Cancer Research and Treatment

Original Articles

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

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.

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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

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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

Abstract PDF PubReader ePub

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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Neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in elderly patients with stage III‐IVa nasopharyngeal carcinoma: A real‐world study based on medical comorbidities
Ya‐Nan Jin, Zhi‐Wen Xiao, Wei Yao, Jing Yu, Wang‐Jian Zhang, Tia Marks, Hong‐Yu Zhang, Ji‐Jin Yao, Liang‐Ping Xia
Head & Neck.2024; 46(8): 2020. CrossRef
Therapeutic Approaches to Increase the Survival Rate of Cancer Patients in the Younger and Older Population
Tharrun Paul, Kanagaraj Palaniyandi, Dhanavathy Gnanasampanthapandian
Current Aging Science.2024; 17(1): 16. CrossRef
Lobaplatin-based concurrent chemoradiotherapy in elderly nasopharyngeal carcinoma
Yi-Feng Yu, Ping Zhou, Rui Zhou, Qin Lin, San-Gang Wu
Annals of Medicine.2024;[Epub] CrossRef
Elderly nasopharyngeal carcinoma patients (aged ≥70 years): Survival and treatment strategies
Gang Yang, Jingjing Huang, Ji Sun, Li Wang
Cancer Medicine.2023; 12(19): 19523. CrossRef
Management of Nasopharyngeal Carcinoma in Elderly Patients
Wing Lok Chan, James Chung Hang Chow, Zhi-yuan Xu, Jishi Li, Wing Tung Gobby Kwong, Wai Tong Ng, Anne W. M. Lee
Frontiers in Oncology.2022;[Epub] CrossRef
Institutionally Validated Nomogram Predicting Prognosis for Older Patients with Nonmetastatic Nasopharyngeal Carcinoma
Chao Yan, Ziwei Tu, Zixian Zhang, Xi Ouyang, Dou Li, Shiyi Peng, Jun Zhong
Future Oncology.2022; 18(15): 1829. CrossRef
The Interplay between Age and Viral Status in EBV-Related Nasopharyngeal and HPV-Related Oropharyngeal Carcinoma Patients
Stefano Cavalieri, Paolo Bossi, Gabriele Infante, Rosalba Miceli, Nicola Alessandro Iacovelli, Eliana Ivaldi, Laura Deborah Locati, Cristiana Bergamini, Carlo Resteghini, Imperia Nuzzolese, Salvatore Alfieri, Elena Colombo, Rossana Ingargiola, Marzia Fran
Cancers.2022; 14(24): 6170. CrossRef
Clinical characteristics and prognosis of elderly nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy
Yingchen Lyu, Mengshan Ni, Ruiping Zhai, Fangfang Kong, Chengrun Du, Chaosu Hu, Hongmei Ying
European Archives of Oto-Rhino-Laryngology.2021; 278(7): 2549. CrossRef
Development of a Comorbidity-Based Nomogram to Predict Survival After Salvage Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era
Run-Da Huang, Zhuang Sun, Xiao-Hui Wang, Yun-Ming Tian, Ying-Lin Peng, Jing-Yun Wang, Wei-Wei Xiao, Chun-Yan Chen, Xiao-Wu Deng, Fei Han
Frontiers in Oncology.2021;[Epub] CrossRef
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 Research and Treatment.2021; 53(3): 657. CrossRef
Development of a Nomogram Model for Treatment of Elderly Patients with Locoregionally Advanced Nasopharyngeal Carcinoma
Jia Kou, Lu-Lu Zhang, Xing-Li Yang, Dan-Wan Wen, Guan-Qun Zhou, Chen-Fei Wu, Si-Si Xu, Wei-Hong Zheng, Zhen-Yu Qi, Ying Sun, Li Lin
Journal of Personalized Medicine.2021; 11(11): 1065. CrossRef
MicroRNA-424-5p inhibits the proliferation, migration, and invasion of nasopharyngeal carcinoma cells by decreasing AKT3 expression
Chong Zhao, Feng Zhao, Huiying Chen, Yuehua Liu, Jiping Su
Brazilian Journal of Medical and Biological Research.2020;[Epub] CrossRef
Acute Toxicities and Prognosis of Elderly Patients with Nasopharyngeal Carcinoma After Intensity-Modulated Radiotherapy: Prediction with Nomogram

Yu Liang, Kai-hua Chen, Jie Yang, Jing Zhang, Ru-rong Peng, Song Qu, Ling Li, Xiao-dong Zhu
Cancer Management and Research.2020; Volume 12: 8821. CrossRef
Genome-Wide Association Study of Susceptibility Loci for Radiation-Induced Brain Injury
Tong-Min Wang, Guo-Ping Shen, Ming-Yuan Chen, Jiang-Bo Zhang, Ying Sun, Jing He, Wen-Qiong Xue, Xi-Zhao Li, Shao-Yi Huang, Xiao-Hui Zheng, Shao-Dan Zhang, Ye-Zhu Hu, Hai-De Qin, Jin-Xin Bei, Jun Ma, Jianbing Mu, Yin Yao Shugart, Wei-Hua Jia
JNCI: Journal of the National Cancer Institute.2018;[Epub] CrossRef

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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

Abstract PDF Supplementary Material PubReader ePub

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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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

Abstract PDF Supplementary Material PubReader ePub

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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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

Abstract PDF Supplementary Material PubReader ePub

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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