Cancer Research and Treatment

Original Articles

Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003-2013: Lu-Lu Zhang, Guo-Hong Li, Yi-Yang Li, Zhen-Yu Qi, Ai-Hua Lin, Ying Sun; Cancer Res Treat. 2019;51(3):982-991. Published online October 11, 2018; DOI: https://doi.org/10.4143/crt.2018.298

Purpose
The incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized.
Methods
and Materials Consecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival.
Results
Of the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and >5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (≥50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival.
Conclusion
This large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.

Citations

Citations to this article as recorded by

Age-specific characteristics of head and neck second primary malignancies in patients treated for nasopharyngeal carcinoma: a retrospective study
Q. Jiang, T. Xu, M. Zeng, Y. He, Y. Cai, Z. Huang
International Journal of Oral and Maxillofacial Surgery.2024; 53(1): 11. CrossRef
The prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma
Peter K. M. Ku, Alexander C. Vlantis, Thomas S. C. Hui, Zenon W. C. Yeung, Ryan H. W. Cho, Marc H. K. Wong, Alex K. F. Lee, David C. M. Yeung, Simon Y. P. Chan, Becky Y. T. Chan, Wai‐tsz Chang, Florence Mok, Kam‐hung Wong, Jeffrey K. T. Wong, Victor Abdul
Head & Neck.2024; 46(7): 1637. CrossRef
Maxillary sinus anterior wall recurrence after intensity-modulated radiotherapy for nasopharyngeal carcinoma
Y Fang, L Wang, X Chen, C Cao
International Journal of Radiation Research.2024; 22(3): 803. CrossRef
Detection and staging of recurrent or metastatic nasopharyngeal carcinoma in the era of FDG PET/MR
Yongfeng Piao, Caineng Cao, Yuanfan Xu, Shuang Huang, Feng Jiang, Ting Jin, Qifeng Jin, Yonghong Hua, Qiaoying Hu, Xiaozhong Chen
European Archives of Oto-Rhino-Laryngology.2022; 279(1): 353. CrossRef
Second Primary Lung Adenocarcinoma After Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma
Fen Xue, Xiaoshuang Niu, Chaosu Hu, Xiayun He
Frontiers in Oncology.2022;[Epub] CrossRef
Racial and ethnic disparities in nasopharyngeal cancer with an emphasis among Asian Americans
Qian Wang, Hui Xie, Yannan Li, Nicholas Theodoropoulos, Yaning Zhang, Changchuan Jiang, Chi Wen, Laura S. Rozek, Paolo Boffetta
International Journal of Cancer.2022; 151(8): 1291. CrossRef
Factors associated with the development of second primary tumours in head and neck cancer patients
Inmaculada Salcedo‐Bellido, Pilar Requena, Rocío Mateos, Carmen Ortega‐Rico, Rocío Olmedo‐Requena, Macarena Lozano‐Lorca, Juan Pedro Arrebola, Rocío Barrios‐Rodríguez
European Journal of Cancer Care.2022;[Epub] CrossRef
Nasopharyngeal carcinoma: an evolving paradigm
Kenneth C. W. Wong, Edwin P. Hui, Kwok-Wai Lo, Wai Kei Jacky Lam, David Johnson, Lili Li, Qian Tao, Kwan Chee Allen Chan, Ka-Fai To, Ann D. King, Brigette B. Y. Ma, Anthony T. C. Chan
Nature Reviews Clinical Oncology.2021; 18(11): 679. CrossRef
The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma
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Cancer Communications.2021; 41(11): 1195. CrossRef
Radiation-induced second primary squamous cell carcinoma of the oral cavity after radiotherapy for nasopharyngeal carcinoma
Chao Liu, Lieqiang Liao, Guoying Wu, Honghong Yan, Xiaoqi Chen, Chao Wang, Xiajing Zheng, Ziyi Zeng, Zheng Zhao, Di Wu, Xuekui Liu
Oral Oncology.2020; 109: 104863. CrossRef
Second primary cancer after intensity-modulated radiotherapy for nasopharyngeal carcinoma: A territory-wide study by HKNPCSG
James C.H. Chow, Anthony H.P. Tam, Ka-Man Cheung, Victor H.F. Lee, Chi-Leung Chiang, Macy Tong, Edwin C.Y. Wong, Alice K.W. Cheung, Sunny P.C. Chan, Jessica W.Y. Lai, Roger K.C. Ngan, Wai-Tong Ng, Anne W.M. Lee, Kwok-Hung Au
Oral Oncology.2020; 111: 105012. CrossRef

