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Head and Neck cancer
The Impact of Infectious Mononucleosis History on the Risk of Developing Lymphoma and Nasopharyngeal Carcinoma: A Retrospective Large-Scale Cohort Study Using National Health Insurance Data in South Korea
So Hee Kang, Yun-Hee Lee, Jun-Pyo Myong, Minsu Kwon
Cancer Res Treat. 2024;56(4):1077-1083.   Published online April 23, 2024
DOI: https://doi.org/10.4143/crt.2023.1356
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to assess the long-term risks associated with a history of infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV). Specifically analyzing the potential increase in developing nasopharyngeal cancer (NPC) and lymphoma in patients with a history of IM and exploring the prevalence of other EBV-associated conditions.
Materials and Methods
The Korean National Health Insurance Service (NHIS) database was utilized for a retrospective analysis, covering data from 2002 to 2021. A total of 25,582 IM patients and controls were included, with 1:1 propensity score matching. The study monitored outcomes, including lymphoma, NPC, gastric cancer, multiple sclerosis, and all-cause mortality.
Results
Patients with a history of IM demonstrated a significantly higher incidence of lymphoma (hazard ratio [HR], 5.320; 95% confidence interval [CI], 3.208 to 8.820; p < 0.001) and NPC (HR, 7.116; 95% CI, 1.617 to 31.314; p=0.009) during the follow-up period compared with the control group. Additionally, the IM group showed an increased rate of all-cause mortality (HR, 2.225; 95% CI, 1.858 to 2.663; p < 0.001).
Conclusion
This study suggests that individuals with a history of IM have an elevated risk of developing lymphoma and NPC in South Korea, emphasizing the importance of vigilant follow-up and monitoring. The results advocate for heightened awareness and potential national monitoring policies to address the long-term health implications of EBV infection and to implement preventive measures.
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Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma
Yi-Feng Yu, Peng Wu, Rui Zhuo, San-Gang Wu
Cancer Res Treat. 2024;56(4):1058-1067.   Published online February 19, 2024
DOI: https://doi.org/10.4143/crt.2023.1343
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC).
Materials and Methods
We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses.
Results
A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2.
Conclusion
It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC.

Citations

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  • Reply to Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”
    San-Gang Wu
    Cancer Research and Treatment.2025; 57(1): 291.     CrossRef
  • Commentary on “Metronomic S-1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma”
    Erkan Topkan, Efsun Somay, Nilufer Kılıc Durankus, Ugur Selek
    Cancer Research and Treatment.2025; 57(1): 289.     CrossRef
  • Short-term versus long-term metronomic adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A propensity score-matched real-world study
    Shuhui Dong, Weixin Bei, Lanfeng Lin, Yaofei Jiang, Nian Lu, Guoying Liu, Yanqun Xiang, Weixiong Xia
    Oral Oncology.2024; 156: 106908.     CrossRef
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Individualized Concurrent Chemotherapy for Patients with Stage III-IVa Nasopharyngeal Carcinoma Receiving Neoadjuvant Chemotherapy Combined with Definitive Intensity-Modulated Radiotherapy
Pengjie Ji, Qiongjiao Lu, Xiaoqiang Chen, Yuebing Chen, Xiane Peng, Zhiwei Chen, Cheng Lin, Shaojun Lin, Jingfeng Zong
Cancer Res Treat. 2023;55(4):1113-1122.   Published online May 11, 2023
DOI: https://doi.org/10.4143/crt.2022.1651
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This retrospective study aimed to re-evaluate the effect of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT).
Materials and Methods
A total of 498 patients who received neoadjuvant chemotherapy (NCT) combined with concurrent chemoradiotherapy (CCRT) or IMRT were retrospectively reviewed. The distribution of baseline characteristics was balanced using propensity score matching. Additionally, the results of NCT+IMRT and NCT+CCRT were compared using Kaplan-Meier survival analysis, and differences in survival rates were analyzed using the log rank test.
Results
There were no significant differences in overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LRFS) between the two groups. Patients were further categorized into risk subgroups based on pretreatment Epstein-Barr virus (EBV) DNA cutoff values using receiver operating characteristic curve analysis. There were no statistically significant differences in OS, PFS, DMFS, and LRFS between patients who received NCT+CCRT and NCT+IMRT in the high-risk group. In the low-risk group, although there were no differences between NCT+CCRT and NCT+IMRT in OS, PFS, and LRFS, patients who received NCT+CCRT had better DMFS than those who received NCT+IMRT.
Conclusion
Pretreatment EBV DNA level can be used to individualize concurrent chemotherapy for patients with locally advanced NPC. Patients with low pretreatment EBV DNA levels may benefit from concurrent chemotherapy, whereas those with high levels may not. Other treatment modalities need to be explored for high-risk patients to improve their prognosis.

Citations

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  • Global trends in research of nasopharyngeal carcinoma: a bibliometric and visualization analysis
    Guilin An, Jie Liu, Ting Lin, Lan He, Yingchun He
    Frontiers in Oncology.2024;[Epub]     CrossRef
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Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiation Therapy: A Retrospective Study with 15-Year Follow-up
Lin Wang, Jingjing Miao, Huageng Huang, Boyu Chen, Xiao Xiao, Manyi Zhu, Yingshan Liang, Weiwei Xiao, Shaomin Huang, Yinglin Peng, Xiaowu Deng, Xing Lv, Weixiong Xia, Yanqun Xiang, Xiang Guo, Fei Han, Chong Zhao
Cancer Res Treat. 2022;54(1):118-129.   Published online June 7, 2021
DOI: https://doi.org/10.4143/crt.2021.101
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients.
Materials and Methods
Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010.
Results
With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group.
Conclusion
Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

