Comparison of Treatment Modalities in Frontline Therapy of Stages I/IE Extranodal NK/T-Cell Lymphoma-Nasal Type (ENKTL-N): An up-to-Date Network Meta-Analysis

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.