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25.07.2019 | Original Article | Ausgabe 11/2019

European Journal of Nuclear Medicine and Molecular Imaging 11/2019

Prognostic and theranostic 18F-FDG PET biomarkers for anti-PD1 immunotherapy in metastatic melanoma: association with outcome and transcriptomics

Zeitschrift:
European Journal of Nuclear Medicine and Molecular Imaging > Ausgabe 11/2019
Autoren:
Romain-David Seban, John S. Nemer, Aurélien Marabelle, Randy Yeh, Eric Deutsch, Samy Ammari, Antoine Moya-Plana, Fatima-Zohra Mokrane, Robyn D. Gartrell, Grace Finkel, Luke Barker, Amélie E. Bigorgne, Lawrence H. Schwartz, Yvonne Saenger, Caroline Robert, Laurent Dercle
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00259-019-04411-7) contains supplementary material, which is available to authorized users.
Yvonne Saenger, Caroline Robert, and Laurent Dercle shared co-senior authorship.
This article is part of the Topical Collection on Oncology–General.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Purpose

An imaging-based stratification tool is needed to identify melanoma patients who will benefit from anti Programmed Death-1 antibody (anti-PD1). We aimed at identifying biomarkers for survival and response evaluated in lymphoid tissue metabolism in spleen and bone marrow before initiation of therapy.

Methods

This retrospective study included 55 patients from two institutions who underwent 18F-FDG PET/CT before anti-PD1. Parameters extracted were SUVmax, SUVmean, HISUV (SUV-based Heterogeneity Index), TMTV (total metabolic tumor volume), TLG (total lesion glycolysis), BLR (Bone marrow-to-Liver SUVmax ratio), and SLR (Spleen-to-Liver SUVmax ratio). Each parameter was dichotomized using the median as a threshold. Association with survival, best overall response (BOR), and transcriptomic analyses (NanoString assay) were evaluated using Cox prediction models, Wilcoxon tests, and Spearman’s correlation, respectively.

Results

At 20.7 months median follow-up, 33 patients had responded, and 29 patients died. Median PFS and OS were 11.4 (95%CI 2.7–20.2) and 28.5 (95%CI 13.4–43.8) months. TMTV (>25cm3), SLR (>0.77), and BLR (>0.79) correlated with shorter survival. High TMTV (>25 cm3), SLR (>0.77), and BLR (>0.79) correlated with shorter survival, with TMTV (HR PFS 2.2, p = 0.02, and HR OS 2.5, p = 0.02) and BLR (HR OS 2.3, p = 0.04) remaining significant in a multivariable analysis. Low TMTV and TLG correlated with BOR (p = 0.03). Increased glucose metabolism in bone marrow (BLR) was associated with transcriptomic profiles including regulatory T cell markers (p < 0.05).

Conclusion

Low tumor burden correlates with survival and objective response while hematopoietic tissue metabolism correlates inversely with survival. These biomarkers should be further evaluated for potential clinical application.

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