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Background <p>The prognostic impact of excessive muscle loss (EML) during neoadjuvant chemoradiotherapy (NCRT) in locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains unclear.</p> Methods <p>This multicenter retrospective study analyzed consecutive patients with LA-ESCC undergoing NCRT followed by esophagectomy (2014–2023). Skeletal muscle index was measured longitudinally on computed tomography at the L3 vertebra at three time points: pre-NCRT (T1), post-NCRT (T2), and pre-surgery (T3). EML was evaluated across two intervals: stage A (T1 to T2) and stage B (T2 to T3). Survival outcomes were evaluated using Cox proportional hazards and Kaplan–Meier analyses, with a two-sided <i>P</i> &lt; 0.05 threshold for significance.</p> Results <p>Among 421 eligible patients (median follow-up 39.1 months), the 5-year overall survival (OS) and progression-free survival (PFS) rates were 60.0% and 53.9%, respectively. EML incidence was 26.6% in stage A and 37.1% in stage B. Multivariate analysis confirmed EML in both stages as independent predictors of poorer OS (stage A: hazard ratio [HR] 1.78; 95% confidence interval [CI] 1.18–2.69; <i>P</i> = 0.006; stage B: HR 1.83; 95% CI 1.23–2.72; <i>P</i> = 0.003). Stage B EML was also independently associated with worse PFS (HR 1.75; 95% CI 1.24–2.46; <i>P</i> = 0.001). Among patients without stage A EML, stable muscle mass in stage B predicted improved OS (HR 0.49; 95% CI 0.38–0.81; <i>P</i> = 0.005). No such survival benefit was observed if EML had already occurred in stage A (<i>P</i> &gt; 0.05).</p> Conclusions <p>EML during either NCRT or the subsequent preoperative period independently predicts worse survival in LA-ESCC. Nutritional intervention post-NCRT may improve outcomes, particularly for patients who maintain muscle mass during initial therapy.</p>

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Impact of Muscle Mass Loss on Survival During Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: A Multi-center Retrospective Study in China (TIMES Study)

  • 期刊论文

  • 发表日期：

    2026年5月20日

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  • Guiyu Huang,
  • Jie Zhu,
  • Bingrong He,
  • Wencheng Zhang,
  • Wei Huang,
  • Xiaoli Tang,
  • Long Zhang,
  • Qifeng Wang

摘要

Background

The prognostic impact of excessive muscle loss (EML) during neoadjuvant chemoradiotherapy (NCRT) in locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains unclear.

Methods

This multicenter retrospective study analyzed consecutive patients with LA-ESCC undergoing NCRT followed by esophagectomy (2014–2023). Skeletal muscle index was measured longitudinally on computed tomography at the L3 vertebra at three time points: pre-NCRT (T1), post-NCRT (T2), and pre-surgery (T3). EML was evaluated across two intervals: stage A (T1 to T2) and stage B (T2 to T3). Survival outcomes were evaluated using Cox proportional hazards and Kaplan–Meier analyses, with a two-sided P < 0.05 threshold for significance.

Results

Among 421 eligible patients (median follow-up 39.1 months), the 5-year overall survival (OS) and progression-free survival (PFS) rates were 60.0% and 53.9%, respectively. EML incidence was 26.6% in stage A and 37.1% in stage B. Multivariate analysis confirmed EML in both stages as independent predictors of poorer OS (stage A: hazard ratio [HR] 1.78; 95% confidence interval [CI] 1.18–2.69; P = 0.006; stage B: HR 1.83; 95% CI 1.23–2.72; P = 0.003). Stage B EML was also independently associated with worse PFS (HR 1.75; 95% CI 1.24–2.46; P = 0.001). Among patients without stage A EML, stable muscle mass in stage B predicted improved OS (HR 0.49; 95% CI 0.38–0.81; P = 0.005). No such survival benefit was observed if EML had already occurred in stage A (P > 0.05).

Conclusions

EML during either NCRT or the subsequent preoperative period independently predicts worse survival in LA-ESCC. Nutritional intervention post-NCRT may improve outcomes, particularly for patients who maintain muscle mass during initial therapy.