通讯作者: 吴鸣, drwuming@163.com; 钟森, pumchzhongsen@163.com

DOI：10.12074/202309.00238V3

• 目的: 早期子宫颈神经内分泌癌的治疗主要包括手术及化疗；常规术后放疗的应用仍有争议。本研究评估早期子宫颈神经内分泌癌术后放疗的价值。
  方法：回顾性队列研究，入组2006年-2022年的早期子宫颈神经内分泌癌患者；按术后是否放疗分为术后未放疗组（组A）和术后放疗组（组B）。使用Kaplan-Meier方法计算无进展生存期、总生存期、总生存率。
  结果: 入组66例患者，组A共32例 (48.5%)，组B共34例 (51.5%）。术后随访35 (区间12-116) 个月, 26例 (39.4%) 复发。与组A相比，组B的盆腔复发率略低 (12.5% vs 2.9%, p = 0.142)，远处转移率略高 (28.1% vs 44.1%, p = 0.177)，总复发率相似 (29.4% vs 31.3%, p = 0.871)。组B的宫颈间质浸润≥1/2更常见 (28.0% vs 63.0%, p = 0.012)，此类患者（宫颈间质浸润≥1/2）术后放疗可延长无进展生存期 (33.9个月 vs 47.9个月) 和总生存期 (40.7个月 vs 70.0个月) 但结果无统计学差异 (p = 0.963, p = 0.636)。淋巴脉管间隙受累是术后肿瘤复发的高危因素 (HR 9.13, p = 0.005)，但此类患者术后放疗未改善无进展生存期 (51.5个月 vs 48.8个月, p = 0.942) 和总生存期 (53.9个月 vs 60.6个月, p = 0.715) 。
  研究局限性: 回顾性队列研究，样本量偏小。
  结论: 早期子宫颈神经内分泌癌术后放疗可改善宫颈间质浸润深度≥1/2患者的无进展生存期和总生存期；淋巴脉管间隙受累是术后肿瘤复发的高危因素，但此类患者术后放疗可能并无生存获益。

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• 序号	提交日期	编号	操作
  1	2023-09-28	biomedAxiv:202309.00238v1	下载
  2	2024-07-02	biomedAxiv:202309.00238v2	下载
  3	2025-02-17	biomedAxiv:202309.00238V3	下载

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  V1版本

  第1轮

  专家 ： 匿名专家

  专家意见：The research article by Song and colleagues aimed to compare the postoperative radiation s... More

  专家意见：The research article by Song and colleagues aimed to compare the postoperative radiation situation in neuroendocrine carcinoma. They collected some patients and classified in detail into early stage and with postoperative rotation or not. Then they analyzed the survival curve including OS and PFS to find that no significant difference with or without postoperative radiation. However, they should provide more solid evidence and validate the observations in additional clinical cohorts. They also need to describe their motivation and perspective and answer the following questions:
  Major comments
  1.Table 5 lists clinical cases with various pathological factors. You should use complete information about the patient for further analysis. In the current version, statistical compassion may be unfair.
  2.In Table 1, all variables of your collected cohort were not significant. Please add a significant factor for your positive control or explain the possible reasons.
  3.In this study, they should explain in detail the strategies of pelvic radiation and postoperative chemotherapy. The dose, frequency, drug options of each patient should be listed in this manuscript.
  4.In their study, group A and group B have some difference in recurrence rate. So, what about the possible role of postoperative radiation? Please cite some references to support or refute their observations. For example, they mentioned that “Although LVSI is a high-risk factor for tumor recurrence, the radiation therapy after surgery of the LVSI patients had no survival benefit.”. They need to perform more evidence.
  5.In this study, the authors further divided the cohort (n=66) into Group A and Group B for further analysis. They should also recruit another group of people to verify and predict the same trends.
  6.They should perform some immunohistochemical results with some corresponding pathological factors (histological type, pelvic lymph nodes status and LVSI. So that readers and reviewers can realize their criteria and standard.
  7.The current classification is only stage I and stage II, which are divided by the radiation therapy of not. If all stages are recruited for analysis, will the trend be the same as previously observed?
  Does the article fall within the aims and scope of the journal? Yes
  Are the Title, Abstract and Introduction clear? Yes
  Is the objective / hypothesis clearly stated? Yes
  Is the methodology sufficiently detailed and reproducible? Yes
  Is the statistical methodology appropriate? Yes
  Do the figures and tables presented in the article accurately represent the findings of the article? Yes
  Are the results and analysis sound? Yes
  Is the interpretation and discussion sound? No
  Are the conclusions of the article supported by the results? Yes
  Are the results of the article supported by the raw data (if available)? Yes
  Are references relevant and appropriate throughout, with all key references included? Yes
  Competing interests: No competing interests were disclosed by reviewer.
  Copyright: © [2024, Yu-Chan Chang]. This is an open access report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Close

