Early detection of poor outcome in patients with metastatic colorectal cancer: tumor kinetics evaluated by circulating tumor cells

Abstract

BackgroundColorectal cancer (CRC) is the third most prevalent cancer worldwide. New prognostic markers are needed to identify patients with poorer prognosis, and circulating tumor cells (CTCs) seem to be promising to accomplish this.Patients and methodsA prospective study was conducted by blood collection from patients with metastatic CRC (mCRC), three times, every 2 months in conjunction with image examinations for evaluation of therapeutic response. CTC isolation and counting were performed by Isolation by Size of Epithelial Tumor Cells (ISET).ResultsA total of 54 patients with mCRC with a mean age of 57.3 years (31–82 years) were included. Among all patients, 60% (n=32) were carriers of wild-type KRAS (WT KRAS) tumors and 90% of them (n=29) were exposed to monoclonal antibodies along with systemic treatment. Evaluating CTC kinetics, when we compared the baseline (pretreatment) CTC level (CTC1) with the level at first follow-up (CTC2), we observed that CTC1-positive patients (CTCs above the median), who became negative (CTCs below the median) had a favorable evolution (n=14), with a median progression-free survival (PFS) of 14.7 months. This was higher than that for patients with an unfavorable evolution (CTC1− that became CTC2+; n=13, 6.9 months; P=0.06). Patients with WT KRAS with favorable kinetics had higher PFS (14.7 months) in comparison to those with WT KRAS with unfavorable kinetics (9.4 months; P=0.02). Moreover, patients whose imaging studies showed radiological progression had an increased quantification of CTCs at CTC2 compared to those without progression (P=0.04).ConclusionThis study made possible the presentation of ISET as a feasible tool for evaluating CTC kinetics in patients with mCRC, which can be promising in their clinical evaluation.

Circulating tumor cells as an independent prognostic factor in advanced colorectal cancer: a retrospective study in 121 patients

“…Another limitation is the lack of dynamic enumeration of CTCs. The dynamic enumeration of CTCs could better reflect the aggressiveness and prognosis of the disease than the isolated enumeration of CTCs [36]. However, it was difficult for us to compare the baseline (pretreatment) level of CTCs with the level at follow-up.…”

Single-cell genetic analysis validates cytopathological identification of circulating cancer cells in patients with clear cell renal cell carcinoma

“…The reliable detection of CCC in the blood of individuals at risk of developing cancer by using ISET ® has allowed early detection of lung, breast, renal and ovarian cancers before tumor detection by imaging [ 13 , 59 ]. The prognostic relevance of CCC detected by ISET ® has been demonstrated for patients with melanomas [ 60 ] as well as lung [ 30 , 61 ], colorectal [ 62 ], liver [ 16 ], pancreatic [ 63 ], head and neck [ 64 ] and ovarian cancers [ 65 ]. Furthermore, the utility of theranostic characterization of CCC detected by ISET ® has been demonstrated for non-small-cell lung cancers [ 66 ], castration-resistant prostate cancers [ 67 ], colorectal cancers [ 17 ], hepatocellular carcinomas [ 68 ] and melanomas [ 69 ].…”

Evaluation of incidence, significance, and prognostic role of circulating tumor microemboli and transforming growth factor‐β receptor I in head and neck cancer

“…Assessment of the presence of CTMs ( Figure 3A,C) at 2 serial collections allowed an analysis of CTM kinetics, as made in our previous work with CTC counts in metastatic colorectal cancer. 34 Comparing the presence of CTMs at baseline (CTM1) with their presence at first follow-up (CTM2), patients with CTM-positive at baseline who became CTM-negative in the first follow-up were classified with a favorable evolution and had a median PFS of 20 months. This was higher than the PFS of patients with an unfavorable evolution (CTM1-negative and CTM2-positive), with a median PFS of 17.5 months.…”