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中华胸部外科电子杂志

中华胸部外科电子杂志 ›› 2020, Vol. 07 ›› Issue (01) : 1 -11. doi: 10.3877/cma.j.issn.2095-8773.2020.01.001

所属专题： 文献；

论著

非小细胞肺癌患者术中发现胸膜播散的预后分析
范力文1, 杨海堂1, 韩轲1, 姚烽1, 赵洋1, 高文1, 赵珩1,†()   
  1. 1. 200030　上海交通大学附属胸科医院胸外科
  • 收稿日期:2020-01-10 出版日期:2020-02-28
  • 通信作者: 赵珩

Prognosis of surgery in the treatment of non-small cell lung cancer with unexpected pleural dissemination

Liwen Fan1, Haitang Yang1, Ke Han1, Feng Yao1, Yang Zhao1, Wen Gao1, Heng Zhao1,†()   

  1. 1. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
  • Received:2020-01-10 Published:2020-02-28
  • Corresponding author: Heng Zhao
  • About author:
    Corresponding author: Zhao Heng, Email:
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引用本文：

范力文, 杨海堂, 韩轲, 姚烽, 赵洋, 高文, 赵珩. 非小细胞肺癌患者术中发现胸膜播散的预后分析[J]. 中华胸部外科电子杂志, 2020, 07(01): 1-11.

Liwen Fan, Haitang Yang, Ke Han, Feng Yao, Yang Zhao, Wen Gao, Heng Zhao. Prognosis of surgery in the treatment of non-small cell lung cancer with unexpected pleural dissemination[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2020, 07(01): 1-11.

目的

评估手术切除肿瘤对非小细胞肺癌(NSCLC)伴恶性胸膜播散患者预后的影响。

方法

收集2011年1月至2015年12月上海市胸科医院NSCLC手术患者的临床资料，将术中意外发现胸膜播散的患者纳入研究。

结果

通过术中或术后病理学检查，共有160例NSCLC患者被诊断为胸膜播散。71例(44.4%)仅行胸膜结节活检(活检组)，89例(55.6%)行原发肿瘤切除术(切除组)。中位无进展生存期(PFS)和总生存期OS)分别为13个月和41个月，3、5年的无进展生存率分别为13.1%和5.7%，总生存率分别为56.0%和28.7%。切除组患者的PFS和OS均明显优于活检组(19个月vs 10个月，P＝0.000；48个月vs 33个月，P＝0.000)。切除组的3、5年无进展生存率和总生存率均高于活检组(20.8% vs 3.2%，10.8% vs 0；67.8% vs 41.0%，37.7% vs 18.2%)。接受亚肺叶切除术与肺叶切除术患者的生存差异无统计学意义(P＝0.34)。单因素和多因素分析结果显示：辅助靶向治疗、无恶性胸腔积液、T1/T2期和N0期是独立的预后因素。

结论

术中诊断为NSCLC伴胸膜播散的患者可通过手术切除原发肿瘤和包括靶向治疗在内的多学科治疗获益。辅助靶向治疗、无恶性胸腔积液、低T分期、低N分期患者的预后较好。在可行的情况下，楔形切除术可能是一个合适的选择，虽然不同手术方式亚组的预后差异无统计学意义，但其创伤更小。

关键词: 胸膜播散, 非小细胞肺癌, 手术治疗, 预后
Objective

To evaluate the effect of surgical resection on the prognosis of non-small cell lung cancer (NSCLC) patients with malignant pleural dissemination (PD).

Methods

Clinical data of consecutive patients who underwent surgeries for NSCLC between January 2011 and December 2015 at Shanghai Chest Hospital were collected. The patients who were found unexpected PD intraoperatively were enrolled in this study.

Results

A total of 160 patients diagnosed with unexpected malignant PD through intraoperatively or postoperatively histological examinations were enrolled in the present study. 71 (44.4%) patients received pleural nodule biopsy only, and 89 (55.6%) received primary tumor resection. The median progression-free survival(PFS) and median overall survival (OS)were respectively 13 months and 41 months. The 3- and 5-year PFS and OS rates for all patients were 13.1%, 5.7% and 56.0%, 28.7%, respectively. In comparison, patients in the resection group had better PFS (19.0 months vs 10.0 months, P < 0.001) and OS (48.0 months vs 33.0 months, P < 0.001) than those in the biopsy group. The 3- and 5-year PFS rates of resection group were higher than biopsy group (20.8% vs 3.2%, 10.8% vs 0). Similar results were found for OS rates(67.8% vs 41.0%, 37.7% vs 18.2%). There was no significant difference in survival between patients with sublobectomy and lobectomy (P = 0.34). Univariate and multivariate analyses showed that adjuvant targeted therapy, absence of malignant pleural effusion (MPE), stage T1/T2, and stage N0 were independent prognostic factors.

Conclusions

NSCLC patients with malignant pleural dissemination diagnosed intraoperatively may be beneficial from surgical resection of main tumor and multidisciplinary adjuvant therapy, especially targeted therapy. Patients with adjuvant targeted therapy, no MPE, lower T stage, and lower N stage may have a better prognosis. Wedge resection tends to be a proper choice if feasible, although there is no difference in survival among different types of resection.

