NOTICE: This document contains correspondence generated during peer review and subsequent revisions but before transmittal to production for composition and copyediting:
• Comments from the reviewers and editors (email to author requesting revisions)
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*The corresponding author has opted to make this information publicly available.
Personal or nonessential information may be redacted at the editor’s discretion.
Questions about these materials may be directed to the Obstetrics & Gynecology editorial office:
Date: Mar 26, 2020 To: "Jennifer J Mueller"
From: "The Green Journal" [email protected] Subject: Your Submission ONG-20-455
RE: Manuscript Number ONG-20-455
Radical Trachelectomy for the Treatment of Early Stage Cervical Cancer: A Systematic Review Dear Dr. Mueller:
Your manuscript has been reviewed by the Editorial Board and by special expert referees. Although it is judged not acceptable for publication in Obstetrics & Gynecology in its present form, we would be willing to give further consideration to a revised version.
If you wish to consider revising your manuscript, you will first need to study carefully the enclosed reports submitted by the referees and editors. Each point raised requires a response, by either revising your manuscript or making a clear and convincing argument as to why no revision is needed. To facilitate our review, we prefer that the cover letter include the comments made by the reviewers and the editor followed by your response. The revised manuscript should indicate the position of all changes made. We suggest that you use the "track changes" feature in your word processing software to do so (rather than strikethrough or underline formatting).
***Due to the COVID-19 pandemic, your paper will be maintained in active status for 30 days from the date of this letter.
If we have not heard from you by Apr 25, 2020, we will assume you wish to withdraw the manuscript from further consideration.***
REVIEWER COMMENTS:
Reviewer #1: This is a very nicely done review of the available literature regarding the role of radical trachelectomy for early stage cervical cancer among patients who desire fertility preservation. The methods for article selection are clearly stated and appropriate for selection of quality articles. This review significantly adds to the current understanding of this topic. However, prior to acceptance and publication, I think the authors should include additional discussion regarding the role of simple conization or simple trachelectomy when managing similar patients. As seen in Table 1, the number of patients with LVI was roughly 30%. That said, some of these patients may have been appropriate for non-radical surgery.
This should be addressed in the discussion. Further, while some criteria are different (i.e. +LVI), many of the criteria that generally are used to select a patient suitable for a radical trachelectomy (e.g. early stage, tumor less than 2 cm) are similar to the criteria used to select patients for simple cone and nodes. The safety of simple cone and nodes in well selected patients has been published by this same group (PMID 24335661) and several others (PMIDs 28498240 and 24041877). In addition, there are prospective trials (ConCerv and GOG 278) that have/are looking at this same topic. The authors would greatly enhance the current manuscript by discussing this topic with specifics centered on who needs radical surgery vs non-radical surgery?
Reviewer #2: Thank you for the opportunity to review an interesting manuscript titled Radical Trachelectomy for the treatment of early stage cervical cancer." This comprehensive meta-analysis attempts to collate and review the published literature regarding radical trachelectomy with lymph node assessment.
This is a clinically important question since there is a great deal of heterogeneity in surgical approach and reported data/outcomes for fertility sparing surgery for early cervical cancer.
This study is not an original inquiry, but the authors deserve commendation for the diligent work in attempting to include all pertinent studies by narrowing the large number of studies to 47 studies with 2966 patients. My understanding is that only studies that included lymphadenectomy were included but I would ask to author to clarify what the most common reasons were to exclude studies that were identified during literature search.
The focus of this review was on oncologic outcomes and as the editors realize has been reported previously. Also, a quick literature search reveals a systematic review of the literature with a focus on pregnancy outcomes; Bentivegna et al.
Fertility results and pregnancy outcomes after conservative treatment of cervical cancer. Fertility and Sterility, 2016.
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1 of 5 4/28/2020, 2:30 PM
Although perhaps outside the inclusion criteria for this meta-analysis, the authors may acknowledge the option of neoadjuvant chemotherapy followed by conization or trachelectomy as a potential alternative fertility sparing option.
How do the authors explain the difference in pregnancy rates with various approaches? Do they believe it is more that reporting bias?
Regarding this paper, I have the following detailed comments for the authors.
1. Precis/abstract/introduction clear
2. Perhaps in introduction since small numbers of patients have reported oncologic outcomes is there any indication of what are the most common approach in the United States from national registry database or prior reports?
