90% with better sparing of the surrounded normal tissue.However,the metastasis rate is still 20%-25%,which limits the improvement of overall survival(OS).To consolidate the local control rate and reduce the metastasis rate,it is necessary to combine chemotherapy with radiotherapy.According to clinical randomized studies and meta-analysis,chemotherapy can improve the OS of loco-regionally advanced nasopharyngeal carcinoma by more than 6% with radiotherapy alone as baseline.Concurrent chemo-radiotherapy is the most promising strategy to cope with the disease.This review has summarized the progress in the area of combination of chemotherapy and radiotherapy for the treatment of loco-regionally advanced nasopharyngeal carcinoma.

Objective To evaluate the outcomes and toxicities of early stage nasopharyngeal carcinoma(NPC)patients treated with intensity-modulated radiotherapy(IMRT)alone. Methods From February 2001 to January 2008, 198 early stage NPC patients according to AJCC/UICC 2002 staging system were treated by radical radiotherapy with IMRT technique in our institute, the clinical data were analyzed retrospectively. Results The 5-year disease-specific survival, local recurrence-free survival(LRFS)and distant metastasis-free survival(DMFS)were 97.3%, 97.7% and 97. 8% respectively. The 5-year LRFS for T1, T2 patients were 100%, 96. 7%(x2 = 2. 24 ,P = 0. 135)respectively. The 5-year DMFS for T1 N0,T2N0, T1N1, and T2N1 patients were 100%, 98. 8%, 100% and 93. 8%(x2= 2. 35, P= 0. 125)respectively. Grade 1 and 2 mucositis and pharyngitis were most common acute toxicities. Radiation encephalopathy and cranial nerve injury were not observed in all patients. Conclusions IMRT alone for early stage NPC patients can produce satisfactory results and acceptable treatment-relative toxicities. Patients with T2b and T2bN1 had a relatively higher incidence of local recurrence and distant metastasis, which suggested that combination of IMRT and chemotherapy may improve clinical results in those patients.

Objective To evaluate the long-term outcomes of patients with advanced N-stage nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT) and the effects of IMRT combined with different chemotherapies on the patients' prognosis.Methods A retrospective analysis was performed on the clinical data of 179 patients with advanced N-stage NPC who were admitted to our hospital from January 2001 to January 2008.Of the 179 patients,33 received IMRT alone,and 146 received chemoradiotherapy (CRT).Among the 146 patients,71 received concurrent chemoradiotherapy (CCRT),66 received induction chemotherapy (IC) plus CCRT,and 9 received CCRT plus adjuvant chemotherapy (AC).Results The follow-up rate was 96.5％,and 133 patients were followed up for at least 5 years.The 5-year overall survival rate was 69.0％.The patients receiving IMRT alone and patients receiving CRT had 5-year overall survival rates of 47.7％ and 73.7％ (x2 =13.91,P =0.000),5-year distant metastasisfree survival (DMFS) rates of 49.2％ and 68.3％ (x2 =4.97,P =0.026),relapse-free survival rates of 74.5％ and 92.4％ (x2 =9.87,P =0.002),and progression-free survival rates of 37.5％ and 65.1％ (x2 =11.65,P =0.001).Among the patients receiving CRT,those receiving CCRT,IC plus CCRT,and CCRT plus AC had similar survival rates.IC plus CCRT resulted in a significantly higher DMFS than IMRT alone (x2 =4.65,P =0.031).Conclusions The distant metastasis rate is still high in patients with advanced N-stage NPC after IMRT,for whom IC plus concurrent chemotherapy and IMRT may be a better treatment regimen.

Objective To investigate the long-term outcomes of patients with nasopharyngeal carcinoma (NPC) in different stages treated by intensity-modulated radiotherapy (IMRT) and explore their treatment strategies.Methods A retrospective analysis was performed on the clinical data of 868 NPC patients without distant metastasis who received radical IMRT from May 2001 to October 2008.These patients were divided into early N0 (T1-2N0) group (n =137),early N1 (T1-2N1) group (n =129),locally advanced (T3-4N0-1) group (n =322),regionally advanced (T1-2 N2-3) group (n=107),and locoregionally advanced (T3-4 N2-3) group (n =173).There groups were compared in terms of treatment outcome and treatment strategy.Results The follow-up rate was 91.4％,and 314 patients completed 5-years follow-up.The 5-year overall survival rate,local recurrence-free rate,and distant metastasis-free rate (DMFR) were 83.5％,91.8％,and 84.6％,respectively.The early N0 group had the best treatment outcome,with a 5-year disease-specific survival (DSS) rate up to 99.1％.Each group had a similar outcome after receiving either IMRT alone or IMRT combined with chemotherapy.The locally advanced group and regionally advanced group had similar failure patterns and treatment outcomes.The locoregionally advanced group had the worst treatment outcome,with a 5-year DMFR of 67.2％ and a DSS of 68.0％.The regionally advanced group and locoregionally advanced group had a similar treatment outcome after receiving IMRT alone,induction chemotherapy plus IMRT,or concurrent chemotherapy and IMRT.Conclusions Patients with NPC in different stages have different survival outcomes.It is recommended that different treatment strategies should be adopted according to the T and N stages of NPC.IMRT alone can produce satisfactory results in patients with T1-2N0 NPC,but a more effective medication should be added to IMRT in patients with advanced NPC,particularly those with T3-4N2-3 NPC who have a relatively low DMFR.

Objective To compare the long-term efficacy between two radiochemotherapy regimens for locally advanced nasopharyngeal carcinoma (NPC):intensity-modulated radiotherapy with concurrent chemotherapy (CCRT) versus neoadjuvant chemotherapy (NACT) followed by CCRT.Methods A retrospective analysis was performed on the clinical data of 278 patients with locally advanced NPC who were admitted to our hospital from 2001 to 2008.Of the 278 patients,133 received CCRT,and 145 received NACT followed by CCRT (NACT + CCRT).Results The follow-up rate was 96.6％.The 5-year overall survival (OS),distant metastasis-free survival (DMFS),recurrence-free survival (RFS),and progression-free survival (PFS) were 78.1％,78.0％,90.6％,and 72.0％,respectively.There were no significant differences between the CCRT group and NACT + CCRT group in 5-year OS (79.9％ vs.76.4％,P =0.443),DMFS (77.1％ vs.78.9％,P=0.972),RFS (91.6％ vs.89.8％,P=0.475),and PFS (71.6％ vs.72.2％,P=0.731).Subgroup analysis showed that compared with CCRT,NACT + CCRT did not significantly improve 5-year RFS in T3-4N0-1 patients (90.7％ vs.86.9％,P=0.376) and did not significantly improve 5-year DMFS in patients with advanced N-stage disease (57.6％ vs.69.7％,P =0.275).There were significantly higher numbers of individuals with neutropenia,decrease in hemoglobin,and upper gastrointestinal reactions in patients treated with NACT + CCRT than in those treated with CCRT (100 vs.52,P=0.000;64 vs.35,P=0.010;90 vs.63,P=0.044).Conclusions Compared with CCRT,NACT + CCRT does not significantly improve the prognosis in patients with locally advanced NPC and leads to significant increases in grade ≥ 3 toxicities (neutropenia,decrease in hemoglobin,and upper gastrointestinal reactions).The role of NACT in the treatment of locally advanced NPC needs further study

Objective To analyze the treatment result of radiotherapy alone for patients with early stage nasopharyngeal carcinoma (NPC) and discuss the impact of T and N stages on the prognois. Methods From January 1999 to December 2001, clinical data of 362 patients with early stage (T1-2N0-1M0,92'Fuzhou staging system) NPC treated by radiotherapy alone were reviewed. Results Median follow-up time was 70 months. The 5-year overall survival (OS) rate of the whole group was 85%. The 5-year OS rates of patients with T1N0,T2N0 and T1N1 disease were 96.6% ,91.3% and 85.8% ,which were not statistically different ( χ2 = 3.83, P ＞ 0.05). The 5-year OS rate of those with T2N1 disease was 73.1%,which was sta tistically different from the former three groups ( χ2 = 30.0 ,P ＜ 0.05 ). The 5-year local-recurrence free sur vival and 5-year regional-recurrence free survival rates had no significant difference among the four groups.The 5-year distant-metastasis free survival rates of the former three, groups were 94.9% ,97.5% and 95.6% (χ2 = 0.53, P ＞0.05). The rate of patients with T2N1 disease was 81.2%, which was significantly different from the others (χ2 =26.6,P 0.05).Conclusions Radiotherapy alone for T1N0,T2N0 and T1N1 naso pharyngeal carcinoma has a satisfactory result. With more failure of distant metastasis, patients with T2N1 disease has obviously poorer outcome than the others. Patients who have high risk of distant metastasis may need combined treatment instead of radiotherapy alone in the future study.

Objective To investigate the volume of prophylactic irradiation to the neck for stage N0 nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT).Methods Retrospective analysis was performed on the clinical records of 270 patients with stage N0 NPC (based on the 6th version of AJCC/UICC staging system),who underwent IMRT as the initial treatment in our center from 2003 to 2008.Among all the patients,171 received prophylactic upper-neck irradiation,and 99 prophylactic whole-neck irradiation.All of them received 6-MV X-ray IMRT to the primary focus of NPC and the lymphatic drainage area in the upper neck (Levels Ⅱ,Ⅲ,and Ⅴ A lymph nodes) at doses of 68 Gy/30fractions and 54 Gy/30 fractions over 6 weeks.In addition,the patients receiving prophylactic whole-neck irradiation had the lower neck and supraclavicular fossae treated by anterior neck semi-field conventional technique at a dose of 50 Gy/25 fractions.Results The median follow-up was 65.1 months (range 4-106months),and the follow-up rate was 93％.The patients undergoing prophylactic upper-neck irradiation and prophylactic whole-neck irradiation had 5-year disease specific survival rates of 95.3％ and 91.9％ (x2 =0.76,P =0.384),relapse-free survival rates of 99.4％ and 99.0％ (x2 =1.18,P =0.278),and distant metastasis-free survival rates of 98.8％ and 94.9％ (x2 =2.31,P =0.128).The 5-year distant metastasisfree survival rate was significantly higher in patients without retropharyngeal lymph node (RLN) metastasis than in those with RLN metastasis (99.4％ vs.93.7％,x2 =8.96,P =0.003).Grade 1-2 mucositis and pharyngitis were the most common acute adverse reactions in patients.At 24 months after IMRT,no grade 3 or 4 xerostomia and trismus were developed.Conclusions Prophylactic irradiation to the upper neck may be feasible for stage N0 NPC patients treated with IMRT.It is reasonable in the 7th version of AJCC/UICC staging system that NPC with negative cervical lymph nodes and positive RLNs is reclassified to stage N1.

Objective To compare the Chinese'92 and 2008 staging systems of nasopharyngeal carcinoma (NPC) based on the long term survival of the patients. Methods Clinical data of 498 NPC patients treated with definitive IMRT were retrospectively analyzed. The distributions of patients in the two staging systems were compared. The long term outcomes according to T, N and overall stages in each system were evaluated. Kappa value and Pearson coefficient were used to evaluate the agreement and correlation of the two systems. Results The distributions of both T and N stage between'92 and 2008 stage systems were different. In both staging systems, the local recurrence-free survival (LRFS) curves of T_1, T_2 andT_3 were close up (even overlaped), though they were apart from T_4. The distant metastasis-free survival (DMFS) curves overlaped of N_1 and N_2 in the'92 staging system, while separated of N_1, N_2 and N_3 in the 2008 staging system. Significant difference of DMFS was not found between N, and N_2 in'92 staging system, while did exist among N_0, N_1, N_2 and N_3 stages in 2008 staging system. In the both staging systems, the disease-specific survival (DSS) of stage Ⅰ did not significantly differ from that of stage Ⅱ or Ⅲ. The statistical analysis showed the conformality of DSS curves in the two system was 89% (Kappa =0. 833 ,P <0.01), with agood relative rate (r=0. 919,P<0. 01). Conclusions The difference between'92 and 2008 staging system is mainly in N stage. The 2008 N stage seems more reasonable compared with'92 N stage, which is able to better forecast the DMFS. There are some agreements and correlations between the two staging systems.

Objective To evaluate the long-term efficaey of radiotherapy (RT) alone for nasopharyngnal eareinoma(NPC). Methods 934 NPC patients initially treated by conventional RT alone in 1999 were reviewed retrespeetively, including 676 males and 258 females. According to 92' Fuzhou staging system,there were 35 stage Ⅰ,215 stage Ⅱ ,488 stage Ⅲ and 196 stage Ⅳ diseases. All patients were treated by conventional RT alone with two opposing parallel faeio-eervical fields. The total dose delivered to the nasopharynx was 66-88 Gy. The dose to the cervical lymph nodes was 60-70 Gy, while the prophylactic dose to the neck was 50-56 Gy. Results The median follow-up was 67.1 months. The 5- and 8-year overall survival(OS), disease-free sutural, relapse-free survival and metastasis-free survival rates were 68.30%, 67.3% ,64.4% ,72.4% ,and 48.0% ,66.6% ,50.8% ,68.0% (χ2=49.74, P=0.000), respectively. For stage N1patients,the 5-and 8-year overall survival(OS) ,disease-free survival ,relapse-free survival and metastasis-free survival rates were significantly lower than those of stage NO patients [66.0% : 77.4% and 50.3%:59.8%(χ2=33.34,P=0.000);66.8%:76.1% and 66.1%:76.1%(χ2=29.08,P=0.000); 63.4%:72.9% and 48.9% : 58.7% (χ227.65,P=0.000);71.0%:80.8% and 63.4%:68.0%(χ2=26.13,P=0.000)]. And the corresponding rates of stage N<1-2>were significantly higher than stage N3,while no statistical difference was observed between stage N1 and N2. Multivariate analysis showed that sex, age, pathology,T stage and N stage were independent prognisitie factors for OS. Conclusions Radical RT alone could obtain good long-term results in early stage NPC. Tlowever,OS for local-regionally advanced stage NPC was still unsatisfactory because of the high relapse and metastatic rate. Clinical stage and N stage were valuable prognostic factors.

Objective To investigat the prognostic value of overall treatment time (OTT) for locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT).Methods From May 2001 to April 2007, 376 patients with locally advanced NPC treated with IMRT were retrospectively analyzed.All patients were divided into OTT≤45 days group and OTT >45 days group.The treatment outcomes between the two groups were analyzed.Results Between the groups with OTT≤45 days and OTT > 45 days, the 2-year local control rate (LCR) was 94.9% and 93.1% (χ2= 2.83, P > 0.05) for all patients, 96.3% and 98.7% (χ2=2.83, P>0.05) for patients with T3 disease, 92.2% and 83.1%(χ2= 6.30, P < 0.05) for T4, and 93.1% and 97.5% (χ2= 4.69, P = 0.030) when chemotherapy was concurrently administered.The 2-year LCR was 98%, 96% and 93% (χ2= 2.20, P = 0.531) for patients with treatment interruption before, within and after the 3rd week of IMRT, The Cox regression analysis found that OTT was an independent prognostic factor for LCR in T4 disease.The Linear regression showed that the 2-year LCR was decreased by 2.7% per day of delay.Between the groups with OTT≤45 days and OTT >45days, the 2-year estimated disease-specific survival (DSS), distant metastasis-free survival (DMFS) and overall survival (OS) were 84.1% vs.78.7% (χ2= 0.02, P = 0.881), 87.0% vs.86.1% (χ2= 0.85,P = 0.358), and 91.7% vs.92.2% (χ2= 0.06, P = 0.806), respectively.The further stratified analysis found that the DSS, DMFS and OS were similar between the two groups in T3 (83.7% vs.83.2%, χ2=0.07, P=0.798;86.6% vs.85.7%,χ2=0.02, P = 0.898 ; and 93.7% vs.94.8%,χ2=0.03, P=0.862) and T4 disease (81.4% vs.72.3%, χ2= 0.16, P = 0.687 ;82.6% vs.86.9%, χ2= 1.78, P =0.182;and 88.3% vs.87.5% ,χ2=0.60, P =0.438).In multivariate analysis, T-stage and N-stage were the independent prognostic factors for both DFS and OS, and N-stage was the independent prognostic factor for DMFS.Conclusions The prolongation of the overall treatment time decrease the local control of patients with T4 NPC.