Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer.

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-ß receptor I (TGF-ßRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS- was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-ßRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

A higher platelet-to-lymphocyte ratio is prevalent in the presence of circulating tumor microemboli and is a potential prognostic factor for non-metastatic colon cancer.

Colorectal cancer is a common and often deadly cancer. Circulating tumor cells (CTCs) have been implicated as a potentially valuable prognosis factor. The detection of circulating tumor microemboli (CTM) and of simple blood component parameters that reflect inflammatory status, such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), may provide information about tumor progression. The aim of this study was to explore the importance of CTCs, CTM, PLR, and NLR prospectively in non-metastatic colon cancer progression. CTCs were enriched using ISETⓇ (Isolation by SizE of Tumor cells) and identified by immunocytochemical exclusion of leukocytes. We evaluated CTCs and blood cell parameters in a cohort of 69 stage I-III colon cancer patients (52.2% men; median age, 61 years; age range, 19-87 years) at a baseline timepoint prior to resection surgery. The median of CTC levels at baseline was 20 cells/8 mL (0-94) and higher levels were associated with CTM presence (p = 0.02). CTM were found in 18 (26.1%) patients. Of 18 stage I patients, 33.3% had CTM and of 51 stages II or III patients, 13.7% had CTM (p = 0.08). Patients with a high PLR (>124) were mostly (75.6%) diagnosed with high-risk stages II/III cancer (stages I/low-risk II, 24.4%; p = 0.014). All 8 patients that had disease recurrence during follow-up had a high PLR (p = 0.02 vs. low PLR). NLR was not significantly associated with disease stage or recurrence. The present results indicate that CTCs and PLR analyses may be clinically useful for colon cancer management and risk stratification.