[18F]FDG PET/CT in head and neck squamous cell carcinoma: a head-to-head between visual point-scales and the added value of multi-modality imaging
Authors: Ferrari Cristina , Santo Giulia , Mammucci Paolo , Rubini Dino , Sciacqua Alessio , Sardaro Angela , Pisani Antonio Rosario , Rubini Giuseppe 
Published: February 2023

Abstract
Background
Head and neck squamous cell carcinoma (HNSCC) represents the 6th leading cancer worldwide. In most cases, patients present a locally advanced disease at diagnosis and non-surgical curative treatment is considered the standard of care. Nowadays, [18F]FDG PET/CT is a validated tool in post-treatment evaluation, with a high level of evidence. However, to standardize imaging response, several visual scales have been proposed with none of them approved yet. The study’s aim is a head-to-head comparison between the diagnostic performance of the Hopkins criteria, the Deauville score, and the new proposed Cuneo score, to establish their prognostic role. Secondly, we investigate the possible value of semiquantitative analysis, evaluating SUVmax and ΔSUVmax of the lymph node with the highest uptake on the restaging PET scan. Moreover, we also considered morphological features using the product of diameters measured on the co-registered CT images to assess the added value of hybrid imaging.

Methods
We performed a retrospective analysis on histologically proven HNSCC patients who underwent baseline and response assessment [18F]FDG PET/CT. Post-treatment scans were reviewed according to Hopkins, Deauville, and Cuneo criteria, assigning a score to the primary tumor site and lymph nodes. A per-patient final score for each scale was chosen, corresponding to the highest score between the two sites. Diagnostic performance was then calculated for each score considering any evidence of locoregional progression in the first 3 months as the gold standard. Survival analysis was performed using the Kaplan–Meier method. SUVmax and its delta, as well as the product of diameters of the lymph node with the highest uptake at post-treatment scan, if present, were calculated.

Results
A total of 43 patients were finally included in the study. Sensitivity, specificity, PPV, NPV, and accuracy were 87%, 86%, 76%, 92%, and 86% for the Hopkins score, whereas 93%, 79%, 70%, 96%, and 84% for the Deauville score, respectively. Conversely, the Cuneo score reached the highest specificity and PPV (93% and 78%, respectively) but the lowest sensitivity (47%), NPV (76%), and accuracy (77%). Each scale significantly correlated with PFS and OS. The ROC analysis of the combination of SUVmax and the product of diameters of the highest lymph node on the restaging PET scan reached an AUC of 0.822. The multivariate analysis revealed the Cuneo criteria and the product of diameters as prognostic factors for PFS.

Conclusions
Each visual score statistically correlated with prognosis thus demonstrating the reliability of point-scale criteria in HNSCC. The novel Cuneo score showed the highest specificity, but the lowest sensibility compared to Hopkins and Deauville criteria. Furthermore, the combination of PET data with morphological features could support the evaluation of equivocal cases.