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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

Times to response, progression and death among the 27 patients in the study. For patients where the changes in CTC numbers were evaluated, the bars were coloured red for an increase or grey for a decrease.
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Figure 3: Times to response, progression and death among the 27 patients in the study. For patients where the changes in CTC numbers were evaluated, the bars were coloured red for an increase or grey for a decrease.

Mentions: Log-rank Mantel-Cox tests (Figure 2A, B and C) demonstrated that a decrease in CTCs after treatment (negative slope) is associated with longer OS (HR 7.7, 95% CI 1.6-36.8, log-rank P = 0.0099) and shorter time to respond to treatment (HR 0.19, 95% CI 0.04-0.93, log-rank P = 0.0406). No association was observed between changes in CTCs and PFS (P = 0.3508). A sub-analysis of only vemurafenib treated patients produced similar results (Figure 2D, E and F). A decrease in CTCs in patients treated with vemurafenib was associated with longer OS (HR 12.7, 95% CI 1.2-135.5, log-rank P = 0.0348). Of note, none of the vemurafenib treated patients with a decrease in CTCs died during the follow up period (Figure 3). Moreover, patients with a decrease in CTCs had a faster response to treatment (HR 0.12, 95% CI 0.02-0.86, log-rank P = 0.0344). All vemurafenib treated patients with a decrease in CTCs had a documented objective response within the first 12 weeks after treatment. Data from a representative patient is shown in Figure 4, illustrating the concomitant reduction in metastatic growth and the number of CTCs after 2 months of treatment with vemurafenib.


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)

Times to response, progression and death among the 27 patients in the study. For patients where the changes in CTC numbers were evaluated, the bars were coloured red for an increase or grey for a decrease.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Times to response, progression and death among the 27 patients in the study. For patients where the changes in CTC numbers were evaluated, the bars were coloured red for an increase or grey for a decrease.
Mentions: Log-rank Mantel-Cox tests (Figure 2A, B and C) demonstrated that a decrease in CTCs after treatment (negative slope) is associated with longer OS (HR 7.7, 95% CI 1.6-36.8, log-rank P = 0.0099) and shorter time to respond to treatment (HR 0.19, 95% CI 0.04-0.93, log-rank P = 0.0406). No association was observed between changes in CTCs and PFS (P = 0.3508). A sub-analysis of only vemurafenib treated patients produced similar results (Figure 2D, E and F). A decrease in CTCs in patients treated with vemurafenib was associated with longer OS (HR 12.7, 95% CI 1.2-135.5, log-rank P = 0.0348). Of note, none of the vemurafenib treated patients with a decrease in CTCs died during the follow up period (Figure 3). Moreover, patients with a decrease in CTCs had a faster response to treatment (HR 0.12, 95% CI 0.02-0.86, log-rank P = 0.0344). All vemurafenib treated patients with a decrease in CTCs had a documented objective response within the first 12 weeks after treatment. Data from a representative patient is shown in Figure 4, illustrating the concomitant reduction in metastatic growth and the number of CTCs after 2 months of treatment with vemurafenib.

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