Citations

Citations to this article as recorded by  
  • Retrospective analysis of 1539 nasopharyngeal carcinoma cases: chemotherapy should not be excluded for non-Asian patients with T1-2N1M0 stage
    Xin-Yu Li, Chang-Ying Zhong, Hui-Xian Xu
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • Genistein and chlorin E6-loaded versatile nanoformulation for remodeling the hypoxia-related tumor microenvironment and boosting photodynamic therapy in nasopharyngeal carcinoma treatment
    Qiang Zhou, Quazi T. H. Shubhra, Peng Lai, Jiayi Shi, Chenhao Fang, Qian Guo, Wanqing Li, Rui Chen, Xinkun Shen, Lina Huang, Xiaojun Cai, Sen Lin
    Advanced Composites and Hybrid Materials.2025;[Epub]     CrossRef
  • Vaccine-Based Immunotherapy for Oropharyngeal and Nasopharyngeal Cancers
    Daria Maria Filippini, Elisabetta Broseghini, Carlotta Liberale, Giulia Gallerani, Giambattista Siepe, Elisabetta Nobili, Manuela Ferracin, Gabriele Molteni
    Journal of Clinical Medicine.2025; 14(4): 1170.     CrossRef
  • Radiation oncology for the rhinologist
    Helena Levyn, Fan Yang, Nancy Y. Lee
    Current Opinion in Otolaryngology & Head & Neck Surgery.2024; 32(1): 5.     CrossRef
  • Examining patient-reported late toxicity and its association with quality of life and unmet need for symptom management among nasopharyngeal cancer survivors: a cross-sectional survey
    Victor C. W. Tam, Jerry C. F. Ching, Sindy S. T. Yip, Virginia H. Y. Kwong, Catherine P. L. Chan, Kenneth C. W. Wong, Shara W. Y. Lee
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Multifactorial clinical analysis of factors affecting necrosis of nasal septal mucosal flap after salvage surgery for recurrent nasopharyngeal carcinoma
    Qilin Gong, Huaying Li, Hui Liu, Youyuan Shi
    Scientific Reports.2024;[Epub]     CrossRef
  • Long noncoding RNA LINC00173 induces radioresistance in nasopharyngeal carcinoma via inhibiting CHK2/P53 pathway
    Jingjing Miao, Boyu Chen, Yunyun Xiao, Runda Huang, Xiao Xiao, Shunzhen Lu, Lu Zhang, Xuguang Wang, Ying Ouyang, Xiangfu Chen, Qiuyan Chen, Yanqun Xiang, Xiang Guo, Xiaowu Deng, Lin Wang, Haiqiang Mai, Chong Zhao
    Cancer Gene Therapy.2023; 30(9): 1249.     CrossRef
  • Therapeutic hyperthermia regulates complement C3 activation and suppresses tumor development through HSPA5/NFκB/CD55 pathway in nasopharyngeal carcinoma
    Chengcong Chen, Anbang Ren, Qi Yi, Jiazuo Cai, Muhammad Khan, Yunen Lin, Zhong Huang, Jie Lin, Jian Zhang, Wei Liu, Anan Xu, Yunhong Tian, YaWei Yuan, Ronghui Zheng
    Clinical and Experimental Immunology.2023; 213(2): 221.     CrossRef
  • Immunotherapy for nasopharyngeal carcinoma: Current status and prospects (Review)
    Huageng Huang, Yuyi Yao, Xinyi Deng, Zongyao Huang, Yungchang Chen, Zhao Wang, Huangming Hong, He Huang, Tongyu Lin
    International Journal of Oncology.2023;[Epub]     CrossRef
  • Quality of life and swallowing outcomes after early proactive swallowing rehabilitation by either transcutaneous neuromuscular electrical stimulation or exercise‐based swallowing training in patients with nasopharyngeal carcinoma after radiotherapy
    Peter K. M. Ku, Alexander C. Vlantis, Rita W. M. Wong, Thomas S. C. Hui, Thomas Law, Louisa K. Y. Ng, Eddy W. Y. Wong, W. T. Chang, David R. Johnson, Florence S. T. Mok, K. H. Wong, Victor Abdullah, Andrew van Hasselt, Kathy Y. S. Lee, Michael C. F. Tong
    Laryngoscope Investigative Otolaryngology.2023; 8(6): 1532.     CrossRef
  • Prognostic nutritional index and serum lactate dehydrogenase predict the prognosis of nasopharyngeal carcinoma patients who received intensity-modulated radiation therapy
    Chunxia Zhang, Zhouwei Zhan, Yunxiang Fang, Yuanyuan Ruan, Mingan Lin, Zhisen Dai, Yanping Zhang, Shanshan Yang, Shuxiang Xiao, Bijuan Chen
    Journal of Cancer Research and Clinical Oncology.2023; 149(20): 17795.     CrossRef
  • A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma
    Yao-Can Xu, Kai-Hua Chen, Zhong-Guo Liang, Xiao-Dong Zhu
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Minimally Invasive Surgery for Early-Stage Nasopharyngeal Carcinoma
    Jinping Liu, Zesheng Zeng, Dingting Wang, Gang Qin
    Journal of Craniofacial Surgery.2022; 33(8): e834.     CrossRef
  • External Validation of a Nomogram to Predict Survival and Benefit of Concurrent Chemoradiation for Stage II Nasopharyngeal Carcinoma
    Pui-Lam Yip, Shing-Fung Lee, Cheuk-Wai Horace Choi, Po-Chung Sunny Chan, Ka-Wai Alice Cheung, Chung-Hang James Chow, Ka-Man Cheung, Wing-Yu Jessica Lai, Ho-Fun Victor Lee, Ka-On Lam, Chi-Leung Chiang, Chun-Yin Edwin Wong, Ming-Chun Darren Poon, Macy Tong,
    Cancers.2021; 13(17): 4286.     CrossRef
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Re-irradiation with Moderate Hypo-fractionation Using Intensity Modulated Photon or Proton Radiation Therapy in Locally Recurrent Squamous Cell Carcinoma of Nasopharynx
Heerim Nam, Yong Chan Ahn, Kyungmi Yang, Dongryul Oh, Jae Myoung Noh
Cancer Res Treat. 2022;54(1):96-108.   Published online March 26, 2021
DOI: https://doi.org/10.4143/crt.2020.1349
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to analyze the treatment outcomes of locally recurrent nasopharyngeal cancer (NPC) patients following moderate hypo-fractionation re-irradiation (re-RT).
Materials and Methods
Sixty locally recurrent NPC patients underwent hypo-fractionation re-RT. Forty-eight point three percentage had rT3-4, and 30.0% did keratinizing squamous cell carcinoma. Intensity-modulated radiation therapy (IMRT), with or without intensity-modulated proton therapy (IMPT), was used in 66.7% of patients.
Results
With the median follow-up of 22 months (range, 2 to 254 months), 31 patients (51.7%) died, 38 (63.3%) developed further treatment failure, and 30 (50.0%) developed ≥ grade 3 toxicity (including seven grade 5) at time of analysis. The 2- and 5-year rates of overall survival, local failure-free survival, and ≥ grade 3 toxicity-free survival were 57.9% and 45.8%, 64.1% and 52.5%, and 54.8% and 44.9%, respectively. In multivariate analyses, worse factors for overall survival (OS) were iT3-4 (p=0.010) and age at re-RT ≥ 53 years (p=0.003), those for local failure-free survival (LFFS) were rT3-4 (p=0.022) and rN0-1 (p=0.035), and those for toxicity-free survival (TFS) were iT3-4 (p=0.020) and re-IMRT/IMPT (p=0.030), respectively. Cumulative dose or fraction size ≥ 3 Gy at re-RT, however, showed no significance for OS, LFFS and TFS.
Conclusion
Current re-RT with modern RT techniques by moderate hypo-fractionation scheme seemed feasible in treating locally recurrent NPC patients.

Citations

Citations to this article as recorded by  
  • Case Report: Unresectable recurrent nasopharyngeal cancer treated with immuno oncology
    Fabiano Flauto, Rosa Maria Di Crescenzo, Vincenzo Damiano
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • Radiation oncology for the rhinologist
    Helena Levyn, Fan Yang, Nancy Y. Lee
    Current Opinion in Otolaryngology & Head & Neck Surgery.2024; 32(1): 5.     CrossRef
  • Identifying the prognostic value of MRI-based tumor response and predicting the risk of radio-resistance in re-radiotherapy for locally recurrent nasopharyngeal carcinoma
    Zi-Jian Lu, Ting Liu, Jie-Yi Lin, Sheng-Ting Pei, Ling Guo, Sai-Lan Liu, Hai-Qiang Mai
    Radiotherapy and Oncology.2023; 183: 109635.     CrossRef
  • Low-dose radiotherapy effects the progression of anti-tumor response
    Lei Gao, Anqi Zhang
    Translational Oncology.2023; 35: 101710.     CrossRef
  • The Role of Hypofractionation in Proton Therapy
    Alexandre Santos, Scott Penfold, Peter Gorayski, Hien Le
    Cancers.2022; 14(9): 2271.     CrossRef
  • Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Nasopharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy
    Xingzhe Li, Sarin Kitpanit, Anna Lee, Dennis Mah, Kevin Sine, Eric J. Sherman, Lara A. Dunn, Loren S. Michel, James Fetten, Kaveh Zakeri, Yao Yu, Linda Chen, Jung Julie Kang, Daphna Y. Gelblum, Sean M. McBride, Chiaojung J. Tsai, Nadeem Riaz, Nancy Y. Lee
    JAMA Network Open.2021; 4(6): e2113205.     CrossRef
  • 6,776 View
  • 200 Download
  • 5 Web of Science
  • 6 Crossref
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Head and Neck Cancer
Prognostic Value of Serum Epstein-Barr Virus Antibodies and Their Correlation with TNM Classification in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma
Wan-Ru Zhang, Yu-Yun Du, Chun-Yan Guo, Han-Xing Zhou, Jie-Yi Lin, Xiao-Han Meng, Hao-Yuan Mo, Dong-Hua Luo
Cancer Res Treat. 2021;53(4):991-1003.   Published online January 13, 2021
DOI: https://doi.org/10.4143/crt.2020.1298
AbstractAbstract PDFPubReaderePub
Purpose
This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients.
Materials and Methods
Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS).
Results
Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05).
Conclusion
Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.

Citations

Citations to this article as recorded by  
  • Antibody Profiling of Pan-Cancer Viral Proteome Reveals Biomarkers for Nasopharyngeal Carcinoma Diagnosis and Prognosis
    Te Liang, Hao Chen, Lei Liu, Yongqiang Zheng, Zhaoen Ma, Ling Min, Jiahui Zhang, Lianfu Wu, Jie Ma, Zexian Liu, Qingfeng Zhang, Kai Luo, Di Hu, Tianxing Ji, Xiaobo Yu
    Molecular & Cellular Proteomics.2024; 23(3): 100729.     CrossRef
  • A clinical–radiomics nomogram based on multisequence MRI for predicting the outcome of patients with advanced nasopharyngeal carcinoma receiving chemoradiotherapy
    Liucheng Chen, Zhiyuan Wang, Ying Meng, Cancan Zhao, Xuelian Wang, Yan Zhang, Muye Zhou
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • 15,887 View
  • 175 Download
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Development and Validation of Web-Based Nomograms to Precisely Predict Survival Outcomes of Non-metastatic Nasopharyngeal Carcinoma in an Endemic Area
Ji-Jin Yao, Li Lin, Tian-Sheng Gao, Wang-Jian Zhang, Wayne R. Lawrence, Jun Ma, Ying Sun
Cancer Res Treat. 2021;53(3):657-670.   Published online December 7, 2020
DOI: https://doi.org/10.4143/crt.2020.899
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to develop web-based nomograms to precisely predict survival outcomes in patients with non-metastatic nasopharyngeal carcinoma (NPC) in an endemic area.
Materials and Methods
A total of 10,126 patients who underwent radical intensity-modulated radiotherapy at Sun Yat-sen University Cancer Center (SYSUCC) from 2009 to 2015 were analyzed. We assigned patients into a training cohort (SYSUCC-A, n=6,751) and an internal validation cohort (SYSUCC-B, n=3,375) based on computer-generated random numbers. Patients collected from Wuzhou Red Cross Hospital (WZRCH) between 2012 and 2015 were used as the independent external validation cohort (WZRCH, n=450). Concordance index (C-index) was used to determine predictive accuracy and discriminative ability for the nomogram. The web-based clinicopathologic prediction models for predicting survival were based on Cox regression.
Results
The C-indexes for SYSUCC-A, SYSUCC-B, and WZRCH cohorts for the established nomograms to predict 3-year overall survival (OS) was 0.736, 0.715, and 0.691. Additionally, C-indexes to predict 3-year distant metastasis-free survival (DMFS) was 0.717, 0.706, and 0.686, disease-free survival (DFS) was 0.713, 0.697, and 0.656, local relapse-free survival was 0.695, 0.684, and 0.652, and regional relapse-free survival was 0.672, 0.650, and 0.616. The calibration plots showed great agreement between nomogram-predicted 3-year survival outcomes and actual 3-year survival outcomes. Moreover, C-indexes of the nomograms for OS, DMFS, and DFS were significantly superior than TNM stage (p< 0.001 for all).
Conclusion
These user-friendly nomograms can precisely predict survival endpoints in patients with non-metastatic NPC. They may serve as a useful tool for providing patient counseling and help physicians to make individual follow-up plans.

