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Large Cell Neuroendocrine Carcinoma of the Lung:Outcomes after Surgical Resection and Prognostic Factors
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摘要:
目的 探讨肺大细胞神经内分泌癌(large cell neuroendocrine carcinoma, LCNEC)的临床特点及手术治疗经验并分析相关预后因素。 方法 2000年1月至2014年1月在北京协和医院诊治并经手术病理证实为LCNEC的患者35例, 其中男性29例, 女性6例, 回顾性总结其临床资料, 分析以手术为主综合治疗的结局并分析相关预后因素。 结果 35例患者就诊时中位年龄为63岁(47~77岁), 中位病程为2个月(1~14个月)。临床症状不具特异性, 术前活检病理难以明确诊断。手术方法根据肿瘤具体情况采用开胸或胸腔镜下肺叶切除及淋巴结清扫。术后病理分期Ⅰ期12例, Ⅱ期7例, Ⅲ期13例, Ⅳ期3例。23例患者行辅助治疗。患者中位生存期17个月(95% CI:11.4~22.6), 1、3、5年生存率分别为60.6%、29.0%、24.8%。肿瘤分期对LCNEC患者生存期存在显著影响(Cox多因素分析HR 2.608, 95% CI:1.572~4.327, P=0.000)。 结论 LCNEC为一种罕见的侵袭性强、预后差的恶性肿瘤, 分期是影响其预后的独立危险因素, 对于早期病变尤其是Ⅰ、Ⅱ期病变采用手术为主的综合治疗可获得较好的治疗效果。 Abstract:Objective To investigate the clinical manifestations, outcomes after surgical management, and prognostic factors of large cell neuroendocrine carcinoma (LCNEC) of the lung. Methods We retrospectively analyzed the data of 35 consecutive cases (29 males, 6 females) of LCNEC of the lung surgically treated and pathologically confirmed in Peking Union Medical College Hospital from January 2000 to January 2014. Their outcomes after receiving surgery-based comprehensive therapy and related prognostic factors were explored. Results The median age of patients was 63(47-77)years and the median duration of disease was 2(1-14)months. No specific symptom was found and preoperative pathological diagnosis was not definitive. Surgical methods included open or thoracoscopic lobectomy and lymph node dissection based on the specific conditions of tumor in each case. Postoperative pathological staging showed stage Ⅰ in 12 cases, stage Ⅱ in 7, stage Ⅲ in 13, and stage Ⅳ in 3. Twenty-three patients received adjuvant therapy. Median survival was 17 months[95% confidence interval (CI):11.4-22.6 months]. The 1-year, 3-year, and 5-year survival rates were 60.6%, 29.0%, and 24.8%, respectively. Tumor stage was significantly related with the overall survival (Cox regression analysis, hazard ration=2.608, 95% CI:1.572-4.327, P=0.000). Conclusions LCNEC is a rare malignancy with tremendous aggressiveness and poor prognosis. Stage of tumor may be the independent risk factor affecting the prognosis. Surgery-based comprehensive therapy could achieve good survival for patients of early stages, especially stages Ⅰ and Ⅱ. -
Key words:
- neuroendocrine carcinoma /
- lung /
- surgery /
- prognosis
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表 1 35例肺大细胞神经内分泌癌患者临床资料
项目 数值 年龄(M，岁) 63(47~77) 性别(男/女，例) 29/6 病程(M，月) 2(1~14) 吸烟(是/否，例) 28/7 症状[例(%)] 咳嗽、咳痰 21(60.0) 胸背痛 3(8.6) 发热 2(5.7) 无症状查体发现 9(25.7) 病变类型(周围型/中心型，例) 21/14 手术方式[例(%)] 肺叶切除+淋巴结清扫 24(68.6) 复合肺叶切除+淋巴结清扫 5(14.2) 袖式肺叶切除+淋巴结清扫 3(8.6) 亚肺叶切除+淋巴结清扫 3(8.6) 肿瘤最大径(M，cm) 4(1.2~12.0) TNM分期[例(%)] Ⅰ 12(34.3) Ⅱ 7(20.0) Ⅲ 13(37.1) Ⅳ* 3(8.6) 辅助治疗[例(%)] 无 12(28.6) 化疗 20(62.8) 化疗+放疗 3(8.6) 复合肺叶切除：肺叶+肺叶或肺叶+段切除；亚肺叶切除：肺楔形切除或解剖性肺段切除；*3例Ⅳ期患者为肿瘤胸膜腔播散 
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表 2 肺大细胞神经内分泌癌患者预后因素的Cox多因素分析结果
因素 P值 HR值(95 CI) 病变部位(周围型与中央型) 0.242 0.602(0.257~1.410) 是否行辅助治疗 0.569 1.324(0.504~3.476) 肿瘤分期* 0.000 2.608(1.572~4.327) HR：相对危险度；*肿瘤分期按照连续变量带入Cox多因素分析模型，P=0.000提示差异存在统计学意义，HR为2.608提示分期每提高一期其死亡风险较前一期增加约1.6倍
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