Reviewer ’s report  
 
Title: Alterations in ERBB2 and BRCA and microsatellite instability as new personalized 
treatment options in small bowel carcinoma  
 
Version: 1 Date: 19 Oct 2018  
 
Reviewer: Thomas Aparicio  
 
Reviewer's report:  
 
This is an interresting report that confirms the  potential presence of BRCA targetable mutation in 
SBA.  
 
The major concern is the low number of patients enrolled.  
The ERBB2 target and MSI have already been describe in previous studies.  
 
Others comments:  
 
1) Recent epidemiological data were reported fro m a Netherland registry showing a 0.7 / 
100,000 incidence (Legue L 2016 Acta Oncologica 1183 -89) 
 
2) The citation regarding prognostic of distal SBA are incorrect: ref 7 (Wheeler) does not 
reported prognostic data, ref 8 (Alvi) does not reported localizatio n data, ref 9 (Yuan) is only 
dedicate to proximal tumour. A trend to a worst prognosis of ileal tumour was reported in a 
previous clinico -biologic study (Aparicio T 2013 Br J Cancer 3057 -66). On the other end a 
recent large study report that duodenum local isation is a negative predictor of survival after 
resection of SBA (Wilhelm A 2017 J Surg Oncol  397 -408). A general comparison of all 
localisation of SBA and colon carcinoma was reported by Overman M et al (2012 Ann Surg 
Oncol 1439 -45) 
 
3) The classificati on of NET has change. MANEC have ben replace by MiNEN (mixed 
neuroendocrine -non neuroendocrine neoplasm)   
 
4) Conclusion should be moderate. First screening for mutation make sens only if the drug is 
availlable, second the proof of efficacy of targeted the rapy remains to be done in SBA  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in yo ur comments to the authors.  
 
Yes 
 
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 manus cript or would you recommend an 
additional statis tical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written 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 reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in  an organisation t hat 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.  
 
no competing interest  
 
I agree to the open peer review po licy of the journal. I understan d that my  name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
respons es. 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 confid ential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Alterations in ERBB2 and BRCA and microsatellite instability as new personalized 
treatment options in small bowel carcinoma  
 
Version: 1 Date: 19 Oct 2018  
 
Reviewer: Thomas Aparicio  
 
Reviewer's report:  
 
This is an interresting report that confirms the  potential presence of BRCA targetable mutation in 
SBA.  
 
The major concern is the low number of patients enrolled.  
The ERBB2 target and MSI have already been describe in previous studies.  
 
Others comments:  
 
1) Recent epidemiological data were reported fro m a Netherland registry showing a 0.7 / 
100,000 incidence (Legue L 2016 Acta Oncologica 1183 -89) 
 
2) The citation regarding prognostic of distal SBA are incorrect: ref 7 (Wheeler) does not 
reported prognostic data, ref 8 (Alvi) does not reported localizatio n data, ref 9 (Yuan) is only 
dedicate to proximal tumour. A trend to a worst prognosis of ileal tumour was reported in a 
previous clinico -biologic study (Aparicio T 2013 Br J Cancer 3057 -66). On the other end a 
recent large study report that duodenum local isation is a negative predictor of survival after 
resection of SBA (Wilhelm A 2017 J Surg Oncol  397 -408). A general comparison of all 
localisation of SBA and colon carcinoma was reported by Overman M et al (2012 Ann Surg 
Oncol 1439 -45) 
 
3) The classificati on of NET has change. MANEC have ben replace by MiNEN (mixed 
neuroendocrine -non neuroendocrine neoplasm)   
 
4) Conclusion should be moderate. First screening for mutation make sens only if the drug is 
availlable, second the proof of efficacy of targeted the rapy remains to be done in SBA  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in yo ur comments to the authors.  
 
Yes 
 
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 manus cript or would you recommend an 
additional statis tical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written 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 reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in  an organisation t hat 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.  
 
no competing interest  
 
I agree to the open peer review po licy of the journal. I understan d that my  name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
respons es. 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 confid ential 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: Alterations in ERBB2 and BRCA and microsatellite instability as new personalized 
treatment options in small bowel carcinoma  
 
Version: 1 Date: 19 Oct 2018  
 
Reviewer: Thomas Aparicio  
 
Reviewer's report:  
 
This is an interresting report that confirms the  potential presence of BRCA targetable mutation in 
SBA.  
 
The major concern is the low number of patients enrolled.  
The ERBB2 target and MSI have already been describe in previous studies.  
 
Others comments:  
 
1) Recent epidemiological data were reported fro m a Netherland registry showing a 0.7 / 
100,000 incidence (Legue L 2016 Acta Oncologica 1183 -89) 
 
2) The citation regarding prognostic of distal SBA are incorrect: ref 7 (Wheeler) does not 
reported prognostic data, ref 8 (Alvi) does not reported localizatio n data, ref 9 (Yuan) is only 
dedicate to proximal tumour. A trend to a worst prognosis of ileal tumour was reported in a 
previous clinico -biologic study (Aparicio T 2013 Br J Cancer 3057 -66). On the other end a 
recent large study report that duodenum local isation is a negative predictor of survival after 
resection of SBA (Wilhelm A 2017 J Surg Oncol  397 -408). A general comparison of all 
localisation of SBA and colon carcinoma was reported by Overman M et al (2012 Ann Surg 
Oncol 1439 -45) 
 
3) The classificati on of NET has change. MANEC have ben replace by MiNEN (mixed 
neuroendocrine -non neuroendocrine neoplasm)   
 
4) Conclusion should be moderate. First screening for mutation make sens only if the drug is 
availlable, second the proof of efficacy of targeted the rapy remains to be done in SBA  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in yo ur comments to the authors.  
 
Yes 
 
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 manus cript or would you recommend an 
additional statis tical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written 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 reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in  an organisation t hat 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.  
 
no competing interest  
 
I agree to the open peer review po licy of the journal. I understan d that my  name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
respons es. 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 confid ential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant