The optimal timing of radiotherapy in the combination treatment of limited-stage extranodal natural killer/T-cell lymphoma, nasal type: an updated meta-analysis

This study was designed to explore the relative efficacy and toxicity of upfront radiotherapy (RT) and late RT in combination treatments for patients with limited-stage extranodal natural killer/T-cell lymphoma nasal type (LS-ENKTL). We searched for clinical trials in the PubMed database that compared upfront RT with late RT in the combined treatment of patients with LS-ENKTL. We systematically evaluated the differences in survival, treatment response, and treatment-related adverse events (AEs) between these two groups. Ten retrospective studies with a total of 1752 patients were included. Upfront RT significantly prolonged the overall survival (OS) and progression-free survival (PFS) of patients compared to late RT in combination with chemotherapy (CT) (HR = 0.72, 95% CI 0.59-0.88, P = 0.001 for OS; HR = 0.57, 95% CI 0.41-0.79, P = 0.0007 for PFS). The complete remission (CR) rate in the upfront RT group was superior to that in the late RT group (HR = 1.61, 95% CI 1.09-2.37, P = 0.02). Patients experienced similar local recurrence-free survival (LRFS), objective response rates (ORR), and toxicity between these two arms (P > 0.05 for all) in the analysis of each subgroup. The survival benefit of upfront RT was not correlated with the RT dose, concurrent chemoradiotherapy (CCRT) (or not), or the CT regimen (P > 0.05 for all). Without compromises in terms of toxicity, RT dose, and treatment modality, upfront RT can significantly benefit OS, PFS, and CR compared to late RT in combination treatment. These findings verified that the upfront RT regimen is more suitable for patients with LS-ENKTL.