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Both reviewers have thoroughly reviewed your revised manuscript and are very satisfied with the improvements made. They have confirmed that you have successfully addressed all their comments and concerns.
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The quality of the manuscript has significantly improved following the revisions. I recommend its acceptance.
The author has made effective responses and constructive revisions to the opinions, which I think have basically solved my concerns.
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After careful consideration of the reviewers' critiques, a decision of major revision has been made. The authors will need to thoroughly address the substantive concerns raised by both reviewers. A point-by-point response detailing how each reviewer's comment was handled, along with the revised manuscript, will be required for re-review.
1.The manuscript writing is generally good and allows people to understand the author's intention.The study seems to highlight the significance of a Nomogram in determining the prognosis of patients with TD-positive gastric cancer (GC). This Nomogram, by considering both TD status and tumor stage, outperformed the eighth edition of the TNM stage in predicting outcomes, indicating its potential clinical value. The study underscores the importance of not only considering the presence of TD but also taking into account the tumor stage when assessing the prognosis of TD-positive GC patients. overall data suggests that postoperative adjuvant chemotherapy could be beneficial for TD-positive GC patients regardless of their stage.
2.The references can basically support the content of the manuscript, and have good attention to the research in recent years.
3.The structure of the article conforms to the standard chapter format, which allows people to obtain interesting information very clearly. The figures, tables, and raw data generally fit the bill. The font of the chart needs to be consistent.In addition, the Figure Legend needs to provide a detailed description.The HE results in Figure 2 suggest an increase in scale, not just an indication of magnification.
4.The manuscript stands alone and is complete, rather than adding to the subdivision of the publication.
5.The title of this study should indicate that it is a prognostic model established based on tumor deposits in GC. In the Background of the Abstract, the author descripted that “The impact of the number and distribution of tumor deposits (TD) on the prognosis of gastric cancer (GC) patients is still a topic of debate. This study aimed to develop a specific prognostic model for GC patients with TD based on the number and location of TD.” The author should indicate what model needs to be established in this article to address which controversial issues while not develop a specific prognostic model for GC patients with TD based on the number and location of TD.
6. In the Introduction, the author should describe the existing prognostic models and shortcomings of GC. In addition, the author needs to describe whether TD is used for prognosis in other tumors and the feasibility of using TD for prognosis.
7.Overall, the study highlights the importance of considering not only the traditional TNM staging but also the presence and characteristics of TD in predicting the prognosis of GC patients. The nomogram developed through this study could serve as a valuable tool for clinicians in assessing the prognosis of TD-positive GC patients and making informed treatment decisions. However, the study was conducted at a single center (Wannan Medical College’s Yijishan Hospital), which might limit the generalizability of the findings to broader populations. Different patient populations, treatment protocols, and healthcare settings could yield different results.
8.These findings in Figure 4 suggest that the location of the tumor within the stomach influences the pattern of TD distribution, with a higher likelihood of TD in the lymphoid fat tissue near the tumor, particularly in the lesser curvature region. Understanding these patterns can aid in the diagnosis, staging, and management of gastric cancer patients.
9.The study suggests that postoperative adjuvant chemotherapy is associated with improved 5-year OS rates in TD-positive GC patients, particularly in stage II-III cases. However, the benefit in stage I patients combined with TD couldn't be directly assessed due to limited sample size. The author should delete this section of content.
10.The discussion of the prognostic model for GC patients with TDs is essential for its clinical implications, personalized medicine applications, improved patient management, comparative analysis with existing staging systems, validation and reliability assessment, and research implications. It underscores the significance of the model in enhancing prognostic accuracy and guiding clinical decision-making in the management of GC patients with TDs. By comparing the prognostic model with traditional staging systems like the TNM staging, the discussion should highlight the potential advantages and improvements offered by the new model. This comparison underscores the clinical utility and relevance of the developed model in enhancing prognostic accuracy.
11.The study shows that as the number and distribution of TD increase, the overall survival rates in GC patients decrease. For stage I-II GC, the number and distribution of TD seem to have little impact on prognosis. However, in more advanced stages (IIIa, IIIb), an increased number of TD is associated with a poorer prognosis, and the distribution (Q1 vs. Q2) also plays a role. In stage IIIc, the impact of TD seems to be less pronounced. These findings suggest that in clinical decision-making, the stage of the disease and the extent of TD might be crucial factors to consider when evaluating a patient's prognosis. The author may consider the number or distribution of TD in the prognosis of GC alone.
12.While the construction and validation of the prognostic model for gastric cancer patients with tumor deposits (TDs) offer valuable insights, several limitations should be acknowledged, such as Sample Size and Generalizability, Variable Selection and Measurement, Follow-Up Duration and Clinical Utility and Interpretability. Addressing these limitations through rigorous study design, larger sample sizes, diverse cohorts, robust validation methods, and consideration of additional variables would enhance the reliability and applicability of prognostic models for gastric cancer patients with tumor deposits.
This study was primarily a retrospective analysis to classify patients with gastric cancer (GC) according to the distribution of tumor deposit (TD) counts and to compare sample characteristics. In this study, samples were first categorized according to TD characteristics. Subsequently, the effects of TD quantity and anatomical location on the prognosis of GC patients were revealed by survival analysis. Then, factors affecting the prognosis of GC patients were revealed by univariate analysis, and a novel GC staging system was constructed. In conclusion, this study provides guidance for the diagnosis and staging of cancer, and the overall idea is complete, but the following issues still need to be addressed before publication:
1. The research topic is to construct a TD-related GC prognostic model, and the text focuses on evaluating and analyzing TD-positive samples; please indicate whether the model is predictive of other types of GC samples, and add literature to illustrate this.
2. This study was a single-center retrospective analysis, and although the constructed model performed well in internal validation, it lacked external validation, thus it is recommended that the limitations section briefly describes the general idea of conducting a follow-up study, such as what analytical tools were used to further validate the model.
3. TD is a neoplastic nodule that is discontinuous with the primary lesion and lacks recognizable lymphoid tissue structure, so it is not included in the current GC staging system. So, what is the essence of this study? In other words, the characteristics of TD are not obvious, and it is not reasonable to use it as a basis for cancer staging.
4. Given the lack of a basis for prognostic assessment of TD-positive GC patients, has the literature examined the basis for prognostic assessment of other TD-positive cancer types? Please clarify this point and explain the lack of a basis for prognostic assessment of TD-positive GC patients.
5. Does Figure 6, which illustrates the nonsignificant benefit of postoperative adjuvant chemotherapy for the subgroup with stage I combined TD, indicate that the result is not of any substantial significance? Why is it important to systematically state results that are not meaningful? Please provide a rational explanation.
6. External validation, conducted on separate cohorts or datasets, confirms the model's applicability to diverse patient populations. After constructing the model, it is essential to validate its performance using independent datasets to assess its generalizability and reliability. Internal validation techniques, such as bootstrapping or cross-validation, can evaluate the model's performance within the same dataset used for construction.
7. Please make the intent of this paper clearer by describing the characteristics of this study compared to other studies in the Discussion section and the Introduction section, and in particular by describing what are the distinguishing features of the GC staging model constructed in this paper compared to existing staging systems.
8. The Discussion section of this study suggests the addition of a summary statement, especially at the end of each paragraph summarizing the findings, focusing on the advantages of the model in this study in the assessment of patients with TD-positive GC, as well as the advancement of this assessment metric in existing studies, demonstrating its importance and criticality in GC typing and staging.
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