objective:Two cycles of induction chemotherapy(IC)followed by 2 cycles of platinum-based concurrent chemoradiotherapy(CCRT)(2IC+2CCRT)for locoregionally advanced nasopharyngeal carcinoma(LA-NPC)is widely adopted but n...objective:Two cycles of induction chemotherapy(IC)followed by 2 cycles of platinum-based concurrent chemoradiotherapy(CCRT)(2IC+2CCRT)for locoregionally advanced nasopharyngeal carcinoma(LA-NPC)is widely adopted but not evidence-confirmed.This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy,toxicity and cost-effectiveness.Methods:This real-world study from two epidemic centers used propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)analyses.The enrolled patients were divided into three groups based on treatment modality:Group A(2IC+2CCRT),Group B(3IC+2CCRT or 2IC+3CCRT)and Group C(3IC+3CCRT).Long-term survival,acute toxicities and cost-effectiveness were compared among the groups.We developed a prognostic model dividing the population into high-and low-risk cohorts,and survivals including overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS)and locoregional relapse-free survival(LRRFS)were compared among the three groups according to certain risk stratifications.Results:Of 4,042 patients,1,175 were enrolled,with 660,419,and 96 included in Groups A,B and C,respectively.Five-year survivals were similar among the three groups after PSM and confirmed by IPTW.Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A(52.1%vs.41.5%vs.25.2%;41.7%vs.32.7%vs.25.0%)as were grade 3-4 nausea/vomiting and oral mucositis(29.2%vs.15.0%vs.6.1%;32.3%vs.25.3%vs.18.0%).Cost-effective analysis suggested that 2IC+2CCRT was the least expensive,while the health benefits were similar to those of the other groups.Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients,while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals,mainly reflected by LRRFS.Conclusions:In LA-NPC patients,2IC+2CCRT was the optimal choice regarding efficacy,toxicity and costeffectiveness;however,2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high-and low-risk populations,respectively.展开更多
Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the deve...Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the development of nasopharyngeal cancer(NPC)is still unclear.Methods:The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus(GEO)database and immunohistochemical analysis of clinical specimens collected from a patient cohort.Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15‑knockdown cell models.CCK8 assay,flow cytometry,wound healing,Transwell and clone formation assays were used to detect the proliferation,apoptosis,migration,invasion and colony formation of NPC cells in vitro.A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study.Furthermore,the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis,and several in vitro and in vivo functional assays were performed to explore its role in NPC.Results:The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues.High levels of KIF15 expression were also associated with short overall survival(OS)and progression-free survival(PFS).Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2(G2)phase,inhibition of cell proliferation,migration,invasion,colony formation,and enhanced cell apoptosis.The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC.Moreover,the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC.Rescue assays indicated that Pifithrin-αcould counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15.Conclusion:This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases.Therefore,KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC.展开更多
Background:Nasopharyngeal carcinoma(NPC)is one of the most prevalent cancers in Southeast Asia.Sirtuin 2(SIRT2)is a member of the NAD+-dependent deacetylase family and has been shown to play important roles in numerou...Background:Nasopharyngeal carcinoma(NPC)is one of the most prevalent cancers in Southeast Asia.Sirtuin 2(SIRT2)is a member of the NAD+-dependent deacetylase family and has been shown to play important roles in numerous biological processes.However,Its function in NPC remains uncertain.The primary aim of this study is to clarify the role of SIRT2 in NPC.Methods:In this research,we examined the effect of SIRT2 silencing on NPC cell proliferation and colony formation using vitro NPC cell lines.Co-immunoprecipitation and mass spectrometry was applied to identify SIRT2-interacting proteins in NPC cells.Results:In comparison to nasopharyngeal epithelial NP69 cells,SIRT2 was up-regulated in multiple NPC cell lines,particularly in CNE2 cells.SIRT2 knockdown abrogated CNE2 cell proliferation and colony formation,whereas SIRT2 overexpression promoted HNE1 cell proliferation and colony formation.The SIRT2-interacting proteins were gathered in gene expression and regulation processes including RNA processing and translation.Among the SIRT2-interacting proteins,there were multiple DEAD-box(DDX)family members.Of note,silencing of DDX24 phenocopied the effect of SIRT2 knockdown on NPC growth.Overexpression of DDX24 restored SIRT2-depleted CNE2 cells to proliferative and colony formation.Conclusions:Our study indicates that SIRT2 can interact with DDX24 to enhance NPC growth.The clinical relevance of SIRT2 and DDX24 in NPC warrants further investigation.展开更多
BACKGROUND Recent reports have described cases of metachronous breast metastasis in patients with nasopharyngeal carcinoma.However,no similar cases of synchronous breast metastasis have been reported,and evidence that...BACKGROUND Recent reports have described cases of metachronous breast metastasis in patients with nasopharyngeal carcinoma.However,no similar cases of synchronous breast metastasis have been reported,and evidence that can be used to support the clinical diagnosis of stage IV nasopharyngeal carcinoma in patients with concurrent breast metastasis remains lacking.Therefore,additional evidence is required to elucidate the clinical characteristics of this condition and aid in the development of optimal management strategies.CASE SUMMARY We report the case of a 46-year-old woman who visited our hospital with a right breast mass as the first symptom.The first pathological biopsy report suggested triple-negative breast invasive carcinoma.Subsequent imaging revealed a nasopharyngeal mass.Further puncture biopsy of the nasopharyngeal mass,molecular pathological Epstein–Barr virus in situ hybridization,and immunohistochemistry confirmed the diagnosis of nasopharyngeal carcinoma with breast metastasis.The patient did not undergo a mastectomy and achieved complete remission after chemotherapy and radiotherapy.She continued to receive oral chemotherapy as maintenance therapy and experienced no recurrence or metastasis during the 6-month follow-up period.CONCLUSION This case report suggests that breast specialists should carefully rule out secondary breast cancers when diagnosing and treating breast masses.Furthermore,clinicians should aim to identify the pathological type of the tumor to obtain the most accurate diagnosis and prevent excessive diagnosis and treatment.展开更多
[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentratio...[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentrations of cisplatin were set as 2.5,5.0,10.0,25.0,40.0μg/mL,and those of metformin were set as 0.625,1.25,2.5,5,10,and 20 mmol/L.After 48 h of intervention in nasopharyngeal carcinoma SUNE-1 cells,the proliferation inhibitory rate and the median inhibitory concentration(IC_(50))of SUNE-1 cells were measured by the CCK-8 method.[Results]It was found that different concentrations of cisplatin and metformin all had an inhibitory effect on the proliferation of SUNE-1 cells,and the inhibitory effect became more significant with the increase of concentration.The IC_(50)values of cisplatin and metformin were 43.57μg/mL and 6.855 mmol/L,respectively.[Conclusions]Cisplatin and metformin inhibited the proliferation of SUNE-1 cells in a concentration-dependent manner,providing a theoretical guidance for the clinical treatment of nasopharyngeal carcinoma.展开更多
Introduction: Nasopharyngeal carcinomas are the most radiation-sensitive tumours, and radiotherapy alone provides better local control. Objectives: To evaluate the clinical efficacy and acute and late toxicities of tw...Introduction: Nasopharyngeal carcinomas are the most radiation-sensitive tumours, and radiotherapy alone provides better local control. Objectives: To evaluate the clinical efficacy and acute and late toxicities of two different treatment regimens for locally advanced nasopharyngeal carcinoma. Methods: From 2014 to 2017, 150 cases of stage III and 68 cases of stage IVA nasopharyngeal carcinoma were treated. Of these, 137 received conventional radiotherapy plus chemotherapy, and 81 received intensity-modulated radiotherapy plus chemotherapy. Chemotherapy was given either as induction, concurrent or adjuvant therapy. Survival rates were calculated according to Kaplan Meier and compared with the Log-rank test. The RTOG or EORTC criteria were used to assess acute and late toxicities. Results: The median follow-up time was 21.5 months, and the 2-year locoregional relapse-free survival, distant metastases-free survival, and overall survival rates in the conventional radiotherapy plus chemotherapy group were 76%, 71% and 77%, respectively;in the intensity-modulated radiotherapy plus chemotherapy group, they were 97%, 84%, and 100%, respectively. The difference in survival between the two groups was significant (χ<sup>2</sup> = 5.06, P = 0.028). The incidence of grade 2 and 3 xerostomia one year after radiotherapy was 45.1% and 30.9% versus 33.3% and 0%. Conclusion: Compared with conventional radiotherapy plus chemotherapy, intensity-modulated radiotherapy plus chemotherapy offers better locoregional relapse-free survival and overall survival in patients with stage III and IVA nasopharyngeal carcinoma, and may significantly reduce the occurrence of radiation-induced xerostomia.展开更多
Objective The aim of this study was to clarify the outcomes of stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma and to promote scientific clinical treatmen...Objective The aim of this study was to clarify the outcomes of stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma and to promote scientific clinical treatment and research on it in China and other countries by creating a large data resource.Methods This Meta-analysis conducted a literature search using the China National Knowledge Infrastructure database for all clinical research articles on stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma in China.Data on patient cohort numbers and other research factors were recorded for every relevant clinical research article.Calculated and analyzed these fact sheets to pave the way for the objective of this project.Results A total of 40 clinical research articles including 1,371 patients in China from 1998 to 2012 were identified.The average cohort size was 34 patients(range 9-98 patients).The average total radiation dose range was 16-33.6 Gy.The average study or treatment duration was 3.51 years.The calculated average follow-up time was 31.59 months.Conclusion The study provided the largest resource for further research and Meta-analyses to determine the clinical pathway of stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma.The results indicated that variability in the total radiation dose,treatment or research time,and follow-up duration may have contributed to the complications and side effects of stereotactic radiotherapy for local residual and(or) local recurrent nasopharyngeal carcinoma in China.The calculated average total radiation dose,follow-up time,and treatment and research durations may be referenced for future treatment and research.This study also proposed worldwide cooperation for the metaanalysis of research articles on stereotactic radiotherapy for treating local residual and(or) local recurrent nasopharyngeal carcinoma.展开更多
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 ...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.展开更多
Background: Nasopharyngeal carcinoma(NPC) is a commonly diagnosed cancer in Southeast Asia. Many studies have examined the risk factors for NPC, yet the roles of some risk factors remain inconclusive. The purpose of t...Background: Nasopharyngeal carcinoma(NPC) is a commonly diagnosed cancer in Southeast Asia. Many studies have examined the risk factors for NPC, yet the roles of some risk factors remain inconclusive. The purpose of this study was to examine associations between modifiable lifestyle factors and the risk of NPC in the Singaporean population.Methods: We conducted a case–control study in Singapore with 300 patients and 310 controls who were recruited between 2008 and 2012. Each control was selected and individually matched to each patient based on sex, ethnicity, and age(±5 years). A total of 290 pairs of cases and controls were matched successfully. We examined lifestyle factors such as tobacco smoking, alcohol drinking, various salted and preserved food consumption, and weaning practices.Results: After adjusting for covariates, multivariate analysis showed that those participants who were current smokers and had ever smoked tobacco had a higher risk of NPC than participants who had never smoked, with odds ratios(ORs) of 4.50(95% confidence interval [CI] 2.58–7.86; P < 0.001) and 2.52(95% CI 1.54–4.12; P < 0.001), respectively. Those who consumed salted vegetables at least once a week also showed a significantly increased risk of NPC than those who never or rarely consumed salted vegetables, with an OR of 4.18(95% CI 1.69–10.38; P = 0.002).Conclusion: Smoking(currently and ever-smoked) and consuming salted vegetables once a week or more were lifestyle risk factors for NPC, and changes of these factors for the better may reduce the risk of NPC.展开更多
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 effica...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.展开更多
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 NP...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.展开更多
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 p...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.展开更多
Background:The current World Health Organization(WHO) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic information.This study aimed to propose an NPC histopathologic classification that can p...Background:The current World Health Organization(WHO) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic information.This study aimed to propose an NPC histopathologic classification that can poten?tially be used to predict prognosis and treatment response.Methods:We initially developed a histopathologic classification based on the morphologic traits and cell differentia?tion of tumors of 2716 NPC patients who were identified at Sun Yat?sen University Cancer Center(SYSUCC)(training cohort).Then,the proposed classification was applied to 1702 patients(retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients(prospective validation cohort) from SYSUCC.The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes.We used Cox proportional hazards models to estimate hazard ratios(HRs) with 95% confidence intervals(CI) for overall survival(OS).Results:The 5?year OS rates for all NPC patients who were diagnosed with epithelial carcinoma(EC;3708 patients),mixed sarcomatoid?epithelial carcinoma(MSEC;1247 patients),sarcomatoid carcinoma(SC;823 patients),and squamous cell carcinoma(SCC;253 patients) were 79.4%,70.5%,59.6%,and 42.6%,respectively(P < 0.001).In mul?tivariate models,patients with MSEC had a shorter OS than patients with EC(HR = 1.44,95% CI = 1.27–1.62),SC(HR = 2.00,95% CI = 1.76–2.28),or SCC(HR = 4.23,95% CI = 3.34–5.38).Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC(HR 49–0.75),and possibly for those with SCC(HR = 0.67,95% CI = 0.56–0.80),MSEC(HR = 0.58,95% CI = 0..74–1.28).= 0.63;95% CI = 0.40–0.98),but not for patients with SC(HR = 0.97,95% CI = 0Conclusions:The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associ?ated with a poor prognosis.展开更多
Background:The increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible(RIOSM) has become a significant problem that can limit long-term survival.The purpose of this study was to analyze the ...Background:The increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible(RIOSM) has become a significant problem that can limit long-term survival.The purpose of this study was to analyze the association of clinicopathologic characteristics with treatment outcomes and prognostic factors of patients who developed RIOSM after undergoing radiotherapy for nasopharyngeal carcinoma(NPC).Methods:We reviewed the medical records of 53,760 NPC patients admitted to Sun Yat-sen University Cancer Center during the period August 1964 to August 2012.Of these patients,47 who developed RISOM and met inclusion criteria were included in this study.Two of these 47 patients refused treatment and were then excluded.Results:For all patients treated for NPC at Sun Yat-sen University Cancer Center during the study period,the total incidence of RIOSM after radiotherapy was 0.084%(47/53,760).Two patients(4.4%) had metastases at the diagnosis of RIOSM.Thirty-nine of the 45(86.7%) patients underwent surgery for RIOSM;most patients(24/39;61.5%) who underwent resection had gross clear margins,with 15 patients(38.5%) having either a gross or microscopic positive margin.All patients died.The 1-,2-,and 3-year overall survival(OS) rates for the entire cohort of 45 patients were 53.3%,35.6%and 13.5%,respectively.The independent prognostic factors associated with high OS rate were tumor size and treatment type.Conclusions:RISOM after radiotherapy for NPC is aggressive and often eludes early detection and timely intervention.Surgery combined with postoperative chemotherapy might be an effective treatment to improve patient survival.展开更多
Background: The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM st...Background: The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopathologic factors for predicting the overall survival(OS) of non-metastatic nasopharyngeal carcinoma(NPC) patients after curative treatments.Methods: We retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy(IMRT) between 2001 and 2010 were also retrieved to examine the extensibility of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index(c-index).Results: We identiied and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging system for predicting the survival in both the primary cohort(0.69 vs. 0.62) and the IMRT cohort(0.67 vs. 0.63).Conclusion: We developed and validated a novel nomogram that outperformed the TNM staging system in predicting the OS of non-metastatic NPC patients who underwent curative therapy.展开更多
The value of adding induction chemotherapy(IC) to concurrent chemoradiotherapy(CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma(NPC) remains unclear.In our recent article entitled "Indu...The value of adding induction chemotherapy(IC) to concurrent chemoradiotherapy(CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma(NPC) remains unclear.In our recent article entitled "Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma:a phase 3,multicentre,randomised controlled trial" published in the Lancet Oncology,we reported the results of a phase Ⅲ,multicenter,randomized controlled trial comparing cisplatin,5-fluorouracil,and docetaxel(TPF) IC plus CCRT versus CCRT alone in patients wit hT3-4N1/TxN2-3M0 NPC(Clinical Trials.gov registration number NCT01245959).The IC-plus-CCRT group showed significantly higher 3-year failure-free survival,overall survival,and distant failure-free survival rates than the CCRT-alone group,with an acceptable toxicity profile.Our study suggests that adding TPF IC to CCRT could increase survival rates and reduce distant failure in patients with locoregionally advanced NPC.However,long-term follow-up is required to assess the eventual efficacy and toxicity of this strategy,and a more accurate method to determine prognosis is needed to enable better tailoring of treatment strategy for individual patients.展开更多
Objective: In our previous work, we incorporated complete blood count(CBC) into TNM stage to develop a new prognostic score model, which was validated to improve prediction efficiency of TNM stage for nasopharyngeal c...Objective: In our previous work, we incorporated complete blood count(CBC) into TNM stage to develop a new prognostic score model, which was validated to improve prediction efficiency of TNM stage for nasopharyngeal carcinoma(NPC).The purpose of this study was to revalidate the accuracy of the model, and its superiority to TNM stage, through data from a prospective study.Methods: CBC of 249 eligible patients from the 863 Program No.2006AA02Z4B4 was evaluated.Prognostic index(PI) of each patient was calculated according to the score model.Then they were divided by the PI into three categories: the low-, intermediate-and high-risk patients.The 5-year disease-specific survival(DSS) of the three categories was compared by a log-rank test.The model and TNM stage(7th edition) were compared on efficiency for predicting the 5-year DSS, through comparison of the area under curve(AUC) of their receiver-operating characteristic curves.Results: The 5-year DSS of the low-, intermediate- and high-risk patients were 96.0%, 79.1% and 62.2%,respectively.The low- and intermediate-risk patients had better DSS than the high-risk patients(P<0.001 and P<0.005, respectively).And there was a trend of better DSS in the low-risk patients, compared with the intermediate-risk patients(P=0.049).The AUC of the model was larger than that of TNM stage(0.726 vs.0.661,P=0.023).Conclusions: A CBC-based prognostic score model was revalidated to be accurate and superior to TNM stage on predicting 5-year DSS of NPC.展开更多
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 ...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.展开更多
For decades, the selection of chemotherapeutic regimens for the treatment of recurrent or metastatic nasopharyngeal carcinoma has been mainly empirical. To our knowledge, there is no phase 3 trial that has been conduc...For decades, the selection of chemotherapeutic regimens for the treatment of recurrent or metastatic nasopharyngeal carcinoma has been mainly empirical. To our knowledge, there is no phase 3 trial that has been conducted to determine the optimal treatment for these patients before our publication. Recently, we published an article in The Lancet entitled "Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial." The results of our study indicate that gemcitabine plus cisplatin could improve the survival of patients with recurrent or metastatic nasopharyngeal carcinoma compared with conventional fluorouracil plus cisplatin.展开更多
Objective:For locally advanced nasopharyngeal carcinoma(LA-NPC)patients,high incidences of distant metastases and severe treatment related toxicities are the main obstacles needed to be overcome.Raltitrexed,a specific...Objective:For locally advanced nasopharyngeal carcinoma(LA-NPC)patients,high incidences of distant metastases and severe treatment related toxicities are the main obstacles needed to be overcome.Raltitrexed,a specific thymidylate synthase inhibitor with a convenient administration schedule,has an acceptable and manageable toxicity,and possesses radio-sensitizing properties.To investigate the efficacy and safety of raltitrexed and cisplatin induction chemotherapy and concurrent chemoradiotherapy(IC+CCRT)in patients with LA-NPC,a phaseⅡclinical study was conducted.Methods:Sixty eligible patients with LA-NPC were enrolled into this study.A raltitrexed-cisplatin combination was used as part of an IC+CCRT regimen.Raltitrexed-cisplatin IC was given once every 3 weeks(q3 w)for two cycles,followed by raltitrexed-cisplatin based CCRT q3 w for two cycles.Intensity-modulated radiotherapy(IMRT)was given for all enrolled patients.Results:All patients were included in survival analysis according to the intent-to-treat principle.The objective response rate(ORR)3 months after treatment was 98%.The 2-year overall survival(OS)rate was 92%.The median relapse-free survival(RFS)time was 30.5[95%confidence interval(95%CI),28.4-32.3]months.The 2-year RFS rate was 85%.The 2-year local failure-free survival(LFFS)rate was 97%and the 2-year distant metastasis-free survival(DMFS)rate was 88%.Acute toxicities were mostly grade 2 and 3 reactions in bone marrow suppression,gastrointestinal side effect and oropharyngeal mucositis.Only two patients occurred grade 4 acute toxicities,one was bone marrow suppression and the other was dermatitis radiation.Conclusions:The combination of raltitrexed and cisplatin has a comparable efficacy to those in standard firstline therapy.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81872375 and 82172863)the Natural Science Foundation of Guangdong Province(No.2021A1515010118).