Citations

Citations to this article as recorded by  
  • Adverse prognosis of nasopharyngeal carcinoma following long-term exposure to multiple air pollutants
    Xiao Lin, Yanan Jin, Jijin Yao, Xurui Sun, Tian Tian, Zhiqiang Li, Shimin Chen, Jie Jiang, Weihua Hu, Yuantao Hao, Liangping Xia, Wangjian Zhang
    Environmental Chemistry Letters.2024; 22(1): 21.     CrossRef
  • The development and external validation of a web-based nomogram for predicting overall survival with Ewing sarcoma in children
    Yi Chen, Zirui Liu, Yaobin Wang, Hongwei Zhan, Jinmin Liu, Yongkang Niu, Ao Yang, Fei Teng, Jinfeng Li, Bin Geng, Yayi Xia
    Journal of Children's Orthopaedics.2024; 18(2): 236.     CrossRef
  • The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis
    Ya-Nan Jin, Meng-Yun Qiang, Ying Wang, Yu-Jing Lin, Ren-Wei Jiang, Wan-Wei Cao, Wang-Jian Zhang, Si-Yang Wang, Hong-Yu Zhang, Ji-Jin Yao
    Cancer Immunology, Immunotherapy.2024;[Epub]     CrossRef
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    Xurui Sun, Xiao Lin, Jijin Yao, Tian Tian, Zhiqiang Li, Shimin Chen, Weihua Hu, Jie Jiang, Hui Tang, Huanle Cai, Tong Guo, Xudan Chen, Zhibing Chen, Man Zhang, Yongqing Sun, Shao Lin, Yanji Qu, Xinlei Deng, Ziqiang Lin, Liangping Xia, Yanan Jin, Wangjian
    International Journal of Cancer.2024; 155(9): 1558.     CrossRef
  • ALYREF promotes the metastasis of nasopharyngeal carcinoma by increasing the stability of NOTCH1 mRNA
    Yanan Jin, Jijin Yao, Jianchang Fu, Qitao Huang, Yilin Luo, Yafei You, Wangjian Zhang, Qian Zhong, Tianliang Xia, Liangping Xia
    Cell Death & Disease.2024;[Epub]     CrossRef
  • The continuous improvement of digital assistance in the radiation oncologist’s work: from web-based nomograms to the adoption of large-language models (LLMs). A systematic review by the young group of the Italian association of radiotherapy and clinical o
    Antonio Piras, Ilaria Morelli, Riccardo Ray Colciago, Luca Boldrini, Andrea D’Aviero, Francesca De Felice, Roberta Grassi, Giuseppe Carlo Iorio, Silvia Longo, Federico Mastroleo, Isacco Desideri, Viola Salvestrini
    La radiologia medica.2024; 129(11): 1720.     CrossRef
  • Selection of induction chemotherapy cycles for stage N3 nasopharyngeal carcinoma based on pre-treatment plasma EBV DNA
    Youliang Weng, Sunqin Cai, Chao Li, Yun Xu, Yuhui Pan, Zongwei Huang, Ying Li, Zijie Wu, Yu Chen, Sufang Qiu
    Scientific Reports.2024;[Epub]     CrossRef
  • A Nomogram for Predicting Recurrence in Stage I Non‐Small Cell Lung Cancer
    Rongrong Bian, Feng Zhao, Bo Peng, Jin Zhang, Qixing Mao, Lin Wang, Qiang Chen
    The Clinical Respiratory Journal.2024;[Epub]     CrossRef
  • Individualized number of induction chemotherapy cycles for locoregionally advanced nasopharyngeal carcinoma patients based on early tumor response
    Yu‐Ting Jiang, Kai‐Hua Chen, Zhong‐Guo Liang, Jie Yang, Song Qu, Ling Li, Xiao‐Dong Zhu
    Cancer Medicine.2023; 12(4): 4010.     CrossRef
  • The feasibility of reduced-dose radiotherapy in childhood nasopharyngeal carcinoma with favorable response to neoadjuvant chemotherapy
    Ji-Jin Yao, Ya-Nan Jin, Yu-Jing Lin, Wang-Jian Zhang, Tia Marks, Ian Ryan, Hong-Yu Zhang, Liang-Ping Xia
    Radiotherapy and Oncology.2023; 178: 109414.     CrossRef
  • Conditional survival nomogram for monitoring real-time survival of young non-metastatic nasopharyngeal cancer survivors
    Jianing Luo, Xiaonan Hu, Xiaofeng Ge
    Journal of Cancer Research and Clinical Oncology.2023; 149(12): 10181.     CrossRef
  • Construction of Prognostic Nomogram in Patients with N3-Stage Nasopharyngeal Carcinoma
    Wenmiao Cao, Xiaoxin Li, Jianqi Yang, Enming Xing, Wenjuan Wu, Yizhi Ge, Buhai Wang
    ORL.2023; 85(4): 195.     CrossRef
  • Regional lymph node density-based nomogram predicts prognosis in nasopharyngeal carcinoma patients without distant metastases
    Jie Ma, Rong Zhao, Yu-Lan Wu, Yang Liu, Guan-Qiao Jin, Dan-Ke Su
    Cancer Imaging.2023;[Epub]     CrossRef
  • Does three cycles of neoadjuvant chemotherapy prior to concurrent chemoradiotherapy provide benefits for all childhood patients with locoregionally advanced nasopharyngeal carcinoma?
    Ya-Nan Jin, Hui-Jiao Cao, Xiao-Hua Gong, Wang-Jian Zhang, Tia Marks, Ji-Jin Yao, Liang-Ping Xia
    Journal of Cancer Research and Clinical Oncology.2022; 148(10): 2569.     CrossRef
  • Development of a web-based prognostic model to quantify the survival benefit of cumulative cisplatin dose during concurrent chemoradiotherapy in childhood nasopharyngeal carcinoma
    Ya-Nan Jin, Qian-Qiong Yang, Zi-Qian Li, Xue-Qing Ou, Wang-Jian Zhang, Tia Marks, Ji-Jin Yao, Liang-Ping Xia
    Radiotherapy and Oncology.2022; 166: 118.     CrossRef
  • A predictive web-based nomogram for the early death of patients with lung adenocarcinoma and bone metastasis: a population-based study
    Zhehong Li, Junqiang Wei, Haiying Cao, Mingze Song, Yafang Zhang, Yu Jin
    Journal of International Medical Research.2021;[Epub]     CrossRef
  • The Role of Pretreatment 18F-FDG PET/CT for Early Prediction of Neoadjuvant Chemotherapy Response in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma
    Jijin Yao, Ying Wang, Yujing Lin, Yingying Yang, Jingjing Wan, Xiaohua Gong, Fanwei Zhang, Wangjian Zhang, Tia Marks, Siyang Wang, Hongjun Jin, Hong Shan
    Drug Design, Development and Therapy.2021; Volume 15: 4157.     CrossRef
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Establishment and Validation of a Nomogram for Nasopharyngeal Carcinoma Patients Concerning the Prognostic Effect of Parotid Lymph Node Metastases
Chao Lin, Xue-Song Sun, Sai-Lan Liu, Xiao-Yun Li, Nian Lu, Xin-Ling Li, Lin-Quan Tang, Ling Guo
Cancer Res Treat. 2020;52(3):855-866.   Published online March 10, 2020
DOI: https://doi.org/10.4143/crt.2019.772
AbstractAbstract PDFPubReaderePub
Purpose
The prognosis of nasopharyngeal carcinoma (NPC) patients with parotid lymph node (PLN) metastasis remains unclear. This study was performed to investigate the prognostic significance and optimal staging category of PLN metastasis and develop a nomogram for estimating individual risk.
Materials and Methods
Clinical data of 7,084 non-metastatic NPC patients were retrospectively reviewed. Overall survival (OS) was the primary endpoint. A nomogram was established based on the Cox proportional hazards regression model. The accuracy and calibration ability of this nomogram was evaluated by C-index and calibration curves with bootstrap validation.
Result
Totally, 164/7,084 NPC patients (2.3%) presented with PLNs. Multivariate analyses showed that PLN metastasis was a negative prognostic factor for OS, progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Patients with PLN metastasis had a worse prognosis than N3 disease. Five independent prognostic factors were included in the nomogram, which showed a C-index of 0.743. The calibration curves for probability of 3- and 5-year OS indicated satisfactory agreement between nomogram-based prediction and actual observation. All results were confirmed in the validation cohort.
Conclusion
NPC patient with PLN metastasis had poorer survival outcome (OS, PFS, DMFS, and LRFS) than N3 disease. We developed a nomogram to provide individual prediction of OS for patients with PLN metastasis.

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  • Risk factors analysis and nomogram for predicting recurrence in periocular basal cell carcinoma
    Xincen Hou, Alexander C. Rokohl, Katharina Berndt, Senmao Li, Xiaojun Ju, Philomena A. Wawer Matos, Wanlin Fan, Ludwig M. Heindl
    Canadian Journal of Ophthalmology.2025;[Epub]     CrossRef
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    Binhao Wu, Xiaozhong Chen, Caineng Cao
    Current Oncology Reports.2025;[Epub]     CrossRef
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    Sezin Yuce Sari, Melek Tugce Yilmaz, Gozde Yazici, Sepideh Mohammadipour, Gokhan Ozyigit, Ibrahim Gullu, Mustafa Cengiz
    Strahlentherapie und Onkologie.2024; 200(12): 1057.     CrossRef
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    Lixia Liang, Yan Li, Yansui Hong, Tianxing Ji, Hao Chen, Zhifang Lin
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  • A Randomized Controlled Trial on Evaluation of Plasma Epstein-Barr Virus Biomarker for Early Diagnosis in Patients With Nasopharyngeal Carcinoma
    Wen Liu, Huilan Li, Hui Sheng, Xiaohua Liu, Peidong Chi, Xueping Wang, Minjie Mao
    Advances in Therapy.2020; 37(10): 4280.     CrossRef
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    Qianqian Xia, Hua Jin, Xing Zhang, Wenjing Yan, Dan Meng, Bo Ding, Jian Cao, Dake Li, Shizhi Wang
    International Immunopharmacology.2020; 88: 106935.     CrossRef
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Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma
Liyuan Dai, Qigen Fang, Peng Li, Junfu Wu, Xu Zhang
Cancer Res Treat. 2020;52(1):109-116.   Published online May 30, 2019
DOI: https://doi.org/10.4143/crt.2019.202
AbstractAbstract PDFPubReaderePub
Purpose
The main goal of this study was to analyze the prognosis of secondary oral squamous cell carcinoma (SCC) with a comparison with sporadic oral SCC by a matched-pair design.
Materials and Methods
Records of patients with surgically treated primary oral SCC were reviewed, and a total of 83 patients with previous history of radiotherapy for nasopharyngeal carcinoma (NPC) were retrospectively enrolled. A matched-pair study was performed, each NPC survivor was matched with two sporadic oral SCC patients by age, sex, primary tumor site, adverse pathologic characteristics, disease stage, neck node status, and tumor stage. The overall survival (OS) and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method; independent prognostic factors were evaluated by the Cox proportional hazards method.
Results
Compared with sporadic oral SCC patients, NPC survivors were less likely to be smokers (p=0.004), perineural invasion and lymphovascular invasion were more common in NPC survivors (both p < 0.001). The 5-year OS and DSS rates in NPC survivors were 47% and 54%, respectively; the 5-year OS and DSS rates in sporadic oral SCC patients were 62% and 67%, respectively; the difference was significant (both p < 0.05). In survival analysis, disease stage remained to be independent prognostic factor for both the OS and DSS.
Conclusion
NPC survivors had worse OS and DSS than sporadic oral SCC patients, NPC survivors were less likely to be smokers, but had higher opportunity of perineural invasion and lymphovascular invasion. Disease stage was the most important predictor for the survival in NPC survivors.

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    Qian Wang, Tao Huang, Xudong Wei, Niraj Babu
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    Qigen Fang, Junhui Yuan, Wei Du, Liyuan Dai, Xu Zhang, Ruihua Luo
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    Peng Li, Qigen Fang, Yanjie Yang, Defeng Chen, Wei Du, Fei Liu, Ruihua Luo
    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Chunmiao Xu, Hailiang Li, Dongjie Seng, Fei Liu
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    Wenli Yang, Minglei Sun, Qiaoyan Jie, Haixia Zhou, Peng Zhang, Juanfang Zhu
    Frontiers in Oncology.2020;[Epub]     CrossRef
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    Guo Zhao, Jianli Sun, Kai Ba, Yunxiang Zhang
    Frontiers in Oncology.2020;[Epub]     CrossRef
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    Wei Du, Qigen Fang, Shanting Liu, Defeng Chen, Ruihua Luo, Xu Zhang
    Frontiers in Oncology.2020;[Epub]     CrossRef
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    Bo Gu, Qigen Fang, Yao Wu, Wei Du, Xu Zhang, Defeng Chen
    BMC Cancer.2020;[Epub]     CrossRef
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Patterns of Failure and Survival Trends in 3,808 Patients with Stage II Nasopharyngeal Carcinoma Diagnosed from 1990 to 2012: A Large-Scale Retrospective Cohort Study
Xue-Song Sun, Di-Han Liu, Sai-Lan Liu, Qiu-Yan Chen, Shan-Shan Guo, Yue-Feng Wen, Li-Ting Liu, Hao-Jun Xie, Qing-Nan Tang, Yu-Jing Liang, Xiao-Yun Li, Jin-Jie Yan, Ming-Huang Hong, Jun Ma, Lin-Quan Tang, Hai-Qiang Mai
Cancer Res Treat. 2019;51(4):1449-1463.   Published online March 7, 2019
DOI: https://doi.org/10.4143/crt.2018.688
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate the survival trends and patterns of failure in patients with stage II nasopharyngeal carcinoma (NPC) treated with radiotherapy (RT) and chemotherapy over the last 20 years.
Materials and Methods
Thirty-eight hundred and eight patients diagnosed with stage II NPC between January 1990 and December 2012 were involved in this retrospective cohort study. All patients were treated with RT. According to the main imaging techniques and RT technology, we categorized these patients into four calendar periods: 1990-1996, 1997-2002, 2003-2007, and 2008-2012. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis–free survival (DMFS) were served as the clinical outcome.
Results
After a median follow-up period of 84.7 months, we observed increasing trends in survival and disease control. The 3- and 5-year OS rates increased from 87.1% and 78.7% in the first calendar period to 97.4% and 94.5% in the last calendar period, respectively (p<0.001). Additionally, significant increasing trends could be seen in the PFS and LRFS during the four calendar periods. In the subgroup analysis, the LRFS in patients older than 50 years at diagnosis showed greater improvement than younger patients. However, the rate of distant metastasis was stable and relatively low, as the 5-year DMFS ranged from 90.5% to 94.7% among the four calendar periods.
Conclusion
The survival rates in patients with stage II NPC showed increasing trends from 1990 to 2012. The advance of RT provided excellent locoregional control and enhanced OS.

Citations

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    Jiachen Sun, Sai kit Edmond Lam, Xinzhi Teng, Jiang Zhang, Francis Kar-ho Lee, Celia Wai-yi Yip, James Chung-hang Chow, Victor Ho-fun Lee, Ying Sun, Jing Cai
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    Zhi-Hui Wang, Xiao-Feng Pei, Zhi-Quan Zhu, Zhong Lin, Yin-Yan Mao, Xiao-Lu Xu, You-Li Luo, Li Zhang, Pei-Jian Peng
    OncoTargets and Therapy.2020; Volume 13: 3325.     CrossRef
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    Molecular Cancer.2020;[Epub]     CrossRef
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The Prognostic Value of Albumin-to-Alkaline Phosphatase Ratio before Radical Radiotherapy in Patients with Non-metastatic Nasopharyngeal Carcinoma: A Propensity Score Matching Analysis
Jae Sik Kim, Bhumsuk Keam, Dae Seog Heo, Doo Hee Han, Chae-Seo Rhee, Ji-hoon Kim, Kyeong Cheon Jung, Hong-Gyun Wu
Cancer Res Treat. 2019;51(4):1313-1323.   Published online January 29, 2019
DOI: https://doi.org/10.4143/crt.2018.503
AbstractAbstract PDFPubReaderePub
Purpose
We first analyzed the prognostic power of albumin-to-alkaline phosphatase ratio (AAPR) before radical radiotherapy (RT) in non-metastatic nasopharyngeal carcinoma (NPC) patients.
Materials and Methods
The records of 170 patients with biopsy-proven, non-metastatic NPC treated by radical RT between 1998 and 2016 at our institution were retrospectively reviewed. Median follow-up duration was 50.6 months. All patients received intensity-modulated RT and cisplatin based chemotherapy before, during, or after RT. The major treatment of patients was based on concurrent chemoradiotherapy (92.4%). The AAPR was calculated by the last value of both albumin and alkaline phosphatase within 1 month immediately preceding RT. The optimal cut-off level of AAPR was determined by using Cutoff Finder, a web-based system. Propensity score matching (PSM) analysis was performed.
Results
The optimal cut-off level of AAPR was 0.4876. After PSM analysis of whole cohort, an AAPR was not related to survival outcomes. In PSM analysis for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC), an AAPR ≥ 0.4876 was related to better overall survival (OS), progression-free survival (PFS), and locoregional relapse–free survival (LRRFS) (OS: hazard ratio [HR], 0.341; 95% confidence interval [CI], 0.144 to 0.805; p=0.014; PFS: HR, 0.416; 95% CI, 0.189 to 0.914; p=0.029; and LRRFS: HR, 0.243; 95% CI, 0.077 to 0.769; p=0.016, respectively).
Conclusion
The AAPR, inexpensive and readily derived from a routine blood test, could be an independent prognostic factor for patients with LA-NPC. And it might help physicians determine treatment plans by identifying the patient's current status. Future prospective clinical trials to validate its prognostic value are needed.

