Title: Correlation between KRAS and NRAS mutational status and clinicopathological features
in 414 cases of metastatic colorectal cancer in Morocco: the largest North African case series
Version: 2 Date: 16 Nov 2022
Reviewer's report:
I read with interest the manuscript and noted the great efforts made by the authors in designing
and executing this study. The authors presented from literature that RAS mutation negatively
affects response to anti-EGFR agents. They sought to determine correlation of KRAS and NRAS
with Clinicopathological characteristics of their patient population. To a very large extent, this
objective was achieved.
The authors may please note the following observations presented according to the sections
affected.
The Abstract.
The background section of the abstract is well articulated but seems to have multiple paragraphs.
It could all be collapsed into just one paragraph. A statement about the statistics employed in the
study should be added in the methodology while the result section could be populated with more
findings. Some trends in the outcome variable may be worth noting regardless of its p value.
Lastly on the abstract, the conclusion part appears lengthy.  The report of non contributive
cases should belong to the result section while the explanation regarding use of Idyla and NGS
platforms should be deleted. Its already well placed in the discussion of the study.
The Keyword
I would suggest that the words colorectal and cancer be made one keyword.
The Body of the manuscript
Background
There seems to be multiple paragraphs in the background subsection. Some of these can be
merged to produce fewer paragraphs. Secondly, the literature used to arrive at the background
to the study are not cited in this section. Additionally, it may be necessary to state why KRAS
and NRAS but not HRAS were evaluated.
Method
The term macro or microdissection might need a brief description.
Result
What amino acids substitution were observed in the mutated codons? What proportion of the
metastatic tumors had mutations compared with primary tumors? Were the primary tumors of
the metastatic cases analyzed to determine which is more likely to harbour RAS mutations. Table
6 may be wrongly placed.
Discussion
The discussion captured the clinicopathologic factors studied. Additional benefit could be
achieved by discussing the implications of the overall RAS mutation status to the studied
population. Also statements regarding possible differences in patient outcome between KRAS
and NRAS mutants might be of interest. How does the mutation pattern seen in this study
compare with others in terms of codons and amino acids affected? What could the age cut-
off of 50 years mean in patients with or without RAS mutations as this was significant? What
limitations could be ascribed to the study especially using Idylla.
Conclusion
Lastly, there was no conclusion for the study.
Title: Correlation between KRAS and NRAS mutational status and clinicopathological features
in 414 cases of metastatic colorectal cancer in Morocco: the largest North African case series
Version: 2 Date: 16 Nov 2022
Reviewer's report:
I read with interest the manuscript and noted the great efforts made by the authors in designing
and executing this study. The authors presented from literature that RAS mutation negatively
affects response to anti-EGFR agents. They sought to determine correlation of KRAS and NRAS
with Clinicopathological characteristics of their patient population. To a very large extent, this
objective was achieved.
The authors may please note the following observations presented according to the sections
affected.
The Abstract.
The background section of the abstract is well articulated but seems to have multiple paragraphs.
It could all be collapsed into just one paragraph. A statement about the statistics employed in the
study should be added in the methodology while the result section could be populated with more
findings. Some trends in the outcome variable may be worth noting regardless of its p value.
Lastly on the abstract, the conclusion part appears lengthy.  The report of non contributive
cases should belong to the result section while the explanation regarding use of Idyla and NGS
platforms should be deleted. Its already well placed in the discussion of the study.
The Keyword
I would suggest that the words colorectal and cancer be made one keyword.
The Body of the manuscript
Background
There seems to be multiple paragraphs in the background subsection. Some of these can be
merged to produce fewer paragraphs. Secondly, the literature used to arrive at the background
to the study are not cited in this section. Additionally, it may be necessary to state why KRAS
and NRAS but not HRAS were evaluated.
Method
The term macro or microdissection might need a brief description.
Result
What amino acids substitution were observed in the mutated codons? What proportion of the
metastatic tumors had mutations compared with primary tumors? Were the primary tumors of
the metastatic cases analyzed to determine which is more likely to harbour RAS mutations. Table
6 may be wrongly placed.
Discussion
The discussion captured the clinicopathologic factors studied. Additional benefit could be
achieved by discussing the implications of the overall RAS mutation status to the studied
population. Also statements regarding possible differences in patient outcome between KRAS
and NRAS mutants might be of interest. How does the mutation pattern seen in this study
compare with others in terms of codons and amino acids affected? What could the age cut-
off of 50 years mean in patients with or without RAS mutations as this was significant? What
limitations could be ascribed to the study especially using Idylla.
Conclusion
Lastly, there was no conclusion for the study.
Please review this paper.
user
Title: Correlation between KRAS and NRAS mutational status and clinicopathological features
in 414 cases of metastatic colorectal cancer in Morocco: the largest North African case series
Version: 2 Date: 16 Nov 2022
Reviewer's report:
I read with interest the manuscript and noted the great efforts made by the authors in designing
and executing this study. The authors presented from literature that RAS mutation negatively
affects response to anti-EGFR agents. They sought to determine correlation of KRAS and NRAS
with Clinicopathological characteristics of their patient population. To a very large extent, this
objective was achieved.
The authors may please note the following observations presented according to the sections
affected.
The Abstract.
The background section of the abstract is well articulated but seems to have multiple paragraphs.
It could all be collapsed into just one paragraph. A statement about the statistics employed in the
study should be added in the methodology while the result section could be populated with more
findings. Some trends in the outcome variable may be worth noting regardless of its p value.
Lastly on the abstract, the conclusion part appears lengthy.  The report of non contributive
cases should belong to the result section while the explanation regarding use of Idyla and NGS
platforms should be deleted. Its already well placed in the discussion of the study.
The Keyword
I would suggest that the words colorectal and cancer be made one keyword.
The Body of the manuscript
Background
There seems to be multiple paragraphs in the background subsection. Some of these can be
merged to produce fewer paragraphs. Secondly, the literature used to arrive at the background
to the study are not cited in this section. Additionally, it may be necessary to state why KRAS
and NRAS but not HRAS were evaluated.
Method
The term macro or microdissection might need a brief description.
Result
What amino acids substitution were observed in the mutated codons? What proportion of the
metastatic tumors had mutations compared with primary tumors? Were the primary tumors of
the metastatic cases analyzed to determine which is more likely to harbour RAS mutations. Table
6 may be wrongly placed.
Discussion
The discussion captured the clinicopathologic factors studied. Additional benefit could be
achieved by discussing the implications of the overall RAS mutation status to the studied
population. Also statements regarding possible differences in patient outcome between KRAS
and NRAS mutants might be of interest. How does the mutation pattern seen in this study
compare with others in terms of codons and amino acids affected? What could the age cut-
off of 50 years mean in patients with or without RAS mutations as this was significant? What
limitations could be ascribed to the study especially using Idylla.
Conclusion
Lastly, there was no conclusion for the study.
assistant