Adolescent and childhood nasopharyngeal carcinoma(NPC)is a rare malignancy with unique biological and genetic characteristics,often associated with Epstein-Barr virus(EBV).This CACA guideline provides an integrative a...Adolescent and childhood nasopharyngeal carcinoma(NPC)is a rare malignancy with unique biological and genetic characteristics,often associated with Epstein-Barr virus(EBV).This CACA guideline provides an integrative approach to the management of adolescent and childhood NPC,focusing on biology,diagnosis,staging,and treatment strategies.The incidence of NPC is higher in adolescent boys and is more frequently diagnosed at an advanced stage in adolescent and childhood population compared to adults.However,adolescent and childhood NPC generally have a better prognosis.The primary treatment is radiotherapy(RT),with intensity-modulated radiation therapy(IMRT)being the preferred technique due to its reduced damage to normal tissues.Chemotherapy,particularly induction chemotherapy,plays a significant role,especially in locally advanced disease.Personalized treatment strategies,including adjusting RT dosage based on chemotherapy outcomes,may reduce long-term adverse effects.The role of adjuvant therapy post-RT remains unclear and requires further research.The main objective of this guideline is to standardize the clinical diagnosis and treatment process of adolescent and childhood nasopharyngeal carcinoma,with a multidisciplinary approach to optimize therapeutic outcomes and quality of life for this disease.展开更多
Background:Capecitabine was previously used as a second-line or salvage therapy for metastatic nasopharyngeal carcinoma(NPC)and has shown satisfactory curative effect as maintenance therapy in other metastatic cancers...Background:Capecitabine was previously used as a second-line or salvage therapy for metastatic nasopharyngeal carcinoma(NPC)and has shown satisfactory curative effect as maintenance therapy in other metastatic cancers.This study aimed to explore the role of capecitabine as maintenance therapy in de novo metastatic NPC patients with different plasma Epstein-Barr virus(EBV)DNA levels before treatment.Methods:We selected de novo metastatic NPC patients treated with locoregional radiotherapy(LRRT)for this retrospective study.The propensity score matching(PSM)was applied to balance potential confounders between patients who underwent capecitabine maintenance therapy and those who did not with a ratio of 1:3.Overall survival(OS)was the primary endpoint.The association between capecitabine maintenance therapy and survival was assessed using the log-rank test and a Cox proportional hazard model.Results:Among all patients eligible for this study,64 received capecitabine maintenance therapy after LRRT.After PSM,192 patients were identified in the nonmaintenance group.In the matched cohort,patients treated with capecitabine achieved a higher 3-year OS rate compared with patients in the non-maintenance group(68.5%vs.61.8%,P=0.037).Multivariate analysis demonstrated that capecitabine maintenance therapy was an independent prognostic factor.In subgroup analysis,3-year OS rate was comparable between the maintenance and non-maintenance groups in patients with high pretreatment EBV DNA levels(˃30,000 copies/mL)(54.8%vs.45.8%,P=0.835),whereas patients with low pretreatment EBV DNA levels(≤30,000 copies/mL)could benefit from capecitabine maintenance therapy in OS(90.0%vs.68.1%,P=0.003).Conclusion:Capecitabine maintenance therapy may be superior to non-maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA≤30,000 copies/mL.groups in patients with high pretreatment EBV DNA levels(˃30,000 copies/mL)(54.8%vs.45.8%,P=0.835),whereas patients with low pretreatment EBV DNA levels(≤30,000 copies/mL)could benefit from capecitabine maintenance therapy in OS(90.0%vs.68.1%,P=0.003).Conclusion:Capecitabine maintenance therapy may be superior to non-maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA≤30,000 copies/mL.展开更多
Background:Currently,the diagnosis and treatment of nasopharyngeal carcinoma(NPC)patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging.We investiga...Background:Currently,the diagnosis and treatment of nasopharyngeal carcinoma(NPC)patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging.We investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus(EBV)DNA in these patients.Methods:This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor therapy.Their plasma EBV DNA levels were measured using quantitative polymerase chain reaction(qPCR)before the initiation of treatment and before neck dissection.Fine needle aspiration cytology(FNAC)was performed in 21 patients.All patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical lymphadenopathy.The overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS),and locoregional relapse-free survival(LRRFS)were calculated using the Kaplan-Meier method and compared using the log-rank test.The Cox proportional hazards model was used to calculate hazard ratios(HRs)with 95%confidence intervals(CIs).Multivariable analysis was used to estimate the effect of potential prognostic factors on survival.Results:Following a median follow-up of 52.6 