Primary Tumor Sidedness, RAS and BRAF Mutations and MSI Status as Prognostic Factors in Patients with Colorectal Liver Metastases Treated with Surgery and Thermal Ablation: Results from the Amsterdam Colorectal Liver Met Registry (AmCORE)
, Sanne Nieuwenhuizen 1, Robbert S. Puijk 1, Florentine E. F. Timmer 1, Bart Geboers 1, Evelien A. C. Schouten 1, Jip Opperman 2, Hester J. Scheffer 1, Jan J. J. de Vries 1, Kathelijn S. Versteeg 3, Birgit I. Lissenberg-Witte 4, M. Petrousjka van den Tol 5 and Martijn R. Meijerink 1
Round 1
Reviewer 1 Report
The work by Dijkstra and colleagues reports on a single-center prospective cohort study based on the Amsterdam Colorectal Liver Met Registry (AmCORE) aimed at detecting the potential role of RAS and BRAF mutations in affecting the outcome of Colorectal Cancer (CRC) tratment.
In particular, the authors conducted the study enrolled 520 patients who underwent local treatment (resection and/or thermal ablation) from 2000 to 2021 and subjected to up to a 5-years follow up.
in particular, the authors wanted to assess if the presence of mutations at the level of either one of the proteins, RAS and BRAF, may affect the outcome of the treatment.
Overall the work is clear and well presented. The authors indeed find a worsening of the conditions in patients affected by mutations.
However, in my opinion, the robustness of the results presented is affected by the the fact that the protein state (wild type vs mutant) was unknown in more that 80% of the patients
(RAS status (any) RAS wildtype 8.3
RAS mutation 6.9
Unknown 84.8
BRAF V600 status BRAF wildtype 12.1
BRAF mutation 1.2
Unknown 86.8)
Due to this high percentage of blindness in the state of RAS and BRAF it is hard for me to judge if the effect observed by the authors is reliable
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Congralulations for this interesting paper.
The article analizes the AmCORE Registry including 520 patients to assess primary tumor sidedness of CRC, RAS and BRAF mutations and microsatellite inestability status as pronostic factors predicting complications, survival outcomes and local tumor progression following surgery and thermal ablation in patients with colorrectal liver metastases.
Authors conclude that for patients undergoing partial hepatectomy and /or thermal ablation for CRLM, BRAF mutations and, if not treated with immunotherapy, MS inestability were asociated with higher probability of released and death.
In my opinion, the article is relevant and it is suitable for publication in the present form.
Author Response
Dear reviewer,
We would like to sincerely thank you for your high-quality review and for the time you spent on our manuscript. We were honored to read your enthusiastic review and the overall recommendation of the reviewers to the status 'minor revisions'.
On behalf of all co-authors,
Yours sincerely,
Madelon Dijkstra
