Reproducibility of dynamic contrast enhanced MRI derived transfer coefficient Ktrans in lung cancer

Jean-Philip Daniel Weber; Judith Eva Spiro; Matthias Scheffler; Jürgen Wolf; Lucia Nogova; Marc Tittgemeyer; David Maintz; Hendrik Laue; Thorsten Persigehl

doi:10.1371/journal.pone.0265056

Peer Review History

Original SubmissionSeptember 28, 2021
10 Jan 2022 Decision Letter - Pascal A. T. Baltzer, Editor PONE-D-21-31257Reproducibility of dynamic contrast enhanced MRI derived transfer coefficient Ktrans 5 in lung cancerPLOS ONE Dear Dr. Weber, 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 Feb 24 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. 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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: 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: 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: In this study, the authors examined intra- and interreader variability of Ktrans, a DCE-MRI based quantitative biomarker of tissue perfusion and vascular permeability, in solid lung tumors. Ktrans showed a moderate to good reliability overall, which correlated with tumor size. The manuscript is well written and the technical and analytical approaches are sound. I only have a few minor suggestions which should be adressed prior to publication. 1. The abstract conveys the most important information in a very comprehensible manner. There is a minor grammatical mistake in the last sentence, as it says „DCE MRI offers with Ktrans a reliable quantitative biomarker“, which should rather read „With Ktrans, DCE MRI offers a reliable quantitative biomarker“, i.e. the words should be repositioned. 2. The authors should look into the distributions of Ktrans values around their means per timepoint, specifically their deviations from normality, since the calculation of confidence intervals for ICCs assumes a normal distribution. Since Ktrans values are zero-bound, a truly normal distribution is not possible. For Fig. 3, a graphical representation of medians (i.e. a box plot in the style of Tukey) should be chosen, rather than means and SDs. 3. The dataset is quite heterogenous, as it consists of both extra- and intrapulmonary lesions with variable sizes. Due to the low number of intrapulmonary lesions, reliability measures on these might not be conclusive. The authors might consider to exclude these lesions from their analyses. Alternatively, for table 3 and 4, lesions could be grouped according to both size and location, i.e. showing data for for intrapulmonary lesions larger than 3 cm, extrapulmonary lesions larger than 3 cm, intrapulmonary lesions smaller than 3 cm and extrapulmonary lesions smaller than 3 cm. 4. Table 4 is titled „Intraclass agreement“, whereas the corresponding paragraph in the text is titled „Intrarater agreement“. The authors should change the title of the table to avoid confusion. 5. In the dicussion, the authors claim that Ktrans is „probably the most used and most established DCE-MRI biomarker“, to justify why they chose this parameter over other semiquantitative biomarkers. Is this claim based on purely experience, or if there literature available? 6. This might not concern the authors directly, but I was not forwarded the supporting information and can therefor not validate that all data is fully available. For this reason I chose „No“ in the corresponding review box. ****** 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: Yes:** Martin L. Watzenböck [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.0265056.r001
Revision 1
8 Feb 2022 Author Response Responses to Review Comments 1. We apologize for the grammatical mistake. The sentence structure has been modified in the revised manuscript according to your suggestion. The correction was made both in the abstract on page 2, line 41 and in the discussion on page 16, line 340. 2. Thank you for the legitimate suggestion for improvement. In both Table 2 and Fig 3, due to the heterogenous distribution, the means and standard deviations for Ktrans were misleading. Table 2 now shows the median values of Ktrans and the interquartile ranges (IQR). Fig 3 has also been renewed and now shows the Ktrans values in form of boxplots in the style of Tukey. 3. We thank you for the concrete and legitimate proposals. The division of the lesions and the resulting structure of our work was subject of intense debates in our research group. In fact, the extrapulmonary metastases are small in number, which reduces statistical significance. This point is therefore explicitly taken up again in the discussion section on page 14, line 302-309. Nevertheless, we did not want to undermine the poor reproducibility of extrapulmonary metastases, with the aim of pointing out that future measurements of such lesions may require adjustments to protocols and study settings. Furthermore, we also considered subdividing the extrapulmonary lesions according to their size. In contrast to the intrapulmonary lesions, however, there does not seem to be a meaningful cut-off analogous to the T stage or the RECIST criteria. This would make any subdivision look arbitrary. Since in our dataset the lymph nodes are already rather small (2.6 ± 0.5 cm) and the bone metastases are rather larger (4.3 ± 0.8 cm), a natural split is already given here in a certain respect. While we fully understand your concerns, we hope this provides some explanation of our perspective to illustrate why we want to keep the extrapulmonary lesion as part of our work and refrain from making any further subdivisions. 4. Thank you for the kind notice. To avoid possible confusion, it is important to us to use a uniform vocabulary. The designation was therefore adjusted according to your suggestion. 5. We acknowledge that this was a vague wording. References 28 (Di N et al.) and 29 (Jiang T et al.) have been added to support our statement. The corresponding changes were added to the reference list. 6. According to the PLOS Data Policy the full dataset of Ktrans values underlying the statistical ICC and wCOV calculation has been added to the Supporting information named “S1_Dataset”. The dataset contains Ktrans values measured by every single reader of all 107 tumor lesions sorted by location and size. Attachments Attachment Submitted filename: Rebuttal letter.docx https://doi.org/10.1371/journal.pone.0265056.r002
23 Feb 2022 Decision Letter - Pascal A. T. Baltzer, Editor Reproducibility of dynamic contrast enhanced MRI derived transfer coefficient Ktrans in lung cancer PONE-D-21-31257R1 Dear Dr. Weber, 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, Pascal A. T. Baltzer, M.D. Academic Editor PLOS ONE Additional Editor Comments (optional): I have reviewed your revised manuscript and found the changes to my full satisfaction. This paper is a worthy contribution to its field. Please excuse my apology for the long review process that was entirely due to me being overloaded by work - next time I will be faster... Reviewers' comments: https://doi.org/10.1371/journal.pone.0265056.r003
Formally Accepted
28 Feb 2022 Acceptance Letter - Pascal A. T. Baltzer, Editor PONE-D-21-31257R1 Reproducibility of dynamic contrast enhanced MRI derived transfer coefficient K^trans in lung cancer Dear Dr. Weber: 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. Pascal A. T. Baltzer Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0265056.r004

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