Baseline total lesion glycolysis identifies high-risk patients with immunosuppressive signatures in early-stage natural killer/T-cell lymphoma.

Background: The post-treatment Deauville scale (DS) and circulating Epstein-Barr virus (EBV)-DNA were used for prediction of long-term remission in natural killer/T-cell lymphoma (NKTCL). However, the baseline biomarkers still remain lacking for clinical application. Here, we hypothesized that 18F-FDG PET/CT, as a measure of total tumor burden, would be a baseline biomarker to identify high-risk NKTCL patients.

Methods: We analyzed PET/CT data in early-stage NKTCL patients (n = 192) receiving pegaspargase-based regimens from 2 independent clinical trials. The prognostic values of radiomic markers including total lesion glycolysis (TLG), standardized uptake value, and metabolic tumor volume were evaluated in the training (n = 127) and validation cohorts (n = 65) with a median follow-up of 37 months.

Results: Total lesion glycolysis was a prognosticator of progression-free survival (PFS) and overall survival (OS), with 86.11% and 91.30% sensitivity and 55.77% and 53.25% specificity, respectively, which outperformed the risk model based on posttreatment DS and circulating EBV-DNA (sensitivity 53.85% and specificity 54.24% for PFS, sensitivity 43.75% and specificity 52.34% for OS). Five-year PFS and OS were 92.19% and 96.82% in the low TLG group (<75 g), versus 69.46% and 77.24% in the high TLG group (≥75 g). ScRNA-seq (n = 10) and bulk RNA-seq (n = 65) data from patients in the trials both revealed that inflammatory dendritic cells, as immunosuppressive signature, were significantly infiltrated in patients with high TLG compared with patients with low TLG.

Conclusions: Baseline TLG reflected an immunosuppressive microenvironment and was an effective radiomic marker for long-term remission in patients with early-stage NKTCL.