De Jaeghere, Emiel A., Laloo, Frederiek, Lippens, Lien, Van Bockstal, Mieke, De Man, Kathia, Naert, Eline, Van Dorpe, Jo, Van de Vijver, Koen, Tummers, Philippe, Makar, Amin, De Visschere, Pieter J.L., De Wever, Olivier, Amant, Frédéric, Denys, Hannelore G., and Vandecasteele, Katrien
The spleen represents an important contributor to tumor immune escape, but the relevance of increased splenic metabolic activity remains to be fully elucidated. We retrospectively measured the spleen-to-liver standard uptake value (SLR) on 18F-FDG PET/CT examinations of 92 consecutive patients with FIGO stage IB1 to IVA cervical cancer and integrated the results with survival, response to treatment, tumor immune infiltrate, and baseline characteristics. SLR max > 0.92 (p =.026) and SLR mean > 0.94 (p =.005) were significantly associated with decreased DFS in univariable analysis. Multivariable models were built using best subset selection; ΔSLR max and either SLR max or SLR mean were consistently selected, strongly reinforcing the association between SLR variables and DFS in relation to potential confounders (all models p ≤.002). Independent associations were found for SLR max using multivariable Cox regression models for DFS (all p ≤.003). Further, uni- and multivariable analyses demonstrated the negative impact of higher SLR values on pathological complete response. A statistically significant higher proportion of patients with high SLR max had a dense infiltrate of CD20+ (p =.036) and CD68+ (p =.015) immune cells, as well as PD-L1+ tumor cells (p =.019) as compared to those with low SLR max. Finally, high SLR max status was neither associated with systemic inflammatory markers (except for an increased white blood cell count; p =.038), nor with clinically overt infection. This hypothesis-generating study provides the first evidence that increased splenic metabolic activity is a negative prognostic and predictive biomarker in locally advanced cervical cancer. In addition, it might help to discriminate immunologically 'hot' from 'cold' cervical tumors. • Splenic metabolic activity was a prognostic factor for recurrence in cervical cancer. • Splenic metabolic activity was a predictive factor for pathological complete response in cervical cancer. • Splenic metabolic activity was associated with the cervical tumor immune infiltrate. [ABSTRACT FROM AUTHOR]