Objective To analyze the 10-year survival outcome and failure patterns for patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT),aiming to provide reference for optimized treatment for NPC.Methods Clinical data of 866 patients with NPC receiving IMRT from January 2001 to December 2008 were retrospectively analyzed.Survival analysis was performed using the Kaplan-Meier estimator.Univariate analysis was carried out by log-rank test and multivariate analysis was performed using Cox proportional hazards model.Results The median follow-up time was 132 months.The 10-year local recurrence-free survival (LRFS),distant metastasis-free survival (DMFS),progression-free survival (PFS) and disease specific survival (DSS) were 92.0％,83.4％,75.7％ and 78.6％,respectively.A total of 210 patients died including 124 patients (59.0％) from distant metastasis,which was the primary cause of death,and 47 (22.3％) from local regional recurrence.Independent negative factors of DSS included age＞50 years (P=0.00),LDH ≥ 245 IU/L (P=0.00),Hb＜ 120 g/L (P=0.01),T2-T4 staging (P=0.00),N1-N3 staging (P=0.00) and GTV-nx＞20 cm3(P=0.00).The 10-year LRFS,DMFS and DSS of stage Ⅱ NPC patients did not significantly differ after IMRT alone and chemoradiotherapy (P=0.83,0.22,0.23).For patients with stage Ⅲ NPC,the 10-year LRFS and DSS in the chemoradiotherapy arm were significantly higher than those in the IMRT alone (P=0.01,0.01),whereas no statistical significance was observed in the DMFS between two groups (P=0.14).The overall survival of stage Ⅳa+Ⅳb NPC patients is relatively poor.Conclusions IMRT can improve the long-term survival of NPC patients.Distant metastasis is the primary failure pattern.Patients with stage Ⅰ-Ⅱ NPC can obtain satisfactory survival outcomes after IMRT alone.The addition of chemotherapy can further enhance the LRFS and DSS of stage Ⅲ NPC patients.However,the optimal therapeutic strategy remains to be urgently investigated for stage a+ Ⅳb NPC patients.

Background: Salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC) is complicated and relatively limited. Radiotherapy, combined with effective concomitant chemotherapy, may improve clinical treatment out?comes. We conducted a phase II randomized controlled trial to evaluate the efcacy of intensity?modulated radio?therapy with concomitant weekly cisplatin on locally recurrent NPC. Methods: Between April 2002 and January 2008, 69 patients diagnosed with non?metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group (n = 34) or radiotherapy alone group(n= 35). All patients received intensity?modulated radiotherapy. The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days (range 23–53 days). The concomitant chemotherapy schedule was cisplatin 30 mg/m2 by intravenous infusion weekly during radiotherapy. Results: The median follow?up period of all patients was 35 months (range 2–112 months). Between concomitant chemoradiotherapy and radiotherapy groups, there was only significant difference in the 3?year and 5?year overall survival (OS) rates (68.7% vs. 42.2%, P = 0.016 and 41.8% vs. 27.5%, P = 0.049, respectively). Subgroup analysis showedthat concomitant chemoradiotherapy significantly improved the 5?year OS rate especially for patients in stage rT3–4 (33.0% vs. 13.2%, P = 0.009), stages III–IV (34.3% vs. 13.2%, P = 0.006), recurrence interval >30 months (49.0% vs. 20.6%,P= 0.017), and tumor volume >26 cm3 (37.6% vs. 0%, P = 0.006). Conclusion: Compared with radiotherapy alone, concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC, especially those with advanced T category (rT3–4) and stage (III–IV) diseases, recurrence intervals >30 months, and tumor volume >26 cm3.

Objective To establish a post?treatment prognostic score model for newly diagnosed metastatic nasopharyngeal carcinoma, and to investigate the feasibility of stratified therapy. Methods A total of 263 eligible patients with newly diagnosed metastatic nasopharyngeal carcinoma from 2002 to 2010 were enrolled as subjects. The primary tumor was treated with conventional radiotherapy, three?dimensional conformal radiotherapy, or intensity?modulated radiotherapy, and radiation areas included nasopharyngeal tumor and cervical lymphatic drainage region. The metastatic bone tumor was mainly treated with conventional external radiotherapy, while the metastatic liver or lung tumor was mainly treated with surgical resection, radiotherapy, or radiofrequency ablation. The first?line therapy for most of patients was cisplatin?based combination chemotherapy. Factors including the general characteristics, tumor status, and therapy for patients were involved in multivariate analysis, and a prognostic model was established based on the n value (HR=en ) of the prognostic factors. Results The factors influencing the overall survival (OS) in patients were a Karnofsky performance score (KPS) not higher than 70(P= 0?? 00), multiple organ metastases (P=0?? 00), combination with liver metastasis (P= 0?? 00), a number of metastases not less than 2(P= 0?? 00), a level of lactate dehydrogenase (LDH) higher than 245 IU/ L (P= 0?? 00), a number of chemotherapy cycles ranging between 1 and 3( P= 0?? 00), a poor response for metastatic tumor ( stable disease or progressive disease)(P= 0?? 00), and primary tumor not treated with radiotherapy (P= 0?? 01). Based on the prognostic score, patients were divided into low?risk group (0?1?? 5 points), intermediate?risk group (2?? 0?6?? 5 points), and high?risk group (≥7?? 0 points), and the 5?year OS rates in the three groups were 59?? 0%, 25?? 1%, and 0%, respectively. Conclusions The prognostic score model based on the KPS, serum level of LDH, multiple organ metastases, combination with liver metastasis, and number of metastases can effectively predict the survival in patients. Active treatment including at least 4 chemotherapy cycles and radiotherapy for primary tumor can prolong the survival time of patients in the low?and intermediate?risk groups. However, patients in the high?risk group were mainly treated with palliative radiotherapy due to no improvement in the survival by radiotherapy for primary tumor.

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

OBJECTIVETo explore the acute toxic effects and early curative efficacy of concurrent chemotherapy with different doses of cisplatin for Chinese nasopharyngeal carcinoma (NPC) patients using intensity-modulated radiation therapy (IMRT).

METHODSEighty-eight untreated stage II/III nasopharyngeal cancer patients receiving IMRT and concurrent cisplatin were randomized into two groups receiving different doses of cisplatin. The standard group (DDP 100 mg/m² q3w, n = 44) and the study group (DDP 80 mg/m² q3w, n = 44). The acute toxic effects and 3-month therapeutic efficacy (early curative efficacy) in patients of the two groups who completed treatment were compared and analyzed.

RESULTSDuring the treatment, grade III-IV acute toxic effects were observed in more patients of the standard group compared with that in the study group (72.7% vs. 59.1%), but the difference was statistically not significant (P = 0.18). Significant difference was only seen in upper gastrointestinal reaction (P = 0.01) and anemia (P = 0.03) among the non-hematological and hematological adverse events. No significant differences in other adverse events were found between the two groups (P < 0.05). Three months after the completion of radiotherapy, 80 cases of the whole group achieved complete remission (CR) in the nasopharynx and neck MRI. In both the standard group and study group, 40 patients had CR and 4 patients had residual disease, respectively, showing a non-significant difference (P = 0.51) between the two groups.

CONCLUSIONSDuring the IMRT course, patients received cisplatin 80 mg/m² q3w, experienced less grade III-IV acute toxic effects. Concurrent chemoradiotherapy with cisplatin 80 mg/m² q3w or 100 mg/m² q3w, demonstrate similar early curative efficacy in II/III stage NPC patients in endemic regions of China.

Anemia ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma ; Chemoradiotherapy ; China ; Cisplatin ; administration & dosage ; therapeutic use ; Humans ; Nasopharyngeal Neoplasms ; therapy ; Neoplasm Staging ; Prospective Studies ; Radiotherapy, Intensity-Modulated ; Remission Induction

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.

Early diagnosis,early treatment and the correct therapeutic approch are the keys for metastatic nasopharyngeal carcinoma(NPC) treatment.Currently,PET-CT is the best modality for distant metastasis staging of NPC.Cispalatin-based chemotherapy is the standard treatment method of metastatic NPC.Molecular targeted therapy is possible to further increase curative effect.When the lesions are limited,local palliative treatment may improve prognosis if patient's illness is controled by chemotherapy.

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 evaluate the safety of cetuximab combined with intensity-modulated radiotherapy (IMRT) plus concurrent cisplatin chemotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC) in a Chinese multicenter clinical study.MethodsFrom July 2008 to April 2009,100Patients with primary stage Ⅲ- Ⅳb non-keratinizing NPC were enrolled.The planned dose of IMRT to gross tumor volume and positive cervical lymph nodes was 66.0-75.9 Gy and 60-70 Gy in 30-33 fractions.Cisplatin (80 mg/m2,q3 week (w)) and cetuximab (400 mg/m2 one w before radiation,and then 250mg/m2 per w) were given concurrently.The adverse events (AEs) were graded according to common terminology criteria for adverse events v3.0.ResultsThe compliance of the entire group of patient was satisfactory.Actual median dose to gross tumor volume was 69.96 Gy,and the median dose to positive cervical lymph nodes was 68 Gy.Median dose of cisplatin was 133 mg,median first-dose of cetuximab was 690 mg,and median weekly dose was 410 mg.AEs were well tolerated and manageable,mainly consisting of acneiform skin eruptions,dermatitis and mucositis.Grade 4 mucositis was observed in 2％ of the patients and no other grade 4 AEs were observed.ConclusionsThe combined treatment modality of IMRT +concurrent chemotherapy + cetuximab in loco-regionally advanced NPC is well tolerated.