Reviewer ’s report  
 
Title: Elevated preoperative platelet -to-lymphocyte ratio predicts poor prognosis of patients with  
primary gastrointestinal stromal tumor  
 
Version: 0 Date: 21 Feb  2019  
 
Reviewer: Ferdinando Carlo Maria Cananzi  
 
Reviewer's report:  
 
In this paper the Authors reported their experience on GIST, evaluating an intriguing, although 
not novel, topic as the  role of pre -operative serum inflammation markers on predicting the 
prognosis of patients affected by GIST.  
 
The results could be interesting also given the large number of analyzed patients. However some 
major issue may significantly affect the relevance o f the study.  
 
- We see the point on the exclusion of patients who had post -operative TKI therapy but 
this could represent a treatment bias probably excluding patients with high -risk disease. Also 
adjuvant imatinib is the current standard therapy in high -risk GIST and it could be of some 
benefit to evaluate the role of serum inflammation markers in these patients. Given such large 
series, Authors could run analysis both in treated and un -treated patients. Moreover, they should 
better specify the reason why th e patients did not receive any post -operative treatment.  
 
- Did any patients receive pre -operative imatinib in this series?  
 
- Importantly, the results reported by the Authors could be justified by the showed 
correlation between NLR and PLR with well -known p rognostic factors as site, size, mitosis and 
class risk. Therefore it may be helpful running - at least -a DFS and OS analysis stratified by 
tumor risk (i.e. test the role of NLR and PLR in each risk class)  
 
- Including both NLR and PLR (which are correlat e to each other) in the same 
multivariable model may cause multicollinearity leading to wrong estimation.  
 
- Giving the natural history of GIST, including only patients with an adequate follow -up 
(i.e. 3 or 5 years) could be more appropriate.  
 
- The choice of cut -off is a crucial point and there are several methods to do that 
including dependent ROC curve analysis, best log ‐rank approach, clustering analysis, and so on. 
However a cutoff value retrospectively computed may be not safely applied in a prospectiv e 
manner, irrespective of the statistical method. The Authors could try to randomly split the data 
generating two distinct dataset: the first to calculate and the second to validate the cut -off. 
 
 
 
Minor points:  
 
- The results about PLR are not really novel a s previously studies already reported 
similar results both at univariate (Racz et al. Ann Surg Oncol 2015; Stotz et al. PLOS One 2016; 
Feng et al. Medicine 2016; Goh et al. Surgery 2016) and multivariate analysis (Goh et al. 
Surgery 2016; Cananzi et al. J Surg Oncol 2018).  
 
- Clarify if metastatic patients were included or not.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the  manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of w ritten English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received r eimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal . I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Elevated preoperative platelet -to-lymphocyte ratio predicts poor prognosis of patients with  
primary gastrointestinal stromal tumor  
 
Version: 0 Date: 21 Feb  2019  
 
Reviewer: Ferdinando Carlo Maria Cananzi  
 
Reviewer's report:  
 
In this paper the Authors reported their experience on GIST, evaluating an intriguing, although 
not novel, topic as the  role of pre -operative serum inflammation markers on predicting the 
prognosis of patients affected by GIST.  
 
The results could be interesting also given the large number of analyzed patients. However some 
major issue may significantly affect the relevance o f the study.  
 
- We see the point on the exclusion of patients who had post -operative TKI therapy but 
this could represent a treatment bias probably excluding patients with high -risk disease. Also 
adjuvant imatinib is the current standard therapy in high -risk GIST and it could be of some 
benefit to evaluate the role of serum inflammation markers in these patients. Given such large 
series, Authors could run analysis both in treated and un -treated patients. Moreover, they should 
better specify the reason why th e patients did not receive any post -operative treatment.  
 
- Did any patients receive pre -operative imatinib in this series?  
 