months,compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy,the patients with positive findings had a significantly lower 3-year PFS rate(49.9%vs.83.3%,P=0.008).Among NPC patients with residual cervical lymphadenopathy,the patients with preoperative plasma EBV DNA>0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA(43.7%vs.61.1%,P=0.031).In addition,combining FNAC with preoperative EBV DNA detection improved the diagnostic sensitivity.Multivariable analysis demonstrated that residual cervical lymphadenopathy with positive postoperative pathological result was an independent prognostic factor for PFS and that detectable preoperative plasma EBV DNA was an independent prognostic factor for OS.Conclusions: Using FNAC combined with preoperative EBV DNA detection improves the sensitivity in diagnosing NPC with residual cervical lymphadenopathy. Compared with patients with undetectable EBV DNA, patients with detectable preoperative plasma EBV DNA have worse prognosis and may require a more aggressive treatment strategy.展开更多
Main text In the past decades,there have been several studies con-cerning the efficacy of sequencing of chemotherapy on disease control and survival in locoregionally advanced(LA)nasopharyngeal carcinoma(NPC).The addi...Main text In the past decades,there have been several studies con-cerning the efficacy of sequencing of chemotherapy on disease control and survival in locoregionally advanced(LA)nasopharyngeal carcinoma(NPC).The addition of concurrent cisplatin to radiotherapy has demonstrated survival improvements that are attributable to both dis-tant metastasis and locoregional control.Specific to the latter,the advent of intensity-modulated radiotherapy has resulted in superior tumor control given the bet-ter dosimetry compared to conventional techniques[1].However,distant recurrence still occurs in 20-30%patients and accounts for the main cause of death.To address this,several groups have explored the advantages of adding neoadjuvant chemotherapy(NACT)or adju-vant chemotherapy(ACT)to the backbone of concurrent chemoradiotherapy(CCRT).展开更多
Background:Intratumor heterogeneity is common in cancers,with different cell subtypes supporting each other to become more malignant.Nasopharyngeal carcinoma(NPC),a highly metastatic cancer,shows significant heterogen...Background:Intratumor heterogeneity is common in cancers,with different cell subtypes supporting each other to become more malignant.Nasopharyngeal carcinoma(NPC),a highly metastatic cancer,shows significant heterogeneity among its cells.This study investigates how NpC cell subtypes with varying metastatic potentials influence each other through exosome-transmitted molecules.Methods:Exosomes were purified and characterized.MicroRNA expression was analyzed via sequencing and qRT-PCR.The effects of miR-30a-5p on migration,invasion,and metastasis were evaluated in vitro and in vivo.Its impact on desmoglein glycoprotein(DSG2)was assessed using dual-luciferase assays and Western blotting.Immunohistochemistry(IHc)and statistical modeis linked miR-30a-5p/DSG2levelstopatientprognosis.Results:Different NPC ceil subtypes transmit metastatic potential via exosomes.High-metastatic cells enhance the migration,in-vasion,and metastasis of low-metastatic cells through exosome-transmitted miR-30a-5p.Plasma levels of exosomal miR-30a-5p are reliable indicators of NPC prognosis.miR-30a-5p may promote metastasis by targeting DsG2 and modulating Wnt signaling.Plasma exosomal miR-30a-5p inversely correlates with DsG2 levels,predicting patient outcomes.Conclusion:High-metastatic NPC cells can increase the metastatic potential of low-metastatic cells through exosome-transmitted miR-30a-5p,which is a valuable prognostic marker assessable via liquid biopsy.展开更多
基金funded by grants from the National Key Research and Development Program of China(2022YFC2705005)the Sanming Project of Medicine in Shenzhen(SZSM202211017).
文摘Adolescent and childhood nasopharyngeal carcinoma(NPC)is a rare malignancy with unique biological and genetic characteristics,often associated with Epstein-Barr virus(EBV).This CACA guideline provides an integrative approach to the management of adolescent and childhood NPC,focusing on biology,diagnosis,staging,and treatment strategies.The incidence of NPC is higher in adolescent boys and is more frequently diagnosed at an advanced stage in adolescent and childhood population compared to adults.However,adolescent and childhood NPC generally have a better prognosis.The primary treatment is radiotherapy(RT),with intensity-modulated radiation therapy(IMRT)being the preferred technique due to its reduced damage to normal tissues.Chemotherapy,particularly induction chemotherapy,plays a significant role,especially in locally advanced disease.Personalized treatment strategies,including adjusting RT dosage based on chemotherapy outcomes,may reduce long-term adverse effects.The role of adjuvant therapy post-RT remains unclear and requires further research.The main objective of this guideline is to standardize the clinical diagnosis and treatment process of adolescent and childhood nasopharyngeal carcinoma,with a multidisciplinary approach to optimize therapeutic outcomes and quality of life for this disease.
