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Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma.

Klinac D, Gray ES, Freeman JB, Reid A, Bowyer S, Millward M, Ziman M - BMC Cancer (2014)

Bottom Line: Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival.However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy.A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Medical Sciences, Edith Cowan University (ECU), 270 Joondalup Drive, Joondalup, Perth, WA 6027, Australia. e.gray@ecu.edu.au.

ABSTRACT

Background: New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes.

Methods: CTCs were captured by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled prospectively and CTC counts performed at baseline (prior to treatment), during and after treatment.

Results: Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival. However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy. A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients.

Conclusions: Measuring changes in CTC numbers during treatment is useful for monitoring therapy response in melanoma patients and for providing prognostic information relating to overall survival. Further studies with larger sample sizes are required to confirm the utility of CTC quantification as a companion diagnostic for metastatic melanoma treatment.

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Related in: MedlinePlus

Kaplan-Meier curves for (A, D) OS, (B, E) PFS and (C, F) time to response of all melanoma patients with > =2 cells and <2 CTCs in 4.5 ml of blood. (C) Only patients undergoing system therapies were analysed for treatment response, N = 17. Patients treated with the B-Raf inhibitor vemurafenib were analysed separately (D, E and F).
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Figure 1: Kaplan-Meier curves for (A, D) OS, (B, E) PFS and (C, F) time to response of all melanoma patients with > =2 cells and <2 CTCs in 4.5 ml of blood. (C) Only patients undergoing system therapies were analysed for treatment response, N = 17. Patients treated with the B-Raf inhibitor vemurafenib were analysed separately (D, E and F).

Mentions: A Kaplan-Meier analysis was performed to determine the association between baseline CTCs and prognostic values such as OS, PFS and response to treatment (Figure 1A, B and C). Log-rank test did not show an association between the number of baseline CTCs and any of these three outcome measurements. The analysis was performed repeatedly using different cut off values to define a favourable or unfavourable CTC number, at 3, 4 or 5 CTCs, but no statistical significance was found in any of these comparisons.


Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma.

Klinac D, Gray ES, Freeman JB, Reid A, Bowyer S, Millward M, Ziman M - BMC Cancer (2014)

Kaplan-Meier curves for (A, D) OS, (B, E) PFS and (C, F) time to response of all melanoma patients with > =2 cells and <2 CTCs in 4.5 ml of blood. (C) Only patients undergoing system therapies were analysed for treatment response, N = 17. Patients treated with the B-Raf inhibitor vemurafenib were analysed separately (D, E and F).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4060872&req=5

Figure 1: Kaplan-Meier curves for (A, D) OS, (B, E) PFS and (C, F) time to response of all melanoma patients with > =2 cells and <2 CTCs in 4.5 ml of blood. (C) Only patients undergoing system therapies were analysed for treatment response, N = 17. Patients treated with the B-Raf inhibitor vemurafenib were analysed separately (D, E and F).
Mentions: A Kaplan-Meier analysis was performed to determine the association between baseline CTCs and prognostic values such as OS, PFS and response to treatment (Figure 1A, B and C). Log-rank test did not show an association between the number of baseline CTCs and any of these three outcome measurements. The analysis was performed repeatedly using different cut off values to define a favourable or unfavourable CTC number, at 3, 4 or 5 CTCs, but no statistical significance was found in any of these comparisons.

Bottom Line: Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival.However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy.A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Medical Sciences, Edith Cowan University (ECU), 270 Joondalup Drive, Joondalup, Perth, WA 6027, Australia. e.gray@ecu.edu.au.

ABSTRACT

Background: New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes.

Methods: CTCs were captured by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled prospectively and CTC counts performed at baseline (prior to treatment), during and after treatment.

Results: Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival. However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy. A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients.

Conclusions: Measuring changes in CTC numbers during treatment is useful for monitoring therapy response in melanoma patients and for providing prognostic information relating to overall survival. Further studies with larger sample sizes are required to confirm the utility of CTC quantification as a companion diagnostic for metastatic melanoma treatment.

Show MeSH
Related in: MedlinePlus