Review for 10.1186/s12876-021-02016-9 (2021)

Title: Impact of Chemotherapy and Radiotherapy on the Survival of Elderly Esophageal Cancer
Patients Undergoing Surgery: A SEER Database Analysis
Version: 3 Date: 07 Apr 2021
Reviewer's report:
Review comments to authors:
In the manuscript titled “Impact of Chemotherapy and Radiotherapy on the Survival of Elderly
Esophagus Cancer Patients after Surgery: A SEER Database Analysis”, the authors using
statistical models to evaluate survival benefit of chemotherapy or radiation therapy for elderly
esophagus cancer patients receiving chemotherapy and radiation therapy using SEER data.
General comments:
1. The paper will be interesting to audiences who treat elderly esophagus cancer patients.
However the paper was not very well written and not well organized. A scientific editor’s review
to improve the readability of this paper is needed.
2. Authors used a lot of abbreviations in this paper. It makes the paper hard to read. If a short
words or phrases is appeared more than five times in the paper, an abbreviation can be used.
The first time you use the abbreviation, put the abbreviation in parentheses after the full term.
Authors sometimes would use the abbreviation first, then introduced it in later text.
Review comments by sessions:
Abstract:
The abstract did not include study method. Lack of information on study design, how did study
cohort was collected, what statistics methods were used, and what outcomes for the study. No
explanation of what PSM, and sHR stands for. In the results of the abstract, no information about
the study population.
Introduction:
1. In the 1st paragraph, authors mentioned about increasing incidence in Asia and Africa, what
is the trend of esophagus cancer in the United States and Europe?
2. In the 2nd paragraph, please provide detailed treatment guidelines and its associated timeline
on the surgical or chemotherapy or radiation recommendations for esophagus cancer.
3. In the 3rd paragraph, please state the study purpose or hypothesis for the paper. What are the
outcomes of the paper such as estimate hazard ratio comparing patients received chemotherapy
treatment with non treatment, or building a model adjusting for covariates to classify patients’
into high or low-risk groups? The current paragraph stated study method or approaches used to
obtain certain estimates, however, it didn’t provide information on why those estimations are
needed for the study. Please tie the study outcome variables with study purposes.
4. Please spell out SEER when it first appeared in the text.
Materials and Methods:
Overall, the materials and methods session was not well written. The flow of this session would
start with how study cohort was selected (selection and exclusion criteria), time windows used
to define study outcomes, risk factors evaluated in the study, statistical methods/models were
used in the study, statistical software or packages used, what are the results of the study, and
how to interpret them. Has the study been approved by authors’ Institutional Review Board?
1. What are selection criteria for this study? Is there any restriction on stage at diagnosis,
histology, or grade? Please describe the steps to select study cohort and draw a cohort selection
diagram.
2. The study purpose is to evaluate esophagus survival and chemotherapy and radiation
treatment.  Authors used chemotherapy/non-chemotherapy, and radiation/non-radiation therapy
for nearest neighbor propensity match, what is a patient had both chemotherapy and radiation
therapy? Also, what variables are included in the propensity match?  Is there a reference using
this method to calculate sub-distribution hazard ratio (sHR) to evaluate survival analysis? and Is
there any difference for patients’ survival if a patient received both radiation and chemotherapy?
Are What kind of statistical methods is used to analyze the data?
3. Authors used nomogram model to classify patients into high or low-risk groups. Please
provide a reference for variables authors choose to include to build the nomogram. Why authors
need to estimate sHR for CSD and hazard ratio for overall survival?
Results:
The first paragraph of results session described the exclusion criteria and it can be moved to
method session. What is the 1-year, 3-year, and 5 year survival of the study cohort? How were
these patients treated? Were any patients had both radiation and chemotherapy or patients with
neither of these two treatment? What is the distribution of cancer stage? The c-indexes of the
competing risk regression model were <0.7 for both training and validation dataset. This is
not a very good model. What is the c-index if using TNM staging-system in the competing
risk regression model? Please provide a cross-tabulation table with high and low risk group by
patients’ TNM stage. Were high risk group with more advanced stage patients?
When describing the relationship between sHR or HR, please use better survival instead of
negative related with cancer specific death or overall survival. The term “negative” may confuse
readers who are not familiar with the interpretation of hazard ratio.
Discussion:
The study evaluated the survival benefit of using chemotherapy and/or radiation in treatment
of elder esophagus patients. The survival benefit was mainly for the high-risk patients defined
by the nomogram developed by the authors. Since the cohort generated using the propensity
score matching approach was small, the C-index of the model was <0.7. Authors should discuss
whether other propensity matching methods can result in a bigger sample size for the competing
risk regression model. In this study, the survival benefit for chemotherapy and radiation were
evaluated separately. In real world, patients may receive both chemotherapy and radiation
therapy. Authors should list this as a limitation.