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Subdivision of Nasopharyngeal Carcinoma Patients with Bone-Only Metastasis at Diagnosis for Prediction of Survival and Treatment Guidance
Xue-Song Sun, Yu-Jing Liang, Sai-Lan Liu, Qiu-Yan Chen, Shan-Shan Guo, Yue-Feng Wen, Li-Ting Liu, Hao-Jun Xie, Qing-Nan Tang, Xiao-Yun Li, Jin-Jie Yan, Lin-Quan Tang, Hai-Qiang Mai
Cancer Res Treat. 2019;51(4):1259-1268.   Published online January 4, 2019
DOI: https://doi.org/10.4143/crt.2018.652
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to subdivide M1 stage nasopharyngeal carcinoma (NPC) patients with bone-only metastases for prognosis prediction while identifying the treatment effect of locoregional radiotherapy (LRRT) and metastasis radiotherapy (MRT) among patients with different risk.
Materials and Methods
From November 2006 to October 2016, a total of 226 patients with bone-only metastasic NPC were retrospectively enrolled. All patients developed distant lesions before receiving treatment. All potential prognostic factors were considered and the correlation of the M1 subdivisions with overall survival (OS) was determined by Cox regression hazards model. Kaplan–Meier curves were used to appraise survival condition and log-rank testing was used to compare the differences.
Results
The median follow-up time was 33.9 months (range, 3 to 126 months). According to multivariate Cox proportional hazard analysis, the number of metastatic lesions and Epstein-Barr virus (EBV) DNA status after palliative chemotherapy (PCT) were independent prognostic factors for OS. Thus, we subdivided patients into three risk groups according to these two factors. Systemic chemotherapy combined with LRRT may benefit patients in low- and intermediate-risk groups but not in the high-risk group. Further aggressive MRT based on systemic chemotherapy showed no survival benefit in any risk group.
Conclusion
The stratification of NPC patients with bone-only metastasis based on EBV DNA after PCT and the number of metastatic lesions provided promising prognostic value and could aid clinicians in person-specific treatment.

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  • Efficacy of metastatic lesion radiotherapy in patients with metastatic nasopharyngeal carcinoma: A multicenter retrospective study
    Yang Liu, Jie Ma, Xiao-Yi Zeng, Zhi-Chao Zuo, Rui-Zhong Chen, Xiao-Yu Li, Zhong-Guo Liang, Kai-Hua Chen, Xin-Bin Pan, Su Pei, Bin-Bin Yu, Ling Li, Song Qu, Yun-Li Yang, Xiao-Dong Zhu
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Prognostic Value and Staging Classification of Lymph Nodal Necrosis in Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy
Yanru Feng, Caineng Cao, Qiaoying Hu, Xiaozhong Chen
Cancer Res Treat. 2019;51(3):1222-1230.   Published online December 27, 2018
DOI: https://doi.org/10.4143/crt.2018.595
AbstractAbstract PDFPubReaderePub
Purpose
The aim of the present study was to evaluate the prognostic value of magnetic resonance imaging (MRI)‒determined lymph nodal necrosis (LNN) in nasopharyngeal carcinoma (NPC) and explore the feasibility of an N-classification system based on the 8th edition of the American Joint Committee on Cancer (AJCC) system.
Materials and Methods
The MRI scans of 616 patients with newly diagnosed stage T1-4N1-3M0 NPC who were treated with definitive intensity-modulated radiotherapy (IMRT) were reviewed.
Results
Multivariate analysis showed that LNN was an independent negative prognostic predictor of distant metastasis free survival (hazard ratio, 1.634; 95% confidence interval, 1.023 to 2.609; p=0.040) and overall survival (hazard ratio, 2.154; 95% confidence interval, 1.282 to 3.620; p=0.004). Patients of classification N1 disease with LNN were reclassified as classification N2, and classification N2 disease with LNN as classification N3 in the proposed N-classification system. Correlation with death and distant failure was significant, and the total difference between N1 and N3 was wider with the proposed system.
Conclusion
MRI-determined LNN is an independent negative prognostic factor for NPC. The proposed N classification system is powerfully predictive.

Citations

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Reduction of Target Volume and the Corresponding Dose for the Tumor Regression Field after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
Lei Wang, Zheng Wu, Dehuan Xie, Ruifang Zeng, Wanqin Cheng, Jiang Hu, Shaomin Huang, Shu Zhou, Rui Zhong, Yong Su
Cancer Res Treat. 2019;51(2):685-695.   Published online August 13, 2018
DOI: https://doi.org/10.4143/crt.2018.250
AbstractAbstract PDFPubReaderePub
Purpose
This study aims to investigate the feasibility of contouring target volume according to residual tumor and decreasing the dose to the tumor regression field after induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC).
Materials and Methods
From August 2009 to August 2013, patients with stage III–IVB NPC were treated with IC and concurrent chemoradiotherapy. Gross tumor volume of nasopharynx (GTVnx)–residual and gross tumor volume of cervical lymph node (GTVnd)–residual were contoured according to post-IC residual primary tumor and any N+ disease, respectively. The tumor regression field was included in CTVnx1/CTVnd1 and prescribed a dose of 60 Gy. Outcomes and toxicities of all patients were evaluated.
Results
A total of 57 patients were enrolled. At a median follow-up of 68 months, three cases displayed locoregional recurrence and one case showed both distant metastasis and locoregional recurrence. All locoregional recurrences were in the GTVnx-residual/GTVnd-residual and in-field. The 5-year overall, locoregional relapse-free, distant metastasis-free, and progression-free survival rates were 82.2%, 87.7%, 85.8% and 80.3%, respectively.
Conclusion
After IC, contouring of GTVnx-residual/GTVnd-residual as residual tumor volume and distribution 60 Gy ofradiation dose to the tumorregression field may be feasible and need further investigation.

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Feasibility of Selective Neck Irradiation with Lower Elective Radiation Dose in Treating Nasopharynx Cancer Patients
Won Kyung Cho, Dongryul Oh, Eonju Lee, Tae Gyu Kim, Hyebin Lee, Heerim Nam, Jae Myoung Noh, Yong Chan Ahn
Cancer Res Treat. 2019;51(2):603-610.   Published online July 18, 2018
DOI: https://doi.org/10.4143/crt.2018.240
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to report the clinical outcomes following selective neck irradiation (SNI) with lower elective radiation therapy (RT) dose in treating nasopharyngeal cancer (NPC) patients.
Materials and Methods
A total of 347 NPC patients received definitive RT according to our SNI policy and were retrospectively analyzed. The clinical target volumes (CTVs) were subdivided into CTV at high risk (CTV-HR) and CTV at low risk (CTV-LR). The typical doses to gross tumor volume (GTV), CTV-HR, and CTV-LR were 68.4-70.0 Gy, 54.0-60.0 Gy, and 36.0 Gy.
Results
With the median follow-up of 68.1 months (range, 2.3 to 197.1 months), the 5-year rates of loco-regional control and progression-free survival in all the patients were 85.0% and 70.8%, respectively. Thirty patients developed regional failure and the regional control rates at 3 and 5 years were 92.6% and 91.4%, respectively. The sites of regional failure in relation to the target volume were exclusively inside GTV/CTV-HR in 20, inside and outside GTV/CTVHR in three, and exclusively outside GTV/CTV-HR in seven, which were 5.7%, 0.9%, and 2.0% of total patients, respectively.
Conclusion
The clinical outcomes by the current SNI policy were feasible and comparable to those following classic elective nodal irradiation policy.

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    Kangpyo Kim, Yong Chan Ahn
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    Yang Liu, Wenbin Yan, Chaosu Hu, Xiaodong Huang, Kai Wang, Yuan Qu, Xuesong Chen, Runye Wu, Ye Zhang, Jianghu Zhang, Jingwei Luo, Yexiong Li, Jingbo Wang, Junlin Yi
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    Mincheol Ko, Kyungmi Yang, Yong Chan Ahn, Sang Gyu Ju, Dongryul Oh, Yeong-bi Kim, Dong Yeol Kwon, Seyjoon Park, Kisung Lee
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    Dongryul Oh
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    MJ García-Anaya, S. Segado-Guillot, J. Cabrera-Rodríguez, MD Toledo-Serrano, JA Medina-Carmona, J. Gómez-Millán
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    Yang Liu, Ziou Du, Shiyu Song, Junlin Yi
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    Yang Liu, Yaqian Han, Feng Liu, Desheng Hu, Zhijian Chen, Peiguo Wang, Jingao Li, Jiyong Qin, Feng Jin, Yexiong Li, Jingbo Wang, Junlin Yi
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    Karol Jelonek, Katarzyna Mrowiec, Dorota Gabryś, Piotr Widłak
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  • Oncological and Functional Outcomes of Larynx-preserving Surgery for Hypopharyngeal Cancer: A Comparison with Definitive Radiation-based Treatment
    Donghyeok Kim, Nalee Kim, Sungmin Koh, Man Ki Chung, Young-Ik Son, Dongryul Oh, Han-Sin Jeong, Yong Chan Ahn
    Cancer Research and Treatment.2022; 54(1): 84.     CrossRef
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    Heerim Nam, Yong Chan Ahn, Kyungmi Yang, Dongryul Oh, Jae Myoung Noh
    Cancer Research and Treatment.2022; 54(1): 96.     CrossRef
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    Teng Hwee Tan, Huili Zheng, Timothy Cheo, Jeremy Tey, Yu Yang Soon
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    Wen-Shan Liu, Ju-Chun Chien, Yu-Hsien Huang, Po-Chun Chen, Wei-Lun Huang, Shao-Wei Chiang, Ching-Chih Lee, Bor-Hwang Kang, Yu-Chang Hu
    Cancer Management and Research.2022; Volume 14: 1063.     CrossRef
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    Deng-Yu Kuo, Yen-Wen Wu, Chen-Hsi Hsieh, Li-Jen Liao, Pei-Wei Shueng
    Reviews in Cardiovascular Medicine.2022;[Epub]     CrossRef
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    Wen-Shan Liu, Kuo-Wang Tsai, Bor-Hwang Kang, Ching-Chieh Yang, Wei-Lun Huang, Ching-Chih Lee, Yu-Chang Hu, Kuo-Ping Chang, Hsiu-Min Chen, Yaoh-Shiang Lin
    International Journal of Radiation Oncology*Biology*Physics.2021; 109(2): 495.     CrossRef
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    Kyungmi Yang, Yong Chan Ahn, Heerim Nam, Sang Duk Hong, Dongryul Oh, Jae Myoung Noh
    Oral Oncology.2021; 114: 105180.     CrossRef
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    Wai Tong Ng, Raymond K. Y. Tsang, Jonathan J. Beitler, Remco de Bree, Andrés Coca‐Pelaz, Avraham Eisbruch, Orlando Guntinas‐Lichius, Anne W. M. Lee, Antti A. Mäkitie, William M. Mendenhall, Sandra Nuyts, Alessandra Rinaldo, K. Thomas Robbins, Juan P. Rodr
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    Ji-Jin Yao, Li Lin, Tian-Sheng Gao, Wang-Jian Zhang, Wayne R. Lawrence, Jun Ma, Ying Sun
    Cancer Research and Treatment.2021; 53(3): 657.     CrossRef
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    Radiotherapy and Oncology.2020; 148: 140.     CrossRef
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    Seung Gyu Park, Yong Chan Ahn, Dongryul Oh, Jae Myoung Noh, Sang Gyu Ju, Dongyeol Kwon, Kwanghyun Jo, Kwangzoo Chung, Eunah Chung, Woojin Lee, Seyjoon Park
    Cancer Science.2019; 110(9): 2867.     CrossRef
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Plasma Macrophage Migration Inhibitory Factor and CCL3 as Potential Biomarkers for Distinguishing Patients with Nasopharyngeal Carcinoma from High-Risk Individuals Who Have Positive Epstein-Barr Virus Capsid Antigen-Specific IgA
Ning Xue, Jian-Hua Lin, Shan Xing, Dan Liu, Shi-Bing Li, Yan-Zhen Lai, Xue-Ping Wang, Min-Jie Mao, Qian Zhong, Mu-Sheng Zeng, Wan-Li Liu
Cancer Res Treat. 2019;51(1):378-390.   Published online May 29, 2018
DOI: https://doi.org/10.4143/crt.2018.070
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to identify novel plasma biomarkers for distinguishing nasopharyngeal carcinoma (NPC) patients from healthy individuals who have positive Epstein-Barr virus (EBV) viral capsid antigen (VCA-IgA).
Materials and Methods
One hundred seventy-four plasma cytokines were analyzed by a Cytokine Array in eight healthy individuals with positive EBV VCA-IgA and eight patients with NPC. Real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry were employed to detect the expression levels of macrophage migration inhibitory factor (MIF) and CC chemokine ligand 3 (CCL3) in NPC cell lines and tumor tissues. Plasma MIF and CCL3 were measured by ELISA in 138 NPC patients, 127 EBV VCA-IgA negative (VN) and 100 EBV VCA-IgA positive healthy donors (VP). Plasma EBV VCA-IgA was determined by immunoenzymatic techniques.
Results
Thirty-four of the 174 cytokines varied significantly between the VP and NPC group. Plasma MIF and CCL3 were significantly elevated in NPC patients compared with VN and VP. Combination of MIF and CCL3 could be used for the differential diagnosis of NPC from VN cohort (area under the curve [AUC], 0.913; sensitivity, 90.00%; specificity, 80.30%), and combination of MIF, CCL3, and VCA-IgA could be used for the differential diagnosis of NPC from VP cohort (AUC, 0.920; sensitivity, 90.00%; specificity, 84.00%), from (VN+VP) cohort (AUC, 0.961; sensitivity, 90.00%; specificity, 92.00%). Overexpressions of MIF and CCL3 were observed in NPC plasma, NPC cell lines and NPC tissues.
Conclusion
Plasma MIF, CCL3, and VCA-IgA combination significantly improves the diagnostic specificity of NPC in high-risk individuals.

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  • Nasopharyngeal carcinoma-associated inflammatory cytokines: ongoing biomarkers
    Chuwen Liang, Jun Kan, Jingli Wang, Wei Lu, Xiaoyan Mo, Bei Zhang
    Frontiers in Immunology.2024;[Epub]     CrossRef
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    Dongyu Chuo, Dapeng Lin, Mingdi Yin, Yuze Chen
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    Caihong Wei, Dan Guo, Huayun Pu
    Journal of Biomaterials and Tissue Engineering.2021; 11(7): 1388.     CrossRef
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Longitudinal Assessment of Intravoxel Incoherent Motion Diffusion Weighted Imaging in Evaluating the Radio-sensitivity of Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiation Therapy
Youping Xiao, Ying Chen, Yunbin Chen, Zhuangzhen He, Yiqi Yao, Jianji Pan
Cancer Res Treat. 2019;51(1):345-356.   Published online May 14, 2018
DOI: https://doi.org/10.4143/crt.2018.089
AbstractAbstract PDFPubReaderePub
Purpose
Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI)was evaluated regarding its ability to preliminarily predict the short-term treatment response of nasopharyngeal carcinoma (NPC) following intensity-modulated radiation therapy.
Materials and Methods
IVIM-DWI with 14 b-factors (0-1,000 sec/mm2 ) was performed with a 3T MR system on 47 consecutive NPCs before, during (end of the 5th, 10th, 15th, 20th, and 25th fractions), and after fractional radiotherapy. IVIM parametrics (D, f, and D*) were calculated and compared to the baseline and xth fraction. Patients were categorized into responders and non-responders after radiotherapy. IVIM parametrics were also compared between subgroups.
Results
After fractional radiations, the D (except D5 and D at the end of the 5th fraction) after radiations were larger than the baseline D0 (p < 0.05), and the post-radiation D* (except D*5 and D*10) were smaller than D*0 (p < 0.05). f0 was smaller than f5 and f10 (p < 0.001) but larger than fend (p < 0.05). Furthermore, greater D5, D10, D15, and f10 coupled with smaller f0, D*20, and D*25were observed in responders than non-responders (all p < 0.01). Responders also presented larger ΔD10, Δf10, ΔD*20, and δD*20 than non-responders (p < 0.05). Receiver operating characteristic curve analysis indicated that the D5, D*20, and f10 could better differentiate responders from non-responders.
Conclusion
IVIM-DWI could efficiently assess tumor treatment response to fractional radiotherapy and predict the radio-sensitivity for NPCs.

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Paranasal Sinus Invasion in Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy
Caineng Cao, Feng Jiang, Qifeng Jin, Ting Jin, Shuang Huang, Qiaoying Hu, Yuanyuan Chen, Yongfeng Piao, Yonghong Hua, Xinglai Feng, Xiaozhong Chen
Cancer Res Treat. 2019;51(1):73-79.   Published online February 26, 2018
DOI: https://doi.org/10.4143/crt.2017.607
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study is to evaluate the prognostic significance of paranasal sinus invasion for nasopharyngeal carcinoma (NPC) and its suitable position in the T classification.
Materials and Methods
The magnetic resonance imaging (MRI) scans of 695 patients with previously untreated, biopsy-proven, non-metastatic NPC that was treated with intensity-modulated radiotherapy (IMRT) were reviewed retrospectively.
Results
The incidence of paranasal sinus invasion was 39.4% (274 of 695 patients). Multivariate analysis showed that paranasal sinus invasion was an independent negative prognostic factor for local failure-free survival (LFFS) (p < 0.05). According to the eighth American Joint Committee on Cancer (AJCC) staging system, 275 patients were classified as T3 classification. Of these, 78 patients (28.4%) developed paranasal sinus invasion (T3b) and 197 (71.6%) didn’t (T3a). The estimated 5-year LFFS and overall survival (OS) rates for the patients with T3b and T3a classification were 88.6% versus 95.0% (p=0.047), and 84.5% versus 93.3% (p=0.183), respectively. The estimated 5-year LFFS and OS rates for the patientswith T4 classificationwere 89.5% and 83.2%,whichwere similarwith the outcomes of patients with T3b classification.
Conclusion
MRI-determined paranasal sinus invasion is an independent prognostic factor of NPC treated by IMRT. Paranasal sinus invasion is recommended to classify as T4 classification in the 8th AJCC staging system for NPC.

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  • Use of 18F‐FDG PET/MRI as an Initial Staging Procedure for Nasopharyngeal Carcinoma
    Caineng Cao, Yuting Fang, Bocheng Yu, Yuanfan Xu, Mengyun Qiang, Changjuan Tao, Shuang Huang, Xiaozhong Chen
    Journal of Magnetic Resonance Imaging.2024; 59(3): 922.     CrossRef
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    Xiao-Yi Wang, Si-Yu Zhu, Wei-Jie WU, Hao-Jiang Li, Jiao Li, Xiao-Feng Lin, Li Li, Li-Zhi Liu
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    Chi Leung Chiang, Qiaojuan Guo, Wai Tong Ng, Shaojun Lin, Tiffany Sze Wai Ma, Zhiyuan Xu, Youping Xiao, Jishi Li, Tianzhu Lu, Horace Cheuk Wai Choi, Wenqi Chen, Eric Sze Chun Chau, Peter Ho Yin Luk, Shao Hui Huang, Brian O’Sullivan, Jianji Pan, Anne Wing
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    Caineng Cao, Yuanfan Xu, Shuang Huang, Feng Jiang, Ting Jin, Qifeng Jin, Yonghong Hua, Qiaoying Hu, Xiaozhong Chen
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    Liqing Wu, Shuiqing Zhuo, Weike Zeng, Shaobo Liang, Shunxin Wang, Chunyan Cui, Jian Zhou, Guangyin Ruan, Shuoyu Xu, Lifei Wang, Ling Huang, Lizhi Liu, Haojiang Li
    Head & Neck.2019; 41(12): 4088.     CrossRef
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The Characteristics and Survival Outcomes in Patients Aged 70 Years and Older with Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era
Ya-Nan Jin, Wang-Jian Zhang, Xiu-Yu Cai, Mei-Su Li, Wayne R. Lawrence, Si-Yang Wang, Dong-Mei Mai, Yu-Yun Du, Dong-Hua Luo, Hao-Yuan Mo
Cancer Res Treat. 2019;51(1):34-42.   Published online February 6, 2018
DOI: https://doi.org/10.4143/crt.2017.551
AbstractAbstract PDFPubReaderePub
Purpose
We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era.
Methods
and Materials From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses.
Results
For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05).
Conclusion
Our findings suggest IMRT +/– chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.

