Efficacy of radical radiotherapy for primary tumors in patients with newly diagnosed oligometastatic nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To investigate the prognostic factors for survival in patients with newly diagnosed oligometastatic nasopharyngeal carcinoma who received radical radiotherapy for primary tumors. Methods From 2008 to 2011,39 patients with newly diagnosed oligometastatic nasopharyngeal carcinoma received 1-6 cycles of chemotherapy and radical radiotherapy for primary tumors. In those patients,10 received conventional radiotherapy and 26 received intensity-modulated radiotherapy. The Kaplan-Meier method was used to calculate survival rates. The log-rank test and Cox model were used for univariate and multivariate prognostic analyses,respectively. Results The median follow-up time was 38 months. The 1-, 2-,and 3-year overall survival rates were 97%,87%,and 70%,respectively,while the 1-,2-,and 3-year progression-free survival rates were 87%,65%,and 59%,respectively. Age,number of metastatic lesions, scheme of induction chemotherapy,and use of concurrent chemotherapy or not were independent prognostic factors for survival. The patients with no more than 3 metastatic lesions had a higher survival rate than those with more than 3 metastatic lesions(P=0.023).The patients undergoing chemotherapy with docetaxel had a significantly higher survival rate than those undergoing chemotherapy without docetaxel (P= 0.041). Conclusions Induction chemotherapy and radical radiotherapy for primary tumors can still achieve long-term survival in patients with newly diagnosed oligometastatic nasopharyngeal carcinoma,particularly in young patients with no more than 3 metastatic lesions. Compared with chemotherapy without docetaxel, chemotherapy with docetaxel may provide a greater survival benefit for patients.

Translational study and clinical application of precision medicine in nasopharyngeal carcinoma / 中华放射肿瘤学杂志

The application of precision medicine in cancer treatment is becoming increasingly common as a result of the continuous advancement in basic research and physical techniques.The revolution of radiotherapy techniques, development of multimodal imaging technology, application of biological target dose carving and adaptive radiotherapy, availability of big data-based radiotherapy planning systems, and selection of chemotherapy regimen have all made the treatment of nasopharyngeal carcinoma increasingly precise.The growing interaction between laboratory research and clinical practice not only underscores the importance of translational medicine, but also prompts the development of biological immunotherapy and screening of prognostic factors.As a result, these changes mark the beginning of a new era for the diagnosis and treatment of nasopharyngeal carcinoma.This review provides a summary from 61 articles on the current progress in translational study and clinical application of precision medicine in nasopharyngeal carcinoma.

Comparison of efficacy and safety between intensity-modulated radiotherapy combined with chemotherapy plus targeted therapy and intensity-modulated radiotherapy combined with chemotherapy for locally advanced nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To retrospectively compare the efficacy and toxicity between intensity?modulated radiotherapy ( IMRT ) combined with chemotherapy plus targeted therapy and IMRT combined with chemotherapy in the treatment of patients with locally advanced nasopharyngeal carcinoma ( NPC) , and to preliminarily evaluate the necessity of adding targeted drugs to standard chemoradiotherapy . Methods Forty?two patients with stage Ⅲ?Ⅳb NPC who received IMRT combined with concurrent ± adjuvant chemotherapy plus targeted molecular therapy from January 2007 to December 2012 were assigned to experiment group,while 168 patients who received IMRT combined with concurrent ±adjuvant chemotherapy within the same period were assigned to control group. The experiment group was paired with the control group at a ratio of 1vs.4.The survival rates were caculated using Kaplan?Meier method and analyzed using log?rank method,other comparison was perfomed by χ2?test. Results The follow?up rate was 100%.The sample size of experiment group and control group were 42 patients and 168 patients. There were no significant differences in the 3?year OS, LRFS, or DMFS rates between the experiment group and the control group (94?3% vs. 87?3%, P=0?647;100?0% vs. 94?6%,P=0?193;92?2% vs. 89?1%, P=0?744).There were also no significant differences in the incidence rates of grade Ⅲ?Ⅳ gastrointestinal reaction or marrow suppression between the two groups ( 7?1%( 3/42 ) vs. 3?6%( 6/168 ) , P=0?388;26?2%( 11/42 ) vs. 17?3%(29/168),P=0?272).However,the experiment group had significantly higher incidence of grade Ⅲ?Ⅳoral mucositis than the control group ( 40?5%( 17/42 ) vs . 14?9%( 25/168 ) , P=0?000 ) . Conclusions The preliminary results indicate that IMRT combined with chemotherapy plus targeted molecular therapy is not able to substantially improve the OS, LRFS, or DMFS rates in patients with locally advanced NPC. Moreover, it may aggravate radiochemotherapy?induced oral mucositis.

Prognostic values of 18 F-FDG PET/CT parameters in patients with nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective At present,nasopharyngeal carcinoma (NPC) is a head and neck cancer with special geographical distribution and biological behavior.Studies have shown that 18 F-FDG PET/CT parameters have certain prognostic values in patients with NPC in high-incidence areas.The aim of this study is to investigate the prognostic values of 18 F-FDG PET/CT parameters in patients with NPC in low-incidence areas.Methods The clinical data of 83 NPC patients who were diagnosed and treated in Beth Israel Medical Center, Albert Einstein Medical College from January 2003 to December 2013 were analyzed retrospectively.Based on 18 F-FDG PET/CT images,gross tumor volume (GTV) was delineated using the gradient method to obtain 18 F-FDG PET/CT parameters:maximum standardized uptake value (SUVmax ), metabolic tumor volume ( MTV),and total lesion glycolysis ( TLG).Results The number of patients followed was 37 at 3-years time.For all patients,the 3-year failure-free survival,locoregional relapse-free survival,and metastasis-free survival rates were 74%,88%,and 85%,respectively.The univariate analysis showed that SUVmax of the primary tumor (P=0.004) and TLG (P=0.014) were prognostic factors for 3-year locoregional relapse-free survival rate,and SUVmax of the primary tumor (P=0.024) and TLG (P=0.033) were prognostic factors for 3-year failure-free survival rate.The multivariate analysis showed that SUVmax of the primary tumor was the independent prognostic factor for 3-year failure-free survival rate. Conclusion SUVmax of the primary tumor before treatment is the independent prognostic factor for failure-free survival in patients with NPC.

A multicenter, prospective, randomized study of intensity-modulated radiother apy combined with different chemotherapy regimens for locally advanced nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To evaluate the efficacy and toxicity of induction chemotherapy with nedaplatin and docetaxel plus concurrent intensity?modulated radiotherapy ( IMRT) with nedaplatin or cisplatin in the treatment of locally advanced nasopharyngeal carcinoma (NPC). Methods A total of 223 patients with pathologically diagnosed locally advanced NPC in five treatment centers from 2011 to 2012 were randomly divided into two groups. In the test group, one hundred and thirteen patients received two cycles of induction chemotherapy with docetaxel (65 mg/ m2 on day 1) and nedaplatin (80 mg/ m2 on day 1) plus concurrent IMRT with nedaplatin (40 mg/ m2 on day 1). In the control group, 110 patients received two cycles of induction chemotherapy with the same regimens plus concurrent IMRT with cisplatin (40 mg/ m2 on day 1). The survival rates were calculated with the Kaplan?Meier method and the differences in the survival rates between the two groups were analyzed using the log?rank test. Comparison of the incidence rates of adverse reactions between the two groups was made by the chi?square test. Results The follow?up rate was 99?? 1%.The response rates at 3 months after treatment in the two groups were both 100%. The 2?year local recurrence?free, regional recurrence?free, distant metastasis?free, and overall survival rates were 94?? 0%, 94?? 2%, 88?? 2%, and 90?? 3%, respectively, in the test group, versus 93?? 4%, 94?? 1%, 86?? 7%, and 87?? 3% in the control group ( P= 0?? 757、 0?? 478、 0?? 509、 0?? 413). The incidence rates and severity of leucopenia, neutropenia, and thrombocytopenia were significantly higher in the test group than in the control group ( P= 0?? 027 , 0?? 028 , 0?? 035 ) . The incidence rates and severity of hemoglobin reduction and nausea /vomiting were significantly lower in the test group than in the control group (P= 0?? 000,0?? 023). There were no significant differences in the incidence rates of mucositis and xerostomia between the two groups ( P=0?? 483,0?? 781). Conclusions The short?term efficacy of induction chemotherapy with nedaplatin and docetaxel plus concurrent IMRT with nedaplatin is similar to that with cisplatin in the treatment of locally advanced NPC. The mild gastrointestinal reactions can be tolerated by patients. However, the severe myelosuppression should be closely monitored during the treatment.

Prognostic impact of degree of bone metastasis in patients with nasopharyngeal carcinoma after radiochemotherapy / 中华放射肿瘤学杂志

Objective To analyze the prognostic impact of degree of bone metastasis in patients with nasopharyngeal carcinoma (NPC) after radiochemotherapy.Methods A retrospective analysis was performed on the prognosis of 109 NPC patients who had bone metastases after radiochemotherapy in Nanfang Hospital from June 1997 to December 2007.The Kaplan-Meier method was used to calculate survival rates; the log-rank test was used for univariate prognostic analysis; the Cox regression model was used for multivariate prognostic analysis.Results The 5-year follow-up rate was 97.2％.The 1-,2-,3-,and 5-year overall survival rates for all patients were 67.9％,48.6％,32.9％,and 17.4％,respectively.The 1-,2-,3-,and 5-year survival rates for the 43 patients with not more than 3 bone metastases and the 66 patients with more than 3 bone metastases were 90.7％ vs.53.0％,81.4％ vs.27.3％,72.1％ vs.6.2％,and 34.9％ vs.4.2％,respectively (P=0.000).In the patients with more than 3 bone metastases,the 1-,2-,3-,and 5-year survival rates for those with and without other metastatic sites were 56.5％ vs.72.1％,21.7％ vs.30.2％,3.1％ vs.13.0％,and 0.0％ vs.6.5％,respectively (P=0.866).The multivariate analysis showed that more than 3 bone metastases were an adverse prognostic factor in the patients (P =0.000).Conclusions The number of bone metastases is an important prognostic factor in NPC patients after radiochemotherapy.Patients with not more than 3 bone metastases have better survival than those with more than 3 bone metastases,and aggressive treatment should be considered.In addition,the staging system of NPC needs to be improved.

Therapeutic effect of concurrent chemotherapy and intensity-modulated radiotherapy following induction chemotherapy in patients with locally advanced nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To investigate the therapeutic effect and side effects of concurrent chemotherapy and intensity-modulated radiotherapy (IMRT) following induction chemotherapy (IC) in patients with locally advanced nasopharyngeal carcinoma (NPC).Methods From January 2005 to January 2009,62 cases of locally advanced NPC confirmed by pathological and cytological examination received IC with vinorelbine (25 mg/m2) plus cisplatin (25 mg/m2) for 2-4 cycles and then concurrent chemotherapy and IMRT.Conventional fractionated radiotherapy was adopted in IMRT.The radiotherapy for the nasopharyngeal region was performed a dose of 72-76 Gy/36-38 fractions,and additional 5-Gy gammaknife treatment was carried out in case of local tumor residue.Prophylactic irradiation to the cervical lymph nodes was performed at a dose of 50 Gy,and the dose was increased to 60-70 Gy in case of lymph node enlargement.Results The follow-up rate was 100％.The patients showed a response rate (RR) of 89％ in the nasopharyngeal region and an RR of 90％ in the cervical lymph nodes.The 1-,2-,and 3-year overall survival rates,disease-free survival rates,local relapse-free survival rates,and distant metastasis-free survival rates were 97％,92％,and 82％,94％,73％,and 65％,97％,89％,and 87％,and 97％,84％,and 77％,respectively.The incidence rates of grade 3-4 acute reactions were 37％ for leucopenia,18％ for thrombocytopenia,and 6％ for mucositis.No grade 3-4 long-term temporomandibular joint injury and xerostomia were observed.Conclusions Concurrent chemotherapy and IMRT following IC with vinorelbine (25 mg/m2) plus cisplatin (25 mg/m2) have tolerable adverse effects and can achieve high survival rate in the patients with locally advanced NPC.

