Scalp dose analysis for transient and permanent alopecia following conventional cranial irradiation using Image Guided Radiotherapy (IGRT): A prospective study

Bongkot Jia-Mahasap; Wannapha Nobnop; Patumrat Sripan; Ekkasit Tharavichitkul; Somvilai Chakrabandhu; Pitchayaponne Klunklin; Wimrak Onchan; Pooriwat Muangwong; Imjai Chitapanarux

doi:10.1371/journal.pone.0311855

Peer Review History

Original SubmissionDecember 14, 2023
10 Jul 2024 Decision Letter - Li-Ping Liu, Editor PONE-D-23-41670Scalp dose analysis for transient and permanent alopecia following conventional cranial irradiation using Image Guided Radiotherapy (IGRT): A prospective studyPLOS ONE Dear Dr. Chitapanarux, 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 Aug 24 2024 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. 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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 [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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. 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Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0311855.r001
Revision 1
11 Jul 2024 Author Response Reviewer #1 The manuscript is good interesting and good designed. Introduction is good written. Material and methods are good designed. Results are good written and illustrated. Discussion is good written and include the conclusion of the study. Response: Thank you for your kind comments. Additionally, this manuscript has been revised in accordance with the formatting guidelines of PLOS ONE and stated the Ethics statement at the beginning of the Methods. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0311855.r002
23 Jul 2024 Decision Letter - Li-Ping Liu, Editor PONE-D-23-41670R1Scalp dose analysis for transient and permanent alopecia following conventional cranial irradiation using Image Guided Radiotherapy (IGRT): A prospective studyPLOS ONE Dear Dr. Chitapanarux, 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. We apologize that due to a system error, the reviewer comments were not fully attached in the previous decision letter. I have included the comments below, and kindly request that you provide a comprehensive response letter addressing the feedback from all three reviewers. Additionally, please carefully proofread the revised manuscript to check for any grammatical issues. Please submit your revised manuscript by Sep 05 2024 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, Li-Ping Liu Academic Editor PLOS ONE Journal Requirements: REVIEWER COMMENTS Reviewer 1 The manuscript is good interesting and good designed Introduction is good written Material and methods are good designed Results are good written and illustrated Discussion is good written and include the conclusion of the study. Reviewer 2 Strengths Study design: The prospective study design is robust and the inclusion/exclusion criteria are well defined. The use of detailed dosimetric analysis for both the entire scalp and localized areas of hair loss is commendable. Results: Clear and concise presentation of results with appropriate descriptive statistical analysis. Differentiation between transient and permanent alopecia provides valuable insights. Major review: 1. Definition of permanent alopecia: The manuscript defines permanent alopecia as hair loss assessed at 6 months after RT. However, permanent alopecia is typically defined as hair loss that persists for more than 9-12 months. This discrepancy should be addressed in the discussion or the results should be modified taking into account the time cutoff. 2. I don't understand the "Sample size" paragraph, the only steady-state analyses performed are univariate so why did the authors bother to include Harris' recommendations for independent variables typically used for multivariate analyses? 3. Use of ROC curve analysis: To define dose cutoffs, ROC curve analysis and AUC should be included in the study. 4. English careful proofreading and possibly professional editing is recommended to refine grammar and simplify complex sentences for better readability. Minor review: 1. The manuscript does not clearly explain the specific advantages of IGRT over nonimage-guided radiotherapy. It should be explicitly stated and explained in the context of alopecia minimization. 2. Median follow-up time should be entered 3. It would have been interesting to also include other factors that may justify influencing toxicity i.e., cigarette smoking, tumor target volume and RT techniques used (VMAT, IMRT etc) Reviewer 3 In my opinion, this is an interesting prospective study with appropriate method and statical analysis. It is well written on general knowkedge and previous studies about this theme. Totally, this is a good manuscript. I have one comment about statical analysis. In discussion, authors mentions the V20 and V40 of scalp. Have you considered obtaining these parameters and comparing them with D2, Dmean, and D50? [Note: HTML markup is below. Please do not edit.] [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.0311855.r003
Revision 2
23 Aug 2024 Author Response August 20, 2024 RE: PONE-D-23-41670 Dear Academic Editor PLOS ONE I would like to thank you for sending the comments of the reviewers following the peer review of our Original Article entitled “Scalp dose analysis for transient and permanent alopecia following conventional cranial irradiation using Image Guided Radiotherapy (IGRT): A prospective study” Please find attached the revised manuscript. We have addressed the reviewers’ comments in the order they were provided, the reviewer’s comments are in italic. All changes are highlighted. According to the changes the in manuscript, we have also modified tables as follows: Table 2 has been revised to “The dosimetric parameter of the entire scalp volume that predicted the occurrence of alopecia” using ROC curve analysis. We have converted the previous Table 2 to Table 3, and Table 3 to Table 4. Review Comments to the Author Reviewer 1 The manuscript is good interesting and good designed. Introduction is good written. Material and methods are good designed. Results are good