PONE-D-20-35492

Use of advanced PET-volume metrics predicts risk of local recurrence and overall survival in anal cancer

PLOS ONE

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PLOS ONE

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Reviewers' comments:

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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: Yes

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: No

Reviewer #2: Yes

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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: Dear editor,

Thank you for giving me the opportunity to review for your prestigious journal.

The manuscript under review is a well written and well performed study on the prognostic significance of FDG PET/CT in anal canal cancer.

The methodology is sound. As anal canal cancer is very rare, studies on this cancer can be very helpful.

My comments can be found below to improve the manuscript.

1- There is a systematic review and meta-analysis on this subject (https://doi.org/10.1155/2018/9760492). The authors may discuss the difference or similarity of their results to the this systematic review.

best wishes,

Ramin Sadeghi ,MD

Reviewer #2: The Authors have retrospectively evaluated the usefulness of advanced PET metrics (SUVmax, MTV and TLG) in predicting the outcome of patients with anal cancer in the absence of distant metastases. They found that higher MTV2.5 and TLG are associated with elevated rates of local recurrence and worse PFS and OS in both pre-treatment and post-treatment settings, therefore making PET-CT a reliable imaging tool in evaluating and following-up patients with localized disease addressed to radiation therapy. Overall the paper is well written, results are clearly written and compared with existing literature in the discussion section.

However some minor concerns should be addressed to give this paper a higher scientific impact:

1) Due to the retrospective design of the paper, it is expected that the 35 patients performing 2 follow-up PET-CTs were in a more advanced T and N stage of disease than the ones performing only one follow-up PET-CT: it is possible that a second follow-up PET-CT was preferred in patients who showed a higher disease burden at first follow-up PET-CT or even at baseline one. It is evident from Table 2 that PET metrics on second follow-up PET-CT are slightly higher than on first follow-up PET-CT: is it justified by the inclusion of patients with a higher burden of disease and consequently worse PET metrics on baseline and/or first follow-up PET-CT, or not? Or these of PET metrics are justified by initial lack of response? Please explain.

2) Has a sub-analysis in terms of outcome for HIV-positive and HIV-negative patients been performed separately? Indeed, it should be useful to know whether PET metrics are the only predictive factors for local recurrence or PFS regardless of HIV infection status (in this case, predictive role has to be maintained at separated evaluation), althogh it has been showed that PET metrics are not quite diffeent between the two groups. HIV status was not included in IPW factors.

3) It is interesting that relative baseline and post-treatment % changes of PET metrics did not reveal anly significant differences in terms of local recurrence, PFS or OS, while absolute values did it: in terms of repeatibility of results using different technical equipment, this could be a limitation; this aspect should be underlined also in the discussion section.

I suggest a terminological correction: in the interoduction section, last paragraph, the Authors use the term "radiographic" features talking about SUV, MTV and TLG: the term "functional" is, in my opinion, more appropriate.

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Reviewer #1: Yes: Ramin Sadeghi, MD

Reviewer #2: No

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Use of advanced PET-volume metrics predicts risk of local recurrence and overall survival in anal cancer

PONE-D-20-35492R1

Dear Dr. Susko,

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,

Giorgio Treglia, MD, MSc

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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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: (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: Yes

Reviewer #2: 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: (No Response)

Reviewer #2: (No Response)

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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: Ramin Sadeghi, MD

Reviewer #2: No