Analysis of clinical features, prognosis and comprehensive therapeutic strategies in 261 patients with limited-stage esophageal small cell carcinoma

Di LIU; Jianjiao NI; Kuaile ZHAO; Jiaqing XIANG; Zhen ZHANG; Junhua ZHANG

doi:10.19401/j.cnki.1007-3639.2025.05.005

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Analysis of clinical features, prognosis and comprehensive therapeutic strategies in 261 patients with limited-stage esophageal small cell carcinoma

Original article | 更新时间：2025-12-31

- Analysis of clinical features, prognosis and comprehensive therapeutic strategies in 261 patients with limited-stage esophageal small cell carcinoma
- China Oncology Vol. 35, Issue 5, Pages: 465-477(2025)
- 作者机构：
  
  1. 复旦大学附属肿瘤医院放射治疗中心，上海市放射肿瘤学重点实验室，上海市放射治疗临床医学研究中心，复旦大学上海医学院肿瘤学系，上海 200032
  2. 复旦大学附属肿瘤医院胸外科，复旦大学遗传工程国家重点实验室，复旦大学胸部肿瘤研究所，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2025.05.005
  CLC： R735.1
- Received：08 January 2025，
  
  Revised：2025-03-18，
  
  Published：30 May 2025
- 稿件说明：
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Di LIU, Jianjiao NI, Kuaile ZHAO, et al. Analysis of clinical features, prognosis and comprehensive therapeutic strategies in 261 patients with limited-stage esophageal small cell carcinoma[J]. China Oncology, 2025, 35(5): 465-477.
DOI：

Di LIU, Jianjiao NI, Kuaile ZHAO, et al. Analysis of clinical features, prognosis and comprehensive therapeutic strategies in 261 patients with limited-stage esophageal small cell carcinoma[J]. China Oncology, 2025, 35(5): 465-477. DOI： 10.19401/j.cnki.1007-3639.2025.05.005.

摘要

背景与目的：

局限期（limited-stage，LS）-食管小细胞癌（small cell esophageal carcinoma，SCEC）恶性程度高、患者预后极差，由于其罕见性，目前无特异性分期，亦无法通过设计随机对照临床试验来指导治疗，很多临床经验是借鉴于相对成熟的小细胞肺癌（small cell lung cancer，SCLC）治疗体系，然而患者预后仍较差，疗效始终无法突破。本研究旨在分析LS-SCEC患者的生存及预后因素、失败模式，并探讨其治疗策略。

方法：

回顾性分析2006年1月—2023年6月于复旦大学附属肿瘤医院确诊并接受治疗的原发性LS-SCEC患者的病例资料，具备诊断、分期、随访所需的临床资料。小细胞癌成分并非主要成分（

50%）的混合型食管肿瘤患者不纳入本研究。所有计数资料采用频数和百分比进行统计描述，计量资料采用$\bar{x} \pm s$进行统计描述。分类变量采用

检验或Fisher确切概率法进行组间比较。生存分析应用Kaplan-Meier法，采用COX回归分析影响预后的相关因素，采用1∶1最近邻匹配法分析根治性放化疗组患者与根治性手术联合术后辅助化疗组患者的生存差异。

0.05为差异有统计学意义。

结果：

261例符合要求的LS-SCEC患者纳入本研究，中位随访时间为72.7个月（95% CI：52.0~92.4），中位癌症特异性生存（cancer-specific survival，CSS）为24.5个月（95% CI：19.7~29.3），5年CSS率为32.8%；中位无进展生存（progression-free survival，PFS）为12.0个月（95% CI：10.7~13.3）。未复发患者67例，可统计到首次治疗失败模式的患者169例，远处转移是最常见的复发模式，首次治疗失败模式中有远处转移的患者为131例（77.5%），局部区域复发患者仅38例（22.5%）。最常见的远处转移器官是肝（54例），其次是骨（25例）、脑（24例）及肺（23例）。化疗周期数和TNM分期（第8版）是LS-SCEC患者CSS和PFS的独立预后因素。本研究进一步比较了接受根治性手术联合术后辅助化疗患者与接受根治性放化疗患者的预后，发现倾向性匹配前后的CSS和PFS差异均无统计学意义（