  专家 ： 匿名专家

  专家意见：OBJECTIVE - Full research articles: is there a clear objective that addresses a testable r... More

  专家意见：OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research question(s) (brief or other article types: is there a clear objective)?
  Yes - there is a clear objective
  DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the objective?
  Not sure - key details are missing from the manuscript
  EXECUTION - Are the experiments and analyses performed with technical rigor to allow confidence in the results?
  No - there are minor issues
  STATISTICS - Is the use of statistics in the manuscript appropriate?
  Yes - appropriate statistical analyses have been used in the study
  INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not overstated?
  No - there are minor issues
  OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound? If not, can revisions be made to make the work technically sound?
  Probably - with minor revisions
  PEER REVIEWER COMMENTS:
  GENERAL COMMENTS: This is an interesting study in a rare disease , neuroendocrine carcinoma of the cervix, examining the effect of adjuvant radiotherapy in early stage disease. Neuroendocrine carcinoma of the cervix is believed to be highly biologically aggressive. Even in early stage, multimodality therapies are often recommended. It is unclear of the role of adjuvant radiotherapy in this disease. Retrospective design was used in the study with appropriate methodology to study the research questions. The manuscript is relatively well written with clearly defined goals and objectives. Appropriate limitations were acknowledged. A number of clarifications and revisions are needed before the manuscript can be considered for publications purpose as listed below.
  REQUESTED REVISIONS:
  1. Line 15 : Please further elaborate on the mentioned “The four-factor model” in this disease at the authors institution. Has this model been validated ? If so please provide a reference regarding this model. Also please defined “deep stromal invasion”
  2. Line 24-31 : “For women with early-stage NECC, there is no known frame that predicts rate of tumor recurrence. For example, a frame which was commonly used for describing the value of patients with squamous cell carcinoma or adenocarcinoma of the cervix to radiation therapy after surgery” is confusing and need to be reworded
  3. Line 42 -45 : Please confirm if lymph node dissection is part of the inclusion criteria. If so also please elaborate on the extent of lymph node dissection ? Sentinel lymph node ? full lymphadenectomy ? Pelvic versus para-aortic versus both ?
  4. Line 52-54 : Please clarify the chemotherapy regimen use postoperatively for early stage disease
  5. Please provide details regarding radiation treatment protocol
  6. For the calculation of PFS and OS, please clarify the timing of when the evaluation started ? at the start of primary treatment or at the end of primary treatment ?
  7. Page 8 : Please confirm that the “four-factor model” was used to triage the use of adjuvant radiotherapy consistently across the cohort ? What was the distribution of risk factors in patients who are found to be positive in this model ?
  8. Page 9 : Please provide the median tumor size in this cohort and the proportion of microscopic versus microscopic tumor at time of diagnosis in the text ? Was there any criteria to select patient for laparotomy versus minimal invasive surgical technique at the authors’ institution ?
  9. Page 9 : “We conducted a detailed evaluation of the pathologic factors in patients without preoperative chemotherapy” - please clarify if the 66 patient in the current cohort included those who had NOT been treated with “preoperative chemotherapy”. If so what was the reason for preoperative chemotherapy and what was the regimen used ?
  10. Based on the survival statistics, no significant difference was observed in either PFS or OS despite patients in group B were treated with adjuvant radiotherapy. Patients in group B were clearly having “high risk features” for recurrences. Can the authors comment on the potential benefit of radiotherapy in improving survivals in this poorer prognosis group compared to group A ? It would be difficult to show statistical significance with low number of patients in each cohort
  11. The authors identified “LVSI is an independent predictor for postoperative recurrence”. It would be interesting to examine the recurrent pattern in patient with LVS I in term of local versus systemic recurrences. Do patients with LVSI have a lower local pelvic recurrence rate when treated with radiation versus no adjuvant radiotherapy as pelvic radiotherapy can be much more effective to improve pelvic recurrences ? Does the article fall within the aims and scope of the journal? Yes
  Are the Title, Abstract and Introduction clear? Yes
  Is the objective / hypothesis clearly stated? Yes
  Is the methodology sufficiently detailed and reproducible? No
  Is the statistical methodology appropriate? Yes
  Do the figures and tables presented in the article accurately represent the findings of the article? Yes
  Are the results and analysis sound? No
  Is the interpretation and discussion sound? No
  Are the conclusions of the article supported by the results? No
  Are the results of the article supported by the raw data (if available)? Not applicable Are references relevant and appropriate throughout, with all key references included? Yes
  Competing interests: No competing interests were disclosed by reviewer.
  Copyright: © [2024, Tien Le]. This is an open access report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  Open Peer Review – Editor Decision
  Editor name: Dr Hao Zhang
  Affiliation: Jinan University, Guangzhou, China
  Journal: Annals of Medicine, Taylor & Francis
  Decision: Revise
  Copyright: © [2024, Hao Zhang]. This is an open access report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Close

