Assessing immune organs on F-FDG PET/CT imaging for therapy monitoring of immune checkpoint inhibitors: inter-observer variability, prognostic value and evolution during the treatment course of melanoma patients.

Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival in advanced melanoma. There is a need for robust biomarkers to identify patients who do not respond. We analysed 14 baseline F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) metrics and their evolution to assess their correlation with patient outcome, compared with 7 established biological markers and 7 clinical variables.

Methods: We conducted a retrospective monocentric observational study of 29 patients with advanced melanoma who underwent baseline F-FDG PET/CT, followed by an early monitoring PET/CT (iPET) scan after 1 month of treatment and follow-up studies at 3rd (M3PET) and 6th month (M6PET). F-FDG uptake in immune organs (spleen, bone marrow, ileocecal valve) and derived spleen-to-liver (SLR) and bone-to-liver (BLR) ratios were reviewed by two PET readers for reproducibility analysis purposes including 14 PET variables. The most reproducible indexes were used for evaluation as predictors of overall survival (OS) in comparison with PET response using imPERCIST5, whole-body metabolic active tumour volume (WB-MATV) and biological parameters (lactate dehydrogenases (LDH), reactive protein c (CRP), white blood count (WBC), absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and derived neutrophils to lymphocyte ratio).

Results: Strong reproducibility's (intraclass coefficients of correlation (ICC) > 0.90) were observed for spleen anterior SUV, spleen MV, spleen TLG, spleen length and BLR. ICC for SLR and ileocecal SUV were 0.86 and 0.65, respectively. In the 1-year OS 1 group, SLR tended to increase at each time point to reach a significant difference at M6-PET (p = 0.019). The same trends were observed with spleen SUV anterior and spleen length. In the 1-year OS 0 group, a significative increase of spleen length was found at iPET, as compared with baseline PET (p = 0.014) and M3-PET (p = 0.0239). Univariable Kaplan-Meier survival analysis found that i%var spleen length, M3%var SLR, baseline LDH, i%var NLR and response at M6PET were all predictors of 1-year OS.

Conclusions: SLR is recommended as a prognosticator in melanoma patients under immunotherapy: its increase greater than 25% at 3 months, compared with baseline, was associated with poor outcome after ICIs.