PONE-D-24-42939Comparative Analysis of VMAT Plans on Halcyon and Infinity for Lung Cancer RadiotherapyPLOS ONE

Dear Dr. Qiu,

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.

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Hesham M.H. Zakaly, Ph.D.

Academic Editor

PLOS ONE

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2. Thank you for stating the following financial disclosure: 

This research was supported by Zhejiang Province Natural Science Foundation of China under Grant No. LGF21H180014, the Medical and Health Research Project of Zhejiang Province under Grant No.2021PY002, and Zhejiang Provincial Basic Public Welfare Research Project (No. LGF22H160070).  

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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: Partly

Reviewer #2: Partly

Reviewer #3: Yes

Reviewer #4: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: I Don't Know

Reviewer #4: Yes

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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

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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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

Reviewer #3: Yes

Reviewer #4: Yes

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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: The text complies with the standard English language and was written in a clear and objective manner. The work presents a current and relevant subject and contributes to knowledge in the area covered. The objectives are clear, but could be better defined. The Introduction is well-founded and is appropriate to the proposed theme, although the reason for selecting the two treatments under study (Halcyon and Infinity) is not clear. The research method used, however, is not clearly defined and is probably not consistent with the objective of the work. The text of the manuscript does not make it clear whether this is a clinical trial (retrospective?) or a retrospective cohort. The inclusion or selection criteria for patients are not clarified, as well as the criteria for their allocation to the treatment groups. Information on blinding is also not presented. The initial characteristics of the patients are also not presented in the results. Are the distribution of sociodemographic characteristics and the severity and characteristics of the disease similar between the groups at the beginning of the research? The conclusion is based on the research results, however the methodology is fragile.

Reviewer #2: I have read the article entitled: “Comparative Analysis of VMAT Plans on Halcyon and Infinity for Lung Cancer Radiotherapy “ which is about a retrospective study comparing two linear accelerators ( and Infinity) used for VMAT in NSCLC, in terms of target dose coverage, normal tissue protection, and plan complexity.

The results of the study show that the Halcyon system offers enhanced protection for normal tissues and performs well in low-dose regions, while the Infinity system provides greater treatment efficiency and better control in high-dose areas.

Although the research methodology appears generally sound, there are some concerns that need to be addressed:

Confounding Factors:

The study does not mention case matching by stage, tumor size, or tumor location, which could introduce variability in dose requirements across cases. This could be a significant confounding factor impacting dose comparisons.

The authors could consider using regression models to account for variability, which would strengthen the analysis by reducing biases due to these unaccounted differences in patient characteristics.

Study Limitations:

Inter-Operator Variability: The skill and experience of planners and operators can significantly affect treatment planning quality, and this variability may influence the findings.

Case Selection Bias: If the study does not cover a diverse range of case types (e.g., varying tumor locations or complexities), it may not be possible to generalize the results. This selection bias could limit the applicability of the findings to broader clinical contexts.

Reviewer #3: This study conducted a comparative analysis of VMAT plans on two linear accelerator platforms, Halcyon and Infinity, for non-small cell lung cancer (NSCLC) radiotherapy, aiming to provide data support for clinical equipment selection. Overall, this paper has a clear structure and relatively complete content, but there are some issues and areas for improvement in the following aspects:

1.Research Design and Methods

The authors conducted a retrospective analysis of VMAT plans for NSCLC patients, which is a reasonable design. However, it lacks detailed descriptions of key information such as patient inclusion and exclusion criteria, tumor staging, and pre-treatment physical condition. It is recommended to add detailed descriptions of patient selection, inclusion and exclusion criteria, as well as specific steps and methods of the research design, to improve the reproducibility and transparency of the study.

When optimizing VMAT plans, the authors mentioned the use of RayStation 9A software, but it didn’t elaborate on the specific process of data collection and processing, including data sources, collection methods, and processing steps. It is recommended to supplement specific details of data collection and processing to ensure the reliability and accuracy of the study.

2.Results

Although the authors provided some key data in the results section, it lacks in-depth analysis and interpretation of these data. For example, regarding the differences between Halcyon and Infinity in target dose, normal tissue protection, etc., the authors didn’t provide sufficient explanation and discussion. It is recommended to increase in-depth analysis and interpretation of the results.

3.Discussion

In the conclusion section, the authors pointed out that Halcyon and Infinity each have advantages in NSCLC radiotherapy, but it fails to clearly provide key factors and specific recommendations to consider when selecting the optimal radiotherapy equipment. It is recommended to strengthen the content of the discussion section, including exploring the clinical significance of the research results, comparisons with other studies, limitations of the study, and potential future research directions.

