Chemoradiotherapy Versus Radiotherapy Alone in Stage II Nasopharyngeal Carcinoma: A Systemic Review and Meta-analysis of 2138 Patients

Abstract

Background: To explore the value of chemoradiotherapy (CRT) in stage II nasopharyngeal carcinoma (NPC) compared to radiotherapy (RT) alone which includes two-dimensional radiotherapy (2D-RT) and intensity-modulated radiotherapy (IMRT). Methods: All topic-related comparative articles were identified by a comprehensive search of public databases (MEDLINE, EMBASE, Cochrane Library and CBMdisc). The primary outcomes were overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS). Secondary outcomes were grade 3-4 acute toxicity events. We performed subgroup analysis of CRT versus 2D-RT/IMRT alone to investigate the optimal modality. Sensitivity analysis focused on CRT versus IMRT alone was used to assess stability of the study results. Results: Eleven comparative studies (2138 patients) were eligible. CRT had significantly higher OS (HR = 0.67, 95% CI = 0.45-0.98, P = 0.04) and LRRFS (HR = 0.61, 95% CI = 0.46-0.80, P = 0.0003) than RT alone, but no significant difference was observed in DMFS (HR = 0.83, 95% CI = 0.52-1.31, P = 0.41). Meanwhile, CRT was associated with higher frequencies of grade 3-4 leukopenia, mucositis and nausea (P = 0.005, 0.03, < 0.0001, respectively). Subgroup analysis showed that IMRT alone could achieve equivalent OS, LRRFS and DMFS compared to CRT (P = 0.14, 0.06, 0.89, respectively). Significant value was only observed in LRRFS for CRT compared to 2D-RT alone (P = 0.01). Sensitivity analysis for the comparison of CRT and IMRT alone demonstrated generally stable outcomes, in support of the final conclusions. Conclusions: In the treatment of patients with stage II NPC, CRT was better than 2D-RT alone with significant benefit in LRRFS. IMRT alone was superior to CRT with equivalent survival outcomes and fewer grade 3-4 acute toxicities.

Keywords: chemoradiotherapy; intensity-modulated radiotherapy; meta-analysis.; nasopharyngeal carcinoma; radiotherapy; stage II.

Figure 1

Flow diagram of study identification, exclusion and inclusion.

Figure 2

Forest plot and meta-analysis of overall survival (OS) in subgroup analysis. (A) CRT versus IMRT alone; (B) CRT versus 2D-RT alone. Squares are the point estimates of the HRs with the 95% CIs indicated by horizontal bars. Diamonds are the summary estimates and 95% CIs from the pooled studies. CRT: chemoradiotherapy; IMRT: intensity modulated radiotherapy; 2D-RT: two-dimensional radiotherapy; CI: confidence interval; SE: standard error; IV: inverse variance method.

Figure 3

Forest plot and meta-analysis of loco-regional relapse-free survival (LRRFS) in subgroup analysis. (A) CRT versus IMRT alone; (B) CRT versus 2D-RT alone. Squares are the point estimates of the HRs with the 95% CIs indicated by horizontal bars. Diamonds are the summary estimates and 95% CIs from the pooled studies. CRT: chemoradiotherapy; IMRT: intensity modulated radiotherapy; 2D-RT: two-dimensional radiotherapy; CI: confidence interval; SE: standard error; IV: inverse variance method.

Figure 4

Forest plot and meta-analysis of distant metastasis-free survival (DMFS) in subgroup analysis. (A) CRT versus IMRT alone; (B) CRT versus 2D-RT alone. Squares are the point estimates of the HRs with the 95% CIs indicated by horizontal bars. Diamonds are the summary estimates and 95% CIs from the pooled studies. CRT: chemoradiotherapy; IMRT: intensity modulated radiotherapy; 2D-RT: two-dimensional radiotherapy; CI: confidence interval; SE: standard error; IV: inverse variance method.

Figure 5

Begg's funnel plot for assessing publication bias of overall survival (OS) in overall meta-analysis. The size of the circles indicates the weight of each study. HR: hazard ratio.