Impact of monitor unit optimization in volumetric modulated arc therapy planning for nasopharyngeal carcinoma

Huaqu Zeng; Zhen Li; Zongyou Chen; Shukui Tang; Qifu Lin; Minzhi Zhong; Zunbei Wen

doi:10.1371/journal.pone.0327153

Peer Review History

Original SubmissionMarch 24, 2025
Decision Letter - Chung-Ta Chang, Editor PONE-D-25-12726Research on the Impact of Monitor Unit Optimization in Volumetric Modulated Arc Therapy Planning for Nasopharyngeal CarcinomaPLOS ONE Dear Dr. zeng, 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 Jun 08 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. 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Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access. 3. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [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: Yes Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know Reviewer #3: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: 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: This manuscript presents a technically sound and clinically relevant analysis of monitor unit (MU) optimization in VMAT planning for nasopharyngeal carcinoma (NPC). The study leverages a well-described retrospective dataset of 21 patients and offers a thorough comparison between base plans and three optimization scenarios (S50, S80, and S100) using the Eclipse TPS's MUO tool. The methodology is rigorous and clearly reported, with a reasonable range of Strength parameter values and fixed Maximum MU constraints. Dose coverage for target volumes, organ-at-risk sparing, MU reduction, beam-on time, and gamma passing rate (GPR) are assessed and interpreted appropriately. The data supports the conclusion that MU optimization—particularly with moderate Strength settings like S50 and S80—can meaningfully reduce total MUs without compromising clinical quality or delivery efficiency. The inclusion of multiple evaluation metrics and clear statistical treatment enhances the study's reliability. Strengths: -Clear clinical relevance: the findings directly support decision-making in VMAT plan optimization for NPC. -Detailed dose comparisons for both target volumes and OARs. -Inclusion of gamma index analysis under multiple criteria strengthens the dosimetric QA aspects. -Ethical approval and data availability are appropriately addressed. Areas for Improvement: -Language and Style: While the manuscript is generally intelligible, some grammatical issues, tense inconsistencies, and awkward phrasing could be improved for clarity and flow. A light language edit by a native English speaker or language service would help. -Discussion Depth: The discussion could benefit from a slightly more in-depth comparison with existing studies that evaluated Strength variation in MUO parameters—notably the clinical implications of underdosing in S100 could be expanded. -Figures and Tables: The legends for Figures 1–5 could be made more detailed. Also, a summary figure or schematic explaining the MUO tool settings and their clinical impact would enhance readability. Overall, the manuscript presents meaningful results that advance understanding of VMAT optimization in NPC and warrant publication after minor revisions. Reviewer #2: The manuscript is nicely written by the author. some minor corrections I have mentioned on the original pdf as well as separate pdf file. As of my knowledge, MU reduction is achievable with this technique but many time, at the cost of target coverage (excluding S50). Reviewer #3: This study investigates the dosimetric and delivery efficiency impacts of monitor unit (MU) optimization in VMAT for nasopharyngeal carcinoma (NPC). The topic is clinically relevant, as MU reduction can enhance treatment efficiency and potentially lower secondary cancer risks. The manuscript is well-structured, with clear methodology and robust statistical analysis. However, several areas require clarification and expansion to strengthen the scientific rigor and clinical applicability. 1.Clarify whether MUO was applied during initial optimization or as a post-hoc re-optimization. This affects reproducibility and clinical implementation. 2.Specify if OAR constraints were adjusted during MUO re-optimization. The observed increases in brainstem/spinal cord Dmax (≤1.5%) suggest constraints may need tightening. 3.Justify the choice of gamma criteria (1%/1 mm, 2%/2 mm, 3%/3 mm). While 1%/1 mm is stringent, its clinical relevance should be discussed (e.g., is 3%/2 mm more practical for routine QA?). 4.For OARs, discuss if the increases in brainstem Dmax (≤1.5%) or thyroid V40 are acceptable given clinical tolerances. 5.Highlight that S100’ MU reduction (30.9%) comes at the cost of target underdosing in 8/21 patients, making S50 or S80 more viable. 6.Explain why MU reduction did not shorten delivery time (e.g., fixed gantry speed, dose rate limitations). 7.Fixed MUO parameters (e.g., Maximum MU = 30% of base plan) may not be optimal for all cases. It is suggested to increase the discussion on the influence of the Maximum MU parameter on the results 8.Suggest prospective validation with larger cohorts, long-term toxicity outcomes, and exploration of adaptive MUO strategies. 9.In the Abstract, emphasize the improvement in gamma passing rates with MU reduction, as this is a notable practical outcome. 10.Ensure consistent formatting (e.g., italicize journal names, use "et al." correctly). The citation formats are inconsistent. Some authors use their full names while others use abbreviations. ****** 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: Cosima C. Hoch Reviewer #2: No Reviewer #3: 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. Attachments Attachment Submitted filename: Reviewers comments.pdf Attachment Submitted filename: PONE-D-25-12726_reviewer.pdf https://doi.org/10.1371/journal.pone.0327153.r001
Revision 1