3. Line 144 how can be sure same cases are no reported multiple times in the literature
4. Line 171 how would the results change if only "good" quality studies were included in the review 5. Line 187 were patient who received adjuvant treatment included in the analysis
6. Line 217 why did the authors decide to include IA1 with LVSI who underwent trachelectomy?
7. Line 236 how were studies that did not report lymph node assessments included? Were they presumed to be negative and therefore not reported? Or were lymphadenectomy not performed?
8. line 351 explain IRTA study
Table 1 is there any patients that received adjuvant therapy?
Table 3 why did the authors decide on a 3 year follow up requirement? How many reports missed this cutoff?
Table 4,5,6 are excellent detailed data likely best served as supplemental tables.
Overall, this a well written paper. It increases our understanding of this rare surgical procedure. This study confirms that a conservative/fertility sparing discussion with early stage cervical cancer patient will highlight the limited high quality data but that published reports are promising.
Reviewer #3: In this manuscript, the authors present a systematic review on the outcomes of radical trachelectomy for the treatment of early cervical cancer. The study question is of interest, made more interesting given the recent outcomes discouraging laparoscopic approaches to the treatment of early cervical cancer by way of hysterectomy. The effort is registered with PROSPERO and the reporting follows guidance from PRISMA. The literature sources and search strategies are well described and reasonable. This perspective is true of the approach to study selection. By and large this effort is stymied by limited high-quality studies but given a prospective effort on the way, what is presented does serve as a good base of reference. It is curious the experience across surgical approaches wherein the vaginal approach has as good or better outcomes (and likely possesses substantially lower procedure costs). It seems counterintuitive to attempt to remove an organ through or around another one (i.e. the uterus) thus the abdominal/laparoscopic approach would never seem to make much sense. The fact that conversions were more common when the surgical approach was from above would seem an obvious "availability" bias. The general lack of vaginal hysterectomy skills among gyn oncologists would seemingly make these results hard to apply; but then in the setting of benign hysterectomy, the overuse of the robot to perform hysterectomies reflects a similar trend among benign OB/GYNs. While perhaps beyond the scope of this review at some point this matter should be considered. Overall, assuming this topic is of pertinence to a general OB/GYN
readership, the effort is good.
STATISTICAL EDITOR COMMENTS:
The Statistical Editor makes the following points that need to be addressed:
Tables (All, except Table 3): Should write the complete name for ART, LRT and VRT.
Table 2: Should include the "N" for each column for number of patients.
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Table 3: Should break down the quality rating to include the three surgical approaches separately, then as the total.
Tables 4, 5 & 6 could be on-line supplemental material.
EDITOR'S COMMENTS:
We no longer require that authors adhere to the Green Journal format with the first submission of their papers. However, any revisions must do so. I strongly encourage you to read the instructions for authors (the general bits as well as those specific to the feature-type you are submitting). The instructions provide guidance regarding formatting, word and reference limits, authorship issues, and other things. Adherence to these requirements with your revision will avoid delays during the revision process, as well as avoid re-revisions on your part in order to comply with the formatting. Please avoid idiosyncratic abbreviations that the specialist in Ob GYN or general reader (as opposed to gyn oncologist( may not know such as VRT, LRT, ART which could be confused with Assisted Reproductive Technology.
The numbers below refer to manuscript line numbers.
P Values vs Effect Size and Confidence Intervals
While P values are a central part of inference testing in statistics, when cited alone, often the strength of the conclusion can be misunderstood. Whenever possible, the preferred citation should be in terms of an effect size, such as odds ratio or relative risk or the mean difference of a variable between two groups, expressed with appropriate confidence intervals.
When such syntax is used, the P value has only secondary importance and often can be omitted or noted as footnotes in a Table format. Putting the results in the form of an effect size makes the result of the statistical test more clinically relevant and gives better context than citing P values alone.
This is true for the abstract as well as the manuscript, tables and figures.
Please provide absolute values for variables, in addition to assessment of statistical significance.
We ask that you provide crude OR’s followed by adjusted OR’s for all relevant variables.
Please limit p values to 3 decimal places.
Numbers below refer to line numbers 79: please include units for age.
82. The journal style does not support the use of the virgule ( / ) except in mathematical expressions. Please remove here and elsewhere.
