不同放化疗方案对局部晚期鼻咽癌患者早期生存结果的影响

Effects of Different Chemoradiotherapy Regimens on Early Survival Outcomes in Patients with Locally Advanced Nasopharyngeal Carcinoma

目的比较局部晚期鼻咽癌患者采用EPF(表柔吡星、顺铂及氟尿嘧啶)诱导化疗联合CNRT(放疗同步尼妥珠单抗)方案或DPF(多西他赛、顺铂及氟尿嘧啶)诱导化疗联合CCRT(同步放化疗)方案的早期生存结果差异。方法收集2010年3月-2017年9月我院收治的局部晚期鼻咽癌(Ⅲ期至Ⅳb期)患者,主要研究终点为无疾病生存(disease-free survival, DFS),次要研究终点包括远处无转移生存(distant metastasis-free survival, DMFS)、局部无复发生存(local recurrence-free survival, LRFS)、总生存(overall survival, OS)以及治疗相关不良反应。采用倾向性评分匹配平衡两组间临床特征的差异。采用Kaplan-Meier法和log-rank检验比较两组的生存差异。采用多因素Cox比例风险模型筛选潜在的独立预后因素。结果经匹配后,共纳入153例患者,其中EPF联合CNRT组51例,DPF联合CCRT组102例。在2年无进展生存(82.4%vs. 85.3%,P=0.880)、LRFS(100.0%vs. 92.1%,P=0.278)、DMFS(82.3%vs. 88.2%,P=0.120)、OS(88.2%vs. 96.0%,P=0.410)方面,EPF联合CNRT组与DPF联合CCRT组相比无明显差异。治疗方案(EPF联合CNRT与DPF联合CCRT)不是DFS的独立预后因素。亚组分析中,在T3〔风险比(hazard ratio, HR)=0.174,95%置信区间0.031~0.959,P=0.045〕、N1/N2(HR=0.432,95%置信区间0.197~0.946,P=0.036)、男性(HR=0.437,95%置信区间0.195~0.978, P=0.044)人群中,EPF联合CNRT方案相较于DPF联合CCRT方案可减少病情进展风险。同步放疗期间,在3~4级中性粒细胞减少方面,EPF联合CNRT组较DPF联合CCRT组发生率低(P=0.007)。结论与DPF联合CCRT方案相比,EPF联合CNRT方案可带来相似的生存获益,但T3、N1/N2、男性局部晚期鼻咽癌患者可能从EPF联合CNRT治疗方案中获益,且耐受性良好。

Objective To compare the early survival outcomes of patients with locally advanced nasopharyngeal carcinoma received EPF(epirubicin, cisplatin and fluorouracil) induced chemotherapy combined with concurrent nimotuzumab with radiotherapy(CNRT) or DPF(docetaxel, cisplatin and fluorouracil) induced chemotherapy combined with concurrent chemoradiotherapy(CCRT). Methods Patients with locally advanced nasopharyngeal carcinoma(stage Ⅲ to ⅣB) from March 2010 to September 2017 were included. The primary endpoint was disease-free survival(DFS). The secondary endpoints were distant metastasis-free survival(DMFS), local recurrencefree survival(LRFS), and overall survival(OS). Propensity score matching was used to balance the differences in clinical characteristics between the two groups. Kaplan-Meier method and log-rank test were used to compare the survival differences between the two groups. Multivariate Cox proportional hazards model was used to identify potential prognostic factors. Results After matching, a total of 153 patients were enrolled, including 51 patients in the EPF combined with CNRT group and 102 patients in the DPF combined with CCRT group. There was no difference in 2-year DFS(82.4% vs. 85.3%, P=0.880), OS(88.2% vs. 96.0%, P=0.410), LRFS(100.0% vs. 92.1%, P=0.278), and DMFS(82.3%vs. 88.2%, P=0.120) between EPF combined with CNRT group and DPF combined with CCRT group. Treatment regimen(EPF combined with CNRT vs. DPF combined with CCRT) was not an independent prognostic factor of DFS(hazard ratio(HR)=0.530, P=0.075). In the subgroup analyses, EPF combined with CNRT could reduce the risk of disease progression in T3(HR=0.174, P=0.045), N1/N2(HR=0.432, P=0.036), and male patients(HR=0.437, P=0.044). During concurrent radiotherapy, the incidence of grade 3-4 neutropenia in EPF combined with CNRT was significantly lower than that of DPF combined with CCRT(P=0.007). Conclusion EPF combined with CNRT regimen is similar to DPF combined with CCRT regimen in survival outcomes, but the patients with T3, N1/N2, and male nasopharyngeal carcinoma may benefit from EPF combined with CNRT regimen.