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    Ya‐Nan Jin, Zhi‐Wen Xiao, Wei Yao, Jing Yu, Wang‐Jian Zhang, Tia Marks, Hong‐Yu Zhang, Ji‐Jin Yao, Liang‐Ping Xia
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Induction Chemotherapy Plus Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma in Children and Adolescents: A Matched Cohort Analysis
Yang Li, Lin-Quan Tang, Li-Ting Liu, Shan-Shan Guo, Yu-Jing Liang, Xue-Song Sun, Qing-Nan Tang, Jin-Xin Bei, Jing Tan, Shuai Chen, Jun Ma, Chong Zhao, Qiu-Yan Chen, Hai-Qiang Mai
Cancer Res Treat. 2018;50(4):1304-1315.   Published online January 8, 2018
DOI: https://doi.org/10.4143/crt.2017.463
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to evaluate the long-term clinical outcome and toxicity of induction chemotherapy (IC) followed by concomitant chemoradiotherapy (CCRT) compared with CCRT alone for the treatment of children and adolescent locoregionally advanced nasopharyngeal carcinoma (LACANPC).
Materials and Methods
A total of 194 locoregionally advanced nasopharyngeal carcinoma patients youngerthan 21 years who received CCRT with or without IC before were included in the study population. Overall survival (OS) rate, progression-free survival (PFS) rate, locoregional recurrence-free survival (LRFS) rate, and distant metastasis-free survival (DMFS) rate were assessed by the Kaplan-Meier method and a log-rank test. Treatment toxicities were clarified and compared between two groups.
Results
One hundred and thiry of 194 patients received IC+CCRT. Patients who were younger and with more advanced TNM stage were more likely to receive IC+CCRT and intensive modulated radiotherapy. The addition of IC before CCRT failed to improve survival significantly. The matched analysis identified 43 well-balanced patients in both two groups. With a median follow-up of 51.5 months, no differences were found between the IC+CCRT group and the CCRT group in 5-year OS (83.7% vs. 74.6%, p=0.153), PFS (79.2% vs. 73.4%, p=0.355), LRFS (97.7% vs. 88.2%, p=0.083), and DMFS (81.6% vs. 81.6%, p=0.860). N3 was an independent prognostic factor predicting poorer OS, PFS, and DMFS. The addition of IC was associated with increased rates of grade 3 to 4 neutropenia.
Conclusion
This study failed to demonstrate that adding IC before CCRT could provide a significant additional survival benefit for LACANPC patients. Further investigations are warranted.

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Proposal of a Pretreatment Nomogram for Predicting Local Recurrence after Intensity-Modulated Radiation Therapy in T4 Nasopharyngeal Carcinoma: A Retrospective Review of 415 Chinese Patients
Lu-Lu Zhang, Yi-Yang Li, Jiang Hu, Guan-Qun Zhou, Lei Chen, Wen-Fei Li, Ai-Hua Lin, Jun Ma, Zhen-Yu Qi, Ying Sun
Cancer Res Treat. 2018;50(4):1084-1095.   Published online November 15, 2017
DOI: https://doi.org/10.4143/crt.2017.359
AbstractAbstract PDFPubReaderePub
Purpose
Local relapse-free survival (LRFS) differs widely among patients with T4 category nasopharyngeal carcinoma (NPC). We aimed to build a nomogram incorporating clinicopathological information to predict LRFS in T4 NPC after definitive intensity-modulated radiation therapy (IMRT).
Materials and Methods
Retrospective study of 415 Chinese patients with non-metastatic T4 NPC treated with definitive IMRT with or without chemotherapy at our cancer center between October 2009 and September 2013. The nomogram for LRFS at 3 and 5 years was generated based on multivariate Cox proportional hazards regression, and validated using bootstrap resampling, assessing discriminative performance using the concordance index (C-index) and determining calibration ability via calibration curves.
Results
Five-year LRFS was 88.8%. We identified and incorporated four independent prognostic factors for LRFS: ethmoid sinus invasion, primary gross tumor volume, age, and pretreatment body mass index. The C-index of the nomogram for local recurrence was 0.732 (95% confidence interval, 0.726 to 0.738), indicating excellent predictive accuracy. The calibration curve revealed excellent agreement between nomogram-predicted and observed LRFS probabilities. Risk subgroups based on total point score cutoff values enabled effective discrimination of LRFS.
Conclusion
This pretreatment nomogram enables clinicians to accurately predict LRFS in T4 NPC after definitive IMRT, and could help to facilitate personalized patient counselling and treatment strategies.

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Combination of Tumor Volume and Epstein-Barr Virus DNA Improved Prognostic Stratification of Stage II Nasopharyngeal Carcinoma in the Intensity Modulated Radiotherapy Era: A Large-Scale Cohort Study
Qiu-Yan Chen, Shao-Yan Guo, Lin-Quan Tang, Tong-Yu Lu, Bo-Lin Chen, Qi-Yu Zhong, Meng-Sha Zou, Qing-Nan Tang, Wen-Hui Chen, Shan-Shan Guo, Li-Ting Liu, Yang Li, Ling Guo, Hao-Yuan Mo, Rui Sun, Dong-Hua Luo, Chong Zhao, Ka-Jia Cao, Chao-Nan Qian, Xiang Guo, Mu-Sheng Zeng, Hai-Qiang Mai
Cancer Res Treat. 2018;50(3):861-871.   Published online September 13, 2017
DOI: https://doi.org/10.4143/crt.2017.237
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors.
Materials and Methods
By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above.
Results
Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm3; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm3; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm3) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm3). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant.
Conclusion
Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.

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Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area
Cheng Xu, Shi-Ping Yang, Yuan Zhang, Ling-Long Tang, Guan-Qun Zhou, Xu Liu, Yan-Ping Mao, Rui Guo, Wen-Fei Li, Lei Chen, Ai-Hua Lin, Ying Sun, Jun Ma
Cancer Res Treat. 2018;50(3):777-790.   Published online July 24, 2017
DOI: https://doi.org/10.4143/crt.2017.255
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC).
Materials and Methods
Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS.
Results
Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel–cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect.
Conclusion
Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.

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    Tingting Yu, Yiwei Zhang, Jiawen Li, Zhuo Li, Rui Tong
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Pretreatment Serum Amyloid A and C-reactive Protein Comparing with Epstein-Barr Virus DNA as Prognostic Indicators in Patients with Nasopharyngeal Carcinoma: A Prospective Study
Qiu-Yan Chen, Qing-Nan Tang, Lin-Quan Tang, Wen-Hui Chen, Shan-Shan Guo, Li-Ting Liu, Chao-Feng Li, Yang Li, Yu-Jing Liang, Xue-Song Sun, Ling Guo, Hao-Yuan Mo, Rui Sun, Dong-Hua Luo, Yu-Ying Fan, Yan He, Ming-Yuan Chen, Ka-Jia Cao, Chao-Nan Qian, Xiang Guo, Hai-Qiang Mai
Cancer Res Treat. 2018;50(3):701-711.   Published online July 14, 2017
DOI: https://doi.org/10.4143/crt.2017.180
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The measuring Epstein-Barr virus (EBV) DNA is an important predictor of nasopharyngeal carcinoma (NPC). This study evaluated the predictive value of pretreatment serum amyloid A (SAA) and C-reactive protein (CRP) comparing with EBV DNA in patients with NPC.
Materials and Methods
In an observational study of 419 non-metastatic NPC patients, we prospectively evaluated the prognostic effects of pretreatment SAA, CRP, and EBV DNA on survival. The primary endpoint was progress-free survival (PFS).
Results
The median level of SAA and CRP was 4.28 mg/L and 1.88 mg/L, respectively. For the highSAA group (> 4.28 mg/L) versus the low-SAA (≤ 4.28 mg/L) group and the high-CRP group (> 1.88 mg/L) versus the low-CRP (≤ 1.88 mg/L) group, the 5-year PFS was 64.5% versus 73.1% (p=0.013) and 65.2% versus 73.3% (p=0.064), respectively. EBV DNA detection showed a superior predictive result, the 5-year PFS in the EBV DNA ≥ 1,500 copies/mL group was obviously different than the EBV DNA < 1,500 copies/mL group (62.2% versus 77.8%, p < 0.001). Multifactorial Cox regression analysis confirmed that in the PFS, the independent prognostic factors were including EBV DNA (hazard ratio [HR], 1.788; p=0.009), tumour stage (HR, 1.903; p=0.021), and node stage (HR, 1.498; p=0.049), but the SAA and CRP were not included in the independent prognostic factors.
Conclusion
The results of SAA and CRP had a certain relationship with the prognosis of NPC, and the prognosis of patients with high level of SAA and CRP were poor. However, the predictive ability of SAA and CRP was lower than that of EBV DNA.

