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

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

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2298-2310
Number of pages13
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume46
Issue number11
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

Keywords

  • FDG-PET/CT
  • Immune checkpoint inhibitors
  • Metabolic tumor burden
  • Metastatic melanoma
  • Prognosis
  • Systemic inflammatory response

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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