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Which treatment is better than concurrent chemoradiotherapy about survival for stage III or IV locally advanced nasopharyngeal carcinoma? An updated Bayesian network meta-analysis of randomized controlled trials

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European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Objective

To speculate whether induction chemotherapy (IC) or adjuvant chemotherapy (AC) with concurrent chemoradiotherapy (CCRT) could obtain better survival benefit for stage III or IV locally advanced nasopharyngeal carcinoma (LA-NPC).

Methods

Only randomized controlled trials were incorporated. There were five treatments (CCRT, IC + CCRT, CCRT + AC, IC + RT and RT alone) recruited for analysis. Overall survival (OS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) with a hazard ratio (HR) were selected as endpoints. First of all, we performed a traditional meta-analysis and subsequently conducted network meta-analysis based on the Bayesian method.

Results

Totally, 15 studies, including 6182 patients, were incorporated for analysis. There was a statistically significant benefits in favor of IC + CCRT, compared with CCRT alone, for OS [HR = 0.75, 95% CI = 0.63–0.89], LRFS [HR = 0.70, 95% CI = 0.56–0.86], and DMFS [HR = 0.65, 95% CI = 0.54–0.78]. What's more, we did not observed any significant differences between CCRT + AC and CCRT alone for all the endpoints. Unsurprisingly, it was RT alone that demonstrate the poorest survival benefit. Strange to say, survival benefit, between IC + CCRT and IC + RT, or between IC + CCRT and CCRT + AC, did not significantly exist.

Conclusion

Induction chemotherapy IC + CCRT provided better survival benefit than CCRT alone. CCRT + AC failed to increase survival benefit significantly compared to CCRT alone. More research about comparing IC + CCRT with IC + RT or CCRT + AC are needed.

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References

  1. Chen Y-P, Chan ATC, Le Q-T, Blanchard P, Sun Y, Ma J (2019) Nasopharyngeal carcinoma. Lancet 394:64–80

    Article  PubMed  Google Scholar 

  2. Peng L, Liu J, Chen Y, Ma J (2019) The next decade of clinical trials in locoregionally advanced nasopharyngeal carcinoma. British J Radiol 92:20181031

    Article  Google Scholar 

  3. Chen Y, Sun Y, Liang S, Zong J, Li W, Chen M et al (2013) Progress report of a randomized trial comparing long-term survival and late toxicity of concurrent chemoradiotherapy with adjuvant chemotherapy versus radiotherapy alone in patients with stage III to IVB nasopharyngeal carcinoma from endemic regions of China. Cancer 119:2230–2238

    Article  CAS  PubMed  Google Scholar 

  4. Lee A, Tung S, Ng W, Lee V, Ngan R, Choi H et al (2017) A multicenter, phase 3, randomized trial of concurrent chemoradiotherapy plus adjuvant chemotherapy versus radiotherapy alone in patients with regionally advanced nasopharyngeal carcinoma: 10-year outcomes for efficacy and toxicity. Cancer 123:4147–4157

    Article  CAS  PubMed  Google Scholar 

  5. Li W, Chen N, Zhang N, Hu G, Xie F, Sun Y et al (2019) Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: long-term results of phase 3 randomized controlled trial. Int J Cancer 145:295–305

    Article  CAS  PubMed  Google Scholar 

  6. Lin J, Liang W, Jan J, Jiang R, Lin A (2004) Another way to estimate outcome of advanced nasopharyngeal carcinoma—is concurrent chemoradiotherapy adequate? Int J Radiat Oncol Biol Phys 60:156–164

    Article  PubMed  Google Scholar 

  7. Colevas A, Yom S, Pfister D, Spencer S, Adelstein D, Adkins D et al (2018) NCCN guidelines insights: head and neck cancers version 1.2018. JNCCN 16:479–490

    PubMed  Google Scholar 

  8. Zhang Y, Chen L, Hu G-Q, Zhang N, Zhu X-D, Yang K-Y et al (2019) Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med 381:1124–1135

    Article  CAS  PubMed  Google Scholar 

  9. Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C et al (2020) Mapping of reporting guidance for systematic reviews and meta-analyses generated a comprehensive item bank for future reporting guidelines. J Clin Epidemiol 118:60–68

