Poster Session at ECC 2013 – Circulating tumour cell counts in advanced and metastatic colorectal cancer by immunomagnetic labelling: Results reflect the reality?

Solange M Sanches et al, AC Camargo Cancer Center, São Paulo, Brazil.
The suggestion that bevacizumab treatment may reduce the prognostic value of circulating tumour cells (CTC) in patients with metastatic colorectal cancer (mCRC) may have a considerable impact on clinical practice and warrants further investigation. A team of researchers at the AC Camargo Cancer Center in São Paulo, Brazil have developed a diagnostic tool for monitoring CTC response to chemotherapy plus bevacizumab in real time; their results were presented as a poster at ECCO 2013.

Colorectal cancer is one of the leading causes of cancer death in the world [1]. The first-line treatment strategy is complete resection of the lesion. However, despite advances in surgical techniques and adjuvant therapy, recurrent disease is common and there is a need for reliable markers to detect the presence of residual micrometastases and monitor the therapeutic response after relapse. One such marker that has been proposed is CTC count [2]. However, reports have indicated that the antiangiogenetic effect of bevacizumab may alter CTC biology sufficiently to prevent currently available tools for detecting CTC in patients with mCRC from working [3].

The objective of the Brazilian study was to correlate CTC counts as detected by isolation by size of epithelial tumour cells (ISET) with progression free survival (PFS). A total of forty patients with mCRC who were about to begin combination chemotherapy with folinic acid and fluorouracil and either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) plus bevacizumab were included in the study. The majority of patients were male (55%) at disease stage IV (82.5%), median age 62 years (range 30–81 years). The median CTC count at baseline was 4.5 CTCs/mL. Following treatment, the median PFS was found to be 9.6 months (range 1.18–14.74 months). Patients with CTC counts above the median at baseline had poorer PFS (7.04 months) compared with patients with lower CTC counts (10 months) although this difference was not statistically significant. No difference was observed at the first follow-up (9.70 vs 9.07 months, p=ns). Chi-square analysis showed a significant correlation between CTC counts and the development of visceral metastases (p=0.015).

The Brazilian investigators hypothesised that the correlation between low CTC counts and poor PFS can be explained by the inhibition of tumour angiogenesis by bevacizumab, which may result in hypoxia, invasive cell behaviour and epithelial mesenchymal transition (EMT) [3]. The ISET methodology used in the Brazilian study relies on epithelial markers and one possible explanation could be that the patients who showed the worst PFS were undergoing EMT. The investigators suggested that future work in this field should focus on defining a target genotype for predicting treatment response and CTC behaviour during antiangiogenetic therapy, as well as optimising ISET as a monitoring tool by quantifying the expression of EMT and endothelial cells markers in filtered CTCs.

The study also comprised an analysis of multidrug resistance-associated protein 5 (MRP-5) expression; although four patients tested positive, no significant correlation with PFS could be established, and the investigators pointed out that greater patient numbers would be required for a full analysis.

 

References

1.   Jemal, A., et al., Global cancer statistics. CA Cancer J Clin, 2011. 61(2): p. 69-90.

2.   Cohen, S.J., et al., Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol, 2009. 20(7): p. 1223-9.

3.   Gazzaniga, P., et al., Circulating tumor cells, colon cancer and bevacizumab: the meaning of zero. Ann Oncol, 2011. 22(8): p. 1929-30.