3 Jun 2025 Author Response Dear Editors and Reviewers: Thank you for your letter and for the reviewers’ comments concerning our manuscript entitled “Research on the Impact of Monitor Unit Optimization in Volumetric Modulated Arc Therapy Planning for Nasopharyngeal Carcinoma” (ID: PONE-D-25-12726).Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in red in the paper. The main corrections in the paper and the responds to the reviewer’s comments are as fllowing: Responds to the reviewer’s comments: Reviewer #1: 1. -Language and Style: While the manuscript is generally intelligible, some grammatical issues, tense inconsistencies, and awkward phrasing could be improved for clarity and flow. A light language edit by a native English speaker or language service would help. This document has undergone comprehensive grammatical refinement and tense optimization, with final polishing conducted by professional English language editors. 2. -Discussion Depth: The discussion could benefit from a slightly more in-depth comparison with existing studies that evaluated Strength variation in MUO parameters—notably the clinical implications of underdosing in S100 could be expanded. In the Discussion section, we have added comparative analyses with existing studies and further elaborated on the clinical implications of underdosage in Plan S100. 3. -Figures and Tables: The legends for Figures 1–5 could be made more detailed. Also, a summary figure or schematic explaining the MUO tool settings and their clinical impact would enhance readability. The captions of Figures 1 to 5 have been supplemented with additional details. Additionally, a schematic diagram of the MUO tool's parameter settings has been added. Reviewer #2: 1. In the manuscript draft section, the Author mentioned that the patient's data used in the study was treated between October 23 to March 24. In contrast, the main abstract, manuscript, and ethics statement were mentioned as October 2020 to March 2021. The patient data used in this study were collected from those treated between October 2020 and March 2021, not October 2023 to March 2024. The manuscript draft has been revised accordingly and resubmitted. 2. In the main manuscript, under the heading 'VMAT planning,' how did the author decide to take the maximum MU 30 %?, Can it be more elaborate? The maximum MU constraint was set at 30% of the base plan's total MU based on prior studies, which has now been referenced in the manuscript. 3. Oar is written in small letters. It must be in capital letters. As requested, "Oar" has been corrected to "OAR" in all sections. 4. Under the heading “Comparison of the target and OAR doses….” The sentence “excluding setup time and gantry rotation time….” Can be written as excluding the setup time and gantry repositioning time, or beam mode up time. As requested, the “gantry rotation time” has been written as “beam mode up time”. 5. Under the heading “ pretreatment plan verification,” 10% threshold in the 3% 3mm criteria? I doubt it is given in the cited reference 24. The literature citations have now been corrected and properly referenced throughout the manuscript. 6. Table 4 can be rearranged. Table 4 has been rearranged to improve clarity and logical flow of the presented data. 7. In Tables 5 and 6, what are t1, t2, and t3? The author must mention it and elaborate on these terms. The t1, t2, and t3 values presented in Tables 5 and 6 have been clearly defined in the corresponding figure captions to ensure proper interpretation. Reviewer #3: 1. Clarify whether MUO was applied during initial optimization or as a post-hoc re-optimization. This affects reproducibility and clinical implementation. The MUO was implemented during the initial optimization phase before subsequent refinements. 2. Specify if OAR constraints were adjusted during MUO re-optimization. The observed increases in brainstem/spinal cord Dmax (≤1.5%) suggest constraints may need tightening. During MUO re-optimization, the original constraints for both target and OARs remained unchanged, with adjustments applied solely to monitor unit optimization. 3. Justify the choice of gamma criteria (1%/1 mm, 2%/2 mm, 3%/3 mm). While 1%/1 mm is stringent, its clinical relevance should be discussed (e.g., is 3%/2 mm more practical for routine QA?). The clinical significance of applying 1%/1mm gamma criteria was further elaborated, highlighting its stringent sensitivity in detecting teep dose gradients near critical structures compared to more lenient criteria. 4. For OARs, discuss if the increases in brainstem Dmax (≤1.5%) or thyroid V40 are acceptable given clinical tolerances. While the re-optimized plans demonstrated modest increases in brainstem Dmax and thyroid V40, all values remained well within institutional clinical tolerance limits. It has been supplemented in the discussion. 5. Highlight that S100’ MU reduction (30.9%) comes at the cost of target underdosing in 8/21 patients, making S50 or S80 more viable. The discussion has been revised to emphasize that compared to S100, S50 or S80 may represent more feasible compromise solutions. 6. Explain why MU reduction did not shorten delivery time (e.g., fixed gantry speed, dose rate limitations). Additional discussion has been incorporated to address why MU reduction did not shorten delivery time. 7. Fixed MUO parameters (e.g., Maximum MU = 30% of base plan) may not be optimal for all cases. It is suggested to increase the discussion on the influence of the Maximum MU parameter on the results. The impact of the Maximum MU parameter on the planning results has been supplemented in the discussion. 8.Suggest prospective validation with larger cohorts, long-term toxicity outcomes, and exploration of adaptive MUO strategies. Future studies will include prospective validation with more cases and long-term toxicity outcome assessments. 9.In the Abstract, emphasize the improvement in gamma passing rates with MU reduction, as this is a notable practical outcome. In the abstract, key emphasis has been placed: the significant improvement in Gamma passing rate achieved by reducing MU (Monitor Units), a result with important clinical significance. 10.Ensure consistent formatting (e.g., italicize journal names, use "et al." correctly). The citation formats are inconsistent. Some authors use their full names while others use abbreviations. The manuscript formatting has been carefully reviewed, and the reference style has been corrected accordingly. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0327153.r002
Decision Letter - Chung-Ta Chang, Editor Impact of Monitor Unit Optimization in Volumetric Modulated Arc Therapy Planning for Nasopharyngeal Carcinoma PONE-D-25-12726R1 Dear Dr. zeng, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Chung-Ta Chang Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0327153.r003
Formally Accepted
Acceptance Letter - Chung-Ta Chang, Editor PONE-D-25-12726R1 PLOS ONE Dear Dr. Zeng, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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 customercare@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. Chung-Ta Chang Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0327153.r004

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