Value of Baseline Metabolic Tumor Volume for Survival Prognosis and Optimization of Risk-Adapted Treatment Therapy in Patients with Extranodal Nasal-Type Natural Killer/T-Cell Lymphoma

Abstract

To assess the association of baseline metabolic tumor volume (MTV) with overall survival (OS) and to explore its potential role in optimization of existing risk-adapted therapy in ENKTCL. A total of 133 ENKTCL patients mainly treated by radiotherapy (RT) alone (33.8%) or RT combined with chemotherapy (combined-modality therapy [CMT]) (60.9%) were prospectively included. The impacts of MTV, SUVmax derived from 18F-FDG PET/CT image and clinical factors on OS were investigated. Survival analyses were conducted using Kaplan-Meier method with log-rank tests. Cox proportional hazards regression analysis was used to identify multivariate predictors of OS. Regression-based mediation analysis estimated the hazard ratio (HR) of death for direct effect (not through distant metastasis or locoregional recurrence) and indirect effect (through distant metastasis or locoregional recurrence) of the pathway MTV→distant metastasis→OS and pathway MTV→locoregional recurrence→OS. Inverse probability of treatment weighting (IPTW) analysis was employed to make covariate adjustments. MTV and SUVmax were correlated with LDH, PTI, Ann Arbor stage, and NRI score. In univariable analysis, SUVmax, MTV, ECOG PS, PTI and Ann Arbor stage were statistically significantly prognostic factors for OS. Multivariate analysis showed that MTV was the only independent factor of short OS (HR 4.98, 95% CI (1.85 - 13.42), p = 0.002). Mediation analysis showed that distant metastasis played a complete mediating role in the increased death caused by higher MTV (HR of indirect effect 3.15, 95% CI (1.34 - 7.41), p = 0.009; HR of direct effect 2.88, 95% CI (0.80 - 10.32), p = 0.767), with proportion of mediation 76.7%, while locoregional recurrence was not a mediating factor (HR of indirect effect 1.16, 95% CI (0.90 - 1.48), p = 0.255; HR of direct effect 4.48, 95% CI (1.30 - 15.44), p = 0.017) . After adjusting the clinical factors by IPTW between RT alone group and CMT group in early intermediate and high risk ENKTCL, CMT had no PFS and OS benefits compared with RT alone in the low-MTV group (MTV < 49.6ml), while in the high-MTV group (MTV ≥ 49.6ml), the use of CMT compared with RT alone prolonged PFS and OS. Baseline metabolic tumor volume is an independent prognostic factor for overall survival and distant metastasis rather than locoregional recurrence mediated increased risk of death in patients with MTV higher than 49.6ml. For early-stage intermediate and risk ENKTCL patients with MTV lower than 49.6ml, omission of chemotherapy may not result in loss of PFS and OS.