Review Reports

Round 1

Reviewer 1 Report

Title: A practical guide for the systemic treatment of biliary tract cancer in Canada

 

This paper describes practical guide for the systemic treatment of BTC in Canada, providing valuable insights into the current and future treatment landscape for this challenging disease. 

 

The manuscript cites many references and is well written. However, there are some questions and the author is requested to add the descriptions according to comments as below.

 

1. Definition in Figure 2

What`s the definition of unresectable disease BTC in early stage or locally advanced?

The author should address the difference between the definitions of resectable and unresectable BTC.

 

2. Capecitabine after surgery

How long capecitabine is administered after curative resection in BTC as adjuvant therapy ?

Author Response

Thank you for reviewing our manuscript and for your thoughtful suggestions. A description of how we have addressed your comments in the revised manuscript are listed below:

• Comment 1 (In reference to figure 2): What`s the definition of unresectable disease BTC in early stage or locally advanced? The author should address the difference between the definitions of resectable and unresectable BTC.
  • There is no clear definition of unresectable disease. We acknowledged this complexity in determining whether a patient’s tumour can be resected by including a footnote linked to the boxes for “resectable disease” and “unresectable disease” in Figure 2: “Eligibility for resection is based on a number of factors including presence of distant metastasis, vascular invasion, feasibility of reconstruction, expected volume and function of liver remnant, and performance status. It should be assessed by a hepatobiliary surgeon in consultation with a multidisciplinary team.”
• Comment 2: How long capecitabine is administered after curative resection in BTC as adjuvant therapy ?
  • We have included the following on lines 374-377 to reflect the typical administration of capecitabine among the authors: “It [capecitabine] is typically administered at a dose of 1,250mg/m² , twice-daily on days 1-14 for eight 21-day cycles (as per the BILCAP protocol); however, a dose reduction to 1,000 mg/m² may be considered at initiation or during treatment based on anticipated or observed toxicity.

Reviewer 2 Report

Biliary cancer is often complicated with obstructive jaundice, and many cases require biliary drainage. Endoscopic (percutaneous) biliary drainage and chemotherapy should also be mentioned. In recent years, there have also been reports of endoscopic biliary RFA and chemotherapy. Please touch on that point.

No comments.

Author Response

Thank you for reviewing our manuscript and for your thoughtful suggestions. The following describes how we have addressed your comment in the revised manuscript:

• Comment 1: Biliary cancer is often complicated with obstructive jaundice, and many cases require biliary drainage. Endoscopic (percutaneous) biliary drainage and chemotherapy should also be mentioned. In recent years, there have also been reports of endoscopic biliary RFA and chemotherapy. Please touch on that point.
  • In the original submission we had included a short discussion on complications due to bile duct obstruction and the need for biliary drainage; however, we have modified this paragraph to clarify the different types of biliary drainage and its potential value for allowing patients to become eligible for systemic therapy. We had previously included discussion on intraluminal brachytherapy for improving stent patency and, on your suggestion, we have also included the potential value of radiofrequency ablation with or without chemotherapy for improving stent patency and patient outcomes. The following modified paragraph can be found on lines 346-360: “Radiologists additionally play an important role in managing disease-related complications and symptoms. For symptoms related to disease metastasis, randomized studies have provided evidence for low-dose palliative radiation in improving symptoms and potentially survival for patients with metastatic disease failing systemic therapy [78, 79]. Patients with BTC frequently have complications relating to bile duct obstruction, causing jaundice (and related symptoms of diarrhea, sleep disturbances, anorexia, and pruritus), infection, and liver dysfunction. Biliary drainage can relieve these symptoms and may have an impact on survival by allowing patients to be eligible for systemic therapy . In the setting of unresectable disease, it may be performed percutaneously or endoscopically (with stenting) depending on institutional experience, anatomical and biological factors, and the presence of cholangitis [80]. Tumour progression can lead to decreased stent patency requiring stent replacement [81]. Several studies have shown prolonged stent patency with the use of local therapies including intraluminal brachytherapy and radiofrequency ablation (both with or without chemotherapy), leading to improved outcomes for patients [82-85].”

Reviewer 3 Report

 The authors presented a treatment guideline for biliary tract cancer (BTC). They described an algorism of systemic treatment for BTC with sufficient evidence and enough recommendations for each therapy. The guideline they have laid out has practical utility. Therefore, this paper is an important contribution for clinical practice of BTC treatment.

The main issue addressed in this paper is the recommendations of standard treatment for biliary tract cancer (BTC). Sufficient data collection is needed to determine a treatment strategy for BTC, a rare tumor. They are integrating clinical trials of treatment for BTC, including preoperative and postoperative systemic treatment, in an attempt to provide treatment guidelines.

I think that the topic is not so original, but it is relevant and important in this field. Their recommendations would be meant to guide the clinical handling of treatment. Additionally, they finally showed a usable algorithm of systemic treatment for BTC.

This article adds accumulated findings on treatment of BTC, an infrequent carcinoma, and provides guidelines for systemic treatment of BTC.

They systematically present a selection of treatment options, including the latest molecular therapies, for a rare tumor, BTC. In addition, they provide a level of evidence and summarize recommendations in systemic treatment for BTC.

They fully cited the reports of important clinical trials for BTC and presented their conclusions with evidence.

The citations they gave are appropriate and sufficient.

They provided appropriate references in the tables and summarized the data in an easy-to-understand manner. In addition, the treatment guideline schemas are also very clearly presented.

Author Response

Thank you for reviewing our manuscript. We acknowledge there are no comments to address.

Round 2

Reviewer 2 Report

No additional comments.