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PONE-D-19-15950

Early mortality after diagnosis of cancer of the head and neck – A population-based nationwide study

PLOS ONE

Dear MD, PhD Farnebo,

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.

For acceptance the revision will need to include modification of the methods section and improved statistical review as documented by reviewer one.  I also agree with reviewer 2 that salivary gland cancers can have entirely different histologies and therefore prognosis from SCC and therefore would consider excluding them or doing a sub-analysis excluding them that is reported in the manuscript.  Finally, reviewer 2 mentions that it may be helpful to do a sub-analysis of those receiving curative treatment to see who does not benefit - while not mandatory for publication, I agree could be an interesting finding.

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Jessica D McDermott, MD, MSCS

Academic Editor

PLOS ONE

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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: No

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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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: Overall an interesting article which some gaps in the methodological presentation. Also, the presentation of the results could benefit from being more precise because otherwise they sound in part trivial, which is not really the case.

Methods:

The description of the statistical analysis is presented in four lines. Given that by using this method all results have been obtained this looks odd. More details need to be added and also relevant literature needs to be cited. So far only a citation to Stata is provided which is a software package. Please cite original papers introducing the used methods.

It seems no Cox proportional hazard model has been used. Why is it not appropriate in this case?

What statistical test has been used to identify a difference in the survival times? Why has this test been selected (discuss and compare with alternatives)?

A discussion about censoring is completely missing. How has this been handeled? What type of censoring is present?

Results:

The figures of the survival curves do not include information about censoring.

For all statistical test, please add the actual p-values and not just p<0.xyz.

Conclusions:

Identification of patients at i 52 ncreased risk of early death shows that older

53 patients with advanced disease, increased WHO score, primary tumour in the hypopharynx,

54 and those given palliative treatment, are more likely than the others to die from head and neck

55 cancer within six months of diagnosis.

This does not sound surprising. What aspect of this is none trivial? Adding quantitive results would make this actually interesting.

We think that it would be

327 beneficial to identify patients at risk early and bear this information in mind when planning

328 their treatment and follow up.

I wonder if there is any disease for which this would NOT be beneficial? If there is none, this is trivial.

Reviewer #2: The authors reported that old age, advanced stage, poor performance status and no curative treatment were the clinical risk factors associated with early death 6 months after diagnosis of head and neck cancer using a nationwide data although the incidence and case number of head and neck cancer are relatively smaller than those of other countries. It is really helpful for clinicians to think about who are not the candidate to recieve the curative treatment, especially in old people or people with poor performance so that will be better if this study describes or analysis the outcome of these people with curative treatment.

Salivary gland cancer is also a totally different cancer from other head and neck cancer so the story is possibly different if salivary gland cancer is excluded.

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Reviewer #1: No

Reviewer #2: No

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Early mortality after diagnosis of cancer of the head and neck – A population-based nationwide study

PONE-D-19-15950R1

Dear Dr. Farnebo,

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

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Jessica D McDermott, MD, MSCS

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 #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 #2: Yes

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

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 #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 #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 #2: I think that the authors answered all quesitons and the revised manuscript is well done and can be accepted for publication

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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 #2: No