Quantitative and clinical implications of the EARL2 versus EARL1 [ 18 F]FDG PET-CT performance standards in head and neck squamous cell carcinoma

Background The EANM Research Ltd. (EARL) guidelines give recommendations for harmonization of [ 18 F]FDG PET-CT image acquisition and reconstruction, aiming to ensure reproducibility of quantitative data between PET scanners. Recent technological advancements in PET-CT imaging resulted in an updated version of the EARL guidelines (EARL2). The aim of this study is to compare quantitative [ 18 F]FDG uptake metrics of the primary tumor and lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC) on EARL2 versus EARL1 reconstructed images and to describe clinical implications for nodal staging and treatment. Methods Forty-nine consecutive patients with HNSCC were included. For all, both EARL1 and EARL2 images were reconstructed from a singular [ 18 F]FDG PET-CT scan. Primary tumors and non-necrotic lymph nodes ≥ 5 mm were delineated on CT-scan. In the quantitative analysis, maximum standardized uptake values (SUV max ) and standardized uptake ratios (SUR max , i.e., SUV max normalized to cervical spinal cord uptake) were calculated for all lesions on EARL1 and EARL2 reconstructions. Metabolic tumor volume (MTV) and total lesion glycolysis were compared between EARL1 and EARL2 using different segmentation methods (adaptive threshold; SUV2.5/3.5/4.5; SUR2.5/3.5/4.5; MAX40%/50%). In the qualitative analysis, each lymph node was scored independently by two nuclear medicine physicians on both EARL1 and EARL2 images on different occasions using a 4-point scale. Results There was a significant increase in SUV max (16.5%) and SUR max (9.6%) of primary tumor and lymph nodes on EARL2 versus EARL1 imaging ( p < 0.001). The proportional difference of both SUV max and SUR max between EARL2 and EARL1 decreased with increasing tumor volume ( p < 0.001). Absolute differences in MTVs between both reconstructions were small (< 1.0 cm 3 ), independent of the segmentation method. MTVs decreased on EARL2 using relative threshold methods (adaptive threshold; MAX40%/50%) and increased using static SUV or SUR thresholds. With visual scoring of lymph nodes 38% (11/29) of nodes with score 2 on EARL1 were upstaged to score 3 on EARL2, which resulted in an alteration of nodal stage in 18% (6/33) of the patients. Conclusions Using the EARL2 method for PET image reconstruction resulted in higher SUV max and SUR max compared to EARL1, with nodal upstaging in a significant number of patients.