Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of chan...Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of changes in the CONUT score during treatment and theΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011;the patients underwent radical concurrent chemoradiotherapy(CCRT)at Sun Yat-sen University Cancer Center and were grouped based on theirΔCONUT andΔCONUT-EBV DNA scores.Kaplan-Meier curves were used to compare the patient outcomes according to the cut-offΔCONUT score and theΔCONUT-EBV DNA scoring system.Results:Among all patients,overall survival(OS)was independently predicted by a highΔCONUT score(P=0.031)and high EBV DNA(P<0.001).TheΔCONUT-EBV DNA score[OS area under the curve(AUC)=0.621;progression free survival(PFS)-AUC=0.612;distant metastasis-free survival(DMFS)-AUC=0.622]was more predictive of OS,PFS,and DMFS in patients with advanced NPC than theΔCONUT score(OS-AUC=0.547;PFS-AUC=0.533;DMFS-AUC=0.522)and pretreatment plasma EBV DNA levels alone(OS-AUC=0.600;PFS-AUC=0.591,DMFS-AUC=0.610).TheΔCONUT-EBV DNA score was significantly correlated with OS,PFS,and DMFS in patients with advanced NPC treated with CCRT.Conclusions:TheΔCONUT-EBV DNA score may be useful in clinical practice as a convenient biomarker for predicting the outcomes in patients with advanced NPC treated with CCRT.展开更多
Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eig...Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eight patients subjected to neck dissection from 2003 to 2017 were included for study.Clinicopathologic information for each patient was analyzed.Independent prognostic factors were selected using the Cox proportional hazards model and incorporated into the scoring model.Concordance index(C-index)and calibration curves were used to verify discrimination and calibration,respectively and the results validated using bootstrap resampling.Results:Microscopic positive lymph node>2[hazard ratio(HR),2.19;95%confidence interval(CI),1.30–3.68;P=0.003],extranodal extension(HR,2.75;95%CI,1.69–4.47;P<0.001),and lower neck involvement(HR,1.78;95%CI,1.04–3.04;P=0.034)were identified from multivariate analysis as independent factors for overall survival(OS).A qualitative 4-point scale was generated to stratify patients into 4 risk groups for predicting OS and progression-free survival(PFS).The novel scoring model demonstrated enhanced discrimination(C-index=0.69;95%CI,0.62–0.76)relative to the original recurrent tumor-node-metastasis(rTNM)staging system(C-index=0.56;95%CI,0.50–0.62),and was internally validated with a bootstrap-adjusted C-index of 0.70.The calibration curve showed good agreement between predicted probabilities and actual observations.Conclusions:The scoring system established in this study based on a large regionally recurrent NPC cohort fills a gap regarding assessment of risk and prediction of survival outcomes after neck dissection in this population and could be further applied to identify high-risk patients who may benefit from more aggressive intervention.展开更多
Objective:This study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index(SII)in non-metastatic nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed the data of 83...Objective:This study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index(SII)in non-metastatic nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed the data of 839 patients with non-metastatic NPC recruited from two independent institutions.The training-set cohort and the external validation-set cohort was comprised of 459 and 380 patients from each institution,respectively.The optimal cut-offvalue of SII was determined,and a prognostic risk stratification model was developed based on the training cohort and further assessed in the validation cohort.The propensity score matching(PSM)method was applied to minimize the confounding effects of unbalanced covariables.Results:The optimal cut-offvalue of the SII in the training cohort was 686,which was confirmed using the vali-dation cohort.Multivariate analysis showed that both before and after PSM,SII values>686 were independently associated with worse progression-free survival(PFS)ratio in both cohorts(before PSM,P=0.008 and P=0.008;after PSM,P=0.008 and P=0.007,respectively).Based on the analysis of independent prognostic factors of SII and N stage,we developed a categorical risk stratification model,which achieved significant discrimination among risk indexes associated with PFS and distant metastasis-free survival(DMFS)in the training cohort.There was no significant difference in PFS between RT alone and combined therapies within the low-and intermediate-risk groups(5-year PFS,77.5%vs.75.3%,P=0.275).Patients in the high-risk group who received concurrent chemoradiotherapy experienced superior PFS compared with those who received other therapies(5-year PFS,64.9%vs.40.3%,P=0.003).Conclusion:Pretreatment SII predicts PFS of patients with non-metastatic NPC.Prognostic risk stratification incorporating SII is instructive for selecting individualized treatment.展开更多