written and illustrated. Discussion is good written and include the conclusion of the study. Response: Thank you for your kind comments. Additionally, this manuscript has been revised in accordance with the formatting guidelines of PLOS ONE and stated the Ethics statement at the beginning of the Methods. Reviewer 2 Strengths Study design: The prospective study design is robust and the inclusion/exclusion criteria are well defined. The use of detailed dosimetric analysis for both the entire scalp and localized areas of hair loss is commendable. Results: Clear and concise presentation of results with appropriate descriptive statistical analysis. Differentiation between transient and permanent alopecia provides valuable insights. Major review: 1. Definition of permanent alopecia: The manuscript defines permanent alopecia as hair loss assessed at 6 months after RT. However, permanent alopecia is typically defined as hair loss that persists for more than 9-12 months. This discrepancy should be addressed in the discussion or the results should be modified taking into account the time cutoff. Response: Thank you for your impressive advice. The definition of permanent alopecia has been discussed. Please see the discussion session [Page 16-17, Line 253-260]. 2. I don't understand the "Sample size" paragraph, the only steady-state analyses performed are univariate so why did the authors bother to include Harris' recommendations for independent variables typically used for multivariate analyses? Response: Thank you for your comment. Initially, we suspected that clinical alopecia may be influenced by a variety of factors. Subsequently, it is imperative to implement both univariate and multivariate analyses. Consequently, we determined the sample size in accordance with Harris' recommendations. However, after we analyzed all characteristics, only the radiation dose factor was associated with clinical alopecia. Therefore, this study did not implement any multivariable analysis. 3. Use of ROC curve analysis: To define dose cutoffs, ROC curve analysis and AUC should be included in the study. Response: Thank you for this important recommendation. The ROC curve analysis has been implemented, as shown in Table 2 [Page 12]. We have also made modifications to the abstract, the statistical analysis section, the result, and the discussion in accordance with your advice. 4. English careful proofreading and possibly professional editing is recommended to refine grammar and simplify complex sentences for better readability. Response: Thank you for your comment. We have revised English in this manuscript with professional editing. Minor review: 1. The manuscript does not clearly explain the specific advantages of IGRT over nonimage-guided radiotherapy. It should be explicitly stated and explained in the context of alopecia minimization. Response: Thank you for your comment. This critical issue has been addressed in the discussion session [Page 17, Line 261-269]. The radiation technique utilized in this research was IGRT, as it was implemented in all curative-intent radiotherapy at our center. 2. Median follow-up time should be entered Response: Thank you for your suggestion. The median follow-up time has been stated in the result session [Page 10, Line 162]. 3. It would have been interesting to also include other factors that may justify influencing toxicity i.e., cigarette smoking, tumor target volume and RT techniques used (VMAT, IMRT etc) Response: Thank you for your advice. The tumor target volume and RT techniques have been examined. Please refer to Table 1 for the data. To our regret, the cigarette consumption was not document as a patient characteristic. Reviewer 3 In my opinion, this is an interesting prospective study with appropriate method and statical analysis. It is well written on general knowkedge and previous studies about this theme. Totally, this is a good manuscript. I have one comment about statical analysis. In discussion, authors mentions the V20 and V40 of scalp. Have you considered obtaining these parameters and comparing them with D2, Dmean, and D50? Response: Thank you for your suggestion. V20 and V40 to the entire scalp have been further analyzed and discussed, following your advice. Please see the additional data in Tables 1 to 4, as well as the discussion [Page 15, Line 222-230] and the conclusion [Page 19, Line 285-286]. We thank you for your careful review. Sincerely, Imjai Chitapanarux Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0311855.r004
25 Sep 2024 Decision Letter - Li-Ping Liu, Editor Scalp dose analysis for transient and permanent alopecia following conventional cranial irradiation using Image Guided Radiotherapy (IGRT): A prospective study PONE-D-23-41670R2 Dear Dr. Chitapanarux, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. 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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 #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 #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 #2: The authors have adequately addressed the revisions, making improvements to the manuscript where necessary. The changes implemented have enhanced the clarity and quality of the paper. In my opinion, the manuscript is now suitable for publication. Reviewer #3: Thank you for addressing my suggestion regarding V20 and V40 of the scalp. I appreciate the additional analysis and the integration of these parameters in your manuscript. The updated tables and discussion have strengthened the overall analysis, providing more comprehensive insights. The manuscript is now even more robust, and I am pleased with the revisions. ****** 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 Reviewer #3: No ******** https://doi.org/10.1371/journal.pone.0311855.r005
Formally Accepted
30 Sep 2024 Acceptance Letter - Li-Ping Liu, Editor PONE-D-23-41670R2 PLOS ONE Dear Dr. Chitapanarux, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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. Li-Ping Liu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0311855.r006

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