Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy

Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma(NPC) in the intensity?modulated radiotherapy(IMRT) era.Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center(South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging(MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results: The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac?tor for local failure(P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure(all P < 0.05). Intracranial extension had signiicant prognostic value for distant failure(P = 0.040).Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.

Significant value of 18F-FDG-PET/CT in diagnosing small cervical lymph node metastases in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emission tomography/computed tomography(PET/CT).The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients.Methods: Magnetic resonance images(MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage.Results: In total, 2082 SCLNs were identified, with 808(38.8%) ≥ 5 and < 6 mm in diameter(group A), 526(25.3%)≥ 6 and < 7 mm in diameter(group B),374(18.0%)≥ 7 and < 8 mm in diameter(group C), 237(11.4%) ≥8 and<9 mm in diameter(group D),and 137(6.5%) ≥ 9 and <10 mm in diameter(group E).The overall metastatic rates examined by using PET/CT for groups A, B,C,D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively(P< 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135(28.7%) and 46(9.8%) patients, respectively. The areas under curve of MRIdetermined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival.Conclusions: PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.

Prognostic value and predictive threshold of tumor volume for patients with locally advanced nasopharyngeal carcinoma receiving intensity-modulated radiotherapy

Background: Gross target volume of primary tumor(GTV?P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma(NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity?modulated radiotherapy(IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to ind a suitable cut?of value of GTV?P for prognosis prediction.Methods: Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver oper?ating characteristic(ROC) curves were used to identify the cut?of values of GTV?P for the prediction of diferent end?points [overall survival(OS), local relapse?free survival(LRFS), distant metastasis?free survival(DMFS), and disease?free survival(DFS)] and to test the prognostic value of GTV?P when compared with that of the American Joint Committee on Cancer T staging system.Results: The 358 patients with locally advanced NPC were divided into two groups by the cut?of value of GTV?P as determined using ROC curves: 219(61.2%) patients with GTV?P ≤46.4 mL and 139(38.8%) with GTV?P >46.4 mL. The 3?year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV?P ≤46.4 mL than in those with GTV?P > 46.4 mL(all P < 0.05). Multivariate analysis indicated that GTV?P >46.4 mL was an independent unfavorable prognostic factor for patient survival. The ROC curve veriied that the predictive ability of GTV?P was superior to that of T category(P < 0.001). The cut?of values of GTV?P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4 mL, respectively.Conclusion: In patients with locally advanced NPC, GTV?P >46.4 mL is an independent unfavorable prognostic indi?cator for survival after IMRT, with a prognostic value superior to that of T category.

Clinical treatment considerationsin the intensity-modulated radiotherapy era for patients with NO-category nasopharyngeal carcinoma and enlarged neck lymph nodes

Background:Nasopharyngeal carcinoma(NPC) shows a high proportion of lymph node metastasis,and treatment guidelines have been developed for positive nodes.However,no irradiation guidelines have been proposed for patients with enlarged neck lymph nodes(ENLNs) that do not meet the radiological criteria of 10 mm in diameter for positive lymph nodes.This study aimed to determine the prognostic value and radiation dose for ENLNs in NO-category NPC patients treated with intensity-modulated radiotherapy(IMRT).Methods:We reviewed the medical data of 251 patients with non-metastatic,NO-category NPC treated with IMRT.Receiver operating characteristic curves were used to calculate the cut-off value of the ENLN diameter for the prediction of disease failure.The biological equivalent dose(BED) for ENLNs was calculated.Patient survival was compared between the small and large ENLN groups.Independent prognostic factors were identified using the Cox proportional hazards model.Results:The estimated 4-year regional relapse-free survival rate was higher in patients with ENLNs ≥5.5 mm than in those with ENLNs <5.5 mm(100%vs.98.8%,P=0.049),whereas disease-free,overall,and distant metastasis-free survival rates were similar between the two groups.After adjusting for various factors,ENLN diameter was not identified as an independent prognostic factor(P > 0.05 for all survival rates).In the subgroup analysis,patients receiving BED ≥72 Gy had a similar prognosis as patients receiving BED <72 Gy in both the small and large ENLN groups.The multivariate analysis also confirmed that BED≥72 Gy was not associated with significantly improved prognosis in patients with NO-category NPC.Conclusions:A BED of 72 Gy to ENLNs is considerably sufficient to provide a clinical benefit to patients with NO-category NPC.Prospective studies are warranted to validate the findings in the present study.

