Study of PD-1 Inhibitors in Combination with Chemoradiotherapy/Chemotherapy in Patients with Esophageal Squamous Carcinoma

Round 1

Reviewer 1 Report

Interesting results, series is retrospective and non randomized and you put together patients treated with exclusive chemotherapy and others with CRT plus ICI or not. Even if numbers would be smaller in order to reduce bias would not be appropriate to compare only patients treated in the same way? 

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

The authors investigated efficacy of combining immune checkpoint inhibitors (ICIs) with CRT/CT by propensity score matching and concluded ICIs plus CRT/CT group showed better RFS and OS than CRT/CT group. This is an important message for clinicians; however, this manuscript suffers some problems.

 

<Major problems>

・The follow-up time was too short. Median follow-up time was just 9 months in ICIs group, and 11 months in entire cohort. These were too short to investigate OS and PFS rate in 12 months after treatment. The authors should follow longer time.

 

<Minor problems>

・How many patients underwent second-line therapy? Were there some patients who underwent ICIs as second-line therapy in CRT/CT group?

 

・Was chemotherapy using platinum and paclitaxel a standard therapy in China?

 

・The authors described high BMI as a favorable factor for OS and PFS. What was the cut-off value of BMI?

 

・The authors should describe adverse effect of Grade 1 or 2 in Table 3.

 

・How did the author decide using glucocorticoid? Was it the physician’s choice?

 

・Were there patients who underwent glucocorticoids as a antiemetics for chemotherapy?

 

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

The authors investigated the efficacy and safety of combining PD-1 inhibitor (ICI) and chemoradiotherapy (CRT) / chemotherapy (CT) in locally advanced, unresectable or medically inoperable esophageal squamous cell carcinoma patients. The study design was retrospectively comparing two groups (ICI + CRT/CT vs. CRT/CT only) using propensity score matching (PSM) method. They reported that combining ICI with CRT/CT resulted in better overall survival (OS) and progression-free survival (PFS) than those of CRT/CT only group. In the ICI + CRT/CT group, higher body mass index (BMI) was associated with better OS and PFS, but this was not found in CRT/CT only group.

This article is original in its contents but there are some limitations in study methods as the authors admitted and they should clarify the followings.

1. The authors used ‘age, gender, ECOG score, tumor location, endoscopic classification, stage of disease, and concurrent therapy (CRT/CT)’ in PSM. I suggest that ‘recurrent/primary disease and combined/single chemotherapeutic agent(s)’ should be included in PSM. Please describe PSM method more clearly in the Methods section.
2. Surgical resection is recommended for those who had good objective response after CRT/CT for locally advanced esophageal cancer patients. After CRT/CT +/- ICI, how many patients underwent surgical resection?
3. After progression of the disease, was there any salvage therapy (ex. Palliative chemotherapy or radiotherapy) for the patients?
4. Why do you think that the objective response rate (ORR) was not significantly better in the ICI group compared with CRT/CT only group, but the OS and PFS were different?
5. In the ICI group, several different PD-1 inhibitors were used. Do you think they all have similar efficacy in esophageal cancer?

Author Response

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Author Response File: Author Response.pdf

Reviewer 4 Report

I apreciate your work on manuscript revision.

Round 2

Reviewer 2 Report

The authors revised carefully and I felt nothing to revise.