-->PONE-D-26-17187

Diagnostic Performance of Machine Learning Models Based on Dual-Phase 99mTc-MIBI SPECT/CT Semiquantitative Parameters for Differentiating Benign and Malignant Pulmonary Nodules

PLOS One

Dear Dr. Xing,

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Reviewers' comments:

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

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Reviewer #1: Partly

Reviewer #2: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

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

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Reviewer #1: Yes

Reviewer #2: Yes

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

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Reviewer #1: Yes

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: This paper assesses the diagnostic performance of different ML models using Dual-Phase 99mTc-MIBI SPECT/CT semiquantitative Parameters for the differential diagnosis of benign and malignant pulmonary nodules. Here are my suggestions:

In the whole paper, the authors should use precise EANM radiopharmaceutical nomenclature https://eanm.org/publications/guidelines/overview/nomenclature/

The authors should specify in the methods section which SPECT/CT scanner was used (i.e., vendor, model, and so on).

Did you use MIBI in a clinical trial, or is it normal practice in your country?

From which company did you purchase MIBI?

Please clarify whether the study was retrospective or prospective, detailing the EC ID number.

Please clarify which was the acquisition field of view for each patient (i.e., head-to-toe, only thorax,…).

Why did you acquire each step using a 20s interval per projection? How did you select this duration?

Did you assess data distribution before representing it or selecting the best test?

Do the authors have the final histology of the included nodules? Otherwise, they should specify this among the limitations.

“First, malignant nodules showed significantly higher early-phase MIBI uptake than benign nodules” Ok, but please compare this considering the MIBI assessment for thyroid nodules that are considered suspicious/malignant when the early uptake is confirmed/increased in late acquisition (see PMID 28733644).

I would suggest that authors be more cautious with their conclusion statements, as this is a single-centre, preliminary study.

Please double-check all figure legends and titles (i.e. figure 4 “Example text for the main manuscript”).

Reviewer #2: Dear Authors,

Overall, the manuscript is well written, and the methodology is clearly described and scientifically interesting. I particularly appreciated your transparent acknowledgment of the study’s multiple limitations. Nevertheless, the clinical utility of MIBI SPECT/CT in this context appears limited, and its potential role in clinical decision-making should be more clearly defined and discussed. I suggest to try to overcome some of the explicited limitations to ameliorate the manuscript.

Minor comments:

- line 91 and 93 the statement is repeated

- line 91 and 95: prospective or retrospective study?

- line 104-105 this is a result

Best regards

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Reviewer #1: Yes:  Giorgia Ricciardello

Reviewer #2: No

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Diagnostic Performance of Machine Learning Models Based on Dual-Phase 99mTc-MIBI SPECT/CT Semiquantitative Parameters for Differentiating Benign and Malignant Pulmonary Nodules

PONE-D-26-17187R1

Dear Dr. Xing

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,

Riccardo Laudicella

Academic Editor

PLOS One

Additional Editor Comments (optional):

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: 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: (No Response)

Reviewer #2: Yes

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

Reviewer #1: (No Response)

Reviewer #2: Yes

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-->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: (No Response)

Reviewer #2: Yes

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-->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: (No Response)

Reviewer #2: Yes

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-->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: (No Response)

Reviewer #2: Dear Authors,

Thank you for addressing the comments and revising the manuscript in accordance with the suggestions provided. The manuscript is now more comprehensive and precise.

Best regards

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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: Yes:  Giorgia Ricciardello

Reviewer #2: No

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