术前新辅助化疗对局限期小细胞肺癌预后的影响研究

摘要

Objective To evaluate the effect of preoperative neoadjuvant chemotherapy on the prognosis of limited _stage small cell lung cancer(LD-SCLC). Methods From January 1990 to December 2012,we enrolled 119 LD-SCLC patients who underwent thoracotomy or thoracoscopic surgery in Tianjin Chest Hospital. Among them,39 patients who were diagnosed as SCLC by cytological/ histological pathological diagnosis were enrolled as preoperative neoadjuvant chemotherapy group( group A),and 80 patients who were not definitely diagnosed were enrolled as direct surgery group( group B). Group A was administrated with cisplatin plus etoposide chemotherapy for two periods with 21 days in each period,and received comprehensive reexamination to evaluate the efficacy;the patients who could tolerate surgery underwent excision and continued to take cisplatin plus etoposide chemotherapy for 4 periods after the surgery. Group B underwent excision directly and took cisplatin plus etoposide chemotherapy for 6 periods one months after surgery. Kaplan _ Meier method was used to conduct survival analysis,Log _ rank method was used to compare the survival rate,and Cox proportional hazards regression model was used to analysis the influencing factors for prognosis. Results Among 119 patients,patients of different genders,ages,smoking index,surgical methods and tumor sites were not significantly different in prognosis(P > 0. 05);patients with different TNM stages and treatment methods were significantly different in prognosis(P < 0. 05). The results of Cox proportional hazards regression model showed that TNM staging and treatment methods were influencing factors for the prognosis of LD-SCLC patients( P < 0. 05). In group A,the number of patients at TNM stage Ⅰ,Ⅱ and Ⅲ was 7,19 and 13 respectively,and in group B,the number of patients was 9, 39 and 32 respectively. The two groups were not significantly different in the survival rates of patients at stage Ⅰ(χ2 = 0. 042,P= 0. 838);the two groups were not significantly different in the survival rates of patients at stage Ⅱ(χ2 = 1. 084,P = 0. 298);the two groups were significantly different in the survival rates of patients at stage Ⅲ( χ2 = 5. 966,P = 0. 015). Among 45 patients at stage Ⅲ,patients with different ages,surgical methods and tumor sites were not significantly different in prognosis(P> 0. 05),and patients with different genders,smoking index and treatment methods were significantly different in prognosis(P< 0. 05). Cox proportional hazards regression model showed that treatment methods was an influencing factor for the prognosis of patients at stage Ⅲ( P < 0. 05). In group A,there were 26 patients who had CR + PR and 13 patients who had SD;the remission rate was 66. 7% (26 / 39). CR + PR patients and SD patients were significantly different in the survival rates( χ2= 4. 309,P = 0. 038). Among patients at stage Ⅲ in group A,there were 7 patients who reached CR + PR and 6 patients who reached SD;CR + PR patients and SD patients were significantly different in the survival rates( χ2 = 4. 772,P = 0. 029). Conclusion Preoperative neoadjuvant chemotherapy has no significant influence on the prognosis of LD-SCLC patients at stage Ⅰand Ⅱ,whereas it can improve the postoperative survival rate of patients at stage Ⅲ and bring marked benefit for the survival of patients who reach CR + PR through preoperative neoadjuvant chemotherapy.%目的：评价术前新辅助化疗对局限期小细胞肺癌（LD-SCLC）预后的影响。方法选取1990年1月—2012年12月天津市胸科医院收治的行开胸手术或胸腔镜手术的LD-SCLC患者119例，其中39例患者术前经细胞学或组织学病理诊断为 SCLC，作为术前新辅助化疗组（A 组）；80例患者术前未获得明确病理，作为直接手术组（B 组）。A 组行2个周期的足叶乙甙加顺铂化疗，每21 d 为1个周期，1个月后全面复查进行疗效评估，身体状况可以耐受手术者予以手术切除，术后1个月继续予以足叶乙甙加顺铂方案化疗4个周期。B 组直接行手术切除，术后1个月予以足叶乙甙加顺铂方案化疗6个周期。应用 Kaplan _ Meier 方法进行生存分析，Log-rank 检验比较生存率，Cox 比例风险回归模型分析影响预后的因素。结果119例患者中，不同性别、年龄、吸烟指数、手术方式、肿瘤位置者预后比较，差异均无统计学意义（P >0.05）；不同 TNM 分期、治疗方式者预后比较，差异有统计学意义（ P <0.05）。Cox 比例风险回归模型结果显示，TNM 分期和治疗方式是影响LD-SCLC患者预后的影响因素（P <0.05）。A 组中 TNM 分期Ⅰ期7例，Ⅱ期19例，Ⅲ期13例；B 组分别为9、39、32例。Ⅰ期患者中，两组生存率比较，差异无统计学意义（χ2=0.042，P =0.838）；Ⅱ期患者中，两组生存率比较，差异无统计学意义（χ2=1.084，P =0.298）；Ⅲ期患者中，两组生存率比较，差异有统计学意义（χ2=5.966，P =0.015）。45例Ⅲ期患者中，不同年龄、手术方式、肿瘤位置者预后比较，差异无统计学意义（ P >0.05）；不同性别、吸烟指数、治疗方式者预后比较，差异有统计学意义（ P <0.05）。Cox 比例风险回归模型结果显示，治疗方式是影响Ⅲ期患者预后的影响因素（P <0.05）。A 组化疗后达到完全缓解（CR）+部分缓解（PR）者26例，稳定（SD）者13例，缓解率为66.7%（26/39）。CR + PR 者与 SD 者生存率比较，差异有统计学意义（χ2=4.309，P =0.038）。A 组Ⅲ期者中达到 CR + PR 7例，SD 6例，CR + PR 者与 SD 者生存率比较，差异有统计学意义（χ2=4.772，P =0.029）。结论术前新辅助化疗对于Ⅰ期和Ⅱ期LD-SCLC患者预后没有明显影响，而对于Ⅲ期LD-SCLC患者可以提高其术后生存率，并且经过术前新辅助化疗后达到 CR + PR 的患者生存获益。