Colorectal Liver Metastases: A Literature Review of Viable Surgical Options with a Special Focus on Microwave Liver Thermal Ablation and Mini-Invasive Approach
, Francesco Enrico D’Amico 3, Maurizio Romano 1, Marco Brizzolari 1, Michele Scopelliti 1 and Giacomo Zanus 1
Round 1
Reviewer 1 Report
The study is well written
All factors that are still in controversy are well listed and cited with appropriate references.
The analysis of complications and recurrences after local treatment is well explained and documented.
The work seems adequate
Author Response
Thank you for your comments.
Reviewer 2 Report
This is a literature review summarizing the locoregional theraphy of colorectal cancer with liver metastases.
The authors summarized the contents of the literature and extracted the experimental data, then concluded the advantages and disadvantages of different locoregional theraphies and the scope of application. To some extent, the review can guide the selection of clinical treatments. However, I also have the following comments:
In the introduction section, epidemiologic and prognostic factors of colorectal cancer were carefully mentioned, but not associated with liver metastases. Did it detach from the topic of this review?
The multilevel numbering was incomplete and the content scope of the same level was not uniform.
The lack of subscripts in Table 3 and Table 4 made the abbreviations unclear.
In the part of efficacy and overall survival of MWA, authors introduced the contents and data of the experiment but lacked a summary. Moreover, the lack of comparison objects made it impossible to determine the excellence of WMA directly.
Most of the cited literature is not published within the last 5 years, especially included trials, whether it will affect the results？
Author Response
Point-by-point replies
This is a literature review summarizing the locoregional theraphy of colorectal cancer with liver metastases.
The authors summarized the contents of the literature and extracted the experimental data, then concluded the advantages and disadvantages of different locoregional theraphies and the scope of application. To some extent, the review can guide the selection of clinical treatments. However, I also have the following comments:
In the introduction section, epidemiologic and prognostic factors of colorectal cancer were carefully mentioned, but not associated with liver metastases. Did it detach from the topic of this review?
Reply: thank you for the comment. We modify the introduction, epidemiologic and prognostic factors mainly reducing the information that can be redundant.
The multilevel numbering was incomplete and the content scope of the same level was not uniform.
The lack of subscripts in Table 3 and Table 4 made the abbreviations unclear.
Reply: We modified Tables 3 and 4 adding the abbreviations.
In the part of efficacy and overall survival of MWA, authors introduced the contents and data of the experiment but lacked a summary. Moreover, the lack of comparison objects made it impossible to determine the excellence of WMA directly.
Reply: Thank you for the comments, that’s a great point. I completely agree with the comment, one of the most important limitations of the MWA procedure is the difficulty to compare its efficacy among the different studies. We added in table 3 the number and size of the lesions, the most important factors that influence the MWA efficacy. Furthermore, in the last part of the efficacy and overall survival the following part:
Considering the efficacy and survival benefit of MWA in the treatment of CRLMs, most of the studies showed a success rate of ablation between 88% and 97%, where size (> or < 3cm), number of nodules and the role of micromestastasis are reported to be the most important predictive factors of incomplete ablation and recurrence. When the treatment is associated with the correct chemotherapy regimen, MWA ablation is an effective tool to control the disease especially in non resectable disease. However, the heterogeneity of the studies (patient selection, period, type of approach, biological features of the tumor, chemotherapy) makes the comparison among them difficult. Randomized trials are needed to determine in the most rigorous way the cause-effect relation between the MWA treatment and patient outcome
Most of the cited literature is not published within the last 5 years, especially included trials, whether it will affect the results？
Reply: Thank you for the comment. Tables 3 and 4 are now updated with the most recent literature, as well as the literature discussed in the text.
Reviewer 3 Report
Dear authors,
thanks for the opportunity to review you review paper "Colo rectal liver metastases: a literature review of viable surgi- 1 cal options with a special focus on microwave liver thermal ab- 2 lation and mini-invasive approach."
There is a need for a minor revision of the english of the paper where there are multiple grammatical errors and use of the definate form.
Introduction:
According to globocan the age standardised incidense of colorectal cancer is not decreasing worldwide allthough survival is getting better. Ref 3 does not contain data on the role of dietary and environmental factors for the development of colorectal cancer. Ref 1 and 24 do not present data on incidence of liver metastases in colorectal cancer patients and should be changed to original works that deal with that issue. Ref 25 does not present the survival rates and median survival reported. It is important to reference correctly!! and there is a general weekness with this in the paper.
Methods.
A metaanalysis should optimally conform to the PRISMA guidlines which this paper does not.
Allthough patient selection is the most important factor for good outcomes, it is still always better to have your liver metastases treated with a curative intent than leaving them for palliative chemotherapy, so selecting patients for treatment based on predicitive factors is not generally done. The section with risk scores does not add anything to the paper and for me seems malplaced.
NON RESECTABLE COLORECTAL...
Ref 47 is based on twenty year old data and is no longer approriate. More than 20% of patients with liver metastases are treatable.
European guidelines for metastastic colorectal cancer includes ablative techniques as a first line therapy with oligometastastic disease and this was the first time that local ablative techniques were regarded as equal with surgical resection. (Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Köhne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Österlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taïeb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5. PMID: 27380959.)