EDITORIAL OFFICE COMMENTS:
1. The Editors of Obstetrics & Gynecology are seeking to increase transparency around its peer-review process, in line with efforts to do so in international biomedical peer review publishing. If your article is accepted, we will be posting this revision letter as supplemental digital content to the published article online. Additionally, unless you choose to opt out, we will also be including your point-by-point response to the revision letter. If you opt out of including your response, only the revision letter will be posted. Please reply to this letter with one of two responses:
A. OPT-IN: Yes, please publish my point-by-point response letter.
B. OPT-OUT: No, please do not publish my point-by-point response letter.
2. As of December 17, 2018, Obstetrics & Gynecology has implemented an "electronic Copyright Transfer Agreement"
(eCTA) and will no longer be collecting author agreement forms. When you are ready to revise your manuscript, you will be prompted in Editorial Manager (EM) to click on "Revise Submission." Doing so will launch the resubmission process, and you will be walked through the various questions that comprise the eCTA. Each of your coauthors will receive an email from the system requesting that they review and electronically sign the eCTA.
Please check with your coauthors to confirm that the disclosures listed in their eCTA forms are correctly disclosed on the manuscript's title page.
3. Please submit a completed PRISMA checklist.
4. Standard obstetric and gynecology data definitions have been developed through the reVITALize initiative, which was
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3 of 5 4/28/2020, 2:30 PM
convened by the American College of Obstetricians and Gynecologists and the members of the Women's Health Registry Alliance. Obstetrics & Gynecology has adopted the use of the reVITALize definitions. Please access the obstetric and gynecology data definitions at https://www.acog.org/About-ACOG/ACOG-Departments/Patient-Safety-and-Quality- Improvement/reVITALize. If use of the reVITALize definitions is problematic, please discuss this in your point-by-point response to this letter.
5. Because of space limitations, it is important that your revised manuscript adhere to the following length restrictions by manuscript type: Review articles should not exceed 25 typed, double-spaced pages (6,250 words). Stated page limits include all numbered pages in a manuscript (i.e., title page, précis, abstract, text, references, tables, boxes, figure legends, and print appendixes) but exclude references.
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* All financial support of the study must be acknowledged.
* Any and all manuscript preparation assistance, including but not limited to topic development, data collection, analysis, writing, or editorial assistance, must be disclosed in the acknowledgments. Such acknowledgments must identify the entities that provided and paid for this assistance, whether directly or indirectly.
* All persons who contributed to the work reported in the manuscript, but not sufficiently to be authors, must be
acknowledged. Written permission must be obtained from all individuals named in the acknowledgments, as readers may infer their endorsement of the data and conclusions. Please note that your response in the journal's electronic author form verifies that permission has been obtained from all named persons.
* If all or part of the paper was presented at the Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists or at any other organizational meeting, that presentation should be noted (include the exact dates and location of the meeting).
7. The most common deficiency in revised manuscripts involves the abstract. Be sure there are no inconsistencies between the Abstract and the manuscript, and that the Abstract has a clear conclusion statement based on the results found in the paper. Make sure that the abstract does not contain information that does not appear in the body text. If you submit a revision, please check the abstract carefully.
In addition, the abstract length should follow journal guidelines. The word limits for different article types are as follows:
Reviews, 300 words. Please provide a word count.
8. Only standard abbreviations and acronyms are allowed. A selected list is available online at http://edmgr.ovid.com /ong/accounts/abbreviations.pdf. Abbreviations and acronyms cannot be used in the title or précis. Abbreviations and acronyms must be spelled out the first time they are used in the abstract and again in the body of the manuscript.
9. The journal does not use the virgule symbol (/) in sentences with words. Please rephrase your text to avoid using
"and/or," or similar constructions throughout the text. You may retain this symbol if you are using it to express data or a measurement.
10. In your Abstract, manuscript Results sections, and tables, the preferred citation should be in terms of an effect size, such as odds ratio or relative risk or the mean difference of a variable between two groups, expressed with appropriate confidence intervals. When such syntax is used, the P value has only secondary importance and often can be omitted or noted as footnotes in a Table format. Putting the results in the form of an effect size makes the result of the statistical test more clinically relevant and gives better context than citing P values alone.
If appropriate, please include number needed to treat for benefits (NNTb) or harm (NNTh). When comparing two procedures, please express the outcome of the comparison in U.S. dollar amounts.
Please standardize the presentation of your data throughout the manuscript submission. For P values, do not exceed three decimal places (for example, "P = .001"). For percentages, do not exceed one decimal place (for example, 11.1%").
11. Please review the journal's Table Checklist to make sure that your tables conform to journal style. The Table Checklist is available online here: http://edmgr.ovid.com/ong/accounts/table_checklist.pdf.
12. Figure 1 may be resubmitted with the revision as-is.
13. Authors whose manuscripts have been accepted for publication have the option to pay an article processing charge and publish open access. With this choice, articles are made freely available online immediately upon publication. An
information sheet is available at http://links.lww.com/LWW-ES/A48. The cost for publishing an article as open access can be found at http://edmgr.ovid.com/acd/accounts/ifauth.htm.
