Immunotherapy as a Neoadjuvant Therapy for a Patient with Hepatocellular Carcinoma in the Pretransplant Setting: A Case Report

Round 1

Reviewer 1 Report

ICIs have revolutionized the treatment of several solid tumors. The mechanism of action of these anticancer agents acts on different pathways involved in tumor immune escape which is involved in tumor growth. Programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4), with their ligands (PD-L1/2 and B7-1/2 respectively), play a pivotal role in this process and represent the main targets of several ICIs. Tumor immune escape has a central role also in HCC, as it usually arises in the context of chronic liver inflammation which promotes an immune exhausted microenvironment.

Based on these premises, the study addresses a timely topic in HCC.

Some changes are required in my opinion:

1.     The background of medical treatment for HCC patients should be better discussed in the introduction and discussion sections, and some recent papers added, only for a matter of consistency (PMID: 29968763 ; PMID: 34429006 ; PMID: 34167433). We think it could be important to introduce the topic of this interesting case report

2.     A timeline summarizing the main events of this case report should be included

3.     However, the paper addresses a very current and important topic in HCC immunotherapy, and the authors should be commended for bringing this interesting experience.

4.     The authors should expand the discussion section, including a more personal perspective to reflect upon.

Thank you again for inviting me.

Major changes are necessary.

Author Response

Journal: Current Oncology (ISSN 1718-7729)

Manuscript ID: cancers-1710141

Type: Case Report

Title: Immunotherapy as a Neoadjuvant Therapy for a Patient with Hepatocellular Carcinoma in the Pre-transplant Setting: A Case Report

Dear Dr.Reviewer 1,

We would like to thank you for the consideration of our manuscript for publication and thoroughly appreciate the time taken to provide us with valuable comments to improve the readability of our contribution to literature. We have diligently provided point wise responses to all comments below

 

1. The background of medical treatment for HCC patients should be better discussed in the introduction and discussion sections, and some recent papers added, only for a matter of consistency (PMID: 29968763 ; PMID: 34429006 ; PMID: 34167433). We think it could be important to introduce the topic of this interesting case report

Author’s Response: Thanks a lot for this very important suggestion, we have cited these studies in our introduction (PMID: 29968763 ; PMID: 34429006 ; PMID: 34167433).

 

 

2. A timeline summarizing the main events of this case report should be included

Author’s Response: Thank you very much for this comment, normally we would agree with organizing the case series with the timeline, we plan to do that when we have more cases to be reported.

 

 

3. However, the paper addresses a very current and important topic in HCC immunotherapy, and the authors should be commended for bringing this interesting experience.

Author’s Response: Thanks a lot for this comment.

 

 

4. The authors should expand the discussion section, including a more personal perspective to reflect upon.

Author’s Response: Thank you very much for this comment, we have expanded the discussion section, including a more personal perspective to reflect upon.

 

 

 

Thank you,

The team

Author Response File: Author Response.docx

Reviewer 2 Report

Hepatocellular carcinoma (HCC) is commonly treated by surgical resection or radiofrequency ablation, but only a small fraction of patients are eligible for liver transplantation due to advanced disease and large tumor size.

Immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 antibodies, already used in the treatment of several types of cancer, have recently been approved for the treatment of HCC. These approaches have shown good clinical results in both pre- and post-transplant hepatocellular carcinoma patients.

However, several reports have shown that some patients undergo transplant rejection.

In the present study, Abdelrahim and colleagues showed the results of a case report in which a patient with hepatocellular carcinoma undergoes anti-PD-L1 treatment in combination with anti-VEGF before receiving a liver transplant.

A reduction in tumor mass assessed by magnetic resonance imaging was observed during treatment and no signs of potential rejection were observed one year after liver transplantation.

Despite a single patient was considered, this case report sustains the foundation for prospective trials already approved. 

The use of immune check point inhibitors is now widespread, but as is known not all tumors express the target of this therapy.

- Was PD-L1 expression evaluated on biopsy or organ?

 

As the authors rightly expressed, the risk of rejection in patients undergoing immunotherapy is very high.

- Has any immunological parameter been evaluated at the end of treatment or prior to transplantation?

- What kind of immunosuppressive therapy was used for this patient?

Author Response

Journal: Current Oncology (ISSN 1718-7729)

Manuscript ID: cancers-1710141

Type: Case Report

Title: Immunotherapy as a Neoadjuvant Therapy for a Patient with Hepatocellular Carcinoma in the Pre-transplant Setting: A Case Report

Dear Dr. Reviewer 2,

We would like to thank you for the consideration of our manuscript for publication and thoroughly appreciate the time taken to provide us with valuable comments to improve the readability of our contribution to literature. We have diligently provided point wise responses to all comments below

 

1. Was PD-L1 expression evaluated on biopsy or organ?

Author’s Response: Thanks a lot for this very important point, we haven’t run that in this case, we are planning to do that in the next cases.

 

 

 

2. Has any immunological parameter been evaluated at the end of treatment or prior to transplantation?

Author’s Response: Thank you very much for this comment, we hadn’t run specific immunological parameters to be evaluated at the end of treatment or prior to transplantation.

 

 

3. What kind of immunosuppressive therapy was used for this patient?

Author’s Response: Thanks a lot for this very important point, after completion of OLT, the patient was initiated on tacrolimus 1 mg capsule twice daily and mycophenolate 500 mg tablet twice daily for immunosuppression.

 

Thank you,

The team

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The authors addressed all the queries and issues we raised.

We recommend Acceptance.