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Background <p>The survival benefit of adding radiotherapy (RT) to immunochemotherapy (ICT) in patients with stage IVB esophageal squamous cell carcinoma (ESCC) confined to non-regional lymph node metastases remains uncertain. This study evaluated whether RT combined with first-line PD-1 inhibitor-based ICT improves outcomes.</p> Methods <p>In this multicenter retrospective cohort study, 343 patients with stage IVB ESCC (non-regional nodal metastases only; AJCC 8th edition) treated with PD-1 inhibitors plus chemotherapy between 2019 and 2021 were analyzed. Patients were stratified into RT (ICT + RT, <i>n</i> = 181) and non-RT (ICT alone, <i>n</i> = 162) groups. Propensity score matching (PSM) balanced baseline characteristics (age, sex, metastatic sites, etc.), yielding 125 matched pairs. RT (&gt; 40&#xa0;Gy to primary lesions) was delivered via IMRT/VMAT (median dose, 50.4&#xa0;Gy). Primary endpoints were overall survival (OS) and progression-free survival (PFS).</p> Results <p>After PSM, the RT group showed significantly longer median OS (22.3 vs 14.9&#xa0;months; HR 0.51, 95% CI 0.37–0.71; <i>P</i> &lt; 0.001) and PFS (14.0 vs 6.1&#xa0;months; HR 0.57, 95% CI 0.42–0.77;&#xa0;<i>P</i> &lt; 0.001) versus non-RT. Sequential RT (post-induction ICT) conferred maximal OS benefit (median OS 29.2 vs 12.1&#xa0;months; HR 0.38, <i>P</i> &lt; 0.001). Exploratory analysis indicated that the most significant survival benefit was observed in patients receiving sequential RT targeting the primary tumor with or without metastatic nodes, rather than metastasis-directed RT alone. Grade 3–5 treatment-related adverse events were comparable between groups; however, RT was associated with significantly higher rates of grade 3–4 lymphopenia (15.2% vs 4.0%, <i>p</i> = 0.004) and esophagitis (11.2% vs 0%, <i>p</i> &lt; 0.001).</p> Conclusion <p>Adding RT to first-line ICT improves survival in stage IVB ESCC with non-regional nodal metastases, particularly when delivered sequentially to the primary tumor.</p>

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Comparative analysis of immunochemotherapy with versus without radiation therapy for stage IVB esophageal squamous cell carcinoma confined to non-regional nodal metastases: a multicenter propensity score matching study

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  • 发表日期：

    2025年11月18日

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  • Qi Liu,
  • Junqiang Chen,
  • Yuanji Xu,
  • Wenbin Shen,
  • Jinjun Ye,
  • Honglei Luo,
  • Xizhi Zhang,
  • Wenyang Liu,
  • Yujin Xu,
  • Yingying Zhang,
  • Anwen Liu,
  • Xiaopeng Li,
  • Hong Ge,
  • Qifeng Wang,
  • Hui Luo,
  • Lina Zhao,
  • Conghua Xie,
  • Qin Lin,
  • Congying Xie,
  • Jianping Xiong,
  • Weiwei Chen,
  • Luhua Wang,
  • Kuaile Zhao

摘要

Background

The survival benefit of adding radiotherapy (RT) to immunochemotherapy (ICT) in patients with stage IVB esophageal squamous cell carcinoma (ESCC) confined to non-regional lymph node metastases remains uncertain. This study evaluated whether RT combined with first-line PD-1 inhibitor-based ICT improves outcomes.

Methods

In this multicenter retrospective cohort study, 343 patients with stage IVB ESCC (non-regional nodal metastases only; AJCC 8th edition) treated with PD-1 inhibitors plus chemotherapy between 2019 and 2021 were analyzed. Patients were stratified into RT (ICT + RT, n = 181) and non-RT (ICT alone, n = 162) groups. Propensity score matching (PSM) balanced baseline characteristics (age, sex, metastatic sites, etc.), yielding 125 matched pairs. RT (> 40 Gy to primary lesions) was delivered via IMRT/VMAT (median dose, 50.4 Gy). Primary endpoints were overall survival (OS) and progression-free survival (PFS).

Results

After PSM, the RT group showed significantly longer median OS (22.3 vs 14.9 months; HR 0.51, 95% CI 0.37–0.71; P < 0.001) and PFS (14.0 vs 6.1 months; HR 0.57, 95% CI 0.42–0.77; P < 0.001) versus non-RT. Sequential RT (post-induction ICT) conferred maximal OS benefit (median OS 29.2 vs 12.1 months; HR 0.38, P < 0.001). Exploratory analysis indicated that the most significant survival benefit was observed in patients receiving sequential RT targeting the primary tumor with or without metastatic nodes, rather than metastasis-directed RT alone. Grade 3–5 treatment-related adverse events were comparable between groups; however, RT was associated with significantly higher rates of grade 3–4 lymphopenia (15.2% vs 4.0%, p = 0.004) and esophagitis (11.2% vs 0%, p < 0.001).

Conclusion

Adding RT to first-line ICT improves survival in stage IVB ESCC with non-regional nodal metastases, particularly when delivered sequentially to the primary tumor.