Title: Chemotherapy alone vs definitive concurrent chemoradiotherapy for cT4b esophageal
squamous cell carcinoma: a population based study
Version: 2 Date: 22 Feb 2021
Reviewer's report:
The study by Chien et al addresses an interesting clinical issue: whether Chemotherapy or
radiochemotherapy is the most appropriate treatment for T4bM0 esophageal SCC and this was
studied in a relatively large population. However I suggest several revisions:
General:
English grammar and style should be improved. The text is written in the past, but should be
in the present time, i.e. "esophageal cancer was one of the leading..." schould be "....is one of
the leading...." etc.
Only survival data are analysed. Were grade 3-4 toxicity data not available? Since complications
are a concern of radiotherapy, the incidence of severe toxicity (fistula) is an important aspect
for interpretation of the survival results
Specific:
stick to  mentioning group C/T and group dCCRT, and not group A and B.
Methods: What do the authors mean by "excluding multiple treatment records" and by
"inclusion criteria modified from a relevant ongoing trial". I suggest to explain the exact in and
exclusion criteria.
a subheading is called Study population and intervention. But there is no intervention. I suggest
to skip the word "intervention"
Please mention the factors that were weighted for PS and PSW
Results,
A lot of covariates were analysed, but their impact was not mentioned in the text.
Primary analysis: "what do the authors mean by "the observed HR of 0.36...... could be explained
by an unmeasured confounder.........but weaker confoundering could not do so". This sentence
is unclear to me.
Discussion:
the authors state that the study relieved the concern in using radiotherapy. However no data on
toxicity of radiotherapy were mentioned.
A strong confounding factor is the unability to discriminate whether a patient has had  neo
adjuvant chemotherapy (nCT) or not. More data on the use of nCT, and discussion on the
potential selection bias by the response on nCT will improve the manuscript and the strength
of the main message.
Title: Chemotherapy alone vs definitive concurrent chemoradiotherapy for cT4b esophageal
squamous cell carcinoma: a population based study
Version: 2 Date: 22 Feb 2021
Reviewer's report:
The study by Chien et al addresses an interesting clinical issue: whether Chemotherapy or
radiochemotherapy is the most appropriate treatment for T4bM0 esophageal SCC and this was
studied in a relatively large population. However I suggest several revisions:
General:
English grammar and style should be improved. The text is written in the past, but should be
in the present time, i.e. "esophageal cancer was one of the leading..." schould be "....is one of
the leading...." etc.
Only survival data are analysed. Were grade 3-4 toxicity data not available? Since complications
are a concern of radiotherapy, the incidence of severe toxicity (fistula) is an important aspect
for interpretation of the survival results
Specific:
stick to  mentioning group C/T and group dCCRT, and not group A and B.
Methods: What do the authors mean by "excluding multiple treatment records" and by
"inclusion criteria modified from a relevant ongoing trial". I suggest to explain the exact in and
exclusion criteria.
a subheading is called Study population and intervention. But there is no intervention. I suggest
to skip the word "intervention"
Please mention the factors that were weighted for PS and PSW
Results,
A lot of covariates were analysed, but their impact was not mentioned in the text.
Primary analysis: "what do the authors mean by "the observed HR of 0.36...... could be explained
by an unmeasured confounder.........but weaker confoundering could not do so". This sentence
is unclear to me.
Discussion:
the authors state that the study relieved the concern in using radiotherapy. However no data on
toxicity of radiotherapy were mentioned.
A strong confounding factor is the unability to discriminate whether a patient has had  neo
adjuvant chemotherapy (nCT) or not. More data on the use of nCT, and discussion on the
potential selection bias by the response on nCT will improve the manuscript and the strength
of the main message.
Please review this paper.
user
Title: Chemotherapy alone vs definitive concurrent chemoradiotherapy for cT4b esophageal
squamous cell carcinoma: a population based study
Version: 2 Date: 22 Feb 2021
Reviewer's report:
The study by Chien et al addresses an interesting clinical issue: whether Chemotherapy or
radiochemotherapy is the most appropriate treatment for T4bM0 esophageal SCC and this was
studied in a relatively large population. However I suggest several revisions:
General:
English grammar and style should be improved. The text is written in the past, but should be
in the present time, i.e. "esophageal cancer was one of the leading..." schould be "....is one of
the leading...." etc.
Only survival data are analysed. Were grade 3-4 toxicity data not available? Since complications
are a concern of radiotherapy, the incidence of severe toxicity (fistula) is an important aspect
for interpretation of the survival results
Specific:
stick to  mentioning group C/T and group dCCRT, and not group A and B.
Methods: What do the authors mean by "excluding multiple treatment records" and by
"inclusion criteria modified from a relevant ongoing trial". I suggest to explain the exact in and
exclusion criteria.
a subheading is called Study population and intervention. But there is no intervention. I suggest
to skip the word "intervention"
Please mention the factors that were weighted for PS and PSW
Results,
A lot of covariates were analysed, but their impact was not mentioned in the text.
Primary analysis: "what do the authors mean by "the observed HR of 0.36...... could be explained
by an unmeasured confounder.........but weaker confoundering could not do so". This sentence
is unclear to me.
Discussion:
the authors state that the study relieved the concern in using radiotherapy. However no data on
toxicity of radiotherapy were mentioned.
A strong confounding factor is the unability to discriminate whether a patient has had  neo
adjuvant chemotherapy (nCT) or not. More data on the use of nCT, and discussion on the
potential selection bias by the response on nCT will improve the manuscript and the strength
of the main message.
assistant