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      Individualized concurrent chemotherapy by pretreatment plasma Epstein‐Barr viral DNA in II‐III stage nasopharyngeal carcinoma: A propensity score matching analysis using a large cohort

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          Abstract

          Object

          To ascertain the treatment effect of concurrent chemotherapy (CCT) in stage II‐III nasopharyngeal carcinoma (NPC) patients with different Epstein‐Barr virus (EBV) DNA level in intensity‐modulated radiotherapy (IMRT) era.

          Methods

          A total of 2742 patients diagnosed with stage II‐III NPC were involved in this study. Patients received IMRT with/without CCT. Overall survival (OS) was the primary endpoint. Receiver operating characteristics curve was used to determine the cut‐off value of pre‐DNA based on OS. After propensity score matching, the role of CCT was explored in patients with different EBV DNA level.

          Results

          In our cohort, the cut‐off value of pre EBV DNA was 1460 copies/mL (area under curve [AUC], 0.695‐0.769; sensitivity, 0.766; specificity, 0.599). Patients with high EBV DNA level showed poor survival in OS, progression free survival (PFS), locoregional relapse‐free survival (LRFS) and distant metastasis‐free survival (DMFS). In patients with EBV DNA level >1460 copies/mL, the concurrent chemoradiotherapy (CCRT) group achieved higher 3‐year OS compared with IMRT groups. However, the CCRT and IMRT groups showed comparable OS in patients with EBV DNA ≤1460 copies/mL. In multivariate analyses, CCT was a protective factor for OS, PFS, and LRFS in high‐risk patients (EBV DNA level >1460 copies/mL), while not an independent prognostic factor among the low‐risk patients (EBV DNA level ≤1460 copies/mL).

          Conclusion

          Pre‐EBV DNA could be a useful tool to guide individualized treatment for stage II‐III NPC patients. Additional CCT to IMRT improved the survival for patients with high pre‐EBV DNA, while those with low pre‐EBV DNA could not.

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          Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.

          M Al-Sarraf, M. Leblanc, P Giri … (1998)
          The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.
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            The prevalence and prevention of nasopharyngeal carcinoma in China

            Su-Mei Cao, Malcolm J. Simons, Chao-Nan Qian (2011)
            Nasopharyngeal carcinoma (NPC) has remarkable epidemiological features, including regional, racial, and familial aggregations. The aim of this review is to describe the epidemiological characteristics of NPC and to propose possible causes for the high incidence patterns in southern China. Since the etiology of NPC is not completely understood, approaches to primary prevention of NPC remain under consideration. This situation highlights the need to conduct secondary prevention, including improving rates of early detection, early diagnosis, and early treatment in NPC patients. Since the 1970's, high-risk populations in southern China have been screened extensively for early detection of NPC using anti–Epstein-Barr virus (EBV) serum biomarkers. This review summarizes several large screening studies that have been conducted in the high-incidence areas of China. Screening markers, high-risk age range for screening, time intervals for blood re-examination, and the effectiveness of these screening studies will be discussed. Conduction of prospective randomized controlled screening trials in southern China can be expected to maximize the cost-effectiveness of early NPC detection screening.
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              A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma.

              Gang Peng, Tao Wang, Kun-Yu Yang … (2012)
              To compare clinical outcomes and toxicities of two-dimensional conventional radiation therapy (2D-CRT) and intensity modulated radiation therapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). Between July 2003 and October 2008, 616 patients with non-metastatic stage I to IVb NPC were prospectively randomized to receive 2D-CRT (n=310; mean age, 44.8±13.6 years) or IMRT (n=306; mean age, 46.7±12.5 years). Clinical outcomes and acute and late toxicities were determined and compared. The 2 groups were comparable with respect to all parameters of demographics and disease characteristics (all, p>0.05). Median follow-up was 42 months (range, 1-83 months). The 5-year actuarial local control rate was 90.5% in the IMRT group and 84.7% in the 2D-CRT group. The local control rates were 91% for stage T3 and 81.5% for stage T4 disease in the IMRT group and 80% and 62.2% in the 2D-CRT group, respectively. The 5-year actuarial nodal relapse-free survival (NRFS) rate was 92.4% in the IMRT and 92.9% in the 2D-CRT group (p>0.05). The NRFS was 93.9% for N2 disease in the IMRT group and 91.4% in the 2D-CRT group (p=0.02). The 5-year overall survival (OS) rate was 79.6% for the IMRT group and 67.1% for the 2D-CRT group (p=0.001). When stratified for stage, a significant difference was only noted for stage III disease. In terms of radiation-induced toxicities, patients in IMRT group had significantly lower radiation-induced toxicities than those in 2D-CRT group. IMRT provides improved local-recurrence free survival, especially in late-stage NPC patients and is associated with a lower incidence of toxicities. Copyright © 2012. Published by Elsevier Ireland Ltd.
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                Author and article information

                Contributors
                Hai‐Qiang Mai: maihq@sysucc.org.cn
                Lin‐Quan Tang:
                ORCID: https://orcid.org/0000-0002-9613-7305
                tanglq@sysucc.org.cn
                Journal
                Journal ID (nlm-ta): Cancer Med
                Journal ID (iso-abbrev): Cancer Med
                Journal ID (doi): 10.1002/(ISSN)2045-7634
                Journal ID (publisher-id): CAM4
                Title: Cancer Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2045-7634
                Publication date (Electronic): 18 June 2019
                Publication date Collection: August 2019
                Volume: 8
                Issue: 9 ( doiID: 10.1002/cam4.v8.9 )
                Pages: 4214-4225
                Affiliations
                [ 1 ] Sun Yat‐sen University Cancer Centre Guangzhou P. R. China
                [ 2 ] State Key Laboratory of Oncology in South China Guangzhou P. R. China
                [ 3 ] Collaborative Innovation Centre for Cancer Medicine Guangzhou P. R. China
                [ 4 ] Department of Nasopharyngeal Carcinoma Sun Yat‐sen University Cancer Centre Guangzhou P. R. China
                [ 5 ] Department of Oncology The First Affiliated Hospital, Jinan University Guangzhou China
                Author notes
                [*] [* ] Correspondence

                Hai‐Qiang Mai and Lin‐Quan Tang, Department of Nasopharyngeal Carcinoma, Sun Yat‐sen University Cancer Centre, 651 Dongfeng Road East, Guangzhou 510060, P. R. China.

                Emails: maihq@ 123456sysucc.org.cn (H.‐Q. M.); tanglq@ 123456sysucc.org.cn (L.‐Q. T.)

                Author information
                https://orcid.org/0000-0002-9613-7305
                Article
                Publisher ID: CAM42343
                DOI: 10.1002/cam4.2343
                PMC ID: 6675745
                PubMed ID: 31210417
                SO-VID: 4118f8a9-843d-4f01-bed6-315464dd319a
                Copyright © © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 11 March 2019
                Date revision received : 29 May 2019
                Date accepted : 30 May 2019
                Page count
                Figures: 4, Tables: 4, Pages: 12, Words: 6417
                Funding
                Funded by: National Key R&D Program of China
                Award ID: 2017YFC0908500
                Award ID: 2017YFC1309003
                Funded by: National Natural Science Foundation of China
                Award ID: 81425018
                Award ID: 81672868
                Award ID: 81602371
                Funded by: Sun Yat Sen University Clinical Research 5010 Program
                Award ID: 201707020039
                Award ID: 2014A020212103
                Award ID: 16zxyc02
                Funded by: Sci‐Tech Project Foundation of Guangzhou City
                Award ID: 201707020039
                Funded by: National Key Basic Research Program of China
                Award ID: 2013CB910304
                Funded by: Special Support Plan of Guangdong Province
                Award ID: 2014TX01R145
                Funded by: Sci‐Tech Project Foundation of Guangdong Province
                Award ID: 2014A020212103
                Funded by: Health & Medical Collaborative Innovation Project of Guangzhou City
                Award ID: 201400000001
                Funded by: National Science & Technology Pillar Program during the Twelfth Five‐year Plan Period
                Award ID: 2014BAI09B10
                Funded by: Fund of Natural Science Foundation of Guangdong Province, China
                Award ID: 2016A030310221
                Funded by: Sun Yat Sen University
                Award ID: 16ykpy28
                Funded by: Sun Yat Sen University
                Award ID: 16ykjc38
                Funded by: Fundamental Research Funds for the Central Universities
                Categories
                Subject: Original Research
                Subject: Clinical Cancer Research
                Subject: Original Research
                Custom metadata
                source-schema-version-number 2.0
                component-id cam42343
                cover-date August 2019
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.7 mode:remove_FC converted:01.08.2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: chemotherapy,epstein‐barr virus,nasopharyngeal carcinoma,overall survival
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: chemotherapy, epstein‐barr virus, nasopharyngeal carcinoma, overall survival

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