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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

Abstract PDF PubReader ePub

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.

Citations

Citations to this article as recorded by

Radiomics and Deep Learning in Nasopharyngeal Carcinoma: A Review
Zipei Wang, Mengjie Fang, Jie Zhang, Linquan Tang, Lianzhen Zhong, Hailin Li, Runnan Cao, Xun Zhao, Shengyuan Liu, Ruofan Zhang, Xuebin Xie, Haiqiang Mai, Sufang Qiu, Jie Tian, Di Dong
IEEE Reviews in Biomedical Engineering.2024; 17: 118. CrossRef
Novel prediction model combining PET/CT metabolic parameters, inflammation markers, and TNM stage: prospects for personalizing prognosis in nasopharyngeal carcinoma
Huan Liang, Weilin Tan, Jie Wang, Mengdan Li, Hua Pang, Xiaohui Wang, Lu Yang, Xingguo Jing
Annals of Nuclear Medicine.2024; 38(10): 802. CrossRef
Can Epstein–Barr virus‐deoxyribonucleic acid load after induction chemotherapy combined with American Joint Committee on Cancer stage determine the chemotherapy intensity of locally advanced nasopharyngeal carcinoma?
Qun Zhang, Zhen‐Wei Peng, Zhuo‐Sheng Gu, Yan Wang, Fang He, Wen‐Bin Zhao, Wei Luo, Yong‐Yu Mei
Cancer Medicine.2023; 12(1): 223. CrossRef
Prioritizing sufficient dose to gross tumor volume over normal tissue sparing in intensity‐modulated radiotherapy treatment of T4 nasopharyngeal carcinoma
Yanyan Chen, Quxia Zhang, Tianzhu Lu, Cairong Hu, Jingfeng Zong, Yun Xu, Wei Zheng, Lisha Chen, Senan Lin, Sufang Qiu, Luying Xu, Jianji Pan, Qiaojuan Guo, Shaojun Lin
Head & Neck.2023; 45(5): 1130. CrossRef
Multi-task deep learning-based radiomic nomogram for prognostic prediction in locoregionally advanced nasopharyngeal carcinoma
Bingxin Gu, Mingyuan Meng, Mingzhen Xu, David Dagan Feng, Lei Bi, Jinman Kim, Shaoli Song
European Journal of Nuclear Medicine and Molecular Imaging.2023; 50(13): 3996. CrossRef
Prognostic significance of AKR1C4 and the advantage of combining EBV DNA to stratify patients at high risk of locoregional recurrence of nasopharyngeal carcinoma
Shan-Shan Guo, Yan-Zhou Chen, Li-Ting Liu, Rong-Ping Liu, Yu-Jing Liang, Dong-Xiang Wen, Jing Jin, Lin-Quan Tang, Hai-Qiang Mai, Qiu-Yan Chen
BMC Cancer.2022;[Epub] CrossRef
DeepMTS: Deep Multi-Task Learning for Survival Prediction in Patients With Advanced Nasopharyngeal Carcinoma Using Pretreatment PET/CT
Mingyuan Meng, Bingxin Gu, Lei Bi, Shaoli Song, David Dagan Feng, Jinman Kim
IEEE Journal of Biomedical and Health Informatics.2022; 26(9): 4497. CrossRef
Development and Validation of Prognostic Nomograms Based on Gross Tumor Volume and Cervical Nodal Volume for Nasopharyngeal Carcinoma Patients With Concurrent Chemoradiotherapy
Cui-Dai Zhang, Mei Li, Ying-Ji Hong, Ze-Man Cai, Kai-Chun Huang, Zhi-Xiong Lin, Zhi-Ning Yang
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
Nomogram predict relapse-free survival of patients with thymic epithelial tumors after surgery
Yang-Yu Huang, Lei-Lei Wu, Xuan Liu, Shen-Hua Liang, Guo-Wei Ma
BMC Cancer.2021;[Epub] CrossRef
Establishment and validation of a nomogram with intratumoral heterogeneity derived from 18F-FDG PET/CT for predicting individual conditional risk of 5-year recurrence before initial treatment of nasopharyngeal carcinoma
Bingxin Gu, Jianping Zhang, Guang Ma, Shaoli Song, Liqun Shi, Yingjian Zhang, Zhongyi Yang
BMC Cancer.2020;[Epub] CrossRef
Prognostic Nomogram for Patients with Radical Surgery for Non-Metastatic Colorectal Cancer Incorporating Hematological Biomarkers and Clinical Characteristics

Peiyun Long, Youya Zang, Huan Wang, Xiumei Liang, Xuekun Xie, Zhiwei Han, Dongyi Lin, Zongyu Wang, Shan Huang, Chuang Chen
OncoTargets and Therapy.2020; Volume 13: 2093. CrossRef
Impact of Paranasal Sinus Invasion on Oncologic and Dosimetric Outcomes in Nasopharyngeal Carcinoma Following Intensity-Modulated Radiation Therapy—Implications for Risk Stratification and Planning Optimization
Xin Zhou, Xiayun He, Fen Xue, Xiaomin Ou, Chaosu Hu
Frontiers in Oncology.2020;[Epub] CrossRef
Role of IMRT/VMAT-Based Dose and Volume Parameters in Predicting 5-Year Local Control and Survival in Nasopharyngeal Cancer Patients
Nicola Alessandro Iacovelli, Alessandro Cicchetti, Anna Cavallo, Salvatore Alfieri, Laura Locati, Eliana Ivaldi, Rossana Ingargiola, Domenico A. Romanello, Paolo Bossi, Stefano Cavalieri, Chiara Tenconi, Silvia Meroni, Giuseppina Calareso, Marco Guzzo, Ce
Frontiers in Oncology.2020;[Epub] CrossRef
Development of a Nomogram Model for Treatment of Nonmetastatic Nasopharyngeal Carcinoma
Lu-Lu Zhang, Fei Xu, Di Song, Meng-Yao Huang, Yong-Shi Huang, Qi-Ling Deng, Yi-Yang Li, Jian-Yong Shao
JAMA Network Open.2020; 3(12): e2029882. CrossRef
Radiomics on multi-modalities MR sequences can subtype patients with non-metastatic nasopharyngeal carcinoma (NPC) into distinct survival subgroups
En-Hong Zhuo, Wei-Jing Zhang, Hao-Jiang Li, Guo-Yi Zhang, Bing-Zhong Jing, Jian Zhou, Chun-Yan Cui, Ming-Yuan Chen, Ying Sun, Li-Zhi Liu, Hong-Min Cai
European Radiology.2019; 29(10): 5590. CrossRef
Impact of paranasal sinus invasion on advanced nasopharyngeal carcinoma treated with intensity‐modulated radiation therapy: the validity of advanced T stage of AJCC/UICC eighth edition staging system
Ying Wang, Jie Zhao, Yajie Zhao, Zhen Yang, Mingjun Lei, Zhanzhan Li, Rui Wei, Dengming Chen, Yuxiang He, Liangfang Shen
Cancer Medicine.2018; 7(7): 2826. CrossRef

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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

Abstract PDF Supplementary Material PubReader ePub

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-NLR_min). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLR_min 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-NLR_min (≥ 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-NLR_min ≥ 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-NLR_min during PF/TP IC-1 have prognostic value for poor survival in LANPC.