- Importantly, the results reported by the Authors could be justified by the showed 
correlation between NLR and PLR with well -known p rognostic factors as site, size, mitosis and 
class risk. Therefore it may be helpful running - at least -a DFS and OS analysis stratified by 
tumor risk (i.e. test the role of NLR and PLR in each risk class)  
 
- Including both NLR and PLR (which are correlat e to each other) in the same 
multivariable model may cause multicollinearity leading to wrong estimation.  
 
- Giving the natural history of GIST, including only patients with an adequate follow -up 
(i.e. 3 or 5 years) could be more appropriate.  
 
- The choice of cut -off is a crucial point and there are several methods to do that 
including dependent ROC curve analysis, best log ‐rank approach, clustering analysis, and so on. 
However a cutoff value retrospectively computed may be not safely applied in a prospectiv e 
manner, irrespective of the statistical method. The Authors could try to randomly split the data 
generating two distinct dataset: the first to calculate and the second to validate the cut -off. 
 
 
 
Minor points:  
 
- The results about PLR are not really novel a s previously studies already reported 
similar results both at univariate (Racz et al. Ann Surg Oncol 2015; Stotz et al. PLOS One 2016; 
Feng et al. Medicine 2016; Goh et al. Surgery 2016) and multivariate analysis (Goh et al. 
Surgery 2016; Cananzi et al. J Surg Oncol 2018).  
 
- Clarify if metastatic patients were included or not.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the  manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of w ritten English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received r eimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal . I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Elevated preoperative platelet -to-lymphocyte ratio predicts poor prognosis of patients with  
primary gastrointestinal stromal tumor  
 
Version: 0 Date: 21 Feb  2019  
 
Reviewer: Ferdinando Carlo Maria Cananzi  
 
Reviewer's report:  
 
In this paper the Authors reported their experience on GIST, evaluating an intriguing, although 
not novel, topic as the  role of pre -operative serum inflammation markers on predicting the 
prognosis of patients affected by GIST.  
 
The results could be interesting also given the large number of analyzed patients. However some 
major issue may significantly affect the relevance o f the study.  
 
- We see the point on the exclusion of patients who had post -operative TKI therapy but 
this could represent a treatment bias probably excluding patients with high -risk disease. Also 
adjuvant imatinib is the current standard therapy in high -risk GIST and it could be of some 
benefit to evaluate the role of serum inflammation markers in these patients. Given such large 
series, Authors could run analysis both in treated and un -treated patients. Moreover, they should 
better specify the reason why th e patients did not receive any post -operative treatment.  
 
- Did any patients receive pre -operative imatinib in this series?  
 
- Importantly, the results reported by the Authors could be justified by the showed 
correlation between NLR and PLR with well -known p rognostic factors as site, size, mitosis and 
class risk. Therefore it may be helpful running - at least -a DFS and OS analysis stratified by 
tumor risk (i.e. test the role of NLR and PLR in each risk class)  
 
- Including both NLR and PLR (which are correlat e to each other) in the same 
multivariable model may cause multicollinearity leading to wrong estimation.  
 
- Giving the natural history of GIST, including only patients with an adequate follow -up 
(i.e. 3 or 5 years) could be more appropriate.  
 
- The choice of cut -off is a crucial point and there are several methods to do that 
including dependent ROC curve analysis, best log ‐rank approach, clustering analysis, and so on. 
However a cutoff value retrospectively computed may be not safely applied in a prospectiv e 
manner, irrespective of the statistical method. The Authors could try to randomly split the data 
generating two distinct dataset: the first to calculate and the second to validate the cut -off. 
 
 
 
Minor points:  
 
- The results about PLR are not really novel a s previously studies already reported 
similar results both at univariate (Racz et al. Ann Surg Oncol 2015; Stotz et al. PLOS One 2016; 
Feng et al. Medicine 2016; Goh et al. Surgery 2016) and multivariate analysis (Goh et al. 
Surgery 2016; Cananzi et al. J Surg Oncol 2018).  
 
- Clarify if metastatic patients were included or not.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the  manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of w ritten English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received r eimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal . I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant