Safety and Efficacy of Hepatic Artery Embolization in Heavily Treated Patients with Intrahepatic Cholangiocarcinoma: Analysis of Clinicopathological and Radiographic Parameters Associated with Better Overall Survival

Round 1

Reviewer 1 Report

Intrahepatic cholangiocarcinoma (IHC) is the second most common liver primary tumor after hepatocarcinoma and its incidence is growing worldwide. Unfortunately, the diagnosis often occurs at a late stage in which the tumors are not resettable and at this point non-surgical options are the only possible therapy but with limited benefits. The most used are locoregional therapies (LRT), systemic therapy, hepatic artery infusion (HAI) and radiation therapy. This study, carried out over a large period, involved 34 patients with IHC, subjected to hepatic artery embolization (HAE). The aim of this work was to evaluate the safety and efficacy of HAE in patients with IHC, considering local tumor progression-free survival (L-PFS) and overall survival (OS).

Here are some considerations to improve the manuscript:

·         There are small writing errors in the section dedicated to the abstract, on lines 20-21 a smaller font has been used, and on lines 28-30 the color of the font is lighter.

Ffigures 2 and 3 are reversed compared to the description, as the figure on the right represents overall survival in patients respect to tumor response, while the one on the left represents overall survival based on tumor size. I suggest that figures 2 and 3 can be grouped into a single figure 2, with sections A and B, as they both represent overall survival.

·         A major limitation of this study is the lack of a cohort of control patients, that is, who have not undergone HAE. This failure renders the obtained data unreliable to reference data (controls).

·         As highlighted by the authors themselves in the "Discussion" section, another limitation of this study is the small number of the patient cohort, too small to be able to obtain certain and statistically significant results.

Overall the clinical study presented in the work of Velayati et al is well reported, with well presented and correctly exposed data. However, it is a work that will need further study to properly assess the effectiveness and safety of HAE.

The level of English is good

The bibliographical sources referred to in the manuscript are complete, extensive, well reported and also draw on the most recent works.

Author Response

Respond to reviewer 1:

There are small writing errors in the section dedicated to the abstract, on lines 20-21 a smaller font has been used, and on lines 28-30 the color of the font is lighter.

Respond: Revised as addressed.

Figures 2 and 3 are reversed compared to the description, as the figure on the right represents overall survival in patients respect to tumor response, while the one on the left represents overall survival based on tumor size. I suggest that figures 2 and 3 can be grouped into a single figure 2, with sections A and B, as they both represent overall survival.

Respond: Revised as addressed.

A major limitation of this study is the lack of a cohort of control patients, that is, who have not undergone HAE. This failure renders the obtained data unreliable to reference data (controls).

As highlighted by the authors themselves in the "Discussion" section, another limitation of this study is the small number of the patient cohort, too small to be able to obtain certain and statistically significant results.

Overall the clinical study presented in the work of Velayati et al is well reported, with well presented and correctly exposed data. However, it is a work that will need further study to properly assess the effectiveness and safety of HAE.

The level of English is good

The bibliographical sources referred to in the manuscript are complete, extensive, well reported and also draw on the most recent works.

Respond: We appreciate the comment and agree with it. There are very few studies on safety of HAE in treating patients with IHC. Therefore, the main goal of this study was to see if HAE was safe in treating patients with IHC. We have added a sentence in the discussion and conclusion clarifying that the data here shows that HAE is safe in treating IHC. However, in order to be able to conclude with high certainty that it is effective further study with control is needed.

Page 1 line 44: This sentence has been added: “Further studies with control group are required to confirm the effectiveness of HAE in IHC.”

Conclusion section, line 343: “Given the absence of a control group in this study, some uncertainty regarding the efficacy of HAE as a treatment for IHC exists. Therefore, it is imperative that further studies involving controlled studies be conducted to validate weather HAE indeed constitutes an effective treatment modality.” Was added.

Author Response File: Author Response.docx

Reviewer 2 Report

1. How about the continuity of the chemotherapy  or target therapy after HAE? please decript clearly in the text.

2. The results had too many repeated descriptions in      the text and table special in the section 3.2. and       table 5. It is better to simplify the description of 3.2 section.

3. Part of these patients had metastasis already and please explan the reasons of choice HAE for the main tumor only.

Author Response

Respond to reviewer 2:

1. How about the continuity of the chemotherapy or target therapy after HAE? please describe clearly in the text.

Respond: Post embolization treatments were added. No patient received targeted therapy. This has been clearly described in the text.  

Results section, line 183: “After embolization, 70.5% of the patients were treated with re-embolization, 28 (82.4%) of the patients continued with at least one chemotherapy regimen and Hepatic artery infusion pump was placed in 5 (14.7%) of the patients. Four patients (11.7%) were treated with external beam radiation and 1 (2.9%) patient was treated with radioembolization.”

2. The results had too many repeated descriptions in the text and table special in the section 3.2. and table 5. It is better to simplify the description of 3.2 section.

Respond: Revised as addressed.

3. Part of these patients had metastasis already and please explain the reasons of choice HAE for the main tumor only.

Respond: Revised as addressed.

This was added to Method section, line 81: “Patients with extrahepatic metastatic disease were treated with HAE only if they met the following inclusion criteria: A. Patients who had become chemoresistant and had liver-predominate disease, including those experiencing both intra-hepatic and extra-hepatic involvement; B. Patients with extrahepatic disease whose hepatic disease was progressing while undergoing chemotherapy, with a positive response in their extrahepatic disease; C. Patients with liver dominate disease who exhibited systemic toxicity from chemotherapy; D. Treatment for palliative reasons.”

 

 

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

1. Please change contents in the Table 5 into normal description in this paragraphy instead of formation as a table.

Author Response

The table was deleted and the information was included in the paragraph as addressed.