Gastrointestinal Stromal Tumors: 10-Year Experience in Cancer Center—The Ottawa Hospital (TOH)

Round 1

Reviewer 1 Report

This study analyzes the clinical and pathological data and outcomes of a relatively large number of patients (mostly resected) diagnosed with GIST in a single-center experience. Furthermore, a multivariate analysis was performed to identify potential prognostic factors that can be used in clinical decision-making. Although this paper has no significant novelty (the results are comparable with those reported in the previous papers), the study is well conducted, the methods are adequately used, and the results mainly sustain the conclusions. Thus, the results of the present study would potentially add value to the current literature. Furthermore, the paper is well written and well organized. In conclusion, the paper would be of interest to journal readers. However, a few modifications should be made before potential acceptance for publication.

Major concerns:

The results of the present study do not support a few conclusions. Thus, based on the analyses performed in the present study, we can not conclude that “TKI had significantly improved the OS of advanced GIST.” This conclusion should be removed.

In the authors’ opinion, what is the explanation for the low rate of patients in which the mutations were analyzed? As shown in Table 2.

What were the criteria for Imatinib treatment in the present cohort? (in the adjuvant and neoadjuvant settings)

In the authors’ opinion, what is the explanation for the following result: “Among the intermediate/high-risk group, patients who did not receive adjuvant Imatinib had longer RFS than those who received adjuvant IM with 5 years RFS 89%, 54% respectively, p =0 .059, HR =0.34 (95% 147 CI, 0.11 – 1.04)”?

The results of the uni and multivariate analyses of potential prognostic factors for both overall and recurrence-free survivals are not provided.

 

Minor comments:

Please consider modifying the presentation such as “The most common GIST sites were the stomach 63% (156), followed by the small bowel 29% (73)” to “The most common GIST sites were the stomach (156 patients, 63%), followed by the small bowel (73 patients, 29%)”. Providing data only as “(73)” can confuse the references’ citations.

Abbreviations should be defined in Table 1. In Tables 1-3, column 4, please consider providing the data with %.

In Figures 1-3, please consider replacing “cum survival” with “overall survival” end eliminating “Survival Functions.” Furthermore, on the time axis, please consider setting points at 12, 24, 48, 60, and 120 months to better reflect the survivals at 1-,3-,5-, 10 years.

Reference no 3 should be appropriately provided.

A native English speaker should revise the manuscript to correct a few minor grammar, spelling, or editing errors.

Author Response

Response to Reviewer 1 Comments

We would like to thank you for your valuable comments and recommendation, which will add to our paper.

 

Point 1: The results of the present study do not support a few conclusions. Thus, based on the analyses performed in the present study, we can not conclude that “TKI had significantly improved the OS of advanced GIST.” This conclusion should be removed.

Response 1: Thank you for your suggestion. We have removed “TKI had significantly improved the OS of advanced GIST”. Please see the Track Changes.

Point 2: In the authors’ opinion, what is the explanation for the low rate of patients in which the mutations were analyzed? As shown in Table 2.

Response 2:  Thank you for your comment. We believe this is mainly due to not routinely doing mutational analysis for all patients in our institution. Please see section 3.6, under the Molecular data of results section.

Point 3: What were the criteria for Imatinib treatment in the present cohort? (in the adjuvant and neoadjuvant settings)

Response 3:  Thank you for raising this point. In the adjuvant setting, Moderate/ or high-risk disease was the main indication to treat with adjuvant therapy provided that no contraindication for the drug and the patient accepted to proceed with the treatment. In the neoadjuvant setting, there were no specific criteria; however, if the patient has a bulky disease and is not a candidate for upfront surgery as evaluated by a surgical oncologist, then neoadjuvant therapy is indicated.

Point 4: In the authors’ opinion, what is the explanation for the following result: “Among the intermediate/high-risk group, patients who did not receive adjuvant Imatinib had longer RFS than those who received adjuvant IM with 5 years RFS 89%, 54% respectively, p =0 .059, HR =0.34 (95% 147 CI, 0.11 – 1.04)”?

Response 4: Thank you for correctly highlighting this. In fact, HR was not significant. As we mentioned in the discussion section “no clear explanation, possible reasons could be relatively small sample size, shorter adjuvant duration as only 15/40 (38%) completed three years of adjuvant Imatinib, and more inclusion of intermediate risk (35%, 14) in the adjuvant group. At the same time, no-adjuvant group is a predominantly intermediate risk (68%, 34), lack of mutational testing, and more deaths in the adjuvant group”.

Point 5: The results of the uni and multivariate analyses of potential prognostic factors for both overall and recurrence-free survivals are not provided.

 Response 5: Thank you for correctly highlighting this. We have provided The results of the uni and multivariate analyses of potential prognostic factors for both overall and recurrence-free survivals . As following :

In univariate analysis, ECOG at diagnosis, site, mitosis, secondary malignancy, and size were significant predictors for OS. By multivariate analysis, poor performance status (ECOG 3) was predictor for shorter OS (p<0.005) . The other factors analyzed (patient gender, site, histology, size, mitosis, and presence of secondary malignancy) were insignificant. In Uni and multivariate analysis, high mitosis and large size (>5cm) were associated with worse RFS, for both (p<0.002), (p<0.016) respectively.

