A predictive model of the effect of therapeutic radiation on the human ovary

Thomas W. Kelsey; Chia-Ho Hua; Amber Wyatt; Danny Indelicato; W. Hamish Wallace

doi:10.1371/journal.pone.0277052

Peer Review History

Original SubmissionJune 7, 2022
11 Sep 2022 Decision Letter - Meijia Zhang, Editor PONE-D-22-15540A predictive model of the effect of therapeutic radiation on the human ovaryPLOS ONE Dear Dr. Kelsey, 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. The reviewers are critical of its presentation. There are several criticisms that must be adequately addressed. These require a detailed response and may require additional data or experiments. . Please submit your revised manuscript by Oct 26 2022 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, Meijia Zhang Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. Additional Editor Comments: The reviewers were critical of its presentation. There are several criticisms that must be adequately addressed. These require a detailed response and may require additional data or experiments. [Note: HTML markup is below. Please do not edit.] 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: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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 ****** 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: Yes Reviewer #2: Yes ****** 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: 1.The authors should give a specific definition of the non-growing follicle(NGF). 2.Line 172 and 173: the reference was outdated. 3.Figure 4a: the line chart of the proton plan lacked a Y-axis title. Reviewer #2: The POI caused by radiotherapy for cancer in young women has a significant impact on women's fertility. This study provides a model for predicting the age of occurrence of POI and allows detailed predictions of the impact of various radiotherapy plans on fertility, which helps to understand the fertility risk of patients more clearly. 1 The four cases in this study are fewer, the coverage should be more comprehensive. 2 There seems to be a problem in the description of the method, for example, lines 134-146 seem to be in the result. 3 It is confused that the description of fig.1, fig.2 and fig.3 appear in methods. 4 The results of fig.4-fig.7 are too scattered and should be integrated. Why are the figures separate from each other in fig.4abcd? Also include fig.5 abcd, fig. 6abcd, fig.7abcd? 5 The structure of this manuscript is a little confused. ****** 6. 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 ******** [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. https://doi.org/10.1371/journal.pone.0277052.r001
Revision 1
23 Sep 2022 Author Response Dear Meijia Zhang Academic Editor PLOS ONE, Thank you for your detailed and helpful reviews of our manuscript. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. We have carefully considered PLOS ONE’S style requirements and made any changes that were necessary. See revised manuscript. 2. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. The minimal data set underlying our results is the solution to the Wallace-Kelsey model which is publicly available in Table form in the java script directory of the web page. We have added a data availability statement in the manuscript specifically so that the reader can if required source the original data set. Reviewer 1 and 2 specific comments: 1. Is the manuscript technically sound, and do the data support the conclusions?  Reviewer #1: Yes Reviewer #2: Yes Thank you for these positive assessments. 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Thank you for these positive assessments. 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 Thank you for these positive assessments. See our response above regarding public availability of the data set. 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: Yes Reviewer #2: Yes Thank you for these positive assessments. 5. Review Comments to the Author   Reviewer #1: 1.The authors should give a specific definition of the non-growing follicle(NGF).  An accepted definition of the non-growing human follicle is as follows: Non growing follicles (NGF) contain immature oocytes surrounded by flat, squamous granulosa cells (support cells) that are segregated from the oocyte's environment by the basal lamina. They are quiescent, showing little to no biological activity. They represent the human ovarian reserve. We have inserted this definition into the introduction and standardised our terminology throughout the manuscript using NGF throughout. 2.Line 172 and 173: the reference was outdated. Thank you. We have updated the reference in relation to the assessment of ovarian reserve in those women under 25 years to PMID 32315387, published in 2020. 3.Figure 4a: the line chart of the proton plan lacked a Y-axis title. Thank you. We have corrected this error. The y-axis is % coverage as in the other figures. Reviewer #2: The POI caused by radiotherapy for cancer in young women has a significant impact on women's fertility. This study provides a model for predicting the age of occurrence of POI and allows detailed predictions of the impact of various radiotherapy plans on fertility, which helps to understand the fertility risk of patients more clearly. Thank you for these positive comments. 1. The four cases in this study are fewer, the coverage should be more comprehensive. The four cases are exemplars. The aim of the four cases is to demonstrate the potential application of using our algorithm to predict with confidence intervals the age at POI. This is useful for counselling and for discussions around fertility preservation. We think more cases will not add anything to the manuscript as they illustrate the methodology in four representative patients and are not the results of our manuscript. 2 There seems to be a problem in the description of the method, for example, lines 134-146 seem to be in the result. This comment refers to our methodology for the models that underpin the algorithm as shown in figures 2 and 3. We are happy to accommodate this referee’s comment and have transferred the section that describes Figures 2 and 3 (lines 134-146) to the results section. 3 It is confused that the description of fig.1, fig.2 and fig.3 appear in methods. We have, as above, transferred the description of figures 2 and 3 from the methods to the results section. 4 The results of fig.4-fig.7 are too scattered and should be integrated. Why are the figures separate from each other in fig.4abcd? Also include fig.5 abcd, fig. 6abcd, fig.7abcd? Each of the figures 4 through figure 7 represent patient exemplars with each example having four sub figures. We do not disagree with the sentiment of the reviewer, but if they are combined into a single figure with four panels we cannot retain the fine detail and retain image publication quality required by your journal. 5 The structure of this manuscript is a little confused We hope that by moving the explanation describing figures 2 and 3 into the results section the structure of the manuscript is easier to follow. Attachments Attachment Submitted filename: ResponseToReviewers.docx https://doi.org/10.1371/journal.pone.0277052.r002
19 Oct 2022 Decision Letter - Meijia Zhang, Editor A predictive model of the effect of therapeutic radiation on the human ovary PONE-D-22-15540R1 Dear Dr. Kelsey, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Meijia Zhang 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 ******** 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: Yes Reviewer #2: 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 ****** 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) ****** 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 ******** https://doi.org/10.1371/journal.pone.0277052.r003
Formally Accepted
9 Nov 2022 Acceptance Letter - Meijia Zhang, Editor PONE-D-22-15540R1 A predictive model of the effect of therapeutic radiation on the human ovary Dear Dr. Kelsey: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Meijia Zhang Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0277052.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .