Prognostic Analysis Of Different Cycles Of Induction Chemotherapy For Locally Advanced Nasopharyngeal Carcinoma,and The Exploration On The Efficacy And Safety Of Sequential Adjuvant Chemotherapy Following Radiotherapy Combined With Induction Chemotherapy

Background:Combined radiotherapy and chemotherapy is the major treatment for locoregionally advanced nasopharyngeal carcinoma(LA-NPC).In the era of intensitymodulated radiotherapy(IMRT),the rate of distant metastasis was still as high as20%,which is the main reason for treatment failure and death.Pervious clinical trials had demonstrated that the chemotherapy plus concurrent Chemora-diotherapy(CCRT)can further improves the prognosis of LA-NPC.Objective:This study aimed to assess the effect of IC cycle on survival outcomes of LA-NPC patients receiving IC before CCRT or intensity-modulated radioth-erapy(IMRT),and to evaluate the efficacy and safety of sequential AC Following IC+CCRT/IMRT.Methods:Retrospective analysis of patients newly and pathologically diagnosed as LA-NPC in our hospital from January 2015 to March 2018 was carried out.All patients underwent IC(1-6 cycles)followed by CCRT/IMRT.They were divided into IC<3treatment group and IC≥3 treatment group;and then according to the cycles of IC and Sequential AC,they were divided into 4 groups of treatment modes(IC≥3+AC,IC≥3+non-AC,IC<3+AC,IC<3+non-AC).Kaplan-Meier method and log-rank test,univariate and multivariate Cox regression were used for analyzing the effects of IC cycles on the overall survival(OS)、local recurrence-free survival(LRFS)、 distant metastasis-free survival(DMFS)、 and disease progression-free survival(PFS)rate of LA-NPC,and the prognostic differences of the four treatment groups.Differences in baseline clinical characteristics and toxic reactions between groups were examined by T test and chi-square test.Results:A total of 525 consecutive patients with LA-NPC were recruited and prospectively observed(247 in the IC<3 group and 139 in the IC≥3 group).The median follow-up period was 53 months(range:2-74 months),and the 3-year OS,LRFS,DMFS and PFS rates were 90.4%,88.9%,86.5% and 78.2% respectively.The results of survival analysis showed that the 3-year OS of the IC ≥ 3 group was better than that of the IC<3 group(94.6% VS 89.1%,P=0.020).And based on IC<3,sequential AC following IC +CCRT/IMRT can further improve the patient’s OS(89.3% VS79.7%),P=0.030),which is similar to IC+CCRT(IC≥3)treatment(89.3% VS 95.2%,P=0.150),and does not increase the risk of acute toxicity.Moreover,in the analysis of the prognosis difference among the treatment modes,the OS in the IC<3+non-AC group was significantly lower than the other three groups(all P<0.05).In multivariate analysis,the IC cycle was an independent factor for OS(HR=0.326,P=0.007),and the clinical staging was an independent factor for PFS(HR=0.539,P=0.007).Conclusion:For LA-NPC,IC cycle appeared to be an independent prognostic factor associated with an improvement of survival,the 3-year OS was better in ≥ 3 group;and in patients receiving IC<3 cycles,AC following IC+CCRT/IMRT can improve OS without more acute adverse events.