Abstract 469P
Background
Liquid biopsy could become a useful mean in mCRC patients (pts) in order to weigh tumor heterogeneity. In this study we aimed to investigate the clinical utility of circulating exosomes DNA (exo-DNA) and the role of some cytokines in the management of mCRC during the first-line of chemotherapy.
Methods
Exosomes analysis at different steps (basal, post-therapy and at progression) was assessed in 70 mCRC, in 60 pts KRAS mutational status on exo-DNA was evaluated at baseline (BL) and progression (PD). In 90 pts, 45 all-wild-type (WT) and 45 with a RAS or BRAF mutation (MT) the expression of 5 cytokines (CD44, IL-6, IL-8, CD147 and progranulin) was analysed at different time-points.
Results
Plasma exosomes levels have been significantly modified during the three disease steps, also in an only-liver metastatic disease subgroup which received hepatic resection (p=0,012). Levels significantly correlated with the extension of metastatic sites (p=0,0019) and they were significantly higher in MT compared to WT pts (p=0,026). CEA expression and liver metastasis were correlated with KRAS status and fractional abundance. KRAS-WT (>125 copies) and KRAS-MT (>37 copies) BL levels were related to worse OS (p=0,001; p=0,008). At BL one WT patient and 4 KRAS-MT pts on tissue resulted respectively KRAS-MT and KRAS-WT on exo-DNA. At PD other 4 mutations were revealed in WT cohort and KRAS mutation disappeared in 5 pts in MT cohort. The MT and WT subgroups expressed different CD44, IL-8 and progranulin levels statistically significant in the analysed steps. CD147 and IL-6 concentration was significantly modified during the treatment and at PD only in the WT cohort. Only IL-8 BL expression was identified as a prognostic factor for OS in MT-group (p=0,0135).
Conclusions
In a prospective cohort of mCRC pts, we have shown how exosome-based liquid biopsy and some cytokines analysis might provide relevant clinical information to therapeutic stratification that must be investigated in wide studies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Associazione Stare Accanto, Amici dell'Oncologia Medica del Policlinico Gemelli.
Disclosure
All authors have declared no conflicts of interest.