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
Objective This study investigated the predictive value of tumor volume reduction rates(TVRRs) before and after induction chemotherapy in determining the radiosensitivity and prognosis of patients with locally advanced...Objective This study investigated the predictive value of tumor volume reduction rates(TVRRs) before and after induction chemotherapy in determining the radiosensitivity and prognosis of patients with locally advanced nasopharyngeal carcinomas(NPCs). Methods The clinical data of 172 patients with locally advanced primary NPCs who were treated from January 2009 to December 2012 were collected. Tumor regression was evaluated based on the results of the computed tomography scan or magnetic resonance imaging studies. Data about the tumor diameters before and after induction chemotherapy and after radiotherapy as well as the survival times of the patients were obtained. Results All 172 patients had NPCs. After radiotherapy, the TVRR in patients without residual tumor cells was higher than that in patients with residual tumor cells after induction chemotherapy(median values: 47.7% and 15.1%, respectively), and the 5-year survival rates were 80.3% and 45.6%, respectively. Neck lymph node metastasis was observed in 161 of 172 patients, and the TVRRs were similar(median values: 46.8% in 161 patients without residual tumor cells and 11.1% in 161 patients with residual tumor cells). The 5-year survival rate of the 161 patients without residual tumor cells was 84.5%, and that of patients with residual tumor cells was 37.3%. As shown by the receiver operating characteristic(ROC) curve, the area under the curve(AUC) of the ROC curve for TVRRs in patients with primary NPCs but without residual tumors was 0.851, whereas that for TVRRs in patients with neck lymph node metastasis but without residual tumors was 0.784. This result indicates that TVRR has a high diagnostic performance. The univariate Cox regression analysis showed that clinical stage, TVRR in primary NPCs, neck lymph node metastatic lesions before and after induction chemotherapy, presence or absence of residual tumor cells in primary NPCs, and neck lymph node metastatic lesions after radiotherapy were significantly correlated to overall survival(OS). Results of the multivariate Cox regression analysis showed that clinical stage and presence or absence of residual tumor cells in the lymph nodes after radiotherapy were the independent prognostic factors of OS.Conclusion The TVRR after induction chemotherapy may be an effective predictive indicator of the treatment efficacy of radiotherapy in patients with NPC.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:Accurate prognostic predictions and personalized decision-making on induction chemotherapy(IC)for individuals with locally advanced nasopharyngeal carcinoma(LA-NPC)remain challenging.This research examined t...Objective:Accurate prognostic predictions and personalized decision-making on induction chemotherapy(IC)for individuals with locally advanced nasopharyngeal carcinoma(LA-NPC)remain challenging.This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival(OS)and their value in guiding treatment in patients with LA-NPC.Methods:Individuals with LA-NPC were reviewed retrospectively.Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods,the interpretable eXtreme Gradi-ent Boosting(XGBoost)risk prediction model,and DeepHit time-to-event neural network.The models’prediction performances were compared using the concordance index(C-index)and the area under the curve(AUC).The patients were divided into two cohorts based on the risk predictions of the most successful model.The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone.Results:The 1221 eligible individuals,assigned to the training(n=813)or validation(n=408)set,showed significant respective differences in the C-indices of the XGBoost,DeepHit,and nomogram models(0.849 and 0.768,0.811 and 0.767,0.730 and 0.705).The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS(0.881 and 0.760,0.845 and 0.776,and 0.764 and 0.729,P<0.001).IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group.Conclusion:This research used machine-learning algorithms to create and verify a comprehensive model inte-grating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC.This model could be valuable for delivering patient counseling and conducting clinical evaluations.展开更多
Background:Available data in the literature comparing different induction chemotherapy(IC)regimens on locoregionally advanced nasopharyngeal carcinoma(NPC)are scarce.The purpose of the present study was to evaluate th...Background:Available data in the literature comparing different induction chemotherapy(IC)regimens on locoregionally advanced nasopharyngeal carcinoma(NPC)are scarce.The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane,cisplatin and 5-fluorouracil(TPF)or cisplatin and 5-fluorouracil(PF)as IC followed by concurrent chemoradiotherapy(CCRT).Methods:In total,1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study.We compared overall survival(OS),disease-specific survival(DSS),distant metastasis-free survival(DMFS),and locoregional relapse-free survival,using the pro-pensity score method.Results:In total,1256 patients received TPF or PF as IC backbone.The TPF group showed significantly better OS(hazard ratio[HR],0.660;95%confidence interval[CI]0.442-0.986;P=0.042),DSS(HR,0.624;95%CI 0.411-0.947;P=0.027)and DMFS(HR,0.589;95%CI 0.406-0.855;P=0.005)compared with the PF group in multivariable analy-ses.Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS(88.1%vs.80.7%;P=0.042),DSS(88.5%vs.80.7%;P=0.021)and DMFS(87.9%vs.78.6%;P=0.012)rates compared with the PF group.There were no significant differences in locoregional relapse-free survival before or after matching.Conclusions:In our study,IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen.However,a prospective randomized clinical trial to validate these findings is necessary.展开更多
AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with ind...AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy(CCRT)(22/40 patients)or CCRT alone(18/40)from March 2006 to March 2012.Patients underwent fiberoscopy with biopsy of the primitive tumor,and computed tomography scan of head,neck,chest and abdomen with and without contrast.Cisplatin was used both as induction and as concomitant chemotherapy,while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions(total dose,70 Gy).The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly.This retrospective analysis was approved by the review boards of the participating institutions.Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS:Thirty-three patients were males and 7 were females.Median follow-up time was 58 mo(range,1-92 mo).In the sub-group of twenty patients with a follow-up time longer than 36 mo,the 3-year survival and disease free survival rates were 85%and 75%,respectively.Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%.Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients.Grade 2 mucositis was seen in 29 patients,while grade 2 xerostomia was seen in 30 patients.Overall toxicity was manageable and it did not cause any significant treatment delay.In the whole sample population,long term toxicity included grade 2 xerostomia in 22 patients,grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION:Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC.The role of adjuvant chemotherapy remains to be defined.展开更多
The standard of care for patients with locoregionally advanced nasopharyngeal carcinoma is concurrent platinum-based chemoradiotherapy.Existing literature have demonstrated that the addition of gemcitabine and cisplat...The standard of care for patients with locoregionally advanced nasopharyngeal carcinoma is concurrent platinum-based chemoradiotherapy.Existing literature have demonstrated that the addition of gemcitabine and cisplatin as induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma may have promising efficacy but were from phase 2 clinical trials.Stronger evidence-based data in forms of phase 3 clinical trial investigating the survival benefits of adding gemcitabine and cisplatin induction chemotherapy for such patients have been urgently warranted.In one of our recent studies published in the New England Journal of Medicine,“Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma”,480 locoregionally advanced nasopharyngeal carcinoma patients from 12 hospitals across China were randomly assigned in a 1:1 ratio to receive either chemoradiotherapy alone or gemcitabine plus cisplatin and chemoradiotherapy.Our findings evinced that,as compared to chemora-diotherapy alone,the addition of induction chemotherapy comprising of gemcitabine plus cisplatin to concurrent cisplatin-radiotherapy to patients with locoregionally advanced nasopharyngeal carcinoma was safe,demonstrated improved recurrence-free survival,overall survival,and distant recurrence-free survival,and marginally superior locore-gional recurrence-free survival.展开更多
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.
文摘Objective This study investigated the predictive value of tumor volume reduction rates(TVRRs) before and after induction chemotherapy in determining the radiosensitivity and prognosis of patients with locally advanced nasopharyngeal carcinomas(NPCs). Methods The clinical data of 172 patients with locally advanced primary NPCs who were treated from January 2009 to December 2012 were collected. Tumor regression was evaluated based on the results of the computed tomography scan or magnetic resonance imaging studies. Data about the tumor diameters before and after induction chemotherapy and after radiotherapy as well as the survival times of the patients were obtained. Results All 172 patients had NPCs. After radiotherapy, the TVRR in patients without residual tumor cells was higher than that in patients with residual tumor cells after induction chemotherapy(median values: 47.7% and 15.1%, respectively), and the 5-year survival rates were 80.3% and 45.6%, respectively. Neck lymph node metastasis was observed in 161 of 172 patients, and the TVRRs were similar(median values: 46.8% in 161 patients without residual tumor cells and 11.1% in 161 patients with residual tumor cells). The 5-year survival rate of the 161 patients without residual tumor cells was 84.5%, and that of patients with residual tumor cells was 37.3%. As shown by the receiver operating characteristic(ROC) curve, the area under the curve(AUC) of the ROC curve for TVRRs in patients with primary NPCs but without residual tumors was 0.851, whereas that for TVRRs in patients with neck lymph node metastasis but without residual tumors was 0.784. This result indicates that TVRR has a high diagnostic performance. The univariate Cox regression analysis showed that clinical stage, TVRR in primary NPCs, neck lymph node metastatic lesions before and after induction chemotherapy, presence or absence of residual tumor cells in primary NPCs, and neck lymph node metastatic lesions after radiotherapy were significantly correlated to overall survival(OS). Results of the multivariate Cox regression analysis showed that clinical stage and presence or absence of residual tumor cells in the lymph nodes after radiotherapy were the independent prognostic factors of OS.Conclusion The TVRR after induction chemotherapy may be an effective predictive indicator of the treatment efficacy of radiotherapy in patients with NPC.
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.