A model to predict the risk of lethal nasopharyngeal necrosis after re-irradiation with intensity-modulated radiotherapy in nasopharyngeal carcinoma patients

Background:For patients with nasopharyngeal carcinoma(NPC) who undergo re-irradiation with intensity-modulated radiotherapy(IMRT),lethal nasopharyngeal necrosis(LNN) is a severe late adverse event.The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re-irradiation with IMRT in patients with recurrent NPC.Methods:Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study.Clinical characteristics,including recurrent carcinoma conditions and dosimetric features,were evaluated as candidate risk factors for LNN.Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model.Results:Among 228 patients enrolled in this study,204 were at risk of developing LNN based on risk analysis.Of the 204 patients treated,31(15.2%) developed LNN.Logistic regression analysis showed that female sex(P = 0.008),necrosis before re-irradiation(P = 0.008),accumulated total prescription dose to the gross tumor volume(GTV) ≥ 145.5 Gy(P = 0.043),and recurrent tumor volume >25.38 cm3(P = 0.009) were independent risk factors for LNN.A model to predict LNN was then constructed that included these four independent risk factors.Conclusions:A model that includes sex,necrosis before re-irradiation,accumulated total prescription dose to GTV,and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT.

Three-Dimensional Conformal and Intensity Modulated Dynamic Radiotherapy in Juvenile Nasopharyngeal Angiofibroma

Objective: Juvenile Nasopharyngeal Angiofibroma (JNA) is a benign neoplasm with a high vascularity component, greater craniofacial involvement in adolescent patients, and aggressive local behaviour. In unresectable patients, radiotherapy is a therapeutic option for local control. Our aim in this study was to analyze the clinical benefit and local control provided by two modalities of radiotherapy: the Three-Dimensional Conformal (3DC) technique and volumetric modulated arc therapy (VMAT), applied to pediatric patients with JNA considered unresectable and non-recurrent. Methods: In retrospective study, the information was recorded from pediatric patients with a diagnosis of non-recurrent and unresectable JNA treated with radiotherapy at the Oncology Hospital of the National Medical Center SXXI of Mexico City, from March 2010 to March 2021. Radiotherapy management and its association with clinical outcomes of tumour control, and symptoms were assessed. In addition, an evaluation of acute and chronic toxicity was performed. Results: It was found that the median age was 14 years. 9 patients (37.5%) underwent 3DC and 15 (62.5%) VMAT. In terms of local control, and progression-free survival, we did not find significant difference between radiotherapy modalities (p ≤ 0.57). Acute toxicity for both modalities presented statistical differences for radio epithelitis (p = 0.03). Only Grade I and II radiation-induced acute toxicity was observed. Regarding chronic toxicity, statistical significance was observed for craniofacial hypoplasia, in relation to its absence in the VMAT group (p = 0.001). Conclusion: The VMAT presents improvements in dosimetry parameters that improve patient toxicity. In both techniques adequate tumour control was observed, however, the rarity of the disease is a limitation to establish the most appropriate therapeutic technique.

Selective partial salivary glands sparing during intensity-modulated radiation therapy for nasopharyngeal carcinoma