文摘objective:Two cycles of induction chemotherapy(IC)followed by 2 cycles of platinum-based concurrent chemoradiotherapy(CCRT)(2IC+2CCRT)for locoregionally advanced nasopharyngeal carcinoma(LA-NPC)is widely adopted but not evidence-confirmed.This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy,toxicity and cost-effectiveness.Methods:This real-world study from two epidemic centers used propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)analyses.The enrolled patients were divided into three groups based on treatment modality:Group A(2IC+2CCRT),Group B(3IC+2CCRT or 2IC+3CCRT)and Group C(3IC+3CCRT).Long-term survival,acute toxicities and cost-effectiveness were compared among the groups.We developed a prognostic model dividing the population into high-and low-risk cohorts,and survivals including overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS)and locoregional relapse-free survival(LRRFS)were compared among the three groups according to certain risk stratifications.Results:Of 4,042 patients,1,175 were enrolled,with 660,419,and 96 included in Groups A,B and C,respectively.Five-year survivals were similar among the three groups after PSM and confirmed by IPTW.Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A(52.1%vs.41.5%vs.25.2%;41.7%vs.32.7%vs.25.0%)as were grade 3-4 nausea/vomiting and oral mucositis(29.2%vs.15.0%vs.6.1%;32.3%vs.25.3%vs.18.0%).Cost-effective analysis suggested that 2IC+2CCRT was the least expensive,while the health benefits were similar to those of the other groups.Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients,while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals,mainly reflected by LRRFS.Conclusions:In LA-NPC patients,2IC+2CCRT was the optimal choice regarding efficacy,toxicity and costeffectiveness;however,2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high-and low-risk populations,respectively.
基金supported by Guangxi Key Research and Development Plan(GuiKe-AB18050011)the Grant of Guangxi Science and Technology Base and Talent Project(GuiKe-AD20297069).
文摘Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the development of nasopharyngeal cancer(NPC)is still unclear.Methods:The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus(GEO)database and immunohistochemical analysis of clinical specimens collected from a patient cohort.Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15‑knockdown cell models.CCK8 assay,flow cytometry,wound healing,Transwell and clone formation assays were used to detect the proliferation,apoptosis,migration,invasion and colony formation of NPC cells in vitro.A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study.Furthermore,the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis,and several in vitro and in vivo functional assays were performed to explore its role in NPC.Results:The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues.High levels of KIF15 expression were also associated with short overall survival(OS)and progression-free survival(PFS).Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2(G2)phase,inhibition of cell proliferation,migration,invasion,colony formation,and enhanced cell apoptosis.The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC.Moreover,the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC.Rescue assays indicated that Pifithrin-αcould counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15.Conclusion:This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases.Therefore,KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC.
基金supported by 2017 Guangxi Appropriate Technology Development and Application Project(S2017013)the Project of Guangxi Health Department(Grant Nos.Z20190059 and Z20181011).
文摘Background:Nasopharyngeal carcinoma(NPC)is one of the most prevalent cancers in Southeast Asia.Sirtuin 2(SIRT2)is a member of the NAD+-dependent deacetylase family and has been shown to play important roles in numerous biological processes.However,Its function in NPC remains uncertain.The primary aim of this study is to clarify the role of SIRT2 in NPC.Methods:In this research,we examined the effect of SIRT2 silencing on NPC cell proliferation and colony formation using vitro NPC cell lines.Co-immunoprecipitation and mass spectrometry was applied to identify SIRT2-interacting proteins in NPC cells.Results:In comparison to nasopharyngeal epithelial NP69 cells,SIRT2 was up-regulated in multiple NPC cell lines,particularly in CNE2 cells.SIRT2 knockdown abrogated CNE2 cell proliferation and colony formation,whereas SIRT2 overexpression promoted HNE1 cell proliferation and colony formation.The SIRT2-interacting proteins were gathered in gene expression and regulation processes including RNA processing and translation.Among the SIRT2-interacting proteins,there were multiple DEAD-box(DDX)family members.Of note,silencing of DDX24 phenocopied the effect of SIRT2 knockdown on NPC growth.Overexpression of DDX24 restored SIRT2-depleted CNE2 cells to proliferative and colony formation.Conclusions:Our study indicates that SIRT2 can interact with DDX24 to enhance NPC growth.The clinical relevance of SIRT2 and DDX24 in NPC warrants further investigation.
文摘BACKGROUND Recent reports have described cases of metachronous breast metastasis in patients with nasopharyngeal carcinoma.However,no similar cases of synchronous breast metastasis have been reported,and evidence that can be used to support the clinical diagnosis of stage IV nasopharyngeal carcinoma in patients with concurrent breast metastasis remains lacking.Therefore,additional evidence is required to elucidate the clinical characteristics of this condition and aid in the development of optimal management strategies.CASE SUMMARY We report the case of a 46-year-old woman who visited our hospital with a right breast mass as the first symptom.The first pathological biopsy report suggested triple-negative breast invasive carcinoma.Subsequent imaging revealed a nasopharyngeal mass.Further puncture biopsy of the nasopharyngeal mass,molecular pathological Epstein–Barr virus in situ hybridization,and immunohistochemistry confirmed the diagnosis of nasopharyngeal carcinoma with breast metastasis.The patient did not undergo a mastectomy and achieved complete remission after chemotherapy and radiotherapy.She continued to receive oral chemotherapy as maintenance therapy and experienced no recurrence or metastasis during the 6-month follow-up period.CONCLUSION This case report suggests that breast specialists should carefully rule out secondary breast cancers when diagnosing and treating breast masses.Furthermore,clinicians should aim to identify the pathological type of the tumor to obtain the most accurate diagnosis and prevent excessive diagnosis and treatment.