Citations

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Prospective clinical study of the efficacy and safety of different doses of PEG recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for preventing leukopenia/neutropenia caused by concurrent chemoradiotherapy for cervical cancer
Tingting Yu, Yiwei Zhang, Jiawen Li, Zhuo Li, Rui Tong
Holistic Integrative Oncology.2024;[Epub] CrossRef
Incidence, consequences, and predictors of serious chemotherapy‐induced thrombocytopenia in nasopharyngeal carcinoma
Lu‐Lu Zhang, Xi Chen, Ying‐Ying Huang, Chi‐Xiong Liang, Meng‐Yun Qiang, Zhuo‐Chen Cai, Ze‐Jiang Zhan, Ying Deng, Jia‐Yu Zhou, Hao‐Yang Huang, Xiang Guo, Xing Lv
Cancer Medicine.2023; 12(13): 14084. CrossRef
Chinese expert consensus on the application of pegylated recombinant human granulocyte colony‐stimulating factor during concurrent chemoradiotherapy (2023 edition)
Jun Wang, Baosheng Li
Precision Radiation Oncology.2023; 7(3): 150. CrossRef
Chinese expert consensus on the application of pegylated recombinant human granulocyte colony‐stimulating factor during concurrent chemoradiotherapy (2020 edition)
Jun Wang, Baosheng Li
Precision Radiation Oncology.2021; 5(1): 4. CrossRef
Prognostic value of serum uric acid and tumor response to induction chemotherapy in locally advanced nasopharyngeal carcinoma
Yuanji Xu, Zijie Wu, Wangzhong Ye, Youping Xiao, Wei Zheng, Qinyan Chen, Penggang Bai, Zhizhong Lin, Chuanben Chen
BMC Cancer.2021;[Epub] CrossRef
Time-to-Event Supervised Genetic Algorithm Enables Induction Chemotherapy Decision Making for Nasopharyngeal Carcinoma
Demin Liu, Haojiang Li, Liyang Wu, Shuchao Chen, Tianqiao Zhang, Wenjie Huang, Guangying Ruan, Sai Li, Lizhi Liu, Hongbo Chen
IEEE Access.2021; 9: 98701. CrossRef
Prognostic value of post-radiotherapy neutrophil-to-lymphocyte ratio in locally advanced nasopharyngeal carcinoma
Dan Ou, Xiaoshen Wang, Mingyao Wu, Fen Xue, Yujiao Li, Chaosu Hu, Xiayun He
Strahlentherapie und Onkologie.2020; 196(3): 252. CrossRef
Amelioration of cyclophosphamide-induced myelosuppression during treatment to rats with breast cancer through low-intensity pulsed ultrasound
Wei Wang, Dong Luo, Junlin Chen, Jinyun Chen, Yi Xia, Wenzhi Chen, Yan Wang
Bioscience Reports.2020;[Epub] CrossRef

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A National Study of Survival Trends and Conditional Survival in Nasopharyngeal Carcinoma: Analysis of the National Population-Based Surveillance Epidemiology and End Results Registry: Jia-Wei Lv, Xiao-Dan Huang, Yu-Pei Chen, Guan-Qun Zhou, Ling-Long Tang, Yan-Ping Mao, Wen-Fei Li, Ai-Hua Lin, Jun Ma, Ying Sun; Cancer Res Treat. 2018;50(2):324-334. Published online April 19, 2017; DOI: https://doi.org/10.4143/crt.2016.544

Abstract PDF PubReader ePub

Purpose
Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry.
Materials and Methods
Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method.
Results
For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990- 1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time.
Conclusion
Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.

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