小细胞肺癌预防性脑照射后脑转移高危因素研究

发布时间：2018-08-15 19:28

【摘要】：目的小细胞肺癌(small cell lung cancer,SCLC)患者虽然进行了预防性脑照射(prophylactic cranial irradiation,PCI),但是有部分仍会发生脑转移,导致其容易发生脑转移的危险因素尚不明确。本文旨在研究小细胞肺癌预防性脑照射后发生脑转移的高危因素。方法收集本院2003年7月-2014年6月间收治的接受过预防性脑照射的小细胞肺癌患者,分析其临床特征。采用Kaplan-Meier法计算无脑转移生存期(brain metastases-free survival,BMFS)、无颅外进展生存期(extracranial progression-free survival,ECPFS)、无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。采用单因素和多因素Cox回归分析脑转移的影响因素。结果共有175例符合纳入标准,中位年龄为55岁(范围,29-76岁),其中,36例(20.6%)出现了脑转移。中位随访时间为42.1个月。175例中,单因素分析显示,TNM分期(p=0.009,HR=2.525,95%CI 1.259-5.064),胸部放疗方式(p=0.023,HR=2.171,95%CI1.111-4.243)与脑转移显著相关。使用TNM分期时,多因素分析表明,胸部放疗方式(p=0.014,HR=2.748,95%CI 1.227-6.157)是脑转移的独立预后因素,TNM分期有独立预后趋势(p=0.073,HR=2.119,95%CI 0.932-4.821)。使用两期分期法分期时,多因素分析显示,胸部放疗方式(p=0.026,HR=2.448,95%CI 1.116-5.372)仍是脑转移的独立预后因素,但两期分期呈阴性(p=0.280)。两期分期法与脑转移、无颅外进展生存、无进展生存及总生存(p0.05)均无明显相关性。但TNM分期与脑转移(p=0.009,HR=2.525,95%CI 1.259-5.064)、无颅外进展生存(p=0.006,HR=1.786,95%CI 1.177-2.712)、无进展生存(p=0.005,HR=1.795,95%CI 1.193-2.702)及总生存(p=0.010,HR=2.002,95%CI 1.180-3.395)均显著相关。有症状脑转移患者比无症状脑转移患者生存期显著缩短(中位总生存期:28.2个月比36.3个月,p=0.002)。结论胸部放疗方式、TNM分期是小细胞肺癌预防性脑照射后脑转移的独立危险因素。胸部加速超分割放疗及IIIB-IV期患者更容易发生脑转移。小细胞肺癌患者预防性脑照射后仍应定期进行颅脑影像学检查,尤其是具有预防性脑照射后脑转移高危因素的患者,以便早期发现脑转移,从而提高总生存。TNM分期相较于两期分期法具有更好的预后指导价值。我们建议目前的两期分期法可以进一步修改完善为:局限期:指TNM分期为IA-IIIA的患者;广泛期:指TNM分期为IIIB-IV期的患者。但这些结论还需要更多大型的临床研究进一步证实。目的比较胸部常规分割放疗和加速超分割放疗对小细胞肺癌预防性脑照射后脑转移发生率的影响。方法回顾性分析两家医院中接受过胸部常规分割放疗或加速超分割放疗及化疗和预防性脑照射的小细胞肺癌患者。采用倾向性评分匹配法控制混杂因素。研究的主要终点是脑转移发生率,次要终点是局部复发率、无进展生存期和总生存期。脑转移发生率、局部复发率采用竞争性风险模型进行分析,无进展生存期和总生存期采用Kaplan-Meier法和Cox法进行分析。结果在2003-2014年间,总共有359例接受过预防性脑照射,其中303例符合纳入条件。进行匹配分析后,272例匹配成功(常规分割组192例,加速超分割组80例)。两组患者匹配前后临床特点均衡可比。中位随访时间为28.8个月(范围,3.9-104.9个月),其中166例(61%)死亡,52例(18.8%)出现脑转移,158例(58%)出现颅外进展,112例(41.2%)出现局部复发。常规分割组的3年脑转移发生率为13.0%,加速超分割组为31.8%(p=0.003,HR=2.280,95%CI 1.320-3.920)。常规分割组的3年局部复发率为36.9%,加速超分割组为41.7%(p=0.790,HR=1.060,95%CI 0.710-1.570)。常规分割组的3年总生存率为52.8%,加速超分割组为49.1%(p=0.502,HR=1.120,95%CI 0.804-1.561)。常规分割组的3年无进展生存率为33.2%,加速超分割组为24.8%(p=0.202,HR=1.211,95%CI 0.903-1.626)。两组的放疗副反应发生率差异无统计学意义。结论对预防性脑照射的小细胞肺癌患者,胸部加速超分割放疗组相较于常规分割放疗组虽然在局部复发率、总生存率和无进展生存率方面的差异无统计学意义,但是会增加脑转移发生率。本结论还有待进一步研究加以明确。
[Abstract]:Objective Although patients with small cell lung cancer (SCLC) received prophylactic cranial irradiation (PCI), some of them still suffered from brain metastasis. The risk factors of brain metastasis in SCLC are still unclear. Methods The clinical features of patients with small cell lung cancer who received prophylactic brain irradiation from July 2003 to June 2014 were analyzed. Brain metastases-free survival (BMFS) and extracranial progression-free survival (ECPFS) were calculated by Kaplan-Meier method. Univariate and multivariate Cox regression was used to analyze the factors influencing brain metastasis. Results A total of 175 patients met the inclusion criteria. The median age was 55 (range, 29-76 years), of which 36 (20.6%) had brain metastasis. The median follow-up time was 42.1 months.175. Univariate analysis showed that TNM staging (p = 0.009, HR = 2.525, 95% CI 1.259-5.064), chest radiotherapy (p = 0.023, HR = 2.171, 95% CI 