Study on delineation of tumor volume of primary locally advanced nasopharyngeal carcinoma after induction chemotherapy / 中华放射肿瘤学杂志

ObjectiveTo investigate the delineation of gross tumor volume (GTV) in locally advanced nasopharyngeal carcinoma (LANC) according to imageological changes before and after induction chemotherapy (IC) in order to decrease high dose area and protect normal tissue better.MethodsBetween Mar 2010 to Jan 2011,11 patients with LANC were enrolled and treated with TPF regimen followed by intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy,target volumes were delineated based on fused CT imaging before and after IC following project determination.Tumor target volumes after and before IC were respectively delineated according to imaging tumor residues and were overlaid by CTVnx in order to ensure radical doses for the imaging tumor volume before IC,the resulting differences of tumor target volumes of IC before and after were measured and analyzed by paired t-test.ResultsBefore and after IC,the average volumes of GTVnx were respectively 44.72 cm3 and 28.87 ( t =3.89,P =0.003 ),the average volumes of GTVnd were respectively 32.76 cm3 and 19.82 cm3 ( t =2.47,P =0.033 ),the volumes of maximum dose area in brainstem and spinal cord as well as eyeball decreased ( t =2.93-4.59,all P ＜0.05).ConclusionsLANC treated by 3 cycle TPF regimen followed by IMRT with concurrent chemotherapy showes significant shrinkage of tumor volume.The volume of high dose region which caused by normally recovered tissues were decreased by re-delineation of target volume in brainstem and spinal cord as well as eyeball of CT images after IC.

Phase Ⅱ study of gemcitabine plus cisplatin chemotherapy combined with intensity modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma / 中华放射肿瘤学杂志

ObjectiveTo evaluate the efficacy and toxicity of gemcitabine plus cisplatin (GP)chemotherapy combined with intensity-modulated radiation therapy (IMRT)in locoregionally advanced nasopharyngeal carcinoma (NPC).Methods71 patients (Stage Ⅲ:41,Stage ⅣA:30) with locoregionally advanced NPC were entered this study.Neoadjuvant chemotherapy was consisted of cisplatin 25 mg/m2 intravenously on d1-3 and gemcitabine 1000 mg/m2 in 30 minutes intravenous infusion on days 1 and 8,every 3 weeks for 2 cycles.Adjuvant chemotherapy consisted of 2 cycles of the same GP regimen was given at 28 days after the end of radiotherapy.The prescription doses was 66.0-70.4 Gy to the gross tumor volume,66 Gy to positive neck nodes,60 Gy to the high-risk clinical target volume,54 Gy to the low-risk clinical target volume.ResultsThe overall response rate to neoadjuvant chemotherapy was 91.2％,acute toxicity was mainly grade 1-2 myleosuppression.All patients completed IMRT.The median follow-up duration was 38 months.The 3-year nasopharyngeal local control,regional control,distant metastasis-free survival rate and overall survival rate were 93％,99％,91％,90％,respectively.Severe late toxicities included grade 3 trismus in 1 patient,grade 3 hearing impairment in 2 patients and cranial nerve palsy in 2 patients,respectively.No grade 4 late toxicities were observed.Conclusions The combination of GP chemotherapy and IMRT for locoregionally advanced nasopharyngeal carcinoma is well-tolerated,convenient,effective,and warrants further studies of more proper cycles of GP regimen.

Intensity-modulated radiotherapy combined with chemotherapy for early-stage nasopharyngeal carcinoma patients in northwest China / 中华放射肿瘤学杂志

ObjectiveTo evaluate the therapeutic efficacy and prognostic factors of intensity-modulated radiotherapy combined with chemotherapy for early-stage nasopharyngeal carcinoma patients in northwest China. MethodsFrom January 2006 to December 2009,58 patients with early-stage nasopharyngeal carcinoma were treated with IMRT in Xijing hospital,the clinical data were analyzed retrospectively.Survival rates was calculated by the Kaplan-Meier method and the differences was compared by the Logrank test.Univariate analysis method was use to identify all significant factors.ResultsThe follow-up rate was 100％.The follow-up time of 46 patients was more than 3 years.The 1-,2 and 3-year survival were 98％,94％ and 91％,respectively.The 3-year overall survival (OS),local recurrence-free survival (LRFS),distant metastasis-free surv ival (DMFS) for T1N0-1,T2N0 and T2N1 stage were 100％,100％,100％ and 74 ％,81％,87 ％,respectively ( x2 =5.74,P =0.01 ; x2 =4.95,P =0.03 ; x2 =4.24,P=0.04).The 3-year OS,LRFS,DMFS for IMRT combined with chemotherapy and IMRT alone were 100％,100％,100％ and 85％,85％,88％ respectively ( x2 =4.02,P =0.04; x2 =4.12,P =0.03 ; x2 =4.84,P =0.02).In T2N1 stage,IMRT combined with chemotherapy and IMRT alone were 100％,100％,100％ and 79％,79％,80％ respectively (x2 =5.28,P =0.03 ;x2 =4.84,P =0.04;x2 =4.72,P =0.04).In univariate analysis,N stage,clinical stage,IMRT combined with chemotherapy were significantly associated with the survival ( x2 =5.39,P =0.02 ; x2 =5.74,P =0.01 ; x2 =4.02,P =0.04).Conclusions In all early-stage nasopharyngeal carcinoma,T2N1 stage is a sub-group of high risk of distant metastasis.Combination of IMRT and chemotherapy may improve the LRFS,DMFS and OS in those patients.

Concurrent chemoradiotherapy versus radiotherapy alone for T3-4N0-1M0 and T1-4N2-3M0 nasopharyngeal carcinoma after induction chemotherapy / 中华放射肿瘤学杂志

Objective To compare the efficacy of concurrent chemoradiotherapy versus radiotherapy alone for T3-4 N0-1 M0 and T14 N2-3 M0 nasopharyngeal carcinoma (NPC) after induction chemotherapy.Methods From 2002 to 2005,400 patients with stage Ⅲ and Ⅳa NPC were randomly divided into 2 groups :induction chemotherapy followed by concurrent chemoradiotherapy group (IC/CCRT,201 patients),and induction chemotherapy followed by radiotherapy alone group (IC/RT, 199 patients).Subgroup analysis was conducted for 197 patients with stage T3-4N0-1M0 NPC and 203 with stage T1-4N2-3M0 NPC.Results The follow-up rate were 96.2%, with a median followg-up time of 3.9 years.For T3-4N0-1 M0 NPC patients in IC/CCRT group (104 patients) and IC/RT group (93 patients), the 3-year overall survival, disease-free survival, locoregional recurrence-free survival and distant metastasis-free survival rates were 84.0% and 85.9% (χ2=0.08,P =0.780) ,77.0% and 72.0% (χ2=0.44,P =0.510) ,89.5% and 92.3% (χ2=0.65 ,P = 0.420), and 84.9% and 77.0% (χ2= 1.59, P = 0.210), respectively; For T1-4 N2-3 M0 NPC patients in IC/CCRT group (97 patients) and IC/RT group (106 patients), the corresponding rates were 67.4% and 82.2% (χ2=3.48,P=0.060), 61.5% and 68.0% (χ2= 1.86,P=0.170), 86.2% and 87.0% (χ2=0.57 ,P =0.450) and 66.2% and 75.6% (χ2=2.07 ,P =0.150), respectively.Acute sideeffects were similar except more leucocytopenia in IC/CCRT group than IC/RT group.Conclusions Compared with IC/RT, IC/CCRT dose not improve the overall survival in patients with T3-4N0-1 M0 and T1-4 N2-3 M0 NPC.

Therapeutic results of 46 patients with initially diagnosed metastatic nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To retrospectively analyze the therapeutic results of patients with initially di-agnosed metastatic nasopharyngeal carcinoma (NPC). Methods From January 1995 to December 1998, 46 NPC patients with distant metastases were treated in Fujian provincial cancer hospital. Among these pa-tients, 43 were single site metastasis and 3 were multiple sites metastases;The site of metastasis were 19 pa-tients in the liver, 11 in the bone, 7 in the lung, 1 in the brain, 6 in mediastinal nodes and 6 in axillary lymph nodes. All patients received standard radiotherapy to the primary site and cervical node region with a median dose of 72 Gy. Forty-one patients (89%) received 1-5 cycles chemotherapy (cisplatin and 5-flu-orouracil), and 23 (50%) received palliative irradiation to the metastatic site. Results The median surviv-al time was 20 months. The 1-, 2-, 3-year and 5-year overall survival rates were 66%, 47%, 30% and 19%, respectively. Irradiation to the metastatic sites and KPS were the significant prognostic factors. Pa-tients with palliative irradiation to the metastatic site had longer survival than those without (39 months vs. 13 months, X2=8.63, P=0.012). Patients with good performance status (KPS≥80) had better outcomes thanthose with poor performance status (26 months vs. 12 months, X2= 3.95, P=0.035) . Conclusions Active therapy may prolong the survival of patients with initially diagnosed metastatic NPC, especially for those who have good performance status. Under systematic chemotherapy, radiotherapy to the primary site and supportive care, the palliative irradiation to the metastatic site may also yield a good result.

A randomized controlled multicenter trial of actovegin against acute oral mucositis induced by chemo-radiotherapy for nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To evaluate the efficacy and safety of actovegin against acute oral mucositis through a randomized controlled multicenter trial for nasopharyngeal carcinoma(NPC) patients treated by chemo-radiotherapy. Methods From February 2006 to May 2007,a total of 161 patients with newly diagnosed stage Ⅱ-ⅣA(1992 Fuzhou Stage) NPC were randomly assigned to the prevention group,the treatment group and the control group. All patients received current chemo-radiotherapy ± neoadjuvant chemotherapy. Radiation technique and dose were similar among the three groups. Intravenous infusion of aeovegin was started when radiation started in the prevention group and when grade 2 mueositis occurred in the treatment group,which was given 30 ml daily ,5 times per week until the end of radiotherapy. Criteria of NCI CTC 2.0 and VRS were used to evaluate acute oral mueositis and pain degree,respectively. Results 154 patients were eligible for the efficacy analysis,including 49 in the prevention group,53 in the treatment group and 52 in the control group. In the prevention group and the control group, the incidence was 31% and 56% (P=0.011) for grade 3-4 mucositis,59% and 83% (P=0.009) for grade 2-3 pain. In the treatment group and the control group,the corresponding number was 38% and 60% (P=0.023) ,70% and 90%, (P=0.014). The prevention group had a lower incidence(P=0.021) and longer average interval(P=0.009) of grade 2 mucositis when comparing with the control group. No drug-related adverse event was observed. Conclusions Prophylactic or therapeutic use of actovegin by intravenous infusion can significantly reduce the severity of ehemo-radiotherapy induced oral mucositis and pain. The prophylactic use may also postpone and decrease the incidence of grade 2 mucositis,which deserves clinic application.

Combined hyperfractionated radiotherapy and concurrent chemotherapy for stage Ⅲ-Ⅳ nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To compare the local control and survival rates of hyperfractionated radiotherapy plus concurrent chemotherapy with hyperfractionated radiotherapy alone in the treatment of stage Ⅲ-Ⅳ nasopharyngeal carcinoma (NPC).Methods Between December 1992 and December 1995, 150 NPC patients were randomized into hyperfractionated radiotherapy plus concurrent chemotherapy (R+C) and hyperfractionated radiotherapy alone (R alone) groups. Radiotherapy were similar in the two groups: 1.2 Gy/f, twice a day. Chemotherapy was given to R+C patients before and during the course of radiotherapy. Results The overall 5-year survival (OS), disease-free survival and distant metastasis-free survival rates were 57.3%, 55.9% and 55.9% . The 5-year survival rates of the R+C and R alone groups were 64.0% and 50.7%, with the difference statistically significant (P=0.037). One patient in the R+C group and 5 patients in the R alone group developed nasopharyngeal recurrence and the corresponding 5-year local control rates were 98.7% and 93.4%. The acute mucosal reaction in the R+C patients was severer than that of the R alone, but well tolerated and did not develop any severe complications. Conclusions Hyperfractionated radiotherapy plus concurrent chemotherapy can improve the local control and survival in patients with stage Ⅲ-Ⅳ nasopharyngeal carcinoma with well tolerated mucosal reactions. Chemotherapy gives greater benefit on the survival of stage Ⅳ patients.