    Article  PubMed  Google Scholar 

  10. Hutton B, Salanti G, Caldwell D, Chaimani A, Schmid C, Cameron C et al (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Int Med 162:777–784

    Article  PubMed  Google Scholar 

  11. Woods B, Hawkins N, Scott D (2010) Network meta-analysis on the log-hazard scale, combining count and hazard ratio statistics accounting for multi-arm trials: a tutorial. BMC Med Res Methodol 10:54

    Article  PubMed  PubMed Central  Google Scholar 

  12. Tierney J, Stewart L, Ghersi D, Burdett S, Sydes M (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16

    Article  PubMed  PubMed Central  Google Scholar 

  13. Higgins J, Thompson S (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  14. Higgins J, Thompson S, Deeks J, Altman D (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  PubMed Central  Google Scholar 

  15. Fryback D, Stout N, Rosenberg M (2001) An elementary introduction to Bayesian computing using WinBUGS. Int J Technol Assess Health Care 17:98–113

    Article  CAS  PubMed  Google Scholar 

  16. Spiegelhalter DJ, Best NG, Carlin BP, Van Der Linde A (2002) Bayesian measures of model complexity and fit. J R Stat Soc 64:583–639

    Article  Google Scholar 

  17. Dias S, Sutton A, Welton N, Ades A (2013) Evidence synthesis for decision making 6: embedding evidence synthesis in probabilistic cost-effectiveness analysis. Med Decis Making 33:671–678

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tan S, Bujkiewicz S, Sutton A, Dequen P, Cooper N (2013) Presentational approaches used in the UK for reporting evidence synthesis using indirect and mixed treatment comparisons. J Health Serv Res Pol 18:224–232

    Article  Google Scholar 

  19. Yang Q, Cao S, Guo L, Hua Y, Huang P, Zhang X et al (2019) Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: long-term results of a phase III multicentre randomised controlled trial. Eur J Cancer 119:87–96

    Article  CAS  PubMed  Google Scholar 

  20. Hong R, Hsiao C, Ting L, Ko J, Wang C, Chang J et al (2018) Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study. Ann Oncol 29:1972–1979

    Article  CAS  PubMed  Google Scholar 

  21. Cao S, Yang Q, Guo L, Mai H, Mo H, Cao K et al (2017) Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase III multicentre randomised controlled trial. Eur J Cancer 75:14–23

    Article  CAS  PubMed  Google Scholar 

  22. Hui E, Ma B, Leung S, King A, Mo F, Kam M et al (2009) Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol 27:242–249

    Article  CAS  PubMed  Google Scholar 

  23. Tan T, Lim W, Fong K, Cheah S, Soong Y, Ang M et al (2015) 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 91:952–960

    Article  PubMed  Google Scholar 

  24. Chen L, Hu C, Chen X, Hu G, Cheng Z, Sun Y et al (2017) Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial. Eur J Cancer 75:150–158

    Article  CAS  PubMed  Google Scholar 

  25. Al-Sarraf M, LeBlanc M, Giri P, Fu K, Cooper J, Vuong T et al (1998) Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 16:1310–1317

    Article  CAS  PubMed  Google Scholar 

  26. Wee J, Tan E, Tai B, Wong H, Leong S, Tan T et al (2005) Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety. J Clin Oncol 23:6730–6738

    Article  CAS  PubMed  Google Scholar 

  27. Lee AWM, Tung SY, Chan ATC, Chappell R, Fu Y-T, Lu T-X et al (2011) A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma. Radiother Oncol 98:15–22

    Article  PubMed  Google Scholar 

  28. Huang P, Zeng Q, Cao K, Guo X, Guo L, Mo H et al (2015) Ten-year outcomes of a randomised trial for locoregionally advanced nasopharyngeal carcinoma: a single-institution experience from an endemic area. Europ J Cancer 51:1760–1770

    Article  CAS  Google Scholar 

  29. Lee A, Ngan R, Tung S, Cheng A, Kwong D, Lu T et al (2015) Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma. Cancer 121:1328–1338

    Article  CAS  PubMed  Google Scholar 

  30. 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 progression-free survival. Intern J Radiat Oncol Biol Physic. 1996; 35:463–469.

