONE-D-23-07584Competing-Risks Model for Predicting The Prognostic Value of Lymph Nodes in Medullary Thyroid CarcinomaPLOS ONE

Dear Dr. Shang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Antonino Maniaci

Academic Editor

PLOS ONE

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Additional Editor Comments (if provided):

Please perform all the revisions suggested to improve the paper.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I read with interest the manuscript by Shang et al. on the prognostic value of Lymph Nodes in Medullary Thyroid Carcinoma. The paper is interesting. However, There are some important limitations.

Major

- The manuscript must be edited for English.

- It is not clear what OS and DSS mean, as it is not well specified in the paper. This makes the paper very hard to read and understand.

Minor

- Please specify in the abstract and in the methods that this was a retrospective study.

- Sometimes the word lymph node is abbreviated, sometimes it is not, thus confounding the reader.

Reviewer #2: recommendations to improve the paper:

Provide a systematic review of the relevant literature to establish the need for this study. Discuss the limitations of previous studies that this one aimed to address.

Describe your study design more clearly in the Methods section. Include details like:

Inclusion and exclusion criteria

Data collection procedures

How variables were classified and coded

Statistical analyses, including packages used

Report measures of uncertainty for effect estimates in the Results, e.g. 95% confidence intervals.

Discuss limitations more thoroughly, e.g.:

Potential selection bias in the SEER database

Limited information on treatments

Retrospective study design

Possible residual confounding

Limited generalizability due to predominantly white sample

would be relevant to strengthen your study:

Wells SA Jr, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. This provides guidelines on the diagnosis and management of medullary thyroid carcinoma, including recommendations on the role of lymph node dissection and staging systems.

Dralle H, et al. Lymph node dissection in medullary thyroid cancer. Br J Surg. 1998;85(2):158–164. This study examines the importance of lymph node dissection in medullary thyroid carcinoma and its impact on prognosis. It supports your findings regarding the prognostic value of lymph node status.

Discuss the role of vocal outcomes in neck surgery, especially preserving the recurrent laryngeal nerve. cite doi:10.23812/19-282-L

Momejev Y, et al. Prognostic Value of Competing-Risks Models Compared With Cox Regression for Breast Cancer Patients. JAMA Netw Open. 2020;3(4):e202938. This compares competing risks and Cox regression models for analyzing breast cancer prognosis, finding that competing risks models provide more accurate estimates. It is similar to your study comparing these approaches for medullary thyroid carcinoma.

Provide more nuanced conclusions that qualify your findings and highlight implications for future research and clinical practice.

Consult subject experts and/or epidemiologists on your statistical methods, results and conclusions.

Cite relevant literature throughout to contextualize your study and support claims.

Edit the manuscript for clarity, conciseness and adherence to reporting guidelines for observational studies (e.g. STROBE).

Consider registering the study protocol to improve transparency and reduce reporting bias.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-23-07584R1Competing-risks model for predicting the prognostic value of lymph nodes in medullary thyroid carcinomaPLOS ONE

Dear Dr. Shang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Sep 09 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Antonino Maniaci

Academic Editor

PLOS ONE

Additional Editor Comments:

Dear authors a reviewer suggested to perform all the revisions requried. Please consider to include all the revisions required. Best regards

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for your comments. All issues have been addressed after the revision. I have no more comments to make.

Reviewer #2: Dear reviewer good work was performed but not all the suggestions were addressed. Read another time the comments and address all the modifications proposed.

Best regards.

Reviewer #3: I have read with great interest the manuscript entitled “Competing-risks model for predicting the prognostic value of lymph nodes in medullary thyroid carcinoma”. In this study the authors used the SEER database to review almost 2,500 patients with MTC. The authors identified several factors associated with poor prognosis (age, tumor size, LNs, positive LNs, LN ratio, etc.). When comparing two statistical tools (multivariate Cox hazard and competitive risk factors) the authors identified LNs (number and ratio) as poor prognostic factors.

Of note, this is a revised version with improved English and style.

Comments -

1. This is a retrospective study on the SEER database. As such, many factors are missing such as number of incidental MTC, preoperative and postoperative calcitonin, biological treatment, sporadic vs. hereditary, and more.

2. Other than the competitive risk model there is not much new data here and similar results have been published many times before.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Competing-risks model for predicting the prognostic value of lymph nodes in medullary thyroid carcinoma

PONE-D-23-07584R2

Dear Dr. Shang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Antonino Maniaci

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Well done, the paper is improved and can be accepted. Bests