Key words: Pleural dissemination, Non-small cell lung cancer, Surgery, Prognosis
表1 纳入患者的临床资料及分组比较
参数 总体(n＝160) 活检组(n＝71) 切除组(n＝89) P值
平均年龄(岁，±s) 57.1±9.8 57.9±9.2 56.6±10.2 (30-75) 0.39
性别[n(%)] ? ? ? 0.34
? 男性 87 (54.4) 36 (50.7) 51 (57.3) ?
? 女性 73 (45.6) 35 (49.3) 38 (42.7) ?
肿瘤位置[n(%)] ? ? ? 0.77
? 右肺 98 (61.3) 43 (60.6) 55 (61.8) ?
? 左肺 62 (38.7) 28 (39.4) 34 (38.2) ?
吸烟史[n(%)] ? ? ? 0.89
? 是 54 (33.8) 24 (33.8) 30 (33.7) ?
? 否 106 (66.2) 47 (66.2) 59 (66.3) ?
PS [n(%)] ? ? ? 0.31
? 0分 127 (79.4) 54 (76.1) 73 (82.0) ?
? 1分 33 (20.6) 17 (23.9) 16 (18.0) ?
术前血清肿瘤标志物水平[n(%)] ? ? ? 0.002
? 正常 35 (21.9) 7 (9.9) 28 (31.5) ?
? 升高 102 (63.8) 48 (67.6) 54 (60.7) ?
? 未知 23 (14.3) 16 (22.5) 7 (7.8) ?
新辅助治疗[n(%)] ? ? ? 0.08
? 化疗 9 (5.6) 1 (1.4) 8 (9.0) ?
? 放疗 1 (0.6) 0 (0) 1 (1.1) ?
? 否 150 (93.8) 70 (98.6) 80 (89.9) ?
辅助化疗[n(%)] ? ? ? 0.58
? 是 148 (92.5) 67 (94.4) 81 (91.0) ?
? 否 12 (7.5) 4 (5.6) 8 (9.0) ?
靶向治疗[n(%)] ? ? ? 0.11
? 是 90 (56.3) 35 (49.3) 55 (61.8) ?
? 否 57 (35.6) 27 (38.0) 30 (33.7) ?
? 未知 13 (8.1) 9 (12.7) 4 (4.5) ?
放疗[n(%)] ? ? ? 0.15
? 是 53 (33.1) 21 (29.6) 32 (36.0) ?
? 否 76 (47.5) 33 (46.5) 43 (48.3) ?
? 未知 31 (19.4) 17 (23.9) 14 (15.7) ?
表2 手术情况、病理学检测结果及分组资料比较
参数 总体(n＝160) 活检组(n＝71) 切除组(n＝89) P值
手术方式[n(%)] ? ? ? <0.001
? 仅活检 ? 71 (100.0) 0 (0) ?
? 亚肺叶切除 ? 0 (0) 42 (47.2) ?
? 肺叶切除 ? 0 (0) 41 (46.1) ?
? 扩大切除 ? 0 (0) 6 (6.7) ?
手术入路[n(%)] ? ? ? 0.060
? VATS 89 (55.6) 44 (62.0) 45 (50.6) ?
? 开胸手术 71 (44.4) 27 (38.0) 44 (49.4) ?
淋巴结切除方式[n(%)] ? ? ? <0.001
? 无 97 (60.6) 61 (85.9) 36 (40.4) ?
? 淋巴结采样 23 (14.4) 10 (14.1) 13 (14.7) ?
? 系统性淋巴结清扫 40 (25.0) 0 (0) 40 (44.9) ?
手术时间(min，±s) 82.3±37.0 66.3±25.1 95.3±39.7 <0.001
术中出血[n(%)] ? ? ? 0.002
? ≤100 mL 119 (74.4) 61 (85.9) 58 (65.2) ?
? >100 mL 41 (25.6) 10 (14.1) 31 (34.8) ?
术后住院时间(d，±s) 5.7±3.2 5.1±3.6 6.4±2.6 0.008
病理类型[n(%)] ? ? ? 0.130
? 腺癌 137 (85.6) 58 (81.7) 79 (88.8) ?
? 其他 23 (14.4) 13 (18.3) 10 (11.2) ?
肿瘤大小(cm，±s) 3.4±1.5 3.8±1.5 3.1±1.5 0.004
MPE[n(%)] ? ? ? <0.001
? 是 29 (18.1) 20 (28.2) 9 (10.1) ?
? 否 131 (81.9) 51 (71.8) 80 (89.9) ?
MPN[n(%)] ? ? ? <0.001
? 局限性 35 (21.9) 5 (7.0) 30 (33.7) ?
? 弥漫性 119 (74.4) 63 (88.7) 56 (62.9) ?
? 否 6 (3.7) 3 (4.3) 3 (3.4) ?
最佳T分期[n(%)] ? ? ? 0.330
? T1 11 (6.8) 2 (2.8) 9 (10.1) ?
? T2 82 (51.3) 34 (47.9) 48 (53.9) ?
? T3 28 (17.5) 14 (19.7) 14 (15.7) ?
? T4 35 (21.9) 17 (23.9) 18 (20.2) ?
? Tx 4 (2.5) 4 (5.7) 0 (0) ?