Background:Due to the occult anatomic location of the nasopharynx and frequent presence of adenoid hyperpla-sia,the positive rate for malignancy identification during biopsy is low,thus leading to delayed or missed di...Background:Due to the occult anatomic location of the nasopharynx and frequent presence of adenoid hyperpla-sia,the positive rate for malignancy identification during biopsy is low,thus leading to delayed or missed diagnosis for nasopharyngeal malignancies upon initial attempt.Here,we aimed to develop an artificial intelligence tool to detect nasopharyngeal malignancies under endoscopic examination based on deep learning.Methods:An endoscopic images-based nasopharyngeal malignancy detection model(eNPM-DM)consisting of a fully convolutional network based on the inception architecture was developed and fine-tuned using separate training and validation sets for both classification and segmentation.Briefly,a total of 28,966 qualified images were collected.Among these images,27,536 biopsy-proven images from 7951 individuals obtained from January 1st,2008,to December 31st,2016,were split into the training,validation and test sets at a ratio of 7:1:2 using simple randomiza-tion.Additionally,1430 images obtained from January 1st,2017,to March 31st,2017,were used as a prospective test set to compare the performance of the established model against oncologist evaluation.The dice similarity coef-ficient(DSC)was used to evaluate the efficiency of eNPM-DM in automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images,by comparing automatic segmentation with manual segmenta-tion performed by the experts.Results:All images were histopathologically confirmed,and included 5713(19.7%)normal control,19,107(66.0%)nasopharyngeal carcinoma(NPC),335(1.2%)NPC and 3811(13.2%)benign diseases.The eNPM-DM attained an overall accuracy of 88.7%(95%confidence interval(CI)87.8%-89.5%)in detecting malignancies in the test set.In the prospective comparison phase,eNPM-DM outperformed the experts:the overall accuracy was 88.0%(95%CI 86.1%-89.6%)vs.80.5%(95%CI 77.0%-84.0%).The eNPM-DM required less time(40 s vs.110.0±5.8 min)and exhibited encouraging performance in automatic segmentation of nasopharyngeal malignant area from the background,with an average DSC of 0.78±0.24 and 0.75±0.26 in the test and prospective test sets,respectively.Conclusions:The eNPM-DM outperformed oncologist evaluation in diagnostic classification of nasopharyngeal mass into benign versus malignant,and realized automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images.展开更多
Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previ...Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.展开更多
基金This work was supported by grants from the National Key R&D Program of China(Grant Nos.2017YFC1309003 and 2017YFC0908500)the National Natural Science Foundation of China(Grant Nos.81425018,81672868,and 81802775)+10 种基金the Sci-Tech Project Foundation of Guangzhou City(Grant No.201707020039)the Sun Yat-sen University Clinical Research 5010 Program,the Special Support Plan of Guangdong Province(Grant No.2014TX01R145)the Natural Science Foundation of Guangdong Province(Grant Nos.2017A030312003 and 2018A0303131004)the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar(Grant No.2018B030306001)the Sci-Tech Project Foundation of Guangdong Province(Grant No.2014A020212103)the Health&Medical Collaborative Innovation Project of Guangzhou City(Grant Nos.201400000001 and 201803040003)the Pearl River S&T Nova Program of Guangzhou(Grant No.201806010135)the Planned Science and Technology Project of Guangdong Province(Grant No.2019B020230002)the National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(Grant No.2014BAI09B10)the Natural Science Foundation of Guangdong Province(Grant No.2017A030312003Fundamental Research Funds for the Central Universities。
文摘Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of changes in the CONUT score during treatment and theΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011;the patients underwent radical concurrent chemoradiotherapy(CCRT)at Sun Yat-sen University Cancer Center and were grouped based on theirΔCONUT andΔCONUT-EBV DNA scores.Kaplan-Meier curves were used to compare the patient outcomes according to the cut-offΔCONUT score and theΔCONUT-EBV DNA scoring system.Results:Among all patients,overall survival(OS)was independently predicted by a highΔCONUT score(P=0.031)and high EBV DNA(P<0.001).TheΔCONUT-EBV DNA score[OS area under the curve(AUC)=0.621;progression free survival(PFS)-AUC=0.612;distant metastasis-free survival(DMFS)-AUC=0.622]was more predictive of OS,PFS,and DMFS in patients with advanced NPC than theΔCONUT score(OS-AUC=0.547;PFS-AUC=0.533;DMFS-AUC=0.522)and pretreatment plasma EBV DNA levels alone(OS-AUC=0.600;PFS-AUC=0.591,DMFS-AUC=0.610).TheΔCONUT-EBV DNA score was significantly correlated with OS,PFS,and DMFS in patients with advanced NPC treated with CCRT.Conclusions:TheΔCONUT-EBV DNA score may be useful in clinical practice as a convenient biomarker for predicting the outcomes in patients with advanced NPC treated with CCRT.
