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From synchronous metastasis to metachronous metastasis and from oligometastasis to disseminated metastasis, distant metastatic nasopharyngeal carcinoma (stage IV B) has great heterogeneity. The prognosis of stage IV B nasopharyngeal carcinoma patients with distant metastases is closely related to the anatomical characteristics of metastases. Therefore, it is necessary to subdivide M 1 stage to lay the foundation for individualized treatment of patients with metastatic nasopharyngeal carcinoma. In addition to systemic chemotherapy, the primary tumors and metastatic lesions should be considered during the treatment of newly-diagnosed metastatic nasopharyngeal carcinoma. Currently, there is a lack of recognized treatment modes for newly-diagnosed stageⅣ B nasopharyngeal carcinoma, and more studies are needed to evaluate the clinical benefits of different treatment methods.
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[Abstra ct] Objective To investigate the long-term efficacy and adverse effects of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC).Methods A total of 869 patients with biopsy-proven NPC without distant metastasis who underwent the whole course of IMRT from 2009 to 2010 were enrolled.Of all the patients, 84.8%received cisplatin-based chemotherapy.The prescribed dose to the primary lesion in the nasopharynx was 66-70Gy in 30-32 fractions, and the dose to the positive lymph nodes in the neck was 66 Gy in 30-32 fractions.The Kaplan-Meier method was used to calculate survival rates, the log-rank test was used for difference analysis and univariate prognostic analysis , and the Cox proportional hazards model was used for multivariate prognostic analysis .Rseu lts The 5-year overall survival( OS ) , local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and disease-free survival ( DFS ) were 84.0%, 89.7%, 94.5%, 85.6%, and 76.3%, respectively.In the patients with locally advanced NPC,concurrent chemotherapy tended to reduce distant metastasis (83.6%vs.75.7%, P=0.050) and improve OS (82.6%vs.77.0 %, P=0.082).Induction chemotherapy tended to improve OS ( 80.7% vs.71.4%, P=0.057 ) , and the induction chemotherapy containing docetaxel or gemcitabine tended to improve OS (83.3%vs.72.2%, P=0.058).The patients who received a boost after the initial radiotherapy had a significantly lower DFS rate than those who did not (52.2%vs.71.1%, P=0.004).The concurrent chemotherapy increased the incidence rates of long-term xerostomia and trismus, while a high dose of cisplatin increased the incidence rates of xerostomia and hearing impairment.Conclusions IMRT for NPC provides satisfactory long-term efficacy.Concurrent chemotherapy combined with IMRT tends to reduce the incidence of distant metastasis, and other values need further investigation.The boost therapy after radiotherapy may be associated with poor prognosis.Chemotherapy increases the incidence of long-term toxicities.
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Objective To investigate the role of transoralsonography guiding fine?needle aspiration biopsy in the diagnosis of retropharyngeal or parapharyngeal masses identified on the CT, MRI or PET?CT images of treated patients with malignant carcinoma. Methods From 2002 to 2013,this study recruited fifty?five patients with a history of cancer, of which 50 were treated with radiation treatment, including 46 nasopharyngeal carcinoma, 3 esophagus squamous cell carcinoma and1 lung apex carcinoma. There were 4 patients with a history of 1 thyroid papillary carcinoma, 1 buccal mucosa squamous cell carcinoma,1 glottis squamous cell carcinoma and 1 sigmoid colon adenocarcinoma treated with surgery. The rest one patient with nasal olfactory neuroblastoma was treated by postoperative radiation. The enlarged retropharyngeal lymph nodes in 44 cases and parapharyngeal masses in 10 cases were identified on CT or MRI imges. The enlarged retropharyngeal lymph node in the rest case was identified on PET?CT. With transoral ultrasound examination, all lesions were with hypo?intensity echo. Cystic areas were noted on occasion. Biopsy was performed in all cases. Results After cytology examination, carcinoma cells were detected in 37 retropharyngeal lymph nodes, with a detection rate of 82% (37/ 45). In the 10 parapharyngeal masses, carcinoma cells were detected in 3 lesions, with a detection rate of 30%. Conclusions Transor alsonography guiding fine?needle aspiration biopsy can be useful in the cytopathology diagnosis of retropharyngeal or parapharyngeal masses identified on the CT, MRI or PET?CT images of treated patients with malignant carcinoma,which facilitates, early diagnosis and treatment for patients.
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Background and purpose: With the development of therapy equipments and technology, the treatment for nasopharyngeal carcinoma(NPC) has entered into the era of precision radiotherapy, and setup errors have become a very important factor affecting treatment effects. The purpose of this study was to analyze the set-up errors detected by the kilovoltage cone beam CT(EPID) and the megavoltage electronic portal imaging device(CBCT) using 2 kinds of different immobilization techniques (pillow+head neck shoulder mask and vacuum bag+head neck shoulder mask) for NPC patients. Methods:A total number of 40 NPC patients were randomly assigned into 2 groups (pillow+head neck shoulder mask group and vacuum bag+neck shoulder mask group). Then each group was further divided into CBCT scan group and EPID group for veriifcation before treatment delivery. We matched the EPID images with the DRRs and acquired the set-up errors in x, y, z axis. Setup errors of CBCT were calculated according to its matched and planned CT images in left-right (x), superior-inferior (y) and anterior-posterior (z) directions. Paired t-test was used to evaluate the differences. Results:In the pillow+head neck shoulder mask group, the set-up errors of CBCT in the x, y, z axis were x (0.67±2.01)mm, y (0.51±1.71)mm and z (0.57±2.04)mm, respectively. The errors of EPID were x (0.69±2.19)mm, y (0.54±2.03)mm and z (0.61±2.11)mm. In the vacuum bag+head neck shoulder mask group, the set-up errors of CBCT in the x, y, z axis were x (0.42±1.81)mm, y (0.33±1.55)mm and z (0.50±1.75)mm, respectively. The errors of EPID were x (0.44±1.87)mm, y (0.43±1.70)mm and z (0.54±1.77)mm. The vacuum bag+head neck shoulder mask ifxed technique was more accurate when compared to the pillow + head neck shoulder mask ifxation method (P<0.05). Conclusion:CBCT and EPID were similar in detecting set-up errors for the NPC patients. However, the vacuum bag+neck shoulder mask ifxed technique was more accurate when compared to the pillow+head neck shoulder mask ifxation method.
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Background and purpose:Neoadjuvant chemotherapy with docetaxel was gaining more attention in the treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). The prediction of the sensitivity to neoadjuvant chemotherapy with docetaxel could enable clinicians to individualize treatment protocols for NPC. Recently we found that 99mTc-MIBI imaging in NPC could predict tumor response to chemotherapy with cisplatin plus 5-FU. However, there was no study to support similar findings in NPC patients receiving chemotherapy containing docetaxel. This study was to evaluate the value of double-phase 99mTc-MIBI SPECT/CT in predicting response to neoadjuvant chemotherapy with docetaxel-based regimen for nasopharyngeal carcinoma. Methods:Thirty-one nasopharyngeal carcinoma patients participated in this prospective study. Before treatment, early and delayed single-photon emission computed tomography/compute tomography (SPECT/CT) images were obtained instantly and 2 hours after an intravenous injection of 25-30 mCi 99mTc-MIBI. All patients received neoadjuvant chemotherapy consisting of docetaxel, cisplatin plus 5-FU for two cycles. The relationships between efficacy of neoadjuvant chemotherapy and the early uptake ratio, late uptake ratio and washout rate of 99mTc-MIBI were evaluated.Results:According to the MRI, the early uptake of 99mTc-MIBI (2.67±0.83) in the lesions which were sensitive to chemotherapy was significantly higher compared with that (1.69±0.46) in the insensitive lesions(P=0.003). The difference of the late uptake between the sensitive(1.46±0.39) and the insensitive (1.06±0.62) was also statistically significant (P=0.026). However, the washout rate of 99mTc-MIBI was not significantly different between the two groups (P=0.23). Through ROC curve analysis, the AUC for early uptake of 99mTc-MIBI and late uptake were 0.84. The sensitivity, specificity, positive predictive value and negative predictive value were 74.2%, 87.5%, 95.8%and 46.7%for early uptake when the cut off value of 1.97 was used. Conclusion:The uptake of 99mTc-MIBI in both early phase and late phase could predict the efficacy of neoadjuvant chemotherapy with docetaxel-based regimen.
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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.
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Objective To investigate the value of magnetic resonance sialography (MRS) as a noninvasive tool in evaluating major salivary gland function before and after radiotherapy (RT) for nasopharyngeal carcinoma patients.Methods From August 2009 to June 2010,patients with stage Ⅰ and Ⅱa (AJCC/UICC 2002) nasopharyngeal carcinoma were enrolled.All the patients were treated with intensity modulated radiation therapy alone.MRS with salivary stimulation was performed in patients before and after RT on a 3.0T MR scanner.An MRS categorical scoring system was used to compare the visibility of ducts pre-RT and post-RT.The relationship between MRS score and EORTC Core QOL and EORTC Head and Neck QOL was analyzed.Spearman rank correlation test was performed to analyze the non-stimulated and stimulated MRS findings and the clinical severity of xerostomia.Results All 10 enrolled patients completed planned treatment.The mean dose of the parotid glands and submandibular glands were (37.99 + 3.70) Gy and (55.65 + 2.99) Gy,respectively.Good-quality MRS images were obtained.The visibility scores of both the parotid and submandibular ducts were increased after secretion stimulation.Irradiation decreased the visualization of the salivary ducts and attenuated the response to secretion stimulation.There were specific correlations between post-RT secretion response of the parotid gland and EORTC QLQ scales ( global QOL scale in QLQ-C30 ( rs =0.636,P =0.048 ) and xerostomia scale in QLQ H&N35 ( rs =- 0.694,P =0.026) ).Conclusions MRS can be used as a non-invasive way to evaluated of the functional changes of major salivary glands before and after RT and as a promising approach for investigating radiation-induced xerostomia.
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Objective Nasopharyngeal carcinoma patients with stage N3 disease are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy(CRT).The aim of this study is to compare the ettlcacy of difierent chemotherapy sequences in these patients.Methotis All patients with histologically proven,carcinoma of the nasopharynx treated between July 1999 and November 2003 were restaged according to the AJCC 2002 stage classification system.A total of 114 patients had AJCC N3 diseases were analyzed retrospectively.Patients were treated by conventional RT technique using 6 MV photons or 60 Coγ-ray with 1.8-2.0 Gy per fraction,5 fractions a week,to a planned dose of 70 Gy.The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients received RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The median follow up time was 54 months(3-117months).The 5-year overall survival rate was 59.1%in whole groups,and with 17%,51%,68%and 71%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=15.44,P=0.001).The 5-year relapse-free survival rates were 83%,77%,88%and 93%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=2.34,P=0.505).The 5-year metastasis-free survival rates were 17%,54%,72%and 80%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=19.28,P=0.000).Conclusions The NACT+CRT and CRT+AC regimens were more effective than CRT alone for N3 disease in the current study.Large prospective,randomized clinieal studies are warranted.
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Objective To study the effect of different fraction interval with same total radiation dose on tumor growth delay and survival in C57BL mice implanted with lewis lung cancer,and to determine whether prolonged fraction interval will decrease the tumor response to radiation. Methods Forty-eight mice were implanted with lewis lung cancer in the back legs.When the diameter of transplanted tumor reached 0.8 to 1 cm,the mice were randomized into 6 groups:normal control group,single fraction of 18 Gy group,18 Gy in 2 fractions of 9 Gy at 30 min interval group,18 Gy in 7 fractions of 2.57 Gy at 5 min inter val group,18 Gy in 2 fractions of 9 Gy at 60 min interval group and 18 Gy in 7 fractions of 2.57 Gy at 10 rain interval group.The maximal and minimal diameters of the tumor were measured and record every other day to study the tumor growth tendency,the tumor growth delay and the mice survival time. Results The tumor growth delay of groups at prolonged fraction interval was shorter than the group with single fraction of 18 Gy (P < 0.05).The tumor growth delay of groups at fraction interval of 30 rain was longer than that of groups at interval of 60 rain (P < 0.05).There was no significant difference of the tumor growth delay be tween the groups with same delivery time (P >0.05).The mice survival time of the groups with prolonged fraction interval was shortened when omparing to the group with single fraction of 18 Gy.While the difference was not significant between the groups at fraction interval of 30 min and 60 min. Conclusions The pro longed fraction interval but same total radiation dose shortens the tumor growth delay and survival time in the mice implanted with Lewis lung cancer.The longer fraction interval impairs the tumor control more signifi candy.However the difference of the effect on mice survival time is not significant between the groups at fraction interval of 30 min and 60 min.
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Objective To summarize our experience and treatment results of nasopharyngeal carcinoma treated in a single institution. Methods From Jan. 2000 to Dec.2003,1837 patients with histologically proven nasopharyngeal carcinoma(NPC) were retrospectively analyzed. The disease was staged according to the Fuzhou stage classification. 885 patients received cisplatin (DDP) based chemotherapy. All patients received radiotherapy to the nasopharynx and neck. The dose was 30.6-74.0 Gy, 1.8-2.0 Gy per fraction over 3.5-8.0 weeks to the primary site with 60Co γ rays or 6 MV X-rays. The dose to lymph nodes was 60-68 Gy. The residual disease was boosted by 192Ir afterloading brachytherapy,small external beam fields, conformal radiotherapy,or X-knife. Results The median follow-up time was 54(3-90) months. The 5-year overall survival(OS), disease-free survival (DFS), relapse-free survival (RFS) and distant metastasis free survival(DMSF) rates were 67.42% ,63.25% ,86.47% and 80.31% ,respectively. Clinical stage was the most significant prognostic factor,and OS was 88% ,74.8% ,65.9% ,52.4% and 20% for stage Ⅰ ,stage Ⅱ,stage Ⅲ,stage ⅣA and stage ⅣB,respectively. Gender,T,N and TNM stage were the significant prognostic factors of OS in multivariate analysis. Conclusions For NPC patients,the 5-year OS of 67.4% is achieved by conventional radiotherapy technique in our institution. Both univariate and multivariate analysis shows that gender and clinical stage are the significant prognostic factors of OS.
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Background and purpose:As a new and important radiotherapy technique,intensity-modulated radiation therapy(IMRT) has been widely used in the clinic,but it requires longer time to deliver for one treatment session.The purpose of this study was to investigate the radiobiological effects of CNE and A549 cell lines irradiated by IMRT model.Methods:Part Ⅰ:The radiobiological characteristics of CNE and A549 cell lines were studied with standard clonogenic assays,using standard liner-quadratic model and incomplete repair model to fit the dose-survival curves.Part Ⅱ:a total dose of 8 Gy was given in two fractions with different interfraction intervals to compare the differences of cell surviving fractions(SF).Part Ⅲ:fractionated irradiation of 2 Gy,2 Gy?2,2 Gy?3,2 Gy?4 were given with one fraction per day simulating clinical dose-time-fractionation pattern in 2,20 and 40 min per fraction,respectively.Results:The ?/? of CNE and A549 was 1.76 and 12.41 Gy,respectively;the cell surviving fractions increased when the interfraction interval was longer,The values of SF2 were 0.0237 and 0.0243 in 2 min irradiation group,0.0304 and 0.0296 in 20 min irradiation group,and increased to 0.0378 and 0.0359 in 40 min irradiation group,respectively.Conclusion:The prolonged fraction delivery time would significantly decrease theradiobiological effects,it is strongly recommended that the delivery time be kept as short as possible,or do appropriate dose compensation.
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Purpose:To compare chemoradiotherapy against radiotherapy alone in the treatment of locoregionally advanced nasopharyngeal carcinoma.Methods:From September 1995 to July 1997,eighty-six patients with histologically proven NPC who were staged according to the Fuzhou stage classification to be N 2-3 were entered. Eighty-four patients were evaluable for tumor response and survival. The patients were randomized to receive two cycles of cisplatin (DDP) 20 mg/m 2 on Days 1-3,fluorouracil (5-Fu) 500 mg/m 2 on Days 1-3,before radical radiotherapy (RT),and three cycles of postradiotherapy chemotherapy (39 patients) or radiotherapy alone (45 patients). For chemoradiotherapy (CT-RT) group,the second cycle was given on Day 14 and the radiotherapy was given on Day 27. All patients received radical radiotherapy to the nasopharynx and neck. Radiation therapy consisted of delivering 65.1-70.3 Gy in 35-37 fractions of 1.85-1.9 Gy each over 7-7.5 weeks to the primary site with external beam 60 Co in both groups. The lymph nodes of the neck were given 56.6-65.5 Gy in 7-7.5 weeks. Boost radiotherapy was given to any residual disease. The rates of radiotherapy for boosting primary site or residual lymph nodes were not significantly different in the two arms. Results:The median follow up was 5.04 years. The 5-year actuarial survival rate (ASR) was 72.3% in CT-RT arm and 58.4% in RT arm ( P =0.154). The 5-year disease free survival rate (DFS) was 59.9% in CT-RT arm and 47.7% in RT arm ( P =0.207). The 5-year free from local failure rate (FLF) in nasopharynx was 89.5% in CT-RT arm and 81.4% in RT arm respectively ( P =0.151). The 5-year FLF in neck was 88.3% in CT-RT arm and 75.2% in RT arm respectively ( P =0.134). The 5-year free from distant metastasis rate (FDM) was 76.3% in CT-RT arm and 60.3% in RT arm ( P =0.181). The median time to first distant metastasis was 1.08 years in CT-RT arm and 0.88 year in RT arm. Although the differences did not reach statistical significance,there was some benefit from adjunctive chemotherapy to radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma. Toxicities in CT-RT arm were mainly myelosuppression and nausea and vomiting. There was no significant difference in the incidence and severity of acute mucositis between the two arms during radiotherapy. There was no treatment-related death. Conclusions:This prospective randomized trial demonstrated some benefit in DFS,FLF,FDM from adjunctive chemotherapy to radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma. But the differences were not significant. The chemoradiotherapy increased neither the incidence and severity of acute mucositis nor the late reaction.