Title: Prolonged time interval from neoadjuvant immunotherapy combined with chemotherapy
to surgery is related to unimproved pathological response and poor survival prognosis for
esophageal squamous cell carcinoma
Version: 1 Date: 26 Feb 2025
Reviewer's report:
The authors retrospectively reviewed the outcomes of patients with esophageal squamous cell
carcinoma who receiving neoadjuvant immunotherapy combined with chemotherapy followed
by esophagectomy. The pathological response, survival outcomes, surgical outcomes, and
postoperative complications were compared between the timely surgery group (time interval
 # 6 weeks) and the delayed surgery group (time interval > 6 weeks). The study topics is quit
interesting. There is still no consensus on the optimal timing of surgery after neoadjuvant therapy
for esophageal squamous cell carcinoma. It is well written and presented and I have some
comments:
1. In the section of "2.1 Study population", the inclusion criteria indicated that patients with
complete clinicopathological and follow-up information was included. How long is the follow-
up period in this study at least ? The median follow-up time of esophageal squamous cell
cercinoma patients was 19 months (range: 2–47 months). Is patient with 2 months follow-up
time after esophagectomy with complete follow-up information ? Also,  patients combing with
other malignancies were excluded. Is that patients with other maligancies means synchronous
or metachronous malignancies ?
2. The indication criteria for adjuvant therapy should be shown.
3. All patients underwent esophagectomy via minimally invasive three-incision McKeown
operation procedures with standard two-field lymphadenectomy. There is 7 (5.3%) patients with
tumor location over cervical region (Table 1) in this study. The treatment strategy for tumors
and the pathophysiology of tumors are different from those of thoracic esophageal squamous
cell carcinoma.
4. In Figure 1,  the horizontal axis (time interval (weeks)) should present as "interval" (e.g. 5<
x # 6 not x # 6).
5. Table 5. Univariate and multivariate Cox regression analyses of overall survival and
progression-free survival for esophageal squamous cell carcinoma patients. Disease-Free
Survival (DFS) was defined as the time interval from the date of surgery to the recurrence of
tumor or death in the materials and methods, not progression-free survival. Please correct it.
6. Significant difference at Kaplan-Meier survival analysis in comparison of overall survival
according to cN stage (cN0 versus cN+). How about comparison of disease-free survival ?
Title: Prolonged time interval from neoadjuvant immunotherapy combined with chemotherapy
to surgery is related to unimproved pathological response and poor survival prognosis for
esophageal squamous cell carcinoma
Version: 1 Date: 26 Feb 2025
Reviewer's report:
The authors retrospectively reviewed the outcomes of patients with esophageal squamous cell
carcinoma who receiving neoadjuvant immunotherapy combined with chemotherapy followed
by esophagectomy. The pathological response, survival outcomes, surgical outcomes, and
postoperative complications were compared between the timely surgery group (time interval
 # 6 weeks) and the delayed surgery group (time interval > 6 weeks). The study topics is quit
interesting. There is still no consensus on the optimal timing of surgery after neoadjuvant therapy
for esophageal squamous cell carcinoma. It is well written and presented and I have some
comments:
1. In the section of "2.1 Study population", the inclusion criteria indicated that patients with
complete clinicopathological and follow-up information was included. How long is the follow-
up period in this study at least ? The median follow-up time of esophageal squamous cell
cercinoma patients was 19 months (range: 2–47 months). Is patient with 2 months follow-up
time after esophagectomy with complete follow-up information ? Also,  patients combing with
other malignancies were excluded. Is that patients with other maligancies means synchronous
or metachronous malignancies ?
2. The indication criteria for adjuvant therapy should be shown.
3. All patients underwent esophagectomy via minimally invasive three-incision McKeown
operation procedures with standard two-field lymphadenectomy. There is 7 (5.3%) patients with
tumor location over cervical region (Table 1) in this study. The treatment strategy for tumors
and the pathophysiology of tumors are different from those of thoracic esophageal squamous
cell carcinoma.
4. In Figure 1,  the horizontal axis (time interval (weeks)) should present as "interval" (e.g. 5<
x # 6 not x # 6).
5. Table 5. Univariate and multivariate Cox regression analyses of overall survival and
progression-free survival for esophageal squamous cell carcinoma patients. Disease-Free
Survival (DFS) was defined as the time interval from the date of surgery to the recurrence of
tumor or death in the materials and methods, not progression-free survival. Please correct it.
6. Significant difference at Kaplan-Meier survival analysis in comparison of overall survival
according to cN stage (cN0 versus cN+). How about comparison of disease-free survival ?
Please review this paper.
user
Title: Prolonged time interval from neoadjuvant immunotherapy combined with chemotherapy
to surgery is related to unimproved pathological response and poor survival prognosis for
esophageal squamous cell carcinoma
Version: 1 Date: 26 Feb 2025
Reviewer's report:
The authors retrospectively reviewed the outcomes of patients with esophageal squamous cell
carcinoma who receiving neoadjuvant immunotherapy combined with chemotherapy followed
by esophagectomy. The pathological response, survival outcomes, surgical outcomes, and
postoperative complications were compared between the timely surgery group (time interval
 # 6 weeks) and the delayed surgery group (time interval > 6 weeks). The study topics is quit
interesting. There is still no consensus on the optimal timing of surgery after neoadjuvant therapy
for esophageal squamous cell carcinoma. It is well written and presented and I have some
comments:
1. In the section of "2.1 Study population", the inclusion criteria indicated that patients with
complete clinicopathological and follow-up information was included. How long is the follow-
up period in this study at least ? The median follow-up time of esophageal squamous cell
cercinoma patients was 19 months (range: 2–47 months). Is patient with 2 months follow-up
time after esophagectomy with complete follow-up information ? Also,  patients combing with
other malignancies were excluded. Is that patients with other maligancies means synchronous
or metachronous malignancies ?
2. The indication criteria for adjuvant therapy should be shown.
3. All patients underwent esophagectomy via minimally invasive three-incision McKeown
operation procedures with standard two-field lymphadenectomy. There is 7 (5.3%) patients with
tumor location over cervical region (Table 1) in this study. The treatment strategy for tumors
and the pathophysiology of tumors are different from those of thoracic esophageal squamous
cell carcinoma.
4. In Figure 1,  the horizontal axis (time interval (weeks)) should present as "interval" (e.g. 5<
x # 6 not x # 6).
5. Table 5. Univariate and multivariate Cox regression analyses of overall survival and
progression-free survival for esophageal squamous cell carcinoma patients. Disease-Free
Survival (DFS) was defined as the time interval from the date of surgery to the recurrence of
tumor or death in the materials and methods, not progression-free survival. Please correct it.
6. Significant difference at Kaplan-Meier survival analysis in comparison of overall survival
according to cN stage (cN0 versus cN+). How about comparison of disease-free survival ?
assistant