可手术非小细胞肺癌多学科治疗对预后因素的影响

Analysis of prognostic factors in patients with non-small cell lung cancer treated by surgery and chemotherapy

背景与目的：肺癌为当前最常见的恶性肿瘤之一，其中非小细胞肺癌（NSCLC）占绝大多数，而且大部分在诊断时已属晚期，对Ⅲ期估计不能全部切除的NSCLC，通过新辅助化疗可以使原发肿瘤缩小，提高手术切除率，消灭微小转移，延长NSCLC患者的生存率。所以本文目的在于探讨先化疗后手术对NSCLC预后因素的影响。方法：回顾性收集我院1995年-1997年先化疗后手术的Ⅰ-Ⅲ期NSCLC住院病例98例，其中Ⅰ期35例、Ⅱ期21例、Ⅲ期42例，手术前先进行1和2周期化疗的分别为83例和15例，化疗方案为MVP、MOP或MAP等，化疗缓解率（RR），部分缓解（PR）45例，稳定（SD）53例，手术方式为肺叶切除或全肺切除，分站摘除所有肉眼可见的胸内淋巴结，手术病理提示鳞癌35例、腺癌48例、混合型9例、其他6例，术后化疗2—3个周期（1996年后Ⅰ期NSCLC术后未作化疗）。对先化疗后手术的98例NSCLC患者的临床资料，随访5年以上，运用Kaplan—Meier生存曲线分析，Log Rank检验和Cox多因素分析，对影响预后的因素进行单因素和多因素分析。结果：98例先化疗后手术NSCLC患者的中位随访时间为41．2月，其中36例存活，62例死亡。98例NSCLC患者的1年、3年、5年生存率分别是88．78％、49．63％、18．46％；Ⅰ、Ⅱ、Ⅲ期5年生存率分别为33．23％、20．26％、5．52％（P=0．0002）；N0、N1、N2组5年生存率分别为35．49％、19．08％、4．90％（P=0．0004）。先化疗后手术NSCLC总分期越晚预后越差；术前末次化疗距手术时间为1月内预后好；全肺切除较肺叶切除预后差；肺门固定较肺门活动预后差；胸内淋巴结（＋）预后差，N1较N0预后差，N2较N1预后更差；其它预后不良因素包括肿块侵犯大血管、脏器、胸壁、心包，术中出血量≥400ml，腺癌；化疗后肿块纤维化预后好。本组结果还显示：术前化疗2周期较术前化疗1周期预后好；肿瘤坏死和术后未行化疗者预后差。结论：影响先化疗后手术NSCLC患者的预后因素为：总分期、术前末次化疗距手术时间、术式、肺门活动度、胸内淋巴结、肿块侵犯部位、术中出血量、病理类型及肿瘤纤维化。术前化疗次数、肿瘤坏死和术后化疗亦可能是先化疗后手术NSCLC预后的影响因素。

Background and Purpose： Lung cancer is the most malignant tumour in the world. Its incidence is growing and NSCLC is predominent（80%） in lung cancer. Most patients with lung cancer were diagnosed in late stages. The tumour could be shrunk by neoadjuvant chemotherapy when the case with stage Ⅲ NSCLC was considered not possible for radical operated neoadjuvant chemotherapy may lead to the following, operation could be improved, micrometastasis could be annihilated and survival could be extended. Objective of this paper was to analyse the prognostic factors for survival in patients treated by surgery and chemotherapy for NSCLC. Methods： 98 cases of neoadjuvant chemotherapy combined with surgery for NSCLC, stage Ⅰ- Ⅲ, were collected retrospectively in our hospital from 1995 to 1997. 35 cases were stage Ⅰ. 21 cases were stage Ⅱ. 42 cases were stage Ⅲ. 83 cases had 1 cycle of chemotherapy pre-operatively. 15 cases had 2 cycles chemotherapy pre-operatively. Regimes of chemotherapy were MVP, MOP and MAP et al. Response rate （RR） of chemotherapy was： 45 cases had partial response （PR） and 53 cases were stable disease （SD）. Operative mode was lobectomy and pneumectomy with lymph nodes dissection. Pathologic type was squamous, adeno, adeno-squamous and others. All the patients were treated by chemotherapy for two or three cycles after surgery except for the patients in stage [ in 1996 - 1997. After being followed-up for more than 5 years, data were examined using life table, Kaplan-Meier method, Log Rank statistic and Cox-mantel test. The possible factors affecting survival were tested with univariate and multivariate analysis.Results： The median followed-up time of 98 cases for NSCLC was 41.2 months. 36 cases were alive. 62 cases were dead. The 1-, 3-, 5-year survival rate of 98 cases for NSCLC was 88.78% ,49.63% and 18.46%. The 5-year survival rates of stage Ⅰ,Ⅱ andⅢ were 33.23% ,20.26% and 5.52% respectively（P =0. 0002）. The 5-year survival rates of N0 ,N1 ,N2 were 35.49% ,19.08% and 4.90% respectively（P = 0.0004）. In the 98 cases of NSCLC, better prognosis was correlated with earlier stage. The prognosis was better if the period from last chemotherapy before operation to operation was no more than 1 month. The prognosis of lobectomy, lung hila activity, thorax lymph nodes negativity and squamous cancer was better. The prognosis was poorer if the tumor had invaded big vessels, viscera, chest wall, pericardium and quantity bleeding during≥400ml. The prognosis was better if the tumor was fibrotic. The prognosis of 2 cycles of chemotherapy pre-operatively might be better than 1 cycle. The prognosis of tumor necrosis was poorer and the prognosis of chemotherapy post-operatively was better. Conclusions： The main prognostic factors affecting survival in patients treated by surgery and chemotherapy for NSCLC was stage, the period from last chemotherapy before operation to operation, operation mode, lung hila activity, thorax lymph nodes, site of tumor invasion, bleeding quantity, pathologic type, tumor fibrosis and necrotis, cycles chemotherapy pro-operation and chemotherapy post-operation.