 Please see the Track Changes.

Point 6: Please consider modifying the presentation such as “The most common GIST sites were the stomach 63% (156), followed by the small bowel 29% (73)” to “The most common GIST sites were the stomach (156 patients, 63%), followed by the small bowel (73 patients, 29%)”. Providing data only as “(73)” can confuse the references’ citations.

Response 6: Thank you for correctly highlighting this. We modified the presentation to “The most common GIST sites were the stomach (156 patients, 63%), followed by the small bowel (73 patients, 29%)”.  Please see the Track Changes.

Point 7: Abbreviations should be defined in Table 1. In Tables 1-3, column 4, please consider providing the data with %.

Response 7: Thank you for your comment. We added the definition of abbreviation in table 1. We provided the data with % for tables 1-3, column 4. Please see the track changes

Point 8: In Figures 1-3, please consider replacing “cum survival” with “overall survival” end eliminating “Survival Functions.” Furthermore, on the time axis, please consider setting points at 12, 24, 48, 60, and 120 months to better reflect the survivals at 1-,3-,5-, 10 years.

Response 8: Thank you for your comment. We replaced “cum survival” with “overall survival” end eliminated “Survival Functions as suggested. We changed time axis points to 12, 24, 48, 60, and 120 months. Furthermore, a correction of the RFS curve was made as the previous curve reflects OS based on NIH class. The updated curve reflects RFS based on NIH class.

Point 9: Reference no 3 should be appropriately provided.

Response 9: Thank you for your comment. Reference no 3 is correctly provided. Please see the track changes

Point 10: A native English speaker should revise the manuscript to correct a few minor grammar, spelling, or editing errors.

Response 10: Thanks for your comment. Dr. Asmis has reviewed this version of the manuscript.

 

Author Response File: Author Response.docx

Reviewer 2 Report

The authors conducted a retrospective cohort study about the characteristics and management of gastrointestinal stromal tumors in Canada. The authors analyzed the relatively large data between 2011 and 2021. Although the manuscript is very informative and written professional manner, there are some concerns that should be addressed.

 

Major

1. Introduction. Although the authors describe the general information about GIST, the authors should describe ‘What is unknown’ to explain the aim of the study clearly.

2. Results. Regarding table 1, please show the range or IQR of the age to show the distribution. Moreover, only the median is OK to show the characteristics of the age in the present study.

3. Results. Please add the P value to the table. Moreover, please spell out the abbreviation that is used in the table, and they should be written below the table.

4. Figures 2 and 3. Please clearly indicate the plots that showed statistically significant differences.

5. Were all GIST in the present study diagnosed with biopsies before treatment?

6. What are the new findings in the present study?

 

Minor

1. Some English flaws were seen. 

In the abstract, on page 2, line19 ‘… (206)% 83….’

In the discussion section, on page 8, line22 ‘… of The cost-effectiveness

Author Response

Response to Reviewer 2 Comments

 

We would like to thank you for your valuable comments and recommendation, which will add to our paper.

 

Point 1: Introduction. Although the authors describe the general information about GIST, the authors should describe ‘What is unknown’ to explain the aim of the study clearly.

Response 1: Thank you for pointing this out. We have added this ‘The data from real-world practice from Canada on GIST are limited’.

Point 2: Results. Regarding table 1, please show the range or IQR of the age to show the distribution. Moreover, only the median is OK to show the characteristics of the age in the present study.

Response 2:  Thank you for your comments and recommendation; we eliminated the mean from Table 1 and the range was added to the median.

Point 3: Results. Please add the P value to the table. Moreover, please spell out the abbreviation that is used in the table, and they should be written below the table.

Response 3: Thank you for your comments. The data on the tables represent frequencies which were presented in numbers and percentages; the p-value was not applicable.

Abbreviation definitions were added below the table.  

Point 4: Figures 2 and 3. Please clearly indicate the plots that showed statistically significant differences.

Response 4: Thank you for your comments.  We changed time axis points to 12, 24, 48, 60, and 120 months to better reflect the survivals. Furthermore, a correction of figure 3 for the RFS curve was made as the previous curve reflects OS based on NIH class. The updated curve reflects RFS based on NIH class.

Point 5: Were all GIST in the present study diagnosed with biopsies before treatment?

Response 5: Thank you for your comments. As stated in methods; all GIST had biopsy-proven and immunohistochemistry confirmed diagnosis before treatment.

Point 6: What are the new findings in the present study?

Response 6: The study provides insight about the real-world management of GIST.

Point 7: Some English flaws were seen. 

In the abstract, on page 2, line19 ‘… (206)% 83….’

In the discussion section, on page 8, line22 ‘… of The cost-effectiveness

Response 7: Thanks for your comments. These were corrected. please see track changes.

 

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The authors correctly addressed all the concerns raised by the reviewers

Reviewer 2 Report

The authors have revised the manuscript appropriately.