Complications Following Irinotecan-Loaded Microsphere Chemoembolization of Colorectal Metastatic Liver Lesions Associated with Hepatic-Artery Branch Temporary Stasis

Round 1

Reviewer 1 Report

General comments : the authors seeked to find relationship between complications and the level of embolization (from novisible [grade 1],,,, to grade 4 stasis). While it is interesting, the authors did not consider other important factor, tumor size. Postembolization syndrome or major complication is significantly associated with tumor volume.

This reviewer think that general  outcome (tumor response evaluation, progression-free survival, overall survival with predictive factors etc) of Irinotecan-loaded DEB TACE for CRC liver metastasis would be more informative to readers

Specific comments.

 

1. Please shorten the Abstract, in its present form, it is too lengthy.
2. Figure 1: please provide how these con-beam CT angiographies were obtained briefly.
3. Page 3, in the "indication of treatment" section: how author define "liver failure"? Do the authors mean poor underlying liver function such as Child-Pugh score C?
4. Page 4, "2.1. Procedure section": the sentence "The image wa archived in a picture archiving..." can be removed.
5. Figure 2,3,4: It is very difficult to recognize the level of stasis. Can the author provide corresponding DSA image also?
6. Page 6 in the "2.2. Adverse event assessment section": the sentence "Data were saved in a database... " can be deleted.
7. "2.3. Patient characterisitcs" section should be moved into the first place of the Results section.
8. "2.4. Chemoembolization" section should be moved into the second place of the Results section.
9. Page 8, "Results" section: please change "average" into the "median".
10. Designation method of P-value in this manuscript is unusual, please refer to the literature and change.
11. How the authors defined "significant complications"? Grade 3 AE?
12. From the author's outcome and experience, can you propose DEB embolization  technique to avoid  serious Cx?

Author Response

Thank you  for the critiques and suggestions.

1. Please shorten the Abstract, in its present form, it is too lengthy.
   Done. 

2. Figure 1: please provide how these con-beam CT angiographies were obtained briefly.
Done.

3. Page 3, in the "indication of treatment" section: how author define "liver failure"? Do the authors mean poor underlying liver function such as Child-Pugh score C?

We reserved Irinotecan  TACE procedure for patients who Child-Pugh score A and for highly selected Child-Pugh class B.

4. Page 4, "2.1. Procedure section": the sentence "The image wa archived in a picture archiving..." can be removed.
   Done.

5. Figure 2,3,4: It is very difficult to recognize the level of stasis. Can the author provide corresponding DSA image also?
Unfortunately, we cannot include DSA images as we do not use DSA arterigraphy for stasis assessment.
The administered contrast during arteriography is superimposed on that of the embolizate, making it difficult to assess the stasis. In addition, there is a risk of microspheres migrating.

6. Page 6 in the "2.2. Adverse event assessment section": the sentence "Data were saved in a database... " can be deleted.
      Done.

7. "2.3. Patient characterisitcs" section should be moved into the first place of the Results section.
      Done.

8. "2.4. Chemoembolization" section should be moved into the second place of the Results section.
   Done.

9. Page 8, "Results" section: please change "average" into the "median".
Done. 

10. Designation method of P-value in this manuscript is unusual, please refer to the literature and change.
Done.

11. How the authors defined "significant complications"? Grade 3 AE?

We classified the adverse event according to the Cancer Therapy Evaluation Program     Common Terminology Criteria for Adverse Events, Version 5.0. In particular, AE 3 as being severe or medically important, but not immediately life-threatening, requiring hospitalization or extension of existing hospitalization.

12. From the author's outcome and experience, can you propose DEB embolization  technique to avoid  serious Cx?

 In order to avoid complications, the most important thing is the correct classification of patients.
       To avoid complications,  we recommend:
       - routine CBCT performed to accurately visualize the vascularization of    the liver and tumors.
       -not exceeding the dose of 100 mg irinotecan per procedure.
       - intra-arterial administration of lidocaine prior to each administration of the embolizate
       - avoiding embolizate reflux proximal to the microcatheter tip
       - use of stasis only in the branches of the hepatic artery supplying large tumors
       - avoiding stasis in other cases, especially in the case of diffuse or small lesions

Reviewer 2 Report

The authors conducted a retrospective study to evaluate the correlation between the post embolization complications and the stasis level of hepatic-artery when performing Irinotecan-loaded microsphere chemoembolization (DEBIRI) of colorectal liver metastasis. The manuscript’s presentation is adequate. However, there are several comments and some issues that need to be addressed.

1. A prior multi-institutional study demonstrated factors such as blood flow stasis, and bilirubin level >2.0 were predictors of adverse events. However, in this study, regarding the inclusion criteria, the bilirubin level from 2 to 3 still can be enrolled. How about the bilirubin level of the study cohort?
2. Similarly, since the dose of Irinotecan administered could be the risk factor for side effects, please consider adding it to technical details.
3. Although the Chi-squared test demonstrated a significant relationship between the level of stasis and the severity of PES, the univariate or multivariate model is more robust. Do authors consider perform these methods?

Author Response

Thank you  for the critiques and suggestions.

1. A prior multi-institutional study demonstrated factors such as blood flow stasis, and bilirubin level >2.0 were predictors of adverse events. However, in this study, regarding the inclusion criteria, the bilirubin level from 2 to 3 still can be enrolled. How about the bilirubin level of the study cohort?

We agree with the above. Elevated levels of bilurubine may increase the risk of hepatic failure after TACE. Almost all patients have bilirubin levels below 2mg%. Only two patients had its elevated level: the first 2.3 mg% and the second 2.02 mg%. These patients were qualified for TACE due to their good general condition and the inability to use any other treatment

2. Similarly, since the dose of Irinotecan administered could be the risk factor for side effects, please consider adding it to technical details.
Done.
We also believe that a high dose of irinotecan may cause a greater risk of complications, so we use a routine dose of 100 mg of irinotecan in each TACE procedure.
3. Although the Chi-squared test demonstrated a significant relationship between the level of stasis and the severity of PES, the univariate or multivariate model is more robust. Do authors consider perform these methods?
We agree and have worked on it, but in this situation, after consulting with a statistician, due to the limited number of variables and high statistical significance, it made us chose the Chi-squared test as the most famous and popular non-parametric test.

 

 

Round 2

Reviewer 1 Report

The authors successfully adressed all previous comments.

 

Reviewer 2 Report

The authors have responded to all my questions and made the necessary changes to the manuscript.