基金Supported by Fujian Provincial Young and Middle-aged Teacher Education and Scientific Research Project(JAT200706)Innovation and Entrepreneurship Training Program for College Students of Xiamen Medical College(X202112631068)。
文摘[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentrations of cisplatin were set as 2.5,5.0,10.0,25.0,40.0μg/mL,and those of metformin were set as 0.625,1.25,2.5,5,10,and 20 mmol/L.After 48 h of intervention in nasopharyngeal carcinoma SUNE-1 cells,the proliferation inhibitory rate and the median inhibitory concentration(IC_(50))of SUNE-1 cells were measured by the CCK-8 method.[Results]It was found that different concentrations of cisplatin and metformin all had an inhibitory effect on the proliferation of SUNE-1 cells,and the inhibitory effect became more significant with the increase of concentration.The IC_(50)values of cisplatin and metformin were 43.57μg/mL and 6.855 mmol/L,respectively.[Conclusions]Cisplatin and metformin inhibited the proliferation of SUNE-1 cells in a concentration-dependent manner,providing a theoretical guidance for the clinical treatment of nasopharyngeal carcinoma.
文摘Introduction: Nasopharyngeal carcinomas are the most radiation-sensitive tumours, and radiotherapy alone provides better local control. Objectives: To evaluate the clinical efficacy and acute and late toxicities of two different treatment regimens for locally advanced nasopharyngeal carcinoma. Methods: From 2014 to 2017, 150 cases of stage III and 68 cases of stage IVA nasopharyngeal carcinoma were treated. Of these, 137 received conventional radiotherapy plus chemotherapy, and 81 received intensity-modulated radiotherapy plus chemotherapy. Chemotherapy was given either as induction, concurrent or adjuvant therapy. Survival rates were calculated according to Kaplan Meier and compared with the Log-rank test. The RTOG or EORTC criteria were used to assess acute and late toxicities. Results: The median follow-up time was 21.5 months, and the 2-year locoregional relapse-free survival, distant metastases-free survival, and overall survival rates in the conventional radiotherapy plus chemotherapy group were 76%, 71% and 77%, respectively;in the intensity-modulated radiotherapy plus chemotherapy group, they were 97%, 84%, and 100%, respectively. The difference in survival between the two groups was significant (χ<sup>2</sup> = 5.06, P = 0.028). The incidence of grade 2 and 3 xerostomia one year after radiotherapy was 45.1% and 30.9% versus 33.3% and 0%. Conclusion: Compared with conventional radiotherapy plus chemotherapy, intensity-modulated radiotherapy plus chemotherapy offers better locoregional relapse-free survival and overall survival in patients with stage III and IVA nasopharyngeal carcinoma, and may significantly reduce the occurrence of radiation-induced xerostomia.
文摘Objective The aim of this study was to clarify the outcomes of stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma and to promote scientific clinical treatment and research on it in China and other countries by creating a large data resource.Methods This Meta-analysis conducted a literature search using the China National Knowledge Infrastructure database for all clinical research articles on stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma in China.Data on patient cohort numbers and other research factors were recorded for every relevant clinical research article.Calculated and analyzed these fact sheets to pave the way for the objective of this project.Results A total of 40 clinical research articles including 1,371 patients in China from 1998 to 2012 were identified.The average cohort size was 34 patients(range 9-98 patients).The average total radiation dose range was 16-33.6 Gy.The average study or treatment duration was 3.51 years.The calculated average follow-up time was 31.59 months.Conclusion The study provided the largest resource for further research and Meta-analyses to determine the clinical pathway of stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma.The results indicated that variability in the total radiation dose,treatment or research time,and follow-up duration may have contributed to the complications and side effects of stereotactic radiotherapy for local residual and(or) local recurrent nasopharyngeal carcinoma in China.The calculated average total radiation dose,follow-up time,and treatment and research durations may be referenced for future treatment and research.This study also proposed worldwide cooperation for the metaanalysis of research articles on stereotactic radiotherapy for treating local residual and(or) local recurrent nasopharyngeal carcinoma.
基金supported by grants from the Key Laboratory Construction Project of Guangzhou City,China (121800085)the Health & Medical Collaborative Innovation Project of Guangzhou City,China (201400000001)+2 种基金the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10)the National Natural Science Foundation of China (81201746)the Planned Science and Technology Project of Guangdong Province,China (2013B020400004)
文摘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.
基金This study was funded by a grant from the National Cancer Centre Singapore Research Fund(CEFIA 08113-25260790-CREF-IARC)(Grant No.CEFIA08136).
