Dados do Trabalho

Título

CIRCULATING TUMOR CELLS AS DYNAMIC BIOMARKERS TO EVALUATE RESISTANCE TO NEOADJUVANT TREATMENT WITH CHEMORADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED RECTAL CANCER.

Introdução

Neoadjuvant chemoradiotherapy (NCRT) has established as the main strategy for treatment of locally advanced rectal cancer (LARC). Given the need to stratify patients into responders x non-responders to NCRT prior to its initiation, to select those most likely to obtain a complete pathological response (pCR), several studies have assessed the identification of potential biomarkers.

Objetivo

The primary objective of this prospective study was to analyze whether the absence of RAD23 homolog B expression (RAD23B) and thymidylate synthase (TYMS) in circulating tumor cells (CTCs) would correlate with pCR for patients undergoing NCRT and identify possible responders to treatment. The secondary outcomes were to evaluate the kinetics of CTCs before (C1) and after NCRT (C2), in addition to the correlation of the expression of immune response markers, such as Tumor Growth Factor β Receptor I (TGF-βRI) and Programmed Death ligand- 1 (PD-L1) with disease-free survival (DFS) and overall survival (OS).

Método

Between 2016-2020, 63 patients with LARC were included. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). The expression of RAD23B, TYMS, PD-L1 and TGF-βRI was evaluated in this order, according to the primary objective of the study at each time of collection (C1 and C2) and the availability of cells (CTC count> 0) in the sample.

Resultado

In C1, RAD23B was detected in 54.1% of patients without pCR and its absence in 91.7% of patients with pCR (p = 0.014). In C2, 10/13 patients with pCR did not show RAD23B expression in CTCs. For patients without pCR with NCRT, 51.7% had RAD23B expression in CTCs in C2 (p = 0.06). In the univariate (OR = 0.077; 95% CI, 0.009-0.661; p = 0.019) and multivariate (OR = 0.064; 95% CI, 0.006-0.75; p = 0.029) logistic regression models for pCR, the expression of RAD23B was associated with a lower chance compared to patients with the absence of RAD23B expression in C1. Patients with CTC2> CTC1 (unfavorable kinetics) had worse DFS (p = 0.00025) and OS (p = 0.0036) compared with those with CTC2 ≤CTC1 (favorable kinetics). TGF-βRI expression in any time was correlated with worse DFS (p = 0.059).

Conclusão

We demonstrated a possible correlation between the absence of RAD23B/TYMS expression in CTCs with pCR, being important to identify respondents to NCRT, helping to individualize the therapeutic approach. In addition, the unfavorable kinetics and expression of TGF-βRI in CTCs correlated with worse survival.

Palavras-chave

locally advanced rectal carcinoma; neoadjuvant chemoradiation; liquid biopsy; circulating tumor cell, RAD23B.