Ultrasound classification of non-mass breast lesions following BI-RADS presents high positive predictive value

Mingnan Lin; Size Wu

doi:10.1371/journal.pone.0278299

Peer Review History

Original SubmissionAugust 31, 2022
22 Sep 2022 Decision Letter - Ibrahim Umar Garzali, Editor PONE-D-22-24181Ultrasound classification of non-mass breast lesions following BI-RADS presents high positive predictive valuePLOS ONE Dear Dr. Wu, 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 Nov 06 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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We will update your Data Availability statement to reflect the information you provide in your cover letter. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: No ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: i read the article with an interest. non mass lesions is an important and challenging issue in breast cancer. the authors give the satisfying results for this entity. thanks for all authors for this study. Reviewer #2: The title and objectives are different. the title talks about positive predictive value while the objective is mainly on incident of malignancy in NML by USS. The methodology contains some results like age and bio-demographic characteristics. odd ratio should not have calculated because the study is not trying to ascertain cause or risk factors for breast cancer. The figures reflecting USS findings suggestive of mass lesions should not been part of the result. for the fact that the study is a retrospective one, sensitivity and predictive value should not have considered because standardization could not be made as such the sensitivity would be very low. Discussion was initially off point as the study was on uss findings and not MRI. Most of the analyses were not in keeping with objective of the study. The discussion was mainly analysing microcalcification, punctate hypoechoic foci and posterior acoustic shadow. The author did well by stating the AUC of 0.62 was low compared to other stuydy. the conclusion ought to have qoute the low incidence of malignancy in all patients with NML not just NML with histological confirmation compared to all maligmant breast lesions. The references are very scanty. authors should have qouted copiously from the literature especially during the intrioduction and discussion. the sensitivity and specificity are low and not promising as stated and therefore the conclusion should have reflected this reality since p<0.05 was regarded as statistically significant ****** 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: Kemal EYVAZ 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.0278299.r001
Revision 1
20 Oct 2022 Author Response Response Letter Dear Editor, On behalf of all authors, I would like to resubmitted the revised manuscript (PONE-D-22-24181) entitled Ultrasound classification of non-mass breast lesions following BI-RADS presents high positive predictive value. The manuscript has been revised following the reviewers’ comments, and detailed response was given trackable in the revised manuscript. I believe that the revised manuscript may meet the criteria of the prestigious journal of PLOS ONE for publication in general. Please feel free to contact me (as the corresponding author) should further clarity be needed. I’m looking forward to hearing from you. Sincerely, Prof. Size Wu The corresponding author Responses to the Reviewer's Questions Comments: 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 Responses: Thanks. Reviewer #2: No Responses: The aims of our manuscript were to investigate the performance (diagnostic efficacy) of stratifying the malignancy risk of non-mass breast lesions (NMLs) following breast imaging reporting and data system (BI-RADS), including sensitivity, specificity, area under the receiver operating characteristic curve (AUC) (accuracy), positive and negative predictive values. Among them, positive predictive value is a useful parameter for the interpretation of the role of BI-RADS for NMLs. There are numerous publishing relating to the assessment of breast masses, however, the studies of US for the assessment of breast non-masses are much fewer. In fact, NMLs were not rare, they were frequently overlooked in clinical evaluation, for some physicians regarded them as atypical breast masses. On breast X ray and sonography, some breast mass and NMLs showed similar appearance, on contrast-enhanced MRI, breast mass and NMLs presented different features, and thus the conception and terminology of NML were coined. On ultrasound images, typical breast mass was with distinct appearance, even in small size. While on X ray some typical small size breast mass presented ambiguous contour, and less attention had paid for them in past time. In previous routine clinical practice, expect some case of NMLs were categorized as BI-RADS 0, other cases were actually classified as a certain category (breast mass). Strictly speaking, classifying breast NMLs using BI-RADS is not appropriated. We believe that confusion of breast mass and NML may result in an incomplete and not sound evaluation. In this study, a large sample of population were reviewed to determine the incidence of NMLs, to better understand the NMLs. Majority of NMLs were benign lesions, did not undergo biopsy or operation, and absence of histological results, so it’s hard to determine accurately, while malignant NMLs were undergone biopsy or surgical treatment, with histological results available, thus the diagnosis was sound and vigorous. So we investigated the incidence of malignant NMLs in this study, and the result was sound and vigorous. For the process of data, criteria of inclusion and exclusion were followed strictly, with appropriate design, and the statistical analyses were competent. The protocols of ultrasound imaging for the breast were following standard specification, as descripted in the Methods section (Acquisition of US images of the breast lesions). The conclusions drawn were appropriately. Comments: 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Responses: Thanks. Reviewer #2: No Responses: For the process of data, an appropriate design was conducted, the statistical analyses were performed appropriately, and also with consultation to expertise in statistics. Comments: 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 Responses: Thanks. Reviewer #2: Yes Responses: Thanks. Comments: 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 Responses: Thanks. Reviewer #2: Yes Responses: Thanks. Comments: Reviewer #1: i read the article with an interest. non mass lesions is an important and challenging issue in breast cancer. the authors give the