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14. If you choose to revise your manuscript, please submit your revision through Editorial Manager at
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http://ong.editorialmanager.com. Your manuscript should be uploaded in a word processing format such as Microsoft Word.
Your revision's cover letter should include the following:
* A confirmation that you have read the Instructions for Authors (http://edmgr.ovid.com/ong/accounts/authors.pdf), and
* A point-by-point response to each of the received comments in this letter.
If you submit a revision, we will assume that it has been developed in consultation with your co-authors and that each author has given approval to the final form of the revision.
***Again, your paper will be maintained in active status for 30 days from the date of this letter. If we have not heard from you by Apr 25, 2020, we will assume you wish to withdraw the manuscript from further consideration.***.
Sincerely,
Nancy C. Chescheir, MD Editor-in-Chief
2018 IMPACT FACTOR: 4.965
2018 IMPACT FACTOR RANKING: 7th out of 83 ob/gyn journals __________________________________________________
In compliance with data protection regulations, you may request that we remove your personal registration details at any time. (Use the following URL: https://www.editorialmanager.com/ong/login.asp?a=r). Please contact the publication office if you have any questions.
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1
April 22, 2020
Nancy C. Chescheir, MD Editor-in-Chief
Obstetrics & Gynecology 409 12th Street SW Washington, DC 20024 RE: ONG-S-20-00538 Dear Dr. Chescheir,
Thank you for the opportunity to submit our revised manuscript, entitled “Radical
Trachelectomy for the Treatment of Early Stage Cervical Cancer: A Systematic Review” to Obstetrics & Gynecology. We greatly appreciate the feedback you and the other reviewers have provided, and we have incorporated changes that reflect the reviewers’ comments. Any edits to the originally submitted manuscript are highlighted within this updated version.
Comments from Reviewer #1
Comment: This is a very nicely done review of the available literature regarding the role of radical trachelectomy for early stage cervical cancer among patients who desire fertility
preservation. The methods for article selection are clearly stated and appropriate for selection of quality articles. This review significantly adds to the current understanding of this topic.
However, prior to acceptance and publication, I think the authors should include additional discussion regarding the role of simple conization or simple trachelectomy when managing similar patients. As seen in Table 1, the number of patients with LVI was roughly 30%. That said, some of these patients may have been appropriate for non-radical surgery. This should be addressed in the discussion. Further, while some criteria are different (i.e. +LVI), many of the criteria that generally are used to select a patient suitable for a radical trachelectomy (e.g. early stage, tumor less than 2 cm) are similar to the criteria used to select patients for simple cone and nodes. The safety of simple cone and nodes in well selected patients has been published by this same group (PMID 24335661) and several others (PMIDs 28498240 and 24041877). In addition, there are prospective trials (ConCerv and GOG 278) that have/are looking at this same topic. The authors would greatly enhance the current manuscript by discussing this topic with specifics centered on who needs radical surgery vs non-radical surgery?
Response: We agree that additional discussion should be provided regarding the role of cervical cone biopsy or simple trachelectomy as reasonable, non-radical options for the treatment of early-stage disease. We have edited the Introduction (page 6) and added a paragraph in the Discussion (page 17) to reflect this, emphasizing that the decision for less versus more radical surgery hinges on select histopathologic parameters. We added additional language to clarify that our focus during this review was solely on radical trachelectomy. This additional paragraph also incorporates reference to the excellent articles referenced in your comments, including the
ConCerv trial and GOG 278. Also, thank you for highlighting the percentage of patients with and
2
thus without LVI, which makes the excellent case that there is a large group of patients who may be appropriate for non-radical surgery. We have also added comments to the Discussion (page 17) to highlight this point for the reader.
Comments from Reviewer #2
Comment: Thank you for the opportunity to review an interesting manuscript titled Radical Trachelectomy for the treatment of early stage cervical cancer." This comprehensive meta- analysis attempts to collate and review the published literature regarding radical trachelectomy with lymph node assessment.
This is a clinically important question since there is a great deal of heterogeneity in surgical approach and reported data/outcomes for fertility sparing surgery for early cervical cancer.
This study is not an original inquiry, but the authors deserve commendation for the diligent work in attempting to include all pertinent studies by narrowing the large number of studies to 47 studies with 2966 patients. My understanding is that only studies that included
lymphadenectomy were included but I would ask to author to clarify what the most common reasons were to exclude studies that were identified during literature search.