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  V3版本

  第3轮

  专家 ： 匿名专家

  专家意见：
  Comments to the authors:
  The authors describe on an unreported area of research. ... More

  专家意见：
  Comments to the authors:
  The authors describe on an unreported area of research.
  The article may be accepted in the present form
  Does the article fall within the aims and scope of the journal? Yes
  Are the Title, Abstract and Introduction clear? Yes
  Is the objective / hypothesis clearly stated? Yes
  Is the methodology sufficiently detailed and reproducible? Yes
  Is the statistical methodology appropriate? Yes
  Do the figures and tables presented in the article accurately represent the findings of the article? Yes
  Are the results and analysis sound? Yes
  Is the interpretation and discussion sound? Yes/No
  Are the conclusions of the article supported by the results? Yes
  Are the results of the article supported by the raw data (if available)? Yes
  Are references relevant and appropriate throughout, with all key references included? Yes
  Competing interests: No competing interests were disclosed by reviewer.
  Copyright: ? 2024, Ajeet Kumar Gandhi. This is an open access report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Close

  专家 ： 匿名专家

  专家意见：
  Comments to the authors:
  I have no further concerns or questions.
  Does the a... More

  专家意见：
  Comments to the authors:
  I have no further concerns or questions.
  Does the article fall within the aims and scope of the journal? Yes
  Are the Title, Abstract and Introduction clear? Yes
  Is the objective / hypothesis clearly stated? Yes
  Is the methodology sufficiently detailed and reproducible? Yes
  Is the statistical methodology appropriate? Yes
  Do the figures and tables presented in the article accurately represent the findings of the article? Yes
  Are the results and analysis sound? Yes
  Is the interpretation and discussion sound? Yes/No
  Are the conclusions of the article supported by the results? Yes
  Are the results of the article supported by the raw data (if available)? Yes
  Are references relevant and appropriate throughout, with all key references included? Yes
  Competing interests: No competing interests were disclosed by reviewer.
  Copyright: ? 2024, Yu-Chan Chang. This is an open access report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  Open Peer Review – Editor Decision
  Editor name: Dr Hao Zhang
  Affiliation: Jinan University, Guangzhou, China
  Journal: Annals of Medicine, Taylor & Francis
  Decision: Accept
  Copyright: ? 2024, Hao Zhang. This is an open access report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited Close

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