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

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.