Review for 10.1186/s12876-025-03964-2 (2025)

Title: Dual energy CT-derived quantitative parameters and hematological characteristics predict
pathological complete response in neoadjuvant chemoradiotherapy esophageal squamous cell
carcinoma patients
Version: 3 Date: 12 Feb 2025
Reviewer's report:
This study investigates the potential predictive value of dual-energy CT (DECT)
quantitative parameters and hematological characteristics for pathological complete response
(pCR) in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant
chemoradiotherapy (nCRT). The topic is highly relevant in the field of oncological imaging
and treatment response assessment. The integration of DECT imaging with clinical and
hematological parameters presents an innovative approach. However, the manuscript presents
several critical issues that need to be addressed to meet the standards for publication.
Strengths of the Study
Clinical Relevance: The study addresses an important clinical question by exploring novel
imaging biomarkers for predicting pCR in ESCC patients undergoing nCRT.
Innovative Approach: The combination of DECT-derived parameters with hematological
characteristics could provide new insights into personalized treatment strategies.
Retrospective Cohort with Surgical Confirmation: The inclusion of surgically confirmed pCR
cases adds robustness to the findings.
Major Concerns
1. Methodological Issues
Study Design: The retrospective nature of the study is a limitation that should be more explicitly
addressed in the discussion, along with potential selection bias.
Inclusion and Exclusion Criteria: The manuscript lacks a clear explanation of the inclusion and
exclusion criteria for patient selection, which is essential for reproducibility.
Sample Size Justification: There is no power analysis or justification for the sample size. Given
the relatively small cohort (N=53), it is crucial to demonstrate that the study is adequately
powered to detect significant differences.
pCR Definition: The criteria for defining pCR should be referenced against established
oncological guidelines.
2. Statistical Concerns
Multivariate Analysis: It is unclear whether a multivariate analysis was performed to adjust for
potential confounders. Given that multiple factors may influence pCR, a robust multivariate
model should be included.
Correction for Multiple Comparisons: The study reports multiple statistical tests without
correction for multiple comparisons (e.g., Bonferroni correction or false discovery rate). This
increases the risk of type I errors.
ROC Curve Interpretation: While ROC analysis is performed, the methodology for selecting
the optimal cut-off values is not well justified. A bootstrapping approach could strengthen the
robustness of the reported AUC values.
3. Imaging and Data Processing
Standardization of DECT Parameters: It is not clear whether the DECT parameters were
standardized across all patients, as variability in acquisition settings can affect reproducibility.
Reproducibility and Interobserver Variability: The manuscript does not mention whether intra-
and interobserver reliability analyses were performed for the quantitative DECT parameters,
which are critical for clinical implementation.
Validation Cohort: The study lacks an external validation cohort, which limits the
generalizability of the findings.
4. Interpretation and Discussion
Comparative Analysis with Existing Literature: While the study presents novel findings, the
discussion lacks a thorough comparison with previously published studies on DECT imaging
in ESCC.
Clinical Impact and Limitations: The potential clinical implications should be more explicitly
discussed, including how these findings could influence treatment decision-making in ESCC
patients.
Future Directions: The discussion should address future directions, including prospective
validation and integration with other imaging modalities or biomarkers.
Minor Concerns
Language and Grammar: The manuscript contains several grammatical and syntactical errors
that need revision for clarity and readability.
Figures and Tables: The resolution of the provided figures (especially DECT images) should be
improved for better visualization. The legends should be more descriptive.
Ethical Considerations: The study should clearly state whether it received approval from an
ethics committee and whether informed consent was obtained from patients.
Conclusion and Recommendations
This study presents an interesting approach to predicting pCR in ESCC using DECT-derived
parameters and hematological characteristics. However, several methodological and statistical
issues must be addressed before the manuscript can be considered for publication. Specifically,
the authors should:
Clarify and justify the study design, inclusion/exclusion criteria, and sample size.
Perform a multivariate analysis to control for confounders.
Apply corrections for multiple comparisons to reduce the risk of false-positive findings.
Address reproducibility concerns by including interobserver reliability assessments.
Improve the discussion section by integrating a comparative analysis with existing literature and
providing clearer clinical implications.
Consider an external validation cohort to strengthen the generalizability of the findings.
With these revisions, the study will be significantly strengthened and more suitable for
publication in a high-impact medical journal.