Response: Thank you for this comment. It is true, only studies that included a lymphadenectomy were included in this study. Figure 1 lists reasons for exclusion, but we have also added a
sentence to the Results (page 11) further explaining study exclusions from this review.
Comment: The focus of this review was on oncologic outcomes and as the editors realize has been reported previously. Also, a quick literature search reveals a systematic review of the literature with a focus on pregnancy outcomes; Bentivegna et al. Fertility results and pregnancy outcomes after conservative treatment of cervical cancer. Fertility and Sterility, 2016.
Response: We too realize that oncologic and fertility outcomes with radical trachelectomy have been reported previously and we appreciate this comment. The purpose of our systematic review was primarily to provide an up-to-date review on surgical route of radical trachelectomy. We include oncologic and fertility outcomes when available, based upon mode of surgical procedure.
As outlined in our Introduction, this was motivated by the recent LACC trial and NCDB and SEER publications which demonstrated open surgery as the favorable surgical route for radical hysterectomy. These studies did not include trachelectomy patients and it represents a gap in the current literature.
Comment: Although perhaps outside the inclusion criteria for this meta-analysis, the authors may acknowledge the option of neoadjuvant chemotherapy followed by conization or
trachelectomy as a potential alternative fertility sparing option.
Response: We acknowledge that neoadjuvant chemotherapy followed by fertility-sparing surgery may be a safe alternative strategy. This has been incompletely studied, and there are no
3
clear consensus guidelines in this regard. We therefore opted to exclude these cases as reported in the Study Selection section (page 8).
Comment: How do the authors explain the difference in pregnancy rates with various approaches? Do they believe it is more that reporting bias?
Response: We agree with this supposition, that the differences in pregnancy rates with different surgical approaches are likely related to reporting bias. Despite these differences, live birth rates remain similar across interventions. Edits to the Discussion have been made in response to this comment (page 16).
Comment: Regarding this paper, I have the following detailed comments for the authors.
1. Precis/abstract/introduction clear
2. Perhaps in introduction since small numbers of patients have reported oncologic outcomes is there any indication of what are the most common approach in the United States from national registry database or prior reports?
Response: We agree that the Introduction would benefit from more information regarding the most common approaches to trachelectomy in the United States, and thus have added
information, including reference to a recently published national registry database study (page 6).
3. Line 144 how can be sure same cases are no reported multiple times in the literature
Response: We share your concern about cases being reported multiple times in the literature and have addressed this for the reader. See Study Selection (pages 8-9), which acknowledges this potential, and further explains our methodology to help prevent duplicate patient data in our review.
4. Line 171 how would the results change if only "good" quality studies were included in the review
Response: Although we did not conduct two parallel reviews to determine how results would have changed by only including studies deemed “good” quality, your comment brings up an interesting point. Ultimately, we wanted to provide a thoroughly reviewed, high-quality publication while maximizing the inclusion of the available published literature. As we were reviewing a historical body of literature with wide-ranging case numbers and multiple and varied outcomes, this presented challenges in the synthesis of information. Our primary goal was to be as inclusive as possible. We have added to the Study Selection (page 10) to clarify this. We have also added a paragraph to the Discussion (pages 17-18) to explain how the NIH quality
assessment tool applies to our study.
5. Line 187 were patient who received adjuvant treatment included in the analysis
4
Response: We did not exclude articles if patients received adjuvant therapy, as we wanted results to reflect real-world outcomes for these patients. Our Study Selection addresses this (page 10), and the Discussion has also been amended to reflect this point (page 16).
6. Line 217 why did the authors decide to include IA1 with LVSI who underwent trachelectomy?
Response: We included patients with IA1 tumors with LVSI, as radical trachelectomy with lymph node assessment remains within NCCN consensus guidelines as a treatment, and we felt our thorough review of historical literature would include a significant proportion of these tumors treated with radical trachelectomy. We acknowledge that a move toward less radical surgery is under way in select cases, and have added this point to our manuscript (in response to this comment and comments from Reviewer #1) to help readers better understand this.
7. Line 236 how were studies that did not report lymph node assessments included? Were they presumed to be negative and therefore not reported? Or were lymphadenectomy not performed?
Response: Articles must have reported an operative assessment of lymph nodes, but there were a few that unfortunately did not include the pathologic results of these lymph node assessments.
They were not presumed negative, rather they were excluded from data calculations and the denominator used for reporting percentages was adjusted accordingly. Our method of data synthesis for this large collection of articles that did not all report a standardized set of variables is included in the Study Selection section (page 10).