0.05），而肿瘤位于颈段及胸上段、长度更长、分期更晚的患者更倾向于接受放化疗，且放化疗组接受≥4个周期化疗患者比例更高。

结论：

本研究是一项LS-SCEC较大样本、数据较全面细致且随访时间较长的回顾性分析。接受根治性放化疗与根治性手术+辅助化疗患者的CSS和PFS差异均无统计学意义，接受≥4个

周期化疗患者的获益更大。SCEC远处转移风险高且呈高度异质性，LS-SCEC的治疗应注重个体化。

Abstract

Background and purpose:

Limited-stage (LS)-small cell esophageal carcinoma (SCEC)

characterized by high aggressiveness and an extremely poor prognosis

lacks standardized staging systems due to its rarity. Consequently

no randomized controlled clinical trials exist to guide therapeutic strategies

necessitating reliance on extrapolated protocols from small cell lung cancer (SCLC) paradigms

though clinical outcomes remain dismal. This study aimed to analyse survival outcomes

prognostic factors

failure patterns and therapeutic strategies in patients with LS-SCEC.

Methods:

We conducted a retrospective single-center study of LS-SCEC patients diagnosed and treated at Fudan University Shanghai Cancer Center from January 2006 to June 2023. Clinicopathological data for diagnosis

staging and follow-up were rigorously collected. Patients with mixed esophageal tumors in whom small cell carcinoma was not the predominant histological component (

50%) were excluded. Continuous variables were presented as $\bar{x} \pm s$. Categorical variables were summarized as counts and percentages

with intergroup comparisons performed using

test or Fisher’s exact tests. Survival analysis was performed using the Kaplan-Meier method

and Cox regression was used to analyse factors related to prognosis. A two-sided

0.050 was considered statistically significant. A 1∶1 nearest-neighbour propensity score matching was applied to compare survival outcomes between patients undergoing radical chemoradiotherapy and those receiving radical surgery followed by adjuvant chemotherapy.

Results:

Of 261 eligible LS-SCEC patients included

the median follow-up duration was 72.7 months (95% CI: 52.0-92.4)

with a median cancer-specific survival (CSS) of 24.5 months (95% CI: 19.7-29.3) and a 5-year CSS rate of 32.8%. The media

n progression-free survival (PFS) was 12.0 months (95% CI: 10.7-13.3). Among these

67 patients remained recurrence-free

and 169 patients exhibited disease progression after first-line treatment. Distant metastasis was the predominant recurrence pattern (131 patients

77.5%)

whereas locoregional recurrence occurred in only 38 patients (22.5%). The most frequent metastatic sites were liver (54 patients)

followed by bone (25 patients)

brain (24 patients)

and lung (23 patients). The number of chemotherapy cycle and TNM stage (8th edition) were independent prognostic factors for CSS and PFS in LS-SCEC patients. Comparative analysis of radical surgery with adjuvant chemotherapy versus radical chemoradiotherapy revealed no statistically significant differences in CSS and PFS (

0.05)

even after propensity score matching. Patients with cervical/upper thoracic tumors

longer tumor lengths

and advanced stages were more likely to receive chemoradiotherapy; additionally

the chemoradiotherapy group had a higher proportion of patients completing ≥4 chemotherapy cycle.

Conclusion:

This large-sample retrospective study with comprehensive datasets and long-term follow-up demonstrated comparable survival outcomes between radical chemoradiotherapy and radical surgery plus adjuvant chemotherapy for LS-SCEC. A minimum of 4 chemotherapy cycle was associated with improved prognosis. SCEC is associated with a high risk of distant metastasis and marked heterogeneity. Therefore

the treatment of LS-SCEC should prioritize an individualized approach.

关键词

Keywords

references

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