RMN and MDC have not been explained. All acronyms should be.
'ablation "crater"' should be exchanged with "ablated volume". The safety margin 5-10mm is very difficult to encertain with eyeballing of CT images since both tumour and liver contract with heating. Also it has been shown that intraobserver variability is large and automated systems are being developed and introduced.
Table 3 is problemised with severe differences in indications for mwa in the different studies. This is not evident in the text, but probably greatly affects the differens outcomes.
Overall survival.
The differences in patient selection should be clarified and studies which try to take care of selection bias seperated from studies presenting non-resectable patients and palliative patients with non-curative intent.
Author Response
Point-by-point replies:
thanks for the opportunity to review you review paper "Colo rectal liver metastases: a literature review of viable surgi- 1 cal options with a special focus on microwave liver thermal ab- 2 lation and mini-invasive approach."
There is a need for a minor revision of the english of the paper where there are multiple grammatical errors and use of the definate form.
Reply: Thank you for the comment. The paper was entirely reviewed focusing on the multiple grammatical errors.
Introduction:
According to globocan the age standardised incidense of colorectal cancer is not decreasing worldwide allthough survival is getting better. Ref 3 does not contain data on the role of dietary and environmental factors for the development of colorectal cancer. Ref 1 and 24 do not present data on incidence of liver metastases in colorectal cancer patients and should be changed to original works that deal with that issue. Ref 25 does not present the survival rates and median survival reported. It is important to reference correctly!! and there is a general weekness with this in the paper.
Reply: Thank you for the comments. We reviewed and checked the paper and references, changing them according to the data. In particular, we update reference 3 with the following one: Concise update on colorectal cancer epidemiology Ann Transl Med. 2019 Nov; 7(21): 609. We update reference 1 with Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386 and we modified references 24 and 25. Ref 24 has been changed to the following one: Hepatic Metastasis from Colorectal Cancer Euroasian J Hepatogastroenterol. 2017 Jul-Dec; 7(2): 166–175
Methods.
A metaanalysis should optimally conform to the PRISMA guidlines which this paper does not.
Reply: thank you for the comments. The aim of the paper is not to perform a meta-analysis, as it is a descriptive literature review. We added this part to the Material and Methods. Also, we are working on a future meta-analysis, which we hope will be published soon.
Allthough patient selection is the most important factor for good outcomes, it is still always better to have your liver metastases treated with a curative intent than leaving them for palliative chemotherapy, so selecting patients for treatment based on predicitive factors is not generally done. The section with risk scores does not add anything to the paper and for me seems malplaced.
Reply: I completely agree with you about the importance of the predictive factors to guide the CRLMs treatment. We modified the section: “…Risk scores have limited impact on patient selection on daily bases as the curative intent of the treatment is always the goal. However, it is important to know them to help to categorize and recognize high-risk patients…”. We reduce the length of the section, however, we believe that having an idea of the current risk scores, even if not used in daily practice, is still important.
NON RESECTABLE COLORECTAL...
Ref 47 is based on twenty year old data and is no longer approriate. More than 20% of patients with liver metastases are treatable.
Reply: thank you for the comment. I guess you meant ref 37. We changed it with a more updated one: Jack M, Angelica P, Elizabeth C Smyth, Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol. 2020 Oct 24; 11(10): 761–808.
European guidelines for metastastic colorectal cancer includes ablative techniques as a first line therapy with oligometastastic disease and this was the first time that local ablative techniques were regarded as equal with surgical resection. (Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Köhne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Österlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taïeb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5. PMID: 27380959.)
Reply: Thank you for the comment. We added the reference in the discussion part.
RMN and MDC have not been explained. All acronyms should be.
Reply: we changed the text according to the comment.
'ablation "crater"' should be exchanged with "ablated volume". The safety margin 5-10mm is very difficult to encertain with eyeballing of CT images since both tumour and liver contract with heating. Also it has been shown that intraobserver variability is large and automated systems are being developed and introduced.
Reply: thank you for the comment. We added and changed this part according to your suggestion for the text.
Table 3 is problemised with severe differences in indications for mwa in the different studies. This is not evident in the text, but probably greatly affects the differens outcomes.
Overall survival.
The differences in patient selection should be clarified and studies which try to take care of selection bias seperated from studies presenting non-resectable patients and palliative patients with non-curative intent.
Reply: Thank you for your comments. We added the following part to the discussion, to point out the problem. “…Considering the efficacy and survival benefit of MWA in the treatment of CRLMs, most of the studies showed a success rate of ablation between 88% and 97%, where size (> or < 3cm), number of nodules and the role of micrometastasis are reported to be the most important predictive factors of incomplete ablation and recurrence. When the treatment is associated with the correct chemotherapy regimen, MWA ablation is an effective tool to control the disease, especially in non-resectable diseases. However, the heterogeneity of the studies (patient selection, period, type of approach, biological features of the tumor, chemotherapy, palliative or curative intent of the treatment) makes the comparison among them difficult. Randomized trials are needed to determine most rigorously the cause-effect relation between the MWA treatment and patient outcome..”
Reviewer 4 Report
Accept
Author Response
Thank you for your comments.
Round 2
Reviewer 3 Report
OK. I'm happy with the changes made.
