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Objective There is no consensus the use of pre-or post-IC gross tumor volume of nasopharynx(GTVnx)to plan IMRT after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.We aimed to investigate outcome after reduction of the target volume of intensity modulated radiotherapy following induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma a suitably powered trial.Methods We conducted this prospective open-label,phase Ⅲ,multi-centre,randomized trial at six institutions in China.Written informed consent was obtained from all patients before participation.Patients with previously untreated,histologically confirmed Ⅲ-Ivb nasopharyngeal carcinoma(classification by the seventh edition of the American Joint Committee on Cancer staging system(AJCC)),aged 18-70 years without severe comorbidities were randomly assigned to group A(pre-induction chemotherapy)or group B(post-induction chemotherapy)in this clinical trial.Eligible patients received induction chemotherapy plus concurrent chemoradiotherapy.Induction chemotherapy was two cycles of TP(paclitaxel 175 mg/m2 through intravenous infusion on day 1 and intravenous cisplatin 75 mg/m2 on day 1)or PF(continuous intravenous fluorouracil 1000 mg/m2 per day from day 1 to day 4 and cisplatin 75 mg/m2 Ⅳ over 1 h with hydration on day 1)every 3 weeks before concurrent chemoradiotherapy.IMRT was planned using the images of pre-IC in group A and post-IC in group B and concurrently with cisplatin 40 mg/m2 Ⅳ over 2 h every week.Randomisation was by a computer-generated random number code with a block size of four,stratified by treatment centre and disease stage.Statistical analysis was performed using SPSS18.0.Chi-square testwas used to compare the rank data and rates.Independent test was used to compare the target volumes,the dose encompassing volumes of targets and risk organs between groups A and B.The primary endpoint was locoregional failure-free survial calculated from randomisation to locoregional failure.Survival curves were generated by the Kaplan-Meier method.Log-rank test was used to compare the above indexes between group A and group B.A value of p < 0.05 was considered statistically significant.This trial is registered with ClinicalTrials.gov,number ChiCTR-TRC-12002441.Results Between February 2012 and April 2015,233 patients were randomly assigned to this clinical trial.Finally,212 patients received the allocated intervention and statistical analysis,97 patients in group A,and 115 patients in group B.After a median follow-up of 60(IQR 45-82)months,the 4-year estimated overall survival(OS),progression-free survival(PFS),locoregional failure-free survival(LRFFS),distant metastasis-free survival(DMFS)in group A versus group B were 78.4%vs 82.6%,73.2%vs 80.9%,90.7 vs 93.9%,79.4%vs 86%,respectively.Post-IC GTVnx(25.68 ± 22.20 cc)in group B decreased significantly(p < 0.001)compared with pre-IC GTVnx in group A.The irradiation of adjacent normal tissues in group B was lower than that of group A especially for parotid and inner ear(P < 0.05).The quality of life(QOL)scores in group B were higher than group A.Conclusions Reducing the IMRT target volume after IC could not only ensure a safe radiotherapy dose to critical organs-at-risk,but could also guarantee an encouraging outcome.Our findings warrant validation with more patients in more centers and longer follow-up periods.