  31. Ma J, Mai H, Hong M, Min H, Mao Z, Cui N et al (2001) Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol 19:1350–1357

    Article  CAS  PubMed  Google Scholar 

  32. Sun Y, Li W, Chen N, Zhang N, Hu G, Xie F et al (2016) Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol 17:1509–1520

    Article  CAS  PubMed  Google Scholar 

  33. Chen L, Hu C, Chen X, Hu G, Cheng Z, Sun Y et al (2012) Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol 13:163–171

    Article  PubMed  Google Scholar 

  34. Chen Y, Liu M, Liang S, Zong J, Mao Y, Tang L et al (2008) Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys 71:1356–1364

    Article  PubMed  Google Scholar 

  35. Lee A, Tung S, Chua D, Ngan R, Chappell R, Tung R et al (2010) Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 102:1188–1198

    Article  PubMed  Google Scholar 

  36. Lee A, Tung S, Chan A, Chappell R, Fu Y, Lu T et al (2006) Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 66:142–151

    Article  PubMed  Google Scholar 

  37. Huang P, Cao K, Guo X, Mo H, Guo L, Xiang Y et al (2012) A randomized trial of induction chemotherapy plus concurrent chemoradiotherapy versus induction chemotherapy plus radiotherapy for locoregionally advanced nasopharyngeal carcinoma. Oral Oncol 48:1038–1044

    Article  CAS  PubMed  Google Scholar 

  38. Hong M, Mai H, Min H, Ma J, Zhang E, Cui N (2000) A comparison of the Chinese 1992 and fifth-edition International Union Against Cancer staging systems for staging nasopharyngeal carcinoma. Cancer 89:242–247

    Article  CAS  PubMed  Google Scholar 

  39. Jadad A, Moore R, Carroll D, Jenkinson C, Reynolds D, Gavaghan D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12

    Article  CAS  PubMed  Google Scholar 

  40. Ribassin-Majed L, Marguet S, Lee A, Ng W, Ma J, Chan A et al (2017) What is the best treatment of locally advanced nasopharyngeal carcinoma? An individual patient data network meta-analysis. J Clin Oncol 35:498–505

    Article  PubMed  Google Scholar 

  41. Bocci G, Kerbel R (2016) Pharmacokinetics of metronomic chemotherapy: a neglected but crucial aspect. Nat Rev Clin Oncol 13:659–673

    Article  CAS  PubMed  Google Scholar 

  42. Chen Y, Tang L, Yang Q, Poh S, Hui E, Chan A et al (2018) Induction chemotherapy plus concurrent chemoradiotherapy in endemic nasopharyngeal carcinoma: individual patient data pooled analysis of four randomized trials. Clin Cancer Res 24:1824–1833

    Article  CAS  PubMed  Google Scholar 

  43. Tan T, Soon Y, Cheo T, Ho F, Wong L, Tey J et al (2018) Induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: a systematic review and meta-analysis. Radiother Oncol 129:10–17

    Article  PubMed  Google Scholar 

  44. Wang Q, Xu G, Xia Y, Zuo J, Zeng G, Xue Z et al (2020) Comparison of induction chemotherapy plus concurrent chemoradiotherapy and induction chemotherapy plus radiotherapy in locally advanced nasopharyngeal carcinoma. Oral Oncol 111:104925

    Article  CAS  PubMed  Google Scholar 

  45. Chen F, Wen D, Li F, Lin L, Kou J, Zheng W et al (2019) The role of post-neoadjuvant chemotherapy tumor volume for prognostication and treatment guidance in loco-regionally advanced nasopharyngeal carcinoma. Cancers 24:11

    Google Scholar 

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Fang, L., Shi, L., Wang, W. et al. Which treatment is better than concurrent chemoradiotherapy about survival for stage III or IV locally advanced nasopharyngeal carcinoma? An updated Bayesian network meta-analysis of randomized controlled trials. Eur Arch Otorhinolaryngol 278, 3633–3642 (2021). https://doi.org/10.1007/s00405-021-06614-x

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