Abstract
Introduction: Despite many studies reporting on the optimal therapies for early stage ENKTL-N in the front-line setting, this area continues to be subject to a significant controversy regarding single modalities versus combination or sequential approaches. All these comparative studies were small non-randomized studies that combined stages I & II. The results were often inconclusive and occasionally conflicting. In the absence of direct head-to-head randomized controlled trials in this clinical setting, a network meta-analysis was conducted to compare these therapeutic approaches and their respective impact on 5-year survival in stage I/IE ENKTL-N.
Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of stage I/IE ENKTL-N, treatment with chemotherapy (CT), radiation (RT), sequential CT and RT (SEQ), and chemoradiotherapy (CRT), comparative studies that reported predominantly (>70%) I/IE 5-year overall survival (OS) and disease-free survival (DFS) rates. Studies that reported on mixed samples of early and advanced ENKTL were excluded. A frequentist network meta-analysis was conducted using the netmeta package and random-effects model.
Results: Seven studies comprising a total of 397 participants were included. Our network meta-analysis revealed that upfront RT tended to have better 5-year OS and DFS than CRT, SEQ, though it did not reach statistical significance. However, RT had a significantly superior 5-year OS when compared to CT (RR=0.43, 0.19-0.97). Based on the pair-wise and network meta-analyses, RT was ranked as the most effective first-line treatment approach followed by CRT, SEQ, and CT in decreasing order. Analysis of the 5-year DFS yielded similar findings. Inconsistency analysis did not reveal any significant differences between direct and indirect estimates.
Conclusion: This is the first network meta-analysis to compare all commonly utilized upfront treatment modalities in stages I/IE ENKTL-N. It indicates that upfront RT alone may be sufficient as there was no signal that chemotherapy added any OS or DFS advantages. Adequately powered randomized trials are warranted.
No relevant conflicts of interest to declare.
