08634476

August 30, 2025, 08:43

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Dear Editor, We read with great interest the article “Morphomics in esophageal cancer: Validation and association with muscular and cardiorespiratory fitness” by Tseng et al. This study innovatively explores the correlation between computed tomography (CT)-based morphomics and functional assessments (bioelectrical impedance analysis [BIA], hand grip strength [HGS], cardiopulmonary exercise testing [CPET]) in esophageal cancer patients, providing valuable evidence for preoperative physical fitness evaluation. However, three aspects could be further refined to enhance the study’s clinical applicability and evidence robustness. First, the study lacks analysis of the impact of tumor stage and neoadjuvant therapy on the relationship between morphomics and functional indicators. The cohort includes newly diagnosed esophageal cancer patients, but the article does not specify the distribution of tumor stages (e.g., T stage, N stage) or whether patients received neoadjuvant chemotherapy/radiotherapy before CT and functional assessments. Clinically, advanced tumor stages may directly affect muscle mass (via malnutrition or tumor-related inflammation), while neoadjuvant therapy can cause treatment-related muscle loss (cachexia) or changes in cardiorespiratory fitness. Without stratifying outcomes by tumor stage or adjusting for neoadjuvant therapy status, it is difficult to determine whether the observed correlations between morphomics (e.g., dorsal muscle group [DMG] volume) and CPET/BIA results are confounded by these factors. This gap limits the ability to generalize the findings to patients at different disease stages or treatment phases. Second, the study does not clarify the clinical significance of morphomic parameter thresholds for predicting low cardiorespiratory fitness (CRF). The authors report that morphomics (combining bone mineral density [BMD], visceral fat [VF] area, and DMG volume) predicts low ventilatory anaerobic threshold normalized by body weight (VAT/BW < 11 mL/kg/min) with an optimism-corrected AUC of 0.778. However, they do not provide specific cutoff values for the key morphomic variables (e.g., how much VF area or DMG volume increases/decreases the risk of low CRF) or validate these thresholds in clinical practice. For example, if a VF area > X cm² or DMG volume < Y cm³ is associated with a significantly higher risk of low CRF, such thresholds would help clinicians quickly identify high-risk patients via routine CT scans. Without defining these actionable cutoffs, the predictive model’s practical value for preoperative screening remains limited. Third, the homogeneity of the cohort (98% male, Taiwanese population) raises concerns about generalizability, yet the study does not discuss or address potential sex- or ethnicity-related differences in morphomics-functional correlations. Previous studies have shown that body composition (e.g., muscle-fat distribution) and its association with physical fitness vary by sex—for instance, women may have different muscle density thresholds or fat-mass impacts on CRF compared to men. Additionally, ethnic differences in body composition (e.g., Asian vs. Western populations) could affect morphomic parameter norms and their correlation with BIA/CPET results. By excluding female patients and focusing solely on a Taiwanese cohort, the study’s findings may not apply to more diverse populations. Exploring sex-stratified analyses (if feasible with additional data) or acknowledging these limitations with suggestions for multicenter, multiethnic validation would strengthen the study’s external validity. In conclusion, Tseng et al.’s work makes a meaningful contribution to integrating morphomics into esophageal cancer preoperative assessment. Addressing the above issues—through stratification by tumor stage/neoadjuvant therapy, defining clinical thresholds for predictive morphomic parameters, and expanding cohort diversity—would further enhance the study’s scientific rigor and clinical translational value. We look forward to seeing supplementary analyses or follow-up studies to address these points. Sincerely, Xiong Yuezhihong Yichang Central People's Hospital

First, thank you very much for your professional comments on the article published in World Journal of Gastrointestinal Surgery. Second, we read your comments with great interest. You are welcome to format your valuable comments into a Letter to the Editor and submit it online to World Journal of Gastrointestinal Surgery at https://www.f6publishing.com. There are no restrictions on the number of words, figures (color, B/W) or authors for a Letter to the Editor. In addition, the article processing charge will be exempted for this Letter to the Editor. As with all articles published by the Baishideng Publishing Group, the Letter to the Editor will be published online after completing peer review. The guidelines for a Letter to the Editor can be found at: https://www.wjgnet.com/bpg/GerInfo/219. Finally, we look forward to receiving your high-quality Letter to the Editor, which will promote academic communication and lead the development of this discipline.