不同模式治疗食管癌术后颈部淋巴结寡转移患者预后分析的真实世界研究

Prognosis of patients with cervical lymph node oligometastasis after esophageal cancer surgery who underwent different therapeutic modalities: a real-world study

  • 摘要:
    目的 探讨不同模式治疗食管癌术后颈部淋巴结寡转移患者的预后情况。
    方法 采用回顾性队列研究方法。收集2007年5月至2023年6月中山大学肿瘤防治中心收治的5 692例食管癌患者的临床病理资料;男4 473例,女1 219例;年龄为61(55~66)岁。5 692例患者中,127例发生颈部淋巴结寡转移,其中23例行单纯手术治疗,设为单纯手术组;74例行放疗、化疗或放化疗,设为放化疗组;30例行手术联合放疗、化疗或放化疗,设为联合治疗组。偏态分布的计量资料以M(范围)表示。计数资料以绝对数或百分比表示,组间比较采用χ²检验或Fisher确切概率法。基线资料差异采用逆概率加权法(IPTW)进行校正。采用X‑tile软件(v3.6.1)确定预后最佳截断值。中位随访时间采用逆Kaplan‑Meier法计算,数据缺失值采用多重插补法处理。采用Kaplan‑Meier法绘制生存曲线,Log‑rank检验进行生存分析。单因素和多因素分析采用COX比例风险回归模型,将单因素分析中P<0.2的临床病理因素纳入多因素分析。
    结果 (1)生存情况。127例患者的中位随访时间为47个月,中位无进展生存时间为31个月,中位总生存时间为53个月;1、3、5年无进展生存率分别为61.5%、43.0%、36.5%,1、3、5年总生存率分别为85.6%、60.2%、45.7%。IPTW校正后,单纯手术组、放化疗组、联合治疗组患者中位无进展生存时间分别为55、23、61个月;单纯手术组患者1、3、5年无进展生存率分别为72.9%、69.7%、43.6%,放化疗组患者分别为61.1%、37.3%、32.6%,联合治疗组患者分别为60.9%、52.9%、52.9%,3组患者无进展生存率比较,差异无统计学意义(χ²=0.34,P>0.05)。单纯手术组、放化疗组、联合治疗组患者中位总生存时间分别为未达到、60、45个月;单纯手术组患者1、3、5年总生存率分别为87.6%、82.0%、55.1%,放化疗组患者分别为91.3%、57.4%、46.8%,联合治疗组患者分别为87.1%、64.3%、32.2%,3组患者总生存率比较,差异无统计学意义(χ²=0.10,P>0.05)。(2)预后分析。IPTW校正后,多因素分析结果显示:有合并症、行新辅助治疗是影响颈部淋巴结寡转移患者无进展生存时间的独立危险因素(风险比=2.25,2.74,95%可信区间为1.08~5.65,1.49~5.06,P<0.05),行新辅助治疗、寡转移时间≤24个月是影响颈部淋巴结寡转移患者总生存时间的独立危险因素(风险比=2.85,2.08,95%可信区间为1.52~5.34,1.04~4.17,P<0.05)。进一步分析,行新辅助治疗与未行新辅助治疗患者1、3、5年总生存率分别为83.7%、35.3%、16.4%和91.6%、72.6%、56.2%,两者比较,差异有统计学意义(χ²=9.26,P<0.05);寡转移时间≤24个月和>24个月患者1、3、5年总生存率分别为84.9%、53.9%、40.1%和97.8%、80.5%、59.9%,两者比较,差异有统计学意义(χ²=9.20,P<0.05)。
    结论 单纯手术治疗、放化疗、联合治疗食管癌术后颈部淋巴结寡转移患者预后无差异;有合并症是影响颈部淋巴结寡转移患者无进展生存时间的独立危险因素,寡转移时间≤24个月是影响颈部淋巴结寡转移患者总生存时间的独立危险因素,行新辅助治疗是影响颈部淋巴结寡转移患者无进展生存时间和总生存时间的独立危险因素;未行新辅助治疗、寡转移时间>24个月患者预后更佳。

     

