Evaluating Novel PET-CT Functional Parameters TLG and TMTV in Differentiating Low-grade Versus Grade 3A Follicular Lymphoma

Grading of follicular lymphoma (FL) is important in deciding on a watchful waiting strategy or initiation of chemoimmunotherapy, but accurate determination of grade is complicated by disease heterogeneity and inter-reader variability. Positron emission tomography-computed tomography parameter maximum standardized uptake value (SUVmax) has been studied in differentiating low- versus high-grade FL, but novel parameters total lesion glycolysis (TLG) and total metabolic tumor volume (TMTV) have not been studied and may provide better sensitivity and specificity. SUVmax, TLG, and TMTV were compared in 49 patients with both low-grade and grade 3A FL, and TLG and TMTV had comparable sensitivities and specificities to SUVmax in differentiating low-grade from grade 3A FL. TLG and TMTV are reproducible adjuncts but not replacements for gold-standard biopsy in grading FL. BACKGROUND: Follicular lymphoma (FL) grading, low-grade 1–2 (LG) versus grade 3A (3A), informs management. However, accurate grading is challenging owing to disease heterogeneity and inter-reader variability. The [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) parameter maximum standardized uptake value (SUVmax) has utility in differentiating LG from 3A FL, but the utility of novel parameters total lesion glycolysis (TLG) and total metabolic tumor volume (TMTV) is unknown. PATIENTS AND METHODS: Retrospective review of diagnostic pre-treatment PET-CTs of patients aged > 18 years with FL grades 1–3A from 2009–2017 was performed. PET-CT parameters SUVmax, TLG, and TMTV values were generated using manual (MW) and semi-automated workflows (SW). Poisson regression and receiver operating characteristic curves were used to compare PET-CT parameters between LG and 3A. RESULTS: A total of 49 patients with FL were identified: 38 LG and 11 3A. PET-CT parameters were significantly higher in 3A as compared with LG in both workflows. The cutoff values, sensitivities, and specificities were as follows: SUVmax: 10.4, 64%, and 74% in MW and 11.9, 73%, and 76% in SW; TLG: 543, 82%, and 74% in MW and 371, 73%, and 74% in SW; and TMTV: 141, 73%, and 76% in MW and 93, 64%, and 76% in SW. SUVmax had identical cutoff, sensitivity, and specificity across all 3 SWs, whereas TLG and TMTV had considerable variance across all 3 SWs. CONCLUSIONS: TLG and TMTV are comparable to SUVmax in differentiating LG versus 3A FL. Cutoffs, sensitivities, and specificities varied in MW versus SW. Novel PET-CT parameters serve as reproducible adjuncts but not replacements for biopsy in differentiating grades of FL.