AUTHOR=Jacques Virginie , Dierickx Lawrence , Texier Jean Sebastien , Brillouet Severine , Courbon Frederic , Guimbaud Rosine , Vija Lavinia , Savagner Frederique 

TITLE=Evaluation of a blood miRNA/mRNA signature to follow-up Lu-PRRT therapy for G1/G2 intestinal neuroendocrine tumors

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1385079

DOI=10.3389/fendo.2024.1385079

ISSN=1664-2392

ABSTRACT=Background :177 Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NET) of variable radiological response. Several clinical, biological and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy.Methods: Thirty-five patients received LuPRRT for G1/G2 midgut NET between May 2019 and September 2021. Peripheral blood samples were collected prior to irradiation, before and 48 hours after the second and the fourth LuPRRT and at 6-month follow-up. Multiple regression analyses and Pearson correlations were performed to identify the miRNA/mRNA signature that will best predict response to LuPRRT.Focusing on 4 mRNA and 3 miRNA we identified a miRNA/mRNA signature enabling the early identification of responders to LuPRRT with significant reduced miRNA/mRNA expression after the first LuPRRT administration for patients with progressive disease at 1 year (p <0.001). The relevance of this signature was reinforced by studying its evolution up to 6 months post-LuPRRT. Moreover, nadir absolute lymphocyte count within the first two months after the first LuPRRT administration was significantly related to low miRNA/mRNA expression level (p<0.05) for patients with progressive disease.We present a pilot study exploring an miRNA/mRNA signature that correlates with early hematologic toxicity and therapeutic response 12 months following LuPRRT. This signature will be tested prospectively in larger series of patients.