基金National Key R&D Program of China,Grant/Award Numbers:2016YFC0902003,2017YFC1309003,2017YFC0908500National Natural Science Foundation of China,Grant/Award Numbers:81425018,81672868,81602371+9 种基金Sun Yat-sen University Clinical Research 5010 Program,Grant/Award Numbers:201707020039,2014A020212103,16zxyc02Sci-Tech Project Foundation of Guangzhou City,Grant/Award Number:201707020039National Key Basic Research Program of China,Grant/Award Number:2013CB910304Special Support Plan of Guangdong Province,Grant/Award Number:2014TX01R145Sci-Tech Project Foundation of Guangdong Province,Grant/Award Number:2014A020212103Health&Medical Collaborative Innovation Project of Guangzhou City,Grant/Award Number:201400000001National Science&Technology Pillar Program during the Twelfth Five-year Plan Period,Grant/Award Number:2014BAI09B10PhD Start-up Fund of Natural Science Foundation of Guangdong Province,China,Grant/Award Number:2016A030310221cultivation foundation for the junior teachers in Sun Yat-sen University,Grant/Award Number:16ykpy28foundation for major projects and new cross subjects in Sun Yat-sen University,Grant/Award Number:16ykjc38。
文摘Background:Capecitabine was previously used as a second-line or salvage therapy for metastatic nasopharyngeal carcinoma(NPC)and has shown satisfactory curative effect as maintenance therapy in other metastatic cancers.This study aimed to explore the role of capecitabine as maintenance therapy in de novo metastatic NPC patients with different plasma Epstein-Barr virus(EBV)DNA levels before treatment.Methods:We selected de novo metastatic NPC patients treated with locoregional radiotherapy(LRRT)for this retrospective study.The propensity score matching(PSM)was applied to balance potential confounders between patients who underwent capecitabine maintenance therapy and those who did not with a ratio of 1:3.Overall survival(OS)was the primary endpoint.The association between capecitabine maintenance therapy and survival was assessed using the log-rank test and a Cox proportional hazard model.Results:Among all patients eligible for this study,64 received capecitabine maintenance therapy after LRRT.After PSM,192 patients were identified in the nonmaintenance group.In the matched cohort,patients treated with capecitabine achieved a higher 3-year OS rate compared with patients in the non-maintenance group(68.5%vs.61.8%,P=0.037).Multivariate analysis demonstrated that capecitabine maintenance therapy was an independent prognostic factor.In subgroup analysis,3-year OS rate was comparable between the maintenance and non-maintenance groups in patients with high pretreatment EBV DNA levels(˃30,000 copies/mL)(54.8%vs.45.8%,P=0.835),whereas patients with low pretreatment EBV DNA levels(≤30,000 copies/mL)could benefit from capecitabine maintenance therapy in OS(90.0%vs.68.1%,P=0.003).Conclusion:Capecitabine maintenance therapy may be superior to non-maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA≤30,000 copies/mL.groups in patients with high pretreatment EBV DNA levels(˃30,000 copies/mL)(54.8%vs.45.8%,P=0.835),whereas patients with low pretreatment EBV DNA levels(≤30,000 copies/mL)could benefit from capecitabine maintenance therapy in OS(90.0%vs.68.1%,P=0.003).Conclusion:Capecitabine maintenance therapy may be superior to non-maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA≤30,000 copies/mL.
基金This study was supported by grants from the National Key R&D Program of China(2016YFC0902003,2017YFC1309003,2017YFC0908500)the National Natural Science Foundation of China(No.81425018,No.81672868,No.81602371,No.81572848,No.81772877,No.81372814,No.81773103)+9 种基金the Sun Yat-sen University Clinical Research 5010 Program,the Sci-Tech Project Foundation of Guangzhou City(201707020039)the National Key Basic Research Program of China(No.2013CB910304)the Special Support Plan of Guangdong Province(No.2014TX01R145)the Sci-Tech Project Foundation of Guangdong Province(No.2014A020212103,No.2012B031800255,No.2014A020212528)Guangzhou Science and Technology Planning Project China(No.2014J4100181)the Health&Medical Collaborative Innovation Project of Guangzhou City(No.201400000001)the National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(No.2014BAI09B10)the PhD Start-up Fund of Natural Science Foundation of Guangdong Province,China(2016A030310221)the Cultivation Foundation for Junior Teachers of Sun Yat-sen University(16ykpy28)the Fundamental Research Funds for the Central Universities
文摘Background:Currently,the diagnosis and treatment of nasopharyngeal carcinoma(NPC)patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging.We investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus(EBV)DNA in these patients.Methods:This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor therapy.Their plasma EBV DNA levels were measured using quantitative polymerase chain reaction(qPCR)before the initiation of treatment and before neck dissection.Fine needle aspiration cytology(FNAC)was performed in 21 patients.All patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical lymphadenopathy.The overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS),and locoregional relapse-free survival(LRRFS)were calculated using the Kaplan-Meier method and compared using the log-rank test.The Cox proportional hazards model was used to calculate hazard ratios(HRs)with 95%confidence intervals(CIs).Multivariable analysis was used to estimate the effect of potential prognostic factors on survival.Results:Following a median follow-up of 52.6 months,compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy,the patients with positive findings had a significantly lower 3-year PFS rate(49.9%vs.83.3%,P=0.008).Among NPC patients with residual cervical lymphadenopathy,the patients with preoperative plasma EBV DNA>0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA(43.7%vs.61.1%,P=0.031).In addition,combining FNAC with preoperative EBV DNA detection improved the diagnostic sensitivity.Multivariable analysis demonstrated that residual cervical lymphadenopathy with positive postoperative pathological result was an independent prognostic factor for PFS and that detectable preoperative plasma EBV DNA was an independent prognostic factor for OS.Conclusions: Using FNAC combined with preoperative EBV DNA detection improves the sensitivity in diagnosing NPC with residual cervical lymphadenopathy. Compared with patients with undetectable EBV DNA, patients with detectable preoperative plasma EBV DNA have worse prognosis and may require a more aggressive treatment strategy.
