Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma: A Systematic Review and Meta-analysis

Overview

Journal JAMA Netw Open

Publisher American Medical Association

Specialty General Medicine

Date 2019 Oct 19

PMID 31626318

Citations 19

Authors

Bin Zhang

Min Min Li

Wen Hui Chen

Jian Fu Zhao

Wei Qi Chen

Yu Hao Dong

Xiao Gong

Qiu Ying Chen

Lu Zhang

Xiao Kai Mo

Xiao Ning Luo

Jie Tian

Shui Xing Zhang

Affiliations

Soon will be listed here.

Abstract

Importance: The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial.

Objectives: To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach.

Data Sources: PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019.

Study Selection: Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC.

Data Extraction And Synthesis: Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model.

Main Outcomes And Measures: Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS).

Results: A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC.

Conclusions And Relevance: These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.

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References

Fang F, Zhang Y, Tang J, Lunsford L, Li T, Tang R . Association of Corticosteroid Treatment With Outcomes in Adult Patients With Sepsis: A Systematic Review and Meta-analysis. JAMA Intern Med. 2018; 179(2):213-223. PMC: 6439648. DOI: 10.1001/jamainternmed.2018.5849. View

Song Y, Wang W, Tao G, Zhou X . Survival benefit of induction chemotherapy in treatment for locally advanced nasopharyngeal carcinoma--A time-to-event meta-analysis. Oral Oncol. 2015; 51(8):764-9. DOI: 10.1016/j.oraloncology.2015.05.006. View

Chen Y, Guo R, Liu N, Liu X, Mao Y, Tang L . Efficacy of the Additional Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy for Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: a Bayesian Network Meta-analysis of Randomized Controlled Trials. J Cancer. 2015; 6(9):883-92. PMC: 4532986. DOI: 10.7150/jca.11814. View

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

Mao Y, Xie F, Liu L, Sun Y, Li L, Tang L . Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement based on magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2009; 73(5):1326-34. DOI: 10.1016/j.ijrobp.2008.07.062. View

. Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on.... Int J Radiat Oncol Biol Phys. 1996; 35(3):463-9. DOI: 10.1016/s0360-3016(96)80007-1. View

Li W, Chen N, Zhang N, Hu G, Xie F, Sun Y . Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long-term results of phase 3 randomized controlled trial. Int J Cancer. 2019; 145(1):295-305. DOI: 10.1002/ijc.32099. View

Wang M, Tian H, Li G, Ge T, Liu Y, Cui J . Significant benefits of adding neoadjuvant chemotherapy before concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta-analysis of randomized controlled trials. Oncotarget. 2016; 7(30):48375-48390. PMC: 5217024. DOI: 10.18632/oncotarget.10237. View

Chua D, Sham J, Choy D, Lorvidhaya V, Sumitsawan Y, Thongprasert S . Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal.... Cancer. 1998; 83(11):2270-83. View

10.

Chen Y, Chan A, Le Q, Blanchard P, Sun Y, Ma J . Nasopharyngeal carcinoma. Lancet. 2019; 394(10192):64-80. DOI: 10.1016/S0140-6736(19)30956-0. View

11.

Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J . Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009; 101(7):498-506. DOI: 10.1093/jnci/djp007. View

12.

Wetterslev J, Thorlund K, Brok J, Gluud C . Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol. 2007; 61(1):64-75. DOI: 10.1016/j.jclinepi.2007.03.013. View

13.

Zhang S, Zhou L, Huang X, Lin S . A retrospective study of concurrent chemoradiotherapy plus S-1 adjuvant chemotherapy on curative effect for treatment of patients with N3 stage nasopharyngeal carcinoma. Cancer Manag Res. 2018; 10:1705-1711. PMC: 6025766. DOI: 10.2147/CMAR.S165804. View

14.

Zhang Y, Chen L, Hu G, Zhang N, Zhu X, Yang K . Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019; 381(12):1124-1135. DOI: 10.1056/NEJMoa1905287. View

15.

He J, Wu P, Tang Y, Liu S, Xie C, Luo S . Chemoradiotherapy enhanced the efficacy of radiotherapy in nasopharyngeal carcinoma patients: a network meta-analysis. Oncotarget. 2017; 8(24):39782-39794. PMC: 5503653. DOI: 10.18632/oncotarget.16349. View

16.

Wu X, Huang P, Peng P, Lu L, Han F, Wu S . Long-term follow-up of a phase III study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma. Ann Oncol. 2013; 24(8):2131-6. DOI: 10.1093/annonc/mdt163. View

17.

Vermorken J, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M . Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007; 357(17):1695-704. DOI: 10.1056/NEJMoa071028. View

18.

Kwong D, Sham J, Au G, Chua D, Kwong P, Cheng A . Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study. J Clin Oncol. 2004; 22(13):2643-53. DOI: 10.1200/JCO.2004.05.173. View

19.

Sun X, Su S, Chen C, Han F, Zhao C, Xiao W . Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol. 2013; 110(3):398-403. DOI: 10.1016/j.radonc.2013.10.020. View

20.

Tan T, Lim W, Fong K, Cheah S, Soong Y, Ang M . Concurrent chemo-radiation with or without induction gemcitabine, Carboplatin, and Paclitaxel: a randomized, phase 2/3 trial in locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2015; 91(5):952-60. DOI: 10.1016/j.ijrobp.2015.01.002. View