Prognostic Value of the Combination of Circulating Tumor Cells Plus KRAS in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab

Sastre, Javier; Vidaurreta, Marta; Gómez, Auxiliadora; Rivera, Fernando; Massutí, Bartomeu; López, Margarita Reboredo; Abad, Albert; Gallén, Manuel; Benavides, Manuel; Aranda, Enrique; Rubio, Eduardo Díaz

doi:10.1016/j.clcc.2013.06.001

Cited by 36 publications

(16 citation statements)

References 12 publications

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“…Although the sample for this analysis was restricted to 27 patients, it is important to correlate these data with the study45 that evaluated the first-line treatment of 1589 patients with mCRC. In this study, the first count higher than 3.0 CTCs/7.5 mL, in association with the KRAS mutation, presented worse prognosis when these patients were compared with patients with CTC <3.0/7.5 mL 47. This correlation allows us to support the importance of the CTC kinetics not addressed in this study.…”

Section: Discussionsupporting

confidence: 66%

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

Silva¹,

Chinen²,

Abdallah³

et al. 2016

OTT

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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.

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Section: Discussionsupporting

confidence: 66%

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

Silva¹,

Chinen²,

Abdallah³

et al. 2016

OTT

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“…In this study, patients with less CTC's count (<3 CTCs/7.5mL) and KRAS wt in tumor had higher PFS and overall survival (OS) than patients with more CTCs (>3 CTCs/ 7.5mL) and KRAS mutation in tumor (P D 0.001 and P D 0.004, respectively). 17 The presence of heterogeneous cell population in the blood may be an obstacle to the detection of gene mutation in CTCs. We can note that the leukocyte contamination of CTCs sample and their retention on membrane surface could camouflage the results.…”

Section: Discussionmentioning

confidence: 99%

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Buim

Fanelli

Souza

et al. 2015

Cancer Biology & Therapy

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Background: Quantification of Circulating Tumor Cells (CTCs) as a prognostic marker in metastatic colorectal cancer (mCRC) has already been validated and approved for routine use. However, more than quantification, qualification or characterization of CTCs is gaining importance, since the genetic characterization of CTCs may reflect, in a real time fashion, genetic profile of the disease. Objective: To characterize KRAS mutations (codon 12 and 13) in CTCs from patients with mCRC and to compare with matched primary tumor. Additionally, correlate these mutations with clinical and pathological features of patients. Methods: Blood samples were collected from 26 patients with mCRC from the AC Camargo Cancer Center (São Paulo-Brazil). CTCs were isolated by ISET technology (Isolation by Size of Epithelial Tumors; Rarecells Diagnostics, France) and mutations analyzes were performed by pyrosequencing (QIAGEN). Results: KRAS mutation was detected in 7 of the 21 cases (33%) of samples from CTCs. In matched primary tumors, 9 of the 24 cases (37.5%) were found KRAS mutated. We observed that 5 of the 9 samples with KRAS mutation in their primary tumor had also KRAS mutation in CTCs, meaning a concordance of 71% of matched cases (P D 0.017). KRAS mutation neither on primary tumor nor in CTCs was associated with clinical-pathological parameters analyzed. Conclusion: Faced with a polyclonal disease like colorectal cancer, which is often treated with alternating and successive lines of chemotherapy, real time genetic characterization of CTCs, in a fast and feasible fashion, can provide important information to clinical management of metastatic patients. Although our cohort was limited, it was possible to show a high grade of concordance between primary tumor and CTCs, which suggests that CTCs can be used as surrogate of primary tumors in clinical practice, when the knowledge of mutation profile is necessary and the primary tumor is not available.

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“…There have been numerous studies trying to determine a cutoff-value for the CTC count as a prognostic decision point. Studies have suggested a CTC count of ≥5/7.5 ml of blood to be valid for metastatic breast cancer (11,20), and a count of ≥3/7.5 ml of blood for metastatic colorectal cancer (21). However, the statistical determination method of these cutoff-values along with their prognostic and clinical importance are sources of controversy (22).…”

Section: Discussionmentioning

confidence: 99%

Detection of circulating tumor cells in patients with esophagogastric or pancreatic adenocarcinoma using the CellSearch® system: An observational feasibility study

et al. 2016

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Prognostic Value of the Combination of Circulating Tumor Cells Plus KRAS in Patients With Metastatic Colorectal Cancer Treated With Chemotherapy Plus Bevacizumab

Cited by 36 publications

References 12 publications

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

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

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Detection of circulating tumor cells in patients with esophagogastric or pancreatic adenocarcinoma using the CellSearch® system: An observational feasibility study

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