Four-Year Outcome after Reduction of the Target Volume of Intensity Modulated Radiotherapy Following Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase III, Multicentre, Randomised Controlled Trial

There is no consensus on 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. We conducted this prospective open-label, phase III, multi-centre, randomized trial at six institutions in China. Patients with previously untreated, staged as III–IVb nasopharyngeal carcinoma, aged 18–70 years without severe comorbidities were randomly assigned to group A(pre-IC) or group B(post-IC) 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. The primary endpoint was locoregional failure-free survival calculated from randomisation to locoregional failure. This trial is registered with ClinicalTrials.gov, number ChiCTR-TRC-12002441. 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. 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.