Objective This study evaluated the dosimetric consequences of selective partial salivary gland sparing during intensity-modulated radiotherapy(IMRT) for patients with nasopharyngeal carcinoma(NPC).Methods Ten patients with NPC were enrolled in the study.Two IMRT plans were produced for each patient:conventional(control) and partial salivary glands-sparing(treatment),with dose constraints to the entire parotid glands or partial salivary glands(including the parotid and submandibular glands,delineated with the adjacent distance of at least 0.5 cm between the glands and PTV,the planning target volume) in planning,respectively.Dosimetric parameters were compared between the two plans,including the V_(110%),V_(100%),V_(95%)(the volume covered by more than 110%,100%,or 95% of the prescribed dose),Dmin(the minimum dose) of PTV,homogeneity index(HI),conformity index(CI),and the mean dose and percentage of the volume receiving 30 Gy or more(V_(30)) for the parotid glands and submandibular glands.Results Treatment plans had significantly lower mean doses and V_(30) to both the entire parotid glands and partial parotid glands than those in control plans.The mean doses to the partial submandibular glands were also significantly lower in treatment plans than in control plans.The PTV coverage was comparable between the two plans,as indicated by V_(100%),V_(95%),Dmin,CI,and HI.The doses to critical structures,including brainstem and spinal cord,were slightly but not significantly higher in treatment plans than in control plans.Conclusion A selective partial salivary gland-sparing approach reduces the doses to parotid and submandibular glands during IMRT,which may decrease the risk of post-radiation xerostomia while not compromising target dose coverage in patients with NPC.

Radiotherapy with neoadjuvant chemotherapy versus concurrent chemoradiotherapy for ascending-type nasopharyngeal carcinoma:a retrospective comparison of toxicity and prognosis

Background:In the era of intensity?modulated radiotherapy(IMRT),the role of neoadjuvant chemotherapy(NACT)in treating ascending?type nasopharyngeal carcinoma(NPC)is under?evaluated.This study was to compare the efficacy of NACT followed by IMRT(NACT+RT)with the efficacy of concurrent chemoradiotherapy(CCRT)on ascending?type NPC.Methods:Clinical data of 214 patients with ascending?type NPC treated with NACT+RT or CCRT between Decem?ber 2009 and July 2011 were analyzed.Of the 214 patients,98 were treated with NACT followed by IMRT,and 116 were treated with CCRT.The survival rates were assessed using Kaplan–Meier analysis,and the survival curves were compared using a log?rank test.Results:The 4?year overall survival,locoregional failure?free survival,distant failure?free survival,and failure?free sur?vival rates were not significantly different between the two groups(all P>0.05).However,patients in the CCRT group exhibited more severe acute adverse events than did patients in the NACT+RT group during radiotherapy,includ?ing leukopenia(30.2%vs.15.3%,P=0.016),neutropenia(25.9%vs.11.2%,P=0.011),and mucositis(57.8%vs.40.8%,P=0.028).After radiotherapy,patients in the CCRT group exhibited significantly higher rates of xerostomia(21.6%vs.Conclusions:The treatment outcomes of the NACT+RT and CCRT groups were similar;however,CCRT led to higher rates of acute and late toxicities.NACT+RT may therefore be a better treatment strategy for ascending?type NPC.

Effects of dosimetric inadequacy on local control and toxicities in the patients with T4 nasopharyngeal carcinoma extending into the intracranial space and treated with intensity.modulated radiotherapy plus chemotherapy

Background:To protect neurological tissues,underdosing occurs in most cases of T4 nasopharyngeal carcinoma(NPC) with intracranial extension.In this study,we aimed to evaluate the effect of dosimetric inadequacy on local control and late neurological toxicities for patients treated with intensity-modulated radiotherapy(IMRT) plus chemotherapy.Methods:We prospectively enrolled patients who had non-metastaticT4 NPC with intracranial extension treated between January 2009 and November 2013.The prescribed dose was 66.0-70.4 Gy to the primary planning target volume(primary gross tumor volume [GTVp;i.e.,the nasopharyngeal tumor] +5.0 mm).Dose-volume histogram parameters were calculated,including minimum point dose(D_(min)) and dose to 95% of the target volume(D95).All patients received chemotherapy with the cisplatin,5-fluorouracil,and docetaxel regimen.Survivals were estimated using the Kaplan-Meier method and compared using the log-rank test.Results:In total,41 patients were enrolled.The local partial response rate was 87.8% after induction chemotherapy.With a median follow-up of 51 months,7 patients experienced failure in the nasopharynx;the 3-year local failure-free survival and overall survival rates of the 41 patients were 87.4% and 90.2%,respectively.The actual mean D_(min) to the GTVp was 55.2 Gy(range 48.3-67.3 Gy),and D95 was 61.6 Gy(range 52.6-69.0 Gy).All doses received by neurological organs remained well within their dose constraints.No patients developed temporal lobe necrosis or other neurological dysfunctions.Conclusions:With relative underdosed IMRT plus effective chemotherapy,the patients achieved satisfactory local control with few late toxicities of the central nervous system.Determining the acceptable extent of dosimetric inadequacy requires further exploration.

