Title: The Impact of KRAS Mutations on Risk of Venous Thromboembolism Recurrence in
Patients with Metastatic Colorectal Cancer
Version: 2 Date: 23 Feb 2025
Reviewer's report:
This manuscript describes a study in which the authors explore the Impact of KRAS Mutations
on Risk of Venous Thromboembolism Recurrence in Patients with Metastatic Colorectal Cancer.
It is interesting that this study follows-up on a previous paper from this research group. In
addition they clearly describe the methodology and endpoints. They found that the KRAS G12C,
KRAS G12A, and KRAS G13D mutations are significantly associated with an increased risk
of recurrent VTE.
Kindly find below several comments I would like to raise:
- Can the authors add why they chose to study these 7 specific KRAS mutations? And not NRAS
or HRAS mutations?
- Can the authors elaborate on the effect of primary tumor location on VTE recurrence risk?
Would it be of interest to add this to their models?
- Would be of interest to also study germline genetic risk factors for VTE?
- Can the authors elaborate more on the underlying mechanisms that cause a higher recurrence
risk of VTE in patients with certain KRAS mutations?
- The authors end the conclusion with "Further research is needed to elucidate the mechanisms
connecting KRAS mutations to VTE, such as through heparanase production or elevated
tissue factor expression, and to develop new scores that integrate genetic markers." However,
heparanase is not mentioned in the paper. I would suggest add ing this to the discussion or
introduction, but not to mention new information/terms in the conclusion.
- Can the authors state more clearly how the modified score 2 is calculated? the description
"adding all KRAS mutations on original scores" is not clear to me. Do they mean also a score
of 1 for the KRAS G12A?
- Tables: it might be of interest to mark the significant results with an * or in bold?
- Table 3: I would advise the authors to add the names of the analysis to the table (modified
1 and 2).
- Table 3: typo (b Recmmonded cutoff points based on derivation studies)
Title: The Impact of KRAS Mutations on Risk of Venous Thromboembolism Recurrence in
Patients with Metastatic Colorectal Cancer
Version: 2 Date: 23 Feb 2025
Reviewer's report:
This manuscript describes a study in which the authors explore the Impact of KRAS Mutations
on Risk of Venous Thromboembolism Recurrence in Patients with Metastatic Colorectal Cancer.
It is interesting that this study follows-up on a previous paper from this research group. In
addition they clearly describe the methodology and endpoints. They found that the KRAS G12C,
KRAS G12A, and KRAS G13D mutations are significantly associated with an increased risk
of recurrent VTE.
Kindly find below several comments I would like to raise:
- Can the authors add why they chose to study these 7 specific KRAS mutations? And not NRAS
or HRAS mutations?
- Can the authors elaborate on the effect of primary tumor location on VTE recurrence risk?
Would it be of interest to add this to their models?
- Would be of interest to also study germline genetic risk factors for VTE?
- Can the authors elaborate more on the underlying mechanisms that cause a higher recurrence
risk of VTE in patients with certain KRAS mutations?
- The authors end the conclusion with "Further research is needed to elucidate the mechanisms
connecting KRAS mutations to VTE, such as through heparanase production or elevated
tissue factor expression, and to develop new scores that integrate genetic markers." However,
heparanase is not mentioned in the paper. I would suggest add ing this to the discussion or
introduction, but not to mention new information/terms in the conclusion.
- Can the authors state more clearly how the modified score 2 is calculated? the description
"adding all KRAS mutations on original scores" is not clear to me. Do they mean also a score
of 1 for the KRAS G12A?
- Tables: it might be of interest to mark the significant results with an * or in bold?
- Table 3: I would advise the authors to add the names of the analysis to the table (modified
1 and 2).
- Table 3: typo (b Recmmonded cutoff points based on derivation studies)
Please review this paper.
user
Title: The Impact of KRAS Mutations on Risk of Venous Thromboembolism Recurrence in
Patients with Metastatic Colorectal Cancer
Version: 2 Date: 23 Feb 2025
Reviewer's report:
This manuscript describes a study in which the authors explore the Impact of KRAS Mutations
on Risk of Venous Thromboembolism Recurrence in Patients with Metastatic Colorectal Cancer.
It is interesting that this study follows-up on a previous paper from this research group. In
addition they clearly describe the methodology and endpoints. They found that the KRAS G12C,
KRAS G12A, and KRAS G13D mutations are significantly associated with an increased risk
of recurrent VTE.
Kindly find below several comments I would like to raise:
- Can the authors add why they chose to study these 7 specific KRAS mutations? And not NRAS
or HRAS mutations?
- Can the authors elaborate on the effect of primary tumor location on VTE recurrence risk?
Would it be of interest to add this to their models?
- Would be of interest to also study germline genetic risk factors for VTE?
- Can the authors elaborate more on the underlying mechanisms that cause a higher recurrence
risk of VTE in patients with certain KRAS mutations?
- The authors end the conclusion with "Further research is needed to elucidate the mechanisms
connecting KRAS mutations to VTE, such as through heparanase production or elevated
tissue factor expression, and to develop new scores that integrate genetic markers." However,
heparanase is not mentioned in the paper. I would suggest add ing this to the discussion or
introduction, but not to mention new information/terms in the conclusion.
- Can the authors state more clearly how the modified score 2 is calculated? the description
"adding all KRAS mutations on original scores" is not clear to me. Do they mean also a score
of 1 for the KRAS G12A?
- Tables: it might be of interest to mark the significant results with an * or in bold?
- Table 3: I would advise the authors to add the names of the analysis to the table (modified
1 and 2).
- Table 3: typo (b Recmmonded cutoff points based on derivation studies)
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