诱导化疗治疗≥60岁老年局部晚期鼻咽癌患者的疗效:一项单中心回顾性研究

Efficacy of Induction Chemotherapy for Elderly Patients(≥60 Years Old)with Locoregionally Advanced Nasopharyngeal Carcinoma:A Single-Center Retrospective Study

目的:在调强放射治疗时代,分析诱导化疗治疗≥60岁老年局部晚期鼻咽癌(locoregionally advanced nasopharyngeal carcinoma,LA-NPC)患者的疗效,并从中明确诱导化疗的获益人群和最佳周期数。方法:2010年1月至2020年12月期间,中国人民解放军西部战区总医院共有199例确诊的≥60岁老年LA-NPC患者入组研究,按照治疗方式分为诱导化疗组和非诱导化疗组。两组患者根据年龄、性别、身体质量指数、EB病毒感染状态、T分期、N分期和PGTVnx进行2:1倾向性评分匹配(propensity score matching,PSM)。主要研究终点为无进展生存期(progression-free survival,PFS)。利用Kaplan-Meier方法计算PFS、总生存率(overall survival,OS)、无远处转移生存率(distant metastasis-free survival,DMFS)和无局部复发生存率(local recurrence free survival,LRFS),Log-rank检验比较两组间生存结果的差异。利用COX比例风险回归模型单因素和多因素分析明确影响PFS的相关因素。分析诱导化疗与诱导化疗周期数对不同N分期老年LA-NPC患者的疗效影响。结果:PSM后,诱导化疗组患者87例,非诱导化疗组患者54例。生存分析结果显示,诱导化疗并未改善总体和匹配后≥60岁老年LA-NPC患者的PFS(HR=0.728,95%CI:0.468~1.132,P=0.153;HR=0.757,95%CI:0.464~1.235,P=0.260)、OS(HR=0.673,95%CI:0.421~1.077,P=0.096;HR=0.728,95%CI:0.433~1.225,P=0.228)、DMFS(HR=0.696,95%CI:0.389~1.245,P=0.216;HR=0.692,95%CI:0.367~1.305,P=0.249)和LRFS(HR=1.402,95%CI:0.385~5.100,P=0.606;HR=1.337,95%CI:0.345~5.179,P=0.672)。经PSM后,多因素分析结果显示,N分期(N0-1vs N2-3)和PGTVnx(<66 Gy vs≥66 Gy)与老年LA-NPC患者的PFS显著相关。根据N分期,将匹配后的患者分别纳入T_(3-4)N_(0-1)M_(0)组和T_(1-4)N_(2-3)M_(0)组。亚组生存分析结果显示,诱导化疗能显著提高T1-4N2-3M0期老年NPC患者的PFS(HR=0.562,95%CI:0.315~1.004,P=0.046)和OS(HR=0.532,95%CI:0.288~0.985,P=0.040),但并未改善DMFS(HR=0.606,95%CI:0.299~1.227,P=0.155)、LRFS(HR=0.930,95%CI:0.154~5.606,P=0.937)和T3-4N0-1M0期患者的生存结局。此外,与1~2周期的诱导化疗相比,≥3周期的诱导化疗具有提高T1-4N2-3M0期老年LA-NPC患者DMFS的趋势(HR=0.179,95%CI:0.024~1.363,P=0.060)。结论:经PSM后,诱导化疗并未对总体≥60岁老年LA-NPC患者带来生存获益,但能显著提高T1-4N2-3M0期患者的PFS和OS,且≥3周期的诱导化疗相较于1~2周期具有改善这个亚组人群DMFS的趋势。

Objective:This study aims to investigate the efficacy of induction chemotherapy(IC)for elderly patients(≥60 years old)with locoregionally advanced nasopharyngeal carcinoma(LA-NPC)in the era of intensity-modulated radiation therapy(IMRT),select the beneficiaries from IC and identify optimal number of cycles of IC.Methods:From January 2010 to December 2020,a total of 199 elderly(≥60 years old)LA-NPC patients were collected at the General Hospital of Western Theater Command of PLA,and classified into IC group or non-IC group by the treatments they received.Propensity score matching(PSM)was performed with a ratio of 2:1 according to age,sex,body mass index,Epstein-Barr virus infection status,T and N classifications and PGTVnx.Progression-free survival(PFS)was the primary endpoint.Kaplan-Meier survival curves were applied to evaluate the PFS,overall survival(OS),distant metastasis-free survival(DMFS)and local recurrence-free survival(LRFS),and log-rank test was utilized to assess the differences between groups.Univariate and multivariate Cox regression analyses were preformed to identify factors affecting PFS.Effects of IC and different IC cycles on prognosis of elderly LA-NPC patients with different N stages were analyzed.Results:87 patients were assigned to IC group and 54 to non-IC group after PSM.In the whole elderly LA-NPC patient and the propensity-matched cohort,no significant differences were observed between IC and non-IC groups in PFS(HR=0.728,95%CI:0.468~1.132,P=0.153;HR=0.757,95%CI:0.464~1.235,P=0.260),OS(HR=0.673,95%CI:0.421~1.077,P=0.096;HR=0.728,95%CI:0.433~1.225,P=0.228),DMFS(HR=0.696,95%CI:0.389~1.245,P=0.216;HR=0.692,95%CI:0.367~1.305,P=0.249)and LRFS(HR=1.402,95%CI:0.385~5.100,P=0.606;HR=1.337,95%CI:0.345~5.179,P=0.672).Multivariate analysis indicated that N stage(N_(0-1)vs N_(2-3))and PGTVnx(<66 Gy vs≥66 Gy)were correlated to PFS after PSM.Elderly LA-NPC patients after PSM were classified into T_(3-4)N_(0-1)M_(0)groups or T_(1-4)N_(2-3)M_(0)group by the N stage.Subgroup analysis showed in the T_(1-4)N_(2-3)M_(0)group,IC led to significantly higher PFS(HR=0.562,95%CI:0.315~1.004,P=0.046)and OS(HR=0.532,95%CI:0.288~0.985,P=0.040),but didn't improve DMFS(HR=0.606,95%CI:0.299~1.227,P=0.155)and LRFS(HR=0.930,95%CI:0.154~5.606,P=0.937).While in the T_(3-4)N_(0-1)M_(0)group,PFS,OS,DMFS and LRFS were not significantly improved by IC.The≥3 cycles IC regimen was potentially correlated to better DMFS than the 1~2 cycles IC regimen for elderly patients in the T_(1-4)N_(2-3)M_(0)group(HR=0.179,95%CI:0.024~1.363,P=0.060).Conclusion:After PSM,IC does not lead to better survival results of elderly LA-NPC patients(≥60 years old)can't benefit from IC.However,in the T_(1-4)N_(2-3)M_(0)group,IC leads to significantly higher PFS,OS,and≥3 cycles IC regimen can potentially improve DMFS.