Preliminary Outcome Of Intensitymodulated Radiotherapy For Locally Advanced Nasopharyngeal Carcinoma: A Prospective Multi-center Study

Objective: To evaluate the efficacy,toxicity and prognostic of intensity-modulated radiotherapy(IMRT)for locally advanced nasopharyngeal carcinoma(NPC)from different cancer centers,and try to explore the best chemotherapy modality.Methods: From 4 cancer centers in China including 167 patients from Aug.2012 to Jan.2014,Clinical stage of all of the patient were III-IVb period(seventh edition of AJCC staging)and received radical IMRT combined with concurrent chemotherapy following Neoadjuvant chemotherapy or not.They all received 2-3 cycles of cisplatin-based chemotherapy plus concurrent intensity-modulated radiotherapy(CCRT).Cisplatin-based chemotheapy also were used in both neoadjuvant chemotherapy(NACT)and non neoadjuvant chemotherapy.The prescribed radiation dose was GTV-T D95 66-74Gy(2.1-2.3Gy/f),GTV-N D95 60-70Gy(2.0-2.2 Gy/f),CTV-1 D95 60-66Gy(1.8-2.0 Gy/f),CTV-2 D95 54-60Gy(1.8-2.0 Gy/f),CTV-ln D95 50-55Gy(1.8-2.0 Gy/f),5times/week.χ2 analysis,Kaplan-Meier method and Cox regression model were used for prognostic analysis.We set statistical significance with P<0.05.Results: The follow up rates was 96.4%,the median follow-up time was39.5 months.The 1-,2-and 3-year overall survival rate(OS)were 95.3%,90.0%,83.2%,respectively;loco-regional relapse-free survival rate(LRFS)were96.4%,94.0%,92.2%,respectively;distant metastasis-free survival rate(DMFS)were95.8%,89.2%,85.0%,respectively;progression-free survival rate(PFS)were90.4%,79.6%,71.3%,respectively.In 167 patients CR:160 case,PR: 4 cases,SD: 2 cases and PD: 1 cases.Remission rate of all patients(RR)=98.2%(164/167).The 3-year OS,LRFS,DMFS and PFS were 85.4% and80.3%(P=0.383),94.8% and 87.3%(P=0.082),90.6% and 77.5%(P=0.006),76.0% and 64.8%(P=0.104)between two groups,respectively;there were no statistically significant difference except for DMFS(P=0.006).100%(96/96)for receipt NACT group and 95.8%(68/71)for non NACT group,without a statistically significant difference between two groups(P=0.149).Multivariate prognostic analyses revealed that N stage and Clinical stage were independent risk factors for overall survival(HR,15.112;95%CI,2.059-110.901[P=0.008])and(HR,2.748;95%CI,1.232-6.129[P=0.014]);N stage,etropharyngeal lymph node were independent risk factors for progression-free survival(HR,7.457;95%CI,2.635-21.098[P<0.001])and(HR,2.465,95%CI,1.328-4.575[P=0.004]);T Stage were significant independent risk factors for local recurrence-free survival rate(HR,11.010;95%CI,1.418-85.479[P=0.022]);N stage,Clinical stage,etropharyngeal lymph node and neoadjuvant chemotherapy were independent risk factors for distant metastasis-free rate(HR,16.947;95%CI,2.244-128.367[P=0.006]),(HR,2.620,95%CI,1.136-6.045[P=0.024]),(HR,4.758;95%CI,1.971-11.489[P=0.001])and(HR,0.175;95%CI,0.073-0.421[P<0.001]).The incidence rates of mucositis of grade 3 was41.3%(69/167).There was a lower incidence rates of mucositis of grade 3 by using Chinese Medicine(χ2=3.91,P=0.048).Patients who received neoadjuvant chemotherapy had significantly sever bone marrow suppression(P=0.044).There were no significant differences in the incidence rates of mucositis and xerostomia between two groups(P=0.556,P=0.684).No grade 3-4 toxicities were ovserved in the late toxicities and all of the toxicities were be well controlled and tolerable.Conclusions: 1.Neoadjuvant chemotherapy followed by chemoradiotherapy may improve DMFS in the patients that with locally advanced nasopharyngeal carcinoma.However,a subgroup analysis should be further studied;2.Neoadjuvant chemotherapy followed by chemoradiotherapy only increased a slight bone marrow suppression when compared with concurrent chemoradiotherapy and all of the toxicities were be well controlled and tolerable;3.Dialectical treatment of traditional Chinese medicine was effective in reducing acute oral mucositis caused by concurrent chemoradiotherapy inadvanced nasopharyngeal carcinoma;4.Multivariate analyses revealed that N stage and Clinical stage were independent risk factors for overall survival;N stage,Clinical stage,retropharyngeal lymph node and neoadjuvant chemotherapy were significant independent risk factors for distant metastasis-free rate;T stage was independent risk factors for local recurrence-free survival rate;N stage and retropharyngeal lymph node were independent risk factors for progression-free survival.