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.

At present, the main treatment for recurrent nasopharyngeal carcinoma (rNPC) is re-irradiation. Conventional external irradiation can result in a high incidence of side effects. Intensity modulated radiation therapy and stereotactic radiotherapy can not only reduce the radiation dose to vital organs and surrounding normal tissues, but also improve local control rate. Brachytherapy and surgery are also shown to be effective in early diseases.

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.

Local recurrent nasopharyngeal carcinoma(NPC) presents a troublesome challenge to radiation oncologist. Reirradiation is the primary modality nowadays. However, clinical data on reirradiation are still relatively scarce. This article summarized the treatment advances and the clinical characteristics associated with relapse of NPC, and reviewed the outcomes of different radiation techniques in the management of recurrence of NPC, i.e. conventionalradiotherapy, stereotactic radiotherapy, brachytherapy, three-dimensional conformal radiotherapy and intensity modulate radiotherapy, or some combination of above in recent years.

Objective To study the radiosensitization of histone deaeetylases inhibitor(HDACI) panobinistat in prostate cancer cells in vitro,as well as the possible mechanisms.Methods IC20 of two prostate cancer cell lines(LNCaP and PC-3)was determined using MTI assay.Cells received a single dose irradiation of 0,2,4,6,or 8 Gy using 6 MV X-ray for radiosensitivity experiment,but only 2 Gy for western blot and flow cytometry.Radiosensitization of panobinostat was investigated with clonogenic assay,and sensitizing enhancement ratio(SER)was calculated with single-hit multi-target model.Western blot was used to compare γH2AX expression.Flowcytomctry was used to detect the cell cycle distribution.Results IC20 of LNCaP and PC-3 was 2.5 and 10.0 μmol/L,respectively.SER of panobinostat at IC20 was 1.37(D0 ratio)and 1.11(Dq ratio)for LNCaP cells,and 1.78(D0 ratio)and 1.17(Dq ratio)for PC-3 cells.Expression of γH2AX gradually decreased in the 2 Gy irradiation-alone cells standing for the DSB repair,while γH2AX expression was persistent in the combination group.Irradiation triggered a G2/M arrest 6-12 hours after irradiation in LNCaP and PC-3 cells.G2/M arrest was observed when cells were treated with panobinostat for 24 hours,however,no significant change concerning cell cycle distribution was showed when cells received further irradiation.Conclusions Panobinostat Call radiosensitize prostate cancer cells,which may be related with increased DNA DSB,inhibition of DSB repair and attenuation of cell cycle modulation after irradiation.

Objective To re-evaluate the prognostic value of the 6th edition of UICC/AJCC staging system in patients with nasopharyngeal carcinoma (NPC) treated with intensity-medulated radiation therapy (IMRT). Methods From February 2001 to March 2007, Clinical data of 570 NPC patients initially treated with IMRT in Cancer Center of Sun yat-sen University were reviewed and the long-term survival was analyzed according to T, N and overall stages. Results The median follow-up was 42 months. 184 patients were followed up to 5 years. The 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) of the whole group were 93. 0%, 85.4% and 83. 3% ,respectively. No statistically significant difference of LRFS was detected between the either two of stage T_1, T_(2a) and T_(2b)(100%, 100% and 94. 5% ;T_1 vs. T_(2b), χ~2 = 1.92, P =0. 166 ;T_(2a) vs. T_(2b), χ~2= 0. 35, P =0. 555), stage T_(2b) and T_3 (94. 5% and 91.3% ;χ~2 = 2. 62, P = 0. 106), or stage T_3 and T_4 (91.3% and 89. 5% ; χ~2 = 1.55, P =0. 214). The 5-year DMFS of stage N_2 was similar with stage N_1 or stage N_3(80. 2%, 86. 2% and 61. 4% ; N_2 vs. N_1, χ~2=2.22, P=0.136;N_2 vs. N_3, χ~2= 1.92, P=0.165). No statistically significant difference of 5-year OS was observed among stage Ⅰ , Ⅱ_a and Ⅱ_b(91.7%, 100% and 95. 3% ; Ⅰ vs. Ⅱ_b χ~2 =0.32, P=0.574;Ⅱ_a vs. Ⅱ_b,χ~2-0.25, P=0.617), or between Ⅳ. And Ⅳ_b(67.9% and 75. 0% ;χ~2 = 0.25, P = 0. 616). Conclusions The 6th edition of UICC/AJCC staging system shows poor predictive value for the long-term survival of NPC patients treated with IMRT.

Objective To evaluate the effect of intensity-modulated radiation therapy(IMRT) on parotid function in nasopharyngeal carcinoma(NPC). Methods Eighty-three NPC patients received prima-ry IMRT between 2001 and 2003. Xerostomia before radiotherapy, at the end of radiotherapy, at 6-month, 1-,2-,3-,4- and 5-year after radiotherapy were investigated, respectively. The relation between xerostomia and parotid dose distribution was analyzed. Results Of all the patients,4,31,31 and 17 had stage Ⅰ,Ⅱ,Ⅲ and ⅣA disease, respectively. Sixteen patients received chemo-radiotherapy. The median followed-up time was 65 months. The 5-year local control and regional control rate were 96% and 95% ,respectively. The 5-year overall survival rate was 80%. The mild xerostomia rate at the seven time points was 42%, 51%, 71%, 77%, 58%, 38% and 26%. The corresponding moderate xerostomia rate was 52%, 53%, 21%,8%, 3%, 2% and 2%, respectively. No serious xerostomia was observed. The mean dose of the bilateral parotid glands was 34.34 Gy. Xerostomia at 6-month after radiotherapy was positively correlated with the mean dose of the parotid glands, and D50 was the independent factor in predicting the xerostomia. Parotid function was well protected when the mean dose and D50 were no more than 33 Gy and 29 Gy,respectively. Conclusions IMRT can improve the local-regional control of NPC and protect the parotid glands from radiation-induced in-jury.

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 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 explore the incidence, clinical characteristics, and prognosis of radiation encephalopathy (REP) in nasopharyngeal carcinoma (NPC) patients after intensity-modulated radiotherapy (IMRT). Methods 870 NPC patients confirmed pathologically and without distant metastasis received radical IMRT,570 of which received chemotherapy simultaneously,and followed up for 6 -104 months (with a median of 40 months),undergoing magnetic resonance imaging (MRI) once every 3 months within the first 3 years after treatment and then once every year.The clinical manifestations were observed.In 29 of these 42 patients diagnosed as with REP,the dose distributions of REP lesions were evaluated.Results 4.83％ of the NPC patients (42/870) were diagnosed as with REP.There were 39 cases with pure temporal lesion (bilateral in 6 cases),with a median latency period of 30 months (6 -56 months),2 cases with pure cerebral stem lesion both with a latency period of 14 months,and one case with lesions in temporal lobe and cerebral stem with the latency period of 18 months.REP was not observed in the stage T1-2 patients.The incidence rate of REP was 3.09％ for the stage T3 patients and 14.35％ for the stage T4 patients.Twenty-two patients underwent following-up MRI after initial diagnosis of REP.After medication or surgical treatment the conditions became better or stable in the most cases. Dosimetric analysis of 32 injured temporal lobes in 29 patients found that the maximal dose was in the contrastenhanced lesions in 27 injured temporal lobes and in edema regions in 5 injured temporal lobes.For each patient,the maximal dose in the normal temporal lobe was lower than that in the injured temporal lobe.In the same patient,the maximal dose,minimal dose,and mean dose of contrast-enhanced lesions were all higher than those in the edema region.Conclusions The incidence of REP after IMRT is high,especially in local advanced NPC patients. Active treatment stabilizes or improves the REP condition. REP is positively correlated with dose of irradiation to brain tissue.