Analysis Of Long-term Efficacy And Treatment Mode Of Stage Ⅱ Nasopharyngeal Carcinoma

Purpose : To assess the long-term survival and failure pattern of stage II nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy(IMRT),and to explore the factors that affect the prognosis of stage II nasopharyngeal carcinoma.Methods:This study included 190 patients with stage II nasopharyngeal carcinoma initially treated in the Affiliated Cancer Hospital of Nanjing Medical University from2006 to 2015.The number of cases in each clinical subgroup of T1N1,T2N0 and T2N1 was 84,18 and 88,respectively.All patients received radical IMRT and had complete clinical data.The survival curves of overall survival(OS),local relapse-free survival(LRFS),regional relapse-free survival(RRFS),and distant metastasis-free survival(DMFS)were obtained by Kaplan–Meier method.Univariate and multivariate analysis was performed by log-rank test and COX proportional hazard regression model.P <0.05 was considered statistically significant.Results:The 5-year follow-up rate for the whole group was 94.2%,and the median follow-up time was 90 months(13-159 months).The 5-year OS,LRFS,RRFS,and DMFS of stage II nasopharyngeal carcinoma were 92.0%、94.0%、96.2%,and 91.5%,respectively.Among the three clinical subgroups T1N1,T2N0,and T2N1,there was no significant difference in 5-year OS,LRFS,RRFS and DMFS(OS:92.9% vs 100%vs 89.7%,p=0.332;LRFS: 97.5% vs 88.9% vs 91.7%,p=0.168;RRFS: 95.1% vs 100%vs 96.6%,p=0.629;DMFS: 92.9% vs 100% vs 88.4%,p=0.247).Moreover,compared with radiotherapy alone,the addition of chemotherapy did not significantly improve the 5-year OS,LRFS,RRFS,and DMFS of patients with stage II nasopharyngeal carcinoma(OS: 92.5% vs 89.1%,p = 0.535;LRFS: 94.9% vs 88.7 %,p = 0.219;RRFS: 96.8% vs 92.3%,p = 0.272;DMFS: 91.9% vs 89.0%,p = 0.643).Multivariate analysis showed that the maximum diameter of the lymph nodes(HR=3.312,95%CI1.178-9.307,P=0.023)was related to the OS of stage II nasopharyngeal carcinoma.In addition,age(HR=5.431,95 %CI 1.158-25.482,P=0.032)and NLR(HR=6.686,95%CI 1.733-25.790,P=0.006)were considered to be independent prognostic factors for LRFS in stage II nasopharyngeal carcinoma.Conclusions:In the era of intensity-modulated radiotherapy,stage II nasopharyngeal carcinoma can achieve better outcomes,and distant metastasis is the main mode of treatment failure in patients with stage II nasopharyngeal carcinoma.The addition of chemotherapy failed to bring survival benefits to patients with stage II nasopharyngeal carcinoma.Moreover,Maximum lymph node diameter is an independent prognostic factor for OS in stage II nasopharyngeal carcinoma.In addition,age and NLR were independent prognostic factors for LRFS of stage II nasopharyngeal carcinoma.Purpose:The value of induction chemotherapy in stage II nasopharyngeal carcinoma is still controversial.We performed this meta-analysis to evaluate the efficacy of induction chemotherapy combined with radiotherapy versus radiotherapy alone for stage II nasopharyngeal carcinoma.Methods:We have conducted a comprehensive search of published literature through six databases: Embase,Pubmed,Cochrane Library,Wanfang,Weipu and CBM.The literature search was ended in February 2020.The included literatures explored the prognostic differences of patients with stage II nasopharyngeal carcinoma receiving induction chemotherapy combined with radiotherapy versus radiotherapy alone.Outcome indicators include overall survival(OS),locoregional relapse-free survival(LRRFS),distant metastasis-free survival(DMFS),progress-free survival(PFS),and treatment-related acute toxicity.If there is no heterogeneity between studies,the fixed effect model is used,and if there is heterogeneity between studies,the random effect model is used.Sensitivity analysis and subgroup analysis are used to identify the source of heterogeneity.Publication bias was determined by the Begger test.P <0.05 was considered statistically significant.Results : A total of 628 patients with stage II nasopharyngeal carcinoma from 7studies were included in this meta-analysis.The pooled results show that compared with radiotherapy alone,induction chemotherapy combined with radiotherapy cannot improve OS(HR=0.75,95%CI 0.52-1.07,P=0.11),LRRFS(HR=0.91,95%CI0.59-1.40,P=0.67),DMFS(HR = 1.32,95% CI,0.46-3.80,P = 0.61)and PFS(HR =0.75,95% CI 0.50-1.12,P = 0.16)in patients with stage II nasopharyngeal carcinoma,but significantly increased grade 3-4 leukopenia(OR= 8.79,95% CI 2.26-34.20,P =0.002)And grade 3-4 neutropenia(OR = 7.86,95% CI 2.42-25.49,P = 0.0006).The results of the subgroup analysis showed that compared with conventional radiotherapy alone,induction chemotherapy combined with conventional radiotherapy could not improve the OS(HR=0.66,95% CI 0.44-1.00,P=0.05),LRRFS(HR=0.88,95% CI 0.53-1.45,P=0.61)and DMFS(HR=1.14,95% CI0.30-4.34,P=0.85)of patients with stage II nasopharyngeal carcinoma;Compared with intensity-modulated radiotherapy(IMRT)alone,induction chemotherapy combined with IMRT cannot Improve OS(HR=1.08,95% CI 0.53-2.21,P=0.83),LRRFS(HR=1.00,95% CI 0.44-2.31,P=0.99)and DMFS(HR=1.56,95% CI0.20-12.00,P=0.67).In addition,OS(HR=0.76,95%CI 0.49-1.18,P=0.22),LRRFS(HR=0.64,95% CI 0.19-2.18,P=0.48)and DMFS(HR=1.14,95% CI0.29-4.40,P=0.85)were not significantly improved in patients with stage II nasopharyngeal carcinoma in the T1-2N1M0 subgroup who received induction chemotherapy combined with radiotherapy.Conclusions:Induction chemotherapy combined with radiotherapy cannot improve the efficacy of patients with stage II nasopharyngeal carcinoma,but will cause an increase in severe acute treatment-related toxicity.Regardless of the era of conventional radiotherapy or IMRT,the addition of induction chemotherapy cannot improve the outcome of patients with stage II nasopharyngeal carcinoma.Moreover,patients with stage II nasopharyngeal carcinoma with clinical stage T1-2N1M0 cannot benefit from induction chemotherapy combined with radiotherapy.Prospective randomized controlled trials with large samples and multiple centers are needed to verify this conclusion in the future.