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Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases
BACKGROUND: The objective of this study was to construct a risk classification system integrating cell-free Epstein-Barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC). METHODS: Clinical records of 10,149 biopsy-proven, non-metastatic NPC wer...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554575/ https://www.ncbi.nlm.nih.gov/pubmed/34721672 http://dx.doi.org/10.1177/17588359211052417 |
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author | Chen, Fo-Ping Lin, Li Liang, Jin-Hui Tan, Sze Huey Ong, Enya H.W. Luo, Ying-Shan Huang, Luo Sim, Adelene Y.L. Wang, Hai-Tao Gao, Tian-Sheng Deng, Bin Zhou, Guan-Qun Kou, Jia Chua, Melvin L.K. Sun, Ying |
author_facet | Chen, Fo-Ping Lin, Li Liang, Jin-Hui Tan, Sze Huey Ong, Enya H.W. Luo, Ying-Shan Huang, Luo Sim, Adelene Y.L. Wang, Hai-Tao Gao, Tian-Sheng Deng, Bin Zhou, Guan-Qun Kou, Jia Chua, Melvin L.K. Sun, Ying |
author_sort | Chen, Fo-Ping |
collection | PubMed |
description | BACKGROUND: The objective of this study was to construct a risk classification system integrating cell-free Epstein-Barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC). METHODS: Clinical records of 10,149 biopsy-proven, non-metastatic NPC were identified from two cancer centers; this comprised a training (N = 9,259) and two validation cohorts (N = 890; including one randomized controlled phase 3 trial cohort). Adjusted hazard ratio (AHR) method using a two-tiered stratification by cfEBV DNA and TN-categories was applied to generate the risk model. Primary clinical endpoint was overall survival (OS). Performances of the models were compared against American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 8th edition TNM-stage classification and two published recursive partitioning analysis (RPA) models, and were validated in the validation cohorts. RESULTS: We chose a cfEBV DNA cutoff of ⩾2,000 copies for optimal risk discretization of OS, disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the training cohort. AHR modeling method divided NPC into six risk groups with significantly disparate survival (p < 0.001 for all): AHR1, T1N0; AHR2A, T1N1/T2-3N0 cfEBV DNA < 2,000 (EBV(low)); AHR2B, T1N1/T2-3N0 cfEBV DNA ⩾ 2,000 (EBV(high)) and T1-2N2/T2-3N1 EBV(low); AHR3, T1-2N2/T2-3N1 EBV(high) and T3N2/T4N0 EBV(low); AHR4, T3N2/T4 N0-1 EBV(high) and T1-3N3/T4N1-3 EBV(low); AHR5, T1-3N3/T4 N2-3 EBV(high). Our AHR model outperformed the published RPA models and TNM stage with better hazard consistency (1.35 versus 3.98–12.67), hazard discrimination (5.29 versus 6.69–13.35), explained variation (0.248 versus 0.164–0.225), balance (0.385 versus 0.438–0.749) and C-index (0.707 versus 0.662–0.700). In addition, our AHR model was superior to the TNM stage for risk stratification of OS in two validation cohorts (p < 0.001 for both). CONCLUSION: Herein, we developed and validated a risk classification system that combines the AJCC/UICC 8th edition TN-stage classification and cfEBV DNA for non-metastatic NPC. Our new clinicomolecular model provides improved OS prediction over the current staging system. |
format | Online Article Text |
id | pubmed-8554575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-85545752021-10-30 Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases Chen, Fo-Ping Lin, Li Liang, Jin-Hui Tan, Sze Huey Ong, Enya H.W. Luo, Ying-Shan Huang, Luo Sim, Adelene Y.L. Wang, Hai-Tao Gao, Tian-Sheng Deng, Bin Zhou, Guan-Qun Kou, Jia Chua, Melvin L.K. Sun, Ying Ther Adv Med Oncol Original Research BACKGROUND: The objective of this study was to construct a risk classification system integrating cell-free Epstein-Barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC). METHODS: Clinical records of 10,149 biopsy-proven, non-metastatic NPC were identified from two cancer centers; this comprised a training (N = 9,259) and two validation cohorts (N = 890; including one randomized controlled phase 3 trial cohort). Adjusted hazard ratio (AHR) method using a two-tiered stratification by cfEBV DNA and TN-categories was applied to generate the risk model. Primary clinical endpoint was overall survival (OS). Performances of the models were compared against American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 8th edition TNM-stage classification and two published recursive partitioning analysis (RPA) models, and were validated in the validation cohorts. RESULTS: We chose a cfEBV DNA cutoff of ⩾2,000 copies for optimal risk discretization of OS, disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the training cohort. AHR modeling method divided NPC into six risk groups with significantly disparate survival (p < 0.001 for all): AHR1, T1N0; AHR2A, T1N1/T2-3N0 cfEBV DNA < 2,000 (EBV(low)); AHR2B, T1N1/T2-3N0 cfEBV DNA ⩾ 2,000 (EBV(high)) and T1-2N2/T2-3N1 EBV(low); AHR3, T1-2N2/T2-3N1 EBV(high) and T3N2/T4N0 EBV(low); AHR4, T3N2/T4 N0-1 EBV(high) and T1-3N3/T4N1-3 EBV(low); AHR5, T1-3N3/T4 N2-3 EBV(high). Our AHR model outperformed the published RPA models and TNM stage with better hazard consistency (1.35 versus 3.98–12.67), hazard discrimination (5.29 versus 6.69–13.35), explained variation (0.248 versus 0.164–0.225), balance (0.385 versus 0.438–0.749) and C-index (0.707 versus 0.662–0.700). In addition, our AHR model was superior to the TNM stage for risk stratification of OS in two validation cohorts (p < 0.001 for both). CONCLUSION: Herein, we developed and validated a risk classification system that combines the AJCC/UICC 8th edition TN-stage classification and cfEBV DNA for non-metastatic NPC. Our new clinicomolecular model provides improved OS prediction over the current staging system. SAGE Publications 2021-10-26 /pmc/articles/PMC8554575/ /pubmed/34721672 http://dx.doi.org/10.1177/17588359211052417 Text en © The Author(s), 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Chen, Fo-Ping Lin, Li Liang, Jin-Hui Tan, Sze Huey Ong, Enya H.W. Luo, Ying-Shan Huang, Luo Sim, Adelene Y.L. Wang, Hai-Tao Gao, Tian-Sheng Deng, Bin Zhou, Guan-Qun Kou, Jia Chua, Melvin L.K. Sun, Ying Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases |
title | Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases |
title_full | Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases |
title_fullStr | Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases |
title_full_unstemmed | Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases |
title_short | Development of a risk classification system combining TN-categories and circulating EBV DNA for non-metastatic NPC in 10,149 endemic cases |
title_sort | development of a risk classification system combining tn-categories and circulating ebv dna for non-metastatic npc in 10,149 endemic cases |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554575/ https://www.ncbi.nlm.nih.gov/pubmed/34721672 http://dx.doi.org/10.1177/17588359211052417 |
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