Risk factors of papillary thyroid microcarcinoma that predispose patients to local recurrence

Krzysztof Kaliszewski; Dorota Diakowska; Marta Rzeszutko; Łukasz Nowak; Michał Aporowicz; Beata Wojtczak; Krzysztof Sutkowski; Jerzy Rudnicki

doi:10.1371/journal.pone.0244930

Peer Review History

Original SubmissionJuly 28, 2020
10 Nov 2020 Decision Letter - Paula Soares, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-20-23025 Assessment of the Ultrasound and Histopathological Features of Papillary Thyroid Microcarcinoma for Less Aggressive Management. PLOS ONE Dear Dr. Kaliszewski, 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 accept the apologies for the long time the review process as taken. Both reviewers consider that your Ms needs improvements both in the analysis as well as in the presentation and language. Please address ALL the reviewers concerns in a point by point letter. Take special attention to table 2 where risk factors for minETE, capsular invasion and vascular invasion should be individually analysed and presented. Also data showing how many patients had 1, 2, 3 or 4 risk factors are mandatory. In addition all the remaining points raised by the reviewers must be addressed. Please submit your revised manuscript by Dec 25 2020 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). 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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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know 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: No ****** 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: No Reviewer #2: No ****** 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: Table 1 : a) Presurgical diagnosis of multifocality and bilaterality, number of foci - how it was evaluated ? US ? FNA? b) pTNM stage II - 4; pN1 -73 (pT1N1 = stage II) c) cN ? Table 2: risk factors for minETE, capsular invasion and vascular invasion should be individually analysed To analyse disease free survival time it is necessary to know: a) surgical treatment, CLN dissection b) ablation/adjuvant radiodine therapy c) recurrencies d) the follow up time (min, max, medium) none of these are mentioned and should be specified The english must be improved Reviewer #2: This paper contains some valuable data, but has a number of deficiencies that lessen the impact. (1) The title is misleading. It should be something like: Papillary Thyroid microcarcinomas: risk factors for local recurrence (2) The authors freely express their management opinion but do not discuss the rationale of the opposing point of view.. The topic is mildly controversial. It is unclear that more extensive surgery/treatment results in improved overall survival or that any treatment of PMTC improves overall survival. In fact, they do not offer any survival data, likely because there is no difference. Those promulgating the conservative approach to PMTC provide treatment when the lesions enlarge or LN metastases appear. So the argument, given their data, is whether local recurrence in PMTC is associated with decreased overall survival. They have presented no data on this point. Instead, they argue that local recurrence is a proxy for overall survival in PTC patients in general. (3) The Kaplan Meier curves are so similar that one suspects that many of the patients that had a higher local recurrence rate had all 4 risk factors. Data showing how many patients had 1, 2, 3 or 4 risk factors needs to be presented. (4). The discussion is rambling and very difficult to read. The formula that gives the best readability is: one paragraph of discussion that refers to a single paragraph of results, followed by one paragraph of conclusion. Each paragraph should begin with a sentence telling what the paragraph is about. Each paragraph should end with a conclusion, "Therefore..." (5) Despite the certificate stating otherwise, this needs editing by a native English speaker with some scientific background. ****** 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.0244930.r001
Revision 1
1 Dec 2020 Author Response Dear Editor and Reviewers, First, we truly appreciate the opportunity to resubmit our revised manuscript. Thank you very much for considering our manuscript for potential publication in Plos One. We would also like to thank you for the very thorough reviews, professional advice and constructive criticism, which were highly valuable for improving our paper. All suggestions regarding changes and improvements were very helpful to us, and we revised the manuscript according to the recommendations provided in the reviews. All changed and deleted portions of the manuscript are indicated with track changes. According to the reviewers’ instructions, we have corrected our manuscript point-by-point as follows. Regarding the responses to the concrete comments by the reviewers, we corrected/changed the manuscript in the following ways: Reviewer 1: #Table 1: a) “Presurgical diagnosis of multifocality and bilaterality, number of foci...”