Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023

Round 1

Reviewer 1 Report

In this paper, authors described the consensus statements on emerging and evolving treatment paradigms in Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023.

This paper is well written. This paper includes important information, and I agree with contents of the manuscript. I have some comments on this manuscript.

Comments

In “(1) Immunotherapy in advanced colorectal cancer” section.

Question 1:

It has been well established that dMMR/MSI-H tumors are responsive to treatment with immune checkpoint blockade. In the World, anti-PD1 antibodies are routinely administered and treated to colorectal cancer patients with dMMR/MSI-H tumors. Please discuss.

Question 2:

Authors described that combination immunotherapy with Nivolumab and Ipilimumab has not been shown to be superior to monotherapy and is associated with higher rates of toxicities [4]. Please state the incidence of grade 3 or higher toxicity with combination immunotherapy.

In “(2) Rectal Cancer” section.

Question 3:

Please comment on the optimal follow-up plan (CT, CS, PET, etc.) for patients with NOM/watchful waiting.

I recommend replacing 4 “Treatment of End Stage Colorectal Cancer” with 3 “The Role of Radiation in the Treatment of Pancreatic Cancer”.

Author Response

In “(1) Immunotherapy in advanced colorectal cancer” section.

Question 1:

It has been well established that dMMR/MSI-H tumors are responsive to treatment with immune checkpoint blockade. In the World, anti-PD1 antibodies are routinely administered and treated to colorectal cancer patients with dMMR/MSI-H tumors. Please discuss.

The following was added (underlined) to the paragraph as recommended:

This led to further investigations into what is now known to be a key prognostic biomarker in advanced colorectal cancer, as it has been well established that dMMR/MSI-H tumors are responsive to treatment with immune checkpoint blockade. As a result, anti-PD1 antibodies are now the global standard of care to treat colorectal cancers which are dMMR/MSI-H. Given this, the treatment algorithm of advanced colorectal cancer now depends upon dMMR/MSI-H status, and it is recommended that all patients have timely access to this testing by immunohistochemistry or microsatellite instability by DNA sequencing.  

Question 2:

Authors described that combination immunotherapy with Nivolumab and Ipilimumab has not been shown to be superior to monotherapy and is associated with higher rates of toxicities [4]. Please state the incidence of grade 3 or higher toxicity with combination immunotherapy.

The following was added (underlined) to the paragraph as recommended:

A phase II study evaluating first-line combination immunotherapy with Nivolumab and Ipilimumab for dMMR/MSI-H advanced CRC reported a two-year overall survival rate of 79.4%. While these results are promising, combination immunotherapy has not been shown to be superior to monotherapy and is associated with higher rates of toxicities as grade 3-4 treatment related adverse events occurred in 22% of patients.[4]

In “(2) Rectal Cancer” section.

Question 3:

Please comment on the optimal follow-up plan (CT, CS, PET, etc.) for patients with NOM/watchful waiting.

The following was added (underlined) to the paragraph as recommended

In 2021 international consensus recommendations on key outcomes measures for organ preservation following neoadjuvant chemoradiotherapy in patients with rectal cancer were developed. We endorse these recommendations which include digital rectal examination, endoscopy and MRI every 3-4 months for the first 2 years, then every 6 months for 3 years. They also suggest measuring serum carcinoembryonic antigen levels every 3 months for the first 3 years and then every 6 months for the following 2 years. A surveillance CT of the chest and or abdomen is recommended every 6 months for the first year and then annually for the following 4 years[19].

I recommend replacing 4 “Treatment of End Stage Colorectal Cancer” with 3 “The Role of Radiation in the Treatment of Pancreatic Cancer”.

These sections were switched as recommended.