Splenic 18 F-FDG uptake on baseline PET/CT is associated with oncological outcomes and tumor immune state in uterine cervical cancer.

Objective: The spleen represents an important contributor to tumor immune escape, but the relevance of increased splenic metabolic activity remains to be fully elucidated.
Methods: We retrospectively measured the spleen-to-liver standard uptake value (SLR) on ¹⁸ F-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.
Results: 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.
Conclusion: 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.
Competing Interests: Declaration of Competing Interest E.A.D. reports non-financial support from Pfizer and non-financial support from PharmaMar, all outside the submitted work and institutional (not personal); F.L. and K.D. report non-financial support from Bayer, outside the submitted work and institutional (not personal); E.N. reports non-financial support from Pfizer, non-financial support from Roche, non-financial support from PharmaMar, non-financial support from AstraZeneca, and non-financial support from Novartis, all outside the submitted work and institutional (not personal); H.G.D. reports non-financial support from Pfizer, a grant and non-financial support from Roche, non-financial support from PharmaMar, non-financial support from Teva, non-financial support from AstraZeneca, non-financial support from Eli Lilly and Company, non-financial support from Novartis, non-financial support from Amgen, non-financial support from Tesaro, non-financial support from MSD, and non-financial support from Nutrisan, all outside the submitted work and institutional (not personal); and K.V. reports non-financial support from PharmaMar, outside the submitted work and institutional (not personal). Other authors have nothing to disclose.
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