. Thank you very much for this remark. Clearly, the presurgical diagnosis of PTMC before surgery is sometimes difficult but very important. To establish the most accurate diagnosis of thyroid tumors before surgery in all patients, we performed ultrasonography and ultrasound-guided fine needle aspiration biopsy (UG-FNAB) of all suspected tumors, as indicated for this tumor type. If the results indicate two or more suspected malignant tumors, we performed UG-FNAB in all lesions. Occasionally, we make a cancer diagnosis in more than one thyroid tumor. Thus, in such cases, we know before surgery that the patient has multifocal bilateral PTMC. We added the following adequate explanation to the manuscript: “Preoperative thyroid ultrasonography, ultrasound guided-fine-needle aspiration biopsy (UG-FNAB) and cytological examinations were performed in all cases. All suspected lesions were biopsied, and on this basis, presurgical multifocality and bilaterality were established.” b) We are immensely grateful for this remark. Indeed, we made a mistake when we assessed the patients according to TNM staging. According to the 8th Edition of the TNM Classification, in cases of well-differentiated papillary thyroid cancers, patients with N1 aged 55 years or above at the time of diagnosis are assigned to stage II. Thus, we reassessed and corrected the results in the table. Thank you. c) We decided to not present the clinical classification of lymphatic nodules cN (pathologically changed lymphatic nodules) because these data were not strict and did not influence the results of our analysis. However, if you feel it is necessary to include these data, we will gladly reassess the medical records of all patients and include this clinical observation. #Table 2: We performed separate statistical analyses of minETE, capsular invasion and vascular invasion (Tables 2, 3, and 4). In the Materials and methods, we added information regarding the following: a) Surgical treatment, CLN dissection: “All patients included in the study underwent radical surgery (total thyroidectomy with central lymph node dissection).” b) Ablation/radioiodine therapy: The study was performed in the Surgical Department. After radical surgery, we sent all patients for consultation and potential qualification for RAI therapy at an oncology center in a different place. “All individuals diagnosed with PTMC after surgery were routinely sent to the Oncology Center in Gliwice (Poland) for consultation and possible adjuvant radioiodine (RAI) therapy. The patients with pN0 features did not receive adjuvant RAI therapy, and the individuals with pN1 features received a single dose of ablated RAI in therapeutic amounts. All patients agreed to strict follow-up and remained under observation.” c) Recurrence: “For the purpose of this study, we assessed DFS time as the length of time (months) after primary surgery during which the patient survived without any structural evidence of disease. A p-value less than 0.05 was considered statistically significant.” d) Follow-up time (min, max, medium): “The follow-up duration was a minimum of 12 months and maximum of 144 months, with a median interval of 70 months.” Although our manuscript was reviewed by American Journal Experts as recommended by the journal (we attached the certificate), after making our point-by-point corrections based on the suggestions by the reviewers, we sent our revised manuscript once again to AJE for proofreading (we have attached the new certificate). Thank you. Reviewer 2: First, we thank you very much for the opinion that our manuscript contains some valuable data. This is a very important acknowledgement for us. Thank you. Regarding your remarks, we corrected the text as follows: 1) We agree that the title is misleading. We changed the title to “Risk Factors of Papillary Thyroid Microcarcinoma that Predispose Patients to Local Recurrence.” 2) We absolutely agree that the topic undertaken in our study is controversial and that we do not have data confirming that a more aggressive treatment of PTMC provides better survival for all patients. Indeed, we analyzed only the risk factors for local recurrence and not overall survival time. In our analysis, all patients free of local recurrence were still alive, but the time of observation may be too short. Thus, we changed our discussion to avoid misleading readers. We drew hasty conclusions that local recurrence shortens the overall survival time, and as we know, in PTMC, this finding is not clearly established. Thank you for this valuable remark. 3) We included the data showing how many patients had 1, 2, 3 or 4 risk factors in Table 1 and the supportive data set. 4) We agree that the discussion was not well written; thus, we have rewritten and re-edited the discussion according to your suggestions. Thank you. 5) Although our manuscript was reviewed by American Journal Experts as recommended by the journal (we attached the certificate), after making our point-by-point corrections based on the suggestions by the reviewers, we sent our revised manuscript once again to AJE for proofreading (we have attached the new certificate). Thank you. Best regards, Krzysztof Kaliszewski MD, PhD Attachments Attachment Submitted filename: Response to Reviewers.doc https://doi.org/10.1371/journal.pone.0244930.r002
21 Dec 2020 Decision Letter - Paula Soares, Editor Risk Factors of Papillary Thyroid Microcarcinoma that Predispose Patients to Local Recurrence. PONE-D-20-23025R1 Dear Dr. Kaliszewski, 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, Paula Soares 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: I Don't Know ****** 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 ****** 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: (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 #2: No https://doi.org/10.1371/journal.pone.0244930.r003
Formally Accepted
23 Dec 2020 Acceptance Letter - Paula Soares, Editor PONE-D-20-23025R1 Risk Factors of Papillary Thyroid Microcarcinoma that Predispose Patients to Local Recurrence. Dear Dr. Kaliszewski: 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. Paula Soares Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0244930.r004

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