Small Particle DEBIRI TACE as Salvage Therapy in Patients with Liver Dominant Colorectal Cancer Metastasis: Retrospective Analysis of Safety and Outcomes

Round 1

Reviewer 1 Report

General Comments: In this study, authors aimed to evaluate the safety and efficacy of irinotecan-eluting beads transarterial chemoembolization (DEBIRI TACE) using small particles (40 μm and 75 μm) in patients with unresectable liver metastasis from colorectal cancer (CRC). To do that, they retrospectively analyzed data from 36 patients with metastatic CRC who underwent DEBIRI TACE. A total of 105 procedures were performed. Authors analyzed adverse events occurred, the length of hospitalization and the possible readmission and the overall survival (OS). The topic is quite interesting, but this study, retrospective and based on a very small sample size, needs some important improvements.

Please, see specific comments for further details.

 

Specific comments:

Title: Ok.

Abstract:

• In line 21, the sentence “No 30-day post-DEBIRI mortality was seen” is a repetition of what has already been said in line 17: “with no 30-day post-DEBIRI mortality”.
• According to journal’s guidelines, abstract should be a total of 200 words maximum. Please change it accondingly.

Keywords: Ok.

Introduction:

• Lines 54-55: “Two randomized controlled trials, consisting of heterogenous patients receiving a wide array of treatment algorithms, have been conducted”, you should specify with which results.
• The sentence “At our centre, the first case of DEBIRI TACE using 40 μm beads was performed in January 2018” is disconnected from the text and it does not add anything important to the baseline knowledge described in the introduction.
• In this section, I should recommend to cite and possibly to comment in “Discussion” section some important studies regarding the use of small particles in DEBIRI TACE, even if with 70-150 μm beads, such as Fiorentini G. et al. “Updates of colorectal cancer liver metastases therapy: review on DEBIRI”, Hepat Oncol 2020. This kind of citation would further support the usefulness of this study, considering the lack of studies regarding DEBIRI TACE performed with very small particles such as the 40 μ
• A short paragraph explaining what is the current indication for DEBIRI TACE should be added.

Materials and methods:

Patient Population:

• This part would be clearer mentioning first the 37 patients initially included in the study and then specifying that one of them has been excluded because of lack of information regarding the prior clinical history, obtaining a final population of 36 patients.
• Lines 76-80 need bibliographic support about treatment indication.

Results:

• The final population analyzed is quite inhomogeneous: authors included in this study patients who underwent any kind and line of previous treatment, including locoregional treatments such as surgery, radiation therapy or percutaneous ablation. These “massive” inclusion criteria, even in comparison with other studies on the same topic already published in literature, could affect the analysis regarding OS, local response to therapy and liver function.
• There is not sufficient demonstration of how and if DEBIRI with small particles, performed at the end of a number of treatment lines has actually improved survival.
• The time elapsing between the various treatment performed (chemotherapy, surgery, local ablation, radiotherapy) and the DEBIRI TACE is not clear, it should be precisely specified.
• The acronym “AE” (line 121) has not been spelled out.
• The adverse events grading system used should be specified and supported by scientific literature.
• Data on treatment duration could be interesting, especially considering that super-selective catheterization has been performed.

Discussion:

• In line 182, “Smaller bead size has the potential of delivering higher drug concentrations distally into the tumor bed [13]”, this is a reasonable concept however in Martin et al. article [13] this information is not reported.
• Line 192: “This patient recovered and was then treated with TARE 12 months post-DEBIRI”. This could affect data on survival and response to therapy.
• In the discussion about survival and adverse events, authors compared their DEBIRI TACE with small particles technique to other treatments, first of all DEBIRI TACE using bigger beads, using as basis for comparison other articles, but this kind of comparison is not reliable, as the methods used in other studies (first of all the patients’ selection) is totally different. To evaluate that point, a prospective randomized study with standardized inclusion criteria should be performed.
• Again there is not there is no survival comparison with a control group of patients not receiving DEBIRI as a savage treatment. Liver progression free survival (LPFS) may have been at least a good evaluation argument.
• Appendix:

Procedure:

• Details about CT examination before and after treatment should be more accurate, specifying CT technique and, mostly, the criteria used to assess the response to therapy.
• “Technical DEBIRI success was defined as devascularisation on follow-up imaging with stability or reduction in the size of marker lesions and no new lesions”, but

devascularization in hypovascular hepatic lesions, as CRC metastases, is very difficult to assess, so please specify basing on which criteria you defined “devascularization”.