    Abstract:
    Objective To investigate the prognosis of patients with cervical lymph node oligometastasis after esophageal cancer surgery who underwent different therapeutic modalities.
    Methods The retrospective cohort study was conducted. The clinicopathological data of 5 692 pati-ents with esophageal cancer who were admitted to Sun Yat‑sen University Cancer Center from May 2007 to June 2023 were collected. There were 4 473 males and 1 219 females, aged 61 (rang, 55-66)years. Of 5 692 patients, 127 patients developed cervical lymph node oligometastasis, including 23 cases undergoing surgery alone who were divided into the surgery along group, 74 cases under-going radiotherapy, chemotherapy, or combined chemoradiotherapy who were divided into the chemo-radiotherapy group, 30 cases undergoing surgery combined with radiotherapy, chemotherapy, or chemoradiotherapy who were divided into the combined treatment group, respectively. Measure-ment data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages, and comparisons between groups were performed using the chi‑square test or Fisher exact probability. Baseline differences were adjusted using the inverse probability of treatment weighting (IPTW). The optimal cut‑off value for prognosis was determined using X‑tile software (v3.6.1). Median follow‑up time was calculated using the inverse Kaplan‑Meier method, and missing data were handled by multiple imputations. The Kaplan‑Meier method was used to plot survival curve, and the Log‑rank test was used for survival analysis. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model, and clinicopathological factors with P<0.2 in the univariate analysis were included in the multivariate analysis.
    Results (1) Survival situations. The median follow‑up time for the 127 patients was 47 months, with a median progression‑free survival time of 31 months and a median overall survival time of 53 months. The 1‑, 3‑, and 5‑year progression‑free survival rate were 61.5%, 43.0%, and 36.5%, respectively. The 1‑, 3‑, and 5‑year overall survival rate were 85.6%, 60.2%, and 45.7%, respectively. After IPTW adjustment, the median progression-free survival time of the surgery along group, chemoradiotherapy group, and combined treatment group were 55, 23, and 61 months, respectively. The 1‑, 3‑, and 5‑year progression‑free survival rate of the surgery along group were 72.9%, 69.7%, and 43.6%, versus 61.1%, 37.3%, and 32.6% for the chemoradiotherapy group, and 60.9%, 52.9%, and 52.9% for the combined treatment group, showing no significant difference among the three groups (χ2=0.34, P>0.05). The median overall survival time of the surgery along group, chemoradiotherapy group, and combined treatment group were not reached, 60 months, and 45 months, respectively. The 1‑, 3‑, and 5‑year overall survival rate were 87.6%, 82.0%, and 55.1% for the surgery along group, versus 91.3%, 57.4%, and 46.8% for the chemoradiotherapy group, and 87.1%, 64.3%, and 32.2% for the combined treatment group, showing no significant difference among the three groups (χ2=0.10, P>0.05). (2) Prognosis analysis. After IPTW adjustment, results of multivariate analysis showed that comorbidity and neoadjuvant therapy were independent risk factors affecting progression‑free survival time for patients with cervical lymph node oligometastasis (hazard ratio=2.25, 2.74, 95% confidence interval as 1.08-5.65, 1.49-5.06, P<0.05), and neoadjuvant therapy and oligometastasis occurring ≤24 months were independent risk factors affecting overall survival time for patients with cervical lymph node oligometastasis (hazard ratio=2.85, 2.08, 95% confidence interval as 1.52-5.34, 1.04-4.17, P<0.05). Results of further analysis showed that the 1‑, 3‑, and 5‑year overall survival rate were 83.7%, 35.3%, and 16.4% for patients with neoadjuvant therapy, versus 91.6%, 72.6%, and 56.2% for patients without neoadjuvant therapy, showing a significant difference between them (χ2=9.26, P<0.05). The 1‑, 3‑, and 5‑year overall survival rate were 84.9%, 53.9%, and 40.1% for patients with oligometastasis occurring ≤24 months, versus 97.8%, 80.5%, and 59.9% for patients with oligometastasis occurring>24 months, showing a signifi-cant difference between them (χ²=9.20, P<0.05).
    Conclusions There was no significant difference in prognosis of patients with cervical lymph node oligometastasis after esophageal cancer surgery who underwent surgery alone, chemoradiotherapy or combined treatment. Comorbidity is an inde-pendent risk factor affecting progression‑free survival time for patients with cervical lymph node oligometastasis, oligometastasis occurring ≤24 months is an independent risk factor affecting overall survival time, and neoadjuvant therapy is an independent risk factor affecting both progression‑free survival time and overall survival time.

     

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