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    Jiahui Li, Qianwen Liu, Huiying Qin
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The Prognostic Value of Treatment-Related Lymphopenia in Nasopharyngeal Carcinoma Patients
Li-Ting Liu, Qiu-Yan Chen, Lin-Quan Tang, Shan-Shan Guo, Ling Guo, Hao-Yuan Mo, Ming-Yuan Chen, Chong Zhao, Xiang Guo, Chao-Nan Qian, Mu-Sheng Zeng, Jin-Xin Bei, Jing Tan, Shuai Chen, Ming-Huang Hong, Jian-Yong Shao, Ying Sun, Jun Ma, Hai-Qiang Mai
Cancer Res Treat. 2018;50(1):19-29.   Published online April 5, 2017
DOI: https://doi.org/10.4143/crt.2016.595
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to evaluate the prognostic value of treatment-related lymphopenia in patients with nasopharyngeal carcinoma (NPC).
Materials and Methods
A total of 413 consecutive stage II-IVb NPC patients treated with concurrent chemoradiotherapy (CCRT) were enrolled. The overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test.
Results
A minimum (mini)–absolute lymphocyte counts (ALC) of < 390 cells/μL or ALC after 3 months of CCRT (post3m-ALC) < 705 cells/μL was significantly associated with worse outcome than mini-ALC ≥ 390 cells/μL (OS, p=0.002; PFS, p=0.005; DMFS, p=0.004) or post3m-ALC ≥ 705 cells/μL (OS, p < 0.001; PFS, p < 0.001; DMFS, p=0.001). Patients with lymphopenia (mini-ALC < 390 cells/μL and post3m-ALC < 705 cells/μL) had a worse prognosis than those without lymphopenia (mini-ALC ≥ 390 cells/μL and post3m-ALC ≥ 705 cells/μL) (OS, p < 0.001; PFS, p < 0.001; DMFS, p < 0.001). Multivariate analysis revealed that post3m-ALC was an independent prognostic factor for OS (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.12 to 2.78; p=0.015), PFS (HR, 1.86; 95% CI, 1.23 to 2.82; p=0.003), and DMFS (HR, 1.87; 95% CI, 1.13 to 3.08; p=0.014). Multivariate analysis also revealed that patients with lymphopenia had a high risk of death (HR, 3.79; 95% CI, 1.75 to 8.19; p=0.001), disease progression (HR, 2.93; 95% CI, 1.59 to 5.41; p=0.001), and distant metastasis (HR, 3.89; 95% CI, 1.67 to 9.10; p=0.002). Multivariate analysis performed with time dependent Cox regression demonstrated ALC was an independent prognostic factor for OS (HR, 0.995; 95% CI, 0.991 to 0.999; p=0.025) and PFS (HR, 0.993; 95% CI, 0.988 to 0.998; p=0.006).
Conclusion
Treatment-related lymphopenia was a poor prognostic factor in NPC patients.

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Clinicopathologic Characteristics and Prognosis of Tongue Squamous Cell Carcinoma in Patients with and without a History of Radiation for Nasopharyngeal Carcinoma: A Matched Case-Control Study
Peng Zhang, Li Zhang, Hui Liu, Lei Zhao, Yong Li, Jing-Xian Shen, Qing Liu, Meng-Zhong Liu, Mian Xi
Cancer Res Treat. 2017;49(3):695-705.   Published online October 11, 2016
DOI: https://doi.org/10.4143/crt.2016.317
AbstractAbstract PDFPubReaderePub
Purpose
Previous studies reported an association between an increased risk of tongue cancer and radiation treatment for nasopharyngeal carcinoma (NPC). This study compared the clinicopathologic characteristics and outcomes of tongue squamous cell carcinoma (TSCC) in patients with and without a history of radiotherapy for NPC.
Materials and Methods
From 1965 to 2009, a total of 73 patients were diagnosed with TSCC with a history of radiotherapy for NPC. The patients were matched in a 1:3 ratio with patients with sporadic TSCC according to age, sex, and year of the TSCC diagnosis. The primary endpoint was the overall survival.
Results
The median interval from NPC to TSCC was 82 months. The NPC survivors were more likely to be diagnosed with a more advanced T classification, less likely to have lymph node involvement, and more likely to have the tumor located in the dorsum of the tongue than sporadic TSCC. Regarding the histologic characteristics, the NPC survivors were more likely to have a weak lymphocytic host response, low tumor budding, and low risk of a worse pattern of invasion. The sporadic TSCC patients had a better overall survival (hazard ratio, 0.690; p=0.033) than the NPC survivors. In competing risks analysis, the cumulative incidence functions for the competing event (documented non-tongue cancer death) were significantly higher in the NPC survivors (Gray’s test, p=0.001).
Conclusion
TSCC patients with a history of radiotherapy for NPC appear to have particular clinicopathologic features, a poorer survival, and are more likely to die from non-tongue cancer causes than those with sporadic TSCC.

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Magnetic Resonance Imaging–Detected Intracranial Extension in the T4 Classification Nasopharyngeal Carcinoma with Intensity-Modulated Radiotherapy
Caineng Cao, Jingwei Luo, Li Gao, Junlin Yi, Xiaodong Huang, Suyan Li, Jianping Xiao, Zhong Zhang, Guozhen Xu
Cancer Res Treat. 2017;49(2):518-525.   Published online August 24, 2016
DOI: https://doi.org/10.4143/crt.2016.299
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted is to identify the prognostic value and staging categories of magnetic resonance imaging (MRI)–detected intracranial extension in nasopharyngeal carcinoma (NPC) with intensity-modulated radiotherapy (IMRT) to determine whether it is necessary to subclassify the T4 classification NPC.
Materials and Methods
A total of 335 nonmetastatic T4 classificationNPC patientswith MRI treated between March 2004 and June 2011 by radical IMRTwere included. The T4 classification patientswere subclassified into two grades (T4a, without intracranial extension vs. T4b, with intracranial extension) according to the site of invasion.
Results
The frequency of intracranial extensionwas 40.9% (137 of 335 patients). Multivariate analysis identified subclassification (T4a vs. T4b) as an independent prognostic factor for local failure-free survival (p=0.049; hazard ratio [HR], 0.498) and overall survival (p=0.004; HR, 0.572); however, it had no effect on regional failure-free survival or distant failure-free survival (p > 0.050).
Conclusion
For patients with T4 classification NPC, those with MRI-detected intracranial extension are more likely to experience local failure and death afterIMRT than patientswithout intracranial extension. According to the site of invasion, subclassification of T4 patients as T4a or T4b has prognostic value in NPC.

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ZNF488 Enhances the Invasion and Tumorigenesis in Nasopharyngeal Carcinoma Via the Wnt Signaling Pathway Involving Epithelial Mesenchymal Transition
Dan Zong, Li Yin, Qian Zhong, Wen-jie Guo, Jian-hua Xu, Ning Jiang, Zhi-rui Lin, Man-zhi Li, Ping Han, Lin Xu, Xia He, Mu-sheng Zeng
Cancer Res Treat. 2016;48(1):334-344.   Published online March 12, 2015
DOI: https://doi.org/10.4143/crt.2014.311
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC). Materials and Methods The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef.
Results
ZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/β-catenin signaling pathway. Conclusion Our data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/β-catenin pathway to induce EMT in NPC.

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Role of Chemotherapy in Stage II Nasopharyngeal Carcinoma Treated with Curative Radiotherapy
Min Kyu Kang, Dongryul Oh, Kwan Ho Cho, Sung Ho Moon, Hong-Gyun Wu, Dae-Seog Heo, Yong Chan Ahn, Keunchil Park, Hyo Jung Park, Jun Su Park, Ki Chang Keum, Jihye Cha, Jun Won Kim, Yeon-Sil Kim, Jin Hyoung Kang, Young-Taek Oh, Ji-Yoon Kim, Sung Hwan Kim, Jin-Hee Kim, Chang Geol Lee
Cancer Res Treat. 2015;47(4):871-878.   Published online February 13, 2015
DOI: https://doi.org/10.4143/crt.2014.141
Correction in: Cancer Res Treat 2016;48(1):425
AbstractAbstract PDFPubReaderePub
Purpose
To define the role of neoadjuvant and concurrent chemotherapy in stage II nasopharyngeal carcinoma, we compared the treatment outcomes of patients treated with curative radiotherapy with or without chemotherapy. Materials and Methods From 2004 to 2011, 138 patients with American Joint Committee on Cancer (AJCC) 2002 stage II nasopharyngeal carcinoma were treated with curative radiotherapy in 12 hospitals in South Korea. Treatment methods included radiotherapy alone in 34 patients, neoadjuvant chemotherapy followed by radiotherapy alone in seven, concurrent chemoradiotherapy in 80, and neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in 17. Adjuvant chemotherapy was used in 42 patients. Total radiation dose ranged from 64 Gy to 74.2 Gy (median, 70 Gy).
Results
Median follow-up was 48 months (range, 7 to 97 months) for all patients. At the last followup, 13 patients had died and 32 had experienced treatment failure; locoregional failure occurred in 14, distant failure in 16, and both in two. Five-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 86.2%, 85.5%, 74.4%, and 88.2%, respectively. Multivariate analyses showed that the significant prognostic factors were concurrent chemotherapy and N stage for locoregional relapse-free survival, concurrent chemotherapy for progression-free survival, and age and N stage for overall survival. Neither neoadjuvant nor concurrent chemotherapy improved distant metastasis-free survival. Conclusion Concurrent chemotherapy significantly improved 5-year locoregional relapse-free survival and progression-free survival in stage II nasopharyngeal carcinoma. However, neoadjuvant chemotherapy failed to improve either.

Citations

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