satisfying results for this entity. thanks for all authors for this study. Responses: Thanks. Comments: Reviewer #2: The title and objectives are different. the title talks about positive predictive value while the objective is mainly on incident of malignancy in NML by US. Responses: Agreed. The “objective” was revised. The aims of our manuscript were to investigate the performance (diagnostic efficacy) of stratifying the malignancy risk of non-mass breast lesions (NMLs) following breast imaging reporting and data system (BI-RADS), including sensitivity, specificity, area under the receiver operating characteristic curve (AUC) (accuracy), positive and negative predictive values. Among them, positive predictive value is a useful parameter for the interpretation of the role of BI-RADS for NMLs, to use it as a title can highlight the main finding of this study. Of course, there were other findings that using the BI-RADS for the assessment, the likelihood of malignancy of malignant NMLs is underestimated, and that of benign NMLs is overestimated, these are challenge and drawbacks. To better understand the NMLs, incident of malignancy was analyzed. Majority of NMLs were benign lesions, did not undergo biopsy or operation, and absence of histological results, so it’s hard to determine accurately, while malignant NMLs were undergone biopsy or surgical treatment, with histological results available, thus the diagnosis was sound and reliable. So we investigated the incidence of malignant NMLs in this study, and the result was sound and reliable. Comments: The methodology contains some results like age and bio-demographic characteristics. odd ratio should not have calculated because the study is not trying to ascertain cause or risk factors for breast cancer. Responses: ## To save page and shorted the length of the paper, age and bio-demographic characteristics were incorporated into a table. Similar format style can be found in other article, e.g., (1) Kim et al. Radiology. 2018;288(1):55-63. doi: 10.1148/radiol.2018171987. (2) Zhuang et al. Radiology. 2017;283(3):873-882. doi: 10.1148/radiol.2016160131”. Of course, it had better be apart. ## “odd ratio” has different usages in biomedical study, similar application can be found in articles: (1) Kim et al. Preoperative Axillary US in Early-Stage Breast Cancer: Potential to Prevent Unnecessary Axillary Lymph Node Dissection. Radiology. 2018;288(1):55-63. doi: 10.1148/radiol.2018171987. (2) Stavros, et al. Solid breast nodules: use of sonography to distinguish between benign and malignant lesions. Radiology. 1995;196(1):123-34. doi: 10.1148/radiology. Comments: The figures reflecting USS findings suggestive of mass lesions should not been part of the result. for the fact that the study is a retrospective one, sensitivity and predictive value should not have considered because standardization could not be made as such the sensitivity would be very low. Responses: It’s right that the sensitivity and predictive value are used mainly in a prospective study. On the other hand, in a retrospective study, if the design is adequate, the reference standardization is objective and reliable (e.g., histopathological result), the data were collected adequately, then the sensitivity and predictive value can be calculated properly. E.g., Buda et al. Management of Thyroid Nodules Seen on US Images: Deep Learning May Match Performance of Radiologists. Radiology. 2019;292(3):695-701. doi: 10.1148/radiol.2019181343. Comments: Discussion was initially off point as the study was on USS findings and not MRI. Most of the analyses were not in keeping with objective of the study. Responses: Somewhat agreed. It’s right that the purpose of this study was to discuss USS findings, but to avoid abruption of definition of NML, background knowledge was introduced. On breast X ray and sonography, some breast mass and NMLs showed similar appearance, on contrast-enhanced MRI, breast mass and NMLs presented different features, and thus the conception and terminology of NML were coined. The following words were keeping with the objective of the study and associated findings. Comments: The discussion was mainly analysing microcalcification, punctate hypoechoic foci and posterior acoustic shadow. Responses: Somewhat agreed. The sensitivity, specificity, AUC, PPV and NPV were dominantly with microcalcification, punctate hypoechoic foci and posterior acoustic shadow in NMLs, so these features were discussed intensively. Comments: The author did well by stating the AUC of 0.62 was low compared to other study. the conclusion ought to have qoute the low incidence of malignancy in all patients with NML not just NML with histological confirmation compared to all malignant breast lesions. Responses: Somewhat agreed. To obtain sound and reliable results and conclusion, we did not use breast lesions without histological results, so many benign lesions were excluded, the results were obtained mainly on malignant lesions, and these were the limitations of this study. Comments: The references are very scanty. authors should have qouted copiously from the literature especially during the introduction and discussion. Responses: Agreed. The literature of contrast-enhanced MRI for the assessment of NMLs were rich, but it’s scanty for ultrasound, so there were not enough valuable references for this manuscript. Some references relating to breast mass and US BI-RADS were added, and associated revision was done. Comments: the sensitivity and specificity are low and not promising as stated and therefore the conclusion should have reflected this reality since p<0.05 was regarded as statistically significant. Responses: In this study we believed that the present statement may replace other expression, and more rephrase may be omitted. Attachments Attachment Submitted filename: Response to Reviewers Comments..doc https://doi.org/10.1371/journal.pone.0278299.r002
15 Nov 2022 Decision Letter - Ibrahim Umar Garzali, Editor Ultrasound classification of non-mass breast lesions following BI-RADS presents high positive predictive value PONE-D-22-24181R1 Dear Dr. Wu, 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, Ibrahim Umar Garzali, MBBS, FWACS Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0278299.r003
Formally Accepted
18 Nov 2022 Acceptance Letter - Ibrahim Umar Garzali, Editor PONE-D-22-24181R1 Ultrasound classification of non-mass breast lesions following BI-RADS presents high positive predictive value Dear Dr. Wu: 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. Ibrahim Umar Garzali Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0278299.r004

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