Prognostic value of interim [¹⁸F]FDG PET/CT after immunotherapy-based combinations in extranodal NK/T-cell lymphoma, nasal type

Purpose: To evaluate the prognostic value of interim [¹⁸F]Fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) after immunotherapy-based systemic therapies in extranodal natural killer/T-cell lymphoma (ENKTL).

Patients and methods: We retrospectively recruited 133 newly diagnosed nasal-type ENKTL patients who underwent interim [¹⁸F]FDG PET/CT scans after 2-4 cycles of immunotherapy-based treatments. Interim PET/CT was interpreted by maximum standardized uptake value (SUV_max), Deauville 5-point scale (DS), and early treatment response. The prognostic value of overall survival (OS) and progression-free survival (PFS) was assessed with survival curves generated using Kaplan-Meier analysis and compared using the log-rank test. Univariate and multivariate Cox proportional hazards analyses were performed to evaluate the independent effects for survival. Model performance was assessed with a time-dependent area under the curve (time-AUC), concordance index (C-index), and the Akaike information criterion (AIC).

Results: Patients with high SUV_max (> 9.2), DS 5, or with stable disease (SD) or relapsed/progressive disease (PD) on interim PET/CT showed significantly unfavorable OS and PFS with the Kaplan-Meier estimate, respectively. The interim PET/CT parameters remained independent predictors for both OS and PFS after univariate and multivariate analysis. We combined interim DS with the prognostic index for natural killer cell lymphoma-Epstein-Barr virus (PINK-E) model to stratify our cohort into 3 risk categories: low-risk (0-2 risk factors), intermediate-risk (3 risk factors), and high-risk (≥ 4 risk factors), which showed significant and superior stratifications of OS and PFS than PINK-E.

Conclusion: Interim PET/CT after immunotherapy-based systemic treatments showed independent prognostic value for ENKTL. The model combining interim PET/CT with PINK-E might be an effective prognostic tool.

Key points: Question The prognostic value of interim [¹⁸F]FDG PET/CT in extranodal natural killer/T-cell lymphoma remains uncertain, especially after the introduction of immunotherapy. Findings Deauville 5-point scale on interim [¹⁸F]FDG PET/CT after immunotherapy-based systemic therapies was an independent predictor for newly diagnosed extranodal natural killer/T-cell lymphomas. Clinical relevance Interim [¹⁸F]FDG PET/CT alone or combined with the prognostic index for natural killer cell lymphoma-Epstein-Barr virus (PINK-E) model is an effective and superior prognostic tool for clinical application in the era of immunotherapy.