基金supported by grants from the National Key R&D Program of China(Grant Nos.2017YFC1309003 and 2017YFC0908500)National Natural Science Foundation of China(Grant Nos.81425018,81672868,81802775,and 81602371)+10 种基金Sci-Tech Project Foundation of Guangzhou City(Grant No.201707020039)Sun Yat-sen University Clinical Research 5010 ProgramSpecial Support Plan of Guangdong Province(Grant No.2014TX01R145)Natural Science Foundation of Guangdong Province(Grant Nos.2017A030312003 and 2018A0303131004)Sci-Tech Project Foundation of Guangdong Province(Grant No.2014A020212103)Health&Medical Collaborative Innovation Project of Guangzhou City(Grant Nos.201400000001 and 201803040003)Planned Science and Technology Project of Guangdong Province(Grant No.2019B020230002)National Science&Technology Pillar Program during the Twelfth FiveYear Plan Period(Grant No.2014BAI09B10)Natural Science Foundation of Guangdong Province for Distinguished Young Scholar(Grant No.2018B030306001)Pearl River S&T Nova Program of Guangzhou(Grant No.201806010135)PhD Start-up Fund of Natural Science Foundation of Guangdong Province(Grant No.2016A030310221)。
文摘Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eight patients subjected to neck dissection from 2003 to 2017 were included for study.Clinicopathologic information for each patient was analyzed.Independent prognostic factors were selected using the Cox proportional hazards model and incorporated into the scoring model.Concordance index(C-index)and calibration curves were used to verify discrimination and calibration,respectively and the results validated using bootstrap resampling.Results:Microscopic positive lymph node>2[hazard ratio(HR),2.19;95%confidence interval(CI),1.30–3.68;P=0.003],extranodal extension(HR,2.75;95%CI,1.69–4.47;P<0.001),and lower neck involvement(HR,1.78;95%CI,1.04–3.04;P=0.034)were identified from multivariate analysis as independent factors for overall survival(OS).A qualitative 4-point scale was generated to stratify patients into 4 risk groups for predicting OS and progression-free survival(PFS).The novel scoring model demonstrated enhanced discrimination(C-index=0.69;95%CI,0.62–0.76)relative to the original recurrent tumor-node-metastasis(rTNM)staging system(C-index=0.56;95%CI,0.50–0.62),and was internally validated with a bootstrap-adjusted C-index of 0.70.The calibration curve showed good agreement between predicted probabilities and actual observations.Conclusions:The scoring system established in this study based on a large regionally recurrent NPC cohort fills a gap regarding assessment of risk and prediction of survival outcomes after neck dissection in this population and could be further applied to identify high-risk patients who may benefit from more aggressive intervention.