基金MC reports personal fees from Astellas,personal fees from Janssen,grants and personal fees from Ferring,non-financial support from Astrazeneca,personal fees and non-financial support from Varian,grants from Sanofi Canada,grants from GenomeDx Biosciences,non-financial support from Medlever,outside the submitted workMC is supported by the National Medical Research Council Singapore Clinician-Scientist Award-#NMRC/CSA/0027/2018+2 种基金the Duke-NUS Oncology Academic Program Proton Research ProgramThis work was supported by grants from the National Key R&D Program of China(2017YFC0908500,2017YFC1309003)the National Natural Science Foundation of China(No.81425018,No.81672868,No.81602371).
文摘Main text In the past decades,there have been several studies con-cerning the efficacy of sequencing of chemotherapy on disease control and survival in locoregionally advanced(LA)nasopharyngeal carcinoma(NPC).The addition of concurrent cisplatin to radiotherapy has demonstrated survival improvements that are attributable to both dis-tant metastasis and locoregional control.Specific to the latter,the advent of intensity-modulated radiotherapy has resulted in superior tumor control given the bet-ter dosimetry compared to conventional techniques[1].However,distant recurrence still occurs in 20-30%patients and accounts for the main cause of death.To address this,several groups have explored the advantages of adding neoadjuvant chemotherapy(NACT)or adju-vant chemotherapy(ACT)to the backbone of concurrent chemoradiotherapy(CCRT).
基金supported by grants from the National Key Research and Development Program of China(Grant Nos.2022YFC2505800,2022YFC2705005)the National Natural Science Foundation of China(Grant Nos.32200651,82203776,82203125,82222050,82272739,82272882,82173287,82073003,82003267,82002852)+6 种基金Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2021B1515230002,2022A1515110033)Science and Technology Program of Guangzhou(Grant Nos.202201011561,2023A04J2127)Sun Yat-sen University Clinical Research 5010 Program(Grant Nos.201315,2015021,2017010,2019023)Innovative Research Team of High-level Local Universities in Shanghai(Grant No.SSMU-ZLCX20180500)Postdoctoral Innovative Talent Support Program(Grant No.BX20220361)Planned Science and Technology Project of Guangdong Province(Grant No.2019B020230002)Key Youth Teacher Cultivating Program of Sun Yat-sen University(Grant No.20ykzd24),and Fundamental Research Funds for the Central Universities.
文摘Background:Intratumor heterogeneity is common in cancers,with different cell subtypes supporting each other to become more malignant.Nasopharyngeal carcinoma(NPC),a highly metastatic cancer,shows significant heterogeneity among its cells.This study investigates how NpC cell subtypes with varying metastatic potentials influence each other through exosome-transmitted molecules.Methods:Exosomes were purified and characterized.MicroRNA expression was analyzed via sequencing and qRT-PCR.The effects of miR-30a-5p on migration,invasion,and metastasis were evaluated in vitro and in vivo.Its impact on desmoglein glycoprotein(DSG2)was assessed using dual-luciferase assays and Western blotting.Immunohistochemistry(IHc)and statistical modeis linked miR-30a-5p/DSG2levelstopatientprognosis.Results:Different NPC ceil subtypes transmit metastatic potential via exosomes.High-metastatic cells enhance the migration,in-vasion,and metastasis of low-metastatic cells through exosome-transmitted miR-30a-5p.Plasma levels of exosomal miR-30a-5p are reliable indicators of NPC prognosis.miR-30a-5p may promote metastasis by targeting DsG2 and modulating Wnt signaling.Plasma exosomal miR-30a-5p inversely correlates with DsG2 levels,predicting patient outcomes.Conclusion:High-metastatic NPC cells can increase the metastatic potential of low-metastatic cells through exosome-transmitted miR-30a-5p,which is a valuable prognostic marker assessable via liquid biopsy.
