Title: Neuroendocrine Carcinoma of Esophagus: Systematic Review and Meta-analysis of Case
Series
Version: 1 Date: 19 Apr 2025
Reviewer:  Zixian Jin
Reviewer's report:
This is a systematic review and meta-analysis on esophageal neuroendocrine carcinoma that has
yielded several valuable conclusions. However, I would like to raise a few questions that require
clarification from the authors.
The study primarily relies on retrospective data from China, Japan, and the United States, with
some studies having very small sample sizes. It remains unclear whether there was any patient
overlap across these studies, which requires further clarification from the authors.
Significant heterogeneity was observed in several subgroup analyses. Although a random-effects
model was employed for all patient analyses, this high heterogeneity needs to be properly
addressed - either through additional explanation or sensitivity analyses - otherwise the findings
may lack sufficient persuasiveness.
In the background section, the authors mentioned: "The NANETS guidelines advise resection of
a primary regional gastroenteropancreatic (GEP) NEC only in carefully selected cases, whereas
the ENETS guidelines generally recommend surgery of the primary tumor, except for stage III
esophageal NEC . There are studies reporting surgical resection may not affect the prognosis,
particularly in metastatic cases; however, chemoradiation alone or as adjuvant systemic therapy
has been beneficial and improved survival." For the studies included in this meta-analysis,
more detailed information should be provided regarding the specific surgical approaches and
chemoradiotherapy regimens employed.
Title: Neuroendocrine Carcinoma of Esophagus: Systematic Review and Meta-analysis of Case
Series
Version: 1 Date: 19 Apr 2025
Reviewer:  Zixian Jin
Reviewer's report:
This is a systematic review and meta-analysis on esophageal neuroendocrine carcinoma that has
yielded several valuable conclusions. However, I would like to raise a few questions that require
clarification from the authors.
The study primarily relies on retrospective data from China, Japan, and the United States, with
some studies having very small sample sizes. It remains unclear whether there was any patient
overlap across these studies, which requires further clarification from the authors.
Significant heterogeneity was observed in several subgroup analyses. Although a random-effects
model was employed for all patient analyses, this high heterogeneity needs to be properly
addressed - either through additional explanation or sensitivity analyses - otherwise the findings
may lack sufficient persuasiveness.
In the background section, the authors mentioned: "The NANETS guidelines advise resection of
a primary regional gastroenteropancreatic (GEP) NEC only in carefully selected cases, whereas
the ENETS guidelines generally recommend surgery of the primary tumor, except for stage III
esophageal NEC . There are studies reporting surgical resection may not affect the prognosis,
particularly in metastatic cases; however, chemoradiation alone or as adjuvant systemic therapy
has been beneficial and improved survival." For the studies included in this meta-analysis,
more detailed information should be provided regarding the specific surgical approaches and
chemoradiotherapy regimens employed.
Please review this paper.
user
Title: Neuroendocrine Carcinoma of Esophagus: Systematic Review and Meta-analysis of Case
Series
Version: 1 Date: 19 Apr 2025
Reviewer:  Zixian Jin
Reviewer's report:
This is a systematic review and meta-analysis on esophageal neuroendocrine carcinoma that has
yielded several valuable conclusions. However, I would like to raise a few questions that require
clarification from the authors.
The study primarily relies on retrospective data from China, Japan, and the United States, with
some studies having very small sample sizes. It remains unclear whether there was any patient
overlap across these studies, which requires further clarification from the authors.
Significant heterogeneity was observed in several subgroup analyses. Although a random-effects
model was employed for all patient analyses, this high heterogeneity needs to be properly
addressed - either through additional explanation or sensitivity analyses - otherwise the findings
may lack sufficient persuasiveness.
In the background section, the authors mentioned: "The NANETS guidelines advise resection of
a primary regional gastroenteropancreatic (GEP) NEC only in carefully selected cases, whereas
the ENETS guidelines generally recommend surgery of the primary tumor, except for stage III
esophageal NEC . There are studies reporting surgical resection may not affect the prognosis,
particularly in metastatic cases; however, chemoradiation alone or as adjuvant systemic therapy
has been beneficial and improved survival." For the studies included in this meta-analysis,
more detailed information should be provided regarding the specific surgical approaches and
chemoradiotherapy regimens employed.
assistant