文摘Objective:This study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index(SII)in non-metastatic nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed the data of 839 patients with non-metastatic NPC recruited from two independent institutions.The training-set cohort and the external validation-set cohort was comprised of 459 and 380 patients from each institution,respectively.The optimal cut-offvalue of SII was determined,and a prognostic risk stratification model was developed based on the training cohort and further assessed in the validation cohort.The propensity score matching(PSM)method was applied to minimize the confounding effects of unbalanced covariables.Results:The optimal cut-offvalue of the SII in the training cohort was 686,which was confirmed using the vali-dation cohort.Multivariate analysis showed that both before and after PSM,SII values>686 were independently associated with worse progression-free survival(PFS)ratio in both cohorts(before PSM,P=0.008 and P=0.008;after PSM,P=0.008 and P=0.007,respectively).Based on the analysis of independent prognostic factors of SII and N stage,we developed a categorical risk stratification model,which achieved significant discrimination among risk indexes associated with PFS and distant metastasis-free survival(DMFS)in the training cohort.There was no significant difference in PFS between RT alone and combined therapies within the low-and intermediate-risk groups(5-year PFS,77.5%vs.75.3%,P=0.275).Patients in the high-risk group who received concurrent chemoradiotherapy experienced superior PFS compared with those who received other therapies(5-year PFS,64.9%vs.40.3%,P=0.003).Conclusion:Pretreatment SII predicts PFS of patients with non-metastatic NPC.Prognostic risk stratification incorporating SII is instructive for selecting individualized treatment.
基金supported by the National Natural Science Foundation of China[Grant Nos.81572665,81672680,81472525,81702873]the International Cooperation Project of Science and Technology Plan of Guangdong Province[Grant No.2016A050502011]the Health&Medical Collaborative Innovation Project of Guangzhou City,China(Grant No.201604020003).
文摘Background:Due to the occult anatomic location of the nasopharynx and frequent presence of adenoid hyperpla-sia,the positive rate for malignancy identification during biopsy is low,thus leading to delayed or missed diagnosis for nasopharyngeal malignancies upon initial attempt.Here,we aimed to develop an artificial intelligence tool to detect nasopharyngeal malignancies under endoscopic examination based on deep learning.Methods:An endoscopic images-based nasopharyngeal malignancy detection model(eNPM-DM)consisting of a fully convolutional network based on the inception architecture was developed and fine-tuned using separate training and validation sets for both classification and segmentation.Briefly,a total of 28,966 qualified images were collected.Among these images,27,536 biopsy-proven images from 7951 individuals obtained from January 1st,2008,to December 31st,2016,were split into the training,validation and test sets at a ratio of 7:1:2 using simple randomiza-tion.Additionally,1430 images obtained from January 1st,2017,to March 31st,2017,were used as a prospective test set to compare the performance of the established model against oncologist evaluation.The dice similarity coef-ficient(DSC)was used to evaluate the efficiency of eNPM-DM in automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images,by comparing automatic segmentation with manual segmenta-tion performed by the experts.Results:All images were histopathologically confirmed,and included 5713(19.7%)normal control,19,107(66.0%)nasopharyngeal carcinoma(NPC),335(1.2%)NPC and 3811(13.2%)benign diseases.The eNPM-DM attained an overall accuracy of 88.7%(95%confidence interval(CI)87.8%-89.5%)in detecting malignancies in the test set.In the prospective comparison phase,eNPM-DM outperformed the experts:the overall accuracy was 88.0%(95%CI 86.1%-89.6%)vs.80.5%(95%CI 77.0%-84.0%).The eNPM-DM required less time(40 s vs.110.0±5.8 min)and exhibited encouraging performance in automatic segmentation of nasopharyngeal malignant area from the background,with an average DSC of 0.78±0.24 and 0.75±0.26 in the test and prospective test sets,respectively.Conclusions:The eNPM-DM outperformed oncologist evaluation in diagnostic classification of nasopharyngeal mass into benign versus malignant,and realized automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images.
基金supported by Jiangsu Hengrui Medicine Co.,Ltd[The National Natural Science Foundation of China(Grant No.81230056)The National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(Grand No.2014BAI09B10+4 种基金The Natural Science Foundation of Guangdong Province(Grand Nos.S2013010012220,2017A030312003)the Science and Technology Project of Guangzhou City,China(Grand No.132000507)The Health&Medical Collaborative Innovation Project of Guangzhou City,China(Grand No.201400000001)The Innovation Team Development Plan of the Ministry of Education(Grand No.IRT_17R110)the Program of Introducing Talents of Discipline to Universities(Grand No.B14035)].
文摘Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.
