The Prognostic Effect of Multidisciplinary Team Intervention in Patients with Advanced Gastric Cancer

Round 1

Reviewer 1 Report

MDT is widely acknowledged as a good way to improve the outcome of patients with malignant tumor. In this study, authors provided supporting evidence for the application of MDT in the treatment of advanced gastric cancer by retrospective analysis of a cohort with 394 cases from single center. Although the results were valuable, some modifications needed to be done first.

Major issue 1: This study included patients from January 2007 to December 2014, but the MDT started from 2012. As a result, all patients from 2007 to 2012 would be grouped into non-MDT group. The comparison between non-MDT and MDT groups confounded with time-depended treatment improvement. The survival benefit come from MDT may truly from time-depended treatment improvement. Please describe the distribution of patients in each year and do further analysis to eliminated the effect from time periods.  

Major issue 2:  How about the percentage of the patients fulfilled the treatment plan prescribed by MDT group？And how about the association between the survival outcome and degree of completion of MDT treatment plan?

Minor issue 1: the inclusion criteria should be described more clear. From the context, the stage III/IV was clinical stage, otherwise MDT can't be performed before the treatment. 

Minor issue 2: The English writing needs to be revised.

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

This is a retrospective study of multidisciplinary team (MDT) improving survival time in patients with advanced gastric cancer. There is a big research design problem here.

In this study, the authors included cases from 2007 to 2014, but the researchers started standardizing on the MDT in 2012. Understandably, the vast majority of patients in the MDT group were from 2012 to 2014. During this period, the authors ignored other factors affecting survival time, such as: changes and improvements in surgical methods, combinations and updates of medical treatments, etc. In my opinion, researchers should divide patients in the same period into MDT and non-MDT groups, at least to ensure that the study has only MDT as a variable.

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

Summary:

 

Gastric cancer (GC) is a heterogenous disease that requires an integrated management approach to assure optimal outcomes. Preoperative plans and surgical resection are the standard treatments for early gastric cancer presentation. However, patient assessment and management practices for advanced gastric cancer are actually scarce.

Multidisciplinary team (MDT) intervention is an important and evolving area of oncology. Although the MDT approach has been used as a recurring practice in GC treatment, its effectiveness, especially in more advanced stages, remains controversial due to the lack of strong evidence demonstrating its advantages in improving clinical outcomes.

This study aimed to assess the prognostic impact of such practice on survival rates of patients with advanced GC. More accurately, the authors were able to show that MDT intervention was an independent factor to improve the prognosis of stage III and IV GC.

The results clearly support the adoption of a multimodality approach to clinical decision-making in cases of advanced stages of GC.

 

The genesis of the article proved to be relevant for future cancer risk assessment and counselling of advanced GC patients. The conclusions are preceded by a good statistical analysis of a current up to date issue. However, to be accepted for publication some relevant issues must be clarified and revised.

 

Peer-review Report:

 

In a general way, the article is written in a simple way (lacks point improvements) addressing a modern concept that needs further investigation. Since accompanying GC patients through regular MDT meetings implies significant investment of time and finances, it is crucial to demonstrate its effectiveness in terms of impact in clinical outcomes.

 

The title is appropriate for the content of the article. The abstract is concise and accurately summarizes the essential information of the paper.

Despite this starting point, some topics need to be addressed and defined in a more detailed manner in order to accomplish the standards of the journal.

 

Major issues:

 

1. Considering the descriptive characteristics of the patients with stage III or stage IV GC that that stood out from the multivariate analysis as being independent protective or adverse factors, the authors only focused on those that would give more emphasis to the purpose of the study. However, other baseline tumor characteristics reflect a similar trend and were not described by the authors, for instance middle localization of the primary tumor and carcinoembryonic antigen (CEA) levels. The possibility of succinctly describing these results and discussing them should be considered.

 

2. Furthermore, when these same features were analyzed according to the specific stage of the disease, stage III GC patients reproduce the multivariate analysis of the entire cohort, even with regard to prognostic factors that were not described in the previous point. But then, stage IV GC patient’s multivariate analysis only denotes MDT and radical resection as independent factors that improve the prognosis of the patients and tumor staging as an independent adverse factor. It would be expected that the authors provide an explanation for this difference in the statistical data.

 

3. The overall survival (OS) rate of MDT among stage III GC patients is determined at 5-years, while OS rate of MDT among stage IV GC patients is determined at 3-years. In order to magnify statistical data interpretation, the results must be presented in agreement, that is, both rates must be shown either at 3 or 5 years.

 

Minor issues (General):

 

1. Throughout the text there are many flaws with regard to abbreviations. Either the abbreviations are not mentioned the first time the word is written, or they appear as unabbreviated when their abbreviation has been previously mentioned. To ensure the text is cohesive, authors should correct this lapse considering words such as “multidisciplinary team”, “gastric cancer”, “overall survival” and abbreviations such as “NCCN”, “AJCC” and “CT”.

