Regional Brain Glucose Metabolism and Its Prognostic Value in Pretreatment Extranodal Natural Killer/T-Cell Lymphoma Patients

Abstract

Objective: To explore regional brain glucose metabolic abnormalities of pretreatment stage I/II extranodal natural killer/T-cell lymphoma (ENKTL) patients using positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (¹⁸F-FDG PET/CT) and assess its prognostic value.

Methods: Sixty pretreatment stage I/II ENKTL patients were enrolled in this retrospective study and divided into survival (n = 45) and death (n = 15) groups according to their status at the end of follow-up. A control group consisted of 60 healthy subjects. Regional cerebral glucose metabolism was evaluated on a voxel-by-voxel basis using statistical parametric mapping (SPM8) under a certain significance level (P < 0. 001) and voxel threshold (K = 100 voxels).

Results: Decreased metabolism was noted in patients, involving the bilateral prefrontal and orbitofrontal cortex, partial parietal and occipital cortex, cingulate gyrus and cerebellum; the sensorimotor cortex was largely spared. Increased metabolism was observed in the bilateral putamen, amygdala, and parahippocampal gyrus. Compared with the survival group, the death group had higher metabolism in the bilateral amygdala, putamen, left thalamus, uncus, and parahippocampal gyrus. Only B symptoms were associated with the increased metabolism of basal ganglia and thalamus (BGT). Patients with high metabolic tumor volume, total lesion glycolysis (TLG) and BGT metabolism had a poor prognosis. TLG and maximum standardized uptake value (SUVmax) LBGT/SUVmaxRight cerebellum were associated with Eastern Cooperative Oncology Group (ECOG) and prognostic index of natural killer lymphoma and Epstein-Barr virus-DNA (PINKE) scores. In multivariate analysis, only ECOG was an independent prognostic factor of both progression-free survival (PFS) and overall survival (OS). PINKE was an independent prognostic factor of OS.

Conclusion: Pretreatment stage I/II ENKTL patients exhibited abnormal regional cerebral glucose metabolism. Higher pretreatment glucose metabolism in BGT could predict a relatively poor prognosis but did not surpass the predictive values of ECOG and PINKE in stage I/II ENKTL patients.

Keywords: 18F-FDG PET/CT; extranodal natural killer/T- cell lymphoma; prognostic value; regional cerebral glucose metabolism; statistical parametric mapping.

Figure 1

Cerebral ¹⁸F-FDG Metabolism of a healthy control (A) and a patient (B–D). A 53-year-old male underwent ¹⁸F-FDG PET/CT (A) during a health check, which showed relatively symmetric cerebral ¹⁸F-FDG metabolism. No obvious abnormal metabolism was observed. ¹⁸F-FDG metabolism in the basal ganglia was similar to that in the cortex. A 58-year-old male was diagnosed with stage II nasal type ENKTL, and pretreatment ¹⁸F-FDG PET/CT revealed soft tissue in the left nasal cavity (C) and swollen lymph nodes in the right neck (D) with increased ¹⁸F-FDG uptake. His pretreatment TLG was 36.9. Brain ¹⁸F-FDG PET images demonstrated prominent hypometabolism in the bilateral frontal, parietal, and temporal cortices, with relative sparing of the occipital cortex. The metabolism of the bilateral basal ganglia was prominently higher than the cortex (B). The patient had been disease free for 30 months at the end of follow-up.

Figure 2

Abnormal glucose uptake in ENKTL patients compared with the CG. PET findings were superimposed on an MRI template to facilitate accurate identification of the affected structures. The increased regions are shown in red-to-white color and include both bilateral lentiform nuclei with slight extension to the adjacent claustrum and parahippocampal gyrus, especially in the putamen, amygdala, and hippocampus. The decreased regions are displayed with blue-to-green color and include the bilateral frontal cortex, parietal cortex, occipital cortex, temporal cortex, and cerebellum (p<0.001). Color bar indicates t-values.

Figure 3

Abnormal glucose uptake in the death group compared with the survival group. The PET findings were superimposed on an MRI template to facilitate accurate identification of the affected structures. The cerebral glucose metabolism displayed with red-to-white color was significantly higher in the bilateral amygdala, bilateral putamen, left thalamus, and left uncus (p<0.001). No significantly lower metabolism was found. Color bar indicates t-values.

Figure 4

Kaplan–Meier estimates of PFS and OS. Survival outcomes estimated by using pretreatment MTV: OS in ENKTL (A) and PFS in ENKTL (B); survival outcomes according to pretreatment TLG: OS (C) and PFS (D); survival outcomes according to SUVmaxRBGT/SUVmaxLC: OS (E) and PFS (F); survival outcomes according to SUVmaxLBGT/SUVmaxRC: OS (G) and PFS (H); survival outcomes according to SUVmaxRU/SUVmaxLC: OS (I) and PFS (J); survival outcomes according to SUVmaxLU/SUVmaxRC: OS (K) and PFS (L).