TY - JOUR
T1 - Prognostic and theranostic 18F-FDG PET biomarkers for anti-PD1 immunotherapy in metastatic melanoma
T2 - association with outcome and transcriptomics
AU - Seban, Romain David
AU - Nemer, John S.
AU - Marabelle, Aurélien
AU - Yeh, Randy
AU - Deutsch, Eric
AU - Ammari, Samy
AU - Moya-Plana, Antoine
AU - Mokrane, Fatima Zohra
AU - Gartrell, Robyn D.
AU - Finkel, Grace
AU - Barker, Luke
AU - Bigorgne, Amélie E.
AU - Schwartz, Lawrence H.
AU - Saenger, Yvonne
AU - Robert, Caroline
AU - Dercle, Laurent
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - FDG-PET/CT
KW - Immune checkpoint inhibitors
KW - Metabolic tumor burden
KW - Metastatic melanoma
KW - Prognosis
KW - Systemic inflammatory response
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UR - http://www.scopus.com/inward/citedby.url?scp=85069644192&partnerID=8YFLogxK
U2 - 10.1007/s00259-019-04411-7
DO - 10.1007/s00259-019-04411-7
M3 - Article
C2 - 31346755
AN - SCOPUS:85069644192
SN - 1619-7070
VL - 46
SP - 2298
EP - 2310
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 11
ER -