8. line 351 explain IRTA study
Response: The IRTA study refers to the International Radical Trachelectomy Assessment. This study, for which we are awaiting published results, is referenced in the Introduction (page 6) and, in response to your comment, we have also expanded the acronym in the Discussion for
clarification (page 18).
Comment: Table 1 is there any patients that received adjuvant therapy?
Response: A small percentage of patients received adjuvant therapy, which is reported as a variable in Table 2 (page 29).
Comment: Table 3 why did the authors decide on a 3 year follow up requirement? How many reports missed this cutoff?
Response: We chose three years of follow-up because the majority of early-stage cervical cancers will recur within this window of surveillance, and it is an established follow-up parameter for reporting in oncologic studies. As you have highlighted, it is important to
understand why this was chosen and therefore the Study Selection (page 10) has been modified to explain this. There were 26 articles that missed this cutoff. How this might affect accuracy in reporting has been clarified in the Discussion (pages 17-18).
Comment: Table 4,5,6 are excellent detailed data likely best served as supplemental tables.
5
Response: We agree that Tables 4, 5, and 6 are best served as supplemental tables and have retitled these as Supplementary Tables 1, 2, and 3, respectively.
Comment: Overall, this a well written paper. It increases our understanding of this rare surgical procedure. This study confirms that a conservative/fertility sparing discussion with early stage cervical cancer patient will highlight the limited high quality data but that published reports are promising.
Response: Thank you for your thorough review of our manuscript.
Comments from Reviewer #3
Comment: In this manuscript, the authors present a systematic review on the outcomes of
radical trachelectomy for the treatment of early cervical cancer. The study question is of interest, made more interesting given the recent outcomes discouraging laparoscopic approaches to the treatment of early cervical cancer by way of hysterectomy. The effort is registered with PROSPERO and the reporting follows guidance from PRISMA. The literature sources and search strategies are well described and reasonable. This perspective is true of the approach to study selection. By and large this effort is stymied by limited high-quality studies but given a prospective effort on the way, what is presented does serve as a good base of reference. It is curious the experience across surgical approaches wherein the vaginal approach has as good or better outcomes (and likely possesses substantially lower procedure costs). It seems
counterintuitive to attempt to remove an organ through or around another one (i.e. the uterus) thus the abdominal/laparoscopic approach would never seem to make much sense. The fact that conversions were more common when the surgical approach was from above would seem an obvious "availability" bias. The general lack of vaginal hysterectomy skills among gyn
oncologists would seemingly make these results hard to apply; but then in the setting of benign hysterectomy, the overuse of the robot to perform hysterectomies reflects a similar trend among benign OB/GYNs. While perhaps beyond the scope of this review at some point this matter should be considered. Overall, assuming this topic is of pertinence to a general OB/GYN readership, the effort is good.
Response: We appreciate your comments and review of our manuscript. Our interest in this topic is indeed in response to the recent study outcomes favoring open hysterectomy approaches for treating early-stage cervical cancer. The increased rates of MIS trachelectomy and even open trachelectomy as compared to vaginal trachelectomy reflects a historic shift among gynecologic oncologists. We share in your observation that it is curious how this shift in practice, not only for trachelectomy but for hysterectomy, has occurred despite previous reliable outcomes and likely lower cost for vaginal surgery. The way current providers practice, based on comfort with route of surgery or their surgical training, is an interesting topic for future study.
Comments from the Statistical Editor
6
Comment: Tables (All, except Table 3): Should write the complete name for ART, LRT and VRT.
Response: We have written out the complete names for ART, LRT, and VRT in Table 1 and Table 2.
Comment: Table 2: Should include the "N" for each column for number of patients.
Response: The starting “n” for each column for number or patients has been added to Table 2.
Comment: Table 3: Should break down the quality rating to include the three surgical approaches separately, then as the total.
Response: We have broken down the quality rating to include the three surgical approaches separately and then as the total for Table 3.
Comment: Tables 4, 5 & 6 could be on-line supplemental material.
Response: Tables 4, 5, and 6 have been relabeled as Supplementary Tables 1, 2, and 3, respectively, and will serve as on-line supplemental material.