最佳N分期[n(%)] ? ? ? <0.001
? N0 45 (28.1) 10 (14.1) 35 (39.3) ?
? N1 33 (20.6) 18 (25.4) 15 (16.9) ?
? N2 69 (43.1) 33 (46.5) 36 (40.4) ?
? N3 7 (4.4) 6 (8.4) 1 (1.1) ?
? Nx 6 (3.8) 4 (5.6) 2 (2.3) ?
图1 切除组与活检组术后总生存率比较
图2 切除组与活检组术后无进展生存率比较
表3 预后因素的单因素分析
参数 PFS _OS
HR (95%CI) P值 HR (95%CI) P值
年龄 ? ? ? ?
? ≤59岁vs >59岁 0.910 (0.661～1.252) 0.561 0.625 (0.427～0.916) 0.015
性别 ? ? ? ?
? 男性vs女性 1.118 (0.813～1.538) 0.493 1.146 (0.783～1.678) 0.482
吸烟史 ? ? ? ?
? 否vs是 0.921 (0.661～1.283) 0.626 0.927 (0.628～1.368) 0.702
体力评分 ? ? ? ?
? 0 vs 1 0.578 (0.398～0.840) 0.004 0.493 (0.321～0.760) 0.001
术前血清肿瘤标志物水平 ? ? ? ?
? 正常vs升高 0.795 (0.526～1.202) 0.276 0.508 (0.298～0.867) 0.011
肿瘤位置 ? ? ? ?
? 左肺vs右肺 0.908 (0.655～1.258) 0.561 1.126 (0.766～1.654) 0.545
辅助化疗 ? ? ? ?
? 是vs否 0.446 (0.241～0.825) 0.008 0.493 (0.216～1.125) 0.086
辅助靶向治疗 ? ? ? ?
? 否vs是 1.209 (0.852～1.716) 0.287 2.404 (1.582～3.654) 0.000
EGFR突变 ? ? ? ?
? 否vs是 1.189 (0.789～1.790) 0.408 2.074 (1.227～3.508) 0.005
原发肿瘤切除 ? ? ? ?
? 否vs是 2.094 (1.503～2.919) 0.000 2.183 (1.488～3.203) 0.000
肿瘤大小 ? ? ? ?
? >3 cm vs ≤3 cm 1.864 (1.319～2.633) 0.000 2.165 (1.410～3.325) 0.000
MPE ? ? ? ?
? 否vs是 0.424 (0.285～0.632) 0.000 0.362 (0.236～0.554) 0.000
MPN ? ? ? ?
? 局限性vs弥漫性 0.824 (0.554～1.227) 0.340 1.000 (0.632～1.582) 1.000
病理类型 ? ? ? ?
? 腺癌vs其他 0.657 (0.416～1.036) 0.068 0.651 (0.391～1.083) 0.096
最佳N分期 ? ? ? ?
? N0 vs N1/N2/N3 0.468 (0.322～0.680) 0.000 0.367 (0.226～0.595) 0.000
最佳T分期 ? ? ? ?
? T1/T2 vs T3/T4 0.590 (0.423～0.822) 0.002 0.582 (0.396～0.857) 0.005
表4 预后因素的多因素分析
参数 PFS OS
HR (95%CI) P值 HR (95%CI) P值
年龄 ? ? ? ?
? ≤59岁vs >59岁 ? ? 0.570 (0.281～1.153) 0.118
PS ? ? ? ?
? 0 vs 1 0.747 (0.497～1.123) 0.160 0.597 (0.287～1.241) 0.167
术前血清肿瘤标志物水平 ? ? ? ?
? 正常vs升高 ? ? 0.779 (0.367～1.651) 0.514
辅助化疗 ? ? ? ?
? 是vs否 0.453 (0.229～0.897) 0.023 ? ?
辅助靶向治疗 ? ? ? ?
? 否vs是 ? ? 2.465 (1.061～5.729) 0.036
EGFR突变 ? ? ? ?
? 否vs是 ? ? 2.146 (0.961～4.793) 0.063
原发肿瘤切除 ? ? ? ?
? 否vs是 1.519 (1.049～2.201) 0.027 1.036 (0.491～2.187) 0.925
肿瘤大小 ? ? ? ?
? >3 cm vs ≤3 cm 1.516 (1.058～2.173) 0.023 1.704 (0.847～3.426) 0.135
MPE ? ? ? ?
? 否vs是 0.541 (0.344～0.849) 0.008 0.365 (0.170～0.783) 0.010
最佳N分期 ? ? ? ?
? N0 vs N1/N2/N3 0.617 (0.414～0.920) 0.018 0.339 (0.145～0.792) 0.012
最佳T分期 ? ? ? ?
? T1/T2 vs T3/T4 0.688 (0.482～0.981) 0.039 0.477 (0.232～0.982) 0.045
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