1.111-4.243) were significantly associated with brain metastasis. Multivariate analysis showed that chest radiotherapy (p = 0.026, HR = 2.448, 95% CI 1.116 - 5.372) was still an independent prognostic factor for brain metastasis, but the two-stage staging was negative (p = 0.280). There was no significant correlation between TNM staging and brain metastastasis (p = 0.009, HR = 2.525, HR = 2.525, 95% CI 1.259-5.064), extracranial progression-free survival (p = 0.006, HR = 1.786, 95% CI 1.786, 95% CI 1.177-2.177-2.712), progression-free survival (p = 0.005, HR = 1.795, 1.795, 95% CI 1.193-2.193-2.702) and total survival (p = 0.010, HR = 2.000, HR = 2.002, 2.002, 95% CI 1.180 1.180, 95% CI 1.180 1.1.180-1.180-1.180-1.Symptomatic brain metastasis Patients with asymptomatic brain metastases had significantly shorter survival (median overall survival: 28.2 months vs 36.3 months, P = 0.002). Conclusion Chest radiotherapy and TNM staging were independent risk factors for brain metastasis after brain irradiation in small cell lung cancer. It is suggested that the present two-stage staging method should be further modified to improve the prognostic value of TNM staging compared with the two-stage staging method. Objective To compare the effects of conventional fractionated radiotherapy and accelerated hyperfractionated radiotherapy on the incidence of brain metastasis in small cell lung cancer after preventive brain irradiation. A retrospective analysis was made of patients with small cell lung cancer who had received conventional fractionated radiotherapy or accelerated hyperfractionated radiotherapy plus chemotherapy and prophylactic brain irradiation in two hospitals.Tendency score matching was used to control confounding factors.The primary endpoint of the study was the incidence of brain metastasis, the secondary endpoint was the local recurrence rate, progression-free survival and overall survival. The incidence of brain metastasis and local recurrence were analyzed by competitive risk model, and the progression-free survival and overall survival were analyzed by Kaplan-Meier and Cox methods. The median follow-up time was 28.8 months (range, 3.9-104.9 months), of which 166 (61%) died, 52 (18.8%) had brain metastases, 158 (58%) had extracranial progression, and 112 (41.2%) had local recurrence. The 3-year local recurrence rate was 36.9% in the conventional fractionation group and 41.7% in the accelerated hyperfractionation group (p = 0.790, HR = 1.060, 95% CI 0.710-1.570). The overall 3-year survival rate was 52.8% in the conventional fractionation group and 49.1% in the accelerated hyperfractionation group (p = 0.502, HR = 1.120, 95% CI 0.804-1.561). The 3-year progression-free survival rate was 33.2% in group A and 24.8% in group B (p = 0.202, HR = 1.211, 95% CI 0.903-1.626). There was no significant difference in the incidence of side effects between the two groups. There was no significant difference in survival rate and progression-free survival rate, but it increased the incidence of brain metastasis.
【学位授予单位】：济南大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

【相似文献】