文摘Objective:Accurate prognostic predictions and personalized decision-making on induction chemotherapy(IC)for individuals with locally advanced nasopharyngeal carcinoma(LA-NPC)remain challenging.This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival(OS)and their value in guiding treatment in patients with LA-NPC.Methods:Individuals with LA-NPC were reviewed retrospectively.Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods,the interpretable eXtreme Gradi-ent Boosting(XGBoost)risk prediction model,and DeepHit time-to-event neural network.The models’prediction performances were compared using the concordance index(C-index)and the area under the curve(AUC).The patients were divided into two cohorts based on the risk predictions of the most successful model.The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone.Results:The 1221 eligible individuals,assigned to the training(n=813)or validation(n=408)set,showed significant respective differences in the C-indices of the XGBoost,DeepHit,and nomogram models(0.849 and 0.768,0.811 and 0.767,0.730 and 0.705).The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS(0.881 and 0.760,0.845 and 0.776,and 0.764 and 0.729,P<0.001).IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group.Conclusion:This research used machine-learning algorithms to create and verify a comprehensive model inte-grating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC.This model could be valuable for delivering patient counseling and conducting clinical evaluations.
基金the National Natural Science Foundation of China(NSFC)(program Grants 81472525,81672680 and 81572665)the Science and Technology Planning Project of Guangdong Province,China(program Grant 2014A050503033 and 2016A050502011).
文摘Background:Available data in the literature comparing different induction chemotherapy(IC)regimens on locoregionally advanced nasopharyngeal carcinoma(NPC)are scarce.The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane,cisplatin and 5-fluorouracil(TPF)or cisplatin and 5-fluorouracil(PF)as IC followed by concurrent chemoradiotherapy(CCRT).Methods:In total,1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study.We compared overall survival(OS),disease-specific survival(DSS),distant metastasis-free survival(DMFS),and locoregional relapse-free survival,using the pro-pensity score method.Results:In total,1256 patients received TPF or PF as IC backbone.The TPF group showed significantly better OS(hazard ratio[HR],0.660;95%confidence interval[CI]0.442-0.986;P=0.042),DSS(HR,0.624;95%CI 0.411-0.947;P=0.027)and DMFS(HR,0.589;95%CI 0.406-0.855;P=0.005)compared with the PF group in multivariable analy-ses.Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS(88.1%vs.80.7%;P=0.042),DSS(88.5%vs.80.7%;P=0.021)and DMFS(87.9%vs.78.6%;P=0.012)rates compared with the PF group.There were no significant differences in locoregional relapse-free survival before or after matching.Conclusions:In our study,IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen.However,a prospective randomized clinical trial to validate these findings is necessary.
文摘AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy(CCRT)(22/40 patients)or CCRT alone(18/40)from March 2006 to March 2012.Patients underwent fiberoscopy with biopsy of the primitive tumor,and computed tomography scan of head,neck,chest and abdomen with and without contrast.Cisplatin was used both as induction and as concomitant chemotherapy,while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions(total dose,70 Gy).The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly.This retrospective analysis was approved by the review boards of the participating institutions.Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS:Thirty-three patients were males and 7 were females.Median follow-up time was 58 mo(range,1-92 mo).In the sub-group of twenty patients with a follow-up time longer than 36 mo,the 3-year survival and disease free survival rates were 85%and 75%,respectively.Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%.Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients.Grade 2 mucositis was seen in 29 patients,while grade 2 xerostomia was seen in 30 patients.Overall toxicity was manageable and it did not cause any significant treatment delay.In the whole sample population,long term toxicity included grade 2 xerostomia in 22 patients,grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION:Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC.The role of adjuvant chemotherapy remains to be defined.
文摘The standard of care for patients with locoregionally advanced nasopharyngeal carcinoma is concurrent platinum-based chemoradiotherapy.Existing literature have demonstrated that the addition of gemcitabine and cisplatin as induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma may have promising efficacy but were from phase 2 clinical trials.Stronger evidence-based data in forms of phase 3 clinical trial investigating the survival benefits of adding gemcitabine and cisplatin induction chemotherapy for such patients have been urgently warranted.In one of our recent studies published in the New England Journal of Medicine,“Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma”,480 locoregionally advanced nasopharyngeal carcinoma patients from 12 hospitals across China were randomly assigned in a 1:1 ratio to receive either chemoradiotherapy alone or gemcitabine plus cisplatin and chemoradiotherapy.Our findings evinced that,as compared to chemora-diotherapy alone,the addition of induction chemotherapy comprising of gemcitabine plus cisplatin to concurrent cisplatin-radiotherapy to patients with locoregionally advanced nasopharyngeal carcinoma was safe,demonstrated improved recurrence-free survival,overall survival,and distant recurrence-free survival,and marginally superior locore-gional recurrence-free survival.