文摘Background: Nasopharyngeal carcinoma(NPC) is a commonly diagnosed cancer in Southeast Asia. Many studies have examined the risk factors for NPC, yet the roles of some risk factors remain inconclusive. The purpose of this study was to examine associations between modifiable lifestyle factors and the risk of NPC in the Singaporean population.Methods: We conducted a case–control study in Singapore with 300 patients and 310 controls who were recruited between 2008 and 2012. Each control was selected and individually matched to each patient based on sex, ethnicity, and age(±5 years). A total of 290 pairs of cases and controls were matched successfully. We examined lifestyle factors such as tobacco smoking, alcohol drinking, various salted and preserved food consumption, and weaning practices.Results: After adjusting for covariates, multivariate analysis showed that those participants who were current smokers and had ever smoked tobacco had a higher risk of NPC than participants who had never smoked, with odds ratios(ORs) of 4.50(95% confidence interval [CI] 2.58–7.86; P < 0.001) and 2.52(95% CI 1.54–4.12; P < 0.001), respectively. Those who consumed salted vegetables at least once a week also showed a significantly increased risk of NPC than those who never or rarely consumed salted vegetables, with an OR of 4.18(95% CI 1.69–10.38; P = 0.002).Conclusion: Smoking(currently and ever-smoked) and consuming salted vegetables once a week or more were lifestyle risk factors for NPC, and changes of these factors for the better may reduce the risk of NPC.
基金supported by grants from the Science and Technology Project of Guangzhou City,China(No.14570006)the National Natural Science Foundation of China(Nos.81372409,81402532)the Sun Yat-sen University Clinical Research 5010 Program(No.2012011)
文摘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.
基金supported by the National Natural Science Foundation of China (No.81372792)
文摘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.
文摘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.
基金supported by grants from the National High Technology Research and Development Program of China(863 Program)(No.2012AA02A501)the Chinese State Key Basic Research Project(No.2011CB504805)the National Natural Science Foundation of China(No.81272952 and No.81472522)
文摘Background:The current World Health Organization(WHO) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic information.This study aimed to propose an NPC histopathologic classification that can poten?tially be used to predict prognosis and treatment response.Methods:We initially developed a histopathologic classification based on the morphologic traits and cell differentia?tion of tumors of 2716 NPC patients who were identified at Sun Yat?sen University Cancer Center(SYSUCC)(training cohort).Then,the proposed classification was applied to 1702 patients(retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients(prospective validation cohort) from SYSUCC.The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes.We used Cox proportional hazards models to estimate hazard ratios(HRs) with 95% confidence intervals(CI) for overall survival(OS).Results:The 5?year OS rates for all NPC patients who were diagnosed with epithelial carcinoma(EC;3708 patients),mixed sarcomatoid?epithelial carcinoma(MSEC;1247 patients),sarcomatoid carcinoma(SC;823 patients),and squamous cell carcinoma(SCC;253 patients) were 79.4%,70.5%,59.6%,and 42.6%,respectively(P < 0.001).In mul?tivariate models,patients with MSEC had a shorter OS than patients with EC(HR = 1.44,95% CI = 1.27–1.62),SC(HR = 2.00,95% CI = 1.76–2.28),or SCC(HR = 4.23,95% CI = 3.34–5.38).Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC(HR 49–0.75),and possibly for those with SCC(HR = 0.67,95% CI = 0.56–0.80),MSEC(HR = 0.58,95% CI = 0..74–1.28).= 0.63;95% CI = 0.40–0.98),but not for patients with SC(HR = 0.97,95% CI = 0Conclusions:The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associ?ated with a poor prognosis.
文摘Background:The increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible(RIOSM) has become a significant problem that can limit long-term survival.The purpose of this study was to analyze the association of clinicopathologic characteristics with treatment outcomes and prognostic factors of patients who developed RIOSM after undergoing radiotherapy for nasopharyngeal carcinoma(NPC).Methods:We reviewed the medical records of 53,760 NPC patients admitted to Sun Yat-sen University Cancer Center during the period August 1964 to August 2012.Of these patients,47 who developed RISOM and met inclusion criteria were included in this study.Two of these 47 patients refused treatment and were then excluded.Results:For all patients treated for NPC at Sun Yat-sen University Cancer Center during the study period,the total incidence of RIOSM after radiotherapy was 0.084%(47/53,760).Two patients(4.4%) had metastases at the diagnosis of RIOSM.Thirty-nine of the 45(86.7%) patients underwent surgery for RIOSM;most patients(24/39;61.5%) who underwent resection had gross clear margins,with 15 patients(38.5%) having either a gross or microscopic positive margin.All patients died.The 1-,2-,and 3-year overall survival(OS) rates for the entire cohort of 45 patients were 53.3%,35.6%and 13.5%,respectively.The independent prognostic factors associated with high OS rate were tumor size and treatment type.Conclusions:RISOM after radiotherapy for NPC is aggressive and often eludes early detection and timely intervention.Surgery combined with postoperative chemotherapy might be an effective treatment to improve patient survival.
基金supported by the National High Technology Research and Development Program of China (Grant No.2012AA02A501 and 2012AA02A502)Sun Yat-sen University Clinical Medical Research Project 5010 (Grant No.20130008)
文摘Background: The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopathologic factors for predicting the overall survival(OS) of non-metastatic nasopharyngeal carcinoma(NPC) patients after curative treatments.Methods: We retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy(IMRT) between 2001 and 2010 were also retrieved to examine the extensibility of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index(c-index).Results: We identiied and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging system for predicting the survival in both the primary cohort(0.69 vs. 0.62) and the IMRT cohort(0.67 vs. 0.63).Conclusion: We developed and validated a novel nomogram that outperformed the TNM staging system in predicting the OS of non-metastatic NPC patients who underwent curative therapy.
