Characteristics And Prognostic Factors Of Metastatic Nasopharyngeal Carcinoma Patients After Intensity-Modulated Radiotherapy

Purpose: To analyze the clinical characteristics of nasopharyngeal carcinoma patients with distant metastasis after intensity-modulated radiotherapy(IMRT),develop a prognostic score model for distant metastasis,look for clinical factors that affect distant metastasis,provide clinical evidence to identify high risk metastatic nasopharyngeal carcinoma patients.To evaluate the effect of different sequential chemotherapy and radiotherapy schemes on distant metastasis of locally advanced nasopharyngeal carcinoma patients after IMRT,and to explore the effective treatment to reduce distant metastasis rate.To explore the prognostic factors of overall survival in distant metastatic nasopharyngeal carcinoma patients after IMRT.Methods: Between January 2007 and June 2012,a total of 638non-metastatic nasopharyngeal carcinoma patients treated with IMRT were retrospectively reviewed.The chi-square test was performed to compare difference of clinical parameters between metastasis and non-metastasis patients.The Logistic regression was used to analyze factors that affect distant metastasis.Receiver operating characteristic(ROC)curve was used to develop the prognostic score model for distant metastasis.Kaplan-Meier method with a log-rank test was used to calculate the distant metastasis rate.528 patients with locally advanced nasopharyngeal carcinoma were retrospected,the Kaplan-Meier method with a log-rank test was used to calculate the survival rate.101 cases of nasopharyngeal carcinoma patients with distant metastasis after radical IMRT were retrospected.The Kaplan-Meier method with a log-rank test was used to calculate the survival rate.To explore the effects of the clinicopathological parameters on survival,Cox proportional hazard model was used for univariate and multivariate analyses.Results:Patients were followed up for a median follow-up duration of44 months(range from 3 to 95 months).At the end of this cohort study,13patients(2%)were lost to follow-up,114(17.9%)died during the study,60(9.4%)experienced local-regional failure and 101(15.8%)developed distant metastases.The clinical parameters of 2010 UICC/AJCC T staging,2010UICC/AJCC N staging,2010 UICC/AJCC stage and tumor recurrence were observed differently between metastasis and non-metastasis patients.N2-3,serum albumin(ALB)<42g/L and serum ferritin(SF)>300?g/L were factors that affected distant metastasis.Distant metastasis prognostic score= N2-3+ALB<42g/L+SF>300?g/L.When the risk score was 0-1,the risk of distant metastasis was low,when the risk score was2-3,the risk of distant metastasis was high.Based on the prognostic score model,638 nasopharyngeal carcinoma patients were divided into low risk group and high risk group,the distant metastasis rate for each group was 10.3% and 23.5% respectively(p<0.001).In528 patients with locally advanced,the number of patients in low distant metastatic risk group was 263,while the high distant metastatic risk group was265.In low risk group,compared with concurrent chemotherapy(CCRT)alone,neoadjuvant chemotherapy(NACT)+ CCRT ±adjuvant chemotherapy(AC)and CCRT+AC did not improve distant metastasis-free survival(DMFS),local recurrent-free survival(LRFS)and progression-free survival(PFS)significantly.In high risk group,patients received CCRT+AC had a higher DMFS rate than patients with CCRT alone(p=0.041),compared with CCRT alone,CCRT+AC and NACT+CCRT±AC had a tendency to improve LRFS and PFS.The 1,2,and 3-year overall survival rates of patients with metastases were 92%,70% and41% respectively.Treatment led to a median DMFS of 16 months(range from 1to 44 months).Metastasis to the lung was the most frequent site,followed by bone metastasis and liver metastasis.Univariate analysis showed that DMFS(HR,0.351;95%CI,0.219-0.562;p=0.001),concurrent chemotherapy(HR,0.503;95%CI,0.270-0.939;p=0.031),chemoradiotherapy(HR,0.280;95%CI,0.119-0.657;p=0.003),and cancer metastatic site(HR,5.300;95%CI,1.169-24.034;p=0.031)were significantly associated with overall survival in distant metastatic patients,while the multivariate analysis further showed that DMFS,chemoradiotherapy and cancer metastatic site were independent predictors for overall survival of patients(p=0.001,p=0.022 and p= 0.005,respectively).Conclusion: Distant metastasis is the dominant treatment failure in nasopharyngeal carcinoma patients after treated by IMRT.Distant metastasis prognostic score model comprised of N2-3,ALB<42g/L and SF>300?g/L could effectively distinguish high risk and low risk patients with distant metastasis.In locally advanced nasopharyngeal carcinoma patients,compared with concurrent chemotherapy(CCRT)alone,NACT+CCRT ± AC and CCRT+AC did not decrease distant metastasis rate in low risk group.In high risk group,CCRT+AC could decrease distant metastasis rate.DMFS,chemoradiotherapy and cancer metastatic site were independent prognostic factors with overall survival in distant metastatic nasopharyngeal carcinoma patients after IMRT.