Comments from the Editor
Comment: We no longer require that authors adhere to the Green Journal format with the first submission of their papers. However, any revisions must do so. I strongly encourage you to read the instructions for authors (the general bits as well as those specific to the feature-type you are submitting). The instructions provide guidance regarding formatting, word and reference limits, authorship issues, and other things. Adherence to these requirements with your revision will avoid delays during the revision process, as well as avoid re-revisions on your part in order to comply with the formatting. Please avoid idiosyncratic abbreviations that the specialist in Ob GYN or general reader (as opposed to gyn oncologist( may not know such as VRT, LRT, ART which could be confused with Assisted Reproductive Technology.
Response: We agree that it is best to avoid abbreviations that may be confusing, therefore we have discarded the abbreviations VRT, ART, and LRT and have used the full descriptions of these interventions.
Comment: The numbers below refer to manuscript line numbers.
P Values vs Effect Size and Confidence Intervals
While P values are a central part of inference testing in statistics, when cited alone, often the strength of the conclusion can be misunderstood. Whenever possible, the preferred citation should be in terms of an effect size, such as odds ratio or relative risk or the mean difference of a variable between two groups, expressed with appropriate confidence intervals. When such syntax is used, the P value has only secondary importance and often can be omitted or noted as
7
footnotes in a Table format. Putting the results in the form of an effect size makes the result of the statistical test more clinically relevant and gives better context than citing P values alone.
This is true for the abstract as well as the manuscript, tables and figures.
Please provide absolute values for variables, in addition to assessment of statistical significance.
We ask that you provide crude OR’s followed by adjusted OR’s for all relevant variables.
Please limit p values to 3 decimal places.
Response: We consulted with our Statistics department during the concept and design and again during the review of results and synthesis of the data. Due to a lack of sufficient survival data, we are unable to perform statistical comparisons across groups (meta-analysis) to provide p- values with confidence intervals or odds ratios
Comment: Numbers below refer to line numbers 79: please include units for age.
Response: The unit for age, years, has been added to both the Introduction (page 6) and Table 1 (page 28).
82. The journal style does not support the use of the virgule ( / ) except in mathematical expressions. Please remove here and elsewhere.
Response: We have removed any use of the virgule throughout the text, as requested.
Comments from the Editorial Office
1. The Editors of Obstetrics & Gynecology are seeking to increase transparency around its peer- review process, in line with efforts to do so in international biomedical peer review publishing. If your article is accepted, we will be posting this revision letter as supplemental digital content to the published article online. Additionally, unless you choose to opt out, we will also be including your point-by-point response to the revision letter. If you opt out of including your response, only the revision letter will be posted. Please reply to this letter with one of two responses:
A. OPT-IN: Yes, please publish my point-by-point response letter.
B. OPT-OUT: No, please do not publish my point-by-point response letter.
Response: We choose to OPT-IN and agree to this point-by-point response letter being published.
2. As of December 17, 2018, Obstetrics & Gynecology has implemented an "electronic Copyright Transfer Agreement" (eCTA) and will no longer be collecting author agreement forms. When you are ready to revise your manuscript, you will be prompted in Editorial
Manager (EM) to click on "Revise Submission." Doing so will launch the resubmission process,
8
and you will be walked through the various questions that comprise the eCTA. Each of your coauthors will receive an email from the system requesting that they review and electronically sign the eCTA.
Please check with your coauthors to confirm that the disclosures listed in their eCTA forms are correctly disclosed on the manuscript's title page.
Response: We have confirmed that disclosures listed in the eCTA forms are correctly disclosed on the manuscript’s title page.
3. Please submit a completed PRISMA checklist.
Response: We have completed and included a PRISMA checklist with this submission.
4. Standard obstetric and gynecology data definitions have been developed through the reVITALize initiative, which was convened by the American College of Obstetricians and Gynecologists and the members of the Women's Health Registry Alliance. Obstetrics &
Gynecology has adopted the use of the reVITALize definitions. Please access the obstetric and gynecology data definitions at https://www.acog.org/About-ACOG/ACOG-Departments/Patient- Safety-and-Quality-Improvement/reVITALize. If use of the reVITALize definitions is
problematic, please discuss this in your point-by-point response to this letter.
Response: We adhere to standard Obstetrics & Gynecology data definitions.
5. Because of space limitations, it is important that your revised manuscript adhere to the following length restrictions by manuscript type: Review articles should not exceed 25 typed, double-spaced pages (6,250 words). Stated page limits include all numbered pages in a manuscript (i.e., title page, précis, abstract, text, references, tables, boxes, figure legends, and print appendixes) but exclude references.
Response: Our revised manuscript adheres to the length restrictions for review articles.
6. Specific rules govern the use of acknowledgments in the journal. Please note the following guidelines:
* All financial support of the study must be acknowledged.
