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Background <p>Neoadjuvant chemoimmunotherapy (nCIT) has improved outcomes in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, accessible and reliable biomarkers to predict survival and pathological response remain limited. This study assessed the prognostic and predictive value of the Global Immune-Nutrition Index (GINI), cytokeratin-19 fragment (CYFRA 21 − 1), fibrinogen–albumin ratio index (FARI), and a composite score combining these markers—the GINI–CYFRA 21 − 1–FARI (GCF) score.</p> Methods <p>A retrospective analysis was conducted on 138 LA-ESCC patients who received nCIT followed by radical esophagectomy between 2021 and 2023. Optimal cut-off values for GINI, CYFRA 21 − 1, and FARI were determined using X-tile software. The composite GCF score was developed accordingly. Associations with disease-free survival (DFS) were evaluated using Kaplan–Meier analysis and multivariable Cox regression. Predictive performance was assessed via time-dependent ROC curves. Tumor regression grade (TRG) was analyzed using logistic regression, and a nomogram was constructed to predict pathological response.</p> Results <p>Elevated levels of GINI (median DFS: 20 vs. not estimable [NE] months; <i>p</i> = 0.001), CYFRA 21 − 1 (19 vs. NE months; <i>p</i> &lt; 0.001), FARI (11 vs. 26 months; <i>p</i> &lt; 0.001), and higher GCF scores (0 vs. 1 vs. ≥2: 18 vs. 22 vs. NE months; <i>p</i> &lt; 0.001) were associated with worse DFS. The GCF score was independently predictive of DFS (low vs. high: HR = 0.264; <i>p</i> = 0.028) and demonstrated consistent discriminative capacity. For pathological response, the GCF score showed predictive value for TRG (AUC = 0.625; <i>p</i> = 0.004) and was independently associated with poor TRG (high vs. low: OR = 2.170; <i>p</i> = 0.048). A nomogram incorporating the GCF score outperformed models excluding it (AUC: 0.787 vs. 0.662; <i>p</i> &lt; 0.05).</p> Conclusions <p>The GCF score—a composite of GINI, CYFRA 21 − 1, and FARI—independently predicts DFS and pathological response following nCIT and surgery in LA-ESCC, and may hold potential as a practical, blood-based biomarker. Its integration significantly enhances predictive model performance and may aid in individualized patient risk stratification.</p>

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A composite immune-nutritional and tumor marker score predicts outcomes in LA-ESCC treated with neoadjuvant chemoimmunotherapy and surgery

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月11日

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  • Yiwei Fan,
  • Jiang Zhou,
  • Xiaotian Liu,
  • Qianhe Ren,
  • Shichun Lu,
  • Weiguo Jin

摘要

Background

Neoadjuvant chemoimmunotherapy (nCIT) has improved outcomes in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, accessible and reliable biomarkers to predict survival and pathological response remain limited. This study assessed the prognostic and predictive value of the Global Immune-Nutrition Index (GINI), cytokeratin-19 fragment (CYFRA 21 − 1), fibrinogen–albumin ratio index (FARI), and a composite score combining these markers—the GINI–CYFRA 21 − 1–FARI (GCF) score.

Methods

A retrospective analysis was conducted on 138 LA-ESCC patients who received nCIT followed by radical esophagectomy between 2021 and 2023. Optimal cut-off values for GINI, CYFRA 21 − 1, and FARI were determined using X-tile software. The composite GCF score was developed accordingly. Associations with disease-free survival (DFS) were evaluated using Kaplan–Meier analysis and multivariable Cox regression. Predictive performance was assessed via time-dependent ROC curves. Tumor regression grade (TRG) was analyzed using logistic regression, and a nomogram was constructed to predict pathological response.

Results

Elevated levels of GINI (median DFS: 20 vs. not estimable [NE] months; p = 0.001), CYFRA 21 − 1 (19 vs. NE months; p < 0.001), FARI (11 vs. 26 months; p < 0.001), and higher GCF scores (0 vs. 1 vs. ≥2: 18 vs. 22 vs. NE months; p < 0.001) were associated with worse DFS. The GCF score was independently predictive of DFS (low vs. high: HR = 0.264; p = 0.028) and demonstrated consistent discriminative capacity. For pathological response, the GCF score showed predictive value for TRG (AUC = 0.625; p = 0.004) and was independently associated with poor TRG (high vs. low: OR = 2.170; p = 0.048). A nomogram incorporating the GCF score outperformed models excluding it (AUC: 0.787 vs. 0.662; p < 0.05).

Conclusions

The GCF score—a composite of GINI, CYFRA 21 − 1, and FARI—independently predicts DFS and pathological response following nCIT and surgery in LA-ESCC, and may hold potential as a practical, blood-based biomarker. Its integration significantly enhances predictive model performance and may aid in individualized patient risk stratification.