Microscopic vascular invasion may not be associated with survival of patients undergoing resection for solitary hepatoma of ≤ 2 cm

Wei-Feng Li; Yueh-Wei Liu; Chih-Chi Wang; Chee-Chien Yong; Chih-Che Lin; Yi-Hao Yen

doi:10.1371/journal.pone.0281154

Peer Review History

Original SubmissionNovember 9, 2022
29 Dec 2022 Decision Letter - Ibrahim Umar Garzali, Editor PONE-D-22-30980Microscopic vascular invasion is not associated with survival in solitary hepatoma ≤ 2 cm underwent resectionPLOS ONE Dear Dr. Yen, 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 12 2023 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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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: Thank you for sharing us your valuable study. I have some questions about your manuscript. Please find them below. - Firstly, why did not you prefer local ablative treatment firstly in your study? Because the sizes of the tumors were appropriate for ablative treatment. - Secondly, why did you choose major resection for some patients? As you know, major resection is unexpected result for these size of HCC. - Thirdly what is AFP upper limit in this study and ecog status of patients? Reviewer #2: This is a reasonable study based on a small dataset, as the authors acknowledge. They did not find and significant differences in survival parameters for OS or for the larger cohort of RFS. Therefore it is unsurprising that they found no effect for MVI. That they did not find an effect does not mean there is no effect. Therefore the title should reflect this. They cannot claim there is no effect of MVI, merely that they could not find an effect of MVI - or anything else- on OS, probably due to small cohort size, but likely because of the high OS, regardless of MVI status. As such, this is a small contribution to the literature. ****** 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. 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Revision 1
10 Jan 2023 Author Response Reviewer #1: Thank you for sharing us your valuable study. I have some questions about your manuscript. Please find them below. - Firstly, why did not you prefer local ablative treatment firstly in your study? Because the sizes of the tumors were appropriate for ablative treatment. Response: Thank you for your comments. Our previous study enrolled 143 patients with Barcelona Clinic Liver Cancer (BCLC) very early-stage HCC; of these patients, 52 underwent liver resection (LR) and 91 underwent radiofrequency ablation (RFA). The 3- and 5-year overall survival (OS) rates were 98% and 91.5% for LR and 80.3% and 72% for RFA, respectively (p = 0.073). The 3- and 5-year recurrence-free survival (RFS) rates were 62.1% and 40.7% for LR and 39.8% and 29.3% for RFA, respectively (p = 0.006). We concluded that for patients with Barcelona clinic liver cancer (BCLC) very early-stage HCC, there was no significant difference in OS between LR and RFA. However, LR resulted in better RFS than RFA [1]. Therefore, based on the results of our previous study [1], we recommend LR for patients with BCLC very early-stage HCC if they are good candidates for surgery, i.e., they have good liver function reserve and performance status and do not have severe comorbidities, and RFA as an alternative treatment modality. Reference 1. Wang JH, Wang CC, Hung CH, Chen CL, Lu SN. Survival comparison between surgical resection and radiofrequency ablation for patients in BCLC very early/early stage hepatocellular carcinoma. J Hepatol. 2012;56:412-8. doi: 10.1016/j.jhep.2011.05.020. - Secondly, why did you choose major resection for some patients? As you know, major resection is unexpected result for these size of HCC. Response: As mentioned in the European Association for the Study of the Liver (EASL) guidelines, RFA offers comparable results to those of LR for deeply/centrally located single HCC of ≤ 2 cm. In contrast, laparoscopic–robotic LR for HCC located in superficial/peripheral sites of the liver provides optimal survival outcomes, while minimizing complications and hospital stay [1]. However, based on the results of our previous study [2], we recommend LR for patients with BCLC very early-stage HCC, even for a tumor that is deeply/centrally located and might require major resection. References 1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. European Association for the Study of the Liver. J Hepatol. 2018;69:182-236. doi: 10.1016/j.jhep.2018.03.019. 2. Wang JH, Wang CC, Hung CH, Chen CL, Lu SN. Survival comparison between surgical resection and radiofrequency ablation for patients in BCLC very early/early stage hepatocellular carcinoma. J Hepatol. 2012;56:412-8. doi: 10.1016/j.jhep.2011.05.020. - Thirdly what is AFP upper limit in this study and ecog status of patients? Response: 1. Our institution uses a chemiluminescent microparticle immunoassay (CMIA), manufactured by Abbott, for quantitative determination of alpha-fetoprotein (AFP). The AFP upper limit is 80,000 ng/ml. 2. In our institution, LR is recommended for patients who are good candidates for surgery, i.e., those with an ECOG performance status = 0. All patients in the present study had an ECOG performance status = 0. Patients with inadequate PS would be referred for RFA. Reviewer #2: This is a reasonable study based on a small dataset, as the authors acknowledge. They did not find and significant differences in survival parameters for OS or for the larger cohort of RFS. Therefore it is unsurprising that they found no effect for MVI. That they did not find an effect does not mean there is no effect. Therefore the title should reflect this. They cannot claim there is no effect of MVI, merely that they could not find an effect of MVI - or anything else- on OS, probably due to small cohort size, but likely because of the high OS, regardless of MVI status. As such, this is a small contribution to the literature. Response: Thank you for your comments. We have revised the title to “Microscopic vascular invasion may not be associated with survival of patients undergoing resection for solitary hepatoma of ≤ 2 cm.” Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0281154.r002
16 Jan 2023 Decision Letter - Ibrahim Umar Garzali, Editor Microscopic vascular invasion may not be associated with survival of patients undergoing resection for solitary hepatoma of ≤ 2 cm” PONE-D-22-30980R1 Dear Dr. Yen, 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.0281154.r003

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