* Any and all manuscript preparation assistance, including but not limited to topic development, data collection, analysis, writing, or editorial assistance, must be disclosed in the
acknowledgments. Such acknowledgments must identify the entities that provided and paid for this assistance, whether directly or indirectly.
* All persons who contributed to the work reported in the manuscript, but not sufficiently to be authors, must be acknowledged. Written permission must be obtained from all individuals named in the acknowledgments, as readers may infer their endorsement of the data and conclusions.
Please note that your response in the journal's electronic author form verifies that permission has been obtained from all named persons.
* If all or part of the paper was presented at the Annual Clinical and Scientific Meeting of the
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American College of Obstetricians and Gynecologists or at any other organizational meeting, that presentation should be noted (include the exact dates and location of the meeting).
Response: We have followed the guidelines for acknowledgments.
7. The most common deficiency in revised manuscripts involves the abstract. Be sure there are no inconsistencies between the Abstract and the manuscript, and that the Abstract has a clear conclusion statement based on the results found in the paper. Make sure that the abstract does not contain information that does not appear in the body text. If you submit a revision, please check the abstract carefully.
In addition, the abstract length should follow journal guidelines. The word limits for different article types are as follows: Reviews, 300 words. Please provide a word count.
Response: The Abstract has been carefully reviewed and meets the standards you have advised.
The Abstract word count is 299 words.
8. Only standard abbreviations and acronyms are allowed. A selected list is available online at http://edmgr.ovid.com/ong/accounts/abbreviations.pdf. Abbreviations and acronyms cannot be used in the title or précis. Abbreviations and acronyms must be spelled out the first time they are used in the abstract and again in the body of the manuscript.
Response: Only standard abbreviations and acronyms have been used.
9. The journal does not use the virgule symbol (/) in sentences with words. Please rephrase your text to avoid using "and/or," or similar constructions throughout the text. You may retain this symbol if you are using it to express data or a measurement.
Response: Any use of the virgule symbol has been removed and the text rephrased, where applicable.
10. In your Abstract, manuscript Results sections, and tables, the preferred citation should be in terms of an effect size, such as odds ratio or relative risk or the mean difference of a variable between two groups, expressed with appropriate confidence intervals. When such syntax is used, the P value has only secondary importance and often can be omitted or noted as footnotes in a Table format. Putting the results in the form of an effect size makes the result of the statistical test more clinically relevant and gives better context than citing P values alone.
If appropriate, please include number needed to treat for benefits (NNTb) or harm (NNTh).
When comparing two procedures, please express the outcome of the comparison in U.S. dollar amounts.
Please standardize the presentation of your data throughout the manuscript submission. For P values, do not exceed three decimal places (for example, "P = .001"). For percentages, do not exceed one decimal place (for example, 11.1%").
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Response: As mentioned in response to the comments from the editor, the use of p-values and expressions of effect size are not applicable to our manuscript. Also, percentages do not exceed one decimal place.
11. Please review the journal's Table Checklist to make sure that your tables conform to journal style. The Table Checklist is available online
here: http://edmgr.ovid.com/ong/accounts/table_checklist.pdf.
Response: The journal’s Table Checklist has been reviewed to ensure that our tables conform to journal style.
12. Figure 1 may be resubmitted with the revision as-is.
Response: Figure 1 is submitted with the revision.
13. Authors whose manuscripts have been accepted for publication have the option to pay an article processing charge and publish open access. With this choice, articles are made freely available online immediately upon publication. An information sheet is available
at http://links.lww.com/LWW-ES/A48. The cost for publishing an article as open access can be found at http://edmgr.ovid.com/acd/accounts/ifauth.htm.
Please note that if your article is accepted, you will receive an email from the editorial office asking you to choose a publication route (traditional or open access). Please keep an eye out for that future email and be sure to respond to it promptly.
Response: We will promptly respond to the choice of publication route if our article is accepted.
14. If you choose to revise your manuscript, please submit your revision through Editorial Manager at http://ong.editorialmanager.com. Your manuscript should be uploaded in a word processing format such as Microsoft Word. Your revision's cover letter should include the following:
* A confirmation that you have read the Instructions for Authors (http://edmgr.ovid.com/ong/accounts/authors.pdf), and
* A point-by-point response to each of the received comments in this letter.
Response: Revisions have been submitted through the Editorial Manager and point-by-point responses have been addressed for review comments.
Again, thank you for all comments provided. We look forward to your response regarding our revised submission and are available to respond to any additional questions or comments you may have.
Sincerely,