4.Ethics

Although the authors mentioned the approval of ethical review, it didn’t elaborate on how patient privacy and rights are protected during the research process. It is recommended to add detailed descriptions of ethical review and compliance, including how patient privacy and rights are protected during the research process.

Reviewer #4: This study provides a coherent and useful summary of a study that compares two linear accelerator platforms for the treatment of NSCLC. The authors have explicitly articulated their purpose, methodology, principal findings, and conclusions.

Rationale for Acceptance:

The comparison of Halcyon and Infinity platforms for NSCLC treatment is pertinent to radiation oncology, offering critical insights for doctors in equipment selection.

The methodology is robust, featuring an adequate sample size and a well-defined planning and review process. Employing uniform dose restrictions and optimization parameters enhances the credibility of the comparison.

Notable Discoveries: The findings underscore significant disparities between the two systems, especially with normal tissue preservation and high-dose management. These findings possess significant ramifications for treatment planning and patient outcomes.

The research presented unequivocally substantiates the conclusions, offering significant information for practitioners. The authors duly recognize the constraints of their work and provide avenues for subsequent investigation.

This abstract effectively advocates for the publishing of the complete manuscript. The study looks into an important clinical question, uses a solid method, and comes up with interesting results that could change the way radiotherapy is done in the future.

Nonetheless, I recommend that the authors contemplate a little expansion of the "plan complexity" component in the study. Although they reference a reduced number of monitor units for Halcyon, a quick mention of additional complexity metrics, such as the modulation complexity score, would enhance their argument.

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Reviewer #1: Yes: Érika Carvalho de Aquino

Reviewer #2: Yes: Ghania Belaaloui

Reviewer #3: No

Reviewer #4: No

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PONE-D-24-42939R1Comparative Analysis of VMAT Plans on Halcyon and Infinity for Lung Cancer RadiotherapyPLOS ONE

Dear Dr. Qiu,

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 19 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Hesham M.H. Zakaly, Ph.D.

Academic Editor

PLOS ONE

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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 #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

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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 #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

Reviewer #4: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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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 #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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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 #1: After revision, the manuscript meets the criteria for publication. The text is written in a fluent and grammatically correct manner. The introduction adequately presents the topic and the knowledge gap to be addressed, while also contextualizing the relevance and justification of the research. The problem is appropriately described, as are the study objectives. The methodology employed is suitable for the objective and is clearly described. However, the analyses could benefit from incorporating classical association measures for cohort studies. The results are adequately presented and are directly related to the article's objective. In the discussion section, the authors examine the results in light of other similar studies, correctly present the research limitations, and provide suggestions for further advancements. The conclusion appropriately addresses the research objectives.

Reviewer #2: I have read the revised version of the article: “Comparative Analysis of VMAT Plans on Halcyon and Infinity for Lung Cancer Radiotherapy “, and can say the following regarding the answers to my comments made on the original version.

The authors tried to answer to the comments, however, I still have a concern about the existence of confounding factors (comment 1). The authors answered by calculating the correlation coefficient between dose metrics and other factors. This calculation showed that, indeed, there may be possible confounding factors. They didn’t realise a logistic regression, but they recognise the possibility the existence of such confounding factors in the discussion. Scientifically, I think that authors should, at least, mention this in the abstract to avoid any misleading of the readers.

Reviewer #3: (No Response)

Reviewer #4: This article presents a relevant comparison of two linear accelerator platforms used in radiotherapy for NSCLC. However, there are several areas that need improvement before it's ready for publication:

Strengths:

Relevant Topic: The comparison of Halcyon and Infinity is clinically relevant, as these are widely used platforms, and understanding their strengths and weaknesses can aid in treatment planning and equipment selection.

Clear Objective and Methodology: The study clearly defines its objective and methodology, making it easy to understand the study design and analysis.

Detailed Analysis: The article provides a detailed analysis of various dosimetric parameters and treatment efficiency factors.Acknowledges Limitations: The authors acknowledge the limitations of their study, including the small sample size and retrospective design. The article has the potential to be a valuable contribution to the literature. The article can now be suitable for publication.

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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: Erika Carvalho de Aquino

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes: Sanusi Mohammad Bello

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[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.

Comparative Analysis of VMAT Plans on Halcyon and Infinity for Lung Cancer Radiotherapy

PONE-D-24-42939R2

Dear Dr. Qiu,

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.

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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,

Hesham M.H. Zakaly, Ph.D.

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

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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

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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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: I have read the revised version R2 of the article: “Comparative Analysis of VMAT Plans on Halcyon and Infinity for Lung Cancer Radiotherapy “, and I was satisfied to see that the authors addressed my scientific request.

From my side, I do not have further comments regarding the work.

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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

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