文摘The value of adding induction chemotherapy(IC) to concurrent chemoradiotherapy(CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma(NPC) remains unclear.In our recent article entitled "Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma:a phase 3,multicentre,randomised controlled trial" published in the Lancet Oncology,we reported the results of a phase Ⅲ,multicenter,randomized controlled trial comparing cisplatin,5-fluorouracil,and docetaxel(TPF) IC plus CCRT versus CCRT alone in patients wit hT3-4N1/TxN2-3M0 NPC(Clinical Trials.gov registration number NCT01245959).The IC-plus-CCRT group showed significantly higher 3-year failure-free survival,overall survival,and distant failure-free survival rates than the CCRT-alone group,with an acceptable toxicity profile.Our study suggests that adding TPF IC to CCRT could increase survival rates and reduce distant failure in patients with locoregionally advanced NPC.However,long-term follow-up is required to assess the eventual efficacy and toxicity of this strategy,and a more accurate method to determine prognosis is needed to enable better tailoring of treatment strategy for individual patients.
基金supported by Hi-Tech Research and Development Program of China (863 Program) (No.2006AA02Z4B4)
文摘Objective: In our previous work, we incorporated complete blood count(CBC) into TNM stage to develop a new prognostic score model, which was validated to improve prediction efficiency of TNM stage for nasopharyngeal carcinoma(NPC).The purpose of this study was to revalidate the accuracy of the model, and its superiority to TNM stage, through data from a prospective study.Methods: CBC of 249 eligible patients from the 863 Program No.2006AA02Z4B4 was evaluated.Prognostic index(PI) of each patient was calculated according to the score model.Then they were divided by the PI into three categories: the low-, intermediate-and high-risk patients.The 5-year disease-specific survival(DSS) of the three categories was compared by a log-rank test.The model and TNM stage(7th edition) were compared on efficiency for predicting the 5-year DSS, through comparison of the area under curve(AUC) of their receiver-operating characteristic curves.Results: The 5-year DSS of the low-, intermediate- and high-risk patients were 96.0%, 79.1% and 62.2%,respectively.The low- and intermediate-risk patients had better DSS than the high-risk patients(P<0.001 and P<0.005, respectively).And there was a trend of better DSS in the low-risk patients, compared with the intermediate-risk patients(P=0.049).The AUC of the model was larger than that of TNM stage(0.726 vs.0.661,P=0.023).Conclusions: A CBC-based prognostic score model was revalidated to be accurate and superior to TNM stage on predicting 5-year DSS of NPC.
基金supported by the National Natural Science Foundation of China(No.81472525 and 81572665)the Science and Technology Planning Project of Guangdong Province,China(No.2014A050503033)
文摘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.
文摘For decades, the selection of chemotherapeutic regimens for the treatment of recurrent or metastatic nasopharyngeal carcinoma has been mainly empirical. To our knowledge, there is no phase 3 trial that has been conducted to determine the optimal treatment for these patients before our publication. Recently, we published an article in The Lancet entitled "Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial." The results of our study indicate that gemcitabine plus cisplatin could improve the survival of patients with recurrent or metastatic nasopharyngeal carcinoma compared with conventional fluorouracil plus cisplatin.
基金supported by The Radiation Therapy Major Project of the Ministry of Science and Technology of China(No.2016YFC0105711)supported partly by Natural Science Foundation of China(No.81401913)。
文摘Objective:For locally advanced nasopharyngeal carcinoma(LA-NPC)patients,high incidences of distant metastases and severe treatment related toxicities are the main obstacles needed to be overcome.Raltitrexed,a specific thymidylate synthase inhibitor with a convenient administration schedule,has an acceptable and manageable toxicity,and possesses radio-sensitizing properties.To investigate the efficacy and safety of raltitrexed and cisplatin induction chemotherapy and concurrent chemoradiotherapy(IC+CCRT)in patients with LA-NPC,a phaseⅡclinical study was conducted.Methods:Sixty eligible patients with LA-NPC were enrolled into this study.A raltitrexed-cisplatin combination was used as part of an IC+CCRT regimen.Raltitrexed-cisplatin IC was given once every 3 weeks(q3 w)for two cycles,followed by raltitrexed-cisplatin based CCRT q3 w for two cycles.Intensity-modulated radiotherapy(IMRT)was given for all enrolled patients.Results:All patients were included in survival analysis according to the intent-to-treat principle.The objective response rate(ORR)3 months after treatment was 98%.The 2-year overall survival(OS)rate was 92%.The median relapse-free survival(RFS)time was 30.5[95%confidence interval(95%CI),28.4-32.3]months.The 2-year RFS rate was 85%.The 2-year local failure-free survival(LFFS)rate was 97%and the 2-year distant metastasis-free survival(DMFS)rate was 88%.Acute toxicities were mostly grade 2 and 3 reactions in bone marrow suppression,gastrointestinal side effect and oropharyngeal mucositis.Only two patients occurred grade 4 acute toxicities,one was bone marrow suppression and the other was dermatitis radiation.Conclusions:The combination of raltitrexed and cisplatin has a comparable efficacy to those in standard firstline therapy.