 

2. Line spacing is not consistent throughout the entire text. Between lines 28 and 65 one type of spacing is shown, from this point onwards the reader is presented with another spacing option between lines. This discrepancy must be corrected so that the entire text is formatted accordingly.

 

Minor issues (Introduction):

 

1. The introduction nicely summarizes present concerns regarding MDT practice in GC treatment and why this idea should be further explored in terms of more advanced stages. Still, the bibliography should be up to date in order to include the most recent Global Cancer Observatory estimations for GC (2020).

 

2. To enhance the introduction section, the authors should identify the few clinical studies on the therapeutic impact of MDT in advanced GC (Lines 66-67).

 

Minor issues (Materials and Methods):

 

1. For simplicity, in line 87 the first sentence should be changed to “Since 2012, we have held weekly discussions with the MDT board”.

 

2. In the same paragraph an identical sentence appears (lines 90-91 and lines 96-97). Authors should discard one of them so that the reading does not become confusing.

 

3. In line 110, the authors should consider to choose a synonym of “analyzed” so that 2 similar words do not appear side by side («Multivariate analysis analyzed…»).

 

4. In line 150, the authors must delete the repeated word “most”.

 

Minor issues (Results):

 

1. To improve the interpretation of the results the article would benefit from the inclusion of a flow-chart showing the process of patient’s enrolment and data collection.

 

2. For a better description, the title of the Table 1 should additionally include “Demographic or Basic and clinical characteristics of…”. The same applies to the Supplementary Table 1 and Supplementary Table 2.

 

3. The order in which the clinical characteristics of the patients are presented should follow the same pattern for all tables, as well as the spacing between the columns. In order for there to be an agreement, the tables must be rectified and reformatted.

Additionally, for a better and direct interpretation of the results it is suggested to include the corresponding sign (*,**,*** or ****) on the p-values with statistical significance.

 

4. It is recommended to revise the subtitles of the Kaplan-Meier curves presented in Figure 1, Figure 2 and Figure 3. As an example, the x-axis could be displayed as “Cumulative Survival Probability” and the y-axis could be displayed as “Time (months)”. Importantly, the x and y axis scale are not consistent displayed, nor is the size of individual graphs the same. It is evident that all figures need to be reformatted considering the aforementioned points.

 

5. In the second, fourth and sixth sections of the results the Hazard Ratio (HR) values and significance (p-value) should not only be described for the factors that offer improved clinical outcome, but also for those that promote an increase in mortality of advanced GC patients.

 

6. In the same paragraph the sentence « between the two groups…» appears twice (line 124 and line 126). For the reading to be clear, one of them needs to be deleted.

 

7. In line 136 the word “multivariate” must be written in capital letters.

 

8. In line 173 the letter “P” must be written in lowercase.

 

Minor issues (Discussion):

 

1. The different statistical proportion of patients with T4 and N3 stages in both groups subject to analysis (non-MDT and MDT) was envision by the authors as a “more complicated” issue. I would like to see a more elaborate discussion around this subject, taking into account how it can interfere with statistical data.

 

2. The authors were able to very accurately correlate their own results with other clinical studies established in the gastric cancer setting. However, the effectiveness of MDT assessment in terms of prognostic has been also highlighted by studies in patients with lung, breast, colorectal, colon, oesophageal, and prostate cancer. To enhance the discussion of the article and strengthen their own results, the authors should additionally identify reports in other oncological setting in whom MDT practices have been shown to result in improved OS compared with non‑MDT care.

 

3. Throughout the discussion, reference to other bibliography is mostly made by citing the first author of the report. For a better text fluidity, it is suggested that authors find alternative ways of refer to the bibliography that it is not always the same.

Moreover, the bibliographic references indicated by the numbers [18, 23, 24, 25 and 26] must appear at the end of the corresponding sentence.

 

4. A misleading interpretation was ascribed to reference [17]. This is not a prospective randomized phase III study, but rather a retrospective cohort study.

 

5. For simplicity, in line 228 the word “supplement” should be changed to “complement”.

 

6. In my point of view the term “veteran clinicians” (line 237) is not very well appropriated in this context. Perhaps it would be better to find another definition, for instance, “trained clinicians” or “specialized clinicians”.

 

7. In line 246, the sentence « (median survival time. 53 months vs 14 months) » must be removed. The inclusion of these results does not add anything to the discussion beyond what has already been mentioned.

 

8. During the discussion (lines 245 to 254) the term “OS time” or “survival time” is used recurrently and in a very frequent way. Authors should find alternative ways to refer to these terms.

 

9. The sentence from line 255 to 257 is confusing and can lead to misinterpretation. I would like this sentence to be reworded. As a suggestion, “Therefore, for potentially resectable GC and stage IV GC able to receive conversion treatment, MDT practice can improve the prognosis rate and it should be conducted throughout the treatment process.”

 

10. In line 258, the sentence “MDT intervention could improve the prognosis of patients with advanced gastric cancer” needs to be deleted. This sentence already appears earlier in the line 256-257.

 

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

suggest to accept.

Reviewer 2 Report

It is recommended to receive publication after checking grammar and refining language by a native English speaker.