Comparison of efficacy between two boost treatments in residual tumor of nasopharyngeal carcinoma after radical radiotherapy

Objective: To compare the efficacy between stereotactic radiotherapy (SRT) and intracavitary brachytherapy (brachytherapy) in residual tumor of nasopharyngeal carcinoma (NPC) after treating with conventional external beam radiotherapy. Methods: 60 patients with residual tumor of NPC after radical external beam radiotherapy (range 68 to 72 Gy) were randomized into SRT group (27 patients) and brachytherapy group (33 patients). Patients in SRT group received boost treatment of 10–20 Gy, 2–3 fractions, once every other day; patients in brachytherapy group were treated with boost 10–20 Gy, 5 Gy per fraction, twice a week. Results: Efficacy in the near future: in SRT group, the complete recession (CR), partial recession (PR) and no change (NC) rates were 77.8% (21/27), 18.5% (5/27), 3.7% (1/27), respectively and the efficacy rate was 96.3% (CR + PR); in brachytherapy group: the CR, PR and NC rates were 75.8% (25/33), 18.2% (6/33), 6.1% (2/33), respectively and the efficacy rate was 93.9% (CR + PR). The efficacy rates of the above two groups were compared (χ2 = 0.032, P > 0.05). Long term efficacy: in SRT group, 1-year and 3-year survival rates were 96.3%, 66.5% respectively and the median live time was 48 months; in brachytherapy group: 1-year and 3-year survival rates were 93.9%, 60.2% respectively and the median live time was 46 months. The survival rates of two groups were compared (χ2 = 0.172, P > 0.05). Conclusion: Both boost techniques of SRT and brachytherapy had elevated efficacy in patients with residual tumor of NPC and there was no obvious difference between the efficacy of the near and long term in SRT and brachytherapy group.

Technical and Dosimetric Study of Four Facio-cervical Fields Conformal Radiotherapy for Nasopharyngeal Carcinoma

Objective: The aim of this study is to establish the methods of four facio-cervical fields′conformal radiotherapy(4F-CRT) for nasopharyngeal carcinoma (NPC), and to optimize the methods for clinical practice. Methods and Materials: 40 patients with untreated NPC of T1-T4 (1997AJCC Staging System) were rolled into this study. Conventional and four facio-cervical fields conform plans were designed for each patient using Pinnacle 8.0 three-dimension treatment planning system(3D-TPS): 1) Improved plan, four facio-cervical fields′conform plans, anterior, posterior facio-cervical and 2 lateral opposing facio-cervical fields; 2) Conventional plan, two lateral opposing facio-cervical fields only with the same dose delivered to the target in each plan, dose volume histograms(DVHs) of the targets and normal organs, brain stem, spinal cord, parotid glands, and temporal mandibular joints(TMJs) were compared and the dose distribution were evaluated. Results: 1) The dose distribution of the improved plan could meet the requirements for the target volume. 2) There was not any significant difference in the dose of spinal cord between the two plans. The mean doses of Dmax for brain stem in conventional plan were much lower than those in the improved plan, though both were within safety limits. 3) Compared with the conventional plans, the improved plan significantly decreased the hotspot areas in the target volume and had better parotid glands and temporal mandibular joints sparing effect. Conclusion: Compared with the conventional plan, the improved plan provides satisfactory dose coverage to the tumor volume and better sparing of the parotid gland, TMJs and other normal tissues in external beam radiotherapy of NPC.

Dosimetry Comparison between Volumetric Modulated Arc Therapy with RapidArc and Fixed Field Dynamic IMRT for Local-Regionally Advanced Nasopharyngeal Carcinoma

Objective: A dosimetric study was performed to evaluate the performance of volumetric modulated arc radiotherapy with RapidArc on locally advanced nasopharyngeal carcinoma (NPC). Methods: The CT scan data sets of 20 patients of locally advanced NPC were selected randomly. The plans were managed using volumetric modulated arc with RapidArc and fixed nine-field coplanar dynamic intensity-modulated radiotherapy (IMRT) for these patients. The dosimetry of the planning target volumes (PTV), the organs at risk (OARs) and the healthy tissue were evaluated. The dose prescription was set to 70 Gy to the primary tumor and 60 Gy to the clinical target volumes (CTV) in 33 fractions. Each fraction applied daily, five fractions per week. The monitor unit (MU) values and the delivery time were scored to evaluate the expected treatment efficiency. Results: Both techniques had reached clinical treatment’s requirement. The mean dose (Dmean), maximum dose (Dmax) and minimum dose (Dmin) in RapidArc and fixed field IMRT for PTV were 68.4±0.6 Gy, 74.8±0.9 Gy and 56.8±1.1 Gy; and 67.6±0.6 Gy, 73.8±0.4 Gy and 57.5±0.6 Gy (P<0.05), respectively. Homogeneity index was 78.85±1.29 in RapidArc and 80.34±0.54 (P<0.05) in IMRT. The conformity index (CI: 95%) was 0.78±0.01 for both techniques (P>0.05). Compared to IMRT, RapidArc allowed a reduction of Dmean to the brain stem, mandible and optic nerves of 14.1% (P<0.05), 5.6% (P<0.05) and 12.2% (P<0.05), respectively. For the healthy tissue and the whole absorbed dose, Dmean of RapidArc was reduced by 3.6% (P<0.05), and 3.7% (P<0.05), respectively. The Dmean to the parotids, the spinal cord and the lens had no statistical difference among them. The mean MU values of RapidArc and IMRT were 550 and 1,379. The mean treatment time of RapidArc and IMRT was 165 s and 447 s. Compared to IMRT, the delivery time and the MU values of RapidArc were reduced by 63% and 60%, respectively. Conclusion: For locally advanced NPC, both RapidArc and IMRT reached the clinic requirement. The target volume coverage was similar for the different techniques. The RapidArc technique showed some improvements in OARs and other tissue sparing while using reduced MUs and delivery time.

THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY FOR LOCALLY RECURRENT NASOPHARYNGEAL CARCINOMA

Objective: To investigate the safety and effectiveness of three-dimensional conformal radiation therapy (3-D CRT) for locally recurrent nasopharyngeal carcinoma (NPC). Methods: From April 1998 to March 2000, 34 patients who had undergone previous external beam radiation therapy were retreated with 3-D CRT for locally recurrent NPC (33 poorly differentiated squamous cell carcinomas, 1 adenoma). The patients were re-staged according to Huaqing staging system with the following distribution: T1N0M0 in 5 cases, T2N0M0 in 11 cases, T3N0M0 in 12 cases, T4N0M0 in 6 cases. The maximal dimension of the gross tumor volume (GTV) ranged from 1.0 cm to 5.0 cm (median: 2.9 cm). CT simulation and 3-D planning were used to ensure full and conformal coverage of the planning target volume (PTV) by treated volume, while minimizing the absorbed dose of the adjacent normal tissue. 5–7 static conformal coplanar or noncoplanar portals were delivered for each fraction irradiation. The total dose delivered ranged from 65–70 Gy, with 2.5 Gy per fractionation, one fractionation per day, 5 days a week. Median follow-up time from 3-D CRT was 25 months (range: 12–36 months). Results: Over the follow-up period, local recurrence was observed in 3 patients, regional failure in 3, distant metastasis in 3, and six patients died; 88.2% (30/34) of the patient maintained local control, 82.4% (28/34) survived, and 76.5% (26/34) survived with no evidence of tumor. Acute complications were minor and few. The overall incidence of late complication was 20.6% (7/34), and severe complication was 14.7% (5/34), after re-irradiation with 3-D CRT. Conclusion: 3-D CRT is safety and effectiveness for most of the patients with locally recurrent NPC. Our preliminary results indicate a high local control rate and a low complication rate. The long-term curative effect and sequelae await further study.

Minimally invasive surgery alone compared with intensity-modulated radiotherapy for primary stage I nasopharyngeal carcinoma

Background:The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy(IMRT)as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma(NPC),but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients.Endoscopic nasopharyngectomy(ENPG)was successfully applied in recurrent NPC with radiation free and relatively low medical costs.In this study,we examined whether ENPG could be an effective treatment for localized stage I NPC.Methods:Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center.Simultaneously,the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort.The survival outcomes,quality of life(QOL),and medical costs between two groups were compared.Results:After a median follow-up of 59.0 months(95%CI 53.4-64.6),no death,locoregional recurrence,or distant metastasis was observed in the 10 patients treated with ENPG.The 5-year overall survival,local relapse-free survival,regional relapse-free survival,and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients(100%vs.99.1%,100%vs.97.7%,100%vs.99.0%,100%vs.97.4%,respectively,P>0.05).In addition,compared with IMRT,ENPG was associated with decreased total medical costs($4090.42±1502.65 vs.$12620.88±4242.65,P<0.001)and improved QOL scores including dry mouth(3.3±10.5 vs.34.4±25.8,P<0.001)and sticky saliva(3.3±10.5 vs.32.6±23.3,P<0.001).Conclusions:ENPG alone was associated with promising long-term survival outcomes,low medical costs,and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy.However,the application of ENPG should be prudent,and prospective clinical tri-als were needed to further verify the results.

调强放射治疗局部晚期鼻咽癌489例远期预后影响因素及晚期安全性研究

目的探讨行调强放射治疗(IMRT)初治局部晚期鼻咽癌远期预后影响因素及晚期安全性。方法回顾性纳入2012年1月至2017年12月于梅州市人民医院行IMRT一线治疗的局部晚期鼻咽癌病人共489例,分析随访生存情况、复发转移及晚期损伤情况,采用单因素和多因素评价局部区域控制率、总生存(OS)率及无复发生存(DFS)率独立影响因素。结果489例病人随访5年局部区域控制率为92.64%(453/489),5年DFS率为84.05%(411/489),5年OS率为91.00%(445/489)。随访过程中死亡65例,其中因局部区域复发死亡25例,因远处转移死亡35例,因其他事件死亡5例。随访3~4级晚期损伤发生率为2.04%(10/489);单因素分析结果显示,临床分期与IMRT一线治疗局部晚期鼻咽癌病人5年局部区域控制率有关(P<0.05);性别、EB DNA拷贝数、临床分期及N分期均与IMRT一线治疗局部晚期鼻咽癌病人5年DFS率有关(P<0.05);年龄、EB DNA拷贝数、临床分期及N分期均与IMRT一线治疗局部晚期鼻咽癌病人5年OS率有关(P<0.05)。Cox模型多因素分析结果显示,临床分期是IMRT一线治疗局部晚期鼻咽癌病人5年局部区域控制率独立影响因素(P<0.05);性别、年龄、吸烟和EB DNA拷贝数均是IMRT一线治疗局部晚期鼻咽癌病人5年DFS率独立影响因素(P<0.05);年龄、N分期和EB DNA拷贝数均是IMRT一线治疗局部晚期鼻咽癌病人5年OS率独立影响因素(P<0.05)。结论IMRT一线治疗局部晚期鼻咽癌远期预后与多种因素有关,包括性别、年龄、EB DNA拷贝数及分期情况,而随访晚期损伤以1~2级为主。

症状管理动态模型在鼻咽癌同步放化疗病人口咽部症状群管理中的应用研究

目的:探讨症状管理动态模型对鼻咽癌同步放化疗病人口咽部症状群中的干预效果。方法:将104例鼻咽癌同步放化疗病人随机分为干预组(53例)和对照组(51例)。对照组给予常规护理及症状管理日志,干预组在对照组基础上采用症状管理动态模型进行干预。干预从病人放疗第1天开始,至病人出院后2周结束,共8周。比较2组病人在干预实施后第2、4、6周末及出院后第2周末4个时间点,各种口咽部症状严重程度的差异,以及2组病人在干预实施前、干预结束后生活质量的差异。结果:2组病人的疼痛、味觉异常、吞咽困难、唾液黏稠及口干症状得分均存在时间、组间效应,疼痛、味觉异常症状得分同时有交互效应(P<0.05~P<0.01)。干预后干预组病人生活质量在躯体、认知、情绪等领域均高于对照组(P<0.05~P<0.01)。干预后病人生活质量在社会、躯体、角色功能等领域高于干预前(P<0.05)。结论:症状管理动态模型能够显著降低鼻咽癌同步放化疗病人口咽部症状群的严重程度,提高病人的生活质量。

Concurrent chemoradiotherapy with weekly docetaxel versus cisplatin in the treatment of locoregionally advanced nasopharyngeal carcinoma:a propensity score-matched analysis

Background:Promising efficacy and manageable toxicity of docetaxel-based concurrent chemoradiotherapy(CCRT)were reported in head and neck cancer.In addition,the effect of CCRT in combination with cisplatin and/or 5-fluorouracil on both locoregionally advanced and metastatic/recurrent nasopharyngeal carcinoma(NPC)was verified.However,CCRT with docetaxel for locoregionally advanced NPC are not well studied.This study aimed to compare effectiveness and toxicities of CCRT with weekly docetaxel versus tri-weekly cisplatin for locoregionally advanced NPC.Methods:Clinical data of patients with locoregionally advanced NPC newly diagnosed between January 2010 and December 2014 receiving CCRT with either weekly docetaxel(15 mg/m2)or tri-weekly cisplatin(80-100 mg/m2)were reviewed.Propensity score matching at a 1:1 ratio was performed to balance baseline characteristics.Adverse events and survival were compared between the two groups.Results:A total of 962 patients were included as the whole cohort,and 448 patients were matched and were regarded as the matched cohort.The median follow-up duration was 48 months for the whole cohort.The 3-year nodal recurrence-free survival rate was significantly increased for patients treated with docetaxel in both the whole(hazard ratio[HR]=0.37,95%confidence interval[CI]0.19-0.72,P=0.030)and matched cohorts(HR=0.33,95%CI 0.14-0.79,P=0.023).However,no significant differences were observed in overall survival,local recurrence-free survival,and distant metastasis-free survival between the two groups in both cohorts.Significantly higher rates of grade 3 radiodermatitis(6.7%vs.1.8%,P=0.001),mucositis(74.5%vs.37.9%,P<0.001),and leucopenia(2.2%vs.11.6%,P<0.001)were observed in the docetaxel group,but any grade of renal injury(1.8%vs.15.1%,P<0.001),vomiting(18.8%vs.88.3%,P<0.001),and ALT elevation(19.2%vs.31.3%,P=0.027)were more common in the cisplatin group.Conclusions:CCRT with weekly low-dose docetaxel is an effective and tolerable therapeutic regimen for locally advanced NPC.It provides a survival benefit mainly by improving the control of regional lymph node metastases,especially for patients with low pretreatment EBV DNA levels.

鼻咽部髓外浆细胞瘤1例

1临床资料患者,女,54岁,主因渐进性鼻塞1年余入院。患者夜间睡眠时张口呼吸伴打鼾,偶有头痛,无发热、血涕、耳鸣及听力下降。鼻内镜检查:右侧鼻咽部淡红色新生物,表面不光滑,质韧,堵塞全部右侧后鼻孔及大部分、左侧后鼻孔,基底位于右侧咽隐窝处(图1A)。耳内镜检查发现右耳鼓膜内陷,入院诊断为鼻咽部肿物。

Clinical outcomes for nasopharyngeal cancer with intracranial extension after taxanebased induction chemotherapy and concurrent chemo-radiotherapy in the modern era