• Why these patients were not evaluated with PET?

References:

• As suggested above, Fiorentini G. et al. “Updates of colorectal cancer liver metastases therapy: review on DEBIRI” Hepat Oncol 2020 should be cited to improve bibliography.

Tables:

• Table 4 is quite confusing, it contains so many words and information, lacking of the very real function of tables, which must be easy and quick to consult.

Figure Legends: Ok.

Figures: Ok.

Language: Ok.

Author Response

Please see the attachment. 

Author Response File: Author Response.docx

Reviewer 2 Report

Authors: Nicholas Voizard, Tiffany Ni, Alex Kiss, Robyn Pugash, Michael Raphael, Natalie Coburn, Elizabeth David  Title: Small particle DEBIRI TACE as salvage therapy in patients with liver dominant colorectal cancer metastasis: Retrospective analysis of safety and outcomes    Comments:  This is a useful study that provides an important information for treatment of liver metastases by means of transarterial chemoembolization. The submitted manuscripted is well written and illustrated. I have only a couple of minor remarks:  It would be nice if the authors provide data (if they have it) on physiological functioning of patients' livers embolized with DEBIRI TACE as compared with control (non-embolized) samples. (First of all, I mean standard biochemical parameters of patients' blood that may reflect liver dysfunction.)     It would be nice if the authors discuss a possibility (if exists) of use of beads with such size and properties for radioembolization of liver metastases. In Discussion, the authors also may theoretically compare the DEBIRI TACE-based method with the method of high-dose hemotherapy on transiently isolated and perfused liver (i.e. which method is more effective according to the authors' opinion).            

Author Response

Please see the attachment. 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Title: Small particle DEBIRI TACE as salvage therapy in patients with liver dominant colorectal cancer metastasis: Retrospective analysis of safety and outcomes

 

Comments: This study has some intrinsecal limitations, first of all the inhomogeneity of population analyzed, despite these limits, adequately reported in the discussion section,

the topic is quite interesting and poorly investigated in literature. Authors changed the manuscript according to the suggestions given within the reviewing process when it has been possible, making the paper clearer and more complete and rectifying small mistakes such as acronyms and bibliographic notes.

Nevertheless, some points of the review have not been properly corrected, such as point 19 regarding the criteria used to assess the response to therapy: these details should be added in the manuscript and not only explained in the cover letter. Also the answer to point 20 of the review, regarding the criteria used to define “devascularization”, based on the Choi criteria studies, should be properly explained in the manuscript with bibliographic note.

Author Response

Point 1: This study has some intrinsecal limitations, first of all the inhomogeneity of population analyzed, despite these limits, adequately reported in the discussion section,

the topic is quite interesting and poorly investigated in literature. Authors changed the manuscript according to the suggestions given within the reviewing process when it has been possible, making the paper clearer and more complete and rectifying small mistakes such as acronyms and bibliographic notes.

 

Nevertheless, some points of the review have not been properly corrected, such as point 19 regarding the criteria used to assess the response to therapy: these details should be added in the manuscript and not only explained in the cover letter.

 

Response 1: Noted, the appendix procedure section has been updated to reflect the details regarding the CT examination and the criteria used to assess the response to therapy.

 

Point 2: Also the answer to point 20 of the review, regarding the criteria used to define “devascularization”, based on the Choi criteria studies, should be properly explained in the manuscript with bibliographic note.

 

Response 2: Noted, citation for the Choi criteria study has been added to the references and an explanation was included in the appendix procedure section.