Oligometastatic prostate cancer patients stratification: A molecular signature identified by liquid biopsy.

Abstract

TPS400 Background: Oligometastatic prostate cancer (OPC) may represent the initial step of an unavoidable, rapid progression to a polymetastatic state, or the expression of a real oligometastatic phenotype related to a condition of stable disease for a long time. In the last scenario, stereotactic body radiation therapy (SBRT) can be considered as a potentially curative treatment option for hormone-naïve OPC. We propose a prospective, explorative trail with the aim of identifying by liquid biopsy a molecular signature (genes or differential expression of miRNA), and related clonal evolution, underlying metastatic prostate cancer progression after a course of SBRT. Methods: Study population will be 30 adult, hormone-naïve OPC undergoing SBRT. Table 1 summarizes gene and miRNA panel for molecular analysis. For each patient, 15 ml of peripheral blood will be collected before and at the end of SBRT, every 3 months for the first year, then every 6 months until disease progression, when another blood sample will be collected in case of instrumental evidence of failure (using PET-Choline or CT-scan plus bone scintigraphy). 7.5 ml of peripheral blood will be centrifuged to separate sera and 7.5 ml of peripheral blood will be centrifuged to separate plasma from the other blood components, respectively. Sera and plasma will be stored at -20°C and centralized to CREA Laboratory at our Institution, then immediately processed for cell free DNA (cfDNA) and miRNA extraction for NGS of target genes (by Illumina platforms MiSeq and MiniSeq) and dPCR analysis. Study duration will be 36 months. This protocol has been written and will be conducted in agreement with either the Declaration of Helsinki and subsequent amendments and ICH Harmonized Tripartite Guideline for Good Clinical Practice, and has received approval of local Ethics Committee. Panel for analysis. [Table: see text]

Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

“…The various roles played by miRNA in neoplasia have been continuously reported and confirmed [109]. Their potential use as circulating biomarkers has been widely speculated, either as cell-free miRNA or when included as vesicle cargo [110][111][112].…”

Stratification of Oligometastatic Prostate Cancer Patients by Liquid Biopsy: Clinical Insights from a Pilot Study

“…Moreover, molecular biology techniques such as next-generation sequencing (NGS) have emerged as a promising issue for characterizing the oligometastatic-state heterogeneity [ 38 , 39 ]. We present our pilot study, the translational analysis of serum-derived circulating cell free DNA (cfDNA) in a population of OPC patients, using a deep target sequencing approach, with the aim of tracking metastatic prostate cancer spread from a molecular point of view, the possible identification of biomarkers that are predictive for a true oligometastatic state, and we assess whether any molecular characterization of OPC may also contribute to select patients that are more likely to benefit from local, metastasis-directed SBRT [ 40 ].…”