Objective:To evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension(ICE)treated with induction chemotherapy(ICT)followed by chemo-intensity-modulated radiotherapy(CTRT)at a tertiary cancer center.Methods:We retrospectively analyzed 45 patients with histologically proven,non-metastatic NPC with ICE treated at our institute between October 2008 and October 2016.Patients were classified as minor ICE or major ICE,based on the extent of ICE.All the patients received 2-3 cycles of a taxane-based ICT regimen followed by CTRT.Radiotherapy was delivered with"riskadapted"intensity-modulated radiotherapy(IMRT)technique in all patients.Results:After a median follow up of 45 months(range:8-113 months),the estimated 5-year DFS,LRFS,DMFS,and OS of the entire cohort was 58%,82%,67%and 74%respectively.On multivariate analysis,histological subtype was an independent predictor of LRFS,and age was an independent predictor of DFS.The extent of ICE showed only a trend towards worse DFS(P=0.06).None of the factors significantly predicted for DMFS or OS.Gender,N-stage,and response to ICT did not significantly affect any of the outcomes.Grade 2 or worse subcutaneous fibrosis was seen in 22%of patients and grade 2 or worse xerostomia was seen in 24%of patients at last follow up.Thirty-three percent of the patients developed clinical hypothyroidism at last follow up.None of the patients experienced any neurological or vascular complications.Conclusions:Taxane-based induction chemotherapy followed by chemo-intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension.Distant metastasis continues to be the predominant problem in these patients.

外周血循环肿瘤细胞和EB病毒-DNA对鼻咽癌患者根治性放化疗后复发转移的评估价值

目的 探讨外周血循环肿瘤细胞(circulating tumor cells,CTCs)和EB病毒(EBV)-DNA对鼻咽癌患者根治性放化疗后复发转移的评估价值。方法 纳入2015年1月-2017年1月在广西壮族自治区桂东人民医院首次接受根治性放化疗鼻咽癌患者160例,利用抗体标记和流式细胞仪联合方法,分别检测患者治疗前后外周血CTCs数量和EBV-DNA拷贝数,且治疗后随访5年,对包括治疗前后CTCs和EBV-DNA在内的预后因子进行Cox单因素和多因素分析,绘制两者预测鼻咽癌患者根治性放化疗后复发转移的ROC曲线,进一步分析其预测效能,采用Kaplan-Meier法分别绘制CTCs阳性和CTCs阴性两组以及EBV-DNA阳性和EBV-DNA阴性两组患者生存曲线,探索CTCs及EBV-DNA与接受根治性放化疗鼻咽癌患者后复发转移的关系。结果 本研究所有患者经临床病理影像学评估美国癌症联合委员会(AJCC)分期为Ⅲ-Ⅳa期,接受根治性放化疗后随访5年。5年内复发转移患者74例,未复发转移患者86例,Cox单因素分析结果显示,年龄、T分级、N分级、AJCC分期、CTCs(治疗后)及EBV-DNA(治疗后)6个指标与鼻咽癌患者根治性放化疗后5年内复发转移可能相关(P<0.05),校正和控制混杂变量后AJCC分期、CTCs(治疗后)及EBV-DNA(治疗后)是影响鼻咽癌患者根治性放化疗后复发转移独立预测因素[HR(95%CI)=5.356(4.817-5.864)、2.425(2.117-2.835)、1.624(1.345-1.975)],CTCs及EBV-DNA预测鼻咽癌患者根治性放化疗后复发转移的曲线下面积(area under the curve,AUC)分别为[0.786(95%CI=0.735-0.855)]、[0.759(95%CI=0.721-0.841)],两者联合预测的AUC为[0.912(95%CI=0.875-0.945)]。Kaplan-Meier生存分析显示,治疗后CTCs阴性患者根治性放化疗后1年、3年、5年无病生存率分别为100%、92.4%、77.2%,明显高于治疗后CTCs阳性患者无病生存率,分别为78.5%、72.6%、48.5%,差异有统计学意义(χ2=6.789,P=0.009)。治疗后EBV-DNA阴性患者根治性放化疗后1年、3年、5年无病生存率分别为100%、81.5%、78.7%,明显高于治疗后EBV-DNA阳性患者无病生存率,分别为78.5%、52.3%、52.3%,差异有统计学意义(χ2=5.891,P=0.021)。结论 治疗后的CTCs和EBV-DNA